VOLUME 77 Suppl.

1 JULY 2022

THE
INTERNATIONAL
LIVER
CONGRESS
TM

Savour science together again

#ILC2022

22–26
JUNE
2022
LONDON

easl.eu/ilc2022
EDITOR IN CHIEF DEPUTY EDITOR CO-EDITORS
Paolo Angeli, Italy Patrizia Burra, Italy Vlad Ratziu, France | Bruno Sangro, Spain I
Frank Tacke, Germany | Stefan Zeuzem, Germany

ASSOCIATE EDITORS
Alcohol and Drug-Related Liver Diseases Gut-Liver Axis Liver Fibrosis Statistics, A.I. and Modelling Outcomes
Einar S. Björnsson, Iceland Bernd Schnabl, USA Massimo Pinzani, UK Anna Chiara Frigo, Italy
Alexandre Louvet, France Jonel Trebicka, Germany Raphaël Porcher, France
Liver Surgery and Transplantation
Cholestasis and Autoimmune Diseases Hepatic and Biliary Cancer Vascular Liver Diseases
Pierre-Alain Clavien, Switzerland
Tom H. Karlsen, Norway Jesper Andersen, Denmark Jordi Gracia-Sancho, Spain
Julie K. Heimbach, USA
Ulrich Beuers, Netherlands John Bridgewater, UK
Francesco P. Russo, Italy Viral Hepatitis
Stephen L. Chan, Hong Kong
Complications of Cirrhosis and Liver Failure Thomas Baumert, France
Jean-Charles Nault, France
Paolo Caraceni, Italy NAFLD Maria Buti, Spain
Maria Reig, Spain
Javier Fernández, Spain Quentin Anstee, UK Markus Cornberg, Germany
Constantine Karvellas, Canada Imaging and Non-Invasive Tests Elisabetta Bugianesi, Italy Edward John Gane, New Zealand
Annalisa Berzigotti, Switzerland Jacob George, Australia
Disease Burden and Public Health Man Fung Yuen, Hong Kong
Rita Golfieri, Italy Wajahat Mehal, USA
Gregory Dore, Australia Maxime Ronot, France Consultants
Genetics Immunology Pathology Julius Chapiro, USA
Matías Ávila, Spain Barbara Rehermann, USA Christine Sempoux, Switzerland Peter Jepsen, Denmark

SPECIAL SECTION EDITORS

Reviews Snapshot Website/Social Media
Michael Trauner, Austria Sara Montagnese, Italy Jesus Bañales, Spain
Alexander Ploss, USA Eliott B. Tapper, USA

EDITORIAL BOARD Puneeta Tandon, Canada

Reiner Wiest, Switzerland
Vincenzo Mazzaferro, Italy
Rajender K. Reddy, USA
Elisabet García, Spain
Jeremie Guedj, France
Alcohol and Drug-Related Liver Diseases Alberto Sánchez-Fueyo, UK
Epidemiology/Public Health Vascular Liver Diseases
Raul Andrade, Spain Gonzalo Sapisochin, Canada
Jeffrey Lazarus, Spain Yasuko Iwakiri, USA
Michael R. Lucey, USA Christian Toso, Switzerland
Uwe Siebert, Austria Vincenzo La Mura, Italy
Philippe Mathurin, France
NAFLD Pierre-Emmanuel Rautou, France
Laura E. Nagy, USA Genetics Leon Adams, Australia
Georges-Philippe Pageaux, France Frank Lammert, Germany Viral Hepatitis
Guruprasad Aithal, UK
Mark R. Thursz, UK Stefano Romeo, Sweden Alessio Aghemo, Italy
Helena Cortez-Pinto, Portugal
Sandra Ciesek, Germany
Basic Science Gut-Liver Axis Henning Grønbaek, Denmark
James Fung, Hong Kong
Javier Cubero, Spain Rohit Loomba, USA
Sofia Forslund, Germany Jason Grebely, Australia
Giulio Marchesini, Italy
Josè Fernandez-Checa, Spain Aleksander Krag, Denmark Ira Jacobson, USA
Philip N. Newsome, UK
Chandrashekar Gandhi, USA Patrick Kennedy, UK
Hepatic and Biliary Cancer Elizabeth E. Powell, Australia
Mathias Heikenwälder, Germany Pietro Lampertico, Italy
Ann-Lii Cheng, Taiwan Manuel Romero-Gómez, Spain
Irene Ng, China Darius Moradpour, Switzerland
Laura Dawson, Canada Arun Sanyal, USA
Cecilia Rodrigues, Portugal Jean-Michel Pawlotsky, France
Peter R. Galle, Germany Jörn Schattenberg, Germany
Detlef Schuppan, Germany Thomas Pietschmann, Germany
Tim Greten, USA Giovanni Targher, Italy
Charles Rice, USA
Chiun Hsu, Taiwan Luca Valenti, Italy
Cholestatic and Autoimmune Diseases Jian Sun, China
Katie Kelley, USA Grace Wong, Hong Kong
Martti Färkkilä, Finland Robert Thimme, Germany
Josep Llovet, USA Vincent Wong, Hong Kong
Michael Heneghan, UK Stephan Urban, Germany
Shira Zelber-Sagi, Israel
Gideon Hirschfield, Canada Tom Luedde, Germany Heiner Wedemeyer, Germany
Pietro Invernizzi, Italy Tim Meyer, UK Non-invasive Diagnoses and Imaging Fabien Zoulim, France
Verena Keitel, Germany Pierre Nahon, France Jérôme Boursier, France
Ansgar Lohse, Germany Hayato Nakagawa, Japan Laurent Castera, France EDITORS EMERITUS
Xiong Ma, China Lorenza Rimassa, Italy Thierry de Baere, France Dame Sheila Sherlock†, Founding
Aldo J. Montano-Loza, Canada Jinsil Seong, Republic of Korea Richard (Dick) L. Ehman, USA Editor, UK (1985-1989)
Atsushi Tanaka, Japan Beicheng Sun, China Salvatore Petta, Italy Jean-Pierre Benhamou†, France (1990-1994)
Juan Valle, UK Jordi Rimola, Spain Gustav Paumgartner, Germany (1995-1999)
Complications of Cirrhosis and Liver Failure Riad Salem, USA Juan Rodés†, Spain (2000-2004)
Juan G. Abraldes, Canada Immunology
Massimo Colombo, Italy (2005-2009)
Banwari Agarwal, UK Mala Maini, UK Pathology Didier Samuel, France (2010-2014)
Jasmohan S. Bajaj, USA Elsa Solà, Spain Karoline Lackner, Austria Rajiv Jalan, UK (2015-2019)
William Bernal, UK Valerie Paradis, France
Liver Fibrosis
Andrés Cárdenas, Spain Scott Friedman, USA
Peter Schirmacher, Germany EDITORIAL OFFICE
Claire Francoz, France Dina Tiniakos, UK Manager
Tatiana Kisseleva, USA
Guadalupe Garcia-Tsao, USA Achim Weber, Switzerland Joël Walicki
Isabelle Leclercq, Belgium
Pere Ginés, Spain Robert E. Schwartz, USA Coordinators
Pediatrics
Thierry Gustot, Belgium Thierry Tordjmann, France Jiyeong Adams
Emmanuel Jacquemin, France
Wim Laleman, Belgium Holger Willenbring, USA Duncan Anderson
Pietro Vajro, Italy
Mattias Mandorfer, Austria Assistant
Sebastian Marciano, Argentina Liver Surgery and Transplantation Statistics, A.I. and Modeling Outcomes Kristina Jajcevic
Salvatore Piano, Italy Martina Gambato, Italy Alex Amoros, Spain Scientific Illustrator
Shiv K. Sarin, India Giacomo Germani, Italy Calogero Camma, Italy Pablo Echeverria

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SCIENTIFIC COMMITTEE EDUCATIONAL COUNCILLOR Journal of Hepatology Editorial Office
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Saskia van Mil, Netherlands
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 JOURNAL OF HEPATOLOGY
VOLUME 77, SUPPLEMENT 1, PAGES S1–S1080

Abstracts of The International Liver Congress™ 2022

22–26 June 2022, London, United Kingdom

Publication of this Abstract supplement was supported by the European Association for the Study of the Liver (EASL)

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2022
No. 4 APRIL
VOLUME 76

VOLUME 76
No. 3 MARCH
2022

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 JOURNAL OF HEPATOLOGY
VOLUME 77, SUPPLEMENT 1, PAGES S1–S1080

CONTENTS
Oral Presentations

General Session I ........................................................................................................................................ S1

General Session II ....................................................................................................................................... S5

Late-Breaker .............................................................................................................................................. S10

Hepatitis C: Clinical aspects and therapy ............................................................................................................ S15

Cirrhosis and its complications: Other clinical complications except ACLF and critical illness .............................................. S18

Non-invasive assessment of liver disease except NAFLD .......................................................................................... S22

Immune-mediated and cholestatic: Experimental and pathophysiology ....................................................................... S26

Non-invasive assessment/treatment and liver related outcomes in NAFLD/ALD .............................................................. S29

Alcoholic liver disease .................................................................................................................................. S33

Fibrosis .................................................................................................................................................... S36

NAFLD: Clinical aspects except therapy .............................................................................................................. S39

Viral hepatitis elimination ............................................................................................................................. S42

Primary Liver Cancer: Experimental and pathophysiology ....................................................................................... S45

Cirrhosis and its complications: ACLF and Critical illness ......................................................................................... S48

Liver Immunology ....................................................................................................................................... S53

Rare liver diseases (including paediatric and genetic) ............................................................................................. S58

Nurses and AHP ......................................................................................................................................... S63

Gut microbiota in liver disease and liver regeneration ............................................................................................ S65

Hepatitis B emerging therapies ....................................................................................................................... S69

NAFLD: Diagnostics and non-invasive assessment ................................................................................................. S73

Liver tumours: Clinical aspects except therapy ..................................................................................................... S75

Public health ............................................................................................................................................. S80

Molecular and cellular biology ........................................................................................................................ S83

NAFLD Therapy .......................................................................................................................................... S86

Cirrhosis and its complications: Portal Hypertension ............................................................................................. S89

Immune-mediated and cholestatic disease: Clinical aspects ..................................................................................... S93

Viral hepatitis basic science ............................................................................................................................ S97

 Hepatitis B clinical aspects ............................................................................................................................. S100

Cirrhosis and its complications: Experimental and pathophysiology ........................................................................... S103

Liver tumours: Therapy ................................................................................................................................. S107

NAFLD: Experimental and pathophysiology ......................................................................................................... S111

Liver transplantation and Acute liver failure: Clinical aspects .................................................................................... S114

Poster Presentations

Alcoholic liver disease .................................................................................................................................. S119

NAFLD: Clinical aspects except therapy .............................................................................................................. S144

Gut microbiota and liver disease ...................................................................................................................... S173

Immunology ............................................................................................................................................. S183

Public Health ............................................................................................................................................. S200

Viral hepatitis A/E: Clinical aspects ................................................................................................................... S269

Viral hepatitis B/D: Clinical aspects except therapy ................................................................................................ S271

Immune-mediated and cholestatic disease: Clinical aspects ..................................................................................... S305

Cirrhosis and its complications: ACLF and Critical illness ......................................................................................... S339

Cirrhosis and its complications: Experimental and pathophysiology ........................................................................... S358

Liver tumours: Therapy ................................................................................................................................. S372

Acute liver failure and drug induced liver injury ................................................................................................... S389

NAFLD: Diagnostics and non-invasive assessment ................................................................................................. S409

Fibrosis .................................................................................................................................................... S463

Non-invasive assessment of liver disease except NAFLD .......................................................................................... S495

Nurses and Allied Health Professionals .............................................................................................................. S509

Rare liver diseases (including paediatric and genetic) ............................................................................................. S513

Viral hepatitis C: Clinical aspects except therapy ................................................................................................... S541

Viral Hepatitis C: Post SVR and long term follow up ............................................................................................... S561

Viral hepatitis C: Therapy and resistance ............................................................................................................ S579

Immune-mediated and cholestatic: Experimental and pathophysiology ....................................................................... S599

Cirrhosis and its complications: Portal Hypertension ............................................................................................. S608

Liver tumours: Experimental and pathophysiology ................................................................................................ S636

NAFLD: Experimental and pathophysiology ......................................................................................................... S665

NAFLD: Therapy ......................................................................................................................................... S713

Liver development, physiology and regeneration .................................................................................................. S734

Molecular and cellular biology ........................................................................................................................ S745

Liver transplantation and hepatobiliary surgery: Clinical aspects ............................................................................... S767

Liver transplantation and hepatobiliary surgery: Experimental and pathophysiology ....................................................... S818

Viral hepatitis B/D: therapy ............................................................................................................................ S823

Cirrhosis and its complications: Other clinical complications except ACLF and critical illness .............................................. S882
 Liver tumours: Clinical aspects except therapy ..................................................................................................... S912

Author Index ............................................................................................................................................... S940

Disclosures: no commercial relationships . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S1021

Disclosures: commercial relationships . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S1065

Reviewers list . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S1080

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 The A-TANGO project - featuring G-TAK, a novel
combinatorial therapy for acute-on-chronic liver failure (ACLF)
Expected Impact

• More than 10 million people suffer from decompensated cirrhosis worldwide.

• Effective treatment of ACLF is an urgent and unmet need.
• A-TANGO performs Phase II clinical studies of G-TAK, a novel and innovative therapeutic
strategy that aims to reduce inflammation and improve hepatocyte proliferation.
• A-TANGO also strives to identify reliable biomarkers for better patient stratification and
increased survival.

14 partners, one goal:

Helping cirrhosis patients
in Europe!

www.a-tango.eu
[email protected]

This project has received funding from the European Union’s Horizon 2020
research and innovation programme under grant agreement No 945096.
 kick-off
1st April 2020

project duration
5 ½ years

10 countries
21 institutions

grant amount
6 million € Follow us on Twitter and LinkedIN:

www.decision-for-liver.eu Decision4Liver

decision-project

The objective of DECISION is to better understand the pathophysiology of decompensated

cirrhosis leading to acute-on-chronic liver failure (ACLF) or death. This consortium will
take advantage of already existing large and clinically well-characterised patient cohorts to
develop reliable prognostic and response tests and combinatorial therapies tailored to the
needs of individual patients to decrease the risk of short-term death.
Pathophysiologic elucidation of acute decompensated cirrhosis at the systems level
(genetics, epigenetics, transcriptomics, metabolomics, lipidomics, miR, and analysis
of extracellular vesicles)

Integration of existing clinical data and new multi-omics data from 2,200 patients
with more than 8,600 measurements

Development of new combinatorial therapies

Optimization of therapies using existing and new animal models

Development of novel and robust tests for prediction of outcome following traditional treatment
versus response to new therapies
Phase II clinical trials to test new combination therapies

Creation of new guidelines for outcome prediction and personalized treatment of acute
decompensated cirrhosis to prevent ACLF to death

This project has received funding from the European Union's Horizon 2020
research and innovation programme under grant agreement No 847949.

Keyvisual composing: © eranicle (liver) and Matjaz Slanic (light spots)

 Liver Investigation: Testing Marker Utility in Steatohepatitis

• 54 partners
• 14 countries for clinical recruitment
• True public-private co-funding model

The overarching aim of LITMUS is to develop, robustly

validate and advance towards regulatory qualification
biomarkers that diagnose, risk stratify and/or monitor
NAFLD/NASH progression and fibrosis stage.

litmus-project.eu
imi.europa.eu

The LITMUS project has received funding from the

Innovative Medicines Initiative 2 Joint Undertaking
under grant agreement No. 777377. This Joint Under-
taking receives support from the European Union’s
Horizon 2020 research and innovation programme
and EFPIA.
 Screening for liver fibrosis
population-based study
across European Countries
A project that will change the paradigm
of diagnosis of chronic liver diseases

AIM:
To assess the prevalence of liver fibrosis in the general population
using Transient Elastography, with the objective of establishing
criteria for screening for liver fibrosis in the population.

An Horizon 2020 funded project - Grant Number 847989

MICROBiome-based biomarkers
to PREDICT decompensation of
liver cirrhosis and treatment response

Project duration
6 ¼ years

Grant amount
Start
15 million €
01 January 2019

10 Countries
Follow-us on Twitter and LinkedIN:
22 Partners
@MicrobPredict
MICROB-PREDICT www.microb-predict.eu

will investigate
the human microbiome to identify predictors and mechanisms associated with the
development of decompensation of cirrhosis and progression to
acute-on-chronic liver failure (ACLF) and death.
New microbiome-based tests for better stratification of cirrhosis patients
Personalized prediction and prevention of decompensation and ACLF
Clinical trial to predict response to treatment
Modern, effective nanobiosensors as clinical tools with improved specificity
More personalized treatment
Increased survival times
Decreased costs for the health systems

This project has received funding from the European Union's Horizon 2020
research and innovation programme under grant agreement No 825694. Picture: 3D-Illustration © ag visuell | Fotolia.com
ORAL PRESENTATIONS JOURNAL OF
HEPATOLOGY

Thursday 23 June

General Session I

GS001
Efficacy and safety of ALXN1840 versus standard of care in Wilson
disease: primary results from an ongoing phase 3, randomized,
controlled, rater-blinded trial
Karl Heinz Weiss1, Michael Schilsky2, Anna Czlonkowska3,
Fred Askari4, Aftab Ala5, Peter Ferenci6, Peter Ott7,
Dzhamal Abdurakhmanov8, Ferenc Szalay9, Piotr Socha10,
Norikazu Shimizu11, Jeff Bronstein12, Danny Bega13, Sihoun Hahn14,
Eugene Swenson15, Yi Chen15, Aurelia Poujois16. 1Krankenhaus Salem
der Evang. Stadtmission Heidelberg gGmbH, Heidelberg, Germany; 2Yale
School of Medicine, New Haven, United States; 3Institute of Psychiatry
and Neurology, Warsaw, Poland; 4University of Michigan Health System,
Ann Arbor, United States; 5Royal Surrey County Hospital, Guildford,
United Kingdom; 6Medical University of Vienna, Vienna, Austria;
7
Aarhus University Hospital, Aarhus, Denmark; 8Sechenov First Moscow
State Medical University, Moscow, Russian Federation; 9Semmelweis
University, Budapest, Hungary; 10The Children’s Memorial Health
Institute, Warsaw, Poland; 11Toho University School of Medicine, Tokyo,
Japan; 12Ronald Reagan UCLA Medical Center, Los Angeles, United States;
13
Northwestern University Feinberg School of Medicine, Chicago, United
States; 14University of Washington/Seattle Children’s Hospital, Seattle,
United States; 15Alexion, AstraZeneca Rare Disease, Boston, United
States; 16Rothschild Foundation Hospital, Paris, France
Email: [email protected]

Abstract GS001 is under embargo until the start of the

General Session I on Thursday 23 June 2022, 13:30 BST. It
will be made publicly available on the congress website once
the embargo has lifted.

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 © 2022 All rights reserved.
ORAL PRESENTATIONS
GS002
Anti-fibrotic effect of rifaximin in early alcohol-related liver
disease: a double-blind, randomised, placebo-controlled trial
Mads Israelsen1, Bjørn Stæhr Madsen1, Nikolaj Torp1,2,
Stine Johansen1,2, Camilla Dalby Hansen1,2, Sönke Detlefsen1,2,
Peter Andersen1, Johanne Kragh Hansen1,2, Katrine Prier Lindvig1,2, GS003
Ditlev Nytoft Rasmussen1, Katrine Thorhauge1,2, Maria Kjærgaard1,2, The spatial distribution and detailed composition of infiltrating
Manimozhiyan Arumugam1,3, Torben Hansen3, Jonel Trebicka1,4,5, immune cells define autoimmune- and checkpoint-therapy
Maja Thiele1,2, Aleksander Krag1,2. 1Odense University Hospital, Odense, associated hepatitis
Denmark; 2University of Southern Denmark, Faculty of Health Sciences; Laurenz Krimmel1, Henrike Salie1, Saskia Killmer1,
3
Copenhagen University, CBMR, København, Denmark; 4Goethe Marilyn Salvat Lago1, Nisha Rana1, Peter Bronsert2,
University Frankfurt, Gastroenterology, Frankfurt, Germany; 5European David Rafei-Shamsabadi3, Frank Meiss3, Ursula Ehmer4,
Foundation for the study of chronic liver failure, Barcelona, Spain Angela Krackhardt5, Marius Schwabenland6, Marco Prinz6,7,
Email: [email protected] Christoph Neumann-Haefelin1, Maike Hofmann1,
Michael Schultheiss1, Robert Thimme1, Carolin Mogler8,
Bertram Bengsch1,7. 1Freiburg University Medical Center, Department of
Internal Medicine II (Gastroenterology, Hepatology, Endocrinology und
Abstract GS002 is under embargo until the start of the Infectiology), Freiburg, Germany; 2Freiburg University Medical Center,
General Session I on Thursday 23 June 2022, 13:30 BST. It Institute of Pathology, Freiburg, Germany; 3Freiburg University Medical
will be made publicly available on the congress website once Center, Department of Dermatology, Freiburg, Germany; 4Klinikum
rechts der Isar Technical University Munich, Department of Internal
the embargo has lifted. Medicine II, Munich, Germany; 5Klinikum rechts der Isar Technical
University Munich, Department of Internal Medicine III, Munich,
Germany; 6Freiburg University Medical Center, Institute of
Neuropathology, Freiburg, Germany; 7Signalling Research Centres BIOSS
and CIBSS, Freiburg, Germany; 8Technical University Munich, Institute of
Pathology, Munich, Germany
Email: [email protected]

Abstract GS003 is under embargo until the start of the

General Session I on Thursday 23 June 2022, 13:30 BST. It
will be made publicly available on the congress website once
the embargo has lifted.

S2 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS

GS004
Prospective randomized controlled trial of biomarkers for early
detection of hepatocellular carcinoma
Hooman Farhang Zangneh1, Orlando Cerocchi1, Korosh Khalili2,
Lima Awad El-Karim2, Mara Vecchio3, Jeffrey Winick3, Yasuhiro Mori4,
Hiroyuki Yamada4, Harry Janssen1, Bettina Hansen1,5,
Morris Sherman1, Jordan Feld1. 1University Health Network, Toronto
General Hospital, Toronto Centre for Liver Disease, Toronto, Canada;
2
University Health Network, Joint Department of Medical Imaging,
Toronto, Canada; 3Fujifilm Healthcare Americas Corporation, United
States; 4Fujifilm Wako Pure Chemical Corporation, Osaka, Japan;
5
University of Toronto, Institute of Health Policy, Management and
Evaluation, Toronto, Canada
Email: [email protected]

Abstract GS004 is under embargo until the start of the

General Session I on Thursday 23 June 2022, 13:30 GS005
Development and validation of the gender-equity model for liver
BST. It will be made publicly available on the congress
allocation (GEMA) to prioritize liver transplant candidates
website once the embargo has lifted. Manuel Rodríguez-Perálvarez1, Antonio M. Gómez-Orellana2,
Avik Majumdar3, Geoff McCaughan3, Paul Gow4, David Guijo-Rubio2,
César Hervás2, Michael Bailey5, Emmanuel Tsochatzis6. 1Hospital
Universitario Reina Sofía, University of Córdoba, IMIBIC, CIBERehd,
Department of Hepatology and Liver Transplantation, Córdoba, Spain;
2
University of Córdoba, Department of Computer Science and Numerical
Analysis, Córdoba, Spain; 3Royal Prince Alfred Hospital, Morrow
Gastroenterology and Liver Centre and Australian National Liver
Transplant Unit, Sydney, Australia; 4The University of Melbourne, Austin
Health, Victorian Liver Transplant Unit, Melbourne, Australia;
5
Australian and New Zealand Intensive Care Research Centre (ANZIC RC),
Department of Epidemiology and Preventive Medicine, Melbourne,
Australia; 6Royal Free Hospital and University College London (UCL),
Sheila Sherlock Liver Unit and UCL Institute for Liver and Digestive
Health, London, United Kingdom
Email: [email protected]

Abstract GS005 is under embargo until the start of the

General Session I on Thursday 23 June 2022, 13:30 BST. It
will be made publicly available on the congress website once
the embargo has lifted.

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S3

ORAL PRESENTATIONS
Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy;
17
CRC “A. M. and A. Migliavacca” Center for Liver Disease, University of
Milan, Department of Pathophysiology and Transplantation, Milan, Italy
Email: [email protected]

Abstract GS006 is under embargo until the start of the

General Session I on Thursday 23 June 2022, 13:30 BST. It
will be made publicly available on the congress website once
the embargo has lifted.

GS006
Efficacy and safety of bulevirtide monotherapy given at 2 mg or
10 mg dose level once daily for treatment of chronic hepatitis
delta: week 48 primary end point results from a phase 3
randomized, multicenter, parallel design study
Heiner Wedemeyer1, Soo Aleman2, Maurizia Brunetto3,4,
Antje Blank5, Pietro Andreone6, Pavel Bogomolov7,
Vladimir Chulanov8, Nina Mamonova8, Natalia Geyvandova9,
Morozov Viacheslav10, Olga Sagalova11, Tatyana Stepanova12,
Dmitry Manuilov13, Vithika Suri13, Qi An13, John F. Flaherty13,
Anu Osinusi13, Julian Schulze zur Wiesch14, Markus Cornberg1,
Stefan Zeuzem15, Pietro Lampertico16,17. 1Medizinische Hochschule
Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie,
Hannover, Germany; 2Karolinska University Hospital/Karolinska
Institutet, Department of Infectious Diseases, Stockholm, Sweden;
3
University Hospital of Pisa, Hepatology Unit, Reference Center of the
Tuscany Region for Chronic Liver Disease and Cancer, Pisa, Italy;
4
University of Pisa, Department of Clinical and Experimental Medicine,
Pisa, Italy; 5Heidelberg University Hospital, Clinical Pharmacology and
Pharmacoepidemiology, Heidelberg, Germany; 6University of Modena
and Reggio Emilia, Internal Medicine, Modena, Italy; 7State budgetary
institution of health care of Moscow region “Moscow regional research
clinical institute after M.F. Vladimirsky”, Moscow, Russian Federation;
8
FSBI National Research Medical Center for Phthisiopulmonology and
Infectious Diseases of the Ministry of Health of the Russian Federation,
Moscow, Russian Federation; 9Stavropol Regional Hospital, Stavropol,
Russian Federation; 10LLC Medical Company “Hepatolog,” Samara,
Russian Federation; 11Federal state-funded institution of higher
education “Southern Ural State Madical University of Ministry of Health
of the Russian Federation”, Chelyabinsk, Russian Federation; 12Limited
liability company “Clinic of Modern Medicine,” Moscow, Russian
Federation; 13Gilead Sciences, Foster City, United States;
14
Universitätsklinikum Hamburg-Eppendorf, Medizinische Klinik
Studienambulanz Hepatologie, Hamburg, Germany; 15University
Hospital Frankfurt, Department of Medicine, Frankfurt am Main,
Germany; 16Foundation IRCCS Ca’ Granda Ospedale Maggiore

S4 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS

Friday 24 June

General Session II

GS007
Transcatheter arterial chemoembolization (TACE) followed by
conformal radiotherapy versus TACE alone for hepatocellular
carcinoma: a western controlled trial
Cyrille Feray1, Loic Campion2, Isabelle Mabile-Archambeaud3,
Philippe Mathurin4, Xavier Mirabel5, Emmanuel Rio2,
Jean-Pierre Bronowicki6, Yann Touchefeu3, Jérôme Gournay3,
Agnès Rode7, Francoise Mornex8, Philippe Merle9. 1Centre Hepato
Biliaire, Villejuif, France; 2CRLCC, Nantes, France; 3IMAD, Nantes, France;
4
Hepatology, Lille, France; 5CRLCC, Lille, France; 6Hepatology, Nancy,
France; 7Radiology, Lyon, France; 8Radiotherapy, Lyon, France;
9
Hepatology, Lyon, France
GS008
Email: [email protected]
The global burden of liver cancer (LC) and chronic liver diseases
(CLD) is driven by non-alcoholic steatohepatitis (NASH) and
alcohol liver disease (ALD)
James Paik1,2, Linda Henry1,2,3, Youssef Younossi3, Janus Ong3,4,
Abstract GS007 is under embargo until the start of the Saleh Alqahtani3,5,6, Zobair Younossi1,2,7. 1Inova Health System, Center
General Session II on Friday 24 June 2022, 13:40 BST. It for Liver Diseases, Department of Medicine; 2Betty and Guy Beatty
will be made publicly available on the congress website Center for Integrated Research, IHS; 3Center for Outcomes Research in
once the embargo has lifted. Liver Disease; 4University of the Philippines, College of Medicine; 5Johns
Hopkins Medical Center; 6King Faisal Specialist Hospital and Research
Center; 7Inova Health System, Medicine Service Line
Email: [email protected]

Abstract GS008 is under embargo until the start of the

General Session II on Friday 24 June 2022, 13:40 BST. It
will be made publicly available on the congress website
once the embargo has lifted.

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S5

ORAL PRESENTATIONS

S6 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS
Pharmacology ITMP, Fraunhofer Institute for Translational Medicine and
Pharmacology ITMP, Theodor-Stern-Kai 7, 60956 Frankfurt, Germany,
Frankfurt am Main, Germany; 17University of Lisbon, Research Insitute
for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Lisbon,
Portugal, Lisbon, Portugal; 18Newcastle University, Bioinformatics
Support Unit, Faculty of Medical Sciences, Newcastle University,
Newcastle upon Tyne, United Kingdom, Newcastle upon Tyne, United
Kingdom; 19Newcastle University, Translational and Clinical Research
Institute, Faculty of Medical Sciences, Newcastle University, Newcastle
upon Tyne, United Kingdom, Newcastle upon Tyne, United Kingdom;
20
Cambridge University Hospitals NHS Foundation Trust, Liver Unit,
Cambridge NIHR Biomedical Research Centre, Cambridge, United
Kingdom; 21AstraZeneca, Bioscience Metabolism, Research and Early
GS0009 Development Cardiovascular, Renal and Metabolism (CVRM),
Is there a murine model that fully recapitulates human NASH? An BioPharmaceuticals RandD, AstraZeneca, Gaithersburg, MD, USA,
unbiased bioinformatics approach to rank pre-clinical models Gaithersburg, MD, United States; 22Pfizer, Inflammation and
based on proximity to human disease Immunology Research Unit, Pfizer Worldwide Research and
Michele Vacca1,2, Ioannis Kamzolas1,3, Lea Mørch Harder4, Development, Cambridge Massachusetts, Cambridge Massachusetts,
Fiona Oakley5, Christian Trautwein6, Maximilian Hatting6, United States; 23Sanyal Biotechnology LLC, Sanyal Biotechnology LLC,
Trenton Ross7, Barbara Bernardo8, Anouk Oldenburger9, Norfolk, Virginia, USA, Virginia, United States; 24Virginia commonwealth
Sara Toftegaard Hjuler4, Iwona Ksiazek10, Daniel Linden11,12, university, Department of Internal Medicine, Virginia commonwealth
Detlef Schuppan13, Sergio Rodriguez-Cuenca1, university, Richmond, VA, United States; 25Takeda Pharmaceuticals
Maria Manuela Tonini14, Aimo Kannt15,16, International AG, Takeda Pharmaceuticals International AG, Takeda
Tamara Rodriguez-Castaneda15, Cecília M. P. Rodrigues17, Pharmaceutical Company Limited, Fujisawa, Japan, Fujisawa, Japan;
Simon Cockell18, Olivier Govaere19, Ann K. Daly19, Michael Allison20, 26
Université Paris-Diderot, Department of Imaging and Pathology,
Kristian Honnens de Lichtenberg4, Yong Ook Kim13, Anna Lindblom11, Hôpital Beaujon, Paris, France; 27Cambridge University Hospitals NHS
Stephanie Oldham21, Anne-Christine Andréasson11, Foundation Trust, Department of Cellular Pathology, Cambridge
Franklin Schlerman22, Jonathon Marioneaux23, Arun Sanyal24, University Hospitals NHS Foundation Trust, Cambridge, United
Marta B. Afonso17, Anthony Rinaldi7, Yuichiro Amano25, Kingdom; 28University of Antwerp, Department of Pathology, University
Valérie Paradis26, Alastair Burt19, Davies Susan27, Ann Driessen28, of Antwerp, Antwerp, Belgium, Antwerp, Belgium; 29Takeda
Hiroaki Yashiro29, M. Julia Brosnan7, Carla Yunis7, Pierre Bedossa30, Pharmaceuticals International AG, Takeda Pharmaceuticals
Dina Tiniakos31,32, Quentin Anstee31,33, Evangelia Petsalaki3, International AG, Takeda Pharmaceutical Company Limited, Cambridge,
Peter Davidsen4, Jim Perfield34, Antonio Vidal-Puig1. 1University of Massachusetts, Cambridge, Massachusetts, United States; 30Newcastle
Cambridge, WT/MRC Institute of Metabolic Science, United Kingdom; University, LiverPat, Paris, France and Translational and Clinical Research
2
University of Bari Aldo Moro, Interdisciplinary Department of Medicine, Institute, Newcastle University, UK, France; 31Newcastle University,
Bari, Italy; 3European Molecular Biology Laboratory, European Translational and Clinical Research Institute, Faculty of Medical Sciences,
Bioinformatics Institute (EMBL-EBI), European Molecular Biology Newcastle University, Newcastle upon Tyne, UK, Newcastle upon Tyne,
Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome United Kingdom; 32National and Kapodistrian University of Athens,
Genome Campus, Hinxton, UK, Hinxton, Cambridge, United Kingdom; Department of Pathology, Aretaieion Hospital, Medical School, National
4
Novo Nordisk, Research and Early Development, Novo Nordisk A/S, and Kapodistrian University of Athens, Greece, Athens, Greece;
Denmark, Måløv, Copenhagen, Denmark; 5Newcastle University, 33
Newcastle University, Newcastle NIHR Biomedical Research Centre,
Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, United
Medical Sciences, Newcastle University, Newcastle upon Tyne, UK, Kingdom, Newcastle upon Tyne, United Kingdom; 34Eli Lilly and
Newcastle, United Kingdom; 6Aachen University Hospital, Department of Company, Lilly Research Laboratories, Eli Lilly and Company,
Medicine III, Aachen; 7Pfizer IMRU, Internal Medicine Research Unit, Indianapolis, Indiana, Indianapolis, Indiana, United States
Pfizer Worldwide Research and Development, Cambridge Massachusetts, Email: [email protected]
United States; 8Pfizer, Internal Medicine, Pfizer Worldwide Research and
Development, 558 Eastern Point Road, Groton, CT, 06340, USA, Groton,
United States; 9Boehringer Ingelheim Pharma GmbH and Co. KG,
CardioMetabolic Diseases Research, Boehringer Ingelheim Pharma Abstract GS009 is under embargo until the start of the
GmbH and Co. KG, Biberach a.d. Riss, Germany, Biberach an der Riß, General Session II on Friday 24 June 2022, 13:40 BST. It
Germany; 10Novartis Pharma AG, Novartis Institutes for BioMedical
Research, Novartis Pharma AG, 4056 Basel, Switzerland, Basel, will be made publicly available on the congress website
Switzerland; 11AstraZeneca, Bioscience Metabolism, Research and Early once the embargo has lifted.
Development Cardiovascular, Renal and Metabolism (CVRM),
BioPharmaceuticals RandD, AstraZeneca, Gothenburg, Sweden,
Gothenburg, Sweden; 12University of Gothenburg, Division of
Endocrinology, Department of Neuroscience and Physiology,
Sahlgrenska Academy, University of Gothenburg, Sweden, Gothenburg,
Sweden; 13Institute of Translational Immunology and Research Center
for Immunotherapy, Johannes Gutenberg University Medical Center,
Mainz, Germany; 14Integrated Biobank of Luxembourg (IBBL),
Luxembourg Institute of Health, Translational Medicine Operations Hub,
Luxembourg, Dudelange, Luxembourg; 15Sanofi-Aventis Deutschland
GmbH, RandD Diabetes, Sanofi-Aventis Deutschland GmbH,
Industriepark Hoechst, 65926 Frankfurt, Germany, Frankfurt am Main,
Germany; 16Fraunhofer Institute for Translational Medicine and

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S7

ORAL PRESENTATIONS
GS010
Efficacy and safety of finite 48-week treatment with the siRNA JNJ-
3989 and the capsid assembly modulator (CAM-N) JNJ-6379 in
HBeAg negative virologically suppressed (VS) chronic hepatitis B
(CHB) patients: results from REEF-2 study
Kosh Agarwal1, Maria Buti2, Florian van Bömmel3, Pietro Lampertico4,
Ewa Janczewska5, Marc Bourliere6, Thomas Vanwolleghem7,8,
Oliver Lenz9, Thierry Verbinnen9, Thomas Kakuda9, Cristina Mayer9,
John Jerzorwski9, Maria Beumont-Mauviel9, Ronald Kalmeijer9,
Michael Biermer9, Isabelle Lonjon-Domanec9. 1Institute of Liver
Studies, King’s College Hospital; 2Hospital Universitario Valle de Hebrón;
3
University Hospital Leipzig; 4Fondazione IRCCS Ca’ Granda, Ospedale
Maggiore Policlinico, University of Milan; 5Medical University of Silesia;
6
Hôpital Saint Joseph; 7Antwerp University Hospital (UZA); 8Viral
Hepatitis Research Group, Laboratory of Experimental Medicine and
Pediatrics, University of Antwerp; 9Janssen Research and Development
Email: [email protected]

Abstract GS010 is under embargo until the start of the

General Session II on Friday 24 June 2022, 13:40 BST. It
will be made publicly available on the congress website
once the embargo has lifted.

S8 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS
GS011 GS012
Microbial produced ethanol: an underestimated burden on the A non-calorie restricted low carbohydrate high fat diet improves
liver non-alcoholic fatty liver disease (NAFLD) activity score (NAS) and
Stijn Meijnikman1, Mark Davids2, Hilde Herrema1, Omrum Aydin1, HbA1c in type 2 diabetes: a six-month randomised controlled trial
Valentina Tremaroli3, Joanne Verheij1, Maurits De Brauw4, Camilla Dalby Hansen1,2, Eva-Marie Gram-Kampmann2,3,
Sven Francque5, Christophe De Block5, Fredrik Backhed3, Johanne Kragh Hansen1,2, Mie Balle Hugger1, Bjørn Stæhr Madsen1,
Victor Gerdes1, Bert Groen1, Max Nieuwdorp1. 1Amsterdam UMC, Jane Jensen1, Sara Olesen2, Nikolaj Torp1, Ditlev Nytoft Rasmussen1,
locatie AMC, Amsterdam, Netherlands; 2Amsterdam UMC, locatie AMC, Maria Kjærgaard1,2, Stine Johansen1,2, Katrine Prier Lindvig1,2,
Vascular Medicine, Amsterdam, Netherlands; 3Gothenburg University, Peter Andersen1, Katrine Thorhauge1,2, Jan Christian Brønd2,
Gothenburg, Sweden; 4Spaarne Hospital Hoofddorp, Hoofddorp, Pernille Hermann3, Henning Beck-Nielsen3, Sönke Detlefsen2,4,
Netherlands; 5Antwerp University Hospital, Edegem, Belgium Torben Hansen5, Kurt Højlund3, Maja Thiele1,2, Mads Israelsen1,
Email: [email protected] Aleksander Krag1,2. 1Odense University Hospital, Gastroenterology and
Hepatology, Odense, Denmark; 2University of Southern Denmark,
Clinical Institute, Odense, Denmark; 3Odense University Hospital,
Endocrinology, Odense, Denmark; 4Odense University Hospital,
Abstract GS011 is under embargo until the start of the Pathology, Odense, Denmark; 5The Novo Nordisk Foundation Center for
General Session II on Friday 24 June 2022, 13:40 BST. It Basic Metabolic Research, København, Denmark
Email: [email protected]
will be made publicly available on the congress website
once the embargo has lifted.

Abstract GS012 is under embargo until the start of the

General Session II on Friday 24 June 2022, 13:40 BST. It
will be made publicly available on the congress website
once the embargo has lifted.

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S9

ORAL PRESENTATIONS

Saturday 25 June

Late-Breaker

LB001
Semaglutide 2.4 mg once weekly improved liver and metabolic
parameters, and was well tolerated, in patients with non-
alcoholic steatohepatitis-related cirrhosis: a randomised,
placebo-controlled phase 2 trial
Rohit Loomba1, Manal F. Abdelmalek2, Matthew Armstrong3,
Maximilian Jara4, Mette Kjaer4, Niels Krarup4, Eric Lawitz5,
Vlad Ratziu6, Arun Sanyal7, Jörn Schattenberg8, Philip N. Newsome3.
1
University of California at San Diego, NAFLD Research Center, Division
of Gastroenterology, La Jolla, CA, United States; 2Duke University,
Durham, United States; 3University of Birmingham and University
Hospitals Birmingham NHS Foundation Trust, Birmingham, United
Kingdom; 4Novo Nordisk A/S, Søborg, Denmark; 5Texas Liver Institute,
University of Texas Health San Antonio, San Antonio, TX, United States;
6
Sorbonne Université, Hôpital Pitié-Salpêtrier̀ e, Paris, France; 7Virginia
Commonwealth University School of Medicine, Richmond, VA, United
States; 8Metabolic Liver Research Program, I. Department of Medicine,
University Medical Centre, Mainz, Germany
Email: [email protected]

The late breaker abstracts are under embargo until the start
of the session on Saturday 25 June 2022 at 14:00 BST. They
will be made publicly available on the congress website once
the embargo has lifted.

S10 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS
LB002 Department of Gastroenterology and Hepatology, Zurich, Switzerland
Genetic variation in TERT modifies the risk of hepatocellular Email: [email protected]
carcinoma in alcohol-related cirrhosis: results form a genome-
wide case-control study
Stephan Buch1, Hamish Innes2, Philipp Lutz3, Hans Dieter Nischalke4,
Jacob Nattermann4, Jens U. Marquardt5, Janett Fischer6,
Karl Heinz Weiss7, Jonas Rosendahl8, Astrid Marot9,
Marcin Krawczyk10, Markus Casper10, Frank Lammert10,
Florian Eyer11, Arndt Vogel12, Silke Marhenke12, Johann von Felden13, The late breaker abstracts are under embargo until the start
Rohini Sharma14, Stephen Atkinson15, Andrew McQuillin15, of the session on Saturday 25 June 2022 at 14:00 BST. They
Clemens Schafmayer16, Christian Strassburg17, Heidi Altmann1, will be made publicly available on the congress website once
Stefan Sulk1, Veera Raghavan Thangapandi1, Mario Brosch1,
the embargo has lifted.
Carolin Lackner18, Rudolf E. Stauber18, Ali Canbay19, Alexander Link20,
Thomas Reiberger21, Mattias Mandorfer21, Georg Semmler21,
Bernhard Scheiner21, Christian Datz22, Stefano Romeo23,
Stefano Ginanni Corradini24, Luca Valenti25, Sascha Müller26,
Marsha Morgan15,27, Jean-Francois Dufour28, Jonel Trebicka29,
Thomas Berg30, Pierre Deltenre31, Sebastian Mueller32,
Jochen Hampe1, Felix Stickel33. 1University Hospital Dresden, TU
Dresden, Medical Department 1, Dresden, Germany; 2Glasgow
Caledonian University, School of Health and Life Sciences, Glasgow,
United Kingdom; 3University of Bonn, Department of Internal Medicine I,
Bonn, Germany; 4University of Bonn, Department of Internal Medicine I,
Bonn, Germany; 5University of Luebeck, Department of Medicine,
Lübeck, Germany; 6Leipzig University Medical Center, Division of
Hepatology, Department of Medicine II, Leipzig, Germany; 7Salem
Medical Center Heidelberg, Department of Internal Medicine,
)
Heidelberg, Germany; 8University Hospital Halle/Saale, Department of
Gastroenterology, Halle/Saale, Germany; 9Université Catholique de
Louvain, Department of Gastroenterology and Hepatology, CHU UCL
Namur, Belgium; 10Saarland University, Department of Medicine II,
Saarland University Medical Center, Homburg, Germany; 11Technical
University of Munich, Department of Clinical Toxicology, Klinikum Rechts
der Isar, München, Germany; 12Hannover Medical School, Department of
Gastroenterology, Hepatology and Endocrinology, Hannover, Germany;
13
University Medical Center Hamburg-Eppendorf, First Department of
Medicine, Hamburg, Germany; 14Imperial College London, London,
United Kingdom; 15University College London, UCL Institute for Liver and
Digestive Health, Division of Medicine, London, United Kingdom;
16
Rostock University Medical Center, Department of General, Visceral,
Vascular and Transplant Surgery, Rostock, Germany;
17
Universitätsklinikum Bonn, Medical Department 1, Bonn, Germany;
18
Medical University of Graz, Institute of Pathology, Graz, Austria;
19
University Hospital, Ruhr University Bochum, Department of Medicine,
LB003
Bochum, Germany; 20Otto-von-Guericke University, Department of
Reprogramming necroptosis limits immune responses and
Gastroenterology, Hepatology and Infectious Diseases, Magdeburg,
prevents liver cancer development
Germany; 21Medical University of Vienna, Division of Gastroenterology
Mihael Vucur1, Ahmed Ghallab2, Anne Schneider1, Jakob Kather3,
and Hepatology, Department of Internal Medicine III, Vienna, Austria;
22 Olivier Govaere4, Augusto Villanueva5, Achim Weber6,
Teaching Hospital of the Paracelsus Medical University Salzburg,
Thomas Longerich7, Frank Tacke8, Christoph Roderburg1,
Department of Internal Medicine, General Hospital Oberndorf,
Johannes Bode1, Fabian Geisler9, Ulf Neumann10, Jan G. Hengstler2,
Oberndorf, Austria; 23University of Gothenburg, Department of
Mathias Heikenwälder11, Tom Lüdde1. 1University Hospital
Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska
Duesseldorf, Department of Gastroenterology, Hepatology and Infectious
Academy, Wallenberg Laboratory, Gothenburg, Sweden; 24Sapienza
Disease, Germany; 2Leibniz Research Centre for Working Environment
University of Rome, Division of Gastroenterology, Department of
and Human Factors (IfADo) at the Technical University Dortmund,
Translational and Precision Medicine, Gastroenterology Unit, Rome,
Germany; 3Department of Medicine III, University Hospital RWTH
Italy; 25Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico,
Aachen, Germany;, Germany; 4Translational and Clinical Research
Internal Medicine and Metabolic Diseases, Milan, Italy; 26Clinic Beau-
Institute, Faculty of Medical Sciences, Newcastle University; 5Division of
Site, Department of Surgery, Berne, Switzerland; 27UCL Institute for Liver
Liver Diseases, Department of Medicine, Icahn School of Medicine at
and Digestive Health, Department of Medicine, Royal Free Campus,
Mount Sinai, United States; 6Department of Pathology and Molecular
London, United Kingdom; 28University of Bern, Hepatology, Department
Pathology, University Hospital Zurich, Switzerland; 7Institute of
of Biomedical Research, Bern, Switzerland; 29Goethe University
Pathology, University Hospital Heidelberg, Germany; 8Department of
Frankfurt, Department of Internal Medicine I, Frankfurt, Germany;
30 Hepatology and Gastroenterology, Charité-Universitätsmedizin, Berlin,
Leipzig University Medical Center, Division of Hepatology, Leipzig,
Germany; 9Second Department of Internal Medicine, Klinikum rechts der
Germany; 31Centre Hospitalier Universitaire Vaudois, Division of
Isar, Technische Universität München, Germany; 10Visceral and
Gastroenterology and Hepatology, Switzerland; 32Salem Medical Center,
Center for Alcohol Research, University of Heidelberg and Medical
Department, Heidelberg, Germany; 33University Hospital of Zurich,

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S11

ORAL PRESENTATIONS
Transplant Surgery, University Hospital RWTH Aachen, Germany; LB004A
11
Department of Chronic Inflammation and Cancer, German Cancer Efficacy and safety of bepirovirsen in patients with chronic
Research Institute (DKFZ), Heidelberg, Germany hepatitis B virus infection not on stable nucleos (t)ide analogue
Email: [email protected] therapy: interim results from the randomised phase 2b B-Clear
study
Seng Gee Lim1, Cristina Pojoga2,3, Harry Janssen4, Denis Gusev5,
Robert Plesniak6, Keiji Tsuji7, Ewa Janczewska8,
The late breaker abstracts are under embargo until the start Corneliu Petru Popescu9, Pietro Andreone10, Jinlin Hou11,
of the session on Saturday 25 June 2022 at 14:00 BST. They Manuela Arbune12, Adrian Gadano13, Diana Petrova14, Jun Inoue15,
Teerha Piratvisuth16, Young-Suk Lim17, Apinya Leerapun18,
will be made publicly available on the congress website
Masanori Atsukawa19, Ji-Dong Jia20, Eternity Labio21,
once the embargo has lifted. Jennifer Cremer22, Robert Elston23, Tamara Lukic24, Geoff Quinn23,
Stuart Kendrick23, Punam Bharania23, Fiona Campbell23,
Melanie Paff22, Dickens Theodore22. 1National University Health
System, Singapore; 2Regional Institute of Gastroenterology and
Hepatology, Romania; 3Babeș-Bolyai University, Department of Clinical
Psychology and Psychotherapy, International Institute for Advanced
Study of Psychotherapy and Applied Mental Health, Romania; 4Toronto
General Hospital, Canada; 5Center for Prevention and Control of AIDS
and Infectious Diseases, Russian Federation; 6University of Rzeszow
Centrum Medyczne w Lancucie Sp. z o.o., Poland; 7Hiroshima Red Cross
Hospital, Japan; 8Faculty of Heath Sciences in Bytom, Medical University
of Silesia, ID Clinic, Poland; 9Dr Victor Babes Clinical Hospital of
Infectious and Tropical Diseases, Carol Davila University of Medicine and
Pharmacy, Romania; 10Azienda Ospedaliero-Universitaria di Modena,
Italy; 11Nanfang Hospital, Southern Medical University, China; 12Sf.Cuv.
Parascheva Infectious Diseases Clinical Hospital, Romania; 13Hospital
Italiano de Buenos Aires, Argentina; 14Diagnostic Consultative Centre
Alexandrovska, Bulgaria; 15Tohoku University Hospital, Japan; 16NKC
Institute of Gastroenterology and Hepatology, Thailand; 17Asan Medical
Center, University of Ulsan College of Medicine, Korea, Rep. of South;
18
Chiang Mai University, Thailand; 19Department of Internal Medicine,
Division of Gastroenterology and Hepatology, Nippon Medical School,
Japan; 20Bejing Friendship Hospital, Capital Medical University, China;
21
Makati Medical Center, Philippines; 22GlaxoSmithKline, United States;
23
GlaxoSmithKline, United Kingdom; 24GlaxoSmithKline, United Arab
Emirates
Email: [email protected]

The late breaker abstracts are under embargo until the start
of the session on Saturday 25 June 2022 at 14:00 BST. They
will be made publicly available on the congress website once
the embargo has lifted.

S12 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS

LB004B
Efficacy and safety of bepirovirsen in patients with chronic
hepatitis B virus infection on stable nucleos (t)ide analogue
therapy: interim results from the randomised phase 2b B-Clear
study
The late breaker abstracts are under embargo until
Man-Fung Yuen1, Robert Plesniak2, Seng Gee Lim3, Keiji Tsuji4,
Gheorghe Diaconescu5, Adrian Gadano6, Ju Hyun Kim7, the start of the session on Saturday 25 June 2022 at
Tarik Asselah8, Hyung Joon Yim9, Jeong Heo10, Giuliano Rizzardini11, 14:00 BST. They will be made publicly available on
Harry Janssen12, Corneliu Petru Popescu13, Diana Petrova14, the congress website once the embargo has lifted.
Alexander Wong15, Nevin Indriz16, Cristina Pojoga17,
Yasuhito Tanaka18, Denis Gusev19, Ewa Janczewska20,
Jennifer Cremer21, Robert Elston22, Tamara Lukic23,
Lauren Maynard22, Stuart Kendrick22, Punam Bharania22,
Fiona Campbell22, Melanie Paff22, Dickens Theodore21. 1Queen Mary
Hospital, China; 2University of Rzeszow, College of Medicine, Centrum
Medyczne w Lancucie Sp. z o.o., Poland; 3National University Health
System, Singapore; 4Hiroshima Red Cross Hospital, Japan; 5Spitalul
Clinic de Boli Infectioase si Pneumoftiziologie, Romania; 6Hospital
Italiano de Buenos Aires, Argentina; 7Department of Gastroenterology,
Gachon University Gil Medical Center, Korea, Rep. of South; 8Hôpital
Beaujon, France; 9Korea University Ansan Hospital, Korea, Rep. of South;
10
College of Medicine, Pusan National University and Biomedical
Research Institute, National University Hospital, Korea, Rep. of South;
11
Luigi Sacco Hospital, Italy; 12Toronto General Hospital, Canada; 13Dr
Victor Babes Clinical Hospital of Infectious and Tropical Diseases, Carol
Davila University of Medicine and Pharmacy, Romania; 14Alexandrovska,
Bulgaria; 15Department of Medicine, University of Saskatchewan,
Canada; 16UMHAT Sofiamed, Bulgaria; 17Regional Institute of
Gastroenterology and Hepatology, Romania; 18Kumamoto University,
Japan; 19Center for Prevention and Control of AIDS and Infectious
Diseases, Russian Federation; 20ID Clinic, Poland; 21GlaxoSmithKline,
United States; 22GlaxoSmithKline, United Kingdom; 23GlaxoSmithKline,
United Arab Emirates
Email: [email protected]

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S13

ORAL PRESENTATIONS
LB005 LB006
Primary data analyses of MAESTRO-NAFLD-1 a 52 week double- Reduction of intra-hepatic Z-AAT synthesis by fazirsiran decreases
blind placebo-controlled phase 3 clinical trial of resmetirom in globule burden and improves histological measures of liver
patients with NAFLD disease in adults with alpha-1 antitrypsin deficiency
Stephen Harrison1, Rebecca Taub2, Guy Neff3, Sam Moussa4, Pavel Strnad1, Mattias Mandorfer2, Gourab Choudhury3,
Naim Alkhouri5, Mustafa Bashir6. 1Pinnacle, Clinical Research, San Griffiths Bill4, Christian Trautwein1, Rohit Loomba5, Romil Saxena6,
Antonio, United States; 2Madrigal Pharmaceuticals, RandD, Thomas Schluep7, Ting Chang7, Min Yi7, Bruce Given7,
Conshohocken, United States; 3Covenant Research, Sarasota, United James Hamilton7, Javier San Martin7, Jeffrey Teckman8. 1RWTH
States; 4Adobe Gastroenterology, Tucson, United States; 5Arizona Liver University Hospital Aachen, Aachen, Germany; 2Medical University of
Institute, Phoenix, United States; 6Duke University, Radiology, Raleigh, Vienna, Wien, Austria; 3The University of Edinburgh, United Kingdom;
4
United States Cambridge University Hospitals, United Kingdom; 5University of
Email: [email protected] California San Diego, La Jolla, United States; 6Emory University Hospital,
Pathology and Laboratory Medicine, Atlanta, United States; 7Arrowhead
Pharmaceuticals, Inc., Pasadena, United States; 8Saint Louis University,
Pediatrics, St. Louis, United States
The late breaker abstracts are under embargo until the start Email: [email protected]
of the session on Saturday 25 June 2022 at 14:00 BST. They
will be made publicly available on the congress website once
the embargo has lifted. The late breaker abstracts are under embargo until the start
of the session on Saturday 25 June 2022 at 14:00 BST. They
will be made publicly available on the congress website
once the embargo has lifted.

S14 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS
Thursday 23 June while for GT1b and GT2 only individual cases were detected between
2009 and 2014. MSM were mainly infected with HCV GT1a (82%, 115/
140) or GT4d (16%, 23/140 with sequencing data available). In
contrast, HCV GT were almost equally distributed in non-MSM
patients. Here, 36% were infected with HCV GT1a, 21% each with GT1b
Hepatitis C: Clinical aspects and therapy or GT3a and 16% had GT2. Phylogenetic analyses in NS5B showed a
diverse sequence pattern in patients with HCV GT1b and GT3a. In
contrast, HCV strains among MSM infected with HCV GT1a and 4d
OS001 were more closely related. Based on the comparison of HCV GT or
Results of a ten year prospective observational study on acute NS5B sequences, 24 patients (15%) were diagnosed with an HCV
hepatitis C in HCV-mono- and HIV/HCV-coinfected patients reinfection. The incidence rate in MSM for a first HCV infection
Christiana Graf1, Lara Fuhrmann2,3, Lutz Thomas4, declined in the period between 2017 and 2019 (3.6/1000PY)
Christoph Stephan5, Gaby Knecht4, Peter Gute4, Markus Bickel4, compared to the DAA era between 2013 and 2017 (6.8/1000 PY)
Kai-Henrik Peiffer1, Fabian Finkelmeier1, Georg Dultz1, and to the interferon era (2008–2013; 10.1/1000 PY). Conversely, the
Nils Wetzstein5, Natalie Filmann6, Eva Herrmann6, Stefan Zeuzem1, incidence of HCV reinfections among MSM increased slightly from
Niko Beerenwinkel2,3, Julia Dietz1, Christoph Sarrazin1,7. 1Goethe 1.9/100PY to 2.8/100PY over time.
University Hospital Frankfurt, Department of Internal Medicine I, Conclusion: During the last 5 study years the prevalence of GT4
Frankfurt, Germany; 2ETH Zurich, Department of Biosystems Science and infections increased, while annual acute hepatitis C incidences
Engineering, Basel, Switzerland; 3SIB Swiss Institute of Bioinformatics, decreased. HCV reinfection is an issue of major concern in HIV-
Basel, Switzerland; 4Infektiologikum, Frankfurt, Germany; 5Goethe positive MSM and may have implications for HCV elimination.
University Hospital, Department of Infectious Diseases, Frankfurt,
Germany; 6Goethe University Frankfurt, Institute of Biostatistics and OS002
Mathematical Modeling, Frankfurt, Germany; 7St. Josefs-Hospital, Multicenter prospective study for the use of shortened pre-
Medizinische Klinik II, Wiesbaden, Germany emptive therapy with Glecaprevir/Pibrentasvir (G/P) and
Email: [email protected] Ezetimibe in hepatitis C (HCV) seronegative non-liver solid organ
transplant recipients of HCV viremic grafts
Background and aims: Οver the last two decades, a persistent
Bashar Aqel1, Surakit Pungpapong2, Adyr Moss1, Rolland Dickson1.
epidemic of acute Hepatitis C virus (HCV) infections has been 1
Mayo Clinic, Gastroenterology, Hepatology and Liver Transplant,
observed in HIV-positive men who have sex with men (MSM) in
Phoenix, United States; 2Mayo Clinic, Jacksonville, United States
several metropolitan areas worldwide. In this study, epidemiological
Email: [email protected]
and clinical parameters as well as phylogenetic analyses were
conducted to characterize HCV transmission among MSM.
Method: This prospective observational study analysed clinical and
epidemiological parameters of patients with confirmed acute HCV
This abstract is under embargo until Thursday 23 June
infection between 2009 and 2019 from 3 centers in Frankfurt. NS5B 2022, 13:30 BST. This abstract has been selected to be
population-based sequencing was performed at the time of diagnosis highlighted during official EASL Press Office activities or
to determine HCV genotype (GT) and for phylogenetic analyses. in official EASL Press Office materials that will be made
Results: A total of n = 161 patients diagnosed with acute HCV- publicly available on the congress website at 13:30 (BST).
infection were included in the study, of whom n = 140 (87%) were
HIV-positive and n = 145 (90%) were MSM. We observed a different
distribution of HCV genotypes over time. In the first eight years, HCV
GT1a was most common (58–100%) but decreased to 30% in 2018. In
contrast, the proportion of GT4d cases increased. While no GT4d
cases were diagnosed in 2013, the proportion rose to 40% in 2019.
There was a slight trend towards more GT3a cases in 2018 and 2019,

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S15

ORAL PRESENTATIONS
Method: All consecutive patients with HCV retreated with VOX/VEL/
SOF after DAA failure were enrolled in 153 centers in Germany,
Austria, Switzerland and Belgium between May 2015 and November
2020. Sustained virological response (SVR) was defined as undetect-
able HCV RNA 4 (SVR 4) or 12 (SVR12) weeks after the end-of-
treatment.
Results: A total of 416 patients were included: median age was 55
(21–84) years, 79% were male, median HCV RNA was 383, 000 (10–58,
300, 000) IU/ml. HCV genotype (GT) was 1 in 54% (1a in 26%, 1b in
28%), 2 in 1%, 3 in 39% and 4 in 6%. Patients received VOX/VEL/SOF for
12 weeks, ribavirin was added in 4% of treatment schedules. Overall,
365/416 (87.7%) patients by intention to treat analysis and 401/416
(96.4%) by per protocol analysis achieved SVR12, respectively.
Genotype 3a ( p = 0.008) and hepatocellular carcinoma ( p = 0.0034)
were the only predictors of a treatment failure. Treatment effective-
ness was not significantly affected by the type of previous DAA
regimen, by liver cirrhosis, HCV GT 1a and baseline HCV-RNA viral
load. Virologic relapse was observed in 20 patients (10% GT1a, 15%
GT1b, 75% in GT3a). The presence of resistance-associated substitu-
tions within NS3, NS5A, and NS5B genes did not impact SVR12 ( p =
0.06).
Conclusion: VOX/VEL/SOF is an effective retreatment for patients
with HCV who have failed on a previous DAA course in a real-life
setting. We identified HCV GT 3a and HCC as the main predictors of
VOX/VEL/SOF failure.

OS004
Glecaprevir/pibrentasvir and sofosbuvir for 16 weeks without
ribavirin is safe and highly effective retreatment for patients who
have failed an NS5A inhibitor containing antiviral regimen
Edward J. Gane1, Bridget Faire2, Sherine Helmy3, James Freeman4.
1
University of Auckland, Grafton Campus, Liver Unit, Auckland, New
Zealand; 2New Zealand Liver Transplant Unit-Ward 71, Auckland, New
OS003 Zealand; 3Pharco Corporation, Cairo, Egypt; 4GP2U, Australia
Effectiveness of voxilaprevir/velpatasvir/sofosbuvir in hepatitis C Email: [email protected]
patients previously treated with direct-acting antiviral agents
(DAA) Background and aims: Oral DAA therapy has been available in New
Zealand since mid-2016 for treatment of chronic hepatitis C. Over the
Christiana Graf1, Julia Dietz1, Beat Müllhaupt2, Peter Buggisch3,
last 5 years, more than 10,000 New Zealanders have been treated
Jörn Schattenberg4, Christoph Antoni5, Stefan Mauss6,
with NS5A inhibitor- based DAA therapy, of whom more than 300
Elena Durmashkina7, Claus Niederau8, Thomas Discher9,
have had virologic failure. Retreatment of patients with confirmed
Julian Schulze zur Wiesch10, Tobias Müller11, Thomas Berg12,
antiviral resistance requires a triple DAA combination of a polymer-
Christoph Neumann-Haefelin13, Christoph Berg14, Stefan Zeuzem1,
ase, a protease and an NS5A inhibitor.
Christoph Sarrazin1,7. 1Goethe University Hospital, Department of
Method: In an open-labelled, ethics-approved study, 100 New
Internal Medicine I, Frankfurt am Main, Germany; 2University Hospital
Zealanders who had failed DAA therapy with confirmed NS5A
Zürich, Swiss-Hepato-Pancreato-Biliary Center and Department of
resistance will be retreated with glecaprevir/pibrentasvir (GLE/PIB)
Gastroenterology and Hepatology, Zürich, Switzerland; 3Institute of
from Feb 2019) plus sofosbuvir for 16 weeks. Patients with
Interdisziplinary Medicine IFI, Hamburg, Germany; 4University Medical
decompensated cirrhosis or hepatocellular carcinoma or post-
Center Mainz, I. Department of Medicine, Mainz, Germany; 5University
transplant are excluded.
Hospital Mannheim, Department of Internal Medicine II, Mannheim,
Results: To-date, 57 patients have been enrolled in the study. Median
Germany; 6Center of HIV and Hepatogastroenterology, Düsseldorf,
age was 56 years (38–80), 78% were male and 44% had established
Germany; 7St. Josefs-Hospital, Wiesbaden, Germany; 8St. Josefs-Hospital,
cirrhosis. Thirty-five patients had previously failed GLE/PIB, 19 failed
Katholisches Klinikum Oberhausen, Oberhausen, Germany; 9Justus
ombitasvir, paritaprevir, dasabuvir, and ritonavir (PrOD) and 1 each
Liebig University Gießen, Department of Medicine, Gießen, Germany;
10 failed grazoprevir/elbasvir (GRZ/ELB), ledipasvir/sofosbuvir (LDV/
University Medical Center Hamburg-Eppendorf, I. Department of
SOF) and sofosbuvir/velpatasvir (SOF/VEL). Six patients had failed
Medicine, Infectious Disease Unit, Hamburg, Germany; 11Charité
multiple regimens. Most frequently detected NS5A resistance-
Universitätsmedizin Berlin, Department of Hepatology and
associated substitutions (RASs) were Y93H (57%), A30 K (26%),
Gastroenterology, Berlin, Germany; 12University Hospital Leipzig,
Q30 K/H (26%, M28 T/F/V (11%). Multiple NS5A RASs were detected
Department of Gastroenterology and Rheumatology, Leipzig, Germany;
13 in 39% patients. Resistance profiles were similar in PrOD and GLE/PIB
University Hospital Freiburg, Department of Medicine II, Freiburg,
failures.
Germany; 14University Hospital Tübingen, Department of
One patient died from opioid overdose during treatment. There were
Gastroenterology, Hepatology and Infectiology, Tübingen, Germany
no other SAEs or AE-related treatment discontinuations. Two other
Email: [email protected]
patients stopped treatment within 4 weeks because of psychosocial
Background and aims: Voxilaprevir/velpatasvir/sofosbuvir (VOX/ issues, one of whom has started retreatment.
VEL/SOF) is approved for HCV retreatment of direct-acting antiviral 45 patients have completed therapy and 37 have reached the SVR12
agents (DAA)-experienced patients. However, real-life data are still timepoint, of whom 36 (98%) are cured (complete SVR results will be
limited. The aim of the study was to analyse the effectiveness of VOX/ available in early 2022). The only treatment failure to-date was a 53-
VEL/SOF in a real-world setting. year-old noncirrhotic female, previously treated with PrOD.

S16 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS
Conclusion: Glecaprevir/pibrentasvir plus sofosbuvir for 16 weeks is population (GP). We also quantified the proportion of excess death
a safe and highly effective retreatment regimen for patients who have attributable to: a) death from liver cancer; b) death from liver disease
previously failed GLE/PIB and other DAA regimens regardless or unrelated to cancer; c) and death from drug-related causes. Finally,
cirrhosis status, or NS5A RAS profile. There is no indication for adding Poisson regression was used to identify factors associated with excess
ribavirin. mortality.
Results: Our analysis included 20, 031 patients, of which 1, 402 (7%)
OS005 died during follow-up. Mean follow-up duration was 2.2–3.9 years,
Excess mortality risk among hepatitis C patients after being and mean age ranged from 46.3 (SC) to 56.7 (BC). Mortality rates
“cured” in the interferon-free era: results from three population- varied considerably according to disease stage. For example, the age-
based cohorts standardised mortality rate ranged from 12 to 23, 27–38, and 62–118
Victoria Hamill1,2, Stanley Wong3, Jennifer Benselin4,5, deaths per 1000 person-years in non-cirrhosis, compensated
Mel Krajden3,6, Peter Hayes7, David Mutimer8, Amanda Yu3, cirrhosis and ESLD patients, respectively. SMRs indicated that all-
John Dillon9, Will Gelson10, Hector Velasquez3,11, Philip Johnson12, cause mortality was 3.4–3.5 times higher than the GP in non-
Stephen Barclay13, Maria Alvarez3, Hidenori Toyoda14, cirrhosis patients, 4.2–5.9 times higher in compensated cirrhosis
Kosh Agarwal15, Andrew Fraser16,17, Sofia Bartlett3,11, patients, and 8.7–15.3 times higher in ESLD patients. For non-
Mark Aldersley18, Andrew Bathgate7, Mawuena Binka3,11, cirrhosis patients, drug-related causes were responsible for the
Paul Richardson19, Joanne Morling4,5,20, Stephen Ryder4, greatest proportion of excess death (77% SC; 41% BC). Conversley, for
Douglas Macdonald21, Sharon Hutchinson1,2, Eleanor Barnes22, cirrhosis patients, liver-related causes were the key driver, respon-
Neil Guha4,5, William Irving4,5, Naveed Janjua3,11,23, sible for 30–95% of excess deaths. In the regression analysis, younger
Hamish Innes1,2,20. 1Glasgow Caledonian University, School of Health age, drug use and comorbidities were associated with greater excess
and Life Sciences, Glasgow, United Kingdom; 2Public Health Scotland, mortality (see Figure).
Glasgow, United Kingdom; 3British Columbia Centre for Disease Control,
Vancouver, British Columbia, Canada; 4Nottingham University Hospitals
NHS Trust and the University of Nottingham, NIHR Nottingham
Biomedical Research Centre, Nottingham, United Kingdom; 5University
of Nottingham, School of Medicine, Nottingham Digestive Diseases
Centre, Nottingham, United Kingdom; 6The University of British
Columbia, Department of Pathology and Laboratory Medicine,
Vancouver, British Columbia, Canada; 7Royal Infirmary of Edinburgh,
Edinburgh, United Kingdom; 8Queen Elizabeth Hospital Birmingham,
Liver and Hepatobiliary Unit, Birmingham, United Kingdom; 9University
of Dundee, School of Medicine, Division of Molecular and Clinical
Medicine, Dundee, United Kingdom; 10Cambridge University Hospitals
NHS Foundation Trust, Cambridge Liver Unit, Cambridge, United
Kingdom; 11University of British Columbia, School of Population and
Public Health, Vancouver, British Columbia, Canada; 12University of
Liverpool, Department of Molecular and Clinical Cancer Medicine,
Liverpool, United Kingdom; 13Glasgow Royal Infirmary, Glasgow, United
Kingdom; 14Ogaki Municipal Hospital, Department of Gastroenterology,
Ogaki, Japan; 15King’s College Hospital NHS Foundation Trust, Institute of
Liver Studies, London, United Kingdom; 16Aberdeen Royal Infirmary,
Aberdeen, United Kingdom; 17Queen Elizabeth University Hospital, Conclusion: In the largest study performed to-date, we show that
Glasgow, United Kingdom; 18St James’s University Hospital, Leeds Liver individuals achieving SVR in the interferon-free era have a consid-
Unit, Leeds, United Kingdom; 19Royal Liverpool and Broadgreen erably higher mortality risk than the GP, driven mainly by drug-
University Hospitals NHS Trust, Liverpool, United Kingdom; 20University related mortality (in non-cirrhosis patients) and liver-related causes
of Nottingham, Lifespan and Population Health, Nottingham, United (in cirrhosis patients).
Kingdom; 21Royal Free London NHS Foundation Trust, Gastroenterology
and Hepatology, London, United Kingdom; 22University of Oxford, OS006
Nuffield Department of Medicine and the Oxford NIHR Biomedical Impact of direct-acting antiviral treatment for hepatitis C on
Research Centre, Oxford, United Kingdom; 23St Paul’s Hospital cardiovascular diseases and extrahepatic cancers
Vancouver, Centre for Health Evaluation and Outcome Sciences, British Laurent Lam1, Helene Fontaine2, Nathanaël Lapidus1,2,
Columbia, Canada Dorival Celine1, Jonathan Bellet1, Dominique Larrey3, Pierre Nahon2,4,
Email: [email protected] Alpha Diallo5, Carole Cagnot5, Clovis Lusivka-Nzinga1,
Background and aims: Although the number of people living with a François Teoule1, Gilles Hejblum1, Marc Bourliere6,7, Stanislas Pol2,8,
hepatitis C sustained viral response (SVR) has increased dramatically, Fabrice Carrat1,2. 1Sorbonne Université, INSERM, Institut Pierre Louis
mortality rates in this patient group remain poorly understood. Here, d’Épidémiologie et de Santé Publique, IPLESP, Paris, France; 2Assistance
our goal was to assess excess mortality after SVR achievement in the Publique-Hôpitaux de Paris, France; 3Hôpital Saint Eloi and IBR, INSERM,
interferon (IFN)-free era. Montpellier, France; 4Inserm, UMR-1162, “Génomique fonctionnelle des
Method: We performed data analysis on patients achieving SVR in tumeurs solides”, Paris, France; 5ANRS, Emerging Infectious Diseases,
the IFN-free era (2014–2018/19) from three population-based cohorts Paris, France; 6Hôpital Saint Joseph, Marseille, France; 7INSERM, UMR
in Scotland (SC), England (EN), and British Columbia (BC). Patients 1252 IRD SESSTIM, Aix Marseille Université, Marseille, France;
8
were divided into three disease stage groups: no cirrhosis (SC and BC Université de Paris, Paris, France
only); compensated cirrhosis; and end stage liver disease (ESLD). Email: [email protected]
Age-standardised mortality rates were calculated to take account of Background and aims: The impact of direct-acting antivirals (DAAs)
different age/sex structures between cohorts and disease stage on extrahepatic complications in chronic hepatitis C (CHC) patients
groups. Further, we calculated standardised mortality ratios (SMRs) remains poorly described. We estimated the association of DAAs with
to compare the frequency of mortality in SVR patients to the general cardiovascular events and extrahepatic cancers.

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S17

ORAL PRESENTATIONS
Method: The prospective ANRS CO22 HEPATHER cohort was enriched
with individual data until December 2018 from the French National
Health Insurance Database (SNDS), which contains medical informa-
Cirrhosis and its complications: Other clinical
tion regarding ambulatory care and hospital admissions. CHC patients complications except ACLF and critical illness
were enrolled between August 2012 and December 2015 in 32 French
hepatology centers. A total of 8148 CHC adults were selected.
Cardiovascular events (stroke, acute coronary syndrome, pulmonary OS007
embolism, heart failure, arrhythmias and conduction disorders [ACD], Etiological cure prevents further decompensation and mortality
peripheral arterial disease [PAD]) and cancers (colorectal, bladder, in cirrhotic patients with ascites as the single first
prostate, kidney, lung, pancreas, thyroid, head/neck, breast) were decompensating event
derived from the SNDS. Associations between DAAs and extrahepatic Marta Tonon1, Lorenz Balcar2,3, Georg Semmler2,3, Valeria Calvino1,
events were estimated using marginal structural models, with Bernhard Scheiner2,3, Simone Incicco1, Rafael Paternostro2,3,
adjustments for clinical confounders and medications. Carmine Gabriele Gambino1, David JM Bauer2,3, Antonio Accetta1,
Lukas Hartl2,3, Alessandra Brocca1, Mathias Jachs2,3,
Michael Trauner2,3, Mattias Mandorfer2,3, Paolo Angeli1,
Adjusted hazard ratios Thomas Reiberger2,3, Salvatore Piano1. 1University of Padua,
associated with DAAs Department of Medicine, Padova, Italy; 2Medical University of Vienna,
Outcomes (95% Confidence Interval) Division of Gastroenterology and Hepatology, Department of Internal
Total population (n = 8148) Medicine III, Vienna, Austria; 3Medical University of Vienna, Vienna
Acute stroke 1.30 (0.82, 2.08) Hepatic Hemodynamic Laboratory, Division of Gastroenterology and
Acute coronary syndrome 1.00 (0.63, 1.60) Hepatology, Department of Internal Medicine III, Vienna, Austria
Acute pulmonary embolism 2.10 (0.64, 6.85) Email: [email protected]
Acute heart failure 1.15 (0.74, 1.78)
Arrhythmias and conduction disorders 1.46 (1.04, 2.04) Background and aims: Etiologic treatment reduces the risk of
Peripheral arterial disease 0.54 (0.33, 0.89) decompensation and mortality in compensated cirrhosis. However,
Major cardiovascular events 1.03 (0.81, 1.31) in the setting of decompensated cirrhosis the impact of etiologic
Any cardiovascular event 1.10 (0.90, 1.36) treatment is less predictable, in particular in patients with ascites,
Any extrahepatic solid cancer 1.23 (0.50, 3.03) who remain at high risk of developing further decompensating
Patients with advanced fibrosis (n = 3586) events and death. The aim of the study was to evaluate the impact of
Acute stroke 0.58 (0.29, 1.18) etiological treatment in decompensated patients with cirrhosis and
Acute coronary syndrome 0.59 (0.29, 1.19)
ascites as the single index decompensating event. The end points
Acute pulmonary embolism 0.79 (0.16, 3.97)
were the occurrence of further decompensation (i.e. refractory
Acute heart failure 0.47 (0.27, 0.81)
Arrhythmias and conduction disorders 1.02 (0.57, 1.84) ascites, spontaneous bacterial peritonitis [SBP], hepatorenal syn-
Peripheral arterial disease 0.36 (0.17, 0.73) drome [HRS-AKI], variceal bleeding [VB] and hepatic encephalopathy
Major cardiovascular events 0.50 (0.36, 0.71) [HE]) and mortality.
Any cardiovascular events 0.58 (0.42, 0.79) Method: Cirrhotic patients with ascites as single first decompensa-
Any extrahepatic solid cancerc 0.39 (0.09, 1.71) tion event at the University Hospital of Padova or the Vienna General
Hospital between 2003–2021 were included and followed until
Results: Analyses of 12 905 person-years (PY) of no DAA exposure death, liver transplantation or September 2021. The etiology was
and 22 326 PY following DAA exposure showed a reduced risk of PAD considered as “cured” in case of removal of the primary etiological
after DAAs (HR, 0.54; 95% CI, 0.33 to 0.89), a beneficial effect of DAAs factor (e.g. HCV: virological cure, HBV: virological suppression, ALD:
on overall cardiovascular outcomes in patients with advanced fibrosis alcohol abstinence) and as “controlled” in case of partial removal of
(aHR, 0.58; 95% CI, 0.42 to 0.79), and an increased risk of ACD (hazard etiologic factor (e.g. HBV: partial suppression of HBV-DNA, ALD:
ratio [HR], 1.46; 95% CI, 1.04 to 2.04) predominant after the first year mostly abstinent but with drinking episodes).
following DAA initiation. There was no association between DAAs and Results: We included 622 patients (mean age: 57 ± 11 years, male
extrahepatic cancer (HR, 1.23; 95% CI, 0.50 to 3.03). 68%, mean MELD 15 ± 6), the most common etiology were ALD (59%)
Conclusion: DAAs were associated with a decreased risk of and HCV (23%). Etiology was “cured” in 146 patients (24%),
cardiovascular outcomes in patients with advanced fibrosis, a “controlled” in 170 (27%) and uncontrolled in 306 (49%). During a
decreased risk of PAD regardless of the fibrosis stage, and an median follow-up of 33months, 350 patients (56%) developed further
increased risk of ACD, supporting long-term cardiac monitoring decompensation (33%refractory ascites, 29% HE, 17% SBP, 13% HRS-
after DAA therapy. DAAs were not associated with extrahepatic cancer AKI, 9% VB). The incidence of further decompensation at 5 years was
development or reduction. significantly lower in patients with “cured” vs “controlled” vs
uncontrolled etiology (38% vs 64% vs 72%, respectively; p < 0.001;
Fig. 1A). In multivariable analysis (adjusted for age, varices, etiology,
Child Pugh class, creatinine and sodium), “cured” (aHR = 0.52; p <
0.001) and “controlled” etiology (aHR = 0.60; p < 0.001) were both
independently associated with a lower risk of further decompensa-
tion. Considering response to etiological treatment as time-depend-
ent covariates, 5-year cumulative incidence of survival was
significantly higher in patients with cured vs controlled vs uncon-
trolled etiology (83% vs 58% vs40%, respectively; p < 0.001; Fig. 1B). In
multivariable analysis, etiological cure (aHR = 0.35, p < 0.001) and
controlled etiology (aHR = 0.61, p = 0.003) were independently
associated with lower mortality.

S18 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS
United Kingdom; 28Queen Elizabeth University Hospitals, United
Kingdom; 29Gaziantep, Turkey; 30Asian Institute of Gastroenterology,
Hyderabad, India; 31Upenn (University of Pennsylvania), United States;
32
Perelman School of Medicine at the University of Pennsylvania,
Gastroenterology and Hepatology, Philadelphia, United States; 33Royal
Berkshire Hospital, United Kingdom; 34Marmara University, Turkey;
35
xx, Turkey; 36Sir Ganga Ram Hospital, Delhi, India; 37Ibn. Sina Hospital,
Khartoum, Sudan, Sudan; 38Centro Médico la Raza, Mexico; 39Singapore
General Hospital, Gastroenterology and Hepatology, Singapore,
Singapore; 40Singapore General, Singapore; 41Mayo Scottsdale, United
States; 42Mercy Medical Centre, United States; 43Jaslok Hospital, Delhi,
Delhi, India; 44Mayo Jacksonville, United States; 45VA Richmond, United
Conclusion: In cirrhotic patients with ascites as single first decom- States; 46xx, South Africa; 47xx, United Kingdom; 48xx, India; 49xx,
pensating event, the cure or control of etiology of liver disease Ethiopia; 50xx, Canada; 51xx, United States; 52Centro Medico Issemym,
reduces the risk of further decompensations and mortality. Gastroenterology, Mexico; 53Department of infectious disease, Ruijin
hospital, Shanghai Jiao Tong university school of medicine, Shanghai,
OS008
China; 54xx, Israel; 55xx, Chile; 56xx, Argentina
Risk factors for short-term post discharge clinical outcomes in
Email: [email protected]
patients hospitalized with decompensated chronic liver disease:
interim results from Global CLEARED study Background and aims: Decompensated chronic liver disease (DCLD)
Jasmohan S. Bajaj1, Patrick S. Kamath2, Florence Wong3, Peter Hayes4, is associated with poor outcomes, but no global study has addressed
Ramazan Idilman5, Aldo Torre6, Mark Topazian7, Jacob George7, this after hospitalization. We prospectively evaluated non-elective
Mario Reis Álvares-da-Silva7, Qing Xie8, Shiv Kumar Sarin9, hospitalized patients with DCLD to determine disease profile,
Abha Nagral10, Sumeet Asrani11, Mohammad Amin Fallahzadeh11, predictors of readmission and 30 days mortality post discharge
Somaya Albhaisi12, CE Eapen13, Ashish Goel13, Ajay Kumar Duseja14, following index hospital admission under “Chronic Liver disease
Anoop Saraya15, Jatin Yegurla16, Mohd. Rela17, Dinesh Jothimani18, Evolution And Registry for Events and Decompensation (CLEARED)
Marie Jeanne Lohoues19, Belimi Hibat Allah20, Ricardo Cabello20, consortium.
Ruveena Bhavani21, Nik MA Nik Arsyad22, Sombat Treeprasertsuk23, Method: Data were prospectively collected from 49 centres from 6
Salisa Wejnaruemarn24, Jose Luis Perez Hernandez25, continents of non-elective admissions in DCLD patients with or
Godolfino Miranda Zazueta26, Neil Rajoriya27, Rosemary Faulkes28, without cirrhosis, aged ≥18 years. We performed an interim analysis
Abdullah Emre Yıldırım29, Sezgin Barutcu29, Anand Kulkarni30, to predict readmission and mortality within 30 days following index
Mithun Sharma30, Rajender Reddy31, Suditi Rahematpura31,32, hospital discharge. World Bank data were used to stratify countries
Adebayo Danielle33, James Kennedy33, Feyza Gunduz34, according to income.
Rahmi Aslan35, Anil Arora36, Ashish Kumar36, Dalia Allam37, Results: 1383 patients, mean age 54.97 ± 13.55 years; 64% male;
Yashwi Haresh Kumar Patwa37, Mauricio Castillo38, Hiang Keat Tan39, diverse ethnicity [White 39%, Asian 30%, Hispanic 10%, Black 9%] were
Liou Wei Lun40, Hugo E. Vargas41, David Bayne41, Paul J. Thuluvath42, analyzed. Alcohol was the most common etiology (46%), followed by
Somya Sheshadri42, Ajay Haveri43, Andrew Keaveny44, Jawaid Shaw45, NASH (23%), HBV (13%) and HCV (11%). Admissions were almost
Edith Okeke46, David Nyam P7, Aloysious Aravinthan47, exclusively for liver related complications i.e. GI bleed (30%), HE
Suresh Vasan Venkatachalapathy47, Amey Sonavane48, (34%), AKI (33%), and anasarca (24%). Mean admission CTP was 10 (5–
Hailemichael Desalegn49, Henok Fisseha46, Dominik Bettinger50, 14) and MELD-Na 23 (6–40). Only 11% were listed for transplant. 51%
Michael Schultheiss50, Scott Biggins51, Natalia Filipek51, had hospitalization in previous six months. 24% were infected at
Damien Leith47, Ewan Forrest47, Maria Sarai González-Huezo6,52, admission and another 13% developed infections subsequently.
René Malé Velazquez6, Lilian Torres Made7, Diana Yung47, During hospitalization, organ failures were: AKI 46%; as brain 16%,
Zeki Karasu35, Zhujun Cao53, Helena Katzman54, Liane Rabinowich54, circulatory 14%, and respiratory 13%; 25% needed ICU admission.
Carlos Benitez55, Andres Duarte Rojo51, Sebastián Marciano56, Median hospital stay was 7 days (1–140) and 11% lost to follow-up
Akash Gandotra48, Brian Bush51, Leroy Thacker51, Ashok Choudhury9. after discharge. 33% were readmitted, 3% were transplanted while
1
Virginia Commonwealth University, Department of Hepatology, United 26% of patients died within 30 days. The most significant independ-
States; 2Mayo Rochester, United States; 3University of Toronto, Toronto, ent factors predicting readmission within 30 days were being in low/
Canada; 4Royal Infirmary of Edinburgh, United Kingdom; 5Ankara lower middle income country ( p < 0.0001), a high discharge MELD-
University School of Medicine, Department of Hepatology, Ankara, Na ( p = 0.0005), and hospitalization ≤6 M (p = 0.006). The most
Turkey; 6xx, Mexico; 7xx; 8Ruijin Hospital, Department of Hepatology, significant independent predictors of 30-day-mortality post index
China, China; 9Institute of Liver and Biliary Sciences, Department of discharge were age, discharge MELD-Na ( p < 0.0001 for both), and
Hepatology, Delhi, India; 10Jaslok Mumbai, India; 11Baylor Dallas (Baylor various organ failures during index admission ( p < 0.01).
University Medical Center), United States; 12Virginia Commonwealth Conclusion: The clinical outcomes of patients with DCLD following
University, Internal Medicine, Richmond, United States; 13CMC Vellore, index hospital admission vary widely around the world. Mortality
Tamil Nadu, India; 14PGIMER, India; 15AIIMS, Deptt. of Gastroentrology within 30 days post discharge is largely dependent on patient and
and Human Nutrition, New Delhi, India; 16All India Institute of Medical disease factors. Readmission post discharge, however, is variable
Sciences New Delhi, Department of Gastroenterology and Human across continents and inversely correlates socio-economic status.
Nutrition Unit, New Delhi, India; 17Dr. Rela Institute and Medical Centre, Global characterization of patients at high risk of readmission should
Deptt. of Liver Transplant Surgery, Tamil Nadu, India; 18Dr. Rela Institute include further study of socio-economic factors in addition to
and Medical Centre, Tamil Nadu, India; 19CHU de Cocody, South Africa; severity of liver disease.
20
Mustapha Bacha University HospitaL, Algeria; 21University of
Malaysia; 22University of Malaysia, Kuala Lumpur, Malaysia;
23
Chulalongkorn University and King Chulalongkorn Memorial Hospital,
Bangkok, Thailand; 24Chulalongkorn University and King Chulalongkorn
Memorial Hospital, Thailand; 25Hospital Genereal “Gerardo Liceaga”,
Mexico; 26Instituto Nacional de Ciencias Médicas y Nutrición “Salvador
Zubirán, Mexico; 27Queen Elizabeth University Hospitals, Birmingham,

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S19

ORAL PRESENTATIONS
OS009 and proerythroblasts (7 vs. 17.9, p < 0.001) in the erythroid colonies of
Dyserythropoiesis is underrecognized and contributes to severe patients with DE. The DE was significantly related with low GATA.1
anemia in liver cirrhosis (7.7 ± 4.3 vs 13.6 ± 7.8; p = 0.001) non-nuclear localization of HSP70
Chhagan Bihari1, Sumit Garg1, Shiv Kumar Sarin2. 1Institute of Liver ( p = 0.04) and excess erythroferrone (23.4 ± 7 vs 14.2 ± 5.2, p < 0.001)
and Biliary Sciences, Pathology and Hepatology, Delhi, India; 2Institute of as compared to no-DE.
Liver and Biliary Sciences, Hepatology, Delhi, India Conclusion: Approximately 13.2% patients with cirrhosis with severe
Email: [email protected] anemia show dyserythropoiesis. Standard hematological and iron
studies fail to identify it and bone marrow examination is merited.
Background and aims: Moderate to severe anemia is one of the Alternations in the erythroid colonies, HSP70 localization and
common complication in liver cirrhosis and is often multifactorial. diminished GATA.1 in BM are associated with dyserythropoiesis.
Contribution of dyserythropoiesis (DE) in cirrhosis related anemia is
often neglected and has not been studied. We aimed to investigate OS010
the prevalence, severity and mechanisms of dyserythropoiesis in Effect of recruitement and selection policies on the volume of
cirrhosis patients. outcome of patients transplanted with ACLF-3
Method: We studied the bone marrows (BM) of cirrhosis patients Baptiste Michard1, Thierry Artzner1, Pietro Addeo1,
(n = 517), who underwent a BM aspiration/biopsy between Jan 2014– Philippe Bachellier1, Camille Besch1, Vincent Castelain1,
Dec 2018, for investigation of anemia, hypersplenism or other clinical Raphael Clere-Jehl1, Mathilde Deridder1, Max Guillot1,
indications. Cases of haematological or non-hematological neopla- Jean-Étienne Herbrecht1, Ralf Janssen-Langenstein1,
sias, chronic kidney disease, chronic or acute drug injury, acute and Maleka Schenck1, Francis Schneider1, François Faitot1. 1Hopitaux
chronic hepatitis and granulomatous pathology were excluded. Universitaires de Strasbourg
Morphological analysis of BM aspirate, biopsies, erythroid colony Email: [email protected]
assessment were done. A >5% dyserythropoiesis in erythroid lineage
was considered and categorized as mild: 5–10%; moderate: 10–15% Background and aims: Liver transplantation (LT) for critically ill
and marked: >15%. cirrhotic patients is a debated issue, which raises complex medical,
Results: A 68/517 (13.2%) cirrhosis patients had dyserythropoiesis surgical and ethical challenges. In particular, it is crucial to achieve
and none from control group. Of them 44% had mild; 35.4% moderate high post-LT survival in order to justify allocating livers to these
and 20.6% marked dyserythropoiesis in the BM. Cirrhosis patients patients, especially given the current organ shortage. To date, there is
with DE had significantly lower hemoglobin than those without DE no granular data concerning the 3-year post-LT outcome of ACLF-3
(7.6 ± 1.4 gm/dl vs 8.9 ± 1.9 gm/dl, p < 0.001), but comparable serum patients.
iron (83.7 ± 42 vs 90.2 ± 46.6 mcg/dl, p = 0.997); total iron binding Method: This study describes the three-year post-LT survival of a
capacity (243.2 ± 85.1 vs 231 ± 87.2 mcg/dl, p = 0.291); and transferrin single center granular cohort of patients with ACLF-3 at the time of LT
saturation (50.9 ± 27.9 vs 55.6 ± 30.8 %, p = 0.206) and serum folate and compares it to the post-LT survival of all the patients who were
(16 ± 3.8 vs 15.8 ± 4.4 ng/ml) levels. The former however, had higher transplanted without ACLF-3 in the same center between 2007 and
vitamin B12 (2339.2 ± 1406 vs 1842 ± 1411.9 pg/ml, p = 0.010) levels. 2018. Over this period of time, two policies were gradually
Further, other confounding factors for anemia like lactate dehydro- implemented in this center: (i) developing a network of peripheral
genase ( p = 0.494), reticulocyte count ( p = 0.808), thyroid stimulating centers that transferred critically ill cirrhotic patients for LT
hormone ( p = 0.208), hepcidin ( p = 0.16), erythropoietin ( p = 0.23), assessment and (ii) increasing use of the transplantation for ACLF-3
and spleen size ( p = 0.310) were comparable. Grades of dyserythro- model (TAM) score criteria to identify the optimal transplantability
poiesis were associated with Child’s score ( p = 0.003) with marked window.
dyserythropoiesis being noted in Child C. Dyserythropoiesis was Results: A total of 828 first time single LTs were performed over the
mainly associated with alcohol and non-alcoholic steatohepatitis (51/ study period. 91 patients had ACLF-3 at the time of LT. The overall
68, 75%) as compared to viral, autoimmune and other etiologies. BM three-year survival of ACLF-3 patients was 66% vs 82% (p < 0.001) for
examination showed fewer erythroid colonies (8 vs. 10.7, p < 0.001) the rest of the cohort. Over the study period, both the number of

Figure: (abstract: OS010)

S20 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS
patients transplanted with ACLF-3 and their 3-year post-LT survival per patient per year) of other major complications was also reported
increased over time: 2007–2009: 7 patients, 43% survival; 2010– in LTA patients: spontaneous bacterial peritonitis (0.19 vs 0.09),
2012: 20 patients, 60% survival; 2013–2015: 28 patients, 54% hepatorenal syndrome (0.28 vs 0.16) and hepatic encephalopathy
survival; 2016–2018: 36 patients, 83% survival (no significant (0.40 vs 0.31). Hospitalisations were 2.40 and 2.85 per patient per
difference in survival between the ACLF-3 and the non ACLF-3 year in LTA and non-LTA groups, respectively. Differences were
group in the last period). This increase in the number of patients maintained when comparing patients within age groups (≤39, 40–
transplanted and in their post-LT three-year survival was not 59, ≥60 years).
observed in the general population of patients transplanted Conclusion: These real-word data captured through an audit
without ACLF-3 (cf. Figure). A total of 12 ACLF-3 patients were methodology indicate that Italian hepatologists consider LTA a
transplanted with TAM scores>2. However, in the last period (2016– valuable approach for the medical management of decompensated
2018), in which both the number of patients transplanted with ACLF- cirrhosis, as LTA is currently prescribed in a vast proportion of patients
3 and the post-LT survival were the highest, no patient was with ascites. Although the present study does not allow the
transplanted with a TAM score>2. comparison of the two groups, the lower incidence of paracentesis
and complications observed in patients receiving LTA is consistent
Conclusion: This study, which originates from the largest single with the benefits documented by the ANSWER trial. Considering this,
center cohort of patients transplanted with ACLF-3, illustrates how the cost-effectiveness of LTA and potential for reducing the economic
gradually building a network of peripheral centers to refer critically ill burden upon healthcare systems should be assessed.
cirrhotic patients to an expert ICU and LT center can lead to a dramatic
increase in the number of patients transplanted with ACLF-3. It also OS012
shows that there is a learning curve when transplanting patients with Impact of cirrhotic cardiomyopathy and severity of liver cirrhosis
ACLF-3 and that the implementation of the TAM score to help identify on the development of acute kidney injury
the optimal transplantability window at the time of organ proposal Simona Bota1, Marcel Razpotnik1, Philipp Wimmer2, Michael Hackl2,
contributes to optimizing post-LT outcomes. The combination of Gerald Lesnik3, Hannes Alber2, Markus Peck-Radosavljevic1.
these strategies can help centers increase the number of patients 1
Klinikum Klagenfurt am Wörthersee, Department of Internal Medicine
transplanted with ACLF-3 while reaching post-LT outcomes for these and Gastroenterology (IMuG) and Emergency Medicine (ZAE),
patients that are similar to those of non ACLF-3 patients. Klagenfurt, Austria; 2Klinikum Klagenfurt am Wörthersee, Department
of Internal Medicine and Cardiology (IMuK), Klagenfurt, Austria;
OS011 3
Klinikum Klagenfurt am Wörthersee, Institut for diagnostic and
Real-world evidence on long-term albumin treatment in patients
interventional Radiology, Klagenfurt, Austria
with decompensated liver cirrhosis in Italy
Email: [email protected]
Wim Laleman1, Jonel Trebicka2, Alastair O’Brien3, Paolo Caraceni4,
Sandra Santos5, Tatiana Vilchez6, Kyle Rodney7, Sofia Schweiger8, Background and aim: New criteria of cirrhotic cardiomyopathy
Paolo Angeli9. 1University Hospitals Leuven, Department of (CCM) were published from a multidisciplinary consortium (Izzy et al.
Gastroenterology and Hepatology, Section of Liver and Biliopancreatic Hepatology 2019 Nov 11. doi: 10.1002/hep.31034) and define systolic
Disorders, Leuven, Belgium; 2Goethe University Hospital Frankfurt, dysfunction of the left ventricle as ejection fraction (EF) ≤50% and/or
Translational Hepatology Department of Internal Medicine, Frankfurt, global longitudinal strain (GLS) <−18%, while the diastolic dysfunc-
Germany; 3University College London, Institute for Liver and Digestive tion is diagnosed when three of the following conditions are present:
Health, London, United Kingdom; 4University of Bologna, Department of average E/e’ >14, peak tricuspid regurgitation velocity >2.8 m/s, septal
Medical and Surgical Science, Bologna, Italy; 5CSL Behring, Lisbon, e’<7 cm/s, left atrial volume index >34 ml/m2.
Portugal; 6CSL Behring, Barcelona, Spain; 7Adivo Associates LLC, Our aim was to assess the influence of CCM, severity and etiology of
California, United States; 8Adivo Associates LLC, Buenos Aires, Argentina; liver cirrhosis on the development of acute kidney injury.
9
University of Padova, Department of Medicine, Unit of Internal Method: Our prospective study included consecutive patients with
Medicine and Hepatology, Padova, Italy liver cirrhosis without structural heart disease, arterial hypertension,
Email: [email protected] HCC outside Milan criteria, portal vein thrombosis, presence of TIPS
and with optimal acoustic echocardiography window. The patients
Background and aims: Human albumin plays an important role in were evaluated between 12/2018–11/2021 in our in- and out-patient
the management of patients with decompensated liver cirrhosis. Department. Conventional and speckle-tracking echocardiography
Guidelines recommend short-term albumin in specific acute condi- (Vendor GE, EchoPAC PC software) were performed by a single
tions, but clinical trial data have also shown benefits of long-term
investigator (EACVI TTE certified).
albumin (LTA) treatment. This study aimed to analyse real-world data Acute kidney injury (AKIN) was defined according to the
on LTA treatment in patients with cirrhosis across Italy. International Ascites Club as increase to serum creatinine of
Method: Data from an independent audit platform was collected on
0.3 mg/dL in <48 h or 50% increase in serum creatinine from baseline
patients with cirrhosis and ascites who received non-LTA, defined as value within ≤3months.
standard medical treatment with diuretics and albumin only for
The follow-up was performed until the patient was last seen or death.
acute indications, or LTA, with infusions at weekly intervals for ≥6 Results: 412 cirrhotic patients were evaluated during the study
months. Audits were performed between 2018 and 2020, using period and 133 fulfilled the inclusion criteria and were included in
institutional data and callbacks with healthcare professionals in Italy
the final analysis. The mean age of patients was 57.1 ± 10.2 years
from 43 locations (hospitals, pharmacies and health units). (60.1% males), 70.1% with alcoholic etiology and 48.1% with Child-
Retrospective analysis was conducted on patient demographics,
Pugh A liver cirrhosis.
treatment dose and regimen, complication rates and hospitalisation The median follow-up was 21 (0.5–36) months. Acute kidney injury
outcomes. was diagnosed in 26/133 (19.5%) of patients, while CCM (systolic and/
Results: Data were captured for 6660 patients (non-LTA: 4305; LTA:
or diastolic dysfunction) was present on 15% of patients.
2355). Main etiologies of cirrhosis were alcoholic (33%), viral (29%) The presence of acute kidney injury was correlated in univariate
non-alcoholic steatohepatitis (30%) and other (7%). In LTA patients, analysis with presence of CCM, Child-Pugh score, MELD score,
the mean (range) treatment duration was 14 (6–36) months and alcoholic etiology of liver cirrhosis and prothrombin time (Table).
initial dose was 87 (10–280) g/week, followed by 37 (10–60) g/week. In multivariate logistic regression analysis only CCM and alcoholic
The need for paracentesis (3.1 vs 6.2 per patient per year) and the
etiology remained significantly associated with AKIN: CCM -OR = 13.6
incidence of refractory ascites (0.57 vs 0.71 per patient per year) were
lower in LTA than in non-LTA patients. A lower incidence (episodes

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S21

ORAL PRESENTATIONS
(95% CI: 3.8–54.0), p = 0.0001 and alcoholic etiology-OR = 5.3 (95% CI: Results: Of 999 patients included (mean age 60.8 ± 12 years, 622
1.1–26.3), p = 0.03. females (62.3%)), 976 had valid TE values; 149 (15.3%) had liver
stiffness ≥7.9 KPa. Of 892 with available ELF, 262 had ELF score ≥9.8
(29.4%). Age and BMI were independently associated with elevated
Spearman r liver stiffness and ELF. Diabetes was associated with significant
correlation fibrosis defined by liver stiffness ≥7.9 KPa, OR = 3.21 (1.96–5.21), p <
coefficient 0.001. But, neither MTX cumulative dose nor duration of exposure
Age r = 0.089, p = 0.30 was associated with elevated liver stiffness [OR = 1.02 (0.93–1.12) and
Male gender r = 0.052, p = 0.54 1.00 (0.99–1.0), respectively] and ELF score [OR = 1.06 (1.0–1.12) and
BMI r = 0.103, p = 0.23 1.00 (0.99–1.0), respectively]. Regular use of non-steroidal anti-
Alcoholic etiology r = 0.186, p = 0.03 inflammatory drugs was associated with ELF score ≥9.8, OR = 1.78
Spleen size r = 0.082, p = 0.34 (1.22–2.60), p = 0.003.
Presence of CCM r = 0.323, p = 0.0001 Conclusion: Lack of association of MTX cumulative dose and duration
Child-Pugh score r = 0.259, p = 0.002 with liver fibrosis in RA or PS indicates that the risk of liver fibrosis
MELD score r = 0.237, p = 0.005
due to MTX itself might have been overestimated. The degree of
Presence of portal r = 0.107, p = 0.21
hypertension inflammation in RA and PS may confound ELF as a marker to detect
Albumin r = −0.169, p = 0.06 fibrosis.
Platelet count r = 0.037, p = 0.67
Table: Demographic and phenotypic features for cases and controls
Prothrombin time r = −0.197, p = 0.02
Control
MTX group group (n =
Conclusion: The presence of CCM is a strong predictor of acute kidney Characteristics (n = 876) 123) p
injury development among cirrhotic patients.
Age (years), mean (SD) 61.6 (11.6) 55.6 (13.5) <0.001
Female, n (%) 560 (63.9) 62 (50.4) <0.01
Diagnosis, n (%) 55 (44.7) <0.001
RA 615 (70.2) 67 (54.5)
PS 241 (27.5) 1 (0.8)
Non-invasive assessment of liver disease except Both 20 (2.3)
Type 2 Diabetes 100 (11.5) 21 (17.1) NS
NAFLD Hyperlipidaemia 225 (25.9) 28 (22.8) NS
2
BMI (kg/m ), mean (SD) 29.9 (6.7) 30.9 (7.5) NS
Alcohol >14 units/week, n (%) 83 (9.5) 25 (20.3) <0.001
Fibrosis markers
OS013 TE groups, n (%) 731 (85.5) 96 (79.3) 0.08
Association of long term methotrexate therapy with liver fibrosis Low <7.9 124 (14.5) 25 (20.7)
markers: a multi-centre prospective case-control study High ≥ 7.9
ELF groups, n (%) 562 (71.4) 68 (64.8) NS
Edmond Atallah1,2, Jane Grove1,2, Colin Crooks1,2, Esther Burden-teh3, Low risk <9.8 202 (25.7) 34 (32.4)
Ruth Murphy4, Sulleman Moreea5, Abhishek Abhishek6, Moderate risk (≥9.8 to <11.3) 23 (2.9) 3 (2.9)
Kelsey Jordan7, Aftab Ala8, David Hutchinson9, Richard Aspinall10, High risk ≥11.3
Guruprasad Aithal1,2. 1University of Nottingham, Nottingham Digestive
Diseases Centre, School of Medicine, Nottingham, United Kingdom; NS: Not significant.
2
Nottingham University Hospitals NHS Trust and the University of
OS014
Nottingham, National Institute for Health Research (NIHR) Nottingham
Development and validation of a machine learning-based model
Biomedical Research Centre, Nottingham, United Kingdom; 3University
for varices screening in compensated cirrhosis (CHESS2001): an
of Nottingham, Centre of Evidence Based Dermatology, School of
international multicenter study
Medicine, Nottingham, United Kingdom; 4Sheffield Dermatology
Yifei Huang1, Jia Li2, Tian-lei Zheng3, Dong Ji4, Yu Jun Wong5,
Research, University of Sheffield, Sheffield, United Kingdom; 5Bradford
Hong You6, Ye Gu7, Musong Li8, Lili Zhao2, Shuang Li2, Shi Geng3,
Teaching Hospitals NHS Foundation Trust, Bradford, United Kingdom;
6 Na Yang3, Guofeng Chen4, Yan Wang7, Manoj Kumar9, Ankur Jindal9,
Nottingham University Hospitals NHS Trust Queen’s Medical Centre
Qin Wei8, Zhenhuai Chen8, Yongning Xin10, Zicheng Jiang11,
Campus, United Kingdom; 7Brighton and Sussex University Hospitals
Xiaoling Chi12, Jilin Chen13, Mingxin Zhang14, Huan Liu14, Ming Lu15,
NHS Trust, Brighton, United Kingdom; 8Royal Surrey County Hospital,
Li Li15, Yong Zhang16, Chunwen Pu16, Deqiang Ma17, Qibin He18,
Surrey, United Kingdom; 9Royal Cornwall Hospitals NHS Trust, Cornwall,
Shanghong Tang19, ChunYan Wang19, Shiv Kumar Sarin9, Xiaolong Qi1.
United Kingdom; 10Portsmouth Hospitals University NHS Trust, 1
The First Hospital of Lanzhou University, CHESS Center, Institute of Portal
Portsmouth
Hypertension, Lanzhou, China; 2Tianjin Second People’s Hospital,
Email: [email protected]
Department of Gastroenterology and Hepatology, Tianjin; 3The Affiliated
Background and aims: Incidence of acute drug-induced liver injury Hospital of Xuzhou Medical University, Artificial Intelligence Unit,
due to methotrexate (MTX) reduces significantly after the first year of Department of Medical Equipment, Xuzhou, China; 4The Fifth Medical
treatment. However, decompensated cirrhosis attributed to MTX Center of Chinese PLA General Hospital, Department of Liver Diseases,
accounts for 0.07% of patients listed/transplanted in the USA. We Beijing, China; 5Changi General Hospital, Duke-NUS Academic Clinical
evaluated the risk of long-term MTX therapy on liver fibrosis Program, SingHealth, Department of Gastroenterology and Hepatology,
prospectively in a case-control study. Singapore, Singapore; 6Beijing Friendship Hospital, Capital Medical
Method: Between 2014–2021, adult patients diagnosed with University, Liver Research Center, Beijing Key Laboratory of Translational
Rheumatoid Arthritis (RA) or Psoriasis (PS) were recruited prospect- Medicine in Liver Cirrhosis, National Clinical Research Center of Digestive
ively from six UK sites. Patients on MTX for ≥6 months were defined Diseases, Beijing, China; 7The Sixth People’s Hospital of Shenyang, Portal
as cases, whereas those with RA or PS for ≥2 years who never received
MTX were controls. All patients underwent full liver profile,
enhanced liver fibrosis (ELF) markers, and transient elastography
(TE). Multivariate analysis was performed using logistic regression
and results were presented as adjusted odds ratio (OR) and 95%
confidence interval.

S22 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS

Figure: (abstract: OS014)

Hypertension Center, Shenyang, China; 8Baoding people’s Hospital, ML EGD. By receiver operator characteristic curve, the most accurate
Department of Gastroenterology, Baoding, China; 9Institute of Liver and cut-off to rule out patients with VNT was chosen as a ML EGD below
Biliary Sciences (ILBS), Department of Hepatology, New Delhi, India; 0.50 with a negative predictive value of 96.4%. In the training cohort, a
10
Qingdao Municipal Hospital, Qingdao University, Department of ML EGD below 0.50 could spare 607 (52.6%) unnecessary EGD with a
Infectious Disease, Qingdao, China; 11Ankang Central Hospital, missed VNT rate of 3.6%. In the validation cohort, test cohort 1 and
Department of Infectious Diseases, Ankang, China; 12Guangdong test cohort 2, a ML EGD score below 0.50 could spare 75 (58.1%), 506
Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of (52.4%), 224 (41.1%) EGD with a missed VNT rate of 1.4%, 2.8%, and
Guangzhou University of Chinese Medicine, Department of Hepatology, 3.1%, respectively. Comparing with Baveno VI criteria, ML EGD
Guangzhou, China; 13Shanghai Public Health Clinical Center affiliated to improved the proportion of avoided EGD (training cohort, 52.6% vs
Fudan University, Department of Gastroenterology and Hepatology, 29.4%; validation cohort, 58.1% vs 44.2%; test cohort 1, 52.4% vs 26.5%;
Shanghai, China; 14The First Affiliated Hospital of Xi’an Medical test cohort 2, 41.1% vs 21.1%).
University, Department of Gastroenterology, Xi’an, China; 15Mengzi Conclusion: We developed a robust machine learning-based model,
People’s Hospital, Department of Gastroenterology, Mengzi, China; named ML EGD, with excellent performance to exclude VNT in
16
Dalian Public Health Clinical Center, Dalian, China; 17Taihe Hospital, patients with compensated cirrhosis.
Hubei University of Medicine, Department of Infectious Diseases, Shiyan,
China; 18Second Hospital of Nanjing, Nanjing Hospital of Chinese OS015
Medicine, Department of Gastroenterology, Nanjing, China; 19General Diagnostic performance of non-invasive liver fibrosis biomarkers:
Hospital of Western Theater Command PLA, Department of a bayesian individual patient data meta-analysis of hepatitis B
Gastroenterology, Chengdu, China cohorts in sub-saharan Africa (HEPSANET)
Email: [email protected] Alexander Stockdale1,2, Asgeir Johannessen3,4, Marc Henrion2,5,
Edith Okeke6, Moussa Seydi7, Gilles Wandeler8, Mark Sonderup9,
Background and aims: Only a few patients with compensated
Wendy Spearman9, Michael Vinikoor10,11, Edford Sinkala10,
cirrhosis who underwent esophagogastroduodenoscopy (EGD) Hailemichael Desalegn12, Fatou Fall13, Nicholas Riches5,
screening for varices were found to have varices needing treatment
Davwar Pantong Mark14, Mary John Duguru15,
(VNT). Our study aimed to identify a novel machine learning-based
Tongai Gibson Maponga16, Jantjie Taljaard16, Philippa Matthews17,
model (ML EGD) for ruling out VNT and avoiding unnecessary EGD in Monique Andersson17, Roger Sombie18, Yusuke Shimakawa19,
patients with compensated cirrhosis.
Maud Lemoine20. 1University of Liverpool, Liverpool, United Kingdom;
Method: A total of 2794 patients from China, Singapore and India 2
Malawi-Liverpool-Wellcome Trust Clinical Research Programme,
were enrolled. Of them, 1283 patients in a real-world cohort from one
Blantyre, Malawi; 3Sykehuset i Vestfold, Norway; 4University of Oslo
university hospital, 966 in a multicenter cohort (test cohort 1) from
Faculty of Medicine, Norway; 5Liverpool School of Tropical Medicine,
14 university hospitals, and 545 in an international cohort (test United Kingdom; 6Faculty of Medical Sciences, Jos, Nigeria; 7Hospital
cohort 2) from Singapore and India were included, respectively. For
Center University De Fann, Dakar, Senegal; 8Institute of Social and
the real-world cohort, patients were shuffled and sampled randomly Preventive Medicine (ISPM), Bern, Switzerland; 9UCT Faculty of Health
into training and validation cohort with a ratio of 9:1. In the training
Sciences, Cape Town, South Africa; 10The University of Zambia, Lusaka,
cohort, a light gradient boosting machine algorithm was used to
Zambia; 11University of Alabama at Birmingham, Birmingham, United
develop the pre-model to detect VNT based on clinical data. A shapley
States; 12St. Paul’s Hospital Millennium Medical College, Addis Ababa,
value method was used to evaluate the importance of included
Ethiopia; 13Hopital Principal de Dakar, Dakar, Senegal; 14University of
variables according to pre-model. ML EGD was furthermore devel-
Jos, Jos, Nigeria; 15University of Jos, Jos, Nigeria; 16Stellenbosch
oped based on the most related variables to detect VNT using light
University, Stellenbosch, South Africa; 17University of Oxford, United
gradient boosting machine algorithm. Then, we validated it in the
Kingdom; 18Hospital Center Universitaire Yalgado Ouédraogo,
validation cohort and tested it in the two external test cohorts.
Ouagadougou, Burkina Faso; 19Pasteur Institute, Paris, France;
Results: The main etiology of cirrhosis was hepatitis B infection in the 20
Imperial College London, United Kingdom
training (68.02%), validation cohort (68.99%) and test cohort 1
Email: [email protected]
(79.19%) and the main etiology in test cohort 2 was hepatitis C
infection (47.16%). Liver stiffness, platelet count and total bilirubin Background and aims: In sub-Saharan Africa, hepatitis B is the
were evaluated as the most related variables to detect VNT to develop principal cause of liver disease, and associated mortality is rising.

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S23

ORAL PRESENTATIONS
Low-cost non-invasive biomarkers of liver fibrosis are needed to due to the rarity of this outcome. Existing prediction tools are
identify patients at risk of HBV-related mortality who therefore suboptimal and there is a need for improvement. Here, we aimed to
require antiviral treatment. We evaluated the performance of the identify subgroups of persons in the general population with high
biomarkers APRI (AST to platelet ratio index), FIB-4 and GPR (GGT to risks for development of severe liver disease using commonly
platelet ratio) in an individual patient data (IPD) meta-analysis. available biomarkers.
Method: We included data from HEPSANET, a network comprised of Method: We used laboratory and clinical data on 126, 925 individuals
12 cohorts of HBsAg-positive individuals in 8 sub-Saharan African aged 35–79, in Stockholm, Sweden, with clinical examinations
countries. We used transient elastography as a reference test for between 1985 and 1996. No individuals had known chronic liver
cirrhosis (≥12.2 kPa) and significant fibrosis (≥7.9 kPa). We excluded disease, a drug- or alcohol use disorder at baseline. Nationwide
patients who were pregnant, had hepatitis C, D, or HIV co-infection, registries were used to ascertain ten-year cumulative incidence of
were on hepatitis B therapy or had acute hepatitis. Upper limits of severe liver disease, a composite of diagnoses corresponding to
normal were 40 U/L for AST/AST and 61 U/L for GGT. We fitted a cirrhosis or its complications. Candidate biomarkers were selected
bivariate Bayesian IPD model with patient-level covariates and study- based on if they meaningfully improved prediction of severe liver
level random effects. disease in addition to the established FIB-4 score. They were then
Results: We included 3549 patients. Median age was 33 years (IQR categorized and combined, creating subgroups with different risk
28–41) and 60% were male. The prevalence of significant fibrosis and profiles.
cirrhosis among included cohorts was 18% and 7% respectively. APRI Results: During a follow-up of average 9.3 years, we ascertained 630
and GPR had the best discriminant performance (area under curve incident cases of severe liver disease (0.5%). On top of the FIB-4 score
0.81 and 0.82) relative to FIB-4 (0.77) or ALT alone (0.70) for cirrhosis. we identified age, impaired glucose, and gamma-glutamyl transfer-
The World Health Organization (WHO) threshold of APRI>2.0 was ase (gGT) to meaningfully improve a classification of risk. 24 risk
associated with sensitivity of 16.5% (95% credible interval 12.5–20.5) groups were created, with a cumulative incidence of severe liver
and specificity of 99.5% (99.2–99.7) for cirrhosis. At rule-in thresholds disease at ten years ranging from 0.2% (age 35–65, low FIB-4, no
for cirrhosis APRI (cut-off 0.65) had sensitivity of 56.2% and specificity impaired glucose and normal gGT) to 32.1% (age 35–65, high FIB-4,
of 90.0%; GPR (cut-off 0.47) had sensitivity of 58.6% and specificity impaired glucose and high gGT). A heatmap of these risk groups was
90.9%. At rule out-thresholds for cirrhosis APRI (0.33) had sensitivity created (Figure 1).
and specificity of 80.6% and 64.3%; GPR (0.23) had sensitivity 80.6%
and specificity of 66.7% (Figure). The subset of asymptomatic patients
who were diagnosed with HBV through routine screening had a mean
cirrhosis prevalence of 2.5%, and APRI (cut-off 0.65) had a positive
predictive value (PPV) of 13.2% and negative predictive value (NPV) of
98.8%. Among patients diagnosed with HBV due to suspected liver
disease, cirrhosis prevalence was 27%; with APRI cut-off 0.65, PPV
was 59.6% and NPV 84.5%.
Conclusion: APRI at the WHO-recommended threshold of 2.0 has a
poor sensitivity for the diagnosis of cirrhosis in sub-Saharan Africa;
WHO guidelines should be revised for the WHO African region to
reflect these findings. APRI and GPR had equivalent diagnostic Figure 1: Heatmap of subgroups with differing risk for severe liver disease
performance and performed best at ruling out cirrhosis but were less at ten years, in percent.
good at correctly identifying cases. Programs need to be aware of the Conclusion: Estimates of risk of severe liver disease in the general
significant trade-offs between under- and over-diagnosis of liver population using the FIB-4 score can be substantially improved by
cirrhosis when implementing low-cost fibrosis markers in hepatitis B adding age and biomarkers commonly available in the primary care
programs in sub-Saharan Africa. setting.

OS017
Gadoxetic acid-enhanced MRI-derived Functional Liver Imaging
Score (FLIS) and spleen diameter provide complementary
information for risk stratification in ACLD
Nina Bastati1, Lucian Beer1, Ahmed Ba-Ssalamah1,
Sarah Poetter-Lang1, Raphael Ambros1, Antonia Kristic1,
David Lauber1, Lorenz Balcar1, Katharina Pomej2, Teresa Binter2,3,
Benedikt Simbrunner2,3, Georg Semmler2,3, Yesim Bican1,
Jacqueline C. Hodge1, Thomas Wrba4, Michael Trauner2,
Thomas Reiberger2,3, Mattias Mandorfer2,3. 1Department of
Biomedical Imaging and Image-Guided Therapy, Medical University of
Vienna, Vienna, Austria; 2Division of Gastroenterology and Hepatology,
Department of Internal Medicine III, Medical University of Vienna,
Vienna, Austria; 3Vienna Hepatic Hemodynamic Lab, Division of
OS016 Gastroenterology and Hepatology, Department of Internal Medicine III,
Prediction of ten-year risk of severe liver disease in the general Medical University of Vienna, Vienna, Austria; 4IT-Systems and
population using commonly available biomarkers Communications, Medical University of Vienna, Vienna, Austria
Hannes Hagström1, Jacinth Yan2, Mats Talbäck2, Anna Andreasson3, Email: [email protected]
Göran Walldius2, Matteo Bottai2, Niklas Hammar2. 1Karolinska Background and aims: The Functional Liver Imaging Score (FLIS)
Institutet; 2Karolinska Institutet, Sweden; 3Stockholm University, derived from gadoxetic acid-enhanced MRI (GA-MRI) correlates with
Sweden hepatic function in chronic liver disease (CLD) patients. Splenic
Email: [email protected] metrics, i.e., volume and craniocaudal diameter (SCCD) are markers of
Background and aims: Estimating risk for severe liver disease, portal hypertension, a key driver of disease progression.
including cirrhosis, in the general population is complicated in part

S24 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS
We aimed to investigate the prognostic utility of FLIS and SCCD for OS018
hepatic decompensation and transplant-free mortality in CLD. ADAPT, a score incorporating PRO-C3, for the early detection of
Method: Three hundred ninety-seven CLD patients undergoing GA- liver fibrosis in a large population-based study
MRI were included. The FLIS was calculated by summing the points Ann T. Ma1,2,3, Guillem Pera3,4, Martina Perez1,2,3,5,
(0–2 each) assigned to three hepatobiliary phase features: hepatic Mette Juul Nielsen6, Morten Karsdal6, Diana Leeming6,
enhancement, biliary excretion, and portal vein signal intensity. Carmen Expósito4, Alba Martínez-Escudé4,7, Isabel Graupera1,2,3,
Patients were stratified into 3 clinical groups according to FIB-4 and Maja Thiele8,9, Aleksander Krag8,9, Núria Fabrellas2,3,5,
presence/history of decompensation: non-advanced CLD (non- Llorenç Caballeria3,4, Pere Ginès1,2,3,5. 1Liver Unit, Hospital Clínic de
ACLD), compensated ACLD (cACLD), and decompensated ACLD Barcelona, Barcelona, Spain; 2Institut d’Investigacions Biomed ̀ iques
(dACLD). The associations between SCCD/FLIS and decompensation/ August Pi i Sunyer (IDIBAPS), Barcelona, Spain; 3Centro de Investigavción
transplant-free mortality were investigated using Cox regression Biomédica en Red de Enfermedades Hepática y Digestivas (CIBEREHD),
analysis and log-rank test. Madrid, Spain; 4Unitat de Suport a la Recerca (USR) Metropolitana Nord,
Results: We observed a strong correlation between spleen volume Fundació Institut Universitari d’Investigació en Atenció Primària Jordi
and SCCD (Spearman’s rho: 0.887; p < 0.001), and thus, the simple Gol i Gurina (IDIAP Jordi Gol), Mataró, Spain; 5Facultat de Medicina-
measure SCCD was used for further analyses. The inter-reader Universitat de Barcelona, Barcelona, Spain; 6Nordic Bioscience, Herlev,
(intraclass coefficient, ICC: 0.982; n = 241) and intra-reader (ICC: Denmark; 7Centre d’Atenció Primària La Llagosta, La Llagosta, Spain;
0.997; n = 41) agreement for the SCCD were excellent. Median SCCD 8
Department of Gastroenterology and Hepatology, Odense University
showed stepwise increases from non-ACLD (11.8 cm), cACLD Hospital, Denmark; 9Department of Clinical Research, Faculty of Health
(13.3 cm), to dACLD (15.2 cm; p < 0.001). Sciences, University of Southern Denmark, Odense, Denmark
Since non-ACLD patients are at negligible risk of decompensation/ Email: [email protected]
liver-related death, we abstained from analysing direct end points in
this subgroup. In patients with cACLD, SCCD predicted decompensa- Background and aims: Non-invasive screening of liver fibrosis in the
tion (adjusted-hazard-ratio, [aHR]: 1.1, 95% confidence interval [95% general population has become an important target in order to
CI]: 1.02–1.18; p = 0.014) in an analysis adjusted for MELD and identify liver disease early and avoid its progression. Novel biomar-
albumin; dichotomizing SSCD resulted in an aHR of 2.51 (95%CI: kers of extracellular matrix formation, including PRO-C3, a marker of
1.22–5.21, p = 0.01) for those with a SCCD >13 cm. In patients with type III collagen formation, have emerged as accurate predictors of
ACLD (i.e., cACLD/dACLD combined), FLIS (0–3 vs. 4–6 points) was a advanced fibrosis in NAFLD and alcohol-related liver disease. A
risk factor for transplant-free mortality (aHR: 2.64, 95%CI: 1.61–4.01, composite score known as ADAPT, that includes PRO-C3, age, platelet
p < 0.001), even after adjusting for age, MELD, and albumin. Of note, count, and diabetes, has recently been validated in both these patient
FLIS (0–3 vs. 4–6 points; aHR: 1.74, 95%CI: 1.18–2.58, p = 0.005) and populations, but its effectiveness to screen for liver fibrosis in
SCCD (>13 vs. ≤13 cm; aHR: 2.16, 95%CI: 1.44–3.24, p < 0.001) were asymptomatic subjects in the general population is unknown.
independently predictive of the composite end point of decompen- Method: This study was performed in a large population-based
sation/transplant-free mortality, even after adjusting for the previ- cohort of randomly selected subjects aged 18–75 in the Barcelona
ously mentioned prognostic indicators. Grouping patients according metropolitan area without known liver disease (mean age 54, 43%
to FLIS/SCCD accurately stratified the risk of decompensation/ male, 10% with type 2 diabetes, 28% with metabolic syndrome, 9%
transplant-free mortality (Figure). with at-risk alcohol consumption). Serum PRO-C3 levels were
measured by enzyme-linked immunosorbent assay in 2670 subjects.
Liver fibrosis was estimated by measuring liver stiffness with
transient elastography (TE). Significant fibrosis was defined as a TE
≥9.2 kPa based on previous data supporting that this cut-off had the
best diagnostic accuracy for fibrosis ≥F2 on liver biopsy (Clin.
Gastroenterol. Hepatol. 2018 PMID 29452268).
Results: The prevalence of significant fibrosis was 3.1% (83/2670). The
median level of PRO-C3 was higher in subjects with significant
fibrosis compared to those without (14 vs. 12 ng/ml, p < 0.001). The
ADAPT score predicted significant fibrosis with moderate accuracy
(AUROC 0.76; 95% CI 0.71–0.82), higher than scores frequently used to
identify fibrosis in the general population, such as FIB-4 or APRI, and
similar to NAFLD Fibrosis Score (NFS). Fatty liver index (FLI) exhibited
the highest discriminative ability (AUROC 0.87; 95% CI 0.84–0.91;
Figure 1). Amongst subjects with metabolic/alcohol risk factors and a
high FLI≥60, the sequential use of ADAPT using the best cut-off of 6.1
had an excellent negative predictive value for significant fibrosis (Se
51%, Sp 82%, PPV 20%, NPV 95%).

Conclusion: The FLIS and SCCD are simple GA-MRI-based imaging

markers providing complementary information for risk stratification
in patients with advanced chronic liver disease.
N.B. and L.B. contributed equally.

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S25

ORAL PRESENTATIONS
(OCA + ASBTi). After sacrifice, liver injury was determined by plasma
liver enzymes, RT-qPCR and liver histology, while HPLC analysis was
used to quantify bile salt concentrations in plasma, liver, small
intestine and feces.
Results: ASBT KO mice had reduced liver necrosis, reduced bilirubin
and alkaline phosphatase (ALP) levels compared to wild-type mice
after BDL. ASBT KO mice also showed a trend to reduced bile salt pool
size, and increased urinary bile salt excretion. OCA + ASBTi treatment
reduced the total bile salt pool size before cholestasis-onset and
resulted in reduced bilirubin, ALP and a ∼60% reduction in liver
necrosis compared to placebo control in a BDL model. Besides, OCA +
ASBTi treatment decreased fecal bile salt excretion compared to
monotherapy with ASBTi.
Conclusion: Systemic ASBT inhibition effectively reduces BDL-
induced liver damage. Combined OCA + ASBTi treatment lowers the
Figure: ROC curves of non-invasive fibrosis scores for prediction of signifi-
bile salt pool size and improves liver health after BDL-induced
cant fibrosis.
cholestasis, while it also shows therapeutic potential by reducing
Conclusion: In this population-based study, the ADAPT composite fecal bile salt excretion.
score that includes PRO-C3 offers superior predictive accuracy for the
diagnosis of significant liver fibrosis as compared to other recom- OS020
mended screening tools such as FIB-4 and APRI. The individual Low-dose IL-2 alleviates drug-induced primary biliary cholangitis
components of ADAPT are easily accessible clinical parameters and as in mice by improving Treg and Th17 balance
such could be used as a tool for the early detection of liver fibrosis in Zilong Wang1, Bo Feng1, Yandi Xie1, Rui Jin1, Zhicheng Liu1. 1Peking
the general population, particularly in a sequential-type approach. University Hepatology Institute, Beijing, China
Email: [email protected]
Background and aims: The imbalance of regulatory T (Treg) and T
helper 17 (Th17) cells correlates with increased risk of autoimmune
Immune-mediated and cholestatic: diseases. Their imbalance was also reported in primary biliary
Experimental and pathophysiology cholangitis (PBC) patients. Previous studies have suggested that
low-dose IL-2 can alleviate disease severity through modulating
CD4+T cell subsets in patients with autoimmune diseases. However,
the efficacy of low-dose IL-2 in PBC remains unexplored. Hence, the
OS019
present study aimed to examine effects of low-dose IL-2 in PBC
Novel anti-cholestatic treatment strategies by combining
mouse models.
inhibition of the Apical sodium-dependent bile acid transporter
Method: PBC was induced in female C57BL/6 mice by two
with stimulation of urinary bile salt excretion or lowering bile salt
immunizations with 2-nonynoic acid (2OA-BSA) at two-week
synthesis
intervals. Besides, polyinosinic polycytidylic acid ( poly I:C) was
Roni Kunst1,2, Esther Vogels1, Isabelle Bolt1, Ronald Oude-Elferink1,2,
injected i.p. every three days. The control group was injected with PBS
Stan van de Graaf1,2. 1Tytgat Institute for Liver and Intestinal Research,
instead of 2OA-BSA and poly I:C. PBC mice were divided into the
Department of Gastroenterology and Hepatology; 2Amsterdam
treated and untreated groups, and low-dose IL-2 was injected s.c.
Gastroenterology Endocrinology Metabolism, Amsterdam, Netherlands
every three days after four weeks from modeling in the treated group
Email: [email protected]
(Fig. A)and the untreated group was replaced with saline. The serum
Background and aims: The apical sodium-dependent bile acid was isolated from blood sampled by eyeball extirpating for
transporter (ASBT) is primarily expressed in the small intestine and biochemical detection. Th17 and Tregs were analyzed by flow
kidney, where it prevents bile salts from being excreted in cytometry, and the related cytokines were analyzed by ELISA. Liver
respectively feces and urine. Intestine-restricted drugs that inhibit histopathology was examined by HandE and immunohistochemical
ASBT are currently clinically explored to reduce toxic accumulation of staining. The experimental data were analyzed by SPSS 24.0 software.
bile acids during cholestasis. Intestine-restricted ASBT inhibitors P < 0.05 indicated statistical significance.
(ASBTi) may be less effective in severe cholestasis and also yield Results: Eight weeks after modeling, the serum AMA was positive
gastrointestinal side-effects in case of high bile salt load in the colon. and the ALP was significantly increased in PBC mice compared with
Here, we test two ASBT-targeting treatment strategies in pre-clinical control group. The pathology showed lymphocyte infiltration in the
models with cholestasis-induced liver injury. First, systemic ASBT portal area, and damage and reactive proliferation of small bile duct,
inhibition, to increase renal bile acid excretion and second a and CD4+ and CD8+ T cells were infiltrated around the bile duct. Flow
combination treatment with obeticholic acid (OCA) to limit bile salt cytometric examination of spleen cells revealed recovery of reduced
synthesis and reduce colonic bile acid load. Tregs and increased Th17 after low-dose IL-2 treatment (Treg/
Method: Systemic ASBT inhibition was tested by performing a bile CD4%:9.26 ± 0.50 vs 6.10 ± 0.14 vs 8.24 ± 0.04; Th17/CD4%: 0.29 ±
duct ligation (BDL) in adult ASBT knock-out (KO) mice (129P2/OlaHsd 0.20 vs 1.00 ± 0.17 vs 0.33 ± 0.09) ( p < 0.05) (Fig. B). Low-dose IL-2
background, Jackson) and wild-type littermates to induce severe treatment inhibited IL-17A levels (0 vs 4549 ± 597.5 vs 1928 ± 387) ( p
cholestasis. In our second strategy, BDL was performed in adult wild- < 0.05) and improved serum biochemical index (ALP: 119.1 ± 6.20 vs
type C57Bl/6 mice after 2 days oral gavage pre-treatment with OCA 82.36 ± 12.6 U/L) (Fig. C). Histopathological examination of liver
and ASBTi. In a different model, wild-type C57Bl/6 mice were fed a revealed the improvement of portal area inflammation and reactive
0.1% 3, 5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC) diet while bile duct hyperplasia and damage after low-dose IL-2 treatment
receiving daily treatment with either placebo, OCA, ASBTi or both (Fig. D).

S26 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS
in KRT19 + bile duct regions (Ctrl, 7–40%; PSC, 11–94%). In contrast,
CD100 protein expression measured by IHC was nearly undetectable
in diseased periductal areas of the PSC livers. Moreover, surface
expression of CD100 on biliary infiltrating immune cells was reduced
and accompanied by increased sCD100 in plasma and bile from PSC
patients, suggesting that CD100 is cleaved from the surface of
immune cells in regions adjacent to the bile ducts. In co-culture
experiments, we observed that activated immune cells adhered to
cholangiocytes and correlated with the death of large but not small
cholangiocytes. T cells were dominant (49.9–64.4%) in the adherent
immune population and lost their surface CD100 expression. RNA
sequencing data showed increased Adamts4 in co-cultured cholan-
giocytes which appeared to cleave CD100. Genes involved in anti-
apoptosis and T-helper 17 (Th17) differentiation were enriched in
adherent T cells and further upregulated in T cells with mutated
Conclusion: The PBC mouse model was successfully induced by the CD100.
combination of 2OA-BSA and poly I:C and it can model human Conclusion: Cholangiocytes induce cleavage of CD100 on biliary
disease early status. Low-dose IL-2 inhibited PBC by augmenting Treg infiltrating T cells that facilitates persistent inflammation and local
and decreasing Th17 numbers, which paly important role in the Th17 differentiation. These findings highlight a novel pathway in the
pathogenesis of the PBC. The improvement of biochemical indexes liver with cholangiocyte-driven Th17 cell differentiation that is
and liver histopathology, suggesting that low-dose IL-2 treatment associated with CD100 cytoplasmic signaling. Targeting this patho-
may be considered as novel therapy for PBC in the future. genic pathway serves as an attractive target for mitigating bile duct
inflammation in PSC.
OS021
Cholangiocytes cleave surface CD100 from biliary infiltrating T OS022
cells and mediate pathogenic Th17 differentiation Novel approach combining whole liver single-cell RNA
Xiaojun Jiang1,2,3, Kari Otterdal2, Brian K. Chung1,2,3, sequencing and spatial gene profiling using Nanostring GEOMX
Christopher Maucourant4, Christine Zimmer4, Sverre Holm2, enables identification of specific cell sub-populations and
Daniel Geanon4, Annika Bergquist5, Tom Hemming Karlsen1,3, pathways regulated by CCL24
Niklas Björkström4, Espen Melum1,2,3,6,7. 1Norwegian PSC Research Michal Segal-Salto1, Raanan Greenman1, Arnon Aharon2, Ophir Hay3,
Center, Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway; Amnon Peled3, Adi Mor4. 1Chemomab Therapeutics Ltd., RandD, Tel
2
Research Institute of Internal Medicine, Oslo University Hospital Aviv, Israel; 2Chemomab Therapeutics Ltd., Clinical, Tel Aviv, Israel;
Rikshospitalet, 0424 Oslo, Norway; 3Institute of Clinical Medicine, 3
Hadassah Hebrew University Hospital, Genetic Therapy Institute,
University of Oslo, 0318 Oslo, Norway; 4Center for Infectious Medicine, Jerusalem, Israel; 4Chemomab Therapeutics Ltd., Tel-Aviv, Israel
Department of Medicine Huddinge, Karolinska Institutet, Karolinska Email: [email protected]
University Hospital, 141 52 Stockholm, Sweden; 5Department of
Background and aims: CCL24 (Eotaxin-2) is a chemokine that
Gastroenterology and Hepatology, Karolinska University Hospital
regulates profibrotic and proinflammatory activities through the
Huddinge, Karolinska Institutet, 171 77 Stockholm, Sweden; 6Section of
CCR3 receptor. We previously demonstrated that CM-101, a CCL24
Gastroenterology, Department of Transplantation Medicine, Division of
blocking antibody, improves liver inflammation, fibrosis and cholan-
Surgery, Inflammatory Diseases and Transplantation, Oslo University
gitis in the Mdr2 knockout (Mdr2 -/-) mouse model. Characterization
Hospital Rikshospitalet, 0424 Oslo, Norway; 7Hybrid Technology Hub-
of CCL24 expression in relation to the different cell populations in
Centre of Excellence, Institute of Basic Medical Sciences, Faculty of
Mdr2-/- mice and its inhibition effect on cholangiocytes and immune
Medicine, University of Oslo, 0317 Oslo, Norway.
response was studied using two gene expression methods.
Email: [email protected]
Method: Identification of cell population, including immune cells
Background and aims: Chronic inflammation surrounding bile ducts and CCL24 expressing cells in livers of Mdr2-/- mice was done by
contributes to the disease pathogenesis of most cholangiopathies, but scRNA seq from whole liver. NanoString’s technology was utilized for
the mechanism enabling pathogenic immune cells to adapt and gene expression studies, focusing on the bile-duct injury sites. In this
survive in the biliary environment remains largely unknown. We system segmenting of cholangiocytes (Pan-CK+) and immune cells
have recently reported a variant of CD100 to be the causal mutation (Pan-CK−) cells was done in liver sections from Mdr2-/-mice non-
for a familial form of primary sclerosing cholangitis (PSC). Herein, we treated or treated with CM-101.
investigate how CD100 participates in the biliary local inflammation Results: Mdr2-/- mice treated with CM-101 resulted in reductions in:
and its relevance to the differentiation of pathogenic immune cells. serum ALP, liver inflammation, liver peribiliary collagen deposition
Method: CD100 expression was assessed by spatial transcriptomics and cholangiocytes proliferation. Using whole liver scRNA seq we
(10x Genomics) and in situ immunohistochemistry (IHC) in explanted demonstrated that CCL24 is expressed in macrophage cells. This
livers of patients with PSC (n = 4–6) and other cholangiopathies (Ctrl, analysis identified a few specific disease relevant immune sub-
n = 4–5). Soluble CD100 (sCD100) was measured by ELISA in paired populations, however it is missing crucial information that relates to
serum, plasma, and bile samples (n = 11–19). Biliary infiltrating cell localization. To overcome this, we used NanoString to character-
immune cells were collected from endoscopic retrograde cholangio- ize the alternations in peribiliary transcriptome following CM-101
pancreatography brush samples (Ctrl, n = 6; PSC, n = 6) and surface treatment. Spatial profiling separated cholangiocytes (PanCK+) and
expression of CD100 was evaluated by flow cytometry. To model non-cholangiocytes (PanCK−) peribiliary cells, distinguishing chola-
pathogenic interactions between immune cells and cholangiocytes, static, proinflammatory and profibrotic effects. Gene set enrichment
splenic cells isolated from C57BL/6 wild-type (WT) and CD100 analysis showed reduction in proliferation and senescence pathways
mutated mice were co-cultured with small or large cholangiocytes. in PanCK+ cells, whereas PanCK- cells showed reduction in ECM
Altered gene expression was assessed with RNA sequencing of remodeling pathways and increased metabolic pathways. Cell
purified cell subsets after co-culture. deconvolution of the heterogeneous PanCK- population revealed
Results: Spatial transcriptomics revealed SEMA4D/CD100 RNA alternation in the peribiliary immune cells, marked by reduction in
expression in all examined livers and demonstrated the localization macrophages and monocytes following treatment with CM-101.

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ORAL PRESENTATIONS
Conclusion: Augmenting whole liver scRNA seq with spatial confirmed with immunohistochemistry showing a two-fold reduc-
transcriptome analysis, is a novel approach to identify cell popula- tion in the number of Yap and Sox9 expressing Ck19+ cholangiocytes.
tions and pathways specific to the damaged peribiliary area. Using The Foxp3 fate mapping experiments showed that the labelled Tregs
this approach we demonstrated that CCL24 regulates cholestatic, population reduces Foxp3 expression after DDC diet indicating that
inflammatory and fibrotic liver damage, and its underling mechan- the stability of Tregs decreases during liver injury.
isms. Understanding the underling mechanisms of CCL24 blockade Conclusion: Our results demonstrated that the role of Tregs in
and its ability to prevent liver injury in animal supports its role in PSC promoting bile duct regeneration by modulating ductular reaction
and its potential beneficial effect for PSC patients. through the Hippo-Yap pathway. Furthermore, the observation that
Foxp3 Tregs become unstable in an injured microenvironment in
mice may explain the lack of Tregs seen in PSC patients. These show
the potential of using Tregs to promote liver regeneration but also
highlights the stability of Tregs should be taken into consideration
when designing cell based Tregs therapy.

OS024
Deep learning for automatic diagnosis and morphologic
characterisation of malignant biliary strictures using digital
cholangioscopy: a pilot study
Miguel Mascarenhas1, João Afonso1, Tiago Ribeiro1, Ana Santos1,
Hélder Cardoso1, João Pedro Sousa Ferreira2, Filipe Vilas-Boas1,
Pedro Pereira1, Guilherme Macedo1. 1Centro Hospitalar Universitário
de São João, Department of Gastroenterology, Porto, Portugal;
2
Faculdade de Engenharia da Universidade do Porto, Department of
OS023 Mechanical Engineering, Porto, Portugal
T regulatory cells promote bile duct regeneration through Email: [email protected]
modulating ductular reaction in a model of cholestatic liver
Background and aims: Patients with indeterminate biliary strictures
injury
(BS) pose a significant diagnostic challenge. Digital cholangioscopy
Naruhiro Kimura1,2,3, Gareth Hardisty1, Atsunori Tsuchiya3, (DC) has enabled morphologic characterization as well as the
Shuji Terai3, David Withers2, Wei-Yu Lu1,2. 1University of Edinburgh, performance of visually guided biopsies. However, the diagnostic
Centre for Inflammation Research, Edinburgh, United Kingdom; yield of DC remains suboptimal, and the visual characterization of
2
University of Birmingham, Institute of Immunology and these lesions has significant interobserver variability. Recently, the
Immunotherapy, Birmingham, United Kingdom; 3Niigata University, development of artificial intelligence (AI) algorithms, particularly
Division of Gastroenterology and Hepatology, Niigata, Japan convolutional neural networks (CNNs) for interpretation of endo-
Email: [email protected] scopic images has generated intense interest. We aimed to develop a
Background and aims: Reduced regulatory T cells (Tregs) and CNN-based system for simultaneous automatic detection of malig-
increased bile duct senescence are observed in primary sclerosing nant BS in D-SOC images and identification of three morphologic
cholangitis (PSC) patients, with the degree of cholangiocyte senes- features: nodules (NN), papillary projections (PP) and tumor vessels
cence linking to disease severity and prognosis. Cholangiocytes can (TV).
act as facultative liver progenitor cells through ductular reaction Method: We developed and validated a CNN based on DC images
during extensive liver damage, whether this process is impaired (Spyglass DS II, Boston Scientific, USA). Each frame was labeled as
during PSC remains to be investigated. The role of Tregs in modulating normal/benign finding or as a malignant lesion if definite histologic
tissue resident progenitor cells have been shown in multiple organs, evidence of biliary malignancy was available. Moreover, we evaluated
but this remains unclear in the context of liver regeneration. We aim the performance of the CNN for the detection of morphologic
to use transgenic murine models to investigate the cause of reduced features associated with histology-proved biliary malignancy: NN, PP,
Tregs in the liver and whether the lack of Tregs in the liver affect bile and TV. The image dataset was split for constitution of training and
duct regeneration and senescence. validation datasets. The performance of the CNN was measured by
Method: Foxp3GFPDTR transgenic mice were used to reduce Tregs calculating the accuracy, area under the curve (AUC), sensitivity,
number in a dose dependant manner. 50% of Tregs were depleted to specificity, positive and negative predictive values (PPV and NPV,
avoid triggering systematic autoimmunity whilst cholestatic liver respectively).
injury was induced by the feeding of 3, 5-diethoxycarbonyl-1, 4- Results: We included 23 595 images from 125 patients (20719 of
dyhydrocollidine (DDC) diet and compared to the control group with malignant BS and 2876 of normal or benign findings). The model had
intact Tregs population. We generated the a sensitivity of 98.9%, a specificity of 97.7% and an overall accuracy of
Foxp3GFPCreERTtdTomloxSTOPlox mice to investigate Tregs stability. 98.7%. The AUC was 1.00.
Tamoxifen was injected intraperitoneally to induce tdTom expression Additionally, the model comprised 2876 images of NN, 1675 images
in Foxp3 Tregs and cell fate was investigated after DDC diet to showing PP, and 4153 images of YV. The accuracy for the automatic
determine Tregs stability. CD4 T-cells were isolated and co-cultured detection of each of these features was, respectively, 96.9%, 96.1%, and
with intrahepatic cholangiocytes organoids to confirm the effect of 91.5%.
CD4 T-cells on cholangiocytes. Conclusion: We developed a combined CNN for automatic detection
Results: Mice with reduced Tregs have a lower tolerance to the of malignant BS as well as the automatic identification of morpho-
feeding of DDC diet, with rapid weight loss and two times higher logic features associated with increased probability of malignancy.
periportal fibrosis than the control group. Histological findings The application of AI models to DC may increase its diagnostic yield
showed that the reduction in Tregs decrease the magnitude of for patients with indeterminate BS. Furthermore, accurate real-time
Ck19+ ductular reaction by 30%. A two-fold increase in Ck19+p21+ automatic identification of features associated with increased
senescing cholangiocytes was observed in the group with reduced probability of malignancy may help to guide biopsies, thus increasing
Tregs after DDC induced liver injury. Transcriptional analysis of liver their rentability.
tissue revealed downregulation of Yap1, Sox9 and Ctgf, suggesting the
Yap pathway is affected following Tregs reduction. This is further

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 ORAL PRESENTATIONS
hospitalisation or death [liver event], CV hospitalisation or death [CV
Table 1: Performance metrics of the combined convolutional neural event] or all-cause death) recorded in HES or Office for National
network Statistics Death Registration, database migration, 10 years’ follow-up
or 1 January 2020, whichever came first. Fibrosis-4 Index (FIB4), the
Malignant
strictures (vs. NN (vs PP (vs normal/ TV (vs normal/ score of focus, was categorised as low (<1.30), indeterminate (1.30–
normal/benign normal/other other other 2.67) or high (>2.67) risk. Cumulative incidence functions were
findings) findings) findings) findings) calculated and hazard ratios (HRs) estimated using Cox proportional
hazards models with calendar time as underlying timescale.
Sensitivity 98.9% 96.1% 98.2% 85.7%
Results: In total, 44 481 eligible patients (46% male, median age 58.8
Specificity 97.7% 98.9% 94.8% 100%
PPV 99.7% 99.5% 91.7% 100% years) had measures available for FIB4 calculation. There were 979
NPV 92.8% 91.4% 98.9% 82.5% liver events, of which ascites (n = 412), cirrhosis (n = 201) and gastro-
Accuracy 98.7% 96.9% 96.1% 91.5% oesophageal varices (n = 160) were most common. The risk of an
AUC 0.987 1.000 1.000 1.00 incident liver event was highest in the first years after FIB4
measurement in the high FIB4 group and relatively constant over
Abbreviations; PPV-positive predictive value; NPV-negative predictive value; time in the other two groups (Figure). The incidences of a liver event,
AUC-area under the curve. CV event and death in the high FIB4 group were 15%, 33% and 61%,
respectively. Patients in the indeterminate and high FIB4 groups were
at greater risk of liver events vs the low-risk group (HR 2.81 [95%
confidence interval 2.43, 3.26] and 18.42 [15.67, 21.65], respectively).
An increased risk was also seen for CV events and all-cause mortality
Non-invasive assessment/treatment and liver in these groups. HRs remained higher for the high vs low FIB4 group
related outcomes in NAFLD/ALD after adjustment for sex and age. For the other scores, risk of an
outcome event was also elevated for patients with a high vs low score.

OS025
Non-invasive fibrosis scores as prognostic biomarkers of liver
events, cardiovascular events and all-cause mortality in people
with obesity and/or type 2 diabetes in the UK: a longitudinal
cohort study
Quentin Anstee1,2, Tina Landsvig Berentzen3, Louise Nitze3,
Maximilian Jara3, Mette Kjaer3, Kamal Kant Mangla3, Jens M. Tarp3,
Kamlesh Khunti4. 1Translational and Clinical Research Institute, Faculty
of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United
Kingdom; 2Newcastle NIHR Biomedical Research Centre, Newcastle
Upon Tyne Hospitals NHS Trust, Newcastle Upon Tyne, United Kingdom;
3
Novo Nordisk A/S, Søborg, Denmark; 4Diabetes Research Centre,
University of Leicester, Leicester General Hospital, Leicester, United
Kingdom
Email: [email protected]
Background and aims: Progression of non-alcoholic steatohepatitis
to cirrhosis may lead to life-threatening liver-related complications,
increased liver-specific and all-cause mortality and cardiovascular
(CV) disease. An important predictor of severe outcomes is biopsy-
confirmed liver fibrosis, but biopsies are not scalable outside of
specialist practice. This real-world study investigated the prognostic
utility of six non-invasive fibrosis scores on clinical outcomes in
patients with obesity and/or type 2 diabetes (T2D) seen in routine
general practice.
Method: In a longitudinal cohort design, patients ≥18 years with
obesity and/or T2D, ≥1 fibrosis score calculable from the UK Clinical
Practice Research Datalink (CPRD) after 1 January 2001, no alcohol- Conclusion: In this real-world population of patients with obesity
related disorders and/or other chronic liver diseases in Hospital and/or T2D, and no other clinically recognised liver disease, the risk of
Episodes Statistics (HES) and/or no prescriptions of drugs inducing a clinical event was significantly higher in patients with high vs low
liver disease in CPRD were included. Patients were followed from FIB4 score, highlighting the prognostic potential of FIB4 (and other
inclusion date until time of first clinical outcome event (liver-related non-invasive fibrosis scores) in this population.

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ORAL PRESENTATIONS
OS026 Results: Patients (median age 46 years, 59% men) had a median LSM
Liver stiffness predicts incident severe liver disease in patients of 5.9 (interquartile range 4.6–8.0) kPa. Etiologies consisted of
with chronic liver disease hepatitis C (n = 6849, 52.0%), hepatitis B (n = 3497, 26.6%), alcohol-
Hannes Hegmar1,2, Axel Wester2, Soo Aleman3, Jens Backman4, related liver disease (n = 211, 1.6%), autoimmune liver disease (n =
Erik Degerman5, Håkan Ekvall6, Katarina Lund7, Åsa Lundgren8, 624, 4.7%), non-alcoholic fatty liver disease (n = 699, 5.3%) and other
Patrik Nasr2,9, Afshin Shahnavaz10, Johan Vessby11, Johan Westin12, or uncertain etiologies (n = 1290, 9.8%). Patients without baseline
Kristina Önnerhag13, Hannes Hagström1,2,14. 1Division of Hepatology, cirrhosis (n = 11, 883) had 333 (2.8%) events of severe liver disease
Department of Upper Gi, Karolinska University Hospital, Huddinge, during a median follow-up time of 2.9 years. Patients with cirrhosis at
Sweden; 2Karolinska Institutet, Department of Medicine, Huddinge, baseline (n = 1287) had 206 (16.0%) events of decompensation or
Stockholm, Sweden; 3Karolinska Institutet/Karolinska University HCC. In patients without cirrhosis, a LSM of 12–15 kPa was associated
Hospital, Department of Infectious Diseases, Stockholm, Sweden; with a 42-fold higher rate of severe liver disease than a LSM of <6 kPa
4
University Hospital of Umeå, Department of Infectious Diseases, Umeå, (Figure A). In patients with cirrhosis, a LSM >30 kPa was associated
Sweden; 5Falun Hospital, Department of Infectious Diseases, Falun, with a 5.4-fold higher rate of decompensation compared to a LSM of
Sweden; 6Sundsvall-Härnösand Regional Hospital, Department of 15–17 kPa (Figure B). Incidence rates per 1000 person-years in severe
Infectious Diseases, Sundsvall, Sweden; 7Northern Älvsborg County liver disease ranged from 2.1 (95%CI 1.6–2.8) to 88.9 (95%CI 73.2–
Hospital, Department of Infectious Diseases, Trollhättan, Sweden; 107.9) for LSM <6 kPa and 12–15 kPa, respectively. Incidence rates per
8
Central Hospital Kristianstad, Department of Infectious Diseases, 1000 person-years in decompensated cirrhosis ranged from 18.2 (95%
Kristianstad, Sweden; 9Linköping University, Department of CI 10.3–32.0) to 109.6 (95%CI 88.9–135.1) for LSM 15–17 kPa and
Gastroenterology and Hepatology, Department of Health, Medicine and >30 kPa, respectively. In patients without cirrhosis, the cumulative
Caring Sciences, Linköping, Sweden; 10Southern Älvsborg Hospital, incidence at two years ranged from 0.4 (0.3–0.6)% to 19.1 (15.1–23-
Department of Infectious Diseases, Borås, Sweden; 11Uppsala University, 5)%, and at five years from 1.1 (0.8–1.6)% to 32.9 (26.9–38.9)%,
Department of Medical Sciences, Gastroenterology Research Group, respectively.
Uppsala, Sweden; 12University of Gothenburg and Sahlgrenska Conclusion: Increased LSM by VCTE is associated with higher rates of
University Hospital, Dept of Infectious Diseases, Gothenburg, Sweden; progression to cirrhosis and decompensation in a dose-response
13
Skåne University Hospital, Department of Gastroenterology and manner. The results can be used to guide follow-up and treatment
Hepatology, Malmö, Sweden; 14Karolinska Institutet, Clinical decisions.
Epidemiology Unit, Department of Medicine, Solna, Stockholm, Sweden
Email: [email protected] OS027
Linear slope of serial FIB-4 measurements predicts liver-related
Background and aims: Prognosis in chronic liver disease is complications and correlates with cirrhosis-associated genetic
heterogenous, and fibrosis stage is the best predictor of liver-related variants among patients with ALT-based NAFLD phenotype
events. Liver stiffness measurement (LSM) by Vibration-Controlled
Craig Teerlink1, David E. Kaplan2, Marijana Vujkovic3,
Transient Elastography (VCTE) is a non-invasive biomarker of fibrosis.
Benjamin Voight4, Kyong-Mi Chang3, Julie Lynch5, Scott Duvall5,
It is uncertain if LSM can predict risk for future liver-related events.
Tori Anglin5, Timothy Morgan6, Linus Schwantes-An Tae-Hwi7,
The aim was to investigate the prognostic ability of LSM.
Trina Norden-Krichmar8, Daniel Dochterman9, Poornima Devineni9,
Method: This was a Swedish multi-center cohort study including
Philip Tsao10, Carolin Victoria Schneider11. 1University of Utah Health,
patients (n = 13, 170) with chronic liver disease who underwent LSM
Internal Medicine, Salt Lake City, United States; 2Perelman Center for
by VCTE between 2008 and 2019. Exclusion criteria were an
Advanced Medicine, Gastroenterology, Philadelphia, United States;
unreliable LSM, congestive heart failure, and decompensated 3
University of Pennsylvania, Medicine, Philadelphia, United States;
cirrhosis at baseline. Liver-related events were ascertained from 4
University of Pennsylvania, Genetics, Philadelphia, United States; 5VA
Swedish national health registers. In patients without baseline
Health Care System, VINCI, Salt Lake City, United States; 6University of
cirrhosis, we investigated progression to “severe liver disease,”
California Irvine, Medicine, Irvine, United States; 7Indiana University,
defined as a diagnosis of cirrhosis, decompensated cirrhosis or
Medicine, Indianapolis, United States; 8University of California Irvine,
hepatocellular carcinoma (HCC). In patients with baseline cirrhosis,
Epidemiology and Biostatistics, Irvine, United States; 9VA Health Care
we investigated progression to decompensation or HCC. Incidence
System, GenISIS, Boston, United States; 10Stanford University, Medicine,
rates and cumulative incidence at two and five years were calculated.
Palo Alto, United States; 11University of Pennsylvania, Translational
Cox regression was used to evaluate the rate of outcomes for
categories of LSM values.

Figure: (abstract: OS026): A. Patients without cirrhosis at baseline. B. Patients with cirrhosis at baseline.

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 ORAL PRESENTATIONS
Medicine and Human Genetics, Philadelphia, United States visits in the STELLAR 3 and STELLAR 4 clinical trials (n = 1097 patients
Email: [email protected] with all end points). A continuous score for fibrosis was extracted
using convolutional neural networks (CNN) trained to predict
Background and aims: FIB-4 is a clinically relevant marker to track
pathologist scores from HandE-stained biopsies (Casale et al, EASL
fibrosis in patients with chronic liver disease including NAFLD/NASH.
2020). We identify genes associated with fibrosis state by testing for
Here, we first defined Fib-4 trajectory by linear slope of serial FIB-4
associations between baseline expression and baseline fibrosis
measurements as a measure of fibrosis progression, then examined
scores, controlling for age and sex. Fibrosis progression/regression
its correlation with liver-related complications and genetic associa-
genes are identified by testing for associations between baseline
tions with a non-invasive ALT-based proxy NAFLD phenotype
expression and the difference between baseline and followup fibrosis
recently defined among participants in the VA’s Million Veteran
scores after controlling for both ML and pathologist baseline fibrosis
Program (MVP) with available clinical and genetic data (Serper et al,
scores, age, sex, and treatment.
PLOS ONE 2020).
Results: The continuous ML fibrosis scores are highly correlated with
Method: Individual FIB-4 slopes were estimated via linear regression
pathologist Ishak scores (correlation = 0.88). Variation of the ML
for MVP participants with greater than 4 outpatient FIB-4 values who
fibrosis score within Ishak scores exhibits similar transcriptomic
met criteria for proxy NAFLD phenotype based on previously
associations as variation in Ishak scores (correlation of z scores =
validated algorithm for chronic ALT elevation without other known
0.88), suggesting that the ML score identifies intra-score variability
causes of chronic liver disease. Linear models were constructed
consistent with pathologist assessed fibrosis. We identify 12, 862
excluding outliers at >2 Cook’s distances from predicted. Patients
genes associated with ML fibrosis state (likely driven in part by
whose initial FIB-4 values exceeded the 90% percentile (baseline
changes in cell type composition) and 37 genes associated with ML
advanced fibrosis) were assigned slopes equivalent to the 99th
fibrosis progression/regression (A, B). Using the same covariates,
percentile of the sample. The AUROCs for the coefficient of FIB-4 slope
analysis of the ML score identifies a superset of the progression/
for predicting development of cirrhosis, hepatocellular carcinoma,
regression genes identified with the pathologist score (37 vs 3 genes).
ascites and death were generated. MFIB4 was then used as a
Notably, the progression/regression-associated genes are not the top
quantitative phenotype in a genome-wide association analysis
state-associated genes. Progression associated genes include
using REGENIE software. Variants were restricted to MAF >0.01 and
expected extracellular matrix and cytoskeletal function-related
INFO >0.30. Three distinct racial/ethnic groups were defined for the
genes. Lipid metabolism genes identified include the progression
cohort (European, African, and Hispanic ancestry) and analyzed
associated gene AKR1B10 (involved in hepatic carcinogenesis) and
separately; a trans-ancestry meta-analysis was performed with
the regression associated gene AKR1D1 (involved in resistance to
METAL software.
oxidative stress). Other regression associated genes identified include
Results: FIB-4 slopes were obtained from 61, 689 subjects (10, 594
metallothionein genes, involved in the protection against oxidative
African, 46, 137 European, and 4, 958 Hispanic ancestry subjects).
stress, and CLEC4M, a liver sinusoidal endothelial cell-specific gene.
AUROC of FIB-4 slope for prediction of cirrhosis, hepatocellular
Conclusion: ML assessment of liver biopsies and the statistical
carcinoma or ascites were 0.75–0.76. Among European ancestry
inference framework introduced herein produced insights on
subjects, FIB-4 slope was associated with 6 genome-wide significant
baseline gene expression signatures that are predictive of and
loci ( p value <5 × 10−8) including 3 with previously known associa-
potential drivers for NASH fibrosis progression or regression.
tions to NAFLD and hepatic fibrosis (GCKR, HSD17B13, and PNPLA3).
The GWAS of African and Hispanic ancestry did not return any
significant results, however, the trans-ancestry meta-analysis iden-
tified an additional signal.
Conclusion: Fibrosis progression based on FIB-4 trajectory correlated
with clinically meaningful complications of liver disease progression,
as well as known markers of cirrhosis among patients with non-
invasive ALT-based NAFLD phenotype. Further work is ongoing to
define the use of FIB-4 trajectory and genetic risk factors as predictors
for long term outcome of chronic liver disease.

OS028
Machine learned histological fibrosis score empowers
characterization of baseline gene signatures associated with
fibrosis progression or regression in a NASH F3/F4 clinical trial
Michael D. Bereket1, Francesco Paolo Casale1, Lorn Kategaya1,
Anna Shcherbina1, Navpreet Ranu1, Alicia Lee1, Kelly Haston1, OS029
Rohit Loomba2, Arun Sanyal3, Stephen Harrison4, Zobair Younossi5, Fibroscan-AST (FAST) score predicts liver-related outcomes in
Catherine Jia6, David Lopez6, Li Li6, Robert Myers6, 1683 HIV-infected patients at risk for NAFLD
David Breckinridge6, Andrew Billin6, Ellen Berg1, Santhosh Satapati1, Giada Sebastiani1,2, Jovana Milic3, Dana Kablawi1, Claudia Gioe’4,
Eilon Sharon1, Theofanis Karaletsos1, Daphne Koller1, Al Shaima Al Hinai2, Bertrand Lebouche5, Amine Benmassaoud1,
Matthew Albert1. 1Insitro, South San Francisco, United States; Marc Deschenes1, Antonio Cascio4, Giovanni Mazzola4,
2
University of California San Diego, La Jolla, United States; 3Virginia Giovanni Guaraldi3. 1McGill University Health Centre Glen Site (MUHC),
Commonwealth University, Richmond, United States; 4University of Medicine, Montréal, Canada; 2McGill University, Division of
Oxford, United Kingdom; 5Inova Fairfax Medical Campus, Fairfax, United Experimental Medicine, Montréal, Canada; 3University of Modena and
States; 6Gilead Sciences, Inc., Foster City, United States Reggio Emilia, Modena, Italy; 4Università degli Studi di Palermo, Health
Email: [email protected] Promotion Sciences and Mother and Child Care “Giuseppe D’Alessandro”,
Background and aims: We characterized disease severity with a Palermo, Italy; 5McGill University Health Centre Glen Site (MUHC),
machine learning (ML) analysis of liver biopsy images, and used it to Family Medicine, Montréal, Canada
identify baseline gene signatures that are predictive of fibrosis Email: [email protected]
progression or regression in NASH. Background and aims: Non-alcoholic fatty liver disease (NAFLD)
Method: Bulk RNA-seq, HandE stained biopsy images, and patholo- affects 35% of people living with HIV (PWH) in absence of viral
gist Ishak fibrosis scores are curated from screening and week 48

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ORAL PRESENTATIONS
hepatitis coinfection. About 15% of these PWH have also significant
liver fibrosis. Natural history studies employing accurate non-
invasive tools are lacking. The FibroScan-AST (FAST) score was
developed to identify patients with histologic NASH with advanced
fibrosis and elevated NAFLD activity score (NAS) associated with
higher risk of end-stage liver disease. We estimated prevalence and
evolution of severe NAFLD defined by FAST score in a large
multicenter cohort of PWH.
Method: FibroScan was performed in consecutive PWH without viral
hepatitis coinfection from three prospective cohorts in Canada and
Italy (LIVEHIV in Montreal; liver pathologies in HIV in Palermo;
Modena HIV metabolic clinic) as part of a routine screening program
for NAFLD. We compared prevalence of FAST>0.35 (90% sensitivity
and 50% specificity for NASH with ≥F2 fibrosis and NAS≥4) and
FAST≥0.67 (50% sensitivity, 90% specificity). Incidence of liver-related
outcomes (ascites, encephalopathy, variceal bleeding, hepatocellular
carcinoma) and extra-hepatic events (cancer, cardiovascular disease) Figure: Survival curves for incidence of liver-related outcomes by FAST
was evaluated by survival analysis. score category.
Results: We included 1683 PWH (mean age 50.1 years, HIV duration
15.5 years, BMI 25.3 Kg/m2; 74.5% male, diabetes prevalence 32%). Conclusion: A significant proportion of PWH without viral hepatitis
Prevalence of FAST>0.35 and FAST≥0.67 was 8.1% and 1.5%, coinfection are at risk for severe NAFLD. FAST score predicts liver-
respectively. At baseline, on multivariable logistic regression higher related in this population. Non-invasive testing can help risk
BMI (adjusted odds ratio [aOR] 1.15, 95% CI 1.10–1.20), longer duration stratification and management in this population at risk for NASH
of HIV infection (aOR 1.05, 95% CI 1.02–1.07), lower CD4 cell count and associated liver-fibrosis.
(aOR 0.99, 95% CI 0.99–0.99) and male sex (2.11, 95% CI 1.22–3.65)
were associated with FAST >0.35. During a median follow-up period OS030
of 3.5 years, incidence of liver-related and extra-hepatic outcomes Impact of resmetirom-mediated reductions in liver volume and
was 7% and 11.5%, respectively. Incidence of liver-related outcomes steatosis compared with placebo on the quantification of fibrosis
significantly increased according to FAST score category (see Figure). using second harmonic generation in a serial liver biopsy study
There was no difference in extra-hepatic events by FAST score Dean Tai1, Mustafa Bashir2, Rebecca Taub3, Yayun Ren1, Elaine Chng4,
category. On multivariable Cox regression analysis, FAST score >0.35 Stephen Harrison5. 1Histoindex, Research; 2Duke University, Radiology;
3
was an independent predictor of liver-related outcomes (adjusted Madrigal Pharmaceuticals, RandD, Conshohocken, United States;
4
hazard ratio 4.44, 95% CI 1.66–11.9) after adjusting for sex, BMI, Histoindex, 5Pinnacle, Clinical Research
diabetes, duration of HIV infection, protease inhibitors exposure and Email: [email protected]
CD4 cell count. Background and aims: Resmetirom (MGL-3196) is a liver-directed,
orally active selective thyroid hormone receptor-β agonist that
reduces steatosis by MRI-PDFF (−43% (80 mg); −53% (100 mg),
Phase 3) and liver volume (LV) −20% (Phase 2 serial liver biopsy

Figure: (abstract: OS030)

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 ORAL PRESENTATIONS
study) that were elevated at baseline. Assessment of histological who were evaluated and then declined for early LT for severe AH
features that stage NASH fibrosis may be impacted in the setting of between 2012 and 2021. All had MELD>20 and less than 6 months of
decreased steatosis and LV following therapeutic intervention. abstinence at LT evaluation. Recompensation was defined as
Artificial intelligence (AI)-based algorithms such as qFibrosis can MELD<15 without evidence of variceal bleeding, or ascites requiring
incorporate normalization procedures to account for steatosis area diuretics, or overt hepatic encephalopathy requiring medication.
and LV reduction, thereby improving the detection of fibrosis Analyses were adjusted for center clustering.
changes. The aim of this analysis is to quantify and correct fibrosis Results: Among 134 patients (median age 49 [IQR 39–57]; 57% male;
changes related to resmetirom-mediated steatosis and LV changes median abstinence time 36 [IQR 14–70] days; median MELD-Na 33
that are not captured by NASH-CRN scoring system. [IQR 28–38]), the most common reasons for LT decline were:
Method: Fibrosis was estimated as a continuous variable using psychosocial (62%), clinical improvement (16%), medical co-morbid-
second harmonic generation (SHG) (qFibrosis)/two photon excited ities (9%), and financial/insurance (4%). Probability of 3-month, 6-
fluorescence of 102 paired biopsy samples from MGL-3196-05, a 36- month, and 1-year survival was 58%, 55%, and 48%. Probability of 3-
week randomized double-blind, placebo-controlled resmetirom month, 6-month, and 1-year recompensation was 4%, 4%, and 6%. In
phase 2 serial liver biopsy study. qFibrosis (normalized by tissue multivariable analysis, lower MELD-Na (aOR 0.8; p = 0.01) and
area) was subsequently corrected for steatosis (tissue area-steatosis absence of grade 3 or 4 hepatic encephalopathy (aOR 0.02; p =
area), or LV reduction determined by PDFF (volume/average volume 0.004) were associated with 3-month survival. In multivariable
raw parameter based on all samples). In the final model, steatosis and analysis, lower MELD-Na (aOR 0.9; p < 0.001), married/stable partner
LV were both corrected prior to assessment of qFibrosis. Relative (OR 2.0; p = 0.001), and private (aOR 3.4; p = 0.01) or Medicare (aOR
changes in 184 fibrosis parameters were determined as (P) progres- 4.7; p = 0.002) vs. Medicaid (reference) insurance were associated
sing (≥10%), (R) regressing (<10%) or (N) no change. with 6-month survival. Among patients declined due to clinical
Results: In normal qFibrosis without correction, resmetirom treat- improvement during LT evaluation, 93% were alive at 6 months, but
ment resulted in a significant reduction in fibrosis (≥1-point only 15% were recompensated. Among survivors, median MELD at 1-
reduction) in F3 patients compared to placebo. With LV correction, month, 3-months, 6-months, and 1-year were: 28 (IQR 22–38), 26
45/184 regression parameters demonstrated significant changes after (IQR 19–33), 15 (IQR 12–23), and 12 (IQR 8–18).
resmetirom treatment (top panel). When steatosis and LV correction Conclusion: Liver recompensation is very rare among patients with
factors were combined, 111/184 ( p < 0.05) regression parameters severe AH declined for early LT. Lower MELD was predictive of short-
were reduced significantly with resmetirom (bottom panel). Fibrosis and long-term survival, and marital and insurance status emerged as
regression was observed in all regions ( portal, per-portal, zone 2, strong predictors of long-term survival. The distinction between
peri-central, central). Progression patterns were different from survival and liver recompensation after LT evaluation for severe AH
regression and also significantly impacted by correction. would benefit from further attention.
Conclusion: Quantification of changes in NASH fibrosis are impacted
by therapeutic interventions that reduce LV. Correcting the AI-based OS032
algorithm of qFibrosis for LV and steatosis reveals the significant Role of macrophage-derived MLKL in alcohol-associated liver
impact of resmetirom across treated patients in this phase 2 study, disease
regardless of NASH fibrosis stage. Xiaoqin Wu1, Xiude Fan1, Megan McMullen1, Tatsunori Miyata1,
Adam Kim1, Vai Pathak1, Jianguo Wu1, Nicole Welch1,
Jaividhya Dasarathy2, Srinivasan Dasarathy1, Laura Nagy1. 1Cleveland
Clinic; 2Case Western Reserve University, Department of Family
Medicine, Metro Health Medical Center
Alcoholic liver disease Email: [email protected]
Background and aims: Mixed Lineage Kinase Domain like
OS031 Pseudokinase (MLKL), a key downstream effector of necroptosis,
Survival and liver recompensation after declined for early liver also has non-necroptotic functions in regulating intracellular and
transplantation for severe alcohol-associated hepatitis extracellular vesicle trafficking that disrupts the balance between cell
Christine Hsu1, Ethan Weinberg2, Gene Im3, William Davis1, Jimin Ko4, death and survival, critical for regulating liver injury and inflamma-
Stephanie Rutledge3, Matthew Dukewich2, Mohamed Shoreibah5, tion in alcohol-associated liver disease (ALD). Previously, we
Mahmoud Aryan5, Aidan Vosooghi6, Michael R. Lucey7, John Rice7, observed that Mlkl −/− mice were partially protected from ethanol-
Norah Terrault8, Brian Lee6. 1Medstar Georgetown University Hospital, induced injury. Immunohistochemical staining of liver biopsies from
Medicine, District of Columbia, United States; 2University of patients with alcohol-associated hepatitis (AH) revealed that
Pennsylvania, Medicine, Philadelphia, United States; 3Mount Sinai, phospho-MLKL was localized to both hepatocytes and mononuclear
Medicine, New York, United States; 4Georgetown University School of immune cells. Moreover, MLKL co-localized with macrophage marker
Medicine, Medicine, District of Columbia, United States; 5University of F4/80 in liver of ethanol-fed mice. Given the important contribution
Alabama at Birmingham, Medicine, Birmingham, United States; of macrophages to the pathogenesis of ALD, we hypothesized that
6
University of Southern California, Medicine, Los Angeles, United States; macrophage-derived MLKL has a potential role in ethanol-induced
7
University of Wisconsin, Medicine, Madison, United States; 8University injury.
of Southern California, Medicine, Los Angeles, United States Method: Primary mouse Kupffer cells (mKCs) isolated from Mlkl −/−
Email: [email protected] and wild type (WT) mice and peripheral monocytes from healthy
controls (HC) and patients with AH, treated or not with an inhibitor of
Background and aims: Early liver transplantation (LT) for alcohol- MLKL, were used in phagocytosis assays. Bone marrow transplants
associated hepatitis (AH) is controversial in part because some between Mlkl −/− mice and littermates were conducted to distinguish
patients may recover, and obviate the need for LT. We aimed to (i) the role of myeloid vs non-myeloid MLKL in the Gao-binge murine
determine factors associated with survival and liver recompensation model of ALD.
among patients with severe AH declined for early LT; (ii) delineate the Results: Challenge of macrophages with lipopolysaccharide (LPS)
trajectory of recompensation and MELD recovery among survivors. induced STAT1-mediated expression and phosphorylation of MLKL,
Method: In this retrospective, multi-center study among 5 American as well as translocation and oligomerization of MLKL to intracellular
Consortium of Early Liver Transplantation for Alcohol-Associated compartments including phagosomes and lysosomes, but not the
Hepatitis (ACCELERATE-AH) sites, we randomly sampled 134 patients plasma membrane. LPS enhanced uptake and degradation of pHrodo

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ORAL PRESENTATIONS
red E.coli bioparticles by mKCs, whilst ethanol impaired this
phagocytic process. Pharmacological or genetic inhibition of MLKL
suppressed phagocytic capability of mKCs both at baseline or in
response to LPS with/without ethanol, as well as peripheral
monocytes isolated from both HC and patients with AH.
Additionally, in vivo study showed that Mlkl deficiency in non-
myeloid cells (WT→Mlkl −/−) had no effect on Gao-binge ethanol-
induced injury; in contrast, ethanol-induced hepatic injury, steatosis
and inflammation were exacerbated in Mlkl −/−→WT chimeric mice.
Mlkl −/−→WT mice also had elevated numbers of hepatic macro-
phages, monocytes and neutrophils in response to ethanol. Flow
cytometry analysis of non-parenchymal cells demonstrated that Mlkl
deficiency in myeloid cells suppressed Gao-binge-triggered F4/80+
macrophage death via necrosis/necroptosis. Furthermore, Mlkl
deficiency in myeloid cells exacerbated ethanol-mediated bacterial
burden in livers, likely through inhibiting expression of phagocytic
receptors.
Conclusion: Together, these data indicate that macrophage-derived
MLKL restricts ethanol-induced liver inflammation and injury by
OS034
regulating hepatic innate cell homeostasis and phagocytosis of
Il-1beta Signal Inhibition in acute alcoholic hepatitis: a
macrophage. multicentre, randomised, double-blind, placebo-controlled phase
OS033 2 trial of canakinumab therapy (ISAIAH)
Baseline plasma metabolic phenotype of patients with severe Nikhil Vergis1, Vishal C. Patel2,3,4, Karolina Bogdanowicz5,
alcoholic hepatitis and its association with outcome Justyna Czyzewska-Khan5, Rosemary Keshinro5,
Manisha Yadav1, Gaurav Tripathi1, Nupur Sharma1, Babu Mathew1, Francesca Fiorentino5, Emily Day5, Paul Middleton1,
Vasundhra Bindal1, Jaswinder Maras1, Shiv Kumar Sarin2. 1Institute of Stephen Atkinson1, Mary Cross5, Daphne Babalis5, Neil Foster1,
Alberto Quaglia6, Josephine Lloyd1, Robert D. Goldin1,
Liver and Biliary Sciences, Molecular and Cellular Medicine, New Delhi,
India; 2Institute of Liver and Biliary Sciences, Hepatology, New Delhi, William Rosenberg7, Richard Parker8, Paul Richardson9,
India Steven Masson10, Gavin Whitehouse11, Cyril Sieberhagen12,
Email: [email protected] David Patch7, Ashwin Dhanda13, Emma Lord1, Ewan Forrest14,
Nikolai Naoumov15, Mark Thursz1. 1Imperial College, Metabolism,
Background and aims: Severe alcoholic hepatitis (SAH) has a high Digestion and Reproduction, London, United Kingdom; 2King’s College
mortality and corticosteroid therapy is effective in reducing 28-day London, School of Immunology and Microbial Sciences, Faculty of Life
mortality in only about 60% of patients. There are reliable clinical Sciences and Medicine, United Kingdom; 3King’s College Hospital NHS
indicators predicting steroid non-response after 7 days of therapy Foundation Trust, Institute of Liver Studies, United Kingdom; 4The Roger
(Lille score >0.45). Williams Foundation for Liver Research, Institute of Hepatology, London,
Method: Plasma metabolic phenotype was studied using ultra-high- United Kingdom; 5Imperial Clinical Trials Unit, United Kingdom; 6Royal
performance liquid chromatography and high-resolution mass Free Hospital NHS Foundation Trust; 7University College London, United
spectrometry to identify corticosteroid non-responders at baseline. Kingdom; 8Leeds Teaching Hospitals NHS Trust, United Kingdom;
Altogether, 223 SAH patients were included, 70 in derivative [50 9
Liverpool University Hospitals Foundation NHS Trust, United Kingdom;
responders (R) and 20 non-responders (NR)] and 153 in validation 10
The Newcastle Upon Tyne Hospitals Foundation NHS Trust, United
cohort [136 R, 17 NR]. Temporal change in the metabolic profile and Kingdom; 11Chelsea and Westminster Hospitals NHS Foundation Trust;
Weighted Metabolome Correlation Network Analysis (WMCNA) were 12
Liverpool University Hospitals Foundation NHS Trust; 13University of
performed and correlated to disease severity. Plymouth, United Kingdom; 14Glasgow Royal Infirmary, United
Results: Of the 713 annotated features (metabolomic/biochemical/ Kingdom; 15London, United Kingdom
spectral databases), 8 plasma metabolites significantly discriminated Email: [email protected]
non-responders; most importantly high urobilinogen (13-fold),
cholesterol sulfate (6.9-fold), AMP (4.7-fold), N-Formimino-L-glu- Background and aims: Short-term mortality in acute alcohol-related
tamate (4.3-fold), tryptophan (4.7 folds), and low 4-imidazoleacetate hepatitis (AAH) patients is high and available therapy does not result
(10 fold), urocanic acid (2.2 fold) and thymine (2.4 fold) levels. in durable benefit. A role for IL-1beta has been demonstrated in the
Additionally, plasma urobilinogen, AMP, and cholesterol sulfate pathogenesis of alcohol-induced steatohepatitis in mice. This study
discriminated non-survivors ( p < 0.01). Temporal change in metab- explored the safety and potential benefits of canakinumab (CAN), a
olite expression was higher in responders ( p < 0.05). WMCNA monoclonal antibody targeting IL-1beta, for patients with AAH in a
identified metabolite modules and linked pathways specific to NR double-blind placebo (PBO)-controlled randomised trial.
and mortality with disease severity (r > 0.7; P < 0.01). In validation Method: Patients with biopsy-confirmed AAH and discriminant
cohort, baseline plasma urobilinogen (C05791) showed high reliabil- function ≥32 but MELD ≤27 were randomly allocated 1:1 to receive
ity [AUC = 0.94, 0.91–0.97] for predicting non-response with hazard- either CAN 3 mg/kg or PBO once in 4 weeks. Liver biopsies were taken
ratio of 1.5 (1.2–1.6) for mortality prediction. C05791 at 10 log before and 28 days after treatment. The primary end point was
(arbitrary units) cut-off reliably segregated non-survivors ( p value histological improvement at 28 days compared to baseline, adjudi-
<0.01, log-rank test) and showed 98% accuracy, 99% sensitivity and cated by 3 independent histopathologists who were blinded to
98% specificity using Random Forest-based Machine-Learning model. treatment allocation. Key secondary end points were the proportions
Conclusion: Plasma metabolome signatures can predict pre-therapy of Lille responders; changes in MELD; and death within 90 days.
steroid response and disease outcome in patients with SAH. Baseline Adverse events, including infections, were compared between groups.
plasma urobilinogen levels should be used for determining cortico- Results: Fifty-seven patients were randomised: 29 CAN vs 28 PBO.
steroid response. Two patients were withdrawn with negative biopsy results; 1 did not
receive allocated intervention due to an adverse event and a further 6
did not attend for second biopsy. Data were therefore available for 48
patients for primary end point analysis. In CAN-treated patients, 14/

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 ORAL PRESENTATIONS
24 (58.3%) demonstrated histological improvement compared to and restored by LDNP treatment. Importantly, the beneficial effects of
10/24 (41.7%) PBO-treated patients, a difference of 16.7% ( p = 0.248). LDNP were eliminated in intestinal FxrΔIEC and Fgf15−/− mice.
Regression models did not identify significant improvement of CAN- Conclusion: Our results demonstrate that increased intestinal
therapy on prognostic scores of liver function such as Lille model or miR194 suppresses Fxr expression resulting in a defective FXR-
MELD. Four of the 55 AAH patients (7.3%) in the intention-to-treat FGF15 gut-liver signaling in ALD. LDNP treatment inhibits alcohol-
analysis died within 90 days: 2 in each group. There were 20 vs 29 induced liver injury by suppressing intestinal miR194 and improving
serious adverse events occurring in 10 vs 10 patients (CAN vs PBO). BA profile that lead to an activated FXR-FGF15 signaling to suppress
There were no safety signals: of the 49 serious adverse events, 6 were BA de novo synthesis and lipogenesis during ALD development.
infectious complications of which 1/20 (5%) occurred in CAN-treated
and 5/29 (17%) occurred in PBO-treated patients. In exploratory OS036
analyses after adjustment for baseline prognostic factors, CAN Does screening for liver fibrosis change alcohol consumption,
therapy was associated with overall histological improvement ( p = diet, and exercise? A prospective cohort study on the
0.04), improvement in mononuclear cell infiltrate ( p = 0.06), and consequences of screening in 2, 764 individuals
reduction in serum AST ( p = 0.02). Maria Kjærgaard1,2, Katrine Prier Lindvig1,2, Johanne Kragh Hansen1,
Conclusion: CAN therapy in AAH demonstrated a good safety profile Simon Langkjær Sørensen1, Stine Johansen1,2, Katrine Thorhauge1,2,
but did not alter biochemical or clinical outcomes compared to PBO. Peter Andersen1, Isabel Graupera3, Pere Ginès3, Aleksander Krag1,2,
After adjustment for baseline prognostic factors, CAN was associated Maja Thiele1,2. 1Odense University Hospital, Department of
with histological improvements that did not translate into improved Gastroenterology and Hepatology, Odense, Denmark; 2University of
prognostic scores of liver function nor survival. Southern Denmark, Institute of Clinical Research, Odense, Denmark;
3
Hospital Clínic de Barcelona, Institut D’investigacions Biomédiques
August Pi I Sunyer (IDIBAPS), Barcelona, Spain
Outcome Canakinumab Placebo P Email: [email protected]
Histological Improvement (%) 58.3 41.7 0.25 Background and aims: There is a growing interest in screening for
Lille response (% Lille score<0.45) 22.2 25.0 0.8 liver fibrosis, and a belief that early disease detection will lead to
Day 28 median MELD change −5.07 −6.50 0.14 lifestyle changes in screening-positive individuals. However, this
Day 28 median GAHS change −2 −2 0.69 assumption is not based in evidence. We therefore evaluated self-
SAEs (n) 20 29 - reported lifestyle changes after screening for liver fibrosis.
Infection SAEs (n) 1 5 0.38
Method: Prospective study of participants from the general popula-
tion at risk of alcohol related (ALD) or non-alcoholic fatty liver disease
(NAFLD). All were screened with transient elastography (TE) and all
OS035 participants, independently on TE, were given information on
Probiotic LGG-derived exosome-like nanoparticles inhibit ALD recommended lifestyle changes. We considered TE ≥8 kPa as screen-
through intestinal FXR activation in mice: role of miR194 and bile ing positive. All participants received an online questionnaire on
acids lifestyle changes one week and six months after the screening visit.
Wenke Feng1, Mengwei Jiang1, Fengyuan Li1, Craig J. McClain1, Results: We included 2, 764 participants, 1, 273 at risk of ALD and 1,
Lihua Zhang1, Jiyeon Lee1. 1University of Louisville, Medicine, Louisville, 491 at risk of NAFLD. Median age was 58 years (52–64), 54% were
United States male, and 268 (10%) had an elevated TE ≥8 kPa. Response rate was
Email: [email protected] high, at 89% after one week and 85% after six months. After one week,
half of the ALD group (50%) reported abstinence, or a decrease in
Background and aims: Patients with alcohol-associated liver disease alcohol consumption, while only 0.8% reported an increase in alcohol
(ALD) often exhibit excessive bile acid (BA) accumulation and consumption. Screening sustained its effect on alcohol consumption
steatosis. Farnesoid X receptor (FXR)-fibroblast growth factor 15/19 after six months (figure), with a reported median alcohol intake
(FGF15/19) signaling plays a critical role in hepatic lipid and BA decreasing 8 units/week in the ALD group. Screening-positive
metabolism. In this study, we aimed to investigate whether alcohol subjects disclosed more pronounced reductions in alcohol intake
exposure reduced BA-mediated intestinal FXR activation and than screening negatives (decreased 13 vs 6 units/week), and a
increased intestinal miR194 expression that suppressed Fxr mRNA positive screening test predicted alcohol abstinence (odds ratio 2.9,
expression, and whether Lactobacillus rhamnosus GG-derived 95% CI 1.8–4.7). We observed the same pattern for diet and exercise:
exosome-like nanoparticles (LDNPs) attenuated ALD through regu- After one week, 26% of all respondents reported that they consumed
lation of intestinal miR194-FXR-FGF15 signaling in mice. less food and/or more healthy food, increasing to 34% after six
Method: C57BL/6, global Fgf15 knockout (Fgf15−/−), and intestinal months. This was most pronounced in the at-risk of NAFLD group
epithelial cell-specific Fxr knockout (FxrΔIEC) mice were administered (Figure), where a positive screening test predicted improved diet (OR
the NIAAA binge-on-chronic model alcohol exposure protocol. 1.8, 1.3–2.4). Both groups reported comparable improvements in
Probiotic strain Lactobacillus rhamnosus GG was cultured and LDNPs exercise (figure). In the NAFLD group, 23% reported a weight loss
were isolated from the culture supernatant. exceeding 3 kg after six months, and a positive screening test
Results: Alcohol feeding increased intestinal miR194 expression, predicted a weight loss above 3 kg (OR 3.5, 1.2–10.5).
which suppressed intestine Fxr and subsequently Fgf15 expression,
resulting in a reduced circulation FGF15 protein level. Gut microbiota-
mediated BA transformation was dysregulated by alcohol leading to
the decreased ligand-mediated FXR activation. Reduced FXR-FGF15
signaling resulted in an increase in hepatic BA synthesis and
lipogenesis and liver injury. Importantly, three-day oral administra-
tion of LDNPs suppressed hepatic BA synthesis and lipogenesis and
protected the liver from alcohol-induced injury. We further showed
that LDNP treatment decreased intestinal miR194 and increased FXR-
FGF15 signaling. miR194 suppressing intestinal Fxr mRNA expression
was further confirmed in in Caco-2 cells and mouse enteroid. miR194
mimic decreased, and miR194 inhibitor increased, Fxr mRNA Figure: Lifestyle changes after 6 months.
expression. Fecal and serum FXR activity was decreased by alcohol

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ORAL PRESENTATIONS
Conclusion: After being screened for liver fibrosis, participants injured liver. Elevation of these cytokines is an indicator for higher
report improved lifestyle, with both acute and sustained changes in recruitment of pro-healing and anti-HCC macrophage to the site of
alcohol consumption, diet, exercise, and weight loss. The changes are injury.
most pronounced in participants with elevated liver stiffness, but not Conclusion: Our findings demonstrate that PXDN deficiency is
limited to this. associated with the induction of the hypoxia and TNFα signaling
pathways and the recruitment of pro-healing and anti-HCC macro-
phages to the liver. This results in significantly decreased collagen
stabilization during liver fibrosis and accelerates fibrosis reversal. In
addition, recruited macrophages-controlled T cell response and
Fibrosis inhibited HCC formation in Pxdn−/− mice.

OS038
OS037 Targeting the liver circadian clock by REV-ERB-alpha activation
Peroxidasin deficiency re-programs macrophages toward pro- improves liver fibrosis by circadian gating of TGF-beta signaling
fibrolysis function and promotes collagen resolution in liver Mayssa Dachraoui1, Frank Jühling1, Natascha Roehlen1,
Mozhdeh Sojoodi1, Derek J. Erstad1, Stephen Barrett1, Shadi Salloum2, Emilie Crouchet1, Romain Martin1, Nicolas Brignon1, Laurent Mailly1,
Shijia Zhu3, Tongqi Qian3, Eric Gale4, Veronica Clavijo Jordan4, Antonio Saviano1, Sarah Durand1, Catherine Schuster1,
Yongtao Wang1, Shen Li1, Michael Lanuti1, Peter Caravan4, Emanuele Felli2, Patrick Pessaux2, Joachim Lupberger1,
Yujin Hoshida3, Raymond Chung2, Gautam Bhave5, Georg Lauer2, Atish Mukherji1, Thomas Baumert3. 1Université de Strasbourg, Inserm,
Bryan C. Fuchs1, Kenneth K. Tanabe1. 1Massachusetts General Hospital, Institut de Recherche sur les Maladies Virales et Hépatiques Inserm,
Surgery, Boston, United States; 2Massachusetts General Hospital, UMR_S1110, Strasbourg, France; 2Université de Strasbourg, Inserm,
Gastroenterology, Boston, United States; 3University of Texas Institut de Recherche sur les Maladies Virales et Hépatiques Inserm,
Southwestern Medical Center, Internal Medicine, United States; UMR_S1110, Institut Hospitalo-Universitaire, Pôle Hépato-digestif,
4
Massachusetts General Hospital, Radiology, Boston, United States; Nouvel Hôpital Civil, Strasbourg, Strasbourg, France; 3Université de
5
Vanderbilt University Medical Center, Division of Nephrology and Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et
Hypertension, United States Hépatiques Inserm, UMR_S1110, Institut Hospitalo-Universitaire, Pôle
Email: [email protected] Hépato-digestif, Nouvel Hôpital Civil, Strasbourg, and Institut
Background and aims: Non-alcoholic liver disease (NAFLD) is Universitaire de France, Paris, Strasbourg, France
stimulated by excessive fat deposition in hepatocytes. During Email: [email protected]
NAFLD, inflammation and activation of tissue repair mechanisms Background and aims: Liver fibrosis is the key risk factor for
replaces necrotic tissue with extracellular matrix (ECM), which are hepatocellular carcinoma, a leading cause of cancer death world-
stabilized into a complex fibrotic scar and creates fibrosis. Peroxidasin wide. Approved anti-fibrotic therapies are absent and most com-
(PXDN) is a peroxidase enzyme that is known to stabilize ECM pounds in clinical development have limited anti-fibrotic efficacy.
proteins through cross-linking of collagen molecules. In this project, The circadian clock (CC) is a major regulator of liver metabolism, but
we aim to investigate the expression and function of PXDN during the its role in the pathogenesis of liver fibrosis and as a potential
development of liver fibrosis. therapeutic target is unknown.
Method: Pxdn−/− and Pxdn+/+ mice were fed with a choline-deficient Method: We utilized liver specific CC-mutant mice to establish the
L-amino acid-defined high-fat diet (CDAHFD) for 16 weeks to create a molecular relationship between the CC-oscillator and TGF-beta
NAFLD-HCC preclinical model. Liver histology, collagen content, flow signaling under physiological conditions. Moreover, we profiled the
cytometry, immunostaining of immune cells, RNA-seq, and liver circadian gene expression pattern in patient-derived models for
function tests were analyzed. In vivo imaging of liver reactive oxygen NASH and fibrotic liver disease including primary human hepato-
species (ROS) was performed using a redox-active iron complex, Fe- cytes, human myofibroblasts, spheroids and a human liver chimeric
PyC3A. mouse model for diet-induced fibrotic liver disease. Furthermore, we
Results: Genome-wide expression analysis of liver tissue and performed functional studies using small molecules targeting CC
differential gene expression (DGE) combined with Gene Ontology components.
(GO) analysis identified significant upregulation of genes associated Results: Here we show that the physiological liver CC-oscillator is
with hypoxia and TNFα signaling pathways already in Pxdn−/− sham temporally restricting (gating) TGF-beta signaling and that this
livers (without injury). Using Fe-PyC3A as an MRI contrast agent, we regulation is lost in metabolic liver disease progressing to fibrosis. The
detected a higher content of ROS in Pxdn−/− livers (healthy) that could loss of TGF-beta signaling regulation leads to constitutive expression
activate hypoxia-related molecular pathways. In addition, we of genes driving fibrosis in patients. Mechanistic studies in primary
observed an upregulation of genes involved in the innate immune human hepatocytes and myofibroblasts revealed a reciprocal rela-
response, leukocyte activation, and chemotaxis. After 16 weeks of tionship between increased TGF-beta-driven fibrotic-signaling and
CDAHFD, gross analysis of collected liver showed no HCC nodule the CC, which we confirmed in patient-derived liver spheroids and in
formation in Pxdn−/− mice while 60% of the WT mice had HCC tumors. two mouse models for NASH-driven fibrosis. Remarkably, a pharma-
Collagen staining showed less collagen accumulation in Pxdn−/− mice. cological restoration of REV-ERB-alpha activity markedly inhibited
Flow cytometry of macrophages showed Pxdn−/− mice had increased fibrosis in a human liver chimeric NASH mouse model in vivo and
pro-healing M2 macrophages recruitment in early- and mid-stage spheroids generated from patients with liver fibrosis.
NAFLD (4 weeks and 8 weeks on CDAHFD) compared to WT controls. Conclusion: We discovered that the perturbation of the liver CC plays
In addition, we observed a significant decrease in the number of CD3+ a key role in the pathogenesis of liver fibrosis. Furthermore, our in
T cells and CD8+ cytotoxic T cells in the late-stage of NAFLD in Pxdn KO vivo and ex vivo studies in patient-derived models suggest that
mice. DGE analysis revealed that IL-12 is highly expressed in Pxdn−/− targeting REV-ERB-alpha is an effective approach for treatment of
injured livers. Additionally, multiple other T cell-related molecules liver fibrosis-an important and rising global unmet medical need.
such as IL-10, IL-6, CCL2, IL-7, and CD4 were elevated in Pxdn−/−

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 ORAL PRESENTATIONS
OS039 OS040
The proteomic analysis of hepatic stellate cell differentiation from Stellate cell dynamics in progression and regression of hepatic
iPSCs identifies RORalpha as an antifibrogenic target fibrosis
Raquel A. Martinez Garcia de la Torre1, Julia Vallverdú1, Laura Almale del Barrio1, Emma A.H. Scott1, Frederik Adam Bjerre1,
Silvia Ariño Mons1, Beatriz Aguilar-Bravo1, Mikel Azkargorta2, Mike Terkelsen1,2, Kim Ravnskjaer1,2. 1University of Southern Denmark,
Felix Elortza2, Laura Zanatto1, Paula Cantallops Vilà1, Juanjo Lozano3, Department of Biochemistry and Molecular Biology, Odense, Denmark;
Benedicte Antoine4, Isabel Graupera3,5,6, Pere Ginès3,5,6,7, 2
University of Southern Denmark, Center for Functional Genomics and
Pau Sancho-Bru1,3,7. 1Institut d’Investigacions Biomed̀ iques August Pi i Tissue Plasticity (ATLAS), Odense, Denmark
Sunyer (IDIBAPS), Liver Cell Plasticity and Tissue Repair Group, Email: [email protected]
Barcelona, Spain; 2CIC bioGUNE-Centro de Investigación Cooperativa en
Background and aims: Non-alcoholic steatohepatitis (NASH) is a
Biociencias, Proteomics Platform, Derio, Spain; 3Centro de Investigación
metabolic liver disease characterized by hepatic lipid accumulation,
Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd),
chronic inflammation and fibrosis, in which fibrogenic myofibro-
Barcelona, Spain; 4Sorbonne Université, INSERM, Paris, France; 5Hospital
blasts are central players. These scar-forming cells are derived mainly
Clínic de Barcelona, Chronic Liver Diseases Group, Barcelona, Spain;
6 ̀ iques August Pi i Sunyer (IDIBAPS), from activated hepatic stellate cells (HSCs). NASH and cirrhosis were
Institut d’Investigacions Biomed
traditionally considered irreversible conditions, but clinical studies
Barcelona, Spain; 7Universitat de Barcelona, Barcelona, Spain
have demonstrated that they can be reversed. HSC inactivation seems
Email: [email protected]
to be a key mechanism, but the inactivation process is poorly
Background and aims: Understanding the embryonic development understood. This prompted us to characterize HSC dynamics at
of Hepatic stellate cells (HSCs) and their activation is fundamental to single-cell resolution during the induction and regression of NASH-
develop new therapeutic strategies. We developed a protocol to associated fibrosis in vivo.
differentiate iPSCs to HSCs by sequential addition of growth factors. Method: Lrat-cre/mCherry knock-in mice were fed a western diet
We hypothesis that the differentiation protocol may be an excellent (WD) combined with carbon tetrachloride (CCl4) for eight weeks
tool for drug discovery. By performing a time course proteomic (treated) or chow diet (untreated). Regression of liver disease was
characterization, we envision to understand the protein dynamics studied four weeks after WD/CCl4 cessation (reversal). RNA-sequen-
across differentiation and identify transcription factors involved in cing, single-cell RNA-sequencing and immunohistochemistry/
the maintenance HSC phenotype and cell activation. immunofluorescence were performed to investigate HSC activation
Method: MS proteomics was performed in 4 independent differ- and inactivation.
entiations of iPSC to HSCs and primary human HSCs. Seven staggerer Results: NASH regression led to profound changes at histological,
mice (RORA−/−) and their wildtype littermates were treated with whole-liver transcriptional, and single-cell levels. We annotated 14
CCl4 during 4 weeks. Fourteen mice were treated with CCl4 and 7 discrete hepatic populations including activated and quiescent HSCs
were treated with the RORA agonist SR1078. qPCR, immunofluores- in our single-cell data set obtained from treated, reversal, and
cence and immunohistochemistry assays were used as validation. untreated mice. We next performed gene expression distribution
RORA expression was evaluated in a cohort of 25 patients with analyses of cells within and across treatment groups to stratify the
alcohol and metabolic associated chronic liver disease. HSC population. We here identified HSC subpopulations relating to
Results: Proteomic results indicated that iPSC-HSC differentiation NASH regression; potentially inactivated HSCs and HSCs that had
occurred in three stages: undifferentiated phase (Day 0 to 4), reverted towards a more quiescent state. Additionally, using single-
intermediate fetal stage (Day 6 to 8) and final maturation stage cell gene regulatory network analysis we determined specific gene-
(Day 10 to 12). Developmental markers of fetal HSC, such as VIM, regulatory networks for the aforementioned HSC subpopulations.
ALCAM, FBLN1 and DCN were sequentially expressed and followed by Conclusion: Our results broaden our understanding of HSC transi-
mature HSC markers, indicating the recapitulation of the embryonic tions in the liver during induction and regression of NASH, and
development in vitro. Pathway analysis of iPSC-HSCs and primary suggest new molecular mechanisms that could mediate the HSC
HSCs revealed RORA as an important transcription factor in HSC inactivation and reversion during NASH resolution.
phenotype and commitment. Experimentally, we first evaluated the
effect of RORA on HSC development. iPSC-HSC across differentiation OS041
were treated with SR1078, which increased the expression of HSC Machine learning methods for detailed characterization of TGF-
phenotype and quiescence markers such as RELN, PCDH7, LRAT and beta-induced signatures in a large iPSC-derived hepatic stellate
LHX2. Next, we evaluated the role of RORA on HSC activation by cell cohort
treating iPSC-HSCs, which decreased the expression of ACTA2 and Panagiotis Stanitsas1, Kara Marie Liu1, Lorn Kategaya1, Kelly Haston1,
increased the expression of quiescent markers (LRAT and LHX2). In Alicia Lee1, Shahin Mohammadi1, Haoyang Zheng1,
vivo studies with the staggerer mice, showed an increased fibrotic Francesco Paolo Casale1, Navpreet Ranu1, Ahmed Sandakli1,
content by Sirius Red staining and an increased gene expression of Pooja Prasad1, Owen Chen1, Anne Baldwin1, Albert Kim1,
fibrogenic markers such as ACTA2, collagens and MMPs in the mutant Eilon Sharon1, Ajamete Kaykas1, Daphne Koller1, Matthew Albert1.
1
group. In addition, SR1078 treatment of CCl4 mice showed a Insitro, South San Fransisco, United States
reduction of collagen deposition and aSMA staining, together with Email: [email protected]
a reduced expression of fibrogenic markers. In patients, expression of
Background and aims: Activation of hepatic stellate cells (HSCs) by
RORA correlated negatively with fibrogenic markers and MELD Score.
TGF-beta plays a central role in fibrotic changes related to Non-
These results suggest that RORA plays a role in the progression of liver
Alcoholic Steatohepatitis (NASH). We aimed to establish a screenable
fibrosis.
in vitro system for identification of anti-fibrotic targets in activated
Conclusion: The present study demonstrates that the differentiation
HSCs. This required the development of a novel machine learning
protocol is a new and reliable tool for the study of HSC biology and the
(ML) framework which was used to characterize a large cohort of
discovery of new antifibrogenic targets. Moreover, we identify RORA
control and NASH induced pluripotent stem cell-derived HSCs
as a targetable transcription factor to mitigate liver fibrosis.
(iHSCs).
Method: We differentiated iHSCs from 56 iPSC lines and character-
ized them using high content imaging and single cell (sc) RNA-seq
analysis. For ML image analysis, we derived a novel deep learning
method that was tasked with producing informative featurizations of
segmented cell images, followed by covariate correction.

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S37

ORAL PRESENTATIONS
Transcriptomic datasets were featurized using a state-of-the-art system. Surprisingly, it is also commonly associated with increased
archetypal analysis based framework. Using each of our transcrip- risk of fibrosis, cirrhosis and liver cancer. The Receptor for Advanced
tomic and imaging datasets separately, and viewing pHSCs as ground Glycation End Products (RAGE, encoded by Ager) was identified as a
truth, we quantified three quality metrics for iHSCs: (i) predictiveness critical mediator of DR during chronic injury and carcinogenesis
of TGF-beta response in an ML classifier trained on pHSCs; (ii) (Pusterla et al. Hepatology. 2013.). Nevertheless, whether DR is
separation between TGF-beta and DMSO in an unsupervised ML reparative or detrimental to the liver during cholestasis remains
model; (iii) similarity of the overall cell state distribution between elusive. Thus, we aimed to delineate the specific function of RAGE on
iHSCs and pHSCs. DR and its potential association with fibrosis in the context of
Results: The established ML framework provided informative cholestasis.
featurizations of our cellular assays and allowed for the correction Method: We utilized a biliary tracing reporter murine model
of experimental artifacts. We showed robustness of TGF-beta- (R26TomHnf1bCreER) and deleted Ager conditionally in BECs.
induced ML phenotype in pHSCs both in imaging and transcriptomics Choline-deficient ethionine-supplemented (CDE) diet was fed to
(mean AUC 0.96 for out-of-line assessment in imaging, Figure 1A; the mice for three weeks to induce cholestasis. RNA-seq of FACS-
mean AUC 0.98 in transcriptomics, data not shown). Interpretation of sorted primary BECs from CDE-challenged mice, immunofluores-
learned ML phenotypes revealed insights into the TGF-beta respon- cence (IF) staining and multi-modal 3D architectural staining were
siveness of pHSCs. This allowed us to utilize multi-parametric criteria employed to investigate the role of BEC-specific RAGE activity in DR
to evaluate the cohort of iHSCs. We observed a strong correlation and fibrosis. In vitro co-culture assays of BECs and hepatic stellate cells
between transcriptomic and imaging characterizations used for the (HSCs) combined with flow cytometry and mass spectrometry
ranking of iHSC lines (spearman = 0.66, p = 8.7 * 10−5, Figure 1B). analysis were utilized to delineate the newly identified RAGE-
dependent paracrine crosstalk between BECs and HSCs.
Results: BEC-specific deletion of Ager strongly impairs ductular
reaction. Remarkably, the number of stellate cell is substantially
diminished concomitantly with an attenuation of bridging fibrosis.
RNA-seq data revealed a RAGE-dependent mechanistic role of BECs in
the modulation of cholestasis-induced fibrosis. Classical fibrotic
mediators and ECM genes were differentially expressed between
Ager wildtype and knockout BECs. Flow cytometry of direct co-
culture assay demonstrated that HSCs were activated by BECs in
RAGE-dependent manner. Mass spectrometry and indirect co-culture
analysis, combined with immunohistochemistry analyses of livers
from CDE-treated mice showed that BEC-derived secretory JAG
protein activates Notch signalling in HSC in trans.
Conclusion: This present study provides a novel insight into the
adverse consequence of DR in cholestasis-associated fibrosis.
Although hypothesized to provide a regenerative mechanism
during cholestasis, it is evident that BEC-specific RAGE activity
Conclusion: We developed a state-of-the-art approach for the
enhances DR- associated fibrosis via a trans-regulatory mechanism in
characterization of HSC morphological and transcriptional pheno-
the current CDE diet model. We demonstrate that Notch signaling in
types. Using the developed framework, we successfully modeled
HSCs is activated by BEC in RAGE-dependent manner via paracrine
TGF-beta-induced activation signatures in HSCs. These image-based
JAG protein, thereby turning HSCs into a myofibroblastic phenotype
phenotypic assays paired with high-performance ML models present
to establish a profibrotic milieu.
unique opportunities for genetic and chemical screens and the
discovery of novel fibrosis targets.

OS042
Biliary epithelial cell-specific RAGE controls ductular reaction-
mediated fibrosis during cholestasis
Wai Ling Macrina Lam1,2, Amruta Damle-Vartak1, Gisela Gabernet3,
Doris Schneller1, Tanja Poth4, Simone Jörs5, Melanie Sator-Schmitt1,
Aurora De Ponti1, Lena Weiß1, Mathias Heikenwälder6,
Nachiket Vartak7, Jan G. Hengstler7, Fabian Geisler5, Sven Nahnsen3,
Peter Angel1. 1German Cancer Research Center, Division of Signal
Transduction and Growth Control, Heidelberg, Germany; 2Ruprecht Karl
University of Heidelberg, Faculty of Biosciences, Heidelberg, Germany;
3
Eberhard Karls University of Tübingen, Quantitative Biology Center,
Tübingen, Germany; 4University Hospital Heidelberg, Center for Model
System and Comparative Pathology, Heidelberg, Germany; 5Technical
University of Munich, Clinic and Polyclinic for Internal Medicine II,
Germany; 6German Cancer Research Center, Division of Chronic
Inflammation and Cancer, Heidelberg, Germany; 7Leibniz Research
Centre for Working Environment and Human Factors at the Technical
University Dortmund (IfADo), Systems Toxicology, Germany
Email: [email protected]
Background and aims: Ductular reaction (DR) is the hallmark of
cholestatic diseases characterized by the proliferation of bile ductules
lined by biliary epithelial cells (BECs). DR is thought to serve as a
reparative and regenerative mechanism in the damaged liver to
compensate for the anatomical or functional loss of the biliary

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 ORAL PRESENTATIONS
Friday 24 June OS044
Non-alcoholic fatty liver disease patients have worse health-
related quality of life compared to the general population
irrespective of their fibrosis stage: results from a prospective
multicenter UK study
NAFLD: Clinical aspects except therapy Margarita Papatheodoridi1, Giada Pallini1, Guruprasad Aithal2,
Hong Kai Lim3, Jeremy Cobbold4, Maria Corina Plaz Torres1,
Marta Guerrero Misas1, John Ryan1, Jeremy Tomlinson4,
OS043
Michael Allison3, Louise Longworth5, Emmanuel Tsochatzis1.
Young-onset diabetes mellitus increases the risk of liver-related 1
University College of London, Royal Free Hospital, Institute for Liver and
events in patients with non-alcoholic fatty liver disease
Digestive Health, United Kingdom; 2Nottingham University, Digestive
Xinrong Zhang1, Grace Lai-Hung Wong1, Terry Cheuk-Fung Yip1, Diseases Centre, United Kingdom; 3Cambridge University Hospital NHS
Yee-Kit Tse1, Vicki Wing-Ki Hui1, Huapeng Lin1, Che To Lai1, Foundation Trust, Liver Unit, Department of Medicine, NIHR Cambridge
Henry LY Chan1, Alice Pik-Shan Kong1, Vincent Wai-Sun Wong1. 1The Biomedical Research Centre, Cambridge, United Kingdom; 4Oxford
Chinese University of Hong Kong University Hospitals NHS Foundation Trust, Oxford Liver Unit,
Email: [email protected] Department of Gastroenterology and Hepatology, Oxford, United
Background and aims: The prevalence of type 2 diabetes (T2D) in Kingdom; 5PHMR Limited, United Kingdom
young people is increasing, but little is known regarding the Email: [email protected]
association between age of onset of T2D and risk of liver-related Background and aims: Health-related quality of life (HRQL) is
events. This study aimed to determine the incidence of liver-related impaired in patients with chronic liver disease, including those with
events of patients of different ages of onset of T2D. non-alcoholic fatty liver disease (NAFLD). The primary aim of the
Method: We conducted a retrospective territory-wide cohort study study was to assess the HRQL of patients with NAFLD and compare
of adult patients with non-alcoholic fatty liver disease (NAFLD) this to the general population. Secondary aims were to examine the
diagnosed between January 1, 2000 and June 30, 2021. T2D was associations of fibrosis severity and metabolic comorbidities with
defined by exposure to any antidiabetic agents, haemoglobin A1c impairments in HRQL.
≥6.5%, fasting plasma glucose ≥7.0 mmol/L in two measurements at Method: We included 561 consecutive patients with NAFLD
least one month apart, and/or ICD-9-CM diagnosis codes. The prospectively evaluated in 4 UK secondary care centres between
primary end point was liver-related events, defined as a composite 2016 and 2019. Patients completed two HRQL questionnaires: the EQ-
end point of HCC and cirrhotic complications. Fine-Gray model was 5D-5L and the Chronic Liver Disease Questionnaire (CLDQ).
used to adjust for competing risk of death. Demographic and clinical information, liver stiffness by transient
Results: We analysed data from 30, 360 NAFLD patients (mean age, elastography and/or liver biopsy results and history of cirrhosis were
56.4 ± 13.4 years; 46.0% men); a total of 15, 430 cases of T2D and 456 recorded. A general population sub-cohort of the Health Survey of
cases of liver-related events were recorded over a follow-up of 151, England 2018 without alcohol misuse who had completed the EQ-
051 person-years. Starting the follow-up at age 60 years, liver-related 5D-5L was used as a comparator. For the comparison of HRQL in
event rates per 1, 000 person-years were 1.05 in patients without T2D NAFLD patients and the general population, propensity-score (PS)
at age 60 years, 2.90 for patients with T2D onset ≤5 years earlier, 2.77 matching was performed, according to age, sex and body mass index
for 6 to 10 years earlier, and 4.26 for >10 years earlier. In multivariable (BMI).
analysis adjusting for gender, hypertension, dyslipidaemia, cirrhosis, Results: The EQ-5D-5L index was significantly lower in 514 NAFLD
use of metformin, insulin and aspirin, compared with patients patients compared to the 514 PS-matched healthy controls (0.762 ±
without T2D at age 60, the adjusted hazard ratio of liver-related 0.276 vs 0.844 ± 0.200, p < 0.001). The difference was also significant
events was 2.58 (95% confidence interval [CI], 1.49–4.45; p < 0.001) in in a subgroup of NAFLD patients without advanced fibrosis (F < 3 or LS
patients with T2D onset ≤5 years earlier, 2.70 (95% CI, 1.45–5.03; p = <8 kPa) compared to the general population (0.781 ± 0.276 vs 0.845 ±
0.002) for T2D 6 to 10 years earlier, and 5.00 (95% CI, 2.35–10.60; p < 0.200, p < 0.001). Among NAFLD patients, the EQ-5D-5L index, EQ-
0.001) for diabetes onset >10 years earlier (Figure). Linear trend test visual analogue scale (VAS) and CLDQ scores were significantly lower
( p < 0.001) indicated a graded association between age of onset of in patients with cirrhosis compared to patients without cirrhosis ( p =
T2D and risk of liver-related events. 0.021, p = 0.011 and p = 0.001 respectively). However, in patients with
Conclusion: Younger-onset T2D increases the risk of liver-related NASH, there was no difference between patients with and without
events. Further studies should determine the role of fibrosis advanced fibrosis on any of the HRQL measures.
assessment and more aggressive treatment of steatohepatitis in this Liver stiffness was the only factor significantly associated with lower
high-risk group. scores in all HRQL measures, both in the whole patient population
and in non-cirrhotic patients.
In multivariate analysis, the EQ-5D-5L index was negatively asso-
ciated with type II diabetes, depression and osteoarthritis both in the
whole patient population and in patients without cirrhosis. EQ-VAS
was associated with age, sex, BMI, depression and osteoarthritis in all
patients and non-cirrhotic patients.
Lower CLDQ scores were associated with lower age, male sex,
presence of type II diabetes, ischemic heart disease, depression and
osteoarthritis in all patients; in the sub-group of non-cirrhotic
patients, lower CLDQ was associated with male sex, type II diabetes
and depression.
Conclusion: HRQL is similar for NASH patients with or without
advanced fibrosis. However, even those without advanced fibrosis (LS
Figure: Association between age of onset of T2D and risk of liver-related <8 kPa or F < 3) have worse HRQL compared to the general
events (reference group was patients who did not have T2D at the corre- population, implying that a multi-disciplinary management is
sponding ages). required for NAFLD patients, irrespectively of their disease severity.

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S39

ORAL PRESENTATIONS
OS045 Results: We confirmed four previously identified liver fat variants
Genetics of liver fat and volume associate with altered TM6SF2 rs8107974, TM6SF2 rs188247550, APOE rs429358 and PNPLA3
metabolism and whole body magnetic resonance imaging rs738408. A positive and highly specific relationship was observed
Shafqat Ahmad1, Germán Carrasquilla2, Taro Langner3, Uwe Menzel3, between liver fat-associated variants and fat fraction in liver area
Filip Malmberg3, Ulf Hammar3, Jenny C. Censin4, Sergi Sayols3, (PNPLA3 rs738408 Figure 1). The liver fat-increasing allele of all four
Diem Nguyen3, Andrés Martínez Mora3, Jan W. Eriksson3, genetic variants were positively associated with alanine aminotrans-
Robin Strand3, Joel Kullberg3, Håkan Ahlström3, Tove Fall3. 1Uppsala ferase, conjugated bilirubin while negatively associated with total
University, Medical Sciences, Uppsala, Sweden; 2The University of cholesterol, triglycerides and low-density lipoprotein cholesterol
Copenhagen, Faculty of Health and Medical Sciences, København, biomarkers. For liver volume, we identified two novel independent
Denmark; 3Uppsala University, Uppsala, Sweden; 4University of Oxford, variants CENPW rs1490384, ADH4 rs6858148 and confirm eight
United Kingdom previously identified variants SFN rs75460349, GCKR rs1260326,
Email: [email protected] TNFSF10 rs79287178, PPP1R3B rs4240624, REEP3 rs7896518, TNKS2
rs10881959, and PDIA3 rs139974673. We observed a heterogeneous
Background and aims: An improved understanding of the under- pattern for association with body composition and biomarkers, as for
lying biological mechanisms of genetic variation linked to liver fat CENPW rs1490384, with strong positive association with muscle
and volume is pivotal for translational and prevention efforts to tackle tissue volume in neck, abdomen, thigh and hip as well as heart and
liver disease. Here we aim to gain biological insight of liver fat and liver volume among both males and females (Figure 1). Two liver fat
volume loci using a novel image analysis approach allowing whole- and three liver volume-associated genetic variants were positively
body voxel-wise associations to tissue volume and fat content as well associated with non-alcoholic fatty liver disease and chronic liver
as a large set of other phenotypes. disease.
Method: Liver volume was measured from neck-to-knee water-fat Conclusion: We report two novel liver volume loci and provide
MRI images collected in UK Biobank cohort using a deep learning- specific association with voxel-based maps body composition
based segmentation approach. Liver proton density fat fraction architecture while confirming previously reported liver fat and
(PDFF) were readily available for 4, 613 subjects. Using deep volume genetic variants. Liver fat-associated variants were positively
regression on the above mentioned neck-to-knee MRI images, liver associated with liver injury markers and negatively associated with
PDFF was inferred for remaining subjects. We conducted a genome- dyslipidemia biomarkers.
wide association analysis (GWAS) of liver fat (n = 27, 243) and liver
volume (n = 24, 752) on non-related European participants of the UK
Biobank cohort. We further investigated the associated genetic loci in
association with whole body composition in high-resolution ana-
tomical correlation voxel-based maps (“Imiomics”). We also analyzed
these loci with various biomarkers and liver disease using independ-
ent UK Biobank participants (n = 310, 239).

Figure: (abstract: OS045)

S40 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS
OS046 Results: We included 4.093 elderly participants (aged 74.4 ± 6.6;
Hepatic steatosis is not associated with increased mortality in the 42.7% male, BMI 27.6 ± 4.2 kg/m2, 44.9% metabolic syndrome), 36.8%
elderly-time for a paradigm shift? had ultrasound-based steatosis and 7.1% had liver stiffness ≥8.0 kPa.
Laurens van Kleef1, Milan Sonneveld1, Maryam Kavousi2, During the median follow-up of 6.9 years, 793 participants died,
Arfan Ikram3, Robert De Man1, Robert De Knegt1. 1Erasmus MC, resulting in a mortality rate of 29.6 per 1.000 person-years. Among
University Medical Center, Gastroenterology and Hepatology, Rotterdam, the elderly, steatosis was not associated with impaired survival in
Netherlands; 2Erasmus MC, University Medical Center, Cardiology, multivariable analysis (aHR:0.87, 95%CI:0.73–1.03), similar results
Rotterdam, Netherlands; 3Erasmus MC, University Medical Center, were obtained for MAFLD and NAFLD. Furthermore, findings were
Epidemiology, Rotterdam, Netherlands consistent across a range of clinically relevant subgroups, including
Email: [email protected] age categories, sex, and in participants with metabolic syndrome,
elevated liver enzymes, or cardiac disease, as shown in Figure 1.
Background and aims: Fatty liver disease has been associated with
Sensitivity analyses showed similar results for mortality beyond five
excess mortality. Screening for hepatic steatosis in patients with years of follow-up and for both cancer-related and cerebro-
metabolic dysfunction is therefore widely advocated. However, the
cardiovascular mortality. Furthermore, among participants with
association between hepatic steatosis and mortality amongst steatosis, higher liver stiffness (aHR:1.02 per kPa, 95%CI:0.93–1.12)
community-dwelling elderly individuals is unclear.
was not associated with mortality.
Method: We studied participants of an ongoing prospective cohort:
Conclusion: The presence of fatty liver disease was not associated
the Rotterdam Study. Individuals aged ≥65 years were enrolled from with increased mortality risk in this cohort of community-dwelling
2009 to 2014 and were followed through 2018. Steatosis was assessed
elderly subjects. Findings were consistent across a range of clinically
by ultrasound, and liver stiffness by transient elastography. relevant subgroups. This indicates that screening for fatty liver
Subsequently, NAFLD was defined as steatosis in the absence of
disease is unlikely to improve outcomes in the elderly.
excessive alcohol consumption, viral hepatitis, or steatogenic drug
use; and MAFLD was defined as steatosis with either overweight, OS047
diabetes, or at least two minor metabolic dysfunction criteria. The Burden of hepatocellular cancer in patients with type-2 diabetes
association between steatosis and liver stiffness with mortality risk mellitus: a 2011–2020, french, longitudinal, retrospective,
was assessed using Cox regression analysis adjusted for age, sex, national, cohort study
education, smoking, the individual components of the metabolic Lucia Parlati1, Samir Bouam2, Michael Schwarzinger3,
syndrome, heart failure, coronary heart disease, and stroke. Emmanuel Tsochatzis4, Philippe Sogni5, Stanislas Pol5,
Vincent Mallet2,5. 1Institut Cochin, Paris, France; 2Assistance Publique
Hôpitaux de Paris, Paris, France; 3Inserm UMR 1219, Bordeaux, France;
4
UCL Institute for Liver and Digestive Health, Royal Free Hospital and
UCL, London, United Kingdom; 5Université de Paris, France, France
Email: [email protected]
Background and aims: There are uncertainties on the burden of
hepatocellular cancer (HCC) in patients with type-2 diabetes (T2D) in
France. We therefore measured national incidences and risks of in-
hospital HCC.
Method: The data source was the 2011–2020 National Hospital
Discharge database. We selected all T2D patients. HCC and competing
death incidences were measured overall and without well-identified
risk factors of liver disease progression, including alcoholic liver
disease. Risks were computed with multinomial logistic regression
models.
Results: The sample comprised 2, 883, 684 adults. Mean (IQR) age
was 67 (58, 77) years and 54% were men. HCC incidence (95% CI) was
1.19 (1.17–1.21) per 1000 person-years at risk, totaling 26, 136 (0.9%)
cases over 12, 504, 690 patient-years. A history of alcohol use
disorders and non-metabolic liver-related risk factors were recorded
among 55% and 21% of incident cases, respectively. In patients
without well-identified risk factors of liver disease progression, HCC
incidence was 0.57 (0.55–0.58) per 1000 person-years at risk. Male
sex, age in the 40–70 years category, alcohol use disorders [aOR 20.8
(20.0–21.5)], and obesity [aOR 1.24 (1.2–1.28)] were independently
associated with a higher risk of HCC than of competing mortality.
Conclusion: A history of alcohol use disorders was the main driver of
liver disease progression to HCC in French patients with T2D. Obesity
increased the risk of HCC by ∼25%. Patients with T2D should be
advised to abstain from alcohol.

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S41

ORAL PRESENTATIONS
with increased risk of any primary outcomes. In univariate analysis,
Table: Multivariate risks for HCC and competing mortality in 2011– advanced liver fibrosis identified via all scores was associated with
2020 French residents1 with T2D increased ACM (HR 2.34–2.90). NFS and FIB-4 were associated with
elevated risk of CVE (HR 2.49 [2.11–2.93], p < 0.0001 and 1.94 [1.53–
Hepatocellular carcinoma Competing mortality
Predictors 2.45], p < 0.0001) and ESRD (HR 6.85 [4.29–10.94], p < 0.0001 and
Age categories at P P 2.35 [1.19–4.67], p < 0.05). Following full adjustment FIB-4 was
cohort inception3 aOR2 Value aOR2 Value associated with increased incidence of CVE (HR 1.39 [1.06–1.82], p
(30, 40] 2.34 (1.25–4.38) 0.008 1.29 (1.17–1.43) <0.001 < 0.05), notably heart failure (HR 1.65 [1.16–2.33], p < 0.01); both FIB-
(40, 50] 6.29 (3.49–11.37) <0.001 2.12 (1.94–2.32) <0.001 4 and APRI were associated with ACM (HR 1.55 [1.21–2.00], p < 0.001
(50, 60] 12.69 (7.06–22.83) <0.001 4.33 (3.97–4.72) <0.001 and 2.83 [1.95–4.11], p < 0.0001) and NFS ≥−1.455 was associated
(60, 70] 20.02 (11.14–36.00) <0.001 7.98 (7.33–8.70) <0.001 with progression to ESRD (HR 1.89 [1.13–3.17], p < 0.05).
(70, 80] 23.47 (13.05–42.20) <0.001 18.14 (16.65–19.77) <0.001 Conclusion: In people with CKD and NAFLD, elevated non-invasive
(80, Inf] 17.41 (9.66–31.39) <0.001 37.66 (34.55–41.04) <0.001 markers of liver fibrosis are associated with an increased risk of CVE,
Male sex 3.22 (3.07–3.37) <0.001 1.38 (1.37–1.39) <0.001 ESRD and worse survival.
Alcohol use 20.76 (20.02–21.54) <0.001 1.72 (1.69–1.74) <0.001
disorders
Obesity 1.24 (1.20–1.28) <0.001 0.86 (0.86–0.87) <0.001
Non-liver-related 1.05 (1.01–1.10) 0.014 1.79 (1.78–1.80) <0.001
risk factors4 Viral hepatitis elimination
Smoking 0.71 (0.68–0.74) <0.001 1.48 (1.46–1.49) <0.001
1
T2D patients with alcoholic liver disease or non-metabolic liver-related risk
factors were excluded from the analysis. HCC cases were recorded after a 2011– OS049
2013 (3-year) washout period to reduce the risk of non-incident cases. Randomized controlled trial of home-based hepatitis C self-
2
Risks were computed with multinomial logistic regression models. testing for key populations in Malaysia
3
Reference was the [18, 30] age category. Xiaohui Sem1, Sonjelle Shilton1, Huan-Keat Chan2, Han Yang Chung3,
4
Non-liver risk factors were extrahepatic cancer; AIDS; connective tissue
disorders; ischemic heart disease; and stage 3–5 chronic kidney disease.
Anu Karunanithy4, Jessica Markby1, Po-Lin Chan5, Niklas Luhmann6,
Cheryl Johnson6, Pamela Nabeta1, Nazrila Hairizan Binti Nasir7,
Stefano Ongarello1, Elena Ivanova1, Muhammad Radzi Abu Hassan2.
OS048 1
FIND; 2Clinical Research Centre, Hospital Sultanah Bahiyah; 3Drugs for
The impact of non-alcoholic fatty liver disease and liver fibrosis Neglected Diseases Initiative South-East Asia Regional Office;
on adverse clinical outcomes and mortality in patients with 4
Malaysian AIDS Council; 5World Health Organization Regional Office
chronic kidney disease: a prospective study using UK Biobank for Western Pacific; 6World Health Organization, Global HIV, Hepatitis
data and STI Programmes; 7Ministry of Health
Theresa Hydes1, Oliver Kennedy2, Ryan Buchanan2, Email: [email protected]
Daniel Cuthbertson1, Julie Parkes2, Simon Fraser2, Paul Roderick2.
1
University of Liverpool, Department of Cardiovascular and Metabolic Background and aims: Malaysia is an upper middle-income country
Medicine, Liverpool, United Kingdom; 2University of Southampton, and has been expanding and decentralizing HCV care to the
School of Primary Care, Population Sciences and Medical Education, community. HCV self-testing (HCVST), recommended by the World
Southampton, United Kingdom Health Organization, provides an additional way to increase access
Email: [email protected] and uptake of HCV testing among key populations who are
disproportionately affected by HCV. We integrated HCVST with an
Background and aims: Chronic kidney disease (CKD) is a well- existing online HIV self-testing platform to assess the impact of
known extra-hepatic manifestation of non-alcoholic fatty liver home-based HCVST on the uptake of HCV testing among key
disease (NAFLD), independent of common cardio-metabolic risk populations nationwide.
factors, and the two diseases frequently co-exist. Systematic review Method: This is a randomized controlled trial comparing HCVST sent
data has shown that there is minimal and conflicting data regarding via post (intervention arm, n = 500) with standard of care testing at a
the clinical implications of living concomitantly with these two facility (control arm, n = 250). In the intervention arm, participants
conditions. We aimed to assess the impact of having of NAFLD and received either an oral fluid- or blood-based HCVST; in the control
NAFLD fibrosis on adverse clinical outcomes and all-cause mortality arm, participants were provided information about the nearest HCV
for people with CKD. testing center. All participants also received HCV information and
Method: Data from 26, 074 individuals from the UK Biobank support resources (e.g. access to a call center). We describe
identified to have CKD (eGFR <60 ml/min/1.73 m2 or albuminuria preliminary findings for this study reporting on the primary
>3 mg/mmol) was analysed. Participants completed questionnaires outcome-the uptake of HCV testing. Acceptability, feasibility and
relating to medical history, demographics and lifestyle factors and attitudes around HCV testing were also evaluated via a series of
were prospectively followed-up by electronic linkage to hospital and surveys.
death records. Cox-regression was used to estimate the hazard ratios Results: To date, 258 individuals, with a median (IQR) age of 26 (22–
(HR) associated with having NAFLD (hepatic steatosis index >36, or 30.75) years, were recruited, of whom 88.8% were MSM. Most
ICD-code) and advanced liver fibrosis (elevated fibrosis-4 (FIB-4) participants were male (97.6%), completed university (46.9%), and
score, or NAFLD fibrosis score (NFS) or AST to platelet ratio index were employed (61.4%). Prior to this study, 60.6% of the participants
(APRI)) on cardiovascular events (CVE), progression to end-stage were not tested for HCV; of these, the top reason why they did not get
renal disease (ESRD) and all-cause mortality (ACM). tested was they did not know how (57.1%). Additionally, acceptability
Results: Overall 54.5% of individuals with CKD had NAFLD at baseline, of HCVST was high-71.7% of the participants stated that they
and 7.0% (NFS ≥0.676), 3.2% (FIB-4 >2.67) and 1.1% (APRI ≥1.0) had preferred to test for HCV by themselves at home; 98.4% were
evidence of advanced fibrosis. Median follow-up was 10 years. In willing to test themselves at home if they had a test kit and
univariate analysis NAFLD was significantly associated with an instructions on how to do it. After either receiving a HCVST or
increased risk of CVE (HR 1.39 [1.29–1.51], p < 0.0001) and ACM (HR information about the nearest testing center, 99.0% (119/120) in the
1.10 [1.01–1.19]), but not ESRD (HR 1.22 [0.95–1.56], p > 0.05). intervention arm and 30.9% (13/42) in the control arm reported
Following multivariate adjustment for demographics, metabolic completing HCV testing ( p < 0.01) (see Figure).
factors and baseline renal function, NAFLD was no longer associated

S42 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS
Markov models that utilize country specific inputs to estimate the
natural history of the disease and future burden. Where data were
unavailable, regional averages were applied to the total population of
the country.
Results: 166 country level HBV and 110 HCV models were available.
At the current trends, the prevalence of HBV is expected to decrease
from 282 million in 2015 to 247 million in 2030, representing an 11%
decrease globally with Africa’s prevalence to remain relatively
constant. The incidence of chronic HBV is expected to decline by
43% from 1, 459, 000 to 827, 000 new cases per year with all
continents seeing a decline. Globally, the mortality of HBV is expected
to increase by 39% between 2015 and 2030 from 850, 300 to 1, 109,
500 deaths annually. Similarly, the incidence of HCC is expected to
increase by 34% from 682, 000 to 912, 000 cases per year. For both
indicators all continents are expected to increase in this time frame.
The prevalence of HCV is expected to decrease from 64 million in
2015 to 54 million in 2030, representing a 15% decrease globally. The
incidence of chronic HCV is expected to decline by 7% from 1, 521, 000
to 1, 409, 000 new cases per year with Asia and North America
increasing. Globally the mortality of HCV is expected to increase by
3% between 2015 and 2030 from 284, 000 to 293, 000 deaths
annually. The incidence of HCC is expected to increase by 9% from
202, 000 to 220, 000 cases per year. Increases are expected in Asia,
Oceania, and South America for both indicators.
Conclusion: Progress has been made particularly in regard to
prevalence and incidence. However, without additional interventions
almost 12 million individuals will die early from preventable deaths.
Early gains made by Egypt, high income countries, and other early
Conclusion: Preliminary results show that HCVST via an online adopters, for HCV elimination, are offset by raising disease burden in
distribution model, compared with standard testing services, the rest of the world. Innovative guidelines and funding mechanisms
significantly increased the uptake of HCV testing among key are necessary to meet countries where they are to live up to
populations. The outcomes of this study can further provide critical international commitments to elimination.
evidence about testing uptake, linkage to care, acceptability and any
social harm due to HCVST. Updated data will be presented at the OS051
conference. The HCV care cascade for children and young people in British
Columbia, Canada: a large, linked administrative population-
OS050 based cohort study
The disease burden of hepatitis B and hepatitis C from 2015 to Dahn Jeong1, Margo Pearce2, Amanda Yu2, Laura Sauvé3,4,
2030: the long and winding road Richard A. Schreiber3,4, Sofia Bartlett2,5,
Devin Razavi-Shearer1, Sarah Blach1, Ivane Gamkrelidze1, Chris Estes1, Muhammad Furqan Waleed6,7, Makuza Jean Damascene1,
Ellen Mooneyhan1, Kathryn Razavi-Shearer1, Homie Razavi1. 1Center Prince Adu1,2, Jane Buxton1,2, Hector Velasquez1,2, Mawuena Binka2,
for Disease Analysis Foundation, Lafayette, United States Chelsea Elwood8,9, David GoldFarb3,5, Hasina Samji2,10,
Email: [email protected] Stanley Wong2, Maria Alvarez2, Neora Pick8,11, Naveed Janjua1,2,7. 1The
Background and aims: This study aims to estimate the future disease University of British Columbia, School of Population and Public Health,
burden of HBV and HCV at the global and continental level through Vancouver, Canada; 2BC Centre for Disease Control, Vancouver, Canada;
3
2030. 2015 was used as a baseline in line with the WHO targets to BC Children’s Hospital, Vancouver, Canada; 4The University of British
show what progress has been made to date. Columbia, Department of Pediatrics, Vancouver, Canada; 5The University
Method: The results of a literature review and Delphi expert of British Columbia, Department of Pathology and Laboratory Medicine,
interviews were integrated into country-specific PRoGReSs and Vancouver, Canada; 6Youthco HIV and Hep C Society, Vancouver, Canada;
Bright Models for the HBV and HCV analyses respectively. Both are

Figure: (abstract: OS050)

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S43

ORAL PRESENTATIONS
7
The Canadian HIV Trials Network, Vancouver, Canada; 8BC Women’s OS052
Hospital, Vancouver, Canada; 9The University of British Columbia, Clinical impact and cost-effectiveness of hepatitis C testing in an
Department of Obstetrics and Gynaecology, Vancouver, Canada; 10Simon emergency department in Barcelona, Spain
Fraser University, Faculty of Health Sciences, Burnaby, Canada; 11The Jordi Llaneras1, Ana Barreira2,3, Ariadna Rando-Segura4,
University of British Columbia, Division of Infectious Diseases, Raquel Domínguez-Hernández5, Francisco Rodríguez-Frías3,4,
Vancouver, Canada Magda Campins6, Miguel Ángel Casado3,5, Mar Riveiro Barciela2,3,
Email: [email protected] Maria Arranz1, Rafael Esteban2,3, Maria Buti2,3. 1Hospital Vall Hebron,
Emergency Department, Barcelona, Spain; 2Hospital Vall Hebron, Liver
Background and aims: In high income countries, new hepatitis C
Unit, Barcelona, Spain; 3Centro de investigación biomédica en red de
virus (HCV) infections have been occurring at the highest rate among
people under 30 years of age, driven by the ongoing opioid crisis and enfermedades hepáticas y digestivas, Madrid, Spain; 4Hospital Vall
Hebron, Microbiology Department, Barcelona, Spain;
other co-occurring socioeconomic conditions. The clinical experi- 5
ences of young people living with HCV are underrepresented in Pharmacoeconomics and Outcomes Research Iberia (PORIB), Madrid,
Spain; 6Hospital Vall Hebron, Epidemiology Department, Barcelona,
research. We aimed to build the HCV care cascade for children and
Spain
young people under age 30 living with HCV in British Columbia (BC),
Canada. Email: [email protected]
Method: We used data from the BC Hepatitis Testers Cohort, a large Background and aims: In primary care centers in Spain the
population-based administrative dataset linked with data on primary prevalence of anti-HCV is approximately 0.8% and HCV-RNA positive
care visits, hospitalizations and medication dispensations. This study 0.22%. In the emergency department (ED) of our hospital, an HCV-
includes all BC residents under age 30 who have been diagnosed with RNA+ screening program was initiated with linkage to antiviral
HCV by the end of 2019. The HCV care cascade was defined as: 1) HCV treatment assessment, with the aim of increasing HCV detection and
antibody (Ab) diagnosed 2) ribonucleic acid (RNA) tested 3) RNA safeguarding the hospital from this infection. Results of the HCV
positive 4) genotyped 5) initiated treatment and 6) achieved screening strategy were analyzed and a cost-effectiveness evaluation
sustained virologic response (SVR). We estimated the number and performed.
proportion of people in each stage. Method: Prospective study conducted in a university hospital ED
Results: There were 1, 350 children and young people (aged 4 to 29) (FOCUS-A, hospital free of hepatitis C study). All individuals >16 years
diagnosed as HCV Ab positive living in BC at the end of 2019. Of these, of age attending the ED and requiring blood extraction underwent
82.2% (1, 110/1, 350) had received an RNA test, and 60.6% (673/1, 110) anti-HCV screening, HCV-RNA reflex testing, and FIB-4 calculation if
were RNA positive. Among those who were RNA positive, 79.9% (538/ anti-HCV+. Individuals with detectable viral load were linked to a
673) had their HCV genotyped; however, only 40.3% (217/538) specialist for HCV treatment evaluation. A Markov model was
initiated treatment. SVR was achieved by 87.7% (121/138) of developed to analyze the cost-effectiveness of opt-out HCV testing
individuals for whom data on SVR assessment was available. In using the data obtained and a National Health Care System
2019, the proportion of HCV RNA positive persons receiving perspective. Lifetime liver-related mortality, hepatic complications,
treatment varied by age group: 17.1% (6/35) in 14–19 years, 34.4% and associated costs were assessed.
(45/131) in 20–24 years, and 34.1% (164/481) in 25–29 years. Results: In total, 13, 479 individuals screened (February/20–
Treatment initiation increased over time, with the majority of September/21): 49% male, mean age 70 years. Anti-HCV detected in
treatments started between 2018 and 2019: 3.7% (8/217) treated 553 (4%) cases and HCV-RNA in 100 (0.7%). Risk factors associated
between 2009–2011, 7.8% (17/217) between 2012–2014, 25.8% (56/ with anti-HCV: 58 (10%) HIV co-infection, 98 (18%) injecting drug
217) between 2015–2017, and 62.7% (136/217) between 2018–2019. users, 128 (23%) abusive alcohol consumption, and 205 (37%)
Many young people living with HCV were socioeconomically diagnosed with a psychiatric disorder. Among viremic patients, 34%
marginalized, had other comorbidities, particularly mood and (n = 34) were unaware of HCV infection and 48% had an FIB-4 score
anxiety disorders, and were accessing harm reduction services such suggestive of cirrhosis (FIB-4 >3.25). Among HCV-RNA+ cases, 53
as opioid agonist therapy. (53%) were selected for treatment. Reasons for non-selection were
Conclusion: By the end of 2019, more than two-thirds of people short life expectancy or cognitive impairment (40 cases), and loss to
under age 30 in BC with chronic HCV remained untreated. The follow-up due to serious social problems (7 cases). Of the 53
approval of highly effective pangenotypic direct-acting antiviral candidates linked to a specialist, 27 have received treatment and
regimens provides the opportunity for early treatment for young the 14 who completed treatment have achieved a sustained
people. Identifying and addressing the barriers that young people virological response. This strategy reduced liver-related mortality
experience would be crucial to optimizing access to HCV care and by 56% and avoided 50%-67% of liver complications with a related cost
services in this population. saving of €247, 942.
Conclusion: The prevalence of chronic HCV among in adults in the ED
is almost four times higher than in primary care. Almost half the
viremic individuals had advanced fibrosis. Screening in the ED is a
cost-effective intervention. These findings are of value for informing
testing guidelines.

OS053
High Intensity Test and Treat (HITT): an overview of the initiative
as part of the hepatitis C elimination programme in England
Beatrice Emmanouil1, Sean Cox2, Rachel Halford2,
Georgia Threadgold1, Mark Gillyon-Powell1, Graham Foster1. 1NHS
England and NHS Improvement; 2Hepatitis C Trust, United Kingdom
Email: [email protected]
This abstract is under embargo until Thursday 23 June
Figure 1: The HCV care cascade for people under 30 years of age and 30
2022, 13:30 BST. This abstract has been selected to be
years and older in 2019, British Columbia Hepatitis Testers Cohort. highlighted during official EASL Press Office activities or
in official EASL Press Office materials that will be made
publicly available on the congress website at 13:30 (BST).
S44 Journal of Hepatology 2022 vol. 77(S1) | S1–S118
 ORAL PRESENTATIONS
Results: By excluding those who were unable to enter the program
such as deaths, aging, and mobility, the screening targets total 10, 684
people. The HCV antibody screening rate reached 93.4% (9, 978
people), with HCV antibody positive rate of 6.1% (608 people), HCV
RNA referral rate of 93.4% (568 people), HCV RNA virus checking rate
of 92.1% (523 people), detectable HCV RNA rate of 69.6% (364 people),
eligible treatment rate was 97.5% (355 people), and final treatment
rate was 92.1% (327 people). When compared with the situation
before intervention of program, the screening rate and treatment rate
have been significantly improved which achieve the goal of HCV
elimination. The risk of HCV infection is 1.27 (95%CI: 0.793–2.035),
1.64 (95%CI: 1.057–2.536), 1.90 (95%CI: 1.232–2.937), for patients of
50–59 years, 60–69 years, and over 70 years respectively when
compared with patients less than 50 years. Furthermore, the risk of
HCV infection is 0.43 (95%CI: 0.253–0.712, p = 0.0012) in patients of
senior high school; and 0.26 (95%CI: 0.108–0.624, p = 0.0026) in
patients of university when compared with patients of illiterate. HCV
risk is not associated with other factors such as gender, the duration
of diabetes, cigarette smoking, presence of chronic kidney, retinop-
athy, and foot disease at all. We further evaluated the heterogeneity
among townships by using the random effect model, and found that
the antibody positive rate was significantly different among town-
ships, but not different on the RNA positive rate and treatment rate.
Conclusion: A novel model was successfully implemented for HCV
elimination on diabetic population in the community of Changhua
county in Taiwan, by using a series of indicators for caring cascade.
This population-based service was provided to the 26 townships with
a homogenous quality.

OS054 Primary Liver Cancer: Experimental and

Hepatitis C elimination in diabetic population from a shared care pathophysiology
cascade cohort- under Changhua-Integrated Program to Stop
hepatitis C infection (CHIPS-C)
Tsung-Hui Hu1, Yo-Yu Tsao2, Wei-Wen Su3, Chi-Chao Yang4, OS055
Chi-Chieh Yang5, Sam Li-Sheng Chen6, Yen-Po Yeh7, Hsiu-Hsi Chen8. PMEPA1: an oncogene in hepatocellular carcinoma linked to TGF-
1
Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University beta signaling
College of Medicine, Kaohsiung, Taiwan, Kaohsiung, Taiwan; 2Changhua Carmen Andreu-Oller1,2, Marta Piqué-Gili2, Marina Barcena-Varela1,
County Public Health Bureau, Changhua, Taiwan, Changhu, Taiwan; Roser Pinyol2, Roger Esteban-Fabró1,2, Judit Peix2,
3
Changhua Christian Hospital, Changua, Taiwan, Changhu, Taiwan; Katherine E. Lindblad1, Miguel Torres-Martín2, Daniela Sia1,
4
Changhua Hospital, Ministry of Health and Welfare, Changhua, Taiwan; Amaia Lujambio1, Josep M. Llovet1,2,3,4. 1Icahn School of Medicine at
5
Show Chwan Memorial Hospital, Changhua, Taiwan, Changhu, Taiwan; Mount Sinai, Division of Liver Diseases, New York, United States; 2Institut
6
School of Oral Hygiene, College of Oral Medicine, Taipei Medical d’Investigacions Biomed̀ iques August Pi i Sunyer (IDIBAPS), Translational
University, Taipei, Taiwan; 7Changhua County Public Health Bureau, Research in Hepatic Oncology, Liver Unit, Barcelona, Spain; 3Universitat
Changhua, Taiwan; 8Graduate Institute of Epidemiology and Preventive de Barcelona, Barcelona, Spain; 4Institució Catalana de Recerca i Estudis
Medicine, College of Public Health, National Taiwan University, Taipei, Avançats (ICREA), Barcelona, Spain
Taiwan, Taipei, Taiwan Email: [email protected]
Email: [email protected]
Background and aims: Transforming growth factor beta (TGF-beta)
Background and aims: Several clinical studies have suggested an has a dual role in cancer, including hepatocellular carcinoma (HCC). It
association between chronic HCV infection and diabetes mellitus acts as a tumor suppressor in early stages of hepatocarcinogenesis,
(DM). HCV micro-elimination approach, which focuses treatment on but promotes epithelial-to-mesenchymal transition, angiogenesis
DM population was rarely reported. We aim to conduct HCV and immunosuppression in advanced stages. PMEPA1 ( prostate
elimination for population with diabetes mellitus in a county of transmembrane protein androgen induced 1), a direct target gene
Taiwan via 27 local health centers under Changhua-Integrated of the TGF-beta pathway that negatively regulates TGF-beta signaling
Program to Stop Hepatitis C Infection (CHIPS-C). by interacting with SMAD proteins, has been shown to promote TGF-
Method: Changhua County, has 26 townships and a total of 1, 289, beta oncogenic effects in other cancers. Here, we explored its role in
000 residents. In addition to hospitals and local clinics in the county, HCC pathogenesis.
there are 27 local health centers handled by the Changhua County Method: We analyzed transcriptomic, genomic, epigenomic and
Public Health Bureau of government. Taking the diabetic cases in the clinicopathological data of a discovery cohort of 228 HCCs and a
clinics of various township health centers from 2018 to 2020 as the validation cohort of 361 HCCs. PMEPA1 levels were quantified by
tracking generation, combined with the Changhua County Diabetes qPCR and IHC in the discovery cohort. PMEPA1 overexpression was
Common Care Network since 1996, HCV screening and treatment validated in 6 independent cohorts (n = 916) using microarray and
were implemented and evaluated. The achievement rate of HCV care RNAseq data. We evaluated PMEPA1 expression at the single-cell level
chain-related indicators, and the difference in HCV positive rate and using a publicly available scRNAseq dataset from 25 HCCs. Genetically
treatment rate under different influencing factors were analysed. engineered mouse models were generated through hydrodynamic

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S45

ORAL PRESENTATIONS
tail-vein injection. Equal amounts of plasmids overexpressing Institute, Cruces University Hospital, Barakaldo, Spain; 13Institute of
PMEPA1, TGFB1 and MYC were injected in mice to evaluate survival. Pathology, University of Regensburg, Regensburg, Spain; 14Department
Molecular and histopathological analyses of the murine tumors are of Internal Medicine, Yale Liver Center (YLC), School of Medicine, Yale
currently ongoing. University, New Haven, CT, United States; 15IKERBASQUE, Basque
Results: PMEPA1 was overexpressed in 18% of human HCCs [FC >2; n Foundation for Science, Bilbao, Spain; 16Faculty of Medicine and Nursing,
= 203/1144], a feature associated with TGF-beta signaling ( p < 0.001). University of the Basque Country (UPV/EHU), Leioa, Spain; 17Department
PMEPA1 was expressed by both malignant and tumor microenviron- of Biochemistry and Genetics, School of Sciences, University of Navarra,
ment (TME) cells including endothelial cells, cancer associated Pamplona, Spain
fibroblasts, T cells and B cells. Overexpression of PMEPA1 was Email: [email protected]
associated with gene body hypermethylation ( p < 0.0001). HCCs
Background and aims: Cholangiocarcinoma (CCA) comprises a
displaying both TGF-beta signaling and high PMEPA1 levels (11% of
heterogeneous group of malignant tumors with dismal prognosis.
cases) were significantly enriched in signatures of immune exhaus-
Alterations in post-translational modifications (PTMs), including
tion, late TGF-beta activation, TME response to TGF-beta and active
NEDDylation, result in abnormal protein dynamics, cell disturbances
stroma ( p < 0.05), compared to HCCs with TGF-beta signaling alone
and disease. Here, we investigate the role of NEDDylation in CCA
(8% of cases) or PMEPA1 high levels alone (11% of cases). In vivo,
development and progression.
overexpression of MYC+PMEPA1 led to HCC development in 9/16 mice
Method: Levels and function of NEDDylation, together with response
and showed a lower survival when compared to the control arm,
to Pevonedistat (NEDDylation inhibitor) or CRISPR/Cas9 against NAE1
overexpression of MYC alone, ( p = 0.014) (Figure). On the contrary,
were evaluated in vitro, in vivo and/or in patients with CCA.
only 1/12 mice in the MYC+PMEPA1+TGFB1 condition developed HCC
Development of preneoplastic lesions in Nae1± mice was investigated
and none of the MYC+TGFB1 mice.
using an oncogene-driven CCA model. The impact of NEDDylation in
CCA cells on tumor-stroma crosstalk was assessed using CCA-derived
cancer-associated fibroblasts (CAFs). Proteomic analyses were carried
out by mass spectrometry.
Results: NEDDylation machinery was found overexpressed and
overactivated in human CCA cells and tumors, correlating with poor
prognosis. Most NEDDylated proteins found upregulated in CCA cells,
after NEDD8-immunoprecipitation and further proteomics, partici-
pate in cell cycle, proliferation or survival. Genetic (CRISPR/Cas9-
NAE1) and pharmacological (pevonedistat) inhibition of NEDDylation
Conclusion: PMEPA1 upregulation is linked to TGF-beta activation reduced CCA cell proliferation and impeded colony formation in vitro.
and an aggressive phenotype in human HCC. Overexpression of NEDDylation depletion ( pevonedistat or Nae1± mice) halted tumori-
PMEPA1 in combination with MYC in vivo led to HCC development, genesis in subcutaneous, orthotopic, and oncogene-driven models of
showing for the first time the oncogenic role of PMEPA1 in this cancer. CCA in vivo. Moreover, pevonedistat potentiated chemotherapy-
induced cell death in CCA cells in vitro. Mechanistically, impaired
OS056
NEDDylation triggered the accumulation of cullin RING ligase or
Targeting NAE1-mediated protein hyper-NEDDylation halts
NEDD8 substrates, inducing DNA damage and cell cycle arrest.
cholangiocarcinogenesis and impacts on tumour-stroma
Furthermore, NEDDylation impairment in CCA cells reduced the
crosstalk in experimental models
secretion of proteins involved in fibroblast activation, angiogenesis,
Paula Olaizola1, Pui-Yuen Lee-Law1,2, Maite G. Fernandez-Barrena3,4,5,
and oncogenic pathways, ultimately hampering CAF proliferation and
Laura Alvarez3, Massimiliano Cadamuro6, Mikel Azkargorta5,7,
migration.
Colm O. Rourke8, Francisco J. Caballero1, Rocio IR Macias5,9,
Conclusion: aberrant protein NEDDylation contributes to cholangio-
Jose Marin5,9, Marina Serrano-Macia10,
carcinogenesis by promoting cell survival and proliferation.
María Luz Martínez-Chantar5,10, Matías A. Avila3,4,5,
Moreover, NEDDylation impacts the CCA-stroma crosstalk.
Patricia Aspichueta5,11,12, Diego Calvisi13, Luca Fabris6,14,
Inhibition of NEDDylation with pevonedistat may represent a
Felix Elortza5,7, Jesper Andersen8, Luis Bujanda1,5,
potential therapeutic strategy for patients with CCA.
Pedro Miguel Rodrigues1,5,15, María Jesús Perugorria1,5,16,
Jesus Maria Banales1,5,15,17. 1Department of Liver and Gastrointestinal OS057
Diseases, Biodonostia Health Research Institute-Donostia University Induction of branching morphogenesis in cholangiocarcinoma
Hospital-, University of the Basque Country (UPV/EHU), San Sebastian, organoids in vitro improves similarity with the original tumour
Spain; 2Department of Gastroenterology and Hepatology, Radboud
Gilles van Tienderen1, Kathryn Monfils1, Floris Roos1,
University Nijmegen Medical Center, Nijmegen, Netherlands;
3 Luc J.W. van der Laan1, Monique M.A. Verstegen1. 1ErasmusMC
Hepatology Program, CIMA, University of Navarra, Pamplona, Spain;
4 Transplant Institute, Department of Surgery, Rotterdam, Netherlands
Instituto de Investigaciones Sanitarias de Navarra (IdiSNA), Pamplona,
Email: [email protected]
Spain; 5National Institute for the Study of the Liver and Gastrointestinal
Diseases (CIBERehd, “Instituto de Salud Carlos III”), Spain; 6Department Background and aims: Cholangiocarcinoma (CCA) is an aggressive,
of Molecular Medicine (DMM), University of Padua, Padua, Italy; heterogeneous cancer with low survival rates. Patient-derived
7
Proteomics Platform, CIC bioGUNE, CIBERehd, ProteoRed-ISCIII, Bizkaia cholangiocarcinoma organoids (CCAOs) hold potential for under-
Science and Technology Park, Derio, Spain; 8Department of Health and standing disease progression and developing novel treatment
Medical Sciences, Biotech Research and Innovation Centre (BRIC), options, based on their ability to mimic the original tumor.
University of Copenhagen, Copenhagen, Denmark; 9Experimental Currently, most organoid expansion protocols focus on stimulation
Hepatology and Drug Testing (HEVEPHARM) Group, Institute of of the canonical WNT/β-catenin pathway, however there is growing
Biomedical Research of Salamanca (IBSAL), University of Salamanca, evidence showing that non-canonical WNT pathways also play a
Salamanca, Spain; 10Liver Disease Laboratory, CIC bioGUNE, Basque crucial role in cancer progression. This project aims to establish a
Research and Technology Alliance (BRTA), Spain; 11Department of novel in vitro model for CCA, better recapitulating the in vivo tumor,
Physiology, Faculty of Medicine and Nursing, University of the Basque by stimulating both canonical and non-canonical WNT pathways.
Country (UPV/EHU), Leioa, Spain; 12Biocruces Bizkaia Health Research Method: Branching cholangiocarcinoma organoids (BRCCAOs) (n = 3
patients) were established with a two-step protocol. First, CCAOs
were initiated and cultured under standard conditions in canonical

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 ORAL PRESENTATIONS
WNT stimulating expansion medium. Next, expansion medium was MerTK expression in Kupffer cells, lipid macrophages, TREM2+
replaced by medium that stimulates canonical WNT-signaling macrophages, and non-classical monocytes.
(through R-spondin) and non-canonical WNT-signaling (with Conclusion: These data suggest a cross-talk between MerTK-
Dickkopf-related protein 1) simultaneously, after which a branch- expressing cells in the stroma and CCA cells, to induce increased
ing-like morphology could be observed. Tumor cell behavior in malignant features.
BRCCAOs and CCAOs was assessed and compared through immuno-
histochemical stainings, bulk RNA-sequencing, and drug response OS059
studies. Mixed HCC-CCA originates from hepatic progenitor cells, is
Results: BRCCAOs presented a distinct branching morphology, dependent on IL6 singling and is ablated by senolytic agents
displaying a morphological architecture similar to in vivo tumors, Nofar Rosenberg1, Matthias Van Haele2, Maria Garcia Beccaria3,
while maintaining tumorigenic potential and expression of cytoker- Mirian Fernández-Vaquero3, Danijela Heide3, Neta Barashi1,
atin-7, with an accompanying lack of defined cellular polarity. Bulk Amnon Peled1, Yuval Nevo4, Shrona Elgavish4, Dirk Schmist-Arras5,
RNA-sequencing of BRCCAOs showed significant upregulation of Hanan Edler1, Alina Simerzin1, Michal Shoshkes-Carmel6,
cancer-associated molecular pathways, including hypoxia, compared Klaus Kaestner6, Hilla Giladi1, Stefan Rose-John5, Tania Roskams2,
to CCAOs and a close correlation (coefficient 0.80 ± 0.05) to the Mathias Heikenwälder3, Eithan Galun1. 1The Goldyne Savad Institute of
transcriptome of the original tumor tissue. BRCCAOs also exhibited a Gene and Cell Therapy, Hadassah Hebrew University, Jerusalem, Israel;
2
strong resistant phenotype to a large panel of 166 anti-cancer drugs, University of Leuven, Department of Translational Cell and Tissue
including multiple drugs that have previously failed in clinical trials Research, Leuven, Belgium; 3DKFZ, Department of Traslational Cell and
for CCA patients (e.g. docetaxel, palbociclib, and irinotecan). Tissue Research, Germany; 4Hebrew University of Jerusalem, Hadassah
Specifically, compared to CCAOs, BRCCAOs showed an approximately Medical School, Bioinformatics Unit, Israel; 5Christian-Albrechts-
10.000-fold ( p < 0.0001) increase in chemo resistance against Universität zu Kiel, Institut für Biochemie, kiel, Germany; 6University of
gemcitabine and cisplatin, first-line chemotherapy drugs for CCA, Pennsylvania Perelman School of Medicine, Penn Center for Molecular
independent of patient variance. Studies in Digestive and Liver Diseases, Philadelphia, United States
Conclusion: These results demonstrate that BRCCAOs better resem- Email: [email protected]
ble in vivo CCA tumor tissue compared to conventional CCAOs,
Background and aims: Primary liver cancer is the 3rd leading cause
particularly with regards to morphology, transcriptome, and drug
of cancer-related death worldwide. Primary liver cancers include:
responses. Gemcitabine and cisplatin combinational therapy only
Hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma
provides CCA patients with a modest benefit in overall survival, and
(CCA) and Mixed HCC-CCA tumors. Chronic liver inflammation,
BRCCAOs appear to mimic this response more closely, thus providing
which develops to cirrhosis, is a risk for the development of primary
possibilities for personalized medicine applications.
liver cancer. It has been suggested that hepatic progenitor cells (HPCs)
OS058 could contribute to hepatocarcinogenesis. However, this has not yet
Cross-talk between MerTK-expressing stromal cells and been proven. HPCs proliferate in response to injury and chronic
cholangiocarcinoma inflammation. In this study, we aimed to determine whether HPCs
contribute to HCC, Mixed HCC-CCA or both types of tumors, in the
Mirella Pastore1, Öykü Gönül Geyik1,2, Jesper Andersen3,
MDR2 KO mouse model of inflammation-induced cancer.
Monika Lewinska3, Ana Lleo4, Paolo Kunderfranco4, Chiara Raggi1,
Method: In order to enable tracing of progenitor cells, we generated a
Fabio Marra1. 1University of Florence, Firenze, Italy; 2Istinye University,
transgenic mouse based on the MDR2 KO that harbours a YFP
Turkey; 3Copenhagen University, København, Denmark; 4Humanitas
reporter gene driven by the Foxl1 promoter. Foxl1 is expressed
University, Italy
specifically in adult HPCs. These mice (MDR2 KOFoxl1CRE; RosaYFP)
Email: [email protected]
develop chronic inflammation by the age of 1 month and develop
Background and aims: A typical feature of cholangiocarcinoma HCCs by the age of 14–16 months, followed by mixed HCC-CCA
(CCA) is a dense stromal reaction populated by fibrogenic myofibro- tumors at the age of 18 months, as we have first observed, suggesting
blasts and immune cells, creating a complex tumor microenviron- that the aged mice are a suitable model for mixed HCC-CCA tumors.
ment where malignant cells survive and proliferate. Cancer stem cells Results: In this model, we show that liver progenitor cells are the
(CSCs) have been proposed as a driving force of tumor initiation, source of mixed HCC-CCA tumors, but they are not the source of HCC
dissemination and drug-resistance in many solid tumors, including in the chronically inflamed liver. By generating mice with a
cholangiocarcinoma (CCA). Increasing evidence indicates that Diphtheria toxin (DT) receptor in HPCs and administering DT, we
myeloid-epithelial-reproductive tyrosine kinase (MerTK) is highly ablated the progenitors, and we observed a significant reduction in
expressed by a macrophage subset defined as M2c. The present study the development of mixed HCC-CCA tumors but no change in HCCs.
aims to investigate whether signals generated by MerTK-expressing RNA-seq analysis revealed enrichment of the IL6 signaling pathway in
macrophages modulate the biology of CCA. mixed HCC-CCA tumors in comparison to HCC tumors. A single cell
Method: 3D-tumor sphere cultures enriched in CSC were generated RNA-seq analysis revealed that in the liver, IL6 is expressed from both,
from intrahepatic CCA cell lines (HuCCT-1 and CCLP-1). Circulating immune cells and parenchymal cells which are in senescence, and
monocytes were differentiated into M2c macrophages in vitro. that IL6 is part of the senescence-associated secretory phenotype
Recombinant Gas-6, a MerTK ligand, was used to activate this receptor. (SASP). Upon administration of anti-IL6 antibodies to the MDR2
MERTK mRNA expression in human CCA tissues was also analyzed. KOFoxl1CRE; RosaYFP mice, we inhibited the development of the mixed
Results: In CCA cell lines cultured with conditioned medium from HCC-CCA tumors. Furthermore, by blocking IL6 transsignaling with
Gas-6-stimulated M2c macrophages, cell survival, invasion, sphere- sgp130, we also decreased mixed HCC-CCA tumors, indicating that
forming efficiency and drug resistance were significantly increased. mixed HCC-CCA tumors are dependent on IL6 transsignaling. The
These effects were reduced following macrophage pre-treatment administration of a senolytic agent to these mice, also inhibited the
with the MerTK inhibitor, UNC2025. Analysis of the transcriptome of development of mixed HCC-CCA tumors.
laser-captured, micro-dissected epithelium and stroma from 23 CCA Conclusion: Our results suggest that mixed HCC-CCA but not HCC
patients showed that MerTK mRNA expression is significantly higher tumors, originate from HPCs in the inflammation induced liver cancer
in intratumoral stroma. Single-cell RNA sequencing of CD45+ sorted model, and that the driver of this process involves the IL6 signalling
cells from paired non-tumoral and tumoral specimens from iCCA pathway that at least in part, derives from SASP of cells in senescence.
patients (n = 6) defined eleven clusters characterized by their gene These findings could enhance the development of new therapeutic
expression profiles. A further reclustering of myeloid cells showed approaches for mixed HCC-CCA liver cancer.

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S47

ORAL PRESENTATIONS
OS060 mitochondrial dynamics and Warburg effect-mediated lactic acid-
MAP17 promotes metastasis in hepatocellular carcinoma by osis, which support a tumour microenvironment conducive to cancer
modulating the epithelial-mesenchymal-amoeboid transition cell proliferation. ROS generation was increased as a protective
Claudia Gil-Pitarch1,2,3, Esther Bertran4,5, Iker Uriarte6,7, mechanism to avoid apoptotic and senescence processes. Rewiring in
Natalia Hermán-Sánchez8, José Manuel García-Heredia5,9,10, the one-carbon metabolic pathway was also identified, proving an
Naroa Goikoetxea1,2,3, Marina Serrano-Macia1,2,3, accelerated metabolism of the cell. Accordingly, overexpression of
Rubén Rodríguez Agudo1,2,3, Sofia Lachiondo-Ortega1,2,3, MAP17 in PLC/PRF/5 cells in the orthotopic model led to the
Maria Mercado-Gómez1,2,3, Miriam Rábano2,11, formation of multiple tumour foci in the liver.
Teresa Cardoso Delgado1,2,3, Jorge Simón Espinosa1,2,3, MAP17 silencing in hepatoma mesenchymal cells provided the
Luis Alfonso Martinez-Cruz1,2, Cesar Augusto Martín12, opposite results, regressing the tumour phenotype and slowing
Maria Vivanco2,11, Matías A. Avila6,7,13, Manuel Gahete Ortiz8,14,15,16, down the cell metabolism and proliferation.
Isabel Fabregat4,17,18, Amancio Carnero10,19, Conclusion: Modulation of MAP17 in epithelial and mesenchymal
María Luz Martínez-Chantar1,2,17. 1CIC bioGUNE, Liver disease lab, cells leads to the reprogramming of the transitional genes that define
Derio, Spain; 2Basque Research and Technology Alliance (BRTA), each phenotype. Our findings have identified the metastatic potential
Mendaro, Spain; 3Centro de Investigación Biomédica en Red de of MAP17 in liver cancer, as it triggers the mesenchymal phenotype
Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Spain; and amoeboid behaviour in HCC.
4
Bellvitge Biomedical Research Institute (IDIBELL), CIBER Enfermedades
hepáticas y digestivas (CIBERehd), Hospitalet de Llobregat, Spain;
5
Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain; 6CIMA,
University of Navarra, Pamplona, Spain; 7CIBERehd, Instituto de Salud Cirrhosis and its complications: ACLF and
Carlos III, Madrid, Spain; 8Maimonides Institute for Biomedical Research
of Cordoba (IMIBIC), Córdoba, Spain; 9Universidad de Sevilla, Critical illness
Departamento de bioquímica vegetal y biología molecular, facultad de
biología, Sevilla, Spain; 10Grupo CIBER de Cáncer, Sevilla, Spain; 11CIC
bioGUNE, Basque Research and Technology Alliance, Cancer OS061
Heterogeneity Lab, Derio, Spain; 12UPV/EHU, CSIC, Department of Liver transplantation within 7-days of listing improves survival in
Molecular Biophysics, Biofisika Institute and Department of ACLF-3
Biochemistry and Molecular Biology, Leioa, Spain; 13IdiSNA, Navarra Joseph Alukal1, Feng Li1, Paul J. Thuluvath1. 1Institute of Digestive
Institute for Health Research, Pamplona, Spain; 14University of Córdoba, Health and Liver Disease, Gastroenterology, Baltimore, United States
Department of Cell Biology, Physiology and Immunology, Córdoba, Email: [email protected]
Spain; 15Reina Sofía University Hospital, Córdoba, Spain; 16CIBER Background and aims: ACLF-3 is associated with a very high short-
Pathophysiology of Obesity and Nutrition (CIBERobn), Córdoba, Spain; term mortality without liver transplantation (LT). The timing of LT,
17
CIBER Enfermedades hepáticas y digestivas (CIBERehd), Spain; therefore, may be critical for optimal outcomes. The objective of our
18
University of Barcelona, Department of Physiological Sciences II, study was to determine if early LT (<7 days from listing), stratified by
Barcelona, Spain; 19Instituto de Biomedicina de Sevilla (IBIS), Hospital the number of organ failures (OF), had an impact on 90-day and 1-
Universitario Virgen del Rocío, Universidad de Sevilla, Consejo Superior year survival in ACLF-3 patients.
de Investigaciones Científicas, Sevilla, Spain Method: United network for organ sharing (UNOS) database was
Email: [email protected] queried to identify adults (>18 years) with ACLF-3 who underwent LT
Background and aims: Epithelial-mesenchymal transition (EMT), a between 2005–2021. We excluded those listed with status 1, 1A, or
key process during embryonic development, promotes cell migration 1B, multi-organ transplant, living donor transplant and HCC. ACLF
and resistance to apoptosis during tumour invasion and metastasis. patients were identified using EASL-CLIF criteria. Unadjusted Kaplan-
In hepatocellular carcinoma (HCC) an amoeboid behaviour tends to Meier (KM) survival curves were used to evaluate patient survival.
increase the aggressiveness and metastatic capacity of epithelial The Cox proportional hazards (CPH) regression model was used to
tumours. evaluate the risk factors for survival
MAP17 is a 17 kDa membrane protein expressed during embryogen- Results: We identified 3, 498 patients with ACLF-3 who underwent
esis, absent in most adult organs. The presence of MAP17 correlates early LT while 1, 485 had transplant >7 days from listing. 90-day and
with an inflammatory environment, hypoxia and increased reactive 1-year survival in ACLF-3 patients who underwent early LT were 92%
oxygen species (ROS). MAP17 has been identified in several types of and 87% respectively. KM survival analysis showed that those who
cancer, including HCC. Modulation of EMT and amoeboid behaviour were transplanted early (≤7 days) had significantly better 90-day and
via MAP17 offers an attractive approach to prevent metastasis. 1-year survival than who underwent late LT (>7 days) (Figure A and
Method: Two separated HCC patient cohorts were used to charac- Figure B). This survival benefit was seen across all sub-groups of
terise MAP17 levels. In vitro, expression of MAP17 was measured in ACLF-3 including those with 5 and 6 OF (Figure C and Figure D). On
mesenchymal and epithelial hepatoma cells, and its levels were multivariable analysis, age (Hazard Ratio [HR]1.02), body mass index
modulated to study its implication in cell proliferation, drug (HR 1.01), donor risk index >1.7 (HR 1.3), respiratory failure (HR1.9),
resistance, mitochondrial dynamics, metabolic rewiring, and prote- and etiology of cirrhosis were independent predictors of higher 90-
ome homeostasis. In vivo, the role of MAP17 in the metastatic capacity day post-transplant mortality. Similarly, age (HR1.01), donor risk
was evaluated using orthotopic HCC mice models. index >1.7 (HR1.3), diabetes (HR1.3), respiratory failure (HR 1.7) and
Results: A positive correlation of MAP17 and mesenchymal markers etiology of cirrhosis were independent predictors of higher 1-year
was established in 751 HCC patients in silico study and by mRNA mortality while higher albumin (HR 0.87) was associated with a
expression in 246 HCC patients. Additionally, MAP17 appeared reduced mortality.
statistically associated with RAC/RHO family genes, markers of
amoeboid movement, in the same patient cohort. MAP17 over-
expression in 3D epithelial cell experiments let to the formation of
rosette invadopodia, proinvasive structures with high metastatic
capacity.
MAP17 overexpression in vitro produced a reprogramming of energy
metabolism in hepatoma cells with epithelial phenotype, increasing

S48 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS

Sixty-two patients with HRS-AKI were treated with terlipressin and

albumin. Among them, patients with uNGAL ≥220 ng/ml had a
significantly lower rate of response to terlipressin and albumin (33 vs
70%; p = 0.015; Fig. C). After adjusting for serum creatinine, uNGAL
Conclusion: Early LT (≤7 days from listing) in ACLF-3 after listing is
≥220 ng/ml was independently associated with a higher risk of non-
associated with a better 90-day and 1-year survival than those who
response (aOR = 4.55, 95% CI = 1.28–16.67; p = 0.02).
were transplanted late (>7 days). This survival benefit was seen even
In multivariable analysis (adjusted for age, MELD, ACLF, leukocytes
in those with 5 and 6 OF.
and type of AKI) uNGAL was an independent predictor of in-hospital
OS062 mortality (aOR = 1.74 [95% CI = 1.26–2.38]; p = 0.001) and 90-day
Neutrophil gelatinase-associated lipocalin predicts response to mortality (aHR = 1.32 [95% CI = 1.13–1.55]; p = 0.001). Probability of
terlipressin and albumin in patients with hepatorenal syndrome survival was significantly lower in patients with uNGAL ≥220 ng/ml
(57% vs 30%; p < 0.001; Fig. D).
Carmine Gabriele Gambino1, Matteo Stenico1, Marta Tonon1,
Conclusion: uNGAL is an excellent biomarker for the differential
Alessandra Brocca1, Valeria Calvino1, Simone Incicco1, Chiara Cosma2,
diagnosis of AKI in cirrhosis, it predicts response to treatment with
Martina Zaninotto2, Patrizia Burra3, Umberto Cillo4, Mario Plebani2,
terlipressin and albumin in patients with HRS-AKI and is an
Paolo Angeli1, Salvatore Piano1. 1Unit of Internal Medicine and
independent predictor of mortality.
Hepatology, Department of Medicine, University of Padova, Padova, Italy,
Padova, Italy; 2Laboratory Medicine Unit, Department of Medicine, OS063
University of Padova, Padova, Italy; 3Multivisceral Transplant Unit, CLEARED Global consortium results highlight regional variation
Department of Surgery, Oncology and Gastroenterology, University of and need for equity in inpatient outcomes in hospitalized patients
Padova, Padova, Italy; 4Hepatobiliary Surgery and Liver Transplantation, with Chronic Liver Disease
Department of Surgery, Oncology and Gastroenterology, University of
Jasmohan S. Bajaj1, Patrick S. Kamath2, Florence Wong3, Peter Hayes4,
Padova, Padova, Italy
Ramazan Idilman5, Aldo Torre6, Mark Topazian2, Jacob George7,
Email: [email protected]
Mario Reis Álvares-da-Silva8, Qing Xie9, Shiv Kumar Sarin10,
Background and aims: Acute Kidney Injury (AKI) commonly occurs Abha Nagral11, Ajay Haveri11, Sumeet Asrani12,
in patients with decompensated cirrhosis. Neutrophil Gelatinase- Mohammad Amin Fallahzadeh13, Somaya Albhaisi14,
associated Lipocalin (NGAL) is a novel urinary biomarker that could Rajender Reddy15, Suditi Rahematpura16, Marie Jeanne Lohoues17,
help in discriminating between different etiologies of AKI. The aim of Belimi Hibat Allah18, Ricardo Cabello19, Ruveena Bhavani20,
this study was to investigate the ability of urinary NGAL (uNGAL) in: Nik MA Nik Arsyad21, Sombat Treeprasertsuk22,
(1) the differential diagnosis of AKI, (2) predicting the response to Salisa Wejnaruemarn23, Jose Luis Perez Hernandez24,
treatment with terlipressin and albumin in patients with Hepatorenal Godolfino Miranda Zazueta25, Neil Rajoriya26, Rosemary Faulkes27,
Syndrome (HRS)-AKI and (3) predicting in-hospital and 90-day Danielle Adebayo28, James Kennedy29, Abdullah Emre Yıldırım30,
mortality. Sezgin Barutcu31, CE Eapen32, Ashish Goel33, Ajay Kumar Duseja34,
Method: We included cirrhotic patients with AKI not solved within Anoop Saraya35, Jatin Yegurla35, Akash Gandotra36, Mohd. Rela37,
48 hours, who were consecutively admitted from 2015 to 2020 at the Dinesh Jothimani38, Anand Kulkarni39, Mithun Sharma39,
University Hospital of Padova. uNGAL and standard urinary biomar- Amey Sonavane40, Hugo E. Vargas41, David Bayne42,
kers were measured. Data on the type of AKI, AKI treatment, Ramazan Idilman5, Feyza Gunduz43, Rahmi Aslan44, Anil Arora45,
resolution of AKI were collected during the hospitalization and Ashish Kumar46, Andrew Keaveny47, Paul J. Thuluvath48,
patients were followed up until transplant, death or 90 days. Somya Sheshadri49, Dalia Allam50, Yashwi Haresh Kumar Patwa50,
Results: We enrolled 162 patients (mean age: 62 ± 10 years, male: Mauricio Castillo51, Hiang Keat Tan52, Liou Wei Lun53, Jawaid Shaw54,
77%; alcoholic etiology: 48%; mean MELD: 25 ± 8). Thirty-five Edith Okeke55, David Nyam P55, Diana Yung56, Scott Biggins57,
patients (22%) had hypovolemic AKI, 64 (39%) HRS-AKI, 27 (17%) Natalia Filipek58, Andres Duarte Rojo59, Carlos Benitez60,
acute tubular necrosis (ATN)-AKI and 36 (22%) a mixed form. uNGAL Sebastián Marciano61, Hailemichael Desalegn62, Henok Fisseha62,
values were significantly higher in patients with ATN-AKI than in Helena Katchman63, Liane Rabinowich63, René Malé Velazquez64,
patients with other types of AKI (1162 [423–2105] vs 109 [52–192] Lilian Torres Made64, Maria Sarai González-Huezo65,
ng/ml; p < 0.001; Fig. A). uNGAL showed a high discrimination ability Aloysious Aravinthan66, Suresh Vasan Venkatachalapathy67,
in predicting ATN-AKI (AUROC = 0.854; [95% CI = 0.767–0.941]; p < Damien Leith68, Ewan Forrest69, Zeki Karasu70, Dominik Bettinger71,
0.001; Fig. B) and the best threshold was 220 ng/ml (sensitivity 89%; Michael Schultheiss71, Zhujun Cao72, Brian Bush73, Leroy Thacker74.
specificity 78%).

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S49

ORAL PRESENTATIONS
1
Virginia Commonwealth University and McGuire VA Medical Center; perspective. Aim to evaluate determinants of inpatient mortality
2
Mayo Clinic; 3University of Toronto; 4Royal Infirmary of Edinburgh; and organ dysfunction in a multi-center worldwide study.
5
Gastroenterology, Ankara University School of Medicine; 6Instituto Method: We prospectively enrolled pts with CLD/Cirrhosis >18 years
Nacional De Ciencias Médicas y Nutrición Salvador Zubirán; 7The without organ transplant or COVID-19 who were admitted non-
University of Sydney; 8Hospital de Clínicas de Porto Alegre; 9Ruijin electively. To maintain equity in outcome analysis, a maximum of 50
Hospital, Shanghai Jiaotong University School of Medicine; pts/site were allowed. Data for admission variables, hospital course,
10
Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India; and inpatient outcomes (ICU, death, organ dysfunction [ODF]) were
11
Jaslok Hospital, Mumbai, India; 12Aylor Simmons Transplant Institute, recorded. This was analyzed for death and ODs using significant
Baylor University Medical Center, Baylor Scott & White All Saints variables on admission and including World Bank classification of
Medical Center; 13Baylor Dallas (Baylor University Medical Center); low/middle-income countries (LMIC). A model for in-hospital
14
Virginia Commonwealth University; 15Medicine, University of mortality for all variables during the hospital course, including
Pennsylvania; 16GI/Hepatology, University of Pennsylvania;; 17CHU De ODs) was analyzed.
Cocody; 18Mustapha University Hospital; 19University of Pittsburgh; Results: 1383 pts (55 ± 13 yrs, 64% men, 39% White, 30% Asian, 10%
20
University of Malaysia, Kuala Lumpur, Malaysia; 21University of Hispanic, 9% Black, 12% other) were enrolled from 49 centers (Fig A).
Malaya Medical Centre, Malaysia; 22Chulalongkorn University; 39% were from high-income while the rest were from LMICs.
23
Hepatology, King Chulalongkorn Memorial Hospital; 24Hospital Admission MELDNa 23 (6–40) with history in past 6 months of
General de México “Dr. Eduardo Liceaga”; 25Gastroenterology, Hospital hospitalizations 51%, infections 25%, HE 32%, AKI 23%, prior LVP 15%,
De Nutrición; 26Liver Unit, University Hospitals Birmingham Queen hydrothorax 8% and HCC 4%. Leading etiologies were Alcohol 46%
Elizabeth, Birmingham, UK; 27NIHR Birmingham Biomedical Research then NASH 23%, HCV 11% and HBV 13%. Most were on lactulose 52%,
Centre, Centre for Liver and Gastroenterology Research, University of diuretics 53%, PPI 49% and statins 11%, SBP prophylaxis 16%, beta-
Birmingham, UK; 28Royal Berkshire Hospital; 29Royal Berkshire NHS blockers 35% and rifaximin 31%. 90% were admitted for liver-related
Trust; 30Gastroenterology, Gaziantep University School of Medicine; reasons; GI bleed 30%, HE 34%, AKI 33%, electrolyte issues 30%,
31
Gaziantep University Faculty of Medicine Gastroenterology anasarca 24% and 25% admission infections. In-hospital course:
Department; 32Gastroenterology, Christian Medical College, Vellore; Median LOS was 7 (1–140) days with 25% needing ICU. 15% died in
33
Hepatology, Christian Medical College, Vellore; 34Hepatology, hospital, 3% were transplanted, 46% developed AKI, 15% grade 3–4 HE,
Postgraduate Institute of Medical Education and Research, Chandigarh; 14% shock, 13% nosocomial infections and 13% needed ventilation.
35
Gastroenterology and Human Nutrition Unit, All India Institute of Logistic Regression: Fig B shows that liver-related/unrelated factors
Medical Sciences, New Delhi; 36PGIMER Chandigarh India; 37Dr. Rela on admission which predicted in-hospital mortality and develop-
Institute and Medical Centre; 38Department of Liver Transplant Surgery, ment of organ dysfunction with MELDNa and Infections being
Dr. Rela Institute and Medical Centre; 39Asian Institute of common among all models. Nosocomial infections and organ
Gastroenterology, Hyderabad, India; 40Apollo Hospital; 41Mayo Clinic, dysfunctions predicted mortality when all variables were considered.
Arizona; 42Gastroenterology, Mayo Clinic Arizona; 43Gastroenterology, High-income countries had better mortality outcomes likely due to
Marmara University School of Medicine; 44Marmara University Pendik transplant and ICU availability. AUCs were >0.75.
Research and Training Hospital; 45Gastroenterology & Hepatology, Sir
Ganga Ram Hospital; 46Gastroenterology, Sir Ganga Ram Hospital, New
Delhi; 47Transplant, Mayo Clinic; 48Mercy Medical Center & University of
Maryland School of Medicine, Baltimore, MD; 49Mercy Medical Center;
50
Ibn Sina Center for Gastroentrology & Liver Disease; 51Hospital De
Especialidades Centro Médico Nacional La Raza, México;
52
Gastroenterology & Hepatology, Singapore General Hospital;
53
Singapore General Hospital; 54McGuire VA Medical Center; 55Jos
University Teaching Hospital; 56Royal Infirmary of Edinburgh;
57
University of Washington, Department of Medicine; 58University of
Washington; 59University of Pittsburgh Medical Center;
60
Gastroenterology, Pontificia Universidad Católica De Chile;
61
Hepatology and Department of Research, Hospital Italiano De Buenos
Aires, Argentina; 62St. Paul’s Hospital Millennium Medical College; 63Tel
Aviv Sourasky Medical Center; 64Instituto De Salud Digestiva y Hepática;
65
Centro Médico ISSEMYM; 66University of Nottingham; 67NIHR
Nottingham Biomedical Research Centre, Nottingham University
Hospitals; 68Glasgow Royal Infirmary; 69Gastroenterology, NHS Greater
Glasgow and Clyde; 70Center of Liver Transplantation, Department of
Gastroenterology, Ege University; 71University Medical Center Freiburg;
72
Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong
University School of Medicine; 73Virginia Commonwealth University; Conclusion: In this worldwide equitable experience, admission
74
Biostatistics, Virginia Commonwealth University; cirrhosis severity and infections are associated with inpatient
Email: [email protected] outcomes, which are greater in low-income settings. Liver-related
Background and aims: A global study with equitable participation and unrelated factors and regional variations are important in
for cirrhosis and chronic liver disease (CLD) outcomes is needed. We defining critical care goals and outcome models in inpatients with
initiated the Chronic Liver disease Evolution And Registry for Events cirrhosis.
and Decompensation (CLEARED) study to provide this global

S50 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS
OS064 OS065
Maladaptive tubular repair is a harbinger of chronic kidney Hyperammonaemia defines the risk of acute-on-chronic liver
disease development in critically-ill cirrhosis patients admitted to failure in clinically stable outpatients with cirrhosis
intensive care unit-a prospective cohort study María Pilar Ballester1,2, Thomas H. Tranah3,
Rakhi Maiwall1, Sama Siva Rao Pasulapeti2, Archana Rastogi3, Juan Antonio Carbonell-Asins2, Annarein Kerbert4,
Ashini Hidam4, Guresh Kumar5, Sherin Thomas3, Anupam Kumar4, Gonçalo Alexandrino5, Paloma Poyatos-Garcia1, Andra Caracostea3,
Shiv Kumar Sarin1. 1ILBS, Hepatology, India; 2Pachhunga University Jose Sanchez-Serrano1, Carmina Montoliu2, Karen L. Thomsen6,
College, Statistics, Aizawl, India; 3ILBS, Pathology, New Delhi, India; Rajiv Jalan4,7, Debbie L. Shawcross3. 1Hospital Clinico Universitario de
4
ILBS, Clinical and Molecular Medicine, New Delhi, India; 5ILBS, Valencia, Digestive Disease Department, Valencia, Spain; 2INCLIVA
Statistics, New Delhi, India Biomedical Research Institute, Valencia, Spain; 3Institute of Liver Studies,
Email: [email protected] School of Immunology and Microbial Sciences, King’s College London,
London, United Kingdom; 4Liver Failure Group, Institute for Liver and
Background and aims: Critically ill cirrhosis (CIC) patients with
Digestive Health, University College London, Royal Free Campus, London,
acute kidney injury (AKI), are predisposed to increased CKD risk.
United Kingdom; 5Gastroenterology and Hepatology Department,
Renal tubular epithelial cells (RTECs) initiate repair mechanisms
Hospital Prof. Doutor Fernando Fonseca, Amadora, Portugal;
following tubular injury and failure of repair causes renal fibrosis. We 6
Department of Hepatology and Gastroenterology, Aarhus University
evaluated serum Cystatin C (CysC), urinary neutrophil gelatinase-
Hospital, Denmark; 7European Foundation for the Study of Chronic Liver
associated lipocalin (u-NGAL) and RTECs as risk factors of progressive
Failure (EF Clif ) and the European Association for the Study of the Liver-
AKI (AKI-Pro) and CKD in CIC.
Chronic Liver Failure (EASL-CLIF) Consortium
Method: At enrolment we performed CysC, u-NGAL and urine
Email: [email protected]
microscopy (repeated at day 7) in all included patients. In a subset
of patients (n = 30, 15-AKI-Prog and 15-AKI resolution), a panel of 17 Background and aims: Ammonia level correlates with the severity of
renal biomarkers (in urine), endothelial injury and repair markers hepatic encephalopathy and organ failure and is an independent
and monocyte-chemoattractant-protein-1 (MCP-1) (in plasma), predictor of mortality in patients with acute decompensation or
mitochondrial biogenesis markers by QRT-PCR in RTECs was acute-on-chronic liver failure (ACLF). However, its utility as a
performed. Immunohistochemistry (IHC) for alpha-smooth muscle prognostic biomarker in patients with cirrhosis remains unclear.
actin (α-SMA) and collagen (col) 1 and 3 was performed on post- We hypothesized that hyperammonaemia predisposes to ACLF in
mortem renal biopsies. outpatients with cirrhosis. We aimed to determine (i) whether
Results: Altogether, 369 CIC patients, aged 47.9 ± 11.4 years, 87% hyperammonaemia is an independent risk factor for ACLF in clinically
males, 84% with AKI at enrolment, sepsis-related AKI in 47%, stable outpatients with cirrhosis, (ii) a threshold value of ammonia
hepatorenal syndrome in 42%, acute tubular necrosis in 27% were that defines this risk of ACLF, and (iii) its association with mortality.
enrolled from august 2016 to September 2020. Of these, 24.9% Method: A prospective observational study of clinically stable
patients had coarse granular casts, 34.4% had RTECs and 5.7% had cirrhotic outpatients followed-up in two tertiary hospitals was
albuminuria (>300 mg) at enrolment. At day seven, 58% had AKI- performed. Main outcomes were development of ACLF and mortality.
Prog. On median follow-up of 204 days [range 43–365]; 46% Ammonia levels were normalized according to the upper limit of
developed CKD and 30% died or underwent liver transplant. uNGAL normality (A_ULN). Multivariable frailty competing risk modelling
and CysC correlated significantly with AKI cause, severity, presence of was performed with ACLF as event of interest and liver transplant-
sepsis and progression at day 7 (p < 0.001). Presence and persistence ation as a competing risk. Cut-off for A_ULN was calculated using
of granular casts and RTECs, u-NGAL, serum CysC, SOFA scores and maximally selected rank statistics and Kaplan-Meier curves with log-
AKI-Prog at day seven were independent predictors CKD develop- rank test were used to compare ACLF in the high and low risk groups
ment in different multivariate competing risk models. Patients with and ACLF as risk factor for mortality.
AKI-Prog showed higher MCP-1, increase in renal endothelial injury Results: 603 patients were included (69% males; mean 56 years) with
and markers of fibrosis, a decrease in repair markers of tubular injury median follow-up of 215 days (range: 2–2453). A total of 68 (11%)
[significantly lower osteopontin, calbindin and epidermal growth patients developed ACLF. A_ULN was an independent predictor of
factor] and failure of mitochondrial biogenesis [figure]. Post-mortem ACLF (HR = 2.62; 95CI = 2.34–3-51; p < 0.001). Other risk factors were
renal biopsies showed a predominance of chronic inflammatory diabetes (HR = 2.6; 95CI = 1.57–4.37; p < 0.001), MELD score (HR = 1.1;
infiltrate comprising of monocyte-macrophages and tubulointersti- 95CI = 1.03–1.10; p < 0.001) and albumin (HR = 0.5; 95CI = 0.30–0.85;
tial fibrosis, which correlated with uNGAL, CysC, AKI duration and IHC p = 0.001). Using 1.48 as cut-off from the training set, statistically
staining for α-SMA, col-1 and 3 [ p < 0.05]. differences were found between high and low levels of A_ULN for
Conclusion: Almost two-thirds of CICs have AKI, which is often ACLF ( p < 0.001) in the test set (Figure 1). Overall survival was
progressive, and associated with sepsis. NGAL and CysC can significantly lower in patients with ACLF (log-rank = 162; p < 0.001)
accurately predict AKI progression and CKD development. and in patients with A_ULN >1.48 (log-rank = 19; p < 0.001).
Persistence of RTECs in urinalysis at day-7 correlates with AKI
progression and CKD development. The RTECs of patients with
progressive AKI show loss of renal repair markers and failure of
mitochondrial biogenesis. Infiltration with monocyte-macrophages
plays a dominant role in renal fibrogenesis in CICs.

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ORAL PRESENTATIONS

Figure: (abstract: OS064)

S52 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS
Conclusion: Ammonia is an independent predictor of ACLF and its
associated mortality in clinically stable outpatients with cirrhosis. An
ammonia level over 1.48 times the ULN defines the high-risk group
for ACLF.

OS066
Predicting prognosis in large cohort of decompensated cirrhosis
of liver (DCLD)- a machine learning (ML) approach
Ashok Choudhury1, Vinod Arora1, Kajali Mishra2,
Harshvardhan Tevethia1, Vishal Kaushik1, Babita Prasad1,
Manoj Kumar1, Shiv Kumar Sarin1. 1Institute of Liver and Biliary
Sciences, New Delhi, India; 2Henry Ford Hospital, Detroit, United States
Email: [email protected]
Background and aims: Onset of decompensation in cirrhosis is
associated with poor outcome. The current clinico-biochemical tools
have limited accuracy in predicting outcomes reliably. Identifying the
predictors with precision model on the big data using artificial
intelligence may improve predictability. We aimed to develop a
machine learning (ML) based prognostic model for predicting 90 day
survival in patients of cirrhosis presenting with decompensation.
Method: We analysed electronic medical records retrospectively of
hospitalised cirrhosis patients at the ILBS, with a complete 90-day Liver Immunology
follow-up. Clinical data, laboratory parameters and organ involve-
ment were serially noted. AI-modelling was done after appropriate
mining, feature engineering, splitted randomly into train and test- OS067
sets (20:80). The class imbalance problem was handled by random Differential changes in global and antigen-specific B cell
over-sampling technique, to make balanced 50:50 ratios. After 10- frequencies and function associate with the outcome of HBV
fold cross validation, 3 repetitions and grid search for optimal hyper nucleos (t)ide analog treatment withdrawal
parameters, the XGB-CV model was chosen. AUC was the primary Sabela Lens1,2, Alice Burton1, Jessica Davies1, Mireia García-López2,
selection criteria and confusion matrix was used to compare AUCs Anna Jeffery-Smith1, Nikolai Novikov3, Simon Fletcher3,
between AI-models and existing indices; CTP and MELD-score. Sofía Pérez-del-Pulgar4, Xavier Forns2, Mala Maini1. 1University
Results: Total of 6326 patients [mean age 48.2 ± 11.5 years, 84% male, College of London, Division of Infection and Immunity, United Kingdom;
Mean CTP 10.4 ± 2.2 and MELD Na-30.4 ± 11.9, alcohol 49.4%] were 2
Hospital Clinic, Liver Unit, Barcelona, Spain; 3Gilead Sciences, United
included. Ninety day mortality was 29.2%. Acute insult was identified States; 4Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS,
in 80% cases; of which extra-hepatic 49%, hepatic 46% and unknown CIBERehd, Barcelona, Spain
5% cases respectively. The XGB-CV model had the best accuracy for Email: [email protected]
prediction of 90 days event in the train set 0.90 (0.90–0.93),
validation set 0.80 (0.79–0.81) and for overall dataset 0.80 (0.79– Background and aims: Despite HBsAg loss and the development of
0.81). The AUC of the XGB-CV model was better than CTP and MELD anti-HBs being the hallmark of natural resolution of HBV or
Na-score by 16% and 15% respectively. The prediction model achievement of ‘functional cure’, humoral immunity has not yet
considered 43 variables; 18 of which predicted the outcome, and 10 been examined in the setting of nucleos (t)ide analog (NA)
maximum contributors are shown in concordance classifier. The discontinuation. We analysed HBcAg and HBsAg-specific frequencies
most contributors to poor outcome included, index presentation as and functional potential longitudinally in HBeAg-negative chronic
HE, diagnosis of AD/ACLF/ESLD, PT-INR, serum creatinine, total Hepatitis B (CHB) patients stopping NA therapy to assess whether
bilirubin, acute insult etiology, prior decompensation, acute hepatic HBsAg loss ± off-treatment viral control associated with a recovery of
or extrahepatic insult, leukocyte count and present duration of the defective B cell response characteristic of CHB.
illness. In the Decision Tree Model, the presence of HE, PT-INR and Method: Twenty-one HBeAg- CHB patients with complete viral
syndromic diagnosis of AD or ACLF/ESLD was able to stratify the suppression (>3 years) and without cirrhosis were studied prospect-
patients into low (22%), intermediate (23–46%) and high risk (>75%) ively. 16-colour flow cytometry was used to quantitate and
of mortality at 90 days. phenotype circulating HBsAg- and HBcAg-specific B cells (dual
Conclusion: The AI based current model developed using a large data fluorochrome-labelled antigen baits), global B cells, plasmablasts
base of CLD patients presenting with decompensation immensely and Tfh at baseline, 12 and 48 weeks after stopping NA (W12 and
adds to the current indices of liver disease severity and can stratify W48). Cultured ELISPOTs were used to longitudinally evaluate
patients at admission. Simple ML algorithms using HE and INR antibody-secreting cells against HBsAg and HBcAg.
besides syndromic presentation, could help treatment decisions and Results: After a median follow-up of 34 months (IQR 26–37), 16 (76%)
prognostication. patients remained off-therapy, with 5 (24% of the total cohort) losing
HBsAg, whilst 5 (24%) required NA reintroduction. Frequencies of
HBsAg and HBcAg-specific B cells were comparable between groups at
baseline and did not correlate with levels of qHBsAg or HBcrAg
respectively, but did show differential temporal dynamics according
to clinical outcome. HBcAg-specific B cells increased at W12 in all
groups in association with viral rebound, but decreased to baseline
values by W48 only among those achieving HBsAg loss or being re-
treated. By contrast, patients remaining off-therapy had a significant
increase in HBsAg-specific B cells by W48 compared to re-treated
patients. Compared to patients remaining HBsAg+ after NA discon-
tinuation, B cells in patients with HBsAg loss were enriched for the

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ORAL PRESENTATIONS
activated memory phenotype and had a marked expansion of OS069
plasmablasts by W48. In parallel, ELISPOT data showed an increase Humoral and cellular immune responses to SARS-CoV-2
in SFU against HBsAg in the 3 patients with HBsAg loss and anti-HBs+ vaccination across multiple vaccine platforms and liver disease
by W48, confirming the recovery of antibody-producing functionality. types: an EASL registry multicentre prospective cohort study
Conclusion: Functional cure (HBsAg loss) and viral control following Thomas Marjot1,2,3, Sam Murray4, Elisa Pose5,6, Zixiang Lim7,
NA withdrawal associate with recovery of the low frequencies and Maria Carlota Londoño5,6, Melanie Wittner8,9,
poor functionality of HBV-specific B cells in CHB. These findings Marc Luetgehetmann8,10, Virginia Hernandez-Gea11,12,13,
support larger studies to explore the use of B cells as biomarkers of Juan Carlos Garcia Pagan11,12, Golda Schaub14, Paul Duengelhoef15,
clinical outcome and as targets for further immunotherapeutic Martina Sterneck14, Ansgar W. Lohse8,13,14,16, Palak Trivedi17,
boosting. Khushpreet Bhandal18, Benjamin H. Mullish19, Pinelopi Manousou19,
Patrizia Burra20, Floriana Facchetti21, Susan L. Dobson22,
OS068 Alexandra S. Deeks23, Lance Turtle22, Paul Klenerman4,24,
Enforced cytotoxic signature of HBV pol455-specific CD8+ T cells Susanna Dunachie4, Pere Ginès5,6, Massimo Iavarone25,
in chronic HBV infection Julian Schulze zur Wiesch8,14, Francesco Paolo Russo20,
Kathrin Heim1,2, Sagar Sagar1, Maike Hofmann1, Robert Thimme1. Eleanor Barnes4 and On behalf of the EASL Covid-Hep network,
1
University Hospital Freiburg, Freiburg im Breisgau, Germany; OCTAVE study, and PITCH consortium26. 1Oxford Liver Unit, Oxford
2
University of Freiburg Faculty of Biology, Freiburg im Breisgau, Germany University Hospitals NHS Foundation Trust, Oxford, UK; 2Nuffield
Email: [email protected] Department of Clinical Medicine, University of Oxford, Oxford, UK;
3
Background and aims: T-cell exhaustion represents a distinct T-cell Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM),
differentiation program associated with chronic viral infections. NIHR Oxford Biomedical Research Centre, Churchill Hospital, University
Several studies have shown that exhausted CD8+ T cells are of Oxford, Oxford, UK; 4University of Oxford, Nuffield Department of
heterogeneous. In chronic HBV infection, we and others observed Clinical Medicine, Oxford, United Kingdom; 5Centro de Investigación
major differences in the phenotype and function as well as in the Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd),
degree of dysfunction of HBV-specific CD8+ T cells targeting different Barcelona, Spain; 6University of Barcelona, Institut de Recerca Biomed̀ ica
antigens. The aim of this study was to investigate the molecular August Pi-Sunyer (IDIBAPS), Liver Unit, Hospital Clínic de Barcelona,
heterogeneity of HBV-specific CD8+ Tcells targeting different antigens. Barcelona, Spain; 7Oxford University Hospitals NHS Foundation Trust,
Method: To determine the subset diversification of HBV-specific CD8 Oxford, UK; 8German Center for Infection Research (DZIF), Partner Site
+ T cells targeting different antigens, we performed high-throughput Hamburg-Lübeck-Borstel-Riems, Germany; 9Department of Internal
single-cell RNA sequencing using CEL-Seq2 technology. We obtained Medicine, University Medical Center Hamburg-Eppendorf, Hamburg,
HBVcore18- and HBVpol455-specific CD8+ T cells from HBeAg negative Germany; 10Institute of Medical Microbiology, Virology and Hygiene,
chronically HBV-infected patients who endogenously control the University Medical Center Hamburg-Eppendorf, Hamburg, Germany;
viral infection as well as under NUC treatment. Phenotypic and
11
Institut d’Investigacions Biomed̀ iques August Pi I i Sunyer (IDIBAPS),
functional analyses were performed after pMHCI tetramer-based University of Barcelona, Barcelona Hepatic Hemodynamic Laboratory,
enrichment and peptide-specific expansion. Liver Unit, Hospital Clinic, Barcelona, Spain; 12Centro de Investigación
Results: Cluster analysis of single-cell transcriptomes revealed a Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd),
different subset diversification of HBVcore18- versus HBVpol455- Barcelona, Spain; 13European Reference Network on Hepatological
specific CD8+ T cells. In particular, HBVcore18-specific CD8+ T cells Diseases (ERN RARE-LIVER); 14University Medical Center Hamburg-
were mostly comprised of precursor/memory-like exhausted T-cell Eppendorf, Department of Internal Medicine, Hamburg, Germany;
15
subsets. Within HBVpol455-specific CD8+ T cells, we could identify a Department of Immunology, University Medical Center Hamburg-
cluster of cells that highly expressed cytotoxic genes including GNLY, Eppendorf, Martinistraße 52, 20249 Hamburg, Germany; 16Hamburg
GZMB and PRF1. Moreover, the cytotoxic regulator NKG7 was also Center for Translational Immunology (HCTI); 17National Institute for
elevated in this subset. Interestingly, we further observed that the Health Research Birmingham Biomedical Research Centre, Centre for
cytotoxic subset is restricted to HBVpol455-specific CD8+ T cells Liver and Gastroenterology Research, Birmingham, United Kingdom;
18
obtained from patients who endogenously control the viral infection University Hospitals Birmingham NHS Foundation Trust, Birmingham,
indicating that the enforced cytotoxic signature may be linked to United Kingdom; 19Imperial College London, Department of Metabolism,
virological HBV control in these patients. The differential transcrip- Digestion and Reproduction, London, United Kingdom; 20University of
tional profile of HBVpol455-specific CD8+ T cells was further Padova, Department of Surgery, Oncology and Gastroenterology, Italy;
21
confirmed ex vivo after pMHCI tetramer-based enrichment. Indeed, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca’
at the protein level, we detected a terminal effector differentiation Granda Ospedale Maggiore Policlinico, Milan, Italy; 22NIHR Health
and higher cytotoxic effector capacity of HBVpol455-specific CD8 T Protection Research Unit in Emerging and Zoonotic Infections, Institute
cells obtained from treatment-naïve patients in comparison to of Infection, Veterinary and Ecological Sciences, University of Liverpool,
patients requiring antiviral therapy. UK; 23Peter Medawar Building for Pathogen Research, Nuffield Dept. of
Conclusion: In sum, our data highlight an enforced cytotoxic Clinical Medicine, University of Oxford, UK; 24Translational
signature in HBVpol455-specific CD8+ T cells of treatment-naïve Gastroenterology Unit, University of Oxford; 25Fondazione IRCCS Ca’
patients which may be related to virological control in these patients. Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and
This observation might have potential implications for the design of Hepatology, Milan, Italy; 26Nuffield Department of Medicine, University
immunotherapeutic approaches in HBV cure. of Oxford, Oxford, UK
Email: [email protected]

Abstract OS069 is under embargo until Friday 24 June 2022,

13:40 BST. It will be made publicly available on the congress
website once the embargo has lifted.

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 ORAL PRESENTATIONS

OS070
CD8+ T cell acquisition of the LPS receptor within the hepatic
stroma shapes anti-viral/anti-tumour potential
Laura J. Pallett1, Mariana Diniz1, Leo Swadling1, Jessica Skelton2,
Alexander Maini3, Jessica Davies1, Stephanie Kucykowicz1,
Nathalie Schmidt1, Oliver E. Amin1, Upkar Gill4, Alice Burton1,
Jenifer Sanchez5, Giuseppe Fusai6, Sabela Lens7,
Sofía Pérez-del-Pulgar8, Patrick Kennedy4, Brian R. Davidson6,
Muzlifah Haniffa9, Derek Gilroy3, Marcus Dorner2, Anna Schurich5,
Mala Maini1. 1University College London, Division of Infection and
Immunity, London, United Kingdom; 2Imperial College London,
Department of Medicine, London, United Kingdom; 3University College
London, Division of Medicine, London, United Kingdom; 4QMUL, Barts
and The London School of Medicine and Dentistry, London, United
Kingdom; 5Kings College London, School of Immunology and Microbial
Sciences, London, United Kingdom; 6University College London, Division
of Surgery, London, United Kingdom; 7University of Barcelona, Hospital
Clinic, August Pi i Sunyer Biomedical Research Institute, Barcelona,
Spain; 8Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS,
CIBERehd, Barcelona, Spain; 9Newcastle University, Faculty of Medical
Sciences
Email: [email protected]
Background and aims: Despite being bathed in bacterial products,
the liver maintains a state of tolerance, exploited by HBV and
tumours. The cellular basis mediating immune tolerance,
yet allowing a rapid switch to immunity, needs to be better defined
to deliver successful immunotherapy for the treatment of chronic
HBV infection.
Method: We analysed the phenotype and function of CD14-
expressing CD8 T cells directly ex vivo from resected/explanted
human liver and explored their derivation, functionality, expansion
and LPS-responsiveness in multiple in vitro and in vivo models.
Results: CD8 T cells expressing CD14 (and other LPS receptor
components) were found to be compartmentalised in human liver
and to preferentially accumulate amongst donor lymphocytes
surviving in liver allografts, within HCC-infiltrating lymphocytes,
and in cirrhotic ascites. Moreover, HBV-specific CD8 T cells were
significantly enriched for the expression of CD14 compared to the
residual, global CD8 T cell pool. CD14+CD8 T cells were highly
activated and proliferative, with constitutive immunomodulatory
features at rest (IL-10, IL-2 production) compared to CD14-CD8 T
cells. They selectively expressed receptors (CXCR4/CD49a/CD49b)
supporting retention with the stromal cell network to acquire CD14
from neighbouring macrophages. Human CD8 T cells acquire CD14,
TLR4 and MD-2 from mononuclear phagocytes by actin cytoskeleton-
dependent trogocytosis, promoted by E.coli, stromal cells and
CXCL12. CD14 acquisition conferred the capacity to bind LPS and
respond with a unique functional profile of chemotactic cytokines.
Instead, upon TCR engagement, ex vivo and in vitro-derived CD14+CD8
T cells were poised to mount rapid, potent anti-viral effector function
(IFNg/TNF/MIPI1b). Importantly, CD14 acquisition by HBV-redirected
CD8 T cells (HLA-A0201/HBs183-91) could be exploited to induce
superior immunotherapeutic efficacy, with enhanced lysis of hepa-
toma cells expressing HBsAg (HepG2-PreS1-GFP).
Conclusion: A proportion of CD8 T cells compartmentalised in the
liver express CD14/TLR4/MD2, recapitulated in vitro by trogocytosis
from mononuclear phagocytes. CD14+CD8 T cells have enhanced
TCR-directed effector function and can be induced to target HBV
infection. Thus bacterial products in the gut-liver axis can therefore

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ORAL PRESENTATIONS
fine tune organ-specific immunity by shaping stromal-interacting Results: Nineteen novel tumor neoantigens associated with poor
CD8 T cells with unique functionality. prognosis and infiltration of antigen presenting cells were identified
in HCC, including CDK1, CCNB1, CDC25C, PTTG1, CHEK1, KPNA2,
OS071 MKI67, KIF2C, MCM3, EZH2, CDT1, PES1, PRC1, PPM1G, NEK2, TRIP13,
A novel immunophenotyping of hepatocellular carcinoma based TUBG1, AURKA, G6PD (Fig. A–C). Based on these neoantigens, we
on amplified and mutated neoantigens for mRNA vaccine construct six immune subtypes (IS1-IS6, Fig. D). The immune
development subtypes showed distinct molecular, cellular and clinical character-
He Jing1, Boqiang Liu1, Liang Shi1, Xiujun Cai1. 1Zhejiang University, istics. Patients with IS1 and IS3 tumors had a superior survival than
China those with the other subtypes (Fig. E). IS4 and IS6 tumors had
Email: [email protected] immunosuppressive phenotype, and were also associated with
higher tumor mutation burden and tumor stage (Fig. F–H).
Background and aims: Hepatocellular carcinoma (HCC) is the most
Furthermore, distinct expression of immune checkpoints and
common malignancy with poor prognosis. Genetic and phenotypic
immunogenic cell death modulators was observed between different
heterogeneity is a hallmark of HCC and also poses a daunting
immune subtype tumors (Fig. I).
challenge for treatment. Recently, accumulating evidence suggests
Conclusion: This study constructed a novel immunophenotyping of
that immunotyping can indicate the comprehensive immune
HCC for predicting the prognosis of patients. Meanwhile, CDK1,
microenvironment, which is closely associated with therapeutic
CCNB1, CDC25C, PTTG1, CHEK1, KPNA2, MKI67, KIF2C, MCM3, EZH2,
response and vaccination potential. In this study, we try to identify
CDT1, PES1, PRC1, PPM1G, NEK2, TRIP13, TUBG1, AURKA, G6PD are
potent neoantigens in HCC for tumor immunotherapy, and further
potent neoantigens for HCC-mRNA vaccine development, specifically
distinguish immune subtypes of HCC to construct an immune
for patients with IS4 and IS6 type.
landscape for predicting the prognosis.
Method: Gene expression profiles, clinical information and simple
nucleotide variation data of 328 HCC samples were obtained from
TCGA. GEPIA was used to calculate differential expression levels,
prognostic indices, and compare genetic alterations. TIMER was used
to explore correlation between genes and immune infiltrating cells.
Consensus cluster was used for consistency matrix construction and
data clustering.

Figure: (abstract: OS071)

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 ORAL PRESENTATIONS
OS072A
T cell and humoral immune response to multiple SARS-CoV-2
variants including omicron (B1.1.529) after two doses of COVID-19
vaccine in patients with cirrhosis and liver diseases requiring
immunosuppression: data from the EASL COVID-Hep network
Sam Murray1, Stephanie Longet2, Tom Tipton2,
Maria Carlota Londoño3, Elisa Pose3, Stephen Laidlaw2,
Dung Nguyen2, Georgina Meacham1, Zixiang Lim4,
Stavros Dimitriadis1, Sophie Irwin1, Jonathan Cook5,
Massimo Iavarone6, Pietro Lampertico6, Virginia Hernandez-Gea7,8,9,
Juan Carlos Garcia Pagan7,8,9, Julian Schulze zur Wiesch10,11,
Martina Sterneck10, Francesco Paolo Russo12, Jack Satsangi13,
Susanna Dunachie1,14, Paul Klenerman1,13, Carl Goodyear15,
Iain B. McInnes15, Pere Ginès7, Miles Carroll2, Thomas Marjot1,16,
Eleanor Barnes1,16. 1University of Oxford, Nuffield Department of
Medicine, United Kingdom; 2University of Oxford, Wellcome Centre for
Human Genetics; 3University of Barcelona, Liver Unit, Hospital Clínic de
Barcelona; 4Oxford University Hospitals NHS Foundation Trust,
Department of Gastroenterology; 5University of Oxford, Centre for
Statistics in Medicine and Surgical Interventions Trials Unit, Nuffield
Department of Orthopaedics, Rheumatology and Musculoskeletal
Sciences; 6Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico;
7
University of Barcelona, Liver Unit, Hospital Clinic, Institut
d’Investigacions Biomed ̀ iques August Pi I i Sunyer (IDIBAPS); 8Centro de
Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
(CIBERehd); 9Health Care Provider of the European Reference Network
on Rare Liver Disorders (ERN-Liver); 10University Medical Center
Hamburg-Eppendorf, Department of Internal Medicine; 11German
Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-
Borstel-Riems; 12University of Padova, Department of Surgery, Oncology
and Gastroenterology DISCOG; 13University of Oxford, Translational
Gastroenterology Unit, Nuffield Department of Experimental Medicine;
14
University of Oxford, Oxford Centre for Global Health Research, Nuffield
Department of Medicine; 15University of Glasgow, Institute of Infection,
Immunity and Inflammation; 16Oxford University Hospitals NHS
Foundation Trust, Oxford Liver Unit
Email: [email protected]

Abstract OS072A is under embargo until Friday 24 June

2022, 13:40 BST. It will be made publicly available on the
congress website once the embargo has lifted.

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ORAL PRESENTATIONS
OS072B
Humoral and cellular immune responses to wild-type and
omicron (B.1.1.529) SARS-CoV-2 variants following a fourth
COVID-19 vaccination in liver transplant recipients and patients
with autoimmune hepatitis
Stavros Dimitriadis1, Georgina Meacham1, Sophie Irwin1,
Victoria Walker1, Sam Murray2, Zixiang Lim3, Thomas Marjot1,4,
Jack Satsangi5, Eleanor Barnes2. 1University of Oxford, Nuffield
Department of Medicine, United Kingdom; 2Peter Medawar Building for
Pathogen Research, Nuffield Department of Clinical Medicine, United
Kingdom; 3Oxford University Hospitals NHS Foundation Trust,
Department of Gastroenterology, United Kingdom; 4Oxford University
Hospitals NHS Foundation Trust, Oxford Liver Unit, Oxford, United
Kingdom; 5University of Oxford, Translational Gastroenterology Unit,
United Kingdom
Email: [email protected]

Abstract OS072B is under embargo until Friday 24 June 2022,

13:40 BST. It will be made publicly available on the congress
website once the embargo has lifted.

Rare liver diseases (including paediatric

and genetic)

OS073
In vivo CRISPR/Cas9 editing of the TTR gene with NTLA-2001 in
patients with transthyretin amyloidosis- dose selection
considerations
Edward J. Gane1, Jörg Täubel2, Björn Pilebro3, Marianna Fontana4,
Justin Kao5, Michael Maitland6, Mark Stroh6, Jessica Seitzer6,
Jonathan Phillips6, Kristy Wood6, Yuanxin Xu6, Carri Boiselle6,
Adam Amaral6, Adam Boyd6, Jeffrey Cehelsky6, David Gustein7,
Odelya Pagovich7, Laura Sepp-Lorenzino6, Liron Walsh6,
David Lebwohl6, Gillmore Julian8. 1The University of Auckland, New
Zealand Liver Transplant Unit, Auckland, New Zealand; 2Richmond
Pharmacology Limited, London, United Kingdom; 3Umeå University,
Department of Public Health and Clinical Medicine, Sweden; 4University
College London, National Amyloidosis Centre, Division of Medicine,
United Kingdom; 5Auckland City Hospital, Department of Neurology,
New Zealand; 6Intellia Therapeutics, Inc., Cambridge, United States;
7
Regeneron Pharmaceuticals, Inc., Tarrytown, United States; 8University
College London, United Kingdom
Email: [email protected]
Background and aims: The liver produces the toxic precursor protein
transthyretin (TTR) in ATTR amyloidosis, a fatal disease of misfolded
protein accumulation. Until recently, the only therapeutic

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 ORAL PRESENTATIONS
intervention for variant ATTR amyloidosis (ATTRv) was liver trans- OS074
plantation. Gene-silencing agents targeting TTR mRNA prevent ACOX2 deficiency-induced liver fragility (ADILF), a not-so-rare
disease progression but require lifelong administration. In contrast, inborn error in bile acid metabolism that responds to
gene editing is designed as a single-dose treatment. NTLA-2001 ursodeoxycholic acid treatment
comprises a lipid nanoparticle (LNP) encapsulating mRNA for SpCas9 Marta Alonso-Peña1,2, Ricardo A. Espinosa-Escudero2,
protein and single guide RNA targeting the transthyretin (TTR) gene. Elisa Herraez2,3, Oscar Briz2,3, María Luisa Cagigal4,
After infusion, LNP uptake into hepatocytes results in precise TTR Jesús González Santiago5, Aida Ortega-Alonso6,
knockout regardless of disease-causing mutation. This is the first Conrado Manuel Fernandez Rodriguez7, Luis Bujanda3,8,
report of the dose, exposure and pharmacodynamic (PD) response Marta Calvo9, Delia D’Avola10, Maria Carlota Londoño3,11,
relationship in humans for systemically administered liver-directed Moises Diago12, José Fernandez-Checa13, M. Carmen Garcia-Ruiz13,
gene-editing therapy. Raul J. Andrade3,6, Frank Lammert14, Jesus Prieto3,10,
Method: The first-in-human phase 1 trial (NCT04601051) enrolls Javier Crespo1,3,15, Javier Juampérez Goñi16, Álvaro Díaz-González1,15,
adults with confirmed ATTRv amyloidosis and peripheral neuropathy. Maria Monte2,3, Jose Marin2,3. 1Research Institute Marques de
Safety, pharmacokinetics (PK), and PD of NTLA-2001 are assessed in Valdecilla (IDIVAL), Clinical and Traslational Research in Digestive
3 + 3 dose escalation, with a subsequent expansion cohort. Pathology Group, Santander, Spain; 2University of Salamanca,
Circulating serum TTR was measured in samples collected at baseline, Experimental Hepatology and Drug Targeting (HEVEPHARM),
Days 7, 14, and 28, and every 2 months thereafter. Dose selection for Salamanca, Spain; 3Carlos III National Institute of Health, Center for the
the expansion cohort is based on review of safety, PK and PD in the Study of Liver and Gastrointestinal Diseases (CIBERehd), Madrid, Spain;
escalation phase. 4
Marques de Valdecilla University Hospital, Pathological Anatomy
Results: As of this submission, 14 subjects received NTLA-2001 as Service, Santander, Spain; 5University Hospital of Salamanca,
single-ascending doses [3 subjects each at 0.1, 0.3, and 0.7 mg/kg, and Department of Gastroenterology and Hepatology, Salamanca, Spain;
5 subjects at 1 mg/kg]. Mild and transient infusion reactions were the 6
Institute of Biomedical Research of Málaga (IBIMA), University Hospital
most common adverse event with NTLA-2001. Interim pharmacoki- Virgen de la Victoria, Liver Unit, Gastroenterology Service, Malaga,
netic data suggest that following intravenous (IV) infusion NTLA- Spain, 7Fundación Hospital Alcorcón, Rey Juan Carlos University,
2001 ionizable lipid exhibited a rapid decline from peak levels Gastroenterology Unit, Madrid, Spain; 8Biodonostia Health Research
followed by a secondary peak and then a log-linear phase. Serum TTR Institute. Donostia University Hospital, University of the Basque Country
levels were significantly reduced from baseline in a dose-dependent (UPV/EHU), Department of Liver and Gastrointestinal Diseases, San
manner; patients receiving 0.3 mg/kg achieved durable reductions Sebastian, Spain; 9Segovia General Hospital, Segovia, Spain; 10Clinica
with mean Day 28 TTR reduction of 87% (n = 3) and greater reductions Universidad de Navarra and Center for Applied Medical Research (CIMA),
at higher doses (Figure 1, interim data to Day 28 from 10 subjects as of University of Navarra, Department of Medicine, Pamplona, Spain;
September 13, 2021). Additional data will be available for 11
Hospital Clínic de Barcelona, University of Barcelona, Liver Unit,
presentation. Barcelona, Spain; 12Valencia General University Hospital, Valencia,
Spain; 13Institute of Biomedical Research of Barcelona (IIBB), Barcelona,
Spain; 14Saarland University Medical Center, Department of Medicine II,
Homburg, Germany; 15Marques de Valdecilla University Hospital,
Gastroenterology and Hepatology Department, Santander, Spain; 16Vall
d’Hebron University Hospital (HVH), Universitat Autónoma de
Barcelona, Pediatric Hepatology and Liver Transplantation Unit,
Barcelona, Spain
Email: [email protected]
Background and aims: A variant ( p.Arg225Trp) in peroxisomal acyl-
CoA oxidase 2 (ACOX2), involved in bile acid (BA) side-chain
shortening, has recently been associated with persistent unexplained
hypertransaminasemia and accumulation of C27-BAs, mainly trihy-
droxycholestanoic acid (THCA). Our aim was to investigate the
prevalence of ACOX2 deficiency-induced liver fragility (ADILF)
Conclusion: A single IV infusion of the gene editing therapeutic among patients with hypertransaminasemia of unknown origin
NTLA-2001 resulted in dose-dependent reductions in serum TTR and their response to ursodeoxycholic acid (UDCA), to identify other
protein with predominately mild adverse events reported. NTLA- inborn errors that could cause this alteration and to elucidate its
2001 represents a potential paradigm shift in the treatment of ATTR pathophysiological mechanisms.
amyloidosis. Method: Serum BA profile was determined by HPLC-MS/MS. Genetic
analysis of ACOX2 was performed by exon sequencing. In HuH-7 cells
exposed to THCA, viability was determined by MTT, reactive oxygen
species (ROS) production by flow cytometry and endoplasmic
reticulum (ER) stress by analyzing GRP78 and CHOP levels (RT-
qPCR and Western Blot), and XBP1-S/XBP1-U ratio (RT-qPCR). The
1000-Genomes database and SIFT and Polyphen scores were used to
select ACOX2 variants that were expressed in HuH-7 cells to
determine by HPLC-MS/MS its ability to metabolize THCA.
Results: Among 33 patients with suspected ADILF from 11 hospitals
and 13 relatives, 7 individuals with abnormally high C27-BA levels
(>50% of total BAs) were identified. The p.Arg225Trp variant was
found in homozygosity in 2 patients and 3 relatives. Moreover, other
2 non-related patients were heterozygous carriers of different alleles,
for c.673C>T ( p.Arg225Trp) and c.456_459del (p.Thr154fs). Impaired
expression of ACOX2, but not ACOX3 in the liver of these patients was
found (immunohistochemistry). Treatment with UDCA normalized

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S59

ORAL PRESENTATIONS
transaminases levels. Culture of HuH-7 liver cells with THCA 2
Wake Forest University/North Carolina Baptist Medical Center,
increased ROS production and the ER stress biomarkers GRP78, Winston-Salem, United States; 3Instituto Nacional de Pediatría, Mexico
CHOP and XBP1-S/XBP1-U ratio, whereas decreased cell viability. City, Mexico; 4Royal Melbourne Hospital, Melbourne, Victoria, Australia;
THCA-induced toxicity was higher than that of major BAs. Among 14 5
Medical Genetics Section, Virgen de la Arrixaca University Hospital,
in silico selected genetic variants, in vitro functional tests identified 6 IMIB-Arrixaca, Universidad de Murcia, Murcia, Spain; 6CIBERER-ISCIII,
ACOX2 variants as a potential cause of ADILF. Madrid, Spain; 7University of Milan, Milan, Italy; 8Division of
Conclusion: Dysfunctional ACOX2 is found in a substantial propor- Endocrinology, Diabetes and Porphyria, Stadtspital Zürich, Zürich,
tion of patients with unexplained hypertransaminasemia, suggesting Switzerland; 9Alnylam Pharmaceuticals, Cambridge, United States;
that this disorder of BA metabolism causes enhanced liver fragility, 10
Massachusetts General Hospital, Boston, United States
which can be attenuated by UDCA treatment. Email: [email protected]

OS075
Efficacy and safety of givosiran in patients with acute hepatic
porphyria: 36-month results of the phase 3 ENVISION randomised
clinical trial
Manish Thapar1, Herbert L. Bonkovsky2, Susana Monroy3,
Gayle Ross4, Encarna Guillén-Navarro5,6, Maria Domenica Cappellini7,
Anna-Elisabeth Minder8, Shangbin Liu9, Marianne T. Sweetser9,
David Kuter10. 1Thomas Jefferson University, Philadelphia, United States;
.

This abstract is under embargo until Thursday 23 June 2022,

13:30 BST. This abstract has been selected to be highlighted
during official EASL Press Office activities or in official EASL
Press Office materials that will be made publicly available on the
congress website at 13:30 (BST).

S60 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS

Results: A thrombophilia was identified in 34/118 (29%) patients, of

which 18/118 (15%) were a High-risk Thrombophilia. Thrombosis
recurrence incidence rate was 2.94, 95CI = [0.00–6.22] per 100
patient-years (PY) at one year and 4.75, 95CI = [2.46–7.04] per 100
PY after a median follow-up of 19.5 months. The prevalence of
thrombophilia did not differ significantly between groups with or
without thrombosis recurrence ( p = 0.775). However, presence of at
least a High-risk Thrombophilia was significantly associated with
thrombosis recurrence (RR = 4.2, 95CI = [1.18–14.91], p = 0.026)
OS076 (Figure 1). Absence of portal recanalisation was significantly
High-risk Thrombophilia predict early thrombosis recurrence in associated with thrombosis recurrence as compared to partial
acute non-cirrhotic portal vein thrombosis related to local recanalisation (66.7% vs 32.4%, p = 0.019). Anticoagulation duration
factors: LOCAPORT did not appear to be significantly associated with the risk of
Louise Lebedel1, Aurélie Plessier2, Odile Goria3, Christophe Bureau4, thrombosis recurrence. However, 91/115 (79%) received long-term
Alexandra Heurgue-Berlot5, Pierre-Emmanuel Rautou2, anticoagulation (>6 months) while short-term anticoagulation (≤6
Audrey Payance2, Kamal Zekrini2, Thi Thu Nga Nguyen1, Thong Dao1, months) was administered in 24/115 (21%) patients. Thrombosis
Rémi Morello1, Isabelle Ollivier-Hourmand1. 1University of Caen incidence rate was 5.48, 95CI = [0.00–11.50] per 100 PY in short term
Normandie Hospital Center, Caen, France; 2Beaujon Hospital, Clichy, anticoagulation group as compared to 4.83, 95CI = [2.16–7.50] per 100
France; 3Hospital Center University De Rouen, Rouen, France; 4Hospital PY in long term anticoagulation group ( p = 0.47).
Center University De Toulouse, Toulouse, France; 5CHU Reims, Conclusion: In acute non-cirrhotic PVT secondary to local factors, a
Department of Hepato-Gastroenterology, Reims, France High-risk Thrombophilia is frequently identified, and increase the
Email: [email protected] risk of thrombosis recurrence. The high number of patients treated by
long term anticoagulation in our cohort, does not allow us to draw
Background and aims: A local factor is identified in 21% of acute non- any conclusion about the potential protective role of anticoagulant.
cirrhotic portal vein thrombosis (PVT). We aim to determine the risk
of thrombosis recurrence in this situation, and risk factors associated OS077
with recurrence. Clinical utility of non-ceruloplasmin copper determined by
Method: This is a retrospective multicenter study from the French copper speciation for monitoring Wilson disease therapy:
Vascular Liver Diseases cohort between 1992 and 2021. We included comparative data analysis with 24-hour urinary copper excretion
acute non-cirrhotic portal vein thrombosis (right or left branch or from the CHELATE trial
portal vein extending or not to mesenteric and splenic veins), with at Michael Schilsky1, Aurelia Poujois2, Massimo Giovanni Zuin3,
least one local factor (infectious, inflammatory, traumatic, surgical or Peter Ott4, Karl Heinz Weiss5, David Cassiman6, Aftab Ala7,
neoplasic) identified, either concomitantly or in the last 3 months. We Anna Czlonkowska8, Nicolas Dubois9, Naseem Amin10,
screened for prothrombotic factors such as 1st degree unprovoked C. Omar Kamlin11. 1Yale University, Departments of Medicine and
personal or family history of deep vein thrombosis, High-risk Surgery, Divisions of Digestive Diseases and Transplant and Immunology,
Thrombophilia (myeloproliferative neoplasm, homozygous or com- Conneticut, United States; 2Fondation Hopital Rothschild, Paris, France;
posite heterozygous mutation of factor V Leiden and G20210 3
University of Milan, Milan, Italy; 4Aarhus University Hospital,
prothrombin gene, antiphospholipid syndrome, familial antithrom- Denmark; 5Salem Medical Center, Heidelberg, Germany; 6University of
bin deficiency), Low-risk Thrombophilia (heterozygous factor V Leuven, Belgium; 7Kings College University Hospital, Institute of Liver
Leiden or prothrombin gene G20210 mutation, hyperhomocysteine- Studies, London, United Kingdom; 8Institute of Psychiatry and Neurology,
mia, protein C or S deficiency, homozygous MTHFR mutation), Warsaw, Poland; 9International Drug Development Institute (IDDI),
ongoing oestroprogestative or pregnancy up to 6 weeks post- Belgium; 10Orphalan SA France, Paris, France; 11Orphalan SA France,
partum, paroxysmal nocturnal haemoglobinuria and Behçet’s disease. France
Email: [email protected]
Background and aims: Monitoring efficacy of therapy in Wilson
disease (WD) is challenging; 24-hour urinary copper excretion (24 hr

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ORAL PRESENTATIONS
UCE) is cumbersome, and results show large intra-subject variability. Longitudinal assessment offers an opportunity to improve surrogate
A new non-ceruloplasmin copper assay using liquid chromatography marker utility.
and ICP mass spectroscopy (NCC-Sp) was developed for the CHELATE Method: Using retrospectively collected data on 2519 North
Trial [trientine tetrahydrochloride (TETA4) vs. d-Penicillamine American patients diagnosed as per AASLD criteria with PSC, a
(DPA)]. We aim to describe the intra-patient variability and derivation (Toronto: Jan. 2000 to Dec. 2020) and validation cohort
compare the clinical utility of UCE and NCC-Sp in monitoring WD (Mayo: Apr. 1978 to Dec. 2017) were evaluated to define progressive
therapy. and stable disease states (PDS/SDS). Progressive disease was defined
Method: A multicentre, open label, non-inferiority randomised as death or transplant. Linear mixed-effects regression with random
controlled trial was conducted in which 53 stable adult WD subjects intercept and random slope was used to study biochemical and
were randomly allocated after a 12-week baseline observation period transient elastography (fibroscan) trajectories longitudinally over
to either DPA or TETA4 for 24 w with a primary end point (NCC-Sp). time. Piecewise linear splines and polynomial terms were employed.
An independent adjudication committee blinded to site and Time was calculated backwards from death, transplant, or last follow-
treatment allocation assessed clinical stability at randomisation and up (time zero).
end of study. Paired samples for NCC-Sp and 24 hr UCE were Results: Across combined cohorts median follow-up (IQR) was 8.3
compared pre- and 24w post-randomisation. Validation studies for (3.6–15) yrs, 63% were male, and mean age at diagnosis 39.5 (SD:16.1)
NCC-Sp included 50 healthy adults, identifying a range (2.5% to 97.5%) yrs. 88.3% had large duct disease and 78% had IBD at last follow-up.
of 40–150 mcg/L. This was used as reference target range for the Throughout the 10 yrs prior to death or transplant, patients with PDS
study population and compared to UCE (recommended therapeutic in the derivation cohort had estimated ALP means ranging from 1.87–
range of 200–500 mcg/24 hr). Intra-patient (SD) variability was 2.64 the upper limit of normal (ULN) with major fluctuations ( p <
computed for NCC-Sp and UCE measurements during baseline and 0.01); patients with SDS had lower and stable ALP courses (ALP 1.27–
post-randomisation periods. 1.37 × ULN). A similar pattern existed for the validation cohort, where
Results: The independent adjudication committee unanimously patients with progressive disease had ALP 2.25–3.12 × ULN, while
assessed all subjects as clinically stable at randomisation and study patients with stable disease had ALP around 1.44–1.57 × ULN ( p <
end point. NCC-Sp was in the reference range at randomization versus 0.0001). The derivation cohort experienced bilirubin (TB) elevation
study end in 86% vs. 84% of subjects respectively, while UCE was in the 6 yrs before experiencing death or transplant; similarly for the
recommended therapeutic range in only 41% vs. 37% respectively validation cohort bilirubin elevation was 8 yrs before event. Patients
(Table). Agreement when both NCC-Sp and UCE were in range at with SDS maintained normal bilirubin values. Both cohorts experi-
randomization/study end was 17/49 (35%) and 17/51 (33%) respect- enced increases in the 2 yrs prior to death or transplant to reach an
ively. Mean (SD) NCC-Sp and UCE intra-patient variability during estimated mean TB of ∼5 × ULN (p < 0.0001). ALB and PLT estimated
baseline (all receiving DPA) was 15.5 (7.8) mcg/L and 196 (125) mcg/ means were lower for patients with progressive disease than those
24hr respectively. Mean (SD) NCC-Sp intra-patient variability for DPA with stable disease in both cohorts; estimated AST and ALT means
and TETA4 post randomisation was 17.9 (11.6) and 14.9 (12.1) mcg/L were notably higher for patients with PDS vs those with SDS
respectively ( p < 0.0001). Mean (SD) UCE intra-patient variability for (derivation cohort: AST: 1.64–3.34 × ULN vs 1.21–1.28 × ULN; ALT:
DPA and TETA4 post randomisation was 148.9 (127) and 107 (101) 2–2.83 × ULN vs 1.56–1.7 × ULN; validation cohort AST: 1.66–2.88 ×
mcg/24 hr respectively ( p = 0.74). ULN vs 1.09–1.32 × ULN; ALT 1.65–2.06 × ULN vs 1.15–1.56 × ULN) in
Conclusion: UCE is a test with significant intra-patient variability for both derivation and validation cohorts. In the Toronto derivation
WD patients on chelation therapy with either DPA or TETA4. That cohort patients with PDS had progressively increasing estimated
NCC-Sp had less intra-patient variability than UCE suggests NCC-Sp is transient elastography measurements from 10.8–31.3 kPa between yr
a more reliable biomarker for monitoring chelation therapy in WD. 6 and time of death or transplant. Patients with SDS had transient
elastography measurements over 6 yrs of study ranging from 7.7–
Table: Comparative analysis of “in range” data for NCC-Sp and UCE at 9 kPa.
randomization and study end point.
Primary End point
(wk 24 post
At Randomisation randomisation)

UCE UCE
UCE in not in UCE in not in
range** range** Total range** range** Total
NCC-Sp in range 17 25 42 17 26 43
NCC-Sp not in 3 4 7 2 6 8
range

*range for NCC-Sp = 40–150 mcg/L; **range for UCE = 200–500 mcg/24 hr.

OS078
North American evaluation of 2519 patients with primary
sclerosing cholangitis: longitudinal patterns of disease activity
identify and validate stable and progressive phenotypes
Marwa Ismail1, John Eaton2, Aliya Gulamhusein1,
Morven Cunningham3, Christina Plagiannakos3, Bettina Hansen1, Conclusion: We evaluate progressive and stable disease phenotypes
Gideon Hirschfield1. 1Institute of Health Policy Management and in >2500 PSC patients. A stable disease course was validated for
Evaluation, Health Services Research, Toronto, Canada; 2Mayo Clinic, patients with sustained ALp <1.5 × ULN, as well as those with
Rochester, United States; 3UHN, Toronto Centre for Liver Disease, Toronto, longitudinal transient elastography values <10 kPa.
Canada
Email: [email protected]
Background and aims: Markers of outcome in patients with primary
sclerosing cholangitis fluctuate, reducing utility at single time points.

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 ORAL PRESENTATIONS
OS080
Natural history of hepatic steatosis associated to metabolic
Nurses and AHP syndrome. Longitudinal study with 5 years of follow-up.
Marta Cervera1,2,3,4, Marta Carol1,2,3,4, Ana Belén Rubio1,2,3,
Martina Perez1,2,3,4, Carlota Riba1,2,3, Rosario Hernández5,
OS079
Ann Ma1,2,3, Emma Avitabile1,2,3, Anna Soria1,2,3,
Nurse-led inpatient fibrosis assessment for patients with
Octavi Bassegoda1,2,3, Sara Martinez1,2,3, Jordi Gratacós-Gines1,2,3,
suspected alcohol related liver disease and previous poor
Adria Juanola1,2,3, Laura Napoleone1,2,3, Elisa Pose1,2,3,
engagement with services
Isabel Graupera1,2,3, Pere Ginès1,2,3, Núria Fabrellas1,2,3,4. 1Hospital
Rebecca Fennell1, Dianne Backhouse1, George Abouda1,
Clinic de Barcelona, Liver Unit, Barcelona, Spain; 2Institut
Lynsey Corless1. 1Hull University Teaching Hospitals NHS Trust, Kingston ̀ iques August Pi i Sunyer (IDIBAPS) CIF:
d’Investigacions Biomed
upon Hull, United Kingdom
G59319681, Barcelona, Spain; 3Centro de Investigación Biomédica en Red
Email: [email protected]
de Enfermedades Hepáticas y Digestivas (CIBEReHD), Madrid, Spain;
4
Background and aims: Identification and staging of fibrosis is a University of Barcelona, School of Medicine and Health Sciences,
critical part of assessment for people with alcohol related liver Barcelona, Spain; 5Institut Catalá de la Salut (ICS), Centre d’Assisteǹ cia
disease. For those presenting acutely in hospital, staging tests are Primària La Marina, Barcelona, Spain
frequently deferred until out-patient review. However, engagement Email: [email protected]
with elective services is often poor in those with ongoing alcohol use,
Background and aims: Non-alcoholic fatty liver disease (NAFLD) has
leaving investigation incomplete and the need for hepatology follow-
a wide range of clinical severity from fatty liver to cirrhosis. Most
up uncertain. To mitigate this, we instituted an in-patient fibrosis
cases of fatty liver are diagnosed in the community setting. There is
assessment service within our Alcohol Care Team (ACT) and
lack of information on the evolution of fatty liver in subjects
evaluated the results.
diagnosed in primary care. The objective of this study was to
Method: From February 2020-October 2021, we sought out acutely
perform a longitudinal analysis of hepatic steatosis, as estimated by
admitted patients who had been identified as drinking excessively
controlled attenuation parameter (CAP), in a cohort of patients with
(more than the United Kingdom guidance of 14 units/week) and who
fatty liver associated with metabolic syndrome.
had previously not engaged with the ACT for staging of suspected
Method: Patients with fatty liver with moderate-to-severe steatosis
liver disease. All patients were staged by Fibroscan (Echosens).
(CAP >280 dB/m) without significant fibrosis (liver stiffness meas-
Enhanced Liver Fibrosis (ELF) test was additionally performed when
urement-LSM-<8 kPa) previously included in a population-based
it became available at our facility. Implementation of the pilot was
cohort randomly selected from primary care (Plos One 2018 PMD
delayed and disrupted due to the impact of Covid-19 on service
30226889) were again assessed after a median of 5 years of follow-
delivery, with most patients identified from March 2021 onwards.
up. Demographic, clinical, and laboratory data, as well as CAP and
Results: 70 patients were identified-45 (64%) male, 25 (36%) female,
LSM were assessed at two time points, baseline and 5 years later.
with median age 53 years (range 25–80 yr). Fibroscan results ranged
Nurse education and counseling about NAFLD was provided at time of
from 3.4 kPa–75 kPa. 40 (57%) were normal (<7.0 kPa), 13 (19%) F1–F3
first assessment. Improvement of hepatic steatosis was defined as
(7.1 kPa–18.5 kPa) and 17 (24%) F4 (>18.5 kPa). ELF was performed in
decrease in CAp >10% compared to baseline. Remaining cases were
32 (46%) patients; 19 (59%) showed severe fibrosis (score 9.8–14.3)
considered as persistent or worsening (CAP increase of >10%).
and 13 (41%) moderate fibrosis (score 7.9–9.6). ELF and Fibroscan
Results: Seventy-one patients were included (60 ± 11 years; 49%
were well matched for identification of cirrhosis, with cirrhotic range
female; BMI 29.9 ± 4.8; 22.5% with diabetes). Baseline CAP and LSM
Fibroscan results only found in those with severe fibrosis on ELF,
values were 315 ± 32 dB/m and 4.9 ± 1.4 kPa. Twenty-six of the 71
suggesting either test could be used to rule out cirrhosis in this group.
(37%) patients showed improvement in hepatic steatosis (CAP 320 to
Following Fibroscan assessment, annual ACT follow-up was arranged
231 dB/min; p < 0.001). In 15 of these patients CAP decreased to
for all patients in F1–F3 range, and the 25 patients with a normal
<240 dB/m, the threshold generally used to define presence of liver
Fibroscan who continued to drink excessively. Patients with any
fat. Improvement of steatosis was associated with significant
results in the cirrhotic range were referred to hepatology for ongoing
decrease in ALT and GGT levels. The remaining 45 patients, showed
management.
persistent or worsening of hepatic steatosis (32 and 13 patients,
Conclusion: By performing fibrosis assessment during an inpatient
respectively). LSM increased >8 kPa in 3 patients from the latter
stay, we were able to exclude significant liver disease in many people
group (8.1, 11.6 and 12.2) and none from the former. Patients with
we had previously been unable to stage, providing important
improvement of hepatic steatosis had significantly lower BMI and ALT
information to the patient and avoiding unnecessary hepatology
at baseline compared to values in patients with persistent/worsening
follow-up. Provision of in-patient non-invasive fibrosis assessment
of hepatic steatosis.
may therefore be a valuable addition to hospital ACT services for
Conclusion: In this population-based cohort of patients with fatty
capturing patients who poorly engage.
liver from primary care, a significant proportion of subjects (37%)
show mobilization of liver fat during a 5-yr follow-up period with no
intervention other than nurse education and counseling. The
remaining two thirds of subjects show persistence/worsening of
hepatic steatosis. Reduction of liver fat is associated with improve-
ment in ALT and GGT levels.

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ORAL PRESENTATIONS
OS081 they would feel if they were diagnosed with liver cirrhosis: what
The effort for HCV elimination- dedicated nurse based protocol, would change in their life and what would not? Family role, work and
single center experience social life, economic situation, leisure activities, priorities, future
Assaf Issachar1,2, Evelin Oxtrud1, Yael Harif1, Orly Sneh Arbib1,2, perspective, image ( physical and sexual appearance). The writings
Amir Shlomai1,2, Ran Tur-Kaspa1,2, Marius Brown1,2, were analyzed following a semantic interpretive approach (van
Michal Cohen-Naftaly1,2. 1Rabin Medical Center, Beilinson Hospital, Manem 1977), and compared with the literature on patients’ point of
Liver Institute, Petah Tikva, Israel; 2Tel Aviv University, Sakler Medical view and perception.
School, Tel Aviv, Israel Results: Thirty-three stories were collected of which 30 were written
Email: [email protected] in the first person. Four emerging issues were identified: family,
friends and social circles, work situation and self-esteem. The
Background and aims: As part of the global effort for elimination of expressed emotions showed higher coincidence with those previ-
HCV, Israel, as other countries, adopted a simplified guidelines for ously described by patients with ALD. The most recurrent unit of
HCV treatment. meaning was: “Being diagnosed with cirrhosis would mean a radical
Our center is a referral center for liver diseases, since the introduction change in my life”
of the first generation of DAA (INF based protocols) we adopted a Conclusion: The narrative is a useful pedagogical tool in training and
protocol based on open access for HCV patient, dedicated nurse that provides elements of learning to understand responses to complex
communicate with the patients and primary physician before and situations. In the narratives, issues and emotions coincided with
during treatment, same day fibroscan test for every patient followed those described by patients with ALD were identified. Observing and
by physician recommendation for HCV treatment. Following very analyzing oneself by interpreting the cognitive and emotional
good SVR results after this treatment (higher from SVR reported in processes generated by a disease allows one to identify aspects that
literature), we implement the dedicated nurse protocol for the INF contribute to becoming aware of the other’s reality and thus fostering
free protocols. empathy.
The aim of our study is to present the result of our experience.
Method: Using our prospective collected database of HCV patients OS083
who was treated with DAA in our center, we analyzed SVR rate and Nurse-driven post-discharge intervention reduces risk of
some of the patients were asked to complete a questionnaire about readmission and non-attendance in patients with decompensated
the added value of nurse intervention. liver cirrhosis: a randomized controlled study
Results: During 2011–2013 we treated 105 patients with first Malene Barfod O’Connell1, Lise Hobolth1,
generation Peginterferon based DAA with SVR rate of 81%. In the Anne Broedsgaard Madsen2,3, Flemming Bendtsen1,4, Nina Kimer1.
end of 2014, we started to treat with INF free DAA regimens DAA. 831 1
Copenhagen University Hospital, Amager Hvidovre, Gastro Unit,
patients were treated with SVR rate of 98.9%. 33 of the patients were Medical Division, Hvidovre, Denmark; 2Copenhagen University Hospital,
organ transplant patient. 426 patients were diagnosed to have F3–4 Amager Hvidovre, Department of Paediatrics and Adolescent Medicine,
fibrosis based on their fibroscan results and these patients continue Hvidovre, Denmark; 3Aarhus University, Department of Public Health,
surveillance post SVR. 74 patients completed the questionnaire about Research Unit for Nursing and Health Care, Aarhus C, Denmark;
the value of the dedicated nurse intervention. All patients were 4
Copenhagen University Hospital, Amager Hvidovre, Department of
satisfied with the professionalism of the team. 85% of the patients felt Clinical Medicine, Hvidovre, Denmark
that the explanation provided by the nurse during the appointment Email: [email protected]
contributed to their understanding of their medical situation and the
importance of the treatment. Background and aims: Patients with decompensated liver cirrhosis
Conclusion: SVR rate of DAA based HCV treatment in our center is are on average admitted 3 times per year and 20–37% of the patients
very high. The patients pointed the added value of nurse explana- are readmitted within 30 days from discharge. Repeated admissions
tions, instruction and follow-up for better understanding of the have great personal and societal consequences and non-attendance
disease and the importance of treatment and follow-up. Intervention at out-patient visits may impact clinical outcome. In this study we
by dedicated nurses improves the communication and compliance. investigated how a post-discharge nurse-driven intervention affected
readmissions and outpatient attendance for patients with decom-
OS082 pensated liver cirrhosis
Advanced liver disease: master’s students’ perception. An exercise Method: This randomized controlled intervention was conducted in
of introspection the Gastro Unit of a university hospital in the Capital region of
Eva Roman1,2, Montserrat Guillaumet1, German Soriano2, Denmark. Patients admitted with decompensated liver cirrhosis were
Maria Poca2, Edilmar Alvarado-Tapias2, Àngels Escorsell2. 1School of eligible for inclusion. The control group received standard post-
Nursing. Universitat Autònoma de Barcelona, Spain; 2CIBERehd. Instituto discharge care. The intervention group participated in a nurse-driven
de Salud Carlos III., Madrid post-discharge intervention based on concepts from Family Nursing.
Email: [email protected] Before discharge the patient and family received a pamphlet with
information on preventive measures. After discharge the participants
Background and aims: Advanced liver disease (ALD) produces received three monthly home visits by a nurse specialist in liver
physical and mental changes that drastically affect the lived diseases comprising: therapeutic conversations; evidence-based
experience of people who suffer from it, affects self-image and self- information and help to initialize contact to municipal offers. After
perception, social and affective relationships, activities and the idea three months the patients received three monthly follow-up
of the future. Empathy allows us to understand each other’s telephone calls, to a total of six months follow-up.
experiences, concerns, and perspectives, as well as communicate Results: Between December 2019 and October 2021, 111 participants
this understanding (Moser, Intensive Crit Care Nurs 2003). To analyze were included. Twenty-four participants were excluded due to
the understanding of the losses and changes experienced by persons cancer, death before intervention or withdrawal of consent, leaving
with ALD, their experience and transformation, through the narrative 42 participants in the intervention group and 44 participants in the
based on an exercise of introspection centred on reflection by control group. Fifty-three (62%) were male, mean age was 60.7 years,
resident physicians studying a master on digestive diseases. 81 (94%) had alcohol related cirrhosis, and 43 was classified as Child-
Method: 3rd year resident doctors of the gastroenterology speciality, Pugh C (Child score ≥10), without significant difference between the
students of the master’s degree of the Catalan Society of two groups. Nineteen (45%) participants in the intervention group
Gastroenterology during the 2019–2020 academic year. Students were readmitted within six months compared to 27 (61%) in the
had to do an introspection exercise and tell in the first person how

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 ORAL PRESENTATIONS
control group; (HR 0.42; 95% CI: 0.253 to 0.692; stratified log-rank p regeneration. The induction of IFN-I was also confirmed in the liver of
= 0.002). Therefore, the intervention was associated with a 58% MAGLMye−/− mice 24 h after the injury and in bone marrow derived
reduction in the risk of readmission compared to the control group. macrophages (BMDM) exposed to the MAGL pharmacological
Median time to readmission was 42 days in the intervention group as inhibitor MJN110.. We cultured primary hepatocytes with IFN-α
compared to 21 days in the control group ( p = 0.0596). Five and/or -β and found that both reduce hepatocyte proliferation in vitro
participants in the intervention group did not appear for a total of with a cumulative effect of IFN-α and IFN-β. The link between IFN
six outpatient visits during the follow-up period, compared to 17 pathway and liver regeneration defect was finally demonstrated in an
participants in the control group who did not appear for 29 visits (HR in vivo rescue experiment since the injection of IFN type I receptor
0.21; 95% CI 0.07 to 0.65; stratified log-rank p = 0.007). neutralizing antibodies in MAGLMye−/− mice before and during the
Conclusion: In a randomized controlled study, a nurse-driven post- regeneration process restored hepatocyte proliferation to the level of
discharge intervention for patients with liver cirrhosis proved a control mice.
significant reduction in readmissions and in non-attendance for out- Conclusion: Inhibition of MAGL macrophages compromises liver
patient visits in the intervention group. The period from discharge to regeneration by inducing IFN-I pathway that negatively impacts on
first readmission was longer in the intervention group but not hepatocyte proliferation.
statistically significant from the control group.
OS085
Complete vascular tree reconstruction in rat decellularized liver
scaffolds using differential recellularization pressures
Sandra Melitón Barbancho1,2, Pedro Baptista1,3,4,5,
Gut microbiota in liver disease and liver Alba Pueyo Moliner2. 1Aragón Health Research Institute (IIS Aragón),
regeneration CIBA, Zaragoza, Spain; 2University of Zaragoza, Zaragoza, Spain; 3Centro
de investigación biomédica en red, Hepatic Diseases, Madrid, Spain;
4
Universidad Carlos III de Madrid, Department of Biomedical and
OS084 Aerospace Engineering, Madrid, Spain; 5Fundación ARAID, Zaragoza,
Monoacylglycerol lipase inhibition specifically in macrophages Spain
compromises liver regeneration by inducing interferon type 1 Email: [email protected]
that negatively impacts on hepatocyte proliferation
Background and aims: There are still several challenges slowing the
Manon Allaire1, Rola Al-Sayegh1, Morgane Mabire1, Matthieu Siebert1,
translation of bioengineered livers to the clinic in order to reduce the
Mathilde Cadoux1, JingHong Wan1, Maude Le Gall1, Catherine Postic2,
shortage of organs. One of the most important is to provide the whole
Hervé Guillou3, Pierre de la Grange4, Sophie Lotersztajn1,
organ with a robust vascular network that allows its perfusion and
Hélène Gilgenkrantz1. 1Université de Paris, Centre de Recherche sur
maintenance in vivo. Effective revascularization of decellularized liver
l’Inflammation (CRI), Paris, France; 2Université de Paris, Institut Cochin,
scaffolds (DLS) is still elusive, so this work focused on the
INSERM U1016, CNRS, Paris, France; 3Toxalim (Research centre in Food
revascularization of DLS, presenting an effective approach for
Toxicology), INRAE, ENVT, INP-Purpan, PS, Université de Toulouse,
generating functional vasculature that allows us to be closer to the
Toulouse; 4GenoSplice, Paris, France
bioengineered liver.
Email: [email protected]
Method: Whitin a bioreactor setup, endothelial cells [unlabelled for
Background and aims: Monoacylglycerol lipase (MAGL) is a vena cava and labelled with GFP and tdTomato, for portal vein (PV)
proinflammatory enzyme that reprograms lipid metabolism by and hepatic artery (HA), respectively] ( pUVECs), smooth muscle cells
converting monoacylglycerols into free fatty acids, in particular ( pA-SMCs) and mesenchymal stem cells ( pBM-MSCs) were injected
arachidonic acid. We have previously shown that MAGL displays pro- through HA, PV, and vena cava using distinct seeding pressures to
regenerative properties in the liver by demonstrating the direct target the different vessel diameters. Next, maturation was enhanced
contribution of MAGL from hepatocytes and the indirect effects of by providing growth factors for vasculogenesis and angiogenesis
MAGL from liver macrophages in this impact (Allaire et al, EASL process keeping constant mechanical-stimulation for 14 days.
2021). The aim of this study is to uncover the mechanisms by which Microscopic analysis was performed by hematoxylin-eosin (HandE)
MAGL from macrophages modulates liver regeneration. and immunofluorescence (IF) staining’s. Finally, pUVECs function was
Method: Mice with genetic invalidation in myeloid cells (MAGLMye evaluated by nitric oxide (NO) and prostacyclin (PGI2) secretion and
−/−
) were submitted to a liver regeneration stimulus induced by an the contraction of pA-SMC after carbachol inoculation was observed.
acute intraperitoneal injection of carbon tetrachloride (CCl4). Gene Results: HandE analysis confirmed the lining growth of the different
expression profiling of liver MAGLMye−/− macrophages was assessed kind of cells inside of the decellularized vascular tree. Moreover, IF
by RNASequencing analysis. The role of identified pathways was confirmed the accurate arrangement of pUVECs into vascular-like
confirmed in vitro in primary hepatocyte cell culture and in vivo by structures with pBM-MSCs/pA-SMCs arranged around them. Also,
injecting neutralizing antibodies. pUVEC-TdTomato and pUVECs-GFP differential seeding through HA
Results: Mice with a specific MAGL deletion in myeloid cells showed and PV respectively showed a targeting layout. Secretion of NO and
a regeneration defect compared to their wild type counterparts. prostacyclin was confirmed upon bradykinin challenge and a
RNASeq analysis demonstrated an induction of interferon-stimulated pressure increase in the vascular tree was observed because of the
genes in MAGL depleted liver macrophages, suggesting that inter- contraction of pA-SMC after exposure to carbachol.
feron type I (IFN-I) pathway plays a major role in the delayed

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ORAL PRESENTATIONS
OS086
Orthotopic transplantation of the functional bioengineered liver
prolonged survival in rats with total hepatectomy
Beibei Guo1, Li Jiang2, Jing Jiang1, Qian Zhou1, Jiaxian Chen1,
Jiaojiao Xin1, Dongyan Shi1, Keke Ren1, Xingping Zhou1, Genren Yang2,
Jun Li1. 1The First Affiliated Hospital, Zhejiang University School of
Medicine, State Key Laboratory for Diagnosis and Treatment of Infectious
Diseases, National Clinical Research Center for Infectious Diseases,
Collaborative Innovation Center for Diagnosis and Treatment of
Infectious Diseases, Hangzhou, China; 2The First Affiliated Hospital,
Zhejiang University School of Medicine, Hangzhou, China
Email: [email protected]
Background and aims: Functional bioengineered liver (FBL) is a
promising alternative to orthotopic liver transplantation. This study
aims to determine the therapeutic potency of the FBLs with whole
decellularized liver scaffold (DLS) using orthotopic transplantation in
rat.
Method: The FBLs were developed using the whole rat DLSs with
1.5*107 human umbilical vein endothelial cell lines (HUVECs)
implanted through portal vein, 6*107 human bone marrow mesen-
Figure: Recellularized portal vein (red) and hepatic artery (green) with chymal stem cells (hBMSCs) and 3*108 mouse hepatocyte cell lines
pUVEC-TdTomato and pUVECs-GFP respectively in a bioreactor system implanted through bile ducts. The FBLs evaluated with endothelial
after 14 days. GFP: Green fluorescent protein; RFP: Red fluorescent protein barrier function, bio-synthesis and metabolism were used to
and DAPI: 4 ‘, 6-diamidino-2-phenylindole. orthotopically transplanted into rats for determining survival benefit.
Results: The morphological observation exhibited the well-orga-
Conclusion: The generation of a complete and functional vascular
nized vascular structure lining by HUVECs in vascularized bioengi-
tree in DLS using distinct cell types and seeding pressures in a
neered liver. Histological and scanning electronic microscopy analysis
bioreactor system with defined maturation conditions is now possible
showed endothelial barrier function with lower leakage of blood cells
with the validation of the revascularization method here presented.
of the vascularized bioengineered liver. The new developed bioengi-
neered liver displayed that hBMSCs and hepatocytes were, well-
aligned, and uniformly distributed over parenchymal space, and
HUVECs formed the endothelialized microvascular structure.
Significant increases of urea productions and albumin level in
culture medium demonstrated that FBLs possessed ammonium
translation and albumin synthesis functions. Orthotopic transplant-
ation with FBLs rescued rats with a survival time of up to 100 min,

Figure: (abstract: OS086): A. Schematic diagram of orthotopic transplantation of a functional liver-like organ; B. orthotopic transplantation of decellular-
ized liver scaffolds and functional liver-like organs; C. Survival curve after orthotopic transplantation; D. Histological identification after transplantation.

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 ORAL PRESENTATIONS
whereas all rats transplanted with DLS died within an average of with infection versus uninfected patients and interaction with
25 min. Histological staining showed that most perfused blood cells virome.
were limited into vascular lumen and the implanted cells, with Method: Patients with cirrhosis were recruited, including out-
positive immunofluorescence staining of CD90 and ALB, evenly patients with/without decompensation and inpatients admitted
distributed into the parenchymal space around vessels in the with/without infections. All pts underwent stool collection for
transplanted FBLs, but the transplanted DLSs became a pool entirely metagenomics for bacterial and phage species. In inpts, stool was
filled with blood cells. collected before antibiotics. DESeq2, PCoA, and correlation network
Conclusion: The orthotopically transplanted FBLs effectively pro- analyses were performed between (a) all uninfected vs. infected
longed the survival time of rats with total hepatectomy. This study patients and (b) inpatients with/without infections matched 1:1 by
first determined the therapeutic potency of FBLs using orthotopic MELD score, demographics, and medications.
transplantation, which provides a promising alternative to the liver Results: 231 pts with cirrhosis were recruited, of which 30 were
donor shortage for future clinical therapeutic applications. infected (20 SBP, 10 UTI). Unmatched comparison showed that
infected pts had worse cirrhosis severity. PPI use was similar (Fig A).
OS087 After matching for MELD score, inpatients with infections had similar
Bacterial infections in cirrhosis are associated with reduction in disease severity (Ascites, HE) and medication use compared to those
gut microbial phage-bacterial interactions without infections (Fig A).
Amirhossein Shamsaddini1, Marcela Peña Rodríguez2, Metagenomics: Unmatched analysis: Pathobionts (Enterococcus spp,
Andrew Fagan3, Sara McGeorge3, Masoumeh Sikaroodi1, C.difficile) were higher, while short-chain fatty acid producers
Patrick Gillevet1, Jasmohan S. Bajaj3. 1George Mason University; (Ruminococcus. Alistipes spp) were lower in infected patients.
2
Universidad de Guadalajara; 3Virginia Commonwealth University CrAssphages, Bifidobacterium, and Streptococcus phages were lower
Email: [email protected] in infected patients. There was also a clear separation on β diversity
(PERMANOVA p < 0.0001) between groups on bacterial and phage
Background and aims: The impact of bacterial infections on gut
species. Matched analysis: Higher pathobionts (E.faecalis, E.faecium,
microbiota in cirrhosis is unclear since disease severity and antibiotic
C.difficile) along with Lactobacillus spp and oral-origin taxa (Fig B)
use could affect these changes. There is increasing evidence of the
persisted even after matching. Phages corresponding to these
role of bacteriophages in the modulation of infection risk and as
bacteria were also higher vs. uninfected pts (Fig C). PCoA showed β-
potential treatment strategies. However, changes in the interaction of
diversity changes in bacteria (Fig D) and phages (Fig E) between
the virome with metagenome in infected patients with cirrhosis are
groups. Correlation network: between phages and bacteria showed a
unclear. Determine change in the metagenome of pts with cirrhosis
collapse between linkages in infected patients centred around

Figure: (abstract: OS087): Characteristics and comparisons between infected and uninfected patients.

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ORAL PRESENTATIONS
Enterococcus (Fig G/H) and Veillonella spp (Fig I/J). Network OS089
heterogeneity was higher in infected vs matched uninfected (1.066 In-depth shotgun metagenomic analysis of the oral and gut
vs 1.027) and in unmatched cohorts (1.183 vs 1.025). microbiome identifies striking overlap in microbial community
Conclusion: Collapse of phage-bacterial interactions centred around structure, virulence factors and antimicrobial resistance genes
Enterococcus, Enterobacteriaceae spp and oral-origin taxa are linked based on stage and severity of cirrhosis
with bacterial infections. This pattern persists even when infected pts Sunjae Lee1, Bethlehem Arefaine2, Neelu Begum1,
are compared to disease severity-matched inpatients without Elizabeth Witherden1, Marilena Stamouli2, Azadeh Harzandi1,
infections before antibiotics. Phages directed against pathobionts Ane Zamalloa3, Eleanor Corcoran4, Roger Williams2,5,
could be targeted to prevent these infections. Shilpa Chokshi2,5, Gordon Proctor1, Adil Mardinoglu1,6,
Mathias Uhlen6, Saeed Shoaie1,6, Vishal C. Patel2,5,7. 1Centre for Host
OS088 Microbial Interactions, King’s College London, London, United Kingdom;
Altered gut microbiome, metabolome and bile acid composition 2
The Roger Williams Institute of Hepatology, Foundation for Liver
in sarcopenia in liver cirrhosis Research, London, United Kingdom; 3Institute of Liver Studies and
Benard Aliwa1,2, Nicole Feldbacher1,3, Angela Horvath1,3, Julia Traub4, Transplantation, King’s College Hospital NHS Foundation Trust, London,
Tobias Madl5, Günter Fauler6, Vanessa Stadlbauer1,3. 1Medical United Kingdom; 4Department of Critical Care, King’s College Hospital
University of Graz, Department of Gastroenterology and Hepatology, NHS Foundation Trust, London, United Kingdom; 5School of Immunology
Graz, Austria; 2University of Nairobi, Department of Food Science, and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s
Nutrition and Technology, Nairobi, Kenya; 3CBmed Center of Biomarker College London, London, United Kingdom; 6SciLifeLab, KTH — Royal
Research in Medicine, Area Microbiome Research, Graz, Austria; Institute of Technology, Sweden, Sweden; 7Institute of Liver Studies and
4
University Hospital Graz, Dietology Services, Graz, Austria; 5Medical Transplantation, King’s College Hospital, London, United Kingdom
University of Graz, Gottfried Schatz Research Center for Cell Signaling, Email: [email protected]
Metabolism and Aging Molecular Biology and Biochemistry, Graz,
Austria; 6Medical University of Graz, Klinisches Institut für Medizinische Background and aims: Alterations in the gut microbiome in
und Chemische Labordiagnostik (KIMCL), Graz, Austria decompensated cirrhosis (DC) and acute on chronic liver failure
Email: [email protected] (ACLF) are recognised as being critical in influencing clinical
outcomes (Trebicka et al., Nat Rev Gastro Hepatol, 2020).
Background and aims: 50–70% of liver cirrhotic patients suffer from Knowledge of the oral microbiome is evolving and is increasingly
sarcopenia leading to high mortality risk. The gut microbiome can recognised as predisposing to hepatic decompensation (Acharya
metabolize bile acids and in turn bile acids can shape the gut et al., JCI Insight, 2017). Our aims were to interrogate simultaneously
microbiome community structure. We aimed to study differences in the gut and oral microbiome by shotgun metagenomic sequencing of
gut microbiome, bile acids and metabolite composition between faecal and saliva samples, respectively, in cirrhosis patients of varying
sarcopenia and non-sarcopenia in liver cirrhosis and control. severities, with healthy and positive disease controls.
Method: We analyzed 16 s rDNA sequencing of fecal microbiome and Method: 18 healthy controls (HC), 20 stable cirrhotics (SC), 50 DC, 18
measured bile acids and metabolites of cirrhotic patients with and ACLF and 15 with non-liver sepsis (NLS) i.e. severe infection but
without sarcopenia (n = 78 and n = 38, respectively) as well as control without cirrhosis were prospectively recruited. DNA extractions were
with and without sarcopenia (n = 39 and n = 20, respectively). LEfSe, undertaken from saliva and faecal samples and Illumina sequenced
ANCOM, and LASSO regression, and multivariate logistic regression on a NovaSeq 6000 to a minimum depth of 20 million reads. Filtered
were applied. and trimmed reads were aligned to a human microbiome integrated
Results: We demonstrated that both in cirrhotic and control patients, gene catalogue. Salivatypes and enterotypes were calculated by
sarcopenia associates with a significant reduction in bacteria capable scaling genus profile abundance and clustering by Dirichlet multi-
of generating branched-chain amino acids and short-chain fatty acids nomial mixture models. Comprehensive Antimicrobial Resistance
and a significant increase in bacteria capable of generating secondary Gene (ARG) and KEGG Orthology databases were used to evaluate
bile acid (Sec-BAs). Sutterella species, Vellionella parvula, Bacteroides ARGs and functional annotations, respectively.
(B.) fragilis, and Blautia marseille were associated with sarcopenia and Results: There was a striking decrement in Shannon diversity in the
B. ovatus, Alistipes putredinis, Eubacterium, and Ruminococcaceae were DC and ACLF cohorts vs HC and NLS (Fig A, D). Specific saliva- and
associated with non-sarcopenia. In sarcopenic cirrhotic patients, we enterotypes were identified based on clustering of genera, with a
observed significantly elevated Sec-BAs, including deoxycholic acid greater proportion of pathobionts and simultaneous reduction in
(DCA), glycodeoxycholic acid (GDCA), lithocholic acid (LCA), and autochthonous genera detected in specific clusters as cirrhosis
significantly elevated deoxycholic acid to cholic acid (DCA:CA), severity progressed (Fig B, C, E, F). The degree of overlap between
lithocholic acid to chenodeoxycholic acid (LCA:CDCA), glycolitho- oral and gut microbiome communities (independent of antimicro-
cholic acid to chenodeoxycholic acid (GLCA:CDCA) and reduced total bials, beta-blockers and acid suppressant therapies) and functional
ursodeoxycholic acid to total secondary bile acid (T-DCA:T-sec BAs), changes specific to virulence factor over-expression were signifi-
serum valine, and serum acetate. We further observed that genes cantly higher in DC and ACLF vs SC and HCs. Substantial total
coding for 7α-hydroxysteroid dehydrogenase enzyme (7α-HSDH) numbers of ARGs (1, 218 and 672] were detected in the oral and gut
were significantly increased in sarcopenic controls compared to non- microbiome samples, respectively. 575 of ARGs were common to both
sarcopenic controls. Multivariate logistic regression showed that sites, but a greater proportion of these were harboured in the gut
MAMC, BMI, serum valine, serum acetate, GLCA:CDCA, T-DCA:T-sec (>85%) compared to the oral niche (47%), with overall ARG frequency
BAs, and B. ovatus were independent predictors for sarcopenia in liver incrementing with worsening cirrhosis (Fig G–I).
cirrhosis even when corrected for severity of disease and drug use. Conclusion: Oral and gut microbiome profiles differ significantly
Conclusion: B. ovatus, serum valine, serum acetate and bile acid according to severity of cirrhosis, with specific saliva- and enterotype
profiles are independent predictors for sarcopenia and potential clusters reflecting dominance by pathobionts and loss of commen-
biomarkers for muscle health in liver cirrhosis. Further studies are sals. The degree of microbial community overlap between the mouth
needed to assess whether increasing B. ovatus abundance, serum and gut, virulence factor and ARG frequency all increment signifi-
valine, serum acetate, or altering bile acid composition may affect cantly as cirrhosis worsens. These alterations that predispose to
muscle health. higher infection risk, poorer response to antimicrobial therapy and
triggers for hepatic decompensation now form the rationale for non-
antibiotic-dependant microbiome-modulating targeted therapies.

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 ORAL PRESENTATIONS

Figure: (abstract: OS089)

people worldwide. VIR-2218 is a small interfering ribonucleic acid

Saturday 25 June (siRNA) therapeutic targeting the hepatitis B virus X region of the
HBV genome currently in development for the treatment of HBV
infection. Here, we report preliminary data from an ongoing study
evaluating the safety, tolerability, and antiviral activity of 2 dosing
regimens of VIR-2218 in participants with HBV infection.
Hepatitis B emerging therapies Method: This open-label phase 2 study enrolled adult, virally
suppressed, hepatitis B e antigen (HBeAg)-positive or negative
participants with chronic HBV infection without cirrhosis. Dosing
OS090 regimens of 2 doses (n = 6) or 6 doses (n = 15) of VIR-2218 200 mg
Longer treatment duration of monthly VIR-2218 results in deeper given subcutaneously every 4 weeks were evaluated. Preliminary
and more sustained reductions in hepatitis B surface antigen in data up to the final follow-up visits for the 2-dose (week 48) and 6-
participants with chronic hepatitis B infection dose (week 44) regimens are presented.
Young-Suk Lim1, Man-Fung Yuen2, Daniel Cloutier3, Results: Five of 6 participants receiving the 2-dose regimen
Vaidehi Thanawala3, Ling Shen3, Sneha V. Gupta3, Andre Arizpe3, completed study week 48 and, to date, 7 of 15 participants receiving
Andrea Cathcart3, Carey Hwang3, Edward J. Gane4. 1University of Ulsan the 6-dose regimen have completed study week 44. All participants
College of Medicine, Asan Medical Center, Seoul, Korea, Rep. of South; achieved >1-log reduction in hepatitis B surface antigen (HBsAg). The
2
The University of Hong Kong, Queen Mary Hospital, Hong Kong, China; 6-dose regimen was associated with greater mean maximum HBsAg
3
Vir Biotechnology, Inc., San Francisco, California, United States; reduction (−1.96 vs −1.61 log10 IU/ml), and more sustained HBsAg
4
University of Auckland, Faculty of Medicine, Auckland, New Zealand reductions (−1.76 vs −0.87 log10 IU/ml at week 44) compared with
Email: [email protected] the 2-dose regimen (Figure). In both cohorts, adverse events (AEs)
were generally grade 1 or 2 and no AEs resulted in discontinuation of
Background and aims: Chronic hepatitis B virus (HBV) infection is a
study drug. Most participants had normal alanine aminotransferase
substantial global health issue affecting more than 290 million

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S69

ORAL PRESENTATIONS
(ALT) levels throughout the study; 2 participants in each regimen had CHB patients with 24-week subcutaneous PD-L1 antibody ASC22
grade 1 ALT elevations. No treatment-related serious AEs were (Envafolimab) plus Nucleos (t)ide analogs (NAs) treatment.
reported. Method: This randomized, single-blind, multi-center Phase IIb trial
enrolled a total of 149 CHB patients (negative HBeAg, HBsAg
≤10000 IU/ml and HBV DNA <20 IU/ml) in two cohorts for 24-week
treatment of ASC22 (1 or 2.5 mg/kg) and 24-week follow-up
(NCT04465890). The relationship between ALT flares and HBsAg
reduction/loss was analyzed in patients who completed 24-week
treatment of 1 mg/kg ASC22 Q2W (n = 33) or PBO Q2W (n = 11) + NAs.
An ALT flare is defined as a transient elevation in serum ALT greater
than 3-fold baseline level and more than 2X ULN (upper limit of
normal).
Results: The baseline serum levels of HBsAg, ALT and AST were
comparable between patients receiving ASC22 or PBO plus NAs.
Seven patients had HBsAg reduction >0.5 log10 IU/ml, and were all
with baseline HBsAg ≤500 IU/ml. Three patients even experienced
HBsAg seroclearance (undetectable, <0.05 IU/ml). One patient with
HBsAg loss had seroconversion of HBsAb 6 weeks after the last dosing
of ASC22 (Figure 1A). ALT flares were observed in 5/33 (15%) patients
in ASC22 group compared to none in PBO group. Among the patients
with HBsAg reduction >0.5 log10 IU/ml or HBsAg loss, 4/7 (57%) and 2/
3 (67%) experienced ALT flares, respectively (Figure 1B). No clinically
meaningful changes of total or direct bilirubin were observed in
patients with ALT flares. However, more immune-related AEs (irAEs)
Conclusion: These preliminary data support that a longer duration of occurred in ASC22 group. Most common irAEs were Grade 1 ALT/AST
treatment with VIR-2218 results in deeper and more sustained elevation and rash.
reductions in HBsAg. In both regimens of VIR-2218, no differences in
safety or tolerability were observed.

OS091
ALT flares were linked to HBsAg reduction, seroclearance and
seroconversion: interim results from a phase IIb study in chronic
hepatitis B patients with 24-week treatment of subcutaneous PD-
L1 Ab ASC22 (Envafolimab) plus nucleos (t)ide analogs
Guiqiang Wang1, Yimin Cui2, Yao Xie3, Qianguo Mao4, Qing Xie5,
Ye Gu6, Xin-Yue Chen7, Guoxin Hu8, Yongfeng Yang9, Jiajie Lu10,
Guizhou Zou11, Qin Zhang12, Lei Fu13, Yongping Chen14, Xiaolin Guo15,
Jinlin Hou16, Yuemei Yan17, Handan He17, Jinzi Wu17. 1Peking University
First Hospital, Infectious Diseases Department, Beijing, China; 2Peking
University First Hospital, Clinical Trial Center, Beijing, China; 3Beijing
Ditan Hospital Capital Medical University, Beijing, China; 4Xiamen
Hospital of Traditional Chinese Medicine, Xiamen, China; 5Ruijin Conclusion: ALT flares occurring during ASC22 treatment were
Hospital of Medical College of Shanghai Jiaotong University, Infectious shown to be an indicator of a clinically meaningful immune response,
Diseases Department, Shanghai, China; 6Shenyang Sixth People’s resulting in significant HBsAg reduction and subsequent HBsAg loss/
Hospital, Shenyang, China; 7Beijing YouAn Hospital Capital Medical HBsAb seroconversion.
University, Beijing, China; 8Peking University Shenzhen Hospital,
OS092
Shenzhen, China; 9Nanjing Second Hospital, Nanjing, China; 10West
Lonafarnib combination with peginterferon Lambda diminished
China Hospital of Sichuan University, Chengdu, China; 11The Second
triphasic HDV kinetic pattrn seen under Lambda monotherapy:
Affiliated Hospital of Anhui Medical University, Hefei, China, 12Shanghai
the LIFT HDV study
Tongren Hospital, 上海, China; 13Xiangya Hospital of Central South
University, Changsha, China; 14The First Affiliated Hospital of Wenzhou Sarah Duehren1, Christopher Koh2, Julian Hercun2, Farial Rahman2,
Medical University, Wenzhou, China; 15The First Hospital of Jilin Pallavi Surana2, Anusha Vittal2, Walter Lai2, Ohad Etzion3,
University, Changchun, China; 16Nanfang Hospital of Southern Medical Scott Cotler1, Jeffrey Glenn4, Harel Dahari1, Theo Heller2. 1Program for
University, Guangzhou, China; 17Ascletis BioScience Co., Ltd., Hangzhou, Experimental and Theoretical Modeling, Division of Hepatology,
China Department of Medicine, Stritch School of Medicine, Loyola University
Email: [email protected] Chicago, Maywood, United States; 2Liver Diseases Branch, NIDDK, NIH,
Bethesda, United States; 3Soroka University Medical Center, Beer-Sheba,
Background and aims: Blockade of PD-1/PD-L1 pathway can restore Israel; 4Division of Gastroenterology and Hepatology, Stanford University
T cell functions and lead to a potential cure for chronic hepatitis B School of Medicine, Stanford, United States
(CHB). Hepatitis flares are considered to be mainly immune- Email: [email protected]
mediated and may be linked or mark transitions to HBsAg reduction,
even clearance. Previous studies indicated that PegIFN treatment may Background and aims: We recently reported that Lambda InterFeron
result in 18–24% of patients with ALT flares since it is an immune combination Therapy (LIFT) is safe and tolerable for up to 6 months in
modulators. siRNA, a direct antiviral, however, caused as low as 6% of most patients with HDV. The goal of the current study was to
patients with ALT flares. Here we reported characterization of ALT characterize HDV RNA, HBV DNA, HBsAg and ALT kinetics during and
flares and their relationship with HBsAg reduction, seroclearance and after lonafarnib (LNF) and pegylated IFN-λ (Lambda) combination
seroconversion from the interim analysis of a Phase IIb clinical trial in therapy.
Method: Twenty-six chronic HDV infected patients participated in a
randomized, open-label Phase 2a clinical study of oral LNF 50 mg plus

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 ORAL PRESENTATIONS

Figure: (abstract: OS092)

ritonavir (RTV) 100 mg twice daily and subcutaneous Lambda maintained high levels throughout treatment, and 4 dropped to TND.
180 mcg weekly for 24 weeks, followed by per-protocol post- A 2 log decline (or LoQ, n = 15) from pre-treatment HDV levels at end
therapy monitoring for 24 weeks. Three patients completed <24 of therapy (EOT) was seen in 23 (88%) patients: 9/9 MP, 11/11 BP, 2/
weeks (12, 16, and 20 weeks). All participants were started on 2 TP, 1/4 FPR. Mean ALT level at EOT was 94 IU/ml [IQR 31], similar to
tenofovir or entecavir prior to therapy. Kinetic data were obtained pretreatment levels. At end of follow-up (EFU), 5 (4 MP and 1 BP) out
weekly for the first four weeks, and then every four weeks during and of 15 patients who had HDV LoQ at EOT remained LoQ (Fig. 1A and B),
post treatment. HDV kinetic phase changes were defined as a 2-fold and the remaining had rebound (from EOT) with a mean value of
change in slope. HDV RNA was measured by Robogene 2.0 (limit of 4.83 log IU/ml [IQR 1.9]. Eleven (42%) patients achieved ALT
quantification, LoQ = 14 cp/ml). normalization at EFU.
Results: Mean pretreatment HDV RNA, ALT, and HBsAg were 4.9 log Conclusion: We previously reported in the LIMT-1 study (The Liver
IU/ml [IQR 1.6], 80 U/L [IQR 45], and 3.8 log cp/ml [IQR 0.5], Meeting, AASLD 2019 #LP12) 5 HDV kinetic patterns under Lambda
respectively. Fourteen (54%) patients had pretreatment HBV DNA monotherapy: MP (19%), BP (22%), FPR (19%), and triphasic/staircase
target not detected (TND) and 12 patients had mean HBV DNA 2.6 log (40%). Compared to Lambda monotherapy, including LNF signifi-
IU/ml [IQR 0.38]. During therapy, patients fit into 4 HDV kinetic cantly ( p = 0.009) diminished the HDV triphasic/staircase kinetic
patterns (Fig. 1): monophasic, MP (n = 9, Fig. 1A), biphasic, BP (n = 11, patterns to 8%, suggesting that LNF reduces intracellular HDV
Fig. 1B), triphasic/transient, TP (n = 2, Fig. 1C), and flat-partial production. The LIMT-1 study saw successful HDV viral decline in
response, FPR (n = 4, Fig. 1D). HBsAg remained at pretreatment level only 45% of patients, while the present study showed 88% success in
in all patients (not shown). All patients had a transient ALT increase reducing HDV by more than 2 log.
during therapy (mean 6-fold [IQR 4] from upper limit of normal
(40 IU/ml). Six (of 14) patients maintained HBV serum levels at TND,
while the other 8 had transient increases or fluctuations from
baseline TND. Of the 12 patients with high baseline HBV DNA levels, 8

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S71

ORAL PRESENTATIONS
OS093 was observed in 8 (15%) patients at W4, in 26 (47%) at W8 and in 38
Real life study of bulevirtide in chronic hepatitis delta: (69%) at W12. The biological response was observed in 36 out of 98
preliminary results of the ANRS HD EP01 BuleDelta prospective (37%) patients at W24 (34% and 40%, with and without peg-IFN,
cohort respectively) and the combined response in 25 (26%) patients at W24
Helene Fontaine1, Claire Fougerou-Leurent2,3, Emmanuel Gordien4, (36% and 17%, with and without peg-IFN, respectively).
Caroline Scholtes5, Sophie Metivier6, Victor de Lédinghen7, In the 43 patients without virologic response at W24, Figure 1
Vlad Ratziu8, Laurent Alric9,10, Nathalie Ganne-Carrié11, presents which therapeutic strategy was adopted. No patient had
Veronique Loustaud-Ratti12, Dominique Guyader13, Vincent Leroy14, Peg-IFN add-on.
Jérôme Dumortier15, Karine Lacombe16, Georges-Philippe Pageaux17,
Anne Minello Franza18, Christelle Tual2,3, Alain Renault3,
Estelle Le Pabic2,3, Lucie Marchand19, Dominique Roulot20, Treatment decision
Fabien Zoulim21. 1Cochin Hospital-APHP, Pôle Hépato-gastroentérologie,
Treatment Increase of BLV BLV
Paris, France; 2Rennes University Hospital, Service de Pharmacologie,
HDV viral load at W24 continuation from 2 to 10 mg/d interruption
Rennes, France; 3Inserm, CIC 1414, Rennes, France; 4Avicenne Hospital,
CNR des hépatites B, C et Delta, Bobigny, France; 5Groupement Quantifiable (n = 34) 26 (76.5%) 6 (17.6%) 2 (5.9%)
Hospitalier Nord-HCL, Laboratoire de Virologie, Lyon, France; 6Rangueil Detectable below 8 (88.9%) 0 (0%) 1 (11.1%)
quantification limit
Hospital, Service d’hépato-gastroentérologie, Toulouse, France; 7Haut-
(n = 9)
Lévêque Hospital, Service d’hépato-gastroentérologie, Bordeaux, France;
8
La Pitié Salpêtrier̀ e Hospital-APHP, Service d’hépato-gastroentérologie, Conclusion: In this first real life study, a decrease of HDV viremia
Paris, France; 9Rangueil Hospital, Service de médecine interne, Toulouse, greater than 2 log IU/ml after 24 weeks of treatment of BLV was
France; 10CHU Rangueil, Digestive Department Toulouse 3 University, observed in more than half of patients with CHD and was associated
Toulouse, France; 11Avicenne Hospital, Service d’Hépatologie, Bobigny, with a normalization of ALT in half of them. Updated results will be
France; 12Dupuytren Hospital, Service d’hépato-gastroentérologie, presented at the meeting.
Limoges, France; 13Rennes University Hospital, Service d’hépato-
gastroentérologie, Rennes, France; 14Henri Mondor Hospital-APHP, OS094
Service d’hépato-gastroentérologie, Créteil, France; 15Edouard Herriot Therapeutic vaccine JNJ-0535 induces a strong HBV-specific T-cell
Hospital -HCL, Service d’hépato-gastroentérologie, Lyon, France; 16Saint response in healthy adults and a modest response in chronic HBV-
Antoine Hospital-APHP, Service des Maladies Infectieuses et Tropicales, infected patients
Paris, France; 17Saint Eloi Hospital, Service d’hépato-gastroentérologie,
An De Creus1, Leen Slaets1, Bart Fevery1, Ellen Van Gulck1,
Montpellier, France; 18Bocage Hospital, Service d’hépato-
Linghua Zhou1, Tim Van De Parre1, Celine Van Den Broeke1,
gastroentérologie, Dijon, France; 19ANRS MIE, Paris, France; 20Avicenne
Dessislava Dimitrova2, Isabelle Lonjon-Domanec1, David Blue, Jr3,
Hospital, Unité fonctionnelle d’hépatologie, Bobigny; 21Croix-Rousse
Pieter Van Remoortere2, Stefan Bourgeois4, Patrick Kennedy5,
Hospital-HCL, Service d’hépato-gastroentérologie, Lyon, France
Sandra De Meyer1. 1Janssen Research and Development, Belgium;
Email: [email protected] 2
Janssen Research and Development, United States; 3Janssen Biopharma,
Background and aims: About 5 % of positive-HBsAg patients are Inc.; 4Hospital Network Antwerp (ZNA), Belgium; 5Barts and The London
infected with the hepatitis Delta virus (HDV), leading to an increase of School of Medicine and Dentistry, United Kingdom
2 to 5-fold of cirrhosis and hepatocellular carcinoma, and a higher Email: [email protected]
mortality in comparison with chronic hepatitis B alone. The
Background and aims: JNJ-0535 is a hepatitis B virus (HBV)-specific
management of chronic hepatitis delta (CHD) has improved recently
therapeutic DNA vaccine administered via electroporation (EP)-
in France, with the availability of bulevirtide (BLV) within an early
mediated intramuscular injection. JNJ-0535 comprises 2 plasmids
access program in September 2019 and thanks to a conditional
encoding either HBV core or polymerase ( pol) proteins. Induction of
marketing authorization since September 2020. functional core and pol-specific T cells was evaluated in healthy and
Method: The aim of the BuleDelta cohort, a French multicenter ANRS
chronic HBV (CHB)-infected individuals.
|MIE observatory is to analyze the efficacy and the safety of BLV in
Method: First in human (FIH) study 64300535HPB1001 evaluated
patients treated since September 2019. This preliminary analysis has
total doses of 0.25 mg (n = 6), 1 mg (n = 7) or 6 mg (n = 10) JNJ-0535
been performed in patients treated for at least 24 weeks (W24). The
(containing equal quantities of the 2 plasmids) or placebo (n = 7)
biological response was defined as a normalization of ALT, the
delivered by intramuscular electroporation with TDS-IM v2.0 in CHB
virologic response as a decrease of HDV RNA of at least 2 log IU/ml or
patients who were virologically suppressed, HBeAg- and on stable
HDV RNA undetectability, the combined response as the association
nucleos (t)ide therapy. Study 64300535HPB1003 evaluates the 6 mg
of both. dose of JNJ-0535 in healthy volunteers (HVs) (n = 12). PBMCs
Results: as of October 1st, 2021, 138 patients have been included in
collected at baseline, during the vaccination period (10–14 days
the BuleDelta cohort: 66% were male, mean ± SD age of 42 ± 11 years;
after the 3 vaccinations, and during follow-up were evaluated for T
54 % were of European or Asian origin and 44 % from Sub-Saharan
cell responses against core and pol using ex vivo IFNγ ELISpot and
Africa, 12 % presented HIV coinfection, 73% were treated with nucleo
intracellular cytokine staining (ICS). Results of the vaccination period
(s)tides analogs (NUC) and 42% with pegylated interferon-α (Peg- will be presented for both studies comparing the 6 mg dose.
IFN).
Results: A ≥3-fold increase in ELISpot responses over baseline to core
At baseline (D0), the mean HDV RNA was 6.1 ± 1.4 log IU/ml; HBV DNA
and/or pol was observed in 5/10 CHB patients (50%) and in 11/12 HVs
was above quantification threshold in 38 patients (mean 2.6 ± 1.6 log
(91.7%) at 6 mg JNJ-0535. Six (50%) HV responded to both antigens
IU/ml).
whereas no CHB patients responded to both antigens. JNJ-0535
The preliminary analysis included the 98 out of 138 patients with vaccination induced a higher median (interquartile range) maximum
available data at W24 in whom 54 (55%) were treated with BLV only,
fold-increase in T cell responses from baseline in HV (24.4 [10.1–51])
and 44 (45 %) in association with peg-IFN. Overall 74 (76 %) were
compared to CHB patients (4.8 [4.4–10]). Overall, vaccine-induced
concomitantly treated with NUC. The mean decrease of HDV RNA at
core-specific CD4+ T cells were polyfunctional in both HV and CHB
W24 was of 1.9 ± 1.4 log IU/ml (2.6 and 1.6 log IU/ml with and
patients for ELISpot responses ≥150 SFU/million PBMC.
without peg-IFN, respectively). The virologic response at W24 was Polyfunctional core-specific CD8+ T cells were only induced in HV.
observed in 55 (56%) patients (80% and 37%, with and without peg-
No safety issues have been identified for JNJ-0535 vaccine delivered
IFN, respectively). Among these 55 patients, the virologic response
by intramuscular electroporation.

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 ORAL PRESENTATIONS
Conclusion: T cell responses induced in HV were superior to those in Conclusion: Similar on- and off-treatment HBV DNA antiviral activity
CHB patients at a JNJ-0535 dose of 6 mg in terms of the proportion of was observed between 25 mg and 50 mg cohorts of ATI-2173 + TDF. In
responders, the magnitude of fold-increase from baseline, the the off-treatment period, ATI-2173 + TDF provided prolonged HBV
breadth (number of antigens) and CD4+ and CD8+ core-specific T DNA suppression, longer time to rebound, and absence of ALT flares
cell polyfunctionality. This supports the hypothesis that CHB compared to TDF alone. 24-week off-treatment data will be presented
infection negatively impacts the ability of patients to induce T cells at the conference.
in response to therapeutic vaccination.

OS095
Sustained 12 week off treatment antiviral efficacy of ATI-2173, a
novel active site polymerase inhibitor nucleotide, combined with NAFLD: Diagnostics and non-invasive
tenofovir disoproxil fumarate in chronic hepatitis B patients, a assessment
phase 2a clinical trial
Myreen Tomas1, Alina Jucov2,3, Igor Anastasiy4, Lauren Ogilvie1,
Karen Fusaro1, Katherine Squires1, Douglas Mayers1. 1Antios OS096
Therapeutics, United States; 2ARENSIA Exploratory Medicine, Moldova; Impact of type 2 diabetes on the accuracy of non-invasive tests of
3
Nicolae Testemitanu State University of Medicine and Pharmacy, liver fibrosis: a comprehensive analysis of 1, 051 biopsy proven
Chisinau, Moldova; 4ARENSIA Exploratory Medicine, Ukraine NAFLD patients showing clinical implications
Email: [email protected] Jerome Boursier1, Clémence M. Canivet1, Charlotte Costentin2,
Adrien Lannes3, Adele Delamarre4, Nathalie Sturm5, Brigitte Le Bail6,
Background and aims: ATI-2173 is a novel phosphoramidate liver-
Sophie Michalak7, Frédéric Oberti3, Marie-Noëlle Hilleret2,
targeted prodrug of clevudine that functions as an active site
Marie Irles-Depe4, Isabelle Fouchard3, Paul Hermabessière4,
polymerase inhibitor nucleotide (ASPIN). In Phase 1, ATI-2173
Justine Barthemon2, Bertrand Cariou8, Victor de Lédinghen4,
demonstrated potent hepatitis B virus (HBV) activity with sustained
Marine Roux1. 1Angers University, HIFIH Laboratory UPRES EA3859;
off-treatment responses 4 to 24 weeks after discontinuation. The 2
Grenoble University Hospital, Hepato-Gastroenterology Department;
SAVE-1 Phase 2a trial evaluated the efficacy of ATI-2173 + tenofovir 3
Angers University Hospital, Hepato-Gastroenterology Department;
disoproxil fumarate (TDF) in treatment-naive chronic HBV-infected 4
Bordeaux University Hospital, Hepato-Gastroenterology Department;
(CHB) patients. 5
Grenoble University Hospital, Pathology Department; 6Bordeaux
Method: A randomized, double-blind, placebo-controlled trial
University Hospital, Pathology Department; 7Angers University Hospital,
(NCT04847440) was conducted at sites in Moldova and Ukraine.
Pathology Department; 8Nantes University
Each cohort had 10 CHB patients randomized 8:2 to receive either
Email: [email protected]
25 mg or 50 mg of ATI-2173 + TDF or placebo (PBO) + TDF daily for 90
days. HBV DNA and HBV RNA were measured using a Roche cobas Background and aims: It has been suggested that non-invasive tests
6800 (lower limit of quantification; LLOQ = 10 IU/ml, and 10 copies/ (NITs) of liver fibrosis are less accurate in type 2 diabetes (T2D). We
ml respectively). The Roche RNA assay is investigational use only. aimed to compare the diagnostic accuracy of six NITs between
Hepatitis B surface antigen (HBsAg) was measured using a Roche patients with and without T2D, to explain the observed differences,
Elecsys (LLOQ = 0.05 IU/ml). and to adapt diagnostic algorithms for clinical practice accordingly.
Results: Most patients were hepatitis B e antigen-negative (90%). Method: 1, 051 patients with non-alcoholic fatty liver disease
Change from baseline virologic responses (HBV DNA) at the end of (NAFLD), liver biopsy, blood fibrosis tests (NAFLD fibrosis score,
treatment for TDF alone (N = 4), 25 mg (N = 8) and 50 mg ATI-2173 + FIB4, Fibrotest, FibroMeterV2G), vibration controlled transient elas-
TDF (N = 8) were −3.53, −3.72, and −3.54 log10 IU/ml, respectively. No tography (VCTE), and the combinatory elasto-blood test
changes in HBsAg were observed. HBV RNA mirrored the HBV DNA FibroMeterVCTE were included. The study end point was advanced
responses on treatment. At 12 weeks off treatment, viral load fibrosis (NASH CRN staging) on liver biopsy.
response in the TDF arm was −0.66, while the 25 mg and 50 mg Results: The difference in result for NAFLD fibrosis score was highly
arms had maintained suppression of −3.20 and −3.50 log10 IU/ml, significant between patients with and without T2D, T2D being
respectively (Figure). 0/4 in the TDF alone, 3/8 in the 25 mg cohort included in the test formula. Consequently, only 11% of the patients
and 3/8 in the 50 mg cohort had HBV DNA below the limit of with T2D were included in the rule-out zone of the NAFLD fibrosis
quantification <10 IU/ml at 12 weeks off treatment. By the week 12 score. AUROCs of the five other NITs were significantly lower in
visit, none of the 16 subjects in the ATI-2173 +TDF arms restarted TDF patients with T2D, mostly because of a decrease in specificity. The
compared to 1 of 4 in the TDF alone arm who restarted TDF at week 8 decrease of FIB4 specificity was explained by the significantly higher
due to virologic relapse (HBV DNA >2000 IU/ml). An off-treatment age of patients with T2D. After adjustment for age, there was no
alanine aminotransferase (ALT) flare was observed in the TDF arm but longer significant difference in FIB4 accuracy between patients with
not in the ATI-2173 arms. and without T2D. The decrease of specificity observed for Fibrotest,
FibroMeterV2G, and FibroMeterVCTE was explained by age but also
by higher alpha2macroglobulin level which is known to increase in
T2D. Sensitivity of NITs was not affected by T2D but, because of the
twofold higher prevalence of advanced fibrosis in this group, it
masked a doubled raw number of false negatives in T2D. The
sequential algorithm FIB4-VCTE had 90.3% diagnostic accuracy in
patients without T2D versus only 79.0% in T2D ( p < 0.001). To
maintain rates of false-positives and false-negatives in a similar range
than obtained with the FIB4-VCTE algorithm in patients without T2D,
diagnostic algorithms in patients with T2D required specialized tests
(first-line VCTE or FibroMeterV2G, then second-line
FibroMeterVCTE).
Conclusion: The diagnostic accuracy of NITs is different between
Figure: Mean HBV DNA change from baseline across arms. patients with and without T2D because of the different prevalence of
advanced fibrosis in these two populations, but also because T2D

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S73

ORAL PRESENTATIONS
itself modifies the level of some biomarkers. The diagnosis of robust models for detecting NASH. Validation of the models in the
advanced liver fibrosis in T2D should use first-line specialized tests. prospective LITMUS cohort is underway.

OS097 OS098
Machine learning algorithms identify novel biomarker Head to head comparison of MEFIB, MAST, and FAST for detecting
combinations for NAFLD candidates with stage 2 fibrosis or higher among patients with
Jenny Lee1, Max Westphal2, Yasaman Vali1, Yu Chen3, NAFLD
Leigh Alexander4, Jerome Boursier5, Quentin Anstee6, Beom Kyung Kim1,2, Nobuharu Tamaki1,3, Jinho Jung1, Claude Sirlin1,
Aeilko Zwinderman1, Patrick Bossuyt1. 1Amsterdam UMC, Locatie AMC, Atsushi Nakajima4, Rohit Loomba1. 1University of California San Diego,
Department of Epidemiology and Data Science, Amsterdam, La Jolla, United States; 2Yonsei University College of Medicine, Korea, Rep.
Netherlands; 2Fraunhofer MEVIS, Data Science and Biostatistics, Bremen, of South; 3Musashino Red Cross Hospital, Tokyo, Japan; 4Yokohama City
Germany; 3Eli Lilly and Company Ltd, Lilly Research Laboratories, University Graduate School of Medicine, Kanagawa, Japan
Indianapolis, United States; 4SomaLogic Inc, Boulder, United States; Email: [email protected]
5
Angers University Hospital, Hepatology Department, Angers, France;
6 Background and aims: Non-alcoholic fatty liver disease (NAFLD)
Newcastle University, Translational and Clinical Research Institute,
patients with significant fibrosis (fibrosis stage≥2) are candidates for
Newcastle upon Tyne, United Kingdom
pharmacological trials. Here, we compared head-to-head the
Email: [email protected] diagnostic accuracies of non-invasive models, MEFIB (magnetic
Background and aims: Application of machine learning algorithms resonance elastography [MRE] plus FIB-4), MAST (magnetic reson-
for developing diagnostic tests (or NITs) has grown across multiple ance imaging-aspartate aminotransferase [AST]), and FAST
disciplines, with models achieving promising classification perform- (FibroScan-AST) for detecting significant fibrosis.
ance levels. For non-alcoholic fatty liver disease (NAFLD), detection of Method: This prospective study included 563 biopsy-proven NAFLD
non-alcoholic steatohepatitis (NASH) and advanced fibrosis remains patients undergoing contemporaneous MRE, MRI proton density fat
challenging. We aimed to develop classifiers by applying machine fraction (MRI-PDFF), and FibroScan from two prospective cohorts.
learning algorithms to stage NAFLD patients. Each model was categorized into three classes as rule-in, indeter-
Method: Data from the LITMUS Metacohort, which includes adults minate, and rule-out, using rule-in/-out criteria. Diagnostic perfor-
with biopsy-proven NAFLD were analyzed for NASH (NAS≥4) and mances of models were evaluated by area under the receiver
advanced fibrosis (F≥3), staged according to the NASH-CRN scale. operating characteristic (AUROC).
Thirty-three predictors (clinical characteristics, serum biomarkers Results: The mean age was 56.5 years and 49% were male. Significant
and FibroScan-VCTE) were included in the analysis. Any missing data fibrosis was observed in 51.2%. To predict significant fibrosis, MEFIB
were handled by multiple imputation. Data were randomly split (75/ outperformed both MAST and FAST (both p < 0.001); AUROCs (95%
25) into training and validation sets. Gradient boosting method confidence interval) for MEFIB, MAST, and FAST as categorical
(GBM) was applied to develop a classifier for each component of variables were 0.901 (0.875–0.928), 0.770 (0.730–0.810), and 0.725
NASH (ballooning, inflammation, steatosis) and for advanced fibrosis, (0.683–0.767), respectively. Using rule-in criteria, positive predictive
with repeated 10-fold cross-validation to tune hyperparameters. value of MEFIB (95.3%) was higher than FAST (83.5%, p = 0.001), but
Class predictions for each component of NASH were aggregated to similar to MAST (90.0%, p = 0.056). Notably, MEFIB’s rule-in criteria
obtain a total NASH probability. Area under the receiver operating covered more of the study population than MAST (34.1% vs. 26.6%; p
characteristic (AUC) curve was used to evaluate performance. = 0.006). Using rule-out criteria, negative predictive value of MEFIB
Results: Data from 720 NAFLD adults were analyzed (training set: (90.1%) was higher than either MAST (69.6%) or FAST (71.8%) (both p
540, validation set: 180), of which 53% had NASH and 26% advanced < 0.001).
fibrosis (including 7% cirrhotics). The AUCs for each component of Conclusion: MEFIB showed the reliability of rule-in/-out, with a
NASH in the training/validation sets were: steatosis (0.68/0.66), better predictive performance compared to MAST and FAST. Thus, a
inflammation (0.72/0.80), and ballooning (0.66/0.69). The aggregate two-step strategy by MEFIB (FIB-4 followed by MRE), may be used to
GBM model for NASH achieved an AUC of 0.79 in the training and 0.74 identify ≥2 stage fibrosis.
in the validation set. For the GBM model for advanced fibrosis, the Key words: NAFLD, significant fibrosis, MEFIB, FAST, MAST, diagnosis,
AUC was 0.90 and 0.84 in the training and validation sets, validation
respectively. Different predictors were selected as most informative
for the NASH components and fibrosis models (Table 1). OS099
Validation of the new 2021 EASL algorithm for the non-invasive
Table 1: Top five predictors for NASH components and fibrosis diagnosis of advanced liver fibrosis in non-alcoholic fatty liver
models disease
Steatosis Inflammation Ballooning Fibrosis Clémence M. Canivet1,2, Adrien Lannes1,2, Charlotte Costentin3,
1 Body mass Hemoglobin BMI Liver stiffness Adele Delamarre4, Nathalie Sturm3, Frédéric Oberti1,2,
index (BMI) measurement- Thomas Decaens3, Marie Irles-Depe3, Isabelle Fouchard1,2,
VCTE
2 Cytokeratin- Age Alkaline CK-18 M30 Paul Hermabessière4, Justine Barthemon3, Victor de Lédinghen4,
18 (CK-18) phosphatase antigen Jerome Boursier1,2. 1Angers University Hospital Center, Angers, France;
M30 antigen 2
3 Age Hyaluronic acid Systolic blood Hyaluronic
Université d’Angers, HIFIH, UPRES EA3859, Angers, France; 3Centre
pressure acid Hospitalier Universitaire de Grenoble, La Tronche, France; 4Chu Haut
4 Procollagen P3NP N-terminal type PRO-C3 Leveque, Pessac, France
III peptide III collagen
(P3NP) propeptide (PRO- Email: [email protected]
C3)
5 Alanine Tissue inhibitor Aspartate Haemoglobin Background and aims: EASL recently proposed in its 2021 guidelines
transaminase matrix aminotransferase A1c an algorithm for the diagnosis of advanced liver fibrosis (AF) in
metalloproteinase
1 (TIMP1) patients with non-alcoholic fatty liver disease (NAFLD). This original
algorithm is based on the sequential use of FIB4, then vibration
Conclusion: The GBM algorithm produced a high performing model controlled transient elastography (VCTE) and, innovatively, on the use
for detecting advanced fibrosis, performance was less impressive for of patented serum tests as third-line procedure. Our objective was to
the NASH models. Better predictors, with understood associations to evaluate the diagnostic accuracy of this algorithm (FIB4/VCTE/
steatosis, inflammation and ballooning, are needed to develop more patented serum test) in a large cohort of NAFLD patients.

S74 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS
Method: 1, 051 NAFLD patients with liver biopsy were included in between screening FIB-4 ≥1.0 and ≥1.3 and liver biopsy NAS and
three tertiaries centres. Four non-invasive fibrosis tests were fibrosis stage were assessed.
available: FIB4, VCTE, FibroMeter and Fibrotest. The ELF score was Results: 56.9% F2, 40.3% F3, 24.4% F4 biopsy confirmed patients had
available in a subgroup of 396 patients. AF was defined on liver biopsy FIB-4 < 1.3 and, 46.4% of patients with active NASH (NAS≥4) fibrosis
as fibrosis ≥F3 according to the NASH-CRN classification F2/F3 had FIB-4 < 1.3 (Table). 32.6% of F2 and 18.0% of F3 subjects had
Results: The median age was 58.1 years, half of the patients were FIB-4 < 1.0. In patients with active NASH (NAS≥4), 41.7% of F2 and
diabetic, and 60% were male. The prevalence of AF was 39.5%. 17.3% of F3 subjects had FIB-4 < 1.0. NAS ≥ 4 F2-F3 patients with FIB-
Agreement between two non-invasive fibrosis tests (FIB4 then VCTE, 4 ≥ 1.3 had mean age 61.1 while NAS ≥ 4 F2-F3 patients with FIB-4 <
VCTE then patented serum test) increased specificity and positive 1.3 had mean age 52.2 ( p < 0.001); those with FIB-4 ≥ 1.0 had mean
predictive value to respectively 83–89% and 79–85%, versus 58–75% age 59.9; NASH patients with FIB-4 < 1.0, had mean age 47.6 ( p <
and 56–65% with single fibrosis tests. Within the EASL algorithm, the 0.001). More low risk NAFLD patients (F0, F1A/C) had FIB-4 < 1.3 than
third line testing with a patented serum test allowed to correctly FIB-4 < 1.0 (F0, 84.3% versus 58.1%, respectively). Absolute values of
reclassify 29% (FibroMeter), 42% (Fibrotest) and 65% (ELF) of the false AST ( p < 0.0001), ALT ( p < 0.0001), PRO-C3 ( p < 0.0001), HbA1c ( p =
positive results following the FIB4 then VCTE sequence. All these 0.0001), GGT ( p < 0.0001) and MRE ( p < 0.0001) showed statistically
results justified the sequential use of NITs proposed by the EASL significant differences between low risk (F0) and high risk (F2–F3)
algorithm. Accuracy of the EASL algorithm for the diagnosis of AF is NASH patients and could be used to further stratify risk.
detailed in the Table. In the whole study population, both FIB4/VCTE/ Conclusion: Based on a large Phase 3 data set of biopsy confirmed
FibroMeter and FIB4/VCTE/Fibrotest algorithms performed similarly. NASH patients, FIB-4 ≥ 1.3 lacks the sensitivity to accurately identify
Same results were obtained in the subgroup of 396 patients where patients with at-risk F2–F3 NASH. The influence of age on FIB-4 may
the FIB4/VCTE/ELF algorithm was available. In the whole population, require an age adjustment to ensure younger patients are not
28.7% of F3-F4 patients were false negatives, among whom only 18.5% removed from consideration for therapy.
had cirrhosis. The EASL algorithm provided 85% sensitivity for the
diagnosis of cirrhosis.
Conclusion: Our study validates the algorithm proposed by the EASL FIB-4 (1.3) FIB-4 (1.0)
All Biopsy Subjects n < 1.3/total pts. % n < 1.0/total pts. %
in its latest 2021 guidelines for the diagnosis of AF in NAFLD.
F0 199/236 84.3 137/236 58.1
Figure: Accuracy of the 2021 EASL algorithm for the diagnosis of AF F1A/C 212/293 72.4 147/293 50.2
F1B 119/184 64.7 74/184 40.2
Whole study
F2 253/445 56.9 145/445 32.6
population (n = 1, 051) ELF group (n = 396)
F3 303/752 40.3 135/752 18.0
First line test FIB4 FIB4 FIB4 FIB4 FIB4 F4 21/86 24.4 10/86 11.6
Second line test VCTE VCTE VCTE VCTE VCTE All Subjects 1107/1996 55.5 648/1996 32.5
Third line test FibroMeter Fibrotest FibroMeter Fibrotest ELF Patients with FIB-4 (1.3) FIB-4 (1.0)
Diagnostic accuracy (%) 81.4 82.8 84.1 85.9 87.4 Eligible NAS ≥4 %<1.3/NAS eligible %<1.0/NAS eligible
Sensitivity (%) 71.3 71.3 73.5 73.5 73.5 pts. pts.
Specificity (%) 88.0 90.2 89.4 92.0 94.3 F0 NA NA
Negative predictive value 82.5 82.8 87.1 87.4 87.7 F1A/C 58.9 28.6
(%) F1B 63.9 43.6
Positive predictive value 79.6 82.7 77.6 82.2 86.6 F2 55.8 41.7
(%)
F3 39.2 17.3
Negative likelihood ratio 0.33 0.32 0.30 0.29 0.28
(%) F4 NA NA
Positive likelihood ratio 5.97 7.32 6.93 9.24 12.93 All Subjects 47.9 25.0
(%)
Odd ratio 18.3 23.0 23.4 32.1 46.0
Second line test 57.3 57.3 55.1 55.1 55.1
requirement (%)
Third line test requirement 38.3 38.3 35.4 35.4 35.4
(%)
Biopsy rate (%) 6.8 12.7 7.1 14.4 11.9 Liver tumours: Clinical aspects except therapy

OS101
Utility of FIB-4 thresholds to identify patients with at-risk F2-F3 OS102
NASH based on screening data from a 2000 patient biopsy Radiomic model based on contrast-enhanced CT imaging to
confirmed cohort of resmetirom Phase 3 clinical trial, MAESTRO- predict early recurrence for patients with hepatocellular
NASH carcinoma after radical resection
Jörn Schattenberg1, Naim Alkhouri2, Rebecca Taub3, Jim Hennan4, Liying Ren1, Dongbo Chen2, Tingfeng Xu1, Pu Chen2, Bigeng Zhao1,
Mazen Noureddin5, Stephen Harrison6. 1Johannes Gutenberg- Hongsong Chen2, Weijia Liao1. 1Affiliated Hospital of Guilin Medical
University Mainz; 2Arizona Liver Institute; 3Madrigal Pharmaceuticals, University, Laboratory of Hepatobiliary and Pancreatic Surgery; 2Peking
Conshohocken, United States; 4Madrigal Pharmaceuticals; 5Cedar Sinai University People’s Hospital, Peking University Hepatology Institute,
Medical Center; 6Pinnacle Research, United States Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver
Email: [email protected] Disease, China
Email: [email protected]
Background and aims: MAESTRO-NASH NCT03900429 is a 52-week
Phase 3 registrational double blind placebo controlled NASH clinical Background and aims: Radical resection remains an effective
trial to study the effect of resmetirom in patients with NASH and strategy for patients with hepatocellular carcinoma (HCC), unfortu-
significant liver fibrosis. Eligibility requires at least three metabolic nately, the postoperative early recurrence (recurrence within 2 years)
risk factors, fibroscan VCTE kPa ≥8.5 and biopsy-proven NASH with rate is still high. Therefore, we developed a radiomic model based on
fibrosis stage 1B, 2, or 3 (or 1A/C with PRO-C3≥14), and NAFLD preoperative contrast-enhanced CT (ce-CT) to evaluate the early
activity score (NAS) ≥4 with at least 1 in each NAS component. FIB-4 recurrence for patients with a single tumor.
of ≥1.3 is frequently used to identify potential at-risk NASH patients Method: We enrolled a total of 422 patients from two centers who
and patients with FIB-4 <1.3 may be considered low risk. were diagnosed with single HCC and received radical resection. At
Method: FIB-4 cutoff values of 1.3 and 1.0 were applied to ∼2000 first, the features from venous and arterial phase of ce-CT were
patients who screened for MAESTRO-NASH with screening labs, extracted based on the region of interest (ROI), and the early
fibroscan, MRE, MRI-PDFF and a screening liver biopsy. Relationships recurrence related radiomic features were selected via the Least

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S75

ORAL PRESENTATIONS
Absolute Shrinkage and Selection Operator proportional hazards
model (LASSO Cox) model and determined radiomic scores for each
patient. Then the clinicopathologic data were combined to develop a
model to predict early recurrence by Cox regression. Last we
evaluated the prediction effect of this model by multiple methods.
Results: A total 1915 radiomic features were extracted from ce-CT
images, and 31 of them were used to determine the radiomic scores,
which showed significant difference between early recurrence and
non-early recurrence groups. Univariate and multivariate Cox
regression analyses result showed radiomic scores and serum AFP
were independent indicators and were used to develop a combined
model to predict early recurrence. The area under the receiver
operating characteristic curve (AUC) were 0.77 and 0.74, while C-
indexes were 0.712 and 0.674, respectively in the training and
validation cohorts. The calibration curves and decision curve analysis
showed satisfactory accuracy and clinical utilities, as well. Kaplan-
Meier curves based on the recurrence-free survival (RFS) and overall
survival (OS) showed significant differences.
Conclusion: The preoperative radiomic model showed value to
predict early recurrence for patients with single HCC.

Figure 2:

Figure 1:

Figure 3:

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 ORAL PRESENTATIONS
OS103
Circulating vesicles hold etiology-related protein biomarkers of
cholangiocarcinoma risk, early diagnosis and prognosis
mirroring tumour cells
Ainhoa Lapitz1, Mikel Azkargorta2,3, Ekaterina Zhuravleva4,
Marit M. Grimsrud5, Colm O. Rourke4, Ander Arbelaiz1,
Adelaida La Casta1, Mette Vesterhus5,6, Piotr Milkiewicz7,8,
Malgorzata Milkiewicz8, Raul Jimenez-Aguero1, Tania Pastor1,
Rocio IR Macias1,9, Ioana Riaño1, Laura Izquierdo-Sánchez1,
Marcin Krawczyk10,11, Cesar Ibarra12, Javier Bustamante12,
Felix Elortza2,3, Juan Falcon-Perez3,13,14, María Jesús Perugorria1,3,
Jesper Andersen4, Luis Bujanda1,3, Tom Hemming Karlsen5,
Trine Folseraas5,15, Pedro Miguel Rodrigues1,3,14,
Jesus Maria Banales1,3,14,16. 1Biodonostia Health Research Institute,
Department of Liver and Gastrointestinal Diseases, San Sebastian, Spain;
2
CIC bioGUNE, Proteomics Platform, Derio, Spain; 3National Institute for
the Study of Liver and Gastrointestinal Diseases (CIBERehd), ISCIII,
Madrid, Spain; 4Biotech Research and Innovation Centre, Department of
Health and Medical Sciences, Copenhagen, Denmark; 5Norwegian PSC
Research Center, Department of Transplantation Medicine, Division of
Surgery, Inflammatory Medicine and Transplantation, Oslo, Norway;
6
University of Bergen, Dept. of Clinical Science, Bergen, Norway;
7
Medical University of Warsaw, Department of General, Transplant and
Liver Surgery, Warsaw, Poland; 8Pomeranian Medical University,
Department of Medical Biology, Szczecin, Poland; 9Biomedical Research
Institute of Salamanca (IBSAL), Experimental Hepatology and Drug
Targeting (HEVEPHARM), Salamanca, Spain; 10Saarland University
Medical Centre, Department of Medicine II, Homburg, Germany; 11Centre
for Preclinical Research, Department of General, Transplant and Liver
Surgery, Warsaw, Poland; 12Hospital of Cruces, Bilbao, Spain; 13CIC
bioGUNE, Exosomes Laboratory, Derio, Spain; 14Ikerbasque, Basque
Foundation for Science, Bilbao, Spain; 15Oslo University Hospital,
Department of Transplantation Medicine, Oslo, Norway; 16University of
Navarra, Department of Biochemistry and Genetics, Pamplona, Spain
Email: [email protected]
Background and aims: Cholangiocarcinomas (CCAs), heterogeneous
biliary tumors with dismal prognosis, lack accurate early-diagnostic
methods, especially important for individuals at high-risk (i.e.
primary sclerosing cholangitis (PSC)). Here, we aimed to identify
precise non-invasive CCA biomarkers.
Method: Serum extracellular vesicles (EVs) from patients with: i)
Figure 4: isolated PSC (n = 39); ii) PSC without clinical evidences of malignancy
at sampling who developed CCA overtime (PSC to CCA; n = 10); iii)
concomitant PSC-CCA (n = 14); iv) CCAs from non-PSC etiology (n =
26); and v) healthy individuals (n = 41) were analyzed by mass-
spectrometry. Diagnostic biomarkers of PSC-CCA, non-PSC CCA or
CCAs regardless etiology (pan-CCAs) were defined, and their
expression evaluated in human multi-organs and within CCA
tumors at single-cell level. Prognostic EV-biomarkers for CCA were
described.
Results: High-throughput proteomics identified candidate diagnostic
biomarkers for PSC-CCA, non-PSC CCA or pan-CCA, independent to
sex, age and CCA subtype. Machine learning logit modelling disclosed
PLCH1/FGL1 algorithm with diagnostic value of AUC = 0.903 and OR =
27.8 for early-stage PSC-CCA vs isolated PSC, overpowering CA19–9
(AUC = 0.608, OR = 2.0). An algorithm combining SAMP/A1AT allowed
the diagnosis of early-stage non-PSC CCAs compared to healthy
individuals (AUC = 0.863, OR = 18.5). Noteworthy, the levels of 6
proteins (ALBU;FIBB;FLG1;IGHA1;TLN1;IMA8) showed predictive
Figure 5:
value for CCA development in patients with PSC before clinical
evidences of malignancy. Multi-organ transcriptomic analysis
revealed that serum EV-biomarkers were mostly expressed in
hepatobiliary tissues and scRNA-seq analysis of CCA tumors indicated
that some biomarkers -including PIGR, FGG, SERPINA1, FGL1- were
mainly expressed in malignant cholangiocytes. Multivariable analysis
revealed EV-prognostic biomarkers independent to clinical features,

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ORAL PRESENTATIONS
with FCN2/SDPR/FA9 panel being strongly associated to patients’ OS105
survival. Training, validation and testing of a multiscale three-dimensional
Conclusion: Serum EVs contain etiology-specific protein biomarkers deep learning algorithm in accurately diagnosing hepatocellular
for the prediction, early diagnosis and prognosis estimation of CCA, carcinoma on computed tomography
representing a novel tumor cell-derived liquid biopsy for persona- Wai-Kay Seto1,2,3, Keith Wan Hang Chiu4,5, Wenming Cao1,
lized medicine. Gilbert Lui6, Jian Zhou7, Ho Ming Cheng1, Juan Wu3, Xinping Shen8,
Lung Yi Loey Mak1,2, Jinhua Huang9, Wai Keung Li6,
OS104 Man-Fung Yuen1,2, Philip Yu6,10. 1The University of Hong Kong,
Evaluation of the effectiveness of surveillance according to the Medicine, Hong Kong; 2The University of Hong Kong, State Key
ultrasound liver imaging reporting and data system (US LI-RADS) Laboratory of Liver Research, Hong Kong; 3The University of Hong Kong-
visualization score in patients with chronic hepatitis B Shenzhen Hospital, Medicine, Shenzhen, China; 4The University of Hong
Min Kyung Park1, Yun Bin Lee1, Yoon Jun Kim1, Jung-Hwan Yoon1, Kong, Diagnostic Radiology, Hong Kong; 5Kwong Wah Hospital,
Dong Ho Lee2, Jeong-Hoon Lee1. 1Seoul National University College of Diagnostic and Interventional Radiology, Hong Kong; 6The Education
Medicine, Department of Internal Medicine and Liver Research Institute, University of Hong Kong, Mathematics and Information Technology,
Seoul, Korea, Rep. of South; 2Seoul National University College of Hong Kong; 7Sun Yat-sen University Cancer Center, State Key Laboratory
Medicine, Department of Radiology, Seoul, Korea, Rep. of South of Oncology in South China, Guangzhou, China; 8The University of Hong
Email: [email protected] Kong-Shenzhen Hospital, Medical Imaging, China; 9Sun Yat-sen
Background and aims: Ultrasonography (US) is a standard surveil- University Cancer Center, Department of Minimal Invasive
lance tool of hepatocellular carcinoma (HCC) in the high-risk group. Interventional Therapy, Guangzhou, China; 10The University of Hong
This study evaluated the detection power of the US and the Kong, Computer Science, Hong Kong
occurrence of primary liver cancer (PLC) according to the US Liver Email: [email protected]
Imaging Reporting and Data System (LI-RADS) visualization score. Background and aims: Liver cancer ranks second globally in cancer
Method: Consecutive patients with chronic hepatitis B undergoing death and has a high case-fatality rate. The Liver Imaging Reporting
regular HCC surveillance were included in this cohort study. and Data System (LIRADS) categorizes liver observations on cross-
Outcomes of interest included cumulative incidence of PLC and sectional imaging based on hepatocellular carcinoma (HCC) risk.
false-negative rate of US (defined as no HCC on US conducted within 3 Intermediate-risk observations require repeated scans making an
months prior to PLC diagnosis) according to baseline LI-RADS early diagnosis of HCC difficult. It remains uncertain if artificial
visualization scores (A vs B/C). Risk factors associated with poor intelligence can improve the diagnostic performance of computed
visualization score were also analyzed. tomography (CT) for HCC.
Results: A total of 2, 002 patients were included in this study: 972 Method: We retrospectively collected archived thin-cut (<1.25 mm
were classified as visualization score A and 1, 030 as either slice thickness) contrast triphasic CT images in raw DICOM format
visualization score B or C (score B, 1, 003; score C, 27). During a and relevant clinical information. CT observations were contoured
median follow-up of 75 months (interquartile range, 69–77 months), and categorized via LIRADS, with ground truth diagnosis of HCC
166 patients developed PLC (HCC, 158; others, 8). Patients with poor established via AASLD recommendations and validated by a clinical
visualization score (visualization score B or C) has significantly higher composite reference standard based on subsequent 12-month out-
risk of PLC than those with visualization score A (2.41%/year vs. 0.50%/ comes. We constructed several deep learning algorithms (NVIDIA
year: hazard ratio, 4.83; 95% confidence interval, 3.24–7.21; p < 0.001 Tesla V100 GPUs, Dell Technologies), including the multiscale three-
by log-rank test) (Figure 1A). Higher false-negative rate of US was dimensional convolutional network (MS3DCN, Figure 1) model
observed in the poor visualization group than visualization score A which uniquely considers the multi-phasic nature of CT, and followed
(43.5% vs. 20.0%). Furthermore, among 51.2% (85 of 166) patients the Checklist for AI in Medical Imaging (CLAIM) framework for
diagnosed as very early-stage PLC, merely 13.9% (10 of 72) of patients algorithm training, validation and testing.
with visualization score B/C were detected with US, while in 53.8% (7
of 13) among patients with visualization score A. Poor visualization
score was independently associated with the presence of liver
cirrhosis (adjusted odds ratio [aOR], 3.66) or fatty liver (aOR, 2.31),
high body mass index (aOR, 1.19), high FIB-4 score (aOR, 1.16), and
Child-Pugh score 6 (vs score 5: aOR, 2.24) (Figure 1B).

Conclusion: Chronic hepatitis B patients with US LI-RADS visualiza-

tion score B/C had a higher risk of PLC as well as false-negative rate of
US than those with score A. Surveillance using alternative computed
tomography or magnetic resonance imaging might be highly
recommended for patients with US LI-RADS visualization score B or C.

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 ORAL PRESENTATIONS
Results: Among 2, 796 retrieved scans, 2, 281 were included with 3, approached significance in the non-lean group (heavy vs none: HR
620 liver observations contoured. The cohort’s mean age was 58.4 ± 1.22, 0.98–1.53) while physical activity was not significant for either
14.2 years, 61.0% male, with 1, 214 (53.2%) at-risk for HCC. Median group. Overall, the combined PAR for lifestyle factors was 65.2% in
observation size was 21.0 (IQR 12.6–41.3) mm; 793 (21.9%) had a lean compared to 37.4% in non-lean. The lifestyle factor with highest
ground truth diagnosis of HCC. After randomly dividing observations PAR for both was coffee (45.1% lean, 14.8% non-lean), followed by
into training and validation sets in a 7:3 ratio, MS3DCN was the best- smoking (24.9% lean, 12.3% no-lean). All other lifestyle factors had
performing algorithm at observation level for diagnosing HCC, PAR <10%.
achieving an AUC of 96.9% (95%CI 95.3%–98.2%), sensitivity 95.9%, Conclusion: HCC burden can be substantially reduced through
specificity 98.1%, positive predictive value (PPV) 93.7%, and negative modifiable lifestyle factors, more prominently for lean compared to
predictive value (NPV) 98.8%; compared to AUC 85.3% (95%CI 82.4%– non-lean populations. Drinking ≥2 cups of coffee per day could
88.1%), sensitivity 71.3%, specificity 99.3%, PPV 96.7% and NPV 91.9% reduce up to 45% of HCC burden among lean individuals. Diet and
for LIRADS. Sensitivity analysis found MS3DCN’s diagnostic perform- lifestyle counselling are critical to HCC prevention.
ance to remain robust, achieving an AUC of 96.3% (95%CI 95.8%–
97.6%) at patient level and 97.1% (95%CI 95.3%–98.6%) in the at-risk
cohort. In external testing of an independent cohort of 551 scans and
780 observations, MS3DCN achieved an AUC of 98.0% (95%CI 96.8%–
99.0%) and 97.6% (95%CI 96.0%–98.9%) at observation and patient
level respectively.
Conclusion: The MS3DCN deep learning model deployed to triphasic
CT was highly and robustly accurate in diagnosing HCC, superior to
LIRADS, with performance validated via internal validation and
external testing. Artificial intelligence-based technologies can facili-
tate precise establishment of diagnosis and improve clinical out- OS107
comes. Supported by the Innovation and Technology Fund, the Validation of the prognostic role of a new distinct assessment of
Government of the HKSAR; and United Ally Research Limited, a liver function in non surgical HCC patients
subsidiary of Hong Kong Sanatorium and Hospital Limited.
Bernardo Stefanini1, Benedetta Stefanini2, Andrea De Sinno3,
OS106 Francesco Tovoli4, Franco Trevisani5, Fabio Piscaglia4. 1Division of
Lifestyle factors and population attributable risk of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS
hepatocellular carcinoma in lean vs non-lean populations Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy;
2
Semeiotica Medica, Azienda Ospedaliero-Universitaria di Bologna,
Kali Zhou1, Tiffany Lim1, Jennifer Dodge1, Norah Terrault1,
Bologna, Italy; 3Alma Mater Studiorum-University of Bologna, Bologna,
Veronica Setiawan1. 1University of Southern California, Los Angeles,
Italy; 4Division of Internal Medicine, Hepatobiliary and Immunoallergic
United States
Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna,
Email: [email protected]
Departiment of Medical and Surgical Sciences (DIMEC), University of
Background and aims: Several lifestyle factors are associated with Bologna, Bologna, Italy; 5Semeiotica Medica, Azienda Ospedaliero-
risk of hepatocellular carcinoma (HCC), but actual impact may differ Universitaria di Bologna, Departiment of Medical and Surgical Sciences
in individuals with normal (lean) vs elevated (non-lean) body mass (DIMEC), University of Bologna, Bologna, Italy
index (BMI) due to differential prevalence. We aim to estimate the Email: [email protected]
population attributable risk (PAR) of modifiable lifestyle factors to
Background and aims: While the role of distinct HCC tumor burdens
HCC burden in lean vs non-lean populations to prioritize these factors
is quite consolidated, new insights about the impact of more granular
for patient-level counseling and population-level cancer prevention.
assessment of liver function in the prognosis of HCC patients are
Method: We conducted prospective analysis using data from the
emerging.
Multiethnic Cohort (MEC), a large diverse cohort in Los Angeles
Avery recent review published in Journal of Hepatology described the
County/Hawaii with >20 years of follow-up. Incident HCC was
prognostic relevance of liver functional reserve across the various
identified via cancer registry linkage. Lifestyle factors were obtained
non-surgical HCC treatments. Based on their experience, the authors
from baseline questionnaire: smoking (never/former/current),
proposed a new staging algorithm combining liver functional reserve
alcohol (none/low/heavy), diet quality (alternate Mediterranean
and tumor bulk separating patients even within the Child-Pugh A and
diet (aMED) score: Q1 = lowest to Q5 = highest adherence), physical
B classes. The present study aims to validate the prognostic role of
activity (none/low/high), and coffee intake (0, 1, ≥2 cups per day).
such system.
Lean was defined as BMI <23 kg/m2 for Asians and <25 kg/m2 for non-
Method: We retrospectively evaluated all patients with HCC who
Asians. BMI-stratified multivariable Cox models examined associ-
were not surgically treated in two large Italian centers between 2010
ation of each factor with HCC adjusted for age, sex, race/ethnicity,
and 2021. A Kaplan-Meier survival analysis was carried out
diabetes, and hypertension, followed by calculation of PAR (%).
classifying patients according to the new classification proposed by
Results: Of 181, 346 at risk participants, 753 developed HCC during
D’avola, Piscaglia et al. which identifies four different subclasses
an average follow-up of 19.8 years. 23.1% of cases vs 35.0% of non-
considering the liver functional reserve:
cases were lean. At baseline, prevalence of current smoking was
LIR 1 (optimal) includes CPT class A patients with CPT score A5 and
higher in lean vs non-lean cases (33.2% vs 21.8%); 23.1% in both
with no previous hepatic decompensation, no high risk varices,
groups reported heavy alcohol use. No physical activity was reported
tumor related performance status (PS) ≤1 and ALBI grade = 1.
in 50.3% of lean vs 45.0% non-lean cases, while 76.4% vs 84.6% had
LIR 2 (suboptimal) includes CPT class A patients with ALBI grade ≤2
suboptimal adherence to aMED diet (Q1–4). ≥2 cups/day of coffee
and PS≤1 and either CPT score A5 but with a history of previous
was reported by 14.2% of lean vs 22.0% of non-lean cases. Smoking
hepatic decompensation or score A6 (regardless of previous history of
(former vs. never: HR = 2.08, 95% CI 1.39–3.09; current vs. never: HR
decompensation).
= 4.41, 2.85–6.81) and coffee (≥2 vs 0 cups/day: HR = 0.47, 0.29–0.77)
LIR 3 (intermediate) includes CPT class B patients with a CPT score of
were associated with developing HCC for lean participants, compared
B7 and PS≤1 regardless of any previous decompensation.
to smoking (former: HR = 1.55, 1.26–1.89; current: HR = 2.62, 2.04–
LIR 4 ( poor) includes decompensated CPT B or C cirrhotic patients
3.35), diet quality (Q5 vs Q1: HR = 0.61, 0.46–0.80), and coffee (≥2 vs 0
with a PS≥2.
cups/day: HR = 0.77, 0.60–0.98) for non-lean participants. Alcohol use

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S79

ORAL PRESENTATIONS
Results: A total of 538 patients were analyzed. Median overall Method: SEAL was a prospective cohort study conducted in two
survival was 41 months in LIR 1 (89 pts), 26 months in LIR 2 (209 pts), states in Germany, Rhineland-Palatinate and Saarland, between 01/
20 months jn LIR 3 (84 pts) and 16 months in LIR 4 (156 pts). 2018 and 02/2021. Patients participating in a precautionary program
Interestingly, LIR 1 median OS was significantly higher than LIR 2 (Check-up 35) with their primary care physician were offered
subgroup ( p < 0.05), despite both including only CPT class A patients. additional testing of liver function tests (AST and ALT). If AST/ALT
LIR 2 OS which instead was closer to that of LIR 3 subgroup suggesting levels were elevated, the APRI score was calculated, and patients with
an important prognostic role for ALBI grade and past episodes of a score >0.5 were referred to a gastroenterologist/hepatologist for
hepatic decompensation even for patients within the Child-Pugh A more detailed evaluation of their liver disease. The primary end point
class. Additionally within the CPT B/C classes, a current decompen- of this study was the diagnostic rate of cACLD (F3 and F4) compared to
sation must be kept separated from CPT B7 patients. a retrospective cohort (ICD-10 codes) of patients attending check-up
35 in the two states during 2016–2017 (n = 349, 570).
Results: In total, 11, 859 patients were enrolled into the SEAL
program. Slightly more women (54.5%) than men participated in the
program, and the mean age of the cohort was 60 years. Elevated LFTs
were found in 737 patients (6.1%). The most frequent aetiology of liver
disease was non-alcoholic fatty liver disease (59%) followed by
chronic alcohol abuse (18%). cACLD was detected in 45 patients. The
standardized incidence of cACLD in the SEAL cohort was slightly
higher than in controls (3.832‰, 95% CI 2.475, 5.188 vs. 3.358‰, 95%
CI 3.136, 3.580). In logistic regression analyses, SEAL was not
associated with a higher detection rate of cACLD after adjusting for
age and gender (OR 1.141, one-sided 95% CI 0.801, +Inf ). When
patients with decompensated cirrhosis at diagnosis were excluded
from the control cohort, SEAL was associated with a higher detection
rate of cACLD on logistic regression analysis (OR 1.586, one-sided 95%
CI 1.056, +Inf).
Conclusion: The implementation of a structured screening program
may increase the detection rate of cACLD in the general population. In
this context, the SEAL program may serve as a feasible concept.

OS109
Abdominal obesity is key when evaluating interactions between
alcohol use and obesity for liver disease
Conclusion: This new classification based on more granular Fredrik Åberg1, Veikko Salomaa2, Martti Färkkilä3, Antti Jula2,
assessment of liver functional reserve confirms its significant Satu Männistö2, Markus Perola2, Annamari Lundqvist2,
prognostic impact with significant differences even within the Ville Tapio Männistö4. 1Helsinki University Hospital and University of
same Child-Pugh class. Helsinki, Transplantation and Liver Surgery, Helsinki, Finland; 2Finnish
Institute for Health and Welfare, Helsinki, Finland; 3Helsinki University
Hospital and University of Helsinki, Department of Gastroenterology,
Helsinki, Finland; 4University of Eastern Finland and Kuopio University
Public health Hospital, Departments of Medicine, Kuopio, Finland
Email: [email protected]

OS108
Structured early detection of compensated advanced chronic liver This abstract is under embargo until Friday 24 June 2022,
disease-results of the SEAL program 13:40 BST. This abstract has been selected to be highlighted
Christian Labenz1, Anita Arslanow1, Michael Nagel2, during official EASL Press Office activities or in official EASL
Marc Nguyen-Tat3, Marcus-Alexander Wörns2, Matthias Reichert4, Press Office materials that will be made publicly available on
Franz Josef Heil5, Dagmar Mainz5, Gudula Zimper6, Barbara Römer7,
the congress website at 13:40 (BST).
Johannes Jäger8, Erik Farin-Glattacker9, Urs Fichtner9, Harald Binder9,
Erika Graf9, Dominikus Stelzer9, Reyn van Ewijk10, Julia Ortne10,
Louis Velthuis10, Frank Lammert8,11, Peter Galle1. 1University Medical
Center Mainz, Germany; 2Dortmund Hospital; 3Allgäu Hospital Group;
4
Saarland University Medical Center; 5German Gastroenterology
Association; 6General Practitioners’ Association Saarland; 7General
Practitioners‘ Association Rhineland-Palatinate; 8Saarland University;
9
University of Freiburg; 10Johannes Gutenberg University Mainz;
11
Hannover Medical School
Email: [email protected]
Background and aims: Detection of patients with compensated
advanced chronic liver disease (cACLD) is of pivotal importance to
prevent the occurrence of complications and improve prognosis.
However, a structured screening program to detect patients with
cACLD has not been implemented into daily routine. Therefore, it was
the aim of the SEAL (structured detection of early liver cirrhosis)
program to evaluate the usefulness of a structured screening program
to detect cACLD.

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 ORAL PRESENTATIONS
Michigan, Division of Gastroenterology and Hepatology, United States;
15
University of Kansas Medical Center, United States; 16Mayo Clinic
Rochester, Division of Gastroenterology and Hepatology, United States;
17
University of South Dakota Sanford School of Medicine, Department of
Medicine, Division of Gastroenterology, United States; 18University of
Pittsburgh Medical Center, Center for Liver Diseases, Division of
Gastroenterology, Hepatology and Nutrition, United States
Email: [email protected]
Background and aims: Harmful alcohol consumption cause a
significant burden of disease worldwide. To date, the impact of
alcohol-related public health policies (PHP) in alcohol-associated
liver disease (ALD) has not been adequately addressed. We aimed to
assess the association between alcohol-related PHP and ALD
mortality worldwide.
Method: We performed an ecological multi-national study including
193 countries. We recorded socio-demographic data from the World
Bank Open Data source. We registered the presence of alcohol-related
PHP in each country from the WHO GISAH (in 2016). Data on alcohol
consumption measures and their harmful health consequences were
collected from the WHO Global Information System of Alcohol and
Health (GISAH) and the Global Burden of Disease (GBD) databases
(updated to 2019). We constructed generalized linear models (GLM)
with a Poisson family distribution, logit link, and a robust variance
estimator to assess the association between the number of PHP and
disease burden outcomes. The models were adjusted by population
size and population structure.
Results: We included 193 countries (7, 626, 289, 120 inhabitants); the
median number of PHP was 7 [6–8]. The most developed categories
were drink-driving policies and countermeasures (92.2%), tax
regulations (87%), limiting drinking age (84.5%), and restrictions to
alcohol access (81.9%). Other categories were national license,
production, and selling control (81.9%), government monitoring
OS110 systems and community support (74.1%), control over advertising and
The number of public health policies reduces the burden and promotion (70.5%), and presence of a national plan (50.3%).
mortality of alcohol-associated liver disease worldwide: a call for Importantly, as higher number of PHP was associated with lower
action mortality due to cirrhosis (all causes) ( prevalence ratio [PR]:0.78 95%
CI: 0.67–0.90; p = 0.001), mortality due to ALD (RP:0.81 95%CI: 0.68–
Luis Antonio Diaz1, Eduardo Fuentes2, Francisco Idalsoaga1,
0.98; p = 0.029), cardiovascular mortality (PR:0.81 95%CI: 0.67–0.98;
Jorge Arnold1, Gustavo Ayares1, Macarena Cannistra3, Danae Vio3,
p = 0.029), and alcohol use disorder (AUD) (PR:0.80 95%CI: 0.63–0.99;
Andrea Márquez4, Oscar Corsi1, Alejandro Villalón1,
p = 0.046) (Figure). The association between PHP on alcohol con-
Carolina Ramirez5, María Paz Medel6, Catterina Ferreccio7,
sumption and burden of disease was significantly higher in Africa, the
Mariana Lazo8, Juan Pablo Roblero9, Anand Kulkarni10, Won Kim11,
Americas, and Asia.
Mayur Brahmania12, Alexandre Louvet13, Elliot Tapper14,
Winston Dunn15, Douglas Simonetto16, Vijay Shah16,
Patrick S. Kamath16, Ashwani Singal17, Ramon Bataller18,
Marco Arrese1, Juan Pablo Arab1. 1Pontificia Universidad Católica de
Chile, Departamento de Gastroenterología, Chile; 2Pontificia Universidad
Católica de Chile, Departamento de Ciencias de la Salud, Chile;
3
Pontificia Universidad Católica de Chile, Escuela de Medicina, Chile;
4
Universidad Anáhuac Mayab, Escuela de Medicina, Mexico; 5Clínica Las
Condes, Departamento de Anestesiología, Chile; 6Pontificia Universidad
Católica de Chile, Departamento de Medicina Familiar, Chile; 7Pontificia
Universidad Católica de Chile, Public Health Department, Chile; 8Drexel
University, Department of Community Health and Prevention, Dornsife Figure: Relationship between alcohol-related public health policies and
School of Public Health, United States; 9Hospital Clínico Universidad de (A) deaths due to cirrhosis (all causes), and (B) deaths due to alcohol-
associated liver disease (ALD) in 2019.
Chile, Sección Gastroenterología, Chile; 10Asian Institute of
Gastroenterology, Department of Hepatology, India; 11Seoul National Conclusion: Those countries with a higher number of PHP had lower
University College of Medicine, Division of Gastroenterology and mortality due to cirrhosis (all causes), mortality due to ALD,
Hepatology, Department of Internal Medicine, Seoul Metropolitan cardiovascular mortality, and AUD. Our results strongly encourage
Government Seoul National University Boramae Medical Center, Korea, the development and implementation of PHP on alcohol consump-
Rep. of South; 12Western University, Department of Medicine, Division of tion worldwide.
Gastroenterology, Canada; 13Hôpital Claude Huriez, Services des
Maladies de l’Appareil Digestif, CHRU Lille, France; 14University of

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S81

ORAL PRESENTATIONS
OS111 OS112
Smoking, alcohol consumption and combined association risk for Incidence, prevalence and mortality of chronic liver diseases in
developing liver cancer in chronic hepatitis B: a prospective study Sweden between 2005 and 2019
Cao Maomao1, Wanqing Chen1. 1National Cancer Center/National Patrik Nasr1,2, Nelson Ndegwa3,4,5, Erik von Seth2,6,
Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Jonas Ludvigsson3,7,8,9, Hannes Hagström2,6,10. 1Linköping University,
Medical Sciences and Peking Union Medical College, Office of Cancer Department of Health, Medicine and Caring Sciences, Linköping,
Screening, Beijing, China Sweden; 2Karolinska Institute, Department of Medicine, Huddinge,
Email: [email protected] Sweden; 3Karolinska Institute, Department of Medical Epidemiology and
Biostatistics, Stockholm, Sweden; 4Karolinska Institute, Department of
Background and aims: Evidence of liver cancer with tobacco
Clinical Science, Intervention and Technology, Stockholm, Sweden;
smoking and alcohol consumption remains controversial. We 5
Karolinska University Hospital, Oesophageal and Gastric Cancer Unit,
aimed to investigate associations between liver cancer risk and
Stockholm, Sweden; 6Huddinge Hospital, Division of Hepatology,
alcohol consumption, smoking, and the combined interaction
Department of Upper GI Diseases, Stockholm, Sweden; 7Columbia
between these two risk factors in this prospective study.
University Irving Medical Center, Division of Digestive Disease and
Method: Baseline smoking and alcohol consumption were collected
Transplantation, Division of Digestive and Liver Disease, New York,
from all subjects in a population-based prospective cohort. Cox
United States; 8Örebro University Hospital, Department of Pediatrics,
proportional hazard regression models were used to estimate hazard
Örebro, Sweden; 9University of Nottingham, Division of Epidemiology
ratios (HRs) and 95% confidence intervals (CIs) adjusting for potential
and Public Health, Nottingham, United Kingdom; 10Karolinska Institute,
confounders. The population attributable fractions (PAFs) were
Clinical Epidemiology Unit, Department of Medicine, Stockholm, Sweden
estimated. The cumulative incidences of liver cancer were generated
Email: [email protected]
with the use of Kaplan-Meier methods and compared based on the
log-rank test. Background and aims: Chronic liver diseases affects approximately
Results: A total of 4003 participants were included in this study up to 844 million individuals and causes an estimated two million deaths
3 years of follow-up, 72 liver cancer cases were identified. Alcohol per year. The most common causes are chronic viral hepatitis,
consumption was found to increase the risk of liver cancer with a alcohol-related liver disease and non-alcoholic fatty liver disease.
non-significant difference (Adjusted HR = 1.19, 95% CI = 0.66–2.16, With the availability of curative treatments and effective vaccines for
PAF = 3.83%). Smoking increased the risk of liver cancer in men (HR = viral hepatitis and increasing prevalence of metabolic syndrome-the
1.59, 95% CI = 1.22–2.06, PAF = 26.69%). A dose-responsive pattern landscape of liver diseases is shifting. In this study, we aimed to
between the duration and intensity of smoking and the risk of liver describe the incidence and prevalence of a wide range of chronic liver
cancer was noted. Similar results were also observed in men. Further diseases as well as their role in mortality in Sweden.
statistical analysis revealed interactions between the effect of Method: In this register-based, nationwide cohort study, aggregated
smoking and alcohol consumption on the risk of liver cancer, statistics, stratified on categories of age, sex and geographical
contributing to 11.12% of liver cancer cases in our cohort. locations, on all adult Swedish inhabitants with a diagnosis of liver
Conclusion: The findings further support smoking is an independent disease during 2005 to 2019 were obtained from National registers.
risk of liver cancer with a clear dose-and duration-dependent Results: During 2005 to 2019, there were substantial changes in the
relation. We also showed the combined effect of alcohol consumption epidemiology of liver diseases in Sweden. The incidence of alcohol-
and smoking on the development of liver cancer. related cirrhosis increased by 18% annually (incidence rate 13.1/100,
000 in 2019). The incidence rate of non-alcoholic fatty liver disease
and cirrhosis with unspecified etiology increased by 14% and 20%
annually respectively (incidence rate 15.2 and 18.7/100, 000).
Furthermore, incidence rates of chronic hepatitis C steeply declined,
while autoimmune hepatitis increased (3.4/100, 000). In parallel with
the increasing incidence of liver cirrhosis, liver malignancies have
become more common.
The most common causes of liver related mortality were alcohol-
related disease without a code for cirrhosis, alcohol-related cirrhosis,
and unspecified liver disease with mortality rates of 4.1, 2.9, and 2.8/
100, 000. Most liver diseases were more frequent amongst men.
Furthermore, varying differences was seen in the incidence rate
between regions, with some etiologies (e.g. autoimmune liver
Figure 1: The synergistic effect of smoking and alcohol contributed to diseases) being more common in rural areas.
liver cancer risk (A. All population; B Male sex). Conclusion: The incidence rates of non-alcoholic fatty liver disease,
alcohol-related cirrhosis, unspecified liver cirrhosis has increased
(A) (B)
during the last 15 years, in parallel with a decreasing incidence of
viral hepatitis. The incidence of AIH and hepatobiliary malignancies is
also increasing. Worryingly, mortality in several liver diseases
increased, likely reflecting the increasing incidence of cirrhosis.
Significant disparities of liver diseases exist across sex and geograph-
ical regions, which needs to be considered when allocating
healthcare resources.

Figure 2: The cumulative incidence of liver cancer by drinking and

smoking status (A. Smoking; B. Drinking).

S82 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS
OS113
Association between liver cirrhosis and cardiovascular events in a
large German cohort-a population based study
Molecular and cellular biology
Kabbani Abdul-Rahman1, Hannah Schneider1, Hans Becker1,2,
Heiner Wedemeyer1,2, Benjamin Maasoumy1, Jona T. Stahmeyer3,4.
1 OS114
Hannover Medical School, Department of Gastroenterology, Hepatology
MiR-122, the regulator of the immune privileged liver
and Endocrinology, Hannover, Germany; 2German Liver Foundation
Maytal Gefen1, Shanny Layani1, Emma Klahr1, Mor Hindi1,
(Deutsche Leberstiftung), Hannover, Germany; 3AOK Niedersachsen,
Nofar Rosenberg1, Rinat Abramovitch1,2, Nathalie Nachmansson1,2,
Health Services Research Unit, Germany; 4Hannover Medical School,
Adi Yehezkel1, Amnon Peled1, Jacob Rachmilewitz1, Michal Abraham1,
Institute for Epidemiology, Social Medicine and Health Systems Research,
Michael Berger3, Daniel Goldenberg1, Nicola Gagliani4,
Germany
Samuel Huber4, Irm Hermans-Borgmeyer4, Rebecca Haffner-Krausz5,
Email: [email protected]
Shifra Ben-Dor6, Yuval Nevo7, Shrona Elgavish7, Hadar Benyamini7,
Background and aims: Systemic inflammation has been associated Mathias Heikenwälder8, Stefan Rose-John9, Dirk Schmist-Arras9,
with an increased risk for cardiovascular events. Liver cirrhosis is Achim Krüger10, Michael Stürzl11, Elisabeth Naschberger11,
associated with both systemic inflammation and endothelial dys- Frank Tacke12, Hilla Giladi1, Eithan Galun1. 1Hadassah Hebrew
function. However, a possible link between liver cirrhosis and University Hospital, Goldyne Savad Institute of Gene Therapy, Jerusalem,
cardiovascular diseases remains poorly investigated. We here aimed Israel; 2Hadassah University Medical Center, The Wohl Institute for
to analyze the risk of cardiovascular events (myocardial infarction Translational Medicine, Jerusalem, Israel; 3Israel-Canada Medical
and stroke) in patients with liver cirrhosis compared to non-cirrhotic Research Institute, Faculty of Medicine, the Hebrew University, The
patients in a population-based study from Northern Germany. Lautenberg Center for Immunology and Cancer Research, Jerusalem,
Method: Analysis was based on administrative data from one large Israel; 4University Medical Center, Hamburg-Eppendorf, Hamburg,
German public health insurance fund. All adult individuals continu- Germany; 5Weizmann Institute of Science, Dept. of Veterinary Resources,
ously insured until death or the end of observation period (2010– Rehovot, Israel; 6Weizmann Institute of Science, Bioinformatics Unit,
2019) were included. We used a pre-observation period (2010–2012) Rehovot, Israel; 7Hadassah Hebrew University Medical Center,
to exclude individuals with cardiovascular events prior to the start of Bioinformatics Unit of the I-CORE Computation Center, Jerusalem, Israel;
observation in 2013. The presence of liver cirrhosis and cardiovas- 8
German Cancer Research Centre Heidelberg (DKFZ), Division of Chronic
cular risk factors were identified using ICD-10 codes. Myocardial Inflammation and Cancer, Heidelberg, Germany; 9University of Kiel,
infarction and stroke were analyzed as a composite and as individual Biochemical Institute, Germany; 10Technical University Munich,
end points. To determine the risk of cardiovascular events in patients Institutes of Molecular Immunology and Experimental Oncology,
with liver cirrhosis we used a multivariable Cox regression adjusted Munich, Germany; 11Universitätsklinikum Erlangen, Friedrich-
for age, gender and selected cardiovascular risk factors (hypertension, Alexander University (FAU) of Erlangen-Nürnberg, Division of Molecular
heart failure, atherosclerosis, chronic ischemic heart disease, obesity, and Experimental Surgery, Department of Surgery, Erlangen, Germany;
nicotine abuse, dyslipidemia, diabetes, alcohol abuse and chronic 12
Charité University Medicine Berlin, Department of Hepatology and
renal failure with dialysis). Gastroenterology, Berlin, Germany
Results: A number of 1.29 million patients were included. Liver Email: [email protected]
cirrhosis was present in 6, 517 individuals (0.51%) at the start of the
Background and aims: The liver, an immune privileged organ, is a
observation in 2013. Individuals with liver cirrhosis were older (62.8
sanctuary for acute and chronic infections and a frequent site for
vs. 55.9 yr), more often male (60.4% vs. 44.6%) and had more
metastasis due to its immunosuppressive environment. Chronic liver
comorbidities (e.g. alcohol abuse 39.5% vs. 2.3% or atherosclerosis
inflammation is a major risk factor for primary liver cancer.
11.3% vs. 5.4%). Overall incidence of cardiovascular events was
Hepatocellular carcinoma (HCC) is the fourth leading cause of
significantly higher among patients with cirrhosis (7.7% vs 5.9%, p <
cancer related death, and metastatic liver cancer occurs even more
0.001). This difference was also documented when limiting the
often. Fatty liver is apparent in 30% of the western world due to
analysis to the incidence of strokes (5.1% vs 3.5%, p < 0.001). In
western diet and lifestyle, increasing the risk of non-alcoholic
contrast, myocardial infarctions occurred with a similar frequency in
steatohepatitis (NASH). NASH fuels chronic inflammation which
cirrhotic and non-cirrhotic individuals (2.8% vs 2.6%, p = 0.327). After
could progress to cirrhosis and HCC.
adjusting for potential confounders in the multivariable cox
Method: MicroRNA-122 (miR-122), the liver specific microRNA, plays
regression analysis liver cirrhosis was associated with a 20.9% and
important roles in regulating several liver-specific processes and was
37.3% higher risk of overall cardiovascular events ( p < 0.001) and
reported to be significantly down-regulated in HCC. Our group has
strokes in particular, respectively, while there was no risk difference
shown that: Inflammatory mediators regulate miR-122 expression
with regard to myocardial infarction ( p = 0.703).
and secretion i.e. TNFα (Rivkin M et al Gastroenterology 2016). In
Conclusion: Liver cirrhosis is associated with a higher risk of stroke.
NASH, miR-122 is decreased in livers with increased inflammation,
Importantly, this link is independent from other established
steatosis and fibrosis. Upon increasing miR-122 expression the NASH
cardiovascular risk factors. A correspondingly higher risk of myocar-
pathologies reverse (Chai C et al Gastroenterology 2020). MiR-122
dial infarction could not be demonstrated.
functions as a hormone, it is produced in hepatocytes and affects
remote tissue (Chai C et al Gastroenterology 2017). Concurring with
previous studies, we have shown that miR-122 has tumor suppressive
effects through numerous mechanisms (Simerzin A et al Hepatology
2016).

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S83

ORAL PRESENTATIONS
OS115
The role of OFD1 and loss of primary cilia in cholangiocarcinoma:
a novel promising therapeutic target
Massimiliano Salati1, Anna Barbato2, Francesco Caputo1,
Andrea Spallanzani1, Fabio Gelsomino1, Betrice Ricco’1,
Gabriele Luppi1, Luigi Ferrante2, Roberta Biondi2, Francesco Massaro2,
Antonella Iuliano2, Gennaro Gambardella2, Fabiola Piscopo2,
Pasquale Pisapia3, Antonino Iaccarino3, Maria Salatiello3,
Giancarlo Troncone3, Luca Reggiani-Bonetti1, Massimo Dominici1,
Brunella Franco2, Pietro Carotenuto2. 1University of Modena and
Reggio Emilia, Modena, Italy; 2Tigem, Pozzuoli, Italy; 3University of
Naples Federico II, Napoli, Italy
Email: [email protected]
Background and aims: CCA is a highly lethal primary liver cancer
with an increasing incidence and limited therapeutic options. The
primary cilium has been postulated to have a tumor-suppressor role
in the biliary tract being involved in several cancer-related pathways
including WNT, Hedgehog and NOTCH. Here, we aimed at identifying
and functionally characterizing primary cilium-associated genes with
translational relevance for CCA prognostication and treatment.
Method: Whole-transcriptome profiling was performed with RNA-
Seq on laser micro-dissected FFPE resected tissue specimens.
Knocking-down of OFD1 showed was performed using siRNA
interference transfections of CCA cells. Immunofluorescence staining
of cilia markers was used to analyze and count cilia.
Results: Overall, 70 CCA patients were included, 51% (36) had
intrahepatic and 49% (34) had extrahepatic CCA. Among 3392 and
6315 differentially expressed genes between tumour and normal
tissue and tumour and stroma, OFD1 was the top-ranked cilium-
associated gene (fold-change≥2.5, p < 0.01). siRNA-mediated deple-
tion of OFD1 induced ciliogenesis and suppresses tumour growth
in vitro in normal cholangiocyte and 4 different CCA cell lines. In the
Western blot, OFD1 knockdown significantly increase the expression
of ciliary proteins such as PCM1, ARL13B and Acetylated Tubulin,
while OFD1 overexpression reduced their expression. When asses-
sing the impact of OFD1 on prognosis, higher expression of OFD1 was
significantly associated with a worse overall survival in resected CCA
patients (10 vs 39 months; HR 2.33, 95%CI 1, 01–5, 31, p = 0.03).
Conclusion: We demonstrated that OFD1 acts as an oncogene in CCA
and experimentally-induced depletion of OFD1 stimulated ciliogen-
esis and suppressed tumour growth in vitro. Interestingly, higher
OFD1 expression adversely impacted survival of CCA patients
undergoing curative-intent resection. This work identifies the
primary cilium-associated gene OFD1 as a novel promising thera-
peutic target and prompts ciliotherapy development in CCA.
Results: We generated a genetically modified mouse model by
deleting 60nt of miR-122, (miR-122Δ60). The miR-122Δ60 mice OS116
develop fibrosis and ductular proliferation as well as initiation of an Human antigen R (HuR) is a master regulator of hepatic glucose
inflammatory response already by the age of 3 weeks progressing metabolism
with age. At a later age these mice develop NASH and HCC (age 40–80 Sofia Lachiondo-Ortega1, Miren Bravo1, Irene González-Recio1,
weeks old). In a model of metastasis to the liver, miR-122Δ60 develop María J. González Rellán2, Jorge Simón Espinosa1,3,
significantly more secondary tumors in the liver with an aggressive Naroa Goikoetxea1, Petar Petrov1,3, Rubén Rodríguez Agudo1,
phenotype. RNA-seq analysis revealed enhanced epithelial-to-mes- Arantza Sanz-Parra1, Begoña Rodriguez Iruretagoyena1,
enchymal transmission (EMT). This was associated with an increase Teresa Cardoso Delgado1, Dan A. Dixon4, Myriam Gorospe5,
in ADAM17 expression, a known target of miR-122, which we have Ruben Nogueiras2,6, María Luz Martínez-Chantar1,3. 1Center for
collaboratively shown, induces necroptosis of endothelial cells and Cooperative Research in Biosciences (CIC bioGUNE), Liver Disease Lab,
cause enhanced tumor cell invasion into parenchyma (Bolik J et al, J Spain; 2Center for Research in Molecular Medicine and Chronic Diseases
Exp Med paper in press). All these results teach to the pivotal role of (CIMUS), Department of Physiology, Spain; 3Centro de Investigación
miR-122 in liver tolerance, inflammation and tumorigenesis. Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd);
Conclusion: Overall, miR-122 is on the one hand “anti-inflamma- 4
University of Kansas, Department of Molecular Biosciences, United
tory” and on the other hand a “tumor suppressor.” Understanding the States; 5National Institute on Aging (NIA), National Institutes of Health
regulation of miR-122 and its downstream effects could shed light on (NIH), Laboratory of Genetics and Genomics, United States; 6Centro de
mechanisms of the diseased liver and potentially identify disease Investigación Biomédica en Red de Fisiopatología de la Obesidad y
biomarkers and lead to therapeutic strategies. Nutrición (CIBERobn), Spain
Email: [email protected]
Background and aims: Human antigen R (HuR) or Embryonic Lethal
Abnormal Vision-Like 1 (ELAVL1) is a ubiquitous member of the ELAV/

S84 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS
Hu family of RNA-binding proteins (RBPs). Under normal physio- pre-transplant cold storage conditions, hypoxia and insufficient
logical conditions HuR is primarily nuclear. However, upon specific regeneration of biliary epithelial cells (BEC) following transplant-
stimuli, e.g. stress signals, HuR translocates to the cytoplasm where it ation. BEC have primary cilia (PC), a unique organelle that is crucial to
functions as a potent regulator of the stabilization and translation of sense the extracellular environment and regulate cell proliferation. In
target mRNAs. By binding to U/AU-rich elements (AREs) typically this study we investigate the impact of PC and regeneration in the
present in the 3′-untranslated region (UTR) of mRNAs, HuR post- setting of BC arising post liver transplantation.
transcriptionally controls the expression of many proteins and hence Method: Human biopsies were used to study the structure/function
governs diverse molecular and cellular functions. Thus, in addition to of PC in liver transplant recipients with (N = 7) and without BC (N =
its implication in disease, HuR is involved in physiological processes, 12). We developed novel murine models of liver pre-transplantation
e.g. adipogenesis, myogenesis, senescence, and immune response. stages, where we can study the role of PC in BEC, using conditional
However, the role of HuR in hepatic glucose metabolism remains to ablation of PC (K19CreERT KIF3Aflox/flox mouse model). Lastly,
be addressed and constitutes the main aim of the present work. Tubastatin A was used to stabilise PC and promote BEC regeneration,
Method: HuR expression was modulated in cultured primary mouse in a combination of in vitro and in vivo models of cold storage.
hepatocytes and in the THLE-2 human liver cell line stimulated with Results: BEC’s PC are shortened prior to transplantation in livers that
glucagon, glucose or insulin, as well as in mice fed a high-fat diet later develop BC ( p = 0.006). We identify hypoxia as the main
(HFD) during 4 days or subjected to glucagon administration for 30 molecular mechanism responsible of this damage during cold
min. Next, changes in glucose levels, RNA and protein expression, storage conditions.
HuR localization, fluxomic analysis with 13C-uniformly labelled Hypoxia induced shortening/loss of PC triggers the onset of cellular
glucose, RNA and RNA immunoprecipitation (RIP) and sequencing senescence, impairing the regenerative capacity of BEC in vitro and in
(Seq) assays were performed. vivo. We also explore how hypoxia-independent genetic ablation of
Results: Hepatic HuR expression was increased after intraperitoneal PC induces cellular senescence, indicating the presence of a feedback
administration of glucagon in mice, while it remained unchanged in loop that negatively impacts the regenerative response of BEC after
the glucagon receptor knockout animal model. Conversely, HuR liver transplantation.
expression decreased in mice upon insulin injection into the inferior Inhibition of cellular senescence (using p21−/− mice or by adminis-
cava vein. Importantly, HuR expression was significantly upregulated tration of senolytics) preserves PC during cold storage ( p = 0.0004),
in the liver of a cohort of type II diabetes mellitus (T2DM) patients improving BEC regeneration. We finally show how stabilisation of PC
and in the insulin resistance in vivo model consisting of mice fed a during cold storage improves BEC proliferation in vitro ( p = 0.0005).
HFD during 4 days. HuR was mainly located in the nucleus upon Conclusion: pre-transplantation hypoxic conditions trigger the loss
glucose and insulin stimuli, whereas it translocated to the cytoplasm of PC in BEC, impairing biliary regeneration through cellular
after glucagon administration. Silencing the expression of HuR in the senescence. Our results indicate that PC represent a potential novel
HFD mouse model sensitized the liver to insulin-mediated glucose therapeutic target to improve biliary regeneration and prevent BC
uptake and subsequent glycolysis, while its gluconeogenic capacity development during liver transplantation.
was reduced. Importantly, ablating hepatic HuR expression resulted
in a two-fold reduction of subcutaneous white adipose tissue weight
due to increased lipolysis. Moreover, RNA-Seq analysis revealed
different expression signatures of RNAs involved in glucose metab-
olism upon modulation of HuR expression. Finally, RIP-Seq experi-
ments identified a panel of HuR-interacting mRNAs encoding
proteins with molecular functions that helped explain how HuR
controls liver glucose homeostasis.
Conclusion: Given that HuR appears to be a master regulator of
glucose metabolism, we propose that HuR ought to be considered as a
OS118
potential pharmacological target for the clinical management of
NFATc1 drives progressive liver inflammation and fibrosis by
T2DM.
regulating pro-apoptotic stress responses
OS117 Muhammad Umair Latif1, Geske Schmidt2, Sercan Mercan2,
Primary cilia in biliary regeneration-a potential approach to Kristina Reutlinger2, Elisabeth Hessmann2, Shiv Kumar Singh2,
improve outcomes in liver transplantation Philipp Ströbel3, Volker Ellenrieder2. 1University Medical center
Hannah Esser1, Sofia Ferreira-Gonzalez1, Tak Yung Man1, Göttingen, Department of Gastroenterology, Gastrointestinal Oncology
Alastair Kilpatrick1, Daniel Rodrigo Torres1, Rhona E. Aird1, and Endocrinology, Göttingen, Germany; 2University Medical center
Göttingen, Department of Gastroenterology, Gastrointestinal Oncology
Candice Ashmore-Harris1, Kayleigh Thirlwell2, Benjamin J. Dwyer3,
Gabriel Oniscu4, Stefan Schneeberger5, Luke Boulter6, Stuart Forbes1. and Endocrinology, Göttingen, Germany; 3University Medical center
1
University of Edinburgh, Centre for Regenerative Medicine, Institute for Göttingen, Institute for Pathology, Göttingen, Germany
Email: [email protected]
Regeneration and Repair, Edinburgh, United Kingdom; 2Tissues, Cells
and Advanced Therapeutics Scottish National Blood and Transfusion Background and aims: Chronic liver inflammation lead to fibrosis
Service (SNBTS), Edinburgh, United Kingdom; 3Curtin University, Curtin and cirrhosis, which is the 12th leading cause of death in the world.
Medical School, Curtin Health Innovation Research Institute, Perth, Many acute and chronic liver disorders including hepatic inflamma-
Australia; 4Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, tion originate from stress conditions followed by some complex inter
United Kingdom; 5Innsbruck Medical University, Department of Visceral, cellular processes. Progression of the disease can progress to
Transplant and Thoracic Surgery, Center of Operative Medicine, distinctive cirrhosis and hepatocellular carcinoma development.
Innsbruck, Austria; 6University of Edinburgh, The Institute of Genetics Here, we describe a key role of NFATc1 in liver damage, inflammation,
and Molecular Medicine (IGMM), Edinburgh, United Kingdom and fibrosis. NFATc1, beside its well-established role in inflammatory
Email: [email protected] diseases and inflammation-associated tumors, has not been com-
Background and aims: Biliary complications (BC) are one of the most prehensively studied in liver diseases. This project aimed to
common complications after orthotopic liver transplantation. Up to characterize the functional implications of NFATc1 and its therapeutic
potential in inflammatory liver diseases.
25% of liver transplant recipients will develop BC, a major factor
determining long term patient survival. BC have been associated with Method: To address this, we analyzed NFATc1 activation in patients
with inflammation/fibrosis, cell lines and mice tissues, pretreated

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S85

ORAL PRESENTATIONS
with Thioacetamide (TAA), using immunoblot, RT-PCR and immu- Results: Administration of seladelpar to wild type mice repressed the
nohistochemistry. Liver tissues from vehicle and TAA treated liver expression of cholesterol 7 alpha-hydroxylase (Cyp7a1), a rate
NFATc1wt, NFATC1c.a. and NFATc1fl/fl mice were examined for NFATc1 limiting enzyme for bile acid synthesis, and decreased plasma 7α-
dependent morphological changes by analyzing inflammation, and hydroxy-4-cholesten-3-one (C4), the freely diffusible metabolite
fibrosis. RNA-seq analysis in AML12 cells was performed to identify downstream of Cyp7a1, without affecting Farnesoid X receptor
NFATc1 regulated gene signatures and signaling mechanisms. We pathway in the liver or ileum. In primary mouse hepatocytes,
further highlighted the therapeutic potential of NFATc1 dependent seladelpar significantly reduced the expression of Cyp7a1 and
signaling mechanisms by their inhibition, both in-vivo and in-vitro. upregulated fibroblast growth factor 21 (Fgf21). The effect of
Results: Liver biopsies from patients with inflammation/fiborsis seladelpar on the expression of Cyp7a1 and Fgf21 was observed in
revealed increased NFATc1 expression and nuclear localization in the hepatocytes isolated from Ppar-alpha-/- mice, confirming the
hepatocytes. Moreover, TAA induced NFATc1 activation resulted in effect of seladelpar is not based on PPAR-alpha activation.
progressive inflammation, fibrosis and cirrhosis whereas hepatocyte- Recombinant Fgf21 protein repressed Cyp7a1 gene expression via
specific depletion of the transcription factor prevented mice from an activation of the JNK signaling pathway in primary mouse
liver damage. Mechanistically, hepatocyte specific NFATc1 activation hepatocytes. The suppressive effect of seladelpar on Cyp7a1
drives chronic ER stress-responses and promotes apoptosis (cleaved expression was blocked by both a JNK inhibitor and in the absence
Caspase-3) and pro-inflammatory signaling cascades through PERK- of Fgf21, indicating that Fgf21 plays an indispensable role in PPAR-
CHOP-mediated NLRP3 inflammasome activation. Finally, TUDCA delta-mediated downregulation of Cyp7a1. Reduction of CYP7A1
mediated inhibition of NFATc1-driven signaling prevented hepato- expression by seladelpar was confirmed in primary human
cyte damage and subsequent inflammation/fibrosis. hepatocytes.
Conclusion: Together, our study successfully established the role of Conclusion: Seladelpar reduces bile acid synthesis via an FGF21-
NFATc1 in liver inflammation and fibrosis through terminal ER-stress dependent mechanism that signals, at least partially through JNK, to
signalling and subsequent NLRP3 inflammasome activation in repress Cyp7a1.
hepatocytes. This study also highlighted the therapeutic potential
of ER-stress inhibition by TUDCA. In fact, TUDCA application resulted
in strikingly lower liver damage and fibrosis in mice.

NAFLD Therapy

OS120
Dissecting the effects and mechanism-of-action of statin use on
OS119
fatty liver disease: a multidimensional study
The selective PPAR-delta agonist seladelpar suppresses bile acid
Ibrahim Ayada1,2, Laurens van Kleef3, Huai Zhang4, Pengfei Li3,
synthesis by reducing hepatocyte CYP7A1 through the FGF21
Kuan Liu1, Ling Wang3, Marla Lavrijsen3, Mohsen Ghanbari2,
pathway
Luc J.W. Van Der Laan5, Maikel Peppelenbosch3, Ming-Hua Zheng6,
Tetsuya Kouno1, Xiao Liu2, Tatiana Kisseleva2, Edward Cable3, Robert De Knegt3, Qiuwei Pan3. 1Erasmus MC, Gastroenterology and
Bernd Schnabl1. 1University of California San Diego, Department of
Hepatology, Rotterdam, Netherlands; 2Erasmus MC, Department of
Medicine, La Jolla, United States; 2University of California San Diego,
Epidemiology; 3Erasmus MC, Gastroenterology and Hepatology;
Department of Surgery, La Jolla, United States; 3CymaBay Therapeutics, 4
Medical Quality Management Office, the First Affiliated Hospital of
Newark, United States
Wenzhou Medical University, Wenzhou, China, Department of
Email: [email protected] Biostatistics and Records Room; 5Erasmus MC, Department of Surgery;
6
Background and aims: PPAR-delta agonists exert beneficial effects in The First Affiliated Hospital of Wenzhou Medical University
liver disease and reduce total bile acid levels. Since little is known Email: [email protected]
about the mechanism whereby PPAR-delta agonism reduces bile acid
Background and aims: Statins are widely used for the prevention of
levels, the aim of the current study was to investigate the molecular
cardiovascular events and treatment of dyslipidemia. Previous
pathways responsible for reducing bile acid synthesis in hepatocytes studies have suggested potential beneficial effects of statin use on
following treatment of the selective PPAR-delta agonist, seladelpar.
fatty liver disease, but the evidence is segmented and inconclusive.
Method: Wild type C57BL/6 mice were gavaged with vehicle (PBS) or
This study aims to comprehensively investigate the epidemiological
seladelpar (10 mg/kg body weight), and gene expression in the liver
and clinical evidence in this respect, and to understand the
and ileum was examined 6 hours later by qPCR. For mechanistic
mechanism-of-action in experimental models.
studies, primary mouse hepatocytes isolated from wild type C57BL/6 Method: The association between statin use and fatty liver disease
mice, Ppar-alpha-/- mice, or Fgf21-/- mice were treated with
(FLD) was investigated in the Rotterdam Study (a population-based
seladelpar for 48 hours, and gene expression analysis was performed.
prospective cohort), a biopsy proven FLD cohort and lastly in meta-
The effect of seladelpar on bile acid regulation was also investigated
analysis of published clinical trials and cohort studies. The effect of
in primary human hepatocytes.
simvastatin and lovastatin on lipid accumulation was investigated in

S86 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS
3D cultured human liver organoids fed with lactate, pyruvate and
octanoic acid to mimic steatosis. Since macrophages are the key
drivers of inflammation in FLD, human THP-1 macrophage cell line
was used to study inflammatory gene expression.
Results: In the Rotterdam Study cohort (n = 4352 participants), statin
use among participants with the metabolic syndrome (n = 1700) was
associated with decreased risk for steatosis (OR 0.45, 95%CI 0.33–
0.60, p <0.001) and fibrosis (OR 0.51, 95%CI 0.26–0.90, p = 0.031). In
the biopsy proven patient cohort (n = 569), statin use in a subpopula-
tion with the metabolic syndrome (n = 266) was associated with
decreased risk for non-alcoholic steatohepatitis (OR 0.49, 95%CI 0.25–
0.98, p = 0.04). In meta-analysis, lower levels of AST (mean difference:
−0.74 U/L) and ALT (mean difference: −0.87 U/L) were observed in
fatty liver disease patients using statins. Pooled odds ratio of 0.65
(95%CI 0.35–1.07) was estimated on the association of statin use and
FLD development. In liver organoids model of steatosis, we found
treatment with statins significantly inhibited the number of formed
lipid droplets, although the effect was prominent only at relatively
high concentration (10 microM). Our preliminary results suggest that
statin inhibits the expression of inflammatory genes, including IL-
1beta, IL-6, TNF-alpha and IL-8, but these results require further
confirmation.
Conclusion: Our epidemiological and clinical evidence strongly
supports the beneficial effects of statin use on multiple stages of
fatty liver disease; steatosis, fibrosis and steatohepatitis. This is likely
attributed to multiple mechanisms, including inhibition of steatosis
and inflammatory response.

OS121 OS122
Biomarkers, imaging and safety in a well-compensated NASH Magnesium modulation by CNNM4 silencing in DIAMOND mice
cirrhotic cohort treated with resmetirom, a thyroid hormone via GalNAc-siRNA therapy: a new and effective therapeutic
receptor beta agonist, for 52 weeks approach against MAFLD
Stephen Harrison1, Kris Kowdley2, Rebecca Taub3, Naim Alkhouri4, Rubén Rodríguez Agudo1, Naroa Goikoetxea1, Miren Bravo1,
Guy Neff5. 1Pinnacle Research; 2Liver Institute Northwest, Seattle, United Sofia Lachiondo-Ortega1, Marina Serrano-Macia1,
States; 3Madrigal Pharmaceuticals, RandD, Conshohocken, United Maria Mercado-Gómez1, Marcos Fernandez Fondevila2,
States; 4Arizona Liver Institute, Chandler, United States; 5Covenant Teresa Cardoso Delgado1, Luis Alfonso Martinez-Cruz1,
Research, Sarasota, United States Franz Martin-Bermudo3, Ruben Nogueiras2, Cesar Augusto Martín4,
Email: [email protected] Ute Schaeper5,6, Daniela Buccella7, Jorge Simón1,8,
María Luz Martínez-Chantar1,8. 1Liver Disease Laboratory, CIC
bioGUNE; 2Molecular Metabolism Lab, CIMUS; 3CABIMER, UPO;
4
Instituto Biofisika (UPV/EHU); 5Silence Therapeutics GmbH; 6Silence
This abstract is under embargo until Friday 24 June 2022, Therapeutics GmbH, Berlin, Germany; 7Department of Chemistry, NYU;
13:40 BST. This abstract has been selected to be highlighted 8
CIBER Enfermedades Hepáticas y Digestivas (CIBERehd)
during official EASL Press Office activities or in official Email: [email protected]
EASL Press Office materials that will be made publicly Background and aims: There is mounting evidence that metabolic
available on the congress website at 13:40 (BST). alterations play an important role in non-alcoholic fatty liver disease
(NAFLD), which led to the notion to be renamed metabolic associated
fatty liver disease (MAFLD). When extending the focus of the studies
to systemic physiology, there are relevant comorbidities that
commonly appear with MAFLD such as obesity, insulin resistance
or cardiovascular diseases. Magnesium perturbations have been
characterized in steatohepatitis and associated comorbidities,
together with the role of Cyclin M4 (CNNM4) in modulating
magnesium homeostasis. Based on these results, we evaluated the
disease-modifying effects of a GalNAc-siRNA therapy targeting
CNNM4 in a MAFLD animal model with obesity and insulin
resistance.
Method: In vitro: Primary hepatocytes were stimulated with 400 μM
oleic acid (OA) for a MAFLD phenotype. In vivo: DIAMONDTM mice
were fed a high-fat sugar western diet (HFS-WD) for 25 weeks. Mice
were treated twice, at weeks 17 and 21, with either 1 mg/kg or 5 mg/
kg CNNM4-targeting GalNAc siRNA . Insulin resistance was char-
acterized by intraperitoneal glucose (IPGTT) and insulin (ITT)
tolerance tests and histopathological characterization of NASH was
assessed by determining steatosis, inflammation and fibrosis
development.

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S87

ORAL PRESENTATIONS
Results: Treatment of primary hepatocytes with GalNAc siRNA
targeting CNNM4 reduced the lipid accumulation induced by OA
stimulation. In the in vivo Diamond mouse model, at 17th week,
when GalNAc siRNA treatment was initiated, DIAMONDTM mice had
already developed insulin resistance. siRNA treatment did not affect
weight gain or food consumption pattern. Hepatomegaly induced by
HFS-WD was partially controlled by GalNAc CNNM4-targeting siRNA,
while serum transaminases tended to decrease in treated mice.
Histopathological characterization showed a significant reduction in Conclusion: Once daily TERN-501 at 3, 6, and 10 mg for 14 days was
steatosis and fibrosis development, together with a tendency of overall safe and well-tolerated. TERN-501 increased SHBG, a key
reduced inflammation. marker of hepatic THR-beta engagement, in a dose-dependent
Conclusion: GalNAc CNNM4-targeting siRNA-based treatment fashion. Significant reductions in atherogenic serum lipids with
appears to reduce steatosis, inflammation and fibrosis in a MAFLD favorable PK observed in this study support further investigation of
animal model, in which mice develop comorbidities, such as insulin TERN-501 for NASH treatment alone or in combination with other
resistance or obesity. Ongoing studies will characterize the effect on agents.
systemic alterations in MAFLD such as cardiovascular risk or pancreas
and kidney functionality. OS124
Pemvidutide (ALT-801), a novel GLP-1/glucagon dual receptor
OS123 agonist, achieves rapid and potent reductions in body weight and
Multiple doses of thyroid hormone receptor-beta agonist TERN- liver fat: results of a placebo-controlled, double-blind, first-in-
501 were well-tolerated and resulted in significant dose- human (FIH) clinical trial
dependent changes in serum lipids and sex hormone binding Stephen Harrison1, John Nestor2, Sarah Browne3, Jacques Payne4,
globulin in a first-in-human clinical study Staci Steele5, Robert Casper5, Anvar Suyundikov6,
Cara H. Nelson1, Christopher Jones1, Lois Lee1, Tonya Marmon1, Vyjayanthi Krishnan7, Scot Roberts8, Joyce James9, M. Scott Harris10.
Diana Chung1, Kevin Klucher1, Yizhao Li1, Erin Quirk1, 1
Pinnacle Research, Research, San Antonio, United States; 2Spitfire
Daria Crittenden1. 1Terns Pharmaceuticals, Foster City, United States Pharma, South San Francisco, United States; 3Altimmune, Inc., Clinical
Email: [email protected] Development, Gaithersburg, United States; 4Altimmune, Inc., Clinical
Background and aims: Thyroid hormone receptor-beta (THR-beta) Operations, Gaithersburg, United States; 5Altimmune, Inc., Clinical
agonists reduce low-density lipoprotein cholesterol (LDL-c), decrease Operations, Gaithersburg, United States; 6Altimmune, Inc., Biostatistics,
liver fat, and improve liver histology in patients with non-alcoholic Gaithersburg, United States; 7Altimmune, Inc., Product Development,
steatohepatitis (NASH). TERN-501 is a novel, metabolically stable, Gaithersburg, United States; 8Altimmune, Inc., Research, Gaithersburg,
highly selective THR-beta agonist. In a first-in-human (FIH) study, United States; 9Corvid LLC, Pharmacokinetics, Oakland, United States;
10
single doses of TERN-501 were well-tolerated with significant Altimmune, Inc., Medical, Gaithersburg, United States
changes in LDL-c, apolipoprotein B (Apo B), and sex hormone Email: [email protected]
binding globulin (SHBG). Here we describe multiple ascending dose
results from the TERN-501 FIH study.
Method: Healthy participants (n = 8/cohort) with mildly elevated This abstract is under embargo until Friday 24 June 2022,
LDL-c were randomized 3:1 to receive TERN-501 (3, 6, or 10 mg) or
13:40 BST. This abstract has been selected to be
placebo once daily for 14 days in 3 cohorts. Intensive PK was assessed
on Days 1 and 14, and pharmacodynamic markers were measured highlighted during official EASL Press Office activities or
pre-dose on Days 1, 3, 5, 8, 11, and 13, and on Days 15, 17, and follow- in official EASL Press Office materials that will be made
up. Safety assessments were performed throughout the study. publicly available on the congress website at 13:40 (BST).
Results: All 24 subjects completed the study without study drug
discontinuations. All adverse events (AEs) were mild (Grade 1); no
AEs by preferred term occurred in >1 subject. Vital signs and
electrocardiograms remained stable. Transaminase changes in TERN-
501 groups compared to placebo were unremarkable. Dose-depend-
ent declines in free thyroxine were observed without clear changes in
thyroid stimulating hormone or signs or symptoms of hyper/
hypothyroidism. TERN-501 plasma exposures were dose-propor-
tional with low variability. Median half-life was >15 h in all cohorts.
SHBG increased dose-dependently with least squares mean (LSM)
changes from baseline of 55%, 134%, and 166% on Day 15 in TERN-501
3, 6, and 10 mg groups, respectively (−12% in placebo; see Figure).
Statistically significant dose-dependent LSM reductions in Apo B of
−18%, −23% and -28% in the 3, 6, and 10 mg groups, respectively, were
observed on Day 15 (−6% in placebo). Total cholesterol was reduced in
all TERN-501 groups and maximum LSM LDL-c decreases during
dosing were −22%, −28%, and −27% for 3, 6, and 10 mg (−8% in
placebo; see figure).

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 ORAL PRESENTATIONS
Results: A total of 36 NASH patients were enrolled and completed the
study. After the consecutive administration of ZSP1601 50 mg QD,
50 mg BID or 100 mg BID for 28 days, the plasma concentration
reached steady state on the third day. The AUC increased gradually
with increasing dose. There is a relatively lower accumulation of
ZSP1601. MRI-PDFF was measured at baseline and day 29. The
patients received ZSP1601 50 mg QD or BID or 100 mg BID or placebo
had a mean relative reduction from baseline in MRI-PDFF of 12.43%,
21.88%, 25.50% and 12.80%. ≥30% reduction in MRI-PDFF relative to
baseline was measured in 7 patients received ZSP1601 and 1 patient
received placebo. The mean reduction of ALT from baseline were
24.8 U/L, 38.94 U/L, 55.06 U/L and13.55 U/L. The ALT of 8 patients
decrease to normal, including 1 patient in 50 mg QD cohort, 2
patients in 50 mg BID cohort, 4 patients in 100 mg BID cohort and 1
patient in placebo cohort. And the AST of patients in ZSP1601 cohorts
also showed obvious change from baseline. In addition, the Cap,
HOMA-IR, FIB4, APRI and CK-18 decreased in ZSP1601 cohort.18 of 36
(50%) patients experienced at least one mild or moderate adverse
event (AE), and the incidence rates of AEs were 77.8% and 66.7% in
ZSP161 cohorts and placebo cohort, respectively. No serious adverse
event. ZSP1601 was well-tolerated in this study. The most frequent
AEs were adaptive headaches, creatinine slightly transiently elevated,
diarrhoea and indigestion.
Conclusion: The results of this clinical trial showed that a significant
reduction in liver fat by MRI-PDFF and ALT level of NASH patients
enrolled after 28-days treatment. The phase 1b study suggested that
ZSP1601 is safe and effective. The efficacy of 50 mg BID and 100 mg
BID cohort were better than the 50 mg QD cohort and placebo cohort.
Comparing with the results of other new drugs treating for NASH
clinical study, the efficacy of ZSP1601 are inspiring. (This trial
registered number is NCT04140123).

OS125
Safety, pharmacokinetics and efficacy of the novel pan-
phosphodiesterase inhibitor ZSP1601 in 36 NASH patients: a
double-blinded, placebo-controlled, multiple-dose escalation
phase Ib study
Yue Hu1, Hai Jun Li2, Hong Zhang1, Jinjun Chen3, Zhongyuan Xu3,
Hong You4, Ruihua Dong4, Xiaoxue Zhu1, Hong Chen1, Yun Peng2,
Jing Li2, Xiaojiao Li1, Lei Zhang5, Di Cao4, He Jin4, Dongdong Qiu5,
Aruhan Yang1, Jingrui Liu1, Haiyan Jia1, Jinfeng Lou1, Junqi Niu6,
Yanhua Ding1. 1The First Hospital of Jilin University, Phase I Clinical
Research Center, Changchun, China; 2Guangdong Raynovent Biotech Co.,
Ltd, Guangzhou, China; 3Nanfang Hospital, Nanfang Medical University, Cirrhosis and its complications: Portal
Guangzhou, China; 4Beijing Friendship Hospital, Capital Medical
University, Beijing, China; 5The First Hospital of Jilin University, Hypertension
Radiology, Changchun, China; 6The First Hospital of Jilin University,
Hepatology, Changchun, China
Email: [email protected] OS126
The association between proton pump inhibitor exposure and key
Background and aims: NASH is a serious healthcare burden. liver-related outcomes in patients with cirrhosis: a veterans
Although there has been steady progress in advancing drug affairs cohort study
development, no new drug is approved yet for this condition. The Nadim Mahmud1, Marina Serper1, Tamar Taddei2, David Kaplan1.
primary aim of this clinical trial is to evaluate the safety, pharmaco- 1
Hospital of the University of Pennsylvania, Gastroenterology,
kinetics, and efficacy of ZSP1601 that is a pan-phosphodiesterase Philadelphia, United States; 2Yale University, New Haven, United States
(PDE) inhibitor to decrease producting TNF-α to reduce liver Email: [email protected]
inflammation in NASH patients.
Method: This is a double-blind and randomized phase Ib study in 36 Background and aims: The impact of proton pump inhibitor (PPI)
NASH patients (aged 18–65 years), the study is consisted of three dose use on infection, decompensation, and mortality remains a point of
cohorts (50 mg QD, 50 mg BID, 100 mg BID), 12 patients were controversy in patients with cirrhosis. We aimed to explore these
enrolled for every cohorts of which 9 received ZSP1601 and 3 received associations in a large U.S. dataset while accounting for complex
placebo orally for 28 days.The patients who were diagnosed by liver confounding relationships.
biopsy or met clinical features that contains the following two Method: This was a retrospective cohort study of patients with
criteria: ALT≥1.5 × ULN (male 75 U/L, female 60 U/L) for two compensated cirrhosis in the Veterans Health Administration (VHA).
examinations within 28 days with an interval greater than 7 days; We identified all PPI prescriptions in the VHA and time-updated PPI
BMI≥25 kg/m2 and a baseline MRI-PDFF of liver ≥10% were enrolled. exposure every 30 days, including PPI dose which was normalized to
omeprazole equivalents. Inverse probability treatment weighting

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S89

ORAL PRESENTATIONS
(IPTW) and Cox regression analysis adjusted for time-updated Health Care Provider of the European Reference Network on Rare Liver
cardiovascular comorbidities, statin medications, antiplatelet medi- Disorders (ERN-Liver), Barcelona, Spain; 5August Pi i Sunyer Biomedical
cations, and hospitalized gastrointestinal bleed (GIB) were con- Research Institute (IDIBAPS), Universitat de Barcelona, Barcelona, Spain;
structed for outcomes of infection, decompensation, and all-cause 6
Institute for Medical Statistics, Center for Medical Statistics, Informatics
mortality. and Intelligent Systems, Medical University Vienna, Vienna, Austria;
Results: A total 76, 251 patients were included, 23, 628 (21.0%) of 7
Hospital of Santa Creu and Sant Pau, Autonomous University of
whom were on PPI at baseline. Patients on baseline PPI were more Barcelona, Hospital Sant Pau Biomedical Research Institute (IIB Sant
often white (64.4% vs. 60.0%, p < 0.001), had higher body mass index Pau), Barcelona, Spain; 8Liver Unit, Hospital Universitario Puerta De
(median 29.3 vs. 28.3, p < 0.001), and had more cardiovascular and Hierro Majadahonda, Universidad Autònoma de Madrid, Madrid, Spain;
metabolic comorbidities. In IPTW Cox regression, there was a 9
Department of Gastroenterology and Hepatology, Hospital
significant interaction between hospitalized GIB and PPI exposure Universitario Ramón y Cajal, IRYCIS, University of Alcalá, Madrid, Spain;
such that there was no association between PPI use and all-cause 10
Liver Unit, Hospital Italiano, Buenos Aires, Argentina, Buenos Aires,
mortality in patients without hospitalized GIB (hazard ratio [HR] Argentina 11Unidad de Enfermedades Infecciosas/VIH, Hospital General
0.99, 95% confidence interval [CI] 0.97–1.02, p = 0.58), but PPIs were Universitario Gregorio Marañón, Madrid, Spain; 12Instituto de
associated with reduced hazard of mortality in those who experi- Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain;
enced hospitalized GIB (HR 0.88, 95% CI 0.84–0.92, p < 0.001). PPI 13
Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid,
exposure was associated with increased hazard of cirrhosis decom- Spain; 14Aparato Digestivo/Unidad de Hepatología, Hospital
pensation (HR 1.64, 95% CI 1.61–1.68, p < 0.001) and severe infection Universitario Marqués de Valdecilla, Santander, Spain; 15Servicio de
(HR 1.21, 95% CI 1.18–1.24, p < 0.001), with increased hazard with Aparato Digestivo, Hospital Universitario La Paz, Madrid, Spain; 16Liver
higher dose exposure (each p < 0.001). Among infection types, the Research Center, Beijing Friendship Hospital, Capital Medial University,
strongest observed association was with spontaneous bacterial Beijing, China; 17Beijing Key Laboratory of Translational Medicine on
peritonitis, where PPI exposure conferred a 77% increased hazard Liver Cirrhosis, Beijing, China; 18Department of Gastroenterology, Nara
(HR 1.77, 95% CI 1.66–1.88, p < 0.001). Medical University, Kashihara, Japan; 19Department of Gastroenterology
Conclusion: PPI exposure was associated with an increased risk of and Hepatology, Antwerp University Hospital, Antwerp, Belgium;
severe infection, in particular SBP, as well as cirrhosis decompensa- 20
Laboratory of Experimental Medicine and Paediatrics (LEMP), Faculty
tion. Regarding all-cause mortality, PPI usage had a protective of Medicine and Health Sciences, University of Antwerp, Antwerp,
association in patients with prior hospitalized GIB, but no association Belgium; 21Translational Sciences in Inflammation and Immunology,
with mortality apart from this population. These findings suggest University of Antwerp, Antwerp, Belgium; 22UCL Institute for Liver and
that PPIs should not be avoided in patients with cirrhosis in the Digestive Health, Royal Free Hospital and UCL, London, United Kingdom;
setting of an appropriate indication. 23
Sheila Sherlock Liver Centre, Royal Free Hospital, London, United
Kingdom; 24Department of Visceral Surgery and Medicine, Inselspital,
University of Bern, Bern, Switzerland
Email: [email protected]
Background and aims: Non-invasive tests (NIT) for clinically
significant portal hypertension (CSPH; hepatic venous pressure
gradient [HVPG] ≥10mmHg) have predominantly been studied in
patients with active HCV-infection, while investigations after HCV-
cure are limited and yielded conflicting results. Thus, we conducted
an individual patient data meta-analysis.
Method: 418 patients with pre-treatment HVPG ≥ 6 mmHg who
OS127 achieved sustained virological response (SVR) and underwent post-
Non-invasive tests for clinically significant portal hypertension treatment HVPG-measurement. Paired data on pre-/post-treatment
after HCV-cure-individual patient data meta-analysis and liver stiffness-measurement (LSM)/platelet count (PLT) was available
validation in 324 patients.
Georg Semmler1,2, Sabela Lens3,4,5, Elias Laurin Meyer6, The derived non-invasive criteria were validated against the direct
Anna Baiges3,4,5, Edilmar Alvarado-Tapias3,7, Elba Llop3,8, end point hepatic decompensation in 470 compensated advanced
Javier Martinez3,9, Philipp Schwabl1,2, Ezequiel Mauro10, chronic liver disease (cACLD) patients with SVR.
Laia Escude3,4,5, Cristina Diez11,12, Luis Ibañez3,12,13, Results: At a median of 28.4 (IQR: 24–44) weeks post-treatment,
Jose Ignacio Fortea14, Angela Puente14, Marta Abadia15, HVPG decreased in 79.7%, remained unchanged in 5.5%, and
Ji-Dong Jia16,17, Hitoshi Yoshiji18, Sven Francque19,20,21, increased in 14.8%; median relative difference: −18.8 (IQR: −32.8–
Emmanuel Tsochatzis22,23, Jaime Bosch24, Rafael Bañares3,12,13, [−4.8])%. Among patients with pre-treatment CSPH (84.4%), HVPG-
Gonzalo Crespo3,4,5, Thomas Reiberger1,2, Càndid Villanueva3,7, decreases ≥10% were observed in 208 (64.2%).
Xavier Forns3,4,5, Juan Carlos Garcia Pagan3,4,5, Mattias Mandorfer1,2. In cACLD patients with paired NIT, the correlation between LSM/
1
Division of Gastroenterology and Hepatology, Department of Internal HVPG was significantly stronger post- vs. pre-treatment (Spearman’s
Medicine III, Medical University of Vienna, Vienna, Austria; 2Vienna ρ = 0.68 vs. 0.53; P < 0.001), while that of PLT/HVPG remained
Hepatic Hemodynamic Lab, Division of Gastroenterology and unchanged. HVPG tended to be lower post- vs. pre-treatment for
Hepatology, Department of Internal Medicine III, Medical University of any given LSM/PLT-value within the range relevant for clinical
Vienna, Vienna, Austria; 3Centro de Investigación Biomédica En Red de decision-making, indicating the need for dedicated algorithms after
Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud HCV-cure.
Carlos III, Spain; 4Liver Unit, Hospital Clínic, Universitat de Barcelona, A non-linear model combining post-treatment (FU-)LSM/PLT yielded
a high diagnostic accuracy (AUC: 0.89 [95%CI: 0.85–0.93]) for post-
treatment CSPH in cACLD and can be used to estimate the probability
of CSPH in an individual patient (Figure). Post-treatment LSM <12 kPa
and PLT >150 G/L excluded CSPH (sensitivity: 99.2%), while LSM
≥25 kPa was highly specific (93.6%) for CSPH.

S90 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS
may modulate this effect in patients with clinically-significant portal-
hypertension (CSPH).
Method: Patients with cirrhosis and high-risk varices wereconsecu-
tively included. The hepatic venous pressure gradient (HVPG) was
measured before and after propranolol i.v. and non-responders (i.e.
HVPG-decrease≤20%) were treated with Cv and randomized to
receive simvastatin (Sv) (40 mg/d) or placebo (Pb), under double-
blind conditions. One month later, the chronic hemodynamic
response was assessed. Plasma was obtained in each hemodynamic
study to determine proinflammatory cytokines (IL-6, TNF-α, IL-1ß,
MCP-1) and oxidative stress markers (NO, MDA, FvW).
Results: We included 82 patients, 41 treated with Cv + Sv 41 with Cv
+ Pb. Baseline clinical and hemodynamic characteristics, and cytokine
levels were similar. The inflammatory cytokines IL-6, MCP-1, and
MDA decreased significantly (p < 0.05) in both groups, but sucha
decrease was greater with Cv + Sv ( p < 0.01). No significant changes
were observed in the other markers. HVPG decreased significantly
with both, Cv+Pb (19 ± 3 mmHg to 17 ± 3 mmHg, p < 0.001) and Cv +
Sv (19 ± 4 mmHg to 16 ± 4 mmHg, p < 0.001). The decrease was
greater with Cv + Sv (−17 ± 12% vs −11 ± 8%, p = 0.05). In patients
with chronic decrease in HVPG >20%, Δ% IL-6 was significantly higher
with Cv + Sb (−30 ± 6 vs −11 ± 2, p = 0.04). Significant correlation was
observed between IL-6 and HVPG at follow-up (r = 0.52, p < 0.001).
Conclusion: In patients with cirrhosis and CSPH, carvedilol achieves
a significant reduction in proinflammatory cytokines and oxidative
stress mediators and improves the portal hypertension. All these
changes are significantly increased by adding simvastatin. This
The LSM <12 kPa and PLT >150 G/L-criterion was achieved in 185/470 suggests that the addition of simvastatin to carvedilol may improve
(39.4%) cACLD patients and their 3-year decompensation risk was 0%. clinical efficacy.
In patients with post-treatment LSM ≥25 kPa (77/470 [16.4%]), 3-year
OS129
decompensation risk was 14.2%, while it was 1.3% in those (208/470
Non-invasive diagnosis of clinically significant portal
[44.3%]) meeting none of the above criteria.
hypertension and treatment with non-selective beta-blockers: a
Conclusion: NIT can exclude/rule-in CSPH after HCV-cure and predict
new paradigm
clinical outcomes. Based on these findings, Baveno VII recommends
Elton Dajti1, Federico Ravaioli1, Giovanni Marasco2,
that patients with LSM <12 kPa and PLT >150 G/L (CSPH excluded; no
Vanessa Alemanni3, Luigi Colecchia4, Alberto Ferrarese5,
decompensation risk) may be discharged from portal hypertension
Caterina Cusumano5, Stefano Gemini5, Amanda Vestito3,
surveillance (NIT ± endoscopy), if no co-factors are present, while
Matteo Renzulli3, Rita Golfieri2, Davide Festi4, Antonio Colecchia5.
continuation of carvedilol is warranted in those with LSM ≥25 kPa 1
IRCCS S. Orsola Hospital, Bologna, Italy; Department of Medical and
(CSPH ruled-in; increased decompensation risk). In patients not
Surgical Sciences, University of Bologna, Bologna, Italy; 2IRCCS S. Orsola
meeting these criteria, the presence of post-treatment CSPH can be
Hospital, Bologna, Italy, University of Bologna, Bologna, Italy; 3IRCCS
estimated by the provided 3-D plot/nomogram or determined by
S. Orsola Hospital, Bologna, Italy, Bologna, Italy; 4University of Bologna,
HVPG-measurement.
Bologna, Italy; 5Borgo Trento University Hospital of Verona, Verona, Italy
G.S. and S.L. contributed equally.
Email: [email protected]
J.C.G-P. and M.M. share corresponding/last authorship.
Background and aims: Non-selective beta-blockers (NSBB) may
OS128 reduce the risk of decompensation in patients with clinically
Carvedilol plus Simvastatin modulates systemic inflammation in significant portal hypertension (CSPH). We aimed to improve the
cirrhosis with portal hypertension and non-response to available algorithms for the non-invasive diagnosis of CSPH by
B-blockers: randomised double-blind study evaluating spleen stiffness measurement (SSM) in patients with
Edilmar Alvarado-Tapias1,2, Rosa Montañés1, Anna Brujats1, compensated advanced chronic liver disease (cACLD).
Berta Cuyas1, Marta García Guix1, Claudia Pujol1, Method: This is a retrospective study in patients with liver stiffness
Marianette Murzi-Pulgar1, Maria Poca1,2, Isabel Graupera2,3, measurement (LSM) ≥10 kPa, no previous decompensation, and
Oana Pavel4, Alba Ardevol1, Xavier Torras1,2,5, Paula Bufi Roig1, available measurements of hepatic venous pressure gradient (HVPG),
Àngels Escorsell1,2, Silvia Vidal1, Càndid Villanueva1,2. 1Hospital de la LSM and SSM referring to our tertiary center in Bologna. The
Santa Creu i Sant Pau. Biomedical Research Institute Sant Pau (IIB Sant diagnostic algorithms were adequate if negative (NPV) and positive
Pau). 08025 Barcelona. Universitat Autònoma de Barcelona, Barcelona, predictive value (PPV) >90% when ruling-out and in CSPH, respect-
Spain; 2Centro de Investigación Biomédica en Red de Enfermedades ively; these models were validated in a cohort from Verona. The 5-
Hepáticas y Digestivas (CIBERehd), Madrid, Spain; 3IDIBAPS, Hospital year decompensation rate was reported in each risk group.
Clinic, Barcelona; 4Hospital Universitario Sant Joan de Reus Results: One-hundred-ten patients were included in the derivation
Email: [email protected] cohort (CSPH prevalence 58.6%). Available algorithms based on LSM
Background and aims: Carvedilol (Cv) has greater reducing effect on and platelet count (PLT) (LSM >25 kPa or LSM >20 kPa and PLT
portal hypertension than propranolol and has antioxidant and anti- <150.000/mm3 for ruling-in CSPH and LSM ≤15 kPa or LSM ≤20 kPa
inflammatory properties. Statins reduce intrahepatic vascular resist- and PLT ≥150.000/mm3 for ruling out-CSPH) were validated.
ance. Some proinflammatory cytokines such as IL-6 have been However, a large number of patients (38–59%) remained in the grey
involved in the progression of cirrhosis. The effect of Cv on systemic zone with indeterminate results for CSPH presence. The application
inflammation is unclear and whether combination with simvastatin of SSM cut-off 40 kPa and PLT 150.000/mm3 in the “grey zone”
patients allowed to significantly reduce the rate of indeterminate

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S91

ORAL PRESENTATIONS
results to 16–23%, maintaining adequate NPV and PPV (above 90%) Background and aims: The role of variceal embolization at the time
(Figure 1A). The combined algorithms were validated in an of transjugular intrahepatic portosystemic shunt (TIPS) creation for
independent (Verona) cohort of eighty-one patients. A nomogram the prevention of variceal rebleeding remains controversial. This
based on LSM, SSM and PLT was developed to predict the individual study aimed to evaluate whether adding variceal embolization to TIPS
probability of CSPH presence (AUROC = 0.966) (Figure 1B); the model placement could further reduce the incidence of post-TIPS variceal
performed significantly better than the Anticipate model ( p < 0.05). rebleeding in patients with cirrhosis.
During follow-up, 21–63% of first decompensation events occurred in Method: From June 2014 to February 2016, 134 consecutive cirrhotic
the patients within the “grey zone” according to the models based patients who had variceal bleeding in the past 6 weeks were
only on LSM and PLT, whereas almost all decompensation events randomly assigned (1:1) to receive TIPS alone (TIPS group, n = 65) or
occurred in the “rule-in” zone defined by the models including SSM. TIPS plus variceal embolization (TIPS + E group, n = 69) to prevent
variceal rebleeding. The primary end point was all-cause rebleeding.
A Results: TIPS placement and variceal embolization was successful in
Patient with cACLD
(LSM ≥10 kPa) all patients. During a median follow-up of 63.1 months in the TIPS
group and 61.8 months in the TIPS + E group, the primary end point
was met in 21 patients (32.3%) in the TIPS group and 16 patients
LSM ≤20 kPa AND GREY ZONE
LSM >25 kPa
OR
(23.2%) in the TIPS + E group ( p = 0.324). The 2-year cumulative
PLT ≥150 x109/L LSM >20 kPa AND
PLT <150 x109/L incidence of all-cause rebleeding was not significantly between the
two groups (TIPS + E vs TIPS: 11.6 % vs 16.9%; HR: 0.69, 95%CI, 0.36 to
Discordant SSM and PLT values 1.32; p = 0.264). Neither the incidence of shunt dysfunction (15.9% vs
SSM ≤40 kPa
AND
SSM >40 kPa AND PLT ≥ 150.000/mm3
OR
SSM >40 kPa
AND
18.5%, p = 0.875), overt hepatic encephalopathy (36.2% vs 46.2%, p =
PLT ≥ 150.000/mm3 SSM ≤40 kPa AND PLT <150.000/mm3 PLT <150.000/mm3
0.322), death (34.8% vs 38.5%, p = 0.807) nor other adverse events was
significantly different between the two groups.
NPV PPV
>90% >90%

RULE-OUT CSPH GRAY ZONE RULE-IN CSPH

CONSIDER OTHER TESTS
DO NOT TREAT WITH NSBB (IMAGING, HVPG) TREAT WITH NSBB

Figure 1 (A) Proposed algorithm based on liver stiffness, platelet count

and spleen stiffness for the diagnosis of CSPH in cACLD patients; (B) A
newly proposed nomogram based on liver stiffness, platelet count and
spleen stiffness to predict the presence of CSPH.
Conclusion: In patients with cirrhosis, adding variceal embolization
Conclusion: The addition of SSM significantly improves the clinical to TIPS did not confer further benefit for the prevention of variceal
applicability of the algorithms based on LSM and platelet count for rebleeding. Our study did not support concomitant variceal embol-
CSPH diagnosis. Our models can be used to non-invasively identify ization during TIPS for the prevention of variceal rebleeding.
candidates for NSBB treatment and patients at high-risk of
decompensation. OS131
Clinical course of cirrhotic patients developing ascites as the
OS130 single first decompensation
TIPS with versus without variceal embolization for the prevention Lorenz Balcar1,2, Marta Tonon3, Georg Semmler1,2,
of variceal rebleeding: a randomized controlled trial Katharina Pomej1,2, Valeria Calvino3, Bernhard Scheiner1,2,
Yong Lv1, Hui Chen1, Bohan Luo1,2, Wei Bai1,2, Kai Li1, Simone Incicco3, Rafael Paternostro1,2, Carmine Gabriele Gambino3,
Zhengyu Wang1,2, Dongdong Xia1,2, Wengang Guo1,2, Xiaomei Li1,2, David JM Bauer1,2, Antonio Accetta3, Lukas Hartl1,2,
Jie Yuan1,2, Zhanxin Yin1,2, Daiming Fan1, Guohong Han1,2. 1National Alessandra Brocca3, Mathias Jachs1,2, Paolo Angeli3, Michael Trauner1,
Clinical Research Center for Digestive Diseases and Xijing Hospital of Mattias Mandorfer1,2,4, Salvatore Piano3,4, Thomas Reiberger1,2,4.
Digestive Diseases, Fourth Military Medical University, Department of 1
Medical University of Vienna, Division of Gastroenterology and
Liver Diseases and Digestive Interventional Radiology, Xi’an; 2Xi’an Hepatology, Department of Internal Medicine III, Vienna, Austria;
International Medical Center Hospital of Digestive Diseases, Department 2
Medical University of Vienna, Vienna Hepatic Hemodynamic Lab,
of Liver Diseases and Digestive Interventional Radiology, Xi’an, China Division of Gastroenterology and Hepatology, Department of Internal
Email: [email protected] Medicine III, Vienna, Austria; 3University of Padova, Unit of Internal
Medicine and Hepatology, Department of Medicine, Padova, Italy;
4
Baveno faculty, Baveno cooperation, an EASL consortium, Bologna, Italy
Email: [email protected]

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 ORAL PRESENTATIONS
Background and aims: While ascites is the most frequent first
decompensating event in cirrhosis, the clinical course of patients
with ascites as the index decompensation is not well defined, in
Immune-mediated and cholestatic disease:
particular regarding the occurrence of further decompensation. The Clinical aspects
aim of this multicenter study was to investigate (i) the clinical course
and (ii) the incidence and type of further decompensation in patients
with isolated ascites as the first decompensating event. OS132
Method: 622 patients with cirrhosis presenting with ascites (grade II Incidence and predictors of hepatocellular carcinoma
or III) as the single index decompensating event at the University development in patients with autoimmune hepatitis: a
Hospital of Padova (Italy) or the Vienna General Hospital (Austria) multicenter international study
between 2003 and 2021 were included. Patients with concomitant Francesca Colapietro1,2, Patrick Maisonneuve3, Ellina Lytvyak4,
decompensating event (s) were excluded. Death and transplantation Ulrich Beuers5, Robert Verdonk6, Adriaan Van der Meer7,
were considered as competing risks. Bart Van Hoek8, Sjoerd Kuiken9, Hans Brouwer10,
Results: Mean age was 57 ± 11 years and most patients were male (n Egbert-Jan van der Wouden11, Alessio Aghemo1,2, Aad van den Berg12,
= 423, 68%). 323 (52%) patients presented with grade II and 299 (48%) George Dalekos13, Mercedes Robles-Díaz14, Raul J. Andrade14,
with grade III ascites. Median Child score was 8 (IQR: 7–10) and mean Aldo J. Montano-Loza4, Floris F. van den Brand15,
MELD was 15 ± 6. Guilherme Macedo16, Rodrigo Liberal16, Ynto de Boer15, Ana Lleo1,2.
1
During a median follow-up period of 82 months, 350 (56%) patients Humanitas University, Departments of Biomedical Sciences, Pieve
progressed to further decompensation: refractory ascites (n = 204; Emanuele, Italy; 2Humanitas Research Hospital, Division of Internal
33%), hepatic encephalopathy (n = 183; 29%), spontaneous bacterial Medicine and Hepatology, Department of Gastroenterology, Rozzano,
peritonitis (n = 105; 17%), HRS-AKI (n = 81; 13%) and variceal Italy; 3European Institute of Oncology, Division of Epidemiology and
bleeding (n = 54;9%). Median time to further decompensation was Biostatistics, Milan, Italy; 4University of Alberta, Department of
27 months. Variceal bleeding as an isolated further decompensation Medicine, Division of Gastroenterology and Liver Unit, Edmonton,
was rare (n = 18; 3%), while non-bleeding further decompensation (n Canada; 5Amsterdam UMC, locatie AMC, Department of
= 161; 26%) and ≥2 further decompensation events (n = 171; 27%) Gastroenterology and Hepatology, Amsterdam, Netherlands;
6
were common. Further decompensation occurred more frequently in St. Antonius Hospital, Department of Gastroenterology and Hepatology,
patients with grade III ascites at index decompensation (75% vs. 33% Nieuwegein, Netherlands; 7Erasmus MC, Department of
in grade II ascites; p < 0.001; A). Gastroenterology and Hepatology, Rotterdam, Netherlands; 8Leiden
Stratifying patients according to MELD revealed patients with University Medical Center (LUMC), Department of Gastroenterology and
distinct risks of further decompensation after 5 years: <10: 38% vs. Hepatology, Leiden, Netherlands; 9OLVG location East, Department of
10–14: 56% vs. ≥15: 67% ( p < 0.001; B). In patients with grade II Gastroenterology and Hepatology, Amsterdam, Netherlands; 10Reinier de
ascites, MELD<15 identified patients with intermediate risks (<10: Graaf Gasthuis, Department of Gastroenterology and Hepatology, Delft,
27%; 10–14: 34%; p = 0.510), whereas MELD≥15 identified patients Netherlands; 11Isala, Department of Gastroenterology and Hepatology,
with high risks for further decompensation after 5 years (53%; p < Zwolle, Netherlands; 12University Medical Center Groningen,
0.001). Department of Gastroenterology and Hepatology, Groningen,
Median transplant-free survival was 65 months. Higher MELD Netherlands; 13General University Hospital of Larissa, Department of
translated into an increased risk of liver-related death. Patients with Medicine and Research, Laboratory of Internal Medicine, National
ascites grade II at index decompensation had increased risk of liver- Expertise Center of Greece in autoimmune liver diseases, Larissa, Greece;
14
related mortality in case of impaired liver function (C). In patients Vírgen de Victoria University Hospital-, IBIMA, University of Málaga,
with ascites grade III at index decompensation, the incidence of CIBERehd, Liver Unit, Malaga, Spain; 15Amsterdam UMC, locatie VUmc,
further decompensation and liver-related mortality was similarly Department of Gastroenterology and Hepatology, Amsterdam,
high, regardless of liver function (i.e., MELD; D). Netherlands; 16São João Universitary Hospital Center, Department of
Conclusion: Further decompensation is frequent in patients with Gastroenterology and Hepatology, Porto, Portugal
ascites as a single index decompensation and only rarely due to Email: [email protected]
bleeding. Since further decompensation depends on ascites severity
Background and aims: Autoimmune Hepatitis (AIH) is a rare disease
and MELD at index decompensation, risk stratification must consider
characterized by circulating autoantibodies, hypergammaglobuline-
both initial grade of ascites and hepatic function.
mia and interface hepatitis on histology. Survival is impaired due to
the potential evolution to cirrhosis with its complications, including
hepatocellular carcinoma (HCC). Risk assessment of HCC in AIH still
remains a challenge and available data derive mainly from small
cohorts and single-center studies. Our aim was to investigate the risk
of HCC across a global AIH cohort and identify predictive factors and
potential stratification elements.
Method: We performed a retrospective, observational, and multi-
centric study of data collected within the International Autoimmune
Hepatitis Group Retrospective Registry. The registry is an ongoing,
non-interventional, international, and multicenter study. All patients
with regular and complete follow-up for AIH were included.
Demographic, clinical, biochemical and treatment data were col-
lected both at baseline and during follow-up. Outcomes considered
were HCC development, liver transplantation and death.
Results: 1210 patients from 21 centers were included, with a median
follow-up of 12.3 years. 74.7 % of them were female (905/1210), with
61.7 % of the cohort being over 40 years of age. 36.2 % of patients were
overweight or obese (245/1210 and 196/1210, respectively). Most of
the patients did not have a significant alcohol consumption. 21.2 % of
patients were already cirrhotic at diagnosis (257/1210), with

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ORAL PRESENTATIONS
splenomegaly reported in 116 patients (9.6 %). PBC and PSC overlap Results: Out of 50 women with a history of ICP, 17 (34%) developed
syndromes were observed in 9.7 % and 7.5 % of the cohort. Treatment rICP. Ten of these (59%) were treated with UDCA. Demographics at
at baseline included the use of prednisone in 83.5 % of patients (1010/ inclusion were not different between groups. In rICP, BA metabolites
1210). 22 patients developed HCC during follow-up (22/1210, 1.8 %). and mono- and disulfated PMxS-diols were significantly higher as
Cumulative incidence of HCC of the whole cohort was 0.7% (0.3–1.4) compared to n-rICP and C. Of note, also in n-rICP, PM2DiS and PM3DiS
at 5 and 10-year (95 % CI), 2.6% (1.4–4.4) at 20 years and 5.7 % (2.5– were significantly increased both at V2 and V3. In rICP, the relative
10.9) at 30-years of follow-up. The risk of HCC after cirrhosis abundance of a specific bacterium with 7-beta-hydroxysteroid
development increases proportionally to years from the onset of dehydrogenase (7β-HSDH) activity was decreased by 95% at V1 but
the disease. Age>40 years (HR 5.99, p = 0.02), BMI>30 kg/m2 (HR 4.11, the abundance became increased at V3 in UDCA-treated rICP. In
p = 0.02), splenomegaly (HR 4.03, p = 0.03), and PSC overlap syn- contrast, at V2 the relative abundance of Faecalibacterium prausnitzii
drome (HR 8.63, p < 0.001) resulted independent risk factors for HCC was decreased by 40% which was negatively correlated ( p < 0.01)
development at multivariate analysis balanced by sex. No association with PM4S and PM5S.
was observed between tumor formation and type of treatment, nor Conclusion: Recurring ICP presents a distinct metagenome with
activity on liver histology resulted to have any prognostic value. significant decreases of specific bacteria before the development of
Conclusion: The incidence of HCC in AIH is lower than reported to the ICP phenotype, which is associated with ICP-predictive increases
other chronic liver diseases even after cirrhosis development. Age in sulfated progesterone metabolites and elevated bile acid levels.
more than 40 years, obesity, splenomegaly and PSC variant syndrome Bacterial species were identified as potential targets for microbiome-
represent risk factors for HCC development, but further studies are based interventions for the prevention and/or treatment of ICP.
needed to identify predictive tools for stratification of the at-risk
population. OS134
Quality of life outcomes in patients with primary biliary
cholangitis treated with setanaxib: post-hoc results from a phase
2 randomised, placebo-controlled trial
David Jones1, Marco Carbone2,3, Pietro Invernizzi2,3,
Frederik Nevens4, Mark G. Swain5, Philippe Wiesel6, Cynthia Levy7.
1
Newcastle University Medical School, Newcastle upon Tyne, United
Kingdom; 2University of Milano-Bicocca, Division of Gastroenterology,
Centre for Autoimmune Liver Diseases, Department of Medicine and
Surgery, Monza, Italy; 3San Gerardo Hospital, European Reference
Network on Hepatological Diseases (ERN RARE-LIVER), Monza, Italy;
4
Figure: Development of HCC after diagnosis of AIH and after cirrhosis University Hospital KU Leuven, Department of Gastroenterology and
development in AIH. Hepatology, Leuven, Belgium; 5University of Calgary, Calgary, Canada;
6
Genkyotex, Geneva, Switzerland; 7University of Miami, Schiff Center for
OS133 Liver Diseases, United States
Recurring intrahepatic cholestasis of pregnancy presents with Email: [email protected]
distinct changes in the gut microbiota
Background and aims: Primary biliary cholangitis (PBC) is an
Hanns-Ulrich Marschall1, Peidi Liu2, Sara Malcus2,
autoimmune cholestatic liver disease.1 Fatigue substantially impacts
Mattias Bergentall2, Tanweer Khan2, Anita Lövgren-Sandblom3,
quality of life of patients with PBC, and remains an unmet need with
Peter Malcus4, Gun Lindell4, Fredrik Backhed1, Ewa Wiberg-Itzel5,
currently available treatments.2 We present quality of life results from
Helena Strevens4. 1Gothenburg University, Department of Molecular
a phase 2, double-blind, randomised trial of setanaxib in patients
and Clinical Medicine/Wallenberg Laboratory, Gothenburg, Sweden;
2 with PBC.
Metabogen AB, AZ BioVentureHub, HF3, Mölndal, Sweden; 3Karolinska
Method: This trial (NCT03226067) randomised patients with PBC
University Hospital Huddinge, Department of Clinical Chemistry C1-62,
and inadequate response or intolerance to ursodeoxycholic acid
Stockholm, Sweden; 4Skåne University Hospital Lund, Department of
(UDCA) at baseline (serum alkaline phosphatase and gamma-
Gynaecology and Obstetrics, Lund, Sweden; 5Södersjukhuset,
glutamyl transferase ≥1.5× upper limit of normal) 1:1:1 to setanaxib
Department of Gynaecology and Obstetrics, Stockholm, Sweden
400 mg once/twice daily (OD/BID) or placebo for 24 weeks.3 Quality
Email: [email protected]
of life was assessed using the PBC-40 questionnaire (reported as
Background and aims: Intrahepatic cholestasis of pregnancy (ICP) is mean [standard deviation] scores). Patients from the intention-to-
the most common pregnancy-related liver disease with a high treat (ITT) population were stratified post-hoc by baseline fatigue
recurrence risk (rICP). We aimed to prospectively define distinct score (mild, moderate or severe) using published PBC-40 fatigue
metagenomics and metabolite patterns in rICP and non-recurring ICP domain cut-offs.4 Moderate and severe patients were grouped.
(n-rICP). Correlations between change in fatigue and quality of life domains
Method: Women with a history of ICP (n = 50) were screened at 9–19 from baseline were made.
weeks of gestation (Visit 1, V1) and 1:1 matched to pregnant women Results: Of 111 patients ( placebo: 37; setanaxib 400 mg OD: 38;
without a history of ICP (controls, C). Visits 2, 3 and 4 were performed setanaxib 400 mg BID: 36), 92 had mild and 19 had moderate-to-
at gestational weeks 28 ± 2 and 36 ± 2, and 6 ± 2 weeks postpartum. severe fatigue at baseline. The ITT group had a baseline fatigue score
ICP was defined as otherwise unexplained pruritus and total BA ≥ of 17.2 (11.3) ( placebo: 17.4 [12.1]; setanaxib 400 mg OD: 15.7 [10.7];
10 mmol/L at any time from V2 to delivery, with normalization at V4. setanaxib 400 mg BID: 18.5 [11.3]). The moderate-to-severe subgroup
Blood samples were taken at each visit for targeted metabolomics, i.e. had higher PBC-40 social, emotional and cognitive domain scores vs
bile acid (BA) and sulfated progesterone metabolite (PMxS) profiles the mild subgroup (social: 30.6 [8.8] vs 19.1 [8.0]; emotional: 11.3
and C4, while fecal samples were collected for shot-gun [2.8] vs 6.8 [3.1]; cognitive: 18.3 [6.9] vs 11.3 [5.1]). At Week 24,
metagenomics. patients treated with setanaxib 400 mg BID had greater reductions
from baseline in mean fatigue scores vs patients treated with placebo
or setanaxib 400 mg OD (Figure). Similar observations were made in

S94 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS
social, emotional, cognitive and symptom domains. Patients with Background and aims: Magnetic resonance cholangiopancreatogra-
moderate-to-severe fatigue had larger changes in mean fatigue scores phy (MRCP) is a non-invasive imaging technique commonly used to
from baseline at Week 24 vs patients with mild fatigue; these changes evaluate biliary diseases. Despite its widespread use, MRCP relies on
were greatest amongst setanaxib 400 mg BID patients (−11.0 [11.5; n subjective assessments, lacks quantitative metrics and cannot predict
= 5]; vs setanaxib 400 mg OD: −7.5 [5.3; n = 4], placebo: 0.1 [5.7; n = the onset of liver-related events. Quantitative MRCP (MRCP+™) is a
7]). Fewer patients reported “most of the time” or “always” for all novel technique that automatically segments biliary anatomy and
PBC-40 fatigue items at Week 24 vs baseline. Improvements in fatigue provides quantitative biliary tree metrics. This study sought to
from baseline at Week 24 in patients with moderate-to-severe fatigue understand the utility of MRCP+ in predicting clinical outcomes for
correlated with improved social, emotional, symptom (all r = 0.5) and primary sclerosing cholangitis (PSC).
cognitive (r = 0.4) measures. Method: Patients with PSC underwent standardized MRCP imaging
post-processed with MRCP+ software, which, via artificial intelli-
gence (AI) driven pathfinding algorithms, enhanced tubular biliary
structures to quantify biliary tree volume and dilated and strictured
regions of the biliary tree. The duration (in years) between the MRCP
scan and clinical event (liver transplantation or death) was
calculated. Survival analysis was performed, and a stepwise Cox
regression was used to investigate the optimal combination of MRCP+
metrics for predicting clinical outcomes. The resulting risk score was
compared to the Mayo risk score using the Akaike Information
Criterion (AIC) and expressed as a hazard ratio (HR).
Results: In this retrospective study of 149 PSC patients [32% male;
83% Caucasian; median age 47 years (31.0–61.2)], 29 patients reached
clinical outcomes over the course of the study (18 underwent liver
transplantation and 11 died). Eight quantitative MRCP+ metrics (M)
and total bilirubin (B) were associated with the probability of a
clinical event. When combined as a risk score, the overall discrim-
inative performance of the MRCP+ composite biomarker (M+B) was
excellent for predicting clinical outcomes with at AUC of 0.87 (95%
0.81, 0.94) and a hazard ratio (HR) of 21.1. (95% 6.4, 70.1) This was
Figure: Summary of absolute score changes from baseline to Week 24 of superior to the Mayo risk score with AUC of 79 (95% 0.69, 0.89) and
the PBC-40 domains.
HR of 7.2 (95% 3.24, 16.17).
Conclusion: Setanaxib 400 mg BID, in addition to UDCA, is a
promising treatment for reducing fatigue in patients with PBC and
enhancing quality of life by improving social, emotional and cognitive
function.
References
1. Lleo A Semin Liver Dis 2020;40:34–48.
2. Mells GF Hepatology 2013;58:273–83.
3. Huang JC Hepatology 2019;70:777–9.
4. Newton JL Hepatology 2007;45:1496–505.

OS135
Quantitative magnetic resonance cholangiopancreatography
outperforms Mayo risk score in predicting clinical outcomes in
primary sclerosing cholangitis
Raj Vuppalanchi1, Vijay Are1, Sofia Mouchti2, Carla Kettler1,
Mark Gromski1, Sarah Finnegan2, Fatih Akisik1. 1Indiana University
School of Medicine, Indianapolis; 2Perspectum Ltd, Oxford, United
Kingdom
Email: [email protected]

Figure: (abstract: OS135)

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S95

ORAL PRESENTATIONS
Conclusion: A composite score of MRCP+ metrics and total bilirubin
outperformed Mayo risk score for identifying patients with PSC who
were at the highest risk of liver failure and death.

OS136
Radiomics-based model for outcome prediction in primary
sclerosing cholangitis
Laura Cristoferi1,2,3, Marco Porta4, Davide Bernasconi3,
Leonardi Filippo5, Giacomo Mulinacci1,2, Andrea Palermo1,2,
Alessio Gerussi1,2, Miki Scaravaglio1,2, Camilla Gallo1,2,
Eliana Stucchi1,2, Cesare Maino4, Davide Ippolito4, Daphne D’Amato6,
Carlos Ferreira7, Marija Mavar-Haramija7, Rajarshi Banerjee7,
Laura Antolini3, Maria Grazie Valsecchi3, Stefano Fagiuoli5,
Pietro Invernizzi1,2, Marco Carbone1,2. 1Division of Gastroenterology,
Center for Autoimmune Liver Disease, Department of Medicine and
Surgery-University of Milano Bicocca, Monza, Italy; 2European Reference
Network on Hepatologial Diseases (ERN RARE-LIVER), San Gerardo
Hospital, ASST Monza, Monza, Italy; 3Bicocca Bioinformatics Biostatistics
and Bioimaging Centre, Department of Medicine and Surgery-University
of Milano Bicocca, Monza, Italy; 4Diagnostic Radiology, San Gerardo
Hospital, ASST Monza, Monza, Italy; 5Gastroenterology Hepatology and
Conclusion: A radiomics-based model, which includes the number of
Transplantation Unit, ASST Papa Giovanni XXIII, Bergamo, Italy;
6 strictures and the spleen length, can identify PSC patients at higher
Gastroenterology Unit, Città della Salute e della Scienza, Turin, Italy;
7 risk of adverse outcome and outperforms the available radiological
Perspectum Ltd., Oxford, United Kingdom
scores. MRCP+ features represent a novel biomarker for disease
Email: [email protected]
monitoring and a potential surrogate end point for clinical trials.
Background and aims: Magnetic resonance cholangiopancreatogra-
phy (MRCP) is the gold standard for diagnosis and follow-up of OS137
patients with primary sclerosing cholangitis (PSC). The semi- Critical shortfalls in the management of PBC: results of the first
quantitative MRCP-derived ANALI score, while performant in risk nationwide, population-based study of care delivery across the
stratification, has poor-to-moderate inter-reader agreement. We U.K.
aimed to evaluate the prognostic performance of novel quantitative Nadir Abbas1,2, Rachel Smith3, Steve Flack4, Richard Aspinall5,
MRCP in PSC. Rebecca L. Jones6, Joanna Leithead7, Douglas Thorburn8,
Method: This is a retrospective study of PSC patients with at least one Conor Braniff9, Michael Heneghan10, Andrew Yeoman11,
MRCP available from 2012 to 2019. Images have been analysed using Collette Thain12, Chris Mitchell12, Robert Mitchell-Thain12,
MRCP+ software (Perspectum Ltd, Oxford) which, using AI-driven David Jones13, Palak Trivedi1,2,14, George Mells3,
pathfinding algorithms to enhance biliary structures, provides Laith Al-Rubaiy15,16 and UK-PBC Consortium17. 1University of
quantitative metrics of the bile ducts (number, length and severity Birmingham, Institute of Immunology and Immunotherapy,
of strictures and dilations, and biliary tree volume). The prognostic Birmingham, United Kingdom; 2University of Birmingham, United
value of radiomic biomarkers has been assessed towards both soft Kingdom; 3Cambridge University Hospitals NHS Foundation Trust,
(hepatic decompensation, variceal bleeding, bacterial cholangitis, United Kingdom; 4University of Cambridge, United Kingdom;
5
and hepatobiliary cancer) and hard end points (death or liver Portsmouth Hospitals NHS Trust, United Kingdom; 6Leeds Teaching
transplantation [LT]). Left truncated Cox regression model was used Hospitals NHS Trust, United Kingdom; 7Forth Valley Royal Hospital,
to account for MRCPs performed later than PSC diagnosis. The United Kingdom; 8Royal Free Hospital, United Kingdom; 9Belfast Health
multivariate model was internally validated using k-fold cross- and Social Care Trust, Northern Ireland; 10Institute of Liver Studies,
validation. King’s College Hospital, United Kingdom; 11Aneurin Bevan University
Results: 115 PSC patients with MRCP were evaluated; 90 MRCP Health Board, United Kingdom; 12PBC Foundation, United Kingdom;
13
passed the quality control. Median age was 41 (IQR 26–51) years, 61% Newcastle University, United Kingdom; 14University of Birmingham,
were male, with a follow-up from MRCP to event/censoring of 242 Institute of Biomedical Research, United Kingdom; 15St Mark’s Hospital
patient-years. An adverse outcome occurred in 28 (25%) patients (8 and Academic Institute, United Kingdom; 16Imperial College School of
LT, 3 liver-related death, 5 liver decompensation, 10 bacterial Medicine, United Kingdom; 17UK-PBC Consortium, United Kingdom
cholangitis, 2 cholangiocarcinoma). Univariate analysis showed a Email: [email protected]
good prognostic performance of all radiomics features evaluated. At Background and aims: Herein, we present the first population-
multivariable analysis, adjusted for age and sex, the number of based, nationwide evaluation of healthcare delivery in primary
strictures and the spleen length were independently associated with biliary cholangitis (PBC) since publication of the European (EASL) and
the occurrence of adverse event with a HR of 1.06 ( per unit, CI 95% British guidelines (BSG). Our aim was to assess adherence to
1.03–1.09, p < 0.0001) and 1.34 ( per cm, CI 95% 1.11–1.6, p = 0.002), guideline recommendations and identify gaps in service provision.
respectively and a C-statistic of 0.81. The model was internally Method: This was a cross-sectional study conducted between 01/21
validated and outperformed the ANALI score in our cohort (C-statistic and 01/22. All 154 hospital boards across England, Scotland, Wales,
of 0.72 vs 0.6). The radiomics-based model, using the mean value as and Northern Ireland were invited to participate. Data was accrued
cut-off (−1), enabled risk-stratification of PSC patients (Fig). through the REDcapTM platform, accumulating parameters relating
diagnosis, treatment pathways, symptoms, risk stratification and
clinical end points.
Results: In entirety, data was returned from 120 hospital boards, with
data capture from 8461 pts across the UK. The majority (n = 7084;
83%) tested positive for anti-mitochondrial antibodies (AMA, Figure),
with 2718 (32%) of the latter subgroup also undergoing liver biopsies.
Ursodeoxycholic acid (UDCA) was used as first-line treatment in 7444

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 ORAL PRESENTATIONS
patients (88%) but sub-optimally dosed (<13 mg/kg/day) in 1732 Method: A genome-wide CRISPR/Cas9 screen was performed in
(21.5%). Only 197 pts who were under-dosed were documented to permissive human cell lines harboring newly developed subgenomic
have intolerance to higher dosing. Of individuals who were not taking HEV replicons allowing for positive and negative selection, followed
UDCA, only 214 (23%) were referred for alternative/second-line by next-generation sequencing and bioinformatic analyses.
therapy. Of pts taking UDCA for >12 months (n = 7007), 5475 (78%) Candidates were validated by siRNA-mediated gene silencing and
and 1532 (22%) were classified as low-risk and high risk, respectively, CRISPR/Cas9-mediated gene knockout in cells transfected with
by the contributing hospital. However, on applying the POISE criteria, subgenomic HEV replicons or infected with cell culture-derived HEV.
663 and 285 patients could be reclassified as ‘low-risk and high risk’ Results: The newly developed replicons and a library of 120, 000
respectively. Among all who were deemed high-risk with regards unique guide RNAs were employed in two separate screens,
disease progression (n = 2476; 29%), 1228 (49.5%) commenced identifying 20 top host factor candidates. Validation yielded five
second-line therapy (inc. 551 obeticholic acid; 468 bezafibrate; 68 host factors, including GBF1, which had been identified previously by
fenofibrate; 76 combination therapy) and 35 referred directly to a a directed approach, and the Ras-related early endosomal protein
transplant centre. In all, 1831 pts were identified as having cirrhosis Rab5A. The expression level and functional activity of Rab5A and of
(22%), of which 1304 (71%) participated in hepatocellular carcinoma well-characterized mutants thereof were found to modulate HEV
surveillance. Features of decompensated liver disease were identified RNA replication. Colocalization studies revealed close proximity to
in 272 pts, of which only 46% (n = 67) were discussed with a the HEV replicase of Rab5A and other endosomal components.
transplant centre. With regards symptoms/extrahepatic manifesta- Conclusion: We describe an innovative approach exploiting CRISPR/
tions, n = 3237 and 3690 pts did not undergo any assessment of Cas9 to identify host factors of a noncytolytic virus. Future studies
pruritus (38%) or fatigue (44%) in the 24 months prior to data shall address the mechanisms by which Rab5A modulates HEV RNA
collection. 1803 pts reported ongoing pruritus at the time of replication and define the role of early endosomes in the establish-
assessment, of whom only 1205 (67%) were receiving anti-pruritus ment of a functional replication complex. Altogether, this work yields
therapy. new insights into the HEV life cycle and the virus-host interactions
required for productive infection.

OS139
Novel ultra-potent capsid assembly modulators prevent abnormal
accumulation of empty capsids and associated T-cell mediated
liver injury in a mouse model of hepatitis B virus infection
Romano Di Fabio1,2, Matteo Iannacone3,4,5, Leda Bencheva1,
Matteo Conti6, Katherine Squires7, Mark Lockwood7,
Raffaele De Francesco8,9, Luca Guidotti3,10. 1Promidis, Italy; 2IRBM
Science Park, Pomezia, Rome, Italy; 3IRCCS San Raffaele Scientific
Institute, Division of Immunology, Transplantation and Infectious
Diseases, Milan, Italy; 4IRCCS San Raffaele Scientific Institute,
Experimental Imaging Center, Milan, Italy; 5Vita-Salute San Raffaele
University, Milan, Italy; 6INGM, National Institute of Molecular Genetics
“Romeo ed Enrica Invernizzi,” Milan, Italy; 7Antios Therapeutics, United
States; 8INGM, National Institute of Molecular Genetics, Italy;
9
Università degli Studi di Milano, Department of Pharmacological and
Biomolecular Sciences, Milan, Italy; 10Vita-Salute San Raffaele
Conclusion: Our study of real-world practice identifies significant University, Milano, Italy
gaps in clinical care across the UK PBC population. Potential future Email: [email protected]
strategies to maximise adherence to guideline standards include the
Background and aims: ATI-1428 is a sub-nM active class II capsid
implementation of an integrated care pathway, along with key
assembly modulator (CAM) that safely and durably blocks hepatitis B
performance indicators, and development of a centralised referral
virus (HBV) replication in immunocompetent transgenic (HBV Tg)
network, allowing equitable and virtual access to specialists for all
mice. Different from other CAMs, ATI-1428 induced no in vivo
those living with PBC.
abnormal accumulation of hepatitis B core antigen (HBcAg)-expres-
sing empty capsids (EC) in the hepatocellular cytoplasm. Herein, we
extend our understanding of the functional consequences of EC
accumulation in the presence of HBcAg-specific CD8+ T cells and
Viral hepatitis basic science identify another 4th-generation class II CAM (ATI-1645) that may
foster EC degradation.
Method: HBV Tg mice were treated with ATI-1428 or ATI-1112 (a class
OS138 II CAM causing abnormal EC accumulation) at 50 mg/kg every day
A genome-wide CRISPR/Cas9 screen identifies Rab5A as host (QD) for 16 days. Antiviral potency, drug- or T cell-induced liver injury
factor of the hepatitis E virus life cycle and HBcAg distribution in hepatocytes (HCs) that, divided or not,
Noémie Oechslin1, Nathalie Da Silva1, Maliki Ankavay1, were assessed at autopsy (d7 after T cell transfer). ATI-1645 was
Darius Moradpour1, Jérôme Gouttenoire1. 1Service of Gastroenterology profiled in HepAD38 cells, HBV-infected HepG2-NTCP cells, and HBV
and Hepatology, Lausanne, Switzerland Tg mice.
Email: [email protected] Results: While inhibiting HBV replication, neither ATI-1428 nor ATI-
1112 caused liver injury. T cell transfer in ATI-1112-treated mice
Background and aims: Hepatitis E virus (HEV) is a major cause of induced higher serum alanine aminotransferase peak levels and
acute hepatitis worldwide. Current understanding of the molecular failed to eliminate ECs, even from post-mitotic HCs becoming nuclear
mechanisms allowing for productive HEV infection is limited, HBcAg-negative (see Figure and PMID: 8057429). By contrast, ECs
especially with respect to host factors required for the viral life disappeared from the liver of ATI-1428- and T cell-treated animals.
cycle. Hence, our study aims at identifying host factors required for ATI-1645 showed sub-nM EC50/EC90 potency profiles with low nM
HEV replication. activity against covalently closed circular DNA establishment.

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ORAL PRESENTATIONS
Pharmacokinetic (PK)/pharmacodynamic analyses and safety/effi- characterization of 1645 as an ultra-potent HBV inhibitor that may
cacy studies in HBV Tg mice indicated that 1645 possesses excellent induce cytoplasmic EC degradation makes it a promising candidate
PK and anti-HBV activity. 28-day ATI-1645 treatment (50 mg/kg QD) for clinical development.
cleared ECs from the cytoplasm of most HCs in the absence of any
drug- or immune-mediated liver injury. OS140
Identification of cyclin L1 as a hepatitis B virus host factor
regulating viral transcription
Collins Oduor Owino1, Yi Lin Gian2, Pauline AW Poh Kim1,
Nivrithi Ganesh1, Balakrishnan Chakrapani Narmada2,
Giridharan Periyasamy2, Pablo Bifani3, Ramanuj Dasgupta1. 1Genome
Institute of Singapore (GIS), Singapore, Singapore; 2Experimental Drug
Development Centre, Singapore, Singapore; 3Department of
Microbiology and Immunology (MD4), Singapore, Singapore
Email: [email protected]
Background and aims: HBV remains a global public health threat,
with over 250 million people chronically infected and about 800, 000
deaths reported annually. Even though much work has been done to
understand HBV pathogenesis, how the virus manipulates the host
cell machinery remains underexplored. In this study we aimed to
identify novel host factors that affect HBV replication and gene
expression. We describe the role of cyclin L1 (CCNL1), a non-canonical
cyclin with transcriptional regulatory functions as a novel host cell
factor in the control of HBV transcription.
Method: We employed whole transcriptome analysis of HBV infected
primary human hepatocytes (PHH), as well as reverse genetics to
identify and validate the role of CCNL1 during HBV replication. Using
RNAi and ectopic expression models, we studied the function of
cyclin L1 on HBV replication in hepatoma cells and PHH. We also
analyzed the effect of CCNL1 knockdown on the production and
stability of HBV RNAs. Using RNA immunoprecipitation (RIP),
chromatin immunoprecipitation (ChIP), and immunoprecipitation
(IP) techniques, we evaluated the interaction between cyclin L1 and
HBV RNAs as well as HBx and HBc. Lastly, we explored the expression
profiles of cyclin L1 in chronic HBV patient cohorts and publicly
Conclusion: ATI-1112-related abnormal accumulation of cytoplasmic available microarray datasets GSE83148 and GSE52752.
ECs sensitized HCs to T cell-mediated killing and allowed these Results: Knockdown of cyclin L1 resulted in a remarkable reduction
particles to survive in resting and post-mitotic HCs no longer of HBV gene expression in both hepatoma cells (HepAD38.7 and
replicating HBV. This suggests that CAMs fostering an EC-accumulat- HepG2NTCP) and PHH. We observed a remarkable reduction in the
ing phenotype may generate targets of inadequate immunopathol- levels of HBV surface and e antigens, pre-genomic RNA, and
ogy. Conversely, the lack of cytoplasmic EC accumulation that typifies extracellular HBV DNA. Interestingly, overexpression of CCNL1
the in vivo behavior of ATI-1428 or ATI-1645 should not interfere with resulted in enhanced HBV gene expression with a significant increase
productive T cell-mediated viral clearance. The subsequent in the viral transcripts, thus, corroborating its pro-viral effect.
Furthermore, loss of function of cyclin L1 resulted in reduced levels

Figure: (abstract: OS140)

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 ORAL PRESENTATIONS
of HBV nascent RNA, highlighting its role during HBV transcription. within the liver, with a reduction on prolonged NUC therapy and the
RIP data showed that CCNL1 might be modulating HBV RNA potential for re-expression following treatment withdrawal. The
production through direct interaction with viral RNAs. Lastly, we mechanism by which HBV load associates with global (rather than
observed enhanced expression of cyclin L1 in CHB from our patient just HBV-specific) T cell PD-1 remains to be explored. These findings
cohort data and publicly available data sets underscoring its putative underscore the need for further consideration of NUC-induced
function in HBV replication and virus-induced liver disease. changes in global liver T cell PD-1 when targeting this axis in HBV
Conclusion: Here, we report that cyclin L1 is a novel HBV host factor functional cure.
modulating the production and stability of viral RNAs. Our data
contributes towards the understanding of HBV infection biology and OS142
provide a new perspective towards developing host-directed anti- Phospho-proteomic analysis of HBV infection revealed novel
HBV therapies. mechanisms for the regulation of viral transcription and pro-
fibrotic stellate cell activation
OS141 Alessia Virzi1,2, Zakaria Boulahtouf2,3, Sarah Durand1,2,4,
Liver-resident T cell PD-1 correlates with intrahepatic HBV-DNA Emanuele Felli2,3,4, Patrick Pessaux2,3,4, Oliver Popp5,6,
and is reduced following prolonged antiviral therapy Evelyn Ramberger5,6, Philipp Mertins5,6, Eloi Verrier2,3,
Mireia García-López1, Laura J. Pallett2, Sergio Rodriguez-Tajes1, Catherine Schuster1,2,4, Thomas Baumert2,3,4,7, Joachim Lupberger2,3.
Ernest Belmonte3, Thais Leonel1, Ester García-Pras1, Sabela Lens1, 1
Inserm U1110, Strasbourg, France; 2Université de Strasbourg,
Zoe Mariño1, Concepció Bartres1, Ariadna Rando-Segura4, Strasbourg, France; 3Inserm U1110, Strasbourg, France; 4Institut
Francisco Rodríguez-Frías4, Xavier Forns1, Mala Maini2, Hospitalo-Universitaire, Pôle Hépato-digestif, Nouvel Hôpital Civil,
Sofía Pérez-del-Pulgar1. 1Liver Unit, Hospital Clínic, University of Strasbourg, France; 5Max Delbrück Center for Molecular Medicine,
Barcelona, IDIBAPS, CIBEREHD, Barcelona, Spain; 2Division of Infection Berlin, Germany; 6Berlin Institute of Health, Berlin, Germany; 7Institut
and Immunity, Institute of Immunity and Transplantation, University universitaire de France (IUF), Paris, France
College London, London, United Kingdom; 3Radiology Department, Email: [email protected]
Centro de Diagnóstico por la Imagen (CDI), Hospital Clínic, University of
Background and aims: Chronic hepatitis B virus (HBV) pathological
Barcelona, Barcelona, Spain; 4Liver Pathology Unit, Department of
course are characterized by the dysregulation of fibrogenic and
Biochemistry and Microbiology, Hospital Universitari Vall d’Hebron,
oncogenic signalling. Considering the lack of efficient anti-fibrotic
Universitat Autònoma de Barcelona, CIBERehd, Barcelona, Spain
therapies and treatment to eradicate cccDNA, the understanding of
Email: [email protected]
regulatory pathways is urgently needed. To identify the potential
Background and aims: PD-1 is known to be upregulated on global drivers of this dysregulation, we studied HBV-induced signalling in
and virus-specific T cells in the HBV-infected liver and is a major HBV infection models.
target of current immunotherapies in chronic hepatitis B (CHB). Method: Proteomic and phospho-proteomic analysis of HBV-
However, factors driving its expression in the liver compartment, and infected HepG2-NTCP were performed using liquid chromatog-
potential modulation by antivirals have not been well-defined. Here raphy-mass spectrometry. The deregulated signalling pathways
we therefore investigated the relationship between intrahepatic HBV were examined by gene set enrichment analysis and validated in
load and liver-resident T cell PD-1 and whether this could be reduced primary human hepatocytes. Perturbation studies, trans-dominant
by prolonged NUC suppression. phospho-dead/mimetic mutagenesis and ex vivo experiment were
Method: This study included 22 CHB patients who underwent performed to validate the results.
hepatic fine needle aspiration (FNA) and biopsy, 9 of whom were Results: Our data revealed a strong HBV-induced dysregulation of
treated with NUCs for at least 4 years; a subset had a repeat FNA signalling involved in extra-cellular matrix (ECM) and cell cycle.
following treatment withdrawal. Multiparameter flow cytometry was ECM-associated leading-edge genes comprised collagen VI, which
used for immunophenotyping PBMCs and intrahepatic leukocytes was upregulated in HBV-infected hepatocytes. Interestingly, silencing
extracted from FNAs. Liver biopsies were used to determine total of COL6A1 impairs viral transcription suggesting a pro-viral role of
intrahepatic HBV-DNA (iHBV-DNA) and cccDNA levels. collagen VI. Myofibroblasts account for the majority of collagen I
Results: T cells with a tissue-resident memory (TRM) phenotype were deposed into the ECM. We found that treatment of hepatic stellate
excluded from PBMC but detectable in all FNAs whether treated with cells (HSCs) with collagen VI significantly induced an expression of
antivirals or not, confirming reliable sampling of the intrahepatic HSCs activation markers, revealing a role of collagen VI in promotion
compartment (CD103+CD69+: 3%, IQR 2–7%, CD103−CD69hi: 17%, IQR of liver fibrosis. In addition, our phospho-proteomics provides new
10–23%). PD-1 expression was strikingly higher on intrahepatic than insight on viral life cycle regulation. Although HBV predominantly
circulating CD8 T cells, particularly the tissue-resident fraction replicates in G1/G2 phase, we found linker histones H1.4 among the
(CD103−CD69+ and TRM, p < 0.0001) as described previously top hits of the HBV phospho-proteomic analysis. Linker histones are
(Fisicaro et al. 2010, Pallett et al. 2017). Measurement of liver viral generally phosphorylated during S/M phase and associated to
parameters showed that CD8 T cell PD-1 expression correlated with chromatin relaxation. We found that mimicking H1.4 detachment
both iHBV-DNA (r = 0.6, p = 0.007) and cccDNA (r = 0.7 p = 0.002) but by RNAi augmented viral transcription, while a trans-dominant
not with ALT. Supporting a role for HBV in driving PD-1 expression, phospho-dead mutation S104A in H1.4 inhibited HBV RNA transcrip-
FNAs from the cohort with prolonged viral suppression on NUCs had tion. This suggests that HBV requires H1.4 phosphorylation to
significantly lower proportions of PD-1-expressing T cells and lower maintain cccDNA transcription. Chip experiments with the H1.4
expression levels. By contrast, no significant changes in CD8 T cell PD- mutants are under way.
1 between NUC-treated and naïve patients were detectable in the Conclusion: We identified the phospho-proteomic landscape of
periphery. Therefore, although CD8 T cell PD-1 in PBMC and HBV-host interaction which serves as a resource for the identification
intrahepatic lymphocytes showed an overall correlation, blood of novel drivers regulating viral life cycle and pathogenesis. We
sampling cannot fully predict the impact of NUCs on this immune revealed a previously unrecognized role of collagen VI and linker
target in the liver compartment. In a small subset of patients re- histones in HBV replication with potential impact on liver fibrosis
sampled by FNA 6 months after NUC discontinuation, preliminary progression and cccDNA transcription, respectively.
data suggested the withdrawal of viral suppression had the potential
to drive re-expression of high levels of PD-1 on intrahepatic T cells.
Conclusion: Our results reveal a close association between intrahe-
patic HBV-DNA and global liver-resident T cell PD-1 expression

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ORAL PRESENTATIONS
OS143 of Medicine, Department of Internal Medicine, Seongnam, Korea, Rep. of
CD4 T cell immunity to HEV-infection is characterized by South; 2Soongsil University, Department of Statistics and Actuarial
sustained capsid-specific responses that correlate with Science, Seoul, Korea, Rep. of South; 3the Catholic University of Korea,
neutralizing antibodies Department of Biomedicine and Health Science, Seoul, Korea, Rep. of
Benedikt Csernalabics1, Stefan Marinescu1, Lars Maurer2, South; 4Yonsei University College of Medicine, Department of Internal
Katharina Wild1, Katharina Zoldan1, Marcus Panning3, Medicine, Seoul, Korea, Rep. of South
Philipp Reuken4, Tony Bruns5, Christoph Neumann-Haefelin1, Email: [email protected]
Bertram Bengsch1, Maike Hofmann1, Robert Thimme1,
Background and aims: Metabolic dysfunction-associated fatty liver
Viet Loan Dao Thi2, Tobias Böttler1. 1University Hospital Freiburg,
disease (MAFLD) is a recently proposed concept for fatty liver disease.
Department of Medicine II, Freiburg, Germany; 2Heidelberg University However, heterogeneous disease severity and prognosis might exist
Hospital, Department of Infectious Diseases and Virology, Heidelberg,
even among patients with the same disease category of MAFLD. We
Germany; 3University Hospital Freiburg, Institute of Virology, Freiburg, investigated the risk stratification of long-term outcomes according
Germany; 4Jena University Hospital, Department of Medicine IV, Jena;
5 to MAFLD subgroups based on diagnostic criteria in patients with
University Hospital RWTH Aachen, Department of Medicine III, Aachen,
chronic viral hepatitis using a nationwide cohort.
Germany Method: We included 63, 233 chronic hepatitis B and chronic
Email: [email protected]
hepatitis C patients who underwent health examinations in 2009.
Background and aims: CD4 T cells are key protagonists in shaping an Hepatic steatosis was defined as a fatty liver index ≥60. MAFLD was
antiviral immune response. However, there are only limited insights defined as the presence of hepatic steatosis with any one of the
into their specificity and distinction in the context of a hepatitis E following three conditions, overweight/obesity (body mass index
Virus (HEV) infection. Therefore, we aim to characterize the ≥23 kg/m2), diabetes, two or more metabolic dysregulation. The
specificity, phenotype and differentiation of CD4 T cells targeting primary end points of this study were incident hepatocellular
different epitopes of the HEV polyprotein and their correlation with carcinoma (HCC) and all-cause mortality.
neutralizing antibodies targeting hepatitis E virions. Results: The prevalence of MAFLD was 14.1% (n = 8, 896). During a
Method: HEV-specific CD4 T cells targeting different HEV-specific median 8.4-year follow-up, we documented 3, 732 HCC cases and 4,
CD4 T cell epitopes from the viral polyprotein were identified by 778 deaths. Compared to patients with no MAFLD (n = 54, 377), the
intracellular cytokine staining in 7 acutely infected and 33 resolved risk of HCC and mortality was significantly higher in patients with
patients. Surface markers, relevant costimulatory receptors and MAFLD (adjusted hazard ratio [aHR] = 1.34, 95% confidence interval
transcription factors were analysed by using HEV-specific HLA- [CI] = 1.23–1.46) for HCC; aHR = 1.26, 95% CI = 1.17–1.36 for mortality).
DRB1*01:01 and *04:01 tetramers. Additionally, neutralizing anti- Among patients with MAFLD, 687 HCCs and 861 deaths were
bodies targeting naked (nHEV) and quasi-enveloped (eHEV) virions documented. The prevalence of diabetes among patients with
were determined (n = 72). MAFLD was 25.9% (n = 2, 303). The risk of HCC and mortality was
Results: Robust and multi-specific CD4 T cell responses were significantly higher in patients with diabetes (aHR = 1.36, 95% CI =
identified against the viral capsid and non-structural polyprotein 1.16–1.59 for HCC; aHR = 1.72 95% CI = 1.50–1.97 for mortality)
(NSP). In contrast, only few phosphoprotein-specific responses were compared to patients with no diabetes, among patients with
detectable. Overall, the virus-specific CD4+ T cell response was MAFLD. When we stratified patients with MAFLD according to the
stronger and broader in acutely infected versus resolved patients. other criteria (overweight/obesity or metabolic dysregulations), risk
Moreover, a switch from a highly activated Th1 and Tfh cell phenotype of HCC and mortality was not different across the groups (all p > 0.05).
towards a heterogeneous memory population was observed after viral Conclusion: Concurrent MAFLD was associated with higher risk of
elimination. Noteworthy, the presence of a capsid-specific IFN-γ- or HCC and mortality in patients with chronic viral hepatitis. Our results
IL-21-producing CD4 T cell response positively correlated with IgG- suggest that diabetes can stratify the risk of HCC and mortality in
and neutralizing antibody titers against nHEV. patients with chronic viral hepatitis and concurrent MAFLD.
Conclusion: Collectively, our results reveal important novel insights
into the HEV- specific CD4 T cell response by demonstrating a solid
maintenance of capsid- and NSP-specific CD4 T cell responses with
the formation of a robust HEV-specific memory compartment. They
also reveal a clear immunodominance with phosphoprotein being
less immunogenic.

Sunday 26 June

Hepatitis B clinical aspects

OS145
OS144 Long term persistence of anti-HBs antibodies after vaccination
Metabolic dysfunction-associated fatty liver disease subgroups with a 3-antigen HBV vaccine compared to a single-antigen HBV
and risk of hepatocellular carcinoma and mortality in patients vaccine
with chronic viral hepatitis Timo Vesikari1, Aino Forstén1, Vlad Popovic2, Johanna Spaans2,
Mi Na Kim1, Kyungdo Han2, Juhwan Yoo3, Seong Gyu Hwang1, Francisco Diaz-Mitoma2. 1Nordic Research Network Oy, Tampere,
Sang Hoon Ahn4. 1CHA Bundang Medical Center, CHA University School Finland; 2VBI Vaccines Inc., Canada
Email: [email protected]
Background and aims: Hepatitis B virus (HBV) infection is a serious
public health problem that can be effectively prevented with

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 ORAL PRESENTATIONS
hepatitis B vaccination. The magnitude of the immune response to Method: All patients under CHB therapy at entry in the ANRS CO22
HBV vaccination can be measured by serum levels of anti-HBs, HEPATHER cohort were selected. Patients with history of liver
persistence and durability, which is believed to be dependent upon transplantation or hepatitis D virus co-infection were excluded.
the induced peak levels. PROTECT was a double-blind, randomized, Multiple imputations of GGT, triglycerides, waist circumference and
Phase 3 study to evaluate immunogenicity and safety of a 3-antigen BMI were realized. Outcomes were first, the occurrence of death from
HBV vaccine (3A-HBV, manufactured by VBI Vaccines) and a single- any cause, then death from liver complication ( primary liver cancer,
antigen HBV vaccine (1A-HBV, Engerix-B®). Three doses of vaccine decompensated cirrhosis, and liver transplantation). Proportional
were administered IM at Days 1, 28, and 168. Seroprotection rate hazard adjusted on age, gender and diabetes status. Cox models were
(SPR-% of subjects achieving anti-HBs ≥10 mIU/ml) and geometric performed. Potential non-linear relationships were examined using
mean concentration (GMC) of anti-HBs were evaluated for 12 fractional polynomial models.
months. Following the completion of PROTECT, this follow-up Results: 2877 treated CHB patients were included. Median age was
investigator-initiated study of PROTECT aimed to assess the long- 48.9 years [Interquartile range (IQR): 38.1; 59.8] and 2044 (71.0%)
term persistence of anti-HBs titers 2–3 years after the 3rd dose in were men. Almost all patients were treated by nucleos (t)idic
participants enrolled in Finland. analogues (98%) for a median time of 2.9 years (IQR [0.4; 5.2]) and
Method: Subjects were eligible for the follow-up study if they had 92.0% had an HBV DNA level <2, 000 UI/ml at entry. After a median
been enrolled in PROTECT study in Finland and had achieved follow-up of 7.0 years (IQR [6.2; 7.6]), incidence of all-cause mortality
seroprotection (anti-HBs ≥10 mIU/ml). Between February 2021 and was 7.7/1000 person/years (95% Confidence Interval (CI) 6.6–9.1), and
June 2021, subjects were contacted to participate in the follow-up 4.0/1000 person/years (95% CI 3.2–5.0) for liver-related mortality.
study. Serum samples were tested for Anti-HBs titers at the central After adjustment, an increase of ten points of FLI was significantly
laboratory (LabConnect, USA) using the same validated anti-HBs associated with an increased risk of all-cause mortality (Hazard Ratio
quantitative assay [VITROS, Ortho 3600 NJ, USA] as used in the (HR): 1.09 [1.02–1.16]) and tended to be associated with liver-related
PROTECT study. mortality (HR: 1.08 [0.99–1.19]).
Results: Of the 528 subjects contacted, 465 agreed to participate in
the follow-up study, including 244 [52.5%] vaccinated with 3A-HBV
and 221 [47.5%] vaccinated with 1A-HBV. Baseline characteristics
were well balanced between the groups and consistent with the
PROTECT study population, the mean age for both vaccine groups was
59 years. Data from the PROTECT study demonstrated a peak GMC of
anti-HBs of 8021.9 mIU/ml for 3A-HBV and 3787.3 mIU/ml for 1A-
HBV in study participants one month after the third dose (Day 196).
Data from this follow-up study showed that approximately 2.5 years
following Day 196 in the PROTECT study, the mean concentration of
anti-HBs was 1382.9 mIU/ml for 3A-HBV participants and 251.4 mIU/
ml for 1A-HBV participants. Additionally, more than 2x the number of
subjects vaccinated with 3A-HBV retained anti-HBs ≥100 mIU/ml
compared to 1A-HBV (72.9% vs. 32.6%). After approximately 2.5 years,
27.6% in the 1A-HBV group and 11.9% in the 3A-HBV group no longer
had seroprotective levels of anti-HBs (titers <10 mIU/ml).
Conclusion: 2.5 years after achieving peak seroprotection in the
PROTECT study, the mean anti-HBs titers were five times higher in the
3A-HBV group than in the 1A-HBV group. Additionally, the
Figure: Kaplan-Meier survival estimates according FLI categories. ANRS
percentage of participants who no longer had seroprotective levels CO22 HEPATHER cohort, treated CHB participants.
of anti-HBs (titers <10 mIU/ml) was more than double in the 1A-HBV
group compared to the 3A-HBV group. Conclusion: In this first large prospective cohort of French patients
with treated chronic HBV infection, FLI was independently associated
OS146 with all cause and liver-related mortality.
Fatty liver index as a risk factor for all-cause and liver related
mortality in patients under therapy for chronic hepatitis B (ANRS OS147
CO22 Hepather cohort study) The discriminatory power of risk scores for hepatocellular
Paul Hermabessiere1, Mathieu Chalouni2, Marc Bourliere3, carcinoma in treated chronic hepatitis B patients with and
Pierre Nahon4, François Teoule5, Clovis Lusivka-Nzinga5, without diabetes: a territory-wide study of 48,706 subjects
Helene Fontaine6, Stanislas Pol6, Fabrice Carrat5, Terry Cheuk-Fung Yip1, Mandy Sze-Man Lai1,
Victor de Lédinghen1, Linda Wittkop2. 1Hôpital Haut-Lévêque Vincent Wai-Sun Wong1, Yee-Kit Tse1, Yan Liang2, Vicki Wing-Ki Hui2,
Magellan, Pessac, France; 2ISPED, Bordeaux, France; 3Hospital Paris Henry LY Chan3,4, Grace Lai-Hung Wong1. 1The Chinese University of
Saint-Joseph, Paris, France; 4Jean-Verdier Hospital Ap-Hp, Bondy, Hong Kong, Medical Data Analytics Centre (MDAC), Department of
France; 5Hospital Saint-Antoine Ap-Hp, Paris, France; 6Cochin Hospital, Medicine and Therapeutics, Institute of Digestive Disease, Faculty of
Paris, France Medicine, Hong Kong; 2The Chinese University of Hong Kong, Medical
Email: [email protected] Data Analytics Centre (MDAC), Department of Medicine and
Therapeutics, Faculty of Medicine, Hong Kong; 3Union Hospital,
Background and aims: A quarter of patients with chronic hepatitis B
Department of Internal Medicine, Hong Kong; 4The Chinese University of
(CHB) have associated fatty liver disease and the prognosis of these
Hong Kong, Medical Data Analytics Centre (MDAC), Faculty of Medicine,
patients has been poorly investigated. In the general population, Fatty
Hong Kong
Liver Index (FLI) is a recommended alternative to ultrasonography for
Email: [email protected]
the diagnosis of steatosis (EASL 2016) and predict clinical outcomes
related to non-alcoholic fatty liver disease (NAFLD). The aim was to Background and aims: Patients with chronic hepatitis B (CHB) are
evaluate the association between FLI and all-cause and liver-related aging with a rising prevalence of diabetes mellitus (DM) to over 20%
mortality in treated CHB participants from the ANRS CO22 HEPATHER in recent years. While DM is associated with a doubled risk of
cohort. hepatocellular carcinoma (HCC) in CHB patients, few HCC risk scores

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ORAL PRESENTATIONS
include DM as a factor. We aimed to compare the performance of HCC OS148
risk scores among DM and non-DM patients on nucleos (t)ide Hepatocellular carcinoma incidence is reduced in cirrhotic
analogue (NA) treatment. chronic hepatitis B patients with HBsAg seroclearance comparing
Method: Adult CHB patients on at least 6 months of entecavir or to those with viral suppression
tenofovir treatment from January 2005 to March 2020 were Rachel Wen-Juei Jeng1,2,3, Chien-Hung Chen1,4, Hwai-I Yang5,
identified using a territory-wide database in Hong Kong. DM was Yi-Cheng Chen1,2,3, Yen-Chun Liu1,2,3, Chia-Ying Wu2,3,
defined by any use of non-insulin antidiabetic agents, continuous use Rong-Nan Chien1,2,3, Yun-Fan Liaw1,2. 1Chang Gung University, College
of insulin for ≥28 days, haemoglobin A1c ≥6.5%, fasting glucose of Medicine, Taiwan; 2Linkou Chang Gung Memorial Hospital, Liver
≥7 mmol/L, and/or diagnosis codes. Two HCC risk scores with DM as a Research Unit, Taiwan; 3Linkou Chang Gung Memorial Hospital,
factor for treated CHB patients (i.e., cirrhosis, age, male sex, and DM Department of Gastroenterology and Hepatology, Taiwan; 4Kaohsiung
[CAMD] score and Real-world Effectiveness from the Asia Pacific Rim Chang Gung Memorial Hospital, Division of Hepatogastroenterology,
Liver Consortium for hepatitis B virus [REAL-B] score) were studied; 2 Department of Internal Medicine, Taiwan; 5Academia Sinica, Genomic
other HCC risk scores without DM as a factor (i.e., PAGE-B and Research Center, Taiwan
modified PAGE-B [mPAGE-B] scores) were also examined. The Email: [email protected]
discriminatory power of the scores was assessed by area under the
Background and aims: Cirrhosis is a major risk factor for
time-dependent receiver operating characteristic curves (AUROCs)
hepatocellular carcinoma (HCC) development in chronic hepatitis B
with death as a competing event. Comparisons were done based on 1,
000 bootstrap samples. patients. It remains unknown whether HBsAg seroclearance in
cirrhotic patients reduces the risk of HCC compared to those under
Results: Of 48,706 patients included, the mean age was 54.3 ± 13.6
years; 62.1% were male and 12.7% had cirrhosis. The prevalence of DM long-term Nuc treatment. This study aims to investigate the HCC
incidence between these two groups.
rose steadily from 15.5% to 24.3% in those who started NA treatment
Method: The study recruited chronic hepatitis B patients with
in 2005–08 and 2017–20 respectively. At a median (25th percentile–
75th percentile) follow-up of 4.4 (2.2–5.0) years, 2, 157 (4.4%) cirrhosis undergoing Nuc therapy with viral suppression (Nuc arm,
N = 805) and cirrhotic CHB patients with HBsAg seroclearance (S-loss
patients developed HCC. All the 4 HCC scores were less predictive in
DM patients than non-DM patients (all p < 0.001; Figure). DM was an arm, N = 165, 65 untreated, 90 off-therapy, 10 on-treatment HBsAg
independent risk factor for HCC on top of the risk groups of PAGE-B loss) from two medical centers and REVEAL-HBV cohort. The baseline
in the Nuc arm was set since HBV DNA being undetectable (complete
score (adjusted hazard ratio [aHR] 3.85, 95% CI 2.06–7.18, p < 0.001),
and had an interaction with PAGE-B risk groups (aHR [95% CI]: 0.40 viral suppression) while in the S-loss arm was set since HBsAg loss.
Those with HCC occurred prior to the baseline or within 6 months
[0.21–0.77] for intermediate-risk group and 0.27 [0.14–0.51] for high-
after the baseline were excluded from this analysis. Kaplan Meier
risk group as compared to non-DM patients in low-risk group). DM
was however found to be not associated with HCC after adjusting for analysis and log rank test were done for the cumulative HCC
incidence comparison.
mPAGE-B score (aHR 1.04, 95% CI 0.95–1.14, p = 0.423).
Results: Comparing the baseline features between Nuc arm and S-loss
arm, the mean age (55.5 vs. 56.8, P = 0.14), gender (male: 74.5% vs.
81.2%, P = 0.07) and HBV genotype ( p = 0.27) were comparable. The
median ALT (29 vs. 20 U/L, P < 0.001) and AFP (4.16 vs. 3.0 mg/dL, P <
0.001) level were higher in the Nuc arm while follow-up duration was
longer in the S-loss arm (median: 7.9 vs. 4.3 years, P < 0.001). In
univariate analysis, older age [crude HR (cHR): 1.04, P < 0.0001], higher
FIB-4 level [cHR: 1.1, P = 0.0004], higher AFP level [cHR: 1.02, P < 0.001]
were positively associated with HCC occurrence while HBsAg loss is a
protective factor for HCC [cHR: 0.502, P = 0.0314]. In multivariate
analysis, older age [adjusted HR (aHR): 1.04 (1.02–1.06), P < 0.0001]
and HBsAg loss [aHR: 0.19 (0.05–0.76), P = 0.0193] are the two
independent predictor for HCC. The annual incidence and 8-year
cumulative HCC incidence in cirrhotic patients in Nuc arm versus S-
loss arm were 2.43% and 16% versus 1.16% and 8%, respectively (Log
tank test, P = 0.0282). After propensity score matching with age,
gender and FIB-4 at 1 to 1 ratio with 77 patients at each arm. HBsAg loss
arm still had much lower HCC incidence than those under Nuc arm
(annual incidence: 0.46% vs. 3.2%, log rank test, P = 0.0035).
Conclusion: This is the first study proved the HBsAg seroclearance,
reflecting the inactive transcriptional activity of cccDNA, is a
protective factor for HCC in cirrhotic chronic hepatitis B patients.

Figure: The area under the time-dependent receiver operating character-

istic curves (AUROCs) of A. PAGE-B score; B. mPAGE-B score; C. CAMD
score; and D. REAL-B score for predicting the development of hepatocellu-
lar carcinoma in nucleos (t)ide analogue-treated chronic hepatitis B
patients with and without diabetes mellitus (DM).

Conclusion: HCC risk scores are less accurate in NA-treated diabetic

CHB patients than their non-diabetic counterparts, with a drop of Figure: Cumulative HCC incidence between cirrhotic CHB patients with
AUROCs from around 0.8 to 0.7 regardless of whether DM is a Nuc viral suppressed (blue line) and HBsAg loss (red line) before and after
component in the risk scores or not. propensity score matching.

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 ORAL PRESENTATIONS
OS149
Treatment with bulevirtide improves patient-reported outcomes
in patients with chronic hepatitis delta: An exploratory analysis of
a Phase 3 trial at 48 weeks
Maria Buti1, Heiner Wedemeyer2, Soo Aleman3, Vladimir Chulanov4,
Morozov Viacheslav5, Olga Sagalova6, Tatyana Stepanova7,
Robert G. Gish8, Andrew Lloyd 9, Ankita Kaushik10, Vithika Suri10,
Dmitry Manuilov10, Anu Osinusi10, John F. Flaherty10, Pietro Lampertico11
. 1Hospital Universitario Valle Hebron, Barcelona, Spain; 2Medizinische
Hochschule Hannover, Hannover, Germany; 3Karolinska
Universitetssjukhuset, Karolinska lnstitutet, Stockholm, Sweden; 4Central
Research Institute of Epidemiology, Moscow, Russian Federation;
5
Hepatolog, LLC, Samara, Russian Federation; 6Southern Ural State Medical
University, Chelyabinsk, Russian Federation; 7Clinic of Modern Medicine,
Moscow, Russian Federation; 8Robert G. Gish Consultants, LLC, San Diego,
United States; 9Acaster Lloyd Consulting Ltd, London, United Kingdom;
10
Gilead Sciences, Inc., Foster City, United States; 11Foundation lRCCS Ca’
Granda Ospedale Maggiore Policlinico, CRC “A.M. and A. Migliavacca”
Center for Liver Disease, University of Milan, Milan, Italy
Email: [email protected]
Background and aims: Chronic hepatitis delta (CHD) infection is
caused by a defective RNA virus that requires the presence of the
hepatitis B virus (HBV) surface antigen for replication and transmis-
sion. Compared with HBV monoinfection, patients with CHD have a
greater risk of cirrhosis, hepatocellular carcinoma, liver transplant,
and liver-related mortality. In 2020, the European Medicines Agency
granted conditional marketing authorisation to bulevirtide (BLV)
Conclusion: CHD patients treated with BLV 2 mg showed an
2 mg, a novel NTCP entry inhibitor, as the first treatment approved for
improvement at W48 in all domains of the HQLQ, while patients in
CHD. We report an exploratory analysis of health-related quality-of-
the control group remained largely unchanged, apart from substan-
life outcomes in patients with CHD after 48 weeks of treatment with
tial improvements in health distress and HS health distress. Patients
BLV 2 mg in an ongoing Phase 3 trial.
receiving BLV 2 mg reported significant improvements in quality-of-
Method: MYR301 (NCT03852719; EudraCT 2019-001213-17) is a
life domains, including role-physical, HS limitations, and HS health
randomised, open-label, parallel-group, multicentre trial that
distress, compared with controls.
assigned 150 CHD patients (1:1:1) to 3 exploratory arms (BLV 2 or
Medical writing support was provided by Ellie Manca, AlphaScientia,
10 mg or control) for up to 3 years. (As BLV 10 mg is not an approved
LLC, and was funded by Gilead Sciences, Inc.
dosage, we do not report that treatment arm.) Control patients
received no active anti-HDV treatment until Week (W)48. Patients 1. Wedemeyer H et al. Treatment with bulevirtide improves patient-
completed the Hepatitis Quality of Life Questionnaire (HQLQ), reported outcomes in patients with chronic hepatitis delta (CHD): an
including the SF-36 and 15 supplemental items, at study baseline interim exploratory analysis at week 24. Presented at AASLD Nov 12–
15, 2021. Poster 680.
(BL), W24, and W48. Higher scores on the HQLQ (range 0–100)
indicate better health. Interim results collected at W24 were reported
previously.1
Results: BL characteristics were well balanced between BLV 2 mg (n =
49) and controls (n = 51). For BLV 2 mg, mean age was 44 years, BMI Cirrhosis and its complications: Experimental
was 24 kg/m2, 61% were male, 83% were White, and 47% had and pathophysiology
compensated cirrhosis. Across groups, patients reported varying
scores of HQLQ. From BL to W48, BLV 2 mg was associated with
improvements in all HQLQ domains; notably, >5-point improvements OS150
in mean values were observed for 10 of the 14 items (Figure). Extracellular vesicles from mesenchimal stem cells reduce
Treatment differences vs controls in least-squares mean changes neuroinflammation in hippocampus and restore cognitive
from BL to W48 were statistically significant ( p < 0.05) for role- function in hyperammonemic rats
physical, hepatitis-specific (HS) limitations, and HS health distress. Paula Izquierdo-Altarejos1, Carlos Sanchez-Huertas2,
Improvements with BLV 2 mg seen at W24 were largely maintained Victoria Moreno-Manzano3, Vicente Felipo1,4. 1Centro de Investigacion
or increased at W48. Principe Felipe, Neurobiology, Valencia, Spain; 2Instituto de
Neurociencias CSIC-UMH, Laboratory of Bilateral Neural Circuits,
Alicante, Spain; 3Centro de Investigacion Principe Felipe, Neuronal and
Tissue Regeneration Lab, Valen ̀ cia, Spain; 4CIPF Centro de Investigación
Príncipe Felipe, Valencia, Spain
Email: [email protected]
Background and aims: Chronic hyperammonemia, a main contribu-
tor to hepatic encephalopathy, leads to neuroinflammation which
alters neurotransmission leading to cognitive impairment. Currently
there are no specific treatments for the neurological alterations in
hepatic encephalopathy. Extracellular vesicles (EVs) from mesenchy-
mal stem cells (MSCs) reduce neuroinflammation in some patho-
logical conditions. The aim of this work was to assess if treatment of

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ORAL PRESENTATIONS
hyperammonemic rats with EVs from MSCs reducesneuroinflamma- n = 5), outpatients with refractory ascites (ORA, n = 5) and hospita-
tion, improves neurotransmission in hippocampus and restorescog- lised AD patients (n = 10). Finally, we examined HAI incidence in the
nitive function and to analyzethe mechanisms involved. 47 ATTIRE patients on statins at baseline.
Method: Treatment with EVs from MSCs was performed in vivo by Results: Median time to HAI was 6 days. PLSDA models including
intravenous injection and ex vivo in hippocampal slices in hyper- clinical covariates significantly predicted HAI development, with
ammonemic and control rats. Effects on neuroinflammation (micro- Bilirubin at baseline having a variable importance in projection (VIP)
glia and astrocytes activation and content of inflammatory markers in score of 2.5. Within each metabolite class, only PCAs of Cholesterol
hippocampus) were assessed by immunohistochemistry, immuno- Esters (CEs) and Sphingomyelin (SM) class resulted in separation by
fluorescence and western blot. Learning and memory were assessed HAI status, driven by CE 18.16.0, CE 18.2.1, CE 18.2.2 and SM 42.2.2.
using the following tests: object location, object recognition, Y maze When included in PLSDA models, CE 18.1.0 and CE 18.2.0 were both
and radial maze. important in predicting HAI (VIP >1) (table). RNA-seq showed
Results: The EVs injected reached the hippocampus. reduced blood Sterol O-acyltransferase 1 (SOAT1) expression com-
Hyperammonemia induced neuroinflammation in hippocampus pared to HV (mean ± SD gene count: 384.0 ± 94.9) in ADs (254.9 ±
and impaired learning and memory in the tests performed. 81.0; P = 0.02) and ORA patients (260.0 ± 55.1; P = 0.04, figure). There
Treatment with EVs reduced microglia and astrocytes activation, the was no difference in HAI according to baseline statin use, which
content of IL-1beta and NF-kB activation and restored performance of occurred in 9/47 statin (19.1%) and 141/730 non-statin (19.3%)
hyperammonemic rats in all the behavioral tests. Studies adding EVs patients.
to hippocampal slices ex vivo showed that these beneficial effects
were dependent on TGFbeta present in the EVs, which reduced NF-kB
activation and the subsequent neuroinflammation.

Conclusion: Extracellular vesicles from mesenchymal stem cells

reduce neuroinflammation in hippocampus and restore cognitive Conclusion: Data are consistent with a downregulation of blood
function in hyperammonemic rats. EVs from MSCs may be useful to cholesterol esterification via SOAT1 in AD patients predicting
improve cognitive function in patients with Minimal Hepatic development of HAI. Statins do not affect cholesterol esterification
Encephalopathy. and were non-predictive of HAI status within PLSDA models and had
no effect clinically, although small numbers were analysed. CE may be
OS151 novel and functional biomarkers that predict HAI in AD, providing
Lipidomics analyses of ATTIRE trial patients’ plasma at day 1 mechanistic insight.
demonstrates that reduced cholesterol esterification predicts
development of hospital acquired infection OS152
Harriett Fuller1, Thais Tittanegro2, Alex Maini2, Louise China2, Integrating single-cell RNA and spatial transcriptomic data
James Thorne3, J. Bernadette Moore1, Alastair O’Brien2. 1University of defines altered cell state in human liver fibrosis
Leeds School of Food Science and Nutrition, Leeds, United Kingdom; 2UCL Nigel Hammond1, Sokratia Georgaka1, Syed Murtuza-Baker1,
Institute for Liver and Digestive Health Upper 3rd Floor, University Ali Al-Anbaki1, Elliot Jokl1, Harry Spiers2,3, Ajith Siriwardena1,
College London Division of Medicine, London, United Kingdom; 3School Varinder Athwal1, Neil Hanley1, Magnus Rattray1, Karen Piper Hanley1.
1
of Food Science and Nutrition @ Parkinson ( p2.32), Faculty of The University of Manchester, United Kingdom; 2University of
Environment University of Leeds, Leeds, United Kingdom Cambridge, Department of Surgery, Cambridge, United Kingdom;
Email: [email protected] 3
Addenbrooke’s Hospital, Department of Hepato-pancreato-biliary
Background and aims: Hospital acquired infections (HAIs) are Surgery, Cambridge, United Kingdom
common in acute decompensation (AD) patients and studies Email: [email protected]
support an anti-inflammatory role for statins. We investigated the Background and aims: Advances in single cell technology have
role of lipid metabolism pathways in AD patients that developed revolutionised our understanding of the liver, enabling genome-wide
HAIs. RNA-profiling of thousands of transcriptomes at single cell reso-
Method: Plasma from 56 ATTIRE trial patients (31 male, 25 female) at lution. Recent studies utilising single cell RNA sequencing (scRNA-
day 1 ( pre-albumin infusions or standard care) were analysed using seq) have characterised progenitor cell populations, uncovered gene
Lipotype Shotgun Lipidomics platform. Patients were not diagnosed expression zonation of multiple cell types, and revealed their
with infection nor taking antibiotics at sampling, with 26 subse- contribution to disease pathogenesis. However, scRNA-seq does not
quently developing HAI and 30 not. Lipidomic profiles predicting HAI capture the spatial distribution of transcripts in cells and dissociated
status were analysed via multivariate statistical techniques ( principal tissue can cause transcriptomic changes. In contrast, the recent
component analysis (PCA), partial least squares discriminatory explosion of spatial transcriptomics (ST) technologies has enabled
analyses (PLSDA) and sparse PLSDA (sPLSDA)) on 245 lipids with genome-wide characterisation of cellular heterogeneity at near
<25% missing data prior to imputation. In non-ATTIRE patients single-cell resolution, while preserving spatial information.
without infection and not on antibiotics, we performed whole blood Method: In this study, we have utilised ST to profile the fibrotic niche
bulk RNA sequencing (RNA-seq) comparing healthy volunteers (HV, in human cirrhotic liver. Using 10X Genomics Visium, we

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 ORAL PRESENTATIONS

Figure 1: (abstract: OS152): Spatial trancriptomics of human cirrhotic liver. (A) Human cirrhotic liver resections are fresh frozen, cryo-sectioned and placed
onto Visium ST capture slides. Tissue permeabilisation enables mRNA to be captured, ST libraries constructed, sequenced and mapped back to Visium
spots. (B) Spatially-significant gene clusters were identified by performing dimensionality reduction followed by unsupervised clustering and projecting
clusters back onto the tissue. (C) Gene expression of significant targets representing spatial clusters. Scalebars 1 mm.

demonstrate ST can resolve diseased liver tissue into discrete gene Method: CCl4-induced rat models of cirrhosis were prepared.
expression clusters which correlate with histological landmarks, Molecular and histological studies of the MLVs were performed.
revealing spatial expression profiles of the fibrotic scar and interface rhVEGF-C (10 ug/kg), which binds to VEGF-receptor 3 (VEGFR3) on
with regenerative nodules (Figure 1). To increase the resolution of ST lymphatic endothelial cells (LyECs), was injected intraperitoneally in
data, we generated a complementary human cirrhotic liver scRNA- 5 doses on alternate days in cirrhotic models. CCl4 rats were given
seq dataset. Through Cell2location computational approaches, we saline as vehicle. The sprouting and drainage of MLVs was analyzed
defined cell type clusters and deconvoluted multi-cell ST data to using histology and whole-mount BODIPY of mesentery. To gain
reveal spatial molecular signatures of several scar-associated cell sub- mechanistic insights, gene expression profiling of isolated and sorted
populations. mesenteric LyECs was performed by RT-PCRs. Dendritic Cell (DCs)
Results: Furthermore, our data spatially located impaired extracel- and T cell subsets were quantified in LNs, portal and peripheral
lular matrix (ECM) signalling associated with the pathogenesis of circulation by flow cytometry. Systemic inflammatory cytokines were
progressive liver disease and provided insight into mechanoadaptive examined. Gut bacterial translocation to mesenteric lymph nodes,
mechanisms during myofibroblast activation. liver, and systemic circulation was studied using orally administered
Conclusion: This study demonstrates how comprehensive ST aligned GFP labelled Salmonella typhimurium.
to computational approaches can be used to delineate spatial gene Results: An increased gene and protein expression of VEGF-C was
expression patterns during liver disease. Our data highlights the observed in the mesenteric tissues of treated rats in comparison to
future of ST in studies to understand mechanisms underlying the vehicle. Histology displayed a significant increase in area per field
progressive liver disease as well as its potential in clinical pathology. of the MLVs in treated versus vehicle rats (1.8 vs 3.9, p < 0.001).
Drainage of mesenteric lymph was increased in treated as compared
OS153 to vehicle (30 a.u. vs 60 a.u., p < 0.001) with decreased lymph leakage
Vascular endothelial growth factor C mediated restoration of (50 a.u. vs 20 a.u., p < 0.001) in comparison to vehicle. Sprouting of
mesenteric lymphatic vessels permeability and drainage improves MLVs from pre-existing vessels was observed in treated rats with
gut immunity surveillance in experimental cirrhosis significantly reduced dilation wrt vehicle (200 µm vs 100 µm, p <
Pinky Juneja1, Dinesh Mani Tripathi1, Impreet Kaur1, Sumati Rohilla1, 0.001). Sorted LyECs showed increased expression of LyVE1 (7.4 fc, p
Sukriti Sukriti1, Subham Banerjee2, Shiv Kumar Sarin3, Savneet Kaur1. < 0.01) and Prox1 (7.7 fc, p < 0.05) in treated rats wrt vehicle.
1
Institute of Liver and Biliary Sciences, Department of Molecular and Enhanced expression of adhesion molecules such as VE-CAD (5 fc,
Cellular Medicine, New Delhi, India; 2NIPER Guwahati, Department of p < 0.05) in LyECs correlated with decreased lymph leakage and
Pharmaceutics, Guwahati, India; 3Institute of Liver and Biliary Sciences, permeability of MLVs in treated rats. Expression of CCL21 (2.04 fc p <
Department of Hepatology, New Delhi, India 0.05), a chemoattractant for DCs and T cells, and CD86 (9.36 fc, p <
Email: [email protected] 0.05), an antigen presentation molecule was increased in LyECs of
treated wrt vehicle rats. Among all immune cells, LNs showed an
Background and aims: Mesenteric lymphatic vessels (MLVs) are
increased percentage of activated CD8 T cells (24.07 vs 11.37, p < 0.05)
functionally impaired in cirrhosis. We explored therapeutic effects of
and DCs (67.03 vs 55.52, p < 0.05) in treated versus vehicle. Treated
a human recombinant pro-lymphangiogenic factor, vascular endo-
rats also exhibited increased clearance in LNs as compared to vehicle
thelial growth factor C (rhVEGF-C, Cys156Ser) on MLVs and the
( p < 0.05).
draining lymph nodes (LNs) in experimental cirrhosis.

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ORAL PRESENTATIONS
Conclusion: In cirrhosis, treatment with VEGF-C ameliorates mes- body weight) and subsequently an hemodynamic study was
enteric lymph drainage and permeability owing to the increased performed.
expression of adhesion molecule, VE-CAD in the LyECs. VEGF-C Results: Engineered NO donor PBAE NPs had an average hydro-
modulates gut immunity and bacterial clearance and thus may serve dynamic size of 170 nm and were positively charged; remaining
as an emerging therapy for combating gut infection and inflamma- stable for at least 24 h. After 48 h treatment, the NPs were
tion in cirrhosis. successfully internalized by cirrhotic PCLS. Besides, when adminis-
tered intravenously, engineered PBAE NPs targeted the liver, spleen
and kidney of already after 24 h, although the signal of the two latter
was significantly of lower intensity. Notably, they did not reach the
brain, heart or lung. Finally, the treatment with functionalized NO
donor PBAE NPs resulted in a significant ( p < 0.05) decrease of portal
hypertension (9.6 ± 0.6 mmHg) in comparison to control NPs (13.2 ±
0.9 mmHg) in rats with decompensated cirrhosis. Remarkably, the
treatment did not affect mean arterial pressure, being 96.7 ± 1.1 and
92.3 ± 4.2 mmHg, in cirrhotic rats treated with control or NO donor
NPs, respectively. Likewise, the cardiac output was not affected
(390.7 ± 80.8 L/min vs 301.3 ± 48.9 L/min).
Conclusion: Engineered NO donor PBAE NPs effectively target the
liver, and could be therapeutically useful to mitigate portal
hypertension.

OS155
Neurometabolic and gliovascular changes in murine hepatic
encephalopathy
Wouter Claeys1,2,3, Lien Van Hoecke1,2, Anja Geerts3,
Hans Van Vlierberghe3, Xavier Verhelst3, Sander Lefere3,4,
Helena Degroote3, Griet Van Imschoot1,2, Elien Van Wonterghem1,2,
Roosmarijn Vandenbroucke1,2, Christophe Van Steenkiste5,6. 1VIB
OS154
Center for Inflammation Research, Barriers in Inflammation, Ghent,
Effect of engineered poly (beta-amino ester) nanoparticles
Belgium; 2Ghent University, Department of Biomedical Molecular
containing a nitric oxide donor on systemic and portal
Biology, Ghent, Belgium; 3Ghent University, Department of
hemodynamics
Gastroenterology and Hepatology, Hepatology Research Unit, Ghent,
Meritxell Perramón1, María Navalón2, Guillermo Fernández Varo1, Belgium; 4Ghent University, Basic and Applied Medical Sciences, Gut-
Belén González1, Alazne Moreno-Lanceta1, Cristina Fornaguera2, Liver Immunopharmacology Unit, Ghent; 5Antwerp University,
Pedro Melgar-Lesmes1,3,4, Salvador Borrós2,5, Wladimiro Jiménez1,3. Department of Gastroenterology and Hepatology, Antwerp, Belgium;
1
Biochemistry and Molecular Genetics Service of Hospital Clínic 6
Maria Middelares Hospital, Department of Gastroenterology and
̀ iques August Pi i Sunyer
Universitari, Institut d’Investigacions Biomed Hepatology, Ghent, Belgium
(IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Email: [email protected]
Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; 2Grup d’Enginyeria
de Materials (Gemat), Institut Químic de Sarrià (IQS), Ramon Llull Background and aims: Type C hepatic encephalopathy (HE)
University (URL), Barcelona, Spain; 3University of Barcelona, Medicine develops on the background of cirrhosis. Both hyperammonemia
Faculty, Department of Biomedicine, Barcelona, Spain; 4Institute for and inflammation contribute to disease development. Murine
Medical Engineering and Science, Massachusetts Institute of Technology, models of type C HE are either not available or poorly characterized,
Cambridge, United States; 5Centro de Investigación Biomédica en Red en hampering translational research. This project aims to validate and
Bioingeniería (CIBER-BBN), Barcelona, Spain characterize murine bile duct ligation (BDL) as a model for type C HE.
Email: [email protected] Method: Male C57BL/6j mice (n = 15/timepoint/group) were sub-
jected to BDL or sham surgery. Animals were sacrificed on day 7, 14,
Background and aims: Decompensated liver cirrhosis results from 21 or 28. Standardized motor function tests were performed. Plasma
the worsening of the liver function and is characterized by the samples were isolated for ammonia and cytokine measurement.
appearance of a clinical phenotype, frequently ascites and portal Targeted metabolomics (LC-MS/MS) for amino acids, bile acids,
hypertension. The primary cause of portal hypertension is an increase energy metabolites and redox markers was performed on cerebro-
in the resistance to portal blood flow. Architectural distortion, hepatic spinal fluid (CSF). Brain samples were taken for immunostainings and
stellate cell contraction, and endothelial dysfunction with increased cytokine profiling. In a separate experiment, mice were injected with
vasoconstrictor and deficient nitric oxide (NO) production are major 4 kDa FITC-Dextran 15 min before sacrifice to assess blood-brain
factors governing this process. Here, we assessed the potential barrier (BBB) permeability changes.
therapeutic effect of engineered poly (beta-amino esters) nanopar- Results: BDL induces motor dysfunction, demonstrated by increased
ticles (PBAE NPs) containing an NO donor in experimental decom- beam traversal time (+60%, p = 0.0056 on day 7) and reduced
pensated cirrhosis. travelling in the open field (−71%, p < 0.0001 on day 14).
Method: NO donor pGFP PBAE NPs with retinol moiety were Concomitantly, plasma ammonia increases progressively in BDL
synthetized and characterized by dynamic light scattering. Next, mice ( p = 0.0012 on day 21). CSF metabolomics reveal a significant
liver cirrhosis was induced in male Wistar rats by repetitive carbon glutamine increase from 14 days on ( p = 0.0029). Additionally, a
tetrachloride inhalation (1 g/l) twice a week until the appearance of glutamate decrease is observed. Other osmolytes taurine and creatine
ascites. Cirrhotic rat precision cut liver slices (PCLS) were treated with transiently decrease. Interestingly, plasma ammonia correlates
PBAE NPs and ex vivo transfection was evaluated by fluorescence significantly with CSF glutamine (r = 0.5076, p = 0.0113).
microscopy. In order to assess organ biodistribution, the NPs were AMP is depleted at 14 days ( p = 0.0021), but other energy markers are
also administered intravenously. Finally, another group of cirrhotic not altered in BDL mice. Remarkably, tauro-conjugated bile acids ( p =
rats received functionalized control or NO donor PBAE NPs (30 mg/kg 0.0016), but also tryptophan ( p = 0.0084) accumulate in CSF after 7
days.

S106 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS
Systemic inflammation is evident from 7 days onward with increased transarterial radioembolization (TARE) is a safe and effective
plasma IL-6 levels ( p = 0.0002). From 14 days on, 3D reconstructed alternative. The aim of the study was to compare the efficacy and
cortical microglial cells reveal activated morphology, indicating safety of TARE to TACE for unresectable HCC.
neuroinflammation (Figure 1). CCL2 levels are significantly increased Method: In this single-center prospective randomized controlled
in the cortex 28 days after BDL ( p = 0.0418), coinciding with increased trial (TRACE), Yttrium-90 glass TARE was compared with doxorubi-
BBB permeability ( p = 0.0031). cin-eluting beads TACE (DEB-TACE) in patients with intermediate
stage HCC extended to Eastern Cooperative Oncology Group
performance status 1 and early-stage HCC patients not eligible for
surgery or thermoablation. Participants were recruited between
September 2011 and March 2018. Primary end point was time to
progression (TTP overall; Kaplan-Meier analysis) in the intention-to-
treat (ITT) and per protocol (PP) population.
Results: Ad interim analysis, 38 participants (median age, 67 years;
IQR 63–72; 33 men) were randomized to the TARE arm and 34
(median age, 68 years; IQR 64–74; 30 men) to the DEB-TACE arm (ITT
population). Median TTPoverall was 17.1 months in the TARE arm
versus 9.5 months in the DEB-TACE arm (ITT: HR 0.36; 95% CI: 0.18,
0.70; p = 0.002) (PP: 32 and 34 participants respectively: HR 0.29;
0.14, 0.60; p < 0.001). Median overall survival was 30.2 months after
TARE and 15.6 months after DEB-TACE (ITT: HR 0.48; 0.28, 0.82; p =
0.006). Serious adverse events grade ≥3 (13 of 33 (39%) versus 19 of
36 (53%) after TARE and DEB-TACE respectively, p = 0.47) and 30-day
mortality (0 of 33 (0%) versus 3 of 36 (8%), p = 0.24) were similar in the
safety populations. Ad interim the HR for the primary end point
TTPoverall was <0.39, indicative to halt the study.
Conclusion: With similar safety profile, Yttrium-90 radioemboliza-
tion conferred superior tumor control and survival compared to
drug-eluting beads chemoembolization in selected participants with
early and intermediate HCC.

Conclusion: Murine BDL reproduces clinical, metabolic and gliovas-

cular features of type C HE. Early behavioural changes are obvious
before plasma ammonia and brain glutamine accumulate, and
potentially reflect the effect of systemic inflammation and cerebral
bile acid/tryptophan accumulation on behaviour. Altogether, these
data support the clinical relevance of this HE model, which can now
be used for further neurobiological and intervention studies.

Liver tumours: Therapy

OS156
Yttrium-90 radioembolization versus drug-eluting beads
chemoembolization for unresectable hepatocellular carcinoma: OS157
results from the TRACE phase 2 randomized controlled trial Cholangiocarcinoma landscape in Europe: diagnostic, prognostic
Elisabeth Dhondt1, Bieke Lambert2,3, Laurens Hermie1, Lynn Huyck1, and therapeutic insights from the ENSCCA Registry
Peter Vanlangenhove1, Anja Geerts4, Xavier Verhelst4, Maridi Aerts5, Laura Izquierdo-Sánchez1,2, Angela Lamarca3,4, Adelaida La Casta1,5,
Aude Vanlander6, Frederik Berrevoet6, Roberto Ivan Troisi2,7, Stefan Buettner6, Kirsten Utpatel7, Heinz-Josef Klümpen8,
Hans Van Vlierberghe4, Luc Defreyne1. 1Ghent University Hospital, Jorge Adeva9, Arndt Vogel10, Ana Lleo11, Luca Fabris12,13,
Vascular and Interventional Radiology, Ghent, Belgium; 2Ghent Mariano Ponz-Sarvise14, Brustia Raffaele15, Vincenzo Cardinale16,
University, Faculty of Medicine and Health Sciences, Belgium; 3AZ Jan Chiara Braconi17,18, Gianpaolo Vidili19, Nigel B. Jamieson17,20,
Palfijn and AZ Maria Middelares, Nuclear Medicine, Belgium; 4Ghent Rocio IR Macias21, Philipp Jonas22,23, Marco Marzioni24,
University Hospital, Gastroenterology and Hepatology, Gent, Belgium; Wacław Hołówko25, Trine Folseraas26,27, Juozas Kupcinskas28,
5
University Hospital Brussels, Gastroenterology, Belgium; 6Ghent Zeno Sparchez29, Marcin Krawczyk25,30, Łukasz Krupa31,
University Hospital, General and HPB Surgery and Liver Transplantation, Viorel Scripcariu32, Gianluca Grazi33, Ana Landa-Magdalena1,5,
Ghent, Belgium; 7Frederico II University Hospital, Hepatobiliary and Jan Ijzermans6, Katja Evert7, Joris Erdmann8, Flora López-López9,
Minimally Invasive and Robotic Surgery, Naples, Italy Anna Saborowski10, Alexander Scheiter7, Alvaro Santos-Laso1,
Email: [email protected] Guido Carpino34, Jesper Andersen35, Jose Marin21,
Domenico Alvaro36, Luis Bujanda1,2,37, Alejandro Forner38,
Background and aims: Transarterial chemoembolization (TACE) is Juan Valle3,4, Bas Groot Koerkamp6, Jesus Maria Banales1,2,39,40. 1IIS
the recommended treatment for intermediate hepatocellular carcin-
oma (HCC) in the Barcelona Clinic Liver Cancer guidelines.
Prospective uncontrolled studies suggest that Yttrium-90

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ORAL PRESENTATIONS
Biodonostia, Liver and Gastrointestinal Diseases, San Sebastián, Spain; Method: The ENSCCA Registry is a multicenter observational study.
2
CIBER-Center for Biomedical Research Network, Liver and Patients with histologically-proven CCA diagnosis between 2010–
Gastrointestinal Diseases, Madrid, Spain; 3The Christie NHS Foundation 2019 were included. Demographic, histomorphological, biochemical,
Trust, Department of Medical Oncology, United Kingdom; 4The and clinical studies were performed.
University of Manchester, United Kingdom; 5Donostia Unibertsitate Results: Overall, 2, 234 patients were enrolled (male:female = 1.29).
Ospitalea, Department of Medical Oncology, Donostia, Spain; 6Erasmus iCCA (n = 1, 243) was associated with overweight/obesity (58.5%) and
University Medical Center, Department of Surgery, Rotterdam, chronic liver diseases involving cirrhosis (12.6%) and/or viral hepatitis
Netherlands; 7University of Regensburg, Institute of Pathology, (10.4%); pCCA (n = 592) with primary sclerosing cholangitis (8.8%);
Regensburg, Germany; 8Amsterdam UMC, locatie AMC, Department of and dCCA (n = 399) with choledocholithiasis (10.3%). At diagnosis,
Medical Oncology, Amsterdam, Netherlands; 9University Hospital 42.2% of patients had local disease, 29.4% locally-advanced disease
October 12, Department of Medical Oncology, Madrid, Spain; (LAD), and 28.4% metastatic disease (MD). Serum CEA and CA19–9
10
Hannover Medical School, Department of Gastroenterology, showed low diagnostic sensitivity (69.1% and 40.9% below cutoff,
Hepatology and Endocrinology, Hannover, Germany; 11IRCCS Istituto respectively), but their concomitant elevation was associated with
Clinico Humanitas Humanitas Cancer Center, Division of Internal increased risk of presenting with LAD [OR = 2.16;95%CI:1.43–3.27] or
Medicine and Hepatology, Milan, Italy; 12University of Padua School of MD [OR = 5.88;95%CI:3.69–9.25]. Patients undergoing resection
Medicine and Surgery, Department of Molecular Medicine, Padova, Italy; (50.3%) showed the best outcome, particularly with negative-
13
Yale University School of Medicine, Digestive Disease Section, New resection margin (R0) [median overall survival (mOS) = 45.1
Haven, United States; 14Clinica Universidad de Navarra, Program in Solid months]; however, margin involvement (R1) [HR = 1.92;95%CI:1.53–
Tumors, Pamplona, Spain; 15University Hospitals Pitié Salpêtrier̀ e- 2.41;mOS = 24.7 months] and lymph node invasion [HR = 2.13;95%
Charles Foix, Department of Hepatobiliary and Liver Transplantation CI:1.55–2.94;mOS = 23.3 months] compromised prognosis. Among
Surgery, Paris, France; 16Sapienza University of Rome, Department of patients with unresectable disease (49.6%), the mOS was 10.6 months
Medico-Surgical Sciences and Biotechnologies, Roma, Italy; 17Institute of for those receiving active palliative therapies, mostly chemotherapy
Cancer Sciences, University of Glasgow, Bearsden, United Kingdom; (26.2%). Patients receiving best supportive care (20.6%) had mOS of
18
Royal Marsden Hospital-Sutton, London, United Kingdom; 19Azienda 4.0 months, with iCCAs showing worst outcome compared to p/
Ospedaliero Universitaria di Sassari, Department of Medical, Surgical dCCAs. ECOG performance status [HR = 1.52;95%CI:1.01–2.31], MD
and Experimental Sciences, Sassari, Italy; 20Glasgow Royal Infirmary, [HR = 4.03;95%CI:1.82–8.92] and CA19–9 [HR = 2.79;95%CI:1.46–
West of Scotland Pancreatic Unit, United Kingdom; 21Instituto de 5.33] were independently prognostic for OS.
Investigación Biomédica de Salamanca, Experimental Hepatology and Conclusion: CCA is still diagnosed at advanced stage, a proportion of
Drug Targeting (HEVEPHARM), Salamanca, Spain; 22University Hospital patients fail to receive cancer-specific therapies, and prognosis is
of Zürich, Department of Visceral- and Transplant Surgery, Zürich, dismal. Identification of preventable risk factors and implementation
Switzerland; 23Klinik Favoriten, Department for Surgery, Wien, Austria; of surveillance in high-risk populations are required to decrease
24
Marche Polytechnic University, Department of Gastroenterology, cancer-related mortality.
Ancona, Italy; 25Medical University of Warsaw, Department of General,
Transplant and Liver Surgery, Warszawa, Poland; 26Oslo OS158
universitetssykehus Rikshospitalet, Department of Transplantation PRIME-HCC: phase Ib study of neoadjuvant ipilimumab and
Medicine, Norway; 27Institute of Clinical Medicine University of Oslo, nivolumab prior to liver resection for hepatocellular carcinoma
Division of Surgery, Inflammatory Diseases and Transplantation, Oslo, Antonio D’Alessio1,2, Madhava Pai3, Duncan Spalding3,
Norway; 28Lithuanian University of Health Sciences, Department of Poyyamozhi Rajagopal3, Thomas Talbot1, Robert Goldin4,
Gastroenterology and Institute for Digestive Research, Kaunas, Claudia Angela Maria Fulgenzi1,5, Caroline Ward1, Vincent Yip6,
Lithuania; 29Iuliu Haţieganu University of Medicine and Pharmacy, 3rd Tony Dhillon7, Sarah Slater8, Mikael Sodergren3, Paul Tait9,
Medical Department, Institute for Gastroenterology and Hepatology, Nagy Habib3, Robert Thomas9, Alessio Cortellini1, Rohini Sharma1,
Cluj-Napoca, Romania; 30Saarland University Hospital, Department of David J. Pinato1,10. 1Imperial College London, Division of Cancer,
Internal Medicine II-Gastroenterology, Hepatology, Endocrinology, Department of Surgery and Cancer, London, United Kingdom;
2
Diabetology, and Nutritional Medicine, Homburg, Germany; 31Kliniczny Humanitas University, Department of Biomedical Sciences, Pieve
Szpital Wojewódzki Nr 1 im. Fryderyka Chopina w Rzeszowie, Emanuele, Milan, Italy; 3Imperial College London, Division of Surgery,
Department of Gastroenterology and Hepatology with General Medicine, Department of Surgery and Cancer, London, United Kingdom; 4Centre for
Rzeszów, Poland; 32Universitatea de Medicină şi Farmacie “Grigore Pathology, Imperial College London, Charing Cross Hospital, Fulham
T. Popa”, Department of Morpho-Functional Sciences I, Department of Palace Road, London, UK; 5Division of Medical Oncology, Policlinico
Surgery II, Iași, Romania; 33Regina Elena National Cancer Institute, Universitario Campus Bio-Medico, Rome, Italy; 6Barts and The London
Rome, Italy; 34University of Rome “Foro Italico”, Department of HPB Centre, The Royal London Hospital, Barts Health NHS Trust, London,
Movement, Human and Health Sciences, Roma, Italy; 35Biotech Research UK; 7Faculty of Health and Medical Sciences, University of Surrey and
and Innovation Centre, Department of Health and Medical Sciences, Department of Oncology, Royal Surrey County Hospital, Egerton Rd,
København, Denmark; 36Sapienza University of Rome, Department of Guildford GU2 7XX; 8Department of Medical Oncology, Barts Health NHS
Translational and Precision Medicine, Roma, Italy; 37Donostia Trust, London, United Kingdom; 9Department of Radiology, Imperial
Unibertsitate Ospitalea, Department of Digestive System, Donostia, College NHS Trust, Hammersmith Hospital, Du Cane Road, W120HS
Spain; 38Institut d’Investigacions Biomed̀ iques August Pi i Sunyer London, United Kingdom; 10Department of Translational Medicine,
(IDIBAPS), Liver Unit, Barcelona Clinic Liver Cancer (BCLC) group, Università del Piemonte Orientale “A. Avogadro,” Via Paolo Solaroli, 17,
Barcelona, Spain; 39University of Navarra, Department of Biochemistry 28100, Novara, NO, Italy
and Genetics, School of Sciences, Pamplona, Spain; 40Ikerbasque Basque Email: [email protected]
Foundation For Science, Donostia, Spain Background and aims: Up to 70% of patients with early-stage
Email: [email protected]
hepatocellular carcinoma (HCC) treated with liver resection (LR)
Background and aims: Cholangiocarcinoma (CCA) is a rare and relapse within two years after surgery. Immune checkpoint inhibitors
heterogeneous biliary cancer, with increasing incidence and related (ICPI) are an established treatment for unresectable HCC, but ICPI
mortality. This study investigates the clinical course of CCA and combinations have not been explored in the peri-operatory setting.
subtypes (intrahepatic (iCCA), perihilar ( pCCA), and distal (dCCA)) in Method: PRIME‐HCC is a phase Ib study investigating safety and
a pan-European cohort. bioactivity of the nivolumab (3 mg/kg, day 1 and day 22) plus
ipilimumab (1 mg/kg, day 1 only) combination prior to LR in

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 ORAL PRESENTATIONS
early-stage HCC. The primary safety analysis assessed treatment- (interquartile range [IQR] 1.2–8.2) from listing and 5.0 years (IQR 2.6–
related adverse events (trAE) and delays to surgery. Secondary end 9.8) post-LT.
point included overall response rates (ORR) by RECIST v1.1 and Results: A total of 96 unique patients with a diagnosis of FL-HCC at
pathologic responses on resection specimens. listing or post-LT were extracted. Of these, 53% were female and 76%
Results: At data censoring on the 4th of November 2021, 12 patients adult, with a median age of 25.5 years (range 10–66). Cirrhosis was
were enrolled, of whom 83% (n = 10) were male, with a median age of present in 10 patients (10%) and 8 patients had an underlying disease
65 years (range 47–70). Liver cirrhosis was found in 75% (n = 9) of the (8%): hepatitis C virus (5), non-alcoholic steatohepatitis (2), glycogen
patients, and the most frequent aetiology was viral hepatitis (50%, n = storage disease (1). Of all FL-HCC patients, 72 were diagnosed at
4 with HCV and n = 2 with HBV infection). All patients were Child- listing (75%), 10 post-LT (10.5%), and of 14 the moment of diagnosis
Pugh A, with 58% classified as albumin-bilirubin (ALBI) grade 1. was unknown (14.6%). Sixty-nine patients received a LT, of which 55
Median tumour diameter was 3.4 cm (interquartile range [IQR] 1.4, were post-operatively confirmed of having FL-HCC. Eight patients
range 1.1–7.3), and the median number of liver nodules was 1 (IQR 1, received a living donor LT. WL dropout at 1- and 2-years post-listing
range 1–3). Median baseline AFP was 6 mcg/L (IQR 115, range 2– was 15.3% and 19.4%. ITT OS at 1, 3, 5 years was 86.5%, 67.9%, 55.5%,
11’777). Any-grade trAEs were reported by 75% of the patients (n = 9). where post-LT OS was 98.2%, 84.4%, 61.9% at 1, 3, 5 years. No patients
Four patients (33%) reported grade 2 trAEs including hypothyroidism died within 90 days post-LT. RFS was 85.3%, 69.9%, and 47.5% at 1, 3,
(n = 2), diarrhoea (n = 1), and fatigue (n = 1), and one (8%) grade 3 ALT/ and 5 years. The cumulative incidence of recurrence at 1, 3, 5 years
ASTelevation. After a median follow-up of 9.1 months (IQR 19.1, range was 12.8%, 24.4%, and 44.7%. There was no statistical difference in all
2.5–24.9), no deaths had occurred, and one disease relapse was outcomes between adult and pediatric patients.
recorded 20.8 months after treatment commencement. Median time
to LR from screening was 2.5 months (IQR 0.9, range 2.2–3.6). One
patient had a surgery delay due to liver function worsening (ICPI-
unrelated) and remained progression-free by RECIST 9.6 months
post-screening. In another patient LR was switched to radiofrequency
ablation by the treating surgeon due to surgical risk independent of
ICPI exposure. One patient was found to have cholangiocarcinoma
(CCA) on LR specimen and was excluded from efficacy analyses. ORR
was 18%, with two partial responses. Disease control rate was 91%,
and one patient with mixed HCC/CCA histology showed primary
progression. Of the nine pathologically evaluable patients, seven
(78%) achieved a pathological response, including two (22%)
complete responses.
Conclusion: Neoadjuvant immunotherapy with nivolumab plus
ipilimumab is tolerable and is characterised by evidence of anti-
tumour efficacy in early-stage HCC.

OS159
Liver transplantation for patients with fibrolamellar
hepatocellular carcinoma: a comprehensive multicenter analysis
to support future decision making
Marco Claasen1,2, Tommy Ivanics1, Wojciech Polak2, Jan Ijzermans2,
Gonzalo Sapisochin1. 1University Health Network, Multi-Organ
Transplant Program, Toronto, Canada; 2Erasmus MC Transplant Institute, Conclusion: LT for patients with FL-HCC offers acceptable long-term
University Medical Centre Rotterdam, Department of Surgery, Division of survival outcomes despite a substantial risk of tumour recurrence.
HPB and Transplant Surgery, Rotterdam, Netherlands Further research is needed to determine which patients with FL-HCC
Email: [email protected] would benefit most from LT and potential adjuvant therapies to
reduce the risk of recurrence.
Background and aims: Fibrolamellar hepatocellular carcinoma (FL-
HCC) is a rare tumour accounting for ∼1% of all primary liver cancers. OS160
Due to its rarity, there is a shortage of data on liver transplantation A preferable signature of gut microbiota and bile acids predicted
(LT) for patients with FL-HCC. Previously post-LT outcomes have been better outcomes of unresectable hepatocellular carcinoma to
evaluated based on patients transplanted a decade ago, however immune checkpoint inhibitors
contemporary and intention-to-treat (ITT) and recurrence outcomes Pei-Chang Lee1, Chijung Wu1, Ya-Wen Hung1, ChiehJu Lee1,
are lacking. Therefore, to gain more insight on the management of Chen-Ta Chi1, I-Cheng Lee1, Jiing-Chyuan Luo1, Ming-Chih Hou1,
these patients, we conducted a comprehensive multicenter analysis Yi-Hsiang Huang1. 1Taipei Veterans General Hospital, Division of
of FL-HCC patients looking at both post-listing and post-LT outcomes. Gastroenterology and Hepatology, Department of Medicine, Taipei,
Method: All patients with a diagnosis of FL-HCC and listed for LT or Taiwan
transplanted between 1987–2019 were extracted from the UNOS Email: [email protected]
registry. Re-LT and multi-organ transplants were excluded. Outcomes
of interest were waitlist (WL) dropout and ITT overall survival (OS), Background and aims: Immune checkpoint inhibitors (ICI) are
derived from all patients with a FL-HCC diagnosis at listing, and post- newly emerged, promising therapeutic agents for unresectable
transplant OS, recurrence-free survival (RFS), cumulative incidence of hepatocellular carcinoma (uHCC). However, no effective biomarker
recurrence, and 30-/90-day post-transplant mortality, for all patients has been found to predict treatment response. Gut microbiota could
with a confirmed diagnosis of FL-HCC at explant pathology. WL modulate outcomes of melanoma to immunotherapy. In this study,
dropout was defined as dropping out of the WL due to death, clinical we aimed to investigate the effects of gut microbiota and metabolites
deterioration, or medical unsuitability. Recurrence and death were on ICI-treated uHCC.
the events for predicting RFS. For the cumulative incidence of Method: From May 2018 to February 2020, patients who received ICI
recurrence, death was a competing event. For all other outcomes, therapy for uHCC in Taipei Veterans General hospital were prospect-
death was the only event. Median follow-up times were 4.5 years ively enrolled. Of them, fecal samples collected before treatment from

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S109

ORAL PRESENTATIONS
twenty objective responders and 21 non-responders ( proved by treatment of patients with unresectable hepatocellular carcinoma
radiology) were taken into analyses of microbiota and metabolites. (uHCC). This study also assessed predictors of health-related quality
Since March 2020, 33 consecutive Child-Pugh A, ICI-treated patients of life (HRQoL) using EuroQoL 5-Dimension, 5-Level health state
were investigated for validation. Besides, fecal samples from 17 utility (HSU) index (EQ-5D-5L) and visual analogue scale (VAS).
healthy volunteers were also analyzed as control. Method: EQ-5D-5L data were collected at baseline, every 8 weeks for
Results: A significant bacterial dissimilarity was observed between 48 weeks, then every 12 weeks until treatment discontinuation, and
responders and non-responders before ICI treatment ( p = 0.016 and additional assessments up to 12 weeks for patients with confirmed
0.019 by Anoism and Adonis tests). Lachnoclostridium, progression. Impact of treatment and treatment status on domain
Lachnospiraceae, and Veillonella were predominant faecal microbiota score and proportion of patients reporting any problem by domain at
of responders; whereas, Prevotella 9 was predominant in non- first off-treatment visit were assessed using last on-treatment visit as
responders. Ursodeoxycholic acid and ursocholic acid were found baseline. Impact on HSU was assessed by mixed models for repeated
significantly enriched in the feces of responders, and were strongly measures (MMRM). Univariate and multivariate analyses were
correlated with the abundance of Lachnoclostridium. A fecal signature conducted using treatment as base fixed effect and treatment
of enriched Lachnoclostridium and depleted Prevotella 9 could status (on/off treatment), progression ( progression-free/progressed)
significantly predict better overall survival (OS) in these patients. In and baseline Child Pugh score as covariates. Interactions between
the validation cohort, the best objective response rate (52.6%) was covariates and treatment were considered. A random intercept model
noted in patients with a preferable microbial signature. Besides, the assuming independent within-subject errors was fitted to account
progression-free survival (PFS) and OS were better in patients with a for subject variability. Model performance was compared using AIC/
preferable microbial signature as compared with the counter-group. BIC score. Analysis used algorithms reflecting societal preferences of
(PFS: 8.8 vs. 1.8 months; OS: not reached vs. 6.5 months, both p < UK, US and Canadian populations and validation analysis was
0.001). conducted using VAS.
Results: Treatment and treatment status models were consistently
the best fitting. Mean HSU for STRIDE was 0.815 (95% CI: 0.802, 0.827,
p < 0.0001) and 0.785 (95% CI: 0.766, 0.804, p < 0.0001) for sorafenib,
using a mapping algorithm reflecting Canadian preferences.
Sorafenib treatment was associated with a utility decrement of
−0.030 (95% CI: −0.046, −0.014, p = 0.0002) and a utility increment of
0.055 (95% CI: 0.046, 0.063, p < 0.0001) for those with a status of
remaining on treatment. Results with UK and US algorithms, and
when assessed by VAS, were consistent. Interaction of treatment and
treatment status was non-significant in all models. The proportion of
patients experiencing any problems on each domain of EQ-5D-5L
increased between the last visit prior to- and first visit post-
discontinuation for both regimens. The proportion of patients
experiencing moderate to extreme problems was lower on all
domains with STRIDE vs sorafenib for both on- and off-treatment,
except usual activities (Figure 1).

Conclusion: Pre-treatment fecal microbiota and bile acids are

associated with treatment outcomes of ICIs for uHCC. These findings
provided a potential strategy to enhance the efficacy of immuno-
Conclusion: The best predictors of HRQoL in patients with uHCC
therapy by modifying gut microbiota and metabolites in patients
were treatment received and treatment status, where treatment with
with uHCC.
STRIDE and being on-treatment were associated with better HSUs
OS161 compared to sorafenib treatment and being off-treatment. Results
The impact of treatment and treatment status on health state highlight there are notable HRQoL benefits for maintaining uHCC
utility in patients with unresectable hepatocellular carcinoma: an patients on treatment with STRIDE.
EQ-5D analysis from Himalaya
Lei Qin1, Miguel Miranda2, Cal Shephard3, Abdul-Azeez Ganiyu2,
Vincent Tam4. 1AstraZeneca, Gaithersburg, United States; 2AstraZeneca,
Cambridge, United Kingdom; 3Astrazeneca Canada, Mississauga,
Canada; 4Tom Baker Cancer Centre, Calgary, Canada
Email: [email protected]
Background and aims: The HIMALAYA trial (NCT03298451) showed
that tremelimumab 300 mg added to durvalumab (STRIDE regimen)
significantly improved survival compared to sorafenib for the

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 ORAL PRESENTATIONS
OS163
Unravelling the role of Protein Kinase D2 in the control of hepatic
NAFLD: Experimental and pathophysiology insulin sensitivity
Patricia Rada1,2, Ana B. Hitos1,2, Esther Rey3,4, Elena Carceller-Lopez1,
Julia Pose-Utrilla1,5, Carmelo Garcia-Monzon4, Guadalupe Sabio6,
OS162
Teresa Iglesias1,5, Águeda González3,4, Angela Martinez Valverde1,2.
Heterogeneity of phosphatidylcholine metabolism in non- 1
Instituto de Investigaciones Biomédicas “Alberto Sols” (CSIC-UAM),
alcoholic fatty liver disease
Madrid, Spain; 2Centro de Investigación Biomédica en Red de Diabetes y
Sami Qadri1,2, Sami Blom3, Kari Pitkänen3, Noora Ahlholm1,2,
Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain;
Kimmo Porthan1,2, Panu K. Luukkonen1,2,4, Anne Juuti5, 3
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y
Henna Sammalkorpi5, Anne Penttilä5, Johanna Arola6, Matej Orešič7,8,
Digestivas (CIBEREHD), Spain; 4Liver Research Unit, Instituto de
Tuulia Hyötyläinen9, Hannele Yki-Järvinen1,2. 1University of Helsinki
Investigación Sanitaria Princesa, University Hospital Santa Cristina,
and Helsinki University Hospital, Department of Medicine, Helsinki,
Spain; 5Centro de Investigación Biomédica en Red sobre Enfermedades
Finland; 2Minerva Foundation Institute for Medical Research, Helsinki,
Neurodegenerativas (CIBERNED), Spain; 6Centro Nacional de
Finland; 3Aiforia Technologies Oy, Helsinki, Finland; 4Yale University,
Investigaciones Cardiovasculares Carlos III (CNIC), Spain
Department of Internal Medicine, New Haven, United States; 5University
Email: [email protected]
of Helsinki and Helsinki University Hospital, Department of
Gastrointestinal Surgery, Abdominal Center, Helsinki, Finland; Background and aims: Protein kinase D2 (PKD2) is a Ser/Thr kinase
6
University of Helsinki and Helsinki University Hospital, Department of of the Ca2+-Calmodulin kinase superfamily. Growing evidences
Pathology, Helsinki, Finland; 7Örebro University, School of Medical support that PKD2 participates in the control of glucose homeostasis.
Sciences, Örebro, Sweden; 8University of Turku and Åbo Akademi Two previous studies, one conducted in global PKD2-deficient mice,
University, Turku Bioscience Centre, Turku, Finland; 9Örebro University, and the other in mice lacking PKD2 in intestine, reported opposite
School of Science and Technology, Örebro, Sweden results with metabolic dysfunction or protection against HFD-
Email: [email protected] induced obesity, respectively. However, the role of PKD2 in the liver
in the context of obesity-related insulin resistance has not been
Background and aims: In murine models of non-alcoholic fatty liver
addressed and it is the aim of this study.
disease (NAFLD), liver damage associates with a deficiency of
Method: PKD inhibition by pharmacological and genetic approaches
phosphatidylcholines (PCs), particularly polyunsaturated PCs
was analyzed in primary hepatocytes and in Huh7 cells. To over-
(PUFA-PCs). We studied whether human PC metabolism is altered
express PKD2, Huh7 cells were transfected with EGFP-PKD2-CA, a
by NAFLD or by the protective genetic variant in HSD17B13
constitutively active PKD2 fused to EGFP. Insulin signaling cascade
(rs72613567 T > TA).
was examined by treating hepatocytes with insulin (10 nM, 5–15
Method: In 143 obese patients with a liver biopsy and genotyping for
min). As an in vivo model of hepatic insulin resistance, mice with a
HSD17B13 rs72613567, we analysed the hepatic lipidome (UPLC-MS).
liver-specific PKD2 depletion (PKD2ΔHep) were fed high fat diet (HFD,
As the hepatic parenchymal fat fraction (HPFF) affects apparent
20 weeks). Parameters assessing glucose homeostasis and hepatic
concentrations of amphiphilic lipids, we normalised hepatic
insulin sensitivity were analyzed. PKD2 was overexpressed in liver by
phospholipid concentrations to fat-free liver mass. To this end, we
an injection of AAV bearing EGFP-PKD2-CA and insulin sensitivity
employed a state-of-the-art deep learning image analysis method
was evaluated. PKD signature was analyzed in liver biopsies from
(Aiforia Technologies) to accurately quantify HPFF in liver biopsies.
NAFLD patients.
Results: Total unadjusted hepatic PCs correlated negatively with
Results: PKD pharmacological inhibition resulted in an increased
HPFF (rs = −0.26, P < 0.01), but this association disappeared after
insulin sensitivity showed by a higher AKT phosphorylation after
normalising to fat-free liver mass (rs = 0.02, P = 0.81). With increasing
insulin stimulation in both primary mouse hepatocytes and Huh7
HPFF, concentrations of especially saturated and monounsaturated
cells. Moreover, PKD2 knocking down by siRNA or shRNA-lentiviral
PCs significantly increased, whereas concentrations of PUFA-PCs
particles enhanced the insulin response. Alternatively, EGFP-PKD2-
decreased. Accordingly, the hepatic triacylglycerol composition
CA overexpression in Huh7 cells reduced AKT phosphorylation upon
significantly correlated with that of hepatic PCs. In carriers of the
insulin stimulation compared to EGFP-transfected cells. In this line, in
protective variant in HSD17B13, as compared to non-carriers, the
vivo injection of AAV bearing EGFP-PKD2-CA resulted in a moderate
hepatic lipidome was enriched in especially PUFA-PCs.
impairment of glucose homeostasis and reduced IR and AKT
Conclusion: Patients with NAFLD have a deficiency of PUFA-PCs. The
phosphorylation in the liver. Importantly, HFD-fed PKD2ΔHep mice
protective HSD17B13 rs72613567 variant opposes these changes,
displayed a tendency to improve glucose tolerance and insulin
increasing intrahepatic PC concentrations.
sensitivity compared to control mice. These results were confirmed
by analysis of AKT phosphorylation in liver extracts. Moreover, PKD
immunostaining revealed that PKD2 was increased in NAFLD
patients.

Conclusion: Our results strongly suggest that PKD2 is involved in the

control of hepatic insulin signaling and point PKD2 as a new

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S111

ORAL PRESENTATIONS
therapeutic target in the progression of hepatic insulin resistance- OS165
related pathologies. The inhibition of the epigenetic efectors DNMT1 and G9a as a
potential therapeutic strategy against the non-alcoholic fatty liver
OS164 development
Metabolomic changes in NASH phenotype liver-on-a-chip caused José María Herranz1, Alex Claveria-Cabello2, Leticia Colyn2,
by INI-678, a small molecule HSD17B13 inhibitor, supports a role Maria U. Latasa2, Maite Perez-Araluce2, Bruno Sangro1,3,4,
for HSD17B13 in inflammation and fibrosis Julen Oyarzabal5, Antonio A. Pineda5, Maria Arechederra2,4,
Heather Hsu1, Michael Carleton1. 1Inipharm, Bellevue, United States Carmen Berasain1,2,4, Matías A. Avila1,2,4,
Email: [email protected] Maite G. Fernandez-Barrena1,2,4. 1CIBERehd, Madrid, Spain; 2CIMA-
Background and aims: Polymorphisms producing catalytically University of Navarra, Hepatology Program, Pamplona, Spain; 3Clínica
inactive HSD17B13 protect against non-alcoholic steatohepatitis Universidad de Navarra, Hepatology Unit, Pamplona, Spain; 4Instituto de
(NASH), cirrhosis, and liver cancer and are associated with reduced Investigacion Sanitaria de Navarra, IdiSNA, Pamplona, Spain; 5CIMA-
hepatic inflammation and fibrosis. Preliminary results demonstrated University of Navarra, Molecular Therapies Program, Pamplona, Spain
that INI-678, a novel selective inhibitor of HSD17B13, decreased Email: [email protected]
fibrotic markers in response to high fat media in liver-on-chip (LOC) Background and aims: Non-alcoholic fatty liver disease (NAFLD)
co-cultures The aim of this study was to determine the impact of encompasses a spectrum of histological changes ranging from simple
inhibiting HSD17B13 with a well characterized inhibitor on metab- steatosis to inflammation and ballooning, which define non-alcoholic
olism in a NASH phenotype LOC. steatohepatitis (NASH). NASH can lead to cirrhosis and hepatocellular
Method: NASH LOC co-cultures containing primary human hepato- carcinoma. Currently, no drugs have proven efficacy for NAFLD
cytes, homozygous for the active HSD17B13 allele; Kupffer cells, and treatment. Understanding the mechanisms leading to NAFLD
stellate cells were cultured in a high fat containing media to induce a progression is essential for the identification of effective therapies.
NASH phenotype. LOC were exposed to INI-678 or a DMSO vehicle Epigenetic mechanisms are fundamental for gene expression
control for Days 4–20. LOC co-cultures were analyzed for fibrotic regulation and functional homeostasis, and their impairment is
markers by immunohistochemistry and media samples were ana- recognized to participate in disease. Here we have performed a
lyzed for cell health markers, albumin and lactate dehydrogenase, by systematic transcriptomic analysis of epigenetic genes in human liver
ELISA and activity, respectively. Metabolites were quantified in media tissues from patients with different stages of NAFLD. We identified
samples using electrospray ionization by tandem mass spectrometry. marked alterations in a significant number of epigenetic effectors,
Results: Treatment of NASH LOC with INI-678 and related analog including DNA methyltransferase 1 (DNMT1) and its epigenetic
inhibitors of HSD17B13 decreased fibrotic marker proteins, alpha cofactor UHRF1. DNMT1 and UHRF1 work in concert with the histone
smooth muscle actin and collagen type 1, compared to vehicle control methyltransferase G9a in DNA methylation and gene expression
in LOC co-cultures. Choline consumption remained stable in INI-678- regulation. We evaluated the potential relevance of the DNMT1/G9a/
treated LOC throughout high fat media exposure. Choline consump- UHRF1 complex in in vitro and in vivo models of NAFLD.
tion in the vehicle control was initially elevated and decreased Method: We analyzed four publicly available liver transcriptome
throughout high fat media treatment ultimately lower than INI-678- datasets integrating more than 520 patients. In vitro studies were
treated LOC co-cultures. INI-678 treatment resulted in lower primary performed in HepG2 cells challenged with a NASH cocktail. Cells
bile acids compared to vehicle control. INI-678 treatment signifi- were treated with the DNMT1/G9a/UHRF1 complex small molecule
cantly reduced hexose and increased lactate in the media. inhibitor CM272. In vivo studies were performed in C57BL6 mice fed
Conclusion: The decrease in fibrotic markers in NASH LOC with INI- with normal chow diet (ND) or high-fat diet (HFD, 45% fat) for 4 or 9
678 treatment was accompanied by changes in the metabolome. The months and different regimes of CM272 treatment (one month and
metabolic changes include stabilization of choline, decreases in bile one week, respectively). Transcriptomic profiling, biochemistry and
acids and decreased hexose. The inhibition of HSD17B13 significantly histologycal analyses were performed.
altered metabolism consistent with the hepatoprotective effect and Results: Inhibition of DNMT1 and G9a with CM272 significantly
anti-fibrotic effects observed in LOC. The direct effects of small reduced serum triglyceride and free fatty acids, and hepatic lipids
molecule inhibitors of HSD17B13 are consistent with decreased accumulation in the two HFD models. Liver tissues transcriptomic
fibrosis in NASH subjects carrying inactive HSD17B13 alleles. These analyses revealed that CM272 modulated metabolic pathways
results suggest a potential precision medicine approach to treating fundamentally involved in fatty acids and cholesterol metabolism
NASH. and, intriguingly also the expression of genes involved in immune
pathways, such as antigen presentation and processing. DNMT1 and
G9a inhibition also caused significant changes in the expression of
genes involved in energy expenditure and lipid metabolism in brown
and white adipose tissue. In vitro studies confirmed most of the in
vivo findings, including a robust induction by CM272 of carboxyles-
terase 1 (CES1), a key enzyme in the liver triglyceride metabolism.
Conclusion: A profound dysregulation in the expression of epigenetic
effectors characterizes human NAFLD progression. We show that the
pharmacological modulation of the epigenetic complex DNMT1/G9a/
UHRF1 markedly affects the course of this disease in its early stages.
Our findings suggest that characterization of epigenetic pathways in
NAFLD may help to understand the disease and to expose new
targets.

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 ORAL PRESENTATIONS
OS166
Molecular characterization of metabolic associated fatty liver
disease as an immune-mediated inflammatory disease: IMID
associated fatty liver disease
Enrique García-Nieto1, Juan Carlos Rodriguez-Duque1,2,
Paula Iruzubieta1,2, Agustin García-Blanco1, Coral Rivas1,2,
María Luisa Cagigal3, Javier Rueda-Gotor4, Montserrat Rivero1,2,
Susana Armesto5, Marcos Antonio Gonzalez-Lopez5,
Carlos Duran-Vian5, Anna Esteve Codina6, Marta Gut6,
Jose Pedro Vaqué1,7, Javier Crespo1,2, María Teresa Arias Loste1,2.
1
Research institute Marqués de Valdecilla (IDIVAL), Group of Clinical and
Translational Research in Digestive Diseases Infection, Immunity and
Digestive Pathology Group, Santander, Spain; 2University Hospital
Marqués de Valdecilla, Gastroenterology and Hepatology Department,
Santander, Spain; 3University Hospital Marqués de Valdecilla,
Pathological Anatomy Service, Santander, Spain; 4University Hospital
Marqués de Valdecilla, Division of Rheumatology, Santander, Spain;
5
University Hospital Marqués de Valdecilla, Dermatology Department,
Santander, Spain; 6CNAG-CRG, Centre for Genomic Regulation (CRG),
Barcelona Institute of Science and Technology (BIST), Universitat
Pompeu Fabra (UPF), Barcelona, Spain; 7University of Cantabria,
Molecular Biology Department, Santander, Spain
Email: [email protected]
Background and aims: Growing evidence support an increased Conclusion: MAFLD has a disproportionately high tendency to occur
prevalence of metabolic associated fatty liver disease (MAFLD) in the in IMID populations, which may be explained by its distinctive
context of immune-mediated inflammatory diseases (IMIDs) that can chronic inflammatory burden. Supporting this, we provide a
occur independently of classic metabolic risk factors. We aimed to functional explanation to distinguish between MAFLD groups, and
characterize clinically and mechanistically a prospective cohort of show that IMIDs can trigger a pro-tumoral liver condition that can
IMID-MAFLD patients compared to regular MAFLD patients. lead to an aggressive form of MAFLD independently of classic
Method: Cross-sectional, case-control study including a subset of metabolic pathways.
IMID patients (inflammatory bowel disease, psoriasis, hidradenitis,
and spondyloarthritis). Controls from a random sample drawn from OS167
the general population were age, gender, type 2 diabetes, and BMI EphB2 is a novel signaling receptor in non-alcoholic
matched in a 1:2 ratio. MAFLD was established by the controlled steatohepatitis liver fibrosis
attenuation parameter. Liver biopsies were collected when MAFLD Patrice Mimche1, Severin Donald Kamdem1, Erika Egal1,
with significant liver fibrosis was suspected. Total RNA was obtained Quinian Johanson1, Tuan Pham2, Kimberley Evason3, Sihem Boudina4,
from freshly frozen cases and analyzed by RNA-seq. Differential gene Michael Ortiz5, Francis Sprouse5,
expression was performed with ‘limma-voom’ adjusting for BMI, sex Chinthaka Mahesh Udamulle Gedara5, Karina Cortez5,
and fibrosis severity. Gene set enrichment analysis (GSEA) was Mahmoud Ahmed6, Hesham Sadek6, Mark Henkemeyer5. 1University
performed with fgsea R package with a pre-ranked “limma t-statistic” of Utah, Department of Pathology, Salt Lake City, United States;
2
gene list. Serum protein concentrations were obtained using University of Utah, Department of Internal Medicine, Division of
‘Quantikine ELISA Kit’ in same patients analyzed by mRNA-seq. Gastroenterology, Hepatology and Nutrition, Salt Lake City, United
Results: 1435 IMID patients and 2918 controls were included. MAFLD States; 3University of Utah and Huntsman Cancer Institute, Department
prevalence was significantly higher among IMID patients than of Pathology, Salt Lake City, United States; 4University of Utah,
controls, as well as the prevalence of advanced-MAFLD (LSM Department of Nutrition and Integrated Physiology, Salt Lake City,
>9.7 kPa). In multivariate analysis, concomitant IMID was an United States; 5UT Southwestern Medical Center, Department of
independent and the strongest predictor of advanced-MAFLD. We Neuroscience, Dallas, United States; 6UT Southwestern Medical Center,
compared transcriptomic data from 69 liver biopsies from IMID- Department of Internal Medicine and Molecular Biology, Dallas, United
MAFLD and 40 from MAFLD patients adjusted for BMI, sex, and States
fibrosis severity. We observed 87 highly significant genes differen- Email: [email protected]
tially expressed between the two groups. Whereas genes like IGFBP2
Background and aims: Emerging evidence suggests that the EphB2
or GPX2 showed an upregulated expression in IMID-MAFLD, others
receptor tyrosine kinase regulates tissue inflammation and fibrosis.
like DGCR5 or the Metallotioneins MT1M, MT1G and MT1F were
However, its role in diet-induced non-alcoholic steatohepatitis
downregulated. Normalized expression values of significantly
(NASH) fibrosis has not been explored. We aimed to decipher the
expressed genes and specific clustering of IMID-MAFLD and MAFLD
contribution of EphB2 to non-alcoholic steatohepatitis (NASH)
cases are shown in Figure. A GSEA analysis detected the most relevant
development in mouse NASH models and in patients at various
cellular activities in IMID-MAFLD vs. MAFLD. IMID-MAFLD cases
stages of non-alcoholic fatty liver disease progression.
displayed an enriched expression of genes implicated in pro-tumoral
Method: In NASH patients, hepatic EphB2 and serum sEphrinB2
activities like signaling by Rho-GTPases or the control of the Cell Cycle
ligand were evaluated. Disease phenotyping was performed in male
concomitant with a negative expression of genes related to the
and female wild type (WT), EphB2−/−, EphB2-kinase-dead
metabolism. IGFBP-2 protein levels in serum samples from IMID-
(EphB2K661R), EphB2-kinase-overactive (EphB2F620D) mice, and in
MAFLD and MAFLD validated the transcriptional data.
hepatic stellate cell (HSC) specific EphB2−/− mice fed the obesogenic
Gubra-Amylin NASH (GAN) diet for 22–28 weeks and the Choline
Deficient Amino-acid improved (CDAA) high-fat diet for 10–12
weeks. The crosstalk between EphB2 and TGFβ signaling in primary
human HSC was investigated in vitro. Pharmacological inhibition of
EphB2 for the treatment of NASH was also evaluated in vivo.

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S113

ORAL PRESENTATIONS
Histology, flow cytometry, qPCR, biochemical assays, bulk RNA Background and aims: Cancer, either de novo or recurred, is the
sequencing, and single cell RNA-sequencing were used to dissect leading cause of death after liver transplantation (LT). We aimed to
the molecular mechanism underlying EphB2 function in NASH. evaluate the effect of maintenance immunosuppression on post-LT
Results: Hepatic EphB2 was strongly upregulated in NASH patients malignancy.
and correlated with NASH fibrosis score. Serum sEphrinB2 was also Method: Multicentre case-control nested study involving 16 LT
elevated in NASH patients. In mouse models of NASH, EphB2−/− institutions. The eligible cohort included adult patients undergoing
knockout mice showed a significant reduction in liver steatosis, LT (2010–2015) who received tacrolimus-based immunosuppression.
inflammation, and fibrosis compared to WT mice. This is supported Patients developing malignancy after LT, either de novo or recurred,
by a significant reduction of liver fat content, pro-inflammatory and formed the group of cases. Controls were selected among patients
fibrotic genes in EphB2−/− compared to WT mice. EphB2 forward without cancer after an identical follow-up period. Cases and controls
signaling is likely the main driver of NASH progression as depicted by were matched by propensity score based on age, gender, smoking
the significant increase in steatosis, inflammation, and fibrosis habit, aetiology of liver disease and hepatocellular carcinoma (HCC)
observed in EphB2F620D kinase-overactive mice compared to WT before LT. The exposure to immunosuppressive drugs within the first
and EphB2K661R kinase-dead mice. Flow cytometry and single-cell year after LT was recorded. Cumulative exposure to tacrolimus (CET)
RNA-sequencing reveal that macrophages and mesenchymal popula- was calculated by the area under curve of trough levels (PMID:
tions are reduced in EphB2−/− mice compared to WT mice. Consistent 31107827). The relationship between the immunosuppression
with the above results and upregulated expression in NASH, HSC- protocol and the risk of post-LT malignancy was evaluated using
specific knockout of EphB2−/− also resulted in reduced NASH fibrosis. multivariate logistic and Cox’s regression.
In vitro, rhTGFβ1, 2, and 3 upregulate EphB2 in human HSC and its Results: The eligible cohort included 2, 495 patients. The study
silencing with EphB2-siRNA abrogates TGFβ-mediated HSC trans- cohort comprised 425 patients who developed post-LT malignancy
differentiation into myofibroblasts-producing collagen. Finally, and 425 matched controls. The most frequent types of malignancy
pharmacological inhibition of EphB2 reduced NASH fibrosis in mice. were: HCC recurrence (24%), non-melanoma skin cancer (16.1%), lung
Conclusion: We have identified EphB2 as a key player in the cancer (13.7%) and head and neck tumors (12.6%). Cases and controls
pathogenesis of diet-induced fatty liver disease in human and were comparable in terms of age, gender, smoking habit, aetiology of
mouse and showed that therapeutic targeting of this receptor liver disease and presence of HCC before LT. The immunosuppression
mitigates NASH fibrosis. protocol was similar in cases and controls ( p = 0.51), and there were
no differences in terms of individual drugs. Patients with post-LT
malignancy had increased CET as compared with matched controls,
both within the first 3 months ( p = 0.002) and within the first 12
months ( p = 0.009). An increased CET was the only independent
Liver transplantation and Acute liver failure: predictor of post-LT malignancy after controlling for clinical features
Clinical aspects and concomitant immunosuppressive drugs: the hazard ratio (HR) of
post-LT malignancy for a 20% increase of CET was 1.11 (95%CI 1.05–
1.19; p = 0.001) at 3 months, and 1.10 (95%CI 1.03–1.17; p = 0.004) at
OS168 12 months. These results were consistent when considering
Cumulative exposure to tacrolimus and incidence of cancer after exclusively de novo malignancy (CET at 3 months HR = 1.09; p =
liver transplantation 0.020 and CET at 12 months HR = 1.10; p = 0.016).
Manuel Rodríguez-Perálvarez1, Gonzalo Crespo2, Jesús Rivera2, Conclusion: CET is the most important immunosuppression-related
Antonio González Rodríguez3, Estefanía Berge Garrido3, risk factor of cancer after LT, thus highlighting the relevance of
Mikel Gastaca4, Patricia Ruiz4, Anna Curell5, Cristina Dopazo5, tacrolimus minimization.
Ainhoa Fernández-Yunquera6, Fernando Diaz6,
Ana Sánchez Martínez7, María Luisa Ortiz7, Marina Berenguer8,
Tommaso Di Maira8, Jose Ignacio Herrero9, Mercedes Iñarrairaegui9,
Carolina Almohalla10, Esteban Fuentes Valenzuela10,
Sara Lorente Perez11, Cristina Borao11, Fernando Casafont12,
Emilio Fabrega12, Sonia Pascual13, Patricio Más-Serrano13,
Maria Angeles Lopez Garrido14, Flor Nogueras López14,
Rocio González-Grande15, Javier Zamora1, Rafael Alejandre1,
Antonio M. Gómez-Orellana16, Carmen Bernal17,
Miguel Ángel Gómez Bravo17. 1Hospital Universitario Reina Sofía,
University of Córdoba, IMIBIC, CIBERehd, Department of Hepatology and
Liver Transplantation, Córdoba, Spain; 2Hospital Clínic Barcelona,
IDIBAPS, CIBERehd, Univ. of Barcelona, Spain; 3Hospital Universitario
Ntra. Sra. de Candelaria, Spain; 4Hospital Universitario Cruces, Biocruces
Bizkaia Health Research Institute, Spain; 5Hospital Universitario Vall d
´Hebron, Spain; 6Hospital General Universitario Gregorio Marañón,
CIBERehd, Spain; 7Hospital Universitario Virgen de la Arrixaca, IMIB,
Spain; 8Hospital Universitari I Politec̀ nic La Fe, CIBERehd, Spain; 9Clínica OS169
Universidad de Navarra, CIBERehd, IdSNa, Spain; 10Hospital Multidrug resistant bacterial infections after liver
Universitario Río Hortega, Spain; 11Hospital Lozano Blesa, Spain; transplantation: prevalence, impact and associated risk factors
12
Marqués de Valdecilla University Hospital, Idival, Spain; 13Hospital Rosa Martin-Mateos1,2, Laura Martínez-Arenas3,
General Universitario Alicante, CIBERehd, Spain; 14Hospital Ângela Carvalho-Gomes3,4, Laia Aceituno5,6, Valle Cadahía-Rodrigo7,
Universitario Virgen de las Nieves, Spain; 15Hospital Regional María Magdalena Salcedo8,9, Ana Arias10, Sara Lorente Perez11,
Universitario de Málaga, Spain; 16University of Córdoba, Department of Aitor Odriozola12,13, Javier Zamora14,15, Marino Blanes16,
Computer Science and Numerical Analysis, Spain; 17Hosp. Univ Virgen Óscar Len17,18, Laura Benitez10, Isabel Campos-Varela5,19,
del Rocio, Spain Maria Luisa Gonzalez Dieguez7, Diego Rojo Lázaro1, Jesús Fortún20,
Email: [email protected] Antonio Cuadrado12,13, Natalia Marcos Carrasco21,

S114 Journal of Hepatology 2022 vol. 77(S1) | S1–S118

 ORAL PRESENTATIONS
Manuel Rodríguez-Perálvarez22,23, Emilio Fabrega12,13,
Trinidad Serrano11, Valentín Cuervas Mons10,24, Manuel Rodríguez7, Univariate Multivariate
(p) (p)
Lluis Castells5,19, Marina Berenguer25,26, Javier Graus1,27,
Agustin Albillos1,2. 1Hospital Ramón y Cajal, Gastroenterology, Madrid, Body mass index 0.83 -
Spain; 2IRYCIS. CiberEHD. Alcalá University, Spain; 3IIS La Fe Valencia, Number of packed red blood cells 0.00 0.04
Hepatology and Liver Transplantation Unit, Spain; 4CiberEHD; 5Vall Number of platelet pools 0.31 -
d’Hebron Hospital, Liver Unit, Spain; 6VHIR, Spain; 7Hospital Plasma (cc) 0.93 -
MELD score (biochemical) pre-LT 0.01 0.41
Universitario Central de Asturias, Gastroenterology, Asturias, Spain;
8 Age 0.92 -
Hospital Universitario Gregorio Marañón, Hepatology, Madrid, Spain; Biliary-enteric anastomosis 0.14 -
9
CiberEHD. Universidad Complutense, Madrid; 10Hospital Universitario Renal replacement therapy 0.00 0.02
Puerta de Hierro, Internal Medicine, Transplant Unit, Majadahonda, Rifaximin 0.17 -
Spain; 11Hospital Clínico Universitario Lozano Blesa, Gastroenterology, Carriers of MDRB 0.00 0.21
Zaragoza, Spain; 12Hospital Universitario Marqués de Valdecilla, Diabetes 0.48 -
Gastroenterology; 13IDIVAL; 14Reina Sofía University Hospital, Prophylaxis with norfloxacin 0.33 -
Hepatology and Liver Transplantation, Cordoba, Spain; 15IMIBIC. HIV 0.31 -
CiberEHD; 16Hospital La Fe, Infectious Diseases; 17Vall d’Hebron Hospital, Fulminant etiology 0.44 -
CEP 0.44 -
Infectious Diseases, Spain; 18VHIR. Autonoma University Barcelona,
Retransplantation 0.77 -
Spain; 19VHIR. Autonoma University Barcelona. Ciber EHD; 20Hospital MDRBIs (0–3 months before LT) 0.00 0.03
Ramón y Cajal, Infectious Diseases, Spain; 21Hospital Príncipe de ICU admission (0–3 months before LT) 0.00 0.04
Asturias, Alcalá de Henares; 22Reina Sofía University Hospital, Hospitalization (0–3 months before LT) 0.01 0.74
Hepatology and Liver Transplantation, Cordoba; 23Hospital Universitario
Reina Sofía, University of Córdoba, IMIBIC, CIBERehd, Department of
Hepatology and Liver Transplantation, Córdoba, Spain; 24Universidad
OS170
Autónoma Madrid, Medicina, Madrid, Spain; 25Hospital La Fe,
Modeling ischemic cholangiopathy in human cholangiocyte
Hepatology and Liver Transplantation Unit, Spain; 26IIS La Fe Valencia.
organoid for screening of novel cholangio-protective agents
CiberEHD. University of Valencia; 27Alcalá University
Shaojun Shi1, Henk P. Roest1, Marcel Bijvelds2, Jeroen de Jonge1,
Email: [email protected]
Hugo de Jonge2, Jan Ijzermans1, Monique M.A. Verstegen1,
Background and aims: Infections caused by bacteria resistant to 3 or Luc J.W. van der Laan1. 1Erasmus MC Transplant Institute, University
more antibiotic families (multidrug-resistant bacterial infections or Medical Center, Department of Surgery, Rotterdam, Netherlands;
MDRBIs) are an increasing healthcare issue. Our aim was to analyze 2
Erasmus MC-University Medical Center, Department of
the prevalence, burden, and risk factors associated with MDRBIs after Gastroenterology and Hepatology, Rotterdam, Netherlands
liver transplantation (LT). Email: [email protected]
Method: Retrospective multi-center cohort study including adult
Background and aims: Ischemic cholangiopathy refers to biliary
patients who underwent LT from January 2017 to December 2019.
damage caused by disruption of blood supply in the peribiliary
Risk factors related to pre-LT liver disease, surgical procedure, and
plexus. Detailed knowledge of ischemic cholangiopathy pathogenesis
post-operative stay were recorded. A multivariate logistic regression
remains scarce due to the lack of appropriate in vitro models. We
analysis was performed to identify independent predictors of
aimed to recapitulate ischemia-evoked biliary damage using human
MDRBIs within the first 90-days after LT.
intrahepatic cholangiocyte organoids (ICOs) in vitro for the study of
Results: We included 1, 089 LT (1, 004 patients) performed in 9
ischemic cholangiopathy and preclinical drug discovery.
tertiary Spanish hospitals. Mean age was 56.83 ± 9.31 years, 72.5%
Method: Human ICOs (n = 5) were initiated from liver biopsies.
(784) were male, and alcoholic liver disease was the most prevalent
Cultures were exposed to hypoxia (∼1% O2) for 72 hours and
underlying etiology (42.5% (452)). Bacterial infections occurred in
reoxygenated for 6 (H/R6 h) or 24 hours (H/R24 h). To enable
442 LT (40.6%), that presented a total of 706 infections (respiratory
immediate tracking of hypoxia, ICOs were transduced with a hypoxia-
19.6%, urinary 17.9%, bacteremia 12.7%, cholangitis 10.7% and surgical
inducible factor 1alpha (HIF-1α) reporter. The effect of hypoxia on cell
wound infections 9.3%, among others). MDR were isolated in 230 LT
proliferation, apoptosis, and necroptosis was determined by immu-
(21.1%) (358 infections, 50.7%). E. faecium 88 (24.6%), E. Coli 77 (21.5%)
nostaining with Ki67, active caspase 3, and phosphorylated mixed
and Klebsiella pneumoniae 48 (13.4%) were the most frequent isolated
lineage kinase domain-like protein, respectively, and ATP content.
bacteria. In the multivariate analysis, previous intensive care unit
Results: Extensive activation of the HIF-1α reporter was observed in
admission (0–3 months before the LT), previous MDRBIs (0–3 months
ICOs at 72 h of hypoxia. This signal was partially reduced after H/
before the LT), renal-replacement therapy after LT and the number of
R24 h. Hypoxia- and H/R6h-exposed ICOs were significantly smaller
packed red blood cells units transfused during surgery were
in size ( p < 0.001) than untreated ICOs. Also, the disintegration of the
identified as independent predictors of MDRBIs (table 1). Mortality
cytoskeleton and disrupted epithelial integrity were observed. Cell
at 30, 90, 180 and 365 days was significantly higher in patients with
viability of ICOs undergoing hypoxia or H/R6 h was drastically lower
MDRBIs.
( p < 0.05) than under normoxia and was restored after H/R24 h ( p <
Conclusion: MDRBIs are highly prevalent after LT and have a
0.05). Transcriptional and morphological analysis indicated a clear
significant impact on prognosis. E. faecium is the most frequently
decrease of Ki67 expression after hypoxia or H/R6 h, which recovered
isolated MDR microorganism. New pharmacologic or surveillance
after H/R24 h to normal levels. Immunostaining revealed that
strategies aimed at preventing MDRBIs after LT should be considered
extensive apoptosis, but not necroptosis, was induced by hypoxia
for patients with high-risk factors.
and H/R6 h. Exposure of the ICOs to Emricasan, a caspase inhibitor,
failed to attenuate apoptosis but switched it into necroptosis. We
further identified clinical-grade alpha-1 antitrypsin (AAT) as a potent
inhibitor of hypoxia-induced apoptosis without necroptotic switch
( p < 0.05). Treatment of ICOs with AAT in hypoxia exposed ICOs
increased the cell viability ( p < 0.05) and partially restored the Ki67
expression.
Conclusion: ICOs recapitulate ischemic cholangiopathy in vitro,
featured by extensive apoptosis and reduced cell proliferation,

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ORAL PRESENTATIONS
which could be partially restored by reoxygenation. AAT is identified Background and aims: Among cancer patients on checkpoint
as a novel cholangiocellular protective agent by restoring prolifer- inhibitors (CPI), 1-16% develop checkpoint inhibitor-induced liver
ation and preventing apoptosis. injury (ChILI). However, there are limited accurate reports of the
incidence rate of ChILI as assessed by time on treatment. Using a
OS171 prospective database and review of patient records, we estimated the
The prognostic role of lysophosphatidylcholines and their risk and incident rate of ChILI in all melanoma and renal cancer
immunomodulatory potential in acute liver failure patients who received CPI at Nottingham University Hospitals (NUH)
Francesca Maria Trovato1, Salma Mujib1, Florent Artru1, from 2011–2021.
Anna Cavazza1, Ellen Jerome1, Evangelos Triantafyllou2, Method: Using ‘ChemoCare’, a prospective oncology prescribing
Mark J. W. McPhail1. 1Institute of Liver Studies, Inflammation Biology, database, we identified all adult patients who received CPI for
London, United Kingdom; 2St Mary’s Hospital, Liver Unit, United adjuvant or metastatic melanoma or metastatic renal cell carcinoma
Kingdom (RCC) since 2011. Prescription event monitoring was performed using
Email: [email protected] patient-related records and digital records; ChILI, other immune-
Background and aims: Acute liver failure (ALF) is a life-threatening related adverse events (irAE) and response to rechallenge were
recorded. International Expert Working Group (EWG) for drug-
disease in people without previous liver disease. It is characterised by
inflammation and parallel immunoparesis with a high incidence of induced liver injury case definitions were used to define ChILI cases
and grade severity. Causality was assessed using Roussel Uclaf
death from sepsis and multiorgan failure. In this context, immune cell
Causality Assessment Method (RUCAM).
function is often suppressed by multiple mechanisms, including
inhibitory signalling via immune checkpoint pathways. The aim of Results: Out of 432 patients, ChILI occurred in 38 (8.8%). RUCAM was
‘possible’ in 9, ‘probable’ in 22 and ‘highly probable’ in 7 cases. The
this research was to modulate systemic immune responses through
the immunometabolic Lysophosphatidylcholine (LPC)-Autotaxin incidence rate of ChILI was 10.93 (95% CI 5.66–18.75) per 1000
(ATX)-Lysophosphatidylcholinic acid (LPA) pathway. patient-months of CPI exposure, with most cases occurring in
patients treated with dual checkpoint inhibition. ChILI severity was
Method: 43 ALF, 21 cirrhotics, 24 HC, and 31 septic (as proinflamma-
tory control) patients were included. The pathway of interest was ‘mild’ in 11 and ‘moderate’ in 27 (based on EWG grading); 36 of 38
(94.7%) received corticosteroids. Mean time to resolution of ChILI was
identified on the basis of multivariate analysis of a 180 metabolite
77 days ±59 following steroid therapy compared to 49 days ±21 in
targeted metabolomics panel (Biocrates p180). Autotaxin and LPA
levels were measured by ELISA. Plasma cytokines were analysed with those untreated. Of 38 ChILI cases, 15 (39.5%) were re-treated with a
single CPI, and only one patient developed recurrent ChILI. However,
an MSD V-PLEX kit. PBMCs were cultured with LPA 16:0, 18:0, 18:1,
and their immune checkpoint surface expression (CLTA-4, TIGIT/ three developed colitis, one each developed hypophysitis and severe
neuropathy.
CD155, PD-1/PDL-1, Tim-3) was assessed by flow cytometry.
Results: LPC 16.0 was identified as highly discriminant between ALF Table: Risk and incidence rate of ChILI per CPI regime.
and HC ( principal component analysis (PCA) and Orthogonal partial
Incidence
least squares discriminant analysis (OPLS-DA): R2X 0.592; R2Y 0.666, Person- rate per
Q2 0.613, AUROC 0.969961). There was an increase in ATX (Kruskal- Number Mean Time at 1000
of number of risk ChILI patient-
Wallis test, ALF vs HC p < 0.001) and its product LPA in ALF comparing Cancer CPI Regime Patients cycles (months) cases Risk months
to HC and Sepsis (Kruskal-Wallis test, ALF vs HC p < 0.01). LPC 16.6,
Melanoma Ipilimumab 88 3 210.53 2 2.27% 9.50
18.0 and 18.1 were reduced in ALF patient with poor prognosis (dead Ipilimumab + 102 3 949.23 29 28.43% 30.55
at 90 days or transplanted) (for LPC 16.0 and LPC 18.1 p < 0.05). Nivolumab combination
followed by 8 Nivolumab
Despite increased proinflammatory cytokines in plasma, PBMCs from Nivolumab
ALF patients produced less IL-6 when stimulated with LPS ( p < 0.05), maintenance
Nivolumab 22 12 281.20 0 0% 0.00
and the addition of LPAs failed to reverse this. However, in monocytes Pembrolizumab 108 9 1035.37 3 2.78% 2.90
LPA 16.0 increased and restored PDL-1 expression (% of positive cells, Adjuvant 39 7 316.70 1 2.56% 3.16
p < 0.05), usually reduced comparing to HC ( p < 0.05), and reduced Pembrolizumab
RCC Ipilimumab + 19 3 160.10 2 10.53% 12.49
CD155 expression (% of positive cells and MFI, p < 0.05), without Nivolumab combination
effect on the CD4+ counterparts PD1 and TIGIT. followed by 6 Nivolumab
Nivolumab
Conclusion: Reduced lysophosphatidylcholines (LPC16.0, LPC 18.0 maintenance
and LPC 18.1) are biomarkers of poor prognosis in patients with ALF. Nivolumab 54 12 524.70 1 1.85% 1.91
Total 432 3477.83 38 8.8% 10.93
The LPC-ATX-LPA axis appears to modulate innate immune response (95% (95% CI
in ALF and requires further investigation to identify novel therapeutic CI 6.2– 5.66–
agents. 11.8) 18.75)

OS172 Conclusion: Prescription event monitoring provides an accurate

Prescription event monitoring of checkpoint inhibitor-induced estimate of the risk of ChILI as well as its outcomes. Rechallenge with
liver injury and outcomes of rechallenge: a 10-year experience single-agent CPI is feasible, with most patients not having a
Edmond Atallah1,2, Ana Oshaughnessy3, Dolapo Igboin3, recurrence of ChILI. However, there is a risk of developing other
Yvette Moore3, Joyce Ntata3, Ankit Rao3, Hester Franks4, irAE, especially colitis. The benefits and risks of corticosteroid therapy
Poulam Patel4, Guruprasad Aithal1,2. 1University of Nottingham, should be evaluated in a larger cohort of ChILI patients.
Nottingham Digestive Diseases Centre, School of Medicine, Nottingham,
United Kingdom; 2Nottingham University Hospitals NHS Trust and the OS173
University of Nottingham, National Institute for Health Research (NIHR) Impact of increasing MELD 3.0 beyond 40 on liver transplant
Nottingham Biomedical Research Centre, Nottingham, United Kingdom; outcomes
3
Nottingham University Hospitals NHS Trust, Nottingham, United W. Ray Kim1, Ajitha Mannalithara1, Branden Tarlow1, Allison Kwong1.
Kingdom; 4BioDiscovery Institute, University of Nottingham, Centre for 1
Stanford University School of Medicine, Stanford, United States
Cancer Sciences, Translational Medical Sciences, Nottingham, United Email: [email protected]
Kingdom
Email: [email protected] Background and aims: MELD 3.0 improves upon MELD-Na by
incorporating sex and albumin alongside bilirubin, creatinine, INR,
and sodium, updating the existing coefficients, adding relevant

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 ORAL PRESENTATIONS

Figure: (abstract: OS171)

Journal of Hepatology 2022 vol. 77(S1) | S1–S118 S117

ORAL PRESENTATIONS
interactions, and resetting the upper bound of serum creatinine to 3.0
from 4.0 mg/dL. In the US liver allocation system, previous versions of Within 30 days since
first MELD 3.0 ≥40
MELD including MELD-Na have been capped at 40. We study the
Median survival
impact of increasing MELD score beyond this threshold on liver # # of 30-day time in days (95%
transplant outcomes. MELD 3.0 n Transplanted deaths mortality CI)
Method: Adult waitlist registrations for liver transplantation from 15
Jan 2016 to 30 Jun 2021 were identified using OPTN data. MELD 3.0 = 40–44 5015 3463 1304 65.6% 18 (17–20)
45–49 872 525 327 81.2% 13 (11–14)
1.33 (if female) + 4.56*loge (bilirubin) + 0.82* (137-Na) − 0.24* (137-
50+ 187 74 109 88.7% 5 (3–7)
Na)*loge (bilirubin) + 9.09*loge (INR) + 11.14*loge (creatinine) + 1.85*
(3.5-albumin) − 1.83* (3.5-albumin)*loge (creatinine) + 6. Survival
analysis evaluated the effect of increasing MELD 3.0 beyond 40 on OS174
30-day waitlist mortality. Individual follow-up time started from the Bile duct on a chip: engineering a microfluidic platform for
first qualifying MELD score ≥40; patients were censored after 30 days studying biliary epithelium in a dish
of follow-up, at the time of an approved exception, death, or liver Jorke Willemse1, Mees N.S. de Graaf2, Gilles van Tienderen1,
transplant, whichever occurred first. In a sensitivity analysis, the Cox Luc J.W. van der Laan1, Valeria Orlova2, Jeroen de Jonge1,
regression model was performed to consider MELD 3.0 as a time- Monique M.A. Verstegen1. 1Erasmus MC Transplant Institute University
dependent covariate if MELD remained ≥40. 2-year posttransplant Medical Center, Department of surgery, Rotterdam, Netherlands; 2Leiden
outcomes were also assessed. University Medical Center, Department of Anatomy and Embryology,
Results: There were 54, 060 new waitlist registrations during the Netherlands
study period, 2476 (4.6%) with MELD-Na ≥40 and 2820 (5.2%) with Email: [email protected]
MELD 3.0 ≥40 at listing. 23.9% of candidates with MELD ≥40 met Background and aims: Biliary complications that may arise after
clinical criteria for acute-on-chronic liver failure. An additional 3, 254 liver transplantation, such as non-anastomotic strictures and diffuse
candidates recorded MELD 3.0 ≥40 during their waiting time. 30-day bile leakage, are challenging and complex. Ischemia-related cell
waitlist mortality was higher for each point increase in MELD 3.0 (HR death and impaired regeneration of damaged biliary epithelium is
1.13, 95% CI 1.12–1.15), with a linear relationship from MELD 3.0 of 40 known to be involved in causing these complications. Intrahepatic
up to 55. 30-term waitlist mortality was higher for each increasing cholangiocyte organoids (ICO) allow for the expansion and study of
MELD stratum, from 65.6% to 88.7% for those with MELD 40–44 cholangiocyte-like cells, but access to the lumen of the organoids is
compared to MELD 50+ (Figure). Results were similar when MELD 3.0 limited and can only be studied after disrupting the 3D structure.
considered as a time-dependent covariate. Posttransplant outcomes There are currently no in vitro models mimicking the circumstances
were comparable across MELD strata including MELD 35–39. as exposure of bile ducts to warm ischemia time or cold storage, and
Conclusion: MELD 3.0 is anticipated to increase the proportion of therefore we aimed to establish a microfluidic bile-duct-on-chip
patients reaching or surpassing the maximum allocation score of 40. (BDOC) platform for studying the effect of these conditions on biliary
Patients with MELD >40 may derive greater survival benefit from LT epithelium in vitro.
compared to MELD 40 without necessarily worse post-transplant Method: ICO were initiated from human liver biopsies (N = 5)
outcome. Increasing the maximum score for MELD 3.0 may improve obtained during liver transplant procedures. Three-channel BDOC
risk stratification of waitlist mortality and better represent liver (dimensions; length 1 cm, width and height 500 µm) were prepared
transplant urgency for the sickest patients, including those with by casting polydimethylsiloxane (PDMS) into a mold. Subsequently,
acute-on-chronic liver failure. plasma treated PDMS chips were bonded to glass slides. The BDOC
channels were filled with collagen type I pre-gel and viscous finger
patterning procedures were used to create channels inside these
collagen hydrogels. ICO-derived cells (25·103 cells/channel) were
introduced into the channels and ICO expansion medium was added
to the reservoirs. The BDOC were incubated for up to 21 days. Growth
of epithelial cells was monitored using confocal microscopy and
histology.
Results: ICO-derived cells populated the entire surface of the
channels with a single layer of cells within 7 days after seeding.
Whole mount confocal imaging revealed that cells were columnar in
shape and morphologically looked like biliary epithelium. Zonula
Occludens-1 (ZO-1) staining showed cholangiocyte-like polarization
of cells in honey comb patterns. The cells express the cholangiocyte
markers cytokeratin 7 and 19 on gene and protein level.
Conclusion: The results show that microfluidic approaches com-
bined with cholangiocyte-like (KRT 7 and 19-positive) cells from ICO
can be used to create healthy small diameter intrahepatic bile duct
structures in vitro. This model allows for detailed analysis of epithelial
damage and regeneration during warm and cold ischemic conditions
that are known to cause post transplantation complications to the
Figure: Kaplan-Meier curves: 30-day survival of patients with MELD 3.0 biliary system, and also to study onset and progression of biliary
≥40 at any time on waitlist. diseases.

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POSTER PRESENTATIONS JOURNAL OF
HEPATOLOGY

THU002
Thursday 23 June Biomarkers for prediction of alcohol-related liver cirrhosis in the
Swedish general population
Gustav Jakobsson1,2, Mats Talbäck3, Göran Walldius3,
Niklas Hammar3, Ying Shang4, Hannes Hagström1,4,5. 1Division of
Hepatology, Department of Upper GI, Karolinska University Hospital,
Alcoholic liver disease Stockholm, Stockholm, Sweden; 2Department of Medicine Capio St
Göran’s hospital, Stockholm, Sweden; 3Unit of Epidemiology, Institute of
Environmental Medicine, Karolinska Institutet, Stockholm, Sweden;
4
THU001 Department of Medicine, Huddinge, Karolinska Institutet, Stockholm,
Heavy alcohol intake along with ALDH2 polymorphism increases Sweden; 5Clinical Epidemiology Unit, Department of Medicine, Solna,
the risk of hepatocellular carcinoma and mortality in hepatitis B Karolinska Institutet, Stockholm, Sweden
virus-related cirrhosis Email: [email protected]
Chih-Wen Lin1, Ming Chao Tsai2, Sien-Sing Yang3, Chih-Che Lin2, Background and aims: Alcohol-related liver cirrhosis (ARLC) is a
Wen-Lung Wang2, Yao-Chun Hsu2, Yaw-Sen Chen2, Ming-Lung Yu4, severe and well-known complication to chronic alcohol overconsump-
Jui-Ting Hu3. 1E-Da Hospital, Medicine, Kaohsiung, Taiwan; 2Kaohsiung tion. There are several known biomarkers associated with increased
Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 3Cathay General intake of alcohol and liver damage. There is limited knowledge on
Hospital, Taipei, Taiwan; 4Kaohsiung Medical University Chung-Ho which biomarkers that have the best predictive capabilities for future
Memorial Hospital, Kaohsiung, Taiwan ARLC, especially in a general population setting. Here, we investigated
Email: [email protected] this in a large, population-based Swedish cohort.
Background and aims:Hepatitis B virus (HBV) infection and Method: We used data from the AMORIS cohort, a general population
alcoholism are risk factors for hepatocellular carcinoma (HCC) and cohort with blood samples from routine health care and outpatient
mortality. We investigated the effect of heavy alcohol intake, ALDH2 visits in primary or occupational care collected from 1985 through
polymorphism, and HBV infection on clinical outcomes and risk 1996. The cohort consists of 812 073 individuals, approximately 35%
factors in cirrhotic patients. of the total population in Stockholm county, Sweden, during this
Method: We enrolled 1515 cirrhotic patients (342 patients with HBV period. We included all persons above 18 years old, with a baseline
infection and alcoholism, 796 patients with HBV infection, and 373 blood sample of Alanine transaminase (ALT) and Aspartate trans-
patients with alcoholism) from three tertiary hospitals in Taiwan aminase (AST). We excluded subjects with known liver cirrhosis at
between 2005 and 2020. baseline.
Results: Of patients with concomitant HBV infection and alcoholism, We ascertained incident cases of ARLC by linking the AMORIS cohort
HBV infection alone, and alcoholism alone, 81 (23.7%), 134 (16.8%), to Swedish national health registers. All subjects were followed until
and 55 (14.6%) patients developed HCC and 151 (45.3%), 322 (40.5%), a first event of ARLC, death, emigration or end of the study period,
and 150 (39.8%) patients experienced mortality, respectively. The 15- December 31, 2011. Biomarkers were standardized to increase
year cumulative incidences of HCC (66.4% vs. 46.8% vs. 54.8%, P < comparability. Associations between biomarkers and incident ARLC
0.001) and mortality (88.9% vs. 81.9% vs. 90%, P < 0.001) were were analyzed with Cox regression models and discrimination was
significantly higher in cirrhotic patients with HBV infection and assessed using C-statistics.
alcoholism than in those with HBV infection alone or alcoholism Results: We identified 537 479 individuals with a mean follow-up
alone before and after propensity score matching. The ALDH2 time of 19.0 years. The biomarkers with the best predictive
polymorphism (allele GA/AA) with heavy alcohol intake significantly capabilities in both unadjusted and adjusted analyses were gamma-
increased the risk of HCC and mortality in HBV-related cirrhotic glutamyl transferase (GGT) and mean corpuscular volume (MCV),
patients. Risk factors for HCC were baseline serum HBV DNA (HR = with an adjusted C-index of 0.81 and 0.85 respectively. The AST/ALT-
4.08), antiviral therapy (HR = 0.13), alcohol intake (HR = 1.77 and ratio showed a lower predictive value, with a C-index of 0.70 (Table 1).
1.49), abstinence (HR = 0.41), and ALDH2 polymorphism (HR = 5.09).
Table 1: Hazard ratios (HR) reflect an increase of one standard
Risk factors for mortality were abstinence (HR = 0.22), ALDH2
deviation for each parameter. *Unadjusted; **Adjusted for sex and
polymorphism (HR = 1.49), Child-Pugh class (HR = 1.43 and 1.98),
age;h Harrell’s C-index.
serum albumin (HR = 0.62), and HCC development (HR = 1.57) in
cirrhotic patients with HBV infection and alcoholism. C- C-
Conclusion: Heavy alcohol intake along with the ALDH2 polymorph- Number HR* 95 % CI Index h HR** 95 % CI Index h
ism significantly increased the risk of HCC and mortality in HBV- ALT 537 479 1.05 1.05 1.05 0.81 1.05 1.04 1.05 0.75
related cirrhotic patients. AST 537 479 1.04 1.03 1.04 0.85 1.03 1.03 1.04 0.76
GGT 515 958 1.14 1.14 1.15 0.90 1.14 1.13 1.14 0.81
Bilirubin 121 260 0.71 0.68 0.74 0.58 0.70 0.66 0.73 0.72
Albumin 470 915 1.19 1.17 1.21 0.62 1.18 1.16 1.20 0.71
MCV 172 891 2.14 2.07 2.21 0.80 2.10 2.03 2.17 0.85
AST/ALT ratio 537 479 0.97 0.93 1.02 0.52 1.08 1.05 1.11 0.70

Journal of Hepatology 2022 vol. 77(S1) | S119–S388 © 2022 All rights reserved.
POSTER PRESENTATIONS
Conclusion: The best predictive biomarkers for ARLC in the general THU004
population were MCV and GGT, whereas the commonly used AST/ALT Cyclophilin inhibitor CRV431 as a potential therapy for
ratio had a lower predictive capability. alcohol-related liver disease
Elena Palma1,2, Sara Campinoti1,2, Una Rastovic1,2, Nicola Harris1,2,
THU003 Tsin Shue Koay1,2, Lola Ajayi1,2, Bruna Almeida1,2, Sandra Phillips1,2,
A history of bariatric surgery is independently associated with a Daren Ure3, Melissa Preziosi4, Marjorie Yumol4, Rosa Miquel4,
younger age at onset of severe alcoholic hepatitis Yoh Zen4, Andreas Prachalias4, Krishna Menon4, Nigel Heaton4,
Lukas Van Melkebeke1,2, Annelotte Broekhoven3, Tessa Ostyn4, Luca Urbani1,2, Shilpa Chokshi1,2. 1The Roger Williams Institute of
Minneke Coenraad3, Hannelie Korf1, Tania Roskams4, Hepatology, London, United Kingdom; 2King’s College London, Faculty of
Schalk van der Merwe1,2, Frederik Nevens1,2, Jef Verbeek1,2. 1KU Life Sciences and Medicine, London, United Kingdom; 3Hepion
Leuven, Laboratory of Hepatology, Belgium; 2University Hospitals Pharmaceuticals, United States; 4Institute of Liver Studies, King’s College
Leuven, Department of Gastroenterology and Hepatology, Belgium; London, United Kingdom
3
Leiden University Medical Center, Department of Gastroenterology and Email: [email protected]
Hepatology, Netherlands; 4KU Leuven, Department of Imaging and
Pathology, Translational Cell and Tissue Research, Belgium Background and aims: Cyclophilins are peptidyl-prolyl isomerases
Email: [email protected] that facilitate protein folding and regulate several biological processes
with isoforms A, B, D being best characterised. Cyclophilin inactiva-
Background and aims: Patients with prior bariatric surgery (BS) are tion via therapeutic inhibition or genetic manipulation has been
at risk to develop an alcohol use disorder (AUD). We assessed the shown beneficial at various stages of liver disease, including steatosis,
effect of prior BS on disease profile and outcome of patients with fibrosis, inflammation, cell injury and in hepatocellular carcinoma.
severe alcoholic hepatitis (sAH). CRV431 is a pan-cyclophilin inhibitor (non-immunosuppressant
Method: From 01/2008 to 04/2021, consecutive patients admitted to cyclosporin derivative) that is currently in clinical development for
our tertiary referral center with biopsy-proven sAH were included in NASH (Phase 2A). Our study aims to evaluate the effects of CRV431 in
a prospective database. Student’s t-test, Wilcoxin rank sum test and human experimental models of Alcohol-related Liver Disease (ALD)
Fisher’s exact test were used. A p value <0.05 after multiple testing and on fibrosis in primary hepatic stellate cell (HSC) cultures.
correction was considered significant. Method: Patient-matched Precision Cut Liver Slices (PCLS) and
Results: sAH patients (n = 158) were identified with a median follow- primary HSCs were prepared from human liver specimens (different
up of 366 (68–1656) days. Out of this cohort, 28 (18%) patients had a fibrotic stages, n = 8). PCLS were exposed to hepatotoxic insults
history of BS (BS-group): 27 (96%) underwent bypass surgery and 1 including ethanol 250 mM, fatty acids 0.1 mM, LPS 10 µg/ml
patient gastric banding. No patient underwent sleeve gastrectomy. individually and/or combined for up to 5days and HSCs activated
The proportion of patients with BS increased significantly over time with TGF-β1 for up to 10days, in the presence/absence of 5 µM
reaching a number of 4 (8%) within the first 5 years, 11 (19%) within CRV431. Tissue functionality was evaluated by histology, cytokeratin-
the following 5 years and 13 (28%) during the last 4 years ( p = 0.02) of 18 release and mitochondrial assays. In PCLS and HSCs, fibrosis/HSC
the follow-up period. An important finding from our analysis was that activation status was assessed by gene expression, immunofluores-
patients in the BS-group were significantly younger at diagnosis of cence and secretion of fibrotic markers. Pro-inflammatory cytokines
sAH, were more frequently female, featured an elevated body mass were quantified by Luminex.
index (BMI) and advanced steatosis upon histological evaluation of Results: Features of alcoholic steatohepatitis were observed in human
the liver biopsy (Table 1). Furthermore, there were no differences in PCLS exposed to the insults, and CRV431 profoundly reduced the
sAH disease severity (histological and Maddrey) or corticosteroid expression and secretion of pro-fibrogenic markers and restored a
response (Lille score) (Table 1). Importantly, the correlation between balanced cytokine profile. CRV431 alone was not hepatotoxic and did
BS and a younger age at diagnosis remained significant after not induce cell death. In HSCs, CRV431 reduced αSMA and collagen
correction for sex, steatosis and BMI in a multivariate regression deposition/expression when added simultaneously or after TGF‐β1
analysis ( p <0.001). Notably, survival determined after 28 or 90 days activation. In addition, alignment of collagen fibers deposited by HSCs
following the onset of sAH remained unchanged (Table 1). was significantly affected by the drug treatment.
Conclusion: Our results confirm the role of cyclophilins in liver
fibrosis, including HSC activation, collagen deposition and orienta-
tion. These data reveal for the first time the potential for the
cyclophilin inhibitor CRV431 to reduce ALD-induced fibrosis and
suggest the possibility of using this drug as a therapy in ALD patients.

THU005
UK national service evaluation of transplant assessments for
patients with alcohol related liver disease
Christopher Oldroyd1, Varuna Aluvihare2, Yun Chew3, Andrew Holt4,
Steven Masson5, Richard Parker3, Neil Rajoriya4, Jennifer Ryan6,
Liz Shepherd6, Kenneth J. Simpson7, Clare Wai1, Ian Webzell2,
Michael Allison1. 1Cambridge Liver Unit, Addenbrooke’s Hospital,
Cambridge, United Kingdom; 2Institute of Liver Studies, King’s College
Conclusion: The proportion of sAH patients with prior BS has Hospital NHS Foundation Trust, London, United Kingdom; 3The Liver
increased 3-fold over the last 15 years. Bypass surgery is independ- Unit, St James’s University Hospital, Leeds, United Kingdom; 4The Liver
ently associated with younger age of sAH onset but not with Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom; 5The
corticosteroid response or short-term survival. These novel findings Liver Unit, Freeman Hospital, Newcastle, United Kingdom; 6The Sheila
indicate the need for early and effective prevention of AUD and sAH in Sherlock Liver Unit, Royal Free Hospital, London, United Kingdom;
patients who underwent bypass surgery. 7
Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh,
United Kingdom
Email: [email protected]
Background and aims: Alcohol-related liver disease (ArLD) is
responsible for 60% of all liver disease and 84% of liver related

S120 Journal of Hepatology 2022 vol. 77(S1) | S119–S388

 POSTER PRESENTATIONS
death in the UK. Although we know how many patients with ArLD are remains obscure. Fibroblast growth factor 21 (FGF21) is a liver-
registered for a liver transplant, it is not known how many people derived hormone secreted after alcohol intake. Several lines of
with ArLD are being assessed for liver transplantation. evidence suggest that FGF21 inhibits preference for alcohol and
Method: Prospective data was collected for all patients with a reduces alcohol intake. Using plasma proteomics via proximity
diagnosis of ArLD assessed at the seven UK liver transplant centres extension assay technology, we here establish FGF21 as the main
from 1st Aug 2020 to 31st July 2021. This included: gender, age alcohol responsive peptide hormone in healthy humans and, further,
category, indication for transplant, United Kingdom Model for End- compare the plasma FGF21 response after an acute alcohol challenge
Stage Liver Disease Score (UKELD), co-factors for liver disease, in males diagnosed with AUD, healthy males with paternal AUD, and
duration of abstinence from alcohol at assessment, listing decision healthy males without any predisposition to AUD.
and reasons for decline or deferral. Method: Proteomics was evaluated in plasma sampled before and
Results: 568 patients were included. Median UKELD was 54 (range after alcohol intake (0.7 g per kg body weight) in 12 individuals.
41–76). 144 patients (25%) were female. Median duration of Subsequently, plasma FGF21 concentrations were evaluated before,
abstinence was 12 months (range 0–240), with 18.4% of assessments during and for 10 hours after alcohol exposure (0.5 g per kg body
having ≤6 months abstinence. 329 (58%) were listed for liver weight ingested over 10 minutes) in 15 males diagnosed with AUD
transplantation, with 204 (36%) not listed, and 35 (6%) deferred. (Group A), 15 males with paternal AUD (Group B), and 15 males
Indications for assessment were: UKELD ≥ 49 (90%), ascites (32%), without any predisposition to AUD (Group C). The desire for alcohol
hepatic encephalopathy (19%), hepatocellular carcinoma (16%) and was assessed by visual analogue scale.
other (11%) with most patients having multiple indications. The most Results: Out of 1, 472 proteins, only 11 changed after alcohol exposure
common co-factor was non-alcoholic steatohepatitis (n = 57) with in the 12 individuals, with FGF21 increasing the most (10-fold, p
hepatitis C virus infection second most common (n = 24). Most <0.0001) (Fig. 1A). The three groups were similar with regards to age
common reasons for not listing were: medical co-morbidities (29%), and body mass index, and all participants had normal plasma
potential recoverability (20%), too early to need transplant (19%), concentrations of transaminases and bilirubin. Baseline plasma
active or recent alcohol use (12%), concern about return to harmful FGF21 concentrations did not differ between groups ( p = 0.10). Peak
drinking (11%) and surgical risk (5%). plasma concentration of FGF21 was significantly higher in Group A
Comparing patients listed for transplant with those not listed we (mean ± standard deviation: 4.0 ± 0.8 ng/ml) compared to Group C
noted higher UKELD (Mean 55.66 vs 53.77 p <0.001), longer duration (1.8 ± 0.4 ng/ml) ( p = 0.03) but not compared to Group B (2.2 ± 0.5 ng/
of abstinence (Median 12 vs 11 months U = 35751, p = 0.018) and no ml) ( p = 0.08) (Fig. 1B). Area under the curve for FGF21 was greatest in
significant differences between gender (Chi Sq p = 0.258) or age Group A (763 ± 150 ng/ml × min) followed by Group B (488 ± 120 ng/
distribution (Chi Sq p = 0.53). ml × min) and Group C (356 ± 77 ng/ml × min) with borderline
statistical significant difference between Group A and C ( p = 0.05)
(Fig. 1B). Group A exhibited a greater desire to drink alcohol than seen
in Group B ( p = 0.02) and C ( p = 0.01).

Conclusion: This study provides a complete representation of all

patients with ArLD assessed for liver transplantation over a 12-month
period in the UK. Future work is planned to investigate outcomes of
patients not listed for transplant and better understand reasons for
patients being declined transplantation.
Conclusion: We show that FGF21 is the main alcohol responsive
THU006 peptide hormone in healthy humans and we show greater plasma
Fibroblast growth factor 21 is the main alcohol responsive peptide FGF21 concentrations after alcohol intake in individuals suffering from
hormone in humans and individuals with alcohol use disorder AUD compared to healthy individuals and individuals predisposed to
exihibit increased plasma concentrations after alcohol intake AUD, respectively, implicating FGF21 in the pathophysiology of AUD.
Amalie Lanng1, Lærke Gasbjerg1,2, Andrea Sucksdorff1,
Jens Svenningsen3, Samuel Trammell2, Tina Vilsbøll1,4,5, THU007
Matthew Gillum3, Filip Krag Knop1,3,4,5. 1Gentofte Hospital, Center for Tight junction damage and increased gut permeability in
Clinical Metabolic Research, Hellerup, Denmark; 2University of alcohol-related liver disease may be mediated by gut proteases
Copenhagen, Department of Biomedical Sciences, Faculty of Health and Charlotte Skinner1, Julian Marchesi1, Benjamin H. Mullish1,
Medical Sciences, Copenhagen N, Denmark; 3University of Copenhagen, Hiromi Kudo1, Lauren Roberts1, Haoyu Sun1, Roberta Forlano1,
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Emma Lord1, Mark Thursz1, Nikhil Vergis1. 1Imperial College London,
Health and Medical Sciences, Copenhagen N, Denmark; 4Steno Diabetes United Kingdom
Center Copenhagen, Herlev, Denmark; 5University of Copenhagen, Email: [email protected]
Department of Clinical Medicine, Faculty of Health and Medical Sciences, Background and aims: Recent data have implicated gut-derived
Copenhagen N, Denmark virulence factors in the pathogenesis of ArLD. However, it is not clear
Email: [email protected] how virulence factors gain access to portal circulation. We investi-
Background and aims: Alcohol use disorder (AUD) is responsible for gated if gut-derived proteases enable bacterial translocation in
5.3% of worldwide deaths annually. The pathophysiology of AUD

Journal of Hepatology 2022 vol. 77(S1) | S119–S388 S121

POSTER PRESENTATIONS
patients with ArLD including patients with severe alcohol-related Background and aims: Acute kidney injury (AKI) can complicate
hepatitis (sAH). severe alcohol-related hepatitis (sAH) and has been associated with
Method: Protease activity of faecal water (FW) was assayed using increased mortality. However, the relative impact of AKI at baseline
fluorescently-labelled casein. Madin Darby Canine Kidney (MDCK) compared to AKI that develops on treatment has not been evaluated.
cells grown to confluent monolayers on Transwell plate inserts were Moreover, treatments that may modulate the risk of AKI are poorly
used to create a model of gut barrier function validated against CACO-2 defined. A range of biomarkers have shown promise to predict the
cells. FW was applied to the apical surface of the insert and the development of AKI, but few have been independently validated in
transepithelial electrical resistance (TEER), a marker of monolayer sAH.
integrity, was measured at 120 min. Enterococcus faecalis (GelE+) Method: Data was available from 1051 sAH patients recruited to the
supernatant served as a high-protease positive control while phos- STOPAH trial. AKI was defined by an adapted International Club of
phate buffered solution (PBS) was a negative control. Zymography Ascites definition as either: an increase in creatinine >26.5 micromol/L
allowed differentiation of proteases in FW by substrate protein and above or 1.5x the lowest recorded; creatinine >133 micromol/L; or
molecular weight. Next, MDCK cells were grown to confluence on new renal replacement therapy. Incident AKI was defined as AKI at day
histology slides. FW was applied and the slides fixed and stained for 7 without baseline AKI. We compared baseline and incident AKI to 90-
the tight junction protein zonulin-1 (ZO-1). Finally, patient FWaliquots day mortality using Kaplan-Meier survival analysis and binary logistic
were plated on to protease-indicator agar and the bacterial isolates regression. Further, we identified factors associated with baseline and
showing a protease phenotype were taxonomically characterised. incident AKI by multivariable models. Finally, we tested previously
Results: FW samples were obtained from 38 subjects: sAH n = 14, published and novel serum biomarkers and a micro-RNA panel
decompensated ArLD n = 11 and control subjects n = 13. Protease measured by PCR array to predict incident AKI using AUROC analyses.
activity in FW correlated with change in TEER (ΔTEER) for all subjects Results: Baseline AKI was present in 198/1051 (19%) patients and
(r = − 0.5888, p < 0.001) (Fig. 1). Interestingly, ΔTEER correlated with associated with increased D90 mortality (OR 1.42, 95% confidence
liver function (r = − 0.472, p = 0.0036 for MELD) with the greatest interval 1.02–2.00, p = 0.038). Excluding 282 patients alive at D7
change in TEER seen in sAH FW samples. Strikingly, a broad-spectrum without D7 creatinine available, incident AKI developed in 119/769
protease inhibitor added to the FW abolished the correlation between (15%) patients and was associated with higher D90 mortality (OR 2.61,
ΔTEER and protease activity (r = 0.0897, p = 0.644) (Fig. 1) and MELD 1.72–3.96, p <0.001) and remained associated after adjustment for age
score (r = − 0.0645, p = 0.754). ZO-1 staining was markedly decreased and MELD. After adjustment for MELD score, prednisolone was
in slides treated with sAH FW samples vs controls (Fig. 1b+c). associated with reduction in incident AKI (OR 0.57; 0.37–0.88, p =
Zymography showed the altered pattern of proteases within the FW 0.011) but pentoxifylline was not (OR 1.10, 0.72–1.67, p = 0.656). Use of
of sAH patients. Protease-differential agar culture identified E. beta-blockers at baseline showed a trend to increased incident AKI
faecium, S. epidermidis and E. coli as the putative source of proteases after propensity-score matching for MELD and systolic blood pressure
responsible for tight junction damage. ( p = 0.063). Baseline Cystatin C, NGAL, Beta-2 microglobulin and IL-18
were not predictive of incident AKI but TGF-beta2 and IL-8 were
strongly associated ( p <0.001) and a combination of bilirubin and IL-8
showed AUROC 0.72 (p <0.001) for incident AKI. Several micro-RNAs
had AUROC >0.75, the highest of which was miR-4505 at AUROC 0.78
( p <0.006).

Figure: A:TEER change across MDCK monolayers vs protease activity of

FW samples with and without a protease inhibitor. B: ZO-1 staining in AH
FW samples. C: ZO-1 staining in control FW samples.
Conclusion: Protease activity in patient FW can cause tight junction
damage and increased gut permeability in vitro and correlates
strongly with liver function. This points to a potential mechanism
for gut derived virulence factors to reach the liver in ArLD, and
particularly in sAH.
THU008
Incident acute kidney injury in severe alcohol-related hepatitis is
strongly associated with mortality and can be predicted using
micro-RNAs and markers of systemic inflammation Conclusion: Incident AKI is associated with higher 90-day mortality
compared to AKI present at baseline in patients with sAH. IL-8 and
Luke D. Tyson1,2, Stephen Atkinson1,2, Michael Allison3,
several micro RNAs, including 4505, show promise as biomarkers and
Andrew Austin4, Lily Cross1, James Dear5, Ewan Forrest6, Tong Liu1,
should be validated in independent cohorts.
Emma Lord1, Steven Masson7, Joao Nunes8, Paul Richardson9,
Stephen Ryder10, Mark Wright11, Mark Thursz1,2, Nikhil Vergis1,2. THU009
1
Imperial College London, Department of Metabolism, Digestion and The impact of addiction team integration into the management of
Reproduction, London, United Kingdom; 2St Mary’s Hospital, The Liver patients transplanted for alcohol-related liver disease: results
Unit, London, United Kingdom; 3Addenbrooke’s Hospital, Cambridge, from a multicenter comparative study
United Kingdom; 4Royal Derby Hospital, United Kingdom; 5University of Jules Daniel1, Jérôme Dumortier2, Arnaud Del Bello3, Lucie Gamon4,
Edinburgh, United Kingdom; 6Glasgow Royal Infirmary, United Nicolas Molinari4, José Ursic-Bedoya1, Magdalena Meszaros1,
Kingdom; 7Newcastle Freeman Hospital, High Heaton, United Kingdom; Georges-Philippe Pageaux1, Hélène Donnadieu-Rigole1. 1University
8
Meso Scale Diagnostics, Gaithersburg, United States; 9The Royal Hospital Center Saint Eloi Hospital, Montpellier, France; 2University
Liverpool University Hospital, Liverpool, United Kingdom; 10Queens Hospital Center Édouard Herriot Hospital, Lyon, France; 3University
Medical Centre, Nottingham, United Kingdom; 11University Hospital Hospital Center Rangueil Hospital, Toulouse, France; 4University
Southampton NHS Foundation Trust, United Kingdom Hospital Center La Colombier̀ e Hospital, Montpellier, France
Email: [email protected] Email: [email protected]

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 POSTER PRESENTATIONS
Background and aims: Alcohol-related liver disease (ALD) is the national level for this population are scarce. The aim was to evaluate
commonest indication for liver transplantation (LT) in Western the risk of fractures and post-fracture mortality in patients with
Europe. Up to 40% of patients resume alcohol consumption after LT. alcohol-related cirrhosis compared to individuals from the general
Severe relapse is associated with a poor prognosis. Specific population.
management of alcohol use disorder could reduce the rate of severe Method: In this nationwide population-based cohort study, data
relapse after LT. The aim of this study was to evaluate the effect on were retrieved from the Swedish National Patient Registry on 23, 847
prognosis of the integration of an addiction team into an LT center. patients with alcohol-related cirrhosis from 1969 to 2016. Patients
Method: This retrospective multicenter study included all adult were matched for sex, age, and municipality with 229, 907 controls
patients transplanted for "pure" ALD, excluding mixed cirrhosis, from the Swedish Total Population Registry. Cox regression models
between 2000 and 2015 at the three participating centers. Patients were fitted to investigate the risk of any fracture and post-fracture
transplanted between 2008 and 2015 were managed by an addiction mortality in patients with a fracture during follow-up. The cumula-
team embedded in the LT team at one of the centers (the interest tive incidence of fractures was calculated while accounting for the
group), unlike those at the other centers (control group). Propensity competing risks of death or liver transplantation.
score matching (PSM) was performed to minimize differences Results: A total of 47, 375 fractures occurred during 3, 410, 949
between groups. The primary outcome was the rate of severe person-years of follow-up. Patients with alcohol-related cirrhosis had
alcohol relapse defined as four or more standard drinks per day for a higher incidence of fractures (35.9 per 1000 person-years) than
at least 100 consecutive days. matched controls (13.3 per 1000 person-years; adjusted hazard ratio
Results: 616 patients were included, 195 of whom received specific [aHR] 3.6, 95% confidence interval [CI] 3.5–3.8). Results were
addiction follow-up (entire cohort). 79.4% were men, with a mean consistent for osteoporotic fractures, fractures due to high-energy
age of 55.4 years. 58.3% had Child-Pugh C cirrhosis, their median trauma, and all fracture sites. The cumulative incidence of fractures
MELD score was 19, and 32.7% had HCC. The median follow-up was 9 was higher for patients the first 18 years of follow-up, with a 5-year
years, 6.6 years in the interest group and 11.1 years in the control risk of 9.4% compared to 4.5% for controls. The post-fracture mortality
group. The survival rate of the entire cohort was 97.4%, 83.8%, and rate was elevated in patients with alcohol-related cirrhosis compared
70.1% at 1, 5, and 10 years, respectively. After 1:1 PSM, 170 pairs were to controls who also experienced a fracture at both 30 days (aHR 1.5,
created (matched cohort) comparable for age, gender, smoking 95% CI 1.3–1.8) and 1 year (aHR 1.6, 95% CI 1.5–1.8).
history, duration of pre-LT abstinence ± 6 months, cardiovascular
risk factors, and MELD and Child-Pugh scores. Addiction follow-up
was significantly associated with a reduced risk of severe alcohol
relapse (6.5% vs. 15.5%; HR = 0.33, 95% CI 0.16–0.69; p = 0.0033) and
the occurrence of severe cardiovascular events (10.0% vs. 20.0%; OR =
0.39, 95% CI 0.20–0.79; p <0.001). There were no significant
differences in terms of mortality (HR = 1.00; p = 0.99), occurrence of
de novo cancer (21.7% vs. 24.7%; OR = 0.86; p = 0.17), HCC recurrence
(15.7% vs. 10.7%; OR = 1.67; p = 0.32), or alcohol-related graft cirrhosis
(5.1% vs. 3.5%; OR = 1.60; p = 0.41) between the two groups.

Conclusion: Alcohol-related cirrhosis is associated with a more than

threefold increased fracture rate, resulting in a higher cumulative
incidence of fractures the first two decades after initial diagnosis. In
addition, alcohol-related cirrhosis is associated with a higher post-
fracture mortality rate. Preventive interventions to reduce modifiable
fracture risk factors in this population are justified.

THU011
Conclusion: In this multicenter study of a large cohort of patients Use of statins among patients with cirrhosis due to alcohol-
transplanted for ALD, addiction follow-up was associated with a related liver disease-a danish nationwide cohort study
decrease in severe alcohol relapse. Anna Marine Sølling Ramsing1, Frederik Kraglund1, Peter Jepsen1.
1
Aarhus University Hospital, Department of Hepatology and
THU010 Gastroenterology, Aarhus N, Denmark
Risk of fractures and subsequent mortality in alcohol-related Email: [email protected]
cirrhosis: a nationwide population-based cohort study
Background and aims: Statins reportedly increase the survival of
Axel Wester1, Nelson Ndegwa2, Hannes Hagström1. 1Karolinska
patients with cirrhosis due to alcohol-related liver disease (ALD
Institutet, Department of medicine Huddinge, Stockholm, Sweden;
2 cirrhosis) but may be underutilized due to fear of hepatotoxicity. It
Karolinska Institutet, Department of medical epidemiology and
remains unclear how many patients with ALD cirrhosis use statins,
biostatistics
and which factors predict statin initiation. We aimed to examine
Email: [email protected]
time-trends in prevalence of statin use and predictors of statin
Background and aims: Alcohol-related cirrhosis is linked to an initiation among patients with ALD cirrhosis.
increased risk of fractures. However, fracture risk assessments on a

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POSTER PRESENTATIONS
Method: Using data from the Danish healthcare registries, we to characterize their biophysical and functional features using a SS
conducted a nationwide cohort study, including all Danish citizens approach.
receiving their first diagnosis of ALD cirrhosis (ICD-10: K703 and Method: A cohort of patients affected by alcoholic liver disease (ALD),
K704) between 1995 and 2018. We examined how the prevalence of including steato-fibrosis (n = 49), compensated cirrhosis (n = 54),
statin use has changed during this period and used Cox regression to decompensated cirrhosis (n = 64) and severe alcoholic hepatitis (n =
identify predictors of statin initiation. 45) was studied. Fifty healthy adults were included as controls.
Results: During the 1995 to 2018 period, we identified 30723 Biophysical (titers, isotype, subclass, IgG Fc fragment glycosylation)
patients, of whom 7% used statins at the time of cirrhosis diagnosis, and functional-antibody-dependent complement deposition
and 4% became first-time statin users within 5 years after cirrhosis (ADCD), macrophage phagocytosis (ADCP) and neutrophil phagocyt-
diagnosis. The prevalence of statin use rose sharply during the 1995– osis (ADNP) and NK cell activation (ADCA)-features of M-IgG (E.Coli,
2018 period, reaching more than 15% in late 2018 (Figure). Factors S.Aureus, St.Salivarius, E.Foecalis) were investigated, and compared to
predicting a higher probability of initiating statin use after diagnosis vaccine (Diphtheria Toxoid, Tetanus Toxoid) antigen-specific (V)-IgG
of ALD cirrhosis included diabetes (hazard ratio [HR] = 2.21, 95% CI: as control of passed antigen-exposure.
1.85–2.65) and cardiovascular disease (HR = 2.97, 95% CI: 2.19–4.03), Results: Patients with ALD showed increased titers of M-IgG, M-IgG1
and compensated cirrhosis (HR = 1.40, 95% CI: 1.25–1.55). Socio- and M-IgG2 as compared to healthy controls. M-specific antibody
economic predictors included living with a partner (HR = 1.17, 95% CI: titers correlated with H-IgG. Patients with ALD also had higher M-
1.06–1.30) as opposed to living alone, low educational attainment, specific ADCD than healthy controls and levels of ADCD correlated
i.e., primary school (HR = 1.22, 95% CI: 1.04–1.43) or secondary school with titers of M-IgG. The highest M-IgG titers and ADCD levels were
(HR = 1.23, 95% CI: 1.05–1.44) as opposed to higher education, and observed in patients with decompensated cirrhosis or with severe
older age (HR = 1.18 for every ten-year increase in age, 95% CI 1.11– alcoholic hepatitis. In contrast, similar levels of M-specific ADCP,
1.24). Employment status and sex were not statistically significant ADNP and ADCA were detected amongst the ALD groups, suggesting
predictors. an altered functional profile. The increased titers of M-specific
antibodies in ALD patients were not associated with increased titers
of V-specific antibodies and V-IgG did not correlate with H-IgG.
Patients with ALD also had higher proportions of fucosylated and
agalactosylated total IgG Fc as compared to healthy controls.
Conclusion: These results indicate that the H-IgG observed in ALD
patients involves an increased production of antibodies directed
against microbiome antigens. The biophysical features (subclass, Fc
glycans) of M-IgG and their potent complement activation potential
could promote inflammation and thereby contribute to the patho-
genesis of ALD.

THU013
Socio-economic factors and healthcare setting are independently
associated with medium and long-term outcomes from
alcohol-related hepatitis
Joshua Lambert1, Nikhil Vergis2, Michael Allison2, Andrew Austin2,
Ewan Forrest2, Emma Lord2, Steven Masson2, Paul Richardson2,
Stephen Ryder2, Mark Wright2, Mark Thursz2, Stephen Atkinson2.
Conclusion: Use of statins has become common practice among 1
Imperial College School of Medicine, London, United Kingdom;
patients with ALD cirrhosis in Denmark. Predictors of initiating statin 2
Imperial College London, London, United Kingdom
use were diabetes, cardiovascular disease, compensated cirrhosis, Email: [email protected]
living with a partner, low educational attainment, and older age.
Background and aims: Socio-economic factors are known to
THU012 influence outcomes in liver disease but the impact in severe
Antibody response to gut microbiome bacteria in human alcohol-related hepatitis (sAH) is unknown. Similarly, the healthcare
alcoholic liver disease setting where a patient is treated can modify outcomes in various
Antonella Putignano1,2, Shilpee Sharma2, Anaïs Thiriard2, diseases but its impact in sAH has not been studied. Here, we
Dalila Lakhloufi3, Yiwei Jiang2, Anne Botteaux3, Eric Trépo1, investigate the impact of these two factors on medium and long-term
Delphine Degré1, Christophe Moreno1, Thierry Gustot1, outcomes in sAH.
Arnaud Marchant2. 1CUB Erasme Hospital, Dept of Gastroenterology, Method: Data was available from 1092 sAH patients enrolled in the
Hepato-Pancreatology and Digestive Oncology, Bruxelles, Belgium; STOPAH trial. Variables measured comprised education, housing,
2
Institute for Medical Immunology, ULB-Campus Erasme, Brussels, employment, relationship status, Index of Multiple Deprivation (IMD)
Belgium; 3Molecular Bacteriology Laboratory, ULB-Campus Erasme, and treating hospital setting. The latter was categorised as transplant,
Brussels, Belgium tertiary and secondary care centres using the British Society of
Email: [email protected] Gastroenterology National Liver Disease Survey 2011. Multivariable
logistic regression models were fitted for two distinct time periods:
Background and aims: Hypergammaglobulinemia (H-IgG) is a medium-term mortality between hospital admission to 90 days; and
feature of chronic liver disease (CLD) but its origin remains poorly long-term mortality from 90 to 365 days (806 patients). Statistical
understood. Translocation of microbiome components could trigger adjustments were made for age, MELD and drinking status. Models
B cells to produce microbiome-specific (M)-IgG and thereby were fitted using all available data plus data generated by multiple
stimulate the formation of immune complexes that could contribute imputation for missing MELD scores and drinking status.
to cirrhosis-associated immune dysfunction (CAID). Systems serology Results: In the medium-term, there was no association between IMD
(SS) provides a global approach to profile antigen specific antibodies and 90-day mortality on univariate analysis; however adjustment for
and their relationship with clinical outcomes. The aims of the study age and MELD revealed a significant independent association (OR,
were to investigate the contribution of M-IgG to the H-IgG of CLD and 1.16; 95% CI: 1.01–1.34). In the medium-term, treatment at a
transplant centre was associated with a reduction in 90-day mortality

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 POSTER PRESENTATIONS
in univariate (OR, 0.61; 95% CI: 0.38–0.95) and adjusted models (OR, follow-up of 23.5 (0–24) mo. The overall mean survival in women was
0.47; 95% CI: 0.28–0.78). In the long-term, leaving education at 19 or significantly longer than in men (18.9 mo vs.15.7 mo; p = 0.034).
older was the only factor associated with a reduced risk of death at There was no difference in survival between the men and women
365 days compared to leaving education at 16 or younger in who continued to drink (18.1 mo vs. 18.0 mo) but women who drank
univariate (OR, 0.55; 95% CI: 0.30–0.94) and adjusted models (OR, little or nothing survived significantly longer than their male
0.56; 95% CI: 0.30–0.97). counterparts (20.2 mo vs. 13.4 mo; p = 0.002) (Figure). Age and the
Child-Pugh score were the only independent predictors of survival.

Conclusion: Socio-economic factors and type of healthcare facility in

which an AH patient is treated are associated with medium and long-
term survival outcomes. These findings reinforce the need to reduce
health inequalities in alcohol-related liver disease.

THU014
Sex-related differences in outcomes in alcohol-related cirrhosis Conclusion: Women with decompensated cirrhosis have similar
following an episode of hepatic decompensation do not explain recovery rates to their male counterparts but significantly better
subsequent management inequalities survival rates. Thus, the sex-related inequalities in disease manage-
Aaminah Mohammed1, Nora Khattab1, Clive Jackson2, Jennifer Ryan3, ment likely reflect undue bias and need to be urgently addressed.
Marsha Morgan1. 1UCL Institute for Liver and Digestive Health, Division THU015
of Medicine, Royal Free Campus, University College London, London, Influence of comorbidities and lifestyle factors on health-related
United Kingdom; 2Department of Clinical Neurophysiology, Royal Free quality of life in alcohol-related liver disease: a population-based
Hospital, Royal Free NHS Foundation Trust, London, United Kingdom; survey
3
Department of Gastrointestinal and Liver Services, Royal Free Hospital,
Karen Dombestein Elde1, Natasja Von Wowern2,
Royal Free NHS Foundation Trust, London, United Kingdom
Matilde Winther-Jensen3, Cathrine Lau3, Lone Madsen2, Peter Jepsen4,
Email: [email protected]
Gro Askgaard2,3,4. 1Førde Central Hospital, Department of Internal
Background and aims: There is evidence of sex-differences in the Medicine, Førde, Norway; 2Zealand University Hospital, Section of
management of patients with alcohol-related cirrhosis to the Gastroenterology and Hepatology, Medical Department, Køge, Denmark;
3
detriment of the 30% who are female. Thus, women are less likely Bispebjerg and Frederiksberg Hospital, Center for Clinical Research and
to be selected for liver transplantation; are 10% more likely to be Prevention, Copenhagen, Denmark; 4Aarhus University Hospital,
delisted and have higher wait-list mortality rates (Cullaro et al, Am J Department of Hepatology and Gastroenterology, Aarhus, Denmark
Transplant 2018;18:1214). Erroneous assumptions about the natural Email: [email protected]
history of alcohol-related cirrhosis in women may underlie these
Background and aims: Health-related quality of life (HRQoL) is
observed management inequalities. The aims of this study were to: (i)
impaired in alcohol-related liver disease (ALD). We examined the
determine resolution and survival rates following an episode of
effects of extra-hepatic comorbidities, alcohol, and smoking on
hepatic decompensation, by sex; and, (ii) identify possible predictors
HRQoL in ALD and whether low HRQoL influenced survival.
of outcome.
Method: We used health registers to identify patients with ALD and
Method: All patients with a primary diagnosis of alcohol-related
comparators without ALD among the participants in the Danish
cirrhosis admitted to the Royal Free Hospital in 2016 and 2018 with
National Health Surveys 2010–2017. Survey data on HRQoL (12-item
an episode of hepatic decompensation were reviewed. Patients who
Short Form), comorbidities, alcohol consumption, alcohol use
survived the index admission were followed for 24-months post
disorder (CAGE score ≥ 2), and smoking was linked with vital
discharge specifically in relation to their drinking behaviour, rates of
statistics through 2020. Associations of comorbidities, alcohol, and
hepatic recompensation and survival. Rates of recompensation were
smoking with poor HRQoL (Z-score <1.5) in ALD were studied with
assessed using Box plots to map out the changes in MELD and Child
multivariable logistic regression adjusting for liver disease severity,
Pugh scores by sex and drinking behaviour. Kaplan Meier curves were
age and sex. We calculated adjusted hazard ratios (HR) of mortality
plotted to measure differences in survival by sex and drinking
until 2020 according to stated HRQoL.
behaviour; data were censored at death, transplantation or end of
Results: Poor physical and mental HRQoL were found in 37% and 22%
follow-up; the Mantel-Cox test was used to determine significance.
of 772 ALD patients compared to 10% and 9% of 4319 comparators.
Cox regression analyses were used to identify variables which were
Asthma/COPD, cancer, disc herniation, and osteoarthritis were
significant predictors of survival.
associated with poor physical QoL in ALD, whereas diabetes and
Results: The study cohort comprised of 142 patients with cirrhosis
cardiovascular diseases were not (Figure 1). Osteoarthritis, alcohol
(median [range] age: 54 [30–87] years; 66% men). During the follow-
use disorder, and smoking >20 cigarettes/day were associated with
up period 79 (56%) people continued to drink excessively while 63
poor mental HRQoL. Both poor physical and poor mental QoL were
remained abstinent or else consumed alcohol at low risk levels. There
associated with higher mortality rates [HR 1.6 (95% CI: 1.3–2.0) and
was no significant difference in the proportions of men and women
HR 1.4 (95% CI: 1.1–1.8)] in ALD.
who continued to misuse alcohol (62.5% vs. 52.1%). There were no
significance differences in the rates of recompensation, determined
by changes in the MELD and Child Pugh scores, by sex or drinking
behaviour. Fifty-one of the 142 (35.9%) patients died during a median

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POSTER PRESENTATIONS
agreed. Most Rx initiated was behavioral (n = 78), medication (N = 13)
or both (n = 39). On regression, patients who were offered and
accepted, were more likely to have PTSD (OR 2.1, 1.1–4.0, p = 0.03),
cocaine disorder (2.3, 1.3–4.1, p = 0.004) and were offered Rx as
inpatients (2.6, 1.5–4.7, p = 0.001).

Conclusion: Respiratory and musculoskeletal diseases, cancer,

alcohol use disorder, and smoking are associated with poor HRQoL Conclusion: Most Veterans with cirrhosis and AUD with opportun-
in ALD. Poor HRQoL decrease survival in ALD. These findings should ities to engage were offered AUD Rx but missed opportunities remain.
raise physicians’ awareness on potentially modifiable factors affect- Younger outpatients with co-occurring psychiatric disorders were
ing quality of life and survival in ALD patients. more likely to be offered AUD Rx. When offered, Rx was accepted by
only 40% of Veterans, especially inpatients and those with concomi-
THU016 tant PTSD/cocaine abuse disorder. While system and patient-related
Patient and system-level factors underline offering and factors are linked with Rx offers and initiation, in these three centers
acceptance of alcohol use disorder therapy in veterans with most eligible Veterans with cirrhosis were offered AUD Rx.
cirrhosis
Rahul Chaudhari1, Nikki Duong1, Shreesh Shrestha1, Neerav Dharia1, THU017
Bryan Badal1, James Wade1, Linda Chia2, Patrick Spoutz2, 24-Norursodeoxycholic acid ameliorates experimental alcoholic
Ernesto Robalino Gonzaga2, Shari Rogal2, Jasmohan S Bajaj1. 1Virginia liver disease in both preventive and therapeutic settings
Commonwealth University and Richmond VAMC; 2Pittsburgh VA Medical Christoph Grander1, Moritz Meyer1, Daniel Steinacher2,
Center Thierry Claudel2, Felix Grabherr1, Julian Schwärzler1, Timon Adolph1,
Email: [email protected] Michael Trauner2, Herbert Tilg1. 1Medical University Innsbruck,
Department Internal Medicine I; 2Medical University of Vienna,
Background and aims: Cirrhosis with continued alcohol use Department of Medicine III
disorder (AUD) is linked with poor outcomes. AUD Rx is efficacious, Email: [email protected]
but a recent study showed only 12% of Veterans with AUD and
cirrhosis received it. The reasons behind this are unclear. Background and aims: Alcoholic liver disease (ALD) is the hepatic
Aim: Define patient, and system-level factors associated with AUD Rx. manifestation of alcohol overconsumption. Ethanol toxicity, systemic
Method: Veterans seen in 2020 with 2 ICD codes for cirrhosis/ pro-inflammatory cytokines as well as the intestinal microbiota
complications+AUD at 3 large VA centers were evaluated. Data contribute to the progression of ALD. 24-Norursodeoxycholic acid
regarding demographics, mental health comorbidities, and cirrhosis (norUDCA) is a side chain shortened UDCA with potent choleretic
severity were collected, and an in-depth chart review performed to properties and therapeutic effects in non-alcoholic liver disease and
collect AUD Rx settings and details. Determinants of lack of uptake primary sclerosing cholangitis. Therefore, we hypothesized that
were examined using logistic regression. norUDCA could ameliorate experimental ALD.
Results: We included 654 pts with AUD and cirrhosis (95% men, 64.3 Method: Female wildtype mice were fed an ethanol-containing diet
yrs, 56% white, 8% Hispanic). Common mental health conditions on (Lieber-DeCarli diet) or pair-diet for 15 days. Two different settings of
chart review were depression 47%, PTSD 24%, anxiety 17%, cocaine experiments were performed: First, the diet was supplemented with
use 25%, bipolar 5% and cannabis use disorder 19%. Cirrhosis 1 mg/ml norUDCA starting from day one. In a second experiment,
decompensation was seen in 19%. AUD Rx history: 5% had received mice received norUDCA (1 mg/ml) starting from day ten, mimicking a
prior AUD medications, 24% got behavioral therapy, and 11% both. The therapeutic approach.
remaining 60% were not on prior AUD Rx. At baseline, 24% (n = 174) Results: Ethanol-feeding resulted in hepatic injury, displayed by
were noted in the chart to be in AUD remission, while the remaining elevated ALT concentration, increased number of TUNEL+ hepatic
76% had ongoing alcohol use (Figure). Course: Most pts were seen by cells, indicating augmented apoptosis and hepatic steatosis. NorUDCA
primary care, hepatology, or both (48%, 5%, 35%); 28% were treatment diminished ALT levels ( p < 0.001), reduced the number of
hospitalized in 2020. AUD Rx discussion: Of the 412 patients not on TUNEL+ cells ( p < 0.05) and decreased hepatic steatosis compared to
Rx or in remission at baseline, AUD Rx offered to 264 (64%). Most Rx ethanol-fed controls. Moreover, the hepatic mRNA expression of pro-
offers were made in the outpatient setting (n = 207) then in inpatients inflammatory cytokines like Tnf-alpha ( p < 0.001), Il-1beta ( p < 0.01),
(n = 30). This was most often offered by primary care (n = 162), Il-6 ( p < 0.001) and Il-10 ( p < 0.01) was significantly reduced by
hepatology (n = 45), or both (n = 41); fewer were offered Rx through norUDCA treatment in ethanol-fed mice. Important to note, systemic
mental health (n = 19). The factors significantly associated with AUD ethanol concentration was not altered by norUDCA administration.
treatment offer in the regression model included depression (OR 1.58 NorUDCA treatment enhanced bile acid metabolism in ethanol-fed
95% CI 1.01–2.48, p = 0.05), bipolar disorder (3.0, 1.1–8.4, p = 0.03), mice, displayed by increased gall bladder weight ( p < 0.001),
seen as outpts (6.8, 3.3–14.3, p < 0.0001), and younger age (OR/yr 0.96, circulating bile acids ( p < 0.001) and the mRNA expression of
0.94–0.99, p = 0.003). Decompensation, gender, race, ethnicity, hospi- hepatic Sult2a1 ( p < 0.001), Mrp4 ( p < 0.001) and Cyp7a1 ( p <
talizations, or decompensation were not significantly associated with 0.001), important regulators in bile acid metabolism. Interestingly,
Rx offer. Patient acceptance: Of the 264 pts offered AUD Rx, 40%

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 POSTER PRESENTATIONS
norUDCA induced hepatic Ppar-gamma in ethanol-fed mice, which specific treatment. Regarding mortality, 134 patients (26%) had died
could mechanistically explain the observed protective effects. after one year, 51% of them during the index hospitalization. In the
In a second experiment we tested the efficacy of norUDCA in a multivariate analysis, only male sex, older age, MELD score and failure
therapeutic setting. In ethanol-fed mice the administration of to withdraw alcohol remained independently associated with
norUDCA for 5 days resulted in a 45% reduction of ALT concentration. mortality. Interestingly, women had significantly higher survival at
Furthermore, the hepatic mRNA expression of Tnf-alpha ( p < 0.05) one year (85% vs 71%, p < 0.05). These differences were more
and Il-6 ( p < 0.05) was significantly decreased in ethanol-fed pronounced in the subset of severe AH (79% vs 62%, p < 0.05). No
norUDCA treated mice compared to ethanol-fed mice. differences between men and women were found regarding liver
Conclusion: NorUDCA ameliorates hepatic inflammation and stea- function, alcohol withdrawal or corticosteroid treatment. Twenty-
tosis in experimental ALD and could serve as a therapeutic agent for nine patients (5.5%) presented recurrent episodes of AH. Compared to
ALD in the future. patients with no recurrence, patients with recurrent AH were more
frequently men (93% vs 72%, p < 0.05) and there was a trend to lower
THU018 survival (83% vs 92%, p = 0.091).
Impact of sex and recurrence in the prognosis of alcoholic
hepatitis
Jordi Gratacós-Gines1, Manuel Rodríguez2, Alvaro Giráldez-Gallego3,
Joaquín Cabezas4, Inmaculada Fernández Vázquez5,
Meritxell Ventura Cots6, Diana Horta7, Jordi Sánchez-Delgado8,
Silvia Acosta-López9, Tomás Artaza Varasa10, David Marti-Aguado11,
Vanesa Bernal Monterde12, Rosa Martin-Mateos13, Ana Clemente14,
Javier Tejedor-Tejada15, Jose Pinazo Bandera16, Margarita Sala17,
Esther Badia-Aranda18, Victoria Aguilera Sancho19, Santiago Tomé20,
Conrado Fernández-Rodríguez21, Joan Caballería1, Elisa Pose1.
1
Hospital Clínic de Barcelona, Liver Unit, Barcelona, Spain; 2Central
University Hospital of Asturias, Oviedo, Spain; 3Virgen del Rocío
University Hospital, Sevilla, Spain; 4Marqués de Valdecilla University
Hospital, Santander, Spain; 5University Hospital October 12, Madrid,
Spain; 6Hospital Universitari Vall d’Hebron, Barcelona, Spain; 7Hospital
Universitari MútuaTerrassa, Terrassa, Spain; 8Hospital Parc Taulí de
Sabadell, Sabadell, Spain; 9Our Lady of Candelaria University Hospital,
Santa Cruz de Tenerife, Spain; 10Virgin Health Hospital, Toledo, Spain;
11 ̀ cia, Spain; 12Hospital Universitario
Hospital Clínic Universitari, Valen
Conclusion: AH in a large European cohort typically features young
Miguel Servet, Zaragoza, Spain; 13Hospital Ramón y Cajal, Madrid,
men, presenting with acute decompensation. Recurrent AH was not
Spain; 14Gregorio Marañón Hospital, Madrid, Spain; 15Hospital
exceptional, especially in men, and was associated with a trend to
Universitario de Cabueñes, Department of Gastroenterology, Gijón,
higher mortality, which highlights the relevance of alcohol with-
Spain; 16Hospital Universitario Virgen de la Victoria, Málaga, Spain;
17 drawal and clinical follow-up in this population. In our series, women
Hospital Universitari de Girona Doctor Josep Trueta, Girona, Spain;
18 had higher survival rate; this finding questions the latest studies
Burgos University Hospital, Burgos, Spain; 19La Fe University and
̀ cia, Spain; 20Santiago Clinic Hospital CHUS, suggesting poorer prognosis in this group and deserves further
Polytechnic Hospital, Valen
investigation.
Santiago de Compostela, Spain; 21Hospital Universitario Fundación
Alcorcón, Alcorcón, Spain
THU019
Email: [email protected]
Hepatocyte-derived biomarkers concentrations predict liver-
Background and aims: alcoholic hepatitis (AH) is a clinical syndrome related events within 2 years in patients with Child-Pugh class A
characterized by recent onset of jaundice in the context of heavy alcohol-related cirrhosis
alcohol use that bears a high mortality. Current studies on AH point Laure Elkrief1, Nathalie Ganne-Carrié2, Hana Manceau3,
female sex as associated with poorer prognosis. Also, information on Marion Tanguy4, Nathalie Barget5, Cendrine Chaffaut6,
prognosis and clinical features of recurrent AH is scarce. The aims of Shantha Valainathan7, Alix Riescher7, Katell Peoch3, Thierry Poynard8,
this registry were to gain knowledge on the epidemiology, clinical Sylvie Chevret6, Pierre-Emmanuel Rautou7. 1Tours University
presentation and mortality of AH in Spain, with special focus on the Hospitals, Hepatogastroenterology, France; 2Hôpital Avicenne, Liver
influence of sex and recurrent AH. Unit, France; 3Hôpital Beaujon, Service de Biochimie, France; 4Inserm,
Method: retrospective multicentric Spanish registry of hospitalized Centre de recherche sur l’inflammation, France; 5Hôpital Avicenne,
cases of AH from 2014 to 2020 including 20 centers. Criterion for Centre de ressources biologiques, France; 6APHP Hôpital saint Louis,
inclusion was to meet the defined criteria for “probable HA” of the Service de Biostatistique et Information médicale, France; 7Hôpital
National Institute of Alcohol Abuse and Alcoholism (NIAAA). Clinical, Beaujon, Liver Unit, France; 8Université Sorbonne Paris, France
alcohological, demographic and prognostic data of the cohort were Email: [email protected]
recorded.
Results: Five hundred twenty-five patients were included. The Background and aims: Keratin-18 and hepatocyte derived large
majority were men (72%) with a median age of 51 and about half of extracellular vesicles (lEVs) concentrations reflect disease activity in
them had no previous history of liver disease (51%). Most cases patients with liver disease, and are therefore attractive biomarkers.
presented with hepatic decompensation of established cirrhosis Their ability to predict liver-related events in patients with alcohol-
(61%), mainly ascites and encephalopathy, and had important related cirrhosis is unknown. The aim of the present study was to
impairment in liver function (median MELD score 21). As for evaluate the usefulness of hepatocyte-derived biomarkers, alone or
diagnosis of AH, liver biopsy was performed in 124 cases (21%); combined with MELD and FibroTest, to predict liver-related events in
pathology was consistent with the clinical diagnosis in most of them patients with Child-Pugh class A alcohol-related cirrhosis, taking into
(79%). There were 351 cases of severe AH (63%). Corticosteroids were account the reported alcohol consumption status.
prescribed in 229 patients (65%); enteral nutrition and pentoxifylline Method: We measured plasma keratin-18 and hepatocyte lEVs
were also used (20% and 9%), while 23% of patients remained without concentrations in 500 patients with Child-Pugh class A alcohol-
related cirrhosis, from the prospective multicenter CIRRAL cohort

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POSTER PRESENTATIONS
study. Primary end point was liver-related events at 2 years. Since the THU020
course of liver disease is largely influenced by alcohol consumption, Dynamic multiomics analysis characterizes circulating molecular
patients were separated according to reported active alcohol determinants associated with poor outcome in patients with
consumption at enrollment (i.e. ≥7 glasses/week) or not. severe alcoholic hepatitis
Cumulative incidence of liver-related events was estimated using Jaswinder Maras1, Adil Bhat1,2, Nupur Sharma1, Manisha Yadav1,
the nonparametric cumulative incidence function, considering Gaurav Tripathi1, Babu Mathew1, Vasundhra Bindal1,
hepatocellular carcinoma and liver-unrelated deaths as competing Shvetank Sharma1, Rakhi Maiwall3, Shiv Kumar Sarin3. 1Institute of
events; in patients without active alcohol consumption at enroll- liver and biliary sciences, Molecular and Cellular Medicine, New Delhi,
ment, alcohol relapse was considered as an additional competing India; 2University of California, Los Angeles, Pathology and Lab Medicine,
event. Los Angeles, United States; 3Institute of liver and biliary science,
Results: Both keratin-18 and hepatocyte lEVs concentrations Hepatology, New Delhi, India
increased with alcohol consumption (Fig A and B). In patients Email: [email protected]
without active alcohol consumption at enrollment (n = 419), keratin-
18 concentration predicted liver-related events at 2 years, independ- Background and aims: Severe alcoholic hepatitis (SAH) has high
ently of FibroTest and MELD (Fig C). Patients with both keratin-18 morbidity, with steroid therapy providing 65% 28-day survival.
concentration >285 U/L and FibroTest >0.74 had a 24% cumulative Steroid non-responders (NR) have higher incidence of infections
incidence of liver-related events at 2 years, versus 5% to 14% in and mortality. Faecal microbiota transplant (FMT) is another
patients with other combinations of these two markers (Fig E, G). emerging therapy for SAH patients. We investigated whether multi-
Similar results were obtained when combining keratin-18 concen- omic studies and machine learning (ML) approaches could identify
tration >285 U/L with MELD ≥10 (not shown). In patients with active non-responders to corticosteroid or FMT at baseline.
alcohol consumption at enrollment (n = 81), hepatocyte lEVs con- Method: Thirty SAH patients who were randomized in an on-going
centrations predicted liver-related events at 2 years, independently of steroid vs. FMT protocol (Gov-no.NCT03091010) received either
FibroTest and MELD (Fig D). Patients with both hepatocyte lEVs prednisolone (40 mg/day- 7 days, responders for 4weeks, n = 13) or
concentration >50 U/L and FibroTest >0.74 had a 62% cumulative FMT (daily through nasoduodenal tube for 7 days, n = 17). Multi-omic
incidence of liver-related events at 2 years, versus 8% to 13% for analysis was performed on blinded serial plasma samples collected at
patients with other combinations of these two markers (Fig F, H). baseline, day-7 and day-28. Molecular determinants linked with non-
Combining hepatocyte lEVs concentration >50 U/L with MELD >10 response (NR) to steroid or FMT therapies were identified and
had a lower discrimination ability (not shown). validated for survival outcomes in a separate set of 70 SAH (NR = 21)
patients using artificial neural networking (ANN) and ML.
Results: Baseline characteristics of derivative and validation cohorts
were comparable. FMT treatment temporally increased amino-acid
metabolism, primary bile-acid biosynthesis, energy metabolism and
cori cycle metabolites ( p < 0.05). Steroid therapy temporally induced
vitamin and fat metabolism ( p < 0.05). Circulating meta-proteome
alpha/beta diversity was temporally increased by FMT with increase
in bacterial species; orientia, geobacter and streptococci. Steroid
therapy added ( p < 0.05) desulfovibro, clostridales and other species
at day 28. Compared with steroid therapy, FMT significantly reduced
inflammatory metabolic pathways [arachidonic acid and tryptophan
metabolism, TLR and immune-cell activation, complement cascade
and prostaglandin synthesis ( p < 0.05)] and increased antioxidant,
vitamins, neurotransmitters signalling and energy metabolism ( p <
0.05). Multi-omics profile of non-survivors was distinct, FMT non-
survivors compared to survivors, showed highest alpha-diversity
with increase in actinobacteria and firmicutes ( p < 0.05). Using multi-
omics integration along with ANN and ML, specific molecular clusters
were identified in non-survivors. Cluster-1 specific to complement,
coagulation and leukotriene biosynthesis, cluster-3 (P38-MAPK) in
the FMT arm and cluster-7 (complement, TLR activation) in the
steroid arm significantly predicted mortality (Norm Imp > 95%,
AUC>0.90, log-rank<0.01). Of these clusters;>3Fold increase in
molecules; CD44, 3-Oxosteroid and Proteobacteria; Ecoli for FMT
and protoporphyrinogen-IX, MYCBP2, Proteobacteria; rhizobium for
steroid arm were associated to higher mortality (AUC>0.95; log-
rank<0.01).
Conclusion: Baseline levels of panel; CD44, 3-Oxosteroid, proteo-
bacteria; E.coli, rhizobium protoporphyrinogen-IX and MYCBP2 can
predict NR and non-survival in SAH patients.

Conclusion: In patients with Child-Pugh class A alcohol-related

cirrhosis, combining hepatocyte-derived biomarkers with FibroTest
or MELD score identifies patients at high-risk of liver-related events,
and could be used for risk stratification and patient selection in
clinical trials.

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 POSTER PRESENTATIONS

Figure (abstract: THU020)

THU021 infused over 30 minutes via a nasogastric tube. Ninety-two

Alcohol-induced changes of inflammatory markers in hepatic circulating inflammatory cytokines were quantified using the
and systemic venous blood in early alcohol-related and non- Target-96 ‘Inflammation’ panel from Olink Proteomics, in plasma
alcoholic fatty liver disease samples obtained from two sites (hepatic and systemic vein), at three
Evelina Stankevic1, Mads Israelsen2,3, Helene Bæk Juel1, time points (0, 60 and 180 min). Linear (mixed) models were used
Anne Lundager Madsen1, Nikolaj Torp2,3, Stine Johansen2,3, and significant results ( p < 0.05) reported after correcting for False
Camilla Dalby Hansen2,3, Katrine Prier Lindvig2,3, Discovery Rate (FDR).
Bjørn Stæhr Madsen2,3, Maja Thiele2,3, Aleksander Krag2,3, Results: At baseline, 31 cytokines were differentially expressed in the
Torben Hansen1. 1The Novo Nordisk Foundation Center for Basic ALD group and 16 in the NAFLD group, when compared to the healthy
Metabolic Research, København, Denmark; 2Odense University Hospital, group. Alcohol induced changes for 2 cytokines at 60 min and 11
Department of Gastroenterology and Hepatology, Odense C, Denmark; cytokines at 180 min in hepatic venous blood, and for 4 cytokines at
3
University of Southern Denmark, Department of Clinical Research, 60 min and 24 cytokines at 180 min in systemic venous blood, in all
Faculty of Health Sciences, Odense C, Denmark three groups combined. Fibroblast growth factor 21 (FGF-21) was the
Email: [email protected] only cytokine that increased during the observation period.
Hepatocyte growth factor (HGF) was the first cytokine (after 60
Background and aims: Alcohol consumption is believed to increase min) to decrease in hepatic venous blood, while the concentration of
intestinal permeability, leading to inflow of pathogens and other 8 additional cytokines dropped within three hours (Figure showing
immune-activating compounds to the liver. Further, alcohol intake is volcano plots (upregulated (red) and downregulated (blue) cytokines
known to suppress the immune system, and is related to an increased in hepatic and systemic circulation after 60 and 180 min. The X axis-
risk of systemic infections. Taken together, these factors could play a log fold change and Y axis-log10 p value from a linear mixed model.
central role in the initiation of hepatic inflammation, an important Cytokines, significantly different after alcohol intoxication at FDR 5%
step in the development and progression of alcohol-related liver are labeled)). Moreover, the concentration of 19 cytokines was
disease (ALD). We aimed to investigate the effects of alcohol different in hepatic vein, when compared to systemic vein.
consumption on inflammatory markers in hepatic and systemic
venous blood in people with ALD, non-alcoholic fatty liver disease
(NAFLD) and healthy controls.
Method: We included 40 participants with three distinct hepatic
phenotypes: 15 with ALD, 15 with NAFLD and 10 healthy controls. All
participants received 2.5 ml of 40% ethanol per kg body weight,

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POSTER PRESENTATIONS

Conclusion: Our findings indicate that while ALD and NAFLD are
associated with an increased concentration of inflammatory cyto-
kines at baseline, acute alcohol consumption dampens the hepatic
and systemic inflammatory response, which might affect the ability
of the liver to deal with pathogens arriving from the portal vein.
Differences in cytokine concentrations between hepatic and systemic Results: In countries with a willingness-to-pay threshold of $ 50, 000,
vein suggests direct hepatic production or sequestration of these treatments halting progression in ALD at the fibrosis stage is cost-
cytokines, respectively, further highlighting the central role of the effective upon reaching 30% efficacy contingent on annual treatment
liver in systemic inflammation. costs not exceeding $ 5, 000, or 60% efficacy if costs are less than $ 10,
000 per annum. In the UK, where willingness to pay per quality-
THU022 adjusted life-year is between 20 and 30 000 £, progression-halting
New treatment for alcohol-related liver disease: combinations of treatments should reach an efficacy of 60% at an annual cost between
efficacy and treatment cost required for cost-effectiveness £ 3000 and £ 5000 to be considered cost-effective.
Maja Thiele1, Davit Khlghatyan2, Lars Asphaug3, Stine Johansen4, Conclusion: Our results are useful for research funders and
Hans Olav Melberg2. 1Odense University Hospital, University of producers of new treatments for ALD in determining to reimburse
Southern Denmark; 2University of Oslo, Department of Health or develop a new treatment for advanced liver fibrosis in patients
Management and Health Economics; 3University of Oslo, Department of with alcohol-related liver disease. The calculated ICERs can be
Health Management and Health Economics, Oslo, Norway; 4Odense interpreted across different healthcare systems with varying levels
University Hospital, University of Southern Denmark, Department of of cost-effectiveness thresholds.
Gastroenterology and Hepatology
Email: [email protected] THU023
Active alcohol misuse is linked with lower short-chain fatty acid
Background and aims: Alcohol-related liver disease (ALD) has a poor producing microbiota in a matched study of 450 patients with
prognosis, with a 5-year survival rate below 50%, and substantial cirrhosis
costs for the healthcare system with no effective treatment currently
Jasmohan S Bajaj1, Amirhossein Shamsaddini2,
available. Recently, accurate diagnostic tools have allowed for early
Masoumeh Sikaroodi2, Brian Davis1, Puneet Puri1, Michael Fuchs1,
detection of ALD, further enabling the development of targeted
Andrew Fagan1, Sara McGeorge1, Patrick Gillevet2. 1Virginia
interventions. Without an idea of future value, and by extension the
Commonwealth University and Richmond VAMC; 2George Mason
likelihood of eventual reimbursement, producers and research
University
funders may have less incentive to focus on this opportunity. We,
Email: [email protected]
therefore, aimed to identify the relationship between required
efficacy and the cost of a potential new treatment for early ALD Background and aims: Alcohol use disorder (AUD) alters gut
needed to achieve uptake into clinical practice. microbiota and can lead to cirrhosis development. However,
Method: We simulated excessive drinkers with advanced fibrosis cirrhosis, regardless of etiology is also linked with microbial
over their lifetime using a mathematical computer model. Two change. Several AUD pts continue to drink despite the development
scenarios were applied: 1) no treatment (current standard) and 2) a of cirrhosis but the interaction between active alcohol misuse and
progression-halting treatment modelled on a possible novel treat- cirrhosis is unclear. Bacterial products such as short-chain fatty acids
ment in an ongoing trial. Model input data was in the no-treatment (SCFAs) can strengthen the intestinal barrier and promote abstinence
scenario sourced from the literature and a prospective Danish natural in a small FMT trial. Aim: Determine the impact of active alcohol
history study and the currently unknown treatment efficacy (reduced misuse on gut microbial structure and function in the background of
risk of progression)-and cost (USD) was simulated over a vast range of cirrhosis.
possible values. The simulation allowed the identification of pairs of Method: Outpts with cirrhosis diagnosed on biopsy, fibroscan or
treatment efficacies and costs resulting different ratios of incremental prior decompensation underwent stool collection while drinking
costs to incremental effectiveness (ICERs) compared to current habits (AUDIT-10), demographics, cirrhosis severity and medication
management (Figure). use were collected. Active drinkers were matched with non-drinkers
with respect to cirrhosis details and demographics. Non-drinkers had
to be abstinent for ≥6 mths before stool collection. Microbiota
structure was analyzed using 16SrRNA sequencing and predicted
function using PiCRUST between actively drinking and non-
drinking pts.

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 POSTER PRESENTATIONS
Results: We enrolled 451 patients with cirrhosis (MELD 10.3 ± 4.5, Age excluding patients with decompensation or competing aetiologies
58.8 ± 6.8, 80 actively drinking pts). They were matched 1:4 with at for liver disease. At baseline, we performed liver biopsies along with
least 320 non-drinkers (Fig A). Groups were similar on demographics, clinical investigations. During follow-up, we reviewed patients’
cirrhosis details and medications apart from AUDIT-10 and alcohol- electronic healthcare records for infections, liver-related events, all-
related etiology, which were higher in actively drinking patients. cause mortality, and alcohol intake.
Alcohol use: Actively drinking subjects had constant drinking habits Results: We included 462 patients with a mean age of 57 ± 10 years,
without binges. Abstinent pts had been abstinent for 15 ± 8 years 76% males, with fibrosis stage F0-1/F2/F3-4 = 259/107/96. During a
before enrollment. Microbiota composition: β-diversity was different median follow-up of 54 months (IQR 35–76), 133 patients (29%)
between groups (Fig B) but Shannon diversity was statistically similar. developed a total of 307 infections with a median of two infections
Prevotella, Enterobacter and Streptococcus spp were higher while each (range 1–3). Seventy-six % of infections were treated during
potentially beneficial taxa belonging to Eubacterium, Bifidobacterium, hospitalization, most frequently pneumonia (103/307, 34%) and
Blautia, Roseburia, Alistipes, and Lactobacillus were lower in active urinary tract infections (56/307, 18%). In approximately half of all
drinkers. Short-chain fatty acid producing taxa specifically propionate infections cultures were obtained, and the most common isolated
and butyrate were lower in active drinkers (Fig C). Microbiota bacterium was Escherichia coli. Liver stiffness measured by transient
predicted function: Propanoate metabolism-related enzymes, which elastography was a stronger predictor of infections than fibrosis stage,
are also associated with branched amino acid degradation were higher consequently excessive drinking during follow-up and transient
in patients who were drinking (3-hydroxyisobutyrylCoA hydrolase elastography were the only independent predictors of infections in
and methylmalonylCoA carboxytransferase). multivariable regression (hazard ratio (HR) 2.08; 95%CI 1.33–3.27,
and HR 1.87; 1.54–2.28). Eighty-seven patients (19%) developed a
liver-related event during follow-up and 60 of these patients had 147
infections in total. Patients who developed at least one infection had a
significantly increased risk of death (HR 3.36; 95%CI 2.12–5.33, p
<0.001), but not of developing a liver-related event (HR 1.35; 95% CI
0.84–2.15, p = 0.22). Infections increased the risk of death independ-
ent of baseline fibrosis stage and liver stiffness.

Conclusion: SCFA producing microbiota, especially butyrate and

propionate metabolism, were significantly lower in actively drinking
patients with cirrhosis compared to abstinent patients despite
matching for demographics, cirrhosis severity and medication use.
SCFAs could have a link with continued alcohol intake in this
advanced population.

THU024
Infections are common in patients with early alcohol-related liver
disease and increases the risk of death
Stine Johansen1,2, Simon Langkjær Sørensen1,2,
Ditlev Nytoft Rasmussen1,2, Mads Israelsen1,2,
Katrine Prier Lindvig1,2, Maria Kjærgaard1,2,
Johanne Kragh Hansen1,2, Camilla Dalby Hansen1,2, Conclusion: In patients with early alcohol-related liver disease,
Katrine Thorhauge1,2, Nikolaj Torp1,2, Peter Andersen1,2, infections are frequent and worsen prognosis. Risk of infections
Sönke Detlefsen2,3, Helene Bæk Juel4, Torben Hansen4, increases with liver disease severity and ongoing harmful use of alcohol.
Aleksander Krag1,2, Maja Thiele1,2. 1Odense University Hospital,
Department of Gastroenterology and Hepatology, Denmark; 2University THU025
of Southern Denmark, Department of Clinical Research, Denmark; Abstinence is associated with better outcome in patients with
3
Odense University Hospital, Department of Pathology, Denmark; hepatocellular carcinoma
4
University of Copenhagen, Novo Nordisk Foundation Center for Basic Adeline Donati1, Jean Henrion2, Maxime Regnier3,
Metabolic Research, Denmark Pierre Deltenre1,4,5, Astrid Marot1. 1CHU UCL Namur, Department of
Email: [email protected] Gastroenterology and Hepatology, Yvoir, Belgium; 2Hôpital de Jolimont,
Department of Gastroenterology and Hepatology, Haine St Paul,
Background and aims: Infections are frequent in patients with
Belgium; 3CHU UCL Namur, Department of biostatistics, Yvoir, Belgium;
alcohol-related liver cirrhosis and worsen prognosis. We hypothe- 4
Clinique St Luc Bouge, Department of Gastroenterology and Hepatology,
sized that this also applies in earlier stages of alcohol-related liver
Namur, Belgium; 5CUB Hopital Erasme Université Libre de Bruxelles,
disease (ALD). We therefore aimed to examine 1) the incidence of
Department of Gastroenterology, Hepatopancreatology and Digestive
infections in patients with early ALD, 2) risk factors associated with
Oncology, Bruxelles, Belgium
developing infections, and 3) the impact of infections on the risk of
Email: [email protected]
liver-related events and all-cause mortality.
Method: We performed a prospective cohort study of patients from Background and aims: Data suggest that patients with alcohol-
primary and secondary care with a history of excess alcohol intake, related hepatocellular carcinoma (HCC) have a reduced survival as

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POSTER PRESENTATIONS
compared to those with nonalcohol-related HCC. The role of regenerative cytokines (IL1b, IL6, IL8, IL10, IL22, and TNFa).
abstinence in this setting in unknown. We aimed to compare access Immunohistochemistry was used to identify cell proliferation
to treatment and prognosis of patients with alcohol-related HCC and (Ki67) and senescence ( p16) in liver biopsy sections (n = 29). HandE
nonalcohol-related HCC and to evaluate the impact of abstinence. stains were used to differentiate occasional from marked ballooning of
Method: All patients with HCC were retrospectively included in a hepatocytes. Digital image analysis was used to quantify staining and
single center during a 23-year period. Abstinence was defined as a nuclear morphology algorithm attributed stains to individual cell
discontinuation of alcohol consumption at least 3 months before HCC types.
diagnosis in patients with alcohol-related cirrhosis. Treatment by Results: p16+ hepatocytes were more frequent in sAH compared to
resection, ablation, and transplantation were considered curative. control tissue without steatohepatitis (p <0.05). Moreover, in sAH
Multivariate Fine and Gray proportional hazards models were used to tissue expression of p16 on hepatocytes strongly associated and co-
identify factors associated with 5-year overall mortality after localized with ballooned hepatocytes ( p = 0.005, Figure 1). In contrast,
adjustment for the lead-time bias. A logistic regression model was no correlations were seen in cholangiocyte p16 expression nor with
used to identify factors associated with access to curative treatment. Ki67 expression in any cell type. Components of a secretory
Results: 200 patients were included, 114 (57%) with nonalcohol- phenotype consistent with the SASP (serum IL1, IL6, IL8, TNFa, HGF,
related HCC and 86 (43%) with alcohol-related HCC of whom 35 were EGF, TWEAK) were associated with hepatocyte ballooning ( p <0.05 for
abstainers and 51 were consumers. All of them had a cirrhosis. During all). Serum bilirubin was higher in patients with marked ballooning
a median follow-up of 14 months (95%CI: 11–16), 12 patients were ( p = 0.0003) but prothrombin time was not ( p = 0.24). Strikingly, HGF
transplanted and 156 died. At HCC diagnosis, consumers were levels were >7-fold higher in sAH vs HC and CLD ( p <0.001) and
younger as compared to abstainers and non-alcoholic patients (59 correlated with both baseline MELD (r = 0.21, p <0.001) and Lille score
vs. 63 vs. 68 years, p = 0.001), had a worse liver function (MELD score: (r = 0.16, p <0.001). Conversely, EGF was lower in sAH vs HC vs CLD ( p
11 vs. 10 vs. 8, p = 0.01, Child-Pugh score: 6 vs. 5 vs. 5, p = 0.02), were <0.001) and in sAH patients who died within 28 ( p = 0.01) and 90 days
less likely to be screened for HCC (33% vs. 74% vs. 51%, p < 0.001) and ( p = 0.003) compared to sAH patients who survived.
had more frequently a metastatic disease (16% vs. 0% vs 6%, p = 0.02).
After adjustment for the lead-time bias, the 5-year cumulative
incidence rates of overall death were significantly lower in abstainers
than in consumers and in non-alcoholic patients (51.5% vs. 78.4% vs.
80.5%, respectively, p = 0.04). In multivariate analyses, while abstai-
ners were significantly associated with lower overall mortality as
compared to consumers (HR: 0.47, 95% CI 0.28–0.80, p = 0.005),
patients with nonalcohol-related cirrhosis and consumers had
similar overall mortality (HR: 0.86, 95% CI 0.60–1.24, p = 0.4). The
proportion of patients who received a curative treatment was 65% in
abstainers, 44% in consumers and 57% in non-alcoholic patients ( p =
0.1). In multivariate analyses, preserved liver function (Child Avs. B/C, Figure: A. representative immunohistochemistry of two ballooned (black
arrows) p16+ (red) hepatocytes. B: Comparison of hepatocyte p16 expres-
OR: 3.10 95% CI 1.58–6.26, p = 0.001) and adherence to a screening
sion in sAH liver biopsy samples with marked vs occasional hepatocyte
program (OR: 4.96, 95% CI 2.50–10.15, p < 0.001) were the only two
ballooning
factors associated with a better accessibility to curative treatment.
Conclusion: Abstinence improves the outcome of patients with Conclusion: Serum proteins implicated in hepatocyte regeneration
alcohol-related HCC because of better liver function, less advanced and senescence are associated with clinical outcome in sAH. p16+
tumour disease and better adherence to screening. hepatocytes are prevalent and are strongly associated with hepato-
cyte ballooning in sAH liver biopsies. Further characterization of the
THU026 senescent properties of p16+ cells may stimulate senolytic or SASP-
In severe alcohol-related hepatitis, hepatocyte ballooning modulating therapies in sAH.
correlates with expression of p16 and components of a secretory
phenotype that has been associated with cellular senescence THU027
Nikhil Vergis1, Isabelle Hall1, Callum Arthurs1, Hiromi Kudo1, Targeting cyclin M4 as a new therapeutical approach to treat
Stephen Atkinson1, David Shapiro2, Michael Lutz2, Birgit Jung2, alcoholic liver disease
Markus Weissbach2, Wolfgang Albrecht2, Luke D. Tyson1, Tong Liu1, Irene González-Recio1, Naroa Goikoetxea1, Rubén Rodríguez Agudo1,
Emma Lord1, Lars Zender3, Mark Thursz1, Robert D. Goldin1. 1Imperial Jorge Simón Espinosa1, Marina Serrano-Macia1, Mikel Azkargorta2,
College, United Kingdom; 2HepaRegeniX GmbH, Tuebingen, Germany; Felix Elortza2, Irene Diaz-Moreno3, Antonio Diaz-Quintana3,
3
University Hospital Tübingen, Klinik für Medizinische Onkologie and Ute Schaeper4, Ramon Bataller5, Matías A Avila6,
Pneumologie, Germany Luis Alfonso Martinez-Cruz1, María Luz Martínez-Chantar1. 1CIC
Email: [email protected] bioGUNE, Liver Disease Lab, Derio, Spain; 2CIC bioGUNE, Proteomics
platform, Derio, Spain; 3Instituto de Investigaciones Químicas (IIQ),
Background and aims: Poor outcome in severe alcohol-related
Sevilla, Spain; 4Silence Therapeutics GmbH, Berlin, Germany; 5University
hepatitis (sAH) is frequently attributed to failure of hepatic
of Pittsburgh, Department of medicine, Pittsburgh, United States; 6CIMA,
regeneration. This may be due to lack of trophic factors, inability of
Hepatology program
hepatocytes to proliferate and/or the induction of stable cell cycle
Email: [email protected]
arrest known as senescence. Senescent cells undergo morphological
changes that may be consistent with the hepatocyte ballooning found Background and aims: An excessive alcohol consumption is a main
in steatohepatitis. Here, we investigate the potential causes of reason of chronic liver disease and liver-related deaths in Western
regenerative failure in sAH and seek evidence for markers of countries and causes alcoholic liver disease (ALD), featured by fatty
senescence in ballooned hepatocytes. liver, alcoholic hepatitis (AH), cirrhosis and liver cancer.
Method: Data was available from 731 AH patients with sAH recruited Approximately 50% of liver cirrhosis cases caused by alcohol abuse,
to the STOPAH trial, 37 compensated cirrhotic patients (CLD) and 64 result in 3.3 million deaths. Today, there are no effective treatments
healthy controls (HC). We evaluated serum levels of the senescence other than abstinence or liver transplantation for end-stage ALD.
associated secretory phenotype (SASP) for a range of trophic factors Acute and chronic alcohol consumption are associated with a
(HGF, EGF, IGF, VEGF, TWEAK) plus inflammatory and/or pro- decrease in liver Mg2+ content. The underlying mechanisms remain

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 POSTER PRESENTATIONS
unknown. The alteration of Mg2+ levels in ALD and the key role of Mg2+ (PIMT), was significantly overexpressed in the absence of CNNM4.
transporters in enabling the flux of Mg2+ across cell membranes, have Further experiments will investigate whether Mg2+ homeostasis
prompted us to investigate the role of cyclin M4 in ALD. In this context, mediated by silencing of CNNM4 modulates PIMT activity, which has
the inhibition of CNNM4 by RNA interference emerge as a new been shown to be impaired during excessive ethanol consumption.
therapeutic approach for ALD. Conclusion: CNNM4 magnesium transport appears to be dysregu-
Method: The expression of CNNM4 was studied in ALD patients, in lated in patients with AH and in NIAAA model. Targeting Cnnm4 with
primary hepatocytes under ethanol exposure and in mice under GalNAc siRNA has emerged as a novel therapeutic approach for ALD
chronic and binge ethanol feeding (the NIAAA model). Primary that ameliorates AH in the NIAAA model. Further experiments will
hepatocytes were treated with a GalNAc siRNA targeting Cnnm4 to address the role of CNNM4 in the protein repair machinery mediated
evaluate the effect of silencing Cnnm4 in hepatocytes exposed to by PIMT activity.
50 mM EtOH for 12 h, 24 h and 36 h. NIAAA model mice were divided
into 2 groups after day 5 of the diet and treated with a control THU028
molecule or GalNAc siRNA that specifically silences Cnnm4 in Hepatic transcriptional signature of alcohol on genes involved in
hepatocytes. canonical retinoid metabolism
Results: The expression of Cnnm4 was upregulated in the liver of Marta Melis1, Xia-Han Tang1, Nabeel Attarwala1, Qiuying Chen1,
patients with ALD and correlated with the stages of the disease: early Carlos Prishker1, Lihui Qin2, Steve Gross1, Lorraine Gudas1,
AH, non-severe AH, severe AH, compensated HCV-related cirrhosis, Steven Trasino1,3. 1Weill Cornell Medical College, Pharmacology,
AH explants and cirrhosis hepatitis C virus. Hepatic CNNM4 levels New York, United States; 2Weill Cornell Medical College, Pathology and
were overexpressed in the NIAAA model. Silencing Cnnm4 exhibited a Laboratory Medicine; 3Hunter College, CUNY, Urban Public Health and
reduction in transaminases. Importantly, the absence of cnnm4 Nutrition, New York, United States
resulted in a significant decrease in mitochondrial ROS and ER stress Email: [email protected]
in hepatocytes. High-throughput proteomic analysis performed in
Background and aims: A large body of data show that alcohol abuse
liver tissue from NIAAA models revealed a significant representation
leads to reductions to hepatic vitamin A (retinoids) levels beginning
of the following processes in the absence of CNNM4; oxidation-
in early stages of chronic alcohol abuse (<2–3 weeks), which is
reduction, lipid metabolism, cellular response to oxidative stress,
associated with progression of liver damage, and early stages of
endoplasmic reticulum stress or protein folding families. The
alcohol liver disease (ALD). However, to date, there remains little
machinery for repairing damaged proteins, represented by the
understanding of the genes involved in alcohol-driven hepatic
enzyme protein-L-isoaspartate (D-aspartate) O-methyltransferase
retinoids depletions during early stages of ALD.

Figure 1: (abstract: THU028)

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POSTER PRESENTATIONS
Method: Using a 3-week murine model of chronic alcohol intake and Results: In total, 105 eligible AH admissions were identified. Overall,
RNA sequencing technology, we determined the hepatic transcrip- 90 day mortality was 18% (19/105). AH admission rate for the COVID
tional signature of alcohol on genes involved in canonical retinoid cohort was significantly higher at 3.38 cases/month (n = 44)
metabolism. compared to the historical cohort at 1.22 cases/month (n = 61),
Results: Our results show that 3 weeks of alcohol intake led to p <0.001. The COVID cohort had greater disease severity with a higher
increases in serum retinol levels, but reductions to hepatic retinoids Glasgow Alcoholic Hepatitis Score during admission [8.5 (IQR 7–10)
(retinol, and retinyl-esters), and concomitant increases in plasma AST, vs 7 (IQR 6–9), p = 0.04]. The AH COVID cohort trended towards a
ALT, and macro and microvesicular steatosis. By RNA sequencing greater proportion requiring ICU admission, inotropic support and
technology, we found that 3 weeks of chronic alcohol intake led to longer ICU length of stay. Whilst per-episode adjusted healthcare
modulation of 68 transcripts involved in canonical retinoid metab- costs were similar across the study, monthly costs of the COVID cohort
olism. These transcripts include the genes Ces1d, Ces1g, Rbp1, LRAT, were higher compared to the historical cohort due to increased
Rdh10, Aldh1a1, Cyp26a1. Interestingly, among the 2679 significant admission frequencies [mean (SD) $137, 549 (54, 058) vs $38, 000 (27,
differentially expressed genes (DEGs) in livers of alcohol-fed mice, 448), p = 0.02 (Figure 1)]. No patients in this study were diagnosed
Cyp26a1, the major retinoic acid catabolizing enzyme was the 6th top with COVID-19.
significantly upregulated DEG. We also detected broad hepatic
increases in transcripts of families of Cyp1a, Cyp2a-c, Cyp3a-c
xenobiotic enzymes, capable of retinoid catabolism. Using western
blotting we confirmed that compared to untreated mice, hepatic
protein expression of the retinyl-ester hydrolases CES1D, CES1G, and
a rate-limiting enzyme in retinoic acid synthesis, ALDH1A1, were
significantly increased in livers of alcohol-fed mice. However, protein
levels of RBP1, which is critical to hepatic retinol transport and
homeostasis, was markedly decreased in livers of alcohol-fed mice.
Moreoever, we detected specific reductions to RBP1 in hepatic stellate
cells (HSC) and portal hepatocytes.
Conclusion: These data show for the first time that reductions to
hepatic retinoid in early stages of ALD may be due to pleiotropic effects,
involving impaired retinoid transport and metabolism in portal Figure 1: Alcoholic Hepatitis Healthcare Costs
hepatocyte and HSCs, but also concurrent increases in hepatic
Conclusion: In this study, alcoholic hepatitis admission frequency
retinyl-ester hydrolysis, and oxidative metabolism of retinol to
and healthcare costs were found to have increased since the
retinoic acid, and CYP-mediated retinoid catabolism. Given that
COVID-19 pandemic. These observations provide the impetus for
Cyp26a1 was the 6th top DEG in alcohol-fed mice, our data also
future studies to understand how the COVID-19 pandemic has led to
strongly suggest that retinoid metabolism is among the key micronu-
increased AH presentations and develop preventative strategies that
trient pathways negatively impacted in early stages of ALD. These data
reduce alcohol related admissions and associated costs.
may help develop future therapies aimed at mitigateting hepatic
retinoid losses in individuals that struggle with alcohol cessation.
THU030
THU029 The role of integrated alcohol liver care in the management of
COVID-19 pandemic impact on alcoholic hepatitis healthcare patients with alcohol related liver disease in an acute hospital
setting
utilisation
Khin Han1, Phyo Wah Wah1, Ian Webzell1, Joshua Stapleton2,
Leya Nedumannil1, Sukhdeep Steven Cheema1, Karl Vaz1, Ronald Ma2,
Daryl Jones3, Stephen Warrillow3, Josephine Grace1,4, Darren Wong1, Huyen Adams1, Abid Suddle1, Michael Heneghan1, Nicola Kalk2,
Matthew Choy1,4. 1Austin Hospital, Gastroenterology, Heidelberg, Naina Shah1. 1Kings College Hospital, Hepatology, London, United
Australia; 2Austin Hospital, Clinical Costings, Heidelberg, Australia; Kingdom; 2South London and Maudsley, Psychological Medicine,
3
Austin Hospital, Intensive Care, Heidelberg, Australia; 4University of London, United Kingdom
Email: [email protected]
Melbourne, Department of Medicine, Austin Academic Centre,
Heidelberg, Australia Background and aims: Acute on Chronic Liver failure (ACLF)/Acute
Email: [email protected] decompensation (AD) following Alcohol use disorder (AUD) is a
Background and aims: Alcoholic hepatitis (AH) is associated with common presentation to the Hospital. The office of national statistics
significant morbidity, mortality and healthcare expenditure. The in the UK reported 7, 423 deaths in 2020. 80% of these were attributed
to Alcohol related Liver Disease. Alcohol related admissions and
global SARS-CoV-2 (COVID-19) pandemic and related lockdown
measures have potentially contributed to an increase in alcohol deaths costs the National health service (NHS) over 3.5 billion/year.
As a part of the NHS long term plan, Alcohol care team comprising of
misuse. This study examines frequency and patient outcomes of AH
admissions to an Australian quaternary liver transplant referral Consultants: Hepatologist, Addiction Psychiatrist and clinical nurse
centre. We aimed to ascertain the change in AH severity, ICU specialists was established at Kings College Hospital in 2018, to
manage AUD and prevent recurrent Hospital presentation. Integrated
admission rates and healthcare utilisation costs over the last 5 years
to identify temporal associations with the COVID-19 pandemic. outpatient treatment providing medical treatment and alcohol
interventions has been previously shown to improve abstinence in
Method: A retrospective analysis of patients aged 18 years and older
fulfilling National Institute on Alcohol Abuse and Alcoholism medically ill patients. Explore the utility of an integrated Alcohol
diagnostic criteria for AH between January 2016 and March 2021 Liver clinic led by Consultants: Hepatologist and Addiction
Psychiatrist in facilitating abstinence in patients with ArLD.
was conducted. Data were collected from electronic medical records
and analysed. Primary end points were the frequency of AH Method: 159 patients with Alcohol related cirrhosis were reviewed in
admissions, ICU admission rates and healthcare costs, which were the clinic, male: n = 95 with a median age of 58 (36 ± 83), female, n =
evaluated with a divergence at the beginning of lockdown restric- 64 with a median age of 54 (32 ± 77). 29/159 presented with ACLF.
tions (March 2020-March 2021 “COVID cohort”) versus the “historical Results: Abstinence led to a Liver recovery in patients with ACLF
(table 1). 61/159 (38%) presented to the Hospital with decompensa-
cohort” (January 2016-February 2020).
tion. 51/61 (83%) recompensated following abstinence. Unfortunately
18/159 patients who died had AUD prior to presentation. The overall

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 POSTER PRESENTATIONS
abstinence rate was 104/159 (65%) (table 1). Number of patients to mass spectrometry in patients with SAH participating in the
achieving abstinence has increased following the implementation of STOPAH trial (n = 159), with cirrhosis (n = 81-including compensated
integrated care service as shown in figure 1. and decompensated cirrhosis) and healthy controls (HC, n = 35).
Serum lipidome changes between SAH and cirrhosis were evaluated
Table 1: Alcohol use disorder in patients with Alcohol related Liver in a derivation set (n = 160) and a validation set (n = 80) by principal
disease component analysis (PCA) and orthogonal partial least squares
Harm discriminant analysis (OPLS-DA).
Abstinent Drinking reduction Results: Patients with SAH and cirrhosis had a similar age (51 vs. 51-
ACLF grade 1 (n = 7) 5 2 0 year-old, p = 0.9) but different MELD scores (21.8 vs. 15.3, p < 0.0001).
ACLF grade 2 (n = 15) 6 5 4 According to Lille score, 44.8% of SAH patients were responders to
ACLF grade 3 (n-7) 6 1 0 medical treatment with a 29.1% 90-day survival. The derivation and
Decompensated ArLD (n = 61) 51 6 4 validation sets were well matched for clinical and biological variables.
recompensated (n = 51) 83% In the derivation cohort, PCA accurately discriminated between
Cirrhosis compensated (n = 69) 36 18 15 patients with SAH, cirrhosis and HC. In OPLS-DA both ionisation
mortality (n = 22) 4 18 0 modes accurately discriminated SAH vs. cirrhosis (in positive mode:
R2Y = 0.55 Q2 = 0.49 CV-ANOVA p < 0.0001 AUROC = 0.92; in negative
mode: R2Y = 0.54 Q2 = 0.36 p < 0.0001 AUROC = 0.96). The 20 meta-
bolites showing the greatest variable importance projection in
positive and negative mode were included in multivariate analysis
adjusting for age, sex and MELD score. Three lipids in positive mode
(PC 34:2, PC 36:3 and PE 39:2) and five in negative mode (PC-0-19:0,
PS 41:4, PG 41:0, LPC 16:0, ST 21:4;O2) disclosed independent
associations with SAH. Using these lipids, we derived 2 scores relating
to positive and negative ionisation modes; both accurately discrimi-
nated SAH from cirrhosis with an AUROC of 0.90 and 0.86 in the
derivation set and 0.89 and 0.92 in the validation sets, respectively.
Conclusion: Untargeted lipidomic profiling by MS indicates a
lipidomic signature-mainly composed by glycerophospholipids
Figure 1: Number of patients achieving abstinence species-in patients with SAH distinct from cirrhosis. Since these
lipids are involved liver repair, some immune-modulatory functions
Regular Liver health education, motivational intervention including
and are associated with organ failure in sepsis they urgently require
engagement with the community and Hospital Addictions team has
further exploration in the SAH setting.
helped patients maintain abstinence. Sustained sobriety led to Liver
recovery and prevention of Hospital presentation with complications THU032
related to portal hypertension/ACLF. This has led to a reduction in Toll-like receptor 2 activation in monocytes of alcohol use
monthly readmission rate to 6–8%. In addition to being cost-effective, disorder patients contributes to systemic inflammation and
it has improved the long term prognosis of patients with ArLD. alcohol-associated liver disease
Conclusion: Sustained abstinence leads to Liver recovery, reduced Luca Maccioni1, Joyce Kasavuli1, Sophie Leclercq2,3, Boris Pirlot1,
Hospital presentation and readmission. Facilitating abstinence is vital Géraldine Laloux4, Yves Horsmans5, Isabelle Leclercq1,
in improving the long term prognosis in patients presenting with Bernd Schnabl6,7, Peter Stärkel1,5. 1UCLouvain, Université Catholique de
ArLD. Integrated care approach should be considered as a standard of Louvain, Institute of Experimental and Clinical Research, Laboratory of
care in managing AUD. Hepato-gastroenterology, Brussels, Belgium; 2UCLouvain, Université
There is an unmet clinical need in exploring pharmacological and Catholique de Louvain, Louvain Drug Research Institute, Metabolism and
psycho-social intervention tailored towards treating AUD in patients Nutrition Research Group, Brussels, Belgium; 3UCLouvain, Université
with ArLD thus preventing the development of ACLF/AD. Catholique de Louvain, Institute of Neuroscience, Brussels, Belgium;
4
UCLouvain, Université Catholique de Louvain, de Duve Institute,
THU031
Brussels, Belgium; 5Cliniques Universitaires Saint-Luc, Department of
Untargeted lipidomics unveils a specific plasma signature of
Hepato-gastroenterology, Brussels, Belgium; 6University of California
severe alcoholic hepatitis
San Diego, Department of Medicine, La Jolla, United States; 7University of
Florent Artru1,2, Stephen Atkinson2, Francesca Trovato1, California San Diego, Department of Medicine, VA San Diego Healthcare
Nikhil Vergis2, Vishal C Patel3,4,5, Salma Mujib1, Anna Cavazza1,
System, San Diego, United States
Alexandros Pechlivanis2, Ellen Jerome1, Marc Zentar1, Email: [email protected]
Evangelos Triantafyllou2, Elaine Holmes2, Mark J W McPhail1,2,
Mark Thursz2. 1Institute of Liver Studies, King’s College London, London, Background and aims: A minority of alcohol use disorder (AUD)
United Kingdom; 2Imperial College London, London, United Kingdom; patients develops progressive alcohol-associated liver disease (ALD)
3
The Roger Williams Foundation for Liver Research, Institute of potentially linked to gut barrier dysfunction, microbial translocation
Hepatology, London, United Kingdom; 4King’s College Hospital, Institute and activation of systemic immune responses. Activation of circulat-
of Liver Studies, London, United Kingdom; 5King’s College London, School ing monocytes by microbial products might contribute to systemic
of Immunology and Microbial Sciences, London, United Kingdom and liver inflammation leading to ALD progression. Human data
Email: [email protected] linking monocytes to early stages of ALD are lacking. We explored the
links between changes in monocytes, microbial translocation,
Background and aims: Severe alcoholic hepatitis (SAH) is associated
systemic inflammation and monocyte-derived macrophages in
with systemic inflammation and immune dysfunction. Lipids are early human ALD.
involved in inflammatory and immune responses; however, lipido- Method: We included n = 123 AUD patients following a highly-
mics is understudied in the setting of SAH. We evaluated whether standardized rehabilitation program and n = 26 healthy controls. We
specific changes in the blood lipidome are observed in patients with determined the total number of monocytes and proportion of
SAH.
monocytes subsets by FACS. Serum microbial translocation markers
Method: Untargeted serum lipidomics was performed using and cytokines were measured by ELISA and multiplex assay,
reversed phase ultra-performance liquid chromatography coupled

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POSTER PRESENTATIONS
respectively. Cytokines reflecting activation of monocytes were clinical studies and to diagnose AH in clinical practice. The objectives
assessed by qPCR. Toll-like receptor (TLR) expression in monocytes of this study were to assess the sensitivity and specificity and to
and activation as well as phagocytosis were assessed in vitro. ALD improve the diagnostic accuracy of NIAAA clinical criteria for AH.
severity and liver inflammatory responses were analyzed in liver Method: 268 consecutive patients with Alcohol-related liver disease
biopsies by histology, qPCR, immunohistochemistry and ELISA. (ArLD) that underwent liver biopsy were prospectively included: 210
Results: In AUD patients, the number of blood monocytes increased and 58 in the derivation and validation cohorts. NIAAA criteria and
( p < 0.0001). Among the 3 monocyte subpopulations, intermediate histological diagnosis of AH were independently reviewed by clinical
and non-classical increased while classical monocytes decreased investigators and pathologists from Hospital Clínic and Mayo Clinic.
compared to controls. Monocytes from AUD patients up-regulated Using liver biopsy as gold standard we determined specificity,
IL1β and IL8 together with TLR2, down-stream AP-1 and inflamma- sensitivity and accuracy of the NIAAA clinical criteria. To improve
some NLRP3. IL1β and IL8 were actively secreted by those monocytes the diagnostic accuracy of NIAAA criteria the threshold of quantitative
upon stimulation in vitro with the TLR2 ligand Peptidoglycan. variables was optimized and combinations with categorical variables
Stimulation with E. coli confirmed preserved bacterial phagocytic were tested. Factors associated with 1-year transplant-free survival
activity. Systemic levels of cytokines and alterations in monocytes were evaluated.
correlated with microbial translocation markers. Results: In the study cohort, NIAAA criteria showed a sensitivity of
In parallel, IL1β and IL8 were increased in ALD livers together with 63% (95% CI, 52–73) a specificity of 78% (95% CI, 69–84) and an
activation of intrahepatic macrophages (CD163+, iNOS+, TREM1+). accuracy of 72% (95% CI, 65–78). A significant percentage (37%) of
Liver chemokines (MCP1, CX3CL1) involved in monocytes attraction patients with histological-proven AH did not meet NIAAA criteria.
were induced in liver tissue. IL1β and IL8 correlated with liver These patients had higher MELD score values, higher frequency of
chemokines, iNOS+ up-regulation in macrophages and ALD severity cirrhosis decompensation, higher inflammation in terms of C-
markers (e.g. fibrosis, AST/ALT, CK18-M65 and M30). reactive protein (CRP) levels and lower 1-yr survival compared to
subjects without histological AH (63% vs 91%, p = 0.000). A new
version of the NIAAA criteria, NIAAAs-CRP criteria, was generated by
simplifying the current NIAAA criteria and adding a new parameter as
follows: bilirubin ≥2.5 mg/dl instead of ≥ 3 mg/dl; AST ≥ 50 UI/L and
AST>ALT, instead of AST ≥ 50 UI/L, AST/ALT ratio ≥ 1.5 mg/dl and AST
<400 UI/L; active alcohol consumption or alcohol abstinence less than
120 days instead of 60 days before the inclusion; not considering the
presence of confounding factors and adding C reactive protein ≥
1 mg/dl. These modified criteria showed a good combination of
sensitivity, specificity and accuracy among all the combinations
tested (70%, 83%, 78%, respectively). Factors associated with survival
in the study cohort were histological AH, decompensated cirrhosis,
MELD score and NIAAAs-PCR criteria, but not NIAAA original criteria.
Similar findings were observed in the validation cohort where NIAAA
original criteria showed 52% sensitivity, 82% specificity and 69%
accuracy, while NIAAAs-PCR showed 56% sensitivity, 91% specificity
and 76% accuracy for the clinical diagnosis of AH.
Conclusion: Our results point to a contribution of activated
monocytes to systemic and liver inflammation. Monocytes likely
infiltrate the liver, transform into monocyte-derived macrophages
and release IL1β and IL8 in response to Peptidoglycan and TLR2
activation, ultimately leading to ALD progression.

THU033
Improving NIAAA criteria for the diagnosis of alcoholic hepatitis,
role of systemic inflammation
Elisa Pose1,2,3, Emma Avitabile4, Alba Díaz5, Carla Montironi6,
Martina Perez1,7, Jordi Gratacós-Gines1,7, Helena Hernandéz Evole1,7,
Tejasav Sehrawat8, Harmeet Malhi8, Pol Olivas7,9,
Virginia Hernandez-Gea1,3,7, Vijay Shah8, Patrick S. Kamath8,
Pere Ginès1,3,7,10. 1Hospital Clínic of Barcelona, Liver Unit, Barcelona,
Spain; 2Institut d’Investigacions Biomed ̀ iques August Pi i Sunyer
(IDIBAPS), Chronic liver disease, Barcelona; 3Centro de Investigación
Biomédica en Red, Chronic liver disease, Madrid, Spain; 4Institut
d’Investigacions Biomed ̀ iques August Pi i Sunyer (IDIBAPS), CIF:
Q5856414G, Chronic liver disease, Barcelona, Spain; 5Hospital Clínic of
Barcelona, Pathological Department, Barcelona, Spain; 6Hospital Clínic
of Barcelona, Pathology Department and Molecular Biology CORE,
Barcelona, Spain; 7Institut d’Investigacions Biomed ̀ iques August Pi i
Sunyer (IDIBAPS), Chronic liver disease, Barcelona, Spain; 8Mayo Clinic,
Division of Gastroenterology and Hepatology, Rochester, United States;
9
Hospital Clínic of Barcelona, Psychiatry, Barcelona, Spain; 10University
of Barcelona, Barcelona, Spain
Email: [email protected]
Background and aims: The National Institute of Alcohol Abuse and
Alcoholism (NIAAA) clinical criteria for the diagnosis of probable
alcoholic hepatitis (AH) are commonly used to select subjects for

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 POSTER PRESENTATIONS
Conclusion: A modified version of NIAAA criteria, NIAAAs-CRP Universitaria Colombia; 48Hospital San Vicente Fundación Rionegro;
criteria, with higher sensitivity, specificity and accuracy, improves 49
Fundación Cardioinfantil; 50Hospital San Vicente Fundación Medellín;
non-invasive diagnosis of AH in patients with ArLD and adds 51
Hospital Pablo Tobon Uribe. Univ. De Antioquia; 52Hospital
prognostic value to NIAAA criteria. Universitario Fundación Santa Fe de Bogotá; 53Hospital Clínico
Quirúrgico Carlos Font; 54Instituto Nacional de Gastroenterología;
THU034 55
Pontificia Universidad Católica de Ecuador; 56Hospital Carlos Andrade
Alcohol associated hepatitis in Latin America: results from the Marín; 57Hospital Eugenio Espejo; 58Hospital General San Juan de Dios;
AH-LATIN study 59
Hospital Roosevelt; 60Hospital Roosevelt; 61Hospital Escuela;
Jorge Arnold1, Luis Antonio Diaz1, Francisco Idalsoaga1, 62
Hospital Juárez de México; 63Hospital Juarez de Mexico; 64ISSSTE;
Gustavo Ayares1, Eduardo Fuentes2, Carolina Ramirez3, 65
Centro de Investigación en Enfermedades Hepáticas y
María Paz Medel4, Catterina Ferreccio5, Mariana Lazo6, Gastroenterología; 66Hospital Angeles Torreón; 67Hospital Dublan;
Juan Pablo Roblero7, Mayur Brahmania8, Rodolfo Carbonetti9, 68
Hospital General 450, Secretaría de Salud de Durango; 69Hospital Civil
Sebastián Marciano10, Manuel Mendizabal11, Fernando Bessone12, de Guadalajara; 70Private Clinic; 71Hospital Nacional Hipolito Unanue;
Gustavo Romero13, Ana Palazzo14, Estela Florencia Manero15, 72
HBCASE; 73Hospital Goyoneche Arequipa; 74Hospital Regional Honorio
Melisa Dirchwolf16, Diego Piombino17, María Ayala Valverde18, Delgado; 75Hospital de Emergencias de Villa el Salvador; 76Hospital
Fernando Cairo19, Maria Alejandra Gracia Villamil20, Edgardo Rebagliati Martins; 77Guillermo Almenara Hospital; 78JRA
Maria Mercedes Rodriguez Gazari21,21, Patricia Gallardo22, Gastroenterology; 79Hospital Nacional Daniel Alcides Carrión-Callao;
Geraldine Ramos23,23, Patricia Guerra24, Fabio Silveira25, 80
University of Pittsburgh; 81Service des maladies de l’appareil digestif;
Roberta Chaves26, Giovanni Silva27, Cirley Lobato28, Jozelda Lemos29, 82
Mayo Clinic; 83University of South Dakota; 84Pontificia Universidad
Rogério Alves30, Gustavo Pereira31, Católica de Chile, Gastroenterologia
Rita de Cássia Martins Alves da Silva32, Email: [email protected]
Liliana Sampaio Costa Mendes33, Cláudia Alves Couto34,
Background and aims: Severe alcohol-associated hepatitis (HA) has
Cristina Melo Rocha35, Raul Lazarte36, Pamela Yaquich37,
a high morbidity and mortality, however, the information in Latin
Blanca Norero38, Camila Jure39, Alejandra Dominguez40,
America is limited. We aimed to characterize patients hospitalized for
Marta Mac Vicar41, Violeta Rivas42, Juan Pablo Arancibia43,
AH in a multinational cohort in Latin America.
Armando Sierralta44, Jose Valera45, Sebastian Diaz46,
Method: Multicenter prospective cohort study. We included patients
Carlos Sanchez47, Luis Toro48, Adrian Varon49, Elizabeth Correa50,
admitted with severe AH between 2015–2021. Sociodemographic
Juan Carlos Restrepo51, Monica Tapias52, Ricardo Aguilera Rosales53,
and clinical information was recorded. The analysis included survival
Mirtha Infante54, Galo Pazmiño55, Xiimena Armijos56,
analysis using Kaplan-Meier curves. This study was approved by the
Enrique Carrera57, Regina Ligoria58, Gerson Avila59, Abel Sanchez60,
institutional ethics committee.
Marco Sánchez61, Scherezada Mejia62, Jacqueline Cordova63,
Results: 319 patients from 24 centers (8 countries: Argentina, Bolivia,
Maria De Fatima Higuera de La Tijera64, Raul Contreras65,
Brazil, Chile, Colombia, Ecuador, Mexico, Peru) were included. Age
Francisco Solis66, Jesus Varela67, Janett Jacobo68,
49.9 ± 10.3 years, 84.6% men and 54.1% had a previous diagnosis of
Jose Antonio Velarde-Ruiz Velasco69, Julissa Lombardo Quezada70,
cirrhosis. Median MELD at admission 27 [21–32] points. 25.6% met
Esther Veramendi71, Victor Vela72, Claudia Pamo73, Donny Puma74,
SIRS criteria and 47.6% had acute renal failure on admission. 36.11%
Julio Marcelo75, Laura Tenorio76, Maria Cabrera77, Jose Rivera78,
were treated with corticosteroids. Survival at 30 days was 77.6% (95%
Pedro Montes79, Ramon Bataller80, Alexandre Louvet81, Vijay Shah82,
CI: 69.7–83.7%) and at 90 days 71.6% (95% CI: 62.5–78.9%). 39.6%
Patrick S. Kamath82, Ashwani Singal83, Marco Arrese5,
presented infections. The most frequent locations were urinary
Juan Pablo Arab84. 1Pontificia Universidad Católica de Chile,
(34.1%), respiratory (30.7%), spontaneous bacterial peritonitis (17.1%)
Gastroenterologia, Chile; 2Pontificia Universidad Católica de Chile,
and skin (11.4%). The most frequent pathogens were Escherichia coli
Ciencias de la Salud, Chile; 3Clinica Las Condes, Anestesiología, Chile;
4 (55.6%), Klebsiella pneumoniae (11.1%) and Enterococcus (7.4%). In
Pontificia Universidad Católica de Chile, Medicina Familiar, Chile;
5 the long term, only 2.9% of patients have been transplanted.
Pontificia Universidad Católica de Chile; 6Johns Hopkins University
Conclusion: This multicenter study shows high morbidity and
School of Medicine, Chile; 7Hospital Clínico Universidad de Chile,
mortality in patients with severe HA, which is comparable to other
Gastroenterologia, Chile; 8Western University, London Health Sciences
centers in the world.
Center, Gastroenterology; 9Hospital de Clínicas D. N. Avellaneda;
10
Hospital Italiano Buenos Aires; 11Hospital Universitario Austral; THU035
12
Hospital Provincial del Centenario; 13Hospital de Gastroenterología Dr. Prophylaxis of withdrawal syndrome decreases mortality in
Carlos Bonorino Udaondo; 14Hospital Padilla. Tucuman; 15Hospital Pablo patients with alcohol-associated hepatitis
Soria; 16Hospital Privado de Rosario; 17Hospital de Emergencia Clemente
David Marti-Aguado1, Concepción Gómez1, Amir Gougol2,
Alvarez; 18Hospital el Pino, Medicina Interna, Chile; 19Hospital el Cruce,
Dalia Morales Arraez3, Alejandro Jiménez Sosa3, Anjara Hernandez3,
Argentina; 20Centro Medico Talar y Grupo Medico Santa Clara;
21 Claudia Pujol4, Edilmar Alvarado-Tapias4, Ares Villagrasa5,
Hospital Británico, Argentina; 22Fundación Sayani; 23Instituto de
Meritxell Ventura Cots5, Ana Clemente2, Abo Zed Abdelrhman2,
Gastroenterología Boliviano Japonés; 24Instituto de Gastroenterología
Keith Burns2, Aditi Bawa2, Haritha Gandicheruvu, 2,
Boliviano-Japonés; 25Hospital do Rocio; 26Hospital das Clínicas da
Vikrant Rachakonda2, Ramon Bataller2. 1Clinic University Hospital,
Faculdade de Medicina de Ribeirão Preto-USP; 27Universidade Estadual
Department of Gastroenterology and Hepatology, Valencia, Spain;
Paulista (UNESP)-Botucatu/São Paulo; 28FUNDHACRE-, Serviço de 2
University of Pittsburgh Medical Center, Hepatology Department,
Assistência Especializada-, Acre; 29Hospital Getúlio Vargas-Teresina/
Pittsburgh, Spain; 3Hospital Universitario de Canarias, Liver Unit,
Piauí; 30Hospital do Servidor Público Estadual-São Paulo/São Paulo;
31 Tenerife, Spain; 4Hospital de la Santa Creu i Sant Pau, Hepatology
Hospital Federal de Bonsucesso; 32Unidade de Transplante de Figado e
Department, Barcelona, Spain; 5Hospital Vall d’Hebron, Barcelona, Spain
do Hospital de Base da Faculdade de Medicina de São Jose do Rio Preto/
Email: [email protected]
SP; 33Universidade de Brasília-Distrito Federal; 34Hospital das Clínicas-
Universidade Federal de Minas Gerais; 35Fundação Hospital Adriano Background and aims: Alcohol withdrawal syndrome (AWS) is a
Jorge; 36Hospital Clínico Universidad de Chile; 37Hospital San Juan de serious medical condition that often complicates hospitalized
Dios; 38Hospital Sotero del Rio; 39Hospital de Coquimbo; 40Hospital patients with advanced alcohol-related liver disease including
Padre Hurtado; 41Hospital de Concepción; 42Hospital de Concepción; alcoholic hepatitis (AH). There are no studies evaluating the
43
Hospital Clinico Universidad de Chile; 44Hospital Hernán Henríquez prevalence, impact, and effect of AWS prophylaxis in the setting of
Aravena; 45Hospital de la Serena; 46Fundación Valle del Lili; 47Clinica AH. We aimed at evaluating the incidence and outcomes of AWS in

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POSTER PRESENTATIONS
patients hospitalized with AH from two countries with different AWS treatment of AUD. We wanted to ascertain the current attitude of
management strategies. gastroenterology physicians in Ireland towards pharmacotherapy as a
Method: A multicenter, international, retrospective, case-control treatment option for AUD.
study was performed evaluating consecutive patients hospitalized Method: An anonymous, questionnaire-based survey was sent to
with AH in Spain (four participating centers) and USA (one center). In gastroenterology physicians nationwide. This survey collected demo-
Spain, clomethiazole is used as prophylactic therapy for AWS while in graphic information and assessed prescribing habits towards med-
USA a symptom-triggered approach is followed. Electronic medical ications which have been approved to treat AUD (Naltrexone,
history of all patients hospitalized with the diagnosis code of AH Disulfiram, Baclofen, Librium, Nalmefene and Acamprosate). Where
since 2015 were revised. Diagnosis of AWS was based on the clinician pharmacotherapy was not routinely utilised, we examined factors
criteria and the need for treatment with benzodiazepines to control which may have led to their avoidance.
symptoms. Primary outcome was 28-days mortality. Prescribed Results: We received 60 responses, 56% (n = 32) consultant gastro-
benzodiazepine dose expressed in diazepam-equivalent was com- enterologists, and 40% (n = 23) GI specialist registrars (SpRs). 80% (n =
pared between groups who developed AWS. A propensity score 48) report being frequently (daily/weekly) involved in the manage-
(match by age, sex, BMI, MELD and ACLF score) was performed to ment of AUD. 95% (n = 57) of prescribers believe that there is a role for
compare clinical outcomes between patients who developed WDS in pharmacotherapy in treating AUD, but only 22% (n = 13) routinely use
Spain vs. USA, using stratified logistic regression for matched pairs. these in clinical practice. Librium was commonly used by 88% (n =
Results: Study population included 432 patients (n = 193 from Spain 53), while <10% regularly prescribed Naltrexone, Baclofen, or
and n = 239 from USA), of whom 63% were women with mean age 48 ± Acamprosate. Prohibitive factors identified were lack of hospital
10 years, median BMI 28 (24–32) kg/m2 and mean MELD score at alcohol services (61%) [48% of respondents reported no alcohol
admission of 23.7 ± 7.9. Overall prevalence of AWS and mortality was service or support in their hospital], side effect profile for patients
32% (n = 140) and 17% (n = 74), respectively. Presence of AWS was lower (26%), lack of compliance (26%), lack of adjuvant psychosocial support
in patients receiving prophylaxis (Spain) than in patients who did not in community (47%), and unfamiliarity with medications (61%).
receive it (USA) (26% vs. 37% P < 0.007). In patients receiving Conclusion: Despite the burden of alcohol on our acute hospitals,
prophylaxis, the development of AWS was not associated with worse there is a clear and significant lack of support for alcohol related
clinical outcomes, including mortality (10% vs. 8%, P = 0.52). In patients conditions. Emanating from this is the underutilisation of pharma-
not receiving prophylaxis in the USA, the development of AWS was cotherapy as a treatment for AUD, despite its evidence base. This
associated with higher mortality (33% vs. 19%, P = 0.009) [Figure 1]. survey highlights an urgent need to develop alcohol support services,
After propensity matching, a higher mortality was seen among in conjunction with physician education about the role of pharma-
patients presenting AWS in USA vs. Spain (p = 0.003). Importantly, cotherapy in treating AUD.
patient with AWS in Spain had similar mortality that those who did not
developed AWS in USA (p = 0.35). There were marked differences in THU037
several key parameters in patients with AWD with and without Application of machine learning algorithms to classify
prophylaxis, respectively: the diazepam equivalent dose used (87 ± 119 steatohepatitis on liver biopsy
vs.136 ± 190 mg), ICU admission (16% vs. 48%, P = 0.02) and orotracheal Resham Ramkissoon1, Joseph Ahn1, Yung-Kyun Noh2, Yubin Yeon3,
intubation rate (10% vs. 28%, P = 0.04). Chady Meroueh1, Priya Thanneeru1, Amit Das1, Jason Hipp1,
Alina Allen1, Douglas Simonetto1, Patrick S. Kamath1, Vijay Shah1.
1
Mayo Clinic, Rochester, United States; 2Hanyang Univ., Department of
Computer Science, Korea, Rep. of South; 3Hanyang Univ., Department of
Artificial Intelligence, Korea, Rep. of South
Email: [email protected]
Background and aims: Currently, it is very challenging to distinguish
alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis
(NASH) on liver biopsy alone as they share many of the same
histological characteristics. Artificial intelligence (AI) models utilizing
deep learning have demonstrated superhuman degrees of accuracy in
interpretation of digitized liver histology. The aim of our study was to
develop a deep learning algorithm in the form of a convolutional
neural network (CNN) to classify ASH and NASH on liver biopsy.
Method: We obtained liver biopsy slides from 38 patients with ASH
and 59 patients with NASH. ASH was determined based on the
clinical diagnosis of alcohol-associated hepatitis, and patients with
Conclusion: In AH setting, prophylactic therapy for AWS is associated NASH were identified from a cohort of morbidly obese patients
with lower prevalence of both withdrawal symptoms and short-term undergoing bariatric surgery. The slides were digitized into an
mortality. This data supports that prophylactic therapy is a better electronic database with whole-slide diagnosis labels. Each whole-
approach than symptom-triggered therapy in patients hospitalized slide image was rescaled and randomly cropped to generate 256
with AH. patches of 256 × 256 pixels. Each cropped patch retained the
diagnosis label from the original whole-slide image (0 = NASH, 1 =
THU036 ASH). The patches were randomly split into training and testing sets
The use of pharmacotherapy in the treatment of alcohol use in an 8:2 ratio. Patches in the training set were used to train a 50-layer
disorder CNN (ResNet50), and the CNN’s performance as a binary classifier
Kathryn Allen1, Tobias Maharaj1, John Ryan1. 1Beaumont Hospital, was tested on the patches in the testing set. Gradient-weighted Class
Hepatology, Dublin, Ireland Activation Mapping (Grad-CAM) was used as a method to understand
Email: [email protected] the CNN’s decisions.
Results: The CNN had an outstanding performance in distinguishing
Background and aims: Alcohol use disorder (AUD) is an important ASH versus NASH with an AUC of 0.962. Using an optimal threshold of
cause of preventable morbidity and mortality. The prevalence of AUD 0.504, the CNN had an accuracy of 90.4%, sensitivity of 79.5%, and
and alcohol related liver disease is increasing in Ireland. Several specificity of 96.3%. The positive predictive value is 92.1% and
medications have been demonstrated to be effective for the

S138 Journal of Hepatology 2022 vol. 77(S1) | S119–S388

 POSTER PRESENTATIONS
negative predictive is 89.7%. Grad-CAM highlighted distinct regions Table 1: Predictors of Mortality in SAH
within each patch that the algorithm used to make its decisions.
Death Alive P
Parameter (n = 16) (n = 44) value Multivariate
Demographic Details
Age (yrs) 40.6 ± 8.4 39.5 ± 6.2 0.314
Height (cm) 171 ± 4.7 169 ± 8.9 0.511
2
Dry BMI (kg/m ) 19.7 ± 2.7 22 ± 4.1 0.051 0.048
Weight reduced (kg) 9.47 ± 7.0 8.9 ± 6.3 0.785
Duration of weight loss (mo) 4.87 ± 1.6 8.3 ± 1.29 0.257
Clinical details
Ascites 32 (53.3%) 12 (20%) 0.676
Duration of alcohol intake (yrs) 14.47 ± 5.7 13.08 ± 7.3 0.113
Alcohol Quantity (gm) 571 ± 153 478 ± 194 0.468
Last intake (days) 24 ± 9.45 36.4 ± 15.7 0.001
Biochemical Parameters
Total Bil (mg/dl) 21.3 ± 8.9 15.5 ± 7.2 0.041 0.022
AST (IU/L) 116 ± 54 157 ± 73 0.040
ALT (IU/L) 127 ± 63 162 ± 56 0.031
ALP (IU/L) 91.9 ± 27 157 ± 91 0.001
Total protein (g/dl) 6.28 ± 0.93 6.99 ± 1.09 0.028
Albumin (g/dl) 2.8 ± 0.66 2.8 ± 0.54 0.978
Figure: (a) Receiver operating characteristic (ROC) curve for the CNN’s INR 2.01 ± 0.34 1.96 ± 0.55 0.716
classification of ASH versus NASH. (b) Confusion matrix for the CNN; a Urea (mg/dl) 38.5 ± 16 28 ± 06 0.089
Creatinine (mg/dl) 0.80 ± 0.4 0.73 ± 0.2 0.581
diagnosis of ASH is indicated by “Positive” and a diagnosis of NASH is Sodium (mmol/L) 129.5 ± 4.2 132.3 ± 3.3 0.039
indicated by “Negative.” (c) Activation map for classification of ASH patch Potassium (mmol/L) 4.07 ± 0.68 4.08 ± 0.68 0.963
(top row) and NASH patch (bottom row). Severity Scores
MELD 28.3 ± 2.9 28.3 ± 10.8 0.317
MDF 63.05 ± 18.4 63.05 ± 23.1 0.203
Conclusion: Our deep learning-based AI algorithm had an outstand- CTP 10.4 ± 1.06 10.7 ± 1.5 0.115
ing performance for patch-level classification of liver biopsy images FIB-4 8.4 ± 3.6 6.95 ± 1.08 0.028
from patients with ASH and NASH. After further validation on a larger Body composition parameters
Fat mass (kg) 18.6 ± 4.8 22.6 ± 5.6 0.118
set of liver biopsy images and evaluation of model performance at the Fat free mass (kg) 49.36 ± 13 51.2 ± 13.3 0.720
2
level of whole slides, our AI algorithm may prove to be a novel way to FFMI kg/m 16.8 ± 4.2 18.02 ± 4.6 0.501
Hand grip (kg) 22.1 ± 6.17 23.3 ± 6.2 0.986
distinguish ASH versus NASH histologically. Diet
Energy requirement (kcal) 2289 ± 738 2358 ± 523 0.730
THU038 Protein requirement (g) 85.6 ± 5.7 83.8 ± 10.7 0.511
Energy intake (kcal) 598.8 ± 231 737.3 ± 278.4 0.643
Calorie-protein deficit and body mass index are the independent Protein intake (g) 26.65 ± 10.6 20.3 ± 9.9 0.06 0.022
predictors of mortality in severe alcoholic hepatitis Calorie deficit (kcal) 2035 ± 214 1813 ± 508 0.05 0.045
Protein deficit (g) 70.7 ± 7.5 60.9 ± 19.2 0.02 0.051
Harshita Tripathi1, Jaya Benjamin2, Puja Bhatia1, Rakhi Maiwall3,
Guresh Kumar4, Yogendrakumar Joshi5, Shiv Kumar Sarin3. 1Institute Data expressed as mean ± SD, n (%). P value ≤0.05 is significant.
of Liver and Biliary Sciences, Clinical Nutrition, DELHI, India; 2Institute of
Liver and Biliary Sciences, Clinical Nutrition, New Delhi, India; 3Institute Conclusion: High calorie and protein diet with maintained body
of Liver and Biliary Sciences, Hepatology, DELHI, India; 4Institute of Liver weight improves survival in SAH.
and Biliary Sciences, Biostatistics, DELHI, India; 5Institute of Liver and Results: In 60 patients with SAH [age 40 ± 7.37 yrs; ascites 47 (84%);
Biliary Sciences, Clinical Nutrition and Hepatology, DELHI, India BMI- 21.3 ± 3.8 kg/m2; mDF-62.4 ± 21.4, MELD 28 ± 9.3, CTP 10.6 ± 1.4,
Email: [email protected] on steroids 14 (25%)] there was significantly low calorie intake
Background and aims: Short term mortality is high in severe despite >3 weeks of abstinence (Table 1). Those 16 (26.6%) patients
alcoholic hepatitis (SAH), which is influenced by multiple factors. We who died at 2 mo had significantly lower BMI, higher P and C deficit
planned to assess the independent predictors of 60 day mortality for and total bilirubin compared to survivors; that predicted mortality.
optimizing management.
Method: SAH patients with Maddrey’s discriminant function (mDF) THU039
32–100 were enrolled; excluding sepsis, AKI and malignancy. Alcoholic foamy degeneration: a unique variant of ALD that shows
Baseline clinical, biochemical parameters, disease severity [MELD, a characteristic pattern of gene expression with upregulation of
CTP, MDF, FIB-4], BMI, fat free mass index (FFMI), hand grip strength, lipid metabolism and mitochondrial genes and downregulation
usual diet [calorie (C) and protein (P) intake] and 60 day mortality of fibrosis genes
were assessed. C and P deficit was the difference of ideal requirement Jordi Gratacós-Gines1, Delia Blaya2, Helena Hernandéz Evole1,
[C (35kcal) and P (1.2 g) per kg ideal body weight] and actual intake. Carla Montironi3, Emma Avitabile1, Martina Perez1, Marta Cervera1,
Logistic regression analysis was done. Marta Carol1, Ana Belén Rubio1, Núria Fabrellas1, Anna Soria1,
Octavi Bassegoda1, Laura Napoleone1, Ann Ma1, Adria Juanola1,
Isabel Graupera1, Alba Díaz4, Juan Jose Lozano5, Pere Ginès1,
Elisa Pose1. 1Hospital Clínic de Barcelona, Liver Unit, Barcelona, Spain;
2 ̀ iques August Pi i Sunyer (IDIBAPS),
Institut d’Investigacions Biomed
Barcelona, Spain; 3Hospital Clínic of Barcelona, Pathology Department
and Molecular Biology CORE, Barcelona, Spain; 4Hospital Clínic de
Barcelona, Pathology Unit, Barcelona, Spain; 5centro de investigación
biomedica en red de enfermedades hepáticas y digestivas (CIBERehd),
Barcelona, Spain
Email: [email protected]
Background and aims: alcoholic foamy degeneration (AFD) is a
variant of alcoholic liver disease that is diagnosed based on histology,
with a pattern of microvesicular steatosis in the liver biopsy. Recently,
in one of the largest series reported to date, we described AFD as an
entity with similar clinical presentation to alcoholic hepatitis (AH),
but faster improvement of liver function and markedly better long-

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POSTER PRESENTATIONS
term prognosis. Molecular mechanisms underlying AFD are Conclusion: AFD displays a specific gene signature differentiated
unknown and histological pattern has been scarcely studied. Our from that of AH. Genetic functional pathways associated with lipid
aim was to unveil the histological and transcriptional characteristics metabolism and mitochondrial function are upregulated in patients
of AFD in this series. with AFD. In contrast, there is a downregulation of pathways
Method: liver biopsies from 16 patients with AFD and 20 patients associated with inflammation, fibrosis and senescence. Histological
with AH diagnosed in the same period, were obtained. Results from findings are consistent with genetic profile, with a predominant
RNA sequencing were analyzed with IPA, GO and RA platforms. pattern of steatosis, with scarce fibrosis and steatohepatitis.
Moreover, liver biopsies were reviewed by two pathologists to
describe steatosis, steatohepatitis, degree of inflammation and THU040
fibrosis. Loss of solute carrier family 38 member 4 (SLC38A4) as a driver for
Results: compared to patients with AH, patients with AFD presented the pathogenesis of severe alcoholic hepatitis
with a lower proportion of ascites and had higher levels of Nchimunya Nelisa Tebeka1, Stephen Atkinson1, Luke D. Tyson1,
transaminases, cholesterol and triglycerides. Bilirubin levels were Josepmaria Argemi2, Adam Syanda1, Ramon Bataller2, Tamir Rashid1,
similar but MELD score was lower in patients with AFD. RNA Mark Thursz1. 1Imperial College London, Department of Metabolism,
sequencing analysis revealed that patients with AFD and AH have a Digestion and Reproduction, London, United Kingdom; 2University of
differential gene expression pattern. On PCA analysis using gene Pittsburgh, Medical Center, Pittsburgh, United States
expression, AFD patients clustered apart from AH patients. Moreover, Email: [email protected]
the analysis of the deregulated gene expression showed that AFD
Background and aims: Severe alcohol-related hepatitis (sAH) is a
patients have a significant upregulation of pathways associated with
florid presentation of alcohol-related liver disease with very high
lipid metabolism, such as cholesterol and triglycerides biosynthesis,
short-term mortality. A genome-wide association study identified
stearate and retinol biosynthesis, mitochondrial function and cell
solute carrier family 38 member 4 (SLC38A4) as a potential risk locus
cycle, and a downregulation of pathways related to hepatic fibrosis
for the development of sAH. SLC38A4 is characterised as an amino
such as wound healing signaling, integrin signaling and extracellular
acid transporter and is predominantly hepatically expressed under
matrix deposition. Genes involved in senescence, autophagy and
the regulation of HNF4a. The aim of this project was to investigate
inflammation are also downregulated. Half of the cases (n = 8) had
how changes in SLC38A4 expression may contribute to the patho-
predominant microvesicular steatosis, six (37.5%) had a mixed
genesis of sAH.
pattern of micro and macrovesicular steatosis and the remaining
Method: SLC38A4 expression was determined by RNA-seq in whole
two cases (12.5%) showed microvesicular steatosis (≥40%) with
liver biopsies obtained from patients with alcohol related liver
focally associated steatohepatitis. Fibrosis was uncommon, especially
disease, including sAH, from a published study. In vitro experiments
in the cases of predominant microvesicular steatosis.
were conducted to investigate the effects of known disease mediators
on SLC38A4 expression in Huh7.5 cells. SLC38A4 knock-out lines
(aliases P1.7 and C12 SLC38A4-KO) were generated by CRISPR/Cas9
editing in Huh7.5 cell lines; a control cell line (SCWT) was generated
using a non-targeted scramble guide RNA. The functional impact of
SLC38A4 knock-out was then characterised using gene expression
analysis (RT-qPCR and RNA-seq) and protein expression by immuno-
fluorescence (IF). Assays were performed to assess the impact of
knock out on cell morphology and proliferation in addition to CYP3A4
activity and ureagenesis.
Results: SLC38A4 expression was reduced in whole liver tissue from
cohorts of patients with sAH compared to their early alcoholic
steatohepatitis controls ( p <0.0001). In vitro SLC38A4 expression was
downregulated by mediators of alcoholic hepatitis i.e., IL-1b, TGFb1,
TNFa and sAH patient plasma but upregulated by dexamethasone
(Figure 1A). SLC38A4-KO lines demonstrated upregulation in the
epithelial-mesenchymal transition markers, EPCAM and Vimentin ( p
<0.0001 and p <0.01 respectively) (Figure 1B). SLC38A4-KO resulted in
reduced cell proliferation, ureagenesis, and downregulation of bile
acid transporters, BSEP ( p <0.0001) and MRP2 ( p <0.01). The cell
morphology of knock-out cells exhibited stemness like features and
the upregulation of the foetal isoform of HNF4a, P2 ( p <0.001).
CYP3A4 expression and activity were reduced ( p <0.001). RNA-seq
confirmed the increase of EPCAM and Vimentin and the reduction of
CYP3A4 across the SLC38A4-KO lines. Additionally, SLC38A4-KO
resulted in differential expression of other SLC genes and cell
growth/differentiation regulating genes (Figure 1C). Pathway analysis
indicated changes in amino acid metabolism and cytokine signalling
pathways.

Figure: heatmap of the top upregulated (red) and downregulated (blue)

genes in liver biopsies with AFD (green bar) and AH (orange bar).

S140 Journal of Hepatology 2022 vol. 77(S1) | S119–S388

 POSTER PRESENTATIONS
events (LACE) and major adverse medical events included cancer,
cardiovascular disease or diabetes. Subdistribution hazards were
calculated with univariable and multivariable analyses to understand
factors affecting outcomes. These analyses were used to describe the
cumulative incidence of liver-specific mortality for given MELD
scores.
Results: The WALDO cohort includes 710 patients of whom 423 had
cirrhosis. Alcoholic hepatitis was present in 184 patients at the time
of biopsy, and 216 patients were not cirrhotic and without alcoholic
hepatitis. During a median follow-up of 4.6 years (IQR 1.1–9.5 years,
totalling over 4 thousand patient-years) there were 381 deaths (54%
of the total cohort) and 47 patients (7%) underwent liver transplant-
ation. Deaths were liver related in 144 cases (39% of all deaths). New
LACE occurred in 87 patients during follow-up and new medical
morbidity occurred in 133 patients (19%). When compared to patients
without cirrhosis CIF for liver-related death was significantly higher
in patients with cirrhosis (1.87, 1.56–2.18, p = 0.042), decompensated
cirrhosis (5.88, 5.60–6.165, p < 0.001) and alcoholic hepatitis (6.40,
6.12–6.68, p < 0.001), whereas the CIF of non-liver related deaths was
not significantly different. The strongest baseline predictors of
outcomes were stage of disease, MELD or ALBI scores, and abstinence.
The cumulative incidence of liver-related deaths at sample baseline
Conclusion: SLC38A4, a gene identified as a potential risk locus in MELD scores of 6, 12, and 20 was 8%, 18% and 49% respectively with
sAH through genetic studies, demonstrates reduced hepatic expres- significant differences between patients who were abstinent or non-
sion in patients with disease. This expression is downregulated In abstinent.
vitro by recognised disease drivers. SLC38A4 knock out in cell lines
recapitulates several features considered important in disease
pathogenesis.

THU041
Refining the natural history of alcohol related liver disease: a
competing risk analysis
Richard Parker1, Guruprasad Aithal2, Michael Allison3,
Juan Pablo Arab4, Mayur Brahmania5, Ewan Forrest6,
Hannes Hagström7, Alisa Likhitsup8, Steven Masson9,
Anne McCune10, Neil Rajoriya11, Ian Rowe12. 1Leeds Teaching Hospital
Trust, Leeds Liver Unit, Leeds, United Kingdom; 2NIHR Nottingham BRC,
Nottingham, United Kingdom; 3Addenbrooke’s Hospital, Hepatology,
Cambridge, United Kingdom; 4Pontificia Universidad Católica de Chile,
Departamento de Gastroenterología, Santiago, Chile; 5Western Conclusion: Patients with ALD are at risk of multiple causes of ill
University, Department of Gastroenterology and Multiorgan Transplant, health. Competing risk analysis takes these into account to give a
London, Canada; 6Queen Elizabeth Hospital, Hepatology, Glasgow, more accurate analysis of the probability of outcomes. The risk of
United Kingdom; 7Karolinska University Hospital, Centre for Digestive liver-related mortality increases significantly above that of non-liver
Diseases, Stockholm, Sweden; 8St Luke’s Hospital Kansas City, Kansas related mortality only in decompensated cirrhosis and alcoholic
City, United States; 9Newcastle Upon Tyne Hospitals NHS Foundation hepatitis.
Trust, Liver Unit, Newcastle Upon Tyne, United Kingdom; 10University
Hospitals Bristol NHS Foundation Trust, Department of Liver Medicine, THU042
Bristol, United Kingdom; 11University Hospitals Birmingham NHS Potential biomarkers for differentiating alcoholic hepatitis from
Foundation Trust, Liver and Hepatobiliary Unit, Birmingham, United decompensated cirrhosis by serum metabolomic analysis
Kingdom; 12University of Leeds, Leeds Institute for Medical Research, Adelina Horhat1,2, Fischer Petra1, Mina Ignat2, Bogdan Procopet1,2,
Leeds, United Kingdom Carmen Socaciu3, Stefanescu Horia2. 1Iuliu Haţieganu University of
Email: [email protected] Medicine and Pharmacy, Cluj-Napoca, Romania; 2Regional Institute of
Gastroenterology and Hepatology "Prof. Dr. O. Fodor", Cluj-Napoca,
Background and aims: Alcohol-related liver disease (ALD) is Romania; 3RTD Center for Applied Biotechnology BIODIATECH SC
common throughout the world and is a frequent cause of ill-health Proplanta, Cluj-Napoca, Romania
and death. Alcohol consumption affects multiple organs and systems, Email: [email protected]
therefore, increasing the risk of a wide range of conditions. Previous
systematic review demonstrated that both liver and non-liver related Background and aims: Patients with alcoholic hepatitis (AH) have a
mortality increased depending on the stages of liver disease. We have high risk of short-term mortality. The diagnosis of AH relies on
analysed a cohort of patients with biopsy-proven liver disease using clinical and biochemical parameters, but it is impossible to
competing risk analysis to accurately describe the risks of liver and differentiate from alcoholic related decompensated cirrhosis (ArDC)
non-liver related outcomes in ALD. without liver biopsy. The main objective of this study was to assess
Method: WALDO is an international, retrospective cohort of patients the metabolomic fingerprint of AH; Secondary objective was to
with biopsy-proven liver disease followed up through health records identify potential biomarkers to differentiate between the AH and
to capture outcome data regarding mortality and morbidity. ArDC.
Competing risk analysis was used to estimate cumulative incidence Method: We performed an untargeted metabolomic profiling of
functions (CIF) of mortality (liver-related or non-liver related deaths), blood serum from 36 patients with biopsy proven AH and 36 patients
and morbidity. Morbidity was classed as liver-associated clinical with ArDC, using high performance liquid chromatography and mass
spectrometry. More than 300 metabolites were identified; Eighty-

Journal of Hepatology 2022 vol. 77(S1) | S119–S388 S141

POSTER PRESENTATIONS
three molecules were selected for further analysis and the most this study, the prostaglandin levels were decreased in patients with
significant biomolecules were selected to discriminate the AH versus AH showing that beta-oxidation could be a valuable target pathway.
ArDC phenotype and infection status.
Results: Seventy-two percent of patients were male and 97% of them THU043
had cirrhosis. The main molecules that showed increased levels in AH A phase II, multicenter, open-label, randomized trial of
group comparative to ArDC group were C16 Sphinganine-1-phos- pegfilgrastim for patients with alcohol-associated hepatitis
phate (S1P), Prostaglandin F1a/b (PGF1a/b), Cerotic acid and arachidic Timothy Morgan1, Aliya Asghar1, John Tayek2, Danh Nguyen3,
acid while Prostaglandin D2/E2 (PGD2/E2), Prostaglandin E2-etha- M. Wayne Fleischman2, John Donovan4, Joseph Alcorn5, Daniel Chao6,
nolamide (PGE2-EA), dinor cholic acid, 12-ketodeoxycholic acid 2- Andrew Stolz4. 1VA Medical Healthcare System, Medicine, Long Beach,
hydroxy stearic acid, D-Sphingosine decreased (1a). United States; 2Harbor-UCLA Medical Center, Torrance, United States;
In the multivariate analysis, PLSDA score plot showed a co-variance of 3
University of California-Irvine, Irvine, United States; 4LAC-USC Medical
19.4%, with a good discrimination between AH and ArDC groups Center, Los Angeles, United States; 5VA Healthcare System, Albuquerrque,
(figure 1b) United States; 6VA Healthcare System, Loma Linda, United States
In the subgroup analysis, (infected AH and ArDC and non-infected AH Email: [email protected]
and ArDC), a good discrimination was showed by S1P, with a p value =
Background and aims: In trials conducted in India, recombinant
1.49E-15, Mean Decrease Accuracy (MDA) >0.035 and an area value
granulocyte colony stimulating factor (GCSF) improved survival in
under ROC curve (AUC) of 0.984 (0.943–1) and PGD2/E2, which had a
alcohol-associated hepatitis (AH). The aim of this trial was to
decreased level ( p = 2.56E-1, MDA >0.025 and AUC 0.958 (0.898–
determine the safety and efficacy of pegfilgrastim, a long-acting
0.994)) (Figure 1c, d). The semiquantitative analysis of the combin-
recombinant GCSF, in patients with AH in the United States.
ation between S1PandPGE2 showed increased (95%) diagnostic
Method: This prospective, open label trial randomized patients with
accuracy to discriminate AH from ArDC, with 100% NPV and 100% Se.
a clinical diagnosis of AH and a Maddrey discriminant function score
≥32 to standard of care (SOC) or SOC+pegfilgrastim (0.6 mg
subcutaneously) on Day 1 and Day 8. SOC was 28 days of either
pentoxifylline or prednisolone, as determined by the patient’s
primary physician. The second injection of pegfilgrastim was not
administered if the white blood cell count exceeded 30, 000/mm3 on
Day 8. Primary outcome was survival at Day 90. Secondary outcomes
included the incidence of acute kidney injury (AKI), hepatorenal
syndrome (HRS), hepatic encephalopathy, or infections.
Results: The study was terminated early due to COVID19 pandemic.
Eighteen patients were randomized to SOC and 16 to SOC+pegfil-
grastim. All patients received prednisolone as SOC. Nine patients
failed to receive a second dose of pegfilgrastin due to WBC>30, 000/
mm3 on Day 8. Survival at 90 days was similar in both groups (SOC:
0.83 [95% confidence interval {CI}: 0.57–0.94] vs. pegfilgrastim: 0.73
[95% CI: 0.44–0.89]; p > 0.05). The incidences of AKI, HRS, hepatic
encephalopathy, and infections were similar in both treatment arms
and there were no serious adverse events attributed to pegfilgrastim.
Conclusion: This phase II trial found no survival benefit at 90 days
among subjects with AH who received pegfilgrastim+prednisolone
compared with subjects receiving prednisolone alone.
Figure 1: (a) Main molecules that showed good discrimination between THU044
AH and ArDC (red – increased, blue -decreased). (b) PLSDA score plot
Trends of alcohol-related liver disease hospitalisation during the
showed a co-variance of 19.4%, with a good discrimination between AH
and ArDC groups. (c) AUC curves for S1P 0.984; (0.943-1) and PGD2/E2 COVID-19 pandemic
0.958 (0.898-0.994). Oyekoya Ayonrinde1,2,3, Richard Goodheart1. 1Fiona Stanley Hospital,
Gastroenterology and Hepatology, Murdoch, Australia; 2The University of
Conclusion: Sphingolipids are now known to regulate important Western Australia, Medical School, Crawley, Australia; 3Curtin University,
physiological cellular processes (1). Especially, S1P has an anti- Faculty of Health Sciences, Bentley, Australia
necrotic and anti-inflammatory effects via TNF-a signaling pathway; Email: [email protected]
In an ischemia/reperfusion (I/R) model, plasma S1P levels were noted
to be decreased after hepatic I/R injury (2). Prostaglandins have Background and aims: Alcohol-related liver disease (ALD) is a
protective effects by inhibiting the generation of reactive oxygen common and potentially serious liver disorder associated with
species and regulating the production of inflammatory cytokines. In substantial morbidity and mortality. Recent reports have described
increased alcohol since the onset of the COVID-19 pandemic.
Therefore, the primary aim of this study was to examine trends in
ALD hospital admissions prior to and during the Covid-19 pandemic.
The secondary aim was to assess patient demographic and clinical
characteristics associated with short and medium-term mortality.
Method: We retrospectively analysed data on patients who were
admitted with ALD to a quaternary care hospital in Australia. The
study population comprised adults hospitalised with International
Classification of Diseases, Tenth Revision (ICD-10) principal diagnosis
code K70.1 (alcoholic hepatitis), 70.3 (alcoholic cirrhosis), and 70.4
(alcoholic hepatic failure) between January 2018 and December 2021.
Data recorded included patient demographics, alcohol history,
clinical and laboratory characteristics. The Model for End Stage
Liver Disease (MELD) score was calculated.

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 POSTER PRESENTATIONS
Results: Amongst 345 hospitalisations with ALD, there was a non- femur in older people. Multi-organ involvement and male sex predict
statistically significant rise in cases comparing the two years mortality.
preceding and during the first two years of the COVID-19 pandemic
(Figure 1). There were 104 (30.1%) ARH and 69.9% with decompen- THU045
sated ARC or alcoholic liver failure (ALF). Those with ARH, compared Increased hospital admissions for alcohol-associated hepatitis
with those with ARC and ALF, had a higher mean [standard deviation] during the COVID-19 pandemic in Alberta, Canada: a retrospective
MELD score (22.6 [9.3] vs. 20.3 [7.8], p = 0.02), were younger (47.6 cohort study
[11.7] vs 54.6 [10.6] years, p <0.001), had longer median [interquartile Alexandra Frolkis1, Meredith Borman1, Matthew Sadler1,
range] length of hospital stays (7.7 [4.0–13.0] vs. 6.0 [2.0–9.0] days, Stephen Congly1, Henry Nguyen1, Samuel Lee1, Mark G Swain1,
p = 0.008), and were predominantly male (58.7%). Kelly Burak1, Carla Coffin1, Alexander Aspinall1, Laura Stanton1,
The in-hospital mortality was 12.8% overall, comprising 17.3% with Abdel Aziz Shaheen1. 1University of Calgary, Calgary Liver Unit
ARH, 10.8% with ARC/ALF, and 5/47 (10.6%) aged under 40 years. Email: [email protected]
Patients aged <40 years, compared with those ≥ 40 years had a
Background and aims: Alcohol-associated hepatitis (AH) is the most
similar 30-day mortality (14.9% vs. 20.5%, p = 0.37) but lower one- severe and fulminant form of alcohol-related liver disease with
year mortality (25.5% vs. 43.0%, p = 0.02). Using multivariable logistic
females at greater risk of liver injury from alcohol use. Alcohol
regression analysis, predictors of 30-day mortality were male sex consumption increased during the COVID pandemic. The aim of our
(odds ratio [OR] 2.89, 95% confidence interval [CI] 1.29–6.46, p =
study was to assess the changing epidemiology of hospitalizations for
0.02), age (OR 1.06, 95% CI 1.02–1.10, p = 0.004), serum bilirubin (OR
AH by sex before and during the COVID-19 pandemic.
1.006, 95% CI 1.003–1.008, p < 0.001), respiratory failure (OR 3.64, 95% Method: We identified all hospitalizations for adults >18-years-old in
CI 1.62–8.21, p = 0.002, hepatic encephalopathy (OR 6.43, 95% CI 2.91–
Alberta, Canada using a validated algorithm of international
14.21, p < 0.001), and type 2 hepatorenal syndrome (OR 3.27, 95% CI classification of disease-10 codes and lab values for AH between
1.55–6.87, p = 0.002). March 2018 and September 2020. Severe AH was defined as Model for
End-Stage Liver Disease (MELD) >20. Onset of the pandemic was
defined as March 2020. Logistic regression was used to identify
factors associated with AH severity, and separately mortality,
adjusted for age, sex, and pandemic onset. Binomial regression was
used to assess changes in frequency of admission for AH with the
denominator as all cirrhosis-related admissions over the same time-
period.
Results: There were 991 hospitalizations for AH prior to the
pandemic (n = 381, 38.5% female) and 417 during the pandemic
(n = 144, 34.5% female). Hospitalizations for AH significantly
increased during the pandemic ( p = 0.04) (Figure 1). Overall, a
higher percentage of females (34.5%) had severe AH compared to
males (31.0%) however this difference was not statistically significant
( p = 0.25) (Figure 1). Though the total number of hospitalizations for
AH increased during the pandemic, the odds of severe AH was higher
pre-pandemic (odds ratio [OR] 0.73; 95% confidence interval [CI]
0.55–0.98) after adjusting for age and sex. For every year increase in
age, the adjusted odds of severe AH increased by 1.02 (95% CI 1.01–
1.03). Prior to the pandemic, more females (38.6%) than males (32.2%)
had severe AH; during the pandemic, more males (28.4%) than
females (24.0%) had severe AH though these differences were not
statistically significant ( p = 0.1). Median age at admission was
significantly lower for both male and female during the pandemic
(age 44 and 41, respectively) as compared to prior (age 47 and 45,
respectively) p < 0.05. There was no significant difference in mortality
between sexes before (10.4% in female, 11.5% in male, p = 0.22) and
after the pandemic (9.2% in female, 9.9% in male, p = 0.67).

Conclusion: Admissions with ALD have risen during the COVID-19

period. Young adults with severe ALD requiring hospitalisation, have
a high mortality that is identical to mortality after a fractured neck of

Conclusion: Hospitalizations for AH rose during the pandemic and

occurred at younger ages in both sexes with less severe presentations.

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POSTER PRESENTATIONS
There was no significant difference in mortality by sex before and marker of ACLF in alcoholic cirrhosis, but overall, the histological
during the first wave of the pandemic. Advanced age was associated features of ACLF are not well characterized. We assessed the
with more severe AH. Public health efforts should continue to diagnostic and prognostic value of DB and other histological features
educate about the harms of alcohol excess and offer community in addition to clinical features for the presence and development of
support. ACLF in a well-defined cohort of ASH patients.
Method: Prospective study in consecutive patients admitted with a
THU046 diagnosis of ASH to a tertiary referral center between 03–2008 and
The lysosomal enzyme cathepsin D as a new marker for alcoholic 04-2021. Diagnosis of ASH was based on clinical presentation and
liver disease confirmed by transjugular liver biopsy. All biopsies were assessed by
Mengying Li1, Tom Houben1, Mads Israelsen2, Maria Kjærgaard2, a dedicated liver pathologist who was blinded for clinical data and
Marit Westerterp3, Aleksander Krag2, Maja Thiele2, outcome. Clinical and histological data were collected from time of
Ronit Shiri-Sverdlov1. 1School of Nutrition and Translational Research in biopsy until 1 year follow-up. Diagnosis of ACLF was based on EASL-
Metabolism, Maastricht University, Department of Genetics and Cell CLIF criteria. Differences between patients with and without ACLF at
Biology, Netherlands; 2Center for Liver Research, Odense University baseline were assessed using chi-square test. Predictors for develop-
Hospital and University of Southern Denmark, Odense, Denmark; ment of ACLF within 28 days were assessed using Cox regression.
3
University Medical Center Groningen, University of Groningen, Results: 184 patients with biopsy-confirmed ASH were enrolled, with
Department of Pediatrics, Groningen, Netherlands a median follow-up time of 365 days (IQR 83.5–365). At baseline,
Email: [email protected] ACLF was present in 73 patients (39.7%). Another 30 (16.3%) patients
developed ACLF within 28 days (median 7.5 days, IQR 2–20). At
Background and aims: Alcohol is the seventh leading cause of
baseline, DB was significantly more present in patients with ACLF
premature death worldwide, many of whom die from alcohol-related
compared to patients without ACLF (50.7% vs. 30.6%, p = 0.007).
liver disease (ALD). However, the underlying pathological mechan-
Presence of DB was not correlated with level of c-reactive protein,
isms that cause the early stages of ALD are currently under-
level of white blood cell count, presence of infection or positive blood
investigated. Lysosomal cathepsin D (CTSD) was previously shown
culture (all p > 0.05). None of the other histological features, including
to be useful in detecting NASH, and circulating CTSD is elevated in
the histological severity of ASH, was associated with presence of ACLF.
advanced liver disease. We therefore investigated plasma CTSD in
The CLIF-C AD score predicted the development of ACLF at 28-days
relation to different histological stages of early ALD.
(HRcs 1.09, p <0.001). However, no association between histological
Method: We conducted a cross-sectional study of 305 asymptomatic
features and development of ACLF could be found.
ALD patients with a liver biopsy scored according to the NAS CRN
Conclusion: In this well-defined cohort of patients with biopsy-
system, and compared their plasma CTSD levels with 40 healthy
proven ASH, we show that DB is a histological feature of the presence
controls, matched for age, gender and BMI. We excluded patients
of ACLF. Presence of DB was independent of presence of clinical
with decompensation at baseline. Next, we determined the correla-
features of sepsis within this group. The CLIF-C AD score had a high
tions between plasma CTSD levels and histology scored for fibrosis,
performance in predicting the development of ACLF, while the
ballooning, lobular inflammation and steatosis. Areas under the
additional role of histology seems limited.
receiver operating characteristic curve (AUC) were generated to
investigate the accuracy of plasma CTSD levels alone or in
combination with known non-invasive markers of fibrosis to
predict ALD.
Results: Plasma CTSD levels were significantly higher in ALD patients NAFLD: Clinical aspects except therapy
compared to matched healthy controls (37.7 vs 22.9 ng/ml; AUC
0.84). The highest CTSD levels was measured in ALD patients with no
ballooning and lobular inflammation, and a slightly lower CTSD levels THU048
were observed in patients with more severe inflammatory activity. The most recent and in-depth meta-analytic assessment of the
Further, plasma CTSD levels exhibited a weak negative correlation global epidemiology of non-alcoholic fatty liver disease (NAFLD)
with the ELF test and transient elastography, and did not correlate Zobair Younossi1,2,3, Pegah Golabi1,2,3, James Paik1,2,3, Austin Henry2,
with fibrosis stage. Moreover, transient elastography, ELF, GGT, AST/ Catherine Van Dongen2, Linda Henry3,4. 1Inova Fairfax Medical
ALT, and AST independently correlated with plasma CTSD levels. Campus, Center for Liver Disease, Department of Medicine, Falls Church,
Furthermore, combining plasma CTSD levels with transient elasto- United States; 2Inova Health System, Betty and Guy Beatty Center for
graphy and AST/ALT resulted in a high diagnostic accuracy (ROC-AUC: Integrated Research, Falls Church, United States; 3Inova Health System,
0.908) for predicting ALD. Inova Medicine, Falls Church, United States; 4Center for Outcomes
Conclusion: Lysosomal leakage of CTSD into the circulation may be a Research in Liver Disease, Washington, DC, United States
sensitive marker of early stages of ALD. Email: [email protected]

THU047 Background and aims: NAFLD is a leading cause of liver-related

Ductular bilirubinostasis is a diagnostic biomarker for acute- morbidity and mortality. We assessed the global and regional
on-chronic liver failure: results from a well-defined cohort of prevalence and incidence of NAFLD using an in-depth meta-analytic
patients with alcoholic steatohepatitis approach.
Annelotte Broekhoven1, Tessa Ostyn2, Lukas Van Melkebeke3, Method: We systematically searched PubMed and Ovid MEDLINE®
H.W. Verspaget1, Schalk van der Merwe3, Jef Verbeek1, for population-based studies of NAFLD published 2015–2021 (data
Minneke Coenraad1, Tania Roskams2, Frederik Nevens3. 1Leiden collected: 1988–2020). Two reviewers extracted data according to
University Medical Center, Gastroenterology and Hepatology, Leiden, age, sex, race, diagnostic methods, sample size, data collection year,
Netherlands; 2Translational Cell and Tissue Research, KU Leuven, comorbidities, and other study characteristics. Adjustments were
Imaging and Pathology, Leuven, Belgium; 3University Hospitals KU applied using prevalence of viral hepatitis and ALD from the Global
Leuven, Gastroenterology and Hepatology, Leuven, Belgium Burden of Disease study 2019 to approximate prevalence and
Email: [email protected] incidence of NAFLD in general population. The meta-analysis was
conducted using a random-effects model. Assessment of bias risk
Background and aims: Alcoholic steatohepatitis (ASH) is one of the used the Joanna Briggs Institute Critical Appraisal Instrument for
main precipitating events for the development of acute-on-chronic studies reporting prevalence data.
liver failure (ACLF). Ductular bilirubinostasis (DB) is identified as a

S144 Journal of Hepatology 2022 vol. 77(S1) | S119–S388

 POSTER PRESENTATIONS
Results: Of 1, 857 studies included, 132 studies (N = 9, 945, 423) met heart disease (24.7% vs 17.3%), CVA (3.2% vs 2.8%) and chronic
the eligibility criteria [106 NAFLD prevalence and 26 NAFLD obstructive lung disease (10.1% vs 8.3%) was found among NAFLD
incidence, high-income North America (H-NA, 19.8%), high-income patients. Patients with NAFLD have significant higher rate of the
Asia Pacific (27.4%), East Asia (23.6%), and Western Europe (WE, following malignancy: prostate (1.6% vs 1.2%) breast cancer (2.6% vs
11.3%)]. The pooled global prevalence of NAFLD based on a random- 1.9%), colorectal cancer (1.8% vs 1.4%), uterus (0.4 vs 0.2%) kidney
effects model was 29.1% (95% confidence interval: 26.8–31.5%). The (0.8% vs 0.5%), melanoma (1.6% vs 1.2%), basal cell carcinoma (11.6% vs
highest prevalence was reported in Latin America (n = 3, 44.4% [30.7– 8.6%) thyroid (0.7% vs 0.5%) cancer, non-Hodgkin lymphoma (0.7% vs
59.0%]), followed by Middle East and North Africa (MENA) (n = 9, 0.6%) and lower rate of lung cancer (0.9% vs 1.2%), stomach (0.3% vs
39.9% [32.6–47.6%]), H-NA (n = 21, 32.9% [27.4–38.9%]) and WE (n = 0.4%). The all-cause mortality among NAFLD patients was signifi-
12, 24.6% [19.1–31.0%]). The prevalence of NAFLD increased over time: cantly lower in comparison to general population (10.8% vs 14.7%, p <
1991–2006 (n = 10, 24.4% [19.6–30.0%]), 2007–2010 (n = 28, 25.7% 0.001)
[22.1–29.7%], 2011–2015 (n = 38, 27.9% [24.1–32.0%]) and 2016–2020 Conclusion: Higher rate of comorbidities and malignancy among
(n = 30, 36.0% [31.6–40.7%]. The global prevalence rate of NAFLD NAFLD patients was observed, but lower rate of all-cause mortality
varied between 11.23%–48.61% depending on the diagnostic modality was found.
(Table). The incidence of NAFLD ranged from 19.0–99.0 per 1, 000 Keywords: Fatty liver, comorbidities, malignancy, Israel
person-years. Meta-regression showed that diagnostic method/
criteria ( p < .001), data collection year ( p = 0.004) and geographic THU050
location ( p = 0.015) jointly accounted for 72.1% of the heterogeneity The prevalence of non-alcoholic fatty liver disease in the United
between studies. Kingdom: a systematic review and meta-analysis
Yusef Alenezi1, Timothy Card1,2, Joanne Morling1,2, Rebecca Harris2.
1
University of Nottingham, Lifespan and Population Health, Nottingham,
N. of United Kingdom; 2University of Nottingham, NIHR Nottingham
Diagnostic Modality study Prevalence % (95% CI) I2 Biomedical Research Centre (BRC), United Kingdom
Ultrasound: mild to severe 54 32.61 (30.30 to 35.01) 99.74 Email: [email protected]
steatosis Background and aims: Non-alcoholic fatty liver disease (NAFLD) is a
Ultrasound: moderate to severe 14 15.36 (13.33 to 17.63) 99.07
growing cause of cirrhosis and indication for a liver transplant. Since
steatosis
this growth is putting pressure on hepatology services and healthcare
Controlled Attenuation 9 40.78 (32.22 to 49.93) 99.47
Parameter systems, up-to-date measures of the size of the problem are needed
CAP of ≥248 dB/m 3 46.76 (37.12 to 56.65) 98.50 to plan future services. We have therefore conducted a systematic
CAP of ≥260 dB/m 3 48.61 (43.16 to 54.08) 95.29 review of studies in the UK to estimate the prevalence of NAFLD.
CAP of ≥274 dB/m 3 27.71 (16.41 to 42.80) 99.20 Method: We identified studies that investigate NAFLD prevalence
Computerized Tomography 3 11.23 (8.37 to 14.89) 93.43 among the UK population through a systematic search of electronic
Non-invasive Biomarkers (FLI, 22 31.11 (26.37 to 36.28) 99.95 databases (PubMed, EMBASE via OVID, CINAHL, Web of Science, and
US-FLI, HIS) Google). A random-effects meta-analysis was performed on subsets
Other (ICD-9 or 10) 4 25.23 (23.37 to 27.18) 81.36 of studies limited to populations with specific conditions and those
not so restricted.
Conclusion: The global prevalence of NAFLD is high and growing. Results: Our study included a total of 25, 439 participants from 9
Given its impact on the heterogeneity of the reported studies, it is studies. Our results indicate a pooled prevalence of 23.7% in non-
critical to use standardized diagnostic criteria to provide accurate and disease restricted populations (95% CI 20.6%-26.8%). Of the disease
consistent epidemiologic data across the world. restricted populations, a single study of HIV patients reported a
prevalence of 71.2% (CI: 59.7%-82.7%). Two studies of liver-related
THU049 hospital referral yielded a prevalence of 37.90% (CI: 15.3%-60.5%), a
Comorbidities and malignancy among NAFLD patients compared single study of BMI ≥25 (29.6%) (CI: 27.9%-31.3%), and type-1 diabetic
to general population patients (1.8%) (CI: 0.0%-3.6%). Our results also included three studies
Naim Abu-Freha1, Bracha Cohen2, Michal Gordon3, Alexander Fich2, of type-2 diabetic patients with an overall prevalence of 38.6% (CI:
Daneila Munteanu4, David Yardeni4, Ohad Etzion5. 1Soroka University 25.5%-51.7%).
Medical Center, Department of Gastroenterology and liver diseases, Beer Conclusion: Our major finding is that the prevalence of NAFLD within
Sheva, Israel; 2Soroka University Medical Center, Beer-Sheva, Israel; the UK general population is similar to the average global estimate.
3
Soroka University Medical Center, Beer-Sheva, Israel; 4Soroka There is good evidence that adults with T2DM have a higher
University Medical Center, Beer Sheva, Israel; 5Soroka University Medical prevalence of NAFLD. We were unable to determine time trends in
Center, Beer Sheva, Israel prevalence and so updates to this data will be essential to allow
Email: [email protected] ongoing appropriate service planning.
Background and aims: Non-alcoholic fatty liver disease (NAFLD) is a THU051
common liver disease; we aimed to investigate the frequency of Health-related quality of life is impaired in people living with HIV
comorbidities and malignancy among NAFLD patients compared to and hepatic steatosis
general population.
Maurice Michel1,2, Christian Labenz1,2, Malena Anders1,2,
Method: Retrospective study included all patients older than 18 years
Alisha Wahl1,2, Lisann Girolstein1,2, Leonard Kaps1,2,
with NAFLD diagnosis. A control group was matched in gender and
Wolfgang Maximilian Kremer1,2, Yvonne Huber1,2, Peter Galle1,2,
age. The data were extracted using the MDClone platform of the
Martin Sprinzl1,2, Jörn Schattenberg1,2. 1Metabolic Liver Disease
largest health maintenance organization “Clalit” in Israel.
Research Program, I. Department of Medicine, University Medical Centre
Demographics, comorbidities, malignancy and mortality were col-
Mainz, Mainz, Germany; 2 I. Department of Medicine, University Medical
lected and compared.
Centre Mainz, Mainz, Germany
Results: 211, 955 NAFLD patients (mean age 42.2 ± 15 years, 47.2%
Email: [email protected]
males) were analyzed in comparison to 452, 012 matched general
population controls (mean age 42.4 ± 14.8 years, 48.5% males). Background and aims: People living with HIV (PLWH) show a high
Significant higher rate of diabetes mellitus (23.2% vs 13.3%), obesity prevalence of hepatic steatosis and non-alcoholic fatty liver disease
(58.8% vs 27.8%), Hypertension (57.2% vs 39.9%), chronic ischemic (NAFLD). NAFLD has been linked to impaired health-related quality of

Journal of Hepatology 2022 vol. 77(S1) | S119–S388 S145

POSTER PRESENTATIONS
life (HRQL) and therefore could be an aggravating factor in PLWH. The performed with interview or questionnaires. A highly sensitive and
aim of this study was to determine differences in HRQL between specific alcohol biomarker is phosphatidylethanol in blood (PEth),
PLWH presenting with and without hepatic steatosis and to identify which only forms in the presence of ethanol. PEth has hitherto not
predictors associated with impaired HRQL. been evaluated in longitudinal NAFLD studies. This study aimed to
Method: A total of 245 PLWH were prospectively enrolled at an examine the impact of moderate alcohol consumption on histologic
outpatient clinic. Hepatic steatosis was assessed using vibration progression and to evaluate the utility of PEth in NAFLD.
controlled transient elastography (VCTE) and defined as a controlled Method: A cohort of NAFLD patients with serial biopsies were
attenuation parameter (CAP) of >275 dB/m. The cohort was then reviewed for inclusion in the study. Baseline alcohol consumption
divided into two groups: no steatosis and steatosis. The generic EQ- was <140 g/week in all patients. Anthropometric and biochemical
5D-5L questionnaire was used to determine differences in the HRQL. measurements were performed at baseline and follow-up. Alcohol
It consists of an overall value (UI-value) and five dimensions, each consumption was measured at follow-up, using three different
addressing different aspects of an individual HRQL. Univariable and methods (clinical interview, Alcohol Use Disorder Identification
multivariable linear regression models were applied to identify Test-Concise [AUDIT-C], and analysis of PEth). Patients were reviewed
predictors with impaired HRQL in both groups. for progression of steatosis, ballooning, lobular inflammation, and
Results: In this cohort of PLWH, the prevalence of hepatic steatosis significant fibrosis progression, defined as progression of fibrosis
was 35% (n = 85) of whom 76.5% (n = 65) had NAFLD and 16.5% (n = stage ≥2 stages or development of end-stage liver disease (ESLD).
14) alcoholic liver disease. The median age was 52 years (IQR 42; 58) Results: Eighty-two patients were included. Mean follow-up time
and the majority of PLWH were male (n = 174, 71%). Metabolic risk was 17.2 years (SD ± 6.0). Twenty-two patients were considered to
factors were more prevalent in the steatosis group. The mean UI- have fibrosis progression or developed ESLD. Patients with significant
value in the total cohort was 0.90 (± 0.15). The HRQL (UI-value) was fibrosis progression reported higher alcohol consumption and had
significantly lower in PLWH and steatosis in comparison to no significantly higher PEth. Progression of other histological para-
steatosis ( p = 0.013). The most strongly affected dimensions were meters (i.e., steatosis, ballooning and lobular inflammation) was
mobility ( p = 0.016) and pain/discomfort ( p = 0.012) in the steatosis unaffected during follow-up and showed no significant associations
group, and the dimension anxiety/depression was equally impaired with alcohol consumption. Consumption >66–96 grams per week (i.
in both groups ( p = 0.629) (Figure 1). Unemployment (beta = − 0.270, e., moderate alcohol consumption) was associated with increased risk
p = 0.025) and waist circumference (beta = − 0.289, p = 0.017) for significant fibrosis progression compared with no or low
remained independent predictors of a poor HRQL in the steatosis consumption. PEth ≥50 ng/ml and binge drinking showed the
subgroup. In turn, age (beta = − 0.168, p = 0.045), female sex (beta = highest risk for significant fibrosis progression (aOR 5.2 [95% CI 1.4–
− 0.173, p = 0.030), BMI (beta = − 0.214, p = 0.010) and arterial 19.6], p <0.05, and aOR 5.1 [95% CI 1.4–18.1], p <0.05, respectively).
hypertension (beta = − 0.194, p = 0.025) were independent predic- Conclusion: NAFLD patients consuming moderate amounts of
tors of a low HRQL in the subgroup without steatosis. alcohol are at increased risk for significant fibrosis progression and
development of ESLD. PEth can be used as a reliable biochemical
alcohol marker in NAFLD. Patients reporting moderate consumption
or exhibiting PEth ≥50 ng/ml should be advised to reduce alcohol
consumption.

THU053
Prevalence trends of non-alcoholic fatty liver disease among
young men in Korea: korean military population-based
cross-sectional study
Jaejun Lee1,2, Hyun Yang1, Si Hyun Bae2. 1Eunpyeong St. Mary hospital,
Department of Internal Medicine, Seoul, Korea, Rep. of South; 2College of
Medicine, Eunpyeong St. Mary’s Hospital, The Catholic University of
Korea, Department of Internal Medicine, Seoul, Korea, Rep. of South
Email: [email protected]

Figure 1: Distribution (%) of the EQ-5D-5L dimensions in PLWH and Background and aims: Non-alcoholic fatty liver disease (NAFLD) has
without hepatic steatosis (no HS) or with hepatic steatosis (HS). become a major concern in Korea since its emergence as a dominant
cause of chronic liver disease. However, no study has explored its
Conclusion: Hepatic steatosis and metabolic comorbidities nega- prevalence in adults under 30 years of age. Therefore, we performed a
tively affect HRQL. Addressing these factors may improve patient cross-sectional study to investigate the prevalence of NAFLD in
reported and liver related outcomes in PLWH. Korean men in their early twenties.
Funding: This analysis was in parts supported by a research grant Method: We collected data on 596, 359 Korean soldiers who
from Gilead Sciences. participated in a health examination between January 2015 and
July 2021. A total of 571, 872 individuals were analyzed after
THU052
excluding those with missing data and hepatitis B antigen positivity.
Moderate alcohol consumption is associated with significant
Hepatic steatosis was determined using the hepatic steatosis index
fibrosis progression in non-alcoholic fatty liver disease-a cohort
(HSI). Participants with an HSI >36 were considered to have NAFLD.
study with over 17 years of follow-up
The BARD score was used to determine the presence of advanced
Julia Blomdahl1, Patrik Nasr1, Mattias Ekstedt1, Stergios Kechagias1. fibrosis.
1
Linköping University, Department of Gastroenterology and Hepatology, Results: All participants were men, and the mean age was 20.9 ± 1.3
Department of Health, Medicine, and Caring Sciences, Linköping, years. Of the 571, 872 participants screened, 77, 020 (13.47%) were
Sweden classified as having NAFLD. The prevalence of NAFLD consistently
Email: [email protected] increased from 2015 to 2021 (10.66% vs. 16.44%, P < 0.001). Increases
Background and aims: Non-alcoholic fatty liver disease (NAFLD) from 2015 to 2021 were also noted in the prevalence of hyperchol-
affects approximately 25% of the adult population worldwide. The esterolemia (1.78% vs. 2.56%, P < 0.001), dysglycemia (10.17% vs.
effect of moderate alcohol consumption on NAFLD histology is 11.68%, P < 0.001), and hypertension (2.87% vs. 3.51%, P < 0.001). The
disputed. Assessment of alcohol consumption is commonly mean body mass index (BMI) also increased from 23.3 ± 3.0 kg/m2 to

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 POSTER PRESENTATIONS
23.9 ± 3.1 kg/m2 between 2015 and 2021 ( p <0.001). Finally, 24, 092 The pooled incidence rate of extrahepatic cancers in NAFLD is over
out of 77, 020 (31.2%) participants with NAFLD had a BARD score of 2 eight-fold higher than HCC. Extrahepatic cancer rates are not related
or greater, which was indicative of advanced fibrosis. to liver fibrosis stage thereby implicating the metabolic dysfunction
associated with NAFLD as a risk factor for these malignancies. Given
the high and increasing prevalence of NAFLD, these findings support
a public health focus on its prevention and the early detection of
cancer in adults with NAFLD.

THU055
Association of non-alcoholic fatty liver disease and fibrosis with
incident dementia and cognitive function: the Rotterdam Study
Tian Xiao1, Laurens van Kleef2, Kamran Ikram1, Robert De Knegt2,
Arfan Ikram1. 1Erasmus MC, University Medical Center, Epidemiology,
Rotterdam, Netherlands; 2Erasmus MC, University Medical Center,
Gastroenterology and Hepatology, Rotterdam, Netherlands
Email: [email protected]
Background and aims: Non-alcoholic fatty liver disease (NAFLD)
might affect brain health, via the so-called liver-brain axis. Whether
this results in increased risk for dementia remains unclear. Therefore,
Conclusion: The prevalence of NAFLD and of other metabolic we investigated the association of NAFLD and fibrosis with incident
dysfunctions (hypercholesterolemia, dysglycemia, and hypertension) dementia and cognition among the elderly.
in Korean men in their early twenties increased from 2015 to 2021. Method: We performed longitudinal and cross-sectional analyses
The Korean society should be alert for an increase in the disease within The Rotterdam Study, an ongoing prospective cohort.
prevalence and continue making efforts to reduce the associated Participants visiting between 1997 and 2002 with available fatty
complications. liver index (FLI) (set 1; n = 3, 975; FU = 15.5 years) or participants
visiting between 2009 and 2014 with abdominal ultrasound (set 2;
THU054
n = 4, 577; FU = 5.7 years) and liver stiffness (set 3, n = 3, 300; FU = 5.6
Hepatocellular and extrahepatic cancers in non-alcoholic fatty
years) were included. Exclusion criteria were secondary causes for
liver disease: a systematic review and meta-analysis
steatosis, prevalent dementia and missing alcohol data. NAFLD was
James Thomas1,2, Bradley Kendall1,2, Christine Dalais2, defined as FLI≥60 or steatosis on ultrasound and fibrosis as liver
Graeme Macdonald1,2, Aaron Thrift3. 1Princess Alexandra Hospital, stiffness ≥8.0kPa. Dementia was defined according to the DSM-III-R.
Woolloongabba, Australia; 2The University of Queensland, Saint Lucia, Cox-regression was used to quantify associations for NAFLD, fibrosis,
Australia; 3Baylor College of Medicine, Houston, United States or liver stiffness with incident-dementia and logistic regression for
Email: [email protected] NAFLD and cognitive function.
Background and aims: Non-alcoholic fatty liver disease (NAFLD) Results: NAFLD and fibrosis were consistently not associated with
affects approximately one-quarter of the global adult population. Its increased risk for dementia (NAFLD based on ultrasound, HR:0.84,
prevalence is expected to continue to increase with rising rates of 95%CI:0.61–1.16; NAFLD based on FLI, HR:0.92, 95%CI:0.69–1.22;
obesity and its associated metabolic disorders. Hepatocellular (HCC) fibrosis, HR:1.07, 95%CI:0.58–1.99) in fully adjusted models.
and extrahepatic cancers have been associated with NAFLD however Interestingly, NAFLD was associated with a significantly decreased
the extent and nature of this relationship remain to be clarified. We risk for incident dementia until five years after FLI-assessment
aimed to estimate the absolute incidence rates of these cancers in (HR:0.48; 95%CI:0.24–0.94). Moreover, NAFLD was not associated
adults with NAFLD with respect to key clinical factors. with worse cognitive function (G-factor, mean difference:0.032; 95%
Method: This systematic review and meta-analysis of published CI:-0.029–0.092).
studies reporting the incidence rates of any cancer in adults with
Table 1: Risk of incident dementia for NAFLD and liver stiffness
NAFLD was registered with PROSPERO (CRD42020164725). The
literature search of 4 databases (PubMed, Embase, Cochrane Library Fully adjusted
and Web of Science) was from inception to 31 August 2020. Teams of models
FU
independent reviewers assessed each record for inclusion with
cases (year) HR 95% CI
subsequent extraction of reported data. The main outcomes were
pooled incidences of cancers in NAFLD using a random-effects model NAFLD (FLI ≥60) 753/3975 15.5 0.92 0.69–1.22
with subgroup analyses to examine the effects of NAFLD disease NAFLD (Ultrasound) 262/4557 5.7 0.84 0.61–1.16
Fibrosis 127/3300 5.6 1.07 0.58–1.99
stage.
Liver stiffness (kPa) 127/3300 5.6 1.01 0.92–1.10
Results: The systematic review returned 10, 042 unique records from
which 64 studies including 625, 984 and 41, 027 patients were Results are given as HR and 95% CI for incident dementia as outcome. NAFLD
eligible for analysis of HCC and extrahepatic cancer incidence was either based on FLI ≥60 or on hepatic steatosis assessed with abdominal
respectively. The pooled HCC incidence rate was 1.25 per 1000 ultrasound and was compared to participants with FLI <30 or participants
person-years (95%CI 1.01–1.49; I2 = 94.8%). In NAFLD patients with without hepatic steatosis.
advanced liver fibrosis or cirrhosis, the HCC incidence rate was 14.46 Conclusion: In conclusion, individuals with NAFLD were not at
per 1000 person-years (95%CI 10.89–18.04; I2 = 91.3%). The pooled increased risk of dementia among this general elderly population, nor
extrahepatic cancer incidence rate was 10.58 per 1000 person-years could an association with fibrosis and dementia be demonstrated.
(95%CI 8.14–13.02; I2 = 97.1%). The most frequently occurring extra- Moreover, NAFLD was associated with a reduced risk of dementia for
hepatic cancer sites were uterine, breast, prostate, colorectal and the first five years after the assessment, suggesting that NAFLD
lung. Extrahepatic cancer incidence rates were not higher in NAFLD regression is likely before dementia onset, which could be driven by
patients with advanced liver fibrosis or cirrhosis. weight loss before dementia onset. As yet, NAFLD may have no
Conclusion: The rate of HCC development in NAFLD patients who clinical implications for dementia awareness. Further studies should
have progressed to advanced liver fibrosis or cirrhosis supports focus on NAFLD exposure duration and risk of dementia with longer
current HCC surveillance recommendations targeted for this group. follow-up durations.

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POSTER PRESENTATIONS
THU056 medication was recorded from patient charts. Data were compared to
High meat consumption is prospectively associated with non- the time point of the first available TE measurement.
alcoholic fatty liver disease and liver fibrosis markers Results: 90 patients were recruited (57% female, age 63.9 ± 9.6 years,
Dana Ivancovsky Wajcman1, Naomi Fliss-Isakov2, BMI 31.3 ± 5.0 kg/m2, LSM 7.4 kPa [5.3, 14.1], CAP 315 ± 57 dB/m, FAST
Laura Sol Grinshpan1, Muriel Webb2, Oren Shibolet2, Revital Kariv2, 0.38 [0.18, 0.65]). After 4.2 [3.7, 7.9] years, follow-up data were
Shira Zelber-Sagi1,2. 1University of Haifa, School of Public Health, Haifa, available from 78 cases, the remaining 12 individuals had died.
Israel; 2Tel Aviv Medical center, Gastroenterology, Tel Aviv, Israel At follow-up, patients received the following diabetes medication:
Email: [email protected]
SGLT-2 inhibitors: 17/78 (22%)
Background and aims: Non-alcoholic fatty liver disease (NAFLD) is a GLP-1 agonists: 13/78 (17%)
chronic disease related to lifestyle. The association of meat Metformin: 42/78 (54%)
consumption with NAFLD has been tested. However, the prospective Dipeptidyl-Peptidase-4 (DPP-4) inhibitors: 15/78 (19%)
association between meat consumption and steatosis incidence and Insulin: 42/78 (54%).
remission and liver fibrosis is yet to be tested. Therefore, this study
From these five drug classes, patients took a mean of 1.38 substances
aims to prospectively test the association of meat types consumption
at baseline compared to 1.65 at follow-up (difference 0.27, 95% CI 0.01
with incidence and remission of NAFLD and liver fibrosis markers.
Method: A prospective cohort study among subjects 40–70 years old, to 0.53, p = 0.046).
The net change compared to baseline was an additional 14 (18%), 10
participating in two screening days, at least five years apart. NAFLD
was determined by ultrasonography or CAP≥294 dB/m. Liver fibrosis (13%), and 7 (9%) patients on SGLT-2 inhibitors, GLP-1 agonists, and
insulin, whereas metformin and DDP-4 were used in 9 (12%) and one
was evaluated by Fibrotest (significant fibrosis ≥F2 was defined as a
(1%) fewer individuals.
result of ≥0.48) or Fibroscan (significant fibrosis ≥F2 was defined as a
result of ≥8.2 Kp). Meat consumption was assessed by a detailed food The geometric mean of LSM changed from 8.3 to 7.8 kPa for a relative
change by a factor of 0.94 (95% CI 0.85 to 1.03, p = 0.18).
frequency questionnaire (FFQ), the trajectories of consumption were
calculated as the percent of change from baseline (gr/d). Mean CAP changed from 313 to 306 dB/m for a change of − 7.4 dB/m
(95% CI − 22.8 to 7.9, p = 0.34)
Results: A total of 320 subjects had completed two screening days
The mean of FAST score changed from 0.38 to 0.31 implying an odds
and had valid FFQ. Mean follow-up of 6.65 ± 0.73 years. In
multivariate-adjusted analyses, high consumption of red and/or ratio of 0.74 (95% CI 0.56 to 0.96, p = 0.027).
Conclusion: A relevant and increasing proportion of NAFLD patients
processed meat (gr/d above the baseline consumption median) was
associated with higher risk for NAFLD with elevated ALT incidence with diabetes mellitus is treated with SGLT-2 inhibitors and GLP-1
(OR = 5.97, 1.84–19.37, P = 0.003). Unprocessed red meat consumption agonists in clinical routine. These treatments affect recruitment for
clinical studies and should be considered as confounders in case they
was associated with NAFLD with elevated ALT incidence, lower odds
for NAFLD remission, and greater odds for new or persistent are continued during the study period.
significant fibrosis, evaluated by Fibroscan (OR = 3.52, 1.22–10.17, THU058
P = 0.020; OR = 0.33, 0.14–0.78, P = 0.012; OR = 4.69, 1.43–15.40, P =
Comorbidity severity scores and cardiovascular comorbidities in
0.011, respectively). Regarding meat consumption trajectories, 10%
patients with non-alcoholic steatohepatitis (NASH), with and
daily increments in total or processed meat consumption were without cirrhosis, in a real-world setting
significantly associated with greater risk for new or persistent NAFLD
Jeffrey Lazarus1, Abhishek Shankar Chandramouli2,
(OR = 2.09, 1.20–3.65, P = 0.010; OR = 1.90, 1.04–3.46, P = 0.037,
Kamal Kant Mangla3, Zobair Younossi4. 1Barcelona Institute for Global
respectively).
Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona,
Conclusion: High consumption of red meat or processed meat is
Spain; 2Novo Nordisk Service Centre India Pvt Ltd, Bangalore, India;
associated with NAFLD and significant fibrosis in a prospective study 3
Novo Nordisk A/S, Søborg, Denmark; 4Center for Liver Disease, Inova
THU057 Medicine, Falls Church, VA, United States
Relevance of diabetes medication on recruitment criteria for Email: [email protected]
clinical studies in patients with non-alcoholic fatty disease and Background and aims: NASH is estimated to be present in 3–6% of
type 2 diabetes mellitus the US population and has been linked to end-stage liver disease, type
Michael Holzhey1, David Petroff2, Valentin Blank1, Florian Gerhardt3, 2 diabetes (T2D), and cardiovascular disease (CVD). The AWARE study
Albrecht Boehlig3, Toni Herta3, Florian van Bömmel3, Thomas Berg3, aimed to describe the association of NASH with comorbidity severity
Thomas Karlas1, Johannes Wiegand3. 1University of Leipzig, Division of scores and CVD comorbidities, which has not been well studied
Gastroenterology, Germany; 2University of Leipzig, Clinical Trial Center, previously.
Germany; 3University of Leipzig, Division of Hepatology, Leipzig, Method: Data were collected from a large US healthcare dataset
Germany covering 1 October 2015 to 31 December 2020. Records were
Email: [email protected] included for adult patients diagnosed with NASH (using ICD-10
Background and aims: Guidelines for patients with diabetes CM), with no evidence of hepatitis B or C, excessive alcohol use, or
liver transplant prior to NASH diagnosis, and with no evidence of
mellitus increasingly recommend the use of sodium-glucose cotran-
sporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) pregnancy or cancer in the study period. ICD CM coding was used to
identify all diagnoses. Statistical significance of differences in
agonists to prevent cardiovascular end points. Both drugs are
comorbidities and severity scores between cirrhotic patients (CPs)
promising candidates for treatment of non-alcoholic fatty liver
disease (NAFLD). However, pre-existing therapies with SGLT-2 and non-cirrhotic patients (NCPs) was assessed.
Results: Of 4, 989 patients identified, 489 had evidence of cirrhosis
inhibitors or GLP-1 agonists are often an exclusion criterion for
clinical trials. Thus, we analyzed use of diabetes medications and prior to NASH diagnosis. CPs were older and more progressed in
terms of NASH-relevant biomarkers, glycated haemoglobin (HbA1c),
their adjustment.
and comorbidities (Table). CVD comorbidities were significantly
Method: Patients with type 2 diabetes mellitus and NAFLD were
prospectively recruited from 2011 to 2018 and followed up in 2021. higher in CPs at baseline, including atherosclerotic CVD, as were
severity scores for T2D and comorbidities overall.
They were characterized non-invasively by transient elastography
(TE) including liver stiffness measurement (LSM), controlled attenu-
ation parameter (CAP) and Fibroscan-AST-score (FAST). Diabetes

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 POSTER PRESENTATIONS
Table: Selected baseline characteristics kidney disease (CKD) as an estimated glomerular filtrate rate (eGFR)
NCPs (n = 4, 500) CPs (n = 489) 60 ml/min per 1.73m2. NAFLD was defined as Controlled Attenuation
Parameter (CAP) ≥275 dB/m and/or Fatty liver index (FLI) ≥60 after
Age, years 52.2 (11.0) 59.6 (9.4) exclusion of the other liver diseases and alcohol consumption over 30
Female, % 55.2 62.4 gr/day in males and over 20 gr/ay in females. Multivariate regression
NAFLD, % 56.5 67.4
analysis was performed to identify predictors of extrahepatic
Provider, 20: 17: 16 28: 11: 7
Gastroenterologist: diseases.
Internist: GP, % Results: Patients with T2DM with NAFLD (n = 134) presented higher
Aspartate transaminase: 586; 0.62 (0.96) 86; 1.09 (1.57) rates of arterial hypertension (76.1% vs 61.5%, p 0.047) and obesity-
platelet ratio index* BMI ≥30 kg/m2− (61.2% vs 23.1%, p < 0.001) than T2DM-nonNAFLD
Fib-4* 493; 1.56 (1.42) 71; 4.68 (5.28) (n = 52). Distribution for gender, age and presence of dyslipidemia
NAFLD fibrosis score* 454; − 1.13 (1.63) 66; 1.74 (2.04) were similar between groups. Respect to T2DM complications, 38.6%
Quan-Charlson 1.9 (1.5) 4.4 (1.9) of T2DM-NAFLD patients showed DN compared to 19.6% T2DM-
Comorbidity Index* nonNAFLD subjects ( p 0.014). No statistical differences were found
Adaptive Diabetes 0.1 (0.4) 0.4 (1.0)
for diabetic retinopathy (25.4% vs 30.8%, p 0.45) or peripheral
Complexity Severity
Index* neuropathy (19.4% vs 17.3%, p 0.74). Of note, T2DM-NAFLD patients
BMI (kg/m2) 1, 957; 35.0 (5.7) 243; 35.1 (6.1) showed worse median creatinine and eGFR values (0.85 ± 0.26 vs
Predicted waist 1, 957; 110.4 243; 109.4 0.74 ± 0.14, p 0.001 and 80.1 ± 17.4 vs 86.1 ± 10.1, p 0.004, respect-
circumference, cm (15.0) (15.9) ively), and also presented a higher proportion of RI (71.6% vs 49.0%; p
HbA1c (%) 485; 6.9 (1.7) 64; 7.1 (1.5) 0.004) and CKD (14.2% vs 3.9%, p 0.049) respect to T2DM subjects
T2D* % 40.6 73.4 without NAFLD. Median liver stiffness did not differ among patients
Chronic kidney disease* % 5.9 17.8 with and without RI or CKD. In multivariate analysis the presence of
Diabetic neuropathy* % 6.8 22.1 NAFLD (HR = 2.48; 95%CI 1.61–5.32, p 0.019) was associated with the
CVD* % 29.8 73.0
development of RI, independently of well-known risk factors, such as
Atherosclerotic CVD*† 13.1 25.8
Heart failure* 2.2 13.3 arterial hypertension (HR = 3.23; 95%CI 1.58–6.58, p 0.001) or
Oesophageal varices* 1.2 33.3 advanced age (HR = 2.79; 95%CI 1.40–5.56, p 0.003).
Hypertensive disease* % 64.8 81.8

Data are mean (SD) or n; mean (SD) unless stated

BMI, body mass index; NAFLD, non-alcoholic fatty liver disease.
*Assessed by univariate analysis for statistical significance: p <0.001 for NCPs
vs CPs.
†Multivariate logistic regression analysis for atherosclerotic CVD, adjusted for
demographic factors: odds ratio 1.34 (1.02, 1.78); p < 0.05 for CPs vs NCPs.

Conclusion: This study found that patients with NASH are often not
diagnosed until an advanced stage, suggesting the need for greater
Conclusion: Our results suggest that NAFLD poses an increased risk
disease awareness to avoid diagnostic inertia and to better assess the
of extrahepatic diseases in T2DM patients, including other metabolic
burden associated with NASH. These data also suggest that NASH
conditions and specially kidney disease. Renal function in diabetic
correlates with a higher risk of developing comorbidities, especially
patients with NAFLD should be screened and monitored closely, since
CVD and T2D, particularly as patients progress to cirrhosis.
NAFLD may lead to further worsening of kidney disease.
THU059 THU060
NAFLD association with renal impairment in type 2 diabetes The impact of liver fibrosis on the immune response to SARS-CoV-
patients 2 vaccination in metabolic associated fatty liver disease patients
Jesús Rivera1, Monica Pons1, Alejandra Planas2, Rafael Simo Canonge2, Marta Freitas1,2,3, Tiago Capela1,2,3, Vítor Macedo Silva1,2,3,
Jordi Bañeras3, Ignacio Ferreira3, María José Soler4, Daniel Seron4, Sofia Xavier1,2,3, Joana Teixeira Magalhães1,2,3,
Joan Genesca1, Juan Manuel Pericàs1. 1Vall d’Hebron Hospital Carla Maria Moura Marinho1,2,3, José Cotter1,2,3. 1Hospital da Senhora
Universitari, Liver Unit, Spain; 2Vall d’Hebron Hospital Universitari, da Oliveira, Guimarães, Portugal, Gastroenterology Department; 2School
Diabetes and Metabolism Research Unit, Spain; 3Vall d’Hebron Hospital of Medicine, University of Minho, Braga, Portugal, Life and Health
Universitari, Cardiology Department, Spain; 4Vall d’Hebron Hospital Sciences Research Institute (ICVS); 3PT Government Associate
Universitari, Nephrology Department Laboratory, Braga/Guimarães, Portugal, ICVS/3B’s
Email: [email protected] Email: [email protected]
Background and aims: Non-alcoholic fatty liver disease (NAFLD) and Background and aims: There has been growing concern about the
type 2 diabetes (T2DM) frequently coexists in high-risk metabolic response to severe acute respiratory syndrome coronavirus 2 (SARS-
patients. NAFLD and T2DM share a multisystemic involvement and CoV-2) vaccination in patients with chronic liver disease, as it may
the coexistence of both may increase the organ damage, worsening confer an immunosuppression state, potentially being associated
the patient prognosis. The aim of this study was to evaluate the role of with a lower response to vaccination. However, this issue in
NAFLD in the development and severity of extrahepatic conditions in metabolic associated fatty liver disease (MAFLD) patients remains
a well-characterized T2DM cohort. unestablished. We aimed to assess the impact of liver fibrosis on the
Method: Prospective cohort with case-control analysis comprising immune response to SARS-CoV-2 vaccination in patients with
200 T2DM subjects with 60 non-diabetic subjects matched by age MAFLD.
with available transient elastography data. Patients were selected Method: Prospective cohort study that included MAFLD patients
from the Outpatient Diabetes Clinic of Vall d’Hebron Hospital and the with complete SARS-CoV-2 vaccination. Patients with previous SARS-
Primary Healthcare centres within its catchment area. Diabetic CoV-2 infection were excluded. Serum SARS-CoV-2 immunoglobulins
nephropathy (DN) was defined as the presence of microalbuminuria (Ig), laboratory and transient elastography (TE) data were assessed 1
>30 mg/dl. According KDIGO guidelines, we defined renal impair- month after complete vaccination. Significant fibrosis was defined as
ment (RI) as a urine albumin:creatinine ratio >30 mg/g and chronic

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POSTER PRESENTATIONS
liver stiffness measurement (LSM)≥8.2 kPa, NAFLD fibrosis score≥- 1- and 5-year post-LT and only 2 cases of graft loss due to recurrence
1.455, FIB-4 score≥1.45, or FAST score>0.35. of primary disease. The greatest number of deaths occurred within
Results: Thirty-seven patients were included, 62.2% of male gender, the first year after transplantation (n = 10), none of them related to
with a mean age of 55 ± 9 years. The mean LSM was 6.9 ± 2.9 kPa and primary liver disease.
32.4% of patients had significant fibrosis in TE. The mean SARS-CoV-2
IgG levels were 10048 ± 9395 U/ml and all patients had response to
vaccination (IgG≥50 U/ml). There were no differences in SARS-CoV-2
IgG levels regarding gender ( p = 0.93), presence of obesity ( p = 0.20),
metabolic syndrome ( p = 0.26), diabetes ( p = 0.70), hypertension
( p = 0.52), dyslipidemia ( p = 0.96), and tobacco use ( p = 0.99). There
were no differences in SARS-CoV-2 IgG levels between patients with
or without significant fibrosis ( p = 0.13) in TE, NAFLD fibrosis score
( p = 0.18), FIB-4 score ( p = 0.56), or FAST score ( p = 0.24).
Conclusion: In our cohort, all MAFLD patients had Ig response to
vaccination. Significant liver fibrosis did not compromised response
of MAFLD patients to SARS-CoV-2 vaccination. SARS-CoV-2 vaccin-
ation is serologically effective in MAFLD patients, regardless of
fibrosis.

THU061
Non-alcoholic steatohepatitis is also becoming a major liver
transplant indication in Spain, a historically low risk area
Conclusion: NAFLD is an increasingly common indication for LT in
Laura Martínez-Arenas1, Ângela Carvalho-Gomes2,
our country. However, the incidence is still far from that described in
Fernando Diaz Fontela3, Sara Lorente Perez4, Marta Guerrero5,
countries like the US. As reported, most of these transplant
Jose Ignacio Herrero6, Marina Berenguer7. 1Instituto de Investigación
candidates have significant comorbid conditions associated with
Sanitaria La Fe, Hepatology, Hepatobiliopancreatic Surgery and
posttransplant complications and poorer long-term outcome such as
Transplant, Valencia, Spain; 2Instituto de Investigación Sanitaria La Fe,
obesity, T2DM, HTN, DL and CVD. Yet, in the short-midterm
CIBERehd, Hepatology, Hepatobiliopancreatic Surgery and Transplant,
transplant survival is similar to that reported by the Spanish Liver
Valencia, Spain; 3Hospital General Universitario Gregorio Marañón,
Transplantation Registry, with a survival rate of 87% and 75% at 1- and
Liver Unit and Digestive Department, Madrid, Spain; 4Hospital Clínico
5- year post-LT, respectively.
Universitario Lozano Blesa, Hepatology and Liver Transplantation Unit,
Zaragoza, Spain; 5Hospital Universitario Reina Sofía, Instituto THU062
Maimónides de Investigación Biomédica de Córdoba, CIBERehd, Total healthcare cost and characteristics associated with higher
Department of Hepatology and Liver Transplantation, Córdoba, Spain; change in cost in patients with non-alcoholic steatohepatitis
6
Clínica Universidad de Navarra, Instituto de Investigación Sanitaria de
Zobair Younossi1, Kamal Kant Mangla2,
Navarra, CIBERehd, Department of Internal Medicine, Pamplona, Spain; Abhishek Shankar Chandramouli3, Jeffrey Lazarus4. 1Center for Liver
7
Hospital Universitario y Politécnico La Fe, Instituto de Investigación
Disease, Inova Medicine, Falls Church, VA, United States; 2Novo Nordisk
Sanitaria La Fe, Universidad de Valencia, CIBERehd, Hepatology and Liver A/S, Søborg, Denmark; 3Novo Nordisk Service Centre India Pvt Ltd,
Transplantation Unit, Valencia, Spain Bangalore, India; 4Barcelona Institute for Global Health (ISGlobal),
Email: [email protected]
Hospital Clínic, University of Barcelona, Barcelona, Spain
Background and aims: Non-alcoholic fatty liver disease (NAFLD) is Email: [email protected]
becoming one of the most common chronic liver diseases in Spain,
Background and aims: The economic burden in patients with non-
particularly in individuals with features of metabolic syndrome, yet alcoholic steatohepatitis (NASH) is often underestimated. The AWARE
its exact prevalence and incidence are not completely known. In fact,
study collected baseline data on patients with NASH to determine the
non-alcoholic steatohepatitis (NASH) is a growing indication for liver
associated healthcare cost burden.
transplantation (LT) in our setting. Our aim was to describe NAFLD Method: Data were collected from a large US healthcare dataset
evolution as a LT indication and the most frequently found features
(electronic health records linked with claims) from 1 October 2015 to
associated with this indication. 31 December 2020. Adult patients diagnosed with NASH, with no
Method: Patients undergoing LT for NASH-related cirrhosis from
evidence of hepatitis B or C, excessive alcohol use, or liver transplant
2010 to 2020 in five reference LT centers in Spain were included. The
prior to NASH diagnosis, and with no evidence of pregnancy or cancer
medical records of all these patients were reviewed for determining in the study period, were included. All diagnoses were made using
NASH-associated comorbidities. Survival analyses were performed
ICD CM. Total healthcare follow-up costs and change in total
with SPSS to determine survival rates at different follow-up points healthcare cost post-NASH are reported as mean (standard devi-
after LT. ation). The effect on change in cost by baseline characteristics was
Results: NASH-related cirrhosis was the LT indication in 118 patients
assessed using a multivariate generalised linear model.
from 2010 to 2020. Taking into account the five centers, the Results: Of 4, 989 adult patients diagnosed with NASH, 489 had
percentage of LT for NASH increased 3.8-fold between 2010–2020,
evidence of cirrhosis at baseline. Mean follow-up was 22 months for
from 2.0% to 7.5% (Figure 1). The highest percentage (25.0%) was non-cirrhotic patients (NCPs) and 21 months for cirrhotic patients
registered in 2020 in one of the centers. While there were no (CPs). Annualised follow-up costs (US$) were $28, 707 ($140, 814) for
transplants performed for NASH in some centers in some of the years,
NCPs and $84, 582 ($204, 552) for CPs. Among NCPs, approximately
mainly in the first years of the study, the number has progressively 70% had a high annual cost burden (>$5, 000) and 38% had a very high
increased since 2015. Comorbid conditions were found in most
cost burden (>$15, 000) (Figure). Increases in costs following onset of
patients; 77.1% had obesity, 59.3% type 2 diabetes mellitus (T2DM),
NASH were $13, 202 ($141, 095) for NCPs and $44, 509 ($177, 055) for
61.9% hypertension (HTN), 37.3% dyslipidemia (DL) and 22.0% a CPs. For NCPs, the change in costs post-NASH diagnosis significantly
history of prior cardiovascular disease (CVD). While posttransplant
increased (in %) with increasing Quan-Charlson Comorbidity Index
complications were frequent, survival was similar to that of other score (21% per unit increase) and adaptive Diabetes Complexity
indications with a cumulative proportion surviving of 0.92 and 0.8 at
Severity Index score (36% per unit increase), increasing use of

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 POSTER PRESENTATIONS
cardiovascular (CV) drug classes (8%) and anti-diabetes medication with IPTW adjusted for cirrhosis and malignancy revealed that
classes (12%), and presence (vs absence) of CV disease (71%) and patients without NAFLD/NASH had a significantly shorter mean LOS
osteoarthritis (51%) at baseline. Female (vs male) patients had higher and reduced odds of IMV use with no difference in in-hospital
follow-up costs and a larger change in costs. mortality and readmission vs patients with NAFLD/NASH (Table),
controlled for age, sex, race and other NAFLD-related comorbidities
(eg, diabetes, obesity).

Figure: Annualised follow-up total healthcare cost (US$) for patients with
NASH

Conclusion: NASH correlates with noticeable total healthcare cost Conclusion: Real-world US hospital data suggests that patients
and increases in costs following onset of NASH for all patients. The hospitalised with COVID-19 who also have NAFLD/NASH have worse
costs reported here are reflective of short-term burden. This analysis hospitalisation-related outcomes than those without NAFLD/NASH.
did not include indirect costs or costs associated with loss of work
productivity. Due to the unavailability of approved treatments for THU064
patients with NASH, the cost burden is expected to increase with the Estimating the prevalence of advanced fibrosis due to non-
presence and increasing severity of comorbidities. Therefore, the aim alcoholic fatty liver disease in the United States population
of managing NASH through pharmacotherapy should be to stop Naim Alkhouri1, Julia Yang Payne2, Pankaj Aggarwal1, Prido Polanco1,
progression to cirrhosis and to manage NASH-related comorbidities. Phillip Leff1, Mazen Noureddin3, Phuc Le2. 1Arizona Liver Health,
United States; 2Cleveland Clinic, United States; 3Cedars-Sinai Medical
THU063 Center, United States
Non-alcoholic fatty liver disease (NAFLD)/non-alcoholic Email: [email protected]
steatohepatitis (NASH) is associated with worse outcomes in
Background and aims: Previous estimates of the prevalence of
patients hospitalised for COVID-19: a real-world analysis of a large
advanced fibrosis (AF) due to NAFLD in the general US population
population from the premier healthcare database
utilized non-invasive tests that have relatively low positive predictive
Frank Tacke1, Fady Tanios2, Lin Xie2, Deepa Malhotra2,
value leading to potentially overestimating the true prevalence. The
Simon Dagenais2, Nino Katchiuri2, Birol Emir2. 1Charité University
AGILE 3+ score was developed by combining routine clinical variables
Medical Center, Berlin, 2Pfizer Inc, New York, United States
and vibration-controlled transient elastography parameters to
Email: [email protected]
specifically increase the PPV of predicting AF. Our aim was to estimate
Background and aims: NAFLD and NASH contribute to the global the prevalence of AF due to NAFLD using the AGILE3+ score in the
burden of liver disease. Previous studies suggest an association general US adult population.
between NAFLD/NASH and the severity of COVID-19 illness. This Method: Our study population included participants aged ≥18 years
analysis aimed to characterise the impact of NAFLD/NASH on old who had a complete VCTE exam in the national health and
hospitalisation-related outcomes for patients with COVID-19 using nutrition examination survey (NHANES) 2017–2018 cycle. We
hospital administrative data from the United States (US) Premier excluded pregnant women, patients with excessive alcohol con-
Healthcare Database Special Release (PHD-SR). sumption defined as >2 drinks/day for males and >1 drink/day for
Method: Adults with COVID-19 ( primary or secondary International females, hepatitis B or C, and ALT or AST >500 IU/L.
Classification of Diseases [ICD]-10 diagnosis code U07.1) hospitalised NHANES used FibroScan model 502 V2 Touch equipped with medium
for the first time (index event) and discharged between 1 Apr 2020 and extra-large probes. The presence of NAFLD was based on having a
and 31 Mar 2021 were examined. Pregnant patients and those with CAP score >248 dB/m. NAFLD subjects with AGILE3+ score of ≥0.68
human immunodeficiency virus, alcohol dependence/abuse, viral were considered to have AF (rule-in), 0.45–0.67 were to be the grey
hepatitis, biliary cirrhosis or sclerosing cholangitis were excluded. zone, and <0.45 were considered low risk for AF (rule-out).
Cases with NAFLD/NASH (ICD-10: K75.81, K76.0) at index or 3 months Results: Our cohort consisted of 1244 subjects with evidence of
pre-index (in- or outpatient) hospitalisation were matched to NAFLD and complete data to calculate the AGILE3+ score. The Median
controls without NAFLD/NASH using exact matching for age; age was 52.5 (50.7–54.2) years, 54.9% were male, median BMI was
propensity scores were calculated for sex, race and other variables. 32.7 kg/m2 and 36.2% had type 2 diabetes. Based on AGILE3+ score
Outcomes included length of stay (LOS), invasive mechanical <0.45, 80.3% (95%CI: 77.1–83.2) of the NAFLD population were at low
ventilator (IMV) use, in-hospital mortality and all-cause network- risk for AF. 11.5 (9.2–14.5) of patients were in the grey zone and would
hospital readmission within 30 days of index event discharge. Linear have needed another test to determine the presence of AF. The overall
and logistic regression with inverse probability treatment weight prevalence of AF due to NAFLD was 8.1 (6.2–10.6) corresponding to
(IPTW) compared outcomes in cases and controls. 4.5 million Americans. Patients with AF were older, more likely to be
Results: The PHD-SR dataset included 513, 623 eligible patients; 14, obese and have type 2 diabetes.
672 (2.9%) with a NAFLD/NASH diagnosis. Among 29, 334 patients Conclusion: Using NHANES 2017–2018, our results suggest that
analysed (14, 667 cases with NAFLD/NASH and 14, 667 matched approximately 4.5 million people in the US have AF due to NAFLD
controls), mean (standard deviation) age was 57.5 (15.0) years, 51.0% based on the AGILE3+ score. Evaluating the cost-effectiveness of
were female and 43.8% were white non-Hispanic. Baseline character- using AGILE3+ as a screening tool in high-risk populations is needed
istics (eg, age, sex, race) were similar (standard difference <0.10) in before implementing in clinical practice.
cases and controls, except for cirrhosis (9.7% cases vs 0.5% controls)
and malignancy (13.6% cases vs 10.2% controls). Regression analysis

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POSTER PRESENTATIONS
THU065
Non-alcholic fatty liver disease associated liver fibrosis is linked
with the severity of coronnary artery disease mediated by
systemic inflammation
Xianbin Cai1, Lingzi Chen1. 1The First Affiliated Hospital of Shantou
University Medical College, Department of Gastroenterology, Shantou,
China
Email: [email protected]
Background and aims: Non-alcoholic fatty liver disease (NAFLD) is
an independent risk factor of cardiovascular disease. Hepatic fibrosis
is the most significant determinant of all cause- and liver -related
mortality in NAFLD. However, the relationship between NAFLD
fibrosis and severe coronary artery disease (CAD) remains unclear.
Method: We conducted a retrospective study of 531 patients with
ultrasonogram-confirmed NAFLD who underwent percutaneous
coronary intervention (PCI). Then all patients were separated into
four categories by Gensini score (0, 0–9, 9–48, ≥48) for use in ordinal
logistic regression analysis to determine whether NAFLD fibrosis was Figure 2: Mediated Model of Fibrosis Markers with Gensini Score.
(1) The coefficient a is the effect of fibrosis markers on the inflammation
associated with increased Gensini scores. Mediation analysis were
markers; (2) the coefficient b is the effect of inflammation markers on
used to investigate whether systemic inflammation is a mediating Gensini score after controlling the influence of fibrosis markers; (3) the
factor in the association between NAFLD fibrosis and CAD severity. coefficient c’ is the direct effect of fibrosis markers on Gensini score after
Results: FIB-4 >2.67 (OR = 5.67, 95%CI 2.59–12.38) and APRI >1.5 (OR controlling the influence of inflammation markers. Dash line means the
= 14.8, 95%CI 3.24–67.60) remained to be independent risk factors for pathway is statistically significant.
the severity of CAD after adjusting for conventional risk factors,
whereas among the inflammation markers, only neutrophils and Conclusion: NAFLD patients with advanced fibrosis are at a high risk
neutrophil-to-lymphocyte ratio (NLR) were independently asso- of severe coronary artery stenosis, and inflammation might mediate
ciated with CAD. Multivariable ordinal regression analysis suggested the association between NAFLD fibrosis and CAD severity.
that increasing Gensini score (0, 0–9, 9–48, ≥48) was associated with
advanced NAFLD fibrosis. ROC curve showed that either fibrosis THU066
markers or inflammation markers, integrating with traditional risk Prevalence of portal vein thrombosis in non-alcoholic fatty liver
factors, could increase the predictive capacity for determining CAD disease related cirrhossis: a meta-analysis of observational
(Figure 1). Inflammation markers, especially neutrophils and NLR, studies
were mediators of the relationship between NAFLD fibrosis and CAD Roberta Stupia1, Filippo Cattazzo1, Alessandro Mantovani2,
severity (Figure 2). David Sacerdoti1, Andrea Dalbeni1. 1Azienda Ospedaliera Universitaria
Integrata Verona, General Medicine, Hypertension and Liver Unit,
Verona, Italy; 2Azienda Ospedaliera Universitaria Integrata Verona,
Endocrinology, Diabetes and Metabolism, Verona, Italy
Email: [email protected]
Background and aims: Portal vein thrombosis (PVT) is a common
complication of cirrhosis because of modification in hemodynamics
and hemostatic balance, especially in decompensated stage1.
Furthermore, patients with non-alcoholic fatty liver disease

Figure 1: (abstract: THU065): Receiver Operating Characteristics (ROC) Curve Analysis of the Predictive Power of Fibrosis markers, NLR and Neutrophil for
CAD.
APRI model, FIB-4 model, NLR model, Neutrophil model, APRI + Neutrophil, FIB-4 + Neutrophil: new models integrating non-invasive markers and recog-
nized risk factors for CAD (gender, age, smoking, hypertension, DM, triglyceride, HDL, LDL).

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 POSTER PRESENTATIONS
(NAFLD) related cirrhosis seem to be at higher risk of PVT specialist outpatient clinic; to date, data being available from bariatric
development than patients with cirrhosis due to other causes2. surgery patient series only. For this purpose, we aimed to evaluate the
Nevertheless, definitive data in favor of an increased rate of PVT in prevalence of MAFLD and the applicability of non-invasive tests
NAFLD are missing. This meta-analysis attempted to estimate the (NITs) for fatty liver and liver fibrosis identification in an outpatient
prevalence of PVT in patients with NAFLD related cirrhosis. specialist clinic in Italy.
Method: We systematically searched PubMed, Scopus and Web of Method: We consecutively screened patients with obesity (PwO)
Science databases from the inception date to November 1st 2021 who attended our outpatient obesity clinic from January 2020 to June
using predefined keywords to identify observational cohort studies. 2021. Diagnosis of MAFLD was based on results from abdominal
Meta-analysis was performed using random-effects modelling. ultrasound (US); the anthropometric and laboratory data of the
Results: We included seven articles published over the past 10-year patients were collected, and the Fatty Liver Index (FLI), Fibrosis-4
period reporting a total of 231.399 cirrhotic patients from five (FIB4) and NAFLD (NFS) scores were calculated. Liver fibrosis was
different countries. NAFLD-cirrhosis patients were 26853 (11, 6%), assessed within one month of the first visit using liver stiffness
whith a PVT incidence of 6.5% (n = 1748). Meta-analysis demon- measurements (LSM) by transient elastography (FibroScan); Probe-
strated a significant positive association between NAFLD and PVT (OR specific LSM cut-offs were used to detect significant (F≥2) and
1.37, 95% CI 1.06–1.78 p <0, 001). The between-study heterogeneity advanced (F≥3) fibrosis and NASH cirrhosis. In a subgroup, hepatic fat
was substantial (I2 = 92, 73%). was also evaluated through controlled attenuation parameters (CAP)
After stratifying the eligible cohort studies by country, we observed with the FibroScan Expert 630 apparatus; all patients underwent oral
that, compared to other regions, in European patients the incidence of glucose tolerance test (OGTT).
PVT in NAFLD-cirrhosis was higher (OR: 2.03, 95% CI 0.30–13.53) than Results: Among 249 PwO, according to the WHO obesity classifica-
in North-American patients (OR: 1.42, 95% CI 1.05–1.94) and Arabian tion, obesity I °, II °, III ° was classified in 144 (57.8%), 56 (22.5%), 49
patients (OR: 1.36, 95% CI 0.97–1.91). (19.6%), respectively. In addition, about half of the PwO had type 2
By a meta regression analysis, neither age nor diabetes seemed to diabetes (T2DM) or impaired glucose tolerance (IGT) with a median
impact on the relationship between NAFLD and PVT. HOMA index of 3.6 (IQR 2.44–4.94). According to US or FLI
definitions, the prevalence of MAFLD was 90.4% and 91.6% and did
not differ significantly in the different WHO categories of obesity ( p
value 0.264). The distribution of hepatic steatosis classification on
ultrasound was 25.8%, 38.7%, 35.6% for mild, moderate, and severe
steatosis, respectively. The median CAP values were 287 dB/m (IQR
262–337). According to LSM values, 29%, 18% and 9.8% had significant
fibrosis, advanced fibrosis, and NASH cirrhosis, respectively. The
median LSM value was 5.4 kPa (IQR 4.3–7.5). The liver fibrosis
prevalence significantly increased according to WHO categories of
obesity ( p value <0.0001). Applying the screening with NITs, 10% and
9% of patients are wrongly classified, and this leads to misclassify
about 50% and 11.4% of patients with advanced fibrosis using FIB-4 or
NFS, respectively; moreover, 34.1% and 54.5% of patients with
advanced fibrosis result in the grey area of the two tests respectively.
Conclusion: This meta-analysis suggests that NAFLD-cirrhosis is
associated with an increased risk of developing PVT. Further research
is required to understand the complex link between NAFLD and PVT
development.
References
Englesbe MJ, Kubus J, Muhammad W, Sonnenday CJ, Welling T, Punch JD,
Lynch RJ, Marrero JA, Pelletier SJ. Portal vein thrombosis and survival in Conclusion: The results from the present study in a real-world
patients with cirrhosis. Liver Transpl 2010; 16: 83–90 [PMID: 20035521 setting strongly advocate for routine screening for MAFLD and NASH
DOI: 10.1002/lt.21941]
by LSM in PwO, regardless of WHO category, attending the outpatient
Lin H, Bai Z, Guo X, Qi X. Association between non-alcoholic fatty liver
disease and portal vein thrombosis: a systematic review and meta- specialist clinic for obesity.
analysis. Eur J Gastroenterol Hepatol. 2020 Oct;32 (10):1405–1406. doi:
10.1097/MEG.0000000000001689. PMID: 32858662.

THU067
Real-world prevalence of metabolic associated fatty liver disease
(MAFLD) and fibrotic-non-alcoholic steatohepatitis (NASH) in
patients with obesity (PwO) in an outpatient specialist clinic in
Italy
Federico Ravaioli1, Maria Letizia Petroni1, Francesca Marchignoli1,
Laura Leoni1, Giulia Bocedi1, Federica Sacilotto1, Valentino Osti1,
Dorina Mita1, Francesca Barbanti1, Lucia Brodosi1,
Giulio Marchesini Reggiani1, Loris Pironi1. 1IRCCS Azienda Ospedaliero‐
Universitaria di Bologna, Dipartimento di Scienze Mediche e Chirurgiche
(DIMEC)
Email: [email protected]
Background and aims: Obesity is a major player of "metabolic
dysfunction associated fatty liver disease" (MAFLD); however, scanty
data is available on the prevalence of MAFLD and non-alcoholic
steatohepatitis (NASH) in patients presenting with obesity to a

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POSTER PRESENTATIONS
THU068 THU069
Postprandial dysfunction in metabolic associated fatty liver Lean non-alcoholic fatty liver disease patients from the global
disease (MAFLD) NASH registry
Josephine Grandt1,2, Anne Sofie Jensen1,2, Mikkel Werge1, Zobair Younossi1,2,3, Yusuf Yılmaz4, Ming-Lung Yu5,
Elias Rashu1, Anders Junker1, Lise Hobolth1, Christian Mortensen1, Vincent Wai-Sun Wong6, Marlen Castellanos-Fernandez7,
Maria Kristiansen2, Mogens Vyberg3,4, Reza Serizawa4, Søren Møller5, Vasily Isakov8, Ajay Kumar Duseja9, Nahum Méndez-Sánchez10,
Lise Lotte Gluud1, Nicolai J. Wewer Albrechtsen2,6,7. 1Gastro Unit, Yuichiro Eguchi11, Elisabetta Bugianesi12, Patrizia Burra13,
Copenhagen University Hospital Hvidovre, Denmark, Hvidovre, Jacob George14, Jian-Gao Fan15, George Papatheodoridis16,
Denmark; 2Novo Nordisk Foundation Center for Protein Research, Wah-Kheong Chan17, Khalid Alswat18, Saeed Sadiq Hamid19,
Faculty of Health and Medical Sciences, University of Copenhagen, Ashwani Singal20, Manuel Romero Gomez21, Stuart C Gordon22,
Copenhagen, Denmark, København, Denmark; 3Center for RNA Stuart Roberts23, Mohamed El Kassas24, Marcelo Kugelmas25,
Medicine, Department of Clinical Medicine, Aalborg University, Janus Ong26, Saleh Alqahtani27, Mariam Ziayee2, Brian Lam1,2,
Copenhagen, Aalborg, Denmark; 4Department of Pathology, Copenhagen Issah Younossi28, Andrei Racila1,2, Linda Henry28, Maria Stepanova28.
1
University Hospital Hvidovre, Denmark, Hvidovre, Denmark; Center for Liver Disease, Inova Medicine; 2Beatty Liver and Obesity
5
Department of Clinical Physiology and Nuclear Medicine, Center for Research Program, Inova Health System; 3Inova Medicine, Inova Health
Functional and Diagnostic Imaging and Research, Copenhagen System; 4Marmara Üniversitesi Tıp Fakültesi; 5Kaohsiung Medical
University Hospital Hvidovre, Denmark, Denmark; 6Department of University Chung-Ho Memorial Hospital; 6The Chinese University of
Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark, Denmark; Hong Kong; 7Instituto Nacional de Gastroenterología, La Habana, Cuba;
7 8
Department of Biomedical Sciences, Faculty of Health and Medical Federal Research Center of Nutrition and Biotechnology; 9PGIMER;
10
Sciences, University of Copenhagen, Copenhagen, Denmark, Denmark Medica Sur Clinic and Foundation; 11Saga University; 12University of
Email: [email protected] Torino; 13Padova University Hospital; 14Westmead Hosp/Westmead
Institute; 15Shanghai Jiaotong University School of Medicine; 16Laiko
Background and aims: Fatty liver disease has been associated with
General Hospital; 17University of Malaysia, Department of Medicine;
metabolic disturbances. MAFLD is defined as hepatic steatosis with 18
Liver Disease Research Center, Department of Medicine, College of
either overweight, type 2 diabetes (T2D), or at least two metabolic
Medicine, King Saud University; 19Department of Medicine, Aga Khan
comorbidities. We hypothesized that metabolic disturbances asso-
University; 20University of South Dakota and Avera Transplant Institute;
ciated with liver disease are pronounced in the postprandial phase 21
Digestive Diseases Department. Virgen del Rocío University Hospital.
and may be identified by a standardized meal. We therefore aimed to
Institute of Biomedicine of Seville. University of Seville; 22Henry Ford
study the fasting and postprandial state in biopsy-proven healthy,
Hospital, Department of Hepatology and Gastroenterology; 23The Alfred,
MAFLD and cirrhosis.
Department of Hepatology and Gastroenterology; 24Endemic Medicine
Method: We included 29 participants, 10 healthy controls (age 23 ± 0
Department, Faculty of Medicine, Helwan University; 25South Denver
years, BMI 25 ± 1 kg/m2), 9 patients with non-alcoholic fatty liver
Gastroenterology, PC; 26University of the Philippines, College of
disease (NAFLD) (age 50 ± 5 years, BMI 35 ± 2 kg/m2, no/mild fibrosis)
Medicine; 27King Faisal Specialist Hospital and Research Center;
and 10 patients with cirrhosis (age 62 ± 3 years, BMI 32 ± 2 kg/m2, 28
Center for Outcomes Research in Liver Disease
Child A/B). None of the included participants had T2D. The
Email: [email protected]
participants were randomized 1:1 to “fasting” or “postprandial”
(Nutridrink, Nutricia, 300 kcal). Blood samples were obtained at Background and aims: Although vast majority of patients with
baseline and 15, 45, 60, 90 and 120 minutes. At time point 60, blood NAFLD are overweight and obese, NAFLD can be seen among lean
from the liver vein was collected and a transjugular liver biopsy was individuals. The aim was to assess prevalence of lean NAFLD in
performed. Levels of glucose, insulin, C-peptide, glucagon, and different regions of the world.
fibroblast growth factor 21 (FGF21) were measured in peripheral Method: The Global NASH Registry enrolled patients with an
blood, and glucagon and FGF21 as well in liver vein blood. Results are established diagnosis of NAFLD from real-world practices in 18
presented as ± SEM. Peak concentrations were calculated as mean ± countries (Australia, China, Cuba, Egypt, Greece, Hong Kong, India,
SEM of individual peaks. The analyses compared controls versus Italy, Japan, Saudi Arabia, Malaysia, Mexico, Pakistan, Russia, Spain,
NAFLD and cirrhosis. Taiwan, Turkey, USA) in 6 out of 7 Global Burden of Disease (GBD)
Results: 8/9 patients with NAFLD and 9/10 patients with cirrhosis super-regions. Clinical and patient-reported outcomes (PRO) data
were classified as MAFLD. Postprandial increase in glucose and C- (CLDQ-NASH, FACIT-F, WPAI) were collected. Lean NAFLD was defined
peptide was significantly greater in NAFLD and cirrhosis compared to as NAFLD in patients with BMI <25 kg/m2, or 23 kg/m2 for patients of
controls, with peak glucose of 7 and 10 mmol/L ( p = .006), and peak East Asian origin.
C-peptide of 2675 ± 273 and 3340 ± 1048 pM versus 1689 ± 190 pM. Results: There were 6096 NAFLD patients included (as of November
Postprandial iAUC for insulin was greatest in patients with NAFLD 10, 2021): 48% from High-Income super-region, 24% Middle East and
( p = .037). Patients with NAFLD and cirrhosis had hyperglucagone- North Africa (MENA), 12% Southeast Asia, 7% Latin America, 6% from
mia, a phenotype causally related to prediabetes. FGF21 was Eastern Europe and Central Asia, and 3% South Asia super-region. Of
significantly increased in NAFLD and cirrhosis and correlated to age these, 7.3% were lean. The rates of lean NAFLD were the highest in
(r = .61, p = .001) and fasting glucose (r = .54, p = .006). Glucagon was Southeast Asia (12%) and South Asia (31%), the lowest in Eastern
higher in liver vein compared to peripheral blood while FGF21 levels Europe and Central Asia (<2%) and MENA (4%) ( p < 0.0001). In
were similar in liver and peripheral blood. comparison to overweight/obese patients, lean NAFLD patients were
Conclusion: We found significant metabolic dysfunction after a test older (mean age 53 vs. 51 years) and predominantly of Asian race
meal in patients with MAFLD without diabetes compared to healthy (48% vs. 18%) (p < 0.01). Furthermore, lean patients had lower rates of
controls and that finding that was pronounced in cirrhosis. Patients diabetes (28% vs. 41%), hypertension (35% vs. 52%), hyperlipidemia
with MAFLD had impaired glucose tolerance, hyperinsulinemia and (40% vs. 50%), sleep apnea (8% vs. 33%), clinically overt fatigue (25% vs.
hyperglucagonemia, suggesting MAFLD to be a condition of 36%), and histologic cirrhosis (10% vs. 15%), but more abdominal pain
prediabetes. (25% vs. 18%) and higher FIB-4 scores (mean 1.8 vs. 1.3) (all p ≤0 .02).
In multivariate analysis, having lean NAFLD (as opposed to over-
weight/obese NAFLD) was independently associated with older age
(OR = 1.019 (1.008–1.030) per year), enrollment outside of MENA
region (OR = 0.43 (0.31–0.58)) and from South Asia (OR = 5.01 (3.42–
7.45)) sites (reference: High-Income), absence of type 2 diabetes

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 POSTER PRESENTATIONS
(OR = 0.61 (0.46–0.80)) and hypertension (OR = 0.46 (0.35–0.60)), endocrinology referred 1% of all patients. We noted higher rates of
and presence of regular exercise (OR = 1.55 (1.21–2.00)) (all p < 0.01). fibrotic NAFLD patients with FIB-4 ≥1.3 in current referrals compared
Lean NAFLD also had higher PRO scores than overweight/obese to prior (63% vs 41%). Furthermore, 32% of current referrals were with
NAFLD (all domains of CLDQ-NASH and FACIT-F) (all p < 0.01) (Figure). severe fibrotic disease defined by FIB-4 >2.67 vs 11% previously (Fig
In multivariate analysis, lower total CLDQ-NASH scores (range 1–7) in 1). This suggested an increase in appropriate referrals for specialty
lean NAFLD patients were independently associated with enrollment care. Secondary fibrotic testing using imaging modalities such as
from MENA region, history of anxiety, depression, fatigue, and ultrasound or magnetic resonance elastography was done in 36% of
abdominal pain (beta from − 0.40 to − 0.67 for each condition) ( p < those with FIB-4 ≥1.3, suggesting room for further refinement.
0.01).

Conclusion: Lean NAFLD patients seen in real-world practices across

the world have different clinical and PRO profiles in comparison to
NAFLD patients who are overweight or obese.
Conclusion: Automated FIB-4 score in EHR can improve appropriate
THU070 linkage-to-care for at-risk fibrotic NAFLD, especially when coupled
Automated FIB-4 calculator and targeted provider education with targeted provider education. The durability of such improve-
improved referral of at-risk fibrotic NAFLD patients ment is essential to study along with the need to increase broad
Cindy Piao1, Elvis Arteaga2, Connor Reilly2, Jesse Simpson2, acceptance across health systems.
Ryan Peck2, Trevor Pratt2, Troy Peterson2, Mopelola Adeyemo3,
Shuai Chen2, Aili Guo2, Scott MacDonald2, Souvik Sarkar1. 1UC Davis References
Health-Gastroenterology, Sacramento, United States; 2UC Davis Medical Leung et al., PMID: 3227318
Center, Sacramento, United States; 3University of California, Los Angeles, Srivastava et al., PMID: 30965069
Los Angeles, United States
THU071
Email: [email protected]
Long term outcomes of non-alcoholic fatty liver disease (NAFLD)
Background and aims: Non-alcoholic fatty liver disease (NAFLD) is and metabolic associated fatty liver disease (MAFLD)
the leading cause of chronic liver disease with increasing rates Zobair Younossi1,2,3, James Paik2,3, Issah Younossi4, Pegah Golabi1,2,3,
globally. Patients with a higher degree of liver fibrosis in NAFLD are at Michael Harring1, Linda Henry1,2,4. 1Inova Health System, Inova
an increased risk for liver-related mortality but get missed easily Medicine; 2Beatty Liver and Obesity Research Program, Inova Health
during the referral process, based on our1 and other prior data2. Our System; 3Center for Liver Disease, Inova Medicine; 4Center for Outcomes
project aims to improve early detection and linkage-to-care of fibrotic Research in Liver Disease
NAFLD patients using a combination of automated electronic health Email: [email protected]
record (EHR)-based FIB-4 score and directed provider education
Background and aims: NAFLD and MAFLD are part of the spectrum
within our tertiary care center, serving a large population of Northern
of fatty liver disease (FLD). Our aim was to compare the outcomes of
California.
patients with NAFLD or MAFLD.
Method: We implemented a health-system wide FIB-4 score
Method: Using data from NHANES III and NHANES 2017–2018, FLD
calculator, embedded in the EHR that providers can easily add to
was defined as moderate to severe hepatic steatosis by ultrasound
their workflow for NAFLD patient triaging. Subsequently we provided
(NHANES III) or controlled attenuation parameter (CAP) of ≥285 dB/
targeted education to all relevant providers taking care of NAFLD
m (NHANES 2017–2018). Death data were obtained from National
patients. All referrals for NAFLD (defined by specific ICD 9/10 codes),
Death Index (NDI). NAFLD was defined as FLD without other liver
to the hepatology from February 2020- August 2021, were retrieved.
diseases and excessive alcohol consumption (EAC). MAFLD was
Patient characteristics were determined with FIB-4 score being
define as FLD with metabolic dysfunction-one of the following three
essential for determination of fibrotic NAFLD and comparative
criteria, overweight/obesity, presence of type 2 diabetes mellitus or
analysis with prior data1.
metabolic dysregulation (at least two metabolic risk abnormalities).
Results: A total of 303 referrals were placed for NAFLD, of which 62%
(n = 188) patients had FIB-4 score at the time of referral. Of the 188
patients, 62 patients with diabetes mellitus and 44% of them had FIB-
4 ≥1.3. Compared to prior referrals of 49% with FIB-4 score<1.3, in
current referrals after a 6-month post-FIB-4 triage implementation,
37% had FIB-4 <1.3 (Fig 1). This suggested a decrease in unnecessary
referrals to hepatology. Primary care doctors referred 73% while

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POSTER PRESENTATIONS
in patients with chronic liver diseases. Here, we analyse these fatty
liver-related genes in patients undergoing bariatric surgery.
Method: The study cohort was composed of 165 prospectively
recruited obese individuals (BMI 43.8 ± 5.7 kg/m2, 66% women, 48
with diabetes mellitus) who underwent laparoscopic sleeve gastrec-
tomy The PNPLA3, TM6SF2, MBOAT7, MARC1 and HSD17B13 poly-
morphisms were genotyped performed using TaqMan assays. Liver
biopsies were performed intraoperatively in all patients.
Results: In total, 70.3% of operated patients presented with hepatic
steatosis, whereas NASH was detected in 28.5% of them; none had
cirrhosis. Patients carrying the MARC1 minor allele displayed a lower
risk of developing fibrosis stage 1a (OR = 0.54, p = 0.03), 1b (OR = 0.47,
p = 0.01), 1c (OR = 0.46, p = 0.01), and 2 (OR = 0.42, p = 0.03). The
PNPLA3 risk allele was associated with increased odds of hepatic
steatosis (S2 and S3), fibrosis (1b to 2), and NASH (OR = 2.22, p = 0.04
in multivariate model). This variant was also significantly ( p <0.01)
associated with increased fasting glucose ( p = 0.03) and glycated
haemoglobin (HbA1c) levels. Analysis restricted to 48 carriers of the
Results: In NHANES III, 12, 878 adults (age 43.1 years; 49.5% male; PNPLA3 risk alleles (29.1%) showed that the MARC1 polymorphism
20.3% FLD, 16.5% NAFLD; 18.1% MAFLD, EAC 15.0%) were included. In decreases the odds of developing fibrosis. Furthermore, MARC1 was
NHANES 2017–2018, 4, 328 adults (age 48.0 years; 49.1% male; 36.8% an independent protective factor against fibrosis in multivariate
FLD; 34.2% NAFLD; 36.3% MAFLD). In both cohorts, there was analysis (OR = 0.51, 95% Cl 0.28–0.92, p = 0.04). Carriers of the
excellent concordance between diagnosis of MAFLD and NAFLD HSD17B13 variant presented, in turn, with lower serum ALT ( p =
[Cohen’s kappa coefficient of 0.83 (95% CI: 0.82–0.85) in NHANES III 0.03) and AST ( p = 0.04) activities. The TM6SF2 polymorphism was
and 0.94 (95% CI: 0.93–0.95) in NHANES 2017–2018]. There were no associated with the risk for S3 steatosis (OR = 17.52, p <0.01) and
statistical differences in the characteristics of MAFLD as compared to increased ALT ( p = 0.04).
NAFLD except for presence of obesity and EAC. After 19.2 years of Conclusion: Fatty liver is a frequent condition in patients scheduled
follow-up for NHANES III cohort, there were no significant differences for bariatric surgery, but the MARC1 and HSD17B13 gene variants
in cumulative mortality between MAFLD and NAFLD: all-causes diminish hepatic injury in these individuals. Variant MARC1 might
(45.0% [95% Confidence interval, 41.6–48.3] vs 41.5% [38.3–44.8]); reduce the harmful effects of the major genetic risk factor for fatty
cardiovascular disease (15.5% [13.4–17.6] vs 13.9 [11.8–15.9]); extra- liver, namely, PNPLA3 p.I148M.
hepatic cancer (9.2% [7.5–10.8] vs. 8.6% [6.6–10.5]); liver (3.0% [2.0–
4.0] vs. 1.8% [1.0–2.7]) and diabetes (1.4% [1.4–3.5] vs. 2.5% [1.3–3.8]). THU073
Furthermore, except for diagnosis of ALD among MAFLD, there were The impact of fatigue on mortality of patients with non-alcoholic
no discernable differences in mortality risk factors between NAFLD fatty liver disease (NAFLD): data from national health and
and MAFLD. In fact, independent predictors of mortality for both nutrition examination survey (NHANES) 2005–2018
included presence of central obesity, insulin resistance/T2DM, CKD, Zobair Younossi1,2,3, James Paik1,2,3, Pegah Golabi1,2,3,
CVD as well as high triglycerides and low HDL cholesterol ( p < 0.05). Youssef Younossi4, Linda Henry1,3,4, Fatema Nader4. 1Inova Health
Of 75 liver deaths among MAFLD patients, 66.7% were also classified System, Medicine Service Line; 2Center for Liver Disease, Inova Medicine;
as NAFLD and 33.3% as ALD. Among MAFLD, the strongest predictor of 3
Betty and Guy Beatty Center for Liver and Obesity, Inova Health System;
liver deaths was diagnosis of ALD (HR = 4.50 [1.89–10.75]). 4
Center for Outcomes Research in Liver Disease
Conclusion: MAFLD and NAFLD diagnostic classifications have Email: [email protected]
excellent concordance. Furthermore, there are similar cause-specific
or overall mortality. The strongest predictor of liver mortality among Background and aims: Fatigue is common among patients with
MAFLD is presence of ALD. NAFLD. Fatigue can negatively impact patient reported outcomes and
clinical outcomes.
THU072 Aim: To determine the prevalence of fatigue and its association with
MARC1 and HSD17B13 variants have protective effects on liver all-cause mortality for patients with NAFLD.
injury in the obese: results from a prospective cohort of patients Method: Data for adults (≥18 years) collected as part of the National
undergoing bariatric surgery Health and Nutrition Examination Survey (NHANES 2005–2010 and
Piotr Kalinowski1, Wiktor Smyk2, Małgorzata Nowosad1, 2017–2018) with mortality data via linkage to the National Death
Rafał Paluszkiewicz1, Łukasz Michałowski3, Index (through 2015) were used for this study. For NHANES 2005–
Bogna Ziarkiewicz-Wróblewska3, Susanne N Weber2, 2010, NAFLD was defined by Fatty Liver Index adjusted for the
Frank Lammert2,4, Krzysztof Zieniewicz1, Marcin Krawczyk2,5. multiethnic U.S. population (US-FLI). Additionally, transient elasto-
1
Department of General, Transplant and Liver Surgery, Medical graphy (TE) with a controlled attenuation parameter (CAP) of
University of Warsaw, Warsaw, Poland; 2Department of Medicine II, ≥285 dB/m was used to define NAFLD for NHANES 2017–2018.
Saarland University Medical Center, Saarland University, Homburg, Excluded were patients with other liver diseases and excessive
Germany; 3Department of Pathology, University Clinical Center of alcohol use. Fatigue was assessed through the Patient Health
Medical University of Warsaw, Warsaw, Poland; 4Hannover Health Questionnaire (PHQ-9) question, “Over the last 2 weeks, how often
Science, Hannover Medical School, Hannover, Germany; 5Laboratory of have you been bothered by feeling tired or having little energy?”
Metabolic Liver Diseases, Department of General, Transplant and Liver Significant fatigue was defined as a response of “nearly every day” to
Surgery, Centre for Preclinical Research, Warsaw, Poland the question.
Email: [email protected] Results: Of the NHANES 2005–2010 study cohort (n = 5, 429, mean
age 47.1 years, 49.7% male, 69.9% white), 37.6% had NAFLD. Compared
Background and aims: Hepatic steatosis is modulated by genetic to non-NAFLD group, fatigue was more common in individuals with
variants like PNPLA3 ( p.I148M), TM6SF2 (rs58542926), and MBOAT7 NAFLD (8.35% vs 6.0%, P = 0.002). Among the NHANES 2017–2018
(rs641738). Recently, MARC1 (rs2642438) and HSD17B13 study cohort (n = 3, 830, mean age 48.3 years, 48.6% male, 62.3%
(rs72613567) polymorphisms were shown to have protective effects white), 36.9% had NAFLD and 7.2% had fatigue. Compared to non-

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 POSTER PRESENTATIONS
NAFLD subjects, those with NAFLD were older (51.4 vs 46.4 years), IDIBAPS, University of Barcelona, Barcelona, Spain; 10Gastroenterology
more likely to be male (55.6% vs 44.6%), and more likely to report and Hepatology Department, Hospital Universitari Germans Trias i Pujol,
fatigue (8.7% vs 6.2%), sleep trouble (ST) (34.0% vs 26.7%), metabolic Badalona, Spain; 11Liver Unit, Vall d’Hebron University Hospital, Vall
abnormalities (90.4% vs. 58.4%), asthma (17.3% vs 12.7%), Chronic d’Hebron Institute of Research (VHIR), Barcelona, Spain; 12Department
Obstructive Pulmonary Disease (COPD) (7.7% vs 6.1%), arthritis (34.3% of Physiology, Faculty of Medicine and Nursing, Biocruces Research
vs 24.1%), thyroid disease (13.0% vs 9.9%), cardiovascular disease Institute, University of the Basque Country UPV/EHU, Leioa, Spain;
(CVD) (10.4% vs. 6.3%), significant fibrosis (liver stiffness >8.0 kPa, 13
Department of Gastroenterology and Hepatology, Hospital
17.9% vs 3.5%), and advanced fibrosis (>13.1 kPa, 5.4% vs 0.9%) (all p Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación
< .003). Among NAFLD, multivariate logistic regression analysis Sanitaria (IRYCIS), Madrid, Spain; 14Unit for the Clinical Management of
showed that presence of depression (Odds Ratio = 16.2, 95% Digestive Diseases, Hospital Universitario de Valme. Sevilla, Spain;
Confidence interval, 6.02–43.6), ST (3.34, 1.85–6.05), arthritis (2.25, 15
Hepatology Unit, Consorcio Hospital General Universitario de Valencia,
1.29–3.92), COPD (2.91, 1.47–5.77), CVD (3.64, 2.04–6.51) and sleep Valencia, Spain; 16Hospital Clínico Universitario de Valencia, Universitat
quantity (+7 hours) (0.52, 0.31–0.88) were associated with presence de Valeǹ cia, Valencia, Spain; 17Hospital Universitario Miguel Servet,
of fatigue. Multivariable cox model demonstrated that NAFLD Zaragoza, Spain; 18Department of Hepatology, Hospital Universitario y
patients with fatigue had a 2.3-fold higher mortality than NAFLD Politécnico La Fe, Valencia, Spain; 19Service of Digestive Diseases,
without fatigue (HR: 2.31, 95%CI: 1.37–3.89, P = 0.0024). Complejo Hospitalario Universitario de Pontevedra, IIS Galicia Sur,
Pontevedra, Spain
Email: [email protected]
Background and aims: Cardiovascular disease (CVD) is the main
cause of mortality among patients with Metabolic dysfunction-
Associated Fatty Liver Disease (MAFLD). Currently, clinical evidence
shows that MAFLD could be a precursor for future development of
metabolic syndrome (MS) components, linked to higher cardiovas-
cular risk (CVR), regardless of classical risk factors. For this reason, our
main aim was to determine if patients with MAFLD have a higher CVR
as a consequence of liver disease activity.
Method: Cross-sectional study that includes 1, 587 patients with
MAFLD, diagnosed by liver biopsy from the HEPAmet Registry, and 1,
587 from the general population (ETHON cohort), age- and sex-
matched. The CVR was evaluated with the Systematic Coronary Risk
Evaluation (SCORE) model. In addition, the presence of carotid
plaques and carotid intima-media thickness were analysed by
Conclusion: Fatigue is more common among NAFLD and is driven ultrasound, in a subgroup of MAFLD patients without previous
mainly by depression, sleep trouble, and CVD. Among NAFLD, CVD, to establish their use in reclassification of CVR determined by
presence of fatigue is associated increased risk for mortality. SCORE. Multivariate regression analysis, adjusted for classical CVR
factors, was used to evaluate whether CVR is influenced by liver
THU074 disease activity.
Metabolic dysfunction-associated fatty liver disease increases Results: An increased prevalence of cardiovascular events was
cardiovascular risk regardless of classical risk factors observed among patients with MAFLD compared to general popu-
María Del Barrio Azaceta1, Paula Iruzubieta1, lation (10.3% vs 7.9%; p = 0.02), finding significant differences ( p <
Rocio Aller De La Fuente2, Jesus Maria Banales3, Álvaro Santos-Laso1, 0.001) in CVR regarding SCORE categories (low CVR: 32.5% vs 37.3%;
José Luis Calleja Panero4, Luis Ibañez5, María Teresa Arias Loste1, very high CVR: 36.9% vs 14.6%). NASH presence (OR 1.490 [IC 95%:
Manuel Romero Gomez6, Carmelo García-Monzón7, 1.037–2.141]) and advanced fibrosis (OR 1.442 [IC 95%: 1.001–2.076])
Judith Gómez-Camarero8, Pere Ginès9, Rosa M Morillas10, were independent risk factors associated with high/very high SCORE
Juan Manuel Pericàs11, Patricia Aspichueta12, Rosa Martin-Mateos13, category, after adjusted by classical CVR factors. The Fibrosis-4 (FIB-4)
Rocío Gallego-Durán14, Mercedes De La Torre Sanchez15, index was associated with high/very high SCORE category, maintain-
Desamparados Escudero-García16, Vanesa Bernal Monterde17, ing as an independent and significant risk factor after adjusting by
Salvador Benlloch18, Juan Turnes19, Javier Crespo1. 1Gastroenterology classical factors (OR 1.423 [IC 95%: 1.238–1.634]; p < 0.001), and
and Hepatology Department, Marqués de Valdecilla University Hospital, showing statistically significant discrimination of high/very high CVR
Clinical and Translational Digestive Research Group, IDIVAL, Santander, category (AUC: 0.655 [IC 95%: 0.628–0.682], p <0.001). Using carotid
Spain; 2Center of Investigation of Endocrinology and Nutrition, School of ultrasound, it was observed that 20% of patients with low/moderate
Medicine, and Unit of Investigation, Hospital Clinico Universitario de CVR were reclassified into high-risk category due to the presence of
Valladolid, Valladolid, Spain; 3Department of Liver and Gastrointestinal atheromatosis.
Diseases, Biodonostia Health Research Institute-Donostia University Conclusion: The presence of NASH, advanced fibrosis and a higher
Hospital, University of the Basque Country (UPV/EHU), San Sebastian, FIB-4 index were associated with a high/very high CVR in patients
Spain; 4Gastroenterology Department. Hepatology Unit, Hospital with MAFLD, even after considering classical risk factors. The ability
Universitario Puerta de Hierro, IDIPHISA, Madrid, Spain; of the SCORE model to predict CVD in MAFLD patients may not be as
5
Gastroenterology and Hepatology Department Hospital Universitario powerful as in the general population.
Gregorio Marañon Instituto de Investigacion Sanitaria Gregorio
Marañon (IiSGM) Universidad Complutense de Madrid, Madrid, Spain;
6
UCM Digestive Diseases, Virgen del Rocío University Hospital, SeLiver
group at the Institute of Biomedicine of Seville (IBIS), The University of
Seville. Seville, Spain; 7Liver Research Unit, Hospital Universitario Santa
Cristina Instituto de Investigación Sanitaria Princesa, Madrid, Spain;
8
Department of Gastroenterology and Hepatology, Complejo Asistencial
Universitario de Burgos, Burgos, Spain; 9Liver Unit, Hospital Clínic,

Journal of Hepatology 2022 vol. 77(S1) | S119–S388 S157

POSTER PRESENTATIONS
THU075 THU076
Changes in hepatic fat fraction as assessed by MRI-PDFF are The metabolic dysfunction-associated fatty liver disease
correlated with changes in markers of hepatic inflammation, definition, regardless of its clinical subclassification, identifies
disease activity and fibrosis in biopsy-proven non-cirrhotic NASH patients at high risk for liver disease progression
with fibrosis María Del Barrio Azaceta1, Paula Iruzubieta1, Rocio Aller de la Fuente2,
Samuel Daniels1, Darren Robertson1, Jose Sanchez2, Janeli Sarv2, Jesus Maria Banales3, Álvaro Santos-Laso1, José Luis Calleja Panero4,
Antonio Manzur1, Lutz Jermutus3, Arun Sanyal4, Benjamin Challis5, Luis Ibañez5, María Teresa Arias Loste1, Manuel Romero Gomez6,
Sudha Shankar6. 1Early CVRM, Biopharmaceuticals RandD, Early Carmelo García-Monzón7, Judith Gómez-Camarero8, Pere Ginès9,
Clinical Development, Cambridge, United Kingdom; 2Data Science and Rosa M Morillas10, Juan Manuel Pericàs11, Patricia Aspichueta12,
Artificial Intelligence, RandD, Early Biometrics and Statistical Rosa Martin-Mateos13, Rocío Gallego-Durán14,
Innovation, Gothenburg, Sweden; 3Early CVRM, Biopharmaceuticals Mercedes De La Torre Sanchez15, Desamparados Escudero-García16,
RandD, Cambridge, United Kingdom; 4Virginia Commonwealth Vanesa Bernal Monterde17, Salvador Benlloch18, Juan Turnes19,
University, Division of Gastroenterology, Hepatology and Nutrition, Javier Crespo1. 1Gastroenterology and Hepatology Department, Marqués
Richmond, United States; 5Early CVRM, Biopharmaceuticals RandD, de Valdecilla University Hospital, Clinical and Translational Digestive
Translational Science and Experimental Medicine, Research and Early Research Group, IDIVAL, Santander, Spain; 2Center of Investigation of
Development, Cambridge, United Kingdom; 6Early CVRM, Endocrinology and Nutrition, School of Medicine, and Unit of
Biopharmaceuticals RandD, Early Clinical Development, Gaithersburg, Investigation, Hospital Clinico Universitario de Valladolid, Valladolid,
United States Spain; 3Department of Liver and Gastrointestinal Diseases, Biodonostia
Email: [email protected] Health Research Institute-Donostia University Hospital, University of the
Basque Country (UPV/EHU), San Sebastian, Spain; 4Gastroenterology
Background and aims: MRI-PDFF is the gold standard for non-
Department. Hepatology Unit, Hospital Universitario Puerta de Hierro,
invasive assessment of hepatic fat fraction (HFF) in non-alcoholic
IDIPHISA, Madrid, Spain; 5Gastroenterology and Hepatology
steatohepatitis (NASH) and is commonly used within early clinical
Department Hospital Universitario Gregorio Marañon Instituto de
trials to determine treatment efficacy on steatosis. HFF reduction has
Investigacion Sanitaria Gregorio Marañon (IiSGM) Universidad
been associated with an increased likelihood of NASH resolution.
Complutense de Madrid, Madrid, Spain; 6UCM Digestive Diseases, Virgen
However it is unclear whether reductions in hepatic steatosis bear a
del Rocío University Hospital, SeLiver group at the Institute of
relationship with changes in markers of hepatic inflammation,
Biomedicine of Seville (IBIS), The University of Seville. Seville, Spain;
disease activity and fibrosis. 7
Liver Research Unit, Hospital Universitario Santa Cristina Instituto de
Method: PROXYMO was a 19 week multi-centre phase 2 trial to
Investigación Sanitaria Princesa, Madrid, Spain; 8Department of
investigate the safety and efficacy of cotadutide in 74 participants
Gastroenterology and Hepatology, Complejo Asistencial Universitario de
with biopsy confirmed non-cirrhotic NASH with fibrosis
Burgos, Burgos, Spain; 9Liver Unit, Hospital Clínic, IDIBAPS, University of
(NCT04019561). Post-hoc analysis was performed to investigate
Barcelona, Barcelona, Spain; 10Gastroenterology and Hepatology
whether changes in HFF in the study population were associated
Department, Hospital Universitari Germans Trias i Pujol, Badalona,
with changes in non-invasive markers of hepatic fibrosis, NASH
Spain; 11Liver Unit, Vall d’Hebron University Hospital, Vall d’Hebron
disease activity and inflammation within participants who had
Institute of Research (VHIR), Barcelona, Spain; 12Department of
baseline and week 19 values. Participants were pooled (active and
Physiology, Faculty of Medicine and Nursing, Biocruces Research
placebo) and the relative changes in HFF after 19 weeks were assessed
Institute, University of the Basque Country UPV/EHU, Leioa, Spain;
against percentage change in non-invasive markers. 13
Department of Gastroenterology and Hepatology, Hospital
Results: Within pooled participants, relative change in HFF was
Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación
significantly correlated with markers of hepatic inflammation
Sanitaria (IRYCIS), Madrid, Spain; 14Unit for the Clinical Management of
(ALT R = 0.52 ( p < 0.0001)), NASH disease activity (NIS-4 R = 0.63
Digestive Diseases, Hospital Universitario de Valme. Sevilla, Spain;
( p < 0.0001)) and hepatic fibrosis (PRO-C3 R = 0.44 ( p = 0.0012)). 15
Hepatology Unit, Consorcio Hospital General Universitario de Valencia,
Changes in fibrosis biomarkers were correlated with changes in liver
Valencia, Spain; 16Hospital Clínico Universitario de Valencia, Universitat
enzymes. Change in body weight was significantly correlated with
de Valen ̀ cia, Valencia, Spain; 17Hospital Universitario Miguel Servet,
change in HFF. Relative HFF change was divided into quartiles; those
Zaragoza, Spain; 18Department of Hepatology, Hospital Universitario y
in the quartile of greatest relative HFF reduction had significantly
Politécnico La Fe, Valencia, Valencia, Spain; 19Service of Digestive
greater reductions in ALT, AST, NIS-4 and PRO-C3.
Diseases, Complejo Hospitalario Universitario de Pontevedra, IIS Galicia
Sur, Pontevedra, Spain
Email: [email protected]
Background and aims: Several population studies indicate that
Metabolic dysfunction-Associated Fatty Liver Disease (MAFLD)
diagnostic criteria better identify which patients are at high risk for
liver disease progression. However, the impact of this new definition
on specialized clinical practice is still unknown. Here, our aim was to
Conclusion: Reductions in HFF as assessed by MRI-PDFF were
compare, MAFLD vs non-MAFLD patients, from a cohort of Non-
associated with reductions in non-invasive markers of hepatic
Alcoholic Fatty Liver Disease (NAFLD) patients with liver biopsy.
inflammation, NASH disease activity and fibrosis. Furthermore,
Method: A cross-sectional multicenter study with 2, 148 NAFLD
subjects with improvements in HFF had significantly greater
patients from the HEPAmet Registry with liver biopsy, with no other
reductions in ALT, AST, NIS-4 and PRO-C3.
causes of chronic liver disease and with the necessary clinical data to
reach MAFLD diagnosis. Clinical, analytical and elastographic data,
close to liver biopsy date, were collected. The Non-Alcoholic
Steatohepatitis (NASH) diagnosis was based on the presence at
once of steatosis, ballooning and lobular inflammation.
Results: Only 1.5% of patients did not fulfill MAFLD diagnostic criteria.
Compared to non-MAFLD, MAFLD patients showed a higher mean
value of Fibroscan (12.5 ± 9 vs 6.5 ± 2.3; p = 0.002) and had more
ballooning, lobular inflammation and significant/advanced fibrosis

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 POSTER PRESENTATIONS
(38.6% vs 9.1%; p = 0.001); as well as, NASH (Fig. 1a). Among MAFLD though not significantly different prevalence of diabetes or hyper-
patients, there were no differences in histological diagnosis between tension. Lean NAFLD had lower mean CAP, FAST score, and median
lean MAFLD and the remaining of patients (Fig. 1b). Differences in stiffness than that of non-lean NAFLD. Lean NAFLD had lower
liver affectation between lean MAFLD and non-MAFLD maintained prevalence of fibrosis stage 2 or 3 and higher (≥F2 or ≥F3) and
significant (Fig. 1c). The most powerful independent risk factors for Fibroscan-AST (FAST) score compared to non-lean NAFLD. Neither
advanced fibrosis in MAFLD patients were Type 2 Diabetes Mellitus fibrosis stage 4 (F4) nor FAST score ≥0.67 were significantly different
(OR 2.37; IC 95% 1.79–3.15; p <0.001) and Arterial Hypertension (OR between lean and non-lean NAFLD.
1.47; IC 95% 1.09–1.99; p = 0.01). Alcohol consumption (10–30 g/d)
was the only factor associated with the presence of advanced fibrosis
in lean MAFLD (OR 8.44; IC 95% 1.57–45.39; p = 0.01).

Conclusion: Compared with non-lean NAFLD, lean NAFLD had

significantly higher prevalence of prediabetes and severity of
hyperlipidemia. Although lean NAFLD had significantly decreased
prevalence of ≥F2 and ≥F3 and lower FAST score compared to non-
lean NAFLD, neither fibrotic non-alcoholic steatohepatitis nor
cirrhosis prevalence were significantly different between lean and
non-lean NAFLD. The largest to date to examine this subpopulation,
this study highlights important implications for monitoring disease
progression in the lean NAFLD population.
Conclusion: The metabolic dysfunction that defines MAFLD better
identifies patients at risk for advanced liver disease, regardless of THU078
whether they are overweight/obese or diabetic. Coagulation imbalance is associated with hepatic fibrosis and
vascular complications in patients with type2 diabetes and NAFLD
THU077 Francesca Alletto1,2, Paolo Francione1,2, Gabriele Maffi1,2,
Assessment of the prevalence of non-alcoholic fatty liver disease, Giordano Sigon1,2, Annalisa Cespiati1,2, Daniela Bignamini1,
its severity, and comorbidities in lean americans: national health Mariagrazia Clerici3, Veena Chantarangkul3, Armando Tripodi3,
and nutrition examination surveys (NHANES) with transient Flora Peyvandi2,4, Silvia Fargion1,2, Anna Ludovica Fracanzani1,2,
elastography assessment from 2017 to 2018 Rosa Lombardi1,2. 1Fondazione Ca’ Granda IRCCS, Policlinico Hospital of
Emily Truong1, Galen Cook-Wiens2, Naim Alkhouri3, Milan, Unit of Internal Medicine and Metabolic Diseases, Milan, Italy;
Mazen Noureddin4. 1Cedars Sinai Medical Center, Internal Medicine, 2
University of Milan, Department of Pathophysiology and
Los Angeles, United States; 2Cedars Sinai Medical Center, Los Angeles, Transplantation, Milan, Italy; 3Fondazione Ca’ Granda IRCCS, Policlinico
United States; 3Arizona Liver Health, Phoenix, United States; 4Cedars Hospital of Milan, Angelo Bianchi Bonomi Hemophilia and Thrombosis
Sinai Medical Center, Karsh Division of Gastroenterology and Center and Fondazione Luigi Villa, Milan, Italy; 4Fondazione Ca’ Granda
Hepatology, Comprehensive Transplant Center, Los Angeles, United IRCCS, Policlinico Hospital of Milan, Unit of Internal Medicine
States Hemostasis and Thrombosis, Milan, Italy
Email: [email protected] Email: [email protected]
Background and aims: Previous studies examined lean non- Background and aims: Both non-alcoholic fatty liver disease
alcoholic fatty liver disease (NAFLD), which affects 10–20% of non- (NAFLD) and type 2 diabetes mellitus (T2DM) are characterized by
obese or lean Americans and is associated with lower rates of a pro-coagulant state and expose patients to vascular complications.
hyperlipidemia, hypertension, diabetes, and cirrhosis. We described The interaction between pro-coagulant state, vascular complications
characteristics and NAFLD prevalence and severity in the lean and advanced liver disease has not been defined yet. Aim: to evaluate
population in National Health and Nutrition Examination Surveys in a cohort of patients with T2DM and NAFLD if alterations in
(NHANES) from 2017 to 2018 by using Fibroscan to directly assess coagulation tests are associated with high prevalence of hepatic
steatosis and fibrosis. fibrosis and vascular complications.
Method: We analyzed NHANES data from 2017–2018. Inclusion Method: 96 consecutive outpatients with T2DM and ultrasound fatty
criteria were age ≥18 years and completion of interview, laboratory liver and an age and sex matched control group of 156 healthy
testing, and FibroScan®. Exclusion criteria were excessive alcohol use individuals were enrolled. For all subjects, determination of serum
(≥7 or 14 drinks/week for females or males, respectively) or viral pro- (i.e factor II-FII, factor VIII-FVIII) and anti-coagulant factors (i.e
hepatitis. Non-lean NAFLD was defined as body mass index (BMI) protein C-PC, antithrombin-AT) and test of thrombin generation (ETP
≥25 kg/m2, and lean NAFLD was defined as BMI <25 kg/m2. NAFLD ratio, peak ratio, FVIII/PC) were obtained. In the T2DM cohort,
was defined as controlled attenuation parameter >274 dB/m. significant liver fibrosis (≥F2) was diagnosed by Fibroscan (i.e liver
Results: Of 3899, 120 (3.1%) respondents were lean NAFLD, and 1453 stiffness measurement-LSM>7.0/6.2 kPa M/XL probe). Evaluation of
(37.3%) respondents were non-lean NAFLD. Overall NAFLD prevalence microvascular (i.e retinopathy, nephropathy and neuropathy) and
was 40.34% (non-lean 37.27% vs lean 3.08%). Compared to non-lean macrovascular complications (i.e carotid plaques and history of
NAFLD, lean NAFLD had significantly lower prevalence of prediabetes, cardiovascular (CV) events) was assessed.

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POSTER PRESENTATIONS
Results: In the T2DM group mean age was 65 ± 7 years, 66% male. fibrosis in the setting of health check-up centres should be extended
Mean FII was 95.9 ± 12.8, FVIII 130.3 ± 33.2, PC 112.8 ± 20.8, AT 106 ± to subjects with two or more metabolic risks and/or diabetes, beyond
14.4, ETP ratio 0.64 ± 0.09, peak ratio 0.93 ± 0.05, FVIII/PC 1.2 ± 0.3. those with fatty liver.
Despite only 5% of the cohort had increased transaminases,
significant hepatic fibrosis was present in 14% by LSM. THU080
Microvascular complications were present in 29 (30%) patients Pregnancy as a unique opportunity to identify NAFLD in women: a
(retinopathy in 8%, nephropathy in 23% and neuropathy in 4%) prospective assessment
whereas plaques in 70 (73%) and CV events in 23 (24%). Compared to Tatyana Kushner1, Shaelyn O’Hara1, Marcia Lange1, Carin Carroll2,
the control group, T2DM patients presented a pro-coagulant Emma Rosenbluth1, Pamela Argiriadi1, Rachel Meislin1, Joanne Stone1,
imbalance (ETP ratio 0.64 ± 0.09 vs 0.59 ± 0.18, p = .0.12; FVIII/PC 1.2 Keith Sigel1, Rhoda Sperling1, Scott Friedman1, Norah Terrault3. 1Icahn
± 0.3 vs 1.02 ± 0.3, p = 0.03). In the T2DM cohort, indexes of School of Medicine at Mount Sinai; 2University of Miami School of
procoagulant imbalance as AT and FVIII/PC were independently Medicine; 3University of Southern California Keck School of Medicine
associated with significant fibrosis by LSM>7.0/6.2 kPa with M/XL Email: [email protected]
probe (multivariate analysis for AT corrected for age, sex, T2DM
duration, HbA1c, overweight, hypertension: OR 0.89; CI 95% 0.80– Background and aims: Non-alcoholic fatty liver disease (NAFLD) in
0.98) and microvascular complications (multivariate analysis cor- U.S. women of reproductive age is rising and recent administrative
rected for age, sex, smoking, T2DM duration, HbA1c, overweight, claims-based data suggest a significant association of NAFLD with
hypertension, use of statins, uric acid for AT: OR 0.93; CI 95% 0.88– adverse pregnancy outcomes. We evaluated the prevalence and
0.98; and for FVIII/PC ratio: OR 8.0; CI 95% 1.00–65.8). associated risk factors of NAFLD at a high-volume obstetrics center.
Conclusion: In patients with T2DM and NAFLD a pro-coagulant Method: In this prospective study, a liver ultrasound at time of
imbalance was found compared to healthy controls and it was routine pregnancy anatomy scan at 18–22 weeks’ gestation was
associated with both hepatic and vascular complications, speculating performed to assess for presence of NAFLD. Obstetric sonographers
on a possible common pathogenetic pattern. Further studies and a were trained to obtain liver images that were subsequently graded for
wider cohort are warranted to define the clinical application of these hepatic steatosis by a radiologist blinded to clinical status. The
coagulation alterations. However, our results point on the need of a proportion having elevated hepatic steatosis index (HSI) and meeting
careful evaluation also of hepatic complications in diabetics. recently defined metabolic associated fatty liver disease (MAFLD)
criteria was evaluated. A multivariable logistic regression model
THU079 assessed independent predictors of NAFLD among pregnant women.
Presence of two or more metabolic risks regardless of fatty liver is Results: Among 749 women approached for participation, satisfac-
a risk factor for significant hepatic fibrosis tory liver ultrasounds were obtained on 560 (75%) pregnant
Huiyul Park1, Dae Won Jun2, Eileen Yoon2, Sang Bong Ahn3, individuals; median age 28, 58% Hispanic ethnicity, 65% with pre-
Hyo Young Lee4, Hyunwoo Oh4, Bo-Kyeong Kang5, Mi Mi Kim5, pregnancy BMI ≥25, 22% nulliparous. Seventy-eight (14.3%) had
Chul-min Lee5, Joo Hyun Sohn6. 1Uijeongbu Eulji Medical Center, steatosis on ultrasound; 83% grade 1, 14% grade 2 and 3% grade 3.
Department of Family medicine, Gyeonggi-do, Korea, Rep. of South; Overall, 36% had HSI ≥36; 11% satisfied MAFLD criteria. Only 4 of 560
2
Hanyang University College of Medicine, Department of Medicine, (0.71%) carried a previous diagnosis of NAFLD. Women with steatosis
Seoul, Korea, Rep. of South; 3Nowon Eulji Medical Center, Eulji University were more likely to be of Hispanic ethnicity, have diagnoses of
School of Medicine, Department of Medicine, Seoul, Korea, Rep. of South; chronic hypertension and diabetes and have a pregnancy history of
4
Uijeongbu Eulji Medical Center, Department of Medicine, Gyeonggi-do, gestational diabetes ( p < 0.05; see Table). Women with grade 2/3
Korea, Rep. of South; 5Hanyang University College of Medicine, steatosis were more likely to have a history of preeclampsia (30% vs
Department of Radiology, Seoul, Korea, Rep. of South; 6Hanyang 10%, p = 0.05). In multivariable analyses, Hispanic ethnicity (OR 2.57;
University Guri Hospital, Hanyang University College of Medicine, 95% CI 1.30–5.09) and BMI (OR 1.06; 95% CI 1.01–1.11) were
Department of Medicine, Gyeonggi-do, Korea, Rep. of South independently associated with NAFLD.
Email: [email protected] Conclusion: In this first time U.S. based prospective study of pregnant
women, integration of ultrasound into obstetric care was feasible and
Background and aims: Metabolic syndrome and diabetes are well- effective in identifying women with NAFLD. NAFLD prevalence was 14%,
known risk factors for hepatic fibrosis. However, hepatic fibrosis similar to reports in non-pregnant women of reproductive age with
screening strategies for subjects with these risks have not yet been Hispanic and elevated pre-pregnancy BMI women being at highest risk
established. We aimed to identify the high-risk group for hepatic fibrosis of NAFLD. Most had no prior diagnosis of NAFLD, highlighting a unique
screening, according to the type and number of metabolic risk factors. opportunity to identify and link women to specialized care.
Method: This was a retrospective cross-sectional cohort study using
data from 13 nationwide centres. A total of 5, 111 subjects who No NAFLD NAFLD n = 78 p
underwent both magnetic resonance elastography and abdominal n = 469 (85.7%) (14.3%) value
ultrasound as part of their health check-up were included. Subjects
Age (median, IQR) 28 (24, 33) 28 (24, 33) 0.666
with viral hepatitis and/or a history of significant alcohol consump-
Hispanic ethnicity, n (%) 254 (56%) 60 (77%) 0.002
tion were excluded.
Pre-pregnancy BMI (kg/ 26 (23, 31) 29 (25, 34) 0.001
Results: The prevalence of significant hepatic fibrosis was 7.3%. m2), median
Among subjects with significant hepatic fibrosis, 41.3% did not have Chronic HTN, n (%) 31 (7%) 11 (14%) 0.022
fatty liver. Hepatic fibrosis burden increased according to the number Type II DM, n (%) 9 (2%) 7 (9%) 0.001
of metabolic abnormalities. Nearly 70% of subjects with significant Autoimmune disease, n 23 (5%) 8 (11%) 0.055
hepatic fibrosis also had two or more metabolic risks and/or diabetes. (%)
However, significant fibrosis prevalence did not differ between the Prior Pregnancy History
groups with and without fatty liver among those with healthy Gestational Diabetes 17 (5%) 7 (13%) 0.023
Preeclampsia 34 (10%) 10 (18%) 0.065
metabolic conditions. The presence of two or more metabolic
Cholestasis of Pregnancy 7 (1%) 0 (0%) 0.291
abnormalities was an independent risk factor for significant hepatic
Preterm birth 53 (15%) 6 11%) 0.395
fibrosis, even when the presence of fatty liver was corrected. NAFLD Clinical scores
Conclusion: Health check-up examinees who have two or more Mean HSI (SD) (n = 368) 37.88 (8.44) 40.84 (8.97) 0.013
metabolic risks and/or diabetes are at risk of hepatic fibrosis, No. Satisfying any MAFLD 4 (0.85) 58 (74.36) 0.001
regardless of fatty liver status. Thus, active screening for hepatic Criteria (%) (n = 549)

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 POSTER PRESENTATIONS
THU081 THU082
N-terminal propeptide of type III collagen (PRO-C3) based risk for Genetic risk of fatty liver disease and mortality in the general
liver fibrosis predict cardiovascular events in non-alcoholic fatty population
liver disease Helene Gellert-Kristensen1, Børge Nordestgaard2,
Francesco Baratta1, Giulia Tozzi2, Daniele Pastori1, Anne Tybjaerg Hansen1, Stefan Stender1. 1Rigshospitalet, Clinical
Alessandra Colantoni1, Nicholas Cocomello1, Stefano Cecchi2, Biochemistry, København, Denmark; 2Herlev Hospital, Clinical
Mattia Coronati1, Francesco Angelico1, Maria Del Ben1. 1Sapienza- Biochemistry, Herlev, Denmark
University of Rome; 2Children’s Hospital Bambino Gesù Email: [email protected]
Email: [email protected]
Background and aims: Fatty liver disease associates with increased
Background and aims: N-terminal propeptide of type III collagen mortality due to extrahepatic causes, as well as increased all-cause
(PRO-C3) is cleaved off during the process of collagen III deposition. mortality. However, it remains unclear if these associations reflect a
Serum levels of PRO-C3 properly correlate to biopsy-proven liver causal effect of fatty liver disease rather than confounding due to
fibrosis stage and PRO-C3 was included in some risk scores, namely coexisting comorbidities. The aim of this study was to use genetic
ADAPT, FIB-C3 and ABC3D to predict advanced liver fibrosis. While variants (which are less susceptible to confounding) to assess if fatty
the association between other liver fibrosis risk scores (FIB4 and liver disease per se is likely to causally influence mortality.
NAFLD fibrosis score) and cardiovascular events (CVEs) has been Method: We included participants from two prospective studies of
demonstrated, the association between PRO-C3 derived scores and the general Danish population, the Copenhagen City Heart Study and
CVEs has never been investigated. Aim of the study was to investigate the Copenhagen General Population Study, totaling 110, 913 persons.
the association between scores including PRO-C3, and CVEs inci- All participants were genotyped for six variants with known effects
dence in a large prospective cohort of NAFLD patients. on fatty liver disease: PNPLA3 rs738409, TM6SF2 rs58542926,
Method: The present study is a post hoc analysis of the Plinio Study HSD17B13 rs72613567, MBOAT7 rs641738, MTARC1 rs2642438, and
(ClinicalTrials.gov: NCT04036357). PRO-C3 detection was performed GCKR rs1260326.
in plasma using ELISA commercial kit (Novus Biological). ADAPT,
FIBC3 and ABC3D were calculated. Data on CVEs were prospectively
collected with periodical phone calls (every six months) and visits
(every 12 months).
Results: The median follow-up was 47.8 [25.3–72.8] months yielding
2786.5 person-years of observation. During the follow-up, 41
patients (1.5% year) experienced CVEs. Patients who experienced
CVEs were more frequently males ( p = 0.010) and had higher
prevalence of type 2 diabetes ( p = 0.006), metabolic syndrome ( p =
0.002) and of prior CVE event ( p < 0.001). The prevalence of impaired
ADAPT ( p = 0.038), FIBC3 ( p = 0.015) and ABC3D ( p < 0.001) were
higher in patients with CVEs. At multivariate Cox regression analyses,
the association with CVEs was confirmed for ABC3D>3 (HR: 2.29
[1.17–4.47]) in the whole population and for FIBC3 (HR: 1.40 [1.06–
1.85]) and ABCD3 (HR: 1.40 [1.06–1.84]) only in patients who did not
experience a CV event before enrollment (in primary prevention)
(Table 1). In all the analyses performed in the whole cohort, prior-CVE
was the strongest predictor of new onset CVEs during the follow-up
(data not shown).

Conclusion: This from the Plinio cohort study is the first evidence of
an association between ADAPT, FIBC3, ABC3D and cardiovascular
events in NAFLD. These scores detect high-risk patients for both liver
and cardiovascular complications, may contribute to better identify a
sub-population of NAFLD patients who deserve a more holistic
approach.

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POSTER PRESENTATIONS
Results: During a median of 9.5 years of follow-up, 16, 119 individuals
died, hereof 201 due to liver-related causes, 1, 736 to ischemic heart
disease, and 4, 973 to extrahepatic cancer. The variants at PNPLA3,
HSD17B13, TM6SF2, and MBOAT7 (but not those at MTARC1 and GCKR)
were individually associated with liver-related mortality, with per-
allele hazard ratios of 1.3 to 1.6 ( p values <0.06). The strongest effect
was seen for the PNPLA3 variant, for which homozygous carriers had
a three-fold higher risk of liver-related death compared to non-
carriers. A previously developed genetic risk score comprised of the
variants at PNPLA3, TM6SF2 and HSD17B13 was robustly associated
with stepwise increased liver-related mortality, with a maximum
hazard ratio of 13 (95% CI: 3.8 to 48) for those with 5 or 6 versus 0 risk-
increasing alleles ( p for trend = 9 × 10E-7, see Figure, bottom panel).
The fatty liver disease variants, individually or combined into risk
scores, did not associate with ischemic heart disease-related,
extrahepatic cancer-related, or all-cause mortality (Figure, top panel).
Conclusion: High genetic risk of fatty liver disease increased liver-
related mortality but did not influence the risk of death due to
ischemic heart disease or extrahepatic cancer, nor all-cause mortality
in the general population. These data support that fatty liver disease
is causally associated with liver-related mortality, but not with
mortality due to other causes.

THU083
Role of NAFLD-associated genetic variants on renal function in Conclusion: In our cohort of adult patients with NAFLD, we found no
patients with non-alcoholic fatty liver disease association between CKD and PNPLA3, TM6SF2, MBOAT7 and GCKR
Laura D’Erasmo1, Francesco Baratta1, Alessia Di Costanzo1, gene variants. Hypertension was the stronger predictor of eGFR
Ilaria Umbro1, Alessandra Colantoni1, Nicholas Cocomello1, impairment. Based on these findings, the association between NAFLD
Daniele Pastori1, Marcello Arca1, Francesco Angelico1, Maria Del Ben1. and CKD might be due to the shared metabolic risk factors rather than
1
Sapienza, University of Rome the genetic NAFLD background.
Email: [email protected]
THU084
Background and aims Previous studies demonstrated the associ- The association between non-alcoholic fatty liver disease and
ation between non-alcoholic fatty liver disease (NAFLD) and chronic insulin resistance within normal glucose level population
kidney disease (CKD). Recent studies focused the attention on the role Chun-Yi Wang1, Kuan-Yu Lai1, Wen-Yuan Lin1, Tsung Po Chen1. 1China
of Patatin-like Phospholipase domain-containing 3 (PNPLA3) Medical University Hospital, Department of Community and Family
rs738409 polymorphism in the association between NAFLD and Medicine, Taichung, Taiwan
CKD in non-metabolic adults and children, but the genetic impact on Email: [email protected]
NAFLD-CKD association is still matter of debate. Aim of the study was
to investigate the impact of PNPLA3, Transmembrane 6 Superfamily Background and aims: The study of non-alcoholic fatty liver disease
Member 2 (TM6SF2), Membrane Bound O-Acyltransferase Domain (NAFLD) with association of type 2 diabetes (T2DM) reveals rapid
Containing 7 (MBOAT7) and Glucokinase Regulatory Protein (GCKR) growth of prevalence and incidence in recent years. The mechanism
genes on renal function in a large population of NAFLD patients. of NAFLD shows connection between insulin resistance (IR) and
Method: The present study is a post hoc analysis of the Plinio Study T2DM. The aim of this study was to investigate the association
(ClinicalTrials.gov: NCT04036357). PNPLA3, TM6SF2, MBOAT7 and between NAFLD and IR in normal glucose level population.
GCKR genes were analyzed by using Real Time PCR with TaqMan Method: We recruited participants from community and outpatient
probes. Glomerular filtration rate (GFR) was estimated with CKD-epi department in a hospital from central and northern Taiwan. Those
formula. The effect of the NAFLD genetic background on eGFR was with impaired fasting glucose or with diagnosis of T2DM were
estimated both including each gene individually and considering the excluded from our study. We screened the items of body max index
NAFLD genetic risk score (wGRS). The effect of NAFLD on renal (BMI), systolic/diastolic blood pressure (SBP/DBP), body fat ratio (%)
function was assessed by analyzing two end points: 1) eGFR <90 ml/ and social factors. We performed serum test after 8 hours overnight
min (rGFR) or 2) eGFR <60 ml/min (moderate-to-severe CKD). fasting. NAFLD was diagnosed based on an abdominal ultrasonog-
Results: This analysis was conducted on 564 NAFLD patients with raphy measurement. The calculation of IR used HOMA-IR formula
available renal function data. Among these, the 48.0% had an eGFR and was shown by tertile (T1, T2, and T3). The method of statics
below 90 ml/min while only 6.6% had moderate-to-severe CKD. The counted through analysis of variance (ANOVA) and multivariate
distribution of genotypes was superimposable if considering the logistic regression.
entire group of patients with eGFR <90 ml/min or only those with Results: A total of 485 subjects (mean age 42.0 ± 11.4 years) were
eGFR <60 ml/min. At multivariate regression analyses (table 1), we involved. The prevalence of NAFLD increased significantly among
did not observe any correlation between genotypes and renal increasing level of IR (34.1%, 40.1%, 47.8%, p <0.001). Although fasting
function. Conversely, we found that metabolic syndrome was highly plasma glucose were within normal range among three groups,
associated with rGFR (Odds ratio (OR): 1.52 (1.07–2.18)), whereas higher level of IR presented higher glucose value (81.9 ± 7.4 mg/dL,
prior Atherosclerotic Cardiovascular Disease (ASCVD) with moder- 85.1 ± 7.6 mg/dL, 87.3 ± 6.5 mg/dL, p < 0.0001). After adjusting for age,
ate-to-severe CKD (OR: 3.54 (1.22–10.24)). When introduced in the sex, BMI, exercise, alcohol consumption and cigarette smoking, the
model, arterial hypertension emerged as the strongest risk factor for risk of NAFLD was increased with the increment of IR (T3 v.s. T1: Odd
eGFR decline (OR: 1.45 (1.02–2.06) and OR: 2.85 (1.20–6.79) ratio [OR] 3.87, 95% confidence interval [CI], 2.08 to 7.21; T2 v.s. T1:
respectively for rGFR and moderate-to-severe CKD) (table 1). OR 1.83, 95% CI, 1.11 to 3.00) after adjusting for confounding factors.

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 POSTER PRESENTATIONS
Conclusion: This study shows that in normal sugar level groups, the Scotland-Innovation Centre (PMS-IC), Glasgow, United Kingdom;
significant increasing risk of NAFLD if IR presented even in normal 4
Edinburgh Pathology, Edinburgh, United Kingdom
glucose level groups. The mechanism of NAFLD influenced hepatic Email: [email protected]
enzymes production and further IR involved. We should take early
Background and aims: Studies have correlated liver gene expression
intervention if abnormal IR present.
to pathological and clinical features of NAFLD cross-sectionally, but
THU085 there is a paucity of longitudinal data using molecular features to
Chronic pruritus represents a major burden in non-cholestatic predict patient outcomes. Such data is critical for accurate risk
hepatobiliary disorders stratification and identification of novel treatments for specific
subphenotypes of NAFLD. Using SteatoSITE (https://steatosite.com/),
M. Düll1,2, Vanessa Karlen1,2, Marcel Vetter1,2, Peter Dietrich1,2,3,
a resource containing integrated genetic, clinical and pathological
Jörg Kupfer4, Markus F. Neurath1,2, Andreas E Kremer1,2,5. 1Deutsches
Zentrum Immuntherapie (DZI), Erlangen, Germany; 2Friedrich- data, we studied hepatic RNA-sequencing (RNA-seq) and linked
electronic health record (EHR) data to identify gene expression
Alexander-University Erlangen-Nürnberg, Department of Medicine 1,
Erlangen, Germany; 3Friedrich-Alexander-University Erlangen- patterns across the full histological NAFLD spectrum and to
determine transcriptomic signatures that are associated with
Nürnberg, Institute of Biochemistry, Emil-Fischer-Zentrum, Erlangen,
adverse clinical outcomes. Bulk tissue cell-type deconvolution was
Germany; 4Justus-Liebig-University Giessen, Institute of Medical
Psychology, Giessen, Germany; 5University Hospital Zürich, Department also performed using published single-cell RNA-seq (scRNA-seq)
data to elucidate changes in cellular composition to inform rational
of Gastroenterology and Hepatology, Germany
Email: [email protected] biomarker and drug development.
Method: Bulk RNA-seq data was analysed from 692 liver samples
Background and aims: While previous data indicated a high (normal liver controls (n = 28), isolated steatosis (n = 43), steatosis
prevalence of pruritus in patients with immune-mediated liver with inflammation and/or hepatocyte ballooning (n = 621), including
disorders, there is only limited data on pruritus in hepatobiliary samples from all fibrosis stages). Time until death or censoring was
diseases in general. This study therefore aimed at further investigat- retrieved for each patient. Differentially expressed genes (DEGs)
ing epidemiology, clinical features, and influence on quality of life between alive and dead patients at 1, 2, 3 and 5 years were used to
(QoL) in a large cohort of patients with different liver diseases. generate a transcriptional signature predictive of mortality. Multi-
Method: We performed a prospective, cross-sectional study in a large subject Single-cell Deconvolution (MuSiC) was used to compare
Hepatology outpatient clinic from August 2020-May 2021. We counts from each bulk RNA-seq sample with scRNA-seq data from
collected extended clinical data including characteristics of pruritus healthy and cirrhotic livers to estimate proportions of liver macro-
(e.g. mean/worst itch intensity on a numeric rating scale, NRS) and phage, mesenchyme, endothelial, B- and T-cell subtypes across
questionnaires containing validated scores such as ItchyQoL and discrete NAFLD stages.
SF12. Statistical analyses were performed using Mann-Whitney-U- Results: RNA-seq identified 45 DEGs in early NAFLD (i.e., isolated
test and Spearman`s rank correlation. Data are given as mean ± SEM. steatosis) and 9826 DEGs in advanced NAFLD (i.e., fibrosis stage F4),
Results: In total, 609 patients participated in this study of whom compared with controls. KEGG analysis showed enrichment of
27.3% (N = 166) presented with liver cirrhosis. 24.1% (N = 147) of all inflammatory pathways in early-stage disease (e.g., cytokine-cyto-
patients reported on pruritus with 61.9% (N = 91) being female. In the kine receptor interactions; q <0.01), whilst pathways linked to
pruritus group 52.7% (N = 79) of all patients suffered from non- extracellular matrix were only enriched in advanced disease (q
cholestatic liver diseases such as (non)alcoholic fatty liver disease, <0.0001). Linkage of RNA-seq with EHR data identified DEGs
(non)alcoholic steatohepatitis (N)ASH, viral hepatitis, and associated associated with mortality including potential biomarkers such as
liver cirrhosis. Immune-mediated and cholestatic liver diseases such growth/differentiation factor 15 (GDF15) and fibroblast growth factor
as primary biliary cholangitis, primary and secondary sclerosing 21 (FGF21). Deconvolution analysis revealed statistically significant
cholangitis, and genetic disorders represented 46.3% (N = 68). The correlations between histological fibrosis scores and expanded
majority of all pruritic patients reported on chronic itch with a populations of scar-associated macrophages, myofibroblasts, endo-
duration >6 weeks (80.9%; N = 119). Only 17.7% (N = 26) received oral thelial cells and B-cells.
anti-pruritic therapy with fibrates being most commonly prescribed Conclusion: Using SteatoSITE, the world’s first data commons for
(30.5%, N = 8). Mean and worst itch intensity during the last week NAFLD, we defined hepatic gene signatures across the full disease
were rated at moderates intensities of 3.7 ± 0.2 and 4.2 ± 0.3 on a NRS, severity spectrum. Linkage to EHR-derived outcomes enables
respectively. The QoL of affected patients quantified by ItchyQoL identification of liver transcriptional features associated with
correlated with the mean and worst itch intensities (rs = 0.34; p < increased mortality. This work will underpin future studies aimed
0.001; r = 0.40; p < 0.0001). SF-12 analyses exhibited significantly at developing a stratified medicine approach for NAFLD.
lower median physical ( p < 0.0001) and mental scores ( p < 0.01,
Mann-Whitney-U-test) in the pruritus group. THU087
Conclusion: Pruritus affected almost every fourth patient with Different effects of low muscle mass on the risk of non-alcoholic
hepatobiliary diseases and reduced their QoL. A significant number fatty liver disease and liver cirrhosis in a prospective cohort
of patients remain treated insufficiently. Our findings underscore the Hun Jee Choe1,2, Hyunsuk Lee1,2, DongHo Lee1,2, Soo-Heon Kwak1,2,
need to increase awareness of chronic itch in hepatobiliary disorders Bo Kyung Koo2,3. 1Seoul National University Hospital, Internal Medicine,
and to study this symptom in clinical trials beyond the classical Seoul, Korea, Rep. of South; 2Seoul National University College of
cholestatic liver disorders. Medicine, Internal Medicine, Seoul, Korea, Rep. of South; 3Seoul,
Boramae Medical Center, Seoul, Korea, Rep. of South
THU086 Email: [email protected]
Mortality prediction in non-alcoholic fatty liver disease using
SteatoSITE: an integrated gene-to-patient data commons for high- Background and aims: As non-alcoholic fatty liver disease (NAFLD)
definition non-alcoholic fatty liver disease research and sarcopenia share insulin resistance as a common pathophysi-
ology and have overlapping clinical manifestation of metabolic
Maria Jimenez Ramos1, Frances Turner2, Prakash Ramachandran1,
Donald R. Dunbar2, Lynn McMahon3, Marian McNeil3, Tim Kendall1,4, derangement, it is hard to differentiate the independent effect of
sarcopenia on the development of NAFLD from concomitant
Jonathan Fallowfield1. 1The Queen’s Medical Research Institute, Centre
metabolic disorders. Using a community-based prospective cohort
for Inflammation Research, Edinburgh, United Kingdom; 2Edinburgh
Genomics, Edinburgh, United Kingdom; 3Precision Medicine study, the contributions of low muscle mass and genetic risk factors,

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POSTER PRESENTATIONS
to the development of NAFLD and NAFLD-related liver cirrhosis were In particular, we aim to investigate if the relative importance of liver-
investigated in the Korean population. related deaths is lower in the elderly population such that screening
Method: This prospective community-based cohort study included is no longer meaningful.
40–70-year-old adults, followed-up biennially from 2001–2002 to Method: We conducted a territory-wide retrospective cohort study of
2017–2018. NAFLD was defined as a hepatic steatosis index of 36 or adult NAFLD patients between 2000 and 2021 in Hong Kong. The
higher, and liver cirrhosis was defined based on the fibrosis-4 index. outcomes of interest were all-cause and cause-specific mortality. Age
Sex-specific quartiles of body mass index (BMI)-adjusted muscle at time of death were studied by subgroups of 10-year intervals.
mass were calculated, and low muscle mass was defined as the lowest Results: During 662, 471 person-years of follow-up of 30, 943 NAFLD
quartile (Q1). Cox proportional hazard models for incident NAFLD or patients, there were 2, 097 deaths. The top 3 causes of death were
liver cirrhosis incorporating age, sex, BMI of 25 kg/m2 or higher, pneumonia, extrahepatic cancer and cardiovascular diseases.
metabolic syndrome, and PNPLA3 and TM6SF2 risk alleles were used Extrahepatic cancer was the leading cause of death, followed by
to assess the independent determinants for incident NAFLD and liver pneumonia and cardiovascular diseases before the age of 80.
cirrhosis among individuals with NAFLD at baseline. Pneumonia became the leading cause of death after the age of 80.
Results: Among the 4, 038 participants without NAFLD at baseline Liver disease was the sixth leading cause of death in patients aged 70–
(mean age, 51.5 ± 8.8 years), 920 (22.8%) developed NAFLD during the 79 and 80–89 years, accounting for 5.1% and 5.9% of deaths,
follow-up period of 12 years. As muscle mass decreased, the risk of respectively, but only accounted for about 3% or less of the deaths
NAFLD increased even after adjustment for age, sex, obesity, in the other age groups. The incidence of liver-related death was
metabolic syndrome, and PNPLA3 and TM6SF2 risk alleles (hazard higher in men before the age of 70 but higher in women afterwards.
ratio [HR] per quartile, 1.18, 95% confidence interval (CI), 1.11–1.27, p The incidence of liver-related death in women increased from 0.62 to
<0.001). TM6SF2 also affected the risk of NAFLD (HR 1.19, [95% CI, 7.14 per 10, 000 person-years from age 60–69 to 70–79 years.
1.00–1.40]. Conclusion: The relative importance of liver-related death increases
Of the 1, 176 patients with NAFLD but without hepatic fibrosis at with age in NAFLD patients, especially among women. Thus,
baseline, incident liver cirrhosis was found in 51.8%, 44.7%, 42.6%, and detection of NAFLD and advanced liver disease should be continued
41.0% in Q1, Q2, Q3, and Q4 of BMI-adjusted muscle mass, in the elderly population so far if they remain candidates for
respectively, during the follow-up period ( p for trend = 0.006). treatment.
However, this trend lost its statistical significance when adjusted Key words: non-alcoholic fatty liver disease, liver-related deaths, age
for confounders. The PNPLA3 risk variant and not the TM6SF2
genotype, was an independent risk factor for developing liver THU089
cirrhosis among NAFLD patients (HR 1.17, 95% CI 1.04–1.32, p = 0.010). Hepatic fat as a novel marker for high-risk coronary
atherosclerosis in familial hypercholesterolaemia: a CT-based
study
Gavin Huangfu1, Biyanka Jaltotage1, Jing Pang2, Nick Lan1,
Arun Abraham1, Jacobus Otto3, Abdul Ihdayhid1,4, Jamie Rankin1,
Benjamin Chow5, Gerald Watts2,6, Girish Dwivedi1,2,4,
Oyekoya Ayonrinde2,7. 1Department of Cardiology, Fiona Stanley
Hospital, Murdoch, Western Australia, Australia; 2School of Medicine,
Faculty of Health and Medical Sciences, University of Western Australia,
Australia; 3Department of Radiology, Fiona Stanley Hospital, Murdoch,
Western Australia, Australia; 4Harry Perkins Institute of Medical
Research, Murdoch, Western Australia, Australia; 5Department of
Medicine (Cardiology), University of Ottawa Heart Institute, Ottawa,
Ontario, Canada; 6Lipid Disorders Clinic, Department of Cardiology,
Royal Perth Hospital, Perth, Western Australia, Australia; 7Department of
Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch,
Western Australia, Australia
Email: [email protected]
Background and aims: The liver is a transducer of cardiovascular risk
factors through central regulation of lipid and glucose metabolism,
insulin signalling and the production of inflammatory and thrombo-
genic factors. Individuals with heterozygous familial hypercholester-
olaemia (FH) have accelerated but variable progression of coronary
Conclusion: Both lower muscle mass index and genetic risk variants artery disease (CAD). We investigated the association between
are important contributors to the development of NAFLD. In patients hepatic steatosis (HS) and coronary atherosclerosis, including
already diagnosed with NALFD, however, PNPLA3 conferred a greater plaque burden, composition, and morphology in adults with FH.
risk for progression to liver cirrhosis than did lower muscle mass. Method: High-risk plaque (HRP) features (low attenuation, positive
remodelling, spotty calcification), plaque volume (PV) and pericor-
THU088 onary adipose tissue (PCAT) attenuation were assessed using
Age and the relative importance of liver-related deaths in non- coronary computed tomography angiography (CCTA). From concur-
alcoholic fatty liver disease rently captured upper abdominal images, severity of HS was
Huapeng Lin1, Terry Cheuk-Fung Yip1, Xinrong Zhang1, Guanlin Li1, computed, as liver minus spleen computed tomography attenuation
Yee-Kit Tse1, Vicki Wing-Ki Hui1, Yan Liang1, Che To Lai1, (HUL−S) and stratified into quartiles. Associations were assessed using
Stephen Chan1, Henry LY Chan1, Grace Wong1, logistic regression, adjusting for cardiometabolic and conventional
Vincent Wai-Sun Wong1. 1The Chinese University of Hong Kong, Hong risk factors, lipid-lowering treatment use, coronary artery calcium
Kong (CAC) and obstructive CAD (≥50% stenosis).
Email: [email protected] Results: Of 213 patients with FH (median age 54.0 [46.0–59.5] years,
Background and aims: It is unclear if the leading causes of death in 58.7% female), median HUL-S was 13.17 [6.58–18.33], 59% had CAC
patients with non-alcoholic fatty liver disease (NAFLD) differ by age. score >0, 36% obstructive CAD and 77% HRP features. Increasing HS

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 POSTER PRESENTATIONS
was associated with higher CAC score ( p = 0.008), number of HRP characteristics from non-NAFLD and NAFLD participants were
features ( p = 0.007) and presence of obstructive CAD ( p = 0.01) and compared. Weighted survival was analyzed using univariate and
CAC ( p = 0.02) as demonstrated in Figure 1. HS was associated with multivariate Cox proportional hazards model.
the presence of both HRP (odds ratio [OR]: 1.48; 95% confidence Results: A total of 2299 (weighted 2*107 subjects) NAFLD and 8736
interval [CI]: 1.09–2.00; p = 0.01) and proximal HRP features (OR: (weighted 108 subjects) subjects without NAFLD were included.
1.52; 95% CI: 1.18–1.96; p = 0.001). Associations persisted when NAFLD individuals were older (age 20–39 years 34.8% (standard error
controlling for cardiovascular risk factors, features of metabolic (SE) (1.9) vs 52.5% (1.1), p <0.001), male dominant (54.0% (SE (1.5) vs
syndrome, lipid-lowering treatment use, presence of obstructive CAD 45.3% (0.7), p <0.001), had more often a lower education level (<9
and CAC score. HS was associated with a higher PV (Q4: 499 mm3 vs years 15.6% (1.2) vs 9.6% (0.7), p <0.001), hypertension (33.0% (1.8) vs
Q1: 414 mm3, p = 0.02), driven by low attenuation ( p = 0.03) and non- 18.3% (0.7), p <0.001), type 2 diabetes (10.8% (0.8) vs 3.4% (0.3), p
calcified ( p = 0.03) plaques. No differences in PCAT were observed. <0.001) and CVD history (7.3% (0.7) vs 3.5% (0.3), p <0.001) comparing
to no-NAFLD participants.
Multivariate analysis showed that after adjusting age and gender,
NAFLD was not associated independently with CVD mortality
(adjusted hazard ratio (aHR) 1.079, 95% confidence interval (CI)
0.911–1.279, p = 0.369). This did not differ (aHR 1.109 95% CI 0.892–
1.378, p = 0.345) after adjustment for putative risk factors including
age, gender, race, education, poverty income ratio, hypertension,
diabetes, smoking status and CVD history.
Conclusion: This prospective cohort suggests that the presence of
NAFLD is not associated with CVD mortality among US adults.

THU091
Sarcopenia is associated with the severity of metabolic associated
fatty liver disease in elderly residents
Figure 1: Coronary Artery Disease Characteristics, Stratified by HUL-s Xiaohui Liu1, Jingjing Song1, Shuang Zhang1, Shan Liang1, Zhang Jing1.
1
Quartile Beijing Youan Hospital, Capital Medical University, The Third Unit, The
Department of Hepatology, Beijing, China
Conclusion: HS is associated with multiple indices of coronary
Email: [email protected]
atherosclerosis, particularly HRP features, in patients with FH. This
appears to be independent of conventionally measured risk factors Background and aims: It has been proved that sarcopenia was
and may involve additional mechanisms related to HS. associated with the metabolic associated fatty liver disease (MAFLD),
but their relationship in elderly patients has not been studied in
THU090 which sarcopenia is more prevalent.
Non-alcoholic fatty liver disease impcat on cardiovascular disease Method: A cross-sectional survey was conducted among 1353 elderly
death: a population-based study residents over 65 years old in a community in Beijing. Demographic
Chaonan Jin1, Sheng Bi1, Mei Deng2,3,4, Jifang Sheng1. 1The First data, medical history, physical examination and laboratory examin-
Affiliated Hospital, College of Medicine, Zhejiang University, State Key ation results were collected for all subjects. Fatty liver was detected by
Laboratory for Diagnosis and Treatment of Infectious Diseases, National B type ultrasound. Body composition was detected by Inbody720
Clinical Research Center for Infectious Diseases, Collaborative Innovation (Bios pace, Korea). Liver fat content and liver stiffness was examined
Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, by Fibro Scan. Sarcopenia index (SI) was calculated as total ASM (kg)/
Zhejiang Province, China; 2Guangxi Key Laboratory of Molecular BMI (kg/m2). Sarcopenia was defined as SI<0.789 for men and<0.521
Medicine in Liver Injury and Repair, Affiliated Hospital of Guilin Medical for women.
University, Guilin, Guangxi, China; 3Department of Radiation Oncology, Results: Among the 1353 elderly residents, the mean age is 70.5 ± 5.0
Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China; years old and women account for 66.0%. There were 755 (55.8%)
4
Guangxi Health Commission Key Laboratory of Basic Research in patients were diagnosed as MAFLD. The BMI, waist circumference,
Sphingolipid Metabolism Related Diseases, Affiliated Hospital of Guilin hip circumference, waist-to-hip ratio, upper arm circumference, body
Medical University, Guilin, Guangxi, China fat percentage and visceral fat area in MAFLD group were significantly
Email: [email protected] higher than those in the non-MAFLD group (all p < 0.05). The
proportion of patients with sarcopenia (20.3%) was significantly
Background and aims: Non-alcoholic fatty liver disease (NAFLD)
higher than in non-MAFLD group (15.6%, p = 0.026). MAFLD patients
represents a common risk factor for cardiovascular disease (CVD).
with sarcopenia had higher BMI, waist circumference, hip circum-
However, the impact of NAFLD on CVD mortality remains to be
ference, waist-to-hip ratio, upper arm circumference, body fat rate,
defined. We aimed to investigate whether NAFLD has a negative
visceral fat area, glucose and lipid metabolism indexes than those
influence on CVD mortality.
without sarcopenia (all p < 0.05). They also had higher liver fat
Method: 11035 participants who were aged 20–74 years, completed
content [ (300.6 ± 43.5) vs. (295.1 ± 40.3), p<0.001] and liver stiffness
both interview and examination in mobile examination centers, with
scores [5.3 (4.3, 7.0) vs. 5.0 (4.1, 6.3), p<0.001] when compared to non-
’confident or absolute confident’ reports from clear and gradable
sarcopenia group. According to quartile stratification, Serum creatin-
ultrasound images, from US Third National Health and Nutrition
ine, HbA1c, HOMA-IR, hs-CRP, CAP and LSM increased significantly
Examination Survey (NHANES III: 1988–94) with follow-up of
from subjects with non-MAFLD to subjects with non-sarcopenia in
mortality to 2015 were included.
MAFLD group and subjects with sarcopenia in MAFLD group (all p for
NAFLD was defined as moderate or severe steatosis grade. Mortality
trend <0.001).
and follow-up data were obtained from NHANES III public-use linked
mortality file with underlying cause of death 113 (UCOD_113, 001 or
005 as CVD) recorded. Weighted demographic and clinical

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POSTER PRESENTATIONS
Conclusion: NAFLD Patients with BarSur present a clinically milder
disease phenotype in terms of serum profile and histology in our
large cohort of NAFLD patients after case-control matching and
independently of PNPLA3 genotype. Our observation warrants
further pathophysiological studies in this special subpopulation of
NAFLD.

THU093
Effects of SARS-CoV2 pandemic in a cohort of italian NAFLD
patients
Bernardo Stefanini1,2, Simona Leoni1, Roberta Capelli1,2,
Alice Secomandi1,2, Luca Muratori1,2, Fabio Piscaglia1,2, Silvia Ferri1.
1
IRCCS Azienda Ospedaliero-Universitaria di Bologna, Division of
Figure 1: Association between the status of metabolic dysfunction-asso- Internal Medicine, Hepatobiliary and Immunoallergic Diseases, Bologna,
ciated fatty liver disease (MAFLD)/sarcopenia and SCr, HbA1c, HOMA-IR, Italy; 2University of Bologna, Department of Medical and Surgical
CAP, LSM, hs-CRP by quartile stratification. Sciences (DIMEC)
Conclusion: We found that in elderly MAFLD patients, sarcopenia is Email: [email protected]
closely correlated with liver fat content and fibrosis. We should pay Background and aims: SARS-Cov2 wide and uncontrolled spread in
more attention to the system metabolic abnormal in elderly Italy in winter 2020 forced the authorities to declare an emergency
population. status characterized by a complete lock-down and a massive
temporary conversion of medical resources into COVID-positive
THU092 patients care. Some of the consequences were a great limitation to
NAFLD patients scheduled for bariatric surgery present with a physical activity and a reduced possibility to regularly follow
milder disease phenotype as compared to not morbidly obese outpatients in hospital.
NAFLD patients: analysis of a large real-world cohort Aim of our study was to evaluate the effect of COVID pandemic on
Monika Rau1, Sarah Kaps1, Hans Benno Leicht1, Florian P Reiter1, subjects with stable NAFLD followed in our outpatient liver clinic.
Marcin Krawczyk2, Andreas Geier1. 1University Hospital Würzburg, Method: we enrolled 43 patients (58% females, median age 59 years,
Department of Internal Medicine II, Würzburg, Germany; 2Saarland mean BMI 29) with defined NAFLD in charge to our liver outpatient
University Medical Center, Department of Medicine II, Homburg, unit with these characteristics: a first visit in 2017–2018, a pre-
Germany pandemic visit in 2019, a programmed visit between March and June
Email: [email protected] 2020 not performed due to the pandemic condition and a post-
Background and aims: Non-alcoholic fatty liver disease (NAFLD) is pandemic visit after September 2020.
the leading chronic liver disease worldwide associated with the At first visit all patients were given dietary advice following the
metabolic syndrome. Based on recent findings, one can speculate that Mediterranean approach and encouraged to increase physical activity
patients with morbid obesity might present have a milder NAFLD up to 150 minutes/week of aerobic and/or anaerobic activity of
than those without. Aim of this study is to analyze the clinical moderate intensity. Medications were prescribed when needed. At
phenotype of NAFLD in patients with and without (w/o) bariatric the three time points a complete anamnestic, physical, laboratory and
surgery (BarSur). ultrasound evaluation was performed.
Method: In total, 814 patients were prospectively included (10/12– Patients with advanced disease (decompensated cirrhosis and/or
04/21) in a single-center study at a tertiary hospital. NAFLD was hepatocellular carcinoma) were excluded from the study as they were
diagnosed either clinically by Fibroscan/CAP (n = 413) or histologi- seen in outpatient clinic also during the lock-down period.
cally (n = 348). Routine laboratory parameters were available for all Results: compared to first visit, post-pandemic evaluation in our
patients and 351 patients were genotyped for PNPLA3 p.I148M cohort of patients revealed stable BMI, HOMA index, transaminases,
variant. lipid profile, NAFLD fibrosis score (NFS), FIB-4, B-mode hepatorenal
Results: 761 NAFLD patients were included (n = 512 with and n = 249 ratio (BMHRR) and liver stiffness (2D:SWE:SSI), whereas a reduction
w/o BarSur) in this cohort. A case-control matching for age, sex, and was detected in gammaGT levels ( p = 0.02).
diabetes mellitus (T2DM) was performed to analyse different disease We then considered separately patients that at pre-pandemic visit
phenotypes (n = 202 with and n = 201 w/o BarSur). Patients with had lost >5% of their basal weight (10 patients, mean weight −7.2%,
BarSur had more often arterial hypertension (82% vs. 52%; p < 0.001), mean BMI 27, 0) and those who had not (33 patients, mean weight
hypertriglyceridemia (16% vs. 9%; p < 0.01) and coronary heart +1.4%, mean BMI 29, 4). At post-pandemic control, patients in both
disease (9% vs. 3%; p < 0.01) compared to NAFLD patients w/o groups maintained their weight trend (mean BMI 27, 3 and 29, 6
BarSur. However, BarSur NAFLD patients were characterized by respectively; weight change compared to first visit −6.0% and +2, 1%
significantly lower disease specific serum profile including ALT (32 vs. respectively, p <0.0001). Weight variations were associated to NFS
55U/l; p < 0.001), AST (28 vs. 39U/l; p < 0.001), gGT, ferritin and FIB-4 (but not FIB-4, BMHRR and liver stiffness) modifications (in weight
(1, 00 vs. 1, 17; p < 0, 001). Although higher frequency of PNPLA3 p. losers: −19.4%, in weight maintainers +55.9%, p = 0.034).
I148M genotype was observed in NAFLD patients w/o BarSur Surprisingly, all patients, especially those in the latter group, reported
compared to BarSur NAFLD patients (CC: 46% vs. 58%; CG: 39% vs. an increase in their physical activity after the first visit that was
38%; GG: 15% vs. 4%;p < 0.01), an additional matching for the PNPLA3 maintained also during the pandemic phase (from scarse-moderate
genotype showed the same significantly lower serum ALT, AST, GGT to moderate-good p = 0.004).
and ferritin in BarSur NAFLD patients. Differences in histology were Conclusion: in patients with NAFLD, when the behavioral approach
analysed by case-control matching for age, sex and T2DM only in (in which physical activity may exert an independent protective role)
patients with available histology (n = 74 for each patient group). had been well consolidated in the pre-pandemic phase, it was
NAFLD patients w/o BarSur had significantly higher frequency of maintained also during COVID pandemic even without a strict
NASH (74% vs. 49%; p < 0.01), steatosis, ballooning and fibrosis (F2-F4 medical follow-up, thus allowing a preservation of the results
46% vs. 8%; p < 0.001). Non-invasive liver stiffness assessment by obtained.
Fibroscan was also significantly higher in NAFLD patients w/o BarSur
(8.4 vs. 6.6kPa; p < 0.01).

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 POSTER PRESENTATIONS
THU094 THU095
A higher Fibrosis-4 (FIB-4) score is associated with higher Comparison of hepatic and cardiovascular damage between HIV
healthcare costs and hospitalizations in patients with non- patients with steatosis and NAFLD: role of metabolic alterations
alcoholic steatohepatitis (NASH) and low visceral adiposity
Elliot Tapper1, Jesse Fishman2, Stephen Dodge2, Keith Miller2, Felice Cinque1,2, Rosa Lombardi1,2, Annalisa Cespiati1,2,
Ni Zeng3, Alina Bogdanov3, Machaon Bonafede3. 1University of Paolo Francione2, Erika Fatta2, Cristina Bertelli2, Giuseppina Pisano2,
Michigan, United States; 2Madrigal Pharmaceuticals, United States; Giovanna Oberti1,2, Lucia Colavolpe1,2, Francesca Alletto1,2,
3
Veradigm Paola Dongiovanni2, Marica Meroni2, Giorgio Bozzi3,
Email: [email protected] Alessandra Bandera1,3, Anna Ludovica Fracanzani1,2. 1University of
Milan, Department of Pathophysiology and Transplantation, Milan, Italy;
Background and aims: The cost and complexity of care for patients 2
Fondazione Ca’ Granda IRCCS Ospedale Maggiore Policlinico, Unit of
with Non-alcoholic Steatohepatitis (NASH) increases with disease
Internal Medicine and Metabolic Disease, Milan, Italy; 3Fondazione Ca’
stage. we aimed to study the Fibrosis-4 (FIB-4) score as a proxy for
Granda IRCCS Ospedale Maggiore Policlinico, Infectious Diseases Unit,
disease severity and test its association with increased disease
Milan, Italy
burden.
Email: [email protected]
Method: The Veradigm Health Insights Electronic Health Record
Database and linked Komodo administrative claims data were used to Background and aims: People living with HIV (PLWH) develop
identify adult patients with coded NASH with aspartate aminotrans- metabolic alterations and hepatic steatosis (HS), exposing them to
ferase (AST), alanine aminotransferase (ALT) and platelet results and increased cardiovascular (CV) risk. However, if presentation of HS in
age to compute a FIB-4. The index date was the first coded NASH this category of patients is different from that of non-alcoholic fatty
encounter between 2016 and 2020 with at least 6 months of database liver disease (NAFLD) is unknown. Aim: to evaluate metabolic,
activity pre- and post-encounter and a FIB-4 score. We excluded hepatic and CV alterations in PLWH and to compare them with those
patients coded with viral hepatitis, alcoholism, or alcoholic liver observed in primary NAFLD subjects.
disease. Inpatient hospital admissions and log-transformed costs for Method: forty-two HIV mono-infected patients (mean age 46 ± 12 ys,
pharmacy, hospital inpatient, emergency department, and outpatient male 81%; 90% with viral suppression) were enrolled. The cohort of
services were measured in the 12-month period surrounding index. PLWH underwent hepatic ultrasound (US) and those with evidence of
Multivariate logistic regression for any hospitalization and linear HS were compared to a sex and age matched NAFLD control group
regression for log total cost was performed, controlling for patient (1:2). For all enrolled subjects, anthropometric parameters (BMI,
demographics (age, race, sex, and geography), smoking status, waist circumference-WC), metabolic comorbidities, CV damage by
Charlson comorbidity index (CCI), and diabetes complications carotid ultrasound ( plaques, arterial stiffness by radiofrequency as
severity index (DCSI). pulse wave velocity-pWv) and heart ultrasound (systolic and diastolic
Results: 6, 743 patients met the study criteria; mean age was 56.1 ± function and epicardial adipose tissue-EAT) were assessed. All
13.3, patients were 62.9% female and 53.6% of patients were patients underwent transaminases determination, Fibroscan to
diagnosed with Type 2 Diabetes. Mean FIB-4 at index was 1.79 ± detect advanced fibrosis (LSM >8.9/7.2 kPa M/XL probe) and
1.88. A 1 unit increase FIB-4 at index was associated with a 4.2% bioimpedance (BIA) to quantify sarcopenia (SMI ≤10.75/6.75 kg/m2
increase in mean total annual cost ( p < 0.0001 CI 2.2% to 6.3%) and male/females) and fat mass. CV risk was assessed according to ESC
with an odds ratio of 1.12 ( p < 0.0001 CI 1.08 to 1.15) for guidelines. Genotyping for PNPLA3 was determined by Taqman assay.
hospitalization. CCI and DCSI were also significantly associated with Results: Thirty (63%) PLWH presenting HS were compared with 60
higher odds ratios for hospitalization (OR 1.27, p <0.001 CI 1.23 to 1.31 NAFLD patients. PLWH with HS presented no difference in the
and OR 1.27, p <0.001 CI 1.22 to 1.33). prevalence of metabolic alterations (type 2 diabetes 13% vs 13%, p =
1.0; hypertension 47% vs 42%, p = 0.82; dyslipidemia 83% vs 85%, p =
1.0) and sarcopenia (40% vs 52%, p = 0.81) compared to NAFLD,
despite lower BMI (27.1 ± 4 vs 29.1 ± 4.3 kg/m2, p = 0.04), WC (98 ± 9
vs 103.1 ± 10.3 cm, p = 0.03) and trunk fat mass (9.8 ± 3.3 vs 12.4 ±
4.7 kg, p = 0.02). No difference in the prevalence of increased
transaminases (17% vs 20%, p = 0.78) and advanced fibrosis (17% vs
12%, p = 0.53) was found, as well of high CV risk (84% vs 83%, p = 0.86),
pWv (7.4 ± 2 vs 6.9 ± 1.4 m/s, p = 0.18), carotid plaques (39% vs 28%,
p = 0.33), increased EAT (20% vs 17%, p = 0.77) and systolic (6% vs 5%, p
= 1.0) and diastolic dysfunction (7% vs 6%, p = 1.0). PNPLA3 distribu-
tion was not significantly different between groups ( p = 0.16).
Conclusion: Hepatic steatosis and fibrosis are highly prevalent in
patients with HIV. Interestingly, in PLWH metabolic alterations, liver
and cardiovascular damage are superimposable with those observed
in a primary NAFLD cohort, although in presence of lower visceral
adiposity. Therefore, screening for liver disease in HIV patients is
mandatory independently of obesity, as the increased risk of
metabolic and CV complications.
Conclusion: Higher FIB-4 score across a variety of ranges is associated
with increased costs and hospitalizations in the NASH population.

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POSTER PRESENTATIONS
THU096
Impact of intermittent fasting on anthropometric and clinical
outcomes in non-alcoholic fatty liver disease: systematic review
and meta-analysis
Marcia Lange1, Devika Nadkarni1, Lily Martin1, Carolyn Newberry2,
Sonal Kumar2, Tatyana Kushner3. 1Icahn School of Medicine at Mount
Sinai, New York, United States; 2Weill Cornell Medicine, Division of
Gastroenterology and Hepatology, New York, United States; 3Icahn
School of Medicine at Mount Sinai, Division of Liver Medicine, New York,
United States
Email: [email protected]
Background and aims: Currently, weight loss through caloric
restriction is the cornerstone of initial non-alcoholic fatty liver
disease (NAFLD) management. However, there remains a lack of
evidence-based guidelines on the benefits of intermittent fasting (IF)
for NAFLD. In this systematic review with meta-analysis, we evaluated
the effect of IF on anthropometric and clinical markers of NAFLD.
Method: We conducted a comprehensive search of MEDLINE,
EMBASE, and Cochrane Central databases as well as trial registries
and conference abstracts up to January 31, 2022. The search strategy
included all appropriate controlled vocabulary and keywords for
NAFLD and fasting. No date, language, or article type restrictions were
included in the search strategy. Studies of adults with NAFLD or non- Conclusion: Intermittent fasting interventions may improve BMI and
alcoholic steatohepatitis (NASH) undergoing an intermittent fasting body weight as well as reduce both liver steatosis and serum ALT
intervention reporting at least one anthropometric or clinical levels in adults with NAFLD. Studies with varying types of IF
outcome were included in our review. A random effects model was interventions and varying intervention durations likely contributed
used for meta-analysis to estimate mean differences between to meta-analysis heterogeneity. This data suggests that IF likely
intervention and control group for various outcomes. provides a benefit in NAFLD, but future randomized controlled
Results: Initial literature search yielded 16 294 studies, of which 10 studies are needed to validate the use of IF for NAFLD treatment.
772 were duplicates, leaving 5517 studies to screen for title/abstract.
An additional 5367 studies were excluded after title/abstract review THU097
with moderate concordance (k = 0.53). The remaining 150 studies The burden of liver fibrosis in the obese population
were assessed for full text review with fair concordance (k = 0.24). Gres Karim1, Dewan Giri1, Andrea Delgado Nieves1, Caileen Sennett1,
Twelve studies were included in the systemic review and meta- Andre Khazak1, Bo Hyung Yoon2, Amreen Dinani3. 1Icahn School of
analysis, totaling 908 participants with NAFLD, combined mean age Medicine at Mount Sinai Beth Israel, Department of Medicine, New York,
of 42.50 years (SD 14.54), 50% male. Meta-analysis of anthropometric United States; 2Icahn School of Medicine at Mount Sinai Beth Israel,
outcomes showed that the effect of IF on BMI and body weight was Mount Sinai Morningside, and Mount Sinai West (MSBIMW),
statistically significant (Mean difference (MD) −0.69 kg/m2, 95% CI Department of Gastroenterology, New York, United States; 3Icahn School
−1.29 to −0.09, p < 0.05; MD −2.51 kg, 95% CI −4.44 to −0.58, p < 0.05) of Medicine, Division of Liver Diseases, New York, United States
with moderate though statistically significant heterogeneity for both Email: [email protected]
(I2 = 47%, p = 0.07; I2 = 62%, p = 0.02). Clinical outcome analysis Background and aims: The impact of obesity extends beyond non-
showed that the effect of IF on liver steatosis (CAP, dB/m) and ALT alcoholic fatty liver disease (NAFLD). It is an independent risk factor
levels was also statistically significant (MD −27.52 dB/m, 95% CI for hepatocellular carcinoma (HCC), cirrhosis and liver decompensa-
−42.26 to −12.77, p < 0.01; MD −10.35 IU/L, 95% CI −19.9 to −0.8, p < tion. Liver fibrosis (LF) is linked to overall and liver-related mortality.
0.05) with zero to low heterogeneity for both outcomes (I2 = 16%, p The impact of obesity and LF is not as well established. Identifying LF
<0.01; I2 = 0%, p < 0.05). IF did not have a significant effect on AST in a high risk population with obesity is crucial to prevent disease
levels or liver stiffness (kPa). progression and implement early intervention. We aim to describe
the burden of LF in a population with obesity (BMI ≥30 kg/m2) and
understand the variables that contribute to the development of LF.
Method: Patients with a body mass index (BMI) ≥30 kg/m2 and no
chronic liver diseases (CLD) were identified using electronic medical
records from a tertiary care clinic between 01/2019 to 01/2020.
Demographic information, markers of liver inflammation and
synthetic function, medical conditions, imaging and histology were
recorded. The Fibrosis Index 4 (FIB-4) was calculated to determine the
stage of liver fibrosis; FIB-4 ≥1.3 indicated significant fibrosis. A
univariate and multivariate logistic regression analysis was per-
formed to identify factors contributing to the stage of fibrosis. Other
outcomes of interest were complications of cirrhosis, development of
HCC and mortality.

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 POSTER PRESENTATIONS
THU098
Impact of screening and treatment of obstructive sleep apnea in
non-alcoholic fatty liver disease
Kelsey Collins1, Amreen Dinani1, Horacio Romero Castillo1,
Brooke Wyatt1, Indu Ayappa1, Anne Mooney1. 1Mount Sinai Medical
Center, New York, United States
Email: [email protected]
Background and aims: Obstructive sleep apnea (OSA) has been
recognized as a risk factor for non-alcoholic fatty liver disease
(NAFLD). Oxidative stress and chronic intermittent nocturnal low
oxygen state promotes liver injury, inflammation, and liver fibrogen-
esis. It is estimated that persons with OSA are 2–3 times likely to have
NAFLD. Treatment of NAFLD is based around managing co-morbid-
ities and weight loss. The aim of our study is to prospectively screen
patients with NAFLD for OSA and evaluate the impact of OSA
treatment on NAFLD.
Method: Patients with NAFLD (defined by presence of hepatic
steatosis on imaging, controlled
attenuated parameter [CAP] ≥240 dB/m, or histology) were prospect-
ively screened for OSA using STOP-BANG (SB) and Epworth
Sleepiness Score (ESS) in an outpatient liver clinic. SB ≥3 or ESS
≥10 were characterized as ‘high risk’ for OSA and referred to Sleep
Medicine for home sleep testing with a WatchPAT device. Patients
confirmed with OSA were followed in Sleep Medicine and
Hepatology. Baseline characteristics, demographics and severity of
liver disease were collected and students t test as well as logistic
regressions were used to assess differences. Patients with NAFLD and
OSA were followed over time to determine the impact of OSA
treatment on NAFLD.
Results: Sixty-eight patients with NAFLD from a tertiary hospital
system were screened for OSA from; 41% were male, mean age 49
years, 21% were White Non-Hispanic, 32% Hispanic, 26% Other/
Results: A total of 2999 patients with BMI ≥30 kg/m2 were identified, Unknown. The median BMI was 32.8 kg/m2 with 68% ≥30 kg/m2
of which 1082 patients had no documentation of CLD during the consistent with obesity. At baseline, 53% had ALT above the upper
study period. Majority were female (66%), mean age 57 years (SD 13), limit of normal (ALT ≥30IU/L). Forty patients (59%) screened positive
and mean BMI 35 kg/m2 (SD 4.9). One third were white and 17% for OSA (mean SB = 5 and ESS = 7). There were no differences
Hispanic. Mean ALT and AST were 23 IU/L (3–671). Approximately observed in BMI, ALT, AST, liver stiffness (LF), or CAP scores for
40% (385/1082) had a FIB-4 ≥1.3, of which 80% had normal patients that screened positive and negative for OSA, however, the
aminotransferases (≤30IU/ml). Those with FIB-4 ≥1.3 were likely to group that screened negative for OSA, on average had higher high-
be female, Hispanic or black. Coronary artery disease (2.8[1.9, 4.1]), density lipoprotein (HDL) (44.1 mg/dL vs 52.4 mg/dL, p = 0.01), low-
hypertension (2.1[1.6, 2.7]), impaired renal function (GFR <60) (2.4 density lipoprotein (LDL) (99.1 mg/dL vs 116.9 mg/dL, p = 0.03), and
[1.7, 3.4]), elevated low density lipoprotein (0.99[0.98, 0.99]) and total cholesterol (176.4 mg/dL vs 200.7 mg/dL, p = 0.01). Compared to
cholesterol (0.993 [0.990, 0.997]), were associated with liver fibrosis patients with no diabetes (DM) ( p = 0.015), preDM and DM showed
in univariate analysis, p < 0.001. No association was seen with statistically significant increased odds of screening OSA positive
diabetes. An inverse association was found between BMI and liver (OR = 5.3 [CI:1.535–18.15]; OR = 4.6 [CI:1.12–18.80]). Of those referred
fibrosis (0.96[0.93, 0.99], p = 0.03) in univariate analysis, but not for formal OSA testing, n = 20 (55%) complied, and n = 17 (85%)
statistically significant in the multivariate analysis (0.96[0.92, 1.00], patients were subsequently diagnosed with OSA and underwent
p = 0.08). In the multivariate model, female, older age, black, elevated treatment (mean AHI4 = 19.6/hr). Due to lack of OSA treatment
AST and low platelet count were found to be associated with acceptance/adherence, overall impact could not be assessed.
significant LF. Conclusion: Screening for high risk OSA with a combination of STOP-
Conclusion: In our analysis of an obese population we found a high BANG and ESS was reliable for identifying subjects with OSA
40% degree of significant liver fibrosis in those without known CLD. confirmed by sleep test. Closer attention to lipid profile and insulin
The presence of CAD, HTN, and GFR <60 appear to be significantly resistance ( preDM and DM) were risk factors identified contributing
associated with liver fibrosis. Sex, ethnicity may have a role in to the diagnosis of OSA. Impact of treatment for OSA needs further
development of LF in obesity. Majority of these patients would not evaluation.
have been assessed for liver disease due to normal liver enzymes.
People with obesity should be pro-actively assessed for CLD and
NAFLD.

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POSTER PRESENTATIONS
THU099
Undiagnosed NAFLD in the obese population: in sight, out of mind
Dewan Giri1, Gres Karim2, Andrea Delgado Nieves2, Andre Khazak2,
Caileen Sennett2, Bo Hyung Yoon3, Ilan Weisberg4, Amreen Dinani5.
1
Icahn School of Medicine at Mount Sinai Beth Israel, Department of
Medicine, New York, United States; 2Mount Sinai Beth Israel, Internal
Medicine, New York; 3Mount Sinai Beth Israel, Morningside and West,
Department of Gastroenterology, New York, United States; 4New York
Presbyterian-, Brooklyn Methodist, Department of Gastroenterology and
Hepatology; 5Icahn School of Medicine, Division of Liver Diseases,
New York, United States
Email: [email protected]
Background and aims: Obesity is a leading risk factor for non-
alcoholic fatty liver disease (NAFLD), with estimated prevalence rates
as high as 50–90%. There is a strong correlation between obesity and
hepatocellular carcinoma (HCC), cirrhosis and advanced liver disease.
Despite the rising burden of NAFLD in obesity, no concrete guidance
exists for screening in this high-risk population. Early detection can
facilitate early intervention and development of pathways to
specialty care. Herein, we describe the burden of NAFLD in an
obese population and affirm the need to proactively assess patients
that would otherwise be undiagnosed.
Method: Patients with a diagnosis of obesity (body mass index [BMI]
>30 kg/m2) and no documented chronic liver diseases (CLD) were
identified using electronic medical record (EMR) from a tertiary care
clinic between 01/2019 to 01/2020. Patients who met the criteria for
NAFLD (as per AASLD guidelines) were also identified from the same
cohort with attention to those who had documentation of NAFLD
diagnosis in EMR (ICD-10 codes and review of notes) and those who
did not. Demographic information, markers of liver inflammation and
synthetic function, medical conditions, imaging and histology were
recorded. Fibrosis Index 4 (FIB4) was calculated to determine the
stage of liver fibrosis. We reviewed the reason for referrals,
differences in the two groups of patients with NAFLD who were
and were not diagnosed.
Results: A total of 2999 patients with BMI >30 kg/m2 were identified,
586 (20%) had a diagnosis of NAFLD (D-NAFLD) and 1350 had no
diagnosis of CLD. One-fifth (268/1350, 20%) of patients without Conclusion: We have demonstrated that obesity continues to be an
diagnosis of CLD met diagnostic criteria for NAFLD (UD-NAFLD). underrecognized risk factor for NAFLD. In our cohort, 20% of patients
Baseline characteristics of D-NAFLD and UD-NAFLD were compar- with obesity had missed diagnosis of NAFLD. Based on current
able. Majority of UD-NAFLD had normal (<30IU/L) alanine trans- guidelines, 70% of these patients would not have been worked up for
aminase (ALT) and aspartate transaminase (AST), 65% and 69% NAFLD with normal liver enzymes. NAFLD should be considered as a
compared to 48% and 60% in D-NAFLD, respectively. Mean AST and comorbidity when evaluating patients with obesity.
ALT were higher in D-NAFLD (38 IU/L and 46 IU/L, respectively) versus
UD-NAFLD (33 IU/L and 33 IU/L, respectively). Mean FIB4 was similar, THU100
1.62 and 1.64. FIB4 in the UD-NAFLD group with normal ALT and AST Prevalence of non-alcoholic steatohepatitis in patients
was 1.17 compared to 1.34 in D-NAFLD. Hypertension (55%), coronary undergoing laparoscopic cholecystectomy for gallstone with non-
artery disease (15%) and diabetes mellitus (30%) were more common alcoholic fatty liver disease
in patients in the undiagnosed cohort. Presence of CAD or DM in both Utpal Anand1,1, Aaron John1, Ramesh Kumar1, Rajeev Priyadarshi2. 1All
groups was associated with a higher FIB4. Majority of patients in D- India Institute of Medical Sciences, Patna, Surgical Gastroenterology,
NAFLD were referred to the specialty clinic for either elevated liver Patna, India; 2All India Institute of Medical Sciences, Patna,
tests (24%), radiographic evidence of steatosis (26%) or both (19%). Radiodiagnosis, Patna, India
Email: [email protected]
Background and aims: Gallstone disease (GSD) and non-alcoholic
fatty liver disease (NAFLD) shares common risk factors. Non-alcoholic
steatohepatitis (NASH) is a more progressive form of NAFLD and is
among the most frequent causes of cirrhosis. There is a lack of
prospective studies utilizing liver biopsy during laparoscopic chole-
cystectomy in patients of gallstones and NAFLD for assessing the
prevalence of NASH and factors associated with it. The aim of the
study was to assess the usefulness of liver biopsy for patients with
gallstones and NAFLD who underwent laparoscopic cholecystectomy.
Method: Among the 250 patients with symptomatic GSD, 55 had
associated NAFLD diagnosed by ultrasound. These patients under-
went liver biopsy during laparoscopic cholecystectomy between June
2021 to Feb 2022.

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 POSTER PRESENTATIONS
Results: The mean age of patients was 41.6 ± 11.69 years and 60% of were recorded for each patient. The presence of steatosis was defined
patients were female. The mean BMI of subjects was 26.43 ± 3.84 kg/ with a CAP cut off ≥ 275 dB/m and advanced fibrosis ≥ 8kpa.
m2. Eight patients had hypothyroidism, 7 patients had diabetes Results: We screened 90, 47.3% were male with a median age of 59
mellitus, and 6 patients had hypertension as comorbidities. The years (IQR 52 − 66), most were of black African descent 55.6% (50)
histopathology of NAFLD patients revealed no significant steatosis in with a median BMI of 31.8 kg/m2 (26 − 37). Comorbidities, such as
7 patients, NAFLD in 38 patients and NASH in 10/55 (18.1%). Higher hypertension, coexisted in 61.1% and 58.9% had dyslipidaemia.
AST (44 ± 22.15 vs 31.5 ± 13.0; p = 0.02) and controlled attenuation (Baseline characteristics Figure 1)
parameter (CAP) (294 ± 58.5 vs 202.9 ± 69.6; p <0.001) were The Fibroscan data was valid in 96.7% (87), 56.3% (49/87) had
significantly associated with NASH in GSD patients with NAFLD steatosis and 27.6% (24/87) had advanced fibrosis.
14.4% (13) were aware of NAFLD/NASH, 33.3% were aware that they
Table: Clinical characteristics of NASH and non-NASH patients were overweight or obese and 88.9% stated that they had received
P guidance about having a healthy lifestyle. Of the patients who were
Non-NASH NASH value not aware of NAFLD (85.6%), 58% of these had steatosis and those who
Age (years) 40.9 ± 10.6 44.8 ± 12.0 0.34 were not aware of being overweight/obese (66.7%), 40.6% of these
Female 31 (68%) 8 (80%) 0.48 were overweight and 25% were obese.
Body mass index (kg/m2) 26.46 ± 3.96 26.33 ± 3.46 0.92 38% of patients who had steatosis and 47.8% who had advanced
Laboratory parameters fibrosis were on GLP-1 analogue (24.4% of all patients).
INR 0.97 ± 0.10 0.94 ± 0.07 0.49
ALT (U/L) 31.3 ± 17.9 40.8 ± 24.67 0.18
AST (U/L) 31.5 ± 13.0 44 ± 22.15 0.02*
ALP (U/L) 88 (72.5–102) 76.5 (74–84.5) 0.23
Total bilirubin (mg/dL) 0.61 (0.45–0.8) 0.75 (0.48–0.94) 0.23
Albumin (g/dL) 4.09 ± 0.37 4.10 ± 0.32 0.93
Cholesterol (mg/dL) 164.9 ± 36.64 169.22 ± 33.89 0.73
Triglyceride (mg/dL) 137.24 ± 60.9 161.37 ± 53.7 0.25
HDL (mg/dL) 39.08 ± 11.08 42.78 ± 6.53 0.31
CAP 202.9 ± 69.6 294 ± 58.5 <.001*
LSM (kPa) 5.3 ± 1.8 6.1 ± 1.8 0.19

ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate

aminotransferase; INR: International normalized ratio; HDL: high-density
lipoprotein; LSM: Liver stiffness measurement; CAP: controlled attenuation
parameter

Conclusion: The high prevalence of NASH in patients of GSD with

NAFLD may justify the need of routine liver biopsy during
laparoscopic cholecystectomy in these patients.

THU101
Lack of awareness of a NAFLD pandemic in a high risk group. Is it
time to act in primary care?
Maria Guerra Veloz1, Kosh Agarwal1, Marck Chamley2, Saima Ajaz1.
1
Institute of Liver Studies. King’s College Hospital, London, United
Kingdom; 2Partner, North Wood Group Practice, Lambeth Diabetes
Intermediate Care Team, United Kingdom
Email: [email protected]
Background and aims: Non-alcoholic fatty liver disease (NAFLD)
includes a wide spectrum of conditions and is currently the leading
cause of chronic liver disease. NAFLD is intrinsically associated with
obesity and is particularly common in people with type 2 diabetes
(T2D) with a prevalence ranging from 70 to 80%. As NAFLD is mostly a
silent disease, early diagnosis and the accurate staging of fibrosis is
crucial for patients who are at risk. The complex relationship between
NAFLD and T2D, the risk of cardiovascular disease, raises the question
of the cost effectiveness of screening for NAFLD in the general
population. With current guidelines discouraging screening in the
general population, early recognition and intervention are important
in high-risk groups in order to improve clinical outcomes.
The aim of our project was to evaluate the awareness of NALFD
knowledge, the prevalence of NAFLD, and the prevalence of advanced Conclusion: T2D patients are mostly unaware of this silent epidemic,
fibrosis in patients with T2D who regularly attend a secondary and so do not recognise themselves as being overweight/obese,
diabetes clinic. which is intrinsically linked with NAFLD. Preliminary data suggests
Method: Patients with T2D that have a regular follow-up at the that the screening of NAFLD in patients with T2D can yield important
Lambeth Diabetes Intermediate Care Centre were invited to partici- information regarding the prevalence of advanced fibrosis and factors
pate in the NAFLD screening using a Fibroscan. A structured diet, affecting the progression of NAFLD in this multi-ethnic high-risk
exercise activity and NAFLD knowledge questionnaires were pro- group. It is particularly important to screen the patients who are
vided by a liver doctor to all patients that agreed to participate in this already in our healthcare system due to other pre-existing conditions.
project. Anthropometric measures, medical history, LSM and CAP

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POSTER PRESENTATIONS
THU102 Conclusion: VCTE as a point-of-care test provides a well-validated
Non-alcoholic fatty liver disease and type 2 diabetes: low referral real-time assessment of liver fibrosis as well as steatosis and allows
rate of patients at increased risk of progressive liver disease for timely delivery of the diagnosis and fibrosis risk category (low or
Lucy Gracen1,2, Kelly Hayward1,2, Melanie Aikebuse1,2, increased risk) to the patient’s healthcare team. The high detection
Anthony Russell3,4, James O’Beirne5, Katharine Irvine6, rate of people requiring specialist assessment supports this screening
Suzanne Williams7, Patricia Valery8, Elizabeth Powell1,2. 1Princess approach. However the low GP referral rate in a cohort at increased
Alexandra Hospital, Gastroenterology and Hepatology, Woolloongabba, risk of progressive liver disease calls attention to the need for
Australia; 2Translational Research Institute, The University of improved education, guidelines and referral pathways for NAFLD to
Queensland, Centre for Liver Disease Research, Faculty of Medicine, embed fibrosis assessment in the patient workflow.
Woolloongabba, Australia; 3Princess Alexandra Hospital, Department of
Endocrinology, Woolloongabba, Australia; 4The University of THU103
Queensland, Centre for Health Services Research, Faculty of Medicine, Hypertension and diabetes mellitus are associated with high FIB-
Saint Lucia, Australia; 5Sunshine Coast University Hospital, 4 index in a health checkup examination cohort without known
Gastroenterology and Hepatology, Birtinya, Australia; 6Translational liver disease
Research Institute, Mater Research, Woolloongabba, Australia; 7Inala Shunsuke Sato1, Hidehiko Kawai2, Sho Sato1, Hirohiko Iwasaki2,
Primary Care, Inala, Australia; 8QIMR Berghofer Medical Research Yuji Kita1, Yuji Ikeda1, Ayato Murata1, Yuji Shimada1, Takuya Genda1.
1
Institute, Herston, Australia Juntendo University Shizuoka Hospital, Gastroenterology and
Email: [email protected] Hepatology, Shizuoka, Japan; 2Fuji Town Medical Center, Shizuoka, Japan
Email: [email protected]
Background and aims: Routine assessment of liver fibrosis in people
with non-alcoholic fatty liver disease (NAFLD) is recommended. The Background and aims: Non-alcoholic fatty liver disease (NAFLD) is
aim of this study was to determine whether a community-based usually asymptomatic and lacks a specific biomarker; therefore, many
NAFLD diagnosis, risk-stratification and referral pathway for people individuals might remain undiagnosed even with advanced liver
with type 2 diabetes (T2D) provides targeted detection of advanced fibrosis. The aim of this study was to clarify the prevalence and
fibrosis and appropriate referral to liver clinics. clinical features of subjects with a high risk of advanced liver fibrosis
Method: People with T2D were screened for NAFLD when they in the general population, using the Fibrosis-4 (FIB-4) index.
attended a diabetes clinic appointment in the community, using Method: We retrospectively investigated 6, 183 subjects without
FibroScan (VCTE) as a point-of-care test to assess steatosis (CAP score known liver disease who had participated annual health checkup
≥248) and fibrosis (liver stiffness measurement, LSM). A letter to examination. We analyzed the factors associated with high FIB-4
participants’ general practitioners (GPs) provided the LSM result and index (≥2.67) using a logistic regression analysis.
guidance on appropriate management/follow-up of their patients in Results: Among 6, 183 subjects, 76 (1.2%) had high FIB-4 index.
primary care, as well as investigation of abnormal liver enzymes. Multivariate analysis identified hypertension (odds ratio [OR] =
Referral to a liver clinic was advised if LSM ≥8.0kPa. Patients were 8.926; 95% confidence interval [CI] 4.031–19.768; P < 0.001) and
advised to discuss their liver health and FibroScan result with their GP. A diabetes mellitus (OR = 4.045; 95% CI 1.694–9.660; P = 0.002) as
monthly audit of GP referrals to liver clinics was provided by the central important risk factors for high FIB-4 index. The rates of hypertension
referral hub to assess whether GPs pursued the recommended referral. and diabetes mellitus in subjects with high FIB-4 index were 78.9%
Results: To date, 129 people with T2D (61.9% male, 58.8 ± 9.7 years) and 23.7%, respectively. No significant association was observed
were assessed and VCTE met quality criteria in 126 (97.7%). Referral to between obesity or large waist circumference and a high FIB-4 index.
a liver clinic for further assessment was advised for 28 (22.2%) patients A history of cardiovascular disease was significantly more common in
with LSM ≥8.0kPa and 8 patients with other indications (Figure). 68 subjects with high FIB-4 index. These results were also observed in
(54.0%) of 126 patients had abnormal liver function tests and 13 the subjects with normal aminotransferase (ALT) levels.
(10.3%) had LSM ≥12.0kPa suggestive of advanced chronic liver Conclusion: The present study revealed that approximately 1% of the
disease (CLD). 34 (27.0%) of 126 patients had a prior liver ultrasound general Japanese population has a high risk of advanced liver fibrosis.
(US) of which two-thirds (n = 23) showed steatosis and 2 had clear Many of these patients had hypertension and/or diabetes mellitus.
signs of CLD. None of these patients had been referred for fibrosis The findings suggest that there are many undiagnosed NAFLD
assessment reflecting the need to embed this in routine clinical patients with risk of advanced liver fibrosis in the general population.
pathways. A greater proportion of people with LSM ≥8kPa had a prior
US compared to those with LSM <8kPa (46.4% vs. 21.4%, p = 0.009), THU104
suggesting GPs are identifying patients that need investigation but not Statins, but not aspirin, reduce the risk of hepatocellular
pursuing further management. A GP referral was received for 13 carcinoma and mortality in Danish patients with cirrhosis due to
(36.1%) of the 36 patients with a recommendation for referral. alcohol-related liver disease: a nationwide causal study
Frederik Kraglund1, Diana Hedevang Christensen2, Peter Jepsen1.
1
Aarhus University Hospital, Department of Hepatology and
Gastroenterology, Aarhus N, Denmark; 2Aarhus University Hospital,
Department of Clinical Epidemiology, Aarhus N, Denmark
Email: [email protected]
Background and aims: Observational studies have shown a strong
association between use of statins or aspirin and a lower risk of
hepatocellular carcinoma (HCC). We emulated a trial assessing the
causal link between statin and aspirin use and HCC development and
mortality in Danish patients with cirrhosis due to alcohol-related
liver disease (ALD cirrhosis).
Method: Using nationwide Danish healthcare registries, we identi-
fied all patients diagnosed with ALD cirrhosis, 2000-2018. We
determined their statin and aspirin use through reimbursed
Figure: Proportion of patients with type 2 diabetes recommended for prescriptions. A target trial was designed in which patients were
referral to liver clinic following FibroScan assessment. Circles proportion- randomised to initiate and adhere to statins (and, in a separate
ate to group size; liver function tests (LFTs). analysis, aspirin) or to not initiate treatment. The primary end point

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 POSTER PRESENTATIONS

Figure: (abstract: THU104)

was HCC development, and the secondary end point was death
without HCC. The target trial was emulated using inverse probability
of treatment and censoring weights to create a marginal structural
Gut microbiota and liver disease
model adjusted for comorbid diseases, prescription drugs, proce-
dures, hospital contacts, and prior use of statins among other
covariates. Based on this model we estimated the average treatment THU151
effect (ATE) of statin use (and aspirin use) on the cumulative risk of Altered fecal microbiome and metabolome in hepatitis B related
HCC and of death without HCC. chronic liver diseases
Results: Of 16, 811 patients with ALD cirrhosis, 4, 540 used statins at Wei Jiang1, Yue Shen1, Wu ShengDi1, Jian Wu2,2,2. 1Zhongshan
some point during follow-up, 4, 647 used aspirin, and 899 were Hospital, Fudan University;, Shanghai Institute of Liver Diseases,
diagnosed with HCC. The ATE of statin use was 0.74 (95% confidence Department of Gastroenterology and Hepatology, Xuhui District,
interval [CI] 0.47 to 1.02) for HCC and 0.77 (95% CI 0.70 to 0.83) for Shanghai, China; 2Fudan University Shanghai Medical College, Dept. of
death without HCC. The ATE of aspirin use was 1.08 (95% CI 0.73 to Medical Microbiology and Parasitology, MOE/NHC/CAMS Key Laboratory
1.44) for HCC and 1.10 (95% CI 1.02 to 1.19) for death without HCC. The of Medical Molecular Virology, School of Basic Medical Sciences,
cumulative HCC incidence functions and corresponding relative risk Shanghai, China
estimates reflected the ATEs (Figure). Email: [email protected]
Conclusion: Statin use reduces the risk of HCC and death without Background and aims: It is well accepted that microbiota is a major
HCC in patients with ALD cirrhosis. Conversely, aspirin use does not modulator of liver diseases and is associated with severe clinical
reduce the risk of either HCC or death without HCC in patients with outcomes. However, the influence of gut dysbiosis on chronic
ALD cirrhosis. Thus, statins, but not aspirin, likely have a chemopre- hepatitis B (CHB) progression as well as the interplay between
ventive effect in patients with ALD cirrhosis. While we wait for truly microbiota shift and antiviral treatment remains to be clarified. The
randomized studies, studies such as ours provide the strongest present study aims to provide a comprehensive profile of gut
possible evidence in favour of statins. microbiome and metabolomics in CHB patients at different disease
stages. Taking advantage of a cohort of CHB patients with entecavir

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POSTER PRESENTATIONS
therapy for five years, influence of antiviral treatment on the Results: Compared to healthy controls, community richness, diver-
characteristics of microbial composition and function in CHB patients sity and evenness of gut microbiota were decreased during CHB
was investigated. progression (Fig. 1B and 1C). Overall gut microbial community was
Method: Fecal samples from subjects with CHB (n = 64) and healthy shifted (Fig. 1D). Four genera: Faecalibacterium, Streptococcus,
controls (n = 17) were sequenced with 16 s rRNA analysis. Fecal Sutterella and Ruminiclostridium_9 were enriched in CHB patients.
metabolomics was measured via untargeted LC-MS in subgroups of Eight genera including Blautia, Escherichia-Shigella, Klebsiella,
58 subjects (Fig. 1A). Bifidobacterium, Parasutterella, Eubacterium hallii group,

Figure 1: (abstract: THU151)

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 POSTER PRESENTATIONS
Collinsella and Lactococcus were found to decrease, accompanying
with 206 metabolites statistically different in abundance.
Importantly, distinct patterns of microbiota composition and meta-
bolic activity were identified in subgroup analysis based on disease
stages and the presence of antiviral treatment (Fig. 2 and 3). It was
demonstrated that there was a potential association between
microbial or metabolic signatures and clinical characteristics
(Fig. 4). Notably, disease-enriched genera Streptococcus and metab-
olite 20-hydroxy-leukotriene E4 were negatively correlated with
albumin (ALB) and positively with direct bilirubin (DB). Concordant
depletion of Turicibacter and Adlercreutzia accompanying with 4-
hydroxyretinoic acid tended to correlate with elevated AST and DB in
CHB patients. Potential links between clinical parameters and
restored genera or metabolites in CHB patients receiving antiviral
treatment were detected. In particular, concordant increase of
Ruminococcaceae_UCG-013 and sebacic acid was positively corre-
lated with ALB, suggesting that novel host-microbial interplay was
involved in the antiviral treatment of CHB patients.

Figure 3:

Conclusion: Microbiome and metabolomics analysis was integrated

to provide a comprehensive profile of gut dysbiosis characterized by
microbial and metabolic alterations in CHB patients. CHB progression
and antiviral treatment significantly contributed to the imbalance of
gut microbial community and metabolomics profiles in this study.

Figure 2:

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POSTER PRESENTATIONS
RNA-sequencing analysis revealed that administration of L. plantarum
downregulated genes related to inflammation such as T cell
differentiation and leukocyte activation in liver. In the microbial
analysis of stool samples, the elevated Firmicutes-to-Bacteroidetes
ratio in the vehicle group (21.97) was decreased in the L. plantarum
group (0.86). Furthermore, disrupted intestinal epithelial barrier
function was restored in L. plantarum group and elevated serum
endotoxin level was significantly reduced in L. plantarum group
compared to vehicle group.
Conclusion: Our data demonstrated that administration of L.
plantarum can improve NAFLD associated phenotypes by altering
gut microbiome composition and decreasing serum endotoxin levels.

THU153
Stool microbiota, compared to salivary microbiota, show more
extensive correlations with plasma metabolites in
decompensated cirrhosis in a multinational cirrhosis cohort
I. Jane Cox1,2, Marcela Peña Rodríguez3, Andrew Fagan4,
Mayra Rojas Lara5, Adrien Le Guennec6, Fatima Rodrigez-Alvarez7,
Sara McGeorge4, Ivvone Escalona Nandez5, Aldo Torre5,
Jasmohan S Bajaj4. 1The Roger Williams Institute of Hepatology, London,
United Kingdom; 2King’s College London, United Kingdom; 3Laboratory
for the Diagnosis of Emerging and Reemerging Diseases (LaDEER),
Mexico; 4Virginia Commonwealth University and McGuire VA Medical
Center, United States; 5Instituto Nacional de Ciencias Médicas y
Nutrición Salvador Zubirán; 6King’s College London, Randall Centre for
Cell and Molecular Biophysics, United Kingdom; 7Instituto Nacional de
Ciencias Médicas y Nutrición Salvador Zubirán, Mexico
Email: [email protected]
Background and aims: Cirrhosis is associated with changes in gut
microbiota in both saliva and stool. However, the relative linkage
patterns of stool vs saliva microbiota with systemic metabolomics are
unclear. Moreover, these may differ across countries. We hypothe-
THU152 sized that stool has a greater linkage with plasma metabolites than
The therapeutic effect of Lactobacillus plantarum on metabolic saliva, which is unique depending on country of origin. Aim:
phenotypes in non-alcoholic fatty liver disease mice model Correlation analyses of plasma metabolomics with stool and saliva
DongYun Kim1,2, Jun Yong Park3,4, Heon Yung Gee2. 1Yonsei University microbiota in healthy and cirrhotic subjects from USA vs Mexico
Graduate School of Medicine, Department of Medicine, Physician- (MX).
Scientist Program; 2Yonsei University College of Medicine, Department of Method: Age-balanced outpt cirrhotics, compensated (Comp) and
Pharmacology, Graduate School of Medical Science, Brain Korea 21 decompensated (Decomp), and controls from USAandMX underwent
Project; 3Yonsei University College of Medicine, Department of Internal plasma collection and dietary recall. Plasma metabolomics were
Medicine, Institute of Gastroenterology; 4Yonsei University College of analyzed using NMR spectroscopy. Microbiota in stool and saliva
Medicine, Yonsei Liver Center samples were analyzed using 16SrRNA community analyses.
Email: [email protected] Correlation network differences between both saliva and stool gut
microbiota and plasma metabolites were compared in controls, Comp
Background and aims: Lactobacillus is considered a potential and Decomp pts within/between countries.
probiotic and has shown therapeutic potential for several liver Results: 313 age‐balanced subjects; 135 USA (47 control, 48 Comp, 40
diseases including non-alcoholic fatty liver disease (NAFLD). Decomp) and 178 MX (71 control, 56 Comp, 51 Decomp) were
However, it is not known how dietary supplementation of L. enrolled. MELD/cirrhosis severity including lactulose and rifaximin
plantarum has favoring effect on liver. Therefore, we investigated use was comparable (Fig A). Correlation networks demonstrated
the therapeutic potential of L. plantarum supplementation on NAFLD more microbiome-metabolite linkages in stool compared to saliva in
in a mouse model and aimed to elucidate its mechanism. both populations, while there were no salivary correlations with
Method: We used the choline-deficient high fat diet (CD-HFD)- microbiota across MX and decomp USA (Fig B).
induced murine model that recapitulates key features of human Lactobacillus correlations: Network differences of plasma lactate
metabolic syndrome. To induce NASH status, C57BL/6N mice were fed showed a positive correlation to stool Lactobacillus in MX Decomp.
a CD-HFD for 30 weeks. Then these mice were divided into three For USA Decomp, plasma lactate showed a positive correlation to
groups: vehicle, L. plantarum (109 CFU/day), and empagliflozin, stool Bifidobacterium but no correlation with stool Lactobacillus. Stool
selective SGLT2 inhibitor (10 mg/kg/day). After 12 weeks of treat- Lactobacillus in USA showed a negative correlation with
ment, mice were sacrificed and subjected to blood measurements, Faecalibacterium. Stool Lactobacillus correlations with microbiota in
and liver tissue for RNA isolation, lipid measurements, histology, and stool ( pink) vs saliva (blue) vs metabolites (orange) are shown for
stool for microbiome analysis. USA (Fig C) and MX (Fig D) Decomp.
Results: L. plantarum and empagliflozin treatment significantly
improved several metabolic phenotypes such as insulin tolerance,
and hepatic lipid contents compared to vehicle group, respectively.
However, the histological NAFLD activity score (NAS) was more
improved in the L. plantarum group (3.0, p = 0.0286) than in the
empagliflozin group (4.0, p = 0.0591) compared to vehicle group (5.5).

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 POSTER PRESENTATIONS
discriminate analysis (LDA) effect size method identified the
Phapecoctavirus genus as a potential biomarker (LDA score 3.80),
indicating a lower median relative abundance of Phapecoctavirus in
NAFLD donors when compared to healthy donors (3.54% [IQR 2.93%-
3.98%] vs. 4.15% [3.94%-4.94%], p = 0.038). As a putative host for
Phapecoctavirus, the abundance of Escherichia coli was negatively
associated with Phapecoctavirus (rho = − 0.51, p = 0.012). In the
animal model, mice receiving FMT from obese NAFLD (FMT-ON)
displayed a more severe NAFLD phenotype than those receiving FMT
from healthy control (FMT-HC) (liver triglyceride: median 65.35 [IQR
62.32–73.33] vs. 48.7 [38.61–54.44] mg/g liver tissue, p = 0.015;
blood triglyceride: 207.89 [187.87–216.94] vs. 110.05 [102.16–120.76]
mg/dL, p <0.001). Phapecoctavirus genus was similarly identified as a
potential fecal biomarker when comparing FMT-ON vs. FMT-HC (LDA
score 3.19). It was the only viral genus that distinguished NAFLD from
control in both human donors and mouse recipients. FMT-ON mice
with more severe NAFLD had a significantly lower level of fecal
Phapecoctavirus than FMT-HC mice (median 2.47% [IQR 2.39%-2.75%]
vs. 2.82% [2.6%-3.14%], p = 0.038).
Conclusion: We reported the association of reduced fecal
Phapecoctavirus with NAFLD in both human donors and HMA-mice
recipients. Further interventional studies in animal and human are
warranted to determine its potential causality and function in NAFLD.

THU155
Mitochondrial hyperactivation determines a transferable
protective gut microbiota profile in metabolic-associated fatty
liver disease development
Conclusion: Stool microbiota are more extensively linked with María Juárez-Fernández1, Naroa Goikoetxea2, David Porras1,
systemic metabolites than saliva microbiota, irrespective of cirrhosis María-Victoria García-Mediavilla1,3, Héctor Rodríguez4,
severity and country. These changes are more prominent in Decomp Esther Nistal1,3, Susana Martínez-Flórez1, Mercedes Rincón5,
and are centered around plasma lactate, which might be related to Marta Varela-Rey2, Javier González-Gállego1,3, Leticia Abecia4,5,
interaction of diet and lactulose therapy. Stool microbiota have a Juan Anguita4,6, María Luz Martínez-Chantar2,3,
greater functional footprint associated with the systemic milieu Sonia Sánchez-Campos1,3. 1Institute of Biomedicine (IBIOMED)
compared to salivary microbiota. University of León, Spain; 2Liver Disease laboratory, CIC bioGUNE, Centro
de Investigación Biomédica en Red de Enfermedades Hepáticas y
THU154 Digestivas (CIBERehd), Spain; 3Centro de Investigación Biomédica en Red
The gut virome in non-alcoholic fatty liver disease: distinct de Enfermedades Hepáticas y Digestivas (CIBERehd), ISCIII, Spain;
changes in Phapecoctavirus composition in a human microbiota 4
Inflammation and Macrophage Plasticity laboratory, CIC bioGUNE,
associated animal model Spain; 5University of Vermont, Department of Medicine and
Hau-Tak Chau1, Hein Tun2, Saisai Zhang1, Dengwei Zhang2, Immunobiology, College of Medicine, Burlington, United States;
Fung Yu Huang1, Lung Yi Loey Mak1,3, Man-Fung Yuen1,3, 6
Ikerbasque, Spain
Wai-Kay Seto1,3. 1The University of Hong Kong, Hong Kong, Department Email: [email protected]
of Medicine, Hong Kong; 2The University of Hong Kong, Hong Kong,
Background and aims: Mitochondrial dysfunction plays a key role in
School of Public Health, Hong Kong; 3The University of Hong Kong, Hong
metabolic-associated fatty liver disease (MAFLD). Methylation-
Kong, State Key Laboratory of Liver Research, Hong Kong
controlled J protein (MCJ) is a negative regulator of mitochondrial
Email: [email protected]
complex I. Its deletion increases mitochondrial activity and reduces
Background and aims: There is increasing knowledge on the role of diet or hepatotoxic drug-induced lipid accumulation and hepatic
the gut microbiome in the development of non-alcoholic fatty liver damage. The study aims to determine the microbiome signature
disease (NAFLD), but the role of the gut viral community in disease associated to MCJ deficiency and its capacity to transfer its
development remains poorly understood. We aimed to discover gut hepatoprotective phenotype to germ-free (GF) mice through caecal
virome related to NAFLD development via a human-microbiota- microbiota transplantation.
associated (HMA) rodent model of NAFLD. Method: Wild type (WT) and MCJ-KO C57BL/6J mice were fed with a
Method: Human fecal donors were recruited and classified into control or a choline-deficient high fat diet (CDA-HFD) for 6 weeks.
obese NAFLD, non-obese NAFLD and non-obese healthy controls. Then, a donor mouse from each experimental group was selected
Liver steatosis was assessed by vibration-controlled transient based on MAFLD development parameters. GFm were colonized with
elastography (Fibroscan, Echosens, Paris). The HMA-NAFLD rodent caecal microbiota from donors and subjected to dietary intervention
model was established by high-fat diet and transplantation of human (C or CDA-HFD) for 3 weeks. After that, samples were collected and
fecal microbiota (FMT) for 12 weeks. The profile of the gut virome of processed for assessment of liver disease and gut microbiota
both human donors and rodents was assessed by shotgun metage- composition.
nomic sequencing (Illumina NovaSeq 6000, US). Results: CDA-HFD during 6 weeks induced an inflammatory and
Results: Human donors with NAFLD had a significantly higher fibrotic state compatible with steatohepatitis development. MCJ-KO
controlled attenuation parameter measurement when compared to mice showed a lower liver expression of inflammatory and fibrotic
healthy controls (median 324 [IQR 305.5–355.75] vs. 182.5 [179.25– markers. This effect was reproduced in GFm colonized with
199.25] dB/m, p <0.001). Based on Bray-Curtis distance and microbiota from MCJ-KO donors and fed with CDA-HFD.
PERMANOVA testing, human NAFLD donors had a distinct gut DNA Metagenomic analysis revealed a profound reshaping of gut
virome compared with healthy controls ( p = 0.04). Analysis via linear microbiota due to the diet, but also changes in specific bacterial

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POSTER PRESENTATIONS
taxa attributed to MCJ-KO genotype. Dorea and Oscillospira genera
were increased, while AF12, Allobaculum and Ruminococcus were
decreased. This microbiota profile was also observed in GFm
following microbiota transplantation, highlighting an increase in
the abundance of the genus Dorea in all groups colonized with
microbiota of MCJ-KO mice. Finally, MCJ-KO mice fed with CDA-HFD
showed a higher hepatic and intestinal production of nicotinamide-
adenine dinucleotide (NAD), likewise a higher expression of its
synthesis enzymes. These results were reproduced in GFm trans-
planted with MCJ-KO microbiota.
Conclusion: The protective effect of MCJ deficiency on MAFLD
progression implies a mitochondrial hyperactivation mechanism
associated to a higher NAD production capacity, that determines a gut
microbiota profile, which is transferred by transplantation to GFm.
Supported by BFU2017–87960-R, PID2020-120363RB-I0, GRS2126/
A/2020, LE017-P20. CIBERehd is funded by ISCIII.

THU156
Fecal transplant-related reductions in Alcohol intake from
human to mice are associated with alterations in the intestinal
but not liver or prefrontal cortex transcriptome
Jennifer Wolstenholme1, Maren Smith1, Ryan Balfour Sartor2, Conclusion: FMT from humans, through a successful trial, leads to
Javier Maeso-Gonzalez1, Derrick Zhao1, Huiping Zhou1, Jason Kang1, lower alcohol intake in GF mice colonized with post-FMT stools
Phillip Hylemon1, Jasmohan S Bajaj1. 1Virginia Commonwealth through significant changes in intestinal genes rather than liver or
University and Richmond VA Medical Center; 2UNC Chapel Hill prefrontal cortex. Changes in gut immune-inflammatory response
Email: [email protected] after FMT could strengthen the gut barrier and reduce gut-liver-brain
signaling and underlines the role of the gut in the modulation of
Background and aims: In a recent randomized placebo-controlled behavior that is transmissible from humans.
trial in men with cirrhosis, we found that fecal microbiota transplant
(FMT) reduced alcohol craving and consumption compared to THU157
placebo. We found that transmitting stool post-FMT but not pre- New insights from mapping of the mucosal gut microbiota in
FMT to germ-free mice (GF) reduces alcohol drinking but the primary sclerosing cholangitis before and after liver
metabolic pathways associated with this reduction are unclear. transplantation
Aim: determine the genes activated along the gut-liver-brain axis Mikal Jacob Hole1, Kristin Jorgensen1,2, Kristian Holm1,
after stool transfer into mice. Malin Holm Meyer-Myklestad3, Asle Wilhelm Medhus4,
Method: To test whether FMT can act as a therapy to reduce craving, Dag Henrik Reikvam3, Alexandra Götz1, Krzysztof Grzyb5,
mice were gavaged with fecal microbiota material from the same Kirsten Muri Boberg1, Tom Hemming Karlsen1, Martin Kummen1,
patients described above (Fig A). 30 GF male C57BL/6 mice received Johannes R. Hov1. 1Oslo University Hospital and University of Oslo,
combined stool from pts prior to FMT ( pre-FMT) or stools from the Norwegian PSC Research Center, Department of Transplantation
same pts after FMT ( post-FMT). Initial ethanol acceptance, intake and Medicine; 2Akershus University Hospital, Department of
preference were measured using a 2-bottle choice ethanol drinking gastroenterology; 3Oslo University Hospital and University of Oslo,
assay. A bottle of ethanol (20% v/v) and water were placed on each Department of infectious diseases; 4Oslo University Hospital,
mouse’s cage and readings were taken at 2 (binge), 24 and 48 hours. Department of gastroenterology; 5Oslo University Hospital, Division of
Intestinal mucosa, liver and prefrontal cortex (PFC) were harvested 18 pathology
hours post-alcohol. RNASeq was run on 6 mice that drank the most in Email: [email protected]
the pre-FMT and the least in the post-FMT group for all 3 sites.
Differentially expressed genes (DEG) were further analyzed using GO Background and aims: The fecal microbiota in primary sclerosing
and KEGG pathway analyses with DAVID and Revigo. Finally, cholangitis (PSC) is characterized by low diversity and increased
Ingenuity Pathway Analysis was also performed. relative abundance of Veillonella, while data on the mucosal
Results: Alcohol preference/intake: Exposure to post-FMT stool microbiota are inconsistent. No particular microbiota features have
significantly reduced initial ethanol acceptance, and 24-hour been linked to the presence of PSC-IBD, and little is known about the
ethanol intake and preference compared to those who got pre-FMT impact of recurrent PSC (rPSC-LT) after liver transplantation (LT). We
material (Fig B/C). RNASeq Results: The overwhelming majority of aimed to investigate the mucosal microbiota in PSC and utilize rPSC
DEGs were in the intestine (Fig D) with only 1/20th of genes to define consistent microbiota features associated with PSC
differentially expressed in the liver and PFC pre- vs. post-FMT. irrespective of transplantation.
Overrepresented KEGG pathways were focused on IgA production, Method: We included 84 PSC and 51 PSC-LT patients (of which 25/51
antigen processing and presentation, and cell adhesion molecules [49%] had or developed rPSC median 5.0 years after LT) with biopsies
most of which were significantly higher in post-FMT vs. pre-FMT available from at least two ileocolonic segments. 19 healthy controls
mice (Fig E-G). Specifically, these were related to immune regulators (HC) were included for comparison. Biopsy DNA was subjected to 16S
such as transforming growth factor beta 1 (Tgfb1), interleukin rRNA sequencing (V3-V4) and analyzed using QIIME2.
receptor 10 alpha and 1 beta (Il10ra, Il1b), interferon γ (Infg), and Results: Mucosal gut expansion of Proteobacteria was more pro-
tumor necrosis factor (Tnf ). Sphingosine synthesis was lowered post- nounced in PSC-LT (up to 19%) than in in PSC (up to 11%), compared to
FMT. only ∼5% in HCs (QFDR <0.05). A limited set of genera was significantly
associated with PSC both before (PSC compared with HCs) and after
LT (rPSC-LT compared with PSC-LT). This set consisted of Bilophila,
Eubacterium hallii and two different Lachnospiraceae, which had
reduced relative abundance in PSC, and Enterococcus, Streptococcus,
Eisenbergiella and Hungatella, which had increased abundance in PSC.

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 POSTER PRESENTATIONS
Alpha diversity was reduced ( p <0.05) and Veillonella was signifi- Conclusion: We have shown that the 1H-NMR plasma metabolic
cantly increased in PSC and PSC-LT compared to HCs, but did not profiles of NASH patients and healthy controls are significantly
separate rPSC-LT from PSC-LT. Concomitant IBD was associated with distinctive, which allowed for the construction of a polymetabolic
significantly reduced relative abundance of Akkermansia, irrespective risk-score to separate and distinguish these groups, demonstrating
of LT, ranging from 0.8–1.0% to 4.5–5.6% mean relative abundance. The potential for interventions based on the metabolome.
potential pathobiont Klebsiella was detected in the mucosa in at least
one segment in 18% of the patients before and 41% after LT ( p <0.05) THU159
and associated with significantly reduced transplantation- and Intestinal hyperpermeability in cirrhosis is predictive for survival
recurrence-free survival. and associated with distinct microbiome changes
Conclusion: Liver transplantation does not normalize potentially Rosa Haller1, Benard Aliwa1,2, Angela Horvath1, Vanessa Stadlbauer1,3.
disease-related microbiota features. Multiple bacterial genera asso- 1
Medical University of Graz, Department of Gastroenterology and
ciated with both PSC and rPSC-LT, and Akkermansia associated with Hepatology, Graz, Austria; 2University of Nairobi, Department of Food
PSC-IBD irrespective of transplantation status. Furthermore, Science, Nutrition and Technology, Nairobi, Kenya; 3CBmed Center of
Klebsiella associated with poor outcome both before and after liver Biomarker Research in Medicine, Area Microbiome Research, Graz,
transplantation. Austria
Email: [email protected]
THU158
Background and aims: Liver cirrhosis, the 10th most common cause
Designing a polymetabolic risk score for non-alcoholic
of death in the western world is associated with increased intestinal
steatohepatitis patients by differentiating their metabolic profiles
permeability and alterations of gut microbiome composition. It is
from healthy controls
however not fully understood how intestinal permeability and the
Nadeen Habboub1,1, Pinelopi Manousou1, Roberta Forlano1,
microbiome are interrelated in cirrhosis. We aim to investigate the
Benjamin H. Mullish1, Gary Frost1, Benjamin Challis2, Mark Thursz1,
potential of gut permeability biomarkers to predict mortality and
Marc-Emmanuel Dumas1,3. 1Imperial College London, Metabolism,
their relation to microbiome composition.
Digestion and Reproduction, London, United Kingdom; 2AstraZeneca,
Method: Stool, serum and urine samples from 78 cirrhotic patients
Biopharmaceuticals Research and Early Development, Translational
(56 ± 9 years, 22 female) were obtained at baseline and after six
Science and Experimental Medicine, Cambridge, United Kingdom;
3 months; survival was assessed after 24 months. Intestinal perme-
Imperial College London, Heart and Lung Institute, London, United
ability was assessed by zonulin in stool and diamine oxidase (DAO) in
Kingdom
serum. Kaplan-Mayer survival analysis, group comparisons and
Email: [email protected]
correlation analysis (Spearman) were performed. Gut microbiome
Background and aims: The gut microbiome plays a role in the 16 s rRNA sequencing data were analyzed by diversity metrics,
pathogenesis of non-alcoholic fatty liver disease (NAFLD) and its ANCOM and LEfSe.
progression to non-alcoholic steatohepatitis (NASH). Studies have Results: Neither DAO nor zonulin at baseline were able to predict
shown that changes in gut microbiota result in increased intestinal mortality, but when assessing the dynamics over 6 months, patients
permeability, facilitating the translocation of bacteria and gut whose zonulin levels worsened or did not change (ZWOR, n = 45) had
microbiome-modulated metabolites to the liver, inciting NASH. Our a higher mortality than those whose zonulin levels improved (ZIMP,
aim is to investigate the differences in metabolic profiles of NASH n = 33) (log rank Mantel-Cox p = 0.048). ZWOR patients did not differ
patients in comparison to healthy controls. We designed a metabolic in etiology from ZIMP patients but had significantly worse inter-
profile scoring model based on plasma 1H-NMR metabolic data which national normalized ratio ( p = 0.021) levels, and MELD score at
could distinguish NASH/NAFLD patients from healthy individuals. baseline ( p = 0.032). Microbiome composition (alpha- and beta
Method: Biopsy-proven NASH patients (n = 55) were recruited from diversity) did not differ between ZWOR and ZIMP patients. The
St Mary’s Hospital and were compared to controls (n = 677), selected genus Phascolarctobacterium was more abundant in ZIMP patients
from the AIRWAVE population study by excluding the clinical with both ANCOM and LEfSe. The relative abundance of
characteristics of metabolic syndrome. Metabolic profiling of non- Phascolarctobacterium correlated negatively with calprotectin in
fasted plasma and urine samples were carried out by 1H-NMR stool and sCD14 in serum as biomarker for intestinal inflammation
spectroscopy and UPLC-MS using HILIC and C18 reverse-phase and bacterial translocation.
columns. Untargeted and targeted 1H-NMR metabolic profiles of Conclusion: Worsening of zonulin levels in over 6 months predicted
plasma samples from both cohorts were examined by multivariate mortality in patients with liver cirrhosis, indicating that serial
analysis for signature variation and scoring. assessments of this biomarker improve predictive power in cirrhosis.
Results: We have demonstrated distinct differences in the plasma 1H- The genus Phascolarctobacterium was more abundant in ZIMP
NMR metabolic profiles of NASH patients and healthy controls. patients and correlated negatively with markers for intestinal
Multivariate models of the 1H-NMR data showed a significant inflammation and bacterial translocation. Phascolarctobacterium can
separation between the controls and NASH patients’ clusters (R2 produce short-chain fatty acids and upregulate the mRNA expression
>0.6, Q2 >0.6, pR2Y <0.001, pQ2 <0.001). The polymetabolic based risk of claudin-1, a tight junction protein, indicating a possible link
score was computed using the O-PLS-DA model of the untargeted 1H- between the microbiome and intestinal hyperpermeability.
NMR metabolic profiles of the controls and NASH patients.
THU160
Novel multi-technology meta-analysis identifies gut microbiome
strains associated with clinical fibrosis in NAFLD patients
Nicole Narayan1, Erica Rutherford1, Karim Dabbagh1, Arun Sanyal2,
Todd Z. DeSantis1. 1Second Genome, Brisbane, United States; 2Virginia
Commonwealth University, Richmond, United States
Email: [email protected]
Background and aims: While NAFLD consists of two subtypes (NAFL
and NASH), patients within both subtypes lie on spectrums of
multiple axes of disease severity including fibrosis. NASH diagnosis
typically relies on liver biopsy. However, liver biopsies are not only
invasive but carry substantial risk of complications rendering them

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POSTER PRESENTATIONS
impractical for tracking disease progression in patients. Therefore, evaluated. Liver transcriptomics and predictive functional metage-
there is a substantial need for non-invasive diagnostic tools to nomic studies were then carried out. In the STAM™ study
identify patients with advancing stages of NASH, including clinical administration was performed for 4 weeks, and effects on NASH
fibrosis (fibrosis scores 2–4). While many studies have associated activity and fibrosis were compared to vehicle or Telmisartan at the
members of the gut microbiota with NAFLD and NASH, these studies stage of early fibrosis. A second group of animals was followed for
either do not discriminate by fibrosis score or they focus on advanced another 3 weeks to assess later-stage fibrosis.
disease (fibrosis score 4). Here we integrated samples from multiple Results: In the NASH rats, the bacterial consortium showed a
datasets to find strains specifically associated with clinical fibrosis protective effect on body weight, a trend to improve fasting blood
compared to controls and low fibrotic score NAFLD patients using insulin levels and HOMA-IR, and a marked protective effect on PHT,
multi-technology meta-analysis (MTMA). We hypothesized that namely a significant reduction in portal pressure (10.32 vs. 9.58
patients with clinical fibrosis would display a different microbial mmHg, p <0.05) and intrahepatic vascular resistance (7.58 vs. 4.20
signature and this could constitute the basis of a diagnostic method to mmHg/ml*min*100 g, p <0.05). An improvement in all features of
non-invasively diagnose clinical fibrosis. endothelial function ( p-eNOS, p-Akt and Klf2) and fibrotic markers
Method: We incorporated data from 189 patients across three studies (alpha-Sma and Col1a1) was also observed. Gut microbial compos-
(two public datasets and one collaboration between Arun Sanyal and itional changes revealed that the consortium achieved a more defined
Second Genome). Across this meta-cohort, 42 patients had clinical and richer replacement of the gut microbiome than stool transplant-
fibrosis (fibrosis score 2–4) and 147 patients were either controls or ation. Moreover, liver transcriptomics suggested a beneficial modu-
NAFL with low fibrosis (fibrosis score 0–1). All studies were processed lation of pro-fibrogenic pathways. An improvement in histological
using Second Genome’s sg-4sight platform to harmonize 16S liver fibrosis was then confirmed in the STAM™ study, significantly
amplicon and shotgun metagenomic sequencing, mapping all data reducing collagen- and fibronectin-positive areas in liver sections at
against our proprietary StrainSelect reference database. We devel- 12 weeks. The consortium also improved the NASH activity score,
oped a novel multi-technology meta-analysis (MTMA) procedure to consistent with a decrease in steatosis and ballooning. In addition,
identify the strains which are consistently associated with clinical consortium-treated animals displayed reduced inflammation (as
fibrosis in NAFL patients. measured through macrophage F4/80 positive area) and apoptosis
Results: A total of 996 strains were found common across at least two (reduction in serum cytokeratin 18 levels), suggesting an overall
of the three datasets used for analysis. After adjusting for false beneficial effect on all key aspects of NASH biology.
discovery, MTMA found seven strains from families Lachnospiraceae, Conclusion: Administration of a specific bacterial consortium of
Erysipelatoclostridiaceae, and Ruminococcaceae were associated defined composition can ameliorate NASH, PHT and fibrosis and delay
with clinical fibrosis, with four reduced and three enriched in clinical disease progression.
fibrosis. Two of these strains are within provisionally-named taxa not Funded by Instituto de Salud Carlos III [PI18/00947, PI21/00691] and
identified with existing open access tools, and therefore would not International Flavors and Fragrances Inc.
have been found without leveraging Second Genome’s StrainSelect
database. This demonstrates the utility of using reference databases THU162
which organize both well-documented and emerging taxa. Duodenal permeability is associated with mucosal microbiota in
Conclusion: Second Genome’s proprietary technology (including sg- compensated cirrhosis
4sight, StranSelect, and MTMA) was able to leverage multiple Patricia Bloom1, Krishna Rao1, Shi-Yi Zhou1, Christine Bassis1,
datasets and find a robust signature of strains associated with clinical Borko Nojkov1, Chung Owyang1, Vincent B. Young1, Anna Lok1.
1
fibrosis. University of Michigan, Ann Arbor, United States
Email: [email protected]
THU161
A nine-strain bacterial consortium improves portal hypertension Background and aims: Several complications of cirrhosis result from
and insulin signaling and delays non-alcoholic fatty liver disease the translocation of bacteria or their products across the intestinal
progression in vivo epithelium. However, little is known regarding the precise relation-
ship between mucosal bacteria and epithelial permeability in
Iris Pinheiro1, Aurora Barbera2, Imma Raurell2,3, Federico Estrella2,
cirrhosis. We aimed to assess epithelial permeability and associations
Marcel de Leeuw1, Selin Bolca1, Davide Gottardi1, Nigel Horscroft1,
with mucosal bacteria in patients with compensated cirrhosis.
Sam Possemiers1, Maria Teresa Salcedo4, Joan Genesca2,3,
Method: We obtained duodenal tissue biopsies from patients with
María Martell2,3, Salvador Augustin2,3. 1MRM Health NV, Ghent,
compensated cirrhosis and controls without liver disease. Patients
Belgium; 2Hospital Universitari Vall d’Hebron, Institut de Recerca Vall
were excluded if they used antibiotics or immunosuppression. The
d’Hebron, Universitat Autònoma de Barcelona, Liver Unit, Department of
composition of the mucosal microbiota was determined via 16S rRNA
Internal Medicine, Barcelona, Spain; 3Centro de Investigación Biomédica
gene sequencing and epithelial permeability assessed by measuring
en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid,
transepithelial electrical resistance (TEER) and tight junction protein
Spain; 4Pathology Department, Hospital Universitari Vall d´Hebron,
expression. Associations between microbiota relative abundance and
Universitat Autònoma de Barcelona, Barcelona, Spain
markers of epithelial permeability were assessed in a beta binomial
Email: [email protected]
model.
Background and aims: The current lack of approved therapies Results: We studied 24 patients with compensated cirrhosis and 20
encourages to search for new treatments that allow reversing the controls. Patients with cirrhosis were older than controls (61 vs. 51
progression of non-alcoholic steatohepatitis (NASH). Stool trans- years, p = 0.02), but had a similar number of extra-hepatic comorbid-
plantation has been shown to improve NASH features and portal ities (Charlson Comorbidity Index without points for liver disease: 2.2
hypertension. However, more patient-friendly treatments are vs. 1.4, p = 0.13). Patients with compensated cirrhosis had median
required. Here, we aimed testing the effect of a defined bacterial MELD 7 (IQR 7, 10); 62% were male.
consortium of nine gut commensal strains on two in vivo rodent Patients with compensated cirrhosis had lower duodenal TEER (i.e.
models of NASH (a rat dietary model of NASH and portal increased epithelial permeability; 13.3 Ω/cm2 ± 3.4 vs. 18.9 Ω/cm2 ±
hypertension (PHT), and the STAM™ mouse model). 7.1; p = 0.004) and trended towards diminished expression of tight
Method: The bacterial consortium was administered orally qd after junction proteins: claudin-1 ( p = 0.18), occludin ( p = 0.19), and
disease induction in 2 NASH models. In the NASH PHT rats, the zonulin-1 ( p = 0.09).
consortium was administered for 2 weeks and compared to stool Patients with compensated cirrhosis had lower microbial burden in
transplant, and effects on PHT and endothelial dysfunction were the duodenal mucosa (median: 34, 962 copies vs. 20, 982 copies,

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 POSTER PRESENTATIONS
p = 0.08), as well as lower alpha diversity (median Inverse Simpson: lipotoxic ( palmitate 200 µM) conditions. Co-treatments with diaz-
13.1 vs. 4.6, p = 0.14). Furthermore, patients with compensated oxide (100 µM) or EGTA (10 mM) allowed to investigate the
cirrhosis had a distinct mucosal microbiota community structure involvement of electrogenic effects of PAA in Huh7 cells. ER-
relative to controls based on analysis of molecular variance of the Yue mitochondria interactions were measured by in situ proximity
and Clayton dissimilarity index ( p = 0.09). ligation assay (PLA) targeting VDAC1 (mitochondrial protein) and
The beta binomial model found that 13 microbes associated with IP3R1 (reticular protein) proximity and BODIPY labelling was used to
TEER, when using a false discovery rate of 0.05 (Figure). Relative evaluate hepatocyte lipid accumulation. Fixed cells were analyzed by
abundance of a Lactobacillus and a Bifidobacterium bacteria positively fluorescent microscopy and images analyses were performed using
associated with TEER, indicating that these two microbes are either blobfinder (PLA) or ImageJ (BODIPY) to quantify mitochondria-
associated with a less permeable epithelial layer. endoplasmic reticulum contacts and lipid droplets size respectively.
All experiments were performed in a single time triplicate.
Results: Treatment with PAA reduced MAMs in Huh7 (n = 30 photos,
fold change = − 72 ± 0.025%, p = 0.0001) and PMH (n = 30 photos, fold
change = − 23 ± 0.064%, p <0.0001), it also induced lipid accumula-
tion in Huh7 (n = 30 photos, fold change = +20 ± 0.035%, p = 0.0001)
and PMH (n = 20 photos, fold change = +35 ± 0.047%, p = 0.0001). The
effect of PAA on MAM integrity is observed as soon as one hour of
treatment (n = 30 photos, fold change = − 39% ± 0.029, p <0.0001) in
Huh7. This effect is fully prevented by diazoxide which inhibits
membrane depolarization (n = 30 photos, fold change = +9% ± 0.066%
with diazoxide versus − 30 ± 0.042% without it, p <0.0001) and
partially by EGTA treatment, a Ca2+ chelation agent, (n = 30 photos,
fold change = − 29 ± 0.044% with EGTA versus − 50 ± 0, 022% without
it, p <0.0007). Altogether, these results suggest an electrogenic
mechanism of PAA action on MAMs.

Conclusion: Compensated cirrhosis is characterized by increased

duodenal epithelial permeability, with a distinct mucosal microbial
community. Intriguingly, bacteria previously associated with health,
Lactobacillus and Bifidobacterium, were protective of duodenal
permeability. Future research will be required to extend and validate
these findings in larger cohorts, to investigate if these microbes have
a mechanistic role in epithelial barrier function, and to assess
whether these trends persist or progress in decompensated cirrhosis.

THU163
Impact of phenylacetic acid, a microbiota derived-metabolite, on
hepatic endoplasmic reticulum-mitochondria interactions and
steatosis Conclusion: PAA, a gut-microbiome derived metabolite, induces
Rémy Lefebvre1, Cyrielle Caussy1,2, Jennifer Rieusset1. 1CarMeN MAM disruption and hepatocyte lipid accumulation. The effect of PAA
Laboratory, UMR INSERM U1060/INRA U1393, 69495 Pierre-Bénite, on MAMs is mediated through an electrogenic mechanism. Whether
France; 2Hospices civils de Lyon, département endocrinologie, diabet̀ e et preventing the electrogenic effect of PAA impacts hepatic steatosis is
nutrition, 69495 Pierre-Bénite, France under investigation.
Email: [email protected]
Background and aims: The gut-liver axis has emerged as an THU164
important factor in the development of non-alcoholic fatty liver Dynamics of the gut-liver axis in rats with varying fibrosis severity
diseases (NAFLD). Microbiota-derived metabolites such as phenyla- Hongyan Xiang1, Zongyi Liu1, Huanyu Xiang1, Dejuan Xiang1,
cetic acid (PAA) have been shown to trigger hepatic steatosis in Shuang Xiao1, Jing Xiao1, Wei Shen1, Peng Hu1, Hong Ren1,
human primary hepatocytes but the molecular mechanism involved Ming-Li Peng1. 1The Second Affiliated Hospital, Chongqing Medical
is not elucidated. Moreover, mitochondrial dysfunction is also a key University, Key Laboratory of Molecular Biology for Infectious Diseases
component of NAFLD and oxidative capacities of mitochondria are (Ministry of Education), Institute for Viral Hepatitis, Department of
regulated by the communication of this organelle with endoplasmic Infectious Diseases, Chongqing, China
reticulum at contact points named mitochondria-associated mem- Email: [email protected]
branes (MAMs). Hence, MAMs are nutrient sensitive controlling Background and aims: The classic carbon tetrachloride (CCl4)
mitochondrial oxidative metabolism and ER-mitochondria miscom- -induced liver injury model is widely used to study the pathogenesis
munication was associated with hepatic insulin resistance and of fibrosis and evaluate anti-fibrotic drugs. However, the alterations
steatosis. We hypothesized that PAA may induce hepatic steatosis of gut-liver axis in this model itself remain unclear. Here, this study
through a disruption of MAMs integrity (Figure 1). aimed to explore the dynamic changes of gut microbiota, bile acid
Method: We investigated the impact of PAA (500 µM) on MAMs and gut barrier over fibrosis severity in CCl4-induced rats.
integrity and steatosis in Huh7 cell line and primary mouse Method: Hepatic fibrosis was induced by intraperitoneal injection of
hepatocytes (PMH) incubated for 16 hours in normal (BSA) and CCl4 with 50%CCl4 1 ml/kg body weight, twice weekly for 12 weeks.

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POSTER PRESENTATIONS
Fecal samples lengthways collected at 1, 4, 8 and 12 weeks after China; 10Department of Infectious Diseases, The First Hospital of
modeling were used for gut microbiota 16S rDNA sequencing. Bile Lanzhou University, Lanzhou, China; 11Department of Gastroenterology,
acid profiles in feces and serum were measured by ultra-performance Hospital of Chengdu Office of People’s Government of Tibetan
liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). autonomous Region, Chengdu, China; 12Department of Gatroenterology
Intestinal barrier integrity was assessed by measuring ileal perme- and Hepatology, Guangyuan First People’s Hospital, Guangyuan, China;
ability to FITC-dextran 4 kDa and Lipopolysaccharide. 13
The People’s Hospital of Guangxi Zhuang Autonomous Region, 530021,
Results: Different fibrosis stages from inflammation, mild, moderate Nanning, China; 14Gastroenterology clinic, The Sixth People’s Hospital of
to advanced fibrosis were successfully induced by CCl4 administra- Shenyang, No.85, South Heping Street, Heping District, Shenyang,
tion for 1, 4, 8, 12 weeks respectively. 16S rDNA sequencing revealed Liaoning 110006, P.R.China; 15Department of Gastroenterology, The Sixth
that gut dysbiosis mainly occurred in the early and advanced stages of People’s Hospital of Shenyang, No.85, South Heping Street, Heping
fibrosis, while the composition of the gut microbiota was close to District, Shenyang, Liaoning 110006, P.R.China; 16Department of
normal in the moderate stage of fibrosis. Only the relative Gastroenterology, The Sixth People’s Hospital of Shenyang, No.85, South
abundances of Lactobacillus at different phylogenetic levels were Heping Street, Heping District, Shenyang, Liaoning 110006, P.R.China;
underrepresented in the four fibrosis stages. As fibrosis progressed, 17
Department of Gastroenterology, the First Affiliated Hospital of Nanjing
total bile acids in feces gradually decreased, mainly manifested as a Medical University, Nanjing, Jiangsu 210029, People’s Republic of China;
decrease in unconjugated bile acids such as lithocholic acid (LCA) and 18
Department of Gastroenterology and Hepatology, The Second Affiliated
Deoxycholic acid (DCA). Conversely, serum total bile acids increased, Hospital of Baotou Medical College, Baotou, China; 19Department of
with marked increase in conjugated bile acids such as glycocholic Gastroenterology, Baoding people’s Hospital, Baoding, China; 20CHESS
acid hydrate (GCA) and tauro-alpha-murocholic acid (T-alpha-MCA). Center, Institute of Portal Hypertension, The First Hospital of Lanzhou
The hepatic FXR-SHP and intestinal FXR-FGF15 pathways, the master University, Lanzhou, China
regulators of BA biosynthesis in the enterohepatic circulation, were Email: [email protected]
significantly inhibited with increasing fibrosis. Interestingly, in our
Background and aims: Gut microbial dysbiosis is associated with the
experimental settings, ileal pathology and permeability tests showed
progression of cirrhosis, but the relationship to the risk of variceal
that the intestinal barrier remained relatively intact even in the
bleeding (EVB) remain unknow. Our study aims to evaluate the
cirrhotic stage.
diagnostic value of gut microbiome for EVB in compensated cirrhosis.
Method: A total of 270 compensated cirrhotic patients from 13
centers in China were prospectively recruited between July 2019 and
April 2021. Stool samples and results of endoscopy was collected
following a standard detailed protocol. The total bacterial DNA in
each stool sample was extracted and profiled by sequencing the 16S
rRNA gene V4 region. Then the role of gut microbiome in EVB was
explored and compared with endoscopy, which was considered as
the gold standard for evaluating the risk of EVB.
Results: In this prospective multicenter study (NCT03990753,
CHESS1901), the median age was 53 years (range 20–75 years), and
69.6% (n = 188) were male. 95 patients were assessed as high risk of
Figure 1: Dynamics of the gut microbiota in rats with varying fibrosis EVB, and 175 patients were estimated at low risk. Firstly, patients
severity from Lanzhou (LZ, n = 30), Tianjin (TJ, n = 131), Xingtai (XT, n = 74) and
Chengdu (CD, n = 20) cities were picked out to explored whether
Conclusion: The advances in knowledge of the gut-liver axis of this
regional variation could affect the composition of gut microbiota.
model provide useful supplements for us to apply it for research and
Although alpha diversity was similar in four regions (Fig. A), the
drug evaluation.
relative abundances at the phylum and genus levels of all samples
THU165 were quite different (Fig. B, C). At the phylum level, the relative
Association between gut microbiome and variceal bleeding risk in abundance of Firmicutes was higher in XT than in other cities;
compensated cirrhosis: a prospective multicenter study conversely, Bacteroidetes were relatively less abundant in XT.
Hongwei Zhou1,2, Xiaojiao Chen1, Zewen Li1, Xiang Huiling3, Furthermore, the genus level further reflected the relative differences
Tinghong Li3, Ping Zhu3, Dengxiang Liu4, Qingge Zhang5, Jitao Wang6, in the abundance of microbial composition. Principal coordinate
Xiaoling Zhao7, Xiaorong Mao8, Junfeng Li8, Yongwu Mao8, Jia Li9, analysis (PCoA) based on unweighted UniFrac distance showed that
Yu-Pei Liu9, Ying Ma9, Liting Zhang10, Shiying Yang10, Xiaoqin Gao10, the spatial distributions of patients for four regions were significantly
Hui Huan11, Chao Liu11, Qingli Tu11, Nanping Xiao12, Zheng Zeng12, different from each other overall (p = 0.001, Fig. D). However, we did
Guo Zhang13, Wenjuan Wang13, Yulin Yuan13, Ye Gu14, Tieying Song15, not observe significant differences between high risk and low risk of
Liangyu Pan16, Xiqiao Zhou17, Mengyu Li17, Chengwen Fang17, EVB groups for alpha diversity, beta diversity or the relative
Tong Dang18, Xianmei Meng18, Yi Zhou18, Qin Wei19, abundances of the predominant bacterial taxa (Fig. E-H). In addition,
Zhenhuai Chen19, Musong Li19, Xiaolong Qi20. 1Microbiome Medicine no significant difference was obtained between the groups of high
Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern and low risk of EVB for the single center in TJ and XT, respectively
Medical University, Guangzhou, China; 2State Key Laboratory of Organ (Fig. J, K).
Failure Research, Southern Medical University, Guangzhou, China;
3
Department of Hepatology and Gastroenterology of The Third Central
Hospital of Tianjin, Tianjin, China; 4Personnel Section, Xingtai people’s
Hospital, Xingtai, China; 5Hepatology Department of integrated
traditional Chinese and Western Medicine, Xingtai people’s Hospital,
Xingtai, China; 6Hepatobiliary surgery, Xingtai people’s Hospital,
Xingtai, China; 7Cancer Laboratory, Xingtai people’s Hospital, Xingtai,
China; 8Department of infectious diseases, the First Hospital of Lanzhou
University, Lanzhou, China; 9Tianjin Second People’s Hospital, Tianjin,

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 POSTER PRESENTATIONS
and 19 samples after IS reintroduction) and 38 control LT patients
were studied. The expressions of PD-1, PD-L1, Gal-9, and Foxp3 were
determined by immunohistochemical and immunofluorescence (IF)
staining. The success period of IS withdrawal was calculated using
Kaplan-Meier analysis.
Results: Tolerant and control patients exhibited higher PD-L1, higher
Gal-9, and higher Foxp3 levels than nontolerant patients at the
moment of triggering IS reintroduction. High expression of PD-L1 and
Gal-9 was associated with prolonged success of tolerance (83.3% vs.
36.7%, p <0.01; 73.1% vs. 42.9%, p = 0.03). A strong correlation between
PD-L1 and Gal-9 expression levels was detected (Spearman r = 0.73, p
<0.0001) and IF demonstrated colocalization of PD-L1 and Gal-9 in
the cytoplasm of hepatocytes.

Figure: Gut microbiota composition for four major cities and groups of
EVB risk. Composition of Alpha diversity (A, E). Average relative abun-
dances of the predominant bacterial taxa at the phylum (B, F) and genus
(C, G) levels. Scatter plots of PCoA based on Unweighted UniFrac for gut
microbiota composition to show beta diversity (D, H). Alpha diversity and
PCoA plots for the single center in TJ (J) and XT (K).

Conclusion: The multicenter study suggested that gut microbiome

varies from region to region, but both alpha and beta diversity
weren’t associated to risk of EVB in compensated cirrhosis. Further
studies exploring specific differential bacteria correlated with the risk
of EVB are needed.

Conclusion: The present study demonstrated that an increased

expression of PD-L1 and Gal-9 was associated with sustained
tolerance after IS withdrawal in pediatric liver transplantation.
Immunology
THU168
Acidic microenvironment aggravates the severity of hepatic
THU167 ischemia/reperfusion injury by modulating PPAR-γ signal
Increased expression of programmed cell death ligand 1 and Wei Ding1, Yunfei Duan1, Zhen Qu1, Donglin Sun1, Yunjie Lu1. 1The
galectin 9 in transplant recipients who achieved tolerance after Third Affiliated Hospital of Soochow University, Hepatopancreatobiliary
immunosuppression withdrawal Surgery Department, Changzhou, China
Nguyen Hai Nam1, Kojiro Taura1, Yukinori Koyama1, Takahiro Nishio1, Email: [email protected]
Gen Yamamoto1, Yusuke Uemoto1, Yusuke Kimura1, Li Xuefeng1,
Background and aims: Hepatic injury induced by ischemia and
Daichi Nakamura1, Kenji Yoshino2, Eri Ogawa3, Tatsuya Okamoto3,
reperfusion (HIRI) is a major clinical problem after liver resection or
Atsushi Yoshizawa4, Satoru Seo1, Keiko Iwaisako5, Tomoaki Yoh1,
transplantation. The polarization of macrophages plays an important
Koichiro Hata1, Toshihiko Masui1, Hideaki Okajima6, Hironori Haga7,
role in regulating the severity of hepatic ischemia/reperfusion injury.
Shinji Uemoto8, Etsuro Hatano1. 1Graduate School of Medicine, Kyoto
Recent evidence had indicated that the ischemia induces an acidic
University, Kyoto, Japan, Division of Hepato Biliary Pancreatic Surgery
microenvironment by causing increased anaerobic glycolysis and
and Transplantation, Department of Surgery, Kyoto, Japan; 2Nagahama
accumulation of lactic acid.
City Hospital, Nagahama, Shiga, Japan, Department of Surgery, Japan;
3 Method: We hypothesize that the acidic microenvironment might
Kyoto University Hospital, Kyoto, Japan, Department of Pediatric
cause the imbalance of intrahepatic immunity which aggravated
Surgery, Japan; 4Kansai Electric Power Hospital, Osaka, Japan,
HIRI. The hepatic ischemia/reperfusion injury model was established
Department of Surgery, Japan; 5Faculty of Life and Medical Sciences,
to investigate the effect of the acidic microenvironment to liver
Doshisha University, Kyotanabe, Japan, Department of Medical Life
injury. Liposomes were used to deplete macrophages in vivo.
Systems, Japan; 6Kanazawa Medical University, Ishikawa, Japan,
Macrophages were cultured under low pH conditions to analyze
Department of Pediatric Surgery, Japan; 7Kyoto University, Kyoto, Japan,
the polarization of macrophages in vitro. Activation of the PPAR-γ
Department of Diagnostic Pathology, Japan; 8Shiga University of Medical
signal was determined by Western Blot. PPAR-γ agonist GW1929 was
Science, Otsu, Shiga, Japan
administrated to functionally test the role of PPAR-γ in regulating
Email: [email protected]
macrophage-mediated effects in the acidic microenvironment during
Background and aims: Programmed cell death protein 1 (PD-1)/its HIRI.
ligand PD-L1, concomitant with T cell immunoglobulin and mucin Results: We demonstrate that acidic microenvironment aggravated
domain-containing protein 3 (TIM-3)/its ligand galectin 9 (Gal-9) and HIRI while NaHCO3 reduced liver injury through neutralizing the acid,
the forkhead box protein P3 (Foxp3) might be involved in tolerance besides, liposome abolished the protective ability of NaHCO3 through
after liver transplantation (LT). depleting the macrophages. In vivo and vitro experiment showed that
Method: Liver biopsies from 38 tolerant, 19 nontolerant (including 16 acidic microenvironment markedly promoted M1 polarization but
samples that triggered reintroduction of immunosuppression (IS) inhibited M2 polarization of macrophage. Furthermore, the

Journal of Hepatology 2022 vol. 77(S1) | S119–S388 S183

POSTER PRESENTATIONS
mechanistic study proved that the PPAR-γ signal was suppressed Results: The rs5743305 minor allele A showed significantly lower rGE
during the polarization of macrophages under pH = 6.5 culture of IL10 (A: 8.97, TT: 14.82, p = 0.022) and absolute PPL (A: 6.99 pg/ml,
media. The addition of PPAR-γ agonist GW1929 inhibited M1 TT: 15.6 pg/ml, p = 0.025) after 6 h compared to the wild type (WT) TT.
polarization under acidic environment and reduced HIRI. Additionally, IL1β PPLs were reduced for the minor allele A compared
Conclusion: Our results indicate that acidic microenvironment is a to the WT (A: 43.5 pg/ml, TT: 75.95 pg/ml, p = 0.011) as depicted in
key regulator in HIRI which promoted M1 polarization of macro- figure A. The rs3775291 risk allele T showed increased rGE of IFNβ
phages through regulating PPAR-γ. Conversely, PPAR-γ activation after 6 h (T: 4.32, CC: 2.08, p = 0.017). Interestingly, the relative PPL of
reduced liver injury, which provides a novel therapeutic concept to IFNβ was significantly lower for the T allele than for the WT CC (T: 2.6,
prevent HIRI. CC: 8.52, p = 0.014). Furthermore, the risk allele significantly reduced
the relative PPL of IFNa (T: 1.4, CC: 1.9, p = 0.004) (figure B).
THU169 Conclusion: This study showed significant effects of the two TLR3
Toll-like receptor 3 polymorphisms rs5743305 and rs3775291 SNPs on cytokine expression in the complex whole blood system. The
affect innate immune responses in whole blood analyses minor allele A of rs5743305 decreased pro- and anti-inflammatory
Sophia Barkow1, Madlen Matz-Soja1, Thomas Berg1, Janett Fischer1. cytokine expression. As expected, the rs3775291 risk allele T reduced
1
Division of Hepatology, Department of Medicine II, Leipzig University the synthesis of inflammatory type 1 interferons. This may lead to a
Medical Center, Laboratory for Clinical and Experimental Hepatology, dysbalanced immune system and therefore to a less functional
Leipzig, Germany defense against virus infections. Further research in lager cohorts and
Email: [email protected] in cell culture systems are required to enlighten the impact of the
SNPs on immune responses, especially during HBV infection.
Background and aims: As a part of the innate immunity, the Toll-like
receptors (TLR) 3 signaling has been linked to the outcome of THU170
hepatitis B virus (HBV) infection. Polymorphisms (SNPs) in the TLR3 IL-15 boots HBV-specific CD8+ cell response by activated
gene were associated with an increased risk of developing chronic progenitor pool mitochondrial remodelling in on treatment e-Ag
hepatitis B. This research aimed to assess the impact of the two TLR3 negative chronic hepatitis B
SNPs rs5743305 and rs3775291 on the immune responses in a whole Julia Peña Asensio1,2, Henar Calvo1, Joaquin Miquel1,
blood assay. Eduardo Sanz de Villalobos1, Alejandro González Praetorius1,
Method: The study included 30 healthy volunteers matched Miguel Torralba1,3, Juan Ramón Larrubia1,3. 1Guadalajara University
according to the two functionally relevant TLR3 SNPs (10 TT/10 TA/ Hospital, Translational Hepatology Unit, Guadalajara, Spain; 2University
10 AA for rs5743305 and 11 CC/12 CT/7 TT for rs3775291), and in age of Alcala, Department of Biology of Systems, Alcala de Henares, Spain;
and gender. Heparinized whole blood was treated with 5 µg/ml 3
University of Alcala, Department of Medicine and clinical specialities,
polyinosinic-polycytidylic acid (PolyI:C) for 3 and 6 hours. The Alcala de Henares, Spain
relative gene expression (rGE) of TLR3, IL1β, IL6, IL10, IL12, IFNβ, IFNα Email: [email protected]
and TNFα was analyzed by quantitative real-time polymerase chain
reaction. Normalization (2ΔΔCt) was performed in relation to the Background and aims: In the HBV-specific-CD8+ progenitor pool
housekeeping gene TBP and untreated blood. The plasma protein (PP), mitochondrial remodelling could re-establish the functionality
levels (PPL) of all cytokines were measured after 6 h of stimulation by of the effector proliferative progeny (EPP) in nucleos (t)ide analogue
performing a bead-based sandwich-immunoassay. (NUC) treated eAg (-) chronic hepatitis B (CHBe (-)). We analysed the
role of IL-15 in the metabolic profile of the HBV-specific CD8+ PP after
Ag encounter in CHBe (-) with low probability of T cell restoration
during NUC treatment.
Method: According to clinical variables, level of HBV-specific-CD8+
cell exhaustion was estimated in NUC treated CHBe (-). HBV-specific-
CD8+ cells were visualized by pentameric technology. After Ag-
specific stimulation, activated PP (APP) was detected by TCF1 staining
and FSC level. Metabolic profile, memory-like phenotype and
mTORC1 activation in PP were analysed by Glut1, PGC1a, CPT1, PD-
1, CD127 and prS6-P expression. The effector abilities in the effector
proliferative progeny (EPP) were tested by proliferation ability,
interferon- (IFN)gamma, Tumour necrosis factor (TNF)alpha and
CD107a expression. The role of IL-15 ± anti-PD-L1 in remodelling
metabolic profile and improving effector function was assessed.
Results: During CHBe (-), quiescent PP expresses a memory-like
phenotype (PD-1+/CD127+). After Ag-encounter, APP gives rise to the
EPP. In comparison with IL2, IL-15 decreases the initial boost of
mTORC1 in APP, but maintains its activation longer, which translates
into an inflation of EPP, and improvement in metabolic profile (Glut-
1low, PGC1ahigh, CPT1high). IL-15 induced metabolic changes correlate
with an enhancement in EPP effector abilities (IFN gamma high, TNF
alpha high, CD107ahigh). In those cases with low probability of HBV-
specific-CD8+ cell restoration during NUC treatment, IL-15 plus anti-
PD-L1 restored the proliferation ability of these cells after Ag-specific
in-vitro challenge.

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 POSTER PRESENTATIONS
the HCC microenvironment, suggesting MAIT cells as a potential
target for anti-cancer therapy in HCC. Understanding mechanisms of
local MAIT cell exhaustion in HCC may facilitate the development of
novel immunotherapeutic strategies against HCC.

THU172
Preclinical model for the study of immune responses specific for a
hepatic-self-antigen
Anaïs Cardon1,2, Jean-Paul Judor1,2, Arnaud Nicot1,3,
Sophie Conchon1,3, Amédée Renand1,3. 1INSERM UMR 1064 Centre de
Recherche en Transplantation et Immunologie, Nantes, France;
2
Université de Nantes, Nantes, France; 3INSERM, France
Email: [email protected]
Background and aims: Despite a bias toward immune tolerance in
Conclusion: IL-15 induces an intermediate but sustained mTORC1 the liver, autoimmune liver diseases such as autoimmune hepatitis
activation in HBV-specific CD8+ APP that translates into a catabolic (AIH) can occur. The etiology of this disease is still not well
mitochondrial profile and enhancement in EPP of effector abilities. In characterised, and little is known about the emergence process and
those CHBe (-) cases with low probability of achieving a functional dynamics of self-antigen-specific immune responses. Thus, to better
response during NUC treatment, IL-15+anti-PD-L1 in-vitro treatment understand AIH initiation mechanisms, we developed preclinical
restores their reactivity. murine models allowing the study of specific immune responses
(CD4+ and CD8+ T cells and antibody) against a liver antigen.
THU171 Method: The expression of the antigen hemagglutinin (HA) was
Mucosal-associated invariant T cells are rendered functionally induced with a CRE/LoxP system (cross-breeding of ROSA HA floxed
exhausted within the tumour microenvironment in HCC in a cell- mice with TTR-CREind mice). An adenovirus encoding for the CRE
contact dependent manner recombinase (AdCRE) was injected intramuscularly (i.m.) to induce a
Junika Pohl1, Alexandra Georgieva1, Anna-Marie Pedde2, peripheral immunization or intravenously (i.v.) to induce hepatic HA
Anna Hirschberger2, Sebastian Deschler1, Melanie Laschinger3, expression and inflammation. Feeding mice with tamoxifen dry food
Daniel Hartmann3, Jan Boettcher2, Norbert Hüser3, induced HA expression only in the liver. In the different settings, HA-
Roland M. Schmid1, Percy A. Knolle2, Katrin Böttcher1. 1University specific CD4+ and CD8+ T cells in the spleen and the liver were
Hospital Rechts der Isar, School of Medicine, Technical University of detected and characterized using tetramers, and antibody class
Munich (TUM), Department of Internal Medicine II, München, Germany; switch was assessed by ELISA tests.
2
University Hospital Rechts der Isar, School of Medicine, Technical Results: Peripheral HA immunization (AdCRE i.m.) leads to a strong
University of Munich (TUM), Institute of Molecular Immunology and HA immune response, marked by the emergence of anti-HA
Experimental Oncology; 3University Hospital Rechts der Isar, School of responses (CD4+ T cells and antibodies) and linked to HA expression
Medicine, Technical University of Munich (TUM), Department of Surgery in the muscle (but not in the liver). When HA expression is
Email: [email protected] specifically induced in the liver (tamoxifen), no HA-specific adaptive
Background and aims: Hepatocellular carcinoma (HCC) is still one of response is detected, confirming the tolerogenic environment of the
the major causes of cancer death worldwide. Immunotherapy has liver. However, after a peripheral immunization (AdCRE i.m.),
recently become the first-line treatment for advanced HCC, although tamoxifen-induced liver-specific HA expression leads to a massive
response rates remain low. MAIT cells, innate-like T cells particularly recruitment of HA-specific PD-1+ CD25- CD4+ T cells in the liver.
enriched in the liver, express pro-inflammatory cytokines as well as Finally, AdCRE i.v. causes concomitant hepatic HA expression and
cytolytic molecules and have therefore been attributed anti-tumour inflammation leading to the generation of HA-specific PD-1+ CD25-
properties. In this study, we aim to decipher direct interactions CD4+ T cells in the spleen and liver for over 12 weeks, and anti-HA
between MAIT cells and HCC cells in order to unravel mechanisms of IgG1 antibodies reflecting a chronic reaction against HA.
immune cell exhaustion within the tumour microenvironment in HCC. Conclusion: Our study shows that the conditions of expression of the
Method: MAIT cells were isolated from tumour tissue, adjacent liver antigen in the liver (e.g. inflammatory environment, peripheral
tissue and peripheral blood of human patients with HCC or other liver immunisation) modulate hepatic self-antigen-specific responses.
tumours and healthy controls. Primary MAIT cells were co-cultured Taken together, this could depict a key element in the initiation of
with various HCC cell lines in vitro and MAIT cell phenotype and autoreactive responses toward a hepatic antigen. A long-term
function was analysed by multi-colour flow cytometry. analysis of antigen-specific responses (CD4+ T cells and antibody)
Results: We show that MAIT cells frequency is significantly reduced in our models will provide a better understanding of responses
in peripheral blood of HCC patients compared to healthy controls, as dynamics during AIH development.
well as in HCC tumour tissue compared to the adjacent liver tissue.
Such MAIT cell loss was specific, since frequency of conventional T cell THU173
subsets was unaffected in HCC and MAIT cell frequency was Proximity labelling reveals potential cis interactions of CD52
unchanged in other liver tumours. Whereas MAIT cells from glycoprotein counter-receptors on circulating CD4+HLA-G+
peripheral blood of HCC patients remained functional, tumour- regulatory T cells in acute decompensation of cirrhosis
educated liver-derived MAIT cells showed increased exhaustion Tong Liu1, Gang Wu2, Cathrin Gudd1, Thomas Barbera1,
marker expression and significantly impaired effector function, Rooshi Nathwani1, Francesca Trovato3, Yan Liu1, Mark J W McPhail3,
suggesting MAIT cell exhaustion within the tumour microenviron- Mark Thursz1, Wafa Khamri1. 1Imperial College London, Department of
ment in HCC. Interestingly, such MAIT cell dysfunction could be Metabolism, Digestion and Reproduction, London, United Kingdom;
2
induced by co-culture of MAIT cells with different HCC cell lines, Imperial College London, Department of Life Sciences, London, United
while the hepatocyte-like cell line HepG2 was unable to induce MAIT Kingdom; 3King’s College London, Institute of Liver Studies, London,
cell exhaustion. Mechanistically, induction of MAIT cell exhaustion by United Kingdom
HCC cells was dependent on direct cell-cell contact. Email: [email protected]
Conclusion: Taken together, we show that MAIT cells, innate-like T Background and aims: We have recently described the expansion of
cells with anti-cancer potential, are rendered dysfunctional within a non-classical regulatory CD4+HLA-G+ T cell population and its

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POSTER PRESENTATIONS
potential contribution to defective peripheral immune responses in Results: 64 patients with CLD and 39 healthy volunteers were
patients with acute decompensation (AD) of cirrhosis. Gene profiling included. Both serological and T-cell responses were significantly
of this cell subset revealed an up-regulation of gene encoding for lower in patients with CLD compared to healthy volunteers after the
CD52: a sialylated glycosylphosphatidylinositol-anchored glycopro- 1st and 2nd vaccine dose. 79% and 15% of CLD patients had inadequate
tein known to be involved in lymphocyte functions by ligating its antibody response after the 1st and 2nd vaccine dose respectively.
released soluble form and the sialic acid-binding immunoglobulin- Additionally, 79% and 38% of CLD patients had inadequate interferon-
like lectin 10 (Siglec-10) receptor. However, the impact of cell surface γ production after the 1st and 2nd vaccine dose, respectively. The
CD52 is not fully understood. In this study, we aim to investigate the potency of immune response did not correlate to liver fibrosis grade.
role of membrane-bound CD52 in CD4+HLA-G+ T cells. Nevertheless, patients with higher Child-Pugh (CP) scores had a
Method: First, we examined the cell surface protein expression of worse response to the vaccine. There were no differences in the
CD52 and Siglec-10 in CD4+HLA-G+ versus CD4+HLA-G− T cells of AD occurrence of side effects to the vaccine between the groups.
patients (n = 17) using flow cytometry. Endogenous CD52 N-glycan Conclusion: Patients with CLD have a poorer response to vaccination
was digested with sialidase and binding affinity of CD52 to Siglec-10 against SARS-CoV-2 compared to healthy volunteers regardless of
was measured by flow cytometry using fluorochrome-labelled their fibrosis stage and many continue to be inadequately protected
recombinant Siglec-10. Proximity labelling was used to identify despite full vaccination.
potential membrane counter-receptors of CD52 on CD4+HLA-G+ T
cells. Cells were probed with horseradish peroxidase (HRP) con- THU175
jugated anti-CD52 antibody, biotinyl tyramide was used to biotinylate Efficacy of branched-chain amino acid granules to restore innate
membrane proteins within 100 nm radius of the HRP complex. immunity in cirrhosis-associated immune dysfunction: a
Biotinylated proteins in proximity of CD52 were then enriched by randomized controlled trial
streptavidin beads and identified via mass spectrometry. Natthapat Rujeerapaiboon1,2, Teerha Piratvisuth1,
Results: CD52 cell surface expression was significantly increased in Naichaya Chamroonkul1, Pimsiri Sripongpun1, Apichat Kaewdech1.
CD4+HLA-G+ compared to HLA-G− cells (mean fluorescence intensity
1
Songklanagarind Hospital, Internal Medicine, Tambon Kho Hong,
(MFI) median 25052 IQR [22989–26755] vs. 11529 [9459–14081], Thailand; 2Ramathibodi Hospital, Internal Medicine, Thailand
p <0.0001). Siglec-10 expression was also significantly increased in Email: [email protected]
the same subset (MFI 26987 [23892–28533] vs. 16765 [14534–
Background and aims: Cirrhosis-associated immune dysfunction
17983], p <0.0001). The membrane CD52 on CD4+ T cells showed high (CAID) has been proposed as one of the significant complications in
binding affinity towards Siglec-10, and this affinity could be reversed
cirrhotic patients, demonstrated by an impairment of innate
by digestion of the sialylated N-glycan of CD52. Proximity labelling immunity. Previous studies showed that reduction of phagocytic
revealed the T cell receptor (TCR) complex namely CD3 epsilon, CD3
activity, as a part of innate immunity, might predict infection
gamma, and TCR beta were in the immediate vicinity of CD52 on
occurrence and 90-day survival in cirrhosis. However, there are still
CD4+HLA-G+ T cells from patients with AD. Moreover, the results limited data on immunotherapeutic approaches to modulate the
imply that Siglec-10 interacting with CD52 could depend on TCR
dysfunctional immune response. Our study aims to determine the
stimulation. effect of branched-chain amino acid (BCAA) granules on phagocytic
Conclusion: CD52 and its counter-receptor Siglec-10 are co-
activity in cirrhotic patients.
expressed on the CD4+HLA-G+ T cells of AD patients. Proximity
Method: A double-blinded, randomized-controlled trial was con-
labelling identified potential cis-ligands recruited to the proximity of ducted at a single-centre tertiary care hospital. Thirty-seven cirrhotic
the membrane-bound CD52 likely to have implications on CD4+HLA- patients were randomly assigned in a 1:1 ratio stratified by Child-
G+ T cells responsiveness to TCR stimulation. Pugh status to receive either BCAA granules at a dose of 4.15 grams
thrice daily or placebo. All patients received a multidisciplinary
THU174
approach from hepatology and nutrition specialists. They were also
Humoral and cellular immunity after vaccination against SARS-
assigned to record the adherence to study drug, seven-day food recall,
CoV-2 is reduced in patients with chronic liver disease
and side effects, if occurred, in an interventional diary. At baseline,
Al-Dury Samer1, Johan Waern1, Anna Martner2, Hevar Hamah Saed1,
the 3rd and 6th months of the study, the phagocytic activity was
Marko Alavanja1, Johan Ringlander3, Andreas Törnell2,
assessed by a biochemist using pHrodo Red E. coli BioParticles
Mohammad Arabpour2, Jesper Waldenström4,
Phagocytosis Kit and Image Stream II Imaging Flow Cytometer. The
Hanna Grauers Wiktorin2, Gisela Ringström1, Martin Lagging4.
1 primary end point was the restoration of innate immunity at the sixth
Sahlgrenska University Hospital, Department of Medicine,
month, define by phagocytic activity ≥ 75%. Key secondary end points
Gastroenterology and Hepatology Unit, Gothenburg, Sweden;
2 were the accretion of phagocytic activity and number of hospitaliza-
Gothenburg University, Institute of Biomedicine, Sahlgrenska Academy,
tions due to infection.
Gothenburg, Sweden; 3Sahlgrenska University Hospital, Department of
Results: Of all 37 eligible patients, the patients in Child-Pugh A/B/C
Clinical Microbiology, Gothenburg, Sweden; 4Sahlgrenska University
were 26/8/3, respectively. Eighteen patients were in placebo, and
Hospital, Department of Infectious Diseases, Gothenburg, Sweden
nineteen were in BCAA group, the baseline characteristics and
Email: [email protected]
phagocytic activity were comparable between groups. At 6th
Background and aims: Patients with chronic liver disease are at a month, a significantly higher phagocytic activity restoration was
higher risk of morbidity and mortality in COVID-19 and professional demonstrated in the BCAA group compared with placebo (68.4% vs
societies have recommended the vaccination despite the scarce data 5.6%, p <0.001). The mean phagocytic activity in the BCAA and
from registration trials regarding their efficacy and safety in this placebo group were 75.4% and 63.4%, respectively
vulnerable population. ( p <0.001). The progressive accretion of phagocytic activity was
Method: In a prospective study, we compared the rate of humoral observed during the 3rd and 6th months, as shown in Figure. There
(antibody response to spike protein) and cellular (interferon-γ were no differences in serum albumin and other inflammatory
production) immunity before, after the 1st and 2nd dose of mRNA markers. Despite a higher phagocytic restoration rate in the BCAA
vaccines in patients with chronic liver disease (CLD) with and group, there was no difference in hospitalization due to infectious
without liver cirrhosis and healthy volunteers. We also investigated events in comparison to the placebo group (2 VS 3 events, p = 0.487).
whether the degree of immune response correlates with liver fibrosis
stage using transient elastography.

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 POSTER PRESENTATIONS
paucity of studies that established the effect of sarcopenia on
phagocytic activity. Therefore, our study aims to determine the
correlation between sarcopenia and the phagocytic activity in
cirrhotic patients.
Method: We conducted a randomized controlled trial (RCT)
evaluating the role of BCAA on phagocytic activity. In this study, we
used the baseline data in patients enrolled in the RCT to study the
correlation and factor affecting phagocytic activity. Thirty-seven
cirrhotic patients with sarcopenia were included in this study
(defined with skeletal muscle index [SMI] according to the JSH
criteria). The SMI was measured at L3 vertebra by a cross-sectional CT
scan and calculated by DICOM software. The phagocytic activity
assessment was performed by a biochemist, using the pHrodo Red E.
coli BioParticles Phagocytosis Kit for flow cytometry and Image
Stream Mk II Imaging Flow Cytometer. The correlations between SMI
Figure: Phagocytic activity change from baseline at the 3rd month and 6th and phagocytic activity was analysed using spearman test and
month of the study. adjusted with other covariates by multivariable linear regression
Results: Thirty-seven patients were included, the patients in Child-
Conclusion: BCAA can significantly improve phagocytic activity in Turcotte-Pugh (CTP) A/B/C were 26/8/3, respectively. The baseline
cirrhotic patients across all Child-Pugh stages. This may be an option characteristics were difference as cirrhotic stage progressed from
for immunotherapeutic intervention of CAID. However, whether the CTP-A to C. Our study demonstrated a trend towards lower phagocytic
improvement in phagocytic activity would correlate with a better activity in the more severity of cirrhosis, but not statistically
outcome especially infectious complications may need longer follow- significant, as 62.3%, 60.5%, and 54.3% in CTP A, B, C, respectively
up studies. ( p = 0.12). In a multivariable linear regression analysis, CTP-C and SMI
(cm2/m2) are independent factors associated with the prediction of
THU176
phagocytic activity, with adjusted beta-coefficients of − 14.4% ( p =
The close correlation between sarcopenia and the phagocytic
0.001), and +0.75% (p <0.001), respectively. The strong correlation
dysfunction in respond to bacterial pathogen Ecoli in cirrhotic
between SMI and phagocytic activity was demonstrated in the CTP-A
patients
cirrhosis, r = 0.84 ( p <0.001) whereas there was no significant
Naichaya Chamroonkul1, Natthapat Rujeerapaiboon1,2,
correlation in CTP-B/C cirrhosis, r = − 0.068 ( p = 0.84) as shown in
Pimsiri Sripongpun1, Apichat Kaewdech1, Teerha Piratvisuth1.
1 the figure.
Songklanagarind Hospital, Tambon Kho Hong, Thailand; 2Ramathibodi
Conclusion: In cirrhosis with sarcopenia, our study demonstrated
Hospital, Thailand
that both CTP-C and lower SMI were associated with phagocytic
Email: [email protected]
dysfunction. Emerging data had shown a strong correlation between
Background and aims: Sarcopenia and phagocytic dysfunction were sarcopenic status and phagocytic dysfunction, especially in CTP-A.
demonstrated to be associated with poorer clinical outcomes in Therefore, sarcopenic assessment is essential for all stages of cirrhosis
cirrhotic patients. Branched-chain amino acid (BCAA) is a pivotal despite compensated CTP-A status, to initiate the treatment and
factor that activates the mammalian target of rapamycin (mTOR) prevent further decompensation.
complex, a central node that controls immunity and muscle
synthesis. In cirrhosis with sarcopenia, the BCAA is depleted, which
may associate with phagocytic dysfunction. However, there is a

Figure: (abstract: THU176): The correlation between phagocytic activity and muscle mass in various stages of cirrhosis.

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POSTER PRESENTATIONS
THU177 (45.9%) got heterologous SV/AZ, and 25 (40.9%) received AZ/AZ. The
Heterologous SARS-CoV-2 vaccine triggers more humoral mean age was 53, 62, and 69 years in SV/SV, SV/AZ, and AZ/AZ,
immune responses among patients with liver cirrhosis respectively ( p <0.001). Two patients in AZ/AZ had inadequate
Apichat Kaewdech1, Nawamin Pinpathomrat2, immune response while all patients in SV/SV and SV/AZ had Ab level
Naichaya Chamroonkul1, Teerha Piratvisuth1,3, Pimsiri Sripongpun1. >7.15 BAU/ml. Among 3 different vaccine regimens, the heterologous
1
Prince of Songkla University, Gastroenterology and Hepatology Unit, SV/AZ had the highest anti-spike RBD IgG level at the median level of
Department of Internal Medicine, Faculty of Medicine, Hatyai, Thailand; 801.8 (IQR: 615.1, 1195.6) BAU/ml, significantly higher than SV/SV
2
Prince of Songkla University, Department of Biomedical Sciences, (median 95.8 (IQR: 27.3, 427.6) BAU/ml, p = 0.01) and AZ/AZ (median
Faculty of Medicine, Hatyai, Thailand; 3Prince of Songkla University, NKC 238.3 (IQR: 57.7, 387.2) BAU/ml).
Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Conclusion: Heterologous COVID-19 vaccine with the inactivated
Faculty of Medicine, Hatyai, Thailand vaccine followed by viral vector vaccine had a significant humoral
Email: [email protected] immune response among patients with cirrhosis. This result high-
lighted the prime-boost effect of the vaccine to alleviate the shortage
Background and aims: To control the COVID-19 pandemic, vaccin-
of vaccines in the situation of COVID-19 pandemic.
ation is the principal for general population globally. In patients
suffered from SARS-Cov-2 infection, having cirrhosis has been THU178
associated with a higher risk of poor outcomes, and those with Predictive immune biomarkers to safely discontinue nucleos
cirrhosis were strongly advised affirmatively by international (t)ide analogue treatment in HBeAg negative chronic hepatitis
hepatology societies to receive the SARS-Cov-2 vaccine. However, B (NUC-B study)
cirrhosis-associated immune dysfunction might contribute to hypor- Sandra Phillips1,2, Sameer Mistry1,2, Nicola Harris1,2, Celia Moore3,
esponsive to the vaccine. Moreover, data of immune responses in Gareth Hahn3, Michelle Rosario3, Camilla Carr-Smith4,
those who received the different types of vaccines, especially Maria Cortes Carrillo4, Lavanya Elangovan4, Kosh Agarwal4,
heterologous vaccines are lacking. We studied whether different James Hand5, Chris Sivell5, Patrick Kennedy5, Susan Congreave6,
regimens of COVID-19 vaccines affect the humoral immune response Mathew Barnes6, Stephen Ryder6, Mariam Habib3, Mark Thursz3,
in patients with cirrhosis. Shilpa Chokshi1,2. 1The Roger Williams Institute of Hepatology Foundation
Method: We conducted a prospective observational study, collecting for Liver Research, London, United Kingdom; 2School of Immunology and
blood samples from patients with cirrhosis who were regularly Microbial Sciences King’s College London, United Kingdom; 3St Mary
followed up at our centre, a tertiary care hospital in Thailand, and Hospital Faculty of Life Sciences and Medicine Digestive Diseases Division
received 2 doses of SARS-Cov-2 vaccine. This is a preliminary report of Imperial College London, United Kingdom; 4Kings college hospital NHS
patients enrolled between June and October 2021. Those who were on foundation trust; 5Barts Health NHS trust Royal London hospital;
immunosuppressive agent were excluded. The SARS-Cov-2 vaccin- 6
Nottingham University Hospitals NHS trust London
ation in Thailand is provided by the government; there were 3 major Email: [email protected]
vaccination regimens: inactivated vaccine (CoronaVac; SV/SV), viral
vector vaccine (ChAdOx1 nCoV-19 vaccine; AZ/AZ), and heterologous Background and aims: Discontinuation of long-term nucleos (t)ides
vaccine (SV/AZ), and neither patients nor investigators had involved analogue (NA) treatment can lead to clinical relapse and increased
in the decision of the regimens given. The antibody (Ab) levels were risk of hepatic decompensation in patients with HBeAg negative
measured at two-time points, before and at 4-week after receiving chronic hepatitis B. In others, NA cessation can result in functional
the 2nd dose vaccination. The anti-spike receptor-binding domain cure. It is widely believed that restoration of antiviral immunity
protein (RBD) IgG was measured using the Abbott SARS-CoV-2 IgG underpins this favourable outcome.
II Quant assay to determine Ab response. The Ab level of <50 AU/ml Method: Patients virally suppressed for >3 years were randomised to
(7.15 BAU/ml) is considered to be inadequate immune response. either stop-NA or discontinue NA for 4 weeks followed by 16 weeks of
PEG-IFN-alpha before stopping both treatments (NA/IFN) (see
Figure). Patients with exaggerated flares (ALT>20xULN) were
retreated with NAs (RTx). Longitudinal peripheral blood mono-
nuclear cells (PBMCs) (n = 459) were collected from 23 Stop-NA and
18 NA/IFN patients during a 3-year follow-up. Additional samples
were collected during moderate (ALT>2xULN) and exaggerated flares.
PBMCs were stimulated with 15 overlapping genotype-specific
peptide pools (OPP), HBV core, surface (HBcAg/HBsAg) and recall
antigens. Ex-vivo frequency of HBV-specific IFN-gamma (IFN-g)
producing T-cells was assessed by ELISpot assays, validated and
standardised at GCLP. Virological and clinical parameters were
correlated with immunological assessments.
Results: At week 130, 74% Stop-NA and 94% NA/IFN patients
remained off treatment while 26% and 6% needed RTx respectively.
A lower frequency of IFN-g-specific T-cells at BL, which persisted
during follow-up, was associated with RTx ( p = 0.04). Conversely, one
HBcAg OPP-specific T-cell subset was associated with RTx and
detected at higher frequency at BL ( p = 0.019). PEG-IFN treatment
was associated with a broad loss of T-cell response and epitope
recognition contraction. Whilst this T-cell response recovered after
PEG-IFN cessation, a high proportion of patients experienced viral
rebound (>2000 IU/ml) (63% vs 18%). In the Stop-NA group, NA
withdrawal was associated with moderate flares (52%), accompanied
Results: A total of 61 patients completed their 2nd dose vaccine and by a peak in T-cell response in sharp contrast to NA/IFN group with
had Ab level data available, 61% were male, the major cause of flares (62%) occurring when T-cell response was diminished. Finally,
cirrhosis was chronic hepatitis B (42%), and 51/9/1 patients were in the frequency of 3 OPP-specific T-cells subsets at BL was associated
child A/B/C, respectively. Of those, 8 (13.1%) received SV/SV, 28 with flares in both groups ( p = 0.007; p = 0.005; p = 0.035).

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 POSTER PRESENTATIONS
and decompensation. These findings need to be further validated but
identify MAIT cells as an interesting biomarker for adverse outcomes
in patients with cirrhosis.

THU180
Fatty acids directly limit mucosal-associated invariant T cell
effector function in non-alcoholic fatty liver disease
Sebastian Deschler1, Percy A. Knolle2, Katrin Böttcher1, Ulrike Bauer1,
Marc Ringelhan1, Jan Boettcher2, Lukas Ramsauer2,
Alexandra Georgieva1, Fabian Geisler1, Roland M. Schmid1,
Junika Pohl1. 1University Hospital rechts der Isar, School of Medicine,
Technical University of Munich (TUM), Department of Internal Medicine
II, München, Germany; 2University Hospital Rechts der Isar, School of
Medicine, Technical University of Munich, Institute of Molecular
Immunology and Experimental Oncology, München, Germany
Email: [email protected]
Figure: Created with BioRender.com Background and aims: Non-alcoholic fatty liver disease (NAFLD)
driven by lipotoxicity and inflammation is becoming the most
Conclusion: This is the first study to systematically characterise the
common chronic liver disease worldwide. Besides promoting patho-
HBV-specific T-cell responses during NA withdrawal and assess the
genesis, the unique liver microenvironment allows for the develop-
impact of IFN therapy post-NA cessation on antiviral immunity. The
ment of hepatocellular carcinoma in NAFLD. Here, we aim to decipher
findings reveal that epitope-specific T-cells may effectively predict
novel mechanisms of hepatic immune regulation in NAFLD that could
CHB patients that can safely discontinue NA treatment.
be exploited for therapy. To this end, we analysed how metabolic
THU179 changes in NAFLD affect the phenotype and effector function of
MAIT-cells in blood are associated with a higher risk of infection mucosal-associated invariant T (MAIT) cells, innate-like T cells with
in patients with cirrhosis antimicrobial and anti-cancer potential enriched in the liver.
Method: MAIT cells were isolated from peripheral blood of NAFLD
Bonnie Bengtsson1,2, Christopher Maucourant3, Ying Shang1,
patients or healthy controls and re-stimulated in vitro in presence of
Johan K. Sandberg3, Niklas Björkström3, Hannes Hagström1,2,4.
1 free fatty acids. MAIT cell phenotype and function was analysed by
Karolinska Institute, Huddinge Hospital, Unit of Gastroenterology and
multi-colour flow cytometry. MAIT cell metabolism was investigated
Rheumatology, Department of Medicin, Stockholm, Sweden; 2Karolinska
by metabolic flux analysis.
University Hospital, Huddinge, Division of Hepatology, Department of
Results: We show that MAIT cell frequency is significantly decreased
Upper GI diseases, Stockholm; 3Karolinska Institute, Huddinge Hospital,
in peripheral blood of NAFLD patients and that NAFLD MAIT cells
Center for Infectious Medicine, Department of Medicine, Stockholm;
4 express significantly higher levels of activation markers and effector
Karolinska Institutet, Solna, Clinical Epidemiology Unit, Department of
cytokines ex vivo, suggesting MAIT cell activation in NAFLD in vivo.
Medicine, Stockholm
However, upon in vitro restimulation, these activated MAIT cells are
Email: [email protected]
dysfunctional and fail to produce effector cytokines, such as IFN
Background and aims: Bacterial infection is a common and serious gamma, Granzyme B and TNF alpha. Metabolically, MAIT cell effector
complication in patients with liver cirrhosis. Previous research has function was dependent on glycolysis and oxidative phosphorylation,
found that mucosa-associated invariant T cells (MAIT cells), anti- which was unaffected in NAFLD MAIT cells. Culture with distinct fatty
bacterial T cells, are reduced in numbers in patients with cirrhosis, acid species characteristic of the NAFLD microenvironment, however,
both in liver and in peripheral blood. Little is known if MAIT cell levels impaired expression of effector cytokines by MAIT cells and induced
might predict incident clinically relevant outcomes including infec- MAIT cell death. Mechanistically, these effects were mediated by
tions. The aim of this study was to evaluate if MAIT cell levels in corrupted mitochondrial function and aberrant lipid metabolism.
peripheral blood can serve as a novel biomarker to cirrhotic patients Conclusion: These results show that MAIT cells are highly activated
with a higher risk for adverse outcomes. but dysfunctional in NAFLD and suggest that impairment of MAIT cell
Method: Patients with liver cirrhosis attending the Hepatology effector function is mediated by metabolic signals in the NAFLD
department at the Karolinska University Hospital between 2016 and microenvironment. Our data unravel a connection between lipotoxi-
2019 were included. Levels of peripheral MAIT cells in blood were city and immune cell dysfunction in NAFLD which may facilitate the
determined using flow cytometry. Baseline characteristics and development of therapeutic strategies.
incident outcomes (bacterial infections, hepatic decompensation
and death) were ascertained by manual chart review during a mean THU181
follow-up of 2.6 years. A competing risk regression was performed to Multimodal single cell analysis reveals the basis for butyrate
assess the risk of bacterial infection and hepatic decompensation, induction of TNFα-secreting regulatory T cells
with death and liver transplant as competing events. Cox regression Mo Atif1,2,3, Mustapha Cherai1, Clara Cretet1, Melissa Saichi4,
was performed to evaluate mortality rates. Both models were Lynda Aoudjehane5, Baptiste Fouquet1, Robert Balderas6,
adjusted for age, sex and severity of liver disease. Filomena Conti1,2, Olivier Scatton1,2, Ye Htun Oo3,7, Guy Gorochov1,2,
Results: We included 106 patients with cirrhosis, median age was 63 Makoto Miyara1,2. 1University Hospitals Pitié Salpêtrier̀ e-Charles Foix,
years and 64% were men. Median MAIT-cell percentage was 0.8% Paris, France; 2Sorbonne Université, Paris, France; 3University of
MAIT cells out if T cells. We found an association of higher MAIT cell Birmingham, United Kingdom; 4Institut Curie Hospital, Paris, France;
percentages with the risk of bacterial infections (adjusted sub- 5
Hospital Saint-Antoine Ap-Hp, Paris, France; 6BD Biosciences, San Jose,
distribution hazard ratio (aSHR) 1.20 (95%CI = 1.05–1.38)). Higher United States; 7University Hospitals Birmingham NHS Trust, United
MAIT cell percentages were also associated with a higher risk of Kingdom
hepatic decompensation (aSHR 1.24 (95%CI = 1.08–1.42)) but not with Email: [email protected]
a higher risk of death (adjusted hazard ratio 1.08 (95%CI = 0.96–1.23)).
Background and aims: Short-chain fatty acids (SCFAs) such as
Conclusion: In contrast to our hypothesis, higher MAIT cell
butyrate are increasingly implicated in modulating T cells in the gut
percentage were associated with a higher risk of bacterial infections
and liver. This is particularly relevant for regulatory T (Treg) cells as

Journal of Hepatology 2022 vol. 77(S1) | S119–S388 S189

POSTER PRESENTATIONS
they play an important role in maintaining homeostasis. However, AbT at W2 AbT at M3
Treg cells are phenotypically and functionally heterogeneous. In this
study, we used multimodal single-cell profiling to delineate the <33.8 <200 <33.8 <200
mechanistic basis for the effects of butyrate on Treg cell Median BAU/ BAU/ Median BAU/ BAU/
heterogeneity. (BAU/ ml* ml (BAU/ ml* ml
Method: We studied the whole transcriptome and several surface Clinical features ml) (%) (%) ml) (%) (%)
protein markers of approximately 6000 Treg cells. This was combined CPS A 1090 7.7 23.1 265 16.7 40.0
with experimental studies for biological validation. CPS B/C 1600 5.9 17.6 675 7.7 30.7
Results: We found that butyrate polarised naïve Treg cells into No PHT 1115 6.7 23.3 279 16.7 43.3
heterogeneous subpopulations with both immunosuppressive and PHT 1135 7.7 21.2 304 14.0 34.8
pro-inflammatory subsets. Upon reconstructing the gene regulatory Compensated 1585 8.0 24.0 304 12.7 38.3
disease
networks, we found an upregulation of the hypoxia, NFκB, JAK-STAT,
Previous 1085 6.3 18.8 265 19.2 38.5
TNFα, and MAPK signalling pathways. We also identified the decompensation
individual regulons driving them. These findings were subsequently
validated experimentally. Strikingly, butyrate increased the secretion *Reference laboratory value for negative result.
of TNFα, IL-2, and IL-17A from the activated Treg cells whilst Conclusion: COVID-19 vaccines in cirrhotics were safe and their
maintaining their immunosuppressive capacity. We also uncovered clinical and humoral response seem not different from the observed
the novel capacity of butyrate to acutely inhibit STAT5 and p38. in the general population assessed in clinical trials.
Conclusion: Collectively, our work demonstrates the basis by which
butyrate promotes diverse regulatory and effector cell subpopula- THU183
tions. These mechanisms could be therapeutically targeted to Building a case for pancreas and liver targeted intereukin-22
modulate the effects of SCFAs on Treg cells in the gut and liver. therapy in fatty liver disease
Haressh Sajiir1, Kuan Yau Wong1, Alexandra Mueller1,
THU182 Sahar Keshvari2, Ran Wang1, Percival Wiid1, Grant Ramm3,
COVID-19 vaccination in liver cirrhosis: safety and immune and Graeme Macdonald4, John Prins5, Michael McGuckin5,
clinical responses Sumaira Hasnain1,6. 1Mater Research Institute-The University of
Maria Ines Canha1, Mario Jorge Silva1, Maria Azevedo Silva2, Queensland, Immunopathology group, Brisbane, Australia; 2Mater
Mara Costa3, Rita Catarina Saraiva1, André Ruge2, Mariana Machado4, Research Institute-The University of Queensland, Brisbane, Australia;
Catarina Félix5, Bárbara Morão6, Pedro Narra Figueiredo3, 3
QMIR Berghofer Medical Research Institute, Brisbane, Australia;
Milena Mendes1, Carina Leal2, Filipe Calinas1. 1Centro Hospitalar 4
Princess Alexandra Hospital, Brisbane, Australia; 5The University of
Universitário de Lisboa Central, Gastroenterology; 2Centro Hospitalar de Melbourne, Melbourne, Australia; 6Australian Infectious Diseases
Leiria, Gastroenterology; 3Centro Hospitalar Universitário de Coimbra, Research Centre, Brisbane, Australia
Gastroenterology; 4Hospital de Vila Franca de Xira, Gastroenterology; Email: [email protected]
5
Centro Hospitalar de Lisboa Ocidental, Gastroenterology; 6Hospital
Background and aims: We discovered that the cytokine interleukin-
Beatriz Ângelo, Gastroenterology
22 (IL-22) is an efficient natural inhibitor of cellular stress and
Email: [email protected]
improved insulin quality in pancreatic beta-cells in preclinical models
Background and aims: Available data regarding safety and efficacy of of Type 2 diabetes. Importantly, IL-22 completely restored glucose
COVID-19 vaccination in liver cirrhosis patients is lacking. Their tolerance, suppressed fasting hyperinsulinaemia/hyperproinsulinae-
dysregulated immune system makes them susceptible to serious mia, and restored insulin sensitivity in obese animals. Treatment of
disease and to an attenuated response to certain vaccines. Our goal obese animals with IL-22 also showed significant improvements in
was to study safety, immunological and clinical responses of cirrhotic circulating triglycerides, liver function (AST:ALT ratio) and a reduction
patients to COVID-19 vaccination and assess their relation to in hepatic lipid accumulation. IL-22 has also been shown to be
demographic, clinical and vaccine-related factors. protective in other models of liver disease including alcoholic
Method: Interim analysis of an ongoing multicentric prospective hepatitis, acute-on-chronic liver failure, hepatic fibrosis and para-
study in patients with liver cirrhosis eligible for COVID-19 vaccination cetamol induced liver injury, and there are 3 versions of IL-22 based
without prior infection. Demographic data, liver disease severity, therapeutics in clinical trials for such pathologies. Interestingly, the
comorbidities, medication and adverse events were registered. IL-22 receptor, IL-22Ra1 is highly expressed in the pancreas and liver.
Patients were requested to assess IgG antibody titers (AbT) for Our study aimed to define the role of endogenous IL-22 in the liver
SARS-CoV-2 at 2 weeks (W2), 3 months (M3) and 6 months after and pancreas to provide additional support for IL-22-therapy in non-
completing vaccination. During follow-up, post-vaccination infection alcoholic fatty liver disease (NAFLD).
and severity were registered. We analyzed the patients who Method: To study the role of endogenous IL-22 in the pancreas and
®
completed the M3 assessment, using Stata 15 and a p <0.05. liver, we generated tissue specific IL-22Ra1 knockout mice lacking the
Results: We included 121 patients, 82% males, mean aged 61 years. receptor in pancreatic beta-cells (IL-22Ra1b-cell −/−) and hepatocytes
Alcohol is the most common (61%) cause of cirrhosis. Twenty percent (IL-22Ra1Hep −/−). We then challenged them with a high fat diet, and
have a Child Pugh score (CPS) of B/C; 42% had at least one measured their glycaemic control, hepatic lipid accumulation, and
decompensation and 68% have portal hypertension (PHT) signs. hepatic markers of cellular stress, lipid, and glucose metabolism.
Seventeen percent of the patients reported adverse reactions after Results: We found that IL-22Ra1Hep −/− animals had increased
vaccination, none of them serious. Median [Q1; Q3] AbT were 1115 hepatic markers of inflammation and cellular stress. Interestingly,
[291; 2080] BAU/ml at W2 and 293 [88; 1190] BAU/ml at M3. Group we also observed this phenomenon in IL-22Ra1b−cell −/− mice.
differences in AbT (using 33.8 and 200 BAU/ml as cut-offs) were Additionally, IL-22Ra1b-cell −/−animals also had defective glycaemic
assessed in a multivariable logistic regression considering the control and insulin secretion compared to littermate control animals,
patients’ age, gender, cause of cirrhosis, immunosuppressant drugs, which worsened on a high-fat diet. We also found that whilst female
severity of cirrhosis (Table 1), type of vaccine and adverse reactions. animals did not gain as much weight as male animals on a high-fat
Only older age and type of vaccine proved to be associated with lower diet, female IL-22Ra1b-cell −/− mice had a worsened phenotype
AbT at W2 and M3. None of the patients was diagnosed with COVID- compared to males.
19 infection during a mean follow-up of 137 days.

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 POSTER PRESENTATIONS
THU184
Patients with decompensated cirrhosis and liver transplant
recipients demonstrate poor humoral and cellular immune
response against COVID-19 vaccine
Anand Kulkarni1, Sasikala Mitnala1, Sowmya Iyengar1,
Shashidhar Jaggaiahgari1, Baqar Gora1, Hardik Rugwani1,
Mithun Sharma1, Nagaraja Rao Padaki1, Nageshwar Reddy1. 1AIG
Hospitals, Hyderabad, India
Email: [email protected]
Background and aims: Coronavirus disease-2019 (COVID-19) vac-
cination is recommended for all patients with chronic liver disease
(CLD) and liver transplant recipients (LTR). However, the immuno-
genicity of COVID-19 vaccines such as ChAdOx1 (vector-based) and
BBV152 (inactivated virus) in these immunocompromised patients is
unknown. Therefore, we aimed to compare the humoral and cellular
immune responses of CLD patients, LTR, and healthy individuals
against the available COVID-19 vaccines.
Method: Completely vaccinated (either with ChAdOx1 or BBV152)
non-cirrhotic CLD patients (NCCLD), cirrhotic patients, and LTR were
compared against age-matched healthy controls (HC) for anti-spike
antibody response (by chemiluminescence immunoassay [CLIA]
method) and immune profiling of the T and B cells (by flow
cytometry). Also, we assessed the number of patients developing
breakthrough infections post-vaccination. We excluded patients with
Figure: HandE sections of animal livers at 20 weeks of age
renal failure, active sepsis, patients <2 weeks from the last vaccination
Conclusion: We confirmed the role of endogenous IL-22 in main- dose. An individual with antibody levels <15 AU/ml was considered
taining insulin quality control and healthy hepatic function. We also as a non-responder.
discovered a novel role for endogenous IL-22 in the pancreatic-beta Results: Fifty NCCLD patients, 63 compensated cirrhosis (CC), 50
cell-liver axis and demonstrated the importance of targeting IL-22 to decompensated cirrhosis (DC) patients, 60 HC, and 17 LTR consented
both pancreatic beta-cells and hepatocytes to treat NAFLD. for the study (Fig. A). A similar proportion of patients in NCCLD (16%)
and HC (8.3%) were non-responders ( p = 0.21). CD4 central memory

70
Healthy Non-Cirrhotic CLD
Groups Responders 60
50 *
Healthy controls (n = 60) 91.7% 40
30
Non-cirrhotic CLD (n = 50) 84% 20
10
*
Compensated cirrhosis (n = 63) 82.5% 0

Decompensated Cirrhosis (n = 50) 66%

LT recipients (n = 17) 41.2%

A B

70 70
Healthy Comp. Cirrhosis Decomp. Cirrhosis Healthy LT
60 60
50 50
40
* 40 * *
30 30 * *
20 * * * 20
* *
10 * 10
0
* 0

C D
* P < 0.05
Figure: (abstract: THU184)

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POSTER PRESENTATIONS
cells and CD4 effector cells were lower in the NCCLD patients, while immunocompetent subjects. Nonetheless, studies in patients with
the other immune cells were similar in both groups (Fig. B). Non- chronic liver disease (CLD) are lacking. Our aim was to assess the
response was similar between CC (17.5%) and healthy individuals humoral immune response of two-dose COVID-19 vaccines among
(8.3%; p = 0.18). Only CD4 effector cells were lower in CC patients than CLD patients of different etiologies and identify predictors of “low”
healthy individuals, while the other immune cells were similar in versus “high” humoral response.
both groups. A higher proportion of patients in DC group (34%) were Method: Patients were recruited from clinical centers in 6 EU
non-responders than CC (17.5%; p = 0.04) and HC group (8.3%; p = countries, as part of a large consortium study. Serum levels of IgG,
0.001). CD4 naïve cells, CD4 effector cells, B cells, and B memory cells IgM (nM) and neutralizing antibodies (NA, %) against the SARS-CoV-2
were lower in the DC group. Though the central memory cells were spike S1 protein were determined in samples collected prior to
higher in the DC group, they could not differentiate into effector cells vaccination (T0) and at least 14 days after the second vaccination dose
(Fig. C). Fifty-nine percent in LT group were non-responders (T2). Patients (n = 195) were divided into “low” (51.4%) or “high”
compared to 8.3% in HC group ( p <0.001). On immune profiling, (48.6%) responders according to their IgG antibodies at T2, using 419
CD4 and CD8 naïve cells were higher in the marrow in the LT group, nM (median) as the cut-off value. Logistic regression analysis was
while the CD4 effector memory cells and CD4 and CD8 effector cells used to explore features associated with the vaccine-induced IgG
were lower in the LT group. Furthermore, B cells were lower in the LT levels.
group, suggesting poor antibody response (Fig. D). Breakthrough Results: All patients were fully vaccinated with either BNT162b2
infections were slightly higher in CC and DC group but non- (68%), mRNA-1273 (21.5%) or ChAdOx1 (10.5%). Their median age was
significant (healthy-3.3%; NCCLD-2%; CC-8%; DC-8%; LTR-5.88%). 58 (range 21–85); 57.4% were male. Underlying liver disease etiology
Except for two patients in the DC group, all breakthrough infections included alcohol (28.7%), NAFLD (21%), HCV (29.2%) and HBV (16.9%),
were mild. among others. 61.5% presented with cirrhosis. At T0, spike S1 IgG, IgM
Conclusion: Patients with decompensated cirrhosis and liver and NA levels were 0.76 (95% confidence interval (CI), 0.42–1.10), 0.37
transplant recipients demonstrate poor humoral and cellular (95% CI, 0.30–0.45) and 22.99 (95% CI, 21.39–24.58), respectively,
immune response against COVID-19 vaccines. Therefore, decompen- increasing to 446.07 (95% CI, 400.60–491.53), 3.91 (95% CI, 2.20–5.62)
sated cirrhosis patients and liver transplant recipients require a and 78.88 (95% CI, 74.91–82.85) at T2 ( p <0.0001 for all). In addition,
booster dose of COVID-19 vaccination. IgG and NA levels showed a high positive correlation. Age [odds ratio
(OR) 1.06 (1.03–1.10)], alcohol [OR 2.25 (1.15–4.41)], metabolic drugs
THU185 [OR 2.30 (1.20–4.43)], hepatocellular carcinoma [OR 5.41 (1.15–
Presence of cirrhosis in chronic liver disease patients associates 25.52)] and evidence of cirrhosis [OR 3.85 (1.95–7.61)], as well as type
with a lower immune response to COVID-19 vaccines-a of vaccine, predicted “low” response. In multivariable analysis,
multicenter european study cirrhosis and type of vaccine (ChAdOx1 >BNT162b2 >mRNA-1273)
André L. Simão1, Carolina Santos Palma1, Laura Izquierdo-Sánchez2, remained the only independent predictors of “low” response.
Antonella Putignano3, Ângela Carvalho-Gomes4, Andreas Posch5, Conclusion: CLD patients with cirrhosis exhibit lower immune
Paola Zanaga6, Irina Girleanu7, Carlos Araújo1, Degré Delphine8, responses to COVID-19 vaccination, irrespective of disease etiology.
Thierry Gustot8, Iván Sahuco4, Elia Spagnolo6, Sofia Carvalhana9, Further, the type of administered vaccine appears to predict levels of
Miguel Moura9, Mariana Moura Henrique1, Diogo A. E. Fernandes1, humoral response, although this needs validation in larger cohorts
Francisco Marques1, Jesus Maria Banales2,10,11,12, with a more balanced representation of all vaccines.
Manuel Romero Gomez13, Anca Trifan7, Francesco Paolo Russo6,
Rudolf E. Stauber5, Marina Berenguer4, Christophe Moreno3, THU186
João Gonçalves1, Helena Cortez-Pinto9,14, Rui Castro1. 1Research Heterogeneity of peripheral blood monocytes in patients with
Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, cirrhosis
Universidade de Lisboa, Lisbon, Portugal; 2Department of Liver and Anne Geng1, Robert G Brenig1,2, Mechthild Lütge3, Julien Roux4,
Gastrointestinal Diseases, Biodonostia Health Research Institute, Hung-Wei Cheng3, Patrizia Kuenzler5, David Semela2,
Donostia University Hospital, University of the Basque Country (UPV/ Markus Heim6,7, Burkhard Ludewig3, Christine Bernsmeier1,7.
EHU), San Sebastian, Spain; 3Department of Gastroenterology, 1
University Hospital of Basel, Department of Biomedicine, Translational
Hepatopancreatology and Digestive Oncology, C.U.B. Hôpital Erasme, Hepatology, Basel, Switzerland; 2Division of Gastroenterology and
Université Libre de Bruxelles, Brussels, Belgium; 4Hepatology and Liver Hepatology, Cantonal Hospital St. Gallen, Liver Biology Laboratory,
Transplantation Unit, La Fe University Hospital, University of Valencia, St. Gallen, Switzerland; 3Cantonal Hospital St. Gallen, Institute of
CIBER-EHD and IIS La Fe, Valencia, Spain; 5Department of Internal Immunobiology, St. Gallen, Switzerland; 4University Hospital Basel,
Medicine, Medical University of Graz, Graz, Austria; 6Gastroenterology Department of Biomedicine, Bioinformatics Core Facility, Basel,
and Multivisceral Transplant Unit, Department of Surgery, Oncology and Switzerland; 5Cantonal Hospital St. Gallen, Division Gastroenterology
Gastroenterology, Azienda Ospedale-Università Padova, Padova, Italy; and Hepatology, St. Gallen, Switzerland; 6University Hospital of Basel,
7
"Grigore T. Popa” University of Medicine and Pharmacy, “St. Spiridon” Department of Biomedicine, Hepatology, Basel, Switzerland; 7Clarunis,
Emergency Hospital, Institute of Gastroenterology and Hepatology, Iasi, University Center for Gastrointestinal and Liver Disease, Basel,
Romania; 8Institute for Medical Immunology, Erasme Campus, Brussels, Switzerland
Belgium; 9Departamento de Gastrenterologia, Centro Hospitalar Email: [email protected]
Universitário Lisboa Norte, Lisbon, Portugal; 10National Institute for the
Background and aims: In patients with cirrhosis, we recently
Study of Liver and Gastrointestinal Diseases, CIBERehd, “Instituto de
discovered dysfunctional monocytes (M-MDSC, CD14+HLA-
Salud Carlos III” (ISCIII), Madrid, Spain; 11Department of Biochemistry
DR+AXL+, CD14+MERTK+) prevailing over regular monocytes, which
and Genetics, School of Sciences, University of Navarra, Pamplona, Spain;
12 were associated with reduced capacity to repel microbial challenge
Ikerbasque, Basque Foundation for Science, Bilbao, Spain; 13Digestive
and infection susceptibility. Transcriptome wide single cell RNA
Diseases Department, Virgen del Rocío University Hospital, Institute of
sequencing (scRNA-seq) is expected to further enhance the under-
Biomedicine of Seville, University of Seville, Seville, Spain; 14Clínica
standing of the plasticity of immune cell differentiation processes in
Universitária de Gastrenterologia, Faculdade de Medicina, Universidade
disease conditions. We aimed to systematically dissect the stage
de Lisboa, Lisbon, Portugal
specific heterogeneity of circulating monocytes using scRNA-seq in
Email: [email protected]
cirrhosis with the intension to identify potential future immunother-
Background and aims: Vaccines in the European Union (EU) to apeutic targets.
prevent COVID-19 have been shown to be safe and effective in

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 POSTER PRESENTATIONS
Method: Monocytes (20.000 cells/sample) from compensated General, Visceral and Transplantation Surgery, Aachen, Germany
(CC, n = 5), decompensated (DC, n = 5) cirrhosis patients and Email: [email protected]
healthy controls (HC, n = 5) were prepared for scRNA-seq (10x
Background and aims: Leukocyte extravasation is a hallmark of
Genomics) and analysed (>4000 cells/sample) using R/
hepatic inflammation. Reduced shear stress within hepatic sinusoids
Bioconductor. Flow cytometric analyses were used to confirm
and the specific phenotype of liver sinusoidal endothelial cells (LSEC)
transcriptional findings on a translational level and to further
cumulate in differing adhesion characteristics during liver fibrosis.
evaluate the function of distinct monocytes.
The Junctional Adhesion Molecule A (JAM-A) is a crucial regulator of
Results: Our scRNA-seq data was grouped into eight monocyte
leukocyte extravasation and upregulated in human viral fibrosis. The
clusters, based on the expression of specific genes, of which five
aim of this study was to define the functional role of cell-specific
clusters were annotated to classical (CD14++CD16−), one cluster to
surface JAM-A during hepatic fibrogenesis, applying distinct knock-
intermediate (CD14++CD16+) and one cluster to non-classical
out strategies in a murine model.
(CD14+CD16++) monocyte subsets. One cluster showed a M-MDSC-
Method: Complete, conditional intestinal epithelial, conditional
like gene expression. CD14+CD16++-like monocytes were reduced in
endothelial and bone marrow chimeric Jam-a knockout animals
CC and DC patients, while M-MDSC-like monocytes were increased
(C57Bl/6) were treated with carbon tetrachloride (CCl4, 6 weeks).
and gene expression of MHC class II members was downregulated
Livers were investigated by qRT-PCR, Western blotting, immunohis-
compared to healthy controls. Differentially expressed (DE) gene
tochemistry, immunofluorescent stainings and flow cytometry. The
analysis revealed upregulation of Cd52, a T cell suppressor and
functional relevance of JAM-A was assessed using co-culture models
inhibitor of TLR-signaling, in monocytes from CC/DC compared to HC.
and flow-based adhesion assays.
Upregulation of CD52 on monocytes was confirmed on translational
Results: Complete and bone-marrow derived Jam-a knockout
level in CC/DC patients, but not detected on monocytes of patients
animals showed aggravated fibrosis with increased non-sinusoidal,
with acute decompensation (AD) or acute-on-chronic liver failure
perivascular accumulation of CD11b+F4/80+ monocyte-derived
(ACLF). CD52-expressing monocytes exhibited higher levels of CD16,
macrophages in contrast to wild type mice. Despite being associated
HLA-DR, AXL and CD206, showed higher phagocytosis capacity and
with disturbed epithelial barrier function, an intestinal epithelial
increased cytokine production (TNF-alpha, IL-6 and IL-10) upon
Jam-a knockout did not affect fibrogenesis. In endothelial-specific
microbial challenge (TLR4/TLR2 agonism). T cells co-cultured with
Jam-a knockout animals, liver fibrosis was aggravated alongside
monocytes with high proportion of CD52 expression (>60%) from
CD31-sinusoid capillarization and hepatic stellate cell (HSC) activa-
cirrhosis patients showed reduced proliferation activity compared to
tion. Here, leukocyte infiltration and adhesion to LSECs remained
T cells co-cultured with monocytes from healthy donors with lower
unaffected.
CD52 expression (<40% of monocytes).
Conclusion: Our models decipher cell-specific JAM-A to exert crucial
functions during hepatic fibrogenesis. JAM-A on bone marrow-
derived cells regulates non-sinusoidal vascular immune cell adhesion
and recruitment, while endothelial JAM-A controls liver sinusoid
capillarization and LSEC-linked HSC quiescence.

THU188
Diminished function of cytotoxic T- and NK- cells in severe
alcohol-associated hepatitis
Adam Kim1, Christina Cajigas-Du Ross1, David Streem2, Nicole Welch1,
Jaividhya Dasarathy3, Srinivasan Dasarathy1, Laura Nagy4. 1Cleveland
Clinic, Inflammation and Immunity, Cleveland, United States; 2Cleveland
Clinic, Lutheran Hospital, United States; 3MetroHealth; 4Cleveland Clinic,
Inflammation and Immunity, Cleveland, United States
Email: [email protected]
Background and aims: Severe Alcohol-associated Hepatitis (sAH) is
characterized by inflammation and infiltration of immune cells into
Conclusion: Using scRNA Seq we have identified eight circulating the liver. Peripheral monocytes are a major infiltrating cell type that
monocyte clusters with distinct prevalence between HC and CC/DC. can exacerbate inflammation and damage to the liver. sAH patients
DE gene analysis highlighted plasticity of CD52 expression on have a higher peripheral leukocyte count and an increased
monocytes during disease evolution of cirrhosis. proportion of inflammatory monocytes. Even though there are
more monocytes, sAH patients are often extremely susceptible to
THU187
infections. Cytotoxic NK-cells and CD8 T-cells play an important
JAM-A is a multifaceted regulator in hepatic fibrogenesis,
immunological role in triggering apoptosis in infected cells, particu-
supporting LSEC integrity and stellate cell quiescence
larly monocytes. Cytotoxic cells secrete cytotoxic granules containing
Jonathan Frederik Brozat1, Elisa Brandt1, Myriam Stark1, granzymes, perforin, and in humans, granulysin, to kill cells. We
Petra Fischer1, Theresa Hildegard Wirtz1, Alexander Flaßhove1, hypothesize that in sAH, cytotoxic cells are dysfunctional and unable
Aaron Nikolai Rodenhausen1, Tanja Vajen2, to trigger cell death in target cells.
Alexandra C.A. Heinzmann3, Sophia M. Schmitz4, Method: We performed single-cell RNA-seq (scRNA-seq) in PBMCs
Samira Abu Jhaisha1, Anjali A. Röth4, Rory R. Koenen3, Hacer Sahin1, collected from patients with sAH (n = 4) and healthy controls (HC, n =
Christian Trautwein1, Marie-Luise Berres1. 1University Hospital RWTH 4). Multi-panel intracellular flow cytometry was conducted to
Aachen, Department of Gastroenterology, Digestive Diseases and understand changes in cell proportion, correlated gene expression,
Medical Intensive Care, Internal Medicine III, Aachen, Germany; and cytotoxic granule contents in NK-cells and CD8 T-cells in PBMCs
2
Heinrich-Heine-University, Cardiovascular Research Laboratory, from patients with sAH (n = 9) and HC (n = 7), as well as patients with
Division of Cardiology, Pulmonology and Vascular Medicine, Medical moderate AH (mAH, n = 6), heavy drinkers (HD, n = 8), alcohol-
Faculty, Düsseldorf, Germany; 3Maastricht University, Department of associated cirrhosis (AC, n = 8), and non-alcohol-associated steato-
Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht, hepatitis (NASH, n = 8).
Netherlands; 4University Hospital RWTH Aachen, Department of Results: scRNA-seq revealed receptors required for cytotoxic cell
recognition of activated monocytes were downregulated in all

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POSTER PRESENTATIONS
peripheral immune cells in patients with sAH. Additionally, granu- THU190
lysin was the most downregulated gene in both NK cells and effector Liver cirrhosis and cirrhosis etiology impacts the circulating
CD8 T-cells. In cells from HC, expression of granulysin, perforin, and immune mediators of early stage hepatocellular carcinoma
granzymes A and B was highly correlated, but in sAH these genes lost Boris Beudeker1, Anthony Grooshuismink1, Annemiek Van der Eijk2,
coordination, indicative of dysfunctional cytotoxic granule formation. Jose Debes1, Andre Boonstra1. 1Erasmus MC, Gastroenterology and
Using flow cytometry, we observed a severe decrease in perforin and hepatology, Rotterdam, Netherlands; 2Erasmus MC, Viroscience,
granzyme B expression in sAH patients. Interestingly, NK cells from Rotterdam, Netherlands
patients with mAH, HD, AC, and NASH were not deficient in cytotoxic Email: [email protected]
granules, but perforin and granzyme B were lower in CD8 T-cells from
HD and AC. Background and aims: Novel blood biomarkers to predict and detect
curable, early stage hepatocellular carcinoma (HCC) is the most
Conclusion: Cytotoxic cells from sAH patients are deficient in
effective strategy to improve survival of HCC patients. Others and we
cytotoxic granules, likely impairing their ability to kill target cells.
While sAH patients had both dysfunctional NK-cells and CD8 T-cells, have recently published on the applicability of serum immune
proteins as early HCC biomarkers, but these studies had limited
patients with HD and AC also had dysfunctional CD8 T-cells. Loss of
cell-cell recognition receptors in both cytotoxic cells and monocytes reproducibility. We now study in detail the contribution of the
cirrhotic stage and disease etiology on the circulating immune
is indicative of a loss of cell-cell communication and a possible
response, in order to increase the diagnostic robustness of an early
mechanism for increased inflammatory monocytes in sAH. Together,
these results indicate a loss of cytotoxic cell function in sAH, which HCC immune signature.
Method: A retrospective cohort of 1585 patients with pathology- or
might contribute to increased numbers of inflammatory monocytes
and a decreased ability to kill infected cells. radiology-proven HCC was established of patients diagnosed at our
large tertiary HCC referral center, among them were 522 (33%) with
THU189 BCLC 0/A stage HCC. Immune profiles of a balanced cohort of 188
Multi-omics analysis of human livers reveals variation in cirrhotic patients, and 195 early HCC patients with hepatitis B (HBV),
intrahepatic inflammation across chronic hepatitis B infection hepatitis C (HCV), ALD alcoholic liver disease (ALD) or non-alcoholic
phases liver disease (NAFLD) were determined through serum multiplex
Noé Axel Montanari1, Ricardo Ramirez2, Abhishek Aggarwal2, profiling.
Nicholas Van Buuren2, Michael Doukas1, Christina Moon2, Results: We show that liver cirrhosis had a profound effect on the
Scott Turner2, Lauri Diehl2, Li Li2, Jose Debes1, Becket Feierbach2, levels of circulating immune proteins with significant dysregulation
Andre Boonstra1. 1Erasmus MC; 2Gilead Sciences of 24 out of 59 serum immune mediators. Stratification of cirrhosis
Email: [email protected] patients in groups with distinct etiologies identified 45 significant
immune mediators and heat map revealed obviously distinct
Background and aims: Chronic HBV is clinically defined in 4 phases immune profiles in each etiology. HBV-cirrhosis was characterized
by a combination of serum HBV DNA levels, HBeAg status and ALT: by high levels of circulating TRAIL and IFN-gamma, HCV-cirrhosis by
immunotolerant (IT), immune-active (IA), inactive carrier (IC) and high levels of IP-10 and the immune profiles of ALD-cirrhosis; NAFLD-
HBeAg-negative hepatitis (ENEG). Immune and virological differ- cirrhosis were more comparable with higher levels of IL-8, IL-6,
ences between phases, as detected in blood, have proven useful but CCL25 and LIF.
do not fully explain the interrelation between the clinical phenotype Eight immunological mediators were significant independent pre-
and the immunological mechanism in the liver. We aimed to study dictors of early stage HCC and displayed specificity for one of the four
the intrahepatic immune profile across the clinical phases in order to cirrhosis etiologies. These immune mediators improved existing
better understand the immunological mechanism of HBV. tumors marker efficacy and when combined with AFP detected early
Method: Immunological composition and transcriptional profiles of stage HCC with an AUC of 0.80.
FFPE core needle liver biopsies in chronic HBV phases vs healthy were Conclusion: HCC develops in an inflammatory heterogenetic
evaluated by multiplex immunofluorescence and RNA-Seq (n = 37 background. In our search for predictive HCC markers, we found
and 78, respectively). that liver cirrhosis and cirrhosis etiology had a profound impact on
Results: Irrespective of the phase-specific serological profiles, the circulating immune response and associated with a wide
increased intrahepatic immune-gene expression and frequency repertoire of pro-inflammatory and HCC promoting immune media-
were observed in chronic HBV compared to healthy control livers. tors. Moreover, we identified Immunological markers that differ-
Greater transcriptomic de-regulation was seen in IA and ENEG (172 vs entiated early stage HCC from cirrhosis. Strict stratification resulted in
243 DEGs) than in IT and IC (13 vs 35 DEGs) livers. ISG, immune- a set of immune mediators with good sensitivity for early stage HCC
activation and exhaustion genes (ICOS, CTLA4, PDCD1) together with of different etiologies.
chemokine genes (CXCL10, CXCL9) were significantly induced in IA
and ENEG livers. Moreover, distinct immune profiles associated with THU191
ALT elevation, and a more accentuated immune-exhaustion profile Ebola virus infection promotes reduced gene expression of
(CTLA4, TOX, SLAMF6, FOXP3) found in ENEG and set it apart from IA antigen presentation molecules in hepatic CD68+ macrophages in
phase (LGALS9, PDCD1). Interestingly, all HBV phases showed cynomolgus macaques
downregulation of metabolic pathways vs healthy livers (fatty and Timothy Wanninger1,2, Omar Saldarriaga1, Daniel Millian1,
bile acid metabolism). Finally, we found increased leukocyte infiltrate Jason Comer2, Kamil Khanipov3, George Golovko3,
correlated with serum ALT, but not with HBV DNA or viral proteins. Slobodan Paessler1, Heather Stevenson1. 1University of texas medical
Conclusion: Our comprehensive multi-omics analysis of human branch, Pathology, United States; 2University of texas medical branch,
livers revealed distinct inflammatory profiles and pronounced Microbiology and immunology, United States; 3University of texas
differences in intrahepatic gene profiles across all chronic HBV medical branch, Pharmacology and toxicology, United States
phases in comparison to healthy liver. Email: [email protected]
Background and aims: Ebola virus (EBOV) is an emerging infectious
disease found in West Africa, with the potential for case importation
to other countries. Antigen presenting cells, including macrophages,
are among the first cells infected following EBOV exposure. As a
result, the liver, a macrophage-laden organ, is a key participant in
EBOV infection. While the inflammatory contributions of

S194 Journal of Hepatology 2022 vol. 77(S1) | S119–S388

 POSTER PRESENTATIONS
macrophages have been characterized in vitro or ex vivo, studying leukocyte recruitment, flow-adhesion assays were performed with
these cells within their tissue context is essential for understanding SASP-stimulated HSEC (following siRNA or antibody treatment) and
disease progression. peripheral blood lymphocytes or monocytes.
Method: We compared formalin-fixed, paraffin-embedded liver Results: PLVAP was significantly upregulated in liver endothelium of
tissue from uninfected control and terminal EBOV-infected cyno- CLD and HCC patients compared to healthy controls, correlating with
molgus macaques. We characterized region-specific whole transcrip- increased expression of senescent markers, p21 and p16. Treatment
tome expression in these tissues using GeoMx Digital Spatial Profiling of primary HSEC with RAS-CM significantly increased PLVAP
(NanoString). Biological processes enriched or depleted in infection expression and stimulated recruitment of both lymphocytes and
were identified using gene set analysis (Global Test) and Ingenuity monocytes under physiologically low shear stress. However, these
Pathway Analysis (Qiagen). Macrophage (CD68+) accumulation in processes were morphologically and molecularly distinct.
liver tissue was quantified by immunofluorescence image analysis Lymphocytes predominantly (∼ 60%) transmigrate via the transcel-
using QuPath digital pathology software. lular pathway which was selectively inhibited by ICAM-1 blockade. In
Results: Ebola virus infection was associated with increased CD68+ contrast, >90% monocytes transmigrate paracellularly in a CD31-
macrophage accumulation in the liver. Gene set analysis revealed dependent manner. Furthermore, genetic or antibody-mediated
altered immune, coagulation, metabolism, apoptosis, and tissue inhibition of PLVAP selectively impaired SASP-mediated monocyte
remodeling processes. Within the altered immune processes, key transmigration whilst having no effect on lymphocyte recruitment.
down-regulated genes included multiple MHC-II alleles (HLA-DPA1, Conclusion: These data highlight a previously unreported link
HLA-DQB1, HLA-DRA, HLA-DRB1), CD74, and LGMN. In CD68+ between PLVAP and senescence, in which PLVAP expression is
macrophages, these down-regulations were associated with antigen driven in HSEC by the senescent secretome to facilitate monocyte
presentation, monocyte/macrophage differentiation, as well as T cell recruitment. PLVAP could therefore be a novel target for perturbing
differentiation, activation, and cytotoxicity gene sets. aberrant monocyte recruitment in liver disease.
Conclusion: Down-regulated MHC-II-related gene expression by
THU193
hepatic CD68+ macrophages may reduce T cell activation in EBOV-
Dysfunctional liver-resident CXCR6+ CD8 T cells during persistent
infected cynomolgus macaques. Such impairment, identified by in
viral liver infection
situ regional transcriptomic analysis, may synergize with the known
disruption of dendritic cell-mediated antigen presentation in this Miriam Bosch1, Nina Kallin1, Donakonda Sainitin1,
disease, further compromising the adaptive immune response to Hannah Wintersteller1, Ulrike Protzer2,3, Dirk Wohlleber1,
EBOV infection. Percy A. Knolle1,4. 1Institute of Molecular Immunology, Technical
University of Munich, Munich, Germany; 2Institute of Virology, Technical
THU192 University of Munich; 3Institute of Virology, Helmholtz Center for
Plasmalemma vesicle-associated protein expression is driven by Environment and Health; 4German Center for Infection Resarch, Munich
senescent cell-endothelial crosstalk and shapes the immune Email: [email protected]
landscape in chronic liver disease Background and aims: CD8 T cell-mediated immunity is key for the
Alex Wilkinson1, Daniel Patten1, Sam Hulme1, Matthew Hoare2, clearance of hepatitis B virus infection and other hepatotropic viral
Shishir Shetty1. 1University of Birmingham, Institute of Immunology and infections. Persistent viral liver infections, however, are characterized
Immunotherapy, United Kingdom; 2University of Cambridge, by a lack of a robust anti-viral CD8 T cell response. We aimed at
Department of Medicine, United Kingdom determining the mechanism causing the lack of CD8 T cell function-
Email: [email protected] ality during persistent viral liver infection.
Method: We used Adenovirus-based models (coding for ovalbumin
Background and aims: Chronic liver diseases (CLDs) are driven by
or the HBV genome) to investigate persistent or acute-resolved
leukocyte recruitment and persistent inflammation. Cellular senes-
infection. For virus-specific T cell analysis, we transferred naïve
cence is a key feature of CLD, yet its contribution to liver inflammation (CD44negCD62Lhi) virus-specific CD8 T cells bearing a congenic
is poorly understood. Senescent cells release a secretome (senes-
marker before infection. T cells were analyzed at different time
cence-associated secretory phenotype or SASP) which facilitates their points for phenotypic and functional characterization and RNAseq.
clearance through leukocyte recruitment. This process is mediated by
Results: After acute-resolved viral infection, we identified two distinct
hepatic sinusoidal endothelial cells (HSEC) which undergo pheno-
virus-specific CD8 T cell populations in the liver, i.e. CX3CR1+ and
typic and functional changes in response to SASP treatment. CXCR6+CD69+ CD8 T cells. Contrastingly, virus-specific CD8 T cells
Plasmalemma vesicle-associated protein (PLVAP) is highly expressed
during persistent infection were mainly CXCR6+CD69+ liver-resident
by foetal liver endothelium, playing an important developmental CD8 T cells. Independent of infection outcome, liver CXCR6+CD69+
role, yet human single-cell studies have highlighted its re-emergence
CD8 T cells expressed a tissue-residency gene signature. However,
in liver cirrhosis and hepatocellular carcinoma (HCC). Whilst PLVAP
virus-specific CXCR6+CD69+ CD8 T cells during persistent infection
has previously been proposed as a leukocyte trafficking molecule, its did not produce cytokines, lacked cytotoxicity, and were hence
specific role in hepatic leukocyte recruitment is not known. We
termed dysfunctional liver-resident T cells. Transcriptome analysis
hypothesised that PLVAP expression is driven by the senescent tissue enabled us to define a single pathway marking these dysfunctional
microenvironment in CLD and sought to investigate its potential role
CXCR6+CD69+ T cells in persistent infection when compared to
in SASP-mediated leukocyte recruitment.
cytotoxic liver-resident memory T cells after resolved infection.
Method: PLVAP expression was characterised, in human liver samples
Conclusion: The identification of a single transcription factor
by qPCR and immunohistochemistry, and in primary human HSEC by
distinguishing effector liver-resident memory T cells from dysfunc-
immunocytochemistry. SASP was obtained using a model of
tional tolerized virus-specific liver-resident CD8 T cells in preclinical
oncogene-induced senescence (conditioned media from RAS-senes-
models of persistent expression of ovalbumin and HBV points
cent IMR90 fibroblasts-RAS-CM), and the effects of SASP treatment
towards a liver-specific mechanism mediating immune tolerance
on primary HSEC were determined by qPCR and confocal microscopy.
during persistent hepatocyte infection.
To investigate the molecular mechanisms of SASP-mediated

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POSTER PRESENTATIONS
THU194 THU195
Fate of HDV-specific CD8+ T cells during bulevirtide monotherapy Increased ILT2 expression contributes to dysfunction of
in patients with chronic hepatitis delta CD56dimCD16+NK cells in chronic hepatitis B virus infection
Valerie Oberhardt1, Elisabetta Degasperi2, Marta Borghi2, Wenwei Yin1, Yingzhi Zhang1, Hong Ren1. 1Institute for Viral Hepatitis,
Kathrin Heim1, Roberta Soffredini2, Alessandro Loglio2, Department of Infectious Diseases, Chongqing, China
Özlem Sogukpinar1, Frances Winkler1, Bertram Bengsch1, Email: [email protected]
Maike Hofmann1, Robert Thimme1, Pietro Lampertico2,3,
Background and aims: Natural killer (NK) cells play a crucial role in
Christoph Neumann-Haefelin1. 1Medical Center-University of Freiburg,
the control of human viral infections but their activity is significantly
Department of Medicine II, Freiburg, Germany; 2Foundation IRCCS Ca’
impaired in patients infected with chronic hepatitis B (CHB). The
Granda Ospedale Maggiore Policlinico, Milan, Italy; 3CRC “A. M. and
mechanism that contributes to NK cell dysfunction in CHB needs
A. Migliavacca” Center for Liver Disease, Department of Pathophysiology
further elucidation.
and Transplantation, Milan, Italy
Method: In this study, we analyzed the expression and function of
Email: [email protected]
the novel inhibitory receptor immunoglobulin-like transcript-2
Background and aims: The viral entry-inhibitor bulevirtide (BLV) (ILT2) on NK cells from 110 CHB patients and 36 healthy controls.
leads to a decline of HDV viremia in chronic HDV infection, however, Results: We observed ILT2 expression on circulating
treatment for several years is likely required to prevent relapse. CD56dimCD16+NK cells was increased in immune-tolerant and
Sustained treatment response may be fostered by therapy-induced active CHB patients compared with inactive carriers and controls.
restoration of HDV-specific CD8+ T cell responses that are exhausted The frequency of ILT2+CD56dimNK cells was positively correlated with
due to high viremia and antigen loads during chronic HDV infection. serum viral load in immune-tolerant patients. The percentage of
We thus studied the effect of BLV monotherapy on HDV-specific CD8+ ILT2+CD56dimNK cells decreased along with HBV load in active CHB
T cell repertoire, phenotype, and functionality. patients that received antiviral therapy. Functional analysis showed
Method: HDV-specific CD8+ T cell responses were studied in 35 HDV that ILT2+CD56dimNK cells in CHB patients had significantly reduced
infected patients, of whom 14 cirrhotic patients started treatment degranulation and IFN-gamma production. Up-regulation of ILT2 was
with BLV. Samples were collected from baseline up to 40 weeks on- associated with high levels of apoptosis in CD56dimCD16+NK cells
treatment. HDV-specific CD8+ T cells were analyzed either upon from CHB patients. ILT2 blockade was shown to increase CD107a
stimulation with overlapping peptides (olp), spanning the entire L- expression and cytotoxicity of CD56dimNK cells in CHB patients.
HDAg (51 olps, 15mers) or upon stimulation with optimal epitopes in Finally, ILT2 was found to be up-regulated by TGF-β1, which was
HLA-matched patients, following 14 days of in vitro culture. Ex vivo increased in immune-tolerant and active CHB patients.
high-dimensional flow cytometry analysis of peptide-loaded MHC
class I-specific CD8+ T cells in selected patients throughout therapy is
currently ongoing.
Results: In two-thirds of patients, an HDV-specific CD8+ T cell
response was detectable at baseline. This was characterized by
interferon (IFN) γ and tumor necrosis factor (TNF) co-secretion,
without additional interleukin (IL)-2 production in response to
optimal epitope stimulation in HLA matched patients. Targeted
epitopes were restricted by HLA-B alleles only, predominantly by
HLA-B*35 and HLA-B*18. Direct comparison of patient samples from
an early time point during therapy (week 4) with a later time point
during treatment (week 36–40) did not indicate a restoration or
boosting of HDV-specific CD8+ T cell functionality coinciding with
decreasing HDV viremia. Using the comprehensive olps approach,
half of the patients displayed an HDV-specific CD8+ T cell response at
the late time point during treatment (median of 2 olps recognized per
patient), which is comparable with the response-rate in untreated
patients.
Conclusion: During the first 40 weeks of BLV treatment, no obvious
increase in HDV-specific CD8+ T cell response breadth and magnitude
was observed. This might be due to the slow decline of HDV viremia,
the fact that all patients treated with BLV had liver cirrhosis, and
mostly unchanged HBsAg levels during BLV monotherapy that may
continue to mediate HDV-specific CD8+ T cell exhaustion. In addition,
some of the HDV-specific CD8+ T cell responses target epitopes Conclusion: Our findings imply that high ILT2 expression would
affected by viral escape mutations and these responses are unlikely to facilitate HBV viral persistence by tempering NK cells into silence and
benefit from reduction of viremia. Longer follow-up during con- blockade of ILT2 can enhance NK cell function as an alternative
tinued BLV therapy, high-dimensional analysis of CD8+ T cell approach to treat CHB.
phenotype and function, as well as analysis of patients with BLV/
pegIFN combination therapy will expand our understanding of HDV-
specific CD8+ T cell restoration during BLV therapy.

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 POSTER PRESENTATIONS
THU196
Elevated serum bilirubin levels and aminotransferases are
associated with immuno-modulatory and suppressive subsets in
pregnant females with intrahepatic cholestasis and hepatitis E
virus infection
Anoushka Saxena1, Minal Kashyap2, Prabhjyoti Pahwa1, Fatima Ali1,
Hamda Siddiqui1, E. Preedia Babu1, Y.M. Mala2, Shakun Tyagi2,
Nirupma Trehanpati1. 1Institute of Liver and Biliary Sciences, New Delhi,
India, Department of Molecular and Cellular Medicine, New Delhi, India;
2
Maulana Azad Medical College, New Delhi, India, Department of
Obstetrics and Gynaecology, New Delhi, India
Email: [email protected]
Background and aims: Elevated serum bilirubin levels and liver
functions are well-recognized markers of hepatic damage and
inflammation. Viral hepatitis, intrahepatic cholestasis of pregnancy,
gallstones and pre-eclampsia are the most common causes of
jaundice in pregnant women, inducing significant morbidity and
mortality in both pregnant women and their infants. Therefore, we
aimed to investigate the relationship between deranged liver
function, high bilirubin and the immune dysfunction during
pregnancy.
Method: An observational prospective study was carried out at a
tertiary care hospital on antenatal patients with clinical and
biochemical jaundice over a period of one year. Peripheral immune
cell subsets were analyzed in pregnant women with serum bilirubin
>2.0 mg/dl (Gr.1, n = 20, 25.8 ± 2), positive for IgM/IgG Hepatitis
E virus (AVH-E) (Gr.2, n = 5, 24 ± 2) and healthy pregnant women
(Gr.3, n = 7, 24.5 ± 2) by flow cytometry.
Results: Females with high bilirubin levels; 2–5 mg/dl (64%), 5–
10 mg/dl (16%), >10 mg/dl (12%) had deranged LFT (28%), asymp-
tomatic (12%), jaundice (31%), k/c/o liver disease (3%), k/c/o hepatitis-
E (3%) and 6% presented with other complaints. Pregnant females
with high bilirubin levels showed an overall increased percentage of
Monocytes ( p = 0.0012), CD4+ ( p = 0.0009) and CD8+ T-cells Conclusion: Our results clearly indicate that pregnant females with
( p <0.0001), compared to healthy (Fig. A). However, an increased high bilirubin, including those infected with HEV exhibit increased
expression of inhibitory markers (Fig. B); PD-1 ( p <0.0001), CTLA-4 suppressive T and B cells with diminished BAFFR/APRIL expressing B
( p <0.0001), BTLA ( p <0.0001), BLIMP-1 ( p = 0.0008), SLAM-1 cells.
( p <0.0001), LAG-3 ( p <0.0001), TIGIT ( p <0.0001), TIM-3
( p <0.0001) on Transitional memory subset and PD-1 ( p <0.0001), THU197
CTLA-4 ( p <0.0001), BTLA ( p <0.0001), BLIMP-1 ( p = 0.0006), SLAM-1 Classification of HCV-specific CD8+ T cells by the differential
( p <0.0001), LAG-3 ( p <0.0001), TIGIT ( p <0.0001), TIM-3 ( p <0.0001) expression pattern of Slamf6 and CD69 predicts that the majority
on effector memory subset of T-cells was evident. Compared to of cells are rather preterminally versus terminally exhausted
healthy, myeloid dendritic cell population was significantly higher regardless of disease stage
(Fig. C) in females with high bilirubin (p <0.0001) and infected with Maximilian Knapp1, Christin Ackermann1, Claudia Beisel1,
HEV ( p = 0.0095), as compared to healthy females, indicating Vanessa Ditt2, Melanie Wittner1, Julian Schulze Zur Wiesch1.
immune suppression. An elevated frequency of B-cell subsets ( p 1
University Medical Center Hamburg-Eppendorf, I. Department of
<0.0001) was observed in all females with high bilirubin. Yet, a defect Medicine, Infectious Diseases Unit, Hamburg, Germany; 2University
in activation and proliferation as suggested by diminished expression Medical Center Hamburg-Eppendorf, Center for Diagnostics, Institute of
of BAFF-R ( p = 0.04) and APRIL ( p = 0.02) and rise in PDL1 ( p = Transfusion Medicine, Hamburg, Germany
0.0025) was determined (Fig. D). Email: [email protected]
Background and aims: Exhausted T effector cells, commonly
described in chronic viral infections and cancer, are phenotypically
and functionally heterogeneous cell populations whose develop-
ment, maintenance, and response to immunotherapies are incom-
pletely understood. Today, many differentiations into progenitors,
intermediates and terminal stages of exhausted T cells are already
known based on numerous markers. A better description regarding
different subsets of exhausted T cells will allow a better under-
standing for future cancer therapy and viral cure approaches. Acute
and chronic hepatitis C (HCV) infection are ideal models to examine
the development of T-cell exhaustion and its potential reversibility at
cellular and molecular levels. To assess the molecular fingerprint of
potential populations, we aimed to investigate the interaction of
different immunomodulatory targets.
Method: HCV-specific CD8+ T cells from HLA-A*01:01, HLA-A*02:01
and HLA-A*24:02 positive patients were analyzed with a 21-color

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POSTER PRESENTATIONS

Figure: (abstract: THU197)

FACS-panel evaluating the surface expression of lineage markers THU198

(CD3, CD4, CD8), ectoenzymes (CD38, CD39, CD73), markers of TAPBPR shapes the hepatitis B immunopeptidome presented on
differentiation (CD62L, CD127), and markers of exhaustion and HLA class I molecules
activation (CD96, TIGIT, PD-1, CD69, Slamf6, CD28) and transcription Ricky Sinharay*,1,2, Andreas Neerincx1, Arwen Altenburg1,
factors (T-bet, TCF1, NR2F6, TOX, IRF4). Jens Bauer3,4,5, Mark R. Wills6, Juliane S. Walz3,4,5,7, Will Gelson8,
Results: Analyzing the TIGIT-CD96-axis, the majority of HCV-specific Louise H. Boyle1. 1University of Cambridge, Department of Pathology,
Tet+ CD8+ T cells of all patient groups was TIGIT+ and CD96+. The Cambridge, United Kingdom; 2Cambridge University Hospitals NHS
frequencies of CD96+ cells in the Tet+ T cells were significantly higher Foundation Trust, Cambridge Liver Unit, Addenbrooke’s Hospital,
than in bulk CD8+ T cells for acute, resolved and chronic infection. Cambridge, United Kingdom; 3University Hospital Tübingen, Clinical
Furthermore, HCV-specific CD8+ T cells were stratified into four novel Collaboration Unit Translational Immunology, German Cancer
subsets of exhausted T cells based on expression of the transmem- Consortium (DKTK), Department of Internal Medicine, Tübingen,
brane protein Slamf6 and the early activation antigen CD69 as Germany; 4University of Tübingen, Institute for Cell Biology, Department
currently described by Beltra et. al. (2020, Immunity 52, 825–841) in of Immunology, Tübingen, Germany; 5University of Tübingen, Cluster of
the LCMV mouse model describing progenitor 1 (Tex prog1: Slamf6+ Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed
CD69+), progenitor 2 (Tex prog2: Slamf6+ CD69−), intermediate (Tex int: Tumor Therapies", Tübingen, Germany; 6University of Cambridge,
Slamf6− CD69−) and terminally exhausted (Tex term: Slamf6− CD69+) T Department of Medicine, Addenbrookes Hospital, Cambridge, United
cells. The majority of HCV-specific Tet+ cells in peripheral blood are in Kingdom; 7Margarete Fischer-Bosch Institute of Clinical Pharmacology
the Tex prog2 state and less than 6% of the Tet+ T cells were at the Tex term and Robert Bosch Center for Tumor Diseases (RBCT), Stuttgart, Germany;
state. 8
Cambridge University Hospitals NHS Foundation Trust, Cambridge Liver
Unit, Addenbrooke’s Hospital, Cambridge, United Kingdom
Conclusion: We identified four exhausted T cell subsets defined by
Email: [email protected]
Slamf6 and CD69 in patients with different clinical status of HCV
infection. The frequencies detected in PBMC of our patients are Background and aims: The presentation of virus derived peptides on
similar to those described in the LCMV mouse model by Beltra et. al. HLA class I molecules is crucial for mounting antiviral immune
They could also show that the majority of the Tex term subset is responses. TAPBPR is a recently identified peptide editor involved in
localized in the liver. To investigate the Tex term population in human, optimizing antigen selection on MHC class I molecules. Here, we
analyses from liver biopsies are required. In this context, it will be of present novel data on the impact of TAPBPR on the hepatitis B (HBV)
interest whether the responsiveness of the Tex int subset to PD-1 immunopeptidome presented on HLA class I by using a mass
blockade described in mice can also be confirmed in human. Co- spectrometry approach.
inhibitory receptors like CD96 in the TIGIT-CD155 signaling pathway Method: HeLa cells (HLA-A*68:02, -B*15:03 and -Cw12) and TAPBPR
also shaped the HCV-specific T cells. knock-out HeLa cells (TAPBPRKO) overexpressing individual HBV
proteins HBsAg, Pol, HBcAg and HBx were generated. These cells were
expanded to 5×108 cells, lysed and peptides were eluted using a pan
HLA class I antibody (W6/32). Analysis was performed by liquid

S198 Journal of Hepatology 2022 vol. 77(S1) | S119–S388

 POSTER PRESENTATIONS
chromatography coupled to tandem mass spectrometry (LC-MS/MS). 16) according to Forns. No significant differences were observed in the
Mass spectra data were then searched against a database of possible percentage of CD3-CD16+ NK cells and NKT cells among groups. ALF
peptides that could be derived from the host and/or pathogen patients also presented an increased percentage of HLA-DR+-expres-
proteomes, to identify HBV derived peptides presented on HLA class sing Tregs (38 ± 11.6 and 39.2 ± 11.5) and CD8+ (16 ± 8.3 and 15.6 ± 8.8)
I. The HBV immunopeptidome in TAPBPR depleted cells was compared to Tregs (32.7 ± 9.4 and 32.5 ± 9.3) and CD8+ (12 ± 9.1 and
compared to HeLa cells expressing wild type TAPBPR and individual 12.2 ± 9) in patients without ALF according to Forns and FIB-4,
HBV proteins. respectively. The percentage of HLA-DR+ CD4+ was higher in patients
Results: A greater number of HBV peptides were presented in with ALF (5.1 ± 3.1) than in patients without ALF (3.9 ± 3) according to
TAPBPRKO cell lines compared to wild type cell lines, which was FIB-4. Figure 1 depicts the aforementioned significant differences ( p
consistently observed between cells expressing different HBV <0.05).
proteins. This was despite the fact that no substantial change in the
total cellular peptide count was observed between wild type and
TAPBPRKO cells. Amino acids positions 2 and 9 were clearly preferred
for binding in both wild type and TAPBPRKO cells, and a greater
number of peptides were assigned to HLA-B*15:03 than HLA-
A*68:02. Furthermore, semi quantitative analysis revealed that
depletion of TAPBPR resulted in up-modulation of almost all HBV-
derived peptides identified. In addition, changes in the hierarchy of
the abundance of HBV peptides presented were observed in
TAPBPRKO cells. Of the up-modulated peptides, only four have been
identified previously and are catalogued on IEDB. A total of 26 HBV-
derived peptides were identified, 22 (84.62%) of which were novel. Of
the novel peptides 7 were only identified in the TAPBPRKO cell lines.
Conclusion: These findings strongly support a role of TAPBPR in HBV-
derived peptide selection for presentation on HLA class I. However, it
is still unclear whether this is advantageous for individuals with HBV
expressing HLA alleles where TAPBPR mediates peptide exchange.

THU199
Phenotypes of NK cells and the activation profile of T cells in the
early stages of alcohol liver diseases
Coral Zurera1,2, Anna Hernandez3, Aina Teniente1, Daniel Fuster3, Conclusion: Severe AUD patients with ALF presented an increased
Eva Martínez-Cáceres1, Robert Muga3, Paola Zuluaga*,3. 1investigation NK cytotoxic phenotype concomitant with a decreased immunor-
institute germans trias i pujol, immunology, badalona, Spain; egulatory and cytokine-secreting phenotype, possibly as a compen-
2
Universitat Autònoma de Barcelona, Bellaterra, Spain; 3university sating mechanism of liver fibrosis. Meanwhile, the increased
hospital germans trias i pujol, internal medicine, badalona, Spain activation pattern observed in T cell subsets of patients with ALF
Email: [email protected] could be a mechanism that favors the development and maintenance
of liver fibrosis.
Background and aims: The role of cellular immunity in alcohol-
related liver diseases (ARLD) is currently being characterized. While
THU200
CD8 T cell activation is known to be detrimental, enhancing liver
A spatio-temporal map of malaria infected mouse liver
damage, the decrease of naïve T cells is associated with advanced liver
Franziska Hildebrandt1, Johan Ankarklev1. 1Stockholm University,
fibrosis (ALF) in patients with alcohol use disorder (AUD). Natural
Department of Molecular Biosciences, Stockholm, Sweden
Killer (NK) cells and NKT cells play an important role in the
Email: [email protected]
development of ARLD having subsets with opposing roles in the
development of liver fibrosis. We aimed to evaluate the phenotype of Background and aims: The liver is crucial for malaria parasite
NK and NKT cells and the activation profile of T cells in patients with development in the vertebrate host. Once transmitted by a female
AUD according to the presence of ALF. mosquito, the malaria parasites start their development in the liver,
Method: Patients were admitted to treatment of AUD between 2019 before entering the symptomatic blood stage. Since the liver has high
and 2021 in Germans Trias I Pujol Hospital, Spain. ALF was defined if potential for an effective immune response towards invading
the FIB-4 score was >2.67 (n = 19) or Forns score was >6.9 (n = 21). parasites and other intruders, choosing the liver as a developmental
Patients with HCV infection, HIV infection and history of liver cirrhosis niche is paradoxical. Thus, we aim to delineate host-pathogen
were excluded. Immunophenotyping of NK cells (CD3-CD56+CD16+, interactions during the time course of an ongoing liver infection in
CD3-CD56+, CD3-CD16+), NKT cells (CD3+CD56+), and the activation vivo, with the main aim of studying the host’s response in a spatial
status of CD4+, CD8+ and regulatory T cells (Tregs) was evaluated context.
according to the presence of HLA-DR. Method: To this end we are using Spatial Transcriptomics to describe
Results: 79 patients (51 years, 71% males) were included. Patients had the spatial organization of transcriptomic response in the mouse liver
a mean AUD duration of 18 ± 11 years with a daily alcohol to an ongoing infection, using mosquito salivary gland lysate as a
consumption of 155 ± 77 gr/day. Regarding the immunophenotype control.
in peripheral blood, the mean ± SD absolute values were: 2.1 ± 0.9 Results: Our preliminary data suggests a differential onset of
cells/L for total lymphocytes, 1054.5 ± 501.7 cells/µL for CD4+, 540 ± inflammation between infected and control mice, due to the presence
335.7 cells/µL for CD8+, 49.3 ± 24.8 cells/µL for Tregs, 150.3 ± 97.5 of parasites in the tissue. We further investigated gene expression as a
cells/µL for NK cells and 69.8 ± 78.3 cells/µL for NKT cells. The function of the distance to the site of infection for multiple time
percentage of CD3-CD56+ NK cells of patients with ALF was points and cell type compositions in specific areas of infection but
significantly lower (4.8 ± 3.3 and 4.9 ± 3.4) than in patients without also in the larger tissue context.
ALF (7.8 ± 6.2 and 7.7 ± 6.2) according to Forns and FIB-4, respectively.
The percentage of CD3-CD16+CD56+ NK cells was significantly higher
in patients with ALF (87 ± 11) compared to patients without ALF (80 ±

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POSTER PRESENTATIONS
treatment they had received. Cox proportional hazards models
were used to analyze the patients’ risks of liver cirrhosis and HCC,
with adjustment for age, sex, comorbidities, and Charlson
Comorbidity Index.
Results: A total of 4210 patients with CHB or CHC infection were
recruited; 2535, 568, 427, and 680 were assigned to the NRT only,
varenicline only, varenicline + NRT, and comparison (no treatment)
groups, respectively. The mean follow-up duration was 7.2 ± 4.8 years.
The outcomes were significantly different among the four groups. The
NRT only, varenicline only, and varenicline + NRT groups had a lower
prevalence of liver cirrhosis ( p = .06) and HCC ( p = .03) than did the
no-treatment group in the cumulative incidence analysis (liver
cirrhosis: prevalence = 8.5%, 3.9%, and 2.1% vs 11.3%, respectively;
HR = 0.74[95%CI: 0.33–1.63], 0.63[0.34–1.15], and 0.40[0.19–0.84],
respectively; HCC: prevalence = 15.0%, 11.6%, and 11.5% vs 23.1%,
respectively; HR = 0.62[0.31–1.25], 0.32[0.10–1.00], and 0.26[0.10–
0.69], respectively).

Conclusion: Our data indicates patterns of differential expression

due to the influence of malaria parasites both locally and across
tissues in challenged mice. Our preliminary data further suggests that
the.
immune response towards a Plasmodium infection shows spatio-
temporal patterns on the transcriptional level, providing a promising
outlook for more detailed studies on the influence of the parasite on Conclusion: This study evaluated the effect of one month of NRT,
the surrounding liver environment. varenicline, both, or no treatment on the risk of liver cirrhosis and
HCC in smokers with CBC or CHC infection undergoing a smoking
cessation program. All 3 smoking cessation treatments appeared to
be effective in minimizing the risk of liver cirrhosis and HCC; a low
Public Health prevalence of both conditions was observed in each of the 3
treatment groups.
Cumulative incidence rates of liver cirrhosis and HCC over time among
patients with CHB or CHC infection in the no smoking cessation
THU217
treatment, NRT only, varenicline only, and varenicline + NRT groups.
Reducing the risk of liver cirrhosis and hepatocellular carcinoma
after treatment for smoking cessation in patients with chronic THU218
hepatitis B or C infection: a 12-year follow-up study Testing coverage and strategy required to sustain Hepatitis C
Ruey-Chang Lin1, Chun Hsiang Wang1,2, Kuo-Kuan Chang1, elimination in an injecting network of people who inject drugs: a
Lien-Juei Mou1, Yuan Tsung Tseng3. 1Tainan Municipal Hospital network-based model
(Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan, Chloe Siegele-Brown1, Martin Siegele-Brown2, Charlotte Cook3,
Department of Hepatogastroenterology; 2Chung Hwa Medical Mark Wright1, Julie Parkes3, Salim Khakoo3, Ryan Buchanan3.
University, Tainan, Taiwan, Department of Optometry; 3Tainan 1
University Hospital Southampton NHS Foundation Trust, United
Municipal Hospital (Managed by Show Chwan Medical Care Kingdom; 2University of Sussex, United Kingdom; 3University of
Corporation), Tainan, Taiwan, Committee of Medical Research Southampton, United Kingdom
Email: [email protected] Email: [email protected]
Background and aims: The possible hepatotoxic effect of cigarette Background and aims: The World Health Organisation has set a
smoking in patients with chronic hepatitis B virus (CHB) or chronic target for the global elimination of Hepatitis B (HBV) and C (HCV) by
hepatitis C (CHC) virus infection has been proposed in numerous 2030. To achieve the elimination target, a widespread scale-up of
epidemiological and experimental studies. Varenicline and nicotine testing and treatment services is required. However, little is known
replacement therapy (NRT) are the current first-line treatment for about the level of testing required to sustain the low-prevalence state
smoking cessation. The present study compared the effects of of elimination. In this study we model the testing coverage required
different standard treatments for smoking cessation and of receiving to maintain HCV elimination in an injecting network of people who
no treatment for smoking cessation on the risk of liver cirrhosis and inject drugs (PWID). We also test the hypothesis that a ‘bring your
hepatocellular carcinoma (HCC) among patients with CHB or CHC friends’ testing strategy will be more efficient.
infection. Method: We create a dynamic injecting network structure connect-
Method: We identified patients with CHB or CHC infection who ing 689 PWID based on empirical data. A burn-in period, where PWID
smoked regularly and whose data were input into Taiwan’s National are randomly treated according to empirical parameters until the
Health Insurance Research Database between January 1, 2007, and elimination target is achieved, is followed by the 5-year simulation
December 31, 2018. The patients’ demographic data, medical history period. The primary outcome is the testing coverage required per
(including smoking habits), and paraclinical information were month to maintain prevalence at the elimination threshold over 5
collected. The patients were classified into 4 groups—the no years. We compare two treatment scenarios: 1) random testing, and
smoking cessation treatment, NRT only, varenicline only, and 2) ‘bring your friends’ testing, where 50% of tests are random and 50%
varenicline + NRT groups—according to the smoking cessation of tests in injecting partners of randomly selected individuals.

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 POSTER PRESENTATIONS
Results: After 5 years, without any testing or treatment provision, the MRI. We determined 1-year and 2-year cumulative incidences for
prevalence of HCV increased from the elimination threshold (11.68%) HCC screening overall, by aetiology, and by calendar year of cirrhosis
to a mean of 25.0% (SD 3.0%). To maintain elimination with random diagnosis.
testing, on average 4.92% (SD 0.84%) of the injecting network needs to Results: Among the 7, 739 individuals in the cohort, 56.9% were male,
be tested per month. However, with a ‘bring your friends’ strategy, 75.2% lived in an urban area, and the mean age was 53 years. Most
3.69% (SD 0.63%) of the network needs to be tested per month ( p < individuals had NAFLD/cryptogenic aetiology (43.4%), followed by
0.000001). alcohol-related liver disease (25.1%), hepatitis C virus (21.4%),
The superiority of the ‘bring your friends’ approach was maintained autoimmune hepatitis (8.5%), and hepatitis B virus (1.6%). Nearly
in a sensitivity analysis that adjusted for changes in needle and half of individuals had decompensated cirrhosis (47%). Most
syringe provision and the rate of engagement with treatment individuals (68.9%) received care from a gastroenterologist/hepatol-
following a positive test. ogist during their follow-up time, while 22.4% received care from a
general practitioner alone.
The 1-year and 2-year cumulative incidences were 43.5% and 49.8%,
respectively, for receiving screening by abdominal ultrasound. The 1-
and 2-year cumulative incidences were 53.0% and 60.0%, respectively,
for receiving any HCC screening. Individuals with hepatitis B virus
had the highest 2-year cumulative incidence (73.2%) while those with
NAFLD/cryptogenic aetiology had the lowest 2-year cumulative
incidence (50.6%).
The 2-year cumulative incidence was 66.1% for hepatitis C virus, 63.7%
for autoimmune hepatitis, and 68.4% for alcohol-related liver disease
aetiologies. The 2-year cumulative incidence of HCC screening by
calendar year of cirrhosis diagnosis ranged from 52.5% in 2012 to
63.4% in 2016.

Conclusion: If HCV testing and treatment does not continue after

elimination targets are met, the prevalence of HCV in an actively
injecting network of PWID will increase. A ‘bring your friends’
approach to treatment is a more efficient approach to maintaining
elimination.
Line graph showing change in prevalence at 5 years (y axis) with
increasing testing coverage in two testing scenarios. The elimination
threshold ( prevalence <11.68%) is indicated. Results are from 100
simulations in 100 generated networks.

THU219
Hepatocellular carcinoma screening trends in individuals with
cirrhosis in North Carolina
Christine Hsu1, Jennifer Lund1, Andrew Moon2, Louise Henderson2.
1
University of North Carolina at Chapel Hill, Chapel Hill, United States;
2
UNC School of Medicine, Chapel Hill, United States
Email: [email protected]
Background and aims: The epidemiology of cirrhosis has shifted but
little is known about how these shifts impact hepatocellular
carcinoma (HCC) screening. We characterized patterns of HCC
screening over time and by cirrhosis aetiology among a privately
insured population in North Carolina.
Method: We conducted a retrospective cohort study of individuals
with a diagnosis of cirrhosis using insurance claims data from a large
private insurer in North Carolina that covers 3.5 million people
annually, or 35% of the state’s population. We included individuals
Conclusion: We observed that HCC screening was underutilized
≥18 years with an ICD-9/10 code for cirrhosis between 1 January 2010
among privately insured individuals with cirrhosis in North Carolina,
and 30 June 2018 with continuous enrolment one year before their
indicating a need for targeted interventions to increase HCC screen-
cirrhosis diagnosis and no prior HCC or liver transplant. Cirrhosis
ing rates.
aetiology was defined using a validated claims-based algorithm. The
main outcome was HCC screening by abdominal ultrasound, CT, or

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POSTER PRESENTATIONS
THU220 THU221
Cost- effectiveness evaluation of the hepatitis C elimination Rethinking the management of chronic hepatitis B in the context
strategy in Cyprus in the era of affordable direct-acting antivirals of rural sub-saharan Africa: results from a social justice mixed
Ilias Gountas1, Petros Katsioloudes2, Ioanna Yiasemi3, Evi Kyprianou3, methods study in rural Senegal (the AmBASS-PeCSen study)
Christos Mina3, Chrysanthos Georgiou4, Antri Kouroufexi5, Marion Coste1,2, Cilor Ndong3, Aldiouma Diallo4, Assane Diouf4,
Anna Demetriou6, Eleni Xenofontos7, Georgios Nikolopoulos1. Sylvie Boyer2, Jennifer Prah5. 1Aix Marseille Univeristy, CNRS, AMSE,
1
University of Cyprus, Medical School; 2Evangelistria Medical Centre; Aix-Marseille School of Economics, Marseille, France; 2Aix Marseille
3
Cyprus National Addictions Authority, Cyprus Monitoring Centre; Univ, INSERM, IRD, SESSTIM, Sciences Économiques and Sociales de la
4
Nicosia General Hospital; 5Pharmaceutical Services, Ministry of Health; Santé and Traitement de l’Information Médicale, Marseille, France;
6
Health Monitoring Unit, Ministry of Health; 7Limassol General Hospital, 3
Cheikh Anta Diop University, Anthropology, Dakar, Senegal; 4Campus
Department of Internal Medicine International IRD-UCAD de l’IRD, UMR VITROME, IRD-Université Aix
Email: [email protected] Marseille, AP-HM, SSA, IHU-Méditerranée Infection, Dakar, Senegal;
5
University of Pennsylvania, School of Social Policy and Practice and
Background and aims: In the Republic of Cyprus, the prevalence of
Perelman School of Medicine, Philadelphia, United States
chronic Hepatitis C virus (CHC) among the general population is
Email: [email protected]
estimated at 0.6%, while the CHC prevalence among people who
inject drugs (PWID) is estimated at 43%. A previous mathematical Background and aims: Worldwide, the burden of chronic hepatitis B
modeling study highlighted that to achieve Hepatitis C virus (HCV) (CHB) infection is estimated to reach 800, 000 deaths annually, with
elimination, 3080 (95% Credible intervals (CrI): 3000, 3200) patients highest CHB prevalence found in Western Pacific and Africa. In
need to be diagnosed and treated by 2034 (2680 from the general Senegal, where up to 10% of the adult population lives with CHB, the
population and 400 from PWID)1. For the optimal use of available government aims to treat 30, 000 patients by 2023. In this context,
resources, it is essential to evaluate the cost-effectiveness of any the Ministry of Health is piloting the decentralization of CHB care to
proposed strategy. This study aims to undertake a cost-effectiveness rural populations in the Fatick region drawing from the 2017 EASL
analysis of the proposed HCV elimination strategy in Cyprus. Clinical Practice Guidelines on the management of CHB. This study
Method: A previously published, dynamic, stochastic, individual- documents the CHB cascade of care in rural Senegal after community-
based model of HCV transmission, disease progression, and cascade based testing.
of care was calibrated to data from Cyprus (1). The model stratifies the Method: All residents of households randomly selected in the rural
population into the infected general population and the PWID area of Niakhar (Senegal) were offered at-home hepatitis B testing
population. We assumed that the ongoing HCV transmission is using dried blood sampling and administered socio-economic
limited to the PWID group. The incremental cost-effectiveness ratio questionnaires (ANRS12356 AmBASS survey). Following a free CHB
(ICER) per disability-adjusted life year (DALY) averted for HCV initial check-up, patients were referred to local healthcare facilities-
elimination versus the status quo scenario was computed. Cost- or invited to join a cohort in Dakar if eligible-for CHB management as
effectiveness was determined using Cyprus’ willingness-to-pay per the Senegalese national recommendations adapted from the 2017
(WTP) threshold of €26623 per DALYs averted. EASL guidelines. A few months after referral, purposeful sampling of
Results: Compared to the status quo, the elimination strategy would one-on-one qualitative interviews based on an adaptation of the
prevent 195 (95% CrI: 115, 220) and 2070 (95% CrI: 1600, 2640) new health capability profile were conducted to document perceptions,
infections and DALYs by 2034, respectively. The additional required obstacles and levers in CHB participants linked to care and those who
investment to meet the HCV elimination goals would be €20.4M (95% were not (A*Midex PeCSen study).
CrI: €19.4M, €21.4M)). The cost per averted DALY is estimated at €9915 Results: In 2018–2019, 3, 118 participants representative of the
(95% CrI: €7600, €13100) indicating that the elimination strategy is Niakhar area’s population undertook hepatitis B testing. 206
very cost-effective. In the probabilistic sensitivity analysis, 100% of participants tested positive, and among them, 163 patients (79%)
simulations were below the WTP threshold (Figure). performed the initial CHB check-up. By September 30 2021, 48
patients had gone to at least one visit for CHB management-a 23%
linkage to care. Interviews (n = 34) revealed complex CHB-related
health capability profiles, starring high health-related motivation,
skills, and self-efficacy despite low CHB-related knowledge.
Gendered social norms, shared decision-making, reluctance
towards blood sampling in the absence of treatment prescription,
and limited ability to pay are among the main obstacles to linkage to
care, and retention in CHB follow-up.

Figure: Cost-effectiveness acceptability curve

Conclusion: Scaling-up HCV testing and treatment in Cyprus to reach

the elimination targets is estimated to generate significant health and
economic benefits.
Reference: Gountas et al. WJG 2021.

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 POSTER PRESENTATIONS
Conclusion: As the first mixed-methods study of the cascade of CHB antigen (HBsAg) carriers are changing in low endemic countries
care in rural Sub-Saharan Africa, our results call for action in like the United States. To address this, in the efforts for hepatitis B
rethinking CHB management to make it acceptable, accessible, and virus (HBV) eradication, the American Association for the Study of
affordable to rural populations. Liver Disease has established guidelines pushing for HBV screening in
immigrants from high endemic regions including many Asian
THU222 countries. Yet, many Asian immigrants remain unscreened and
Global survey of healthcare workers’ attitudes to treatment of those with chronic hepatitis B (CHB) are often not linked to care
chronic hepatitis C infection in children and adolescents citing multiple barriers. We sought to determine the impact of
Farihah Malik1, Philippa Easterbrook2, Giuseppe Indolfi3, community-based HBV campaigns on screening and linkage to care
Claire Thorne1. 1UCL Great Ormond Street Institute of Child Health, (LTC) efforts through a large-scale community screening initiative.
London, United Kingdom; 2World Health Organization, Genev̀ e, Method: Asian immigrants from the New Jersey and New York
Switzerland; 3University Hospital Meyer, Firenze, Italy metropolitan areas were screened for HBV using surveys and
Email: [email protected] serological testing from 2009 to 2019. Those participants found to
be positive were followed up by telephone, mail or email. We started
Background and aims: Direct acting antivirals (DAAs) are now
to collect LTC data starting in 2015. In 2017, because of low LTC rates,
approved for treatment of adolescents and children >3 years living
nurse navigators whose role was to help participants navigate
with chronic hepatitis C (HCV) however, there is limited under-
through individual barriers to care were hired to aid in the LTC
standing of the attitudes of health care workers (HCWs) on
process. Those excluded from the LTC data included those who were
expanding treatment, especially to younger age groups. We under-
already linked to care, those who declined to be linked to care and
took the first global survey of HCWs managing HCV infection
those who had moved or passed away.
regarding treatment of children and adolescents, and on key
Results: 13, 566 participants were screened from 2009 to 2019, of
challenges to implementation, to inform updated World Health
which, the results for 13, 466 were available. Of these, 372 (2.7%) were
Organization (WHO) HCV guidelines.
found to have positive HBV status. Approximately 49.3% were female
Method: A cross-sectional online survey was conducted during
and 50.1% were male, and the rest were of unknown gender. A total of
September 2021, distributed to networks providing care to children
1, 191 (10.0%) participants were found to be HBV negative but
and adolescents living with HCV infection, and other key stake-
required vaccination. When we started to track LTC, we found 195
holders. Survey questions were developed to reflect two key
participants that were eligible for LTC between 2015 through 2017
questions: which age groups to treat and prioritise, and which DAA
after the exclusion criteria were applied. It was found that only 33.8%
regimens to use.
were successfully linked to care in that time period. After hiring nurse
Results: There were 142 survey respondents, of whom 94 (66%) had
navigators, we saw LTC rates increase to 85.7% in 2018 and to 89.7% in
cared for children or adolescents with HCV over the past 3 years.
2019.
Every WHO region was represented, with highest proportion of
respondents from the Western Pacific (43%) and the Americas (19%).
There was a trend towards higher preference for treating older age
groups: 60% of respondents reported a strong preference for treating
(i.e., stating they were very likely or likely to treat) children aged 3 to
<6 years, increasing to 81% and 94% for those aged 6 to <12 years and
12 to <18 years respectively. The main reasons reported for preferring
not treating younger age groups were the chance of spontaneous
Figure: Successful linkage to care rates 2009 to 2019. A nurse navigator
clearance, lack of drug approvals and registration for treatment of was hired in 2017 to focus on linkage to care.
younger age groups, slow disease progression and asymptomatic
nature of disease in early childhood, difficulties with administering Conclusion: HBV community screening initiatives are imperative to
medication to young children and lack of clinical trial data. increase screening rates in the Asian immigrant population. We were
The most commonly preferred and used DAA regimens for treatment also able to demonstrate that nurse navigators can successfully help
across all paediatric age groups were: sofosbuvir/velpatasvir, sofos- increase LTC rates. Our HBV community screening model can address
buvir/ledipasvir and glecaprevir/pibrentasvir. The most frequent issues with barriers to care including lack of access in comparable
reasons for these regimen preferences were safety, guideline populations.
recommendations, drug availability, suitability to treat prevalent
HCV genotypes (including pangenotypic) and efficacy. THU224
Conclusion: This survey demonstrates strong HCW support for The prognostic implications of liver function test abnormalities in
treatment of children and adolescents with HCV infection, especially patients admitted to hospital with COVID-19
those 6 years or older. Future priorities include updating national Jason Cohen1, David Uihwan Lee2, Gregory Fan1, David Hastie1,
policies to incorporate case-finding strategies and treatment for Akaash Mittal1, Khanh Le1, Yeeun Jang1, Sarav Daid1, Raffi Karagozian1,
children and adolescents, and access to paediatric DAA formulations. Raza Malik1. 1Tufts Medical Center, Gastroenterology/Hepatology,
Boston, United States; 2University of Maryland Medical Center,
THU223 Gastroenterology/Hepatology, Baltimore, United States
Impact of community-based campaign in United States to Email: [email protected]
increase hepatitis B virus screening and linkage to care among
Asian immigrants from high endemic countries Background and aims: Prior studies have indicated the presence of
hepatic inflammation (as signified by elevated liver function test
Sung Kwon1,2, Aziza Win3, Gregory Wu4. 1Holy Name Medical Center,
(LFT) values), as conferring an escalated risk toward adverse
Teaneck, United States; 2Columbia University Irving Medical Center,
outcomes in patients admitted with COVID-19. In line with this
New York, United States; 3Ross University School of Medicine-Academic
hypothesis, we study the various thresholds of LFTs and its associated
Campus, Bridgetown, Barbados; 4Geisinger Commonwealth School of
prognostic risks toward COVID-19 related hospital deaths.
Medicine, Scranton, United States
Method: This was a single-center retrospective study involving
Email: [email protected]
patients admitted with COVID-19. Univariate Cox regression analysis
Background and aims: With the ongoing population movements of identified the LFT variables significantly associated with our primary
migrants from high (>8%) to low (<2%) endemic regions, the end point, in-hospital death. Subsequently, 500 iterations of thresh-
prevalence and incidence of chronic Hepatitis B virus surface olds were generated for each biomarker to estimate the prognostic

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POSTER PRESENTATIONS
relationship between biomarker and end point. Multivariate Cox categorical terms, the following model iterations were constructed
regression and event-analyses were performed for each threshold to with their respective AUC; model 1 (core only): 0.82 95%CI 0.776–
identify the minimal cutoffs at which the prognostic relationship was 0.82, model 2 (core + demographics): 0.828 95%CI 0.785–0.828,
significant. Event curves were drawn for each significant relationship. model 3 ( prior terms + additional biomarkers): 0.842 95%CI 0.799–
Results: A total of 858 patients with COVID-19 were included with a 0.842, model 4 ( prior terms + comorbidities): 0.851 95%CI 0.809–
median follow-up time of 5 days from admission. From the total, 90 0.851, model 5 ( prior terms + life-sustaining therapies): 0.933 95%CI
patients passed away during admission (10.5%). Upon univariate Cox 0.91–0.933, model 6 ( prior terms + COVID-19 medications): 0.934
analysis, the following LFT parameters were associated with in- 95%CI 0.91–0.934. Model 1 demonstrated the following parameters at
hospital death: Bilirubin ( p < 0.001), AST (p < 0.001), ALT ( p < 0.001). 0.91 TPR: 0.54 specificity, 0.17 PPV, 0.98 NPV. Bootstrapped iterations
However, alkaline phosphatase ( p = 0.449) was not associated with showed the following AUC for the respective models: model 1: 0.82
the primary end point. The iterations of event regression analyses 95%CI 0.765–0.882, model 2 0.828 95%CI 0.764–0.885, model 3 0.842
using 500 sequences of LFT thresholds showed the following cutoffs 95%CI 0.779–0.883, model 4: 0.851 95%CI 0.808–0.914, model 5:
to be significantly associated with in-hospital death (minimally 0.933 95%CI 0.901–0.957, model 6: 0.934 95%CI 0.901–0.961.
significant values): ALT (281.71 IU/L), AST (120.94 IU/L), bilirubin
(2.615 mg/dL). On the multivariate analysis, while controlling for
demographics and cardiopulmonary/medical comorbidities, the
following adjusted hazard ratios were derived for each cutoff: ALT
(aHR: 6.43 95%CI 1.85–22.40), AST (aHR: 3.35 95%CI 1.84–6.11), and
bilirubin (aHR: 2.77 95%CI 1.15–6.65).

Conclusion: The delineated cutoffs for AST, ALT, and bilirubin levels
can serve as clinical benchmarks to help determine when a COVID-19
infection poses significant risk. Given this finding, the cutoffs can be
used as part of a risk assessment for patients to support early
preventative therapies and medical management.

THU225
A novel prognostic model including liver function parameters
accurately predicts 30-day mortality in patients admitted with
COVID-19
David Uihwan Lee1, Jason Cohen2, Gregory Fan2, David Hastie2,
Akaash Mittal2, Khanh Le2, Yeeun Jang2, Sarav Daid2, Conclusion: Model 1 displays high prediction performance (AUC
Raffi Karagozian2, Raza Malik2. 1University of Maryland Medical Center, >0.8) in both regression-based and bootstrapping-enhanced model-
Gastroenterology/Hepatology, Baltimore, United States; 2Tufts Medical ing iterations. Therefore, this model can be adopted for clinical use as
Center, Gastroenterology/Hepatology, Boston, United States a calculator to evaluate the risk of 30-day mortality in patients
Email: [email protected] admitted with COVID-19.
Background and aims: While the relationship between elevated
liver enzymes and COVID-19 related adverse events is well- THU226
established, a liver-dependent prognostic model that predicts the Low health literacy is associated with higher healthcare service
risk of death is helpful to accurately stratify admitted patients. In this utilisation and costs among patients with cirrhosis
study, we use a bootstrapping-enhanced method of regression Patricia Valery1, Christina Bernardes1, Kelly Hayward2,3,
modeling to predict COVID-19 related deaths in admitted patients. Gunter Hartel1, Katelin Haynes4, Louisa Gordon1, Amy Johnson2,3,
Method: This was a single-center, retrospective study. Univariate and Elizabeth Powell2,3. 1QIMR Berghofer Medical Research Institute,
multivariate Cox regression analyses were performed using 30-day Herston, Australia; 2Princess Alexandra Hospital, Woolloongabba,
mortality as the primary end point to establish associated hepatic risk Australia; 3The University of Queensland, Centre for Liver Disease
factors. Regression-based prediction models were constructed using Research, Faculty of Medicine, Woolloongabba, Australia; 4Hepatitis
a series of modeling iterations with an escalating number of Queensland, Coorparoo, Australia
categorical terms. Model performance was evaluated using receiver Email: [email protected]
operating characteristic (ROC) curves. Model accuracy was internally Background and aims: Optimal management of cirrhosis is complex,
validated using bootstrapping-enhanced iterations. and patients often lack knowledge and skills which can affect self-
Results: 858 patients admitted to hospital with COVID-19 were management. We assessed patient knowledge about cirrhosis and
included. 78 were deceased by 30 days (9.09%). Cox regression examined whether knowledge was associated with clinical out-
(greater than 20 variables) showed the following core variables to be comes, healthcare service utilisation, and healthcare costs.
significant: INR (aHR 1.26 95%CI 1.06–1.49), AST (aHR 1.00 95%CI Method: A cross-sectional ‘knowledge survey’ was conducted
1.00–1.00), age (aHR 1.05 95%CI 1.02–1.08), WBC (aHR 1.07 95%CI between Jun-2018 and Aug-2020 with 123 cirrhosis patients with
1.03–1.11), lung cancer (aHR 3.38 95%CI 1.15–9.90), COPD (aHR 2.26 cirrhosis (44.4% of 277 invited and eligible). The ‘knowledge survey’
95%CI 1.21–4.22). Using these core variables and additional questions were derived from prior studies, and an expert panel

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 POSTER PRESENTATIONS
unanimously deemed eight items to be “key knowledge” about model includes estimates of the incidence of at-risk drinking in order
cirrhosis. The proportion of correct answers were calculated (“key to predict morbidity and mortality related to ALD in France.
knowledge” score) and patients were categorized as having ‘good Method: First, we developed a Markov model simulating the
knowledge’ vs ‘poor knowledge’ (cut-off based on median score). trajectory of cohorts starting at-risk alcohol consumption until they
Detailed clinical data (extracted from medical records and through die. It integrates the common risk factors associated with the
linkage to hospital admissions, emergency department presenta- progression of ALD (sex, age, amount of alcohol, genetic polymorph-
tions), healthcare costs, and self-reported health-related quality of ism). Unknown parameters of progression were back-calculated on
life (SF-36) were available. Cumulative overall survival (Kaplan- the 2010–2018 alcohol-related decompensated cirrhosis and HCC
Meier), rates of hospital admissions, emergency presentations and mortality data provided by the French National Hospital Discharge
costs were assessed according to “key knowledge.” Incidence rate database. Second, morbidity and mortality were predicted up to 2026.
ratios (IRR; Poisson regression) were reported. Results: The developed model fits the observed mortality data: 63,
Results: Patients were aged 60.7 ± 10.8 years, 65.9% were male, 47.2% 016 deaths were predicted over 2010–2018 for 62, 934 observed in
had formal education to Junior High School level or less, 43.9% lived in database (Fig. A). Prediction of deaths fits the observed mortality
‘most disadvantaged’ areas, alcohol was a cofactor for 65.9%, NAFLD according to cause of death and sex (Fig. B), as well as age.
was a cofactor for 50.4%, and 29.3% had decompensated cirrhosis. Between 2010 and 2021, annual ALD deaths decreased by 4%, from 7,
58.5% of patients had ‘good knowledge’ about cirrhosis. In multi- 100 to 6, 700. However, while deaths by decompensation decreased
variable analysis, higher level of education was associated with over from 4800 to 4, 300 (−10%), deaths by HCC rose from 2, 300 to 2, 400
5-fold odds of having ‘good knowledge’ about liver disease (adj-OR = (+4%) (Fig. B). Most of the ALD deaths occurred in men: 3 out 4 deaths
5.61, 95%CI 2.47–12.75). Patients with ‘good knowledge’ had a higher by decompensation and 9 out 10 deaths by HCC.
health status in the SF-36 domain related to physical functioning ( p = In addition, the model estimated that, in 2021, 80, 000 French
0.036) compared to those with ‘poor knowledge’. Patients with ‘good individuals have alcohol-related cirrhosis with 7, 900 incident cases.
knowledge’ had 73% fewer all-cause admissions (IRR = 0.27, 95%CI Decompensated cirrhosis and HCC are observed in around 33, 000
0.23–0.33), 57% fewer emergency presentations for cirrhosis (IRR = and 6, 000 cases, respectively. Women represent 30% of the cirrhotic
0.43, 95%CI 0.21–0.89), and more planned one-day cirrhosis admis- individuals.
sions (IRR = 4.47, 95%CI 1.61–12.37; see Table). The total cost of The decline of French per capita consumption would lead in 2026 to
cirrhosis admissions was 45% lower for patients with ‘good knowl- decrease in cirrhosis (∼70, 000) and liver related deaths (6, 400)
edge’ (IRR = 0.55, 95%CI 0.54–0.56) during the follow-up period. compared to currently (Fig. B).

Table: Incidence rate ratios and cost ratios by knowledge score

Conclusion: Low health literacy is associated with increased use of Conclusion: The present model predicts future burden of ALD in the
healthcare services and increased total cost of health care. This may general French population, based on robust epidemiological data.
reflect poorer health status and quality of life. Improving the health This model allows to predict not only liver-related mortality but also
literacy of patients with cirrhosis may be an effective strategy to burdens of cirrhosis and liver-related complications. It may help to
promote a more cost-effective use of healthcare services with fewer propose new health policies targeting patients most at-risk in order
preventable emergency department visits and greater use of planned to obtain further reductions in the burden of ALD.
admissions.
THU228
THU227 A model to predict drinking population at-risk of liver disease in
A modelling approach to estimate alcohol-related liver morbidity France: a tool for decision-making public health policies
and mortality in France
Claire Delacôte1, Line Carolle Ntandja Wandji1,2, Alexandre Louvet1,2,
Claire Delacôte1, Line Carolle Ntandja Wandji1,2, Alexandre Louvet1,2, Pierre Bauvin1, Guillaume Lassailly1,2, Massih Ningarhari1,2,
Pierre Bauvin1, Guillaume Lassailly1,2, Massih Ningarhari1,2, Sebastien Dharancy1,2, Philippe Mathurin1,2, Sylvie Deuffic-Burban1,3.
Sebastien Dharancy1,2, Guillaume Clement3, Amelie Bruandet3, 1
INSERM U1286-INFINITE, Lille, France; 2CHU de Lille, Service des maladies
Xavier Lenne3, Philippe Mathurin1,2, Sylvie Deuffic-Burban1,4. de l’appareil digestif, Lille, France; 3INSERM U1137-IAME, Paris, France
1
INSERM U1286-INFINITE, Lille, France; 2CHU de Lille, Service des Email: [email protected]
maladies de l’appareil digestif, Lille, France; 3Lille University Hospital,
Medical Information Department, Lille, France; 4INSERM U1137-IAME, Background and aims: In France, daily alcohol intake is decreasing
Paris, France among 15–64 y-o whereas consumption of ≥6 drinks per occasion
Email: [email protected] (binge drinking) is becoming more common, especially among 15–35
y-o. Estimating the proportions of individuals with alcohol use with
Background and aims: Harmful alcohol use leads to the develop- intermediate (20–50 g/d) or high (≥50 g/d) risks of alcohol-related
ment of alcohol-related liver disease (ALD). In-depth knowledge of liver disease (ALD) would allow to predict the incident cases of
the natural history of ALD according to patterns of alcohol cirrhosis and provide new tool for decision-making public health
consumption is required to predict the future burden of ALD policies. Our aim was to predict the incidence of French people having
morbidity and mortality. This would allow to implement health an alcohol intake ≥20 g/d.
policies targeting at-risk drinkers. Our aim was to integrate the Method: Daily alcohol intake was calculated from individual data
relevant natural history data of ALD in a mathematical model. This from national surveys (ESPS), conducted on a representative sample

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POSTER PRESENTATIONS
of 15–64 y-o French people. A Markov model was fitted to this data to fatal consequences in vulnerable patients resulting from this disease,
estimate entry into risky drinking, according to the history of binge led to the implementation of blood product-testing in various
drinking or not. Incidences were back-calculated by sex, age and countries. However, many nations, including the U.S. have not yet
annual per capita consumption from ESPS 2002 to 2014 (n = 45, 054). implemented such screening efforts. To assess the need for HEV-
The adequacy of the model was assessed by comparing the predicted screening in blood products worldwide, we conducted a systematic
alcohol patterns and prevalence to those estimated from ESPS. review and meta-analysis comparing the rate of HEV RNA positivity
Entries into at liver-risk drinking were simulated between 1910 and and anti-HEV seroprevalence in blood donors.
2014 considering competitive mortality. At liver-risk drinking Method: Studies reporting the anti-HEV IgG and/or HEV-RNA
incidences and prevalence were predicted until 2026 under 2 positivity rates among blood donors worldwide were identified via
scenarios. predefined search terms ("Hepatitis e" OR "HEV") AND ("blood
Annual distributions of predicted and observed prevalence were donors" OR "transfusion" OR " blood donation" OR "blood testing") in
closed according to daily alcohol intake (Fig. A), sex and age. Pubmed and Scopus. Data were stratified by year of publication,
Results: While per capita consumption dropped from 26L to 12L country/continent, diagnostic assay and methodological quality
(-54%) over 1960–2014, prevalence of at liver-risk drinking among (according to PRISMA). Estimates were calculated by pooling study
15–64 y-o decreased from 8.8% to 5.1% (-42%) (Fig. A). The number of data (separately for each country/continent) via multivariable linear
new intermediate and high at liver-risk drinkers had respectively mixed effects meta regression analysis.
decreased by 35% and 65%. Results: Out of 1, 103 studies, 151 (14%) were included in the final
In 2021, ∼5% of French people have an alcohol intake ≥20 g/d (8/10 analysis. Estimated HEV viremia rate ranged from 0.01% to 0.14%
are men). This prevalence increases with age (Fig. B). Each year, 60, worldwide (56 studies, 3, 438, 276 blood donors). Highest estimated
000 individuals become intermediate at liver-risk drinkers and 9, 500 HEV viremia rates were seen in Asia (0.14%), followed by South
switch from intermediate to high at-risk consumption. America (0.10%), Europe (0.09%), Africa (0.08%), Australia and North
If the current decrease in per capita consumption continues (scenario America (each 0.01%). In Europe highest rates could be found in
1), it will be 10.6L in 2026 (-4.5% over 5 years) and there will be 350, Serbia (0.31%), closely followed by Germany (0.28%) and France
000 new at liver-risk drinkers over 2021–2026. If the per capita (0.18%). Rate of HEV viremia as well as anti HEV seroprevalence were
consumption significantly drops to 10L in 2026 (-10%, scenario 2), 7, significantly lower in North America in comparison to Europe (OR =
400 intermediate at liver-risk drinkers would be avoided and ∼1, 200 0.14 [95% CI 0.03–0.58]; OR = 0.62 [95% CI 0.35–1.10]), independently
intermediate at liver-risk drinkers will not switch into high at liver- of year of publication and methodological quality.
risk drinking (Fig. C).

Conclusion: Our data demonstrate large regional differences regard-

ing the risk of exposure to HEV. Considering the cost-benefit ratio,
Conclusion: Although these 2 scenarios will allow differences in this supports blood-product screening programs in areas of high
terms of incident cases, the expected prevalence will be little changed endemicity, such as Europe or Asia, in contrast to low-endemic
and 4.5% of the 15–64 y-o would be at-liver risk drinkers. regions, such as the U.S.
1/1000 French initiates an alcohol intake ≥20 g/d each year. In 2021,
1.9 million of French people have an alcohol consumption associated THU230
with a risk of cirrhosis and 310, 000 of them have a high risk (≥50 g/d). A population based-study of rates and trends of hepatitis C in
By quantifying for the 1st time the incidence of French people immigrants and the Canadian-born in Quebec, Canada, 1998–2018
drinking ≥20 g/d, this model could help developing new public health Ana Maria Passos-Castilho1,2, Marina B. Klein2,3, Julie Bruneau4,5,
strategies targeting the reduction of ALD morbidity and mortality. Dimitra Panagiotoglou6, Karine Blouin7, Donald Murphy8,
Christina Greenaway1,2,9. 1Lady Davis Institute, Jewish General Hospital,
THU229
Centre for Clinical Epidemiology, Montreal, Canada; 2McGill University,
Blood donors in Europe have substantially higher risk of exposure
Department of Medicine, Montreal, Canada; 3McGill University Health
to HEV than in North America: results from a systematic review
Center, Division of Infectious Diseases, Montreal, Canada; 4Centre
and meta-analysis
Hospitalier de l’Université de Montréal, CHUM Research Centre,
Annika Wolski1, Ann-Kathrin Ozga2, Marylyn Addo1, Samuel Huber1, Montreal, Canada; 5Université de Montréal, Department of Family and
Ansgar W. Lohse1, Sven Pischke1, Thomas Horvatits1. 1University Emergency Medicine, Faculty of Medicine, Montreal, Canada; 6McGill
Medical Center Hamburg-Eppendorf, Center for Internal Medicine University, Department of Epidemiology, Biostatistics and Occupational
I. Medical Clinic and Polyclinic, Hamburg, Germany; 2University Medical Health, Montreal, Canada; 7Institut National de Santé Publique du
Center Hamburg-Eppendorf, Medicine Institute of Medical Biometry and Québec, Unité des infections transmissibles sexuellement et par le sang,
Epidemiology, Hamburg, Germany Québec, Canada; 8Institut National de Santé Publique du Québec,
Email: [email protected]
Background and aims: The increasing number of diagnosed
hepatitis E virus (HEV) infections in Europe, as well as the potentially

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 POSTER PRESENTATIONS
Laboratoire de Santé Publique du Québec, Sainte-Anne-de-Bellevue, THU231
Canada; 9Jewish General Hospital, Division of Infectious Diseases, HBV screening in west african migrant community and faith-
Montreal, Canada based organizations increases HBV vaccination among this high-
Email: [email protected] risk population in greater Barcelona, Spain
Background and aims: Immigrants bear a disproportionate hepatitis Camila Picchio1, Ariadna Rando-Segura2, Emma Fernandez1,
Nélida López1, Silvia Gómez Araujo1, Daniel Kwakye Nomah3,
C (HCV) burden in Canada. They account for 30% of HCV cases and are
at increased risk of end stage liver disease and liver cancer at the time Omar Diatta1,4, Sergio Rodriguez-Tajes5,6, Sabela Lens5,6,
Xavier Forns5,6, Francisco Rodríguez-Frías2, Maria Buti6,7,
of diagnosis. Determining sub-groups of immigrants at highest HCV
Jeffrey Lazarus1. 1Barcelona Institute for Global Health (ISGlobal),
risk will be essential to supporting micro-elimination efforts in this
population. We estimated annual reported rates and trends of HCV Hospital Clínic, University of Barcelona, Barcelona, Spain; 2Liver
Pathology Unit, Biochemistry and Microbiology Service, Hospital
over a 20-year period in Quebec.
Method: A population-based cohort of all HCV cases in Quebec from Universitari Vall d’Hebron, Barcelona, Spain; 3Center for Epidemiological
Studies on HIV/AIDS and STIs in Catalonia (CEEISCAT), Badalona, Spain;
1998 to 2018 reported to public health and the provincial reference 4
laboratory were linked to the provincial health registry and the Community and Public Health Unit, Department of International Health
landed immigrant database. Immigrant status and country of birth Drassanes-Hospital Universitari Vall d’Hebrón. Programa de Salut
were assigned through linkage to the immigrant database. Region of Internacional de l’Institut Català de la Salut (PROSICS), Spain; 5Liver
birth was classified by World Bank regions; East Asia/Pacific (SEA), Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain;
6
South Asia (SA), Middle East/North Africa (MENA), Sub-Saharan CIBER Hepatic and Digestive Diseases (CIBERehd), Instituto Carlos III,
Africa (SSA), Latin America/Caribbean (LAC), Western Europe (EUS), Madrid, Spain; 7Liver Unit, Hospital Universitari Vall d’Hebron,
Other Europe/Central Asia (OECA) and North America/Australia/New Barcelona, Spain
Zealand (NAANZ)]. Annual reported crude cumulative incidence rates Email: [email protected]
of HCV among immigrants and the Canadian-born were estimated Background and aims: African migrant populations living in Europe
using Quebec population census data during the study period. are disproportionately affected by HBV infection and oftentimes use
Comparative rate ratios (RR) with 95% confidence intervals (CI) and health services at lower rates due to structural and/or cultural/
the trend of HCV rates over the study period stratified by immigrant linguistic barriers. Efforts to scale up prevention, testing, and
status were estimated using Poisson regression. treatment are needed to reach the 2030 hepatitis elimination
Results: Among 34, 881 HCV cases identified, 13.5% (n = 4, 720) were targets set by the WHO. The HBV-COMSAVA study aims to use
immigrants. Immigrants were older (median 46.8 vs. 44.1 years; p < point-of-care testing with simplified diagnostic tools in community
0.001) and diagnosed a median of 9.3 (IQR 2.8–17.2) years after arrival settings to identify and link to care or vaccinate west African migrants
in Quebec. Comparing immigrants with Canadian-born: the HCV in the greater Barcelona area.
average annual rate/100, 000 population was 33.1 vs. 30.8 and 18.4 vs. Method: 393 study participants were offered HBV screening in a
12.3 during the periods 1998–2008 and 2009–2018, respectively; and “pop-up” clinic in a community setting from 21/11/20–13/11/21.
the RR was 1.08 (1.03–1.12) in 1998–2008, and 1.50 (1.42–1.57) in Rapid tests to screen for the presence of HBsAg were used and a blood
2009–2018. Between 2009 and 2018, subgroups of immigrants with sample was collected using plasma separation cards and analyzed in
higher HCV rates compared to the Canadian-born were those from a laboratory. The interactive tool, HeparJoc, was used to increase HBV
OECA [rate; RR (95% CI); 45.6; 3.7 (2.0–7.0)], SSA [44.7; 3.6 (1.9–6.8)], knowledge, which was co-created by migrant populations. HBsAg+
and SA [28.8; 2.3 (1.2–4.6)]. Rates decreased more slowly over the patients were given a referral to a specialist on the spot. Remaining
study period among immigrants vs. Canadian-born [-4.84% (-6.17– patients received their results during a second pre-programmed visit
3.49%) vs. − 7.74% (-9.22–6.24%)] per year. and were offered: post-test counselling (PTC) or vaccination of the
first dose of the HBV vaccine in situ. Vaccination cards and referrals to
their primary care center for subsequent doses were provided to all
who received first doses. Sociodemographic and linkage to care data
were collected and basic standard descriptive statistics were utilized
using STATA software.
Results: 354 were included for analysis. 75.1% returned to receive
their results and were linked to care or offered PTC with 44.6% (n =
158) showing evidence of past or current HBV infection. The overall
HBsAg prevalence was 8.8% (n = 31). Of those who were HBsAg-, anti-
HBc positivity was detected in 35.9% (n = 127). The majority (n = 172)
required vaccination against HBV, followed by post-test counselling
(n = 151) and referral to a specialist (n = 31) (Figure 1). The HBV
vaccination acceptance rate was 85.4% and the main reason for not
accepting included having results picked up by a family member and
not being physically present (38, 9%, n = 7).

Figure: Reported rates of HCV cases per 100, 000 people by region of
origin (1998–2018). Smoothed (loess) reported crude cumulative inci-
dence with 95% confidence bounds.

Conclusion: High rates of HCV among immigrants and long delays to

HCV diagnosis after arrival in Canada highlight important gaps in
HCV screening among immigrants. These data can be used to inform
micro elimination efforts among the immigrant population in Quebec
and Canada.

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POSTER PRESENTATIONS
collected utilizing a plasma separation card (PSC) (cobas® PSC, Roche
Diagnostics) which was air-dried and transported to the laboratory.
Those who tested positive for HBsAg were provided an instant referral
to one of two collaborating tertiary hospitals where a full work-up
was done, including liver function tests and liver fibrosis assessment
(Fibroscan®). The proportion of participants with different HBV-
serological status analyzed as of November 16, 2021 are reported
using descriptive stats (STATA 16.0).
Results: 379 participants are included; 314 (82.8%) were Ghanaian
with a mean age of 41.1 years (SD = 10.0), and 41.9% (n = 159) were
female. The overall HBsAg prevalence was 9.0% (n = 34) of which 14
(41.2%) had detectable HBV-DNA and two (5.9%) had anti-HDV
antibodies, none were HBeAg+. The mean HBV-DNA and HBsAg levels
among patients attending a first specialist visit (n = 17) was 125, 834
UI/ml and 8, 190 UI/ml, respectively. Evidence of past resolved
infection (anti-HBc+) was seen in 35.6% (n = 135) of those who were
HBsAg- (Table 1).

Conclusion: Despite the COVID-19 pandemic, by employing a

community-based model of care utilizing novel simplified diagnostic
tools, the HBV-COMSAVA study demonstrated the possibility to
screen and vaccinate African migrants who may otherwise not have
received care, reducing the possible pool of new infections among
this high-risk group.

THU232
Community-based HBV testing among west african migrants in
greater Barcelona, Spain increases linkage to specialist care and
vaccination: the HBV-COMSAVA model
Camila Picchio1, Daniel Kwakye Nomah2, Ariadna Rando-Segura3,
Silvia Gómez Araujo1, Emma Fernandez1, Omar Diatta1,4,
Maria Buti5,6, Sergio Rodriguez-Tajes6,7, Sabela Lens6,7,
Xavier Forns6,7, Nélida López1, Francisco Rodríguez-Frías3,
Jeffrey Lazarus1. 1Barcelona Institute for Global Health (ISGlobal),
Hospital Clínic, University of Barcelona, Barcelona, Spain; 2Center for
Epidemiological Studies on HIV/AIDS and STIs in Catalonia (CEEISCAT),
Badalona, Spain; 3Liver Pathology Unit, Biochemistry and Microbiology
Service, Hospital Universitari Vall d’Hebron, Barcelona, Spain;
4
Community and Public Health Unit, Department of International Health
Drassanes-Hospital Universitari Vall d’Hebrón. Programa de Salut
Internacional de l’Institut Català de la Salut (PROSICS), Barcelona, Spain;
5
Liver Unit, Hospital Universitari Vall d’Hebron, Barcelona, Spain; 6CIBER
Hepatic and Digestive Diseases (CIBERehd), Instituto Carlos III, Madrid,
Spain; 7Liver Unit, Hospital Clínic, IDIBAPS, University of Barcelona,
Barcelona, Spain
Email: [email protected]
Background and aims: Hepatitis B virus (HBV) infection affects an
estimated 250 million people worldwide. Sub-Saharan Africa is
disproportionately affected, particularly west and central African
countries. Migrants arriving to Europe from these high-endemic
areas may be unaware of their HBV status due to the unreliable testing
and vaccination strategies in their home countries and underutiliza- *
Only patients who had a first documented visit with one of the
tion of the host country health services, delaying timely diagnosis
participating hospitals are included here (n = 17) b Fibrosis stage
and linkage to care. The HBV-COMSAVA study aims to use point-of-
determined by Fibroscan® Missing values are not reported
care testing with simplified diagnostic tools in community settings to
identify and link to care or vaccinate west African migrants in the Conclusion: This ongoing community-based HBV screening program
greater Barcelona area. We report the HBV prevalence, associated risk provides an effective model of identifying and providing care to
factors, and the continuum of care. migrant populations at high risk of HBV infection in the greater
Method: From 21/11/20–13/11/21, 397 people were offered HBV
testing in community settings in greater Barcelona. Participants were
first tested with an HBsAg rapid detection test (DETERMINETM HBsAg
2, Abbott Inc.). Then a whole blood sample (140 µl per spot) was

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 POSTER PRESENTATIONS
Barcelona area. who otherwise may not have been previously THU234
engaged in care. Community screening initiatives can increase Negative impact of COVID-19 infection related to life disruption
testing, vaccination, and linkage to care, helping to reach the 2030 events and health scores on patients with chronic liver disease
WHO HBV elimination targets. Zobair Younossi1,2,3, Yusuf Yılmaz4, Mohamed El Kassas5,
Ajay Kumar Duseja6, Saeed Sadiq Hamid7, Gamal Esmat8,
THU233 Nahum Méndez-Sánchez9, Wah-Kheong Chan10, Ashwani Singal11,
The impact of COVID-19 pandemic control measures on HCV Janus Ong12, Brian Lam1,2, Sean Felix1, Elena Younossi1,
treatment initiation in British Columbia, Canada Manisha Verma1,2, Jillian Price1, Fatema Nader13, Issah Younossi13,
Naveed Janjua1,2, Stanley Wong1, Dahn Jeong1,2, Mawuena Binka1, Andrei Racila1,2,3, Maria Stepanova2. 1Betty and Guy Beatty Center for
Terri Buller-Tylor1, Sofia Bartlett1, Prince Adu1, Hector Velasquez1, Integrated Research, IHS; 2Center for Liver Disease, Inova Medicine;
Makuza Jean Damascene2, Amanda Yu1, Maria Alvarez1, Jason Wong1, 3
Inova Health System, Medicine Service Line; 4Department of
Mel Krajden1. 1BC Centre for Disease Control, Vancouver, Canada; 2The Gastroenterology, Marmara University, Turkey; 5Helwan University;
University of British Columbia, School of Population and Public Health, 6
Postgraduate Institute of Medical Education and Research;
Vancouver, Canada 7
Department of Medicine, Aga Khan University; 8Endemic Medicine and
Email: [email protected] Hepatogastroenterology Department, Cairo University; 9Medica Sur
Background and aims: Coronavirus disease 2019 (COVID-19) and Clinic and Foundation; 10University of Malaysia, Gastroenterology and
measures taken to limit the transmission of severe acute respiratory Hepatology Unit; 11University of South Dakota and Avera Transplant
syndrome coronavirus 2 (SARS-CoV-2) have directly and indirectly Institute; 12University of the Philippines, College of Medicine; 13Center
restricted access to healthcare services worldwide. We assessed the for Outcomes Research in Liver Disease
impact of these measures, first introduced in British Columbia (BC), Email: [email protected]
Canada in March 2020, on hepatitis C (HCV) treatment initiation. Background and aims: Patients with chronic liver disease (CLD) may
Method: We used data from the BC Hepatitis Testers Cohort, a large experience a substantial burden from COVID-19 infection as well as
population-based cohort integrating data on HCV testing, primary disruption of life and routine healthcare associated with the
care visits, hospitalizations, and medication dispensations. We pandemic. We assessed the impact of COVID-19 pandemic on patients
compared the monthly HCV treatment initiations during 2020 with with CLD.
those in 2018 and 2019. We compared the sociodemographic and Method: Patients with CLD enrolled in our Global Liver Registry since
clinical characteristics of people initiating HCV treatment during pre- 2018 completed a specifically designed 23-item COVID-19 survey
pandemic time period (Jan 2018-Feb 2020) to those initiating between March 2020-November 2021. Questions included patients’
treatment during pandemic time period (Apr-Aug 2020). COVID-19 infection status and, if infected, characteristics of the
Results: There was a declining trend in HCV treatment initiations pre- illness, along with various aspects of pandemic-related life disrup-
pandemic from 3, 172 in 2018 to 2, 331 in 2019 (26% reduction). tions for everyone regardless of the infection.
However, there was a higher decline in 2020 to 1, 475 treatment Results: As of November 2021, from 11, 200 historic enrollees, 2635
initiations (37% reduction from 2019). HCV treatment initiations from 7 countries completed the survey: 21% chronic hepatitis B, 14%
decreased immediately following the imposition of pandemic control chronic hepatitis C, and 66% non-alcoholic fatty liver disease; mean
measures; monthly pre-pandemic average treatment initiations fell (SD) age 49 ± 13 years, 53% male. Of all survey completers, 10.3%
from 172 to 106 during the pandemic (38% change). reported having had COVID-19. Of those infected, 87% reported being
There were slight decreases in treatment initiations for the 1945–64 diagnosed by a laboratory test, 94% had least one symptom, and 73%
birth cohort (56% to 45%) and for people with HIV coinfection (5.9% to received treatment for their symptoms. The mean (SD) duration of
4.3%) or HBV co-infection (5% to 4.3%). However, there was a slight their illness was 12.5 ± 10.7 days, 66% reported receiving antiviral
increase in treatment initiation among the ≥1975 birth cohort (19% to treatment, 19% were hospitalized, 13% needed oxygen support but no
29%), people who inject drugs (44% to 49%), and people with one was put on mechanical ventilation. Of all included CLD patients
problematic alcohol use (32% to 37%) between pre-pandemic and regardless of COVID-19 infection, 11.4% reported that the pandemic
pandemic time periods, respectively. had an impact on their liver disease ( p = 0.45 between those who
were and were not infected); the majority of those (75%) reported
delays in follow-up care. The Life Disruption Event Perception (LDEP)
questionnaire confirmed that 80% of COVID-19-infected patients vs.
69% patients without history of COVID-19 infection ( p = 0.0001)
experienced worsening in at least one aspect of their life (food/
nutrition, exercise, social life, vocation/education, financial situation,
housing, or healthcare). The most substantial worsening was
observed for social life (73% in infected vs. 61% in not infected),
exercise (49% vs. 42%), and financial situation (36% vs. 30%) (all p <
0.05). Self-assessed health scores were lower in patients with history
of COVID-19 than in those not infected: 6.8 ± 2.1 vs. 7.4 ± 2.2 (on a 1–
10 scale with 10 indicating perfect health) ( p < 0.0001) despite
similar scores reported before the pandemic (8.5 ± 1.4 vs. 8.4 ± 1.6, p =
0.77). In multivariate regression analysis, after adjustment for
country of enrollment, liver disease etiology and severity (assessed
Figure: Monthly HCV treatment initiations 2018–2020, British Columbia, by FIB-4 score), age, sex, BMI, diabetes, and history of psychiatric
Canada comorbidities, having had COVID was found to be independently
associated with lower self-assessed health scores (beta = − 0.62 ±
Conclusion: Similar to other healthcare services and HCV testing,
0.13, p < 0.0001).
there was a reduction in HCV treatment initiation following the
Conclusion: Patients with CLD experienced a substantial burden of
introduction of control measures. Pandemic-related disruptions and
COVID-19 pandemic on their daily lives regardless of actual infection
the overall decline of treatment initiations could have a negative
history. Self-reported health scores were lower in patients with
impact on progress towards HCV elimination goals.
history of COVID-19 infection.

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POSTER PRESENTATIONS
THU235 THU236
Associations of food insecurity and fast-food consumption with Implementation of HCV screening in the 1969–1989 birth-cohort
diet quality in adults with non-alcoholic fatty liver disease in a undergoing COVID-19 vaccination: a pivotal study in Italy
large population-based U.S. cohort Roberta D’Ambrosio1, Giuliano Rizzardini2, Massimo Puoti3,
Ani Kardashian1, Jennifer Dodge1,2, Norah Terrault1. 1University of Stefano Fagiuoli4, Maria Paola Anolli1, Claudia Gabiati5,
Southern California, Division of Gastrointestinal and Liver Diseases, Los Federico D’Amico3, Luisa Pasulo4, Massimo Colombo6,
Angeles, United States; 2University of Southern California, Department of Pietro Lampertico1,7. 1Foundation IRCCS Ca’ Granda Ospedale Maggiore
Population and Public Health Sciences, Los Angeles Policlinico, Gastroenterology and Hepatology, Milan, Italy; 2ASST
Email: [email protected] Fatebenefratelli-Sacco, First Division of Infectious Diseases, Milan, Italy;
3
ASST Grande Ospedale Metropolitano Niguarda, Division of Infectious
Background and aims: Food insecurity (FIS) impacts the quality of
Diseases, Milan, Italy; 4AAST Papa Giovanni XXIII, Gastroenterology,
foods consumed and is associated with greater risk of non-alcoholic
Hepatology and Transplantation, Bergamo, Italy; 5ASST Fatebenefratelli-
fatty liver disease (NAFLD). While racial-ethnic disparities in NAFLD
Sacco, Internal Medicine, Italy; 6Ospedale San Raffaele, Liver Center,
risk have been reported, the interplay between FIS, diet quality (DQ)
Milan, Italy; 7University of Milan, CRC “A. M. and A. Migliavacca” Center
and fast food (FF) consumption in different racial-ethnic groups with
for Liver Disease, Department of Pathophysiology and Transplantation
NAFLD has not been explored.
Email: [email protected]
Method: A cross-sectional analysis of adults (≥20 years) in the U.S.
National Health and Nutrition Examination Survey 2017–2018 with Background and aims: The World Health Organization (WHO) goal
valid transient elastography and food security (FS) measurements of hepatitis C virus (HCV) elimination by 2030 relies on the scaling-up
using the U.S. Department of Agriculture Food Security Survey of policies of both identification and treatment of the infected
Module was performed. NAFLD was defined as controlled attenuated population, worldwide. In Italy, it has been estimated that at least
parameter score≥280 decibels/meter without other known liver 200, 000 people are unaware of their HCV infection thus reinforcing
disease. Diet quality (DQ) was assessed by the healthy eating index the need for broadening population access to effective screening
(HEI)-2015 (score range 0–100), with poor DQ defined as <25th programs.
percentile of possible scores. We used multivariable linear and Method: A pivotal screening program targeting subjects born
logistic regression to examine associations of FIS, FF consumption, between 1969 and 1989 has been conducted in Lombardy,
and race/ethnicity with DQ and its individual components. Northern Italy, where point-of-care (POC) testing was offered for
Results: In total, 1, 420 adults had NAFLD, of whom 520 (37)% were free concomitantly to COVID-19 vaccination.
food insecure. Food insecure compared to food secure adults were Result: Overall, 7, 219 subjects underwent HCV screening in 4
more likely to be non-Hispanic (NH) black (11% vs 7%), Hispanic (33% vaccination hubs. Characteristics of the screened cohort and pivotal
vs 13%), foreign born (28% vs 15%), live in poverty (31% vs 4%), or have strategies are reported in Table. Seven (0.1%) subjects tested anti-HCV
public/no insurance (59% vs 27%). Mean (standard error) DQ score positive and 5 (0.07%) were HCV-RNA positive by standard confirm-
was 49.1 (0.9) and 46.7 (1.2) for food secure and insecure groups, ation tests. Patients with HCV infection were all males, aged 41–46
respectively. Controlling for age, gender, race/ethnicity, poverty, years; only one of them came from Italy. Clinical data were available
education, and alcohol use, FIS was associated with a 2.5-unit lower for 3 patients: all of them have altered transaminases, without HBV or
DQ score, though did not reach statistical significance (95%CI:-5.7 to HIV co-infection; HCV genotypes were 1b, 3 and 4, and liver stiffness
0.7). However, FF consumption was associated with a − 0.7 unit lower ranged between 4.5 and 10.3 kPa. All patients underwent DAA
DQ score ( per additional FF meal consumed weekly; 95%CI:-1.0 to − therapies.
0.4). NH blacks (+2.9 units, 95%CI[0.3–5.4]), NH Asians (+9.3[5.1–
13.6]), and Hispanics (+5.2[1.1–9.2]) all had significantly better Table: Pivotal screening strategies according to each participating
overall mean DQ than NW whites. Odds ratios of poor DQ for Center
individual components are shown in the table. NH blacks, Asians, and Milan Milan FBF- Milan
Policlinico Sacco Niguarda Bergamo
Hispanics had lower odds of saturated fat consumption compared to (N = 4, 000) (N = 1, 222) (N = 1, 000) (N = 997)
NH whites, but differences between groups were also seen for total
Time spent for screening 53 25 128 16
vegetables, whole fruits, whole grains, and total protein. The largest program, hours
§
differences in individual DQ components by FS were seen among NH Daily vaccinations
Any birth-cohort 7, 081 (5, 1, 803 694 (260– 2, 365 (2,
whites; in this group, food insecure (vs secure) adults had a greater 833–9, (427–1, 894) 080–2,
proportion of poorer scores for seafood/plant proteins (60% vs 46%) 440) 978) 650)
1969–1989 birth-cohort 2, 726 (2, 766 (183– 336 (80– 1, 355 (1,
and added sugars (29% vs 11%). 077–3, 447) 923) 605) 325–1,
385)
Proposed anti-HCV POC 4, 721 1, 629 NA 1, 575
Accepted anti-HCV POC 4, 000 1, 222 1, 000 (NA 997 (63%)
(85%) (75%) %)
Age, years 42 (32–52) 44 (32–52) 44 (32–52) 43 (32–52)
Males 1, 840 (46%) 745 (61%) 432 (43%) NA
Screening Team (per day) 9–12 5–6 2–3 9–11
Physicians 3–4 2 1 2
Nurses 3–4 2–3 0–1 3–4
Others 3–4 1 Auxiliary 0–1 4–5
*
Research Nurse Research Volunteers
Assistants Assistant
Anti-HCV positive by POC test 6 (0.15%) 0 0 1 (0.10%)
Lost to follow-up after POC test 1 (0.01%) – – 0
Anti-HCV positive by 4 (0.10%) – – 1 (0.10%)
confirmatory test
Conclusion: There was a trend towards worse DQ in food insecure HCV-RNA positive 3 (0.08%) – – 1 (0.10%)

adults with NAFLD. Fast-food consumption was also associated with

Results are reported as number (n) and percentages (%) or median (range).
lower DQ in NAFLD. NH whites had the lowest DQ with food HCV: Hepatitis C Virus; POC: Point-of-Care; NA: Not Available
insecurity potentiating poor DQ. Exploration of the sociocultural §refers only to screening days, in each vaccination hub;
factors contributing to the observed differences in DQ by race/ *all from patients’ alliance
ethnicity may offer the potential opportunity to mitigate NAFLD
disparities and reduce disease burden. Conclusion: This pivotal study demonstrated the feasibility of a POC-
based anti-HCV screening program in young adults undergoing

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 POSTER PRESENTATIONS
COVID-19 vaccination. The prevalence of HCV infection in subjects THU238
born in the 1969–1989 cohort in Italy seems to be lower than Epidemiology of hepatocellular carcinoma in Portugal
previously estimated, thus raising the question whether more HCV Mario Jorge Silva1,2, Guilherme Simões1, Rita Catarina Saraiva1,
carriers can be identified if screening is moved up to embrace Filipe Calinas1, Paulo Nogueira3,4,5,6. 1Centro Hospitalar Universitário
subjects born before 1969. Lisboa Central, Gastroenterology, Lisboa, Portugal; 2NOVA Medical
School, Lisboa, Portugal; 3Faculdade de Medicina da Universidade de
THU237 Lisboa, Instituto de Medicina Preventiva e Saúde Pública, Lisboa,
Real life pooling of plasma samples for hepatitis C RNA detection Portugal; 4Faculdade de Medicina da Universidade de Lisboa, Instituto de
as a screening strategy of hepatitis C active chronic infection Saúde Ambiental, Lisboa, Portugal; 5Faculdade de Medicina da
A. Aguilera1,2,3, M. Cea1,2,3, A. Fuentes4,5, S. Pereira1,2,3, L. Vinuela4,5, Universidade de Lisboa, Área Disciplinar Autónoma de Bioestatística;
Federico Garcia Garcia4,5,6. 1University Hospital of Santiago de 6
Universidade NOVA de Lisboa, NOVA National School of Public Health,
Compostela, Microbiology, Santiago de Compostela, Spain; 2University of Comprehensive Health Research Center
Santiago de Compostela, Microbiology, Santiago de Compostela, Spain; Email: [email protected]
3
Instituto de Investigación Sanitaria de Santiago, Santiago de
Compostela, Spain; 4University Hospital Cinic San Cecilio, Microbiology, Background and aims: There is scarce data on the burden of
Granada, Spain; 5Instituto de Investigación Biosanitario Ibs. Granada, hepatocellular carcinoma (HCC) in Portugal. We aim to characterize
Granada, Spain; 6Ciber Enfermedades Infecciosas ISCIII, Granada the recent epidemiology of HCC in Portugal.
Email: [email protected] Method: We evaluated HCC-related hospital admissions and mor-
tality in Portugal between 2010 and 2017. We analyzed all hospital
Background and aims: The diagnosis of active hepatitis C virus admissions from patients with HCC in public hospitals (data from
(HCV) infection is the necessary first step for its elimination. In most Portuguese Health System’s Central Administration) and mortality
countries, universal population screening and/or screening by age due to HCC (data from National Statistics Institute)-coded with 155.0
groups have not been adopted due to cost and cost-effectiveness (International Classification of Diseases-ICD-9-CM) or C22.0 (ICD-10).
considerations. Here we show a real-life sample pooling diagnosis Additional analyses were performed to evaluate longitudinal trends
strategy to overcome this challenge, and to contribute to increase the and regional differences.
diagnostic capacity of clinical laboratories and expand access to Results: Between 2010 and 2017, there were 20, 704 hospital
massive screening of hepatitis C. admissions of patients with HCC, ranging annually from 2, 086 in
Method: we have analyzed consecutive samples submitted to 2010 to 2, 989 in 2015. In-hospital mortality rate during admission
microbiology services of CHUS (Santiago de Compostela, Spain) and was 16.7%.
HUCSC (Granada, Spain) for hepatitis C diagnosis during the first Considering individual patients admitted with HCC, the number of
three weeks of November 2022. Samples were tested for HCV patients admitted annually varied from 1, 046 in 2010 to 1, 560 in
antibodies and, in parallel and in a blinded way, were pooled into 100 2017. 7, 739 individual patients were admitted during the 8-year
samples with the following strategy: first, 10 pools of 10 samples period: 80.1% males and with mean age 66 ± 12.2 years.
were built (a); second, two pools comprising five of the previous were In the whole country, both in-hospital and ambulatory, the annual
made (b); finally, these two were pooled together and tested for HCV- number of deaths ranged from 471 in 2010 to 620 in 2017 (4, 316
RNA using Cobas® HCV 6800 (Roche Diagnostics) at CHUS and both deaths during the 8 years). Potential years of life lost ranged annually
Xpert HCV Viral load (Cepheid) and Cobas® HCV 6800 at HUCSC. from 2477 in 2010 to 3838 in 2017.
When positive, the previous two pools (b) were tested and after, a Annual number of admissions, admitted patients, mortality and
strategy to unmask the positive (s) sample (s) that needed up to 15 potential years of life lost are detailed in the table.
total HCV-RNA tests was used. The mean annual mortality rate due to HCC, considering the 8-year
Results: A total of 1700 samples (17 pools) were analyzed, 800 at period, was 5.2/100, 000 inhabitants (9.0/100, 000 inhabitants
CHUS and 900 at HUCSC. The overall anti HCV and HCV-RNA among males and 1.8/100, 000 inhabitants among females). The
prevalence was 0, 24% (4/1700). After our pooling strategy, we could highest regional mortality rate was observed in the Lisbon metro-
detect all samples previously detected by standard diagnosis (anti- politan area (6.3/100, 000 inhabitants overall, 11.2/100, 000 inhabi-
HCV followed by reflex HCV-RNA testing). While 13 master pools tants among males and 2.0/100, 000 inhabitants among females).
were negative, we needed to unmask 4 master pools, resulting in 60
total HCV-RNA tests to finally unmask the positive sample for each
master pool. Specificity and sensitivity of the pooling strategy were Longitudinal
100%. Given median current prices on the market in Spain for anti- trend 2010–
2017 (p
HCV (3€) and HCV-RNA (30€), testing with the pooling strategy would 2010 2011 2012 2013 2014 2015 2016 2017 value)
have resulted in 3420 € save (5220 € by traditional testing vs 1800 € by Hospital admissions (n) 2086 2600 2425 2641 2694 2989 2793 2476 (p = 0.125)
the pooling strategy), and a cost of 1, 05€ per patient screened. Admitted patients (n) 1046 1205 1220 1376 1371 1511 1560 1410 Increasing
Conclusion: The strategy of pooling samples for the diagnosis of (p = 0.003)
Deaths (n) 461 557 558 496 535 536 553 620 (p = 0.073)
active HCV infection has advantages that should be exploited with Potential years of life 2477 3215 3340 2955 3228 3005 3013 3838 (p = 0.126)
the aim of eliminating HCV as a public health threat. Here we lost (n)
demonstrate that in settings with a low prevalence of chronic Conclusion: The burden of HCC in Portugal is high and had an
infection, by substantially improving cost-effectiveness, this strategy increasing trend between 2010 and 2017.
enables and provides the necessary sustainability for use in large-
scale diagnosis of HCV.

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POSTER PRESENTATIONS
THU239 underline the importance of reflex testing for identifying active
“Zero C” hospital project: an innovative screening and referral infection. HCV elimination requires increase of screening in patients
model in hospitalized patients at different divisions who are unaware of the HCV status, but also of the screening and
Valerio Rosato1, Loreta Kondili2, Riccardo Nevola1, Alessio Aghemo3, linkage to care in those with known liver damage yet unaddressed.
Pasquale Perillo1, Ruben Napolitano4, Antonio Sciambra5,
Davide Mastrocinque1, Ernesto Claar1. 1Ospedale Evangelico Betania, THU240
Liver Unit, Naples, Italy; 2Istituto Superiore di Sanità, Center for Global LINK-B: a hepatitis B program to test and link to care patients lost
Health, Roma, Italy; 3Humanitas Clinical and Research Center IRCCS, of follow-up
Division of Internal Medicine and Hepatology, Department of Ana Barreira1,2, Ariadna Rando-Segura3, Anna Feliu-Prius1,
Gastroenterology, Rozzano, Italy; 4Ospedale Evangelico Betania, Francisco Rodríguez-Frías2,3, Elena Vargas Accarino1,
Laboratory Medicine Unit, Naples, Italy; 5Ospedale Evangelico Betania, Judit Vico-Romero1, Mar Riveiro Barciela1,2, Adriana Palom1,
Health Management, Naples, Italy Rafael Esteban1,2, Maria Buti1,2. 1Hospital Universitario Vall de Hebrón,
Email: [email protected] LIver Unit; 2Instituto de Salud Carlos III., Centro de Investigación
Biomédica en Red de Enfemerdades Hepáticas y Digestivas (CIBERehd);
Background and aims: Chronic hepatitis C is a major public health 3
Hospital Universitario Vall de Hebrón, Microbiology Department
problem in Southern Italy. Screening strategies in key populations Email: [email protected]
and birth cohort 1969–1989 has been addressed for free of charge
screening in Italy. However, larger birth population cohorts need to Background and aims: Hepatitis B affects more than 250 million
be screened due to expected high HCV prevalence. We conducted a people worldwide. In Spain an estimated 320, 000 people are living
hospital-based mass screening in order to assess the HCV active with hepatitis B. Most HBsAg-positive individuals are not linked to
infection prevalence and address the feasibility of the opportunistic care in our setting, and this is an obstacle to receiving treatment and
screening in the linkage to care of the infected patients. controlling hepatitis B in the population. The primary aim of this
Method: From January 2020 to May 2021 all consecutive in-patients research was to promote adequate linkage-to-care and treatment of
were screened for HCV antibody (HCV Ab) at hospital admission HBsAg-positive individuals lost to follow-up.
throughout all divisions in the Evangelic Hospital Betania of Naples. Method: This is a single-center retrospective and prospective search
HCV-Ab positive patients were evaluated for previous HCV treatment. of all HBsAg-positive cases in the microbiology database of the
HCV RNA testing was required for those not previously treated. In Northern Health Area of Barcelona (450, 000 inhabitants). The
patients with active infection the linkage to care and treatment start retrospective phase included all HBsAg cases seen between 2018 and
were planned within the hospital admission. 2020 and the prospective phase covered January 2021 to end 2022.
Results: Of 12.665 inpatients consecutively screened, 510 (4%) were Medical records were reviewed to identify and retrieve HbsAg-
HCV Ab positive. The HCV Ab positivity increased with age with the positive cases not linked to care. Candidates for contacting were
highest prevalence in those born before 1947 (9, 49%). In each birth called to offer disease assessment.
cohort, 20–30% of patients have been previously treated whereas 30– Results: Here, we present the data from January 2018 to end April
45% were discharged and not tested for HCV RNA. 194 (38% of HCV +) 2019 (retrospective), and the first month of 2021 ( prospective). In
patients were tested for HCV RNA and 91 patients (46.2%) had active total, 1349 HBsAg-positive individuals were detected by the labora-
HCV infection. 87 patients were treated during hospital admission, tory. The flowchart of patients is summarized in the Figure. After the
while 4 were not evaluated for treatment due to severe comorbidities. initial assessment, 192 patients were referred to a hepatologist: 128
All patients treated achieved sustained virological response at week (66.7%) attended the visit and 33.3% did not. Overall baseline
12 (SVR 12). Among HCV RNA tested patients, 47% of 1969–1989 birth characteristics: mainly males (57.8%), median age 45 (± 14) years.
cohort, 35% of 1948–1968 birth cohort and 53% of those born before Overall, 82.3% (152) were inactive carriers, 6 HBeAg-positive chronic
1947 had active infection. Among 91 HCV RNA positive patients, 33 hepatitis, 4 immune-tolerant and 12 (6.3%) could not be classified in a
(36%) were admitted to liver unit for known liver damage without single determination. Baseline characteristics were similar between
being HCV diagnosed or linked to care (all, except one, were born patients who attended the visit and those who did not.
before 1968). The remaining 58 patients were admitted for
comorbidities in cardiology, internal medicine, ophthalmology,
surgery, orthopedics, senology and intensive care unit. Among
them, 49 (54%) belonged to patients born before 1968 and 9 (10%)
to 1969–1989 cohort. All available patients underwent linkage to care
and treatment start during hospital admission. (Figure 1)

Figure 1: A care cascade during the opportunistic screening in Evangelic

Hospital Betania of Naples (Italy) 2010–2020.

Conclusion: A high prevalence of active infection is observed in

patients with comorbidities in Southern Italy. The possibility of active
infection testing in less than 50% of HCV Ab positive patients

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 POSTER PRESENTATIONS
Conclusion: The link B strategy showed that more than one-third of Conclusion: Current testing for liver disease is inadequate. Pathways
known HBsAg-positive individuals had not been linked to care, and that streamline testing, including testing of persons with normal liver
enabled the retrieval of a large number of patients. blood tests but that are at risk of significant liver disease, will increase
the yield of testing for liver disease in primary care. A “fibrosis first”
THU241 pathway, taking a fast and frugal approach to identify persons with
Testing for liver disease in primary case: fibrosis first prognostically significant liver disease, warrants testing in compari-
Ian Rowe1,2, Richard Parker2. 1University of Leeds, Leeds Institute for son to comprehensive evaluation in primary care.
Medical Research, United Kingdom; 2St James’s Hospital, Leeds Liver
Unit, United Kingdom THU242
Email: [email protected] Hepatitis C care cascade analysis among adult women in Georgia
Ketevan Stvilia1, Shaun Shadaker2, Amiran Gamkrelidze3,
Background and aims: The optimal method to identify persons with
Irma Khonelidze3, Maia Tsereteli3, Vladimer Getia3,
liver disease in primary care is unknown. Approaches to diagnose all
Paige A Armstrong2. 1National Center for Disease Control and Public
persons with abnormal liver blood tests, e.g. intelligent liver function
Health, Tbilisi, Georgia; 2Centers for Disease Control, Department of Viral
tests (iLFT), or screening all those with specific risk factors have been
hepatitis, United States; 3National Center for Disease Control and Public
proposed but each incompletely identifies the population being
Health, Tbilisi, Georgia
tested in primary care. The aim of this study was to define testing
Email: [email protected]
strategies to identify persons with treatable liver disease and/or
advanced fibrosis in primary care using unified pathways. Background and aims: According to the National HCV seroprevalence
Method: A decision model was developed to assess 3 approaches to study of 2015, 3.8% of women in Georgia are positive for hepatitis C
testing in comparison to the current practice of limited testing for virus (HCV) antibodies; however, female-targeted interventions to
liver disease and liver fibrosis in primary care. The outcomes promote HCV testing and treatment have been lacking. Further, women
considered were the incremental cost per diagnosis ratio and the of reproductive age can transmit HCV during pregnancy, making
net benefit of each pathway. Diagnosis was defined by treatable liver outreach to this population particularly important. We constructed the
disease (viral hepatitis, metabolic liver disease, or autoimmune liver HCV care cascade for women age ≥18 years, screened for anti-HCV
disease) and advanced fibrosis (in the case of alcohol-related liver within the National Hepatitis C Elimination Program during January
disease or non-alcoholic fatty liver disease). The tested approaches 2015-October 2021 to compare progress in care and treatment and to
were: 1. “iLFT” (full aetiology testing of persons with abnormal LFTs); assess gaps in the cascade of HCV care and treatment.
2. “Comprehensive” (full aetiology testing for abnormal LFTs and Method: The seven stages of HCV care recommend by WHO were
non-invasive fibrosis tests for all persons tested); 3. “Fibrosis first” assessed for women who tested positive for anti-HCV: (1) HCV
(abbreviated aetiology testing [HBV, HCV, iron studies] and non- antibody positive; (2) tested for viremia; (3) confirmed active
invasive fibrosis testing for all). These approaches were compared infection; (4) initiated HCV treatment; (5) eligible for test for sustained
with current practice patterns where 20% of persons with newly virologic response (SVR), (6) tested for SVR and (7) achieved SVR. HCV
abnormal LFTs undergo downstream testing. Parameters were care cascade results were assessed for women by age group to define
estimated from literature data and costs were derived from the UK gaps, and proportion retained at each step in the care cascade.
NHS. Results: As of October 2021, 2.1 million adults with known sex were
Results: All tested approaches identified more persons with treatable screened for anti-HCV, including 1.1 million women. Among them,
liver disease ± advanced liver fibrosis than the current standard of 38, 881 (3.4%) were positive for anti-HCV, and the majority (65.0%)
care. In the base case scenario, where 80% of the tested population were aged ≥50 years. Overall, 77.3% of women who screened anti-
had abnormal LFTs, the fibrosis first approach made a diagnosis of HCV positive were tested for viremia. The positivity rate for active
treatable disease/advanced fibrosis in 3.9% of the total population HCV infection was 73.2% (21, 978) among all females, ranging from
compared with 3.8% for iLFT and 4.3% in the comprehensive 62.7% among those aged 18–29 years to 75.8% among those aged 40–
approach. Fibrosis first had the lowest incremental cost per diagnosis 49 years. Overall, 76.1% (16, 729) of women with HCV viremia
ratio: fibrosis first, £1349 (€1590); iLFT £3247 (€3828); and initiated treatment, including 63.0% of women aged ≥60 years, and
comprehensive, £2964 (€3494). The number of secondary care ≥84.0% of women in all other age groups. Of women enrolled in
referrals was increased in all approaches above current testing, treatment, 95.6% (15, 986) completed the regimen, and 98.2% of those
greatest in the comprehensive strategy. Considering these trade-offs women were eligible for an SVR test. Women have demonstrated high
the net benefit was greatest for the fibrosis first approach (Figure). uptake of SVR testing; 82.0% were tested for SVR across all age groups
with an overall cure rate of 99.4%.
Conclusion: To reach elimination of hepatitis C by 2025 it is
important to improve access to and support uptake of viremia
testing and enrollment in treatment among anti-HCV positive
women in Georgia, with special attention to ensuring the large
proportion of anti-HCV positive women over 50 years complete
viremia testing. Once enrolled in treatment, Georgian women with
active HCV infection show high rates of compliance resulting in more
than 99% of cases cured.

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POSTER PRESENTATIONS
THU243 in screening for HCV infection, with numbers continuing to decline in
Progress in HCV screening in the national hepatitis C elimination 2021. In response, Georgia intends to increase integrated screening,
program in Georgia during the COVID-19 pandemic, 2019–2021 and seek active approaches to link patients to HCV care and
Amiran Gamkrelidze1, Alexander Turdziladze1, Maia Tsreteli1, treatment. The impact of the pandemic on the HCV elimination
Vladimer Getia1, Ana Aslanikashvili1, Tinatin Kuchuloria2, program demonstrates how a pandemic can be challenging for
Irina Tskhomelidze2, Sophia Surguladze2, Lia Gvinjilia3, different public health programs and highlights the need to employ
Senad Handanagic4, Shaun Shadaker4, Paige A Armstrong4. 1National innovative strategies to avoid slowing of progress towards HCV
Center for Disease Control and Public Health Georgia, Tbilisi, Georgia; elimination.
2
The Task Force for Global Health, Tbilisi, Georgia; 3Eastern Europe and
Central Asia (EECA) Regional Office, Centers for Disease Control and THU244
Prevention, Tbilisi, Georgia; 4Division of Viral Hepatitis, Centers for Could a multi-target blood test make hepatocellular carcinoma
Disease Control and Prevention, Atlanta, United States surveillance programs more effective? A modelling-based virtual
Email: [email protected] trial
Jagpreet Chhatwal1,2,3, Sumeyye Samur4, Ju Dong Yang5,
Background and aims: Georgia, with a population of 3.7 million, had Lewis Roberts6, Mindie Nguyen7, A. Burak Ozbay8, Turgay Ayer9,10,
an estimated 150, 000 adults living with chronic hepatitis C virus Neehar D. Parikh11, Amit Singal12. 1Harvard Medical School, Boston,
(HCV) infection based on a serosurvey conducted in 2015. The same United States; 2Mass General Hospital, Boston, United States; 3Harvard
year, the country initiated the world’s first national HCV elimination Medical School, Boston, United States; 4Value Analytics Labs, Boston,
program, with free screening and treatment available to all citizens. United States; 5Cedars-Sinai Medical Center, Los Angeles, United States;
Despite great progress, the COVID-19 pandemic has created new 6
Mayo Clinic, Rochester, United States; 7Stanford University School of
challenges for the program. This analysis describes the progress made Medicine, Stanford, United States; 8Exact Sciences Corporation, Madison,
in HCV screening since program initiation and the impact of the United States; 9Georgia Institute of Technology, Atlanta, United States;
COVID-19 pandemic on HCV screening. 10
Emory University-School of Medicine, Atlanta, United States;
Method: The Hepatitis C Elimination Program tracks testing and 11
University of Michigan Medical School, Ann Arbor, United States; 12UT
treatment data using two databases, the national HCV Screening Southwestern, Dallas, United States
Registry, and the HCV treatment database. These databases are linked Email: [email protected]
by the national ID. This analysis uses data from both databases and
the 2014 general population census. Background and aims: Hepatocellular carcinoma (HCC) is among the
Results: As of September 30th, 2021, 2, 081, 548 adults have been fastest rising causes of cancer mortality in the Western world.
screened for antibody to HCV (anti-HCV) (75% of the adult Although guidelines recommend biannual ultrasound (U/S)-based
population), of whom 144, 857 (6.9%) were anti-HCV positive. HCC surveillance in at-risk patients, utilization in practice remains
Overall, 118, 398 (81.7%) anti-HCV positive individuals received poor in practice. A recently validated, multi-target HCC blood test
follow-up viremia testing, and 94, 315 (79.7%) were found to have (mt-HBT), may potentially improve adherence to surveillance by
active HCV infection. The number of anti-HCV tests performed among forgoing the need for U/S. Our objective was to evaluate the
adult persons dropped as restrictions were imposed in March of 2020 comparative effectiveness of mt-HBT with the current surveillance
from 74, 815 tests in February 2020 to just 35, 371 in April of the same strategy in cirrhosis patients.
year. Screening increased in the summer, with 106, 212 tests Method: We simulated a virtual trial by developing a clinically valid
performed in July, due in part to relaxed restrictions and intensified microsimulation model of HCC natural history in compensated
integrated screening programs (HCV, tuberculosis, and HIV). cirrhosis patients. Model parameters, including tumor progression,
Compared to 2019, the number of tests performed in 2020 decreased competing risks of mortality, and real-world adherence, were
by 24% (1, 048, 108 vs. 793, 658). As the pandemic progresses, the estimated from the literature. Test performance characteristics of U/
number of tests performed for HCV during January − September 2021 S, AFP, and mt-HBT were informed from a network meta-analysis. We
remained lower than in the same period in 2020 (503, 048 vs. simulated the life course of cirrhosis patients and compared biannual
636, 161). surveillance using (1) AFP only, (2) U/S only, (3) U/S+AFP, and (4) mt-
HBT only. We also simulated a scenario where mt-HBT would improve
adherence by 10% (∼4% absolute improvement) compared to current
utilization.
Results: Per 10, 000 cirrhosis patients simulated in each arm, mt-HBT
detected 225 (+57%) more early-stage HCC cases compared with AFP,
108 (+21%) more early-stage HCC compared with U/S, and 20 (-3%)
less early-stage HCC compared with U/S+AFP. In contrast, mt-HBT
with improved adherence detected 21 (+3%) more early-stage HCC
compared with U/S+AFP (Figure). The remaining HCC cases were
either symptomatically identified or patients died from competing
causes prior to detection. mt-HBT increased life years by 709 per 10,
000 patients screened compared with AFP, 360 compared with U/S,
but decreased life years by 19 compared with U/S+AFP. Of note, mt-
HBT with improved adherence increased life years by 52 compared
with U/S+AFP.

Conclusion: Although the program has made significant progress

towards HCV elimination, the ongoing pandemic has led to a decline

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 POSTER PRESENTATIONS
Table: Factors associated with seropositive of neutralizing antibody
on days 57 and 180, respectively.
D57 D180
Multivariable Multivariable
Univariable analysis analysis* Univariable analysis analysis**
95%
Characteristics OR 95% CI p aOR 95% CI p OR 95% CI p aOR CI p

Age 0.938 0.159- 0.008 0.039 0.900- 0.039 0.984 0.951- 0.364
1.054 0.997 1.019
Male 0.409 0.159- 0.064 2.045 0.981- 0.056
(vs female) 1.054 4.265
Waist 0.943 0.904- 0.006 0.949 0.906- 0.027 0.995 0.963- 0.760
0.984 0.994 1.028
CAP 0.998 0.989- 0.589 1.006 0.999- 0.074
1.006 1.013
LSM 0.882 0.664- 0.383 1.299 1.019- 0.035
1.170 1.656
BMI 0.887 0.791- 0.038 0.981 0.891- 0.703
0.993 1.081
Conclusion: mt-HBT as a single blood test offers similar diagnostic ALT 1.010 0.977- 0.568 1.024 1.003- 0.025
efficacy for early HCC detection compared with the combination of U/ 1.043 1.045
AST 1.009 0.952- 0.769 1.051 1.007- 0.022
S+AFP. Potential improved adherence with use of blood-based 1.069 1.096
biomarkers, such as mt-HBT, would likely further increase real- ALP 0.996 0.974- 0.737 1.010 0.992- 0.275
1.019 1.027
world effectiveness of HCC surveillance. CRP 1.145 0.938- 0.183 1.151 0.989- 0.068
1.399 1.340
Fasting glucose 1.065 0.663- 0.795 0.867 0.595- 0.459
THU245 1.710 1.264
Evaluation of immune response and disease flares in metobolic- HOMA-IR 0.903 0.746- 0.295 1.117 0.931- 0.233
1.093 1.339
associated fatty liver disease patients following SARS-CoV-2 WBC 0.921 0.671- 0.613 1.324 1.025- 0.032
vaccination: a prospective cohort study 1.265 1.710
RBC 0.733 0.309- 0.480 3.461 1.634- 0.001 2.746 1.212- 0.016
Junping Shi1, Qianru Zhu2,3, Jin Gao4, Jiaping Gu5, Lu Shen5, Jing Liu6, 1.736 7.332 6.223
Lymphocyte 0.931 0.421- 0.861 2.758 1.397- 0.003 2.377 1.150- 0.019
Yu Song7, Xiying Gong7, Yutong Chen5, Jie Liao7, Yining He5, Siyi Zhang5, 2.059 5.442 4.914
Li Shao3,5, Yee Hui Yeo8, Jie Li9,10. 1The Affiliated Hospital of Hangzhou Hemoglobin 0.996 0.971- 0.751 1.025 1.003- 0.028
1.021 1.048
Normal University, Department of Hepatology and infectious Disease,
Hangzhou, China; 2Macau University of Science and Technology, Faculty of *Adjusted for age,sex,waist,CAP,LSM,BMI,ALT,AST,Glu,HOMA-IR,ALP;
Chinese Medicine, Macau, China; 3The Affiliated Hospital of Hangzhou **Adjusted for age,sex,CAP,LSM,WBC,RBC,lymphocytes,hemoglobin,ALT,AST.
Normal University, Department of Translation Medicine Platform,
Hangzhou, China; 4The Affiliated Hospital of Hangzhou Normal University, Conclusion: CoronaVac vaccination in MAFLD patients was safe and
Department of Clinical Laboratory, Hangzhou, China; 5Hangzhou Normal well tolerated. MAFLD patients showed a similar immune response to
University, Medical college, Hangzhou, China; 6The Affiliated Hospital of health controls.
Hangzhou Normal University, Department of Hepatology and infectious
Disease, Hangzhou, China; 7Zhejiang Chinese Medical University, The THU246
Fourth School of Clinical Medicine, Hangzhou, China; 8Cedars-Sinai A model, screen test and treat hepatitis C elimination project
Medical Center, Division of General Internal Medicine, United States; among under-served communities in Islamabad-the federal
9
Nanjing University, Institute of Viruses and Infectious Diseases, Nangjing, capital of Pakistan
China; 10The Affiliated Hospital of Nanjing University Medical School, Huma Qureshi1, Hassan Mahmood2, Nabil Ahmed3, Lillian Lou4,
Department of Infectious Diseases, Nangjing, China Francisco Averhoff5, Ameer Abutaleb6, Shyamasundaran Kottilil6.
1
Email: [email protected] Integral Global (IG), Pakistan; 2Integral Global (IG), Public Health,
Islamabad, Pakistan; 3Integral Global (IG), Atlanta, United States; 4John
Background and aims: The safety and efficacy profile of Covid-19 C. Martin Foundation, United States; 5Abbott Diagnostics, United States;
vaccines in patients with MAFLD (metabolic associated fatty liver 6
University of Maryland, United States
disease) remains unclear. We aimed to determine the safety and Email: [email protected]
immunogenicity of an inactivated vaccine in MAFLD.
Method: In this prospective cohort, 50 participants with MAFLD and Background and aims: Pakistan has a large burden of hepatitis C
114 healthy controls received two doses of CoronaVac with a 28-day virus (HCV) infection, and access to care and treatment is limited. In
interval between doses and underwent blood sample collection on order to increase access for underserved populations, a same-day
days 0, 28, 57, and 180. Baseline vibration-controlled transient testing and treatment initiation model program for adults in
elastography as well as the level of neutralizing antibody against the marginalized communities (i.e slums) in Islamabad was launched
SARS-CoV-2 spike receptor-binding domain, fasting metabolic on March 02, 2019. We describe the results of the program.
markers, and liver function test on four assessment dates were Method: A total of 17 slums with an estimated total population of 50,
assessed. Repeated measures ANCOVA was used to estimate the 000 in Islamabad have been selected by the Ministry of National
magnitude of change of these markers throughout study period. Health Services, Regulations and Coordination for the project. This
Results: No significant difference in proportion of patients with project includes free hepatitis C testing and treatment and utilizes
neutralizing antibody was observed between two groups. The trained community health workers (CHWs). The CHWs visit every
proportions of adverse event and liver injury was similar between dwelling in the slum and offer household members aged ≥18 years
both groups. There was no difference between the two groups in the screening for hepatitis C by a rapid hepatitis C antibody (anti-HCV)
change of most biomarkers throughout study period. On multi- test. Those that test positive are referred to an established clinic for
variable analysis, age and waist circumference were negatively diagnosis of active HCV infection (RNA) by GeneXpert. RNA results
associated with seropositivity of neutralizing antibody on day 57 are made available to patients within two hours. If found to be HCV
while RBC and lymphocyte count were independent positive RNA Positive, the Aspartate to Aminotransferase (AST) to Platelet
predictors on day 180 (Table). Ratio Index (APRI) is calculated, subjects receive counseling, and their
first 4-week supply of sofosbuvir plus daclatasvir and the first of three
doses of hepatitis B vaccine during the initial clinic visit. A treatment
regimen of 12 weeks for non-cirrhotic (APRI<1.5) patients is
prescribed. Patients with an APRI ≥1.5 are referred to specialists.

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POSTER PRESENTATIONS
Patients are seen every 4 weeks at the clinic and given refills on their Method: All 27 dialysis centers in the country were invited to
medications and queried about adverse reactions, until the end of participate. Facility questionnaires were completed by the infection
treatment. RNA testing is conducted at 12 weeks following control representatives at each center from April to June, 2021.
completion of treatment to determine viral clearance (cure). The Respondents were asked about HBV and HCV screening practices, and
CHWs ensure referral and follow-up of HCV infected persons. the number of seroconversions among facility patients in the
Results: As of November 15, 2021; a total of 24, 216 participants have preceding year. Data entry, management and analyses were con-
been screened from seventeen slums, 514 (2.12%) tested positive for ducted using the statistical package SPSS v.22.0.
anti-HCV and were referred to receive testing for HCVRNA. Of those, Results: A total of 22 (81.5%) dialysis centers participated in the
440 (85.6%) got tested for HCV RNA and 323 (73.4%) had detected survey. HBV screening is routinely performed upon admission at 21
RNA. Three hundred and eighteen individuals (98.5%) had initiated facilities (95.5%). Susceptible patients are routinely vaccinated with
treatment, of which 284 (89.3%) had completed treatment. To date, the hepatitis B vaccine at about half (13; 59.1%) of facilities. Anti-HCV
257 (90.5%) patients are eligible to test for Sustained Virologic screening is performed at 15 institutions (68.2%) upon admission to
Response (SVR), out of which 250 (97.3%) were tested; 241 (96.4%) the center, and anti-HCV screening is performed once every 6 months
were HCV RNA negative, four (1.6%) were loss to follow-up and five in 12 (54.5%) clinics for patients who were previously anti-HCV
patients were (2%) HCV RNA positive. Those five patients were given negative.
Sofosbuvir and Velpatasvir and are on treatment. Ten (45.5%) of the dialysis facilities included in the study reported
HBV and HCV seroconversions in the prior year. A total of 31 HBV
seroconversions from 8 facilities and 39 HCV seroconversions from 7
facilities occurred. The largest number in a single facility was 25 total
seroconversions of HBV or HCV infection.
Conclusion: The high seroconversion rate of HBV and HCV infections
at dialysis units suggests opportunities for improved infection
prevention practices and need for increased hepatitis B vaccination
efforts. Surveillance could help identify cases and clusters early and
contribute to preventing infection in this high-risk population.

THU248
Innovative linkage model to re-engage loss-to-follow-up
individuals in the national hepatitis C elimination program of
Georgia
Amiran Gamkrelidze1, Alexander Turdziladze1, Maia Tsreteli1,
Vladimer Getia1, Ana Aslanikashvili1, Sophia Surguladze2,
Irina Tskhomelidze2, Shaun Shadaker3, Paige A Armstrong3. 1National
Center for Disease Control and Public Health Georgia, Tbilisi, Georgia;
Conclusion: Same day hepatitis C testing and treatment initiation is 2
The Task Force for Global Health, Tbilisi, Georgia; 3Division of Viral
feasible among underserved communities in urban slums in Pakistan. Hepatitis, National Center for HIV, Viral Hepatitis, STD and TB Prevention,
CHWs can be effective in reaching “hard-to-reach” populations with CDC, Atlanta, United States
limited access to health services and achieving high rates of linkage to Email: [email protected]
care and adherence with treatment for hepatitis C.
Background and aims: The National Hepatitis C Elimination Program
THU247 has made notable progress in Georgia. However, in the setting of
Hepatitis B and hepatitis C testing practices and seroconversions COVID-19 related limitations, the number of individuals registering in
among dialysis facilities in Georgia the treatment program has declined over time, from an average of
Maia Butsashvili1, George Kanchelashvili1, Ana Aslanikashvili2, 996 per month in 2019 to 339 per month in 2021. As of September 30,
Tinatin Kuchuloria3, Shaun Shadaker4, Irina Tskhomelidze3, 2021, 75% (n = 2, 081, 548) of the adult population of Georgia has been
Maia Tsereteli2, George Kamkamidze1, Priti Patel4, screened for hepatitis C virus (HCV), but among antibody positive
Paige A Armstrong4. 1Health Research Union, Tbilisi, Georgia; 2National adults, 20, 913 (15%) had not completed a viremia test.
Center for Disease Control and Public Health, Tbilisi, Georgia; 3The Task In 2019, the National Center for Disease Control and Public Health
Force for Global Health, Tbilisi, Georgia; 4Centers for Disease Control and Georgia piloted a project to link to care those individuals who
Prevention, Atlanta, United States screened positive for anti-HCV but had not completed a viremia test.
Email: [email protected] After success of the initial pilot, the model will be scaled up across
Georgia.
Background and aims: Hemodialysis can facilitate transmission of Method: All anti-HCV positive adults (aged ≥18 years) who did not
hepatitis C and hepatitis B as a result of a large number of patients have record of viremia testing in the national HCV electronic database
receiving treatment in a shared space. Strict adherence to infection 3 months from the date of a positive result, and who were not
prevention and control practices is essential to prevent transmission registered in the HIV/AIDS program or with a correctional facility,
through contaminated equipment and surfaces. Despite a compre- were eligible for follow-up.
hensive hepatitis C Elimination Program in Georgia, there is currently Using the phone number listed in the database, individuals were
no system in place to adequately capture the prevalence of chronic contacted by phone or home visit by patient navigators (trained
HBV infection or chronic HCV infection and to promptly identify cases epidemiologists and primary healthcare physicians) and referred to
of HCV and HBV seroconversion among persons receiving dialysis. HCV care and treatment. If the first attempt was unsuccessful, one
This study evaluates HCV and HBV testing practices among patients repeat attempt was made to contact the individual. Incentives were
receiving dialysis and estimates the number of seroconversion cases
in dialysis units in Georgia.

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 POSTER PRESENTATIONS
provided to regional health personnel for each patient that was
successfully linked to care, defined as presenting for viremia testing.
Results: As of October 1, 2020, 18, 030 persons were not linked to
care; patient navigators attempted to reach 8, 907 (49%) with phone
numbers in the database; 6, 718 (75%) were reached. The remaining 2,
189 could not be reached, had moved, or emigrated. Of those
contacted, 1, 546 (23%) presented for viremia testing, and 811 (52%)
were positive for HCV RNA or core antigen. Overall, 419 (52%) persons
with chronic HCV infection were enrolled in the HCV treatment
program as a result of this effort.
Conclusion: Program-wide implementation of the piloted model
showed that this can be scaled up and is effective for re-engaging
people in care. The main challenge in Georgia remains linkage-to-
care, which is essential to meet elimination goals. Innovative
approaches are necessary to reinforce linkage to care. This is
Figure: Analysis of the combined COVID-19 vaccination and HIV and HCV
especially important during the COVID-19 pandemic when there is screening intervention at the MTU in Madrid
an increased need for programs that can re-engage people in HCV Abbreviations: Ab, antibody; HCV, hepatitis C virus; MTU, mobile testing
care. unit.

THU249 Conclusion: Combining HIV and HCV testing with COVID-19

Combined COVID-19 vaccination and HIV and hepatitis C virus vaccination in high-risk individuals at the MTU was effective, with
screening intervention for high-risk populations at a mobile an acceptability rate of 100%, and safe since there were no adverse
testing unit in Madrid, Spain events. The process was also efficient, since it maximised the use of
Jorge Valencia1, Pablo Ryan1, Guillermo Cuevas1, time that participants would have spent waiting for HIV and/or HCV
Julieta Domingorena2, Álvaro Vicario2, Marcela Villota-Rivas3, test results or post-vaccine administration. This intervention can
Jeffrey Lazarus3,4. 1Hospital Universitario Infanta Leonor, Department of serve as an example of a novel model of care to increase HIV and HCV
Internal Medicine, Madrid, Spain; 2SMASD, Harm reduction Unit, screening and linkage to care as well as COVID-19 vaccination in high-
Madrid, Spain; 3Barcelona Institute for Global Health (ISGlobal), risk populations.
Hospital Clínic, University of Barcelona, Barcelona, Spain; 4University of
Barcelona, Faculty of Medicine, Barcelona, Spain THU250
Email: [email protected] A model to eradicate HCV in undocumented migrants and low-
income refugees in Italy
Background and aims: The COVID-19 pandemic has hindered efforts Mariantonietta Pisaturo1, Margherita Macera2, Loredana Alessio2,
to address HIV and hepatitis c virus (HCV) by reducing testing, Stefania de Pascalis2, Lorenzo Onorato1, Maria Stanzione2,
particularly in marginalised groups, who have some of the highest Gianfranca Stornaiuolo2, Vincenzo Messina3, Nicola Coppola1.
rates of HIV and HCV and lowest rates of COVID-19 vaccination. This 1
university of Campania L.vanvitelli, mental health and preventive
study aimed to explore the acceptability of combining HIV and HCV medicine, Naples, Italy; 2Vanvitelli hospital, Naples, Italy; 3Caserta
testing with COVID-19 vaccination in a mobile testing unit (MTU) in Hospital, Caserta, Italy
Madrid, Spain. Email: [email protected]
Method: From 9/28/2021 to 10/26/2021, 101 individuals from high-
risk populations (e.g., homeless people, those with substance use Background and aims: To validate an innovative eradication model
and/or mental disorders, sex workers, refugees, undocumented for HCV infection in undocumented migrants and low-income
migrants) were invited to get the COVID-19 vaccine at the MTU. If refugees living Southern Italy.
HCV antibody (Ab) positive, they were offered HCV-RNA point-of- Method: a prospective, multicenter, collaborative study was started
care testing to confirm active infection. HIV and HCV-RNA-positive in June 2018 with The study was stopped in February 2020 due to the
patients were offered linkage to care. outbreak of SARS-CoV-2 infection in Italy and was resumed in
Results: All 101 participants accepted the combined intervention of February 2021. At the six 1st level centers participating to the study
which 69.3% were male, 30.7% of Spanish origin, most reported a volunteer associations that deal with the first needs of disadvantaged
precarious living situation or being homeless (59.4%) and being people performed the enrolment and the screening for anti-HCV,
unemployed (70.3%), and 28.7% a history of incarceration. The mean HBsAg and anti-HIV; epidemiological data were collected in an
age was 35.6 (SD: 11.9). Of the total, 11.9% reported a previous COVID- electronic database. Anti-HCV-positive subjects were sent to two 3rd
19 diagnosis, none had been vaccinated for COVID-19 and all level centers for the clinical, virological and therapeutic evaluation.
subsequently received the Janssen vaccine without any adverse For the HCV-RNA-positive subjects HCV genotyping and a clinical,
events (Figure). All individuals were tested for HIV and HCV Ab and biochemical and ultrasound staging was performed. The HCV RNA-
8.9% (n = 9) and 14.9% (n = 15) tested positive, respectively. Of those positive subjects have been treated with sofosbuvir-velpatasvir for 12
HIV positive, none were new diagnoses, and most (55.6%, n = 5) had weeks and followed for 12 months from the end of therapy.
abandoned antiretroviral therapy. Of those HCV Ab positive, all were Results: Of the 3, 991 migrants observed in the study period, 3, 897
tested for HCV-RNA and 60.0% (n = 9) tested positive, of which most (97.6%) accepted to be screened. They were young (median age 26
(55.6%, n = 5) reported that the most likely route of transmission was years), predominantly male (85.9%) and came from North Africa
injecting drug use, 44.4% (n = 4) were reinfection cases and 33.3% (n = (3.8%), from Sub-Saharan Africa (68.4%), from Eastern Europe (8.1%),
3) were HIV co-infected. Everyone with an active infection was from Indo-Pakistan (17%) and from other countries (2.7%). Of the 3,
offered linkage to care and to date 44.4% (n = 4) have started 897 enrolled subjects, 185 (4.7%) resulted anti-HCV positive. The
treatment for HCV. The average intervention duration was 20 Figure shows the HCV-cure cascade. All the 185 anti-HCV-positive
minutes (minimum: 7; maximum: 60). subjects were linked to care at 3rdID and tested for HCV RNA and 53
(28.6%) resulted HCV-RNA positive. Of these, 46 (86.8%) started DAA
regimen with sofosbuvir plus velpatasvir (15 with GT 1b, 10 with 1a,
16 with 3, 3 with 4 and 2 with 2). Forty-two completed the follow-up
and 4 was still pending. Of these 42 subjects, 41 (97.6%) showed a

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POSTER PRESENTATIONS
SVR12 and SVR 24, and one dropped-out in follow-up after the stop of and visited the program site for their prescriptions and assessment of
DAA treatment. No subject had adverse event. sustained virological response. The personnel of the program,
including a peer-navigator, assisted patients through all stages.
Results: In total, 1, 101 unique PWID were recruited. The majority of
participants were current PWID (54.0% with injection in the past 30
days), 15.0% were homeless and 79.7% were not linked to OST. Anti-
HCV prevalence was 62.9% and 6.9% were HCV/HIV coinfected. Only
9.7% of anti-HCV (+) PWID reported previous treatment with DAAs.
Chronic HCV prevalence in anti-HCV (+) PWID was 67.6%. Among
PWID which chronic HCV monoinfection, it was possible to identify
the social security number for 97.4% of them, 96.9% were entered to
the national HCV treatment registry to apply for free treatment with
DAAs, 61.8% were linked to HCV care and 53.6% initiated treatment by
September 2021.
Conclusion: Despite the disruptions due to the COVID-19 pandemic,
ALEXANDROS was successful in reaching rapidly a population of
PWID most in need (current injectors, homeless, low OST coverage)
and in offering HCV testing, linkage to care as well as in encouraging
HCV treatment initiation.

THU252
Conclusion: This model seems to be effective to eradicate HCV
SVR4 and SVR12 monitoring by using dried blood spot test: is it
infection among a difficult-to-manage population, such as undocu-
the best alternative for people who use drugs?
mented migrants and low-income refugees
Andrea Herranz1, María Victoria Fernández-Baca2,
THU251 Maria Dolores Macia Romero3, María Paz Díaz2,
Enhancing the cascade of hepatitis C care in community-recruited Maria Carmen Gallegos Alvarez2, Ricardo M Arcay3, Francisco Salvà3,
high-risk people who inject drugs during the COVID-19 pandemic: Adoración Hurtado4, Maria Buti5,6, Àngels Vilella7, Jeffrey Lazarus1,8.
1
the Alexandros program Barcelona Institute for Global Health (ISGlobal), Hospital Clínic,
Vana Sypsa1, Sotiris Roussos2, Efrossini Tsirogianni3,4, University of Barcelona, Barcelona, Spain; 2Hospital Universitari Son
Despina Trafali5, Dimitra Tsiagka5, Athena Gavalaki5, Llàtzer, Microbiology Service, Palma, Spain; 3Hospital Universitari Son
Zafiris Papanikolaou5, Ioanna Papagiouvanni3,5, Athena Tampaki5, Espases, Microbiology Service, Palma, Spain; 4Hospital Can Misses,
Dimitrios Paraskevis2, George Kalamitsis6, Ioannis Goulis7, Microbiology Service, Eivissa, Spain; 5Universitari Vall d’Hebron, Liver
Angelos Hatzakis1,5. 1Medical School of National and Kapodistrian Unit, Barcelona, Spain; 6Instituto Carlos III, CIBER Hepatic and Digestive
University of Athens, Department of Hygiene, Epidemiology and Medical Diseases (CIBERehd), Madrid, Spain; 7Hospital Universitari Son Llàtzer,
Statistics, Athens, Greece; 2Medical School of National and Kapodistrian Department of Gastroenterology, Palma, Spain; 8University of Barcelona,
University of Athens, Department of Hygiene, Epidemiology and Medical Faculty of Medicine, Barcelona, Spain
Statistics, Athens, Greece; 3Fourth Department of Internal Medicine, Email: [email protected]
Hippokratio Hospital, Aristotle University of Thessaloniki; 4Greek Background and aims: People who use drugs (PWUD) are one of the
Organisation Against Drugs; 5Hellenic Scientific Society for the Study of key at-risk population groups for hepatitis C virus (HCV) infection and
AIDS and Sexually Transmitted Diseases and Emerging Diseases, Athens, typically have difficulties in being linked to care and are often lost to
Greece; 6Hellenic Liver Patients Association "Prometheus"; 7Fourth follow-up. The Hepatitis C Free Balears project carries out micro-
Department of Internal Medicine, Hippokratio Hospital, Aristotle elimination strategies to facilitate the screening, treatment and
University of Thessaloniki, Thessaloniki, Greece follow-up of this population.
Email: [email protected] Method: This project has been implemented in 13 of 17 addiction
Background and aims: Despite the availability of effective treatment service centres in the Balearic Islands and consists of four phases: 1)
for chronic hepatitis C, treatment initiation rates remain low among recruitment and HCV screening onsite via a point-of-care anti-HCV
People Who Inject Drugs (PWID) worldwide, especially among those antibody test (Oraquick®) and a dried blood spot (DBS) test or blood
not linked to opioid substitution treatment programs (OST). A analysis to confirm viremia (HCV-RNA) and detect HBsAg and HIV
community-based program was implemented in Thessaloniki (the antigen/antibody; 2) linkage to care; 3) treatment prescription via
second largest city in Greece) during September 2019-August 2021 telemedicine; and 4) monitoring onsite via DBS test of sustained
with the aim to screen for HCV/HIV and improve access to care among virological response (SVR) at 4 and 12 weeks after treatment and for
high-risk PWID. We aim to provide data on the cascade of HCV care in reinfection monitoring after a year. DBS samples are analyzed in the
this population. microbiology laboratories of the two majors Balearic hospitals with
Method: ALEXANDROS was a “seek-test-treat” community-based chemiluminescent technology for the serological determinations and
program where PWID were recruited using peer-driven chain referral reverse transcription-polymerase chain reaction assay for the HCV
with monetary incentives (Respondent-Driven Sampling). The viral load quantification.
program was implemented in five consecutive rounds during Results: Out of 395 recruited patients, 150 (38%) were anti-HCV+, 1
September 2019-August 2021 and PWID could participate in multiple (0.3%) was HBV-Ag+, 25 (6%) were anti-HIV+ and 60 (15%) had an
rounds but only once in each round. Participation included active HCV infection. Of these 60, 43 (73%) initiated treatment, 17
interviewing, counselling, rapid HCV/HIV test and blood sample (28%) are pending and 21 (35%) have already finished it. SVR4 and
collection for testing of anti-HCV (+) participants (HCV genotype/ SVR12 monitoring were performed in 15 (75%) and 5 (25%) of those
biochemical evaluation). PWID eligible for DAAs with available social patients who completed treatment, respectively. Three (14%) SVR4
security number were entered to the national HCV treatment registry and three (14%) SVR12 tests were not performed, as the patients did

S218 Journal of Hepatology 2022 vol. 77(S1) | S119–S388

 POSTER PRESENTATIONS
not show up at the settled appointments, and 3 (14%) SVR4 tests and
13 (62%) SVR12 tests are pending. The 93% (n = 14) SVR4 monitoring
tests and the 100% (n = 5) SVR12 monitoring tests showed undetect-
able HCV-RNA. At the moment, only four patients performed both
SVR4 and SVR12 tests, and all of them had concordant results.
Conclusion: DBS testing has been proven to be an alternative for HCV
screening in PWUD by the Hepatitis C Free Balears team, since it is
performed onsite and facilitates screening of drug users who
otherwise would have not either reached or received care. It is also
useful as a follow-up control method, since it simplifies circuits and
reduces difficulties faced by PWUD. Although the SVR4 and SVR12
control tests results were concordant, more data are needed to know
if the SVR4 control performed with DBS test is an alternative to lost to
follow-up of this vulnerable population.

THU253
Collateral benefit of Georgia national hepatitis C elimination Figure: Study overview of testing and composition and results
program-improving blood transfusion safety in the country of
Conclusion: This project offers a regional model for NAT implemen-
Georgia
tation, demonstrating the feasibility and clinical utility in a
Maia Alkhazashvili1, Evan Bloch2, Shaun Shadaker3,
nationwide blood screening program. NAT is resource intensive and
Tinatin Kuchuloria4, Tamar Samadashvili1, Vladimer Getia1,
expensive to implement system-wide, and may not be feasible in all
Alexander Turdziladze1, Jan Drobeniuc3, Paige A Armstrong3,
settings. Balancing cost and yield is important, and countries with
Amiran Gamkrelidze1. 1National Center for Disease Control and Public
high prevalence may benefit more from NAT testing implementation.
Health of Georgia, Tbilisi, Georgia; 2Johns Hopkins School of Medicine,
Baltimore, United States; 3Centers for Disease Control and Prevention, THU254
Atlanta, United States; 4The Task Force for Global Health, Tbilisi, Georgia Outcomes of a community led comprehensive HCV and HBV care
Email: [email protected] provision model, including same-day "test and treat" to facilitate
Background and aims: In 2015, a national seroprevalence survey micro-elimination of HCV among people who inject drugs in
identified blood transfusion as a risk factor for transmission of Manipur, India
hepatitis C virus (HCV) and hepatitis B virus (HBV) in Georgia. Based Khumukcham Lokeshwar Singh1, Thangjam Dhabali2,
on recommendations from the HCV elimination program’s Technical Rajkumari Rosie3, Rajkumar Nalinikanta4,
Advisory Group, the EU-funded Technical Assistance and Information Samurailatpam Rajesh Sharma1, Sanjay Sarin5, Giten Khwairakpam6,
Exchange (TAIEX) with the support of the Global Fund, centralized Sonjelle Shilton5. 1Jawaharlal Nehru Institute of Medical Sciences,
nucleic acid testing (NAT) was implemented at the Richard Lugar Manipur, India; 2Babina Diagnostics, Manipur, India; 3Department of
Center for Public Health Research at the National Center for Disease Health Services, Government of Manipur, India; 4CoNE, Manipur, India;
5
Control and Public Health, Tbilisi, Georgia. FIND, the global alliance for diagostics, Geneva, Switzerland; 6TREAT
Method: One year of blood donor screening data (January-December, Asia/amfAR, Thailand
2020) was analysed from the Unified Electronic Donor Database. Two Email: [email protected]
samples were collected from all donors, one for primary serological Background and aims: The prevalence of hepatitis C virus (HCV)
testing by blood centers, and a second for NAT using the infection among people who inject drugs (PWID) in the state capital
Procleix®Ultrio Elite Assay (multiplex for HCV, HBV, and HIV). In of Manipur, India, is 65%; however, access to and uptake of HCV care is
the event of a discordant result between NAT and serology (NAT poor, largely due to lengthy pre-treatment processes. We piloted a
positive, serology negative), additional discriminatory testing was community-led, comprehensive, simplified hepatitis care model that
performed. A subset of the discordant samples was retested using includes same-day HCV testing and treatment initiation (“test and
ARCHITECT i2000SR immunoassay for HBV surface antigen, HBV core treat”) at drug rehabilitation centres in Manipur, to expand access to
antibody, HCV antibody, and HIV 1/2 Ab/Ag. care for chronic hepatitis.
Results: A total of 54, 116 donations representing 39, 164 unique Method: Participants were screened using HCV antibody (Ab) and
donors were evaluated. Overall, 671 donors (1.7%) tested positive for hepatitis B virus (HBV) surface antigen (HBsAg) rapid diagnostic tests.
at least one infectious marker by serology or NAT. Sixty donations Positive HCV Ab samples were tested using a point of care platform for
were serology/NAT discordant (serology-/NAT+). Discordance was HCV RNA (Molbio TrueNat). HCV RNA-positive participants eligible
more likely among females vs. males (adjusted odds ratio [aOR] 2.06; for treatment under national guidelines were initiated on sofosbuvir
95% confidence interval [95%CI]: 1.05–4.05), paid (aOR 10.15; 95%CI: and daclastasvir on the same day and are followed until tests of cure
2.80–36.86) or voluntary (aOR 4.30; 95%CI: 1.27–14.56) vs. replace- (SVR). Participants who were HBsAg negative received HBV vaccine
ment donors, and repeat vs. first time (aOR 13.98; 95%CI: 4.06–48.12) per the WHO rapid regimen. Positive HBsAg samples were sent to a
donors. After repeat serologic testing was performed to confirm referral lab for HBV DNA tests; and will be referred for treatment per
blood center reported results, a total of 12 donations (6 HBV+ national guidelines.
donations, 5 HCV+ donations and 1 HIV+) were deemed NAT yield and Results: Between 12–22 November 2021, 133 individuals were
would not have been detected with serology. Out of the total 54, 116 approached, of whom 103 (77%) were eligible and all consented to
donations, the final NAT yield rate was 1 in 9, 019 for HBV, 1 in 10, 823 participate. To date, 98 (95%) participants have been screened; all
for HCV, and 1 in 54, 116 for HIV. were male and identified as PWID and had a median age of 27 (IQR
22–32) years. A total of 39 (40%) were HCV Ab positive; all were tested
for HCV RNA, of whom 24 (61.5%) were HCV RNA positive. Of those
with viremia, 23 (96%) were initiated on treatment on the same day,

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POSTER PRESENTATIONS
with 1 awaiting HBV DNA results to be initiated on treatment. The THU256
median time from screening to HCV treatment initiation was 8 hours Peer-led hepatitis C services reach poorly served populations at
and 12 minutes (range 6:03–9:58). First SVR tests for sustained scale: a model for tackling health inequalities
virologic response are due in April 2022. A total of 6 (6.1%) were Leila Reid1, Rachel Halford1,2, Stuart Smith1, Sean Cox1. 1The Hepatitis C
HBsAg-positive. Of the 92 participants with negative HBsAg tests, 89 Trust, London, United Kingdom; 2World Hepatitis Alliance, Geneva,
(97%) had not previously been vaccinated and all have completed at Switzerland
least 1 dose of the HBV vaccine. Email: [email protected]
Conclusion: Preliminary results show that community led compre-
Background and aims: England’s approach to HCV elimination
hensive hepatitis care which incorporates same day “test and treat”
for HCV is feasible and effective in this context. HBV screening includes significant involvement-including leadership-from people
with lived experience of hepatitis C. This is unique worldwide, and is
identified a large proportion who had not been vaccinated. Additional
proving very effective, in particular in engaging, diagnosing and
follow-up and implementation research would inform how this
model could be replicable in other settings to increase equity in treating groups typically excluded from health services. This large-
scale, national programme bears out emerging evidence on peer-
access to HCV and HBV screening, treatment, and prevention.
based models for tackling health inequalities.
THU255 Method: England’s elimination programme tasked drug companies
A novel hepatitis C intervention in Denmark to test and treat to not only treat but find people with HCV. This responds to a key
people who inject drugs challenge in the UK and many other countries: most people with HCV
Jeffrey Lazarus1,2, Anne Øvrehus3, Jonas Demant4, are hard to engage and undiagnosed.
Louise Krohn-Hehli5, Jannet van der Veen4, Nina Weis5,6. 1Barcelona Led by The Hepatitis C Trust, a national charity led by people with
Institute for Global Health (ISGlobal), Hospital Clínic, University of lived experience, England’s HCV peers work together nationally as
Barcelona, Barcelona, Spain; 2University of Barcelona, Faculty of well as forming part of local NHS HCV delivery networks to engage
Medicine, Barcelona, Spain; 3Odense University Hospital, Odense, marginalised populations. Launched in 2019, the model has three
Denmark; 4Users Academy, Copenhagen, Denmark; 5Copenhagen core components:
University Hospital, Department of Infectious Diseases, Hvidovre, Peer Support: at its core, HCT provide patient support from another
Denmark; 6University of Copenhagen, Department of Clinical Medicine, person (a peer) with lived experience of HCV, drug use and/or prison.
Faculty of Health and Medical Sciences, Copenhagen, Denmark The Peer provides a bespoke approach, support from testing to
Email: [email protected] diagnosis to treatment and with other conditions.
Partnership: collaboration is paramount to improving systems.
Background and aims: Providing testing and treatment for hepatitis Working closely with services and clinicians, HCT’s peer workers
C (HCV) for people who inject drugs (PWID) is critical in eliminating shorten pathways, ensure accessible clinics, improve patient under-
HCV, but reaching this population with traditional healthcare services standing, and move services ever closer to those who need them
can be challenging. Combining point-of-care (PoC) testing with peer most.
support and counselling is a model of care (MoC) that can be effective Patient-centred innovation: developed from patient feedback, HCT
for PWID. This study aims to investigate if a peer-led mobile van places the needs of people with HCV at the centre, regularly seeking
equipped with rapid PoC tests for HCV antibodies (Ab) and RNA could feedback, adapting and innovating to reach new populations.
simplify testing and link PWID to care and treatment. Results: Since 2019 HCT’s peer teams have:
Method: In Copenhagen, Denmark, a peer-led mobile service engaged almost 75, 000 people at risk of HCV: 33, 324 through
providing counselling, Ab testing (In-Tec™) and linkage to standard outreach and 39, 333 in prisons.
of care was equipped with a PoC HCV-RNA finger-prick test (Xpert Trained 15, 401 health, care and prison staff
HCV Viral Load Finger-Stick Point-of-Care Assay, Cepheid). Eligible tested 18, 467 people in the community, and 17, 691 in prison. 15% of
HCV-RNA+ individuals were offered assisted referral to a fast-track community tests find markers for current/past HCV ( prison data is
hospital clinic for evaluation and treatment, with peer support being collated).
available if needed. Received 6, 517 referrals for support
Results: From 1 May 2019 to 25 October 2021, 1013 people were 62% have started treatment, and 94% for whom an SVR has been
tested for HCV-RNA and 10.2% (n = 103) were positive. Nine obtained (n = 1018) are cured
additional individuals with HCV infection contacted the service to Feedback is consistently positive; patients highlight one to one
be linked to care. Of the 112 individuals with chronic HCV infection, relationships, shared experience and trust as pivotal to engagement.
72.3% (n = 81) were evaluated for treatment at the hospital clinic, of Conclusion: HCT’s highly assertive outreach, partnership-based
whom 86.4% (n = 70) initiated direct-acting antiviral therapy and 3.7% model has seen peers embedded in NHS and prison systems. Links
(n = 3) are waiting to initiate treatment. Major reasons for not being across the peers-who work as part of regional teams and as a national
evaluated for treatment included being undocumented (38.7%; n = body-generates innovation, rapid sharing of good practice and
12) and being lost to follow-up (32.3%; n = 10). Among those who excellent reach.
initiated treatment, 20.0% (n = 14) were connected to drug addiction People experiencing marginalisation and often very complex needs
treatment services. The peer-led service assisted all treated with engage with the peer model, often their first experience of sustained
communication with the hospital nurse, collection of treatment service engagement.
medicine and accompaniment to follow-up visits. This is an effective, transferable and likely cost-effective approach (a
Conclusion: We found that a peer-led mobile PoC service is an MoC study is planned), which stimulates both system-level and individ-
that can engage PWID in HCV testing and link them to treatment, ual-level change, both positively impacting health inequalities.
even during the COVID-19 pandemic. We identified being an
undocumented migrant as a major cause for not accessing care.
This poses a challenge for HCV elimination in Denmark due to the risk
of onward transmission. Next steps include engaging with health
authorities to provide care for these migrants.

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 POSTER PRESENTATIONS
THU257 recently seroconverted and reinfected cases in persons who inject
Cost-effectiveness of integrated treatment for hepatitis C virus drugs (PWID) in selected Georgian harm reduction (HR) sites.
among people who inject drugs in Norway: an economic Method: GHOST uses next-generation deep sequencing of Hyper
evaluation of the INTRO-HCV trial Variable Region 1 (HVR1) of HCV. Genotypes of the HCV strains were
Aaron G. Lim1, Christer F. Aas2,3, Ege Su Çağ lar2,3, Jørn-Henrik Vold2,3, determined by HVR1 sequence data analysis. Two HR sites in the
Lars Thore Fadnes2,3, Kjell Arne Johansson2,3, Peter Vickerman1. cities of Tbilisi and Zugdidi were selected. Samples were collected
1
University of Bristol, Population Health Sciences, Bristol Medical School, from HR beneficiaries with documented reinfection or seroconver-
United Kingdom; 2Haukeland University Hospital, Norway; 3University sion. All participants provided written informed consent for
of Bergen, Norway participation and completed a questionnaire on the relevant
Email: [email protected] epidemiological information.
Overall, 58 people with a history of injecting drugs were invited to
Background and aims: People who inject drugs (PWID) have the participate, including 33 (57%) in Tbilisi and 25 (43%) in Zugdidi; 52%
highest burden of hepatitis C virus (HCV) globally, but are often agreed to participate (n = 30/58).
undertreated due to stigma and lack of access to services. Results: Among the 30 enrolled participants, 17 (57%) had HCV
Implementing efficient treatment algorithms for PWID is required reinfection and 13 (43%) seroconverted during the observation. In the
to reach this population. The INTRO-HCV randomised control trial 6 months prior to the study, 27 participants (90%) reported injecting
conducted in Norway over 2017–2019 found that integrating HCV drugs and 3 (10%) reported needle sharing. Among reinfected
treatment, using direct-acting antivirals (DAAs), into community participants (n = 17), one (6%) received a blood transfusion, 13
settings improved treatment outcomes, but did not compare the (76.4%) had an invasive medical procedure, and 4 (23.5%) were
longer-term health economic benefits. This study analyses the cost- incarcerated. Among participants with new infection, 5 (38.4%)
effectiveness of integrated treatment compared to the standard received blood transfusion, 8 (62%) had an invasive medical
referral pathway of care. procedure more than 1 year ago, and 5 (38%) were incarcerated
Method: A health state transition Markov model of HCV disease prior to seroconversion.
progression and treatment was developed based on the INTRO-HCV Genotype 1a was predominant (n = 8, 44%), followed by 2k/1b
trial. Treatment cost and outcome data were analysed from the trial. recombinant (n = 4, 22%), 2a (n = 3, 17%), 2c (n = 2, 11%), and 1b (n =
Parameters related to disease progression came from published 1, 6%). Using GHOST transmission detection module, a transmission
literature. The incremental cost-effectiveness ratio (ICER) was cluster consisting of 2 participants reinfected with HCV genotype 2c
calculated in terms of cost per quality-adjusted life year (QALY) was identified in Tbilisi. Although no cluster was found in Zugdidi
gained from the health provider’s perspective over a lifetime horizon alone, a reinfected participant from Zugdidi and seroconverted
and compared against a conventional (NOK 500, 000) willingness-to- participant from Tbilisi formed another small transmission cluster.
pay (WTP) threshold for Norway. Probabilistic and univariate The Tbilisi participant carried mixed HCV genotype infection.
sensitivity analyses were undertaken. Additionally, we found two mixed infections, one in each city,
Results: Preliminary results suggest that compared to the standard indicating a very high rate of exposure.
treatment pathway, integrated treatment resulted in an ICER of NOK Conclusion: This is the first molecular epidemiological report among
305, 000 per QALY gained, with an 80.7% probability of being cost- the high risk PWID population of Georgia using GHOST. The detected
effective against the conventional WTP threshold. Sensitivity transmission clusters and mixed genotype infections indicate a very
analyses suggest that the cost of DAA medications strongly affected high rate of exposure in studied communities. GHOST can be utilized
the ICER, with a 30% lower DAA price resulting in integrated for surveillance for early intervention on networks as well as
treatment having an ICER of NOK 176, 000 per QALY gained and a successfully applied to other infectious diseases including HBV,
95.8% probability of being cost-effective. A 60% lower DAA price led to HAV, and HIV.
an ICER of NOK 10, 400 per QALY gained, with a 99.8% probability of
being cost-effective and a 42.4% probability of being cost-saving. THU259
Conclusion: Integrating HCV treatment for PWID in community Prevalence and predictors of significant liver fibrosis : a
settings is likely to be highly cost-effective and may become cost- population-based cross-sectional study
saving even with moderate reductions in DAA price. Aayushi Rastogi1, Manya Prasad1, Umesh Kapil1, Ekta Gupta2,
Sherin Sarah Thomas3, Chhagan Bihari4, Shiv Kumar Sarin5. 1Institute
THU258
of Liver and Biliary Sciences, Epidemiology, Delhi, India; 2Institute of
Characterization of HCV recent infections and re-infections
Liver and Biliary Sciences, Virology, Delhi, India; 3Institute of Liver and
among high-risk population from Georgia using global hepatitis
Biliary Sciences, Biochemistry, Delhi, India; 4Institute of Liver and Biliary
outbreak and surveillance technology
Sciences, Pathology, Delhi, India; 5Institute of Liver and Biliary Sciences,
Adam Kotorashvili1, Amiran Gamkrelidze1, Nato Kotaria1,
Hepatology, Delhi, India
Maia Tsereteli1, Ana Papkiauri1, Ketevan Galdavadze1,
Email: [email protected]
Maia Alkhazashvili1, Paata Imnadze1, Tinatin Kuchuloria2,
Lilia Ganova-Raeva3, Sumathi Ramachandran3, Saleem Kamili3, Background and aims: Liver fibrosis is one of the most common
Shaun Shadaker3, Paige A Armstrong3, Yury Khudyakov3. 1National chronic liver diseases worldwide caused due to alcohol consump-
Center for Disease Control and Public Health (NCDC), Tbilisi Georgia, tions, viruses, diabetes and other metabolic disorders. Steatosis is a
Georgia; 2The Task Force for Global Health, Tbilisi, Georgia; 3Centers for common feature of several liver diseases resulting from different
Disease Control and Prevention (CDC), Atlanta, GA, United States etiologies. Early detection of liver fibrosis can help timely interven-
Email: [email protected] tions to reduce progression to cirrhosis and hepatocellular carcinoma.
Aim: The present study was aimed at assessing the prevalence and
Background and aims: Global Hepatitis Outbreak and Surveillance predictors of significant liver fibrosis among asymptomatic adults in
Technology (GHOST), is a novel technology that identifies transmis-
general population.
sion links between specimens, creating a graphic display. GHOST was Method: A cross-sectional study was undertaken between 26 June
developed by the Centers for Disease Control and Prevention, and the 2021 to 15 November 2021 in the randomly selected primary health
National Center for Disease Control and Public Health of Georgia
clinics of Delhi; the Mohalla Clinics. A mobile screening unit with
became the first GHOST center outside of the United States. trained research staff screened the population in the catchment areas
The study aimed to gain insight into the variability of the hepatitis C
of the clinics. A brief questionnaire was administered which assessed
virus (HCV) and potential transmission networks using GHOST in
the medical and family history, information on life style factors such

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POSTER PRESENTATIONS
as physical activity and alcohol consumption of the participants. In patients with respiratory disease, but it is unclear if it is an
addition, anthropometric measurements, transient elastography and independent prognostic factor. Our aim is to determine whether
blood samples were collected for biochemical tests such as ALT, AST, ALFT have a direct impact on the prognosis of these patients.
total bilirubin, cholesterol, triglycerides and fasting blood sugar in Method: A single-center, retrospective study of COVID-19 hospita-
participants who volunteered for screening. Liver stiffness measure- lized patients with respiratory disease from February 15th, 2020, to
ment (LSM) of ≥8kPa was used to define significant liver fibrosis. February 28th, 2021. Patients with already known liver diseases were
Univariable and multivariable analysis was done to determine the excluded. ALFT were defined as elevated total bilirubin (TBIL),
factors associated with liver fibrosis. aspartate transferase (AST), alanine transferase (ALT), alkaline
Results: A total of 2863 participants were screened with mean age of phosphatase (ALP) and/or gamma-glutamyltransferase (GGT) above
43 ± 13.6 years, with 56% being males. Mean fasting blood sugar was the upper limit of normality (ULN) in our laboratory.
114.5 ± 49.78 mg/dl whereas median triglyceride was found to be COVID-19 respiratory disease was classified as mild (no pneumonia),
130.2 mg/dl (IQR: 95.4–181.2). The prevalence of significant liver moderate ( pneumonia) and severe ( pneumonia with respiratory
fibrosis in the general population was 7.6% (95%CI:6.65%-8.64%). The failure). Worsening of respiratory disease was defined as mild/
following factors were found to have a statistically significant ( p < moderate to severe respiratory disease progression or death. An
0.001) association with significant liver fibrosis after adjusting for association of ALFT with moderate/severe disease, worsening of
other factors: age (aOR:1.03; 95%CI: 1.01–1.04), male gender respiratory disease, hospital stay, need for intensive care unit (ICU)
(aOR:1.73; 95%CI: 1.22–2.43), diabetes (aOR:3.15; 95%CI: 2.23– admission and mortality was assessed. Statistical analysis was based
4.44), morbid obesity (aOR:7.53; 95%CI: 2.28–24.8) as seen in Table 1. on T-test and logistic regression. They included an adjusted multi-
variant model for age, sex, Charlson Comorbidities Index (CCI) and
liver steatosis and fibrosis prior to hospital admission (defined by
Hepatic Steatosis Index and FIB-4 scores respectively). Significance
was set at p <0.05.
Results: The data of 2075 patients (51.5% males), average age 66.5 (SD
17.8) years, were analyzed. Despite excluding patients with already
known liver diseases, the overall prevalence of liver steatosis was
57.8% and that of fibrosis was 18.4%. 1225 patients (51.9%) presented
ALFT at hospital admission and 1572 (75.8%) during hospital stay.
ALFT were significantly associated with moderate/severe disease,
likelihood of worsening of respiratory disease, longer hospital stay (8
vs 11.9 days, p < 0.001) and higher rate of ICU admission, but not with
higher mortality. Higher FIB-4 was also significantly associated with
worsening of respiratory disease (OR = 1.98, p < 0.001). Age and CCI
were associated with higher mortality. Female sex was a protective
factor against unfavorable events. Among ALFT, TBIL was the most
associated with worsening of respiratory disease (OR = 2.4, p < 0.001)
and ALT with ICU admission (OR = 1.42, p < 0.001) and mortality (OR
= 1.03, p = 0.04). The exclusion of patients with elevated ALT/AST prior
to admission did not change the results.

Conclusion: There is high prevalence of fibrosis in the general

population screened for the present study. There is a need for large
scale public health interventions with high-risk approach to detect
and treat liver fibrosis and prevent its complications.

THU261
Prognostic value of liver function test for COVID-19 hospitalized
patients with respiratory disease
Carlos Alventosa Mateu1, Elena Guillen Botaya1,
Cecilia Albert-Antequera2, Irene Perez Alvarez1,
Alejandro Fernandez Soro1, Eva Sanchez Ramos1, Salvador Benlloch2,
Juan Jose Urquijo Ponce1, Francesc Puchades Gimeno3,
Francisco Sanz Herrero4, Miguel García Deltoro5,
Mercedes Latorre Sánchez1, Inmaculada Castelló Miralles1,
Dolores Ocete Mochon6, Concepcion Gimeno Cardona6,
Moises Diago1. 1Consorcio Hospital General Universitario Valencia,
Digestive Diseases, Valencia, Spain; 2Hospital Arnau de Vilanova, Figure: Association of ALFT with the different clinical events.
Digestive Diseases, Valencia, Spain; 3Consorcio Hospital General
Universitario Valencia, Internal Medicine, Valencia, Spain; 4Consorcio Conclusion: According to our study, ALFT can be considered as an
Hospital General Universitario Valencia, Respiratory Diseases, Valencia, independent risk factor for worse evolution in COVID-19 hospitalized
Spain; 5Consorcio Hospital General Universitario Valencia, Infectious patients with respiratory disease. Liver fibrosis had only influence in
Diseases, Valencia, Spain; 6Consorcio Hospital General Universitario worsening of respiratory disease.
Valencia, Microbiology, Valencia, Spain
Email: [email protected]
Background and aims: Abnormal liver function tests (ALFT) have
been associated with worse evolution in COVID-19 hospitalized

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 POSTER PRESENTATIONS
THU262
Effectiveness of COVID-19 viral vector vaccine Ad.26.COV2.S
vaccine and comparison with mRNA vaccines in patients with
cirrhosis
Binu John1,2, Akash Doshi3, Yangyang Deng4, Natalie Mansour2,
A. Sidney Barritt5, Andrew Moon5, George Ioannou6, Paul Martin1,
Hann-Hsiang Chao7, Tamar H Taddei8, David Kaplan9,
Bassam Dahman4. 1University of Miami Hospital And Clinics | UHealth
Tower, Miami, United States; 2Miami VA Medical Center, Miami, United
States; 3University of Miami, Coral Gables, United States; 4Virginia
Commonwealth University Health, Richmond, United States; 5University Conclusion: In participants with cirrhosis, the Ad.26.COV2.S demon-
of North Carolina at Chapel Hill, Chapel Hill, United States; 6University of strated a 64% effectiveness against COVID-19, and a 74% effectiveness
Washington, Seattle, United States; 7Hunter Holmes McGuire VA Medical against severe or critical COVID-19, similar to that associated with
Center, Richmond, United States; 8Yale University, New Haven, United mRNA vaccines.
States; 9University of Pennsylvania, Philadelphia, United States
Email: [email protected] THU263
Background and aims: Viral vector COVID-19 vaccines have been Humoral, cellular, clinical responses and safety to SARS-CoV-2
administered more commonly worldwide but their effectiveness in messanger RNA vaccines in patients with compensated and
participants with cirrhosis is unknown. We explored the effective- decompensated cirrhosis: a long-term single center prospective
ness of vaccination with the Janssen Ad.26.COV2.S compared to the study
mRNA Pfizer BNT162b2 or Moderna 1273-mRNA vaccine in partici- Massimo Iavarone1, Giulia Tosetti1, Floriana Facchetti1, Matilde Topa1,
pants with cirrhosis. Andrea Lombardi2, Roberta D’Ambrosio1, Elisabetta Degasperi1,
Method: This was a test-negative case control study among Alessandro Loglio1, Chiara Oggioni3, Alessandra Bandera2,
participants with cirrhosis. This study design is widely used in Andrea Gori2, Ferruccio Ceriotti4, Luigia Scudeller5,
evaluations of vaccine effectiveness and has the advantage of Antonio Bertoletti6, Pietro Lampertico1. 1Foundation IRCCS Ca’ Granda
minimizing biases associated with access to vaccination or health Ospedale Maggiore Policlinico, Division of Gastroenterology and
care. Cases were those who were SARS CoV2 PCR positive, controls Hepatology, MILANO, Italy; 2Foundation IRCCS Ca’ Granda Ospedale
were those who tested negative during the study period between Maggiore Policlinico, Division of Infectious Disease; 3IRCCS Humanitas
March 15, 2021 and October 3, 2021. Participants who did not Research Hospital, Quality and Patient Safety Unit, Rozzano, Italy;
4
undergo SARS CoV2 PCR testing, who had COVID-19 before the study Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Clinical
period, or received a liver transplant, were excluded. COVID-19 was Laboratory, MILANO, Italy; 5IRCCS Azienda Ospedaliero-Universitaria di
classified based on individual chart review using the National Bologna, Research and Innovation Unit, Bologna, Italy; 6Duke-NUS
Institute of Health (NIH) COVID-19 severity scale as asymptomatic, Medical School, Programme in Emerging Infectious Diseases, Singapore,
mild, moderate, severe or critical illness. Singapore
Propensity score matching was used to match test positive cases and Email: [email protected]
test negative controls. The propensity score of having COVID-19 were
Background and aims: SARS-CoV-2 mRNA vaccines have been
derived from a logistic regression that adjusted for the participant’s
approved to prevent COVID-19 in the general population but little is
sex, age, date of testing, race/ethnicity, location, alcohol as the
known in patients with cirrhosis. We assessed immunogenicity,
etiology of liver disease, body mass index (BMI), diabetes mellitus,
effectiveness and safety of vaccines in patients with compensated and
current tobacco use, current alcohol use, co-morbidities, and the
decompesated cirrhosis with different aetiologies.
Child Turcotte Pugh score. Multinomial logistic regression models
Method: This is a prospective single center study assessing humoral
were fit for COVID-19, to assess the adjusted effect from vaccination
and cellular response, incidence post-vaccination SARS-CoV-2 infec-
with either the Ad.26.COV2.S or the mRNA-1273 or BNT162b2
tions and adverse events to mRNA vaccines in cirrhotics compared to
vaccines.
healthy controls, according to previous SARS-CoV-2 infection.
Results: A total of 955 cases and 955 matched controls were included
Antibodies against the spike- and nucleocapside-protein (anti-S
in the study population. The two groups were well matched to all
and anti-N) of SARS-CoV-2 were tested at baseline, 21 days after the
baseline characteristics.
first and 21 days after the second doses and during follow-up in both
The Ad.26.COV2.S vaccine had an effectiveness of 64% against COVID-
patients and healthy controls. Longitudinal assessment of quantity of
19 (adjusted Odds Ratio [aOR] 0.36, 95% CI 0.20–0.62, p = 0.005).
spike-specific T-cells was conducted by a test based on the
Effectiveness was lowest with asymptomatic illness (aOR 0.42, 0.18–
stimulation of whole blood with peptides covering the SARS-CoV-2
0.73, p = 0.03), and higher against mild (aOR 0.36, 0.15–0.63, p =
spike protein, followed by cytokine (IFN-γ, IL-2) measurement. Side
0.006), moderate (aOR 0.33, 0.14–0.49, p = 0.002) and severe/critical
effects after vaccination were recorded.
(aOR 0.24, 0.08–0.83, p = 0.04) COVID-19. In the same period, mRNA
Results: 182 cirrhotics (61 years, 75% males, 45% viral-related, 74%
vaccines had a 73% effectiveness against overall COVID-19 (aOR 0.27,
Child-Pugh A, 31% HCC) and 38 healthy unmatched subjects were
0.19–0.37, p < 0.0001), progressively higher from asymptomatic (aOR
enrolled. 15% cirrhotics and 32% controls had previously SARS-CoV-2
0.38, 0.23–0.59, p = 0.0004) to mild (aOR 0.29, 0.18–0.42, p < 0.0001),
infection. In both groups, individuals with previous SARS-CoV-2
moderate (aOR 0.27, 0.18–0.36, p < 0.0001), and severe or critical
infection showed higher anti-S titres at all time points after
illness (aOR 0.17, 0.06–0.32, p < 0.0001). There were no statistically
vaccination. Among COVID-19 naïve subjects, patients with cirrhosis
significant differences between the viral vector and mRNA vaccines.
showed significantly lower anti-S titres compared to controls [998.5
(0.4–12, 500) vs 1, 520 (259–12, 500) U/ml, p = 0.048]. In COVID-19
naïve cirrhotics, anti-S titres significantly decreased after a median of
133 (70–182) days [536 (0.4–8, 777) U/ml, p < 0.0001].
Decompensated cirrhotics showed lower anti-S titres compared to
compensated ones [632 (0.4–12, 500) vs 1, 377 (0.4–12, 500) U/ml,
p = 0.028]. By multivariable analysis in COVID-19 naïve cirrhotics,
independent predictors of lower anti-S titres after second dose, were:
active HCC, immunocompromised conditions, Pfizer vaccine and

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POSTER PRESENTATIONS
lower anti-S after first dose. The spike-specific T cell response was THU265
evaluated in 14 cirrhotics, showing a heterogeneous magnitude of Detection of microplastics in cirrhotic liver tissue
response, but on average the quantity and kinetics of decline of the Thomas Horvatits1, Matthias Tamminga2, Beibei Liu1,
spike-specific cellular responses diverged in cirrhotics compared to Marcial Sebode1, Klaus Püschel3, Ansgar Lohse1, Samuel Huber1,
controls, with lower concentrations of both IFN-γ and IL-2, at all time- Elke Fischer2. 1University Medical Center Hamburg-Eppendorf,
points. During follow-up, 4/133 (3%) COVID-19 naïve cirrhotics tested I. Department of Medicine, Gastroenterology and Hepatology, Hamburg,
positive for anti-N: all asymptomatic, no hospitalization required. Germany; 2University of Hamburg, Center for Earth System Research and
Neither unexpected nor severe adverse events emerged in our Sustainability (CEN), Hamburg, Germany; 3University Medical Centre
patients. Hamburg-Eppendorf, Institute of Legal Medicine, Hamburg, Germany
Conclusion: In COVID-19 naïve patients with cirrhosis undergoing Email: [email protected]
SARS-CoV-2 mRNAvaccine, humoral and cellular responses appeared
Background and aims: The contamination of ecosystem compart-
suboptimal compared to healthy controls, but the rates of post
vaccination infection remained low. The response after the third dose ments by microplastics (MPs) is an ubiquitous problem. Tissue
accumulation of MPs has been observed in mice, and recently MPs
will be also presented.
have been observed in human stool and placenta. However, whether
THU264 MPs accumulate in human tissues, and the resulting consequences
The protective role of dairy protein on sarcopenic obesity in are still unclear. Aim of this study was to examine various human
middle-aged and older women: a community-based, 12-year, tissue samples for the presence of MPs, and to determine whether
prospective cohort study MPs may deposit in the liver, kidney or spleen.
Jun-Hyuk Lee1, Joo Hyun Oh2, Sang Bong Ahn2, Huiyul Park3, Method: This proof-of-concept case series was conducted in
Joo Hyun Sohn4, Bo-Kyeong Kang5, Mi Mi Kim5, Chul-min Lee5, Hamburg, northern Germany, Europe. Tissue samples from 6 patients
Dae Won Jun6, Eileen Yoon6, Hyo Young Lee7, Hyunwoo Oh7. 1Nowon with liver cirrhosis and portal hypertension and from 7 individuals
Eulji Medical Center, Eulji University School of Medicine, Department of without underlying liver disease were assessed. A reliable method for
Family medicine, Seoul, Korea, Rep. of South; 2Nowon Eulji Medical detection of MP particles in human tissue was developed. A total of 17
Center, Eulji University School of Medicine, Department of Medicine, samples (11 human liver, 3 kidney and 3 spleen samples) were
Seoul, Korea, Rep. of South; 3Uijeongbu Eulji Medical Center, Department analysed according to the final protocol. Chemical digestion of the
of Family medicine, Gyeonggi-do, Korea, Rep. of South; 4Hanyang tissue samples, staining with Nile red, subsequent fluorescent
University Guri Hospital, Hanyang University College of Medicine, microscopy and Raman spectroscopy were performed. Procedural
Department of Medicine, Gyeonggi-do, Korea, Rep. of South; 5Hanyang blanks were processed and analysed during each series of analyses.
University College of Medicine, Department of Radiology, Seoul, Korea, Shape, size and types of MP polymers were assessed in all tissue
Rep. of South; 6Hanyang University College of Medicine, Department of samples.
Medicine, Seoul, Korea, Rep. of South; 7Uijeongbu Eulji Medical Center, Results: Considering the limit of detection, all samples (liver, spleen,
Department of Medicine, Gyeonggi-do, Korea, Rep. of South kidney) from patients without liver disease tested negative for MPs
Email: [email protected] (n = n.s.), whereas MPs in liver samples from patients with cirrhosis
tested positive and MP concentrations (5 to 12 particles per g tissue)
Background and aims: Changes in body composition during aging were significantly higher than those from blank samples (n = 6, p =
include decreased muscle mass and increased fat mass, especially in 0.009, α = 0.05). Six different microplastic polymers ( polystyrene
women. Individuals with sarcopenic obesity (SO) could be at higher (PS), polyvinyl chloride (PVC), polyethylene terephthalate (PET),
risk of morbidities and mortality than those with either sarcopenia or polymethyl methacrylate (PMMA), polyoxymethylene (POM), and
obesity alone. Dairy products, which contain whey protein and all polypropylene (PP)) ranging from 4 to 30 µm in size have been
essential amino acids, could have a beneficial role in preserving detected, see figure 1.
muscle mass and reducing obesity. We aimed to analyze the effect of
dairy protein on the development of SO in women using a large-scale,
community-based prospective cohort.
Method: Our analysis included 4251 women from the Korean
Genome and Epidemiology Study. Participants were categorized
into three groups by the tertile of dairy protein intake, which was
assessed using a semi-quantitative 103-food item food frequency
questionnaire. Appendicular skeletal muscle mass was estimated
using the anthropometric equation. Obesity was defined as a body
mass index of 25 kg/m2 or greater. Multiple Cox hazard regression
analysis was conducted to examine associations between dairy
protein intake and incident SO.
Results: During follow-up (mean, 9.6 years), 280 women newly
developed SO. Using Cox proportional regression models, the hazard
ratios (95% confidence interval) for incident SO of the middle and
highest tertiles were 0.93 (0.70–1.24) and 0.72 (0.52–0.98) compared
with lowest tertile after adjusting for confounding variables.
Conclusion: These findings indicate high dairy protein intake is
inversely related to SO development in Korean women. Dairy protein
intake could be an effective strategy to prevent incident SO.
Keywords: dairy protein; sarcopenia; obesity; sarcopenic obesity;
women

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 POSTER PRESENTATIONS
Conclusion: This is the first study, assessing MPs in different types of
human tissues. MPs were found only in liver tissues from patients
with cirrhosis. Hepatic deposition may be the consequence of
impaired intestinal barrier function due to portal hypertension and
portal enteropathy. Future studies on the possible effects on human
health are urgently needed.
Examples of MP particles found in human tissue samples displayed as
fluorescence images (left column) and true colour microscope images
(mid column) as well as related Raman-spectra. White scale bar
indicates 10 µm, library reference spectra are displayed in red,
particle spectra are given in green. S/N: signal to noise ratio

THU266
Patient Navigators: an innovative approach to improve hepatitis c
case finding leveraging existing human immunodeficiency virus
service delivery models to reach last mile patients in Nasarawa Conclusion: The use of patient navigators demonstrates the
State, Nigeria feasibility and cost-effectiveness of increasing case-finding through
Chukwuemeka Agwuocha1,2, Olayinka Adisa1, Onyeka Nwobi1, HCV/HIV program integration.
Muhammad-Mujtaba Akanmu1, Caroline Boeke3,
Magdalena Witschi3, Amy Azania3, Jibrin Kama1, Folu Lufadeju1, THU267
Owens Wiwa1. 1Clinton health access initiative, Abuja, Nigeria; 2Clinton The Community Pop-Up Clinic (CPC): a unique strategy to achieve
Health Access Initiative, Abuja, Nigeria; 3Clinton health access initiative, HCV elimination in the inner city
United States Brian Conway1,2, Shawn Sharma1, Leo Yamamoto1, Rossitta Yung1,
Email: [email protected] David Truong1. 1Vancouver Infectious Diseases Centre, Vancouver,
Canada; 2Simon Fraser University, Burnaby, Canada
Background and aims: The natural history of Hepatitis C Virus (HCV) Email: [email protected]
demonstrates an asymptomatic disease that often leads to liver
degeneration in approximately three decades. In HIV/HCV coinfec- Background and aims: A number of strategies have been proposed to
tion, liver degeneration is accelerated with decompensated cirrhosis help identify HCV-infected inner-city residents, engage them in care,
occurring in less than two decades resulting in higher mortality rates. provide them with Hepatitis C Virus (HCV) therapy, and achieve and
The asymptomatic nature of HCV, increased rate of disease progres- measure cure. While many programs have successfully identified
sion in HIV, low awareness, and poor care seeking behaviour large numbers of subjects eligible for treatment, the rate of successful
emphasizes the need to improve HCV case finding in People Living completion and cure is highly variable. The most relevant outcome
with HIV (PLHIV). measure for such programs may be the number of HCV cures
In Nigeria, the Nasarawa State Government has committed to HCV achieved over time, and programmatic changes should be imple-
elimination, with an initial focus on PLHIV, necessitating integration mented and evaluated according to this metric. We have evaluated
of services to screen ART patients for HCV. However, due to the COVID our Community Pop-Up (CPC) program in terms of this outcome
pandemic and the resultant scale-up of Differentiated Service measure, as a function of the resources required for its
Delivery (DSD) models within the HIV program, screening yield implementation.
from facility-based case finding reduced significantly. To ensure last Method: On a weekly basis, a team consisting of a physician, nurse
mile linkage to HCV screening, the Patient Navigator pilot was and three support staff interact with up to 30 individuals over 4 hours
conducted from March-October 2021. This analysis aims to assess in the inner city of Vancouver, at a community centre or single room
screening coverage before and during this pilot period. occupancy dwelling to provide point-of-care HCV testing or ascer-
Method: One healthcare worker across three secondary facilities i.e., tainment of previously identified HCV infection status. Treatment for
General Hospitals Keana, Awe, and Uke, labelled patient navigator HCV infection is offered in the context of a low-barrier treatment
(PN) was charged with the responsibility of identifying unscreened program, with medications delivered daily/weekly, at the place of
PLHIV using facility screening records and enrolment data. These PNs residence, local pharmacy or at our community clinic. Strategies are in
were HIV program defaulter trackers, consequently integrating this place to limit loss to follow-up and maximize engagement in care
service within the HIV program. The PN employed strategic patient throughout treatment and thereafter, to ascertain if cure has been
tracking approaches like phone calls, community engagements and achieved.
peer group meetings. Using laboratory screening registers, screening Results: From 07/20–09/21 (15 months), we conducted 55 commu-
progress was compared pre-intervention (July 2020 to February nity pop-up clinics and screened a total of 774 individuals for their
2021) versus during the intervention (March to October 2021). HCV status. Of 280 HCV-infected individuals by antibody test, 99
Results: A total of 125, 560, and 923 were active on ART care as of (35.4%) had documented HCV viral load result. Key demographic
January 2020 in General Hospitals Keana, Awe, and Uke respectively. characteristics include: median age 43 (28–86) years, 77.5% male, F0/
Across sites, the first 4 months of the pre-intervention phase saw high F1 (22, 55%), opioid antagonist therapy 26 (65%), HIV co-infected 2
screening numbers as all available patients presenting to facilities (5%), fentanyl/cocaine/amphetamine use (24/12/18, 60%/30%/45%).
were screened. Subsequently, a decline in screening numbers across Of 40 individuals on treatment, none have been lost to follow-up, 26
all facilities. However, the intervention phase demonstrated extended have demonstrated cure, with outcome results pending in the other
coverage, reaching the last mile patients leading to an increase in case 14 subjects. Strategies are in place to engage the remaining 49 viremic
finding by 18% in GH Keana, and 23% in GH Awe and GH Uke individuals in HCV treatment
respectively.

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POSTER PRESENTATIONS
Conclusion: In the context of an established, multidisciplinary clinic
serving the inner city, a 4 hour/week initiative staffed with 2 health
care providers and 3 support staff led to successful HCV treatment of
40 individuals, with none lost to follow-up once treatment has been
initiated and the possibility of 40–50 additional treatment starts in
the short term. This represents a very cost effective and productive
initiative to address HCV infection in similar populations.

THU268
Age, gender and region-specific HBsAg and anti-HCV
seroprevalence in Ghana: a nationwide hospital based cross-
sectional study
Yvonne Nartey1,2. 1Cape Coast Teaching Hospital, Internal Medicine,
Cape Coast, Ghana; 2Karolinska Institute, Medical Epidemiology and
Biostatistics, Stockholm, Sweden
Email: [email protected]
Background and aims: Hepatitis B (HBV) and Hepatitis C (HCV) viral
infection continue to pose a significant global health burden and are
responsible for high morbidity and mortality worldwide due to
sequalae of end stage liver disease. Previous estimates in Ghana
report a seroprevalence of anti-HCV of 3.3% and HBsAg of roughly 9%.
These estimates fall short of describing age and gender-specific rates Conclusion: Ghana remains a region of high endemicity for HBV and
and have relied on small sample sizes in few centers. Particularly for moderate-high endemicity for HCV. Northern Ghana consistently
HCV, there is a paucity of data from several regions in Ghana. demonstrates a higher disease burden than the rest of the country.
Numerous challenges, including lack of focused and definitive testing Focused and targeted policies are essential to reach elimination
and treatment strategies and policies limit the impact of current targets.
elimination efforts. Providing a robust programmatic foundation
requires a scale-up of hepatitis testing nationwide, and this in turn THU269
requires up-to-date epidemiologic data to understand the burden of The elimination of hepatitis C in the cherokee Nation: the impact
disease in all parts of the country and across all age groups. This study of harm reduction
aimed to perform an epidemiological assessment of HBV and HCV Jorge Mera1, Whitney Essex1, Molly Feder2, Homie Razavi3,
infection in Ghana to determine age, gender, and region specific Devin Razavi-Shearer3. 1Cherokee Nation Outpatient Health Center,
seroprevalence. Additionally, it aimed to convene a coalition of local Tahlequah, United States; 2Cardea Services, Seattle, United States;
stakeholders for policy development in Ghana. 3
Center for Disease Analysis Foundation, Lafayette, United States
Method: A nationwide cross-sectional study using de-identified data Email: [email protected]
was collated from January 1st to October 30th 2021. Data from health
information management systems for 2017–2021 was reviewed from Background and aims: In the United States, American Indians/
20 centers including teaching, regional, and district hospitals in 11 Alaskan Natives have the highest rates of HCV incidence, liver cancer
regions in Ghana. Sixty thousand labour ward, 54, 000 blood bank, and mortality compared to all other racial/ethnic groups.
and 48, 000 laboratory-based records were reviewed and analyzed The Cherokee Nation (CN) a sovereign tribal nation, began a hepatitis
for age and gender-specific HBV and HCV prevalence. Regional C (HCV) elimination program in 2015 with a 6-fold increase in
differences in seroprevalence were also determined. treatment in 2016. The primary aim of this study is to estimate what
Results: A stakeholder meeting was held in Accra, Ghana bringing would need to be done to meet the World Health Organization’s
together key players from the public and private sector involved in (WHO) 2030 targets by 2025. In addition to examining increase in
viral hepatitis elimination for policy planning. Crude prevalence treatment, the implementation and lack of syringe service programs
among pregnant women was 6.36% (95% CI 5.70–7.02) for HBsAg; (SSP) were considered in the analysis.
among blood donors was 5.09% (95% CI 4.91–5.28) for HBsAg and Method: CN specific input data populated a dynamic Markov model.
3.22% (95% CI 3.08–3.38) for anti-HCV. From laboratory-based Three scenarios were considered. The Base scenario examined the
registers, overall seroprevalence was 8.90 (95% CI 8.65–9.16%) for impact of maintaining the current treatment and diagnosis levels into
HBsAg and 3.39 (95% CI 3.17–3.63) for anti-HCV. Prevalence of both the future. The 2025 w/o SSP scenario examined how much
HBV and HCV were significantly higher in the northern Ghana. HBsAg treatment would need to be increased to attempt to meet the 2030
prevalence was higher in males (9.70%) than females (8.20%) p < 0.05, targets in 2025 without access to SSP. The 2025 w/SSP scenario
but there was no difference in gender-specific seroprevalence for examined the accompanying treatment uptake necessary to meet the
anti-HCV. The highest age preponderance was among 40–49 (13.53%) 2030 goals in 2025 with a robust SSP program.
year olds for HBsAg and 60+ year olds (7.59%) for anti-HCV. Results: In the Base scenario, it was estimated that the 90% diagnosis
Seroprevalence in children <5 years was 1.87% for HBsAg and 1.53% and 80% treatment targets would be met prior to 2025. By 2030, there
for anti-HCV. is estimated to be an 84% reduction in mortality and a 50% reduction
in incidence when compared to 2015 (Figure 1). 2025 w/o SSP
required a large increase in treatment, from 162 to 400 annually. This
scenario resulted in an 89% reduction in mortality by 2025 but only a
50% reduction in incidence by 2025. The 2025 w/SSP scenario
required a modest increase in treatment to 255 individuals annually.
This resulted in a 65% reduction in mortality and an 86% reduction in
incidence by 2025 thus meeting all targets.

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 POSTER PRESENTATIONS
Propensity score matching was used to match test positive cases and
test negative controls. The propensity score of having COVID-19 were
derived from a logistic regression that adjusted for the participant’s
baseline variables.
Results: The study sample included 1, 720 participants, including 860
cases and 860 controls. The effectiveness of mRNA vaccines against
COVID-19 was inversely related to the community prevalence of the
B.1.617.2 variant. For every 10% increase in the community prevalence
of delta, the likelihood of COVID-19 after full vaccination increased by
5% (aOR 1.05, 1.02–1.07, p = 0.0001). At community delta prevalence
of 10%, mRNA vaccines were 70% effective (aOR 0.30, 0.21–0.43, p <
0.0001). Vaccine effectiveness dropped to 62% (aOR 0.38, 0.30–0.48,
p < 0.0001) when the community prevalence of the delta variant
increased to 50%, to 52% (aOR 0.50, 0.38–0.67, p < 0.0001) at a
community delta prevalence of 90% and to 50% (aOR 0.38–0.67, p <
0.0001) with a community delta prevalence of 99%.
Figure: Annual Acute Incidence of HCV on The Cherokee Nation, 2015–
2030

Conclusion: The current HCV elimination program would

meet almost all of the WHO targets prior to 2030. However, in the
absence of SSP that provide access to all of those that need it, it is
estimated that the incidence would not drop substantially enough by
2030. With the CN approving SSP an opportunity has opened for the
CN to meet all targets by 2025. In the first year of the elimination
program 222 individuals were treated thus increasing treatment to
255 for three years would be within the capacity of the program. To
achieve this goal the CN should have a swift broad rollout of SSP. This
combined with a slight increase in treatment will lead to early Conclusion: Vaccine effectiveness is inversely associated with
elimination and a positive impact on the population health of the CN.
community prevalence of the delta variant, with effectiveness
dropping from 30% at delta prevalence of 10%, down to 50% with a
THU270
Effectiveness of mRNA vaccines in patients with cirrhosis with community delta prevalence of 99%. Further studies are needed to
rising prevalence of SARS-CoV-2 delta variant understand if booster doses are able to overcome the drop in vaccine
effectiveness with increasing prevalence of delta variant, among
Binu John1,2, Raphaella Ferreira1, Dustin Bastaich3, Akash Doshi4,
patients with cirrhosis.
Tamar H Taddei5, David Kaplan6, Seth Spector1,4, Bassam Dahman3.
1
Miami VA Medical Center, Miami, United States; 2University of Miami THU271
Hospital And Clinics | UHealth Tower, Miami, United States; 3Virginia Epidemiology and management of hepatitis B and C in primary
Commonwealth University, Graduate School, Richmond, United States; care in the Netherlands-data from the Rijnmond primary care
4
University of Miami, Coral Gables, United States; 5Yale University, New database
Haven, United States; 6University of Pennsylvania, Philadelphia, United Sylvia Brakenhoff1, Robert De Man1, Robert De Knegt1,
States
Patrick Bindels2, Evelien de Schepper2. 1Erasmus MC, University
Email: [email protected]
Medical Center, Gastroenterology and Hepatology, Rotterdam,
Background and aims: The effectiveness of COVID-19 vaccines with Netherlands; 2Erasmus MC, University Medical Center, General Practice,
the increasing prevalence of SARS CoV2 B.1.617.2 delta variant among Rotterdam, Netherlands
patients with cirrhosis is unknown. The aim of the study was to Email: [email protected]
investigate the effectiveness of COVID-19 vaccination at varying
Background and aims: The Dutch guideline for general practitioners
community prevalence of the B.1.617.2 variant among patients with (GPs) advises biannual surveillance of hepatitis B (HBV) patients and
cirrhosis.
referral of every hepatitis C (HCV) patient. We aimed to study the
Method: This study used was a test-negative case control design,
prevalence, incidence and the management of hepatitis B and C in
where adults with cirrhosis who had a diagnosis of COVID-19 as
primary care.
documented by a positive SARS-CoV-2 Polymerase Chain Reaction
Method: This is a retrospective cohort study using the Rijnmond
(PCR) were considered as cases, and those with a negative SARS CoV2 Primary Care database (RPCD), including healthcare data of medical
PCR were considered controls. This study design is widely used in
records of GPs of approximately 200, 000 patients in the area of
evaluations of vaccine effectiveness and has the advantage of
Rotterdam, the Netherlands. Patient records were selected based on
minimizing biases associated with access to vaccination or health laboratory results, International Classification of Primary Care (ICPC)
care. Participants who did not undergo SARS CoV2 PCR testing, who
codes and free text words.
had COVID-19 before the study period, received a vaccine other than Results: In total, 977 patients were included; 717 HBV, 252 HCV, and 8
an mRNA vaccine, or received a liver transplant, were excluded.
HBV/HCV co-infected patients. Between 2013 and 2019, the preva-
Patients were considered fully vaccinated 14 days after receipt of
lence of HBV and HCV declined from 5.21 to 2.99/1, 000 person years
either the Pfizer BNT162b2 or the Moderna 1273-mRNA vaccine. (PYs; − 43%) and 1.50 to 0.70/1, 000 PYs (-53%) respectively. We
COVID-19 was classified based on individual chart review using the
observed that the majority of the patients had been referred to a
National Institute of Health (NIH) COVID-19 severity scale as
medical specialist at least once (71% HBV and 89% HCV patients).
asymptomatic, mild, moderate, severe or critical illness. The weekly
However, among the 406 chronic hepatitis B patients, we observed
proportion of the delta variant in the United States was obtained
that 36.2% of the patients did not receive adequate surveillance by
using data from the Center for Disease Control COVID-19 genomic their GP (≥2 ALT checks within 3 years) or by a medical specialist. In
surveillance data.
addition, among the 153 chronic hepatitis C patients, 113 (73.9%)

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POSTER PRESENTATIONS
received antiviral therapy. However, 68 patients (44.4%) had no THU273
record about successful antiviral treatment and might still be Association of novel lifestyle- and whole foods base inflammation
chronically infected on 31.12.2019. scores with metabolic dysfunction-associated fatty liver disease: a
Conclusion: This study demonstrated a declining prevalence in viral population-based study among iranian adults
hepatitis B and C in primary care in the Netherlands. However, a Ehsaneh Taheri1, Roberd M Bostick2, Behzad Hatami1,
substantial of the patients did not receive adequate surveillance or Mohammadamin Pourhoseingholi1, Hamid Asadzadeh Aghdaei1,
antiviral therapy. It is therefore crucial to involve GPs in the road to Alireza Moslem3, Alireza MosusaviJarahi4, Mohammadreza Zali1.
elimination. 1
Shahid beheshti university of medical sciences, Research institute for
gastroenterology and liver disease center, Tehran, Iran; 2Emory
THU272 University, Epidemiology, Atlanta, United States; 3Sabzevar university of
Point of care testing for hepatitis C in the priority settings of medical sciences, Cellular and molecular research center, Sabzevar, Iran;
mental health, prisons and drug and alcohol facilities 4
Shahid beheshti university of medical sciences, Department of
Catherine Ferguson1, Lucy Ralton1, Erin McCartney1, Joshua Dawe2, community medicine, Tehran, Iran
Jacqui Richmond2, Edmund Tse3, Alan Wigg4, Victoria Cock5, Email: [email protected]
Tom Rees6, David Shaw1. 1Royal Adelaide Hospital, Infectious Diseases,
Adelaide, Australia; 2Burnet Institute, Melbourne, Australia; 3Royal Background and aims: Chronic inflammation, associated with
Adelaide Hospital, Hepatology, Adelaide, Australia; 4Flinders Medical lifestyle and dietary patterns, may contribute to metabolic dysfunc-
Center, Gastroenterology and Hepatology, Adelaide, Australia; 5Drug and tion-associated fatty liver disease (MAFLD) risk. Recently, a novel
Alcohol Services South Australia, Adelaide, Australia; 6Communicable dietary inflammatory score based on weighted inflammatory scores
Disease Control Branch, SA Health, Adelaide, Australia of 19 components (whole foods) from food frequency questionnaire
Email: [email protected] (FFQ) and lifestyle inflammatory score based on weighted inflam-
matory scores of 4 components of lifestyle ( physical activity,
Background and aims: A key barrier to hepatitis C (HCV) diagnosis adiposity, alcohol, and smoking) were proposed. The main aim of
and treatment is the multi-stage process of conventional testing that this study was to evaluate the associations of these novel inflamma-
requires multiple visits to pathology services and healthcare tory scores with MAFLD risk. The secondary aim of our study was to
providers to obtain a HCV antibody (Ab) test, HCV RNA test, diagnosis, compare novel dietary- and lifestyle inflammatory scores-MAFLD
and linkage into care to commence treatment. Point of care testing for associations with previous dietary inflammatory scores.
hepatitis C in the priority settings of mental health, prisons and drug Method: We investigated associations of 19-component dietary and
and alcohol facilities (PROMPt) aims to overcome critical roadblocks 4-component lifestyle inflammatory separately and jointly with
to HCV treatment in the community by providing HCV point-of-care MAFLD risk among Iranian adults aged 35–70 years of age at baseline
testing (POCT) and direct referral into treatment. Over a 12 month phase of PERSIAN cohort study in Sabzevar city. MAFLD was defined
period PROMPt aims to evaluate the effect of POCT on HCV testing as having a fatty liver index (FLI) ≥60, plus one of the following: being
rates, linkage to care and explore the acceptability of HCV POCT in overweight or obese (body mass index [BMI] ≥25 kg/m2), a Type II
facilities and services for individuals at high risk of HCV infection. diabetes mellitus (T2DM) diagnosis, or having any evidence of
Primary end points: 1. Number/proportion of participants who metabolic dysregulation. We also calculated previous well-known
receive rapid POCT HCV Ab plus POC RNA. HCV Ab/RNA positivity at diet-related inflammatory markers such as dietary inflammatory
each site 2. Number/proportion of HCV RNA positive participants index (DII) and empirical dietary inflammatory pattern (EDIP) using
who are linked to care. Secondary end points: 1. Acceptability of HCV information from 115-item FFQ. Higher score were considered more
POCT to participants in each setting. inflammatory status. We assessed inflammatory scores-MAFLD
Method: Participants are offered POC HCV diagnostic testing using SD associations using multivariable unconditional logistic regression.
Bioline fingerstick Ab assay and those returning a positive HCV Ab Results: Of 4241 participants of Persian Sabzevar Cohort study, 968
result are offered a Cepheid finger stick HCV RNA Xpert assay. Project patients with MAFLD and 964 age- and gender adjusted controls
staff, including peer support workers, provide HCV education, pre- were recruited in this nested case-control study. Among participants
and post-test counselling, and linkage to care at the time of diagnosis. in the highest relative to the lowest dietary- and lifestyle inflamma-
Results: Interim analysis at 6 months reports 707 participants tory score tertiles, the adjusted odds ratios (OR) and their 95%
recruited across all 3 priority settings. 125/707 (18%) positive HCV confidence intervals (CI) were 1.84 (1.61–2.07; p-trend <0.001)) and
Ab participants were reflexed to HCV RNA testing, resulting in 35 1.96 (1.69–2.21; p-trend <0.001), respectively. Among those in the
positive RNA participants 35/125 (28%). To date 27/35 (77%) RNA highest relative to the lowest joint dietary- and lifestyle inflammatory
positive participants have commenced treatment. score tertiles, the adjusted OR (95% CI) was 2.56 (95% CI: 2.19–2.93; p-
The complete 12 months of recruitment and final analysis of end interaction <0.001). The third tertile ORs (95% CI) for the DII- and
points will be presented. EDIP-MAFLD associations were 1.63 (1.05–5.62) and 1.71 (1.17–4.62),
respectively.
Conclusion: More pro-inflammatory diets and lifestyles, separately
and particularly jointly, are associated with higher risk of having
MAFLD among adults. The associations of novel dietary- and lifestyle
inflammatory with MAFLD were stronger than DII- or EDIP- MAFLD
associations.

Conclusion: PROMPt has demonstrated high rates of HCV POC testing

and acceptability in 3 high priority settings. The hepatitis C infection
rates have been lower than anticipated and the combined HCV Ab and
RNA POCT approach to testing has allowed for efficient and
economical testing scale up in each site.

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 POSTER PRESENTATIONS
THU274 Conclusion: In Japan, a greater decrease was noticed on HBV and HCV
Assessment of COVID-19 impact and response on hepatitis B virus confirmatory testing, screening than treatment initiation. However,
and hepatitis C virus prevention and treatment from nationwide anxiety and fear of patients, lack of staff and facilities are major
survey in Japan challenges to overcome such situation. Perceived benefits of COVID-
Md Razeen Ashraf Hussain1, Aya Sugiyama1, Lindsey Hiebert1,2, 19 on hepatitis were strengthened health care system, demonstration
Serge Ouoba1,3, Bunthen E1,4, Ko Ko1, Tomoyuki Akita1, of hepatitis infrastructure and improved training in infectious disease
Shuichi Kaneko5, Tatsuya Kanto6, John Ward2, Junko Tanaka1. testing and management.
1
Hiroshima University, Department of Epidemiology: Infectious Disease
Control and Prevention, Graduate School of Biomedical and Health THU275
Sciences, Hiroshima, Japan; 2The Task Force for Global Health, Coalition Knowledge, attitude and practice regarding COVID-19 vaccination
for Global Hepatitis Elimination, Georgia, United States; 3Institut de among HCV infected patients in Georgia
Recherche en Science de la Santé (IRSS), Unité de Recherche Clinique de Lasha Gulbiani1, Tiko Kamkamidze1, Ana Gamezardashvili1,
Nanoro (URCN), Nanoro, Burkina Faso; 4Ministry of Health, Payment George Kamkamidze2, Maia Butsashvili1. 1Health Research Union,
Certification Agency, Cambodia; 5Kanazawa University, Department of Tbilisi, Georgia; 2Clinic NeoLab, Tbilisi, Georgia
Gastroenterology, Graduate School of Medical Science, Japan; 6National Email: [email protected]
Center for Global Health and Medicine, The Research Center for Hepatitis
Background and aims: COVID Vaccination coverage is low in Georgia
and Immunology, Tokyo, Japan
(24.7%). There are different vaccine-related misconceptions, particu-
Email: [email protected]
larly among people with different chronic diseases, who are at
Background and aims: Elimination of Hepatitis B Virus (HBV) and greatest risk of COVID related health complications and death. The
Hepatitis C Virus (HCV) requires continuous diagnosis and treatment. aim of this study was to assess the COVID vaccine knowledge, attitude
Ongoing pandemic COVID-19 has been affecting on health care and practice among HCV infected patients enrolled in HCV
system including on preventive care and testing of HBV and HCV. This elimination program in Georgia
study aimed to assess the impact of COVID-19 on hepatitis prevention Method: The interviewer administered questionnaire was used to
and treatment in Japan. This international joint research conducted survey the random sample of patients at one of the outpatient clinics
by three research groups of Ministry of Health, Labour and Welfare of providing HCV treatment services within HCV elimination program in
Japan with the Task Force for Global Health and in cooperation with Tbilisi, capital of Georgia. The sample included patients at different
Japan Society of Hepatology (JSH). types of visits at the clinic-having diagnostic tests before the
Method: We conducted this cross-sectional study by a questionnaire treatment, receiving the treatment and having sustained viral load
survey in Japanese and English language on online Microsoft forms (SVR) test at 12–24 weeks after treatment. Patients with and without
platform from 24 August to 03 October 2021. The electronic version of liver cirrhosis were enrolled in the survey.
the questionnaire was disseminated by e-mail to all the members of Results: 230 patients were interviewed in total. Only 42 (18.2%)
JSH. The questionnaire was designed to address the impact of COVID- reported to receive two doses and 12 (5.2%)-1 dose of COVID vaccine.
19 on hepatitis testing, screening, treatment; mitigation strategies; Out of 176 not vaccinated patients 45 (25.5%) declared that they do
response to COVID-19; and perceived benefits of COVID-19. not wish to get vaccinated because of their disease (HCV infection);
Results: Total 196 medical doctors participated from 35 prefectures of 32 (18.1%) plan to get the vaccine; 29 (16.4%) patients think they are
whom 49.5% are in administrative positions. 55.6% of participants not at risk of COVID related health problems, 12 (6.8%) did not get the
responded about no interruption while 11.7% reported supply chain vaccine because they had COVID in the past and consider themselves
disruptions during the survey period. 1–25% decrease in HBV defended against the disease, 25 (14.2%) are afraid of side effects and
screening and confirmatory testing was reported by 38.8% and 33 (18.7%) do not trust the vaccine. Among not vaccinated patients 38
43.9% participants, respectively. Decrease of 1–25% in HCV screening (21.5%) had liver cirrhosis.
and confirmatory testing was reported by 39.8% and 43.4% partici- Conclusion: COVID vaccination coverage is very low among patients
pants, respectively. However, no decline to initiate HBV and HCV enrolled in HCV elimination program, including patients with liver
treatment were reported by 53.6% and 45.4%, respectively, but cirrhosis. Targeted educational campaigns for people with chronic
extension of hospital visits was reported by 65.3%. The response diseases are needed to fight vaccine misconceptions among this
illustrated the decrease in patients’ imaging (65.8%), laboratory high-risk population.
testing (68.4%), hepatocellular carcinoma screening (55.1%), gastro-
intestinal endoscopy (87.2%) and liver biopsy (43.4%). Patient anxiety THU276
and fear (67.4%), loss of staff to COVID-19 response (49.0%) and limited CRIVALVIR-FOCUS: low HIV and chronic Hepatitis B and C infection
availability of staff (46.4%) were responded as challenges to resume prevalence among women in reproductive and sexual health
services to pre-COVID-19 level. About COVID-19 response, engage- services in Valencia, Spain
ment in COVID-19 testing and vaccination were reported by 51.5% and Miguel Garcia-Deltoro1, Pilar Obon1, Caterina Canapele2,
61.2%, respectively. For Perceived benefits of COVID-19 response were Jose Maria Mari2, Adela Vidal2, Maria Martinez-Roma3,
strengthening general health care system (45.9%), demonstration of Maria Dolores Ocete4, Concepción Gimeno Cardona4, Moisés Diago5,
hepatitis infrastructure for COVID-19 response (44.4%) and improved Neus Gomez-Muñoz3, Alba Carrodeguas6, Diogo Medina6,
training of infectious disease testing and management (35.7%) Enrique Ortega González3. 1Consorcio Hospital General Universitario de
Valencia, Enfermedades Infecciosas, Valencia, Spain; 2Consorcio Hospital
General Universitario de Valencia, Ginecologia y Obstetricia, Valen ̀ cia;
3
Fundacion de Investigacion HGUV, Valen ̀ cia, Spain; 4Consorcio Hospital
General Universitario de Valencia, Microbiologia, Valen ̀ cia, Spain;
5
Consorcio Hospital General Universitario de Valencia, Hepatologia,
Valeǹ cia, Spain; 6Gilead Science, Madrid, Spain
Email: [email protected]
Background and Aims: In Spain, HIV, HBV, and HCV prevalence are
lower in females. A 2017–2018 Ministry of Health serosurvey in 7, 675
primary care patients found 0.35% and 0.08% chronic HCV infection in
men and women. A previous opportunistic, population-based
screening program in 11, 449 primary care patients seen in our

Journal of Hepatology 2022 vol. 77(S1) | S119–S388 S229

POSTER PRESENTATIONS
health department found 0.18% and 0.06% HIV infection prevalence, positive were considered cases. VE was defined as “1- OR (odds
1.11% and 0.56% chronic HBV infection prevalence, and 0.73% and ratio).”
0.25% chronic HCV infection prevalence in men and women from Results: A total of 136 liver transplant patients were included in the
February to December 2019. study. 13 (9.6%) patients were diagnosed with COVID-19 during the
We aimed to assess HIV, HBV, and HCV prevalence among women study period, out of which 7 (5.2%) needed hospitalization and 5
seeking care in our health department’s 5 Sexual and Reproductive (3.7%) were admitted to the ICU. None of the patients died. The
Health Units (SRHU), in the Human Reproduction Unit (HRU), and the baseline characteristics, transplant history, comorbid conditions, and
Obstetrics and Gynecology Service (OGS). current immunosuppressive treatment for the participants is
Method: We implemented opportunistic HIV, HBV, and HCV screen- summarized in the table.
ing from March to October 2021, despite challenges related to a fifth Among the vaccinated patients, 86 (83.5%) had received Pfizer
wave of the SARS-CoV-2 pandemic. We used existing infrastructure vaccine, and 92 (89.3%) of the patients had received both the doses,
and staff, aided by electronic health record system modifications, to three weeks apart.
identify screening eligibility and request serologies. VE of mRNA based vaccines against any COVID-19 infection,
Patients were eligible for testing upon verbal consent if they were hospitalization and ICU admission is shown. In liver transplant
between 18 and 80, and had no record of testing in the previous year, patients VE was 84.1% (38.2%-96.2%, p = 0.002) for any documented
and required blood tests in their current health care visit. Follow-up infection. VE was 88.9% (26.4%- 98.9%, p = 0.003), and 92.8% (22.8%-
or discharge was given, regardless of test results. A case manager 99.8%, p = 0.003) for COVID-19 related hospitalizations and ICU
contacted positive patients to ensure and monitor linkage to admissions respectively.
specialist medical care.
Herein we analyze data from patients aged 18 to 45 — the maximum
age of patients seen in the HRU.
Results: We screened 934 women, of whom 48.1% (449) in SRHUs,
26.0% (243) in the HRU, and 25.9% (242) in the OGS (26%). Regarding
age and nationality, 14.6.% (136) were aged 18 to 25, 45.5% (425) were
26 to 35, 39.9% (373) were 36 to 45, and 20.6% (192) were foreigners.
We found 1 (0.1%) HIV antibody positive patient (a 45-year-old from
the Dominican Republic), 1 (0.1%) HBV surface antigen positive
patient (a 36-year-old from China), 1 (0.1%) HCV antibody positive
patient, and no HCV RNA positive patients.
Conclusion: HIV prevalence among Valencian women in reproduct-
ive and sexual health services was similar to the general population in
primary health care in the area. In contrast, chronic HBV infection
prevalence was low, and chronic HCV infection was not found.
Our data suggest that opportunistic HBV and HCV screening of
women aged 18 to 45 out of populations at increased risk is an
inefficient public health strategy in our area.

THU277
mRNA COVID-19 vaccine effectiveness in liver transplant patients
Muhammad Khan1, Kamran Mushtaq1, Deema AlSoub1,
Hussam Almasri1, Bisher Sawaf1, Saad AlKaabi1, Yasser Kamel1.
1
Hamad Medical Corporation, Doha, Qatar
Email: [email protected]
Background and aims: There is poor antibody response in up to 61%
of the liver transplant patients after mRNA COVID-19 vaccination, and
almost 20% of liver transplant recipients have undetectable antibody
levels. However, antibodies are surrogate markers of disease
protection and absence of seroconversion does not mean complete
susceptibility to the disease. We hypothesized that COVID-19
vaccines are effective in liver transplant patients despite low
seroconversion rates. Conclusion: In liver transplant patients, two doses of mRNA based
Method: We designed a test-negative case-control study to assess the SARS-CoV-2 vaccines is effective against any documented infection.
vaccine effectiveness (VE) of COVID-19 vaccination in liver transplant The protection is higher against hospitalization and ICU admissions.
recipients followed at our center in Hamad Medical Corporation. All Combined analysis of cellular and humoral response is needed to
liver transplant patients who were tested for SARS-CoV-2 infection identify vaccine responders
between 1st of February till 30th of July in Qatar were included in the
study. Case patients were identified as patients who had positive THU278
SARS-CoV-2 test on nasopharyngeal and throat swab while control Evaluation of global progress towards HBV and HCV elimination
patients were identified as patients who were tested negative during Sarah Blach1, Devin Razavi-Shearer1, Ellen Mooneyhan1, Chris Estes1,
the same period. Information regarding demographic and clinical Kathryn Razavi-Shearer1, Ivane Gamkrelidze1, Homie Razavi1. 1Center
characteristics, transplant history, current immunosuppressive treat- for Disease Analysis Foundation, Lafayette, United States
ment was obtained from the medical records. Also, we recorded the Email: [email protected]
type of COVID-19 vaccination, number of vaccine doses (one or two),
COVID-19 complications, hospitalizations, and ICU admissions. Background and aims: The Polaris Observatory maintains mathem-
VE was estimated by a test-negative case-control design in which atical models for hepatitis B (HBV) and hepatitis C (HCV) viruses
which are updated annually and used to monitor progress towards
symptomatic liver transplant patients who were tested negative for
COVID-19 were recorded as controls, while patients who tested elimination. The outcomes of this work, including country/territory
progress reports are publicly available online. The objective of this

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 POSTER PRESENTATIONS
analysis was to evaluate progress towards elimination (by elimination Conclusion: Nuanced country reports on viral hepatitis elimination
target) among the countries with approved or estimated models, and progress and policies are vital feedback mechanisms for policy
to report on policy assessment surveys returned by country experts. makers. Although most countries were not on track to achieve all HBV
Method: The year of elimination (by target) was extracted from 110 or HCV targets, substantial progress has been made by countries with
HCV and 167 HBV models available on the Polaris Observatory regards to individual targets. Substantial work is needed to increase
website (data from 2020). Results were summarized across countries political will for HBV and HCV elimination.
by disease area and time period of elimination (target achieved
before 2030, target achieved between 2031 and 2050, target achieved THU279
after 2050). Additionally, average country-level results from a The impact of vaccination on the global and regional pediatric
qualitative policy assessment survey (administered in 2020 by the prevalence of hepatitis B from 1985 to 2022
CDA Foundation, with responses from 47 countries) were used to Devin Razavi-Shearer1, Ivane Gamkrelidze1, Sarah Blach1, Chris Estes1,
score national viral hepatitis elimination policies. Ellen Mooneyhan1, Kathryn Razavi-Shearer1, Homie Razavi1. 1Center
Results: Based on 2020 data, no countries were on track to achieve all for Disease Analysis Foundation, Lafayette, United States
HBV elimination targets by 2030; however, 85 countries were Email: [email protected]
expected to achieve the target for prevalence among 5-year-olds,
Background and aims: The first vaccine to prevent the hepatitis B
40 countries were on track to achieve absolute mortality targets, and
virus (HBV) was available in 1981. The rollout and coverage of the
7 were on track to achieve the diagnosis target. Based on 41 survey
vaccine varied by country, but three dose coverage became
responses, only 11 countries (26%) received the highest score of 10 for
widespread in 2001 when Gavi, the vaccine alliance, began to
political will (“Government is fully committed to the elimination in
support these programs. This study aims to examine the impact of
any population who tests positive for the virus”).
prophylaxis measures on the pediatric, under 18 years of age,
Nine countries were on track to achieve all relative HCV elimination
prevalence of HBV between 1985 and 2022.
targets by 2030, with 27 expected to achieve the diagnosis target and
Method: The Polaris Observatory maintains 166 country specific
18 expected to achieve the treatment target. When absolute targets
PRoGReSs Models. These models consider the impact of prophylaxis
were considered, 58 countries would achieve the mortality target and
measures (timely birth dose, three dose, hepatitis B immunoglobulin,
44 would achieve the incidence target. Relative mortality and
and anti-viral treatment of pregnant women) and treatment on the
incidence targets would only be met by 18 and 10 countries,
incidence and disease burden of HBV. These models were utilized to
respectively. Based on 47 survey responses, 17 countries (36%)
estimate the historical and current prevalence among the pediatric
received a score of 10 for political will. Political will was found to
population at the country and regional level. For countries in which
be the strongest predictor of country achieving viral hepatitis
models were not available, a regional prevalence was applied to the
elimination. Unfortunately, across the board, countries reported a
population of said missing country.
lower political will score for HBV elimination as compared to HCV.
Results: Modeled countries represented 99.6% and 99.7% of all
estimated pediatric cases in 1985 and 2022 respectively. Globally it
was estimated that in 1985 the pediatric HBV prevalence was 5.23%,
representing 101.9 million infections, this dropped to 1.0%, 23.8
million infections, by 2022 (Figure 1). This represents an 81%
reduction in prevalence. High income and upper middle-income
countries saw the largest drop, 96%, whereas lower middle- and low-
income countries only saw a reduction of 74–75%. Discrepancies in
regional reductions were also observed of 95% in Europe, 91% in the
Americas, 88% in Asia, 77% in Oceania and 72% in Africa.

Figure 1: The Global HBV Pediatric Prevalence, 1985–2022.

Conclusion: Countries and regions that historically provided timely

birth-dose as well as additional mother to child transmission
prophylaxis measures have greatly reduced the burden of HBV in
their pediatric population. While all regions have reduced the
pediatric prevalence, the reductions have been highly inequitable
with lower-middle- and low-income countries continuing to bear the
brunt of the disease. Without additional assistance to provide timely
birth dose and other prevention measures these inequities will
continue well into the future.

Journal of Hepatology 2022 vol. 77(S1) | S119–S388 S231

POSTER PRESENTATIONS
THU280 made to re-engage individuals released from incarceration that had
Feasibility and effectiveness of hepatitis C micro-elimination not completed all steps in the HCV care cascade.
among 19 prisons of northern India
Kanudeep Kaur1, Gagandeep Singh Grover2, Praveen Kumar Boora3, THU281
V K Bansal3, Veena Singh3, S Suman4, Virendra Singh5, Arka De5, The impact of treatment and health policies for Hepatitis C Virus
Rajashree Sen1, Sanjay Sarin6, Sonjelle Shilton6. 1FIND India, Public on hospitalizations in the last decade: data analysis of records of
Health, Delhi, India; 2Directorate of Health Services, Public Health, hospital discharge (SDO) at Italian national level
Punjab, India; 3Directorate of Health Services, Public Health, Panchkula, Francesco Saverio Mennini1,2, Paolo Sciattella3, Claudia Simonelli1,
India; 4Directorate of Health Services, Public Health, Chandigarh, India; Andrea Marcellusi1, Loreta Kondili4. 1Economic Evaluation and HTA
5
Post Graduate Institute of Medical Education and Research, PGIMER-, (EEHTA-CEIS), Centre for Economic and International Studies, Faculty of
Hepatology, Chandigarh, India; 6FIND, Public Health, Geneva, Economics, University of Rome "Tor Vergata", Rome, Italy; 2Institute of
Switzerland Leadership and Management in Health, Kingston Business School,
Email: [email protected] Kingston University, London, United Kingdom; 3Economic Evaluation
and HTA (EEHTA-CEIS), Centre for Economic and International Studies,
Background and aims: The estimated prevalence of hepatitis C virus Faculty of Economics, University of Rome "Tor Vergata"; 4Center for
(HCV) infection in India is 0.32%, which comprises a considerable Global Health, Istituto Superiore di Sanità, Rome, Italy
proportion of the global HCV burden. The incarcerated population is Email: [email protected]
disproportionately affected by HCV and significant scale-up of access
to testing and treatment is needed in order achieve the 2030 global Background and aims: In the last decade, innovative treatments and
targets for the elimination of HCV. The objective of this intervention health policies for Hepatitis C Virus (HCV) are leading to the
was to provide early diagnosis and management of HCV and evaluate reduction of the burden of HCV-related diseases. Direct-Acting
the feasibility and efficacy of a decentralised HCV micro-elimination Antiviral (DAA) therapy has shown a high rate of viral eradication,
care model in 19 prisons across states of Punjab, Haryana and Union and there is evidence that HCV cure reduces HCV complications and is
Territory of Chandigarh in the northern part of India. cost-saving in most western countries in the long term. The aim of
Method: Anti-HCV antibody rapid diagnostic test (RDT) was this analysis is to evaluate the trend of hospitalizations in patients
performed for the inmates at time of admission or via screening with HCV chronic infection and HCV-related liver complications in
camps. Inmates with positive HCV RDT results received reflex blood Italy and to discuss the impact of the introduction of DAAs in 2015.
draw for HCV RNA testing and pre-treatment investigations. Liver Method: The analysis was based on records of hospital discharge
staging was determined by APRI and FIB-4 scores (non-cirrhotic is (SDO) at national level from 2012 to 2019. SDO collect information
APRI <2 and FIB-4 <3.5 and cirrhotic as APRI >2 and FIB-4 >3.5). Non- related to all discharges from public and private hospitals in Italy.
cirrhotic patients were initiated on treatment by the prison medical Data was extracted based on primary and secondary diagnosis for
officer trained by the health department of the respective states. The HCV, cirrhosis and hepatocellular carcinoma (HCC). We calculated the
cirrhotic cases were referred to specialist care at the model treatment annual incident hospitalizations with diagnosis of HCV and HCV-
centers set up by the states. Test of cure (SVR12) was assessed with an related complications. Analyses were stratified by age cohort (40–59,
HCV RNA test done 12 weeks after completion of treatment. 60–79 and 80+ years) and divided into two distinct periods: (1) 2012–
Results: A total of 30, 670 inmates, which represent 100% of the 2015, in which DAAs were not available or had just been approved,
prison population in the 19 prisons at the time the intervention and (2) 2016–2019, in which DAAs were available initially with
started, were screened from November 2019 to January 2022. Of the prioritized access and later with universal access. The trend of
13.11% (n = 4022) HCV antibody-positive, 90.42% (n = 3637) received a alcoholic liver complications was also evaluated with the same
confirmatory viral load test, of which, 75.19% (n = 2735) were HCV methodology as comparison.
RNA-positive, 74.04% (n = 2052) of those testing HCV RNA positive Results: Annual incident hospitalizations for cirrhosis reduced from
were initiated on treatment, and 56.87% (n = 1167) had completed 73 new cases per 100.000 inhabitants in 2012 to 44 in 2019 (-39%).
treatment as of January 2022. Of those who completed treatment, Each year, patients with age ≥80 years represent around 20% of new
48.67% (n = 568) were assessed for SVR cure assessment, with SVR hospitalizations. For alcoholic liver related complications, a reduction
achieved in 89.26% (n = 507) inmates. of only 9% was observed, and patients with age ≥80 years only
The median days and IQR for the turnaround time from RDT screening represent around 5% of new hospitalizations. From 2012 to 2019,
to viral load result completion was 6 days, IQR 4–12 days (n = 2553); incident cases of HCC also reduced from 52 to 45 per 100.000
between viral load results and treatment initiation was 6 days, IQR 0– inhabitants (-14%) and incident cases of HCV reduced from 113 to 49
15 days (n = 1622) and total median time between RDT screening and per 100.000 inhabitants (-57%). For cirrhosis, HCC, and HCV the
treatment initiation was 16 days with an IQR of 10–30 day (n = 1597). reduction was more marked in the second period (2016–2019) than
in the first period (2012–2015).

Figure: Annual incident hospitalizations for cirrhosis (A) without and (B)
with mention of alcohol, by age cohort

Conclusion: From 2012 in Italy there has been a decreasing trend of

Conclusion: This simple decentralised HCV testing and treatment hospitalizations for chronic HCV infection, cirrhosis complications
model in prison settings has shown to be feasible, effective, and and HCC. This reduction is becoming more evident in recent years.
replicable in the Indian context. As this care model is fully Alcoholic liver related complications are decreasing at a slower rate
transitioned to government partners, additional efforts are being and affect younger patients on average. Overall, these data confirm

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 POSTER PRESENTATIONS
the clinical benefit of viral eradication by DAA and the long-term <10−15) for older than 25 wrt younger than 25), delivery outside the
economic benefit of reduced expenses for severe liver complications. hospitals (OR: 4.6 (3.7 to 5.8), p <10−15) especially home delivery
(OR:2.1 (95% CI: 1.9 to 2.3), p <10−15), born to a primiparous mother
THU282 (OR: 1.8 (1.6 to 2.2), p <10−12) and delivery during the first COVID-19
Hepatitis B birth dose coverage remains dramatically low in The outbreak (17 March 2020–1st August 2020) (OR:1.7 (1.4 to 1.9, p
Gambia and has been disrupted by the COVID-19 pandemic <10−11, among all babies born after June 2019).
Gibril Ndow1, Esu Ezeani1, Cecile de Bezenac2,3, Conclusion: more than 30 years after adoption of the HepB-BD
Julien Randon-Furling4, Umberto D’Alessandro1, Yusuke Shimakawa5, vaccination, only minor progress has been made in HepB-BD
Maud Lemoine6. 1MRC Unit The Gambia at LSHTM, Fajara, Gambia; coverage in The Gambia, putting at risk the HBV elimination goals.
2
Turing Institution, LONDON, United Kingdom; 3The Alan Turing
Institute, LONDON, United Kingdom; 4Sorbonne University, Paris, France; THU283
5
Pasteur Institution, Paris, France; 6Imperial College London, Hepatology, Hepatitis B prevalence and the impact of vaccination in Georgia:
LONDON, United Kingdom results from a nationwide serosurvey
Email: [email protected] Nino Khetsuriani1, Amiran Gamkrelidze2, Shaun Shadaker3,
Maia Tsreteli2, Maia Alkhazashvili2, Nazibrola Chitadze2,
Background and aims: Africa has the lowest coverage of hepatitis B
Irina Tskhomelidze4, Lia Gvinjilia5, Francisco Averhoff6,
birth dose (HepB-BD) vaccination (11%) worldwide and lags far
Gavin Cloherty6, Qian An1, Giorgi Chakhunashvili2, Jan Drobeniuc3,
behind the 90% coverage target recommended by the WHO for viral
Paata Imnadze2, Khatuna Zakhashvili2, Paige A Armstrong3. 1Centers
hepatitis elimination by 2030. We aimed to assess i. the coverage and
for Disease Control and Prevention, Global Immunization Division,
limiting factors of HepB-BD vaccination and ii. the impact of the
Atlanta, United States; 2National Center for Disease Control and Public
COVID-19 pandemic on HepB-BD coverage in The Gambia, the first
Health, Tbilisi, Georgia; 3Centers for Disease Control and Prevention,
African country to introduce in 1990 hepatitis B vaccination at birth.
Division of Viral Hepatitis, Atlanta, United States; 4The Task Force for
Method: we analysed data form the Health and Demographic
Global Health, Tbilisi, Georgia; 5Centers for Disease Control and
Surveillance system (HDSS) in four areas in The Gambia. HepB-BD
Prevention, Eastern Europe and Central Asia Regional Office, Tbilisi,
coverage was calculated at birth (0–1 day), day 7 and day 28 in
Georgia; 6Abbott Diagnostics, Abbott Park, United States
children born between 2015 and 2021. We also performed multiple
Email: [email protected]
comparisons tests and a logistic regression to identify factors
associated with lack of timely delivery. Background and aims: Georgia introduced routine infant hepatitis B
Results: between 1 January 2015 and 31 July 2021, 77, 913 births were (HepB) vaccination in 2001 with >90% coverage over the last decade.
recorded; of them 77, 515 live births with complete information were In 2015, a nationwide serosurvey demonstrated an anti-hepatitis B
analysed. 3, 494/77, 515 babies (4.5%) received a timely HepB-BD core antibody (anti-HBc) prevalence of 25.9% and hepatitis B surface
(D0–1). The median age at first dose was 20 days (IQR: 12–31 days). antigen (HBsAg) prevalence of 2.9% among adults ≥18 years. No
HepB-BD was administrated at D7 and D28, in 7, 308/77, 515 (9.4%) prevalence data were available for children. In 2021, we assessed
and 38, 239/77, 515 (49.3%) babies, respectively. hepatitis B virus (HBV) infection prevalence among children and
Whilst timely HepB-BD coverage steadily increased over time updated estimates for adults in a combined COVID-19, hepatitis C and
(Figure 1), a major disruption was observed between March and hepatitis B serosurvey of persons aged ≥5 years.
August 2020, corresponding to the first wave of COVID-19 outbreak in Method: We used a stratified, multi-stage cluster design. We
The Gambia. Between March and August 2020, the HepB-BD coverage collected data on demographics, medical and exposure history; we
dropped from 9% (July 2019 to Feb 2020) to 5%. tested blood samples for anti-HBc and, if positive, for HBsAg.
Nationally representative weighted proportions and 95% confidence
intervals (CI) for anti-HBc and HBsAg were calculated. Participants
aged 5–20 years had been eligible for routine HepB vaccination as
infants.
Results: Among children aged 5–17 years, 0.7% were anti-HBc+ and
0.03% were HBsAg+ (Table). Among adults ≥18 years, 21.7% were anti-
HBc+ and 2.7% were HBsAg+. Anti-HBc prevalence increased with age
from 1.3% among 18–23-year-olds to 28.6% among ≥60 years. HBsAg
prevalence was lowest (0.2%) among 18–23-year-olds and highest
(8.6%) among 35–39-year-olds. Males had higher HBsAg prevalence
than females (3.6% versus 2.0%; p = 0.003). Anti-HBc prevalence was
highest in Samegrelo-Zemo Svaneti, Adjara, and Imereti regions.
Higher education and income were associated with lower anti-HBc,
and unemployment-with higher HBsAg prevalence.

Figure: Monthly proportion of timely HepB-BD from 1st Jan. 2015 to 31st
July 2021. Circled in red is the disruption observed in the immediate wake
of the first CoViD 19 outbreak (the black vertical line shows the date of
the 1st case, 17 March 2020). Magenta dashed vertical lines are change
points detected using general fluctuations tests (Bai-Perron). Blue hori-
zontal segments show the mean timely BD rate for each period between
change points.
Factors associated with lack of timely HepB-BD were: births on Friday
or Saturday (OR:3.2 (95% CI: 2.0 to 3.5), p value <10−15), high maternal
age (OR:1.5 (1.4 to 1.6), p <10−12 for mothers older than 20 with
respect to (wrt) mothers younger than 20, and OR: 1.8 (1.6 to 2.1), p

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POSTER PRESENTATIONS
Conclusion: The impact of HepB vaccination in Georgia is demon-
strated by a low HBsAg prevalence among children that is below the
0.5% European regional hepatitis B control target and meets
the ≤0 .1% seroprevalence target for elimination of mother-to-child
transmission of HBV. Chronic HBV infection remains a problem
among adults born before routine infant HepB vaccination. Focusing
efforts on screening, treatment, and preventive interventions among
adults, along with sustaining high immunization coverage among
children, can help Georgia achieve elimination of hepatitis B as public
health threat by 2030.

THU284
Progress towards HCV elimination in the country of Georgia:
insights from modelling and national survey Conclusion: HCV prevalence reduction due to treatment and
Josephine Walker1, Irina Tskhomelidze2, Shaun Shadaker3, prevention interventions was greater than originally projected, but
Maia Tsreteli4, Senad Handanagic3, Paige A Armstrong3, treatment numbers must still increase in order to reach HCV
Amiran Gamkrelidze4, Peter Vickerman1. 1University of Bristol, elimination by 2030.
Population Health Sciences, Bristol, United Kingdom; 2Task Force for
Global Health, Tbilisi, Georgia; 3Centers for Disease Control and THU285
Prevention, Division of Viral Hepatitis, Atlanta, United States; 4National Measuring the alcohol related hospital burden in Ireland and the
Center for Disease Control and Public Health, Tbilisi, Georgia impact of Minimum Unit Pricing (MUP)
Email: [email protected] Tobias Maharaj1,2, Olufemi Aoko1,2, Elizabeth Gilligan3,
Siobhan MacHale1,3, John Ryan1,2. 1Royal College of Surgeons in Ireland
Background and aims: A national serosurvey in 2015 found the
(RCSI), Ireland; 2Beaumont Hospital, Hepatology Unit, Dublin, Ireland;
country of Georgia had high hepatitis C virus (HCV) prevalence, with 3
Beaumont Hospital, Liaison Psychiatry, Dublin, Ireland
5.4% of adults (∼150, 000 people) chronically infected. In April 2015,
Email: [email protected]
Georgia launched a national program to eliminate HCV infection
(reduce prevalence by 90%). We developed an HCV transmission Background and aims: Alcohol harms are a significant burden on
model to capture current and historical dynamics of HCV infection in healthcare services and in Ireland alcohol related hospital admissions
Georgia, and project long-term impact of the elimination program. A account for approximately 7% of state health expenditure. Minimum
follow-up serosurvey in 2021 provided data which was used to Unit Pricing (MUP) sets a legally required floor price per alcohol unit.
validate the model and update impact projections. On 4 January 2022, MUP was introduced in Ireland at €1.00 per unit
Method: The original model was calibrated to the 2015 serosurvey (10 grams of alcohol). Accurately determining the hospital burden of
and surveys among people who inject drugs (PWID), accounting for alcohol in Ireland is a challenge due to inadequate clinical
age, sex, PWID status, and liver disease state. We compare model documentation and hospital coding of alcohol harms. Previously
projected prevalence overall and by age group, sex, and among ever published MUP studies have suggested immediate reductions in
injected drugs to 2021 serosurvey prevalence, and filter the original admissions for acute alcohol-related conditions. The objective of this
532 parameter sets to match the serosurvey results. We used logistic study was to accurately determine the alcohol-related hospital
regression to assess which input parameters or model characteristics burden, as well as to measure any immediate impact from the
affect fit. We used program data on 77, 168 persons treated May 2015- introduction of MUP.
February 2022 to estimate current incidence of HCV infection, cases Method: All patients presenting to the emergency department of a
and deaths averted. We project the impact of reductions in treatment major hospital in Dublin city were interviewed by a research clinician
rates that occurred in during the COVID-19 epidemic. from 22:00 to 04:00, over seven consecutive nights before and after
Results: The original modelled adult hepatitis C prevalence for 2021 the introduction of MUP (total of 84 hours). Data collection included a
(2.7%, 1.9–3.5%) was higher than the observed serosurvey prevalence brief clinical history of presenting complaint, time of last alcohol
(1.8%, 1.3–2.4%); across all groups uncertainty bounds overlap. Only consumption, AUDIT-C alcohol screening score, and type of alcoholic
14% of 532 model runs fit within the 95% confidence interval of all beverage preference. Each hospital attendance was determined to be
hepatitis C prevalence estimates; 32% fit overall, 28% fit in females, either alcohol-related or non-alcohol-related using published ICD
43% fit in males, 85% fit in ever-injected drugs. Runs that fit the 2021 codes of alcohol-related conditions from MUP modelling data in
serosurvey data tend to have lower total population and lower Ireland. Alcohol presentations were further categorized into acute or
general population hepatitis C incidence, suggesting the model chronic conditions, and directly related or partially related to alcohol.
overestimated the initial burden of infection. After filtering, modelled Results: Excluding missing data (n = 43), there were 245 presenta-
hepatitis C adult prevalence is slightly higher than the observed tions to hospital: 114 pre-MUP and 131 post-MUP. The median age of
prevalence (2.1%, 1.6–2.4%). Hepatitis C incidence in March 2022 is attendances was 49 years old with 50% females pre-MUP and 51.2%
estimated to be 0.05 (95% credible interval (CrI) 0.03–0.11) per 100 females post-MUP. High risk alcohol consumption (AUDIT-C score ≥
person-years in general population, and 1.14 (0.08–6.4) per 100 5) was similar pre-MUP (43%) and post-MUP (42.0%). Beer was the
person-years in PWID, a 60% decrease since 2015. As of March 2022, most preferred beverage pre-MUP (45.5%) and post-MUP (48.8%)
9, 186 (5, 396–16, 720) infections and 842 (489–1324) deaths have compared to all other beverage types. Since the introduction of MUP,
been averted, with benefit accumulating to 26, 154 (15, 850–47, 627) there was no immediate difference in alcohol-related hospital
infections and 3, 971 (2, 516–5, 536) deaths averted if tracked to 2030. attendances (31.6% versus 27.5%; p = 0.48) and no difference in
Treatment numbers went from 996/month in 2019 to 406/month alcohol-related admissions (8.8% versus 7.6%; p = 0.75). Acute
March 2020-March 2022 during the COVID-19 pandemic, resulting in alcohol-related admissions signaled a 40% reduction (95% CI = 3.9%,
14, 127 fewer treatments, 471 (242–817) fewer infections averted by 76.1%; p = 0.03) with MUP. Alcohol admissions for ‘partially related’,
March 2022. At 406 treatments/month, elimination can be reached in ‘directly related’, and ‘chronic conditions’, as well as beverage
2031. preferences did not show any significant difference with MUP ( p
>0.05).
Conclusion: Almost a third of all hospital attendances and almost a
tenth of all hospital admissions are alcohol related, representing a

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 POSTER PRESENTATIONS
significant burden on healthcare resources. Alcohol is a modifiable screening for CRC after detection of hepatic steatosis for patients. We
risk factor and interventions such as €1.00 MUP may have an recommend prospective studies to understand this positive associ-
immediate impact on reducing admissions for acute alcohol condi- ation better. Further studies would be needed to determine if the
tions. Larger sample sizes and longitudinal data are awaited. increase in adenoma detection lowers the risk for the detection of CRC.

THU286 THU287
Is hepatic steatosis individually a risk factor for colorectal No effect of HBsAg positivity on antibody response after COVID-19
adenoma? vaccine
Yuvaraj Singh1, Maya Gogtay1, Anuroop Yekula1, Kartikeya Tripathi2, Ganbolor Jargalsaikhan1,2, Enkhtuul Batbold1,2,
George Abraham1,3,4. 1Saint Vincent Hospital, Internal Medicine, Delgersaikhan Zulkhuu1,2, Oyungerel Lkhagva-Ochir1,2,
Worcester, United States; 2University of Massachusetts Medical School-, Uurtsaikh Baatarsuren1,2, Myagmarjav Budeebazar1,2,
Baystate campus, Department of Gastroenterology, Springfield, United Khatanzul Ganbold1,2, Sumiya Byambabaatar1,2,
States; 3UMass Chan Medical School, Internal Medicine, Worcester, Byambasuren Ochirsum1,2, Munkhzaya Munkhbaatar1,2,
United States; 4American College of Physicians, Philadelphia, United Purevjargal Bat-Ulzii1,2, Bishguurmaa Renchindorj1,2,
States Andreas Bungert1,2, Naranbaatar Dashdorj1,2, Katy Shaw-Saliba3,
Email: [email protected] Irini Sereti3, Sally Hunsberger3, Renee Ridzon3,
Naranjargal Dashdorj1,2. 1Onom Foundation, Ulaanbaatar, Mongolia;
Background and aims: Most colorectal cancers (CRC) originate from 2
The Liver Center, Ulaanbaatar, Mongolia; 3National Institute of Health,
adenomatous lesions. Data suggests that obesity, insulin resistance, Bethesda, Maryland, United States
and metabolic syndrome are risk factors for CRC. Non-alcoholic fatty Email: [email protected]
liver disease (NAFLD) is one of the manifestations of metabolic
syndrome. Many studies have correlated metabolic syndrome with a Background and aims: Immune responses to vaccines may vary
risk of CRC but there is a paucity of evidence on NAFLD and its based on nutritional status, underlying comorbidities and/or con-
association with CRC. We aim to study the association between comitant infections. Despite the high burden of chronic HBV infection
moderate to severe hepatic steatosis detected on vibration-controlled worldwide it is not known if this affects the immune response
transient elastography (VCTE) and colorectal adenomas. following COVID-19 vaccination. We aimed to evaluate antibody
Method: This retrospective cohort study was approved by the levels in people with chronic Hepatitis B virus (HBV) infection,
institutional review board (IRB). We included adult patients who compared to control group among those receiving either their third
underwent VCTE and colonoscopy. Other causes of liver diseases, or fourth COVID-19 vaccination.
such as autoimmune hepatitis, alcohol use disorder, viral hepatitis, Method: Samples from a subset of participants in the InVITE study
and primary biliary cirrhosis were excluded. Steatosis was categor- (ClinicalTrials.gov Identifier: NCT05096091) were assessed for SARS-
ized as S0-S1 (mild) and S2-S3 (moderate/severe) based on the CoV-2 IgG level (MINIVIDAS 3.0, BIOMEREUX, France) and HBsAg
controlled attenuation parameter (CAP) grade of VCTE. Colonoscopy (HISCL-5000, Sysmex, Japan). Chronic HBV infection was defined as
findings were stratified on the biopsy results i.e., hyperplastic, HBsAg>0.03mIU/ml. T-tests were used to compare mean IgG levels
adenoma, CRC, inflammatory or normal mucosa. Continuous vari- and a regression analysis was performed to control for age, sex,
ables were assessed using the Mann Whitney U test and categorical history of COVID-19, number of vaccines received, obesity, and time
variables using chi-square with p <0.05 considered statistically since previous vaccine.
significant. A multinomial logistic regression analysis (MLRA) was Results: Participants received BBIBP CorV (n = 377), ChAdOx1 nCov-
done between colorectal adenoma and significant covariates. 19 (n = 196), BNT162b2 (23), Sputnik V (n = 17) vaccines as their initial
Results: Out of the 415 patients analyzed, 206 patients met inclusion two-dose COVID-19 vaccine regimen. Of the 613 participants
criteria. 124 had moderate/severe steatosis and 82 had no/mild included in this analysis, 104 with chronic HBV and 504 controls.
steatosis. Descriptive analysis showed that BMI (p = 0.001), aspirin Overall characteristics included: 6.5% older than 60 years, 62% female,
(p = 0.011), smoking (p = 0.004), and adenoma (p = 0.02) were signifi- 20% with history of COVID-19, 17% receiving a fourth dose of vaccine,
cantly different between both groups. In the MLRA model; aspirin had 20% obese, and 48% had greater than 6 months since previous
an odds ratio (OR) = 0.39 [ 0.25–0.84 ] (p = 0.01), moderate/severe vaccine; these were well balanced between groups. The IgG levels
steatosis OR = 3.5 [2.39–10.45 ] (p = 0.03) and obesity OR = 2.9 [ 1.07– between groups were not significantly different ( p = 0.265), with
6.78 ] (p = 0.02) in association with colorectal adenoma. mean (std) of control 32.3 (13.6) BAU/ml, chronic HBV, 34.0 BAU/ml
(14.4). Only history of COVID-19 was significantly associated with
increased antibody levels in the regression model ( p = 3.0 × 10−3).
Conclusion: This study showed no difference in SARS-CoV-2 IgG
levels between control and HBsAg positive groups. SARS-CoV-2 IgG
level was higher in participants with previous COVID-19 infection
than those without COVID-19 infection.

THU288
Prevalence of hepatitis B and C virus in the Uzbekistan Hepatitis
Elimination Program (UHEP) patients
Erkin Musabaev1, Chris Estes2, Shakhlo Sadirova3, Shokhista Bakieva1,
Krestina Brigida1, Kathryn Razavi-Shearer2, Bakhodir Yusupaliev4,
Homie Razavi2. 1Research Institute of Virology, Tashkent, Uzbekistan;
2
Center for Disease Analysis Foundation, Lafayette, United States;
3
Center for Disease Analysis Foundation, Tashkent, Uzbekistan; 4Ministry
Figure: Q-Q plot for MLRA of Health, Tashkent, Uzbekistan
Email: [email protected]
Conclusion: Our study indicated that moderate/severe hepatic
steatosis is associated with an increased risk of colorectal adenoma Background and aims: Chronic infection with hepatitis B and C
detection on colonoscopy. Several patients were excluded due to the viruses (HBV and HCV) is a major contributor to liver disease and
non-availability of colonoscopy reports, many of whom were less than liver-related mortality in Uzbekistan. There is a need to better
45 years of age. Current guidelines do not recommend earlier

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POSTER PRESENTATIONS
quantify the number of undiagnosed cases, the characteristics of patients and 54, 396 HCV patients. Age-adjusted adult prevalence of
infected patients, and the risk factors associated with disease. previously undiagnosed chronic HBV and HCV infection were
Method: In the capital city of Tashkent, 13 clinics were established to estimated at 3.23% (3.00–3.37%) and 3.02% (2.80–3.16%), respectively.
diagnosed and treat chronic HBV and HCV infection among the Prevalence was significantly higher in males for both HBV and HCV,
general adult population. Patients underwent testing for HBV and while increasing age was significantly associated with higher HCV
HCV infection, along with follow-up biochemical measures and prevalence. The most commonly reported risk factors among HCV+
questionnaire items. Nurses were trained to use rapid HCV and HBV patients were dental procedures and medical injections, and 2.5% of
tests to screen large number of people and an electronic medical HCV+ patients had APRI score >2.5. Among HBV+ patients 1.2% had
system was put in place to record the test and questionnaire results. eFGR <30 while for HCV+ patients the portion was 3.3%.
The prevalence of previously undiagnosed HBV and HCV was Conclusion: This program represent the first of its kind in terms of
estimated and adjusted to the Uzbekistan population. Regression scope (HBV and HCV testing) and size providing a detailed estimate of
analyses quantified risk of infection based on demographic factors. viral hepatitis infection. A large population of patients chronically
Results: HBV and HCV screening was conducted on 62, 000 people infected with HBV and HCV remains undiagnosed in Uzbekistan.
over a 12-month period that included a 6-month shutdown due to There should be further efforts to screen, diagnose and treat these
the COVID-19 pandemic. Before the shutdown, 30, 000 people were patients in the general population to achieve the WHO 2030
screened while another 32, 000 were screened in conjunction with elimination targets.
COVID-19 testing. Complete dataset was available for 53, 841 HBV

Figure: (abstract: THU288): aPR = Adjusted prevalence ratio.

S236 Journal of Hepatology 2022 vol. 77(S1) | S119–S388

 POSTER PRESENTATIONS
THU289 THU290
Evaluation of the clinical and economic value of sofosbuvir/ The value of increased HCV testing and treatment strategies in
velpatasvir (SOF/VEL) in patients with chronic hepatitis C in Spain Spain to achieve elimination goals
during the last 5 years José Luis Calleja Panero1, Jaime Espin2, Ankita Kaushik3,
Rafael Esteban1, Raquel Domínguez-Hernández2, Helena Cantero3, Manuel Hernández Guerra4, Rob Blissett5, Adam Igloi-Nagy5,
Miguel Ángel Casado2. 1Hospital Universitari Vall d’Hebron, Barcelona, Alon Yehoshua3. 1Universidad Autónoma de Madrid, Hospital
Spain; 2Pharmacoeconomics and Outcomes Research Iberia (PORIB), Universitario Puerta de Hierro, Madrid, Spain; 2Escuela Andaluza de
Pozuelo de Alarcón, Spain; 3Gilead Sciences, Madrid, Spain Salud Pública, Granada, Spain; 3Gilead Sciences, Inc., Foster City, United
Email: [email protected] States; 4Hospital Universitario de Canarias, Tenerife, Spain; 5Maple
Health Group, LLC, New York City, United States
Background and aims: The introduction of direct-acting antivirals in
Email: [email protected]
the therapeutic arsenal for the treatment of hepatitis C virus (HCV)
infection represented a paradigm shift. Sofosbuvir/velpatasvir (SOF/ Background and aims: In 2015, Spain launched a national
®
VEL; Epclusa ) has added value to HCV treatments, achieving high eradication strategy for Hepatitis C virus (HCV) through prevention,
response rates that lead to a cure in most HCV chronic patients. The screening, diagnosis, and link-to-care, resulting in the highest HCV
aim of this analysis was to evaluate the long-term impact on health treatment rate of any European country and substantial reductions in
and economic outcomes of patients with chronic hepatitis C treated HCV prevalence. To achieve the goal of HCV elimination, it is
with SOF/VEL during the first 5 years after its approval in Spain necessary to scale up the diagnosis, treatment, and management of
(2017–2022). HCV infection in the general population, migrants and people who
Method: A previously developed lifetime Markov model was adapted inject drugs (PWID). Our aim was to assess the prevalence, incidence,
to estimate HCV morbidity and mortality comparing two treatment and cost effectiveness of scaling up compared to status quo scenarios.
alternatives: SOF/VEL versus previous therapies ( peginterferon and Method: A compartmental dynamic transmission model was devel-
ribavirin in double/triple therapy with telaprevir or boceprevir). The oped in visual basic for applications (VBA). The model comprises two
target population (30, 488 patients) entered the model during the modules: the first represents the cascade of HCV care and the second
first 5 years (22% 1st year, 26% 2nd, 22% 3rd, 13% 4th, 17% 5th) and represents the progression of liver disease. Direct and indirect costs,
were distributed among the fibrosis states in treated or untreated. In as well as utilities to estimate quality of life were considered as model
SOF/VEL, all patients (100%) were treated regardless of fibrosis states inputs. Outcomes included the prevalence and incidence of HCV
(F0-F4) with an average weighted sustained viral rate (SVR) of 98.9% infection as well as the incremental cost per quality-adjusted life year
from real-world data. In previous therapies, only 49% of ≥F2 states (QALY) and per life year (LY). Outcomes for a hypothetical elimination
HCV patients were treated, with 61% SVR. All parameters required for strategy were compared to those expected with the status quo staying
the analysis were obtained from real-world data and the literature. in place. Costs and effects were discounted at 3.0%; the model time
Only direct healthcare costs associated with disease management horizon is until the year 2030 in the base case and extended to 2040
were included. A discount rate (3%) was applied to costs and in scenario analysis.
healthcare outcomes. The results were measured as the number of Results: The base case analysis found that scaling up testing and
cases of decompensated cirrhosis (DC), hepatocellular carcinoma treatment reduced both the prevalence and incidence of HCV over
(HCC), and liver transplant as well as their costs associated, in time resulting in incremental costs per QALY and LY of €13, 291 and
addition to liver-related deaths, comparing both alternatives. An €12, 285 respectively, compared to the status quo. Excluding indirect
alternative analysis was performed with a reduction in the SVR rate of costs from the analysis brought the incremental costs per QALY and LY
SOF/VEL to 95%. to €13, 761 and €12, 720, respectively. Main drivers of the cost-
Results: In the analysis of SVR rate (98.9%), the lifetime results effectiveness results included cost of diagnosis, cost of treatment,
showed that SOF/VEL decreased liver-related mortality by 85% (4, 017 proportion of people who are unaware, percentage of population of
cases avoided) as well as avoided cases of liver complications: 3, 467 people who inject drugs, and various calibration parameters related
DC (-92%), 2, 536 HCC (-80%) and 474 LT (-87%), having the greatest to HCV infection prevalence. Scenario analyses found that reducing
impact on DC. In economic terms, the costs associated with SOF/VEL the screening intervals decreased the prevalence of HCV infection
in the management of liver complications generated a total saving of over time; extending screening to include migrants upon arrival in
197 million euros. In the alternative analysis, a variation in the SVR Spain also decreased the prevalence over time with the same or
rate (95%) decreased the impact on the reduction of avoided liver- better cost effectiveness metrics.
related events between 75 and 86%.

Conclusion: SOF/VEL significantly decreases HCV morbidity and

mortality adding value to the management of patients with chronic
hepatitis C reducing the clinical and economic burden of the disease
and contributing to the goal of disease elimination in Spain.

Figure 1: Annual incidence of HCV in Spain over time in the increased

testing scenario compared to status quo.

Conclusion: This analysis demonstrated that scaling up testing and

treatment with direct acting antivirals (DAAs) is an efficient strategy
for reducing the incidence and prevalence of HCV infection among

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POSTER PRESENTATIONS
key populations of interest in Spain. Given the global burden of HCV
infection, and its associated liver-related morbidity and mortality, CH EG ES IT PT
increasing access to testing and treatment among key populations of Simplified care algorithm
interest may be a successful strategy to achieve HCV elimination goals <2 visits Partial (Optional) Partial (Varies No No ✓
in Spain. required across
during country)
THU291 treatment
National hepatitis elimination profiles: progress towards HBV and Non- ✓ ✓ No No No
HCV elimination in five European countries specialists can
prescribe
Lindsey Hiebert1, Isabelle Nassar1, Vanessa Nunez1, Loreta Kondili2, treatment
Sema Mandal3, Graham Foster4, No mandatory No ✓ ✓ Partial (for No
Francisco Javier Garcia-Samaniego Rey5,6, Philip Bruggmann7,8, genotyping key
Paolo Bonanni9, Camila Picchio10, Rui Marinho11, Jeffrey Lazarus10, populations)
John Ward1. 1Task Force for Global Health, Coalition for Global Hepatitis No co- ✓ ✓ ✓ ✓ ✓
Elimination, Decatur, United States; 2Istituto Superiore di Sanità, Italy; payments
3
UK Health Security Agency, United Kingdom; 4Queen Mary University of Removal of restrictions
London, United Kingdom; 5Alianza para la Eliminación de las Hepatitis Based on ✓ ✓ ✓ ✓ ✓
fibrosis
Víricas en España, Spain; 6Hospital Universitario La Paz, Spain; 7Swiss
Based on ✓ ✓ ✓ ✓ ✓
Hepatitis, Switzerland; 8Arud Centre for Addiction Medicine, sobriety
Switzerland; 9University of Florence, Italy; 10University of Barcelona,
Institute of Global Health (ISGlobal); 11University of Lisbon (FMUL)
Conclusion: NHEPs reveal advances and challenges to hepatitis
Email: [email protected]
prevention and care and lessons learned for overcoming barriers.
Background and aims: To achieve WHO goals for hepatitis With NHEPs, local coalitions (CSO, MoH, clinical) can advocate for
elimination, Member States (MS) are in various stages of national policies expanding HBV and HCV services, accelerating progress
planning and policy development. To track country-level progress toward hepatitis elimination.
and identify feasible next steps, CGHE is developing National
Hepatitis Elimination Profiles (NHEPs). The status of hepatitis THU292
elimination in European countries are described. Economic investment and strategies to eliminate hepatitis C in
Method: Together with local partners, profiles were prepared for Mexico
England (EG), Italy (IT), Portugal (PT), Spain (ES) and Switzerland Ellen Mooneyhan1, Alethse De la Torre Rosas2, Daniel Bernal Serrano2,
(CH). For comparison, key indicators include policies for prevention, David Kershenobich3, Maria Jesus Sanchez4, Leandro Soares Sereno5,
testing, and treatment. Country-specific data were collected from Ivane Gamkrelidze1, Sarah Blach1, Homie Razavi1. 1Center for Disease
peer-reviewed reports, ministries of health (MoH), ECDC, WHO and Analysis Foundation, Lafayette, United States; 2National Center for the
other credible sources. Partners in MoH, clinical practice, and civil Prevention and Control of HIV (CENSIDA), Mexico City, Mexico; 3The
society organizations (CSO) validated data. National Institute of Health Sciences and Nutrition Salvador Zubirán
Results: All MS have an HCV action plan; ES, IT, and CH have HBV (INCMNSZ), Tlalpan, Mexico; 4Pan American Health Organization,
action plans. EG, ES, and CH have set HBV and HCV elimination Mexico City, Mexico; 5Pan American Health Organization, Washington
goals, while PT has goals for HCV. For CH and ES, the hepatitis AP DC, United States
and goals were prepared by clinical associations and CSO. All MS Email: [email protected]
have >95% coverage of infant 3-dose HepB vaccination. All MS have
policies for routine HBV screening of pregnant women; IT Background and aims: In July 2020, the Mexican Government
recommends maternal HCV screening. All countries recommend initiated the National Program for Elimination of Hepatitis C (HCV)
HepB birth dose vaccination (Hep-BD-V) for newborns of HBsAg+ under a procurement strategy that secured universal, free access to
mothers. PT recommends universal HepB-BD- V <24 hours of birth; HCV screening, diagnosis, and treatment for 2020–22. This analysis
PT has >50% coverage, the WHO 2020 target. The 4 countries with quantifies the clinical and economic burden of HCV under a
data distribute 27–139 needle-syringes per person who injects continuation (or an end) to this agreement.
drugs (PWID) per year, 14%-70% of the WHO 2020 target. At least Method: A modeling and Delphi approach was used to evaluate the
two MS have safe injection programs for persons who are current and future disease burden (from 2020 to 30) and economic
incarcerated. All countries have risk-based HBV and HCV screening; impact (from 2020 to 35) of the historical paradigm (Historical Base)
IT recommends HCV testing for persons born 1969–1989. All have compared to HCV elimination (Elimination). The elimination cost
removed most restrictions to HCV treatment. However, some MS analysis was stratified assuming the agreement continues
require HCV genotyping (CH, IT, PT) and specialty care (ES, IT, PT) (Elimination-Agreement to 2035) or terminates (Elimination-
(figure). Data suggest 3 countries have reduced HCV mortality rates Agreement to 2022). We also analyzed the price of HCV treatment
approaching or exceeding the 2030 WHO target ( ≤2 /100, 000). As needed to achieve net-zero cost (defined as the difference in
feasible next steps, local partners prioritize community awareness cumulative direct costs between the scenario and the Historical
of hepatitis, expanded adult testing, and micro-elimination Base), starting at a base price of 77, 838 MXN per person per
programs for key populations (PWID, INC). treatment. Elimination is defined by the World Health Organization
as a 90% reduction in new infections, 80% diagnosis coverage, 80%
treatment coverage, and 65% reduction in mortality, by 2030.
Results: A viremic prevalence of 0.55% (0.38–0.60) was estimated in
Mexico on January 1, 2021, corresponding to 745, 000 (677, 000–812,
000) viremic infections. In the Historical Base, cases of advanced liver
disease and liver-related deaths are projected to rise 75%-80% and
annual direct costs are projected to remain at 2.4–2.5 billion MXN,
with cumulative direct costs reaching 39.7 billion MXN. Elimination
could save 23, 500 lives and divert 6.5 billion MXN in healthcare costs.
Under Elimination-Agreement to 2035, annual direct costs are
projected to peak at 2.6 billion MXN, with cumulative direct costs

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 POSTER PRESENTATIONS
of 31.2 billion MXN. Under the Elimination- Agreement to 2022,
annual direct costs would peak at 8.1 billion MXN, estimating 74.2
billion MXN in cumulative direct costs. The price of HCV treatment
must decrease to 11, 000 MXN per patient to achieve net-zero cost by
2035.
Table: Clinical and economic outcomes for integrated screening of three
diseases and hepatitis C screening

Conclusion: This study provides evidence that adherence to the

integrated screening of Hepatitis C, HIV/AIDS, and tuberculosis is
more cost-effective and increases the rate of screening coverage
compared to single hepatitis C screening alone.

THU294
Figure: Direct Medical Costs, 2020–2035 annual direct medical costs, b) Eliminating chronic hepatitis B in the northern territory of
cumulative direct medical cost
Australia through a holistic care package delivered in partnership
Conclusion: To achieve HCV elimination at net-zero cost or below, with the community
the Mexican Government could either extend the procurement Jane Davies1, Joshua Saul Davis1, Kelly Hosking2, Paula Binks1,
agreement through 2035 or reduce the cost of HCV treatment from Catherine Gargan2, Belinda Greenwood-Smith2, Sarah Bukulatjpi3,
77, 838 MXN to 11, 000 MXN per person per treatment, starting in Terese Ngurruwuthun3, Amanda Dhagapan3, Phillip Wilson2,
2023. Otherwise, the Mexican Government must increase national Teresa De Santis2, Karen Fuller4, Melita McKinnon1, Mikaela Mobsby2,
budget allocation to the elimination program in order to achieve Emily Vintour-Cesar1. 1Menzies School of Health Research; 2Northern
elimination by 2030. Territory Government, Department of Health, Darwin City, Australia;
3
Miwatj Health Aboriginal Corporation; 4Katherine West Health Board
THU293 Aboriginal Corporation
Assessing the cost-effectiveness of integrated screening of viral Email: [email protected]
hepatitis C, HIV, and tuberculosis
Background and aims: Hep B PAST is a partnership project
Ketevan Goginashvili1, Ekaterine Adamia1. 1Ministry of Internally
developed to eliminate chronic hepatitis B (CHB) from the
Displaced Persons from the Occupied Territories, Labour, Health and
Aboriginal population of the Northern Territory (NT) in Australia.
Social Affairs of Georgia, Policy Department, Tbilisi, Georgia
Preliminary results from the project demonstrate significant
Email: [email protected]
improvements in the cascade of care for those living with CHB. The
Background and aims: Georgia has made significant progress in project aims to:
reducing the burden of communicable diseases, which is due to Improve hepatitis B related health literacy
effective measures taken to manage these diseases. The aim of the Improve the cascade of care for people living with CHB
study was to evaluate the cost-effectiveness of integrated screening Method: Aim 1: Using a participatory action approach (PAR) the “Hep
for the early detection of hepatitis C, HIV/AIDS, and tuberculosis, B Story” educational app was designed, translated (forward and back
introduced at the level of primary health care since 2018. translation) launched in pilot language Yolηu matha, and evaluated,
Method: A pre and post-intervention study focused on comparing of with the process then repeated for the seven next most widely
two different methods of hepatitis screening using the cost- spoken NT Aboriginal languages.
effectiveness evaluation. For the purpose of the study: the costs, Aim 2: Reviewing existing pathology and vaccination data from
screening coverage, and prevalence rates were compared for two electronic health record systems, individuals in consenting health
different screening methods 1) integrated screening for hepatitis C, services were allocated to one of six hepatitis B sero-status codes
tuberculosis, and HIV/AIDS; 2) Separate screening of all three (Hep B: Fully vaccinated, Hep B: Immune by Exposure, Hep B:
diseases in Samegrelo region. Infected ON Treatment, Hep B: Infected NOT ON Treatment, Hep B:
Method: In Samegrelo region, primary health physicians conducted Non-Immune, No data) triggering an appropriate follow-up response
an average of 0.68 integrated screenings per adult person for hepatitis for all clients. To support primary care to manage recalls and follow-
C, tuberculosis, and HIV/AIDS in 2019–2020, the mean screening cost ups as appropriate, we delivered hepatitis B education to remote
was 9.4 GEL per person and the hepatitis C prevalence rate was 6.5% doctors, nurses, and Aboriginal Health Workers (AHWs). Using a PAR,
( p <0.05). While in 2017–2018, Separate screening of all three a hepatitis B management education course for AHWs was devel-
diseases per adult person in the same region was 0.35, expenditure on oped, delivered, and evaluated.
hepatitis screening was GEL 17.4 and the prevalence rate was 6.9% ( p Results: The Hep B Story App is now available in English and eight
<0.05). The Cost-effectiveness coefficient was 13.8 and 49.7 for Aboriginal languages spoken in the NT and roll out and evaluation is
integrated screening and for hepatitis screening respectively ( p = underway. All client files in participating health services have been
0.01). reviewed, with approximately 30, 000 Aboriginal clients allocated a
Results: In Samegrelo region, primary health physicians conducted hepatitis B serocode and appropriate care pathway. Hepatitis B
an average of 0.68 integrated screenings per adult person for hepatitis education has been delivered to over 150 general practitioners and
C, tuberculosis, and HIV/AIDS in 2019–2020, the mean screening cost nurses in the NT, and to approximately 100 AHWs. The cascade of care
was 9.4 GEL per person and the hepatitis C prevalence rate was 6.5% for those living with hepatitis B in the NT has significantly improved,
( p <0.05). While in 2017–2018, Separate screening of all three now exceeding National Hepatitis B Strategy Targets, with 90%
diseases per adult person in the same region was 0.35, expenditure on allocated a serocode (national target = 80%), 61% engaged in care
hepatitis screening was GEL 17.4 and the prevalence rate was 6.9% ( p (national target = 50%), and 21% receiving antiviral treatment
<0.05). The Cost-effectiveness coefficient was 13.8 and 49.7 for (national target = 20%)
integrated screening and for hepatitis screening respectively ( p = Conclusion: This project is demonstrating the effectiveness of a
0.01). partnership approach with communities, with AHWs at the centre of
the care model, and creating a community led, culturally acceptable,
in-language health promotion tool in improving client outcomes for
CHB. The preliminary findings from the project demonstrate

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POSTER PRESENTATIONS
improvements in clinical care whilst preserving Aboriginal languages THU296
and empowering community through increased health literacy. Association between immunosuppressants and poor antibody
responses to inactivated SARS-CoV-2 vaccines in patients with
THU295 autoimmune liver diseases
Hepatitis C prevalence and elimination in Pakistan; a bottom-up Hu Li1, Yuting Wang1, Ling Ao1, Mingxia Ke1, Zhi-wei Chen1,
approach accounting for provincial variation Min Chen1, Ming-Li Peng1, Ning Ling1, Peng Hu1, Dachuan Cai1,
Ellen Mooneyhan1, Huma Qureshi2, Hassan Mahmood2, Dazhi Zhang1, Hong Ren1. 1Key Laboratory of Molecular Biology for
Samra Mazhar2, Muhammad Tariq3, Nabeel Ahmed Maqbool3, Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis,
Ambreen Khan3, Masood Anwar3, Sarah Blach1, Homie Razavi4, Department of Infectious Diseases, the Second Affiliated Hospital of
Sabeen Shah5, Saeed Sadiq Hamid6, Tanweer Hussain3, Chongqing Medical University
Saira Khowaja5, Uzma Khan7, Syeda Zahida Sarwar3, Email: [email protected]
Khalid Mahmood8,9, Gul Sabeen Azam Ghorezai10, Farooq Azam11,
Ayub Rose12, Mohammad Khalil Akhter13, Aamir Ghafoor Khan13, Background and aims: To evaluate the safety, antibody responses
Mujahid Aslam14, Ahmad Nawaz13,14. 1Center for Disease Analysis and explore the impact of immunosuppressants on inactivated SARS-
Foundation, United States; 2Ministry of National Health Services, CoV-2 vaccines in patients with autoimmune liver diseases (AILD).
Regulations and Coordination, Islamabad, Pakistan; 3Chemonics Method: In this prospective study, 76 adult patients with AILD and
International, Pakistan; 4Center for Disease Analysis Foundation, 136 healthy subjects were enrolled at least 21 days since the second
Lafayette, United States; 5Indus Hospital and Health Network, Karachi, dose of vaccines (BBIBP-CorV or CoronaVac). All adverse events (AEs)
Pakistan; 6Aga Khan University and Hospitals, Karachi, Pakistan; 7IRD after the COVID-19 vaccination were recorded and graded. The anti-
Pakistan, IRD Global, Karachi, Pakistan; Singapore, Singapore, Pakistan; RBD-IgG and neutralizing antibodies (NAbs) were determined. In
8
Punjab Hepatitis Control Programme, Lahore, Pakistan; 9Punjab addition, SARS-CoV-2 specific B cells were also analyzed.
Hepatitis Control Program, Primary and Secondary Healthcare, Lahore, Results: All AEs were mild and self-limiting, and the incidence was
Pakistan; 10Balochistan Hepatitis Control Programme, Quetta, Pakistan; similar between AILD patients and controls within 7 days and 30 days
11
Chemonics International/USAID, Quetta, Pakistan; 12Chemonics after COVID-19 vaccination. The anti-RBD-IgG and NAbs were
International/USAID, Peshwar, Pakistan; 13Health Department Khyber detectable in 74 (97.4%, 100% in healthy controls, p = 0.13) and 48
Pakhtunkhwa, Peshawar, Pakistan; 14Lady Reading Hospital, Peshwar, (63.2%, 84.6% in healthy controls, p <0.001) patients. The titers of anti-
Pakistan RBD-IgG ( p = 0.02) and NAbs ( p <0.001) were both significantly lower
Email: [email protected] in AILD patients than healthy controls. In multiple regression
analysis, immunosuppressive therapy was an independent risk
Background and aims: In Pakistan, substantial changes to hepatitis C factor for the low-level anti-RBD-IgG responses (AOR: 4.7; 95% CI,
virus (HCV) programming and treatment have occurred since the 1.5–15.2; p = 0.01) and reduced probability of NAbs seropositivity
2008 national serosurvey estimated a 4.8% anti-HCV prevalence. (AOR, 3.0; 95% CI, 1.0–8.9; p = 0.04) in AILD patients. However,
However, a recent national serosurvey is unavailable. This analysis regardless of with or without immunosuppressants, the RBD-specific
estimates a national prevalence using a bottom-up approach to MBCs responses were comparable between patients with AILD and
account for provincial variation, coupled with screening, treatment, healthy controls.
and prevention targets needed to achieve elimination by 2030. Conclusion: The COVID-19 inactivated vaccine is safe and achieves
Method: Using a Delphi method, epidemiologic HCV data for the four efficient antibody responses in patients with AILD. In addition,
provinces of Pakistan (accounting for 97% of the country’s popula- immunosuppressants are significantly associated with poor antibody
tion) were reviewed with 21 provincial and national subject-matter responses to the SARS-CoV-2 vaccine.
experts over 10 virtual meetings. Province-level estimates were then
aggregated and inputted into a mathematical model to estimate the THU297
national HCV disease burden in the absence of intervention (Base), “Like what? You think I have that?”-Impact of stigma on
and if the World Health Organization (WHO) elimination targets of a pharmacy-based identification and treatment of hepatitis C in
90% reduction in new infections, 80% diagnosis coverage, 80% Victoria, British Columbia
treatment coverage, and 65% reduction in mortality, are achieved by Marion Selfridge1,2, Tamara Barnett1, Kellie Guarasci1,
2030 (WHO Elimination). Karen Lundgren1, Anne Drost1, Chris Fraser1,3. 1Cool Aid Community
Results: An estimated 9, 746, 000 (7, 573, 000–10, 006, 000) Health Centre, Victoria, Canada; 2University of Victoria, Canadian
Pakistanis are living with viraemic HCV as of January 1, 2021, Institute of Substance Use Research, Victoria, Canada; 3University of
corresponding to a viraemic prevalence of 4.3% (3.3–4.4). Under the British Columbia, Department of Family Medicine, Vancouver, Canada
Base, it is estimated that 21% (2, 010, 000) of the infected Pakistani Email: [email protected]
population has been diagnosed with HCV and only 2% (215, 000) of
those infected received treatment in 2021. WHO Elimination would Background and aims: Canada is currently on target to reach the
require an annual average of 18.8 million people screened, 1.1 million 2030 WHO goal of HCV elimination. Continued high rates of
treated, and 46, 700 new infections prevented between 2021–2030. treatment initiation are required to meet this goal. Novel models
WHO Elimination would reduce total infections by 7, 040, 000, save have proven successful to engage populations who use drugs (PWUD)
152, 000 lives and prevent 104, 000 incidence cases of hepatocellular in HCV therapy with a simplified, task-shifted cascade of care:
carcinoma between 2015 and 2030. Tayside, Scotland pharmacy-based HCV screening and treatment has
Conclusion: Recent blood surveys, programmatic data, and expert demonstrated excellent outcomes and progress towards local HCV
panel input from the four provinces of Pakistan uncovered a higher elimination. The EPIC Study seeks to determine whether pharmacy-
number of HCV infections and lower number of patients treated than based treatment successes can be replicated at community pharma-
has been estimated using national extrapolations, which demon- cies in Victoria BC.
strates the benefits of a bottom-up approach. Screening and Method: Four community pharmacies known to work with PWUD
treatment must increase 20-fold and 5-fold, respectively, from and provide opioid agonist therapy (OAT) were provided training
current levels, to curb the HCV epidemic in Pakistan and achieve sessions to equip staff with a standardized tool kit of resources. In fall
elimination by 2030. 2020, pharmacy staff were trained to provide verbal informed
consent and perform point of care HCV OraQuick antibody screening.
Pharmacies were supported by a study nurse to link to HCV RNA
testing when antibody positive patients were identified, with
initiation of HCV treatment offered to those found to be RNA positive.

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 POSTER PRESENTATIONS

Figure: (abstract: THU296): Antibody responses after the COVID-19 vaccination in patients with AILD and healthy controls. (A-B) The seropositivity rate (A)
and titers (B) of anti-RBD-IgG in patients with AILD and healthy controls. (D-E) The seropositivity rate (D) and titers (E) of NAbs in patients with AILD and
healthy controls. The distribution of anti-RBD-IgG (C) and NAbs (F) antibody titers over time in patients with AILD and healthy controls. AILD, autoimmune
liver disease; anti-RBD-IgG, spike receptor-binding domain IgG antibody; NAbs, neutralizing antibodies.

The study nurse worked with pharmacy staff to strategize adherence THU298
and support as needed by study subjects. Qualitative interviews have Improved clinical and economic outcomes in an intensive care
been conducted with five pharmacy staff to explore their experiences unit with a focus on hepatology through interprofessional
with testing and monitoring HCV treatment and the feasibility of cooperation between physicians, staff nurses, and pharmacists
involving pharmacists in the HCV care cascade. Schmid Stephan1, Schlosser Sophie1, Karsten Guelow1, Vlad Pavel1,
Results: To date pharmacy staff completed 171 HCV OraQuick tests Alexander Mehrl1, Martina Mueller-Schilling1, Alexander Kratzer2.
finding 53 tested positive for HCV antibodies: 23 people were HCV 1
University Hospital Regensburg, Department of Internal Medicine I,
RNA negative, (20 previously treated and 2 self-cleared), 8 unk/LTF. Of Gastroenterology, Hepatology, Endocrinology, Rheumatology, and
the 22 RNA positive participants, 1 is pending treatment start, 21 Infectious Diseases, Regensburg, Germany; 2University Hospital
people have started treatment, with 8 achieving SVR. While great Regensburg, Hospital Pharmacy, Regensburg, Germany
success has been achieved in treating identified people, less than half Email: [email protected]
of projected OraQuick tests have been completed. Although the onset
Background and aims: Since 2015, the medical intensive care unit
of the Covid 19 pandemic was a fundamental barrier incorporating
HCV testing at pharmacies, stigma related to HCV and illicit drug use (ICU) with a focus on hepatology of the Department of Internal
Medicine 1 at the University Hospital Regensburg, Germany, has a
continues to impact this process. Pharmacists described feeling
particular emphasis on interprofessional collaboration with staff
hesitant about approaching participants, especially after receiving
negative responses from clients about HCV testing. Some worried nurses and hospital pharmacists. The hospital pharmacists have
access to the hospital information system and the electronic charting
their relationship would change with clients as asking about HCV
implied risky drug use. program. Consultations take place on daily basis. Furthermore,
weekly joint rounds within the antibiotic stewardship program are
Conclusion: This innovative and novel approach to HCV therapy in
performed. Furthermore, there is a joint training and teaching of
PWUD attempted to use a pharmacy-based approach to find people
with limited connection to primary health care to test and treat HCV. medical, nursing and pharmacy students within the intensive care
training ward Regensburg (I’M A-STAR project). The study aims to
Increased training of pharmacy staff related to stigma around drug
use and HCV is required both before and ongoing for successful investigate to what extent the newly introduced structural changes
affect clinical and economic outcomes.
integration of pharmacy-led HCV testing and treatment in Canada.
Method: We examined clinical performance data and consumption
figures for antibiotics and other drugs over a 10-year period from

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POSTER PRESENTATIONS
2011 to 2021. Data from the hospital pharmacy, hospital administra- Fast approach (50% of the target population each year at years 1, 2, 3
tion, electronic charting, and hospital information systems were and 4).
included in the analyses. An electronic platform was developed Results: The overall estimated number of HCV active infections to be
specifically to improve documentation. The years 2020 and 2021 diagnosed in the target population was 106, 200. The incremental
were considered separately due to the COVID-19 pandemic and the approach scenario estimated 62% of the target population diagnosed
care of numerous COVID-19 patients in the ICU. vs 94% diagnosed in the fast approach scenario. An increase in overall
Results: It could be shown that the pharmacist’s recommendations costs was observed in the fast approach scenario up to year 5, but at
regarding drug administration were mainly related to indication year 6 the cost starts to decrease due to a higher number of diagnosed
(43.6%), dosage (27.6%), interactions (9.4%), and side effects (4.1%). patients versus the incremental approach in which the disease costs
Antibiotic consumption was reduced by 12.2% from 2015 to 2019. continue to increase. (Figure 1). At ten years’ time-horizon, the model
Encouragingly, this included a 23.4% reduction in carbapenem use. estimated a cumulative not mutually exclusive reduction of 5, 406
Antibiotic spending was reduced by 24.9% overall. persons living in the HCC health state, 4, 614 in decompensated
An analysis of the intensive care G-DRGs showed that the case-mix cirrhosis and 11, 081 liver-related deaths. A cost reduction of € 74
points increased significantly by 31.6% during the period under million was estimated if a fast approach was adopted versus the
review. Similarly, patient severity of illness as measured by the SAPS II incremental one.
score increased by 21.4%. The proportion of mechanically ventilated Conclusion: A delay in HCV diagnosis in the general population from
patients exceeded 50%. 1968-to 1948, yet not addressed for the HCV free of charge screening,
In another analysis, antibiotic spending per case-mix point was will have important clinical and economic consequences in Italy.
calculated. While spending was EUR 60.22 per case-mix point in
THU300
2015, this could be reduced by 42.9% to EUR 34.37 per case-mix point
Evaluation of access to treatment for hepatitis C: a large
by 2019.
retrospective cohort from a tertiary care hospital in Turkey
Conclusion: Through close interprofessional collaboration between
physicians, staff nurses, and pharmacists, the consumption of Merve Eren Durmuş1,2, Gökhan Köker3, Yeşim Çekin4, Serkan Ocal5,
antibiotics and other drugs (e.g., albumin) was significantly Ayhan Çekin5. 1Antalya Education and Research Hospital,
reduced, thus improving patient care. There was also a positive Gastroenterology, Antalya, Turkey; 2Antalya Education and Research
economic effect-with a simultaneous increase in case-mix points, Hospital, Gastroenterology, Turkey; 3Antalya Education and Research
expenditure on antibiotics was significantly reduced. Hospital, Internal Medicine, Antalya, Turkey; 4Antalya Education and
Responsible use of resources and high-performance medicine are not Research Hospital, Medical Microbiology, Turkey; 5Antalya Education
contradictory. In our view, a close interprofessional collaboration and Research Hospital, Gastroenterology, Turkey
between physicians, staff nurses, and pharmacists will be of Email: [email protected]
outstanding importance in the future, particularly in intensive care Background and aims: Hepatitis C virus (HCV) infection is a major
medicine. public health issue. According to 2015 data, approximately 71 million
people have chronic HCV viremia in the world. It is one of the leading
THU299 causes of liver-related morbidity and mortality globally. The
Need to implement the screening strategy to advance HCV seroprevalence of anti-HCV in our country has been detected 0.5–
elimination in Italy: a cost-consequences analysis 1%. Due to its silent progress many patients may be unaware of the
Andrea Marcellusi1, Kristi Tata2, Francesco Mennini1, situation. In our study, we aimed to determine the rate of the anti-
Massimo Andreoni3, Loreta Kondili4. 1Tor Vergata University, CEIS, HCV positive patients who were able to access to treatment.
Rome, Italy; 2University Hospital Center of Tirana, Tirana, Albania; 3Tor Method: Subjects who had anti-HCV positivity between 2014–2019
Vergata University, Rome, Italy; 4Istituto Superiore di Sanità, Center for have been reviewed retrospectively. The data of the patients were
Global Health, Rome, Italy recorded and patients referred for further evaluation and accessed to
Email: [email protected] treatment were identified.
Background and aims: In Italy, the HCV disease burden is the highest
of western Europe. A graduated screening strategy that covers the
birth cohort population from 1948-to 1988 is cost-effective to achieve
HCV elimination in Italy. A dedicated fund for HCV screening could
permit free of charge testing of the population from 1969-to 1989, but
if the screening is not implemented to other birth cohorts the HCV
elimination targets could not be achieved. Based on the HCV infection
burden, by a cohort of age and fibrosis stage previously estimated, we
evaluated the cost-consequences of a delay of HCV diagnosis in the
next 5 years in Italy.
Method: We used a previously designed and validated probabilistic
model to estimate the clinical, and economic outcomes of different
screening coverage uptakes, considering the HCV disease costs by the
Figure: Disparity between the number of anti-HCV positive individuals,
fibrosis stage as reported by the PITER cohort real-life data. The model
those who were tested for HCV-RNA viremia, HCV genotypes and the ones
starts with a decision probabilistic tree that simulates 5 years of HCV who could access to the treatment and comparison of two groups contri-
testing in the general population cohort born between the years butions on each stage.
1948–1967 (15, 485, 565 individuals to be tested) with different
coverage rates lower in the lack of active screening and higher in case Results: The clinics that requested anti-HCV tests were divided in to
of screening implementation. The first part of the model identified two groups. Group 1 included gastroenterology, infectious diseases
and categorized HCV chronic patients by the fibrosis stage. A Markov and internal medicine along with its other subspecialties; and the
model was considered for 10 years horizon time. The simulations rest of the clinics are defined as Group 2. There were 3924 anti-HCV
consider two alternative coverage rates and timing during the five positive patients in 5-years period. 2350 of them were tested for HCV
years simulated scenarios: 1) Incremental approach (coverage rates viremia (%59.9). HCV-RNA were positive in 1147 of them (%29.2),
equal to 10%, 20%, 25%, 30% respectively at years 1, 2, 3, and 4) and 2) corresponding to %48.8 of the patients who have been tested. Among
the patients with HCV-RNA positivity, 948 of them were tested for

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 POSTER PRESENTATIONS
100,000

90,000

Cumulative Diagnosed/Undiagnosed patients

80,000

70,000

60,000

50,000

40,000

30,000

20,000

10,000

0
1 2 3 4 5 6 7 8 9 10
Years of Follow-up

Diagnosed Undiagnosed

120,000
Cumulative Diagnosed/Undiagnosed patients

100,000

80,000

60,000

40,000

20,000

0
1 2 3 4 5 6 7 8 9 10
Years of Follow-up

Diagnosed Undiagnosed

1,800 €
MLN

1,600 €

1,400 €
CUMULATIVE DIRECT COSTS

1,200 €

1,000 €

800 €

600 €

400 €

200 €

0€
1 2 3 4 5 6 7 8 9 10
YEARS OF FOLLOW-UP

Incremental approach Fast Approach

Figure: (abstract: THU299) Cumulative diagnosed patients at each year of simulation- Incremental Scenario (Panel A) Fast Scenario (Panel B) and the
respective Costs (Panel C)

HCV genotype (%24.1). Of these patients, 251 were genotype 1A, 438 health threat. According to our study, there are significant deficien-
were genotype 1B, 26 were genotype 2, 193 were genotype 3, 39 were cies in several stages of the treatment cascade, which is consistent
genotype 4 and one patient was genotype 5. Only 589 of them could with world data. The rate HCV- RNA testing was low among all clinics.
access to treatment (%15). Numbers of patients in each step of the However, Group 2 has lower referral rates according to Group 1
treatment cascade are presented in Figure 1. Although the depart- indicating a lower level of awareness. Knowledge of all physicians
ments in Group 2 detected more anti-HCV positivity, the number of should be improved to prevent losses and delays in the diagnosis and
the ones that could access treatment were lower. treatment of HCV infection independent of their departments.
Conclusion: World Health Organization has been set international
targets for the elimination of HCV infection by 2030, which is a public

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POSTER PRESENTATIONS
THU301 Method: HDV viruses were produced by co-transfection of Huh7 cells
Hepatitis E Virus Capsid Antigen (HEV-Ag): a practical diagnostic with HDV genome and HBV envelope plasmids. Subsequently, virus
biomarker in the HEV outbreak scenerio containing supernatant was collected, titered and used to infect
Simon Lytton1, Rakibul Hassan Bulbul2, Mamunur Rashid2. primary human hepatocytes (PHHs). For the HDV phenotyping assay,
1
SeraDiaLogistics; 2Bangladesh Institute Of Tropical And Infectious PHHs were pre-treated with BLV and then infected with clinical
Diseases Hospital, Chittagong, Bangladesh plasma or a lab strain of HDV. After five days, immunofluorescence
Email: [email protected] staining was performed to determine cells that were positive for HDV
antigen (HDAg). The concentration of BLV decreasing the HDV HDAg
Background and aims: The increased global incidence of hepatitis E positive cells by 50% was expressed as a mean EC50 value from at least
virus (HEV) infections, warrants accurate and affordable diagnostics two independent experiments.
across different geographical regions. The soluble and highly Results: For HDV lab strains, the median EC50 of BLV against HDV-1 to
conserved HEV open reading frame 2 (ORF2) capsid antigen (HEV- HDV-8 pseudotyped with HBV GTA-D envelopes ranged from 0.35 nM
Ag) is detectable in self-limited acute enteric hepatitis by HEV-Ag to 0.64 nM. Similarly, for HDV-1 to HDV-8 lab strains pseudotyped
ELISA which is a promising serological assay in settings where HEV- with HBV GTE-H envelopes, the median EC50 of BLV ranged from 0.21
RNA testing is not feasible. Our aim was to assess the HEV-Ag nM to 0.61 nM. Across HDV-1 to HDV-8 lab strains enveloped with
biomarker in an HEV outbreak in a low income country. HBV GTA-H envelopes, the median EC50 of BLV ranged from 0.26 nM
Method: A prospective single center longitudinal study during HEV to 0.64 nM. Additionally, the median EC50 of BLV against HDV-1 with
outbreaks in the Chittagong, Bangladesh region between October envelopes carrying common polymorphisms in the LHBsAg PreS1
2018 and October 2019 was conducted based on recruitment of acute region that corresponds to the BLV sequence region for HBV GTA, GTB,
jaundice cases with clinical signs and symptoms of suspect HEV GTC and GTD were 0.57, 0.59, 0.43 and 0.33 nM, respectively. The
infections. Acute HEV infection was defined as a positive test result activity of BLV was also evaluated against 165 clinical isolates with a
for anti-HEV IgM antibodies. total of 137 out of 165 clinical isolates having sufficient infectivity to
Results: Forty four of the 51 enrolled enteric hepatitis cases (86%) be tested for BLV activity. Most clinical isolates tested (n = 122)
were confirmed HEV by anti-HEV IgM ELISA at day 0 hospital entry. belonged to HBV genotype D/HDV genotype 1 (D/1) and had a
The anti-HEV-IgM and IgG were positive in all patients and did not median EC50 value of 0.33 nM. Similarly, the median EC50 values for
reveal significant differences; neither between the time points day 0 clinical isolates of A/1 (n = 9), E/5 (n = 5) and A/6 (n = 1) were 0.54,
and follow-up hospitalization on day 2–6 or day 7–10 nor between 0.36, and 0.70 nM, respectively (Figure).
RNA-positive (n = 36) versus RNAnegative (n = 8) HEV groups. The
HEV-Ag positivity was higher in viral RNA-positive (29/36, 81%) than
the viral RNA-negative (1/8, 12%) group, p <0.001 and the HEV-Ag
levels positively correlated with viremia, r = 0.77, p <0.0001. All non-
HEV cases; n = 7 tested negative anti-HEV IgM and HEV-Ag and 5 of 7
(71%) tested anti-HAV IgM positive.
Conclusion: The HEV-Ag ELISA is a reliable and practical diagnostic
tool in this acute HEV outbreak.

THU302
Bulevirtide is broadly active against all HDV genotypes expressing
envelopes from HBV genotypes A-H and a large panel of clinical
isolates
Savrina Manhas1, Bin Han1, Simin Xu1, Lindsey May1, Dong Han1,
Tahmineh Yazdi1, Silvia Chang1, Thomas Aeschbacher1, Rishi Aryal1,
Ross Martin1, Yang Liu1, Roberto Mateo1, Vithika Suri1,
Dmitry Manuilov1, John F. Flaherty1, Julius Hollnberger2,3,
Stephan Urban4, Tomas Cihlar1, Evguenia S Svarovskaia1,
Hongmei Mo1. 1Gilead Sciences, Inc., Foster City, United States;
2
University Hospital Heidelberg, Department of Molecular Virology,
Heidelberg, Germany; 3German Center for Infection Research (DZIF),
Heidelberg; 4University Hospital Heidelberg, Heidelberg, Germany
Email: [email protected]
Background and aims: Bulevirtide (BLV) is a 47-amino acid
lipopeptide derived from the HBV large envelope protein (LHBsAg). Conclusion: BLV demonstrated potent broad spectrum antiviral
BLV binds to the HDV/HBV host entry receptor sodium taurocholate activity against HDV-1 to HDV-8 enveloped with HBV GTA to GTH
cotransporting polypeptide and acts as a potent HDV entry inhibitor. and against a larger panel of HDV clinical isolates showing similar
BLV has been approved for treatment of HDV in the European Union EC50 values across different HBV/HDV genotypes irrespective of the
and is under late stage clinical evaluation in the United States. Based presence of polymorphisms. These results support that BLV has broad
on sequence divergence, there are eight HDV genotypes (HDV-1 to genotype coverage potential for the treatment of patients with
HDV-8) and eight HBV genotypes (GTA to GTH). To determine the chronic HDV infection.
activity of BLV against diverse HDV/HBV variants sequences, the
antiviral activity of BLV against HDV-1 to HDV-8 enveloped with HBV
GTA-H and against 137 clinical isolates from study participants with
HDV infection was assessed.

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 POSTER PRESENTATIONS
THU303 THU304
A persistent HBV infection features spontaneous cccDNA loss and Functionnal and mitochondrial dynamics alterations in patients
new rounds of infection with chronic hepatitis B and advanced fibrosis
Bai-Hua Zhang1, Yuanping Zhou2, Stephen Horrigan3, Fabien Zoulim4, Dimitri Loureiro1,2, Issam Tout1,2, Cheikh Mohemed Bed1,2,
David Baltimore5, Yong-Yuan Zhang1. 1HBVtech, Virology, Frederick, Morganer Roinard1,2, Ahmad Sleiman1,2, Boyer Nathalie1,2,
United States; 2Nanfang Hospital, Southern Medical University, Dept. of Stephanie Narguet1,2, Nathalie Pons-Kerjean2,3, Corinne Castelnau1,2,
Gastroenterology and Hepatology Unit, Guangzhou, China; 3Noble Life Nathalie Giuly1,2, Vassili Soumelis4, Jamel El Benna2, Patrick Soussan5,
Sciences, Preclinical Studies, Sykesville, United States; 4Cancer Research Richard Moreau2, Valérie Paradis1,2, Abdel Mansouri1,2,
Center of Lyon, Hepatology, Lyon, France; 5California Institute of Tarik Asselah1,2. 1Hospital Beaujon AP-HP, Hepatology, Clichy, France;
2
Technology, Biology, Pasadena, United States Center Recherche Sur l’Inflammation, U1149, Paris, France; 3Hospital
Email: [email protected] Beaujon AP-HP, Pharmacy, Clichy, France; 4Hospital Saint-Louis,
Laboratoire d’Immunologie et Histocompatibilit, Paris, France; 5Paris
Background and aims: Clinical evidence shows frequent replace-
Diderot University, U1135, Paris, France
ment of serum wild type viral population with mutants in chronic
Email: [email protected]
HBV infection, which indicates cccDNA turnover and new rounds of
infection. We hypothesized that HBV infection is maintained by new Background and aims: Patients with chronic hepatitis B (CHB) have
rounds of infection. This hypothesis can be tested in HBV infected an increased risk of advanced fibrosis and hepatocellular carcinoma
uPA/SCID chimeric mice by blocking new rounds of infection using (HCC). In experimental models, hepatitis B virus (HBV) infection
anti-HBs antibody. Since anti-HBs Ab mainly functions extracellu- causes oxidative stress and alters hepatic mitochondria. The aim of
larly, its administration in HBV infected chimeric mice is expected to the study is to investigate the role of mitochondrial stress in the
have a therapeutic impact on HBV infection level only if it is sustained progression of fibrosis in CHB.
with new rounds of infection. Method: 132 treatment-naïve CHB mono-infected patients with
Method: An optimized AAV vector that carries human anti-HBs Ab available liver biopsies specimen were included in this study. Patient
genes was used to express sustained high level of anti-HBs antibody. demographics and laboratory parameters were recorded at the time
HBV infected uPA/SCID chimeric mice were treated with AAV vector of the biopsy. Liver mitochondrial DNA (mtDNA) damage was
expressing malaria antibody or anti-HBs antibody day 49 post screened by long PCR and sequencing and levels by Slot blot. The
infection. Serum HBV DNA and HBsAg level were monitored until expression of the main genes of cytochrome c oxidase subunits,
day 183 and liver HBV DNA was determined through 20 random mitophagy, mitochondrial peptidases and chaperonins, TNFα and IL6,
samplings of each autopsied liver. inducible NO synthase and MnSOD were investigated by RT-qPCR and
Results: Two key findings were observed: I. Dynamic cccDNA status Western-blotting. Patients with CHB and advanced fibrosis (F3-F4
and spontaneous cccDNA loss: average cccDNA level ≤1 copy/cell was Metavir score;n = 43) were compared to patients with no-mild-
detected in 260 (46%) of 566 cccDNA samplings of 18 HBV infected moderate fibrosis (F0-F2;n = 89). In vitro, HBV and HBx were
human livers from chimeric mice, suggesting cccDNA was already lost transiently expressed in HepG2 cells and the superoxide anion
spontaneously in a fraction of infected cells. II. Anti-HBs treatment formation, peroxynitrite, nitration of mitochondrial chain complexes,
profoundly impacts HBV infection level: i) Viremia was significantly iNOS, MnSOD protein levels and mtDNA depletion were assessed.
lowered by up to >100-fold; ii). Intrahepatic rcDNA level was Results: Whereas 100% of patients with F3-F4 exhibited multiple
significantly lowered by 4, 000 to 10, 000 copies/cell; iii). The mtDNA deletions, 50% of those with F0-F2 (κc2 = 6.8;p <.001) carried
number of cccDNA samplings with cccDNA level ≤1 copy/cell was a single mtDNA deletion. Significant decreases were observed in
significantly expanded (50.2%, 244/486) in anti-HBs treated animals patients with F3-F4 compared to those with F0-F2 for the mRNAs of
compared to malaria antibody animals (20%, 16/80); and iv) HBV MT-CO1 (0.55 ± 0.36 and 1.20 ± 0.75, p < .001), HSPA9 (0.70 ± 0.28 and
functional cure with nearly complete cccDNA elimination was 1.06 ± 0.37, p < .001), HSPD1 (0.83 ± 0.36 and 1.10 ± 0.44, p < .05), Lon
achieved in one animal with baseline viremia of 4.6E HBV DNA Peptidase 1, LONP1 (0.83 ± 0.22 and 1.06 ± 0.33, p < .05), PRKN (0.45 ±
copies/ml (Figure 1). 0.26 and 1.12 ± 0.57, p < .0001), PINK1 (0.59 ± 0.17 and 1.06 ± 0.26,
p < .0001), Liver TNFα (1.72 ± 0.2 and 0.99 ± 0.2;p < .05), IL6 (7.82 ±
0.90 and 1.14 ± 0.26; p < .05). Protein levels significantly decreased in
F3-F4 for MT-CO1 (2.55 ± 0.88 and 3.44 ± 0.80, p < .01), LONP1 (0.67 ±
0.31 and 0.87 ± 0.51, p < .05), HSPA9 (0.67 ± 0.31 and 1.20 ± 0.77,
p < .05) MT-ATP8 (0.14 ± 0.03 and 0.30 ± 0.06, p < .05). iNOS and
MnSOD proteins are significantly increased in patients with F3-F4
with MnSOD activity decreased in these patients ( p < .05).
In HepG2 cells, HBV or HBx expression increase mitochondrial
superoxide formation at 24 and 48 h (p < .05), increase iNOS protein
levels, but only HBV increase MnSOD protein expression by 2-fold
( p < .05). Then, an increase of peroxynitrite as well as mtDNA
depletion ( p < .01) and nitration of the mitochondrial respiratory
chain complexes were observed.

Conclusion: cccDNA level is dynamic with spontaneous cccDNA loss,

which mediates spontaneous HBV clearance and but can be
replenished by new rounds of infection in infected human livers of
chimeric mice. New rounds of infection prolong HBV persistent
infection. Therapeutic blocking of new rounds of infection profoundly
impacts both rcDNA and cccDNA level including a nearly complete
cccDNA elimination in one animal with HBV functional cure. Our
study identifies an opportunity to durably terminate persistent HBV
infection through blocking new rounds of infection.

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POSTER PRESENTATIONS
Results: We demonstrated that FTI treatment of HBV-HDV co-
infected cells leads to an accumulation of intracellular HDV RNAs
and a marked increase in the levels of edited HDV RNAs not only
within the infected cells but also in the viral particles that are
secreted. Interestingly, these viral particles were less infectious,
probably due to an enrichment in edited genomes that are packaged,
leading to unproductive infection given the absence of S-HDAg
synthesis after viral entry.
Conclusion: Taken together, we setup an innovative quantification
method allowing the investigation of HDV RNAs editing during HDV
infection in a simple, fast, clinically-relevant assay and demonstrated
for the first time the dual antiviral activity of FTI on HDV infection.

THU306
Characterization of circulating hepatitis B Virus RNAs in vitro and
chronic hepatitis B patients
Doohyun Kim1, Delphine Bousquet1,2, Marie-Laure Plissonnier1,
Hyoseon Tak1, Xavier Grand1, Chloe Goldsmith3, Françoise Berby1,
Bordes Isabelle1, Alexia Paturel1,2, Aaron Hamilton4, Marintha Heil4,
Massimo Levrero1,2,5, Barbara Testoni1, Fabien Zoulim1,2,6. 1Cancer
Research Center of Lyon, Chronic Viral Hepatitis: virus/host interactions,
pathogenesis and novel antiviral strategies, Lyon, France; 2Université de
Lyon, Lyon, France; 3University of Canberra, Bruce, Australia; 4Roche
Diagnostics, Pleasanton, United States; 5Sapienza University of Rome,
Roma, Italy; 6La Croix-Rousse Hospital, Lyon, France
Email: [email protected]
Background and aims: Circulating HBV RNA (CirB-RNA) is a
promising non-invasive biomarker for cccDNA transcriptional activ-
ity. However, the molecular characteristics and circulating particles
containing cirB-RNA in vitro and in vivo remain to be fully defined.
Method: Supernatants from cultured hepatocytes infected by HBV
Conclusion: Diverse mtDNA damages and alterations of mitochon- and treated or not with lamivudine, and sera from 9 untreated [4
drial function and dynamic seems to be involved in the progression of HBeAg (+) and 5 HBeAg (-)] and 1 HBeAg (+) ETV-treated chronic
fibrosis in patients with CHB. Our results emphasized the importance hepatitis B (CHB) patients were subjected to Iodixanol/Sucrose
on modulating mitochondrial function, and therefore could be an ultracentrifugation for buoyant density. Each density fraction was
attractive therapeutic strategy to block the progression of fibrosis in analyzed for HBV DNA/RNA by specific qPCR and droplet digital (dd)
CHB. PCR. Viral and extracellular vesicles (EVs)-associated proteins were
detected by ELISA and Western Blotting. 5′ RACE PCR followed by ONT
THU305 MinION sequencing was used to identify CirB-RNA species.
Dual antiviral activity of farnesyl transferase inhibitor on Longitudinal serum samples before and at two time points after
hepatitis D virus infection revealed by RT-ddPCR NUC therapy initiation were obtained from two additional patients
Eloi Verrier1, Anna Salvetti2, Caroline Pons2, Michelet Maud3, [HBeAg (+) TDF-treated CHB and HBeAg (-) ETV-treated CHB].
Thomas Baumert1,4, David Durantel2, Julie Lucifora2. 1Université de Results: After ultracentrifugation, CirB-RNA was mainly detected in
Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et core-associated virion-like particles, in 2 log10 less amount than HBV
Hepatiques UMR_S1110, Strasbourg, France; 2CIRI-Centre International DNA. However, CirB-RNA was the predominant species in lighter
de Recherche en Infectiologie, Univ Lyon, Université Claude Bernard Lyon density fractions (1.17–1.18 g/ml) deprived of viral proteins, both in
1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, Lyon, France; 3Inserm, cell supernatant and in serum. The enrichment for EVs in these
U1052, Cancer Research Center of Lyon (CRCL), Université de Lyon fractions was confirmed by detection of CD9 and CD81 by Western
(UCBL1), CNRS UMR5286, Centre Léon Bérard, Lyon, France; 4Institut Blotting, immunoprecipitation assay, Nanoparticle tracking analysis
Hospitalo-Universitaire, Pôle Hépato-digestif, Nouvel Hôpital Civil, and Transmission Electron Microscopy. Distribution of CirB-RNA did
Strasbourg, France not differ significantly according to HBeAg status, while in a patient
Email: [email protected] with low HBsAg level, CirB-RNA was mainly detected in the EVs-
enriched fractions. Lastly, CirB-RNA profiling by 5′ RACE and ONT
Background and aims: Chronic hepatitis D is the most severe form of MinION sequencing identified different proportions of pgRNA-
chronic viral hepatitis and to date, efficient therapeutic approaches derived transcripts according to HBeAg status and HBsAg level.
against hepatitis D virus (HDV) are absent. Among the antiviral Conclusion: Our results indicate that EVs-enriched compartment
molecules currently tested in clinical trials, the farnesyl transferase also contributes to the circulation of HBV-RNAs. Moreover, different
inhibitor (FTI) Lonafarnib inhibits the prenylation of the large delta HBV-RNA transcripts in addition to pgRNA can be detected in vivo.
antigen (L-HDAg), blocking virus assembly. Given the importance of Altogether, these data could significantly contribute to the charac-
L-HDAg in the virus life cycle, terization of cirB-RNAs as new viral biomarker.
We hypothesized that Lonafarnib treatment may have side effects on
virus replication.
Method: Here, we setup an innovative method based on reverse
transcription digital droplet PCR (RT-ddPCR) for the quantification of
HDV RNA allowing the independent quantification of edited and non-
edited versions of the HDV genome upon infection.

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 POSTER PRESENTATIONS
THU307 Method: HCC liver resections were collected from 20 patients, 15%
Identification of shuttle protein hnRNPA1 as a modulating factor were HBeAg-, 10% were treatment naïve, and 75% on nucleos (tide)
of circulating hepatitis B Virus RNAs release in chronic hepatitis B analogue treatment. DNA and RNA were sequenced from tumor/
patients tumor adjacent tissue. We enriched for HBV sequences using a pan-
Hyoseon Tak1, Doohyun Kim1, Delphine Bousquet1,2, genotypic panel of biotinylated oligos from sheared genomic DNA
Marie-Laure Plissonnier1, Françoise Berby1, Bordes Isabelle1, (∼7 kb) and polyA+ reverse transcribed cDNA. Samples were
Aaron Hamilton3, Marintha Heil3, Massimo Levrero1,2,4, sequenced on the PacBio long-read platform and analyzed with a
Barbara Testoni1, Fabien Zoulim1,2,5. 1Cancer Research Center of Lyon, bioinformatic method for identification of VirAL Integrations ANd
Lyon, France; 2Université de Lyon, Lyon, France; 3Roche Diagnostics, Translocations (VALIANT). cDNA was also sequenced using standard
Plesanton, United States; 4Sapienza University of Rome, Roma, Italy; Illumina RNA-Seq. We used Catalogue of Somatic Mutations in Cancer
5 (COSMIC) to identify integrations near cancer-associated genes.
Croix Rousse hospital, Lyon, France
Email: [email protected] Results: We found that nearly all HBV DNA reads (avg. ∼95%) from
tumor and adjacent tissue were derived from integrated HBV. We
Background and aims: Circulating HBV RNA (CirB-RNA) reflects the found integration sites common to paired tumor and adjacent tissue
transcriptional activity of the intrahepatic cccDNA, thus representing in nearly half of samples. We found >20 COSMIC genes with nearby
a promising non-invasive serum biomarker for the reduction or integrations, including HLF, LRP1B, ERBB4, and TERT. Moreover, we
inactivation of cccDNA pool. Although several studies have suggested found numerous HBV-associated translocations, including a chromo-
that cellular releasing pathways may determine the fate of these some 1 to 3 translocation in NAALADL2, a known HBV integration
RNAs, the specific regulators of the shuttle machinery involved hotspot. We further quantified the frequency of translocations and
remain largely unknown. insertions in our HCC cohort and a cohort of chronic hepatitis B
Method: Expression of candidate shuttle proteins were analyzed by patients and found a higher translocation frequency in HCC samples
Western Blotting and RT-qPCR in cell lysate and supernatant from (∼30% vs 15%). Finally, our long-read RNA-seq data captured HBV
HBV-infected HepG2-NTCP cells and Primary human hepatocytes transcripts chimeric with various genes, including HBV-TERT iso-
(PHHs). Shuttle protein interaction with CirB-RNAs was investigated forms which coincided with elevated TERT expression measured by
by RNP-IP (Ribonucleoprotein-Immunoprecipitation) and Biotin pull short-read RNA-seq.
down assay. Adapted Iodixanol/Sucrose density ultracentrifugation Conclusion: We find a substantial amount of HBV integrations in
allowed to isolate exosome-enriched fractions from sera of 5 tumors. Increased translocation frequency in tumors supports the
untreated [2 HBeAg (+) and 3 HBeAg (-)], 2 HBeAg (-) chronic hypothesis that HBV integrations may promote oncogenesis through
infection and 2 NUC-treated chronic hepatitis B (CHB) patients. genomic instability and highlights the importance of treatments that
Results: Among the RNA-binding proteins analyzed, heterogeneous prevent HBV integration. Moreover, our observation of HBV-TERT
nuclear ribonucleoprotein A1 (hnRNPA1) expression was increased in chimeric isoforms and TERT upregulation strengthens the view that
both cell lysates and supernatants of HepG2-NTCP cells and PHHs HBV integrations are a direct driver of HCC.
upon HBV infection. hnRNPA1 was also detected in the serum of CHB
patients and, after density ultracentrifugation of serum samples, THU309
hnRNAP1 was mostly detected in the exosome-enriched fractions. Polymorphic analysis of bulevirtide sequence in PreS1 of large
Loss-of-function studies in HepG2-NTCP cells indicated that HBsAg across HBV genotypes A-H
hnRNAP1 downregulation was associated to reduced expression of Roberto Mateo1, Thomas Aeschbacher1, Yang Liu1, Simin Xu1,
exosome markers CD9 and CD81 in cell supernatant, as well as a Bin Han1, Tahmineh Yazdi1, Savrina Manhas1, Lindsey May1,
decreased secretion of CirB-RNA in exosome fractions. Anti-CD81 IP Dong Han1, Silvia Chang1, Rishi Aryal1, Ross Martin1,
confirmed the association between hnRNAP1 and exosomes. RNP-IP Evguenia S Svarovskaia1, Hongmei Mo1. 1Gilead Sciences, Inc., Foster
experiments revealed that hnRNPA1 was able to bind to 5′ region of City, United States
3.5Kb RNA and to the 3′ region common to all HBV transcripts. Email: [email protected]
Specific binding sites for hnRNAP1 on HBV RNAs were mapped by
Biotin pull-down assays. Background and aims: Bulevirtide (BLV) is a novel 47-amino acid, N-
Conclusion: Altogether, our data suggest that hnRNPA1 directly terminally myristoylated lipopeptide that binds specifically to the
binds to HBV RNAs and can function as a novel shuttling mechanism sodium taurocholate cotransporting polypeptide (NTCP) and acts as a
for the export of HBV RNAs in vivo. potent, highly selective entry inhibitor of HDV into hepatocytes. The
BLV sequence was designed based on the consensus sequence of the
THU308 preS1 domain of the large HBsAg (LHBsAg) of eight different
Long-read sequencing of HCC samples reveals complete genotypes of HBV (A-H). The aim of this study was to investigate
architecture of HBV integrations and chimeric mRNA isoforms the impact of polymorphisms found in the LHBsAg PreS1 region from
associated with oncogenes HBV clinical isolates of eight HBV genotypes on susceptibility to BLV.
Cameron Soulette1, Lindsey May1, Atefeh Khakpoor2, Dong Han1, Method: The polymorphic residues in BLV sequence region of Pre-S1
Ricardo Ramirez1, Narmada Balakrishnan3, Nicholas Van Buuren1, were identified using an alignment of 7427 PreS1 sequences of HBV
Ramanuj Dasgupta3, Vithika Suri1, Li Li1, Hongmei Mo1, genotypes A-H obtained from clinical isolates and public databases.
Becket Feierbach1, Jeffrey Wallin1, Seng Gee Lim2. 1Gilead Sciences, HDV genotype 1 viruses containing these polymorphisms were
Inc., Foster City, United States; 2Yong Loo Lin School of Medicine, generated by transient transfection and analyzed phenotypically for
Singapore, Singapore; 3Genome Institute of Singapore (GIS), Singapore, their susceptibility to BLV in an infectious assay using primary human
Singapore hepatocytes.
Email: [email protected] Results: Polymorphic analyses of HBV sequences from genotypes A-H
revealed a high degree of conservation of the 47aa long peptide, with
Background and aims: Hepatitis B virus (HBV) integrations are a remarkable conservation of the sequence from positions 9-
associated with large-scale genomic rearrangements that dysregulate NPGLFFP-15, which is crucial for binding. Only one amino acid
gene expression and are implicated in hepatocellular carcinoma residue was found to be variable with a frequency above 5% for
(HCC). Our work is aimed towards understanding the development of genotype A; genotypes B, C and D had 2, 5 and 2 amino acids above
oncogenesis mediated by HBV integrations by characterizing integra- the 5% cut-off value, respectively. Within representative sequences
tions in HCC patients. We use a long-read DNA and mRNA sequencing for the most common genotypes A-D, genotype C was the closest to
approach to characterize complete HBV integrations and their the BLV sequence with only one amino acid change (K57Q).
expression from paired tumor and adjacent tissue.

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POSTER PRESENTATIONS
Genotypes A and B had 4 to 6 amino acid changes, respectively, and THU311
genotype D had 8. Despite their sequence differences, HDV genotype Limited value of HBV-RNA levels for the prediction of relapse after
1 viruses containing HBV genotype A-H preS1 representative discontinuation of nucleos (t)ide analogue therapy in HBe antigen
sequences and the most prevalent HBV genotype A-D polymorph- negative chronic hepatitis B patients
isms were fully susceptible to BLV with EC50 values that ranged from Valerie Ohlendorf1, Maximilian Wübbolding1,
0.28 nM to 0.85 nM. Christoph Hoener zu Siederdissen1, Birgit Bremer1, Katja Deterding1,
Conclusion: BLV demonstrated potent activity against HDV harboring Heiner Wedemeyer1, Markus Cornberg1, Benjamin Maasoumy1.
the polymorphisms in the PreS1 region corresponding to the BLV 1
Hannover Medical School, Clinic of Gastroenterology, Hepatology and
sequence across HBV genotypes A-D, indicating the broad-spectrum Endocrinology, Hannover, Germany
antiviral activity of BLV for the treatment of patients infected with Email: [email protected]
HDV viruses.
Background and aims: EASL guidelines suggest that treatment with
THU310 nucleos (t)ide analogue (NA) can be stopped in HBeAg negative
RIPK1 plays a survival role in the liver of mice with active HDV patients after three years of viral suppression. Recently, the
replication combination of HBsAg and HBV-RNA level at the time of NA cessation
Gracian Camps1, Sheila Maestro2, Carla Usai3, Mirja Hommel1, has been linked to a better prediction of off-treatment response
Cristina Olague Micheltorena1, África Vales Aranguren1, compared to HBsAg alone in mixed cohorts of HBeAg negative and
Rafael Aldabe1, Gloria González-Aseguinolaza1. 1CIMA Universidad de positive patients. In this study we investigated the association of
Navarra, Gene therapy and regulation of gene expression, Pamplona, relapse after NA cessation with baseline serum HBV-RNA level in a
Spain; 2Viralgene; 3Blizard Institute large cohort of HBeAg negative patients.
Email: [email protected] Method: Serum level of HBV-RNA, HBsAg and HBcrAg were
determined in 154 HBeAg negative patients, participating in a
Background and aims: Hepatitis delta virus (HDV) infection prospective, multicenter therapeutic vaccination trial (ABX-203,
represents the most severe form of viral hepatitis; however, the NCT02249988) or in an observational register trial (Terminator 2),
molecular mechanisms involved in the severity of the disease remain before stop of NA therapy. Importantly, vaccination showed no impact
unknown. The absence of mouse models in which HDV-induced liver on relapse. HBV DNA >2, 000 IU/ml 24 weeks after NA cessation was
damage occurs has prevented the study of this important aspect of defined as virological relapse, while clinical relapse comprised
the disease. We developed an adeno-associated virus (AAV)- attendant ALT levels ≥2 × ULN. The lower limit for the quantification
mediated HDV/HBV co-infection model in which, for the first time, of HBV-RNA was 10 copies/ml. For the comparison of continuous and
liver damage associated with HDV was detected in mice that was, at categorical variables the Mann-Whitney U and the Fisher’s exact test
least partially, associated with TNF-α production. The aim of the were used. Kaplan-Meyer analysis with the log-rank test was used for
present study is to elucidate the mechanisms involve in HDV- the calculation of cumulative relapse rates.
mediated liver damage. Results: The majority of patients were male (n = 115/154; 75%) with a
Method: Replication competent HBV and HDV genomes were median age of 53 years. Two thirds of patients were treated with
delivered to mouse hepatocytes using AAVs as shuttle vector to entecavir (n = 94/154; 61%), while the rest received tenofovir. Median
stablish an active replication of both viruses. Using blocking agents, HBV-RNA, HBsAg and HBcrAg BL level was 0 copies/ml, 950 IU/ml and
KO mice, and CRISPR Cas9 system to delete the expression of key 1585 kU/ml, respectively. No significant correlation was found
molecules we evaluate the role of different players involve in between HBV-RNA and HBsAg (r = − 0.253, p = 0.055) or HBV-RNA
hepatocytes death. and HBcrAg (r = 0.044, p = 0.73), respectively. Virological relapse
Results: Here, we report that TNF-α was mainly produced by liver occurred in 53% of patients (N = 82/154), including 8 patients (10%)
macrophages and that the death of HDV-hepatocytes occurs developing an ALT flare. BL HBV-RNA level did not differ significantly
predominantly by caspase-8 induced-apoptosis. between relapsers and off-treatment responders ( p = 0.86) or
Upon AAV-HBV/HDV co-injection, RIPK1-edited mice presented with between virological relapsers and clinical relapsers ( p = 0.36),
a significantly higher liver damage than mice receiving control respectively. Further, no significant difference occurred in propor-
CRISPR/Cas9, reflected by higher transaminase serum levels and an tions of detectable HBV-RNA BL level between off-treatment
increased percentage of apoptotic hepatocytes, indicating that RIPK1 responders (N = 10/72; 14%) and relapsers (N = 13/82;16%) ( p =
plays a significant role in hepatocytes survival in an HDV infected 0.68). Relapse prediction could not be improved by combining
liver. The elimination of both caspase 8 and RIPK1 from hepatocytes predefined HBsAg cut-offs (100 IU/ml, p = 0.0016) or HBcrAg cut-offs
resulted in the almost complete absence of hepatocytes death after (3 log U/ml, p = 0.07) with a HBV-RNA cut-off of ≤10 copies/ml ( p =
AAV-HBV/HDV injection, which further corroborated caspase 8- 0.0031) (figure).
induced apoptosis as the main cell death mechanism in RIPK1-
edited mice. Surprisingly, the absence of TNF-α or the depletion of
macrophages had no effect on the exacerbation of liver disease
associated with the RIPK1 downregulation in hepatocytes.
Interestingly depletion of macrophages had a significant detrimental
effect, indicating that these cells play a protective role.
Conclusion: Our investigations demonstrate the protective role of
RIPK1 in HDV-induced liver pathology and strongly suggest that the
RIPK1-caspase-8 axis influences the pathogenesis of HDV infection.
More experiments are needed for a better understating of the
mechanism involved.
Figure: A) Cumulative relapse rates after NA cessation according to end of
treatment (EoT) grouped by serum RNA baseline levels and proportion of
patients with virological relapse grouped by B) BL HBsAg level ± HBV-RNA
level or C) BL HBcrAg level ± HBV-RNA level.

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 POSTER PRESENTATIONS
Conclusion: In a cohort of exclusively HBeAg negative patients no research without using large animal models or genetically modified
improvement in relapse prediction was achieved by considering HBV- rats. Further evaluation of this model for studying antivirals is
RNA BL levels. required.

THU312 THU313
A versatile small animal immunocompromised model for chronic Acquisition of positively charged amino acids in HBsAg C-
hepatitis E terminus correlates with HBV-induced liver cancer, hampers
Siddharth Sridhar1, Shusheng Wu2, Jianwen Situ2. 1The University of HBsAg stability and secretion and promotes cell survival
Hong Kong, Microbiology; 2The University of Hong Kong, Microbiology Lorenzo Piermatteo1, Luca Carioti1, Gianluca Leoni1, Leonardo Duca1,
Email: [email protected] Patrizia Saccomandi1, Daniele Stella1, Eleonora Andreassi1,
Ada Bertoli1,2, Giuseppina Cappiello3, Hervé Fleury4,
Background and aims: Hepatitis E virus (HEV) is an important cause
Pascale Trimoulet4, Simona Francioso5, Ilaria Lenci5,
of chronic hepatitis in immunocompromised persons. We aimed to
Massimo Andreoni5, Mario Angelico6, Sandro Grelli1,2,
develop a small animal model of chronic hepatitis E using
Antonella Minutolo1, Loredana Sarmati6, Claudia Matteucci1,
immunocompromised rats infected with Orthohepevirus species C
Francesca Ceccherini Silberstein1, Valentina Svicher1,7,
(HEV-C; rat hepatitis E virus), which is an emerging cause of human
Romina Salpini1. 1University of Rome "Tor Vergata", Experimental
hepatitis.
medicine, Rome, Italy; 2Tor Vergata University Hospital, Microbiology
Method: Female 6–8 week old Sprague-Dawley rats were divided
and Virology Unit, Rome, Italy; 3"Sandro Pertini" Hospital, Microbiology
into 3 groups (6 rats per group): immunocompetent (group 1), low-
and Virology Unit, Rome, Italy; 4Hôpital Pellegrin tripode, Laboratoire de
dose immunosuppressed (group 2) and high-dose immunosup-
Virologie, Bordeaux, France; 5Tor Vergata University Hospital,
pressed (group 3). Rats in groups 2 and 3 were immunosuppressed
Hepatology Unit, Rome, Italy; 6Tor Vergata University Hospital,
using a combination of tacrolimus (5 mg/kg vs 7.5 mg/kg respect-
Infectious Disesases Unit, Rome, Italy; 7University of Rome "Tor Vergata",
ively), mycophenolate mofetil (25 mg/kg vs 30 mg/kg respectively),
Biology, Rome, Italy
and prednisolone (10 mg/kg vs 4 mg/kg respectively). Drugs were
Email: [email protected]
administered 10 days prior to infection and continued thereafter.
Filtered stool supernatants containing 2.5 × 105 copies/ml of HEV-C Background and aims: HBsAg C-terminus is a hydrophobic
were administered to rats intravenously. Stool supernatants were transmembrane domain, crucial for HBsAg secretion. Gain of
either from infected humans (3 rats per group) or rats (3 rats per charged amino acids (aa) in this domain can alter HBsAg folding,
group). Stool and serum viral loads in infected rats were monitored. and in turn its secretion, a mechanism known to favor HBV-induced
Antibody responses and liver tissue histology were assessed. Ethics hepatocellular carcinoma (HCC). Here, we assess the role of HBsAg C-
approval was obtained. terminus mutations, associated with gain of charged aa, on HCC
Results: HEV-C infections in group 1 rats were fleeting with transient onset.
viremia (figure). Group 2 and 3 rats developed higher viral loads in Method: We analyze HBsAg sequences from 807 CHB patients: 28
both stool and serum (figure). No differences in viral loads between with HCC (78.6%D; 21.4%A) and 779 without HCC (79.8%D; 20.2%A).
human or rat-derived HEV-C strains were observed. Most group 1 and Impact of mutations on HBsAg-secretion is analyzed by transfecting
2 rats cleared virus from stool or serum by day 28, but group 3 rats Huh7 cells with plasmids encoding wt- and mutated-HBsAg. Extra-
maintained high viral loads in stool and serum throughout. Mean and intra-cellular HBsAg is quantified by Liaison immunoassay
viral loads in liver tissue at day 28 were markedly higher in group 3 (DiaSorin) and used to define HBsAg secretion factor (extracellular/
(8.89 log10 copies/ml) compared to group 1 (3.76 log10 copies/ml) and intracellular HBsAg). Cell viability after treatment with etoposide (a
2 (4.35 log10 copies/ml) rats; this was reflected by strongly positive cell death inducer) was evaluated by MTS assay. HBsAg structure and
immunohistochemical staining in liver tissue of group 3 rats. Western stability was assessed by I-Tasser (ΔΔG[wt-mutated]<0 indicates
blot antibody responses to HEV-C were weaker in group 3 rats than decreased stability vs wt, Quan, 2016).
group 1 rats. Alanine aminotransferase was similar in all 3 groups. The Results: The acquisition of ≥1 positively charged aa at HBsAg C-
immunosuppressive regimen was tolerated well by rats in groups 2 terminus positions 204, 207 and 210 strongly correlates with HCC
and 3. A couple of rats in group 3 were monitored beyond day 28 and (71.4% with HCC vs 30.2% without HCC, P < 0.001). Result confirmed
they supported viral infection for up to 3 months without any drop in by multivariable analysis (OR[95%CI]:6.3[2.6–15.3], P < 0.001). These
viral loads. positively charged aa derive from S204R, S207R and S210R, found in
14.3%, 28.6% and 28.6% of HCCs, respectively.
In vitro, all these mutations determine a significant decrease in
extracellular HBsAg compared to wt (42% for S204R, 39% for S207R
and 32% for S210R, P < 0.0001 for all). Moreover, S204R and S210R
cause a 58% and 28% reduction in HBsAg secretion factor respect to wt
( p <0.0001 and P = 0.009), reinforcing their detrimental role in HBsAg
release.
Notably, despite etoposide treatment at 25 and 50 μM, S204R
determines a 50% and 30% increase in cell viability respect to wt ( p
<0.001 for both), supporting its ability to promote cell survival.
Finally, in silico, S204R, S207R and S210R decrease HBsAg
stability (ΔΔG[S204R-wt] = − 0.27; ΔΔG[S207R-wt] = − 0.11; ΔΔG
[S210R-wt] = − 0.14) and determine a shortening of transmembrane
motif ( predicted length: aa209–224 for S204R, S207R and S210R vs
205–225 for wt).
Conclusion: Gain of positively charged aa in HBsAg C-terminus
Conclusion: We designed a versatile gradable immunocompromised tightly correlates with HCC, hampers HBsAg release and promotes
rat model of chronic hepatitis E infection using immunosuppressants cell survival, thus potentially predisposing to HBV-related HCC. The
commonly taken by transplant recipients. This model will enable detection of these mutations may help identifying patients at higher
convenient investigation of pathogenicity and antivirals for HEV HCC-risk, deserving more intense liver monitoring.
infections. This work establishes capacity to perform chronic HEV

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POSTER PRESENTATIONS
THU314 THU315
PAGE-B and FIB-4 predict the occurence of hepatocellular High tolerance of hepatitis E virus towards alcohol-based
carcinoma in HBV patients: a french nationwide cohort study disinfectants
Gautier Boillet1, Mathieu Chalouni2, Clovis Lusivka-Nzinga3, Patrick Behrendt1,2,3, Martina Friesland2, Jan-Erik Wissmann4,
François Teoule3, Helene Fontaine4, Pierre Nahon5, Marc Bourliere6, Volker Kinast4, Yannick Stahl2, Dimas Praditya4, Lucas Hueffner2,
Fabrice Carrat3, Stanislas Pol4, Victor de Lédinghen1, Linda Wittkop2. Pia Maria Nörenberg2, Birgit Bremer1, Benjamin Maasoumy1,3,5,
1
Maison Du Haut-Lévêque-Haut-Lévêque Hospital Group Sud-Chu De Jochen Steinmann6, Britta Becker6, Dajana Paulmann6,
Bordeaux, Pessac, France; 2ISPED, Bordeaux, France; 3Hospital Saint- Florian H. H. Brill6, Joerg Steinmann7,8, Rainer Ulrich9,
Antoine Ap-Hp, UMR-S 1136, Paris, France; 4Gh Cochin-St Vincent De Yannick Brueggemann4, Heiner Wedemeyer1,3, Daniel Todt4,
Paul, Hepatology, Paris, France; 5Hospital Jean-Verdier, UMR-1162, Eike Steinmann3,4. 1Hannover Medical School, Department of
Bondy, France; 6Hôpital Saint Joseph, Hepatology, Marseille, France Gastroenterology, Hepatology and Endocrinology, Hannover, Germany;
2
Email: [email protected] TWINCORE, Institute for Experimental Virology, Hannover, Germany;
3
German Centre for Infection Research (DZIF), Germany; 4Ruhr
Background and aims: Hepatocellular Carcinoma (HCC) is the first
University Bochum, Department of Molecular and Medical Virology,
cause of death among chronic hepatitis B (CHB) patients. PAGE-B and
Bochum, Germany; 5Centre for Individualised Infection Medicine (CIIM),
FIB-4 may predict the occurrence of HCC among all CHB patients. We
Hannover, Germany; 6Dr. Brill + Partner GmbH, Institute for Hygiene and
aimed to compare the predictive capacity of PAGE-B and FIB-4 for the
Microbiology, Bremen, Germany; 7Paracelsus Medical University,
occurrence of HCC in CHB patients at 1, 3 and 5 years of follow-up in
Institute for Clinical Hygiene, Medical Microbiology and Infectiology,
the ANRS CO22 HEPATHER cohort.
Nuernberg, Germany; 8University Hospital Essen, University of
Method: CHB patients included in the ANRS CO22 HEPATHER cohort
Duisburg-Essen, Institute of Medical Microbiology, Germany; 9Friedrich-
between August 6, 2012 and December 31, 2015 were eligible.
Loeffler-Institut, Federal Research Institute for Animal Health, Institute of
Exclusion criteria were chronic HCV, HDV co-infection, liver-
Novel and Emerging Infectious Diseases, Greifswald-Insel Riems,
transplantation, or history of HCC. Primary outcome was the time
Germany
between inclusion and occurrence of HCC. Predictive performances
Email: [email protected]
were compared by the AUROC at year 1, 3 and 5. Two cutoffs were
determined for each score, maximizing respectively sensitivity then Background and aims: The Hepatitis E virus (HEV) is the most
specificity, to establish three different risk groups. common cause of acute viral hepatitis worldwide and mainly
Results: Among 5, 214 patients, with a median follow-up of 5.6 years transmitted via the fecal-oral route or consumption of contaminated
(IQR: 4.3–6.9), 69 experienced HCC. Median scores values were of 10 food products. Due to the lack of efficient cell culture systems for the
(IQR: 6–14) for PAGE-B and 1.0 (IQR: 0.7–1.5) for FIB-4. Corrected propagation of HEV, limited data regarding HEV sensitivity to
AUROCs of PAGE-B and FIB-4 at year 1, 3 and 5, were 0.91 (0.8–0.97), chemical disinfectants are available. Consequently, preventive and
0.85 (0.81–0.97) and 0.81 (0.76–0.86) and 0.85 (0.70–0.97), 0, 83 evidence-based hygienic guidelines on HEV disinfection are lacking.
(0.77–0.89) and 0.80 (0.75–0.86), respectively. No significant differ- In this study we evaluated different principal components of hand
ence between the AUROCs of the two scores was estimated at any disinfectants as well as commercial hand disinfectants for their
time. Best cut-offs to identify patients at lower and higher risk of HCC virucidal activity against HEV using a recently described high titer cell
were 10 and 18 for PAGE-B score, and 1.0 and 2.2 for FIB-4, culture HEV model.
respectively. Cumulative probability of HCC according to these new Method: We used a robust HEV genotype 3 cell culture model which
risk groups are depicted on the figure above. allows quantification of viral infection of quasi-enveloped and naked
HEV particles. For HEV genotype 1 infections the primary isolate
Sar55 in a faecal suspension was applied. Standardized quantitative
suspension tests using end point dilution and large-volume-plating
were performed for the determination of virucidal activity of alcohols
(1-propanol, 2- propanol, ethanol), WHO disinfectant formulations
and five different commercial hand disinfectants against HEV.
Iodixanol gradients were conducted to elucidate the influence of
ethanol on quasi-enveloped viral particles.
Results: Naked and quasi-enveloped HEV was resistant to alcohols as
well as alcohol-based formulations recommended by WHO. Of the
tested commercial hand disinfectants only one product displayed a
virucidal activity against HEV. This activity could be linked to
phosphoric acid as essential ingredient. Finally, we observed that
ethanol and possibly non-active alcohol-based disinfectants dis-
Figure: Incidence curves of HCC among low-risk groups (blue curves), rupted the quasi-envelope structure of HEV particles, while leaving
intermediate risk groups (red curves) and high risk groups (orange
the highly transmissible and infectious naked virions 2 intact.
curves) for PAGE-B and FIB-4, according to the new thresholds founded in
Conclusion: Different alcohols and alcohol-based hand disinfectants
the study.
were insufficient to eliminate HEV infectivity with the exception of
Conclusion: PAGE-B and FIB-4 scores showed good and equivalent one commercially ethanol-based product which including phos-
predictive performances for HCC in chronic hepatitis B patients in a phoric acid. These findings have strong implications for the efficient
French nationwide cohort, and could be used in clinical practice. prevention measures to reduce viral transmission in clinical practice.

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 POSTER PRESENTATIONS
THU316 for the treatment of chronic hepatitis B (CHB). However, the
Multicentre performance evaluation of the Elecsys HCV Duo translational relevance of these models is not well understood. In
immunoassay this study, we compared the intrahepatic transcriptional profiles of
Mario Majchrzak1, Korbinian Bronner2, Syria Laperche3, the woodchuck and AAV-HBV models with a diverse group of CHB
Elena Riester2, Ralf Bollhagen4, Markus Klinkicht4, patients to determine which stage (s) of natural history they most
Christian Voitenleitner5, Marion Vermeulen6, Michael Schmidt7. closely resemble.
1
German Red Cross Blood Donor Service West GmbH, Hagen, Germany; Method: Whole transcriptome profiling (RNA-Seq) was performed
2
Labor Augsburg MVZ GmbH, Augsburg, Germany; 3National Institute of on liver biopsies from mice transduced with AAV-HBV (n = 8) or
Blood Transfusion, Paris, France; 4Roche Diagnostics GmbH, Penzberg, empty AAV (n = 8), as well as from woodchucks chronically infected
Germany; 5Roche Diagnostics International Ltd, Rotkreuz, Switzerland; with WHV (woodchuck hepatitis virus, n = 49) and from uninfected
6 woodchucks (n = 9). These data was compared to a collection of
South African National Blood Service, Roodepoort, South Africa;
7 human liver biopsies from healthy (n = 9), immune tolerant (IT, n =
German Red Cross Blood Donor Service, Frankfurt am Main, Germany
Email: [email protected] 15), immune active (IA, n = 15), inactive carrier (IC, n = 23), and HBeAg
negative (ENEG, n = 16) donors. Pathway analysis was performed
Background and aims: This study evaluated the diagnostic accuracy using gene set variation analysis (GSVA). Cell type deconvolution was
of the Elecsys® HCV Duo immunoassay on the cobas e 801 analyser performed using EPIC. Mouse livers were also analyzed by immuno-
(Roche Diagnostics International Ltd) for the detection of hepatitis C histochemistry (IHC).
virus (HCV) infection vs commercially available comparators. Results: Like most IT patients, AAV-HBV transduction only modestly
Method: This international, multicentre study was conducted at altered the liver transcriptome, despite high intrahepatic expression
seven sites (August 2020-March 2021). Blood donor samples and of HBV RNAs. IHC confirmed there was little-to-no intrahepatic CD3+
clinical laboratory samples (from routine diagnostic testing, pregnant
T cell infiltration in this model. Consistent with previous studies,
women and patients on haemodialysis) were used for specificity
chronic WHV infection was associated with up-regulation of
analyses, while confirmed HCV-positive samples and seroconversion intrahepatic B cell, T cell and neutrophil gene signatures in
panels were used for sensitivity analyses. All samples were
woodchucks, as well as interferon and inflammatory response
pseudonymised or fully anonymised residual serum or ethylenedia- pathways. Globally, the intrahepatic transcriptional signature of
minetetraacetic acid-plasma. The Elecsys HCV Duo immunoassay was chronically infected woodchucks was similar to IA and ENEG patients,
compared with two registered antigen-antibody (Ag-Ab) combin-
although there were some important differences. Most notably, an
ation assays: the Monolisa HCV Ag-Ab ULTRAV2 and Murex HCV Ag/ intrahepatic neutrophil signature was present in chronically infected
Ab Combination. The Elecsys HCV Duo immunoassay provides
woodchucks but neither IA or ENEG patients.
parallel, but separate, read-out of HCV Ag and Ab results (while
Conclusion: Comparative intrahepatic transcriptional analysis
other combination assays show a combined result only). We revealed that the woodchuck and AAV-HBV models of CHB most
compared the HCV Ab (anti-HCV) module with the Elecsys Anti-
closely resemble the IA/ENEG and IT stages of human disease,
HCV II and Alinity s Anti-HCV assays; no neutralisation method was respectively. These fundamental differences in intrahepatic immune
available to test the HCV Ag module singularly.
environment may impact the response to immune modulatory
Results: In all blood donor samples (n = 20634), the specificity of the
therapies.
Elecsys HCV Duo immunoassay was 99.94% (95% confidence interval
[CI], 99.89–99.97). In all clinical laboratory samples (n = 2531), the THU318
specificity of both the Elecsys HCV Duo immunoassay and the Elecsys Hepatitis B virus splice variants are associated with reduced
HCV Duo anti-HCV module was 99.92% (95% CI, 99.71–99.99), vs likelihood of functional cure and differ across phases of chronic
99.84% (95% CI, 99.59–99.96) for the Monolisa HCV Ag-Ab ULTRA V2 hepatitis B infection
and 99.76% (95% CI, 99.48–99.91) for the Elecsys Anti-HCV II assays, Olivia Maslac1, Josef Wagner2, Vitina Sozzi2, Hugh Mason2,
respectively. The sensitivity of the Elecsys HCV Duo immunoassay in Evguenia S Svarovskaia3, Susanna Tan3, Anuj Gaggar3,
confirmed HCV-positive samples (n = 257) was 99.6% vs 96.1% for the Stephen Locarnini2, Lilly Yuen1, Margaret Littlejohn1, Peter Revill1.
Monolisa HCV Ag-Ab ULTRA V2 assay. The Murex HCV Ag/Ab 1
The Peter Doherty Institute for Infection and Immunity, Victorian
Combination assay could not detect 19% of the seroconversion Infectious Diseases Reference Laboratory, Australia; 2The Peter Doherty
panels and the Elecsys Anti-HCV II assay could not detect 20%. The Institute for Infection and Immunity, Victorian Infectious Diseases
former found HCV infections 2 days later (58 panels; 11 undetected) Reference Laboratory; 3Gilead Sciences, Inc., Foster City, United States
and the latter 18 days later (40 panels; 8 undetected) vs the Elecsys Email: [email protected]
HCV Duo immunoassay.
Conclusion: The Elecsys HCV Duo immunoassay had comparable Background and aims: Chronic hepatitis B (CHB) is characterized by
specificity and better sensitivity vs the comparator assays, including progression through different phases of hepatitis B virus (HBV)
anti-HCV tests. The Elecsys HCV Duo immunoassay may be an infection and disease. Although not necessary for HBV replication,
alternative diagnostic tool in countries where nucleic acid testing is there is increasing evidence that HBV splice variants are associated
not possible. with liver disease progression and pathogenesis.
Method: Next generation sequencing data from 404 patient samples
THU317 of HBV genotype A, B, C, or D in Phase I, Phase II or Phase IV of CHB
Intrahepatic transcriptional profiling demonstrates preclinical was analysed for HBV splice variants. Sp1 may include minor splice
models of chronic hepatitis B resemble different stages of natural variants Sp2 and Sp4 = Sp1*, Sp13 may include minor splice variants
history in humans Sp7 and Sp8 = Sp13*, and Sp9 may include minor splice variants Sp 10
Ricardo Ramirez1, Anastasia Hyrina2, Rudolf Beran2, Stephane Daffis2, and Sp12 = Sp9*.
Sarah Gilmore2, Don Kang2, Noé Axel Montanari3, Results: HBV splice variants differed in frequency and type by
Nicholas Van Buuren2, Li Li2, Dara Burdette2, Becket Feierbach2, genotype and phase of natural history. Splice variant Sp1 was the
Andre Boonstra3, Simon Fletcher2. 1Gilead Sciences, Inc., Foster City, most frequently detected (206/404 51% of patients), followed by Sp13
United States; 2Gilead Sciences, Inc., Foster City, United States; 3Erasmus (151/404 37% of patients). These splice variants were detected in all
MC, Rotterdam, Netherlands HBV genotypes, in all three CHB phases except in phase I for genotype
Email: [email protected] A in contrast to Sp5 and Sp9*, which were detected only in genotypes
B and C. The diversity of splice variants was greatest amongst
Background and aims: The woodchuck and adeno-associated virus genotypes B and C, with all splice variants identified, and lowest in
HBV (AAV-HBV) models are commonly used to evaluate novel agents

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POSTER PRESENTATIONS
genotype D with only 2 splice variants identified (Sp1* and Sp13*). to 35 days post infection ( p.i.). HCV RNA was measured using
The frequency of variants was generally highest in Phase II (123/165 quantitative real-time PCR (qRT-PCR) as previously reported (BBRC.
75% of patients), a phase typically associated with enhanced immune 2006; 346 (1):67–73). We developed an ABM that accounts for two
activation, followed by Phase I (69/99 70% of patients). In Phase II types of agents: hepatocytes and virus in the blood, attempting to
there was significantly higher number of patients with splice variants recapitulate the stochastic process of HCV infection of hepatocytes in
across all genotypes A to D compare to the number of patients mice. The ABM simulates a series of infection stages including initial
without splice variants ( p = 0.0004). Splice variants were associated infection of uninfected cells, infected cells in a non-productive viral
with reduced hepatitis B e antigen (HBeAg) levels and statistically eclipse phase, and infected cells in a productive infection phase
reduced likelihood of achieving HBsAg loss (functional cure) in Phase releasing HCV virion, which then proceed to infect additional
II patients for Sp1 and Sp13 ( p = 0.0014 and 0.0156, respectively, hepatocytes. Several model parameters (e.g., virion production
Figure 1 A and B). cycle) were calculated based on the in vivo experimental design.
Model parameter fitting was done using a Genetic Algorithm (GA)
with the EMEWS framework on the Midway2 high-performance
computing cluster at the University of Chicago.
Results: While in SCID-M HCV was rapidly cleared (Fig. 1a, dashed
lines), a productive infection was established in SCID-MhL (Fig. 1a,
solid lines). After an initial viral decline, the virus resurged, followed
by a transient decline (in 4 mice) that eventually stabilized at high
steady state levels (Fig. 1). To account for a transient decline, a
decrease in viral production was assumed reminiscent of our
previous observation of such transient HCV decline seen in
chimpanzees (Gastroenterology.;128 (4):1056–66). The ABM quan-
titatively reproduces the multi-phasic HCV kinetic patterns observed
(Fig. 1b and c). The ABM predicts that: (1) the viral eclipse phase lasts
Figure 1: Sp1* and Sp13* found at statistically lower frequencies in HBsAg between 1 and 20 h; (2) Once the infected cell passes the eclipse
loss patients phase, the viral production rate is not constant, but rather increases
over time. Initially all mice started with a long production cycle of 1
Conclusion: HBV splice variants detected in patient serum are not virion per 9–15 h but gradually reaching 1 virion per hour after 12 hr;
merely a by-product of HBV replication, differing markedly by HBV (3) Within 5 days, the virion production reaches a steady state
genotype and phase of CHB natural history. Their frequency was production rate of 1–3 virions per hour in each infected cell; and (4) a
generally highest in Phase II, the “immune clearance” phase of CHB viral production drop of 83%-98% starting between 2–5 days p.i. in 4
natural history, suggesting an immune escape phenotype. The mice.
contribution of splice variants to the likelihood of achieving
functional cure on therapy requires further investigation.

THU319
Understanding acute HCV infection kinetics in humanized mice
via an agent-based modeling approach
Zhenzhen Shi1, Yuji Ishida2,3, Nicholson Collier4,5, Michio Imamura3,6,
Chise Tateno2,6, Jonathan Ozik4,5, Jordan Feld7, Harel Dahari1,
Kazuaki Chayama3,8,9. 1Program for Experimental and Theoretical
Modeling, Division of Hepatology, Department of Medicine, Stritch
School of Medicine, Loyola University Chicago, Maywood, United States;
2
PhoenixBio Co., Ltd., Higashi-Hiroshima, Japan; 3Research Center for
Hepatology and Gastroenterology, Graduate School of Biomedical and
Health Sciences, Hiroshima University, Hiroshima, Japan; 4Consortium
for Advanced Science and Engineering, University of Chicago, Chicago,
Conclusion: The ABM provides novel insights into the HCV life cycle
United States; 5Decision and Infrastructure Sciences, Argonne National
in vivo. The model suggests a partial block of virion production
Laboratory, Aragonne, United States; 6Department of Gastroenterology
possibly due to an early stage of innate immune response.
and Metabolism, Applied Life Sciences, Institute of Biomedical and
Health Sciences, Hiroshima University, Hiroshima, Japan; 7Toronto THU320
Centre for Liver Disease, Toronto, Canada; 8Collaborative Research Presence of sodium taurocholate co-transporting polypeptide
Laboratory of Medical Innovation, Graduate School of Biomedical and and hepatitis B replication markers on placenta: another home
Health Sciences, Hiroshima University, Hiroshima, Japan; 9RIKEN Center for the virus?
for Integrative Medical Sciences, Yokohoma, Japan Garima Garg1, Meenu Mn1, Kajal Patel1,2, Shashank Purwar1,
Email: [email protected] Sramana Mukhopadhyay3, Nitu Mishra4, Sumit Rawat5,
Background and aims: uPA-SCID chimeric mice with humanized Shashwati Nema2, Debasis Biswas1, Anirudh Kumar Singh1,
livers (SCID-MhL) are a useful tool for studying HCV infection in the Ashish Kumar Vyas1. 1All India Institute of Medical Sciences Bhopal,
absence of an adaptive immune response. Here we sought to analyse Microbiology, India; 2All India Institute of Medical Sciences Bhopal,
and model the HCV kinetics from inoculation to steady state in the Pathology, India; 3All India Institute of Medical Sciences Bhopal,
uPA-SCID mouse model, using an agent-based modelling (ABM) Pathology; 4Gandhi Medical College Bhopal, India; 5Bundelkhand
approach. Medical College Sagar, India
Method: Ten male mice (5 PXB SCID-MhL with hepatocyte donor: JFC Email: [email protected]
[1 year, male Caucasian] and human albumin >9 mg/ml, and 5 SCID Background and aims: The role of sodium taurocholate co-
mice without humanized livers, SCID-M) were inoculated intraven- transporting polypeptide (NTCP), in facilitating the binding of the
ously with HCV (genotype 1a)-infected serum of 1 × 106 copies/ virus on surface of hepatocytes is well documented. Expression of
animal. Viral levels were frequently measured from blood samples up NTCP in extra hepatic cells may make these cells susceptible to HBV

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 POSTER PRESENTATIONS
infection and support cellular proliferation akin to hepatocytes. is growing evidence for their role in predicting treatment durability
Placental replication of HBV is not well explored/studied. In this study and successful cessation of nucleos (t)ide analogue therapy in chronic
we have assessed the expression of NTCP and HBV replication HBV. Limited data exist on their utility predicting outcomes in HBV/
markers (HBeAg, HBcAg, and HBV DNA) in placental cells, to HIV co-infection. We aimed to evaluate the value of longitudinal
investigate if these cells act as host/reservoir for HBV. measurement of HBcrAg and HBV RNA in two cohorts of HBV/HIV co-
Method: Twenty HBsAg+ve pregnant women along with 10 healthy infected patients.
controls were enrolled after obtaining informed consent. The HBV Method: Two cohorts of e-antigen negative HBV/HIV co-infected
DNA in placenta was detected by qPCR using primers for X and core patients were retrospectively studied. Patients were classified into 2
ORF. Expression of NTCP in placenta was analyzed by qRT-PCR and groups: those who started tenofovir (TDF) based antiretroviral
was further investigated by immunohistochemistry (IHC) along with therapy (ART) at baseline (Cohort A, n = 30) and those already
HBV replication biomarkers, HBsAg, HBeAg, and HBcAg. established on TDF based ART with suppressed HBV DNA for 5 years
Results: HBV infected females showed increased expression of NTCP at baseline (Cohort B, n = 37). HBcrAg and HBV RNA were tested at
in trophoblasts of placenta compared to control group (3.62 ± 0.96 Vs baseline, year 3 and year 5. HBcrAg was measured by automated
1.44 ± 0.81). Furthermore, significant difference in NTCP expression CLEIA-method (Lumipulse G 1200 HBcrAg, Fujirebio). HBV RNA was
was also observed between HVL and LVL group (3.62 ± 0.96 Vs 2.06 ± measured by real-time PCR research assay Abbott Diagnostic with
1.3) and it was correlated with the maternal HBV DNA load. LLQ 1.65 log10 U/ml.
Membranous and/or Cytoplasmic immunostaining of NTCP, and Results: Cohort A: at baseline 11 patients (37%) had undetectable
cytoplasmic staining of HBeAg and HBcAg in trophoblasts along HBcrAg and 10 (33%) had HBV RNA below the limit of detection. After
with presence of HBV DNA indicated that trophoblasts are not only 3 years of ART all patients had completely suppressed HBV DNA, 40%
susceptible to HBV infection but may also be a probable site for viral still had detectable HBcrAg and 43% had detectable HBV RNA. After 5
replication. years of therapy there were still 10 patients (33%) with detectable
HBcrAg (median 4.4 log10 U/ml; range 3.3–4.1) and 10 patients (33%)
with detectable HBV RNA (median 1.96 (log10 U/ml; range 1.78–3.6).
Cohort B: at baseline all patients had been on TDF based ART for 5
years and had undetectable HBV DNA, 17 patients (46%) had
undetectable HBcrAg and 20 (54%) had HBV RNA below the limit of
detection. After 3 years 45% still had detectable HBcrAg and 32% had
detectable HBV RNA. After 5 years, there were still 15 patients (41%)
with detectable HBcrAg (median 3.7 log10 U/ml; range 3.0–5.4) and
11 (30%) with detectable HBV RNA (median 2.19 (log10 U/ml; range
1.78–3.6). The impact of HBV genotype, pre therapy HIV viral load and
nadir CD4 count on HBV markers in both cohorts was analysed and no
significant effect found.
Conclusion: HBcrAg and HBV RNA are sensitive biomarkers for
continued transcription of cccDNA in HBeAg negative HBV/HIV co-
infected patients despite long term suppression of HBV DNA by TDF
based ART. TDF withdrawal studies are needed in HBV/HIV cohorts
but as ART moves into a new era of TDF-sparing two drug regimens,
Figure: Fig. (A-D) NTCP Expression at 100X and 400X. A. NTCP expression
these biomarkers may have clinical utility identifying those who can
in liver. B. NTCP expression in placenta of control. C. NTCP expression in
stop TDF safely with minimal risk of HBV reactivation.
placenta of Group B. D. NTCP expression in placenta of Group A. E. NTCP
mRNA fold change among groups.
THU322
Conclusion: This is the pioneer study, which demonstrates expres- Next-generation sequencing of Swiss HEV isolates allows for
sion of NTCP on placenta which may facilitate the entry of HBV. reconstitution of functional clones
Furthermore, the study establishes the presence of HBeAg in Jérôme Gouttenoire1, Roland Sahli2, Daniela Müllhaupt1,
trophoblasts indicating these cells may act as replication host/ Montserrat Fraga Christinet1, Darius Moradpour1. 1Lausanne
reservoir. Correlation of NTCP expression with maternal viral load University Hospital (CHUV) and University of Lausanne, Division of
and presence of HBeAg in placenta indicates its probable role in Gastroenterology and Hepatology, Lausanne, Switzerlan; 2Lausanne
vertical transmission of HBV. Our preliminary finding suggest that University Hospital (CHUV) and University of Lausanne, Institute of
NTCP blocking strategy may be used for therapeutic intervention of Microbiology, Lausanne, Switzerland
vertical transmission. Email: [email protected]
Disclosure-Conflict of interest: There are no conflict of interest
Background and aims: Hepatitis E acquired in Switzerland is caused
among the authors.
primarily by a specific hepatitis E virus (HEV) subtype which has been
THU321 provisionally designated as 3 s and recently assigned as a distinct
Exploring dynamic changes in HBcrAg and HBV RNA in e-Antigen group to 3 h (3 s[ p]/h). Here, we analyzed HEV from patients with
negative HBV/HIV patients on antiretroviral therapy: still evidence severe outcomes of hepatitis E by a newly developed next-generation
of integrated activity after 5 years of treatment sequencing (NGS) protocol and assembled subgenomic replicons as
well as full-length clones.
Ruth Byrne1, Mark Anderson2, Gavin Cloherty2, Kate Childs3,
Method: Illumina RNA sequencing coupled with HEV-specific
Ivana Carey3, Mark Nelson1, Kosh Agarwal3. 1Chelsea and Westminster
sequence enrichment was carried out on plasma samples from 24
Hospital, London, United Kingdom; 2Abbott Diagnostics, Department of
patients with hepatitis E acquired in Switzerland and severe
Infectious Diseases, Chicago, United States; 3Kings College Hospital,
outcomes (severe acute hepatitis, acute-on-chronic liver failure and
Institute of Liver Studies, London, United Kingdom
neurologic complications). Viral genomes reconstituted by DNA
Email: [email protected]
synthesis and molecular cloning were functionally characterized in
Background and aims: Hepatitis B core-related antigen (HBcrAg) cell culture.
and pre-genomic ( pg) HBV RNA are surrogates of covalently closed Results: The entire HEV genomes from plasma of 24 patients could be
circular (ccc) DNA and have emerged as new HBV biomarkers. There sequenced successfully, confirming the predominance of subtype 3 s

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POSTER PRESENTATIONS
( p)/h in Switzerland. The number of reads at each nucleotide position Conclusion: The novel FXR agonist HEC96719 has strong inhibitory
and overall coverage allowed to establish a consensus sequence for 17 effect against HBV replication in PHH cells and AAV/HBV mice, thus
genomes. Subgenomic replicons and full-length genomes derived represent a promising agent for HBV cure.
from some of these replicated in hepatoma cell lines. Functional
clones are being further characterized, in particular for their ability to THU324
produce infectious virus. In addition, selectable replicons are Combined effect of Vonafexor and Interferon-alpha on HBV
currently being investigated with the aim to identify cell culture- replication in primary human hepatocytes
adaptive changes. Romain Barnault1, Raphaël Darteil2, Pietro Scalfaro2,
Conclusion: A newly developed NGS protocol and DNA synthesis Jacky Vonderscher2, David Durantel1. 1INSERM U1111-CIRI, HepVir
allowed to successfully reconstitute functional clones of Swiss HEV team, Lyon, France; 2ENYO pharma SA, Bioserra 1, Lyon, France
isolates. These represent a rare resource and should facilitate further Email: [email protected]
studies on the molecular virology and pathogenesis of hepatitis E.
Background and aims: Despite its adverse safety and tolerance
profile, as well as a limited effect in inducing a HBsAg-loss, pegylated
THU323
interferon-alpha ( peg-IFNα) continues to be used as first line therapy
HEC96719, a novel FXR agonist, inhibits HBV infection in vitro and
in vivo for chronic hepatitis B (CHB) patients. It is hypothesized that an
immune-stimulator will be a necessary component of future
Pu Wang1, Qingying Lai1, Xinye Yang1, Jing Li1, Yunfu Chen1. 1Sunshine
combination therapies for curing CHB, therefore, it is essential to
Lake Pharma Co., Ltd, Department of Pharmacology and Toxicology,
either use alternative compounds to peg-IFNα, or to introduce a
Dongguan, China
second compound which may increase its efficacy and lead to
Email: [email protected]
lowering its dosing, which may reduce associated side effects. Several
Background and aims: Current treatment for hepatitis B virus (HBV) FXR agonists were shown to have some anti-HBV properties in vitro.
infection, including nucleos (t)ide analogues and Interferon, can Moreover, the combination of peg-IFNα2a with Vonafexor, a synthetic
reduce disease progression but have limited effect on achieving HBV non-steroidal, non bile-acid and highly selective FXR agonist, has
functional cure. Therefore, new drugs with differentiated mechan- been shown in an on-going open-label phase II trial (NCT04365933)
isms of action, by targeting HBsAg and cccDNA, are required to to significantly reduce HBsAg levels in HBe-negative patients after
significanlty enhancing the rate of functional cure. only 16 weeks of treatment (Poster 2844, EASL 2021). The aim of this
Method: The in vitro anti-HBV activities of a novel FXR agonist work was to further evaluate the underlying mechanism of action by
HEC96719 were evaluated in HBV-infected primary human hepato- determining whether an increased anti-HBV effect of this combin-
cytes (PHH) model while the in vivo antiviral activities and ation could be recapitulated in cell culture models.
modulation of FXR pathway were studied in the AAV/HBV mouse Method: We used experimentally HBV-infected differentiated
model. HepaRG cells and primary human hepatocytes (PHH), as well as
Results: HEC96719 had significantly enchanced antiviral activities standard molecular and cellular virologic methods to study the
(Table 1) in HBV-infected PHH with mean EC50 values against HBV combination of Vonafexor and peg-IFNα, and compare the combin-
DNA, HBeAg, HBsAg and HBV RNA of <0.001μM, 0.001μM, 0.003 μM ation to respective monotherapies. The cytotoxicity of the combin-
and <0.001μM, respectively, while 0.338 μM, 0.122 μM, 0.509 μM and ation was also evaluated to exclude its contribution to the improved
0.456 μM for GW4064, respectively. Southern blot analysis revealed antiviral effects.
that HEC96719 has no siginificant impact on cccDNA level, indicative Results: The combination of Vonafexor and peg-IFNα led to an
of transcriptional inhibition on cccDNA. CC50 of HEC96719 were improved anti-HBV effect on all parameters analyzed in both
greater than the maximum detected concentration (10μM). In AAV/ dHepaRG and PHH cells, including intracellular decrease in HBV
HBV mouse model, HEC96719 (0.5 mg/Kg and 2 mg/Kg) demon- RNAs, viremia and HBsAg secretion. The effect was more pronounced
strated dose dependent inhibition on viral parameters. Compared to on HBsAg secretion where a synergy between Vonafexor and peg-
vehicle control, mean decline of serum HBV DNA, HBeAg and HBsAg IFNα was observed (see figure below). At therapeutically relevant
at 56 days post treatment were − 0.51 ± 0.09 log, − 0.30 ± 0.06 log, concentrations of the combination Vonafexor and peg-IFNα, no
and − 0.26 ± 0.06 log respectively for the 0.5 mg/Kg dose group, toxicity was observed using 4 different assays (Cell titer Glo,
while − 1.34 ± 0.33 log, − 0.50 ± 0.08log, and − 0.61 ± 0.18 log respect- Neutral red, Sulforhodamine stainings, and LDH release), thus
ively for the 2 mg/Kg dose group. Furthermore, HBV DNA and 3.5 kb ruling out potential toxicity as an alternative explanation for
RNA were also significantly reduced in the liver. Metabolic regulation improved anti-HBV effects. Interestingly, similar improved anti-HBV
related indicators, FXRα were significantly decreased, while SHP and activities were also observed with other FXR agonists, thus
BSEP were significantly increased in the liver. Treatment were well demonstrating the class effect of those observations.
tolerated with no occurance of ALT flares.

Table 1: Antiviral activity of HEC96719 in viro and in vivo

S254 Journal of Hepatology 2022 vol. 77(S1) | S119–S388

 POSTER PRESENTATIONS
Conclusion: We were able to recapitulate, in cell culture models, the frequency (respectively 5.51, 98.60, and 8.20%) in viral QS and were
improved anti-HBV effect of combining Vonafexor and peg-IFNα. We selected in the two patients’ sample.
also observed that the effect is achieved without inducing toxicity.
Conclusion: As expected and considering its role in viral replication,
This study provides support for the existence of a mechanism of
the ribozyme QS was highly conserved without changes between the
action underlying the antiviral activity in combining Vonafexor and
two samples. The mutations observed interested domains involved in
peg-IFNα, details of which should be explored further to eventually
ribozyme excision activity (L3) and structural stabilization (P4), and
assist in identifying efficacy predictive factors in clinical trials.
they could potentially interfere with viral replication. Thanks to its
THU325 high rate of conservation, the ribozyme could be a valuable target of
Hepatitis Delta virus quasispecies conservation and variability in gene therapy. Further in vitro studies are required to evaluate the
ribozyme region effects of the mutations in HDV expression. Funding: Instituto de
Beatriz Pacín Ruiz1,2,3, Maria Francesca Cortese1,2,3, Salud Carlos III (grant PI17/02233), co-financed by the European
Sara Sopena Santisteve3, Josep Gregori1, Selene Garcia-Garcia1,2,3, Regional Development Fund (ERDF).
David Tabernero2,3, Rosario Casillas1,3, Marta Vila1,3,
THU326
Ariadna Rando-Segura3, Adriana Palom4, Mar Riveiro Barciela4,
Exosomal cargo as a key player of the immune response after
Francisco Rodríguez-Frías1,2,3, Maria Buti4. 1Vall D’hebron Research
direct-acting antiviral treatment in chronic hepatitis C patients
Institute, Barcelona, Spain, Liver Unit, Barcelona, Spain; 2InstitutoDe
Eirini Karamichali1, Pelagia Foka1, Vaia Valiakou1, Petros Eiliadis2,
Salud Carlos III, Madrid, Spain, Centro De Investigación Biomédica En
Red, Enfermedades Hepáticas y Digestvas (CIBERehd), Madrid, Spain; Domniki Loukaki-Gkountara1, Konstantina Andresaki1,
3
Vall D’hebron University Hospital, Biochemistry and Microbiology/Liver Georgia Papadopoulou1, Urania Georgopoulou1,
Ioannis-Georgios Koskinas3. 1Hellenic Pasteur Institute, Molecular
Pathology Unit, Barcelona, Spain; 4Vall D’hebron University Hospital,
Liver Unit, Internal Medicine Department., Barcelona, Spain Virology, Athens, Greece; 2Hellenic Pasteur Institute, Laboratory of
Molecular Biology and Immunobiotechnology, Athens, Greece; 3Medical
Email: [email protected]
School of Athens, Greece, 2nd Department of Internal Medicine,
Background and aims: Around the 5% of hepatitis B virus (HBV) Hippokration General Hospital, Athens, Greece
infected patients are co-infected with Hepatitis D virus (HDV). HDV Email: [email protected]
genome is characterized by an 85 nucleotides-length domain with
autocatalytic activity called ribozyme, which covers a key role in HDV Background and aims: HCV infection causes severe liver disease.
Direct-acting antivirals (DAAs) eradicate HCV but host immunity fails
replication. Of note, HDV presents a high rate of evolution and
circulates as a mixture of variants forming a quasispecies (QS). Here, to fully recover. Exosomes are extracellular vesicles secreted by all cell
types. They are masters of intercellular communication in health and
we analyzed by Next Generation sequencing (NGS) the ribozyme QS
disease. It has been demonstrated that HCV infection can be
in longitudinal samples to study its conservation and identify
possible mutations that could potentially affect HDV replication. transmitted by exosomes between hepatocyte-like cells establishing
a productive infection. Viruses exploit exosomes to establish
Method: Thirty-two patients with chronic hepatitis delta (CHD) were
selected and two serum samples were collected per patient with a persistent infection and escape the immune response. Exosomal
cargo promotes disease progression possibly by “dampening down”
mean follow-up of 2.25 years. Viral genotype was determined by
host immune responses.
analyzing HDV delta antigen sequence. The HDV RNA region between
nt 663 and 899, corresponding to ribozyme, was analyzed by NGS We aimed to elucidate the role of exosomes in the immune response
of chronic HCV patients at various stages of liver fibrosis, before and
(MiSeq Illumina, San Diego, USA). Conservation was studied by
calculating QS information content. Nucleotide substitutions were after DAAs treatment.
identified by aligning sample QS with its genotype consensus Method: Whole blood from 40 chronic HCV patients with character-
ized fibrosis was collected before and after DAAs administration and
sequence.
Results: All patients were infected by genotype 1 HDV. A median of used for isolation of exosomes and peripheral blood mononuclear
cells. The existence of specific T-cell subpopulations was assessed by
5040 reads/sample was obtained. The ribozyme was overall highly
FACS. Exosomal cargo was analyzed for immunosuppressive factors
conserved. A hyper-conserved region was identified between nt 715–
745, whereas the more variable portion was between nt 739–769, by immunoblotting, FACS and ELISA.
Results: The (%)-ratio of cytotoxic (CTL) over total T-lymphocytes
although more the 90% of nt showed a maximum of conservation.
When looking QS evolution between the two follow-up samples, (CD3/CD8) remained unaffected by DAAs treatment and fibrosis
stage. Conversely, the Tregs (CD4/CD25/FOXP3) subpopulation post-
limited distance was observed. Eleven mutations were observed. Of
DAAs treatment was statistically decreased in mild fibrosis (stages
them, 3 mutations (T23C, T64del, and T69C) presented a high
F0-F1-F2), but remained stable in advanced fibrosis and cirrhosis

Figure: (abstract: THU325): Logo representation of the nucleotide sequence corresponding to the ribozyme region in the genomic sense (nt 688-771). At
the bottom are indicated the different regions of the ribozyme and to which of them each nucleotide group corresponds

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POSTER PRESENTATIONS
(stages F3-F4). Importantly, the active form of the immunosuppres- THU328
sive cytokine TGF-β was detected in the exosomal cargo and Updated national prevalence estimates of chronic hepatitis B virus
matching serum, albeit varying between fibrosis stages. We observed infection in countries within the European (EU) and European
that the TGF-β levels of both sera and exosomes before DAAs Economic Area (EEA): a systematic review
treatment were statically increased in advanced fibrosis (F3). Sandra Bivegete1,2, Adam Trickey1, Zak Thornton1, Becky Scanlan1,
Treatment with DAAs statistically reduced serum TGF-β levels by Anna McNaughton1, Aaron G. Lim1, Lina Nerlander3, Hannah Fraser1,
50% in the advanced stages of fibrosis and cirrhosis, whereas it did not Josephine Walker1, Matthew Hickman1,2, Peter Vickerman1,2,
alter TGF-β levels in exosomes in the different stages of fibrosis. Helen Johnson3, Erika Duffell3, Ellen Brooks-Pollock1,
Finally, we confirmed the presence of the immunosuppressive PD-L1 Hannah Christensen1. 1University of Bristol, Population Health Science,
molecule in exosomes isolated from the same samples both before Bristol Medical School, Bristol, United Kingdom; 2University of Bristol,
and after treatment. NIHR HPRU in Behavioural Science and Evaluation, Bristol, United
Conclusion: HCV-manipulated exosomes may confer continuing Kingdom; 3European Centre for Disease Control, Stockholm, Sweden
immune suppression in the otherwise cured HCV patients bearing Email: [email protected]
advanced liver disease. Despite DAA-mediated HCV eradication, the
presence of immunosuppressive factors in the exosomal cargo Background and aims: Hepatitis B virus (HBV) is a leading public
supports the notion of a remaining “viral fingerprint” that could health problem globally. In Europe, the burden of HBV dispropor-
promote liver disease in susceptible individuals. tionately affects at-risk groups, including men who have sex with
men (MSM), migrants and prisoners. There are no recent population-
THU327 level estimates of HBV prevalence in Europe.
Therapeutic suppression of HBV transcripts promotes Method: We undertook a systematic review to update estimates of
reappearance of the SMC5/6 complex and cccDNA silencing in vivo chronic HBV (CHB) prevalence for the EU/EEA and UK in key sentinel
without affecting posttranslational modifications of cccDNA- and at-risk population groups. Databases were searched for original
bound histones research articles in English published between 1/1/2018 to 24/2/
Lena Allweiss1,2, Moritz Calaminus1, Katja Giersch3, Tassilo Volz1, 2021. Titles and abstracts were screened to identify articles contain-
Andrea Pirosu4, Marc Luetgehetmann2,3, Maura Dandri1,2. 1University ing relevant information on CHB prevalence in Europe as measured
Medical Center Hamburg-Eppendorf, I. Department of Internal by HBsAg status, with full text screening undertaken to confirm
Medicine, Hamburg, Germany; 2German Center for Infection Research inclusion. Sentinel groups included first-time blood donors (FTB),
(DZIF), Hamburg-Lübeck-Borstel-Riems, Germany; 3University Medical general population (GP) and pregnant women; at-risk groups
Center Hamburg-Eppendorf, Department of Medical Microbiology, included MSM, migrants and prisoners. The updated estimates
Virology and Hygiene, Germany; 4Leibniz Institute for Experimental were incorporated into an existing HBV prevalence database
Virology, Department of Viral Immunology, Hamburg, Germany (spanning 2005–2017) developed by the European Centre for
Email: [email protected] Disease Control using the same inclusion/exclusion criteria.
External grey literature data were obtained from country experts.
Background and aims: There is a strong need to explore interven- Results: A total of 5678 articles were title and abstract screened, of
tions able to suppress the hepatitis B virus (HBV) reservoir, the which 307 were full-text screened. A total of 41 published studies
cccDNA, since its silencing may promote a functional cure of chronic were included in the review, consisting of studies in GP (n = 12),
hepatitis B (CHB). We previously showed that treatments with siRNA migrants (n = 17), pregnant women (n = 5), MSM (n = 3) and prisoners
targeting all HBV transcripts or pegylated interferon α ( peg-IFNα) (n = 4). Additional estimates from grey literature were also included
strongly reduce all HBV markers, including HBx, thus enabling (n = 109), comprising of GP (n = 11), migrants (n = 7), pregnant
reappearance of the host restriction factor “structural maintenance of women (n = 16), MSM (n = 6), prisoners (n = 8) and FTB (n = 61).
chromosome 5/6” (SMC5/6) complex and cccDNA suppression in vivo Weighted CHB prevalence estimates from the existing and updated
(Allweiss/Giersch, Gut 2021). The aim of this study was to investigate database indicated a low HBV prevalence (≤2%) among sentinel
the epigenetic landscape of cccDNA-bound histones in HBV-infected populations in all regions with exceptions in Romania, Bulgaria, Italy
humanized mice after siRNA or peg-IFNα treatment. and Greece (reported prevalences 3.4–7.6%). Prevalence among
Method: HBV-infected human liver chimeric mice received siRNA or prisoners varied considerably across all regions (range 2.1–25.2%)
peg-IFNα for 4 or 6 weeks, respectively, or were left untreated. RNA in and 56% countries lacked data. Studies among migrants recorded
situ hybridisation demonstrated suppression of HBV transcripts in some of the highest HBV prevalences, and estimates in this sub-
human hepatocytes. Active and repressive posttranslational mod- population were typically higher in Southern European regions
ifications (PTMs) of cccDNA-bound histones and SMC5/6 occupancy (range 5.0–12.2%). Reported HBV prevalence among MSM was low
were analysed by chromatin immunoprecipitation-qPCR (ChIP-qPCR) (≤2%), except in Belgium and Estonia (range 2.3–3.4%). Studies on
and compared with PTMs on host genes. MSM and migrants were absent in Eastern Europe.
Results: In untreated mice with high HBV replicative activity,
canonical transcriptionally active PTMs (H3K27ac, H3K4me3) were
highly enriched on the cccDNA minichromosome while the repres-
sive mark H3K27me3 was undetectable. This pattern was consistent
with active transcription and similar to the active host gene promotor
GAPDH. Remarkably, neither siRNA nor peg-IFNα provoked signifi-
cant PTM changes on the cccDNA despite strong reduction of HBV
transcription. Consistent with previous results, only NSE4 occupancy,
a subunit of the SMC5/6 complex, became detectable on the cccDNA Figure: Updated HBsAg prevalence estimates in high-risk groups in the
after siRNA and peg-IFNα treatment. EU/EEA and UK. Maps show the weighted average prevalence in each
Conclusion: Despite shutting down cccDNA transcription in a great country.
proportion of human hepatocytes, siRNA or peg-IFNα treatment did
not alter the pattern of the analysed cccDNA-bound histone PTMs. In Conclusion: This review builds on previous estimates in the EU/EEA
line with the function of SMC5/6 as a DNA micro-compaction and UK, providing an additional 150 prevalence estimates across the
machine (Serrano, Molecular Cell 2020), the data suggest that SMC5/ region (updated total; n = 582). HBV prevalence was higher in
6 could mediate silencing through physical cccDNA compaction Southern and south-Eastern Europe compared to other regions.
rather than through epigenetic changes. Furthermore, CHB prevalence remains high among high-risk groups,

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 POSTER PRESENTATIONS
indicating that further interventions targeting these groups are ejaculate could not be demonstrated so far, it could now be shown
required to reduce the burden of HBV in Europe. that they are infectious in PLC/PRF/5 cells. While there is probably no
danger from this ejaculate for immunocompetent sexual partners,
THU329 safer sex practice should be followed if the sexual partners are
Relevance of HEV detection in ejaculate of chronically infected immunocompromised.
patients
Mathias Schemmerer1, Marc Luetgehetmann2, Hans Bock3, THU330
Jörn Schattenberg4, Samuel Huber5, Susanne Polywka2, M Mader5, HDV-mediated inhibition of HBV in superinfection mouse model:
Ansgar Lohse5, Daniel Todt6,7, Eike Steinmann6, Jürgen Wenzel1, the role of type I Interferon
Thomas Horvatits5, Sven Pischke5. 1University Medical Center Beatriz Pacín Ruiz1,2,3, Gracián Camps4, Maria Francesca Cortese1,2,3,
Regensburg, Institute of Clinical Microbiology and Hygiene, National Josep Gregori1,2, David Tabernero1,3, Selene Garcia-Garcia1,2,3,
Consultant Laboratory for HAV and HEV, Regensburg, Germany; África Vales Aranguren4, Cristina Olague Micheltorena4,
2
University Hospital Hamburg-Eppendorf, Microbiology, Germany; Ariadna Rando-Segura1, Josep Quer2,3, Rafael Esteban3,5,
3
University Hospital Düsseldorf, Gastroenterology, Germany; 4University Mar Riveiro Barciela3,5, Maria Buti3,5, Gloria González-Aseguinolaza4,
Medical Center Mainz, Gastroenterology, Germany; 5University Medical Francisco Rodríguez-Frías1,2,3. 1Vall D´hebron University Hospital,
Center Hamburg-Eppendorf, Department of Medicine, Germany; 6Ruhr- Biochemistry and Microbiology/Liver Pathology Unit, Barcelona, Spain;
2
University Bochum, Department of Molecular and Medical Virology, Vall D´Hebron Research Institute, Liver Unit, Barcelona, Spain;
Germany; 7European Virus Bioinformatics Center (EVBC), Jena, Germany 3
Instituto De Salud Carlos III, Centro De Investigación Biomédica En Red,
Email: [email protected] Enfermedades Hepáticas Digestvas (CIBERehd), Madrid, Spain;
4
University of Navarra, Center for Applied Medical Research (CIMA),
Background and aims: Recently, HEV particles have been detected in
Pamplona, Spain; 5Vall D´Hebron University Hospital, Liver Unit,
the ejaculate of 2 out of 3 chronically infected patients. HEV RNA in
Department of Internal Medicine, Barcelona, Spain
the ejaculate can be significantly higher than in serum or plasma.
Email: [email protected]
However, it was unclear whether these viral particles in the ejaculate
are infectious, and how often HEV generally occurs in the ejaculate of Background and aims: While Hepatitis B virus (HBV) replication
chronically infected individuals. does not significantly activate the innate immune response, it has
Method: After a previous cell culture model failed to demonstrate the been observed that in the presence of Hepatitis Delta virus (HDV)
infectivity of HEV particles from the ejaculate of two chronically there is an increased type I interferon (INF) response. The aim of this
infected patients (Horvatits et al. Journal of Hepatology 2021), we study is to analyze the potential role of the IFN response on the HBV
now used an alternative cell culture model based on overconfluent inhibition upon HDV super-infection in a novel HBV-expressing
PLC/PRF/5 cells (Schemmerer et al. Viruses 2019) to study these transgenic (HBVtg) mouse model knock out for the IFN alpha-
particles for infectivity. Furthermore, we monitored HEV viral load in receptor (IFNαR KO).
blood, urine, stool and ejaculate in 9 chronically HEV infected Method: Wild type (WT) and IFNαR KO HBVtg mice were intraven-
patients. ously administered with 5 × 1010 viral genomes of adeno-associated
Results: For the first time, HEV particles from ejaculate were shown vector (AAV) expressing luciferase (LUC) or HDV. While Hepatitis B
to be infectious in overconfluent PLC/PRF/5 cells (figure). HEV viremia was weekly monitored during the experiment, liver HBcAg
replicated to high viral loads of 10e9 HEV RNA copies per ml. expression and HBV-DNA levels were analyzed at 21 days after AAV
Moreover, HEV was detected in the ejaculate of 7 out of 9 chronically injection. At this timepoint, the complexity of the HBV quasispecies
infected patients (age 36–67 years, median 56 years). In 5 of the (QS) at the 5′ (nt 1255–1611) and 3′ (nt 1596–1912) ends of the X gene
patients the viral loads were significantly higher (more than 2 log) of intrahepatic RNA was analyzed by next-generation sequencing
compared to their serum, while in 2 patients, viral loads were lower (NGS) (MiSeq Illumina, San Diego, USA). Nucleotide substitutions
than in their serum (more than 1 log). were identified by aligning sample QS with its genotype master
sequence and QS complexity was calculated using Rare Haplotype
Load (RHL) index (threshold 1%).
Results: Both liver HBcAg expression and viremia was higher in
HBVtg × IFNαR KO than in WT HBVtg mice under steady state
conditions. AAV-HDV injection induced the decrease of hepatic
HBcAg expression and HBV-DNA levels in HBVtg mice. This effect
disappeared in HBVtg × IFNαR KO mice. Likewise, viremia was
reduced from day 7, reaching the lowest levels at day 21 after
vector administration in HBVtg mice, while HBV serum levels in
HBVtg × IFNαR KO animals remained constant until the end of the
experiment. Similar ALT serum levels presented by HBVtg and
HBVtg × IFNαR KO mice excluded differential liver damage as the
reason for the HBV repression observed in HBVtg animals. An overage
higher number of changes was observed in 5′HBX region than in 3′
HBX region (42.72 vs. 15.61). In 5′HBX the RHL index was higher in
presence of HDV. This index was even more pronounced in wt HBVtg
than IFNαR KO.
Conclusion: The limited inhibition of HBV expression in presence of
HDV in IFNαR KO mice suggested that IFN type I is essential for HDV-
mediated HBV inhibition. The higher QS variability in presence of
Conclusion: In the context of chronic HEV infection, HEV particles HDV might contribute to the inhibition of HBV replication. This
can be detected in the ejaculate of 78% (7/9) of infected men, usually variability is more pronounced in wt mice, thus suggesting a possible
with significantly higher viral loads than in serum. In this regard, it role of IFN-dependent activation of mutagenic enzymes. Further
should be noted that the gap between high viral load in ejaculate studies are required to better characterize the molecular mechanisms
compared to viral load in blood may even be much higher than involved in HBV inhibition and variability, and to identify novel
previously suspected. After the infectivity of HEV particles from therapeutic strategies for HDV-infected patients. Funding: Instituto

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POSTER PRESENTATIONS
de Salud Carlos III (grant PI18/01436), co-financed by the European THU332
Regional Development Fund (ERDF). Concordance of the Xpert hepatitis B viral load test and
conventional quantitative PCR in detecting and quantifying
THU331 viremia using stored plasma and dried blood spot samples in West
Assessment of Myrcludex or heparin antiviral activity on HBV Africa
infection using a 3-dimensional primary human hepatocyte Gibril Ndow1, Amie Ceesay1, Yusuke Shimakawa2,
culture system Alpha Omar Jallow1, Haddy Nyang1, Baboucarr Bittaye1,
Juliette Besombes1, Charlotte Pronier1, Jeremy Bomo1, Francis Mendy1, Ousman Secka1, Umberto D’Alessandro1,
Philippe Gripon1, Vincent Thibault1. 1CHU Rennes-Pontchaillou Mark Thursz3, Isabelle Chemin4, Maud Lemoine3. 1MRC Unit The
Hospital, Virology, Rennes, France Gambia at LSHTM, Disease Control and Elimination, Fajara, Gambia;
Email: [email protected] 2
Institut Pasteur, Unité d’épidémiologie des maladies émergentes, Paris,
Background and aims: Despite effective vaccination, Hepatitis B France; 3Imperial College London, Metabolism, Digestion and
Virus (HBV) infection remains responsible for significant morbidity Reproduction, London, United Kingdom; 4INSERM U1052, Center de
and mortality worldwide. Robust in vitro models mimicking the Recherche en Cancérologie, CNRS UMR5286, Lyon, France
complex liver architecture are still lacking and culture of differen- Email: [email protected]
tiated primary human hepatocytes (PHH) remains fastidious. Three Background and aims: The new Xpert hepatitis B virus (HBV) viral
dimensional (3D) culture models of PHH have been developed load test (Cepheid, USA) provides an opportunity to scale up and
offering a microenvironment closer to in vivo conditions. Here, we decentralise hepatitis B diagnosis, treatment and monitoring in
describe the characterization of a 3D cell culture model based on the resource-limited settings where HBV is endemic and molecular
formation of PHH spheroids supporting HBV infection. We focus on diagnostics to quantify HBV DNA are scarce. We assessed the
the effect of Heparin and Myrcludex B (MyrB) on HBV infection. concordance between the new Xpert HBV viral load test and the
Method: PHH (freshly collected or cryopreserved) were first conventional quantitative PCR (Abbott, USA) in quantifying HBV
incubated overnight in ultra-low-attachment plates to make them viremia using stored plasma and dried blood spot (DBS) samples.
aggregate in spheroids before being embedded in a collagen matrix. Method: Paired plasma and DBS (Whatman 903 Protein Saver cards)
HBV infection was performed 2 days after seeding using a 50-fold samples were collected from adults with chronic HBV infection
concentrated culture supernatant of HepG.2.2.15 cells or HBV purified followed up in the PROLIFICA (Prevention of Liver Fibrosis and Cancer
from chronically infected patients’ plasmas using different multipli- in Africa) programme in The Gambia. Samples were stored in − 80C
city of infection (MOI). Susceptibility to infection was monitored by for at least 12 months before analysis.
HBe antigen (HBeAg) secretion in the supernatant. HBV infection For each plasma sample, HBV DNA was quantified using both realtime
under different concentrations of Heparin (4 and 133 μg/ml) or MyrB qPCR (Abbott, detection limit 26 IU/ml in plasma) and Xpert
(50 to 800 nM) was evaluated. (detection limit 3.2 IU/ml in plasma). For DBS, HBV DNA was
Results: After defining the optimal MOI of 400 HBV genome quantified using Xpert.
equivalents (GE)/cell, long-term HBV infections for at least 38 days Concordance of the Xpert HBV test and the conventional qPCR in
were obtained with this model. The dose-response study showed that detecting and quantifying HBV viremia in plasma was assessed by
infections at a low MOI of 10 GE/cell, similar to the one used in vivo in kappa statistics, and the agreement between the two assays was
animal models, were possible even though HBeAg secretion remains assessed using the Bland-Altman plot. The concordance of HBV
weak. We confirmed that high concentration of heparin (133 μg/ml) viremia between paired plasma and DBS samples was also assessed
blocked HBV infection leading to 85% inhibition of HBeAg secretion by kappa statistics.
( p <0.05) at 14 days post infection (dpi). Conversely, heparin at Results: We analysed 266 stored plasma samples from patients at
therapeutic concentration (4 μg/ml) in the culture medium promoted various hepatitis B disease stages. Of these, HBV viral load results
infection with a 130% increase in HBeAg secretion ( p <0.05). In this were concordant between the Xpert and the conventional qPCR: 130
model, 50 nM MyrB efficiently blocked HBV infection with an average (48.9%) and 63 (23.7%) were detectable and undetectable by both
inhibition of HBeAg secretion of 63%, at 7 dpi. An increase of MyrB assays, respectively. The results were discordant in 71 (26.7%)
concentration from 50 to 800 nM did not improve the inhibition of samples that were detectable by Xpert but not qPCR, and 2 (0.8%)
infection. The level of HBeAg secretion was comparable when MyrB samples that were detectable by qPCR but not Xpert. In 110 samples
(100nM) was present only at the time of infection or maintained with quantified viral load results from both assays, the mean
throughout the culture duration with an inhibition of HBeAg difference between the two assays was 0.316 log IU/ml (95% limits
secretion of 84% at 14 dpi, whatever the condition. Adjunction of of agreement − 1.189, 1.820) with only 6/110 results (5.45%) being
MyrB in the culture medium at 4 and 8 dpi resulted in a decrease in outside the limits of agreement (figure 1), indicating good
HBeAg secretion of 61% and 25%, respectively, at 14 dpi ( p <0.05 agreement.
compared to without MyrB). From 91 paired plasma and DBS samples analysed by Xpert assay, the
Conclusion: This 3D PHH culture system supports long-term HBV mean bias between plasma and DBS was statistically significant at
infection. Activity of MyrB even when added at distance from +1.831 log IU/ml (95% limits of agreement: 0.660–3.001). Bias was
infection suggests late or secondary infections. Heparin activity on smaller at lower viral loads. The kappa statistic was 0.10 indicating
HBV infection depended on its concentration in the medium, yet the very poor agreement between results. After excluding samples with
mechanism underlying this effect remains partially unexplained. error or invalid result by either sample type (n = 40), kappa statistic
Optimization and characterization of this model are warranted. was 0.34 indicating a poor agreement.

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 POSTER PRESENTATIONS
enrichment of virus integration sites was observed in mitochondrial
DNA (mtDNA) both in T ( p <0.0001) and NT ( p <0.0001), after
normalization of the number of integrations to chromosome length.
We found a total of 20 unique HBV integrations in mtDNA from the
tissue samples obtained from 4/7 patients (17 breakpoints in T from
4/4 patients and 3 breakpoints in NT from 2/4 patients). HBV
integration in mtDNA was associated with HBV DNA ( p = 0.01) and
pgRNA amounts ( p = 0.02). In mtDNA, the integration breakpoints
were preferentially located in mitochondrial genes in T (17/17 vs 0/3;
P < 0.0001) and in the D-loop region in NT (2/17 vs 3/3; P = 0.001).
RNR2, ATP6, ND4, and ND5 mitochondrial genes were identified as
recurrent sites of integration in T. Moreover, in T of individual
patients, HBV integrations were detected in CYTB, COX1, ND1, and ND2
genes. Furthermore, we found that HBV RNAs are imported into
mitochondria.
Conclusion: The new HBV integration sequencing method import-
antly increased the detection efficiency of HBV integration breakpoints.
We detected a significant enrichment of virus integrations in mtDMA
Figure 1: Bland-Altmann plot of Xpert HBV minus Abbott qPCR (vertical from both T and NT. HBV integrations in mtDNA preferentially involved
axis) against mean of Xpert HBV and Abbott qPCR (horizontal axis) for OXPHOS mitochondrial genes in T, suggesting that there is selection for
samples with detectable viral load (n = 110).
mitochondria harboring HBV integration in these genes or for cells
Conclusion: The Xpert HBV DNA test provides a reliable alternative containing these mitochondria during hepatocarcinogenesis.
for detecting and quantifying HBV DNAviral load using stored plasma
samples. However, the assay is not reliable for detecting viremia from THU334
DBS samples. Enhanced T cell responses in patients and mouse model of
hepatitis B and comorbid non-alcoholic fatty liver disease
THU333 Nishi Patel1, Dan Boghici2, Micol Rava3, Matteo Iannacone3,
A high-throughput viral integration sequencing method reveals Konstantin Koro4, Craig Jenne2, Carla Osiowy5, Carla Coffin2.
1
that mitochondrial DNA is frequently targeted by HBV integration University of Calgary, Cumming School of Medicine, Calgary, Canada;
2
Domenico Giosa1, Daniele Lombardo1, Cristina Musolino2, University of Calgary, Cumming School of Medicine, Calgary, Canada;
3
Valeria Chines1, Giuseppina Raffa1, Deborah D’aliberti3, San Raffaele Hospital, Division of Immunology, Transplantation and
Francesca Casuscelli di Tocco1, Carlo Saitta1, Riccardo Aiese Cigliano4, Infectious Diseases, Milano, Italy; 4Alberta Precision Laboratories,
Orazio Romeo5, Angela Alibrandi6, Giuseppe Navarra2, Calgary, Canada; 5Public Health Agency of Canada, National
Giovanni Raimondo1, Teresa Pollicino2. 1University Hospital of Microbiology Laboratory, Winnipeg, Canada
Messina, Clinical and Experimental Medicine, Messina, Italy; 2University Email: [email protected]
Hospital of Messina, Human Pathology, Messina, Italy; 3University of Background and aims: Individuals living with hepatitis B and
Milano Bicocca, DIPARTIMENTO DI MEDICINA E CHIRURGIA (SCHOOL OF comorbid non-alcoholic fatty liver disease (NAFLD) are at an
MEDICINE AND SURGERY), Milan, Italy; 4Sequentia Biotech SL, increased risk for hepatocellular carcinoma. Large cohort studies
Barcelona; 5University of Messina, Dipartimento di Scienze chimiche, show a positive association between hepatic steatosis and reduced
biologiche, farmaceutiche e ambientali, Messina, Italy; 6University of hepatitis B virus (HBV) replication. The objective of this study is to
Messina, Dipartimento di Economia, Messina, Italy determine the viral and immune factors and mechanisms that
Email: [email protected] contribute towards lower HBV replication in patients and mouse
Background and aims: Although research on HBV DNA integration model of hepatitis B and NAFLD.
has made relevant progress, important aspects remain unclear. Method: 55 patients with hepatitis B and NAFLD were recruited from
Development of new integration detection methods may help in 3 Canadian liver clinics. Plasma, sera, and peripheral blood mono-
improving knowledge in the field and in better understanding HBV- nuclear cells (PBMCs) were isolated from blood. A parallel mouse
related tumorigenesis. Our aim was to conduct a high-throughput model study of HBV and NAFLD was performed using 1.3.32DH
integration detection on tumor (T) and non-tumor tissues (NT) from transgenic mice that included healthy, NAFLD, and HBV control
HBsAg-positive patients using a highly sensitive method for assaying groups (N = 10/group). The mice were followed for 8 weeks and then
HBV integration. sacrificed to obtain plasma, sera, PBMCs, and liver tissue (for
Method: We studied T from 7 patients with HBV-related HCC and histopathological scoring and viral antigen staining). HBV biomarkers
paired NT from 6 of the 7 cases. HBV integration sites were recovered were quantified using in-house and/or standard clinic assays in both
by semi-nested ligation-mediated PCR from host DNA (fragmented patient and mice samples. Next-generation sequencing of HBV
by sonication and ligated to asymmetric DNA linkers) and the use of surface and core genes was performed using the Illumina MiSeq
forward or reverse HBV-specific primers. Targeted sequences were platform. A panel of 13 pro-and-anti-inflammatory cytokines was
further enriched by nested-PCR with forward or reverse MiSeq HBV measured using multiplex Luminex assay. PBMCs phenotypic profile
primers and forward or reverse MiSeq plinkers. PCR products were and ex vivo HBV-specific T cell responses were characterized through
subjected to paired-end sequencing, and reads were aligned to a flow cytometry and IFN-gamma ELISPOT, respectively.
hybrid genome including human genome (GRCh38.p10) and HBV Results: In 55 patients with hepatitis B and NAFLD (35% female, mean
genome (NC_003977). age of 45 ± 10.6 years), 52 (95%) were HBeAg negative. The mean HBV
Results: A total of 3, 339 unique HBV integration sites were detected DNA, qHBsAg, and HBV pgRNA levels were 3.2 ± 1.8 log10 IU/ml, 2.9 ±
in the 7 patients: 2, 913 integrations in T and 426 in NT. The average 1.2 log10 pg/ml, and 2.1 ± 1.3 log10 copies/ml, respectively. Hepatitis B
number of integration sites in T and NT was 416 and 71, respectively. patients with NAFLD clinical factors (i.e., dyslipidemia, hypertension,
All patients had HBV integrations, with an average of 256.8 and metabolic syndrome) had lower levels of qHBsAg ( p <0.001).
integrations per individual patients. The detected integration sites Similarly, mice with HBV and NAFLD had lower levels of HBV DNA ( p
were randomly distributed across the whole genome and no hotspot = 0.022) and nucleic acid related antigen ( p = 0.044) at 8 weeks.
was detected. Compared to individual chromosomes, a significant Greater frequency of immune escape mutations in HBV surface gene

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POSTER PRESENTATIONS
(i.e., 1277L/T, M133L/I/T, and E164D/G) was detected in hepatitis among their 5–7 years old. High infection prevalence in women of
B patients with severe steatosis ( p <0.05). Elevated levels of childbearing age showed potential of vertical transmission, threaten-
Th1 cytokines like IL-8 ( p = 0.002), TNF-alpha (p = 0.004), IFN- ing WHO target of eliminating hepatitis virus infection by 2030.This
gamma ( p = 0.021), and IL-10 ( p = 0.007) were observed in hepatitis study aimed to estimate HBsAg prevalence among pregnant women,
B patients with NAFLD clinical factors (figure 1). Hepatitis B and and then to examine their genomic structure and the mutation pattern.
NAFLD patients with mild steatosis had higher levels of IL-2 ( p = Method: Hospital based cross-sectional study was performed in a
0.031). In mice with HBV and NAFLD, IL-2 levels declined with HBV total of 1565 pregnant women who visited three hospitals in Siem
DNA at 8 weeks ( p = 0.04). Increased frequency of functional HBV- Reap for their antenatal care from Feb-Sep 2020. The sero-markers
specific T cells was observed in hepatitis B and NAFLD patients such as HBsAg, HBsAb, HBcAb, HBeAg and HBeAb were detected from
compared to control groups ( p <0.05). their blood samples using chemiluminescent enzyme linked. Viral
titer was measured by real-time PCR. Full HBV genomes were
amplified by direct sequencing. The study has been approved by
ethical committees of Hiroshima University and Cambodia.
Results: The age of pregnant women participated in this study ranged
from 15 to 47 years old with the mean age of 28.3 ± 5.6 years old. The
prevalence of HBsAg, HBsAb, and HBcAb were 4.28%, 38.53%, 23.13%,
respectively. Among the HBsAg positives, the prevalence of HBeAg
and HBeAb were 41.79% and 55.22%, respectively. The overall mean
viral titer was 2.22 × 106 copies/ml, where 5.30 × 106 copy/ml for
HBeAg+ and 5.58 x103 copy/ml for HBeAb+. Thirty-seven samples
were able to perform full-genome sequencing. HBV genotype C1 was
predominant (70.27%), followed by B4 (16.22%) and B2 (13.51%). All
HBV genotype B were found to be recombinant B/C. By full genome
analysis on 37 HBV isolates, mutation at a determinant region of
surface protein was 24.32%. Additionally, the combination mutation
was found in 2.70% and double mutation in 29.73% and V149I
mutation at core region in 2.70%, all of which were highly associated
to hepatocellular carcinoma occurrence.

Figure 1: Cytokine levels based on NAFLD clinical factors in hepatitis B

patients (Mann-Whitney U test). *p < 0.05. **p < 0.01. Conclusion: The findings from our study demonstrated the inter-
mediate level of HBV infection endemicity, genotype distribution and
Conclusion: Heightened T cell responses observed in patients and
mutation pattern among pregnant women in Siem Reap. These
mouse model of hepatitis B and NAFLD contribute towards
findings contribute to the establishment of HBV screening program
suppression of HBV replication.
and the management of HBsAg positive for pregnant women in
THU335 Cambodia.
Hepatitis B virus sero-prevalence and genotype distribution
THU336
among pregnant women in Siem Reap, Cambodia
Genotype distribution and mutations associated with
Bunthen E1,2, Ko Ko1, Shintaro Nagashima1, Serge Ouoba1,3, hepatocellular carcinoma risk among hepatitis B carriers in Goto
Kanon Abe1, Aya Sugiyama1, Kazuki Takahashi1, Rattana Kim4, Islands, Japan
Vichit Ork5, Md. Shafiqul Hossain6, Junko Tanaka1. 1Hiroshima
Serge Ouoba1,2, Ko Ko1, Shintaro Nagashima1, Bunthen E1,3,
University, Department of Epidemiology, Infectious Disease Control and
Kazumi Yamasaki4, Kazuki Takahashi1, Junko Tanaka1. 1Hiroshima
Prevention, Graduate School of Biomedical and Health Sciences,
University, Department of Epidemiology, Infectious Disease Control and
Hiroshima, Japan; 2Ministry of Health, Payment Certification Agency,
Prevention, Graduate School of Biomedical and Health Sciences,
Phnom Penh, Cambodia; 3Institut de Recherche en Science de la Santé
Hiroshima, Japan; 2Institut de Recherche en Science de la Santé (IRSS),
(IRSS), Unité de Recherche Clinique de Nanoro (URCN), Nanoro, Burkina
Unité de Recherche Clinique de Nanoro (URCN), Nanoro, Burkina Faso;
Faso; 4Ministry of Health, National Maternal and Child Health Center, 3
Ministry of Health, Payment Certification Agency (PCA), Phnom Penh,
Phnom Penh, Cambodia; 5Ministry of Health, National Immunization
Cambodia; 4National Hospital Organization Nagasaki Medical Center,
Program (NIP), Phnom Penh, Cambodia; 6World Health Organization
Clinical Research Center, Nagasaki, Japan
Country Office, Expanded Program on Immunization, Phnom Penh,
Email: [email protected]
Cambodia
Email: [email protected] Background and aims: Hepatitis B virus (HBV) genotype and specific
mutations are associated with the risk of hepatocellular carcinoma
Background and aims: The latest report hepatitis B virus (HBV)
(HCC). Using stored serum of a cohort of HBsAg-positive patients in
infection prevalence in Cambodia was 4.4% among mothers and 0.56%

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 POSTER PRESENTATIONS
Goto Islands, we studied the genotype distribution and the mutations related to HBV isolates from China and Japan. A total of 92 isolates
related to the progression of liver disease. underwent full genome analysis and mutations related to HCC
Method: A total of 910 samples from a cohort of Hepatitis B surface occurrence were observed. Double mutation (A1762T/G1764A) was
Antigen-positive patients between 1980 and 2017 underwent found in 73.5%, combination mutation (C1653 T and A1762T/G1764A
genomic analyses. Partial and full HBV genomes were amplified by or T1753C and A1762T/G1764A) in 29.4%, and V149I mutation in the
direct sequencing using an in-house developed primer set to identify core region in 26.9% of the isolates.
HBV genotype and mutations related to HCC risk. Phylogenetic tree Conclusion: Genotype C, which is known to be associated with HCC
was performed by the neighbor-joining method. risk, is the predominant circulating genotype in Goto islands,
Results: Men represented 57.4% of the cohort and the mean age at the suggesting a large influence from East Asia. Mutations related to
start of the cohort was 45.5 ± 17.3 years. The median follow-up hepatocellular carcinoma occurrence were also found. In addition to
duration was 14.6 years. At entry, 61% were asymptomatic carriers but the improvement of countermeasures against HBV infection in Goto
a 172% increment of hepatocellular carcinoma was found at the end of Islands, genomic surveillance of HBV is essential to reduce the burden
follow-up. The mean viral load was 2.0 × 104 copies/ml, and the of the infection.
prevalence of HBeAg and HBeAb were 26.5% and 71.2%, respectively.
The predominant circulating genotype was genotype C2 (96.2%),
followed by genotype B (3.4%) and A (0.6%). Three main clusters of
cases were found having 95.61%-99% homology and were closely

Figure: (abstract: THU336)

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POSTER PRESENTATIONS
THU337 Conclusion: In contrast to other studies, consistent ratios of HBsAg
Comprehensive analysis of the different phases of chronic and similar particle densities were observed among the four different
hepatitis B virus infection phases of active HBV infection. In comparison to HBeAg-positive
Michael Basic1,2, Qingyan Wu2, Anja Schollmeier2, genomes, HBeAg-negative genomes are characterized by an
Christoph Sarrazin1,3, Stefan Zeuzem1, Eberhard Hildt2,4, enhanced intranuclear localization of assembled core protein and a
Kai-Henrik Peiffer1,2. 1University Hospital Frankfurt, Frankfurt am perinuclear accumulation of HBsAg in vitro. This is further reflected
Main, Germany; 2Paul Ehrlich Institute, Langen (Hessen), Germany; by an impaired release of HBsAg. Interestingly, neither HBeAg nor
3
St. Joseph’s Hospital in Wiesbaden, Wiesbaden, Germany; 4German presence of precore G1896A mutation seem to be causative for the
Center for Infection Research, Braunschweig observed characteristics in HBsAg and core virology in genomes
Email: [email protected] derived from patients with HBeAg-negative chronic infection.
Further analyses of the underlying mechanisms might also affect
Background and aims: Chronic Hepatitis B virus (HBV) infection was
novel antiviral strategies.
classified into four active phases by the EASL: 1. HBeAg-positive
chronic infection, 2. HBeAg-positive chronic hepatitis, 3. HBeAg- THU338
negative chronic infection and 4. HBeAg-negative chronic hepatitis. Human stem cell-derived hepatic and intestinal culture systems to
Recently, it was observed that released HBsAg amounts, ratios of L-, study HEV transmission along the gut-liver axis
M- and S-proteins and morphology of subviral particles varied by Viet Loan Dao Thi1,2, Michael Dill3,4, Sarah Prallet1,
viral genotype (Gt). Further, HBsAg composition was described to be Ann-Kathrin Mehnert1, Sabrina Schweiggert3. 1Center for Integrative
distinct during the different phases of infection. Here, we character- Infectious Disease Research (CIID) University Hospital Heidelberg,
ized different phases of chronic HBV infection regarding HBsAg, core Department of Infectious Diseases, Virology, Heildeberg, Germany;
and particle assembly in vivo and in vitro. 2
German Centre for Infection Research (DZIF), Heildeberg, Germany;
Method: Sera of patients infected with GtA or GtD of different disease 3
University Hospital Heidelberg, Division of Gastroenterology,
phases according to the EASL classification were analyzed by HBsAg- Heildeberg, Germany; 4German Cancer Research Center (DKFZ),
specific Western Blot (WB) and density gradient centrifugation. For in Experimental Hepatology, Inflammation and Cancer (F240) Deutsches
vitro studies, HBV genomes of GtA, GtB, and GtD of patients with Krebsforschungszentrum, Heidelberg, Germany
HBeAg-negative chronic infection and presence of precore mutation Email: [email protected]
G1896A were cloned into pUC-18 and expressed in Hepatoma cells.
Corresponding HBeAg-positive wildtype genomes were used for Background and aims: The intestine and the liver are anatomically
comparison. Expression and localization of HBsAg and core protein, and functionally linked, often referred to as the gut-liver axis. They
replication, particle morphology and infectivity as well as subcellular cooperate in nutrient uptake and metabolism, as well as provide
localization were analyzed. immunity to pathogens, due to their organization as barrier tissues.
Results: In the sera of patients, the ratio of HBsAg proteins differed Enterically transmitted hepatitis E virus (HEV), the most common
among genotypes but not among the different disease phases. cause of acute hepatitis in the world, is dependent on this axis: Once
Density of HBsAg-particles varied among genotypes but not between in the gastrointestinal tract, HEV passes the intestinal epithelium to
the stage of infection. In vitro, the HBeAg-negative genomes showed gain access to the blood stream from where it reaches the liver and
a reduction in HBsAg expression in comparison to the corresponding infects hepatocytes. Conventional cell culture systems fail to
HBeAg-positive genomes. By WB analyses, intracellular accumulation recapitulate the intricacy of this axis. Human induced pluripotent
of LHBs and core protein was found. Further, perinuclear accumula- and adult tissue stem cell-derived organoid culture systems that
tion of LHBs and core protein was observed in HBeAg-negative reflect in vivo-like organ complexity, allow for better and authentic
genomes by immunofluorescence analyses (see fig.). Reintroduction recapitulation of these human epithelial tissues, including polariza-
of precore G1896A mutation did not restore HBsAg expression and tion and cellular differentiation.
did not affect intracellular distribution of HBsAg. Furthermore, Method: The human induced pluripotent stem cell line iPSC.C3A was
immunofluorescence microscopy analyses and subcellular fraction- differentiated to hepatocyte-like cells (HLCs), which were embedded
ation showed a strong intranuclear localization of assembled core into Matrigel domes to initiate the formation of hepatic organoids.
protein. iPSC.C3A cells were also differentiated to small intestinal organoids
using a commercially available kit. In addition, we differentiated
human LGR5-positive bipotent cholangiocyte organoids to mature
hepatic organoids.
Results: Following organoid formation of iPSC-derived HLCs and
further differentiation of both, HLCs-derived and cholangiocyte
organoids into mature hepatic organoids, we observed a strong
increase in albumin expression, by qRT-PCR analysis and, partially, by
IF staining. Both intestinal and hepatic organoid culture systems
supported authentic HEV infection using the HEV GT3 Kernow-C1 p6
strain, as evidenced by an increase in HEV viral genomes and the
upregulation of interferon-stimulated genes. Interestingly, even
immature, bipotent cholangiocyte organoid progenitors were
readily permissive for HEV infection.
Conclusion: We have established novel hepatic and intestinal culture
systems supporting authentic HEV infection. We will use these
systems to study tissue-specific determinants of HEV infection,
including the analysis of an HEV-induced innate immune response. In
the future, we will combine both systems to study HEV transmission
along the gut-liver axis.
Keywords: Hepatitis E virus, induced pluripotent stem cells, hepatic
organoids, intestinal organoids, cholangiocyte organoids, gut-liver
axis.

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 POSTER PRESENTATIONS
Disclosure-Conflict of interest: On behalf of all authors, I hereby glycosylation site, which is highly conserved between different HEV
confirm that there are no conflicts of interest. genotypes.
Conclusion: Here, we identified a novel subgroup of human mAbs
THU339 neutralising different genotypes of HEV. They specifically bind to
A novel class of glycan-specific human monoclonal antibodies infectious viral particles and neutralisation is not disrupted by the
neutralizing the hepatitis E virus presence of secreted isoforms of pORF2. These antibodies may serve
Katja Dinkelborg1,2, George Ssebyatika3, Elina Muriel Guzmán3, as a novel therapeutic option for severe and chronic HEV infection, for
Prossie Lindah Nankya3, Luisa J Ströh4, Lucas Hueffner1, which effective and specific treatment is currently lacking in the
Volker Kinast5,6, Toni Luise Meister6, Heiner Wedemeyer2,7, clinic. Furthermore, we offer new insights for the development of
Eike Steinmann6,7, Thomas Pietschmann1,7, Thomas Krey3,4,7,8,9, cross-genotype effective vaccines against HEV in the future.
Patrick Behrendt1,2,7. 1TWINCORE, Centre for Experimental and Clinical
Infection Research, a Joint Venture between the Medical School Hannover THU340
(MHH) and the Helmholtz Centre for Infection Research (HZI), Increased lymphocyte trafficking and myeloid activation in
Experimental Virology; 2Hannover Medical School, Department of patients with chronic hepatitis delta
Gastroenterology, Hepatology and Endocrinology; 3Institute of Ester García-Pras1, Thais Leonel1, Sergio Rodriguez-Tajes1,
Biochemistry, University of Lübeck, Center of Structural and Cell Biology Mireia García-López1, Sabela Lens1, Zoe Mariño1, Alba Díaz2,
in Medicine, Germany; 4Hannover Medical School, Department of Yilliam Fundora3, Xavier Forns1, Sofía Pérez-del-Pulgar1. 1Liver Unit,
Medical Microbiology and Virology; 5Carl von Ossietzky University Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona,
Oldenburg, Department of Medical Microbiology and Virology; 6Ruhr Spain; 2 (2)Pathology Department, Biomedical Diagnostic Center,
University Bochum, Department of Molecular and Medical Virology; Hospital Clínic, CIBEREHD, Barcelona, Spain; 3 (3) Hepatobiliopancreatic
7
German Center for Infectious Disease Research (DZIF); 8Hannover and Liver Transplant Department, Hospital Clinic, Barcelona, Spain
Medical School, Excellence Cluster 2155 RESIST; 9Centre for Structural Email: [email protected]
Systems Biology (CSSB)
Background and aims: Hepatitis Delta virus (HDV) is a satellite virus
Email: [email protected]
of hepatitis B virus (HBV), as it requires the HBV envelope proteins
Background and aims: Acute viral hepatitis is most commonly (HBsAg) to form viral particles. Compared to HBV monoinfection,
caused by infection with the hepatitis E virus (HEV). It can lead to chronic hepatitis delta (CHD) represents the most aggressive form of
chronic infection in immunocompromised hosts, as well as severe viral hepatitis leading to a faster progression towards cirrhosis, liver
hepatitis with the risk of liver failure in certain cases. Four main decompensation and hepatocellular carcinoma. Immune-mediated
human pathogenic genotypes (gt 1–4) have been described. They liver damage upon HDV infection is an important factor of HDV
differ in their worldwide distribution and route of infection. HEV pathogenesis. The aim of the study was to analyze intrahepatic gene
infected cells secrete glycosylated isoforms of the viral capsid protein expression in CHD patients compared to HBV-infected patients and
(open reading frame 2, pORF2) that are hypothesized to help the virus healthy controls.
evade the humoral immune response of infected individuals. Method: Formalin fixed paraffin embedded (FFPE) liver biopsies from
However, a gt1 protein-based vaccine has been developed in China 21 anti-HDV positive patients were included in the study. Patients
and large cohort studies showed that the generated antibody titre were classified as HDV+ and HDV- based on whether or not they had
correlated with protection from infection. Here, we aimed to generate detectable HDV-RNA in serum. Untreated HBV monoinfected patients
human monoclonal antibodies neutralising HEV. and healthy donors were used as control groups. Gene expression
Method: Memory B cells of two acutely infected individuals were analysis of immune-regulatory pathways was performed by using the
selected by recognizing the protruding domain ( pdomain) of pORF2. nCounter® Host Response Panel of Nanostring. Differential expres-
Heavy and light chain of the B cell receptor were sequenced and sion between groups was considered if log2 fold-change>1 and p <
single chain variable fragments (scFv) or monoclonal antibodies 0.05, FDR adjusted by Benjamin-Yekutieli.
(mAb) were expressed in Expi293F cells. To analyse binding, Enzyme- Results: The median age of the patients was 51 years; 62% were male,
linked Immunosorbent Assays (ELISA) and Biacore experiments were 62% had liver cirrhosis and 43% were on nucleos (t)ide analog (NA)
performed. Neutralisation assays were performed using three treatment. Gene expression analysis revealed 223 genes significantly
different HEV strains (gt3: Kernow C1 p6 G1634R and HEV-83–2– upregulated in HDV+ patients compared to healthy donors and 198
27; gt1: Sar55). Additionally, selected scFvs in complex with HEV gt3 compared to HDV- patients. Chemokines were the molecules with
pdomain were crystallised and structures were analysed. the highest differential expression between groups, being CXCL9,
Results: In vitro neutralization assays led to the identification of 16 hit CXCL10, CXCL11 (and its cognate receptor CXCR3) the most relevant.
candidates. ELISA confirmed the identification of at least four mAbs Consequently, genes involved in trafficking and activation pathways
specifically recognizing the non-glycosylated, infectious form of of myeloid cells (CCR2, CCR5, CCL18) and lymphocytes (CD2, ICOS,
pORF2. Further experiments confirmed neutralisation of genotype 1 CD40L, CD20, CD79A) were significantly upregulated in HDV+
and 3 viral strains by selected mAbs. Titration of identified mAbs compared to healthy donors and HDV- patients. Consistent with
determined the half-maximal inhibitory concentration of the best increased immunopathogenesis associated with HDV infection,
neutralizers at ≤0.01 μg/ml. ELISA using patient sera over the course apoptotic (BCL-2, TNF), cytotoxic (GZMH, GZMA and PRF-1) and
of acute or chronic infection with HEV confirmed the specificity of a inflammasome (NLRP1, PYCARD y AIM2) pathways were enriched in
subgroup of identified mAbs to infectious viral particles. Additionally, CHD patients. Immune activation and liver damage pathways were
the specific mAbs but not the non-specific mAbs were unaffected in also increased in untreated HBV patients, but signicantly less
their ability to neutralize HEV by glycosylated pORF2 isoforms. pronounced compared to HDV+ patients. Remarkably, some innate
Structure analysis confirmed that specific mAbs directly bind the (IFIT1, IFIT2 and IFIT3) and adaptive (CD2, CCL5 and IL17RE) response
molecules persisted upregulated after HDV clearance.
Conclusion: HDV infection induces innate and adaptive responses
that contribute to aggravating the progression of liver disease. A
strong recruitment and activation of myeloid cells and lymphocytes
elicits inflammation and cell death processes in CHD. The resolution
of HDV infection might not be able to completely reverse altered
signaling pathways, due to molecule sequelae or the persistence of
HBV.

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POSTER PRESENTATIONS
THU341
Discordant serum HBV DNA and RNA correlation with
quantitative HBsAg and high levels of intrahepatic integrated HBV
DNA in HBeAg negative chronic hepatitis B
Daryl Lau1, Elena Kim2, Chosha Bai3, Wendy C King4, Yixiao Cui3,
David E Kleiner5, Marc Ghany6, Thi Thuy Tu Nguyen3,
Amanda S Hinerman4, Zhili Wang7, Raymond Chung8,
Richard Sterling9, Gavin Cloherty10, Ying-Hsiu Su3, Haitao Guo2. 1Beth
Israel Deaconess Medical Center, Harvard Medical School,
Gastroenterology and Hepatology, Boston, United States; 2University of
Pittsburgh School of Medicine, Department of Microbiology and
Molecular Genetics, Pittsburgh, United States; 3The Baruch S. Blumberg
Institute, Translational Medical Science, Doylestown, United States;
4
School of Public Health, University of Pittsburgh, Epidemiology,
Pittsburgh, United States; 5National Cancer Institute, National Institutes Figure:
of Health, Laboratory of Pathology, Bethesda, United States; 6National
Institutes of Health, Liver Diseases Branch, NIDDK, Bethesda, United
States; 7JBS Science Inc, Doylestown, United States; 8Massachusetts
General Hospital, Harvard Medical School, GI Division, Boston, United
States; 9Virginia Commonwealth University, Gastroenterology and
Hepatology, Richmond, United States; 10Abbott Laboratories, Infectious
Disease Research, Abbott Park, United States
Email: [email protected]
Background and aims: Circulating HBsAg can be derived from both
intrahepatic cccDNA and integrated HBV DNA. Functional cure may
be dependent on the origins of the HBsAg. We sought to correlate
cccDNA and integrated DNA from liver tissues of HBeAg (+) and (-)
CHB participants with serum virological parameters and intrahepatic
HBcAg and HBsAg immunostaining patterns.
Method: Liver tissues from untreated CHB participants of the North
American Hepatitis B Research Network (HBRN) were evaluated. For
cccDNA analysis, DNA prep was heat denatured and digested by
plasmid-safe ATP-dependent DNase (PSAD) to remove rcDNA and
Table:
integrated DNA prior to qPCR quantification. Mitochondrial DNA
COX3 gene qPCR was used for cccDNA normalization. For integrated Conclusion: Serum RNA and HBcrAg reflect the intrahepatic cccDNA
DNA detection, 100 ng of total DNA was subjected to HBV-enriched concentrations. Participants with HBeAg (-) CHB had high levels of
next generation sequencing (NGS) assay. Enriched DNA library was integrated HBV DNA in the liver. The HBsAg derived from the
sequenced by Illumina MiniSeq. The resulting HBV-host junction integrated DNA likely contributed to the discordant serum DNA and
sequences were identified by ChimericSeq. Integrated DNA quantity RNA correlations to qHBsAg and the HBsAg immunostaining patterns
was estimated based on percent of HBV-host junction reads per HBV in HBeAg (-) participants. These findings are important for the design
reads and HBV sequence distribution. Serum HBV RNA was measured and monitoring of therapies aiming for HBV functional cure.
by Abbott research assay, HBcrAg by Fujirebio Europe, and qHBsAg by
Roche Diagnostics’ Elecsys platform. THU342
Results: The cohort [24 HBeAg (+), 32 HBeAg (-)] was predominantly Hepatitis B virus-replicating transgenic mice exhibit a functional
Asian (75%) with mean age of 44 years. The intrahepatic cccDNA, but restricted responsiveness to exogenous Tlr3 and Rig-I stimuli
serum HBV DNA, RNA, HBcrAg and qHBsAg were higher among the Stefan Schefczyk1, Xufeng Luo2, Yaojie Liang1, Mike Hasenberg3,
HBeAg (+) participants (Table). HBeAg (-) vs. (+) participants had Bernd Walkenfort3, Martin Trippler1, Mengji Lu4,
larger proportion of integrated HBV DNA in liver (Figure). There were Heiner Wedemeyer5, Hartmut Schmidt1, Ruth Broering1. 1University
significant Pearson’s correlations between cccDNA and serum RNA Hospital Essen, Department of Gastroenterology, Hepatology and
[r = .53, p < .001] and HBcrAg [r = .41, p = .002]. The correlations Transplant Medicine, Essen, Germany; 2Affiliated Cancer Hospital of
between serum DNA and RNA were strong among both HBeAg (+) Zhengzhou University, Institute for Lymphoma Research, China;
3
and (-) CHB (Table). Correlations between serum qHBsAg levels with University Hospital Essen, Institute for Experimental Immunology and
serum DNA or RNA were moderate for HBeAg (+) but very weak for Imaging, Essen, Germany; 4University Hospital Essen, Institute for
HBeAg (-) participants (Table). The majority [88%] of HBeAg (+) Virology, Essen, Germany; 5Medizinische Hochschule Hannover, Klinik
samples had positive intrahepatic HBcAg stain compared to 13% of für Gastroenterologie, Hepatologie und Endokrinologie, Hannover,
HBeAg (-) samples. In contrast, 96% of HBeAg (+) and 88% of HBeAg (-) Germany
livers had positive HBsAg stain. Granular cytoplasmic HBsAg staining Email: [email protected]
was noted in 57% and 64% of HBeAg (+) and (-) livers respectively.
Background and aims: Pathogenesis of Hepatitis B virus (HBV)
Membranous HBsAg stain pattern was noted in only 14% of HBeAg (-)
infection is driven by innate and adaptive immune responses.
compared to 78% of HBeAg (+) samples. There was a significant
Although HBV is suggested to be a stealth virus, recent findings
inverse relationship between HBV RNA and integrated HBV DNA that
indicate that HBV particles activate a Tlr2 response in murine and
may explain the low level of membranous HBsAg stain in HBeAg (-)
human hepatocytes. Furthermore, in HBV-transgenic mice lacking
livers.
the surface antigen (HBsAg) a Tlr3-mediated response in non-
parenchymal liver cells has been described. Aim of this study was
to investigate how HBsAg influence hepatic innate immune
responses in different HBV-transgenic mouse models.

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 POSTER PRESENTATIONS
Method: Liver tissue from C57/Bl6 and HBV-transgenic mouse strains HBV RNA counts/cell). Within HBeAg (+) subjects, cccDNA-positive
(tg[Alb1HBV]44Bri [Alb/HBs], tg1.4HBV-s-mut and tg1.4HBV-s-rec hepatocytes showed higher transcriptomic activity (median: 87 vs 72
[F1 generation Alb/HBs × tg1.4HBV-s-mut]) was analysed using RNA counts/cell) than cccDNA-negative hepatocytes, compared to
transmission electron microscopy (TEM). HBV replication was HBeAg (-) subjects (median: 0 vs 0 RNA counts/cell). Interestingly,
characterized on RNA and protein level. All-in-one liver cell CHB patients with lower (<300 IU/ml) peripheral HBsAg levels had
preparation enabled extraction of primary murine hepatocytes, also the lowest proportion of HBsAg (+) hepatocytes (<32%), whereas
liver sinusoidal endothelial cells and Kupffer cells and remaining patients with peripheral HBsAg levels >1000 IU/ml showed large
non-parenchymal cells (rNPC). Responsiveness to poly (I:C) treat- variation in percentage of HBsAg (+) (range 31–100%). Peripheral
ment (Tlr3) and transfection (Rig-I) was determined using quanti- levels of HBV DNA or alanine aminotransferase were not associated
tative RT-PCR and multiplex-based cytokine assay. with any of the hepatocyte-derived readouts.
Results: TEM visualised viral particles (tg1.4HBV-s-rec), nuclear spot
formations (tg1.4HBV-s-mut and tg1.4HBV-s-rec) and malformation
of the endoplasmic reticulum (Alb/HBs). Viral replication did not
differ comparing tg1.4HBV-s-rec and tg1.4HBV-s-mut, except HBsAg
levels. A distinct cell type-dependent and mouse strain-dependent
gene expression pattern for interferon (Ifnb, Ifiti1), cytokine (Tnf, Il1b,
Il10) and chemokine (Ccl2, Ccl5) was observed by quantitative RT-
PCR and validated using a multiplex-based cytokine assay.
Emphasizing that tg1.4HBV-s-rec-derived liver cells responded to
poly (I:C) with significantly suppressed expression levels, compared Conclusion: We demonstrated that CHB patients at different stages of
to the other mouse strains. Contrary, rNPC of tg1.4HBVs-rec mice disease show diverse profiles of viral markers measured at single
showed the highest induction for Il10, Tnf, Il1b and Ccl5 in response hepatocyte level.
to poly (I:C). In all HBV-transgenic mice, the induction of Ccl2 was
significant lower in PMH but increased in rNPC. THU344
Conclusion: Production of HBV particles and release of HBsAg in Human stem cell-derived hepatocytes as a model for hepatitis D
tg1.4HBV-s-rec mice led to suppressed hepatic Tlr3 and Rig-I virus infection
signaling. However, rNPC seemed be more potent in producing poly Huanting Chi1,2, Bingqian Qu1, Angga Prawira1, Lars Maurrer1,
(I:C)-induced inflammatory cytokines. Rebecca Fu1, Florian Lempp1, Charlotte Decker1, Zhenfeng Zhang1,
Dirk Grimm1,2,3, Viet Loan Dao Thi1,2, Stephan Urban1,2. 1University
THU343 Hospital Heidelberg, Department of Infectious Diseases; 2German Centre
Profiling at single hepatocyte level indicates variance in viral for Infection Research (DZIF), 3German Center for Cardiovascular
replication associated with HBeAg status in chronic hepatitis B Research (DZHK), Partner Site Heidelberg
patients Email: [email protected]
Alfonso Blázquez-Moreno1, Nadia Neto1, Hinrich Göhlmann1,
Background and aims: An estimated 12∼15 million people world-
Cheng-Yuan Peng2,3,3, Jeroen Aerssens1, Marianne Tuefferd1. 1Janssen
wide are suffering from chronic hepatitis D virus (HDV) infection
Research and Development, Beerse, Belgium; 2CMUH (China Medical
without a curative therapeutic regimen so far. Primary human
University Hospital), Taichung, Taiwan, China; 3China Medical
hepatocytes represent the most physiological model for HDV
University, School of Medicine, Taiwan
research, but their application is restricted. Hepatoma cells can also
Email: [email protected]
support the entire HDV life cycle via gene editing techniques, but they
Background and aims: Chronic infection with hepatitis B virus (CHB) only partially resemble hepatocytes due to their aberrant nature.
is characterized by heterogeneity of viral replication across hepato- Recently, human pluripotent stem-cell derived hepatocyte-like cells
cytes. Here we report on an approach that assesses multiple viral (HLCs) have been proposed as an attractive cell culture system for
parameters at single hepatocyte level: status of hepatitis B virus hepatitis B, C, and E viruses. Here, we show that HLCs support the
(HBV) surface antigen (HBsAg) and core antigen (HBcAg), presence of entire HDV life cycle and propose this model as a new platform for the
covalently closed circular DNA (cccDNA) and quantification of HBV study of HDV biology and the evaluation of antiviral treatments.
RNA. We applied this method to liver biopsy samples collected from 7 Method: We optimized a stem cell-based differentiation protocol
treatment-naïve male patients covering for HBV e-antigen (HBeAg) which yields HDV-permissive HLCs (Fig A). Mature HLCs were
positive (n = 4) and negative (n = 3) CHB phases. inoculated with HDV in the presence of 4% Polyethylene Glycol
Method: Cryosections from the liver core biopsies were fluorescently 8000 (PEG8000) and 1.5% dimethyl sulfoxide (DMSO), with samples
stained for 4′, 6-diamidino-2-phenylindole (DAPI), cytokeratin 18 being harvested for immunofluorescence and quantitative RT-PCR
(CK18), HBsAg and adjacent HBcAg. For each patient, up to 96 (range analysis. Adeno-associated viruses (AAVs) encoding hepatitis B virus
60–96, average 85) individual hepatocytes (DAPI and CK18 positive) S antigen (HBsAg) were transduced to HDV infected HLCs for viral
were randomly collected using a RareCyte Finder II, separately assembly and secretion. The supernatant was taken to subsequently
deposited into tubes and subjected to simultaneous DNA and RNA infect Huh7 cells to determine infectivity of secreted HDV particles.
extraction using DNA/RNA Zymo columns. HBV RNA and cccDNA,
together with mitochondrial RNA and DNA as positive controls, were
measured using the Bio-Rad digital droplet polymerase chain
reaction system.
Results: HBeAg (+) vs HBeAg (-) patients showed contrasted
expression of viral markers, with higher percentages of individual
hepatocytes positive for HBsAg (median: 88% vs 16%), HBcAg
(median: 82% vs <1%), HBV RNA (94% vs 21%) and cccDNA (37% vs
17%). The percentage of infected hepatocytes ( positive hepatocytes
for either cccDNA, RNA or HBsAg) was higher in HBeAg (+) vs HBeAg
(-) patients (median: 99% vs 53%). Quantitative assessment of HBV
RNA demonstrated that expression levels within individual hepato-
cytes was higher in HBeAg (+) vs HBeAg (-) patients (median: 84 vs 0

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POSTER PRESENTATIONS
booking (hereafter follow-up VL (FVL)), were identified for inclusion.
Case note review was performed, and patients were excluded for:
inappropriate testing chronology, acute HBV, antiviral therapy started
prior to BVL/FVL, or incomplete clinical records. Changes between
BVL and FVL were analysed using paired Wilcoxon tests.
Results: 306 pregnancies with both BVL and FVL (median of 14.6
weeks later) were identified. After application of exclusion criteria,
241 pregnancies were included for analysis. Median BVL was 2.61
(1.60–3.59) log10 IU/ml, and median FVL 2.47 (1.78–3.30) log10 IU/ml,
with a median reduction from BVL to FVL of − 0.19 log10 IU/ml, 95% CI
− 0.33, − 0.09 ( p < 0.001). Changes according to BVL and e-Antigen
(HBeAg) status are shown below. Of 36 patients with a BVL >5.3 log10
IU/ml, 10 (27.8%) had a FVL <5.3 log10 IU/ml.

p value
for
Number of Median (IQR) Median (IQR) Median (95% Change
Pregnancy- log10 Viral Load log10 Viral Load CI**) Change in in Viral
Episodes* at Baseline at Follow-Up log10 Viral Load Load***

Total 241 2.61 (1.60, 3.59) 2.47 (1.78, 3.30) −0.19 <0.001
(−0.33, −0.09)
Baseline Viral
Load
<5.3 log10 IU/ml 205 2.48 (1.78, 3.03) 2.22 (1.71, 2.92) −0.12 <0.001
(−0.26, −0.01)
>5.3 log10 IU/ml 36 7.78 (7.22, 8.46) 7.23 (5.10, 7.95) −0.57 <0.001
(−1.70, −0.33)
HBeAg Status
Results: HDV infection of HLCs was assessed by measuring HDV RNA Negative 202 2.53 (1.84, 3.05) 2.27 (1.74, 2.95) −0.14 <0.001
(−0.30, −0.03)
by quantitative RT-PCR and immunofluorescence staining of delta Positive 39 7.69 (6.50, 8.39) 6.70 (4.08, 7.92) −0.39 <0.001
antigen (HDAg) (Fig B and C). HDV infection could be completely (−0.94, −0.13)
blocked by Myrcludex B, suggesting NTCP-dependent entry in HLCs.
In agreement, staining with Atto565-NHS-ester-coupled Myrcludex B *34 patients had two pregnancy-episodes and 1 patient had three pregnancy-
episodes.
showed that HLCs express NTCP on their plasma membrane (Fig D), **95% bootstrap confidence interval generated using 10, 000 random
albeit at lower levels than NTCP overexpressing hepatoma cells. Upon resamplings of the change in viral load data.
Adeno-associated virus transduction with the HBsAg, HDV-infected ***Paired Wilcoxon test with alternative hypothesis as change in median not
HLCs assembled and released infectious HDV progeny particles, equal to zero.
showing that HLCs can recapitulate the entire HDV life cycle (Fig E
Conclusion: Median HBV VL falls during pregnancy regardless of
and F). We further found that HLCs could be infected with HDV
baseline factors. No patients with a BVL <5.3 log10 IU/ml required
genotypes 1 from Ethopia, 2 and 4 from Japan, and 3 from Peru.
treatment based on FVL. Falls from above to below treatment
Finally, HDV infection of HLCs could be inhibited by IFN-α and IFN-λ
threshold were noted in some patients. A BVL rules out the need
treatment (Fig G). Further testing of other antivirals is currently being
for treatment in the majority of pregnancies with a BVL <5.3 log10 IU/
performed.
ml. Repeat sampling at 26–28 weeks gestation for those with a BVL
Conclusion: HLCs provide an attractive, genetically tractable, and
>5.3 log10 IU/ml may prevent unnecessary treatment.
physiologically relevant platform for studying pan-genotype HDV life
cycle and evaluating antiviral treatments. THU346
Greater sequence diversity during early hepatitis B virus decline
THU345
on vebicorvir plus entecavir is associated with a lower level of
Hepatitis B viral load variation between the first and third
virus rebound following switch to entecavir monotherapy
trimesters of pregnancy
Lewyn Li1, Peter Revill2, Ran Yan1, Calvin Chan1, Hua Tian1, Julie Ma1,
Stuart Gallacher1, Alan Yeung2,3, Megan Glancy2,3, Ewan Forrest4,
Luisa M Stamm1, Man-Fung Yuen3, Alexander Thompson4,
Stephen Barclay4. 1NHS Greater Glasgow and Clyde, Department of
Kathryn M Kitrinos1. 1Assembly Biosciences, South San Francisco,
Infectious Diseases, Brownlee Centre, Glasgow, United Kingdom;
2 United States; 2Victorian Infectious Diseases Reference Laboratory,
Glasgow Caledonian University, School of Health and Life Sciences,
Melbourne, Australia; 3The University of Hong Kong, Department of
Glasgow, United Kingdom; 3Public Health Scotland, Glasgow, United
Medicine, Hong Kong, China; 4St Vincent’s Health Australia, Fitzroy, VIC,
Kingdom; 4NHS Greater Glasgow and Clyde, Department of
Australia
Gastroenterology, Glasgow Royal Infirmary, Glasgow, United Kingdom
Email: [email protected]
Email: [email protected]
Background and aims: Vebicorvir (VBR) is a first-generation core
Background and aims: Hepatitis B virus (HBV) infection may be
inhibitor being developed for the treatment of chronic hepatitis B
transmitted vertically, with maternal HBV viral load (VL) >5.3 log10
virus infection (cHBV). In Study 202 (NCT03577171), treatment-naïve
IU/ml an indication for prophylactic antiviral therapy in the third
HBeAg positive cHBV patients were randomized to VBR+entecavir
trimester. However, no consensus exists on the optimal time to check
(ETV) or placebo+ETV for 24 weeks. Eligible patients then received
HBV VL in pregnancy. We sought to identify if VL varied between early
open label VBR+ETV in Study 211 (NCT03780543) for ≥52 weeks. In
pregnancy and week 26, when VL is currently checked according to
Study 211, 19 patients discontinued (DCed) VBR and remained on ETV
our local protocol.
at end of study. Following VBR DC, a mean HBV DNA increase of 1.0
Method: HBV screening samples taken at antenatal booking
log10 IU/ml was observed, with 11/19 patients having a maximal
appointments in our health board Jan ‘10 to Jun ‘19 were identified
increase of >1 log10 IU/ml. Here we further characterize the patients
from a virology database. Locally, first detection of HBV surface
who DCed VBR and remained on ETV and describe the results of next
antigen in a patient triggers reflex VL testing (hereafter booking viral
load (BVL)). Patients with a BVL and repeat VL 12–20 weeks after

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 POSTER PRESENTATIONS
generation sequencing (NGS) analyses to characterize viral quasis- THU347
pecies during treatment. Results from a nationwide hepatitis C serosurvey and progress
Method: Viral nucleic acids were purified from Study 202 baseline towards HCV elimination in the country of Georgia
(BL), Week (Wk) 4, and rebound (if possible) patient plasma and Amiran Gamkrelidze1, Shaun Shadaker2, Maia Tsereteli1,
whole genome NGS (Illumina MiSeq) was conducted. 18/19 patients Maia Alkhazashvili1, Nazibrola Chitadze1, Irina Tskhomelidze3,
had NGS data available: 11 with ≥1 log10 IU/ml HBV DNA maximal Lia Gvinjilia4, Nino Khetsuriani5, Francisco Averhoff6,
increase and 7 with <1 log10 IU/ml HBV DNA maximal increase after Gavin Cloherty6, Giorgi Chakhunashvili1, Jan Drobeniuc2,
VBR DC. To determine sequence diversity, Shannon entropy was Paata Imnadze1, Khatuna Zakhashvili1, Paige A Armstrong2. 1National
calculated from demultiplexed FASTQ read files using an in-house Center for Disease Control and Public Health, T’bilisi, Georgia; 2Centers
pipeline with genotype-specific reference sequences. The pipeline for Disease Control and Prevention, Division of Viral Hepatitis, Atlanta,
includes data quality control, read trimming and alignment, variant United States; 3The Task Force for Global Health, Tbilisi, Georgia;
calling, and annotation in a workflow orchestrated by Nextflow. 4
Eastern Europe and Central Asia (EECA) Regional Office, Centers for
Results: Patients with <1 log10 IU/ml HBV DNA increase had Disease Control and Prevention (CDC); 5Global Immunization Division,
significantly lower HBeAg and HBcrAg ( p < 0.05) and trended lower CDC, Atlanta, United States; 6Abbott Diagnostics, Abbott Park, United
for HBV DNA and pregenomic RNA with most having ALT >ULN at BL States
compared to patients with ≥1 log10 IU/ml HBV DNA increase. At BL, Email: [email protected]
similar diversity levels were observed across the viral genome in both
groups. At Wk 4, diversity remained stable for patients with <1 log10 Background and aims: The country of Georgia launched its national
Hepatitis C Virus (HCV) Elimination Program in 2015, and a
IU/ml HBV DNA increases, while diversity declined at Wk 4 for
patients with ≥1 log10 IU/ml HBV DNA increases (p < 0.01) (Figure). serosurvey the same year showed prevalence of HCV antibody
(anti-HCV) and HCV RNA among adults aged ≥18 years was 7.7%,
For patients with a ≥1 log10 IU/ml HBV DNA increase, diversity
and 5.4%, respectively. Since then, over 76, 000 people with chronic
returned towards BL levels at rebound following VBR DC.
HCV have been treated, with a cure rate of 98.9%. To monitor progress,
a second serosurvey was conducted in 2021 to estimate the
prevalence of hepatitis C, hepatitis B, and anti-SARS-CoV-2. This
analysis reports hepatitis C results of the serosurvey and progress
towards elimination.
Method: The serosurvey used a stratified, multi-stage cluster design
with systematic sampling. Adults and children ≥5 years consenting
(or assenting with parental consent) to the interview and blood draw
were eligible to participate. All blood samples were tested for anti-
HCV and if positive, HCV RNA. Nationally representative weighted
proportions and 95% confidence intervals (CI) were calculated and
compared with 2015 age-adjusted estimates for adults.
Results: A total of 7, 237 adults and 1, 473 children participated in the
survey. For adults, the median age was 46 years (interquartile range:
32–60), and 53.3% (95% CI: 51.3–55.2) were female. The prevalence of
anti-HCV was 6.8% (95% CI: 5.9–7.7), which was not significantly
different from 2015 (7.7% [95% CI: 6.6–8.8]; p = 0.20). The HCV RNA
prevalence was 1.8% (95% CI: 1.3–2.4), compared to 5.4% [95% CI: 4.5–
6.3] in 2015 (p < 0.001). This represents a 67% reduction in persons
with chronic HCV infection, despite the program having treated 51%
Figure: The dynamic changes of HBV nucleotide sequence diversity along of the estimated 150, 000 infected. HCV RNA prevalence decreased
with HBV DNA increase after VBR discontinuation. among all age groups, most notably among those aged 40–59 years
(9.3% in 2015 to 2.2% in 2021; p < 0.001). Substantial decreases were
Conclusion: Greater sequence diversity was observed during initial also observed among both males (9.0% to 3.1%; p < 0.001) and females
HBV DNA decline during HBV treatment among patients with lower (2.2% to 0.6%; p < 0.001). HCV RNA prevalence also decreased from
rebound when VBR was DCed and ETV continued. The early 51.1% to 17.8% among persons who ever injected drugs, and 13.1% to
differences in sequence diversity may reflect differences in HBV 3.8% among those who received a blood transfusion (both p < 0.001).
specific immune responses (also reflected in ALT levels) and viral load No children tested positive for anti-HCV or HCV RNA.
set points between these 2 groups, although the mechanism needs to Conclusion: These results demonstrate the substantial progress
be further defined. made since Georgia launched its HCV Elimination Program in 2015.
The 67% reduction in chronic HCV infections during 2015–2021 also
supports treatment as a means for prevention, as the reduction is
larger than would be expected based on those treated alone. These
findings can inform strategies to meet HCV elimination targets.

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POSTER PRESENTATIONS
THU348 THU349
Clinical impact of drug interaction in the use of antipsychotics by Occult hepatitis C infection detection in people who use drugs
HCV patients treated with pangenotypic direct-acting antivirals with or without direct antiviral agents therapy
Juan Turnes1, Antonio Garcia Herola2, Ramón Morillo Verdugo3, Eliane Silva1,2, Sara Marques1, Sofia Salta3, José Pedro Sequeira3,
Marinela Mendez Pertuz4, Cristina De Alvaro5, Candido Hernández5, Joao Madaleno4, Adelia Simao4, Armando Carvalho4. 1Research Center
Antoni Sicras-Mainar6. 1CHU, Pontevedra, Gastroenterology and in Biodiversity and Genetic Resources (CIBIO/InBIO), University of Porto,
Hepatology Department, Spain; 2Hospital Marina Baixa de Villajoyosa, Vairão, Portugal; 2Institute of Biomedical Sciences Abel Salazar (ICBAS)
Villajoyosa, Alicante, Spain; 3Hospital de Valme, AGS Sur de Sevilla, of the University of Porto, Porto, Portugal; 3Portuguese Oncology
Sevilla, Spain; 4Gilead Sciences S.L., Madrid, Spain, Medical Affairs, Institute of Porto (IPO Porto), Porto, Portugal; 4Coimbra Hospital and
Madrid, Spain; 5Gilead Sciences S.L., Madrid, Spain, Medical Affairs, Universitary Center (CHUC), Coimbra, Portugal
Madrid, Spain; 6Atrys Health, Health Economics and Outcomes Research, Email: [email protected]
Barcelona, Spain
Background and aims: Occult hepatitis C infection (OCI) can occur in
Email: [email protected]
anti-HCV (hepatitis C virus) and HCV-RNA peripheral blood mono-
Background and aims: Previous analysis showed that central nuclear cells (PBMCs) positive subjects with normal or abnormal
nervous system drugs were the most prescribed in patients with values of liver enzymes (LE) without serum HCV-RNA. The goal of
hepatitis C. This sub-analysis describes the use, drug-drug interac- HCV therapy is to cure the infection, i.e. achieve a sustained
tions (DDIs), and clinical impact of antipsychotic use in real-world virological response (SVR) after therapy with direct acting antiviral
patients treated with Pangenotypic Direct Action Antivirals (DAAp). agents (DAAs). Here, we evaluate OCI in people who are injection
Method: Retrospective observational study, using the BIG-PAC drug users (IDUs) with or without DAAs therapy.
database (Atrys Health), in HCV patients treated from 2017 to 2020 Method: This study includes 4 patients study groups: AVP-14 patients
with DAAs. Potential DDIs between concomitant medication and the (SVR 12 with DAAs therapy); SEP-2 patients (spontaneously
DAAs, Sofosbuvir/Velpatasvir [SOF/VEL] and Glecaprevir/Pibrentasvir elimination of HCV after acute infection); CNP-4 patients; CPP-10
[GLE/PIB], were evaluated using the University of Liverpool Hepatitis patients (HCV positive patients), all anti-HCV positive (Table). HCV-
Interactions database. The risk of DDIs, the report of related adverse RNA detection from serum at baseline was performed by Real-Time
effects (AEs), and the clinical actions linked to the management of PCR (RT-PCR). After, was performed from serum, plasma, PBMCs and
DDIs with antipsychotics (dose reduction; change of antipsychotic or red blood cells (RBCs) by droplet digital PCR (ddPCR).
DAAp; electrocardiogram-ECG and discontinuation) were analyzed.
Results: 187 patients prescribed antipsychotics were included, 150 Table: Characteristics of IDUs patients (%), except sex and age.
treated with SOF/VEL [median age: 53 years; men: 59%; F3/4: 44%] Total, male 30
and 37 with GLE/PIB [median age 48 years; men: 60%; F3/4: 46%]. The Age, mean 42
mean pill number was 5.0 and 5.9 tablets/patient, respectively. CNP 75
Accounting for all comedication, GLE/PIB was associated with a SEP 50
higher risk of single and multiple DDIs (≥2 comedications with DDIs CPP 100
AVP 86
with pDAAs) compared to SOF/VEL, [73% vs 43% of patients ( p <
*AST/ALT U/ml
0.001)] and [24% vs 15% ( p = 0.002)], respectively. +/+ 60
Regarding antipsychotics, there was a higher number of active ± 3
ingredients with potential DDIs for GLE/PIB vs SOF/VEL (6 vs 2, Normal 30
respectively), linked to a higher percentage of patients at risk of DDIs N.D. 7
(51% vs 23%, p < 0.001, respectively). Two AE were reported with GLE/ *GGT/**ALP U/ml
PIB for quetiapine and paliperidone, and none with SOF/VEL. The AE +/+ 10
reported with quetiapine and GLE/PIB (extrapyramidal symptoms) ± 30
occurred at a dose of <300 mg/day. Normal 57
N.D. 3
Quetiapine was the most prescribed antipsychotic (SOF/VEL, 42 and
***Stage of liver disease
GLE/PIB, 7). Regarding clinical actions reported for patients pre- Mild (F1) 67
scribed quetiapine, a higher percentage of actions were reported for Moderate (F2) 11
GLE/PIB (86%; 6/7 patients) vs SOF/VEL group (5%; 2/42 patients), p < Advanced (F3) 11
0.001. These clinical actions were ECG monitoring (1 vs 0), dose Cirrhosis (F4) 11
reduction (2 vs 1), change of DAA/antipsychotic (2 vs 1), and HCV genotype
comedication discontinuation (1 vs 0) for GLE/PIB vs SOF/VEL, 1a 40
respectively. 3a 20
Conclusion: This analysis confirms that the greater use of SOF/VEL in 4a/4c/4d 13
1b 3
patients with antipsychotic treatment may be due to its favorable DDI
N.D. 23
profile, which implies a lower number of adverse effects and required OCI
clinical actions. CNP 50
SEP 50
CPP 10
AVP 29

*Normal values: AST (aspartate aminotransferase) <35 U/L, ALT (alanine

aminotransferase) <45 U/L, GTT (gamma glutamyl transpeptidase) <55 U/L
**Reference values: ALP (alkaline phosphatase) 30–120 U/L
***Reference values Fibrosis/Fibroscan: F0/F1: <7 kPa; F2: 7–9, 5 kPa; F3: 9, 6–
12, 5; F3/F4: 12, 5–14, 5 kPa; F4: >14, 5 kPa
N.D.- Not determined.

Results: At baseline HCV-RNA was detected in the CPP and AVP (both
100%) groups and was negative for AVP-SVR8 or 12 by RT-PCR.
Although, OCI was shown in 50% of the CNP and SEP groups, 10% in
the CPP group and 29% in the AVP group by ddPCR (Table). Two

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 POSTER PRESENTATIONS
patients-CNP, with normal values of LE; 1-SEP, with abnormal values decline when HBsAg levels are high. This correlation showed
of LE; 1 patient-CPP with normal values of LE, HCV-1a, DAAs therapy; statistical significance across all groups.
4-AVP (1 with abnormal values of LE, HCV-1a, DAAs therapy; 1 with
abnormal values of LE and advanced fibrosis, HCV-3a, DAAs therapy;
and 2-HCV-4a/4c/4d, one with normal values of LE, DAAs therapy,
and the other with abnormal values of LE and cirrhosis, DAAs
therapy). Positive results were shown in serum (71%), plasma (13%),
PBMCs (79%) and RBCs (83%) analyzed samples in the CPP and AVP
groups by ddPCR.
Conclusion: A total of 80% HCV-cure with DAAs was shown in the CPP
and AVP groups, but 10% and 29% of OCI was shown in these groups,
respectively, by ddPCR. HCV/OCI positive results were shown in
patients with HCV 1a, 1b, 3a, or 4a/4c/4d genotypes, with normal or
abnormal values of LE, and/or advanced fibrosis, and/or cirrhosis.
Droplet ddPCR was more sensitive than RT-PCR for OCI detection. OCI
and HCV positive patients should be newly evaluated for a reinfection
or relapse possibility and avoid HCV transmission.

THU350
Strong correlation between HBsAg, ALT and HDV-RNA levels in
patients with chronic hepatitis D. Results of phase 3 D-LIVR study. Conclusion: In untreated chronic hepatitis D, HDV-RNA and HBsAg
Maria Buti1,2, Ohad Etzion3,4, Adriana Palom1, David Yardeni3,4, levels show positive correlation mostly in younger people. Normal
Anat Nevo-Shor3,4, Daniela Munteanu3,4, Ingrid Choong5, ALT levels are associated with significantly increased HBsAg levels.
Lisa Weissfeld6, Mar Riveiro Barciela1,2, Naim Abu-Freha3,4, Monitoring of HDV-RNA and HBsAg serum levels in patients with
Ana Barreira1,2, Rob Howard7, Tarik Asselah8, Pietro Lampertico9,10. chronic hepatitis D provides insight in the design of new therapeutic
1
Hospital Vall Hebron, Liver Unit, Barcelona, Spain; 2Centro de strategies.
investigación biomédica en red de enfermedades hepáticas y digestivas,
Madrid, Spain; 3Faculty of Health Sciences, Ben-Gurion University of the
Negev, Beer-Sheva, Israel; 4Soroka University Medical Center,
Gastroenterology and Liver Diseases, Beer-Sheva, Israel; 5Eiger Viral hepatitis A/E: Clinical aspects
BioPharmaceuticals, Palo Alto, California, United States; 6Statistics
Collaborative Inc, Washington DC, United States; 7Veridical Solutions,
Del Mar, California, United States; 8Hôpital Beaujon, Liver Unit, Clichy, THU351
France; 9CRC “A. M. and A. Migliavacca” Center for Liver Disease, Detection of highly variable RNA-containing viral particles on
University of Milan, Pathophysiology and Transplantation, Milan, Italy; CNT-based electrochemical impedimetric DNA-nanosensors
10
Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Andrei Babenka1, Victor Hryharovich1, Halina Grushevskaya2,
Gastroenterology and Hepatology, Milan, Italy Igor Lipnevich2, Nina Krylova2, Elena Lebedeva3, Uladzimir Davydau1,
Email: [email protected] Svetlana Marchuk1, Dmitry Borisovets4, Sergei Zhavoronok1.
1
Background and aims: Several new treatments for chronic hepatitis Belarusian State Medical University, Minsk, Belarus; 2Belarusian State
B are focused in achieving a decline in HBsAg levels. Some of these University, Minsk, Belarus; 3Vitebsk State Medical University, Viciebsk,
new molecules are evaluated in patients with chronic hepatitis D Belarus; 4Institute of Experimental Veterinary Medicine named after S.N.
(CHD). The aim of this study is to evaluate whether ALT, HBsAg and Vyshelessky, Minsk, Belarus
HDV-RNA levels correlate in untreated patients with CHD. Email: [email protected]
Method: In this study, hepatitis delta virus (HDV)-RNA, hepatitis B Background and aims: Due to the high variability of RNA-containing
surface antigen (HBsAg) and hepatitis B virus (HBV)-DNA were viruses genome, neither PCR nor ELISA methods give a 100%
prospectively quantified in 407 patients with compensated liver guarantee. For example, in the case of infection with the hepatitis E
disease who enrolled in the on-going Phase 3 HDV D-LIVR trial virus (HEV), the likelihood of a false negative diagnosis is considered
(NCT03719313). At baseline, demographic data, clinical and bio- very high. One of the possible ways to overcome this problem in
chemical characteristics were collected. HBV and HDV serological and general and for the diagnosis of HEV in particular, may be the use of
virological markers were measured. Descriptive statistics were used alternative, non-PCR technologies. CNT-based electrochemical impe-
to summarize demographic and clinical baseline characteristics. dimetric DNA-nanosensors make it possible to recognize HEV RNA/
Pearson correlation coefficients were computed for ALT, HBsAg and cDNA using short probes (less than 20 bp), which sharply increases
HDV-RNA in the full population of 407 subjects, the population of 146 the likelihood of capturing variable genomes. This ensures high
subjects over 45, and the population of 261 subjects younger than 45 specificity of recognition. We offer a novel highly-performed and
years old. Significance levels are provided for the test of the null selective impedimetric DNA sensor with redox-active nanoporous
hypotheses when the correlation is 0. transducer based on bundles of carbon nanotubes (CNTs) for
Results: 407 patients were included, mainly male (69%), with a mean diagnosing of HEV RNA in clinical samples.
age of 45 years old, Caucasians (73%) and with liver cirrhosis (26.5%). Method: A target double-stranded (ds) cDNA was synthesized by
At baseline in the entire cohort, mean HDV-RNA levels were 4.98 ± reverse transcription of the total RNA isolated by standard commer-
1.17 logIU/ml, HBsAg levels 10079 IU/ml and mean ALT 100.05 ± 67.7 cial spin-column based kits from the whole blood, serum, feces and
IU/ml. HDV-RNA and HBsAg levels showed positive correlation urine of patients with confirmed acute HEV diagnosis. A non faradaic
(0.154) with strong statistical significance (0.0018) (Table 1). In impedimetric DNA-sensor is fabricated by depositing the two
patients older than 45, HDV-RNA and HBsAg levels did not show a monomolecular layer of carboxylated multiwalled CNTs with probe
statistically significant correlation. However, in patients younger than single-stranded (ss) DNA molecules. A short (24 bp) DNA oligo-
45, HDV-RNA and HBsAg levels showed positive correlation (0.162) nucleotide was used as a probe, which was complementary to the
with strong statistical significance (0.0089). HBsAg levels and ALT most conserved region of the HEV genome and, according to
showed a negative correlation, meaning that ALT levels tend to preliminary estimates, is able to recognize about 99% of all sequences

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POSTER PRESENTATIONS
of the HEV genome presented in the GeneBank database (more than >F2 in 49% of cases, whatever the transaminase level, and for all
500) and sequenced in Belarus (more than 100). DNA-nanosensors patients by 39% of the Gs. The HGE proposed treatment with
are interdigital electrode structures with the sensitive coating. The pegylated interferon in 48.4% of cases, Bulevirtide in 43% of cases, and
electron-dense layers of the probe oligonucleotide and CNTs were a combination of the two in 42% of cases. Half of the HGs referred
fabricated by Langmuir-Blodgett technique. The impedance DNA- their patients to an academic collegue. Among the criteria for
nanosensors are utilized as measured capacitance C entering a treatment efficacy, a decrease or normalization of transaminases was
resistor (R) -capacitor (C) -oscillator. Impedance measurements are retained by 84% of the HGs; 60% of the HGs defined VR by a
performed using the non faradaic impedance spectroscopy at quasi- cancellation or a 2-log decrease of viral replication; and a PVR by a
resonance frequencies of the RC-oscillator. disappearance of RNA after 12 (45.4%) or 24 months (16%) with
Results: The capacitive characteristics of the DNA sensors in the normal transaminase activity. Discussion: The number of respon-
frequency range from 100 kHz to 1 MHz after hybridization with dents to this survey is low despite the number of reminders,
targeted DNA at various concentrations have been investigated. It was reflecting the rarity of the disease or its lack of awareness in non-
found that the addition of molten target DNA at low concentrations academic settings, HGs often refer their patients to another colleague,
leads to a significant decrease in capacity over the entire frequency the search for BD infection is not systematically performed,
range. Interacting the probe ss-DNA and target ss-cDNA molecules elastometry and liver biopsy are most often used to assess fibrosis.
form homoduplexes on the sensor surface that leads to increasing the Conclusion: The results of this survey show a certain degree of
electron density of the nucleotide CNT-cover, providing capacity ignorance of BD hepatitis by non-academic HGs; the modalities of
reduction due to an emerging screening surface effect. diagnosis and the need for systematic screening of BD infection in any
Conclusion: The novel highly-performed and high-sensitive electro- HBsAg patient should be recalled by the learned societies.
chemical method reliably detects the presence or absence of HEV in a
sample in dose-dependent manner and does not demand expensive THU353
consumable materials. Hepatitis E seroprevalence in solid organ transplant recipients in
Croatia
THU352 Petra Dinjar Kujundžic1́ , Tatjana Vilibic-Cavlek2,3, Alan Ayoub2,
Hepatitis B Delta: assesment of knowledge and practices of French Adriana Vince2,4, Anna Mrzljak2,5. 1Merkur Clinical Hospital, Zagreb,
non academic hepato-gastroenterologists Croatia; 2School of Medicine, University of Zagreb, Zagreb, Croatia;
Jean-François David Cadranel1, Honore Zougmore1, 3
Croatian Institute for Public Health, Zagreb, Croatia; 4University
Bertrand Hanslik2, Jean-René Ngele1, Xavier Causse3, Denis Ouzan4, Hospital for Infectious Diseases Dr. Fran Mihaljevic, Zagreb, Croatia;
Thierry Thévenot5, Philippe Halfon6, Dominique Roulot7, 5
University Hospital Centre Zagreb, Zagreb, Croatia
Veronique Loustaud-Ratti8, Tristan Lemagoarou9. 1GHPSO DE CREIL, Email: [email protected]
liver and diseases department, Creil, France; 2cabinet gastroenterologie,
Background and aims: Hepatitis E virus (HEV) is an emerging
liver and diseases department, MONTPELLIER, France; 3Hospital Center
infectious disease and growing concern in Europe. After solid organ
Régional D’orléans Hospital La Source, liver and diseases department,
transplantation (SOT), patients are at greater risk of developing acute
Orléans, France; 4Arnault Institute Tzanck, liver and diseases
and chronic graft hepatitis with progression to cirrhosis. The
department, Saint-Laurent-du-Var, France; 5Centre hospitalier régional
consumption of undercooked or raw pig meat is the main route of
universitaire de Besançon, liver and diseases department, Besançon,
HEV infection in developed countries. However, risk factors for the
France; 6liver and INFECTIOIS diseases department, MARSEILLE, France;
7 acquisition of HEV among SOT recipients are incompletely under-
liver and DIGESTIVE diseases department, bobigny, France; 8liver and
stood. This study aimed to determine the exposure of HEV in the SOT
ANDF DIGESTIVE diseases department, limoges, France; 9GHPSO DE
cohort.
CREIL, DIM, Creil, France
Method: In this cross-sectional study, 639 SOT recipients were
Email: [email protected]
screened during routine post-transplant outpatient visits during
Background and aims: Hepatitis B-Delta (BD) is uncommon or 2002–2017 for anti-HEV IgG seroprevalence; 420 after liver trans-
underestimated in France; there are no data from hepato-gastro- plantation (LT) and 219 after kidney transplantation (KT). Serum
enterologists (HG) practicing in non-university hospitals or in private samples were tested for anti-HEV IgG using an enzyme immunoassay
practice on the management of BD hepatitis in France. The aim of this (Mikrogen, Neuried, Germany). All participants completed a risk
study was to evaluate the knowledge and practices concerning the factor assessment questionnaire.
diagnosis and treatment of BD hepatitis among HGs practicing in Results: Anti-HEV IgG seroprevalence in LT recipients was 21%, and in
non-academic settings. KT recipients was 16.4%. The majority of the recipients were male
Method: A Google form questionnaire was sent to senior or junior (68.4%), median age 58 years (18–80). Anti-HEV IgG positive
non-academic from May to September. The following were evalu- recipients were older ( p = 0.029) and lived more often in a rural
ated: demographic data, predominant specialty, status, modality of area ( p = 0.045) than anti-HEV negative recipients. There was no
virological diagnosis and screening for hepatitis BD according to HBs significant difference in HEV seroprevalence regarding the type of
status, evaluation of hepatic fibrosis, modalities of treatment transplanted organ, gender, level of education, number of household
(Pegylated interferon, Bulevirtide, combination). members, having a farm within a household, type of sewage system,
Results: 129 HGs (H 58, 1%) of age :44, 8 (13, 4) answered this survey. or type of drinking water. Contrary to initial assumptions, production
The number of patients ( pts) followed by HG was: : 1 (0–30). The and/or consummation of cured meat and occupational exposure had
search for delta infection in all HBs antigen positive pts was no statistically significant strength of association with anti-HEV IgG
performed by 89.1% of HGs and not by 10%: juniors 77.8%, seniors seropositivity.
84.4%, p = 0.009; in any pts carrying HBs antigen with anti HBe: Conclusion: Our results show that anti-HEV IgG seroprevalence is
juniors 67%, seniors 92%, p = 0.002, in any pts infected with HIV high among SOT recipients (19, 4%). Socio-demographic factors for
( juniors 83.8%, seniors 95.4%, p = 0.064. Concerning fibrosis assess- exposure to HEV are the basis for further research of sources and
ment, among the non-invasive markers of fibrosis: the fibrotest was routes of transmission and clinical significance of HEV infection after
never used by 47% of the respondents, the fibrometer was never used SOT.
by 55% of the respondents. APRI and FIB 4 were not used; the delta
fibrosis score adapted to hepatitis Delta was used by 13% of the HGE.
Fibrosis assessment was mainly done by Fibroscan® in 77% of cases
and liver biopsy in 81% of cases. Treatment was proposed for patients

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 POSTER PRESENTATIONS
THU354 reflex testing” protocol, consisting of the systematic addition of a
Microarray analysis of virus-specific IgM and IgG antibodies serological HDV test on all samples with a first diagnosis of hepatitis B
significantly improves the serological diagnosis of hepatitis E (HBsAg+). We report the effectiveness of this strategy over a 10-year
virus infection period.
David Springer1, Christian Borsodi1, Stephan Aberle1, Method: This is a single-centre retrospective survey in Avicenne
Lukas Weseslindtner1. 1Medical University of Vienna, Center for University Hospital (Assistance Publique-Hôpitaux de Paris, France).
Virology, Vienna, Austria The hospital is set in a suburban area, home to many patients
Email: [email protected] originating from countries with a high burden of viral hepatitis. Our
laboratory database was screened for all HDV tests performed in
Background and aims: Due to the limited availability of PCR, the HBsAg positive patients from June 2012 to February 2022. Duplicates
rapid decrease of viral RNA in the blood, and the possibility of were excluded based on name, sex and date of birth. Patient serum
unspecific reactivity in serological assays, the laboratory diagnosis of samples were assayed for HBsAg using the Abbott Architect HBsAg
hepatitis E virus (HEV) infection remains challenging. Therefore, we qualitative II and quantitative HBsAg kits, and for total HDV
evaluated a commercial microarray for HEV-specific IgM and IgG antibodies (HDV-Abs) using the ETI-DELTAK or the Diasorin Liaison
antibodies featuring nine target antigens (HEV Virachip®, Viramed). XL Murex anti-HDV kits. HDV viral loads were obtained first by in-
Method: The evaluation panel comprised 408 serum samples first house RT-qPCR, then by using the EurobioPlex HDV kit since 2016.
characterized by HEV-PCR (in-house) and Anti-HEV-IgM- and IgG- Results: A total of 84, 671 patients were screened at least once for
ELISAs (Wantai-HEV-IgG/IgM ELISA®, Wantai Biological Pharmacy HBV during the evaluation period. Among the 3198 HBsAg positive
Ent). Based on these results and additional IgG avidity testing, patients (3.8%, median age 39.0, sex ratio 2.04), 2886 (90.2%) were
samples were staged as early viremic (serum PCR+, IgM ± , IgG ± ; n = screened for HDV-Abs, 172 of them being positive (6.0%, median age
94), progressed non-viremic (serum PCR-, IgM+, IgG+; n = 80) and 39.5, sex ratio 1.92). At least one HDV-RNA assay was available for 149
past HEV infection (PCR-, IgM-, IgG+; n = 117). Additional 117 samples of them (86.6%) and was found positive for 91 patients (61.1%). HDV
negative for all HEV parameters served as controls. screening rate steadily improved with time, from 85–87% in the initial
Results: Microarray results significantly concurred with the ELISAs in 2012–2015 period to 95–98% in the 2019–2022 years, while the
94.8% of IgM positive and 97.7% of IgG positive samples, indicating a annual frequency of HDV-Abs positivity among tested HBsAg+
high concordance of the applied serological assays. However, IgM and samples remained stable (range: 4.4–7.7%).
IgG antibodies against specific antigens included in the microarray (e. Conclusion: HDV reflex testing in our centre was effective, allowing
g., IgM and IgG against O2–1C4 and O2-1N, respectively) were earlier earlier identification of most HBV-HDV infected patients and a fast
detectable in 14.9% of still ELISA-IgM negative and 35.3% of ELISA-IgG referral to hepatologists for adequate clinical management. The
negative samples. In addition, samples with negative PCR but positive prevalence of HDV co-infection in HBsAg positive patients is twice
IgM ELISA results ( progressed HEV infection) were reliably identified higher than that initially reported in France among HBsAg positive
as HEV infection by the microarray and constituted a specific blood donors. Active HDV replication was present in more than 60% of
infection stage based on the serological microarray profile. Finally, co-infected patients identified through our systematic screening. In
we calculated an algorithm to identify HEV infection (with PCR the future, further molecular HDV reflex testing in HDV-Ab positive
positivity as reference) with the highest accuracy using all serological patients may improve the complete HDV screening cascade in our
parameters provided by the microarray (ROC-AUC 0.90, p <0.005). centre.
Conclusion: Microarray analysis of HEV-specific IgM and IgG
antibodies displays high sensitivity to diagnose HEV infection, THU356
especially in the early phase of the infection, and identifies the T cell epitope mapping of hepatitis B virus in chronic infection
progressed infection stage when PCR from serum already tests Marie Viuff1, Marianne Tuefferd2, Christina Heeke1,
negative. Kamilla Kjærgaard Munk1, Mohammad Kadivar1, Georg Lauer3,
Jacques Bollekens2, Sine Reker Hadrup1. 1Technical University of
Denmark, Department of Health Technology, Kgs. Lyngby, Denmark;
2
Janssen Pharmaceuticals, Infectious Diseases and Vaccines, Beerse,
Viral hepatitis B/D: Clinical aspects except Belgium; 3Massachusetts General Hospital, Department of Medicine,
Boston, United States
therapy Email: [email protected]
Background and aims: Affecting more than 250 million patients
THU355 worldwide, chronic hepatitis B virus (HBV) infection still poses a
Hepatitis delta virus reflex testing in patients with hepatitis B substantial global health threat, without available curative therapy.
improves the HDV screening cascade: 10 years of real-world CD8 T cells are known to be crucial for the elimination of the virus,
experience from Avicenne University Hospital, France however, in chronically infected patients, the cellular immune
Segolene Brichler1,2,3, Dominique Roulot2,3,4, Samira Dziri1,3, response proves inefficient. Thus, uncovering the full repertoire of
Athenais Gerber1,3, Frédéric Le Gal1,3, Heloise Delagreverie1,2, HBV epitopes and functionality of the HBV-specific CD8 T cells is
Chakib Alloui1,3, Emmanuel Gordien1,2,3. 1Avicenne Hospital, AP-HP, highly relevant for understanding the immune response.
Virology Unit, Bobigny, France; 2Paris Nord University, Bobigny, France; Identification of HBV epitopes recognized by T cells has historically
3
INSERM U955, Creteil, France; 4Avicenne Hospital, AP-HP, Hepatology been limited to few HLA types and selected viral proteins. Here, we
Unit, Bobigny, France have performed a large-scale screening covering HBV genotypes A-H
Email: [email protected] to identify T cell recognition restricted by 12 different HLA molecules,
in patients with acute and chronic hepatitis. This data is substantially
Background and aims: Chronic infection with Hepatitis delta virus extending the present knowledge about the T cell recognition of HBV.
(HDV) leads to the most severe form of chronic viral hepatitis, with Method: A library of >1, 900 peptide-MHC combinations was used
higher rates of cirrhosis and hepatocellular carcinoma than with generate DNA-barcode labelled multimers to screen CD8 T cells from
Hepatitis B virus (HBV) mono-infection. EASL international guide- peripheral blood for recognition of hepatitis B epitopes in HLA-
lines recommend systematic HDV screening for all HBsAg positive matching patients with either acute, chronic, or resolved chronic
patients. However, it is not performed in most areas. In our university hepatitis (n = 40). The peptide-MHC library was generated by
hospital, hepatologists and virologists have implemented a “HDV

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POSTER PRESENTATIONS
selecting specific 8–11mers from HBV genotypes A-H, predicted to Results: A total of 61 patients received TAF treatment and 73 patients
bind to 12 different HLA types. received TDF.51 pairs of patients were matched by Propensity Score
Results: Performing the large-scale multimer screening we found a Match (PSM). The levels of HBV-DNA decline in TDF-treated mothers
total of 212 unique peptide-MHC, which were recognized by CD8 T were compared to TAF treated mothers (3.70 ± 0.91 log10IU/ml vs
cells across all patient groups. Out of these, 189 peptide-MHC have 3.43 ± 1.30 log10IU/ml, P > 0.05) before delivery. The rates of MTCT in
not previously been described. Furthermore, 45% of the peptide- the TAF group were similar to the TDF group (with the transmission of
MHCs were recognized in multiple patients. T cell recognition was 0.00% [0 of 39] vs 0.00% [0 of 29], p > 0.05) in the per-protocol
detected in both acute and chronic patients, with no significant analysis. As for BMD, no significant difference in the Z value of
difference observed between chronic and HBsAg loss patients. newborns was found between the two groups. However, the
Interestingly, T cells recognizing the identified peptides display expression level of ALP was significantly higher in the TDF group
different level of functional responses upon peptide stimulation, than TAF group.
which will be further investigated.

Conclusion: TDF and TAF use in MTCT for highly viremic mothers was
equally effective and the study showed both two drugs have no
statistically different effect on neonatal BMD. However, TAF has less
influence on serum ALP in pregnant women than TDF.
Conclusion: In this study, we were able to fully map the CD8 T cell
recognition towards HBV genomes A-H and identify >180 novel CD8 T THU358
cell epitopes of potential relevance for viral control and clearance. Detection of notable hepatitis B virus serologic activity after
hepatitis B surface antigen seroclearance
THU357
The Comparison of tenofovir alafenamide fumarate with Danny Ka-Ho Wong1,2, Takako Inoue3, Lung Yi Loey Mak1,2,
tenofovir disoproxil fumarate in preventing hepatitis B Yan Yue James Fung1,2, Ka-Shing Cheung1, Wai-Kay Seto1,2,
transmission in mothers with high viral load: a retrospective Yasuhito Tanaka4, Man-Fung Yuen1,2. 1The University of Hong Kong,
cohort study Medicine, Hong Kong; 2The University of Hong Kong, State Key
Laboratory of Liver Research, Hong Kong; 3Nagoya City University
Yunxia Zhu1, Jinhua Wang2, Ming Wang2, Xin Zhou1,
Hospital, Clinical Laboratory Medicine, Nagoya, Japan; 4Kumamoto
Shuangxia Zhang1, Shujie Zhang1, Bo Yang1, Ping Yang1, Zhongjie Hu3.
1 University, Gastroenterology and Hepatology, Kumamoto, Japan
Beijing Youan Hospital, Capital Medical University, Obstetrics and
Email: [email protected]
Gynecology, Beijing, China; 2Beijing Obstetrics and Gynecology Hospital,
Capital Medical University, Department of Gynecologic Oncology, Background and aims: Undetectable serum hepatitis B surface
Beijing, China; 3Beijing Youan Hospital, Capital Medical University, antigen (HBsAg) measured by conventional assays (lower limit of
Hepatology, Beijing, China detection ∼0.05 IU/ml) is regarded as functional cure to chronic
Email: [email protected] hepatitis B (CHB). It has been demonstrated that some HBV proteins
are detectable in patients after HBsAg seroclearance (SC). We
Background and aims: Tenofovir disoproxil fumarate (TDF) is most
evaluated the use of two novel investigational assays to detect
commonly utilized in the prevention of maternal-to-child transmis-
hepatitis B core-related antigen (HBcrAg) and HBsAg in serial patient
sion of the hepatitis B virus. The previous studies show antiviral
samples collected before and after SC.
prophylaxis with tenofovir alafenamide fumarate (TAF) was also
Method: Serum samples were collected from 98 CHB patients (72
generally safe for both mothers and infants and reduced the mother-
males and 26 females) with SC at the following 7 time-points: 5 years
to-child transmission (MTCT) rate to 0%. However, few safety and
and 3 years before SC, at the time of SC, and 1 year, 3 years, 5 years and
effectiveness results have been published regarding the comparison
10 years after SC. HBsAg and HBcrAg were measured using the iTACT-
of two drugs during pregnancy for the prevention of MTCT of HBV,
(stands for Immunoassay for Total Antigen including Complex via
especially for the early markers of bone metabolism like alkaline
pre-Treatment)-HBsAg and iTACT-HBcrAg assays (Fujirebio, Tokyo,
phosphatase (ALP) and Z value for bone mineral density (BMD) of
Japan) respectively. The lower limit of quantitation (LLOQ) of the
infants.
iTACT-HBsAg and iTACT-HBcrAg assays are 0.0005 IU/ml and 2.1 log
Method: We performed a prospective cohort study involving women
U/ml respectively, which are 100 times and approximately 10 times
who had HBV DNA ≥2*105IU/ml and initiated TAF or TDF for
more sensitive than the current HBsAg and HBcrAg assays (LLOQ 3 log
preventing MTCT during gestational weeks 24∼28 weeks. All enrolled
U/ml). Anti-HBs was measured by the Lumipulse Presto anti-HBs
patients had normal liver function and had not received antiviral
assay (LLOQ 10 mIU/ml).
therapy before pregnancy. We collected the name, ID, age, and drug
Results: The median age of SC was 52 years (IQR: 45–57). A total of
duration of the maternal, monitoring HBV viral load and ALP at the
572 samples (142 collected before SC and 430 collected after SC) were
same time besides infants’ HBV marks and their Z value for BMD. The
tested. HBsAg was detectable by iTACT-HBsAg in all the 142 samples
primary outcomes were the decrease in virus load and the rates for
collected before SC (median level: 10.9 IU/ml) and in 165/430 (38.4%)
MTCT, which was defined as the proportion of infants who had a
samples collected after SC (median level for those with detectable
serum HBV DNA level of more than 20 IU per milliliter (i.e. above the
HBsAg: 0.0082 IU/ml). 61.6% of samples collected after SC had
lower limit of detection) or who were positive for hepatitis B surface
detectable anti-HBs. Of these anti-HBs positive samples, 70 (26.4%)
antigen (HBsAg). The secondary outcomes were the changes in serum
had detectable HBsAg. HBcrAg was detectable in 78.9% of samples
ALP expression of the mother and the BMD of newborns.
collected before SC and 66.4% after SC. There was a positive
correlation between HBsAg and HBcrAg levels (r = 0.330, P <

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 POSTER PRESENTATIONS
0.00001). The detectability rate and median levels of both HBsAg and Conclusion: Among HBV-related liver cirrhosis patients who started
HBcrAg progressively decreased over time from before to after SC, antiviral therapy, complete virological response and improvement of
while the detectability rate of anti-HBs increased after SC (Figure 1). FIB-4 index at one-year was independently associated with future
Of the 98 patients, 9 (9.2%) had detectable HBsAg and HBcrAg at all HCC risk, while ALT normalization and serological biomarkers were
time points after SC, and 11 (11.2%) patients had undetectable HBsAg not. This indicate HBV DNA and FIB-4 index can be better on-
and HBcrAg at all time points after SC. 87 (88.8%) patients had treatment clinical end points of antiviral therapy for cirrhotic patients.
detectable HBsAg and/or HBcrAg at least one time point after SC. Of
note, at 10 years after SC, 21.9% and 65.6% of the patients still had THU360
detectable HBsAg and HBcrAg, respectively. Liver fibrosis burden determines risk of hepatocellular carcinoma
among patients with hepatitis B surface antigen seroclearance
Lung Yi Loey Mak1,2, Ka-Shing Cheung1, Rex Wan-Hin Hui1,
Danny Ka-Ho Wong1,2, Yan Yue James Fung1,2, Man-Fung Yuen1,2,
Wai-Kay Seto1,2,3. 1The University of Hong Kong, Medicine, Hong Kong,
Hong Kong; 2State Key Laboratory for Liver Research, The University of
Hong Kong, State Key Laboratory for Liver Research, Hong Kong, Hong
Kong; 3The University of Hong Kong-Shenzhen Hospital, Medicine,
Shenzhen, China
Email: [email protected]
Background and aims: Hepatitis B surface antigen (HBsAg)
Conclusion: The iTACT-HBsAg assay could detect a low level of HBsAg seroclearance is regarded as functional cure in chronic hepatitis B
in >20% patients even at 10 years after SC. A relatively stable infection (CHB). We investigated the risk of hepatocellular carcinoma
expression of HBcrAg was also detected in >60% patients after SC. The (HCC) in CHB patients after achievement of HBsAg seroclearance.
findings suggested that the threshold of SC may be raised using an Method: 337 Asian CHB patients (69.1% male) who developed
ultrasensitive HBsAg assay and that expression of HBV proteins could spontaneous HBsAg seroclearance between April 1996 to October
still be detected after SC. The association between the expression 2012 with retrievable blood samples before HBsAg seroclearance
levels of these proteins and disease progression deserves further were recruited and prospectively followed up for a median duration
studies. of 12.7 (interquartile range [IQR] 9.5–16.2) years. Blood levels of
Enhanced Liver Fibrosis (ELF) were determined. Variables of interest
THU359 included gender, age of HBsAg seroclearance (ageSC), presence of
Comparison of on-treatment ALT or FIB-4 as an on-treatment diabetes mellitus (DM), ELF score, and antibody to HBsAg (anti-HBs).
biomarker of hepatitis B treatment for liver cirrhosis patients Independent risk factors of HCC were determined by univariate then
Joo Hyun Oh1, Dong Hyun Sinn2, Sang Bong Ahn1, Wonseok Kang2, multivariate Cox regression and Kaplan Meier survival analysis.
Geum-Yon Gwak2, Yong-Han Paik2, Moon Seok Choi2, Results: The median ageSC was 51.6 (IQR 42.6–58.1) years old, and
Joon Hyeok Lee2, Kwang Cheol Koh2, Seung Woon Paik2. 1Nowon Eulji 24.6% patients had DM. ELF at a median interval of 3.4 (IQR 0.4–4.9)
Medical Center, Department of Medicine, Korea, Rep. of South; 2Samsung years before HBsAg seroclearance was 9.5 (IQR 9.0–10.1). 216/337
Medical Center, Department of Medicine, Korea, Rep. of South (64.1%) developed anti-HBs at a median time of 2.3 (IQR 0–4.0) years
Email: [email protected] after HBsAg seroclearance with median level of 42 (IQR 18–138) mIU/
ml. Nine cases of HCC were diagnosed at a median time of 6.6 (IQR
Background and aims: Alanine aminotransferase (ALT) levels are
2.6–7.9) years after HBsAg seroclearance. At Cox regression analysis,
usually mildly elevated in patients with cirrhosis. Therefore, it is
ageSC (hazard ratio [HR] univariate: 1.118, multivariate: 1.096, both
unclear whether ‘normalization of ALT’ with antiviral therapy is
p < 0.01) and ELF (HR univariate: 3.282, multivariate: 3.090, both p <
associated with a lower risk of hepatic events in hepatitis B virus
0.001) were significant variables associated with HCC, while DM (HR
(HBV)-related cirrhosis patients. We tested on-treatment ALT and
2.490, p = 0.273), anti-HBs (HR 1.17, p = 0.876) and gender (HR 1.695,
several other potential on-treatment biomarkers that can be clinical
p = 0.514) were not significant variables. The area under receiver-
surrogate or end point of antiviral therapy.
operating characteristic curve value for ELF was 0.856 (95%
Method: A total of 911 hepatitis B virus-related liver cirrhosis
confidence interval [CI] 0.714–0.997, p < 0.001). By maximizing the
patients who started entecavir or tenofovir were analyzed. We tested
Youden’s index, ELF <10.8 was associated with lower risk of HCC with
‘ALT normalization’, ‘undetectable serum HBV DNA’, ‘fibrosis-4 (FIB-
77.8% sensitivity and 90.2% specificity. Among patients with ageSC
4) index improvement’, and ‘serum HBeAg loss or seroconversion’ at
≥50 (known to be associated with residual risk of HCC; n = 190), ELF
1 year as a potential on-treatment biomarker for future HCC risk.
<10.8 before HBsAg seroclearance was associated with >97%
Results: During 6.6 (3.8–10.2) years of follow-up, 222 patients (24.4%)
reduction in risk of HCC development [Figure 1].
newly developed HCC. Among 747 patients with elevated ALT levels,
ALT normalization was observed in 49.5% at one year. HCC incidence
rate was not different between those with and without ALT
normalization (17.6% vs. 16.8% at 5-years, p = 0.39). Undetectable
HBV DNA level was observed in 73.2% at one year, and HCC incidence
rate was significantly different between those with and without
undetectable HBV DNA levels (16.6% vs. 20.9% at 5-years, p = 0.004).
FIB-4 improvement (FIB-4 <3.25) was observed in 163 patients (34.1%)
among 478 patients with elevated FIB-4 index (FIB-4 ≥3.25). HCC
incidence rate was lower for those with FIB-4 improvement than those
without (14.9% vs. 25.6% at 5-years, p = 0.006), and was associated
with lower risk of HCC (adjusted hazard ratio 0.59, 95% CI 0.55–0.82).
HBeAg loss or seroconversion was observed in 55 patients (15.0%) at
one year among 367 HBeAg positive patients, and the HCC incidence
rate was not different between those with and without HBeAg Figure: Cumulative HCC-free survival in Asian CHB patients who achieved
seroconversion (19.7% vs. 20.1% at 5-years, p = 0.55). HBsAg seroclearance at or after age of 50 years-old

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POSTER PRESENTATIONS
Conclusion: ELF <10.8 was associated with markedly reduced risk of
HCC development upon long-term follow-up among CHB patients
with ageSC ≥50. Ongoing HCC surveillance is required for patients
who achieved HBsAg seroclearance at an older age and had advanced
liver fibrosis before HBsAg seroclearance. [Supported by SK Yee
Medical Foundation (reference number: 2171213)]

THU361
Estimating the prevalence of hepatitis delta infection among
foreign-born adults with chronic hepatitis B in the United States
Robert Wong1, Carol Brosgart2, Steven Wong3, Jordan Feld4,
Jeffrey Glenn5, Saeed Sadiq Hamid6, Kate Moraras7, John Ward8,
Heiner Wedemeyer9, Cihan Yurdaydin10, Robert G. Gish7. 1Stanford
University School of Medicine, Veterans Affairs Palo Alto Healthcare Figure: FB Populations Living in the U.S. and Number of HDV among FB
System, Palo Alto, United States; 2University of California San Francisco with CHB Living in the U.S. by World Region of Origin, 2019.
Parnassus Campus, San Francisco, United States; 3S Wong Consulting, Conclusion: This analysis provides an estimate of the number of FB
LLC, United States; 4University Health Network, Toronto, Canada; adults with CHB living in the US who are also infected with HDV,
5
Stanford University School of Medicine, Stanford, United States; 6Aga which is expected to further grow with patterns of increased
Khan University Hospital, Karachi, Pakistan; 7Hepatitis B Foundation, immigration into the US. The burden of HDV will be even greater
Doylestown, United States; 8The Task Force for Global Health, Decatur, when factoring in US-born CHB patients who have combined HDV
United States; 9Hannover Medical School, Department of infection acquired primarily through high-risk activities.
Gastroenterology, Hepatology and Endocrinology, Germany; 10Koç
University School of Medicine, Department of Gastroenterology and THU362
Hepatology Secular trend of the accuracy of hepatocellular carcinoma risk
Email: [email protected] scores in treated chronic hepatitis B patients in 2005–2020: a
Background and aims: Suboptimal awareness and testing for territory-wide study of 48, 706 subjects
hepatitis delta virus (HDV) infection among adults with chronic Terry Cheuk-Fung Yip1, Mandy Sze-Man Lai1,
hepatitis B (CHB) contributes to the poor understanding of the true Vincent Wai-Sun Wong1, Yee-Kit Tse1, Yan Liang2, Vicki Wing-Ki Hui2,
prevalence of HDV and appropriate policy development. Our recent Henry LY Chan3,4, Grace Lai-Hung Wong1. 1The Chinese University of
study estimated 1.47 million (M) foreign-born (FB) persons with CHB Hong Kong, Medical Data Analytics Centre (MDAC), Department of
were living in the United States (US) in 2018. FB persons with CHB Medicine and Therapeutics, Institute of Digestive Disease, Faculty of
contribute to the majority of the burden of HDV infection in the U.S., Medicine, Hong Kong; 2The Chinese University of Hong Kong, Medical
given the high burden of HDV in many world regions from which CHB Data Analytics Centre (MDAC), Department of Medicine and
patients emigrate from. This study aims to provide an estimate of HDV Therapeutics, Faculty of Medicine, Hong Kong; 3Union Hospital,
prevalence among FB adults with CHB in the US. Department of Internal Medicine, Hong Kong; 4The Chinese University of
Method: We updated analyses of CHB prevalence among FB adults in Hong Kong, Medical Data Analytics Centre (MDAC), Faculty of Medicine,
the US by performing systematic reviews and meta-analyses (surveys Hong Kong
published from 1980 to 2019) that combined country-specific CHB Email: [email protected]
prevalence rates with number of FB living in the US in 2019 by Background and aims: Patients with chronic hepatitis B (CHB) are
country of birth from the US Census Bureau. To estimate HDV aging with more comorbidities such as diabetes mellitus (DM). In
prevalence among FB adults with CHB, we combined country-specific contrast, the reimbursement of antiviral treatment has been less
HDV prevalence rates (anti-HDV or HDV RNA positive) for persons restrictive over time, leading to better coverage. We aimed to examine
with CHB from meta-analyses and applied these estimates to the whether the resulting change in patients’ clinical characteristics over
number of FB with CHB in the US in 2019 by country of birth to time affects the accuracy of risk scores for hepatocellular carcinoma
estimate the number of FB CHB patients with combined HDV (HCC).
infection. Method: Adult CHB patients who received entecavir or tenofovir for
Results: In 2019, the overall FB population in the US was 48.0M, at least 6 months between January 2005 and March 2020 were
among which the estimated prevalence of CHB was 3.10% (95% CI identified using a territory-wide electronic healthcare database in
2.55–3.65), resulting in 1.49M (95% CI 1.22–1.75) FB adults with CHB, Hong Kong. DM was defined by any use of non-insulin antidiabetic
which accounts for nearly 80% of all adults with CHB in the US. agents, continuous use of insulin for ≥28 days, haemoglobin A1c
Among FB adults with CHB, overall estimated pooled prevalence of ≥6.5%, fasting glucose ≥7 mmol/L, and/or diagnosis codes. Four HCC
HDV infection was 9.22% (95% CI 4.90–15.73), resulting in 137, 158 FB risk scores for treated CHB patients including PAGE-B and modified
adults with HDV (95% CI 72, 936–233, 984). World region-specific PAGE-B (mPAGE-B) scores; cirrhosis, age, male sex, and DM (CAMD)
estimates of HDV infection among adults with CHB were 8.73% in score; and Real-world Effectiveness from the Asia Pacific Rim Liver
Asia, 6.98% in the Americas, 22.52% in Oceania, 11.18% in Africa, and Consortium for hepatitis B virus (REAL-B) score were studied. The
14.08% in Europe, representing 76, 817 (Asia), 19, 327 (Americas), 2, accuracy of scores was assessed by area under the time-dependent
789 (Oceania), 25, 442 (Africa), and 12, 782 (Europe), FB CHB adults receiver operating characteristic curves (AUROCs) with death as a
with HDV infection in the US. competing risk. Comparisons were done based on 1, 000 bootstrap
samples.
Results: Of 48, 706 patients included, 2, 792, 11, 563, 15, 471, and 18,
880 patients started antiviral treatment in 2005–08, 2009–12, 2013–
16, and 2017–20 respectively; their mean age at treatment initiation
were 50, 52, 54, and 57 years respectively. DM prevalence rose from
16% in 2005–08 to 19% in 2009–12, 21% in 2013–16, and 24% in 2017–
20, whereas the prevalence of cirrhosis dropped from 21% to 17%, 9%,
and 5% respectively through the 4 periods. The median follow-up
time was 5, 5, 5, and 2 years in 2005–08, 2009–12, 2013–16, and

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 POSTER PRESENTATIONS
2017–20 respectively; 7.4%, 6.8%, 5.2%, and 1.9% of patients developed Method: This multi-center study recruited 9, 058 treatment-naïve,
HCC respectively. PAGE-B and modified PAGE-B scores performed non-cirrhotic CHB patients with ALT <2 × upper limit of normal: 6,
well across the 4 periods with comparable AUROCs ranged from 0.75– 949 for training cohort from Asan Medical Center and 2, 109 for
0.77 for PAGE-B score ( p = 0.726) and 0.76–0.80 for mPAGE-B score validation cohort from two tertiary hospitals in Korea. A risk
( p = 0.150). For the other two scores with DM as a predictor, CAMD prediction model for HCC was developed using predictors based on
score was less predictive in the most recent period ( p = 0.025). REAL- multivariable cox models, and bootstrapping was performed for
B score tended to be less predictive in the most recent period ( p = validation.
0.085) (Figure). Results: In the training cohort, 363 patients (5.2%) developed HCC
during 8.0 years of median follow-up. By multivariable cox regression
analysis, HCC risk was the highest with HBV DNA levels of 6–7 log10
IU/ml (adjusted hazard ratio [aHR] 4.98; P < 0.001), and lowest with
>8 log10 IU/ml (aHR 0.90; P = 0.71) and ≤4 log10 IU/ml (aHR 1.00;
reference). HBV DNA levels, male sex, older age, and lower platelet
counts were independent predictors of HCC but ALT levels did not
predict HCC risk (p = 0.33). An ALT-independent 24-point risk
prediction model (“ABC model 1”) was developed including the 4
independent predictors: sex, age, platelet counts, and HBV DNA levels
combined with HBeAg status. HCC risk was calculated to range widely
(0.19%-72.46%) at 10 years. The model showed good prediction
performance with a concordance index (c-index) of 0.845. The area
under receiver operating curves in the validation cohort was 0.79 (CI,
0.71–0.88) and 0.85 (CI, 0.72–0.99) at 5 and 10 years. A calibration
plot showed a satisfactory calibration function. The model excluding
HBeAg status (“ABC model 2”) showed a c-index of 0.843.
Conclusion: Incorporating the parabolic association between HBV
DNA levels and HCC risk with the risk prediction models for
untreated non-cirrhotic CHB patients is reliable for risk estimation.
Our novel risk prediction model may help identify patients at high
risk but left untreated and serve as a steppingstone to extend
treatment indication.
Funding: Patient Centered Clinical Research Project (grant number:
HC20C0062) and the National RandD Program for Cancer Control
through the National Cancer Center (grant number: HA21C0110),
funded by the Ministry of Health and Welfare, Republic of Korea.
Figure: The area under the time-dependent receiver operating characteris-
tic curves (AUROCs) of A. PAGE-B score; B. mPAGE-B score; C. CAMD THU364
score; and D. REAL-B score for predicting the development of hepatocellu- Suboptimal glycemic control is associated with adverse clinical
lar carcinoma among chronic hepatitis B patients who started nucleos (t) outcomes in patients with chronic hepatitis B and diabetes
ide analogue treatment in the 4 periods.
mellitus
Conclusion: Two PAGE-B scores performed well regardless of the Lung Yi Loey Mak1,2, Rex Wan-Hin Hui1, Ka-Shing Cheung1,
change in clinical characteristics of CHB patients over time. HCC risk Danny Ka-Ho Wong1,2, Yan Yue James Fung1,2, Man-Fung Yuen1,2,
scores that have DM as a predictor may however be less predictive in Wai-Kay Seto1,2,3. 1The University of Hong Kong, Medicine, Hong Kong,
recent years. Hong Kong; 2The University of Hong Kong, State Key Laboratory of Liver
Research, Hong Kong, Hong Kong; 3The University of Hong Kong-
THU363 Shenzhen Hospital, Shenzhen, China, Medicine, Shenzhen, China
Risk prediction of hepatocellular carcinoma in chronic hepatitis B Email: [email protected]
patients outside current treatment criteria
Background and aims: Diabetes mellitus (DM) is common among
Gi-Ae Kim1, Seungbong Han2, Young-Suk Lim3, Gwang Hyeon Choi4,
patients with chronic hepatitis B infection (CHB) and has been
Jonggi Choi3, Dong Hyun Sinn5, Yong Han Paik5, Jeong-Hoon Lee6,
associated with increased risk hepatocellular carcinoma (HCC) and
Ju-Yeon Cho7. 1Kyung Hee University School of Medicine, Department of
liver decompensation. We investigated the factors associated with
Internal Medicine, Korea, Rep. of South; 2Korea University, Department
adverse clinical outcomes among CHB patients with DM.
of Biostatistics; 3Asan Medical Center, Department of Gastroenterology,
Method: 624 Asian CHB patients (64.4% male, 65.1% antiviral-treated
Liver Center; 4Seoul National University Bundang Hospital, Department
for median duration of 5.5 years) who had concomitant DM (median
of Internal Medicine, Seongnam-si, Korea, Rep. of South; 5Samsung
duration of 8.0 years) were prospectively recruited for transient
Medical Center, Department of Medicine, Korea, Rep. of South; 6Seoul
elastography and followed-up (FU) for a median of 3.2 (interquartile
National University College of Medicine, Department of Internal
range [IQR] 2.9–5.3) years. Adverse clinical outcome was defined as
Medicine and Liver Research Institute, Korea, Rep. of South; 7Chosun
any liver decompensation event including ascites, variceal bleeding,
University, Department of Internal Medicine, Korea, Rep. of South
hepatic encephalopathy (HE), HCC, liver transplantation (LT) or death.
Email: [email protected]
Variables of interest included age, cigarette smoking, antiviral
Background and aims: A considerable number of chronic hepatitis B therapy, liver stiffness (LS), controlled attenuation parameter (CAP),
(CHB) patients outside the current treatment criteria develop liver function, renal function, and glycemic control as reflected by
hepatocellular carcinoma (HCC), suggesting many patients at high individual mean glycated hemoglobin (HbA1c) during FU period.
risk are left untreated and risk prediction for this population is called Good glycemic control was defined as mean HbA1c 6.5–7.0%.
for. Thus, we aimed to investigate the risk of HCC in CHB patients who Advanced fibrosis and cirrhosis were defined by LS ≥9.0 and ≥12.0
are not indicated for antiviral treatment including a broader range of kPa, respectively for normal alanine aminotransferase (ALT) or ≥12.0
HBV DNA levels and develop a risk prediction model for them. and 13.5 kPa, respectively for raised ALT.

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POSTER PRESENTATIONS
Results: The median age was 62.1 (IQR 56.0–67.9) years old, and Results: Patients with CHB (N = 12, 314) diagnosed between 2001–
25.2% were smokers or ex-smokers. 17.5% had cirrhosis at recruit- 2020 were included (mean age: 49.5 years, 47% men). The study
ment. Mean HbA1c was 6.9%, with 24.0% and 46.3% patients having comprised Caucasian (39%), Asian (27%), African American (10%) and
levels of <6.5% and >7.0% (both are defined as suboptimal glycemic other races (2%). Mean BMI was 26.1; 17% (n = 2054) of patients had
control), respectively. A total of 45 events (HCC, n = 29; ascites, n = 10; any antiviral use and 4% (n = 505) had sAg loss (median time to sAg
variceal bleeding, n = 7; HE, n = 7; death, n = 13; LT, n = 0) were loss = 820 [121–4516] days). Current statin use (>28 days during
observed during FU. Using multivariate Cox regression analysis, age follow-up) was recorded for 11.5% (n = 1421) of patients (2.4% used
(hazard ratio [HR] 1.038), smoking history (HR 2.814), LS (HR 1.037), statin for 1–2 years and 2.2% for >2 years). Compared to no statin use,
suboptimal glycemic control (HR 3.362) [Figure 1] and albumin (HR current statin use of >28–365 days (odds ratio[OR], 95% confidence
0.921; all p < 0.05) were independently associated with adverse interval [95% CI] = 1.9, 1.5–2.5), and 1 − 2 years (OR, 95% CI = 2.3, 1.4–
clinical outcomes, while CAP (HR 0.995, univariate p = 0.082), 3.4) were associated with sAg loss, but >2 years was not (OR, 95% CI =
antiviral therapy (HR 2.311, multivariate p = 0.088) and HBV DNA 1.2, 0.6–2.0). Current statin use was also associated with sAg loss (OR,
(HR 1.000, univariate p = 0.65) were not significant variables. For the 95% CI = 1.5, 1.2–2.0) after adjusting for age, sex, and race. In a
specific outcome of HCC, multivariate Cox regression showed that stratified analysis, statin use was associated with sAg loss among
smoking history (HR 2.706), LS (HR 1.032) and mean HbA1c >7.0% (HR patients who did not use antiviral (OR, 95% CI = 2.1, 1.6–2.7) but not
2.252; all p < 0.05) were independent variables. among those who did (OR, 95% CI = 0.7, 0.2–1.5).

Table: Statin use and sAg loss in patients with chronic hepatitis B
(N = 12, 314)
95%
Odds Confidence p-
Variable Ratio interval Value
Statin use (yes vs. no) 1.5 (1.2, 2.0) 0.002
Age ≥45 to 65 vs. 18–44 yrs 1.6 (1.3, 2.1) <0.001
Age ≥65 vs. 18–44 yrs 1.5 (1.1, 2.1) 0.013
Male vs. Female 1.3 (1.0, 1.5) 0.027
African American vs. 1.7 (1.3, 2.2) <0.001
Caucasians
Asian vs. Caucasians 1.1 (0.9, 1.4) 0.317
Other race vs. Caucasians 0.9 (0.4, 1.6) 0.683

Figure: Cumulative event-free survival in Asian CHB patients with DM,

stratified by mean HbA1c level. Event was defined as any adverse clinical Conclusion: In this large cohort of CHB patients, while statin use was
outcome including ascites, variceal bleeding, hepatic encephalopathy associated with spontaneous sAg loss with dose response correlation
(HE), HCC, liver transplantation (LT) or death.
up to two years of statin use, the interplay between age, virologic
Conclusion: Suboptimal glycemic control (<6.5% or >7%) and history parameters, antiviral use, and statins need further research. These
of cigarette smoking are associated with liver decompensation and findings provide impetus for exploring the therapeutic role of statins
HCC in CHB patients with DM. in patients with CHB.

THU365 THU366
Statin use and surface antigen loss in patients with chronic Patient engagement in hepatitis B clinical trials: ‘HBV cure’ is a
hepatitis B motivation for participation in all ethnically diverse patients
Shahed Iqbal1, Ruidong Li2, Silpa Suthram2, Jeffrey Wallin1, Almuthana Mohamed1, Akudo Nwaogu1, Dusan Jovovic1, James Lok1,
James Trevaskis3, Anastasia Hyrina4, Simon Fletcher4, Maria Guerra Veloz1, Khin Aye Wint Han1, Jeya Anice Sundararaj1,
Meghan Holdorf4. 1Gilead Sciences, Inc., Biomarker Sciences, FOSTER Andrew Ayers1, Ivana Carey1, Kosh Agarwal1. 1King’s College Hospital,
CITY, United States; 2Gilead Sciences, Inc., Research Data Science, FOSTER Institute of Liver Studies, London, United Kingdom
CITY, United States; 3Gilead Sciences, Inc., Fibrosis Biology, FOSTER CITY, Email: [email protected]
United States; 4Gilead Sciences, Inc., Discovery Virology, FOSTER CITY,
Background and aims: Despite advances in treatment, chronic
United States
hepatitis B (CHB) remains a global health challenge. Clinical trials are
Email: [email protected]
key to the development of novel therapies for ‘HBV cure’. Patient
Background and aims: Statin use has been associated with reduced enrolment can be challenging, especially in ethnic minorities, with
risk of liver outcomes (e.g., cirrhosis, liver cancer). One explanation is reported participation rates of less than 20%. This study aimed to
that the lipid composition of hepatitis B surface antigen (HBsAg) explore the experiences of patients enrolled in phase I or II CHB
contains cellular cholesterol that is modified by statin use. We clinical trials at our hospital, and their motivation for participation.
explored the association between statin use and sAg loss in patients Method: In this study, a constructivist research paradigm was
with chronic hepatitis B (CHB). implemented with the use of questionnaires as the primary modality
Method: Adults (≥18 years) with CHB were identified from the IQVIA of data collection. The questionnaire was carefully designed to
Ambulatory EMR database using International Classification of contain a mixture of question styles, including open and Likert style
Disease (ICD) codes (ICD 9: 070.22–23, 070.32–33, ICD 10: B18.0, questions. Baseline patient characteristics, including age and ethni-
B18.1) or by HBsAg positive test. sAg loss was defined by having a city, were also collected. The questionnaire was sent to all individuals
negative HBsAg or positive hepatitis B surface antibody test. HIV enrolled in phase I or II CHB clinical trials at King’s College Hospital
disease, cancer, long-term steroid use, chronic liver disease, other between 2019 and 2021. Open space answers underwent emergent
hepatitis, or pregnancy were exclusion criteria. Statin use was coding and thematic analysis, whilst the results of the Likert scale
measured using WHO recommended defined daily dose for statin. questions were expressed as median (± IQR). Quantitative data
Multivariate (age, race, sex, statin use) logistic regression was used to analysis was performed using SPSS.
determine association between statin use and sAg loss. Due to limited Results: Online questionnaires were sent to 83 CHB patients who had
data, virologic measures (e.g., HBV DNA) were not included in the recently participated in clinical trials at our hospital and a total of 50
model. patients responded to our survey (60.3%). The ethnic distribution of

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 POSTER PRESENTATIONS
our cohort was representative of our local CHB population spread and Demographics and clinical characteristics were recorded in patients
the global burden of CHB. As shown in figure 1, the majority of our testing anti-HDV, including HDV-RNA.
cohort resided within the Greater London region (80.7%). Most Results: Before implementation of anti-HDV reflex testing, anti-HDV
responders to the survey had undergone higher levels of education had been tested in 7.5% (117/1553) of HBsAg+ individuals: 18% (97/
(86%). However, those from Sub-Saharan Africa were less likely to 532) of those attending an academic hospital and only 2% (20/1021)
respond compared to other ethnicities ( p = 0.0048). Thematic of those in primary care centers. After starting reflex testing, 97%
analysis of the qualitative data found that the concept of finite (572/591) were tested for anti-HDV: 96% (475/493) attending an
therapy and curative options are key drivers that encourage patients academic hospital and in 99% (97/98) in primary care. (Figure 1).
to participate in clinical trials. Whilst most responders to the survey
(78%) would participate in future clinical trials, a significant
proportion (n = 12, 24%) expressed difficulty in attending the extra
clinic appointments.

The overall prevalence of anti-HDV+ among those tested was similar

before and after reflex implementation: 9.4% (11/117) and 8.6% (49/
572), respectively. However, the absolute number of patients
diagnosed with HDV increased from 3 cases in 2018, 2 cases in
2019 and 6 cases in 2020, to 49 cases in 10 months of 2021. Among 56
anti-HDV+ patients, HDV-RNAwas detectable in 33 (66%) of 50 tested.
HDV-RNA positive patients were more likely to be young, white, and
HBeAg-negative, 69% had undetectable HBV-DNA and 58% elevated
ALT.
Conclusion: In summary, anti-HDV reflex testing in all HBsAg+
individuals led to 5-fold increase in chronic hepatitis D diagnoses.
Before reflex testing, a large percentage of HBsAg+ individuals were
not tested for anti-HDV, particularly in primary care centers. The cost-
effectiveness of anti-HDV reflex testing should be evaluated to inform
Conclusion: ‘HBV cure’ is a motivation for patients’ participation in testing guidelines.
early phase clinical trials. Whilst most patients are happy to be re-
involved in clinical trials, provisions must be taken to minimise the THU368
potential disruption of extra clinic appointments. Further work needs HBVoice: a framework to enhance advocacy for patients and
to be done in wider education for CHB patients to optimise communities affected by hepatitis B virus infection
participation in clinical trials. Philippa Matthews1, Kathryn Jack2, Su Wang3, Jane Abbott4,
Kathleen Bryce5, Benny Cheng6, Indrajit Ghosh7, Alistair Story8,
THU367 Jacki Chen9, Chris Munoz10, John Bell11, Steven Riddell11,
Anti-HDV reflex testing increases the number of hepatitis D cases Amanda Goldring11, Chun Goddard12, Kate Moraras13, Chari Cohen13,
diagnosed in both academic and community centers Kenneth Brown11, Ahmed Elsharkawy14, Jeffrey Lazarus15. 1The Francis
Adriana Palom1, Ariadna Rando-Segura2, Crick Institute, London, United Kingdom; 2Nottingham University
Francisco Rodríguez-Frías2,3, Ana Barreira1,3, Jordi Llaneras1, Hospitals NHS Trust Queen’s Medical Centre Campus, United Kingdom;
3
Mar Riveiro Barciela2,3, Rafael Esteban1,3, Maria Buti1,3. 1Hospital Vall World Hepatitis Alliance, United Kingdom; 4Barts Health NHS Trust,
Hebron, Liver Unit, Barcelona; 2Hospital Vall Hebron, Department of United Kingdom; 5Royal Free London NHS Foundation Trust, United
Microbiology, Barcelona; 3Centro de investigación biomédica en red de Kingdom; 6Waverley Care Milestone, United Kingdom; 7Mortimer
enfermedades hepáticas y digestivas, Madrid Market Centre, United Kingdom; 8Find and Treat, University College
Email: [email protected] Hospitals, London, United Kingdom; 9Rutgers Robert Wood Johnson
Medical School, New Brunswick, United States; 10Yellow Warriors
Background and aims: Although EASL guidelines recommend anti-
Society of the Phileppines, Inc.; 11British Liver Trust, United Kingdom;
HDV testing in all HBsAg-positive individuals, HDV still remains 12
Sheffield Children’s NHS Foundation Trust, United Kingdom;
underdiagnosed. In a study in Barcelona (Spain) in a catchment 13
Hepatitis B Foundation, Doylestown, United States; 14University
population of 400, 000 inhabitants, only 9.4% of HBsAg-positive
Hospitals Birmingham, United Kingdom; 15Global Health-Trasplante
(HBsAg+) patients were tested for anti-HDV (Palom et al. AASLD
Capilar en Turquia-1.960 €, Barcelona, Spain
2021). We describe the initial results of a nontargeted HDV screening
Email: [email protected]
program using anti-HDV reflex testing of all HBsAg+ individuals and
compare the results with those obtained before implementation of Background and aims: Hepatitis B virus (HBV) is hidden from public
this strategy. view, with a long history of stigma and neglect, despite an estimated
Method: We reviewed 2144 consecutive HBsAg+ samples sent to a 300 million individuals being chronically infected worldwide. To
central laboratory (January 2018–October 2021). Before reflex testing, make progress towards WHO elimination targets, it is essential to
we determined the rate of anti-HDV testing in 1553 HBsAg+ samples improve awareness of HBV among patients, the public, healthcare
(January 2018–December 2020). Prospective anti-HDV reflex testing workers, funders, industry, academia and policy makers. As new HBV
was done in all HBsAg+ serum samples (January to October 2021). drugs enter clinical trials, the engagement of a diverse community is
urgently required to deliver studies that engage and represent real-
world populations. We present the rationale and groundwork for a

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POSTER PRESENTATIONS
new network, ‘HBVoice’, to increase HBV patient representation. Our better addressed, supporting advances towards 2030 elimination
aim is to develop this activity by promoting dialogue, connecting to a goals.
wider community and relevant stakeholders, and stimulating
engagement between sectors. THU369
Method: We have drawn on the published literature and data, and HBeAg-positive patients with HBsAg < 135IU/ml or HBcrAg <
personal testimony in the public domain, alongside dialogue with 3.6logU/ml have more chance to be HBsAg loss after nucleos (t)ide
patients, The British Liver Trust, Hepatitis B Foundation and the World analogue cessation
Hepatitis Alliance. Context is also provided by the first externally led Yandi Xie1, Minghui Li2, Xiaojuan Ou3, Sujun Zheng4, Yinjie Gao5,
patient forum focused on HBV, convened by the Hepatitis B Xiaoyuan Xu6, Ying Yang7, Anlin Ma8, Jia Li9, Lai Wei10, Yuemin Nan11,
Foundation in partnership with the U.S. Food and Drug Huanwei Zheng12, Bo Feng1. 1Peking University People’s Hospital,
Administration (FDA) in 2020. Peking University Hepatology Institute, Beijing, China; 2Beijing Ditan
Results: We have established an expanding interdisciplinary group, Hospital, Capital Medical University, Department of Hepatology
representing healthcare workers, academia, non-governmental orga- Division, Beijing, China; 3Beijing Friendship Hospital, Capital Medical
nisations, and people living with HBV. We are expanding to increase University, Liver Research Center, Beijing, China; 4Beijing Youan Hospital,
reach into diverse communities and sectors, and to identify and Capital Medical University, Complicated Liver Diseases and Artificial
promote HBV champions. Our developing portfolio of activities Liver Treatment and Training Center, Beijing, China; 5The Fifth Medical
includes hosting webinars, sharing lived experience of HBV infection, Center, General Hospital of PLA, Department of Infectious Diseases,
linking the HBV community to opportunities for involvement in Beijing, China; 6Peking University First Hospital, Department of
clinical research, production of educational materials, political Infectious Diseases, Beijing, China; 7The Second Hospital of Xingtai,
advocacy, and developing plans for industry funding to support a Department of Infectious Diseases, Xingtai, China; 8China-Japan
sustainable platform for patient engagement. Friendship Hospital, Department of Infectious Diseases, Beijing, China;
9
Tianjin Second People’s Hospital, Department of Liver Disease, Tianjin,
China; 10Beijing Tsinghua Changgung Hospital, School of Clinical
Medicine, Tsinghua University, Department of Hepatopancreatobiliary
Disease, Beijing, China; 11The Third Hospital of Hebei Medical University,
Department of Traditional and Western Medical Hepatology,
Shijiazhuang, China; 12Shijiazhuang Fifth Hospital, Department of Liver
Disease, Shijiazhuang, China
Email: [email protected]
Background and aims: Cessation of nucleos (t)ide analogue (NAs)
may increase hepatitis B virus (HBV) surface antigen (HBsAg) loss rate
in chronic hepatitis B (CHB) patients. We aimed to identify predictor
of HBsAg loss using serum quantitative HBsAg, HBV RNA and
hepatitis B core-related antigen (HBcrAg) in CHB patients who
stopped NAs treatment.
Method: Initially HBV e antigen (HBeAg)-positive CHB patients
without cirrhosis who met the stopping criteria were included in 12
hospitals in China. Enrolled patients ceased NAs and were followed
up with clinical and laboratory assessments every 3 months for 24
months after NAs cessation or until clinical relapse (CR).
Results: This is a multicenter prospective cohort study, in which 158
patients were included. Patients were divided into two groups
Figure: Aims of ‘HBVoice’ network according to the HBsAg status when NAs cessation. Group A included
Conclusion: We highlight the urgent need for patient voice to patients with HBsAg positive when NAs cessation (n = 139) and Group
represent HBV infection, supported by interdisciplinary profes- B included patients with HBsAg negative when NAs cessation (n = 19).
sionals. Sharing experiences of HBV infection will inform awareness In Group A, the 12-month and 24-month cumulative rates of HBsAg
and education, and build partnerships to support enhanced clinical loss were 4.3% and 9.4%, respectively. End of treatment (EOT) HBsAg
care, public health initiatives, policy and funding, and patient-centric (hazard ratio (HR) = 0.152, p < 0.001), EOT HBcrAg (HR = 0.257, p =
research. We will provide a platform through which the substantial 0.001) were found to independently predict possibility of HBsAg loss.
physical, emotional and psychosocial impacts of HBV infection can be To predict HBsAg loss, the area under the receiver operating
characteristic (AUROC) value of the EOT HBsAg and HBcrAg were

Figure 1: (abstract: THU369): Cumulative incidences of hepatitis B surface antigen (HBsAg) loss stratified by end of treatment (EOT) HBsAg, hepatitis B
core-related antigen (HBcrAg) and hepatitis B virus (HBV) RNA in Group A patients.

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 POSTER PRESENTATIONS
0.952 ( p <0.001) and 0.765 ( p <0.001), respectively. Cumulative rates utility than total HBsAg in predicting a response to PEG-IFN in HDV
of HBsAg loss stratified by EOT HBsAg, HBV RNA or HBcrAg levels, infection and could be considered before PEG-IFN therapy for HDV.
results showed that patients with EOT HBsAg ≤ 135 IU/ml (59.2% vs
1.3%, P < 0.001) or HBcrAg ≤ 3.6 logU/ml (17% vs 5.4%, P = 0.027) had THU371
higher 24-month cumulative HBsAg loss rate. In Group B, none of the A decision-making model for prediction of a stable disease course
patients had virological relapse (VR) or CR after NAs cessation. Only 1 in chronic hepatitis B patients
(5.3%) patient had HBsAg reversion with HBV DNA detectable but less Imri Ofri1,2, Noam Peleg3, Moshe Leshno4, Amir Shlomai1,2. 1Rabin
than 2000 IU/ml and without ALT elevation. Medical Center, Beilinson Hospital, Department of Medicine D, Petah
Tikva, Israel; 2Tel Aviv University, The Sackler Faculty of Medicine, Tel
Conclusion: Some patients may get HBsAg loss after NAs cessation. Aviv, Israel; 3Rabin Medical Center, Beilinson Hospital, The Institute of
An EOT HBsAg ≤ 135 IU/ml or HBcrAg ≤ 3.6 logU/ml, identified a Gastroenterology, Petah Tikva, Israel; 4Tel Aviv University, The Coller
patient with more chance to be HBsAg loss after NAs cessation. Faculty of Management, Tel Aviv, Israel
Patients with HBsAg negative when NAs cessation had a low risk of Email: [email protected]
HBsAg reversion after NAs discontinuation.
Background and aims: Patients with chronic Hepatitis B (CHB)
THU370 infection are regularly monitored for HBV DNA and liver enzyme
Serum markers of cccDNA transcriptional activity (HBcrAg and levels in order to assess disease progression and the need for antiviral
pre-genomic HBV RNA) and large HBsAg (LHBs) protein are therapy. Identifying patients with a stable course of disease (i.e long-
predicting response to pegylated interferon in HDV infection lasting low HBV DNA and normal liver enzymes) can potentially
Ivana Carey1, Mark Anderson2, Christiana Moigboi1, Gavin Cloherty2, prolong the intervals between visits, withhold unnecessary tests,
Geoffrey Dusheiko1, Kosh Agarwal1. 1King’s College Hospital, Institute resulting in reduced expanses. Accordingly, we aimed to find
of Liver Studies, London, United Kingdom; 2Abbott Diagnostics, predictors for a stable disease course in patients with CHB.
Department of Infectious Diseases, North Chicago, United States Method: An inception cohort of 579 patients with CHB, who were
Email: [email protected] followed in a tertiary referral center between January 2004 to
December 2018, was retrospectively analyzed. Patients with low and
Background and aims: Hepatitis delta virus (HDV) requires HBsAg steady viral load titer (<2000 IU/ml) and normal ALT levels (<40 IU/
envelope for propagation. The large, (LHBs), containing preS1+preS2 ml) in 6 consecutive clinic encounters were considered to have a
+S mediates HBV attachment to the NTCP receptor. A response to stable course of CHB. A stepwise multivariate logistic regression
pegylated-interferon (Peg-IFN) treatment is achieved in less than 50% analysis and a random forest decision tree model were used to
of patients, and unless HBsAg loss is achieved, patients are at a risk of identify predictors of a stable disease course.
late relapse. We aimed to compare baseline and post treatment Results: Following exclusion for various reasons, a total of 220
virological serum biomarkers (total HBsAg and LHBs levels, HBcrAg patients, with no active anti-viral treatment, were included in the
and pgRNA concentrations, HDV genotypes and HDV RNA viral load) final analysis. 64 had a stable disease course, whereas 156 had an
in HDV-positive responders versus non-responders (NR) to Peg-IFN. unstable course. Patients with a stable disease were older and had
Method: Serum samples of 33 HDV RNA-positive patients (median lower baseline levels of AST, ALT and HBV DNA. In a multivariate
age 38 yrs, 21 (63%) males, 2 (6%) HBeAg+, 12 (36%) with analysis, age (OR 0.95, 95% CI 0.928–0.986), baseline ALT (OR 1.083,
compensated cirrhosis) were tested at the start and 3 years after 95% CI 1.041–1.127) and Log HBV-DNA (OR 1.056 95% CI 1.032–1.08),
completing therapy for the following markers: total HBsAg levels by were significantly associated with a stable disease. In a decision tree
Abbott Architect [IU/ml], LHBs levels by in-house ELISA [ng/ml and % model, patients between 46–67 years old, with Log HBV-DNA below 5
of total HBsAg], HBcrAg by CLEIA Fujirebio [log10U/ml] and pgRNA by IU/ML and ALT below 40.5 IU/ML had the best probability (0.91) for a
real-time PCR Abbott Molecular Diagnostic RUO assay (LLQD = 1.65 stable disease course.
log10U/ml), HDV RNA by in-house real-time PCR assay (LLQD = 640
IU/ml) and HDV genotypes by direct sequencing. The outcome was
correlated with the concentrations of these biomarkers. All results are
shown as medians.
Results: 3 years post Peg-IFN therapy, 15 (45%) patients were HDV
RNA negative (responders), (2 patients with HBsAg loss), whereas 18
patients had persistent HDV RNA (NR). Age and total HBsAg levels
(6801 vs. 8326 IU/ml, p = 0.16) at baseline were similar in responders
and NR. Responders were less likely to have cirrhosis (13% vs. 55%, p =
0.03) and were infected with HDV genotype 5 (93% vs. 27%, p < 0.01).
PEG-IFN responders had significantly lower baseline levels of LHBs
(20607 vs. 81106; 7.6% vs. 19%, p < 0.01), HBcrAg (3.1 vs. 4.3, p < 0.01),
pgRNA (1.7 vs. 2.3, p = 0.04) and HDV RNA (23, 300 vs. 671, 000,
p = 0.016) levels than NR. Total HBsAg (6801 to 452, p < 0.01), as well
as LHBs (20806 to. 4316, 7.6% to 2.4%, p < 0.01), HBcrAg (3.1 to 2.2, p <
0.01) and pgRNA (1.7 vs. undetectable, p < 0.01) reduced significantly
in responders. In NR, although we observed a decline in LHBs levels
(81106 to 39506; 19% to 11.5%, p < 0.05), HBcrAg (4.3 to 3.4, p < 0.01)
and pgRNA (2.3 to 1.72, p < 0.01) these did not reach median baseline
levels seen in responders. Total HBsAg and HDV RNA did not change
Conclusion: Integrating baseline viral DNA, ALT levels and patients’
significantly from the start of treatment in NR.
age can predict the disease course in patients with CHB. Thus,
Conclusion: Lower baseline levels of LHBs, HDV RNA, HDV genotype
stratification of CHB patients according to these simple parameters
5 and lower concentrations of markers of cccDNA transcriptional
can determine the required intervals between scheduled clinic visits
activity were associated with response to Peg-IFN. Transcriptional
and may economize patients’ management.
changes induced by PEG-IFN may reduce LHBs and HDV assembly
and thus spreading of hepatitis D. Measurement of cccDNA
transcriptional activity and the LHBs isoform may be of greater

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POSTER PRESENTATIONS
THU372 a need for more effective strategies for the screening, diagnosis, and
Healthcare resource utilization and costs of hepatitis delta in the treatment of HDV, which may translate into cost savings for the
United States: an analysis of all-payer claims database healthcare system.
Joseph Lim1, Vinod Rustgi2, Robert G. Gish3,4, Ira M Jacobson5,
Ankita Kaushik6, Yan Liu6, Emily Acter7, Robert Wong8. 1Yale School of THU373
Medicine, New Haven, United States; 2Rutgers Robert Wood Johnson Validation of an internal hepatitis D virus DNA quantitative assay:
Medical School, New Brunswick, United States; 3University of Nevada, developing assay suitable for global clinical application and
Reno School of Medicine, Kirk Kerkorian School of Medicine at UNLV, Las clinical trials assessment
Vegas, United States; 4UC San Diego Skaggs School of Pharmacy and Natalie Bolton1, Dazhuang Shang1, Kosh Agarwal1, Ivana Carey1.
1
Pharmaceutical Sciences, Hepatitis B Foundation, La Jolla, United States; King’s College Hospital, Institute of Liver Studies, London, United
5
NYU Grossman School of Medicine, New York, United States; 6Gilead Kingdom
Sciences, Inc., Foster City, United States; 7STATinMED, Plano, United Email: [email protected]
States; 8Stanford University School of Medicine, Stanford and VA Palo Background and aims: Patients co-infected with both hepatitis B
Alto Healthcare System, Palo Alto, United States virus (HBV) and hepatitis D virus (HDV) have an increased risk of
Email: [email protected] developing severe liver disease. HDV displays high genetic diversity,
Background and aims: Hepatitis delta is the most severe form of with previous studies identifying eight distinct genotypes. Robust,
viral hepatitis, causing rapid progression to advanced liver disease. standardised assays for quantifying HDV viral load are needed to
Hepatitis delta is caused by the hepatitis D virus (HDV), a defective assess treatment impact, including standardisation of viral load
RNAvirus that requires the presence of the hepatitis B surface antigen reported units; two units currently used are copies/ml and
(HBsAg) for its complete replication and transmission. This study international units (IU)/ml, with differing correction factors
assesses the healthcare resource utilization and costs associated with between these. This retrospective study aimed to assess the quality
HDV infection among adults with chronic HBV infection in the United of an existing internal, pan-genotypic HDV RNA quantitative nucleic
States (US). acid amplification test (NAAT), utilising the World Health
Method: Using the All-Payer Claims Database (APCD), adult patients Organisation (WHO) HDV international standard (WHO-HDV-IS), in
(≥18 years) with ≥1 inpatient claim or ≥2 outpatient claims spaced a diverse South London population.
≥30 days apart for HDV infection based on ICD-9/10-CM diagnosis Method: Data was collected on 163 specimens taken from 89 HBV
codes were identified from 01/01/2015 to 12/31/2019. Patients were and HDV co-infected patients between January 2020 and October
required to have ≥12 months continuous enrolment before and after 2021, with HDV infection confirmed by a positive result on DIA.PRO
their first date of HDV infection diagnosis in the study period. All- Delta Ab (Total) assay. HDV viral load was quantified using an internal
cause healthcare-related resource utilization and costs were assessed HDV RNA quantitative assay (Cobas® TaqMan® 48). Assay quality was
in the 12 months pre- and post-HDV diagnosis period. assessed each run by inclusion of one negative internal control, two
Results: Among 6, 719 adults with HDV who met inclusion criteria, positive internal controls (low and high viral load dilutions of the
mean total number of all-cause healthcare utilization claims were same patient specimen), and the WHO-HDV-IS (genotype 1). Results
significantly greater in the postdiagnosis than pre-diagnosis period for the WHO-HDV-IS were analysed using a previously described
(20.3 vs 15.9, p < 0.0001). Patients had more inpatient admissions calculation to determine the correction factor for the assay. HDV
(mean, 1.6 vs 1.3, p <0.0001), emergency department visits (mean, 1.1 genotyping was performed by direct sequencing and phylogenetic
vs 0.9, p < 0.0001), outpatient visits (mean, 10.6 vs 7.9, p < 0.0001), tree analysis using neighbor-joining distances analyses software.
and pharmaceutical claims (mean, 8.2 vs 6.7, p < 0.0001) postdiag- Results: 84 (52%) of samples had a viral load below the limit of
nosis compared to prediagnosis. Furthermore, the mean total annual detection of the HDV RNA quantitative assay (6.40 × 102 copies/ml)
cost of healthcare services (Figure 1) was significantly greater whilst 5 (3%) did not have viral load analysed. Within the remaining
postdiagnosis than prediagnosis (mean, $20, 230 vs $16, 056, p < 74 (45%) samples with quantifiable viral load the median HDV RNA
0.0001), including inpatient admissions (mean, $8, 748 vs $6, 876, p < level was 1.31 × 105 copies/ml. 40 (45%) and 36 (40%) of the patients
0.0001), outpatient visits (mean, $5, 272 vs $4, 176, p < 0.0001), and were infected with genotype 1 and genotype 5 HDV, respectively. The
pharmaceutical claims (mean, $6, 210 vs $5, 004, p < 0.0001). Mean internal low and high positive controls were found to be genotype 5.
emergency department costs were $657 vs $552 ( p = 0.4346). The correction factor calculation determined that the correction
factor for the in-house HDV RNA quantitative assay was 1.06,
meaning the limit of detection can be recalculated from 6.40 × 102
copies/ml to 6.76 × 102 IU/ml.
Conclusion: The correction factor of 1.06 shows that our internal HDV
RNA quantitative NAAT calibrates extremely well in comparison with
the WHO-HDV-IS. Despite the WHO standard derivation from
genotype 1 HDV (the most prevalent genotype worldwide), our
assay accurately quantitates HDV RNA in genotype 5 patients. More
work is needed in the future to improve sensitivity and further
standardize pan-genotypic HDV RNA quantification, in particular the
introduction of a panel of standards across genotypes 1–8.
Developing standardized assays suitable for HDV RNA quantitation
in clinical trials of new therapeutic agents is an urgent need.

Conclusion: In a large national US healthcare claims database,

representing ∼80% of the US insured population, patients experi-
enced significantly greater overall healthcare resource utilization and
costs following diagnosis of HDV infection. These findings underscore

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 POSTER PRESENTATIONS
THU374 performed to examine differences between the groups and assessed
Early increase in HBcrAg levels after peginterferon withdrawal the predictive value of viral markers.
predicts subsequent ALT flares Results: 199 patients were included in the study, with a mean age of
Sylvia Brakenhoff1, Andre Boonstra1, Robert De Man1, 40 years and infected with a range of HBV genotypes (A-11%, B-5%, C-
Bettina Hansen2, Robert De Knegt1, Harry Janssen1,2, 7%, D-17%, E-51%). 62% were male. 111 patients remained untreated
Milan Sonneveld1. 1Erasmus MC, Gastroenterology and Hepatology, for 5 years and were defined as having HBeAg-negative infection,
Rotterdam, Netherlands; 2Toronto Western and General Hospital, whereas 88 patients started treatment for ostensible HBeAg-negative
Toronto Center for Liver Disease disease. Our analysis showed significant differences at baseline
Email: [email protected] between the groups (table). A logistic regression analysis showed
only HBV DNA and HBV RNA to be significant separators of these
Background and aims: Chronic hepatitis B (CHB) patients are at risk HBeAg-negative states. However, the odds ratio for HBV DNA was 2.0
for ALT flares after antiviral therapy withdrawal. Since serum levels of ( p = 0.006) and for HBV RNA was 10.1 ( p < 0.001). ROC curve analysis
hepatitis B core-related antigen (HBcrAg) and HBsAg may reflect showed these variables to be a good model for prediction, with
intrahepatic transcriptional activity, we hypothesized that early post- AUROC of 0.90 (95% CI 0.85–0.95). HBV RNA concentration <1.65 U/ml
treatment kinetics could predict off-treatment ALT flares. (i.e. below lower limit of quantification) when HBV DNA was between
Method: We included HBeAg-positive CHB patients who achieved 2000–20, 000 IU/ml (so called “grey zone”) had 92.3% sensitivity for
HBeAg loss after one year of peginterferon (± lamivudine) treatment. identifying inactive HBeAg-negative infection.
Serum HBV DNA, HBcrAg and HBsAg were quantified at end of
treatment (EOT) and at weeks 8 and 12 post-treatment; the peak Table: Baseline characteristics, median (range).
value was used for analysis. An ALT flare was defined as ALT ≥5x ULN
HBeAg-negative HBeAg-negative
during the first 6 months after EOT. infection (n = 111) disease (n = 88) P
Results: A total of 67 patients were included, the majority of whom
were Caucasian (78%) and had HBV genotype A/D (52/27%). ALT flares ALT IU/L 23 (5–121) 40 (10–253) <0.001
occurred in 18%, after a median of 20 weeks (IQR 20–24). Patients Mean liver stiffness kPa 4.5 (2.5–8.7) 6.2 (3.7–21.3) 0.001
HBV DNA logIU/ml 2.62 (0.00–5.59) 4.01 (1.37–6.85) <0.001
who experienced flares had a median post-treatment HBcrAg
qHBsAg logIU/ml 3.51 (0.15–4.59) 3.54 (1.89–4.99) 0.296
increase of 0.71 log, compared to a decline of 0.19 log in patients HBcrAg logU/ml 2.80 (2.00–5.60) 3.90 (2.00–6.20) <0.001
without a flare ( p = 0.003). Among patients with an HBcrAg increase HBV RNA logU/ml 0.00 (0.00–1.99) 2.12 (0.00–4.84) <0.001
of >0.5 log, 53% experienced a flare, versus 8% of the patients without
an HBcrAg increase (p < 0.001). In contrast, HBsAg kinetics were not
associated with ALT flares ( p = 0.313). As expected, patients with Conclusion: Serum HBV RNA in addition to HBV DNA provides an
flares also experienced a more prominent HBV DNA rebound; we excellent discriminator between HBeAg-negative phases. This study
observed a median HBV DNA increase of 4.79 log vs 0.66 log in demonstrates the potential of a single-point HBV RNA measurement
patients with and without flares (p = 0.005). Among patients with an to unequivocally define an indication to start treatment reducing
HBV DNA increase of >3 log, 60% experienced a flare, versus 8% of the uncertainty. As HBV RNA measurement at current levels of sensitivity
patients with <3 log HBV DNA increase. Patients with both HBcrAg reflects ongoing cccDNA transcription, the biomarker provides an
and HBV DNA increase experienced a flare in 86% versus 8% in additional tool to refine disease status and aid treatment decisions.
patients without a concomitant increase ( p < 0.001). Consistent
results were observed in the subset of patients with HBV DNA <200 THU376
IU/ml at EOT (n = 36), 67% of the patients with an HBcrAg increase Evaluating hepatitis delta virus disease prevalence and patient
>0.5log experienced a flare, compared to 4% of patients without an characteristics among adults in the United States: an analysis of
HBcrAg increase ( p < 0.001). all-payer claims database
Conclusion: Early increase in HBcrAg levels after therapy withdrawal Robert G. Gish1,2, Ira M Jacobson3, Joseph Lim4, Ankita Kaushik5,
predicts subsequent ALT flares, and a combined increase of HBcrAg Yan Liu5, Anissa Cyhaniuk6, Robert Wong7. 1University of Nevada, Reno
and HBV DNA identifies patients at very high risk of flares. These School of Medicine, Kirk Kerkorian School of Medicine at UNLV, Las Vegas,
findings suggest that HBcrAg could be used to guide off-treatment United States; 2UC San Diego Skaggs School of Pharmacy and
follow-up. Our findings warrant further confirmation among patients Pharmaceutical Sciences, Hepatitis B Foundation, La Jolla, United States;
3
treated with other finite treatment regimens. NYU Grossman School of Medicine, New York, United States; 4Yale
School of Medicine, New Haven, United States; 5Gilead Sciences, Inc.,
THU375 Foster City, United States; 6STATinMED, Plano, United States; 7Stanford
Hepatitis B pre-genomic RNA differentiates HBeAg-negative University School of Medicine, Stanford and VA Palo Alto Healthcare
disease from infection: time to refine disease stages with new System, Palo Alto, United States
biomarkers? Email: [email protected]
Bo Wang1, Mark Anderson2, Natalie Bolton1, Christiana Moigboi1,
Background and aims: Hepatitis delta virus (HDV) infection leads to
James Lok1, Gavin Cloherty2, Ivana Carey1, Geoffrey Dusheiko1,
the most severe form of viral hepatitis and is always associated with
Kosh Agarwal1. 1King’s College Hospital, Institute of Liver Studies, United
hepatitis B virus (HBV) infection. This study estimates the prevalence
Kingdom; 2Abbott Laboratories, Lake Bluff, United States
and describes patient characteristics for HDV-infected adults in the
Email: [email protected]
US using real-world insurance claims data.
Background and aims: Hepatitis B core-related antigen (HBcrAg) Method: Adults (≥18 years) with ≥1 inpatient claim or ≥2 outpatient
and hepatitis B pre-genomic RNA (HBV RNA) are serological claims (ICD-9/10-CM diagnosis codes) ≥30 days apart for HDV
biomarkers of cccDNA transcription in patients with hepatitis B infection or HBV monoinfection in the All-Payer Claims Database
virus (HBV) infection. We examined the potential of these markers to from 1/1/2014 to 12/31/2020 (study period) were identified.
differentiate HBeAg-negative disease from HBeAg-negative infection. Prevalence was the proportion of HDV-infected among HBV-infected
Method: In this single-centre retrospective case-control study, patients. Patient characteristics were reported for a subcohort of
HBeAg-negative patients followed for 5 years from 2014 were patients with HDV. The HDV index date was defined as the first HDV
grouped by whether they started treatment with a nucleos (t)ide diagnosis from 1/1/2015 to 12/31/2019 with ≥12 months pre- and
analogue. Baseline characteristics including patient demographics, post-diagnosis continuous enrolment. Patient characteristics
ALT, liver disease stage, and virological data (HBV DNA, quantitative included age, gender, race, geographic region, and payer type.
HBsAg, HBcrAg and HBV RNA) were collated. Statistical analysis was Socioeconomic status data captured annual household income and

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POSTER PRESENTATIONS
education. Comorbidities were assessed over the 12-months pre- longer overall survival. Therefore, HDV co-infection does not seem to
index (baseline) period. have a significant clinical impact in Portuguese patients.
Results: Among 194, 573 adults with HBV, 9, 376 (4.8%) were
coinfected with HDV. Among 6, 719 adults in the HDV subcohort, THU378
mean age was 51.9 ± 15.1 years, mean Charlson Comorbidity score was Impact of hepatitis B virus infection on liver-related death among
1.7 ± 2.3, 50.5% were female; 44.9% lived in the north-central and people tested for HBV in British Columbia: results from a large
23.7% in the northeast region of US. Among those with available data longitudinal population-based cohort study
on race and socioeconomic status, the majority were white (48.8%), Makuza Jean Damascene1,2,3, Dahn Jeong1,2, Mawuena Binka2,
followed by black (36.6%) and Asian (13.7%); mean annual household Prince Adu2, Sofia Bartlett2, Amanda Yu2, Stanley Wong2,
income was $41, 515 (± $44, 697); 64.0% had high school as the Georgine Cua1,2, Hector Velasquez1,2, Maria Alvarez2, Mel Krajden2,
highest education category. Patients most commonly had commercial Mohammad Ehsanul Karim1, Naveed Janjua1,2. 1The University of
insurance (42.7%), followed by Medicaid (34.2%), or Medicare (19.9%). British Columbia, School of Population and Public Health, Vancouver,
At Baseline, 16.3% of patients had compensated cirrhosis, 10.4% had Canada; 2BC Centre for Disease Control, BC HTC, Vancouver, Canada;
3
decompensated cirrhosis, 2.8% had liver cancer, and 2.2% had liver Rwanda Biomedical Center (RBC), IHDPC, Kigali, Rwanda
transplant. Diabetes (50.5%), hypertension (49.8%), HIV infection Email: [email protected]
(30.9%), substance abuse (28.7%), and smoking history (28.1%) were
Background and aims: A substantial number of people are living
the top five comorbidities.
with hepatitis B virus (HBV) infection in Canada, which may result in
Conclusion: Among a large database capturing approximately 80% of
higher morbidity and mortality among them. However, data on the
the US insured population, HDV infection prevalence was 4.8% among
contribution of HBV infection to liver-related mortality in Canada is
HBV-infected adults. HDV-infected patients had high rates of baseline
limited. We assessed the impact of HBV infection on liver-related
comorbidities and liver complications. Earlier identification of HDV
deaths in British Columbia (BC), Canada.
infection among HBV-infected patients may provide opportunities to
Method: We used data from the BC Hepatitis Testers Cohort (BC-
reduce the risk of liver-related morbidity and mortality.
HTC), a large population-based cohort that integrates data on HCV,
THU377 HBV testing and diagnoses with data on primary care visits,
Hepatitis delta in Northern Portugal-a long-term follow-up study hospitalizations, deaths and medication dispensations. Individuals
who tested for HBV in the BC-HTC were followed from the first test
Isabel Garrido1, Rodrigo Liberal1, Sofia Teixeira1, Carmo Koch1,
date among HBV positive individuals and last test date among HBV
Guilherme Macedo1. 1São João Universitary Hospital Center, Porto,
negative individuals until the end of the study period (2020/06/30) or
Portugal
liver-related death. Liver-related mortality rates were computed for
Email: [email protected]
HBV positive and negative individuals. Multivariable Cox propor-
Background and aims: Hepatitis delta virus (HDV) occurs worldwide tional hazards model was used to assess the impact while adjusting
but prevalence data are limited due to inaccurate reporting and for confounders. Propensity scores (PS) pair matching analysis was
delayed detection. In fact, no data are available on the epidemiologic conducted as a sensitivity analysis to assess the robustness of the
status of HDV infection in Portugal. In addition, long-term data on main findings.
clinical follow-up is limited. This study aimed to investigate the
prevalence, clinical features and long-term outcomes of a cohort of
Portuguese patients with HDV infection.
Method: All adult patients diagnosed with hepatitis B virus (HBV)
infection in the past 10 years at Centro Hospitalar Universitário de São
João were retrospectively evaluated. Demographic and laboratory
data of those with HDV infection were assessed.
Results: Five hundred and eighty individuals tested positive for
hepatitis B surface antigen HBsAg (HBsAg) between January 2010 and
December 2020. Twenty patients (3.4%) had also positive anti-HDV
antibodies. Of these, most were male (80%), former injection drug
users (55%) and native Portuguese (70%). The median age was 42
years old (IQR 33–47). Positive serum hepatitis B e-antigen was
present in 3 (15%) patients and 6 (30%) had undetectable HBV-DNA.
Tenofovir was prescribed as antiviral therapy in 40% of individuals
and entecavir in 15%. Coinfection with human immunodeficiency
virus was found in 9 (45%) patients, and 6 (30%) had hepatitis C virus
antibodies. It is noteworthy that since year 2011 the rate of HDV
diagnosis significantly decreased. Although 7 (35%) patients had
cirrhosis at the time of diagnosis, only one of them had hepatic
decompensation during follow-up, and eventually died. Patients Figure 1: The 30 PYs Cumulative incidence rate for people HBV tested
were followed for a period of 5 years (IQR 2–10). They were positive vs. those HBV tested negative in BC from 1990–2015. (A)
Cumulative incidence of liver-related mortality in individuals with and
periodically screened for hepatocellular carcinoma and none of
without HBV infection, over30 PYs of follow-up. Solid lines: cumulative
them developed it. The majority of individuals (95%) had stable
incidence of liver-related mortality; dashed lines: 95% confidence inter-
disease or improved outcomes during follow-up. Interestingly, 4 vals. (B) Cumulative incidence of liver-related mortality in all individuals,
(20%) patients have cured HBV infection. The overall survival rate of over 30 years of follow-up. Solid lines: cumulative incidence of liver-
this cohort was 90%. related mortality; dashed lines: 95% confidence intervals. PYs, Person
Conclusion: The prevalence of chronic hepatitis delta is currently years; CI, confidence interval; HBV, hepatitis B virus.
very low (<5%) among positive HBsAg carriers in Portugal, with lower
rates in recent years. We show that HDV infection has favorable Results: During the study duration, 40, 704 people tested positive for
outcomes, assuming adherence to therapy and lack of other insults to HBV. Among them, 38, 847 HBV-positive individuals were matched to
their liver, and an adequate quality of life can be achieved, resulting in HBV-negative individuals. The mean follow-up time for the study
sample was 13.46 (standard deviation 6.53) years. A higher

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 POSTER PRESENTATIONS
proportion of those testing positive compared to negative were males THU379
(54% vs 43%), born in 1945–64 (46% vs 30%) and of East Asian Comparable risk of hepatocellular carcinoma between immune-
ethnicity (63% vs 14%). The liver-related mortality rate was higher tolerant and active phase in hepatitis B e antigen-positive patients
among people with HBV infection than those without [2.76 per 1, 000 Han Ah Lee1, Seung Up Kim2, Yeon Seok Seo3, Chai Hong Rim4. 1Inje
PYs (95%CI: 2.64, 2.89) vs. 0.66 per 1, 000 PYs (95%CI: 0.65, 0.68), University College of Medicine, Internal Medicine, Seoul, Korea, Rep. of
respectively]. In multivariable analysis, HBV infection was associated South; 2Yonsei University College of Medicine, Internal Medicine, Seoul,
with increased liver-related mortality [adjusted hazard ratio (aHR): Korea, Rep. of South; 3Korea University College of Medicine, Internal
3.35; 95%CI: 3.02, 3.71]. We found similar results in the PS-matched Medicine, Seoul, Korea, Rep. of South; 4Korea University College of
analysis (aHR: 3.36; 95%CI: 3.17, 3.57). Medicine, Radiation Oncology, Seoul, Korea, Rep. of South
Conclusion: HBV infection is associated with a higher risk of liver- Email: [email protected]
related mortality. Findings highlight an urgent need for HBV
Background and aims: Antiviral therapy is not indicated for patients
screening and diagnosis and continued monitoring for liver-related
diseases to prevent mortality. with chronic hepatitis B (CHB) in the immune-tolerant (IT) phase. We
compared the treatment outcomes between untreated IT-phase and
treated immune-active (IA) phase in patients with CHB.
Method: We systematically searched four databases including
Pubmed, Medline, Embase, and Cochrane database until August,
2021. The cumulative incidence of hepatocellular carcinoma (HCC)
and mortality in IT and IA cohorts and that of CHB phase change in IT
cohort was investigated. Studies regarding patients who have

Figure: (abstract: THU379)

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POSTER PRESENTATIONS
clinically or pathologically diagnosed liver cirrhosis were excluded. highlighting an early occurrence of HBV integration in young patients
Random effects model was used for pooled analyses. The study with no or limited fibrosis. 69.6% of integration events originated
adhered PRISMA and referenced Cochrane handbook v6.2 for from HBx/Core, indicating double stranded linear DNA as a major
methodologic regards. source of HBV integration. Moreover, 20.7% of chimeric transcripts
Results: A total of 13 studies involving 19 cohorts, including 11, 903 involved HBsAg coding region, posing the basis to produce truncated/
patients were included. Quantitative quality assessment was per- aberrant HBsAg forms.
formed and five and eight studies were regarded to have high and Notably, by gene ontology, 18% (189/1048) of HBV-human chimeric
moderate quality; therefore none of 13 studies were dropped from transcripts involved human exons and splicing signals, crucial for
formal analysis for quality issue. The overall median of median gene expression. Among them, 35.4% corresponds to genes playing a
follow-up period was 62.4 months, (range: 51–103 months). The pivotal role in modulating cell survival/proliferation, including genes
overall median value of median age was 40 (range: 29–53.5), and (BIRC6, SYF2, EVI5, BTG1) known to be dysregulated in HCC.
proportion of male was 59.6% (31.8–68.9). Possible publication bias Conclusion: Transcriptionally active HBV integrations occur fre-
was noted in pooled analyses of 5- (Egger’s test p = 0.082) and 10-year quently in the eAg-positive phases of HBV infection, even in young
HCC incidence (Egger’s test p = 0.019). patients with no or limited liver fibrosis. These events result in the
The pooled HCC incidence rate at 5-years was 1.1% (95% confidence production of chimeric HBV-human aberrant transcripts, that mostly
interval [CI]: 0.6–2.0%) in all cohorts. No statistical difference in HCC involve genes regulating crucial intracellular pathways, that could
incidence rate at 5-years was observed between IT [1.1% (95% CI, 0.4– confer a proliferative advantage to the hepatocytes. This is further
2.8%)] and IA cohorts [1.1% (95% CI, 0.5–2.3%) ( p = 0.976). The pooled evidence to support early treatment initiation in eAg positive chronic
odds ratio of comparative series between IT and IA cohorts was 1.05 infection.
(95% CI, 0.32–3.45; p = 0.941). Pooled HCC incidence rate at 10-years THU381
was 3.5% (95% CI, 2.4–5.1%) in all cohorts. No statistical difference in In the setting of HIV-infection, HBV-reactivation is revealed by
HCC incidence rate at 10-years was observed between IT [2.7% (95% highly sensitive assays in a conspicuous fraction of anti-HBc-
CI, 1.0–7.3%)] and IA cohorts [3.6% (95% CI, 2.4–5.5%)] ( p = 0.587). No positive/HBsAg-negative patients switching to Tenofovir-sparing
statistical difference in pooled mortality rates at 5-years was therapy
observed between IT [1.9% (95% CI, 1.1–3.4%)] and IA cohorts [1.0%
Romina Salpini1, Stefano D’Anna1, Mohammad Alkhatib1,
(95% CI, 0.3–2.9%)] ( p = 0.285). Finally, pooled incidence rate of CHB
Lorenzo Piermatteo1, Alessandro Tavelli2, Eugenia Quiros-Roldan3,
phase change in IT cohort was 36.1% at 5 years (95% CI, 29.5–43.2%).
Antonella Cingolani4, Chiara Papalini5, Stefania Carrara6,
Conclusion: The long-term risks of HCC and mortality were similar Massimo Puoti7, Loredana Sarmati8,
between the IT and IA phase. However, various definitions of CHB Antonella d’Arminio Monforte9,10, Francesca Ceccherini Silberstein1,
phase in different studies have to be considered. Carlo Federico Perno11, Valentina Svicher1. 1University of Rome “Tor
Vergata”, Department of Experimental Medicine, Rome, Italy; 2ICONA
THU380 Foundation, Milan, Italy; 3Spedali Civili di Brescia, Division of Infectious
Evidence of extensive transcriptionally active HBV integrations and Tropical Diseases, Brescia, Italy; 4Fondazione Policlinico
involving genetic regions crucial for cell proliferation in the Universitario A. Gemelli, Unit of Infectious Diseases, Roma, Italy;
setting of HBeAg positive infection 5
University of Perugia, Department of Medicine, Perugia, Italy; 6National
Romina Salpini1, Luca Carioti1, Arianna Battisti1,2, Institute of Infectious Diseases Lazzaro Spallanzani, Microbiology
Lorenzo Piermatteo1, Livia Benedetti1, Biobank and Cell Factory Unit, Roma, Italy; 7ASST Great Metropolitan
Francesca Ceccherini Silberstein1, Upkar Gill2, Valentina Svicher1, Niguarda, Unit of Infectious Diseases, Milano, Italy; 8Hospital Tor
Patrick Kennedy2. 1University of Rome Tor Vergata, Department of Vergata Roma, Unit of Infectious Diseases, Roma, Italy; 9ASST Santi Paolo
Experimental Medicine, Rome, Italy; 2Blizard Institute, Barts and The e Carlo, Clinic of Infectious Diseases, Milano, Italy; 10University of Milan,
London SMD, QMUL, London, United Kingdom, Barts Liver Centre, United Department of Health Sciences, Milano, Italy; 11Bambino Gesù Children’s
Kingdom Hospital, Roma, Italy
Email: [email protected] Email: [email protected]
Background and aims: HBV integration into the human genome can Background and aims: Tenofovir-sparing antiretroviral therapy
mediate oncogenic activity. Limited information is available about (ART) is increasingly used in the setting of HIV-infection, raising
initial HBV integration events, particularly in the early phases of the issue to properly identify those anti-HBc-positive/HBsAg-
infection. Here, we characterize chimeric HBV-human RNAs reflect- negative patients ( pts) who can safely suspend this drug. Here, we
ing transcriptionally active HBV integrations in the setting of eAg aim at unravelling HBV replication kinetics after tenofovir withdrawal
positive phases of HBV infection. in HIV-infected anti-HBc-positive/HBsAg-negative pts.
Method: Liver tissues from 42 eAg+ chronically infected patients (27 Method: This study includes 101 HIV-infected anti-HBc-positive/
with eAg+ hepatitis [eAg + CH] and 15 with eAg+ infection [eAg + CI]) HBsAg-negative pts from ICoNA cohort, treated with TDF/TAF-
were studied to perform total RNA-seq by NGS [Illumina, median containing ART for >12 months and switching to TDF/TAF-sparing
(IQR) RNA reads per sample: 22 (18–27) millions]. An ad-hoc ART: 73 with LAM and 28 with no active HBV drugs. At switching (T0)
bioinformatic pipeline was applied to recognize chimeric HBV- 98% of pts has undetectable HIV-RNA.
human transcripts ( present in >2 reads), resulting from HBV For each pt, a plasma sample is analyzed at T0 and during the first 12
integration. Role of genes involved in HBV integration was assessed months of TDF/TAF-sparing ART (T1). HBV-reactivation (HBV-R)
by GeneCards and Protein Atlas. during TDF/TAF-sparing ART is defined as HBV-DNA>1IU/ml in pts
Results: Patients with eAg+CI were significantly younger than eAg with negative HBV-DNA at T0 or a >2-fold increase in HBV-DNA from
+CH [27 (22–29) vs 29 (25–35) years, p < 0.001). Median (IQR) serum T0 to T1. HBV-DNA and -RNA are quantified by highly sensitive
HBV DNA and HBsAg were 8.0 (5.7–8.6) logIU/ml and 4.4 (4.1–4.8) droplet digital PCR (HS-ddPCR, LLOD:1IU/ml) and anti-HBc by
logIU/ml respectively, with no significant difference according to HBV Fujirebio (anti-HBc>15COI indicating active HBV reservoir based on
infection status. Overall, >1 chimeric HBV-human RNA was revealed Salpini, 2020).
in almost all patients (98%, 41/42) for a total number of 1048 unique Results: At T0, despite TDF/TAF therapy, 34 (33.7%) pts have
HBV-human transcripts, reflecting an abundance of transcriptionally detectable HBV-DNA by HS-ddPCR (median[IQR]: 2[1–5]IU/ml).
active HBV integration events. The number of unique chimeric Among the remaining 67 pts, 9% has detectable HBV-RNA (median
transcripts in each patient did not differ in eAg+CH and eAg+CI [IQR]:6[5–7]IU/ml) and anti-HBc>15COI, indicating a transcription-
groups [median (IQR): 13 (11–22) and 14 (10–39); P = 0.46], ally active cccDNA.

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 POSTER PRESENTATIONS
At T1, after TDF/TAF withdrawal, HBV-R occurs in 40 (39.6%) pts Conclusion: Within this vulnerable cohort of HIV-transmitting
(median[IQR] HBV-DNA: 4[2–13]IU/ml) with no difference between mothers, we found evidence of a high HBV prevalence, and
LAM- vs no LAM-group (42.5% vs 32.1%, P = 0.34). Among HBV-R indications that 20% of the HBV-positive mothers are also high-risk
cases, 32.5% has HBV-DNA>10IU/ml (median[IQR]:31[15–73]IU/ml) for HBV MTCT. ART regimens prescribed to the infants early in life
and 25% has ALT>40U/L. contained agents active against HBV (lamivudine), and this may have
Notably, HBV-R is confirmed in 77.3% of pts with an additional sample prevented MTCT in high-risk cases. Larger studies, incorporating
available during TDF/TAF-sparing ART (median [IQR] HBV-DNA:24 long-term follow-up would be informative. Prevention of HBV MTCT
[13–31]IU/ml), supporting persistent HBV replication. at a population level requires consistent antenatal HBV screening and
Finally, pts with a nadir CD4+T cell count <100cells/ul have a higher birth-dose immunisation of infants, together with specific antiviral
risk to develop HBV-R (15/27[55.6%] with vs 25/74[33.8%] without prophylaxis.
nadir <100cells/ul, P = 0.04), suggesting a role of immunecompromis-
sion in promoting reuptake of HBV replication under suboptimal/ THU383
absent drug pressure. Rising clinical and economic burden among hepatitis D patients
Conclusion: A conspicuous fraction of HIV-infected anti-HBc- who attended Spanish hospitals
positive/HBsAg-negative pts has a transcriptionally active intrahepa- Maria Buti1, Ankita Kaushik2, Mertixell Ascanio3, Josep Darba3,
tic reservoir that can predispose to HBV-reactivation under subopti- Nandita Kachru4. 1Hospital Universitario Valle Hebron, Barcelona,
mal/absent drug pressure. The status of HIV-driven Spain; 2Gilead Sciences, Inc., Foster City, United States; 3BCN Health
immunecompromission can exacerbate this phenomenon. Highly Economics and Outcomes Research SL, Barcelona, Spain; 4Gilead
sensitive and accurate assays to measure HBV replicative activity are Sciences, HEOR-Global Value and Access, Foster City, United States
crucial for a proper management of HIV-infected anti-HBc-positive/ Email: [email protected]
HBsAg-negative pts candidate to TDF/TAF-sparing regimen.
Background and aims: Hepatitis D virus (HDV) coinfects with
THU382 hepatitis B virus (HBV) causing the most severe form of viral hepatitis.
Absence of hepatitis B virus (HBV) in at-risk infants receiving early This study examined the epidemiology, baseline characteristics and
antiretroviral therapy in a cohort of HIV-transmitting mothers in healthcare resource use (HRU) and costs among hospitalized HDV
KwaZulu-Natal, South Africa coinfected patients in Spain.
Jane Millar1, Gabriela Cromhout2, Noxolo Mchunu2, Philip Goulder1, Method: Adult patients with ≥1 HDV or HBV diagnosis (ICD-9/10-CM)
Philippa Matthews3,4, Anna McNaughton3,5. 1University of Oxford, were identified retrospectively from Jan 2000 to Dec 2019 (study
Department of Paediatrics, Oxford, United Kingdom; 2University of period) using the Spain hospitalization database that covers 192
KwaZulu-Natal, HIV Pathogenesis Programme, South Africa; 3University private and 313 public hospitals, with >40 million patients. HDV
of Oxford, Nuffield Department of Medicine, Oxford, United Kingdom; patients were identified from Jan 2001 to Dec 2018 (identification
4
Department of Infectious Diseases and Microbiology, Oxford University period) with their first diagnosis defined as the diagnosis date, having
Hospitals NHS Foundation Trust, Oxford, United Kingdom; 5University of ≥12 months of continuous enrollment (CE) before and after the
Bristol, Population Health Science, Bristol Medical School, Bristol, United diagnosis date. Prevalence was measured as the proportion of HDV
Kingdom patients among HBV. Baseline characteristics were assessed over the
Email: [email protected] entire duration prior to diagnosis date. Mean per patient per year
(PPPY) all-cause HRU and costs (pharmacy, inpatient, outpatient, total)
Background and aims: Both HIV and hepatitis B virus (HBV) were obtained over 12 months before and after the diagnosis date.
prevalence are high in KwaZulu-Natal (KZN), South Africa (ZA). HIV Results: The study included 12, 317 patients diagnosed with HDV or
co-infection can negatively impact HBV prognosis, and is associated HBV, of which only 597 had HDV diagnosis, and 536 had a new
with an increased likelihood of HBV mother-to-child-transmission diagnosis (no evidence of HDV during 1 year prior to diagnosis date)-5%
(MTCT) in the absence of appropriate treatment/prophylaxis. This prevalence and 4.7% incidence over the study duration. After applying
study worked with an established cohort of HIV-transmitting CE criteria, the analytical cohort included only 159 HDV patients (mean
mother-child pairs in KZN, in which HIV-positive infants were age 42.7 ± 14.4 years; 73.6% males). High rates of liver disease severity
treated with antiretrovirals (ART) within 48hrs of life. We generated were reported-26.4% compensated cirrhosis, 49.7% decompensated
a detailed characterisation of HBV serological makers in the maternal cirrhosis, 5.7% hepatocellular carcinoma and 5% liver transplant. Other
cohort, and tested the infants at-risk of HBV MTCT. comorbidities included smoking 23.9%, alcohol abuse 19.5%, substance
Method: Maternal serum samples (n = 175) were screened for active abuse 18.9%, HIV 13.8%, HCV 8.8%. Mean PPPY number of admissions,
HBV infection (HBsAg), exposure to HBV (anti-HBc) and vaccination readmissions and length of stay increased significantly from pre- to
responses (anti-HBs-positive in the absence of other HBV markers). post-diagnosis. Mean PPPY all-cause healthcare costs among incident
HBV vaccination has been part of the routine ZA infant immunization patients totaled to €8, 698 (pre-diagnosis) and €12, 684 (post-
schedule since 1995, with the first dose given at age 6 weeks. HBV diagnosis), representing 45.8% increase (p < 0.001). Inpatient costs
infections in HBsAg-positive mothers were further characterised were the major contributors of total pre-diagnosis (41%) and post-
with HBeAg and HBV DNA testing. Infants of HBV infected mothers diagnosis costs (39%), at €3, 569 and €4, 987, respectively.
were screened for HBsAg.
Results: Evidence of HBV exposure was present in 31.4% (55/175)
mothers and HBV infection was present in 8.6% (15/175). Anti-HBc
responses were absent in 53.3% (8/15) HBV-positive cases, suggesting
it may be a poor biomarker in HIV-positive cohorts. A lone anti-HBs
profile, indicating HBV vaccination, was present in 8.0% (14/175)
mothers. HBV DNA was detectable in 46.7% (7/15) HBsAg-positive
mothers, with 26.7% (4/15) also HBeAg-positive. Where HBV-DNA
was detected, median viral load was 3.8log10 IU/ml (range 1.9-
>8.2log10 IU/ml). Among HBV-infected mothers, CD4+ counts were
lower in those also testing HBV DNA positive (mean 264 vs 643; p =
0.003). Using a threshold of >5.3 log10 IU/ml, 20% (3/15) HBV-positive
mothers were defined as high risk of MTCT. Screening of infants found
no cases (0/15) of HBV MTCT.

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POSTER PRESENTATIONS
Conclusion: Hospitalized HDV patients in Spain have a high THU385
comorbidity burden. Total healthcare costs are high, with inpatient Value of intrahepatic HBV markers in virologically suppressed
costs as the primary driver, posing a high economic burden. Novel HBV and HDV infected patients
treatment strategies are needed to improve patient outcomes and Ester García-Pras1, Thais Leonel1, Yabetse Girma1,
reduce the economic burden among HDV coinfected patients in Sergio Rodriguez-Tajes1, Alba Díaz2, Sabela Lens1,
Spain. Mireia García-López1, Maria Saez-Palma1, Yilliam Fundora3,
Xavier Forns1, Sofía Pérez-del-Pulgar1. 1Liver Unit, Hospital Clínic,
THU384 University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain;
Analysis from national hospital discharge records database in 2
Department of Pathology, Centre of Biomedical Diagnosis, CIBERehd,
Spain : increased baseline comorbidity burden including liver Hospital Clínic; 3HBP and Liver Transplant Surgery, IDIBAPS, Hospital
severity among HDV coinfection versus HBV monoinfection Clinic de Barcelona
patients Email: [email protected]
Maria Buti1, Ankita Kaushik2, Mertixell Ascanio3, Josep Darba4,
Nandita Kachru2. 1Hospital Universitario Valle Hebron, Liver Unit, Background and aims: The utility of measuring HBV and HDV
Barcelona, Spain; 2Gilead Sciences, HEOR-Global Value and Access, markers in liver biopsies (including cccDNA levels) to assess clinical
California, United States; 3BCN Health Economics and Outcomes outcomes is currently under evaluation. A recent study has shown
Research SL, Barcelona, Spain; 4University of Barcelona, Department of high variability in cccDNA and HBV-RNA levels in multiple pieces of
Economics, Barcelona, Spain explant liver tissue in patients with different viral loads (Rydell GE
Email: [email protected] et al. 2021). The aim of our study was to investigate whether the liver
biopsy is representative for the detection of cccDNA in patients with
Background and aims: Hepatitis D virus (HDV) is considered as the low levels of HBV replication, either induced by NUCs or in the
most severe form of chronic viral hepatitis, given its relatively rapid context of HDV coinfection.
progression to cirrhosis and liver-related complications. This retro- Method: We included 10 patients undergoing liver transplantation
spective study compares baseline characteristics of adult patients due to end-stage liver disease related to HBV (n = 5) or HDV (n = 5)
with HDV coinfection versus (vs.) hepatitis B virus (HBV) mono- infection. From each liver explant, we obtained 9–10 fresh-frozen
infection in a national hospital database in Spain. tissue pieces and we quantified total intrahepatic HBV-DNA (iHBV-
Method: The study population included subjects ≥18 years having ≥1 DNA), cccDNA and HDV-RNA by Taqman real-time PCR. The presence
ICD-9/10-CM diagnosis code for HDV or HBV in the Spanish National of HBsAg and HDAg was assessed by IHC in FFPE liver samples.
Health System’s Hospital Discharge Records Database (Conjunto Results: HBV replication was suppressed in all patients (undetectable
Mínimo Básico de Datos) from 01/01/2000 to 12/31/2019 (study serum HBV-DNA, n = 4; ≤27 IU/ml, n = 6) either because of NUC
period). HDV and HBV cohorts were identified from 01/01/2001 to 12/ therapy, HDV coinfection or both. iHBV-DNA was detectable in all
31/2018 (identification period) with their first diagnosis defined as HBV and HDV liver samples (n = 98). In contrast, detection of cccDNA
the diagnosis date, having ≥12 months of continuous enrollment in HBV patients was very heterogeneous, ranging from 10% to 80% of
before and after the diagnosis date. Baseline characteristics were liver samples. Remarkably, no cccDNA was detected in any of the
assessed over the entire duration prior to diagnosis date. Descriptive pieces from 4 out of 5 HDV-infected patients despite having higher
statistics were summarized, and comparisons were made via chi- iHBV-DNA levels than HBV monoinfected patients (median 1.342 vs
square tests. 0.004 copies/cell, p = 0.03). Interestingly, HBsAg immunostaining in
Results: The study reported 12, 317 patients diagnosed with HDV or liver tissue samples showed a higher proportion of HBsAg-positive
HBV, of which 3, 079 met the inclusion criteria-159 HDV and 2, 920 hepatocytes in HDV-infected patients compared to HBV-monoin-
HBV patients. HDV patients [mean age 42.7 ± 14.4 | Charlson fected patients (>80% vs 5–60%), suggesting greater HBsAg expression
Comorbidity Index (CCI) score 0.92] were significantly younger from HBV integrants in HDV-infected patients. HDV-RNA was
than HBV patients [mean age 46.6 ± 15.9; p = 0.0034 | CCI score detected in all the liver pieces (n = 49) from the HDV-infected
0.77]. The male to female ratio (roughly 3:1) was similar across the patients, showing higher variability in patients with low serum HDV-
two cohorts. Both the cohorts were largely covered by public RNA levels (2–4 Log IU/ml).
insurance (93.7% HDV vs. 95.4% HBV; p = 0.3311) and roughly half Conclusion: Based on our data, cccDNA detection is highly variable in
were seen by gastroenterologists (44.7% HDV vs. 50.3% HBV; p = virologically suppressed HBV-infected patients, and frequently
0.1673) followed by other specialists (36.5% HDV vs. 29.8% HBV; p = undetectable in HDV-infected patients. The variability of intrahepatic
0.0763). HDV patients were significantly more likely to have viral markers, along with the potential interference of HBV
decompensated cirrhosis (49.7% vs. 29%; p < 0.0001), compensated integrants, should be considered when defining end points for drug
cirrhosis (26.4% vs. 9.8%; p < 0.0001) and liver transplant (5% vs. 1.8%; development studies.
p = 0.0109) than HBV patients, whereas hepatocellular carcinoma
rates were at 5.7% and 3%, respectively. Further, HDV patients THU386
reported significantly higher rates of HCV (8.8% vs. 3.6%; p = Hepatitis Delta virus infection in patients with chronic hepatitis B
0.0043), HIV (13.8% vs. 3.3%, p < 0.0001) and substance abuse is associated with greater risk of liver disease progression and
(18.9% vs. 7%; p < 0.0001) than HBV patients. liver-related mortality: a systematic review and meta-analysis
Conclusion: In a national hospital Spanish database, HDV coinfected Robert G. Gish1, Robert Wong2, Gian Luca Di Tanna3, Ankita Kaushik4,
patients had greater comorbidities and significantly higher liver Nate Smith5, Patrick Kennedy6. 1University of Nevada, Reno School of
disease severity than HBV monoinfected patients. These findings Medicine, Las Vegas, United States; 2Veterans Affairs Palo Alto Healthcare
underscore the need for early screening and diagnosis, and eventual System, Division of Gastroenterology and Hepatology, California, United
treatment of HDV to mitigate future disease progression. States; 3University of New South Wales, The George Institute for Global
Health, Sydney, Australia; 4Gilead Sciences Inc, Foster City, United States;
5
Maple Health Group, LLC, New York, United States; 6Blizard Institute,
Department of Hepatology, Centre for Immunobiology, London, United
Kingdom
Email: [email protected]
Background and aims: Previous studies have suggested more
aggressive liver disease progression in chronic hepatitis B (CHB)
patients with hepatitis delta virus (HDV) infection. We conducted a

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 POSTER PRESENTATIONS
systematic literature review and meta-analysis to examine whether Results: At diagnosis 79% patients had detected HBV pgRNA and
HDV RNA positivity (HDV RNA+) vs. RNA negativity (HDV RNA-) is HBcrAg was detected in all patients. There were strong positive
associated with increased risk of advanced liver disease events correlations between serum pgRNA and HBV DNA levels (r = 0.82 p <
(ALDEs), including compensated cirrhosis (CC), decompensated 0.01), pgRNA and HBsAg levels (r = 0.74, p < 0.01) and pgRNA and
cirrhosis (DCC), hepatocellular carcinoma (HCC), liver transplant HBcrAg concentrations (r = 0.859, p < 0.01). When compared
(LT), and liver-related mortality (LRM). untreated vs. patients who required therapy-pgRNA was detected in
Method: PubMed, Embase and Cochrane Central were searched in 100% of untreated patients vs. 80% of patients needing therapy, but
August 2021. Observational, case-control, and cross-sectional studies patients who needed therapy had higher pgRNA levels than
along with clinical trials reports addressing the clinical question of untreated cohort (median: 3.02 log10U/ml vs. 1.94 log10U/ml, p <
the review were included. Data extraction focused on data related to 0.05). In contrast, HBcrAg was detected in all patients irrespective of
the relative rate of progression to advanced liver disease events for therapy status, but patients who required therapy had lower HBcrAg
HDV RNA+/detectable versus HDV RNA-/undetectable patients and concentrations than untreated patients (median: 3.84 log10U/ml vs.
quality evaluation was based on the modified Risk of Bias in Non- 5.15 log10U/ml, p < 0.05) likely reflecting higher proportion of HBeAg
randomised Studies-of Interventions (mROBINS-I) checklist. Data negative patients in patients needing therapy (80% vs. 29%, p < 0.05).
were pooled using the Hartung-Knapp-Sidik-Jonkman method for Conclusion: The markers of cccDNA transcriptional activity-pgRNA
random-effects models for both risk (RR) and hazard ratios (HRs). We and HBcrAg-combined with the traditional serological/virological
assessed the proportion of variability due to between-study markers (HBeAg, HBsAg and HBV DNA levels) were helpful to predict
heterogeneity with the I2 statistics. at diagnosis patients who might require antiviral therapy in future
Results: Among a total of 2, 034 studies identified, 34 met analysis and represent a valuable tool to be applied in regular diagnostics.
inclusion criteria. After meta-analysis, presence of HDV RNA+ was Studies in larger paediatric cohorts to further assess this are needed.
associated with a significant increased risk of any ALDE (mean effect
[95% CI]: RR: 1.85 [1.11, 3.09]; HR: 2.39 [1.56, 3.68]). When compared THU388
to HDV RNA- patients, HDV RNA+ was associated with a significantly Presence of liver inflammation and fibrosis in Asian patients with
higher risk of progressing to CC (RR 2.19 [1.60, 2.99]), DCC (RR 2.07 chronic hepatitis B in the grey zone
[1.45, 2.96]; HR 3.82 [1.94, 7.49]), HCC (RR: 1.59 [1.02, 2.50]; HR 2.91 Jiacheng Liu1, Jian Wang2, Yiguang Li3, Li Zhu4, Weimao Ding5,
[1.98–4.29]), LT (HR 7.07 [1.61, 31.00]), and LRM (RR 1.92 [1.02, 3.63]; Chuanwu Zhu4, Yuanwang Qiu3, Jie Li2, Rui Huang2, Chao Wu2.
1
HR 4.58 [2.72, 7.70]). Nanjing Drum Tower Hospital Clinical College of Traditional Chinese
Conclusion: This comprehensive systematic review and meta-analysis and Western Medicine, Nanjing University of Chinese Medicine,
demonstrates that HDV RNA+ patients have significantly greater risk of Department of Infectious Diseases, Nanjing, China; 2Nanjing Drum
liver disease progression compared to HDV RNA- patients. These Tower Hospital, The Affiliated Hospital of Nanjing University Medical
findings highlight the need for improved HDV screening in patients School, Department of Infectious Diseases, Nanjing, China; 3The Fifth
with chronic HBV, leading to early detection of HBV/HDV, linkage to People’s Hospital of Wuxi, Department of Infectious Diseases, Wuxi,
care, and timely initiation of appropriate antiviral therapies to reduce China; 4The Affiliated Infectious Diseases Hospital of Soochow
the risk of liver-related morbidity and mortality. University, Department of Infectious Diseases, Suzhou, China; 5Huai’an
No. 4 People’s Hospital, Department of Hepatology, Huai’an, China
THU387 Email: [email protected]
The serum markers of cccDNA transcriptional activity have a role
in predicting long-term outcomes in children with perinatally Background and aims: Over a quarter of chronic hepatitis B (CHB)
acquired HBV infection patients did not meet criteria of the traditional natural phases and
Christiana Moigboi1, Mark Anderson2, Gavin Cloherty2, hence classified as grey zone (GZ). However, few studies reported the
Kosh Agarwal1, Ivana Carey1. 1King’s College Hospital, Institute of Liver liver inflammation and fibrosis of Asian CHB patients in the GZ.
Studies, London, United Kingdom; 2Abbott Diagnostics, Department of Method: This multicenter, retrospective study included 1, 064 CHB
Infectious Diseases, North Chicago, United States patients underwent liver biopsy (LB). Phases of natural history were
Email: [email protected] determined according the AASLD 2018 Guidance. GZ patients were
divided into four categories: HBeAg-positive, normal ALT and HBV-
Background and aims: Perinatally acquired chronic hepatitis B (CHB) DNA ≤ 106 IU/ml (GZ-A); HBeAg-positive, elevated ALT and HBV-DNA
has often indolent course in childhood, but persistent viral infection < 2 × 104 IU/ml (GZ-B); HBeAg-negative, normal ALT and HBV-DNA ≥
leads to progressive liver disease in 40% of patients in adulthood. The 2 × 103 IU/ml (GZ-C); HBeAg-negative, elevated ALT and HBV-DNA <
combination of non-invasive serological (HBeAg, HBsAg levels) and
2 × 103 IU/ml (GZ-D).
virological (HBV DNA) markers together with liver enzyme activity Results: 263 (24.7%) patients were in the GZ with the median age of
(ALT) and liver damage scores (APRI or FIB-4) aids in monitoring disease 41.5 years and male of 67.2%. Among the GZ patients, GZ-D (44.1%)
stages and progression. Novel serological markers of cccDNA transcrip-
was the dominate category, followed by GZ-C (37.6%), GZ-A (9.9%) and
tional activity-HBV core-related antigen (HBcrAg) and pre-genomic GZ-B (8.4%). Surprisingly, as high as 60.4% of GZ patients had
HBV RNA (pgRNA) might add more insight and were not studied in
significant inflammation (≥G2) and 89.7% GZ patients had significant
paediatric populations. We aimed to investigate whether markers of fibrosis (≥S2), which were higher than that of patients with immune-
cccDNA transcriptional activity in serum: HBcrAg and pgRNA can help tolerant and inactive phases. Over half of patients had significant
to predict future disease progression (need for therapy) in patients with
inflammation or fibrosis in each GZ category. GZ-B patients had the
perinatally acquired chronic hepatitis B infection. highest proportions of significant inflammation (95.5%) and fibrosis
Method: A retrospective study was carried out with samples from 29
(81.9%) compared to other GZ categories (GZ-A: 76.9% and 69.3%; GZ-
chronic hepatitis B (CHB) paediatric patients diagnosed in childhood C: 53.5% and 52.5%; GZ-D: 56.1% and 60.4%, respectively).
(median age 12 years, 48% males, 52% HBeAg positive) with long-
term follow-up in the same centre (median follow-up duration 6.5
years, range 3–16 years) with available serum samples at the time of
diagnosis. HBV DNA viral load was tested by TaqMan PCR [IU/ml],
HBeAg status and HBsAg plasma levels by Abbott Architect® [log10IU/
ml], HBcrAg concentrations by CLEIA Fujirebio [log10U/ml] and
pgRNA concentrations by real-time PCR Abbott Molecular
Diagnostic RUO assay (LLQD = 1.65 log10U/ml). Only 5 patients
required to be started on antiviral therapy during follow-up.

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POSTER PRESENTATIONS
based on eGFR (in ml/min/1.73m2): low (60-<90), normal (90-<120)
and high (≥120). Frequency counts, descriptive statistics and 95%
confidence intervals (CI) were used for comparison.
Results: A total of 455 pts were enrolled: 225 +NA and 230 -NA
(Table). Mean age and length of diagnosis was inversely related to
eGFR status for both those +NA and -NA. For both +NA and -NA pts,
the highest proportion of pts with low eGFR were Asian (74% and 70%,
respectively), and within race groups, Asians had the highest
proportion of pts with low eGFR. +NA pts in the high eGFR group
had higher HBsAg (mean [95% CI]: 10, 939.4 [6264.0, 15614.8]) vs pts
in the low eGFR group (2723.5 [1545.9, 3901.1] IU/ml); this was not
observed in -NA pts. In the -NA group, mean eGFR was lower in
HBeAg negative pts (mean [95% CI]: 107.1 [105.0, 109.2]) vs HBeAg
positive pts (114.4 [110.2, 118.6]). The number of pts with baseline
non-steroidal anti-inflammatory drug (NSAID) or angiotensin-con-
verting enzyme inhibitor/angiotensin receptor blocker use, or pts
with diabetes or hypertension were low, but mean eGFR tended to be
lower in these pt groups than in those without concomitant
Figure: Liver inflammation and fibrosis in chronic hepatitis B with differ- medication use or comorbidities, except for -NA pts with baseline
ent phases of natural history and grey zones. NSAID use or diabetes. The most common NA used at baseline was
Conclusion: A substantial GZ patients had significant liver inflam- entecavir (reported by 41% of those on NA).
mation or fibrosis, especially for CHB patients with GZ-B. Using liver Conclusion: Preliminary assessment of pts enrolled in B-Clear
biopsy to assess the liver histological activity should be encouraged in indicates that renal function may be associated with characteristics
GZ patients. such as age, length of CHB diagnosis, race, HBsAg level, HBeAg status,
and concomitant medications/comorbidities. [on behalf of the B-
THU389 Clear study group].
Characteristics and renal function in patients with chronic Funding: GSK (209668).
hepatitis B virus infection: baseline data from the phase 2b B-
Clear study THU390
Seng Gee Lim1, Robert Plesniak2, Keiji Tsuji3, Harry Janssen4, Characterisation of baseline complement values in patients with
Cristina Pojoga5,6, Adrian Gadano7, Corneliu Petru Popescu8, chronic hepatitis B virus infection in the phase IIb B-clear study
Tarik Asselah9, Diana Petrova10, Hyung Joon Yim11, Jennifer Cremer1, Anna Richards2, Tamara Lukic3, Seng Gee Lim4,
Gheorghe Diaconescu12, Jeong Heo13, Alexander Wong14, Robert Plesniak5, Keiji Tsuji6, Harry Janssen7, Cristina Pojoga8,9,
Ewa Janczewska15, Man-Fung Yuen16, Jennifer Cremer17, Corneliu Petru Popescu10, Tarik Asselah11, Diana Petrova12,
Tamara Lukic18, Stuart Kendrick19, Robert Elston19, Geoff Quinn19, Hyung Joon Yim13, Gheorghe Diaconescu14, Jeong Heo15,
Punam Bharania19, Fiona Campbell19, Melanie Paff17, Alexander Wong16, Ewa Janczewska17, Giuliano Rizzardini18,
Dickens Theodore17. 1National University Health System, Singapore; Man-Fung Yuen19, Geoff Quinn2, Punam Bharania2, Melanie Paff1,
2
University of Rzeszow Centrum Medyczne w Lancucie Sp. z o.o., Poland; Dickens Theodore1. 1GlaxoSmithKline, United States; 2GlaxoSmithKline,
3
Hiroshima Red Cross Hospital, Japan; 4Toronto General Hospital, United Kingdom; 3GlaxoSmithKline, United Arab Emirates; 4National
Canada; 5Institutul Regional de Gastroentorologie si Hepatologie prof dr University Health System, Singapore; 5University of Rzeszow Centrum
O Fodor, Romania; 6Babeș-Bolyai University, International Institute for Medyczne w Lancucie Sp. z o.o., Poland; 6Hiroshima Red Cross Hospital,
Advanced Study of Psychotherapy and Applied Mental Health, Romania; Japan; 7Toronto General Hospital, Canada; 8Institutul Regional de
7
Hospital Italiano de Buenos Aires, Argentina; 8Dr Victor Babes Clinical Gastroentorologie si Hepatologie prof dr O Fodor, Romania; 9Babeș-
Hospital of Infectious and Tropical Diseases, Carol Davila University of Bolyai University, International Institute for Advanced Study of
Medicine and Pharmacy, Romania; 9Hôpital Beaujon, Université de Paris, Psychotherapy and Applied Mental Health, Romania; 10Dr Victor Babes
France; 10Diagnostic Consultative Centre Alexandrovska, Bulgaria; Clinical Hospital of Infectious and Tropical Diseases, Carol Davila
11
Korea University Ansan Hospital, Korea, Rep. of South; 12Spitalul Clinic University of Medicine and Pharmacy, Romania; 11Hôpital Beaujon,
de Boli Infectioase si Pneumoftiziologie, Romania; 13College of Medicine, Université de Paris, France; 12Diagnostic Consultative Centre
Pusan National University and Biomedical Research Institute, Pusan Alexandrovska, Bulgaria; 13Korea University Ansan Hospital, Korea, Rep.
National University Hospital, Korea, Rep. of South; 14University of of South; 14Spitalul Clinic de Boli Infectioase si Pneumoftiziologie,
Saskatchewan, Department of Medicine, Canada; 15ID Clinic, Poland; Romania; 15College of Medicine, Pusan National University and
16
Queen Mary Hospital, The University of Hong Kong, China; Biomedical Research Institute, Pusan National University Hospital,
17
GlaxoSmithKline, United States; 18GlaxoSmithKline, United Arab Korea, Rep. of South; 16University of Saskatchewan, Department of
Emirates; 19GlaxoSmithKline, United Kingdom Medicine, Canada; 17ID Clinic, Poland; 18Fatebenefratelli Sacco Hospital,
Email: [email protected] Italy; 19Queen Mary Hospital, The University of Hong Kong, China
Email: [email protected]
Background and aims: Chronic hepatitis B (CHB) infection has been
Background and aims: The immune system plays an important role
associated with the development of chronic kidney disease.
in disease pathogenesis and viral clearance of hepatitis B virus (HBV)
Bepirovirsen (BPV; GSK3228836) is an antisense oligonucleotide
infection, but the impact of HBV on the complement system, the
known to distribute into the kidneys and liver. Here, we aim to
inflammatory/immune state of patients ( pts) and implications for
characterise the baseline renal parameters in patients ( pts) enrolled
disease and treatment are poorly understood. Here we present
in B-Clear and to understand any associations between renal
associations between baseline complement factors, other laboratory
parameters (estimated glomerular filtration rate [eGFR]), nucleos (t)
and clinical characteristics, and nucleot (s)ide analogue (NA)
ide analogue (NA) treatment status and other baseline laboratory/
treatment status in pts screened in the B-Clear trial.
clinical characteristics.
Method: B-Clear is an ongoing phase IIb trial (NCT04449029) to
Method: B-Clear is an ongoing trial (NCT04449029) to assess the
assess the efficacy and safety of bepirovirsen (BPV, GSK3228836), an
efficacy and safety of BPV in pts with CHB infection on stable NA
antisense oligonucleotide, in pts with chronic HBV. Pts on either
treatment (+NA) or not on NA (-NA) at study start. Pts were grouped

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 POSTER PRESENTATIONS

Table: (abstract: THU389)

Journal of Hepatology 2022 vol. 77(S1) | S119–S388 S289

POSTER PRESENTATIONS

Table: (abstract: THU390)

stable NA therapy (+NA), or not receiving NA therapy (-NA) were THU391

enrolled. All pts screened for B-Clear were included in this analysis; Estimations of the global prevalence and clinical burden of occult
pts were grouped based on baseline values of complement C3 ([in g/ hepatitis B infection (OBI): a systematic review and meta-analysis
L] low <0.9; normal 0.9–1.8; high >1.8) and C4 ([in g/L] low <0.1; Yu Ri Im1, Rukmini Jagdish1, Damien Leith2, Jin Un Kim1, Gibril Ndow3,
normal 0.1–0.4; high >0.4) at screening. Descriptive statistics and 95% Kyoko Yoshida1, Amir Majid4, Yueqi Ge5, Yusuke Shimakawa6,
confidence intervals were used for comparison. Maud Lemoine1. 1Imperial College London, Section of Hepatology,
Results: Of the 725 screened pts with data (N = 718 [+NA: n = 286; Division of Digestive Diseases, Department of Metabolism, Digestion and
-NA: n = 432]): 83 had low C3 (+NA: n = 25; -NA: n = 58), 23 had low Reproduction, London, United Kingdom; 2Glasgow Royal Infirmary,
C4 (+NA: n = 4; -NA: n = 19), and 17 had both low C3 and C4 (+NA: n = Department of Gastroenterology, Glasgow, United Kingdom; 3London
2; -NA: n = 15) (Table). A greater proportion of females had low C3 in School of Hygiene and Tropical Medicine, MRC Unit The Gambia, Fajara,
the -NA group versus the +NA group (18%, versus 9%, respectively). Gambia; 4West Middlesex University Hospital, Department of
Most pts with low C3 were Asian (+NA: 68%; -NA: 72%). In the +NA Anaesthetics, Isleworth, United Kingdom; 5Chelsea and Westminster
low C3 group, the mean hepatitis B virus surface antigen (HBsAg; Hospital, Department of Gastroenterology, London, United Kingdom;
5911 IU/ml) and hepatitis B virus e-antigen (HBeAg; 41.5 U/ml) was 6
Institut Pasteur, Unité d’Épidémiologie des Maladies Émergentes, Paris,
higher vs the normal C3 mean HBsAg (4624 IU/ml) and HBeAg (11.9 France
U/ml). In the -NA low C3 group, the mean HBV DNA (12, 276, 923 IU/ Email: [email protected]
ml) and HBeAg (473 U/ml) was higher vs the normal C3 group (HBV
Background and aims: Occult hepatitis B infection (OBI) is defined as
DNA 7, 345, 220 IU/ml; HBeAg 249 U/ml), while HBsAg was lower
the presence of replication-competent hepatitis B virus (HBV) DNA in
(low C3 group 15735 IU/ml; high C3 group 18048 IU/ml).
the blood or liver tissue of individuals who test negative for the
The complement split product C5a and factor Bb were similar, and
hepatitis B surface antigen (HBsAg). Previous studies have suggested
mostly in the normal range, in pts with low, normal or high C3 in both
that individuals with OBI could transmit the virus and may be at
the +NA and -NA groups.
higher risk of hepatocellular carcinoma (HCC). Despite possible
Conclusion: Preliminary findings indicate that gender, race, HBsAg, implications for both affected individuals and global HBV elimination
HBV DNA, and HBeAg level may all contribute to low C3 among pts goals, the prevalence of OBI is not known. Therefore, we performed a
with HBV. Observed differences may be due to different stages of meta-analysis to estimate the global prevalence of OBI.
disease or level of immune status for pts +NA, versus -NA. Due to low Method: We systematically searched the MEDLINE, Embase, Global
numbers of pts with low C4, no conclusions could be made regarding Health and Web of Science databases for articles published between
associations with baseline characteristics. [on behalf of the B-Clear Jan 1, 2010, and August 14, 2019. We included studies on adult
study group]. populations from which the prevalence of OBI could be calculated,
Funding: GSK (209668). regardless of anti-hepatitis B core (anti-HBc) status or viral load. We
excluded studies on individuals <18 years of age and those on
antiviral therapy active against HBV. The prevalence was pooled to

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 POSTER PRESENTATIONS
determine effect estimates and 95%CI weighted by study size for chart review was performed of 86/1390 patients (6.1%) who were
blood donors, low-risk populations, high-risk populations due to positive for HDV infection and had complete data. More than half
increased HBV exposure risk, and patients with advanced liver (58.14%) were male, mean body mass index was 27.88 (SD ± 5.5) units.
disease. We also assessed the effects of study design, HBV serology, After CHB, most common co-existing condition was hepatitis C virus
HBV endemicity and presence of advanced liver disease on OBI (HCV) infection (11.62%). Median FIB-4 score was 1.8 (1.1–4.2) and
prevalence. 53.48% had cirrhosis at the time of HDV diagnosis. Majority (81.4%) of
Results: Our meta-analysis included 400 studies and 143, 980, 492 screening tests were ordered at attending clinics by gastroenterolo-
individuals. Amongst anti-HBc-positive individuals (n = 7, 863), OBI gists (90.7%). Among patients with cirrhosis 17 (37%) developed LD
prevalence was 7.9% (5.3–10.8) in blood samples (n = 7, 345) and with ascites and esophageal varices (82% each) being the most
55.2% (42.9–67.3) in liver samples (n = 367). Amongst anti-HBc- common decompensating events. 12 (13.95%) patients developed
negative individuals (n = 45, 853), OBI prevalence was 1.1% (0.6–1.8) HCC and 16 (18.6%) patients needed LT. No patients died during
in blood samples (n = 44, 637) and 17.9% (5.1–35.2) in liver samples follow-up.
(n = 302). When assessing studies that included all individuals Conclusion: Our study demonstrates that people with HBV who are
negative for HBsAg regardless of anti-HBc status and tested OBI in infected with HDV have high morbidity and increased risk for HCC,
the blood, OBI prevalence was lowest in blood donors (0.2% [0.2– LD, and LT. A small proportion of HBV infected persons are screened
0.4]), followed by low-risk populations (2.5% [1.0–4.5]), high-risk for HDV and many of them develop liver cirrhosis by the time of
populations due to increased HBV exposure risk (6.4% [4.2–9.0]) and diagnosis. Contrary to AASLD guidelines, we found a sizable number
patients with advanced liver disease (15.8% [8.1–25.2]). Endemicity of of HDV-positive people who do not have co-existing high-risk
the country of study was predictive of OBI prevalence in blood conditions like Human Immunodeficiency Virus and HCV. Most of
donors. The presence of advanced liver disease was associated with the screening for HDV occurred in attending clinics vs trainee/mid-
an increased prevalence of OBI across case-control studies of patients level provider clinics, identifying an area for improving knowledge
with cirrhosis or HCC compared to healthy controls ( p < 0.001). around HDV. We describe a significant liver-related disease burden in
Conclusion: OBI is common, clinically significant, and underesti- those with HDV and thus universal screening for HDV in people with
mated. Our study reports a consistently high prevalence of OBI in HBV infection may be reasonable.
HBV-endemic areas and, globally, across high-risk groups. Screening
of blood products with both nucleic acid testing (NAT) and anti-HBc THU393
might be necessary to eradicate this reservoir of HBV infection Distribution of patients by guideline-defined disease phase and/
globally. OBI should no longer be overlooked in regional and global or grey zones in B-Clear, an international multicentre clinical trial
hepatitis B screening, prevention, and elimination programmes. Seng Gee Lim1, Cristina Pojoga2,3, Harry Janssen4, Michio Imamura5,
Ewa Janczewska6, Robert Plesniak7, Keiji Tsuji8,
THU392 Corneliu Petru Popescu9, Diana Petrova10, Adrian Gadano11,
Time for universal screening for hepatitis D? A study describing Alexander Wong12, Tarik Asselah13, Hyung Joon Yim14, Jeong Heo15,
screening patterns, characteristics and outcomes of hepatitis D Man-Fung Yuen16, Gheorghe Diaconescu17, Giuliano Rizzardini18,
virus infection Jennifer Cremer19, Robert Elston20, Stuart Kendrick20, Geoff Quinn20,
Rohit Nathani1, Bo Hyung Yoon2, Carolina Villarroel3, Sidra Salman1, Fiona Campbell20, Melanie Paff21, Dickens Theodore19. 1National
Dewan Giri3, Amreen Dinani4, Ilan Weisberg4. 1Icahn School of University Health System, Singapore, Singapore; 2Institutul Regional de
Medicine at Mount Sinai Morningside-West, Department of Medicine, Gastroentorologie si Hepatologie prof dr O Fodor, Cluj-Napoca, Romania;
New York, United States; 2Icahn School of Medicine at Mount Sinai Beth 3
Babeș-Bolyai University, International Institute for Advanced Study of
Israel-Morningside-West, Division of Gastroenterology, Department of Psychotherapy and Applied Mental Health, Cluj-Napoca, Romania;
Medicine, New York, United States; 3Icahn School of Medicine at Mount 4
Toronto General Hospital, Toronto, Canada; 5Hiroshima University
Sinai Beth Israel, Department of Medicine, New York, United States; Hospital, Hiroshima, Japan; 6ID Clinic, Myslowice, Poland; 7University of
4
Icahn School of Medicine at Mount Sinai Beth Israel, Division of Rzeszow Centrum Medyczne w Lancucie Sp. z o.o., Lancut, Poland;
8
astroenterology, Department of Medicine, New York, United States Hiroshima Red Cross Hospital, Hiroshima, Japan; 9Dr Victor Babes
Email: [email protected] Clinical Hospital of Infectious and Tropical Diseases, Carol Davila
University of Medicine and Pharmacy, Bucharest, Romania; 10Diagnostic
Background and aims: The prevalence of hepatitis D virus (HDV) is
Consultative Centre, Varna, Bulgaria; 11Hospital Italiano de Buenos Aires,
as high as 10% in patients with hepatitis B virus (HBV) infection. Asian
Buenos Aires, Argentina; 12University of Saskatchewan, Regina, Canada;
and European guidelines recommend universal testing for HDV in all 13
Hôpital Beaujon, Clichy, France; 14Korea University Ansan Hospital,
HBV surface antigen positive persons. However, the AASLD guidelines
Ansan, Korea, Rep. of South; 15Pusan National University Hospital,
recommend testing only those at increased ‘risk.’ The aim of our
Busan, Korea, Rep. of South; 16Queen Mary Hospital, Hong Kong, China;
study was to identify patterns of screening for HDV and to understand 17
Spitalul Clinic de Boli Infectioase si Pneumoftiziologie, Craiova,
the characteristics and outcomes of those infected with HDV.
Romania; 18Luigi Sacco Hospital, Milan, Italy; 19GlaxoSmithKline,
Method: A retrospective cohort of patients with chronic hepatitis B
Durham, United States; 20GlaxoSmithKline, Stevenage, United Kingdom;
(CHB) infection was identified using electronic medical record data in 21
GlaxoSmithKline, Collegeville, United States
a tertiary health system from 01/2016 to 10/2021. We also identified
Email: [email protected]
those who were screened with an HDV antibody test. For this
submission, detailed chart review of patients with a confirmed Background and aims: Many patients ( pts) with chronic hepatitis B
diagnosis of HDV infection was performed. Baseline demographic virus (CHB) lie in a grey zone (GZ) (i.e. they do not fit into a guideline-
data, comorbidities, and markers of severity of liver disease defined disease phase). We evaluated the distribution and character-
(determined by FIB 4 score) and cirrhosis status (based on imaging istics of CHB pts enrolled in B-Clear, who were not on nucleos (t)ide
and clinical criteria) at the time of diagnosis was recorded. We also analog (NA) therapy, by guideline-defined disease phase and GZ.
recorded the type of screening test and the type of clinician Method: B-Clear is an ongoing trial (NCT04449029) to assess the
performing the screening. Primary outcome was mortality and efficacy and safety of bepirovirsen (GSK3228836, BPV)-an antisense
secondary outcomes included liver decompensation (LD), develop- oligonucleotide- in pts with CHB. Pts not on NA (N = 230) were
ment of hepatocellular carcinoma (HCC), and need for liver transplant categorised as HBeAg positive (eAg+) chronic infection, eAg+ chronic
(LT). hepatitis, HBeAg negative (eAg-) chronic infection, and eAg- chronic
Results: Over 6 years 11, 110 patients were diagnosed with CHB and hepatitis, based on HBV DNA, alanine aminotransferase (ALT) and eAg
1390 (12.5%) of them had been screened for HDV infection. A detailed status at baseline as per EASL 2017, AASLD 2018 and APASL 2015 CHB

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POSTER PRESENTATIONS
guidelines. In addition, ‘Strict’ or ‘Common’ criteria were applied concomitant HCV infection (genotype 1a:4; 1b:7; 2a/c:3; 3a:7; 4d:2)
based upon eAg status and ALT cut-offs of 35/25 IU/ml [males/ who received DAAs with Sofosbuvir (SOF:13) or without (NO-SOF:10)
females] or 40/33 IU/ml [males/females], respectively. Pts in the GZ for 8 (4), 12 (12) or 24 (7) weeks (w). HBsAg (Abbott) and HBV-DNA
were categorised into four groups: A (eAg+, normal ALT), B (eAg+, (Roche) were measured at: −12w, DAAs baseline (BL), 4w, End of
high ALT), C (eAg-, normal ALT), D (eAg-, high ALT). Therapy (EOT), EOT + 12w (24w), EOT + 24w (36w) and EOT + 48w
Results: Of the four guideline-defined disease phases, the highest (60w).
proportion of pts were eAg+ chronic hepatitis (EASL 16.2%; AASLD Results: No significant difference between ENI and CHB were
18.8%) or eAg- chronic hepatitis (EASL 16.2%; APASL 8.7%) (Figure); observed in BL Liver Stiffness (10.5 vs 15.7 kPa; p = 0, 495), ALT (51
however, the majority of patients (55.5%, 65.9% and 81.2%) fell in the vs 44 U/L; p = 0.495) and HCV-RNA (6.2 vs 6, 0 Log IU/ml, p = 0.561),
GZ using EASL, AASLD and APASL guidelines, respectively. Most pts in whereas HBsAg levels were lower in ENI than in CHB (0.88 vs 2.42 Log
the GZ were eAg-. GZ C was the most common GZ group: 48.5% IU/ml, p = 0.035). At BL HBV-DNA was undetectable or <10 IU/ml in 5
(EASL), 36.2% (AASLD) and 48.5% (APASL); however, the proportion of and 3 ENI; it was undetectable in all NA treated CHB and remained so
pts in other GZ groups differed by guideline. The EASL guidelines had thereafter. All pts achieved SVR for HCV and normalized ALT. During
the lowest proportion of pts in the GZ for Asian (48.8%), Black (75%) DAAs, HBV-DNA increased >1 Log or became detectable >100 IU/ml in
and White (60.8%) pts. The APASL guidelines had the highest 5 and 2 ENI, respectively (overall: 46.7%), showing a trend for higher
proportion in the GZ for Asian (86%) and Black (95%) pts, while mean Log values at 4w ( p = 0.100) and at EOT ( p = 0.104) as compared
AASLD guidelines had the highest proportion of pts in the GZ for to BL (Figure). Mean Log HBsAg levels significantly decreased in ENI
White pts (74.7%). When the criterion for HBV DNA was removed, the from − 12w to BL ( p = 0.002), but not in CHB ( p = 0.564). During DAAs
highest proportion of GZ pts fell into the eAg-, normal ALT category a significant decline occurred at 4w in both ENI ( p = 0.020) and CHB
(52.2% ‘Common’; 40.4% ‘Strict’) and eAg-, high ALT category (21.7% (0.015), followed by a rebound at EOT in ENI only. After DAAs, HBsAg
‘Common’; 33.5% ‘Strict’). returned progressively to pre-DAAs levels in CHB, whereas continued
to decline in ENI (6 cleared HBsAg). Among factors associated to a
HBeAg pos ve chronic HBV infec on HBeAg pos ve chronic hepa sB greater HBsAg decline during DAAs, there was a trend for SOF in the
HBeAg ne ve chronic HBV infec on HBeAg nega ve chronic he sB
Grey zone
schedule ( p = 0.083).
100%

75%
Percentage of pa ents

50%

25%

0%
APASL (n = 229) AASLD (n = 229) EASL (n = 229)
Clinical guideline

Figure: Percentage of patients in each disease phase by clinical guideline.

Conclusion: Most pts enrolled in B-Clear lie in the GZ. There is a need
to understand how best to categorise pts with CHB to improve their
overall management. Observations may be limited by the inclusion
criteria of the study. [on behalf of the B-Clear study group].
Funding: GSK (209668).

THU394
Benign course of HBV reactivations during DAAs in untreated ENI
with HBV-HCV co-infections correlates with different HBsAg Conclusion: In ENI co-infected with HCV, reactivations of HBV during
kinetics compared to NAs treated CHB patients DAAs led to moderate increases of HBV-DNA, without clinically
Piero Colombatto1, Elena Palmisano2, Gabriele Ricco1, relevant events. DAAs caused a significant HBsAg decline during
Daniela Cavallone1, Filippo Oliveri1, Barbara Coco1, Antonio Salvati1, therapy, however, such effect did not appear able to modify the pre-
Veronica Romagnoli1, Lidia Surace1, Maria Linda Vatteroni2, treatment individual profile, which was more favorable in untreated
Mauro Pistello2, Agostino Virdis3, Ferruccio Bonino4, ENI than in CHB under NAs.
Maurizia Brunetto1,5. 1University Hospital of Pisa, Hepatology Unit, Pisa,
Italy; 2University of Pisa, Virology Unit, Pisa, Italy; 3University of Pisa, THU395
Internal Medicine Unit; 4National Reaserch Council; 5University of Pisa Predictors of advanced liver fibrosis in chronic hepatitis B
Email: [email protected] patients in the daily clinical practice
Fadi Abu Baker1, Saif Mahmud Abu Mouch2, Yael Kopelman2,
Background and aims: Direct-acting antivirals (DAA) carry a
Yana Davidov3, Ziv Ben Ari3. 1Hillel Yaffe Medical Center,
potential risk of inducing hepatitis B virus (HBV) reactivations in
Gastroenterology and Hepatology, Hadera, Israel; 2Hillel Yaffe Medical
HBV-HCV co-infected patients ( pts). However, dynamics and out-
Center, Gastroenterology and Hepatology, Israel; 3Sheba Medical Center,
comes may be different according to the phase of HBV infection. Our
Center of liver diseases, Israel
aim was to investigate HBsAg and HBV-DNA kinetics across DAAs
Email: [email protected]
therapy in untreated carriers with HBeAg Negative Infection (ENI)
and in HBeAg negative Chronic Hepatitis B (CHB) pts receiving Background and aims: Staging liver disease severity using liver
Nucleos (t)ide Analogs (NA). biopsy or, more recently, non-invasive tests such as elastography are
Method: We prospectively enrolled 15 (F/M: 4/11, median age: 62.1y) important in guiding surveillance and assisting with treatment
ENI with HBV-DNA persistently 2, 000 IU/ml, and 8 CHB (F/M: 3/6, decisions in chronic hepatitis B (CHB) patients. The use of these tests,
median age: 54.8y) pts under NA (entecavir: 6; tenofovir: 3) with however, is not widely implemented as they are costly, used in
limited centers, and not always covered by health insurances. Thus,

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 POSTER PRESENTATIONS
we aimed to elucidate simple clinical predictors of advanced liver statement. A Body Shape Index (ABSI) was used to the assessment of
fibrosis in patients with CHB in daily practice. abdominal obesity. The International Physical Activity Questionnaire
Method: We conducted a two-center, prospective study, recruiting was used to determine the physical activity level. Associations were
CHB patients presenting to regular clinic visits in our hepatology investigated by logistic regression models.
units. A detailed medical history, including age, gender, ethnicity, Results: Among the 105 outpatients with CHB (mean age, 48.5 ± 12.0
BMI, medical background and medications, HBV infection status and yrs.; 58.1% males; 76.2% without cirrhosis; 23.8% with compensated
treatment, as well as smoking and alcohol drinking habits were cirrhosis), SO, low ALSTI and low HGS were found in 4.8%, 21.9% and
documented. Laboratory results performed within 1 month before or 10.5% patients, respectively. All SO patients had MALFD and
after the clinic visit were documented. During the clinic visit, all sedentary life. In the multivariate analysis, low ALSTI were positively
patients were referred for abdominal ultrasounds and all of them associated with MAFLD, sedentarism and high ABSI. Low HGSBMI was
underwent two-dimensional shear wave elastography (2D SWE) to associated with MAFLD and high ABSI. After adjusting for confoun-
assess hepatic fibrosis. Univariate and multivariable logistic regres- ders, in male patients, cirrhosis was independently associated with
sion analyses were used to determine predictors of advanced fibrosis age >50 yrs., high ABSI and hepatic steatosis.
(F2≤; 7.2KPA<). Conclusion: ASLT abnormalities were associated with MAFLD and
Results: Of the 173 patients included in the final analysis, 40 (22%) abdominal obesity in HBV-chronically infected patients. These
had evidence of advanced fibrosis on 2D SWE. Age > 50 (OR 3.88, CI findings may contribute to the development of effective strategies
1.49–9.73; p = 0.005), ALT > 40 (OR 7.41, CI 2.44–22.4; p = 0.001), HBV to screen the ASLT and metabolic abnormalities in CHB patients,
DNA > 2000 (OR 11.44, CI 3.19–41.02; P < 0.001), moderate to severe independently of the stage of the liver disease.
steatosis on US (OR 5.35, CI 1.82–15.8; P = 0.002) as well as moderate-
excessive alcohol consumption and heavy smoking (>20 pack-years) THU397
were all independent predictors of advanced fibrosis. The course of COVID-19 infection in patients with chronic
Conclusion: We outlined clinical and laboratory variables that may hepatitis B and Delta
effectively identify CHB patients at high risk of advanced liver fibrosis. Yavuz Emre Parlar1, Onur Keskin1, Beril Kirmizigul2, Genco Gencdal3,
These variables, alone or in combination, may guide the use of Mujdat Zeybel3, Mesut Gumussoy4, Ramazan Idilman4,
invasive or non-invasive tests for liver fibrosis assessment in daily Cihan Yurdaydin3. 1Hacettepe University School of Medicine,
clinical practice, especially in low-resource settings. Gastroenterology, Turkey; 2Hacettepe University School of Medicine,
Internal Medicine, Turkey; 3Koc University School of Medicine, Turkey;
THU396 4
Ankara University School of Medicine, Gastroenterology, Turkey
Metabolic associated fatty liver disease is associated with Email: [email protected]
appendicular lean soft tissue abnormalities in patients with
chronic hepatitis B Background and aims: SARS CoV-2-induced COVID-19 disease has
caused as of November 2021 more than 5 Million deaths. Older age
Cecy Maria de Lima Santos1,2, Matheus Duarte Brito2,3,
and co-morbidities such as liver cirrhosis have been associated with
Olívio Brito Malheiro2,4, Tatiana Bering Bering5,
mortality (Bajaj et al, Hepatology 2020, Hamid et al JCG 2021). Among
Maria Isabel Toulson Davidson Correia6, Rosangela Teixeira2,
etiologies of liver disease only alcoholic liver disease was associated
Rodrigo Cambraia2, Gifone Aguiar Rocha7, Luciana Diniz Silva1,2,8.
1 with mortality by multivariate analysis. Chronic hepatitis delta (CHD)
UFMG Faculty of Medicine, Sciences Applied to Adult Health Care Post-
had not been studied in this context. In the current study the course
Graduate Programme, Brazil; 2UFMG Faculty of Medicine, Outpatient
of COVID-19 disease in chronic hepatitis B (CHB) and CHD patients
Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Brazil;
3 was explored in 2 academic hospitals.
UFMG Faculty of Medicine, Medical undergraduate student, Brazil;
4 Method: CHB and CHD patients followed in the gastroenterology
UFMG Faculty of Medicine, Locomotor System Department, Brazil;
5 departments of Hacettepe and Koç University Medical School
UFMT-Universidade Federal de Mato Grosso, Department of Food and
Hospitals in Ankara and Istanbul were included in the study (n:551;
Nutrition, Brazil; 6UFMG Faculty of Medicine, Department of Surgery,
302M/249F). Median age was 47. While 479 of the patients had CHB,
Brazil; 7UFMG Faculty of Medicine, Laboratory of Research in
77 patients had CHD. 372 of 479 CHB patients were receiving nucleos
Bacteriology, Brazil; 8UFMG Faculty of Medicine, Department of Internal
(t)ide analogs (NAs (TDF:221, ETV:107, LMV-TAF:37), 107 patients
Medicine, Brazil
were being followed without treatment. 52 patients had cirrhosis. 52
Email: [email protected]
of 77 CHD patients were receiving NAs. Diagnosis of COVID-19 was
Background and aims: The clinical impact of Metabolic Associated made by PCR detection of SARS CoV-2 RNA in nasopharyngeal swap
Fatty Liver Disease (MAFLD) in patients with chronic hepatitis B (CHB) specimens.
has not been completely clarified. Particularly, the crosstalk between Results: In the CHB group (n:479), 43 patients (5 of them had
sarcopenia and metabolic derangements in CHB is scarcely investi- cirrhosis) were diagnosed with COVID-19 infection. CHB patients
gated. Thus, the aims of this study were to assess the prevalence as with and without COVID-19 infection did not differ in terms of age,
well as the risk factors associated with sarcopenia and its compo- gender and laboratory parameters. No patient had a COVID-related
nents, appendicular lean soft tissue index (ALSTI) and handgrip death. ALT-AST reactivation, defined as an increase of ALT to more
strength (HGS) in HBV-chronically infected patients. than 3x ULN, occurred in 3 patients (6.9%) including hepatic
Method: Sarcopenia was assessed by measurements of appendicular decompensation in 1 cirrhotic patient after COVID-19. None of the
lean soft tissue index [ALSTI; ASLT adjusted for body mass index patients were followed up in the intensive care unit. In CHD patients
(BMI)] and handgrip strength adjusted for BMI (HGSBMI) using dual- (n:77; 37 cirrhotic), 8 patients developed COVID-19 infection and 4
energy-X-ray and dynamometer, respectively. Sarcopenia severity had documented hepatic reactivation. None were receiving treatment
was assessed by gait speed, using the get-up-and-go timed test. for CHD. COVID-19 infection developed in 3 cirrhotic patients, of
Sarcopenia was defined as the lowest quintile for sex specific ALSTI whom one died and one developed hepatic decompensation.
and HGSBMI cut-off values (<0.759 for men and <0.503 for women) Conclusion: The course of COVID-19 infection is not severe in CHB
and (<1.2 for men and <0.65 for women), respectively, modified from patients but maybe so in CHD. This may be due to effective antiviral
the Foundation for the National Institutes of Health Biomarkers treatment in CHB but lack of it in CHD.
Consortium Sarcopenia Project consensus. Sarcopenic obesity (SO)
was defined as the presence of both sarcopenia and body fat
percentage >27, 0% and >38, 0% for men and women, respectively.
MAFLD was defined according to an international expert consensus

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POSTER PRESENTATIONS
THU398 THU399
Serum soluble program cell death-1 is predictive of hepatocellular Parameters related to ALT elevation in patients with HBeAg
carcinoma in untreated chronic hepatitis B patients negative chronic infection
Rachel Wen-Juei Jeng1,2, Yu-Ju Chu3, Mei-Hung Pan3, Hui-Han Hu3, Ulus Akarca1, Merve Gur2, Galip Ersoz1, Zeki Karasu1, Ilker Turan1,
Wun-Sheng Luo3, Chien-Yu Su3, Chen-Tse Chiang3, Chin-Lan Jen3, Fulya Günsar1. 1Ege University, Gastroenterology, Izmir, Turkey; 2Ege
Sheng-Nan Lu2,4, Li-Yu Wang5, Chien-Jen Chen3, Hwai-I Yang3. University, Internal Medicine, Izmir, Turkey
1
Linkou Chang Gung Memorial Hospital, Department of Email: [email protected]
Gastroenterology and Hepatology, Taiwan; 2Chang Gung University,
Background and aims: The majority of patients with chronic
College of Medicine, Taiwan; 3Academia Sinica, Genomic Research
hepatitis B virus infection are in the HBeAg negative chronic infection
Center; 4Kaohsiung Chang Gung Memorial Hospital, Division of
phase. Elevated transaminase levels and exacerbation of hepatitis can
Hepatogastroenterology, Department of Internal Medicine; 5Mackay
be seen in a small number of these patients. Criteria that can predict
Medical College, Taiwan
which patients will have an exacerbation have not yet been clearly
Email: [email protected]
established. If ALT elevation can be predicted in the follow-up of
Background and aims: Soluble programmed cell death 1 (sPD-1) is a patients, recommendations can be made for close follow-up of these
novel immunological marker which has been reported to be patients. In this study, in patients with HBeAg negative chronic
correlated to hepatocellular carcinoma in chronic hepatitis B in a infection who had normal ALT for at least three years, relationships of
case-cohort study. Although it has strong correlations with some viral basal parameters at their first admission with subsequent ALT
markers such as qHBsAg, whether it is a predictor of HCC elevations were investigated.
independent of other known host and viral risk factors remains to Method: The files of all hepatitis B carrier patients who applied to the
be explored. We aimed to investigate the association between sPD-1 Hepatology Clinic since 2005 were reviewed retrospectively. Patients
levels and HCC development. who had at least 4 years of follow-up, had no evidence of advanced
Method: Baseline serum samples from 3408 chronic hepatitis B fibrosis, and had not received antiviral therapy were included in the
subjects in the REVEAL-HBV cohort were assayed for sPD-1 level. study. Those who had other liver disease, who used more than 2 units
Among them, 2934 with available follow-up serum samples were of alcohol per day for men and 1 unit for women, who had HCC and
longitudinally analyzed. The ascertainment of HCC was done through who had systemic disease were excluded from the study. After 3 years
the data linkage with the Taiwan Cancer Registry. Multivariate Cox of normal ALT values, ALT elevation was investigated in patients who
regression analysis was used to estimate the adjusted hazard ratio were followed for at least 1 more year.
(aHR) and 95% confidence interval (CI), adjusted for host and viral Results: A total of 223 patients were included in the analysis. 106
factors. (47.5%) were male and 117 (52.5%) were female. The mean age was 45.1
Results: By end of 2017, 344 HCC cases were newly developed. Both ± 11.8. The mean follow-up period was 7.98 ± 2.91 years. The number of
the baseline and follow-up sPD-1 level were higher in the HCC versus patients whose ALT value exceeded the upper limit of normal was 26
non-HCC patients. Despite there exists linear correlation between (11.7%), and the number of patients with ALT increased more than
sPD-1 and HBsAg level (r = 0.92, P < 0.001) or HBV DNA level (r = 0.59, twice the normal value was 6 (2.7%). While AST, ALP, total protein,
P < 0.001), a dose-dependent increase of adjusted hazard ratio for albumin, urea, creatinine, prothrombin time, cholesterol and HBV DNA
HCC along with higher sPD-1 level was observed [sPD1 <Q1 as levels were significantly different between those with and without ALT
referent, aHR (95% CI) for Q1-Q2, Q2-Q3, ≥Q3: 1.6 (0.9–2.9), P = 0.092; elevations, age and gender were not significant. After three years of
2.9 (1.5–5.5), P = 0.001; and 3.9 (2–7.6), P < 0.001] after adjusting age, follow-up, the parameters associated with ALTelevation were found to
gender, alcohol drinking, cirrhosis, family history, HBeAg serostatus, be ALT > 26 U/L and albumin <4.3 g/dL, the highest HBV DNA level,
HBV DNA and qHBsAg at baseline. This association was even more according to the results of multivariate analysis; It was found that ALT
marked when limited to subjects with low HBV DNA levels (<2000 IU/ > 26 U/L and albumin <4.3 g/dL, the lowest albumin level, and the
ml). By repeat measurement, those with sPD-1 level <944 pg/ml (Q1) lowest leukocyte count were found to be significant in those who
at baseline or subsequent follow-up had minimal or decreased risk of exceeded ALT 2xULN. In our study, prognostic indices were obtained
HCC. according to multivariate analysis in patients with ALT exceeding the
upper limit of normal and ALT >2xULN. The prognostic index obtained
in thosewhose ALTrises more than twice the normal value is = −40.05 +
2.71 (if ALT > 26 and Alb < 4.3)+6.12*Albumin+0.00111*WBC. The
predictive value of ALT elevation of this index was investigated by ROC
analysis. When cut-off >0.13 was taken, AUC = 0.93, sensitivity 83%,
specificity 97% specificity in predicting ALT >2xULN.
Conclusion: A prognostic index derived from ALT, albumin, and WBC
can predict an ALTelevation of >2xULN in patients with HBeAg negative
chronic infection who remained with normal ALT for at least 3 years.

THU400
Clinical evidence for unconventional hepatitis delta virus
infections in endemic countries
Mary Rodgers1, Ana Olivo1, Christopher Lark1, Abbas Hadji1,
Pham Duong2, Nguyen TT Dung2, Acana Susan Elaborot3,
Dora Mbanya4, Mia Biondi5, Jordan Feld5, Gavin Cloherty1. 1Abbott
Laboratories, Lake Bluff, United States; 2National Institute of Hematology
and Blood Transfusion, Hanoi, Viet Nam; 3Uganda Blood Transfusion
Conclusion: sPD-1 is another useful immunological marker in
Service, Kampala, Uganda; 4University of Yaounde I, Yaounde,
addition to the current markers used to predict HCC development
Cameroon; 5Toronto Centre for Liver Disease, University of Toronto,
in untreated CHB patients.
Medicine, Toronto, Canada
Email: [email protected]
Background and aims: Although cell culture and mouse studies have
demonstrated that hepatitis delta virus (HDV) replication can occur in

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 POSTER PRESENTATIONS
the absence of hepatitis B virus (HBV) when other co-infecting 000; and ≥200, 000 IU/ml) and select patients for antiviral therapy in
viruses are present, such as hepatitis C virus (HCV), clinical evidence African patients.
for such unconventional HDV infections has not yet confirmed they Method: Analytical validation was performed using chemilumines-
occur naturally in patients. As conventional HDV infection affects the cent enzyme immunoassay (CLEIA, LUMIPULSE G1200, Fujirebio,
severity and progression of liver disease, it may also have the same Japan) as a reference. Clinical validation was conducted using sera
effects in a potential unconventional co-infection. from 284 treatment-naïve patients with chronic HBV infection and 75
Method: To determine the prevalence of HDV unconventional HDV/ control participants negative for HBV surface antigen (HBsAg)
HCV infections, a series of HBV surface antigen negative (HBsAg-), participated in the PROLIFICA (Prevention of Liver Fibrosis and
anti-HCV positive specimen panels from Cameroon (N = 87), Vietnam Cancer in Africa) programme in The Gambia.
(N = 100), and Uganda (N = 368) were screened for HDV antibodies Results: Using HBcrAg-CLEIA as a reference, the limit of detection of
using two prototype assays on the automated high throughput HBcrAg-RDT was 4.3 log U/ml for serum and plasma, and 4.9 log U/ml
ARCHITECT instrument. for whole blood. None (0/75) of HBsAg-negative samples was
Results: 23 specimens were positive with both anti-HDV assays and 1 detected by HBcrAg-RDT. In 284 treatment-naïve HBsAg-positive
with 1 anti-HDV assay, indicating that the prevalence of potential patients (median age 36 years, interquartile range: 30–45, 66% were
unconventional HDV infections is 3% (11/368) in Uganda, 13.8% (12/ men), hepatitis B e antigen (HBeAg), HBcrAg-RDT, HBcrAg-CLEIA, and
87) in Cameroon, and 2% (2/100) in Vietnam, consistent with the HBV DNA were positive in 13%, 23%, 53%, and 58% of the participants,
higher prevalence of conventional HDV infections in Cameroon and respectively. HBV genotypes were E in 84% and A in 16%. The clinical
Uganda compared to Vietnam. Notably, the reported dual anti-HDV sensitivity and specificity of HBcrAg-RDT to identify highly viraemic
positives identified were also negative for HBV core antigen individuals were: 72.7% and 91.7% to diagnose HBV DNA levels of ≥2,
antibodies (anti-HBc-), evidence that these individuals had not had 000 IU/ml; 86.7% and 88.7% for ≥20, 000 IU/ml, and 91.4% and 86.3%
a past history of HBV infection. However, HDV RNA was not detectable for ≥200, 000 IU/ml, respectively. A simplified HBV DNA-free
in these specimens, confirming that active HDV viremia had been treatment algorithm using HBcrAg-RDT had a sensitivity of 96.6%
cleared in these patients despite detection of active HCV viremia and specificity of 83.2% to identify HBV-infected patients eligible for
(HCV RNA+). antiviral therapy by the European Association for the Study of the
Conclusion: These data serve as the first clinical evidence of Liver (EASL) criteria using the reference tests.
unconventional HDV infections and indicate that unconventional
infections can be cleared even in the continued presence of chronic Table: Performance of HBcrAg-RDT, HBcrAg-CLEIA, and HBeAg-EIA to
HCV infection. This study also highlights the need for additional discriminate clinically important HBV DNA levels in HBsAg-positive
screening for unconventional HDV infections to evaluate their patients (n = 284).
potential impact to patient health. HBV DNA levels

≥2000 IU/ml ≥20 000 IU/ml ≥200 000 IU/ml

THU401
Rapid point-of-care test for hepatitis B core-related antigen HBcrAg HBcrAg HBeAg HBcrAg HBcrAg HBeAg HBcrAg HBcrAg HBeAg
RDT CLEIA EIA RDT CLEIA EIA RDT CLEIA EIA
(HBcrAg) to identify HBV-infected patients eligible for antiviral
therapy. Cut-off values Positive ≥3.6 log Positive Positive ≥4.5 log Positive Positive ≥5.3 log Positive
U/ml U/ml U/ml
Yusuke Shimakawa1,2, Gibril Ndow3,4, Théo Cerceau1, Amie Ceesay3, Sensitivity (%) 72.7 83.3 47.7 86.7 88.9 61.4 91.4 91.4 70.6
Akira Hasegawa5, Atsushi Kaneko5, Katsumi Aoyagi5, Specificity (%) 91.7 83.9 97.6 88.7 90.4 96.0 86.3 93.2 94.9

Jeanne Perpétue Vincent1, Takehisa Watanabe6, Masaya Baba2,

Bakary Sanneh7, Ignatius Baldeh7, Ramou Njie8,9,
Conclusion: HBcrAg-RDT is a rapid (45 minutes), robust (operating
Umberto D’Alessandro3, Maimuna Mendy10, Isabelle Chemin11,
temperature up to 39 °C), and inexpensive alternative to HBV DNA
Mark Thursz4, Maud Lemoine4, Yasuhito Tanaka6. 1Institut Pasteur;
2 quantification potentially allowing the decentralisation of hepatitis
International Research Center for Medical Sciences (IRCMS), Kumamoto
care in areas with limited access to laboratory services.
University; 3Medical Research Council (MRC) Unit The Gambia at the
London School of Hygiene and Tropical Medicine; 4Department of
THU402
Metabolism, Digestion and Reproduction, Imperial College London;
5 Prevalence of HBV infection and receiving antiviral treatment for
Fujirebio Inc.; 6Kumamoto University; 7National Public Health
eligible patients in blood relatives from clustering families of HBV
Laboratories, Ministry of Health, The Gambia; 8Edward Francis Small
infection with unfavorable prognoses and cascading of care
Teaching Hospital, Banjul, The Gambia; 9School of Medicine and Allied
linked to treatment in West China
Health Sciences, University of The Gambia; 10International Agency for
Yuan Yang1. 1The First Affiliated Hospital of Xi’an Jiaotong University,
Research on Cancer (IARC), Lyon, France; 11Centre de Recherche en
Department of Infectious Disease, Xi’an, China
Cancérologie, Université Claude Bernard, Lyon, France
Email: [email protected]
Email: [email protected]
Background and aims: Accumulating evidence had shown that HBV
Background and aims: To eliminate hepatitis B virus (HBV) infection,
infection had the characteristic of family clustering, and higher risk of
it is vital to scale up testing services. However, conventional tools to
progression to cirrhosis or HCC. Although many of the professional
evaluate treatment eligibility, particularly real-time polymerase
organizations provide guidelines related to the prevention and
chain reaction assays (RT-PCR) to quantify HBV DNA, are hardly
treatment of HBV infection, the cascade of care is still poor.
available and affordable in resource-limited settings. We developed a
Method: First- and second-blood relatives from clustering families of
simple, low-cost, lateral flow rapid diagnostic test to detect hepatitis
HBV infection with unfavorable prognoses, which were defined as
B core-related antigen (HBcrAg-RDT) and evaluated its performance
those families in which HBV infection patients occurred in three
to diagnose clinically important HBV DNA thresholds (≥2, 000; ≥20,
successive generations, and there was more than one patient with
HBV-associated cirrhosis of liver or HCC in two generations, were
enrolled in the study, and general information and serum samples
were collected. Biochemical examinations were performed by the

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POSTER PRESENTATIONS
Department of Laboratory, the First Affiliated of Hospital, Xi’an THU403
Jiaotong University. Virologic assessments included, HBV DNA Liver inflammation in asian chronic hepatitis B patients with
(Roche), HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc (Abbott detectable HBV-DNA and normal alanine aminotransferase
Architect quantitative). according to diverse upper limits of normal
Results: Collected the liver function and virological features of the 1, Jiacheng Liu1, Jian Wang2, Li Zhu3, Yiguang Li4, Ming Li5,
568 participants from families with clusters of HBV infection and Zhonghua Lu4, Yuanwang Qiu4, Chuanwu Zhu3, Weimao Ding6, Jie Li2,
unfavorable prognoses included in this study. The patients with Rui Huang2, Chao Wu2. 1Nanjing Drum Tower Hospital Clinical College
positive of HBsAg were 1033, and there were 351 (33.98%) patients of Traditional Chinese and Western Medicine, Nanjing University of
receiving antiviral therapies. There were 451 (43.66%) patients with Chinese Medicine, Department of Infectious Diseases, Nanjing, China;
HBsAg-positive have not received antiviral treatment who should 2
Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing
receive the antiviral treatment according to the 2019 Chronic University Medical School, Department of Infectious Diseases, Nanjing,
hepatitis B Guideline of China, with age over 30 years with family China; 3The Affiliated Infectious Diseases Hospital of Soochow
with cirrhosis or HCC, or less than 30 years and ALT were elevated University, Department of Infectious Diseases, Suzhou, China; 4The Fifth
over upper limit normal (ULN). Patients were lack of awareness of People’s Hospital of Wuxi, Department of Infectious Diseases, Wuxi,
screening before suggesting by the cascading of care linked to China; 5The Affiliated Infectious Diseases Hospital of Soochow
treatment for the blood relatives from clustering families of HBV University, Department of Hepatology, Suzhou, China; 6Huai’an No. 4
infection with unfavorable prognoses. There were 535 participants People’s Hospital, Department of Hepatology, Huai’an, China
with negative of HBsAg, and there were 278 (51.96%) participants Email: [email protected]
with positive anti-HBc and 160 (29.91%) participants with only anti-
HBs positive. Background and aims: Upper limits of normal (ULN) for alanine
aminotransferase (ALT) are different among international guidelines
or recommendations for chronic hepatitis B (CHB). We investigated
the proportion of significant inflammation in Asian CHB patients with
detectable HBV-DNA under diverse ALT ULNs.
Method: CHB patients with detectable HBV-DNA underwent liver
biopsy were included from four hospitals. Liver inflammation and
fibrosis were assessed by Scheuer’s classification. ULN was defined as
40 U/L in EASL 2017 and APASL 2015, 35/25 U/L (male/female) in
AASLD 2018, and 30/19 U/L (male/female) in East Asia recommenda-
tions 2020. The definitions of significant inflammation and fibrosis
were G ≥ 2 and S ≥ 2, respectively.
Results: Of 921 patients included, 640 (69.5%) patients had
significant inflammation, while 577 (62.6%) had significant fibrosis.
85.6% of patients with significant fibrosis and 42.4% of patients
without significant fibrosis had significant inflammation. Among
CHB patients with detectable HBV-DNA and normal ALT, the
proportions of those with significant inflammation was 43.8%
according to the ALT ULN of 30/19 U/L (male/female), while the
corresponding proportions were 53.1% and 48.1% according to the
ULNs of 40U/L and 35/25 U/L (male/female), respectively. In patients
with detectable HBV-DNA and normal ALT levels in absence of
significant fibrosis, the proportions of significant inflammation were
comparable among different ULNs of ALT by 40 U/L (30.7%), 35/25U/L
(27.3%) and 30/19 U/L (25.0%).

Conclusion: There were high prevalence of HBV infection in the

families with clusters of HBV infection and unfavorable prognoses,
and low prevalence of receiving antiviral therapies for patients
eligible for treatment by professional practice guidelines. Cascading
of care linked to treatment in families with clusters of HBV infection,
could improve the treatment initiation rate.

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 POSTER PRESENTATIONS
THU404
Diversity of circulating HBV genomes and impact on viral
infection
Jules Sotty1, Aurélie Schnuriger1, Pierre Bablon1, Bouchra Lekbaby1,
Jeremy Augustin1, Morgane Girier-Dufournier1, Lucas Langlois1,
Celine Dorival2, Fabrice Carrat2, Stanislas Pol3, Helene Fontaine3,
Nazim Sarica4, Christine Neuveut4, Chantal Housset1,
Dina Kremsdorf1, Patrick Soussan1. 1Inserm Sorbonne Université, CRSA
Inserm U938, Paris, France; 2Inserm Sorbonne Université; 3Cochin,
France; 4Institut de génétique humaine, Montpellier, UMR 9002, France
Email: [email protected]
Background and aim: Besides the prototype of HBV infectious
particle containing a 3.2 kb partially double-stranded DNA (wtDNA),
additional circulating virus-like particles containing pregenomic RNA
( pgRNA), spliced-RNA (spRNA) or spliced-derived DNA (defDNA)
genomes have been described. Independently, detection of these
circulating viral genomes may contribute to the clinical management
of HBV infection and/or as a predictive marker of therapy response.
Here, the diversity of circulating viral genomes was investigated in
chronic infected patients then, its impact on viral lifecycle was
explored.
Method: 335 chronic HBV infected patients treated (n = 158) or not
(n = 177) were selected from the Hepather French Cohort.
Pangenomic qPCRs were set up to quantify the four forms of
circulating viral genomes from the same nucleic extract. Principal
component analysis and hierarchical clustering were performed to
characterize the circulating HBV genome diversity. Viral infection of
differentiated HepG2-NTCP cells using blood samples from untreated
patients was achieved to study its impacts on viral replication.
Results: Hierarchical clustering of circulating viral genome diversity
in bloodstream divided untreated patients in 2 clusters. The cluster 1
(C1) was defined by the predominance (>50% of circulating genomes)
of wtDNA while the cluster 2 (C2) contained various amount of the
four viral genomes with a majority of pgRNA, wtDNA and defDNA in
77%, 18% and 5% of cases, respectively. Genomic diversity in C2 was
associated with a higher level of viral load (7.1 ± 7.3 Log10 copies/ml of
wtDNA), compared with C1 (6.6 ± 7.1 Log10 copies/ml of wtDNA; p <
0.001). The greatest proportion of circulating pgRNA forms was
preferentially observed in high replicative patients in C1 and
unexpectedly, in low replicative patients in C2. Analysis of treated
patients reinforced the contribution of HBV replication in the genome
diversity occurrence. In vitro infection with untreated patient samples
from both clusters showed that viral diversity in inoculum modulated
Figure: Liver inflammatory activity in CHB patients with detectable HBV the intracellular viral cycle. Before infection, inoculum enrichment
with different fibrosis stages and ALT levels according to diverse criteria of with pgRNA particles demonstrated their ability to interfere on viral
ALT ULN cycle.
Conclusion: Our data provide evidences for the main role of viral
Conclusion: A quarter of CHB patients with detectable HBV-DNA and
replication in circulating HBV genomes diversity. Novel biomarker of
normal ALT without significant fibrosis had significant inflammation
HBV infection, circulating pgRNA genomes may also contribute to
irrespective of the ALT ULNs. The optimal ULNs of ALT for CHB
modulate the viral cycle in an unconventional process.
patients deserve further investigation and novel biomarkers for liver
inflammation are urgently needed. THU405
Chronic hepatitis delta with normal ALT and hepatitis D viremia
Sena Arici1, Adriana Palom2, Mesut Gumussoy3, Ramazan Idilman3,
Genco Gencdal4, Rafael Esteban5, Mujdat Zeybel4, Maria Buti2,
Cihan Yurdaydin4. 1Gulhane Training and Research Hospital, Internal
Medicine, ANKARA, Turkey; 2Hospital Universitario Valle Hebron,
Department of Gastroenterology, Barcelona, Spain; 3Ankara University,
School of Medicine, Department of Gastroenterology, Ankara, Turkey;
4
Koç University, School of Medicine, Department of Gastroenterology,
ZEYTİNBURNU, Turkey; 5Universitat Autònoma de Barcelona (UAB),
Department of Gastroenterology, Barcelona, Spain
Email: [email protected]
Background and aims: Chronic hepatitis delta (CHD) represents the
most severe form of chronic viral hepatitis and the main cause of
liver-related mortality due to suboptimal therapy. However, there is
data to suggest that CHD runs a less severe course than in the past

Journal of Hepatology 2022 vol. 77(S1) | S119–S388 S297

POSTER PRESENTATIONS
(Rosina et al, Gastro 1999, Wranke et al, JVH 2021). Patients with Median AUROC for use of HBcrAg in predicting HBeAg seroconver-
persistent normal ALT and hepatitis D viremia (PNAV) have been sion, HBsAg loss, treatment response, and relapse after stopping
described for chronic hepatitis C and B but not for CHD. therapy is 0.794, 0.6445, 0.706 and 0.688 respectively. Median
Method: PNAV were arbitrarily defined as patients with normal ALT correlation coefficient (r) of HBcrAg with HBV DNA, qHBsAg, HBV
and hepatitis D viremia on at least four determinations, 3 to 6 months RNA and cccDNA is 0.660, 0.4755, 0.698, and 0.590 respectively.
apart within a duration of 2 years among patients who had never Strength of correlation weakens after antiviral therapy.
received interferon based treatment for CHD. Such patients have been
collected between January 2005 to 2021 in 2 academic hospitals in
Turkey and one in Spain. A total of 19 patients were found out of a
cohort comprising around 420 patients. The 19 patients with PNAV
were compared with sex and age-matched control patients with CHD
at a 1 to 1.5 ratio. Follow*up of patients ranged from 18 months to 12
years.
Results: ALT, AST and GGT levels were lower and platelets were higher
in PNAVs vs control CHD patients (29 IU/L[18–39] vs. 45 [23–178], 30
IU/L[24–43] vs. 52 [21–99] and 18 IU/L [13–48] vs. 57 [14–328], 240
x109/L [88–420] vs.114 [52–309], respectively, p < 0.05 for all
comparisons). HDVRNA levels were similar (3.60 + 1.11 vsç 4.23 +
1.43 IU.ml). Liver biopsy was available in 10 patients. Histologic Conclusion: HBcrAg is a suboptimal biomarker and performs best as
activity index and fibrosis stage were lower in PNAVs vs controls (8[3– predictor of HBeAg seroconversion. Otherwise, its performance is
13] vs 10 [8–14] and 2 [0–4] vs 3 [2–6], p = 0.05 and p = 0.014, moderate at best, and has poor correlation with HBsAg loss and
respectively). In the PNAV group, 2 patients had fibrosis stage 3 and 4 antiviral therapy.
according to Ishak et al and one patient had cirrhosis on biopsy. Three
additional patients had clinical or radiologic evidence of cirrhosis. On THU407
long-term follow-up patients normal ALT persisted. HDV RNA Utilizing phenotyping algorithms as tools for increasing linkage
became undetectable in one patient. to guideline-concordant care in patients at risk for hepatitis B
Conclusion: This study suggests that a small subgroup of CHD Brooke Wyatt1, Anna Mageras1,2, Stephanie Zhang1, Mark Miller1,
patients may present with normal ALT and HD viremia and milder Douglas T Dieterich1, Andrea Branch1. 1Icahn School of Medicine at
liver disease. However, underestimation due to referral bias is also Mount Sinai, New York, United States; 2Icahn School of Medicine at
likely. PNAV patients had compared to CHD patients lower ALT and Mount Sinai, Liver Diseases, New York, United States
GGT and higher platelet counts indicative of milder liver disease. Liver Email: [email protected]
biopsy data confirm the latter. However, 3 out of 19 PNAV had clinical
or histologic cirrhosis and 2 patients had moderate to severe fibrosis Background and aims: An estimated 241, 000 (2.9%) NYC residents
(Ishak score 3 to 4), suggesting that these patients may also need to be are living with chronic hepatitis B virus (HBV) infection. Management
considered for treatment. Thus CHD patients with PNAV represent a of HBV with antiviral drugs can slow disease progression and increase
heterogenous group and need careful assessment. longevity. However, in the United States, only ∼40–60% of patients
with chronic HBV receive guideline-concordant care, and only ∼3% of
THU406 Americans with HBV receive antiviral treatment.
Hepatitis B core related antigen, not as good as it seems: a critique There is a significant need to improve methods for identifying
and systematic review treatment-eligible patients and linking them to care. The Mount Sinai
Yong Chuan Tan1,2, Celina Adraneda1, Ee Jin Yeo1, Guan Sen Kew2, Health System (MSHS) serves the greater NYC area. Through this
Atefeh Khakpoor1, Seng Gee Lim1,2. 1Yong Loo Lin School of Medicine, study, we aim to develop and validate an HBV case-finding algorithm
National University of Singapore, Department of Medicine, Singapore; that identifies diagnosed HBV-infected MSHS patients who are not
2
National University Hospital, Division of Gastroenterology and receiving guideline-concordant antiviral treatment or monitoring, as
Hepatology, Singapore defined by EASL or AASLD. This project builds on our previous success
Email: [email protected] developing an algorithm to identify HCV treatment candidates
performing with a sensitivity of 90.0%, specificity of 97.1%, positive
Background and aims: Hepatitis B core-related antigen (HBcrAg) is a predictive value of 85.7%, and negative predictive value of 98.1%.
new biomarker for Chronic Hepatitis B (CHB) but its performance has Method: We will develop an algorithm to search ∼2.5 million EPIC
not been critically or systematically appraised. electronic medical records (EMRs; data entered 1/2003 to 12/2021).
Method: We reviewed the biological pathway of HBcrAg. We also Death record data will be utilized to identify deceased patients. To
performed a systematic review of PubMed for studies that evaluated enhance impact and portability, the algorithm will be written in SQL a
the role of HBcrAg in predicting important HBV specific clinical versatile, widely used programming language. The algorithm will
events and/or examined the strength of correlation of HBcrAg against automate the interpretation of HBV serological data, ALT values,
other HBV biomarkers. Area under the receiver operating character- demographic information, and data about antiviral medications; and
istic (AUROC) curve values and correlational coefficients were it will estimate fibrosis stage by calculating the FIB-4 score. It will
consolidated to appraise the predictive accuracy and correlational categorize patients as a) receiving AASLD/EASL guideline-concordant
strength of HBcrAg. Median values from the pooled data were used as treatment, b) not receiving guideline-concordant treatment and in
estimates and reported. need of follow-up, c) HBV negative, or d) deceased. Results will be
Results: HBcrAg consists of Hepatitis B core antigen (HBcAg), e stratified by treatment site. The algorithm is being developed
antigen (HBeAg), and 22 kDa precore protein ( p22cr). Individual iteratively, assessing each iteration by performing manual chart
contribution of HBeAg, HBcAg, and p22cr to HBcrAg in HBeAg review at planned stages.
positive CHB patients is 72 ± 10%, 17 ± 8%, and 15 ± 9% respectively. Results: The first iteration of the algorithm identified approximately
The constituent contribution to HBcrAg in HBeAg negative CHB 1, 000 MSHS patients with an HBV DNA viral load >2, 000 IU/ml and
patients is unknown. HBcrAg has a false positive rate of 9.3% and false no record of a prescription for any HBV medication. Manual review of
negative rate of 12–35%. The new iTACT-HBcrAg assay is more a random selection of 100 of these patients’ charts revealed that three
sensitive but does not solve the false positive performance. PubMed patients had died, two were children, and four cleared HBV
search found 58 of 248 papers on HBcrAg suitable for analysis.

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 POSTER PRESENTATIONS
spontaneously; of the remaining 91 patients, only five were on declines of 0.4–0.45 log10IU/ml, both occurring after Grade 3 ALT
treatment. flare. In Cohort C, at Week 48, HBsAg declined by mean 1.4 log10IU/ml
(from mean baseline 4.0 log10IU/ml); 15/18 HBeAg+ vs. 5/10 HBeAg-
patients achieved >1 log10IU/ml HBsAg decline. Larger mean HBsAg
declines were observed in patients with baseline HBsAg >4 log10IU/
ml. Genotype C patients (n = 11) achieved the largest mean HBsAg
decline (1.7 log10IU/ml at Week 48) compared to other genotypes. At
Week 48, 6/28 and 19/28 patients achieved HBsAg <100 IU/ml and
<1000 IU/ml, respectively. At Week 48, HBeAg declined by mean 2.1
log10IU/ml with loss in 7/18 and anti-HBe seroconversion in 6/18.
HBcrAg declined by mean 1.8 log10U/ml. RO7049389+NUC ± Peg-IFN
was safe and well tolerated up to 72 weeks. Two early terminations in
each cohort of A and C were due to non-safety reasons. Grade 2–4
treatment-emergent ALT flares (TEAFs) occurred in 55% of treatment
naïve patients, mainly with concurrent HBsAg declines. Spearman’s
rank correlation analysis showed a significant positive correlation
between Grade 2–4 TEAFs and categorical maximal HBsAg declines
(Cohort B: p = 0.025, rho 0.697; Cohort C: p = 0.017, rho 0.432).
Conclusion: Our preliminary results are highly promising. Once
refined and validated, the algorithm will allow us to identify patients
in need of HBV outreach and care leading to evaluation for hepatitis D
as well. It will also help to highlight clinical settings with suboptimal
HBV care in our healthcare system. Applicable to other health systems
utilizing EPIC EMR, our algorithm will be vital in streamlining case
finding, freeing up resources for patient engagement and care, and
advancing viral hepatitis elimination.

THU408
Hepatitis B virus antigen reduction effect of RO7049389 plus NUC
with/without Peg-IFN in chronic hepatitis B patients
Jinlin Hou1, Edward J Gane2, Wenhong Zhang3, Jiming Zhang3,
Man-Fung Yuen4, Tien Huey Lim5, Rozalina Balabanska6, Qing Xie7,
Piyawat Komolmit8, Xieer Liang1, Wen Zhang9, Xue Zhou9,
Zenghui Xue10, Miriam Triyatni11, Ethan Chen10, Yuchen Zhang9,
Conclusion: RO7049389 did not induce obvious HBV antigen
Qingyan Bo10. 1Nanfang Hospital, Southern Medical University,
reduction in NUC-suppressed patients. RO7049389+Peg-IFN+NUC
Guangzhou, China; 2New Zealand Liver Transplant Unit, The University
led to larger HBsAg declines, especially in difficult-to-treat Genotype
of Auckland, Auckland, New Zealand; 3Huashan Hospital, Fudan
C patients. HBeAg positivity and high HBsAg baseline levels seemed
University, Shanghai, China; 4Queen Mary Hospital, The University of
to positively modulate the ability of RO7049389+Peg-IFN+NUC to
Hong Kong, Hong Kong, China; 5Middlemore Hospital, Auckland, New
reduce HBsAg. Positive correlation between graded TEAFs and
Zealand; 6Acibadem City Clinic Tokuda Hospital EAD, Sofia, Bulgaria;
7 categorical maximal HBsAg declines may be consistent with the
Ruijin Hospital, Shanghai Jiaotong University School of Medicine,
concept of a “good” ALT flare during RO7049389 ± Peg-IFN treatment.
Shanghai, China; 8King Chulalongkorn Memorial Hospital, Bangkok,
Thailand; 9Roche Pharma Research and Early Development, Roche THU409
Innovation Centre Shanghai, Shanghai, China; 10Roche (China) Holding, Presence of HbeAg, HBV DNA in cord blood and down regulation
Shanghai, China; 11F. Hoffmann-La Roche, Basel, Switzerland of TLR9 may act as predictive marker for HBV mother to child
Email: [email protected] transmission
Background and aims: RO7049389 is a Class I HBV core protein Simanta Kalita1, Manash Jyoti Kalita1, Gautam Hazarika1,
allosteric modulator. In addition to potent suppression of HBV Partha Pratim Das2, Sangit Dutta2, Anjan Jyoti Talukdar2,
replication, in mouse model studies, RO7049389 also induced Panchanan Das2, Subhash Medhi3. 1Gauhati University, Bioengineering
HBsAg and HBeAg reduction alongside transient and controlled and Technology, Guwahati, India; 2Gauhati Medical College and
immune responses. Here we report on HBV antigens reduction with Hospital, Guwahati, India; 3Gauhati University, Guwahati, India
RO7049389+NUC ± Peg-IFN in chronic hepatitis B patients Email: [email protected]
(NCT02952924).
Background and aims: Hepatitis B virus infection is a global health
Method: NUC-suppressed patients received RO7043989+NUC
problem which needs special attention mainly due to mother to child
(Cohort A, n = 32); treatment-naïve patients received RO7049389
transmission of HBV. Expression pattern of TLR 9 were analysed in
+NUC without (Cohort B, n = 10) or with (Cohort C, n = 30) Peg-IFN-
venous cum cord blood samples collected from 25 HBsAg+ve mother
alpha for 48 weeks. At Week 48, all patients except those who met
during delivery from Gauhati Medical College and Hospital,
NUC stopping criteria (HBV DNA <LLOQ and HBsAg <100 IU/ml)
Guwahati, Assam.
entered a 24-week NUC-alone follow-up period.
Method: HbsAg, HbeAg and HbeAb were detected using ELISA and
Results: In Cohort A, 30 NUC-suppressed patients completed the
TLR9 mRNA expression is performed by Real time PCR.
study; no obvious changes in HBsAg, HBeAg or HBcrAg were
Results: Serological analysis of the venous blood (N = 25) showed the
observed. In treatment naïve patients, no HBsAg loss occurred
presence of HbeAg in 10 (40%) samples and HBV DNA+ve in 9 (36%)
among 10 Cohort B and 27 Cohort C patients who completed the
samples. Further, in cord blood samples (N = 25) HbsAg was positive
study. In Cohort B, at Week 48, HBsAg, HBeAg and HBcrAg showed
in 17 (68%) and HbeAg was positive in 13 (52%) of the sample. HBV
mean changes from baseline of +0.1, −1.5 log10IU/ml, and −1.2 log10U/
DNA was found to be positive in 13 (52%) of the sample. Among 25
ml, respectively; 2/6 HBeAg+ patients achieved HBeAg loss without
samples, 10 samples (40%) with HbeAg positive status exhibit
anti-HBe seroconversion. Two HBeAg+ patients had maximal HBsAg

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POSTER PRESENTATIONS
downregulation of TLR-9 with mean fold change of 0.55 ± 0.16 ( p =
0.001). Similarly 13 (52%) HbsAg positive cord blood samples (mean
fold change 0.65 ± 0.18, p = 0.007). 14 (56%) venous HBV DNA positive
samples and 12 (48%) cord blood HBV DNA positive samples showed
(mean fold change of 0.53 ± 0.18, p = 0.001; mean fold change 0.58 ±
0.16, p = 0.095) significant alteration in favour of downregulation of
TLR-9 among the study cohort.
Conclusion: In the study, presence of HbeAg and HBV DNA in cord
blood and down regulation of TLR9 may be an indication of vertical
transmission of HBV.
Acknowledgements: The presenting author acknowledges
Department of Science and Technology, Govt. of India, Ministry of
Science and Technology, New Delhi- 110016, for providing DST
INSPIRE Fellowship vide sanction number: No. DST/INSPIRE
Fellowship/2019/IF190163.

THU410 Conclusion: CHD coinfected patients had significantly greater

Patients with CHD coinfection have greater comorbidities, higher comorbidities, HRU and costs than CHB monoinfected patients
healthcare resource use and costs than CHB monoinfection- within an age- and gender-matched cohort of Spanish patients
results from a Spanish national hospital database from a hospital database study over 19 years of duration. These
findings further confirm the need for early linkage to care to alleviate
Maria Buti1, Ankita Kaushik2, Mertixell Ascanio3, Josep Darba4,
future disease progression.
Nandita Kachru2. 1Hospital Universitario Valle Hebron; 2Gilead
Sciences, Inc.; 3BCN Health Economics and Outcomes Research SL; THU411
4
University of Barcelona Clinical features predictive of cirrhosis in a large cohort of
Email: [email protected] patients with chronic hepatitis delta infection- Insights from the
Background and aims: Chronic hepatitis delta (CHD) coinfection D-LIVR trial
among chronic hepatitis B (CHB) patients is associated with higher Ohad Etzion1, Maria Buti2, David Yardeni3, Anat Nevo-Shor4,
morbidity and mortality, given its relatively rapid progression to Daneila Munteanu4, Ingrid Choong5, Lisa Weissfeld6,
cirrhosis and liver-related complications. This retrospective study Naim Abu-Freha7, Rob Howard8, Tarik Asselah9, Pietro Lampertico10,11.
1
aims to compare baseline comorbidities, healthcare resource use Soroka University Medical Center, Department of Gastroenterology and
(HRU) and costs in a matched cohort of adult patients with CHD Liver Diseases, Beer-Sheva, Israel; 2Hospital Universitraio Valle
coinfection versus (vs.) CHB monoinfection in a national hospital Hebronand CIBEREHD del Instituto Carlos III, Liver Unit, Barcelona, Spain;
3
database in Spain. National Institutes of Health, Liver Disease Branch, Bethesda, United
Method: The study included subjects ≥18 years having ≥1 ICD-9/10- States; 4Soroka University Medical Center, Department of
CM diagnosis code for CHD or CHB in the Spanish National Health Gastroenterology and Liver Diseases, Beer Sheva, Israel; 5Eiger
System’s Hospital Discharge Records Database that covers 192 private Biopharmaceuticals, Palo Alto, United States; 6Statistics Collaborative Inc,
and 313 public hospitals, with >40 million patients during the study Washington, DC, United States; 7Soroka University Medical Center,
period (Jan 1, 2000 to Dec 31, 2019). CHD and CHB cohorts were Department of Gastroenterology and Liver Diseases, Beer Sheva, Israel;
8
identified from Jan 1, 2001 to Dec 31, 2018 (identification period) with Veridical Solutions, Del Mar, CA, United States; 9AP-HP, Hôpital Beaujon,
their first diagnosis defined as the diagnosis date, having ≥12 months Department of Hepatology, Clichy, France; 10Foundation IRCCS Ca’
of continuous enrollment before and after the diagnosis date. CHD Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and
and CHB patients were age- and gender-matched (1:3) to evaluate Hepatology, Milan, Italy; 11CRC “A. M. and A. Migliavacca” Center for Liver
incremental differences in HRU and costs. Disease, Department of Pathophysiology and Transplantation, University
Results: The study reported 12, 317 patients diagnosed with CHD or of Milan, Milan, Italy
CHB, of which 3, 079 (159 CHD; 2, 920 CHB) met the inclusion Email: [email protected]
criteria; matching yielded 125 CHD and 312 CHB patients. The male
Background and aims: Chronic hepatitis delta (CHD) infection is the
to female ratio was significantly higher in CHB vs CHD (roughly 10:1
most rapidly progressive form of chronic viral hepatitis. Data
vs. 5:1; p = 0.0281). CHD patients were significantly more likely to
regarding predictors of cirrhosis in chronic HDV is fairly limited
have decompensated (50.40% vs. 20.51%; p < 0.0001) and compen-
especially in those of younger age. The aim of the current analysis was
sated cirrhosis (24.80% vs. 9.62%; p < 0.0001) than CHB patients;
to assess the predictive value of demographic and laboratory
hepatocellular carcinoma and liver transplant rates were at 6.40% vs.
variables as well as non-invasive test scores of liver fibrosis for
2.56% and 5.60% vs. 1.92%, respectively. Charlson Comorbidity Index
diagnosis of biopsy proven cirrhosis in a large cohort of patients CHD.
score was significantly higher for CHD than CHB (0.84 vs. 0.36; p <
Method: We prospectively evaluated 407 patients with compensated
0.0001). CHD patients also reported significantly higher rates of
liver disease who enrolled in the on-going Phase 3 HDV D-LIVR trial
smoking (27.20% vs. 9.94%; p < 0.0001), HCV (11.20% vs. 5.45%; p =
(NCT03719313). At baseline, demographic data and anthropometric
0.0403), HIV (15.20% vs. 5.13%, p = 0.0013), substance abuse (23.20%
measurements were collected. Liver stiffness measurement (LSM)
vs. 5.77%; p < 0.0001) and alcohol abuse (20% vs. 7.37%; p = 0.0003)
and/or Fibrotest were performed, and blood tests were obtained for
than CHB patients. Mean per patient per year (PPPY) all-cause
complete blood count, biochemical panel, and HBV and HDV
healthcare costs totaled to €13, 716 in CHD vs. €7, 177 in CHB,
serologic and viral markers. All patients underwent liver biopsy
representing 91% higher cost in CHD than CHB patients ( p = 0.0002).
within 45 days from non-invasive testing. Descriptive statistics were
Consequently, pharmacy, inpatient and outpatient costs were
used to summarize demographic and clinical baseline patient
significantly higher for CHD vs. CHB patients; all p < 0.05. Mean
characteristics, and chi-square test was used for univariate and
PPPY length of stay was significantly higher for CHD than CHB
multivariate analysis. A series of logistic regression models was fit to
patients (14.20 vs. 10.20; p < 0.0001). Further, mean PPPY number of
the data including cirrhosis status as the outcome, and LSM results,
admissions and readmissions for CHD vs. CHB were at 2.10 vs. 1.80
AST, ALT, platelets, albumin, bilirubin, Fibrotest score, HBsAg, and BMI
and 1.30 vs. 0.90, respectively.
as potential covariates.

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 POSTER PRESENTATIONS
Results: Of the 407 patients enrolled to the study, median age of 42.7 Conclusion: Approximately 20% of patients with chronic HBV
(SE 0.55), 69.4% male, with 108 (26.5%) patients showing biopsy infection in IT phase have significant liver pathological damage. The
confirmed cirrhosis. Of those, 48 (44.4%) were ≤45 years of age. In diagnostic model of YG/S (<0.05 or ≥0.30) has certain evaluation value
patients ≥ 45 years of age (146), 60 (41%) were cirrhotic at baseline. In for significant liver pathological damage and can avoid liver biopsy to
univariate analysis, the following variables were statistically signifi- a certain extent.
cantly associated with cirrhosis: older age ( p < 0.001), BMI ( p = 0.02),
AST ( p < 0.001), but not ALT, platelet count ( p < 0.001), albumin ( p = THU413
0.002), INR ( p = 0.006), HBsAg levels ( p = 0.03) by both LSM and Provider factors shaping hepatitis delta screening
Fibrotest ( p < 0.001 for both). In multivariate logistic regression, the Dewan Giri1, Rohit Nathani2, Randy Leibowitz2, Carolina Villarroel3,
model that best fit the data included age, platelets, and Fibrotest Sidra Salman2, Gres Karim3, Bo Hyung Yoon4, Amreen Dinani5,
result as covariates ( p = 0.04, 0.007 and 0.008, for age, platelets and Ilan Weisberg6. 1Icahn School of Medicine at Mount Sinai Beth Israel,
Fibrotest, respectively). Odds ratio was 1.032 (CI 1.001–1.064) for age, Department of Medicine, New York, United States; 2Mount Sinai
0.98 (CI 0.98–0.99) for platelet count and 7.168 (CI 1.647–31.191) for Morningside/West, Medicine; 3Mount Sinai Beth Israel, New York, United
Fibrotest. In the subgroup of patients ≤ 45 years of age, the model that States; 4Mount Sinai Beth Israel/Morningside/West; 5Icahn School of
best fit the data included LSM results, platelets, and INR ( p = 0.04 for Medicine at Mount Sinai; 6New York Presbyterian Brooklyn Methodist
all). Odds ratio was 1.079 (CI 1.002–1.162) for LSM, 0.99 (CI 0.98–1.0) Hospital, United States
for platelet count and 66.9 (CI 1.176->999.999) for INR. Email: [email protected]
Conclusion: In a large cohort of patients with CHD, alarmingly high
Background and aims: Hepatitis Delta is a defective RNA Virus that
rates of cirrhosis were seen among younger patients with compen-
requires Hepatitis B Virus to propagate. Infection results in the most
sated liver disease. A high index of suspicion for cirrhosis should be
severe form of viral hepatitis and is associated with a high risk of
maintained in this population especially as it ages, and in those
cirrhosis and hepatocellular carcinoma. The global burden remains
showing subtle changes in markers of synthetic liver function and
undefined despite its discovery almost 40 years ago. Increased public
portal hypertension.
health measures saw a decrease in the incidence of HDV in the 1990s
THU412 leading to under-testing and a complacent view of the HDV public
Establishment of a new diagnostic model for significant liver health problem. Despite the resurgence of interest seen in the last few
tissue damage in patients with chronic hepatitis B virus infection years, it continues to remain unrecognized, especially in the primary
in the immune tolerance phase care setting. The objective of our study is to assess physician
knowledge, attitudes, and behaviors toward hepatitis delta screening.
Airong Hu1, Suwen Jiang1, Xiaojun Shi2, Dedong Zhu3, Zheyun He2,
Method: An anonymous 6-question internet-based survey assessing
Chenqian Zhu4, Lukan Zhang4. 1HwaMei Hospital, University of Chinese
knowledge, attitudes, and behavior around HDV was sent to internal
Academy of Sciences, Ningbo Institute of Liver Diseases, Ningbo, China;
2 medicine residents, primary care providers (PCP), gastroenterolo-
HwaMei Hospital, University of Chinese Academy of Sciences, Liver
gists, and Gastroenterology Fellows at tertiary care hospital systems,
Disease Department, Ningbo, China; 3HwaMei Hospital, University of
New York, USA from 2/1/2022 through 03/20/2022.
Chinese Academy of Sciences, Liver Oncology Department, Ningbo,
Results: Approximately 200 surveys were sent, and a total of 121
China; 4Medical School of Ningbo University, Graduate School, Ningbo,
(60%) responses were completed. There were 75 responses from PCP
China
and 46 responses from Specialty Care Providers. Gastroenterologists
Email: [email protected]
and fellows were more likely to order HDV antibody than HDV RNA as
Background and aims: To establish a new diagnostic model for a screening test than PCP (66% and 61% vs 18% and 22%). A substantial
judging significant liver tissue damage in patients with chronic portion of PCPs (50%) and residents (33%) were unsure about
hepatitis B virus (HBV) infection in the immune tolerance (IT) phase. appropriate screening tests for HDV. Less than one-third of PCPs
Method: The clinicopathological data of 275 patients in the IT phase (26%), residents (24%), and fellows (28%) identified chronic hepatitis
who underwent liver biopsy from January 2015 to November 2020 B (CHB) in combination with additional risk factors (CHB +RF) as a
were included. According to the liver pathological changes, patients criterion for HDV screening. Gastroenterologists were evenly divided
were divided into <G2 group and ≥G2 group, <S2 group and ≥S2 between all CHB and CHB +RF patients (48% vs 44%) for screening.
group, non-significant liver pathological damage group (GS0 group, Majority (97%) of the participants acknowledged that HDV infection
<G2 + <S2) and significant liver pathological damage group (GS1 contributed to disease progression, 78% agreed that patients who
group, ≥G2 and/or ≥S2). The liver pathological changes and clinical have cleared HDV are at risk for re-infection and 63% agreed with the
features, the diagnostic models and their evaluation values for statement that the majority of the patients with HDV cleared the
significant liver pathological damage were analyzed. infection with treatment. Lack of knowledge of screening guidelines
Results: Among 275 patients, 43 cases (15.64%) with liver histologic and lack of comfort interpreting results were the two most commonly
activity ≥G2, 30 cases (10.91%) with liver fibrosis ≥S2, and 55 cases cited barriers to HDV screening.
(20.00%) met the liver pathological damage (GS1, ≥G2 and/or ≥S2).
The correlated independent risk factors affecting significant liver
pathological damage were age, levels of hepatitis B e antigen, γ-
glutamyltransferase, platelet, alkaline phosphatase and alanine
aminotransferase ( p <0.05). The established diagnostic models
included YG (≥G2), YS (≥S2), and YG/S (GS1). The diagnostic values
of YG/S were the highest for ≥G2 and GS1, the diagnostic values of YG
and YS were the highest for ≥S2. The threshold of YG/S was 0.18, the
sensitivity, specificity and negative predictive value were 78.18%,
73.64% and 93.10%, respectively. When YG/S <0.05, the sensitivity,
negative predictive value and negative likelihood ratio were 98.18%,
97.96% and 0.08, respectively. When YG/S ≥0.25, the specificity and
positive likelihood ratio were 90.45% and 5.14, respectively. When
YG/S ≥ 0.30, the specificity and positive likelihood ratio were 95.91%
and 9.33, respectively.

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POSTER PRESENTATIONS
Conclusion: There are significant gaps in knowledge among THU415
providers regarding HDV. Our quest to eliminate HDV should start Trends in decompensated cirrhosis and hepatocellular carcinoma
with disease awareness, develop familiarity with guidelines and diagnosis among people with a hepatitis B notification in New
testing. South Wales: a population-based data linkage study
Syed Hassan Bin Usman Shah1, Maryam Alavi2, Behzad Hajarizadeh1,
THU414 Gail Matthews2, Marianne Martinello1, Mark Danta3, Janaki Amin4,
Changes of enhanced liver fibrosis score predict hepatocellular Matthew Law5, Jacob George6, Gregory Dore1. 1The Kirby Institute,
carcinoma in chronic hepatitis B patients receiving antiviral UNSW Sydney, Viral Hepatitis Clinical Research Program, Sydney,
treatment Australia, 2The Kirby Institute, UNSW Sydney, Viral Hepatitis Clinical
Yan Liang1, Terry Cheuk-Fung Yip1, Che To Lai1, Shuk Man Lam1, Research Program, Sydney, Australia; 3St Vincent’s Hospital Sydney,
Yee-Kit Tse1, Vicki Wing-Ki Hui1, Henry LY Chan2, Darlinghurst, Australia; 4Macquarie University, Department of Health
Vincent Wai-Sun Wong1, Grace Wong1. 1Department of Medicine and Systems and Populations, Macquarie Park, Australia; 5Kirby Institute,
Therapeutics, the Chinese University of Hong Kong, Hong Kong; 2Union Kensington, Australia; 6Westmead Hospital, Westmead, Australia
Hospital, Hong Kong Email: [email protected]
Email: [email protected]
Background and aims: Population-level trends and factors asso-
Background and aims: Enhanced liver fibrosis (ELF) score is a widely ciated with hepatitis B virus (HBV)-related decompensated cirrhosis
used non-invasive assessment for liver fibrosis. We aimed to derive (DC), hepatocellular carcinoma (HCC), and liver mortality are crucial
and evaluate an algorithm based on ELF score changes at three years to evaluate therapeutic intervention impacts.
apart to predict hepatocellular carcinoma (HCC). Method: Trends in HBV-DC and -HCC diagnoses and liver-related
Method: Antiviral treated chronic hepatitis B (CHB) patients who had mortality in New South Wales, Australia, were determined through
two stored serum samples at about three years apart were included. linkage of HBV notifications (1993–2017) to hospital admissions
ELF score was assessed by retrieving the two stored serum samples. (2001–2018), mortality (1993–2018), and cancer registry (1994–
Baseline was defined as the date of the first ELF results. The primary 2014) databases. Late HBV notification was defined as notification at
end point was the cumulative incidence of HCC. or within two years of DC and HCC diagnosis. Cox proportional
Results: There were 445 CHB patients (mean age: 51.6 ± 10.3 years; hazards regression and multivariable logistic regression analyses
male: 73.9%) included, among whom 57 (12.8%) patients developed were performed to evaluate factors associated.
HCC during the mean follow-up of 158 months. At baseline, 171 Results: Among 59, 911 people with HBV notification, 1, 196 (2.0%) DC
(38.4%) and 274 (61.6%) patients had mild/moderate and severe and 1, 001 (1.7%) HCC diagnoses, and 1, 158 (1.9%) liver-related deaths
fibrosis respectively by ELF score (cutoff: 9.8). About three years later, were documented. Since early 2000s, DC and HCC diagnoses
35.7%, 59.6% and 4.7% of patients had ELF score improved, stable and numbers increased; however, age-standardised incidence decreased
deteriorated, respectively. 150 patients with continuous low ELF score from 2.58 and 1.99 in 2003 to 0.96 and 0.95 per 1, 000 person-years
had lowest risk of HCC (4.0%). 21 patients with deteriorated ELF score (PYs) in 2017. Similarly, age-standardised liver mortality decreased
had HCC risk increased from 5.8% to 19.0%. 159 patients with ELF score from 2.64 in 2003 to 0.97 per 1, 000 PYs in 2017. Among people with
improved had HCC incidence reduced from 17.2% to 10.7%. 115 DC and HCC diagnoses, late HBV notification declined from 41% and
patients with continuous high ELF score had highest HCC risk (26.1%). 40% during 2001–2009 to 28% and 26% in 2010–2018, respectively.
(Figure) The cumulative incidence of HCC was significantly different Predictors of DC diagnosis included older age (birth <1944, adjusted
between these four groups ( p <0.001). hazard ratio [aHR] 8.15, 95% CI 6.26, 10.61), alcohol-use disorder (aHR
7.19, 95% CI 5.83, 8.86) and HCV co-infection (aHR 2.17, 95% CI 1.74,
2.70). Predictors of HCC diagnosis included older age (birth<1944,
aHR 11.61, 95% CI 8.63, 15.61) and male gender (aHR 3.65, 95% CI 2.90,
4.59).

Conclusion: The algorithm based on ELF score changes at three years

apart is a good predictor of HCC in CHB patients receiving antiviral
treatment.

Conclusion: In an era of improved antiviral therapies, HBV liver

morbidity and mortality risk has declined. HCV co-infection and
alcohol-use disorder are key modifiable risk factors to HBV disease
burden.

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 POSTER PRESENTATIONS
THU416 Conclusion: HBsAg seroprevalence in ethnic minorities is higher
Point of care screening tests for hepatitis B and commitment of a than the general population and warrants targeted screening. Most of
dedicated nurse lead to succesful linkage to care of ethnic the identified patients meet the indication for treatment, counseling
minorities to prevent intrafamilial transmission or HCC surveillance. In addition,
Axelle Vanderlinden1,2, Erwin Ho2,3, Liesbeth Govaerts2, Bo De Fooz2, the use of POCT and commitment of a dedicated nurse can overcome
Pierre Van Damme4, Peter Michielsen2,3, Thomas Vanwolleghem2,3. previously identified barriers for linkage to care.
1
University of Antwerp, Viral Hepatitis Research Group, Laboratory of
Experimental Medicine and Pediatrics, Antwerpen, Belgium; 2Antwerp THU417
University Hospital, Department of Gastroenterology and Hepatology, Prediction of comprehensive prognosis through computed
Edegem, Belgium; 3University of Antwerp, Viral Hepatitis Research tomography analysis using deep learning algorithm in patients
Group, Laboratory of Experimental Medicine and Pediatrics, Antwerpen, with chronic hepatitis B
Belgium; 4University of Antwerp, Vaxinfectio, Antwerpen, Belgium Jeongin Yoo1, Heejin Cho2, Dong Ho Lee1,3, Eun Ju Cho2. 1Department
Email: [email protected] of Radiology, Seoul National University Hospital, Seoul, Korea, Rep. of
South; 2Department of Internal Medicine and Liver Research Institute,
Background and aims: In low endemic countries, screening for Seoul National University College of Medicine, Seoul, Korea, Rep. of
hepatitis B surface antigen (HBsAg) in migrants is cost-effective to South; 3Institute of Radiation Medicine, Seoul National University
reduce the disease burden of hepatitis B virus (HBV) infections, but Medical Research Center, Seoul, Korea, Rep. of South
linkage to care (LTC) remains a challenge. We previously found Email: [email protected]
outreach screenings for HBV using point of care tests (POCT) to result
in a 2.5 times higher LTC compared to venepunctures in an Asian Background and aims: Computed tomography (CT)-based metrics,
migrant population. In the current study we compared LTC between such as spleen, liver volume or body fat area, has been reported to be
different ethnic groups screened for HBsAg with POCT in an outreach associated with liver-related or metabolic outcomes; however, the
setting. A secondary objective, was to compare the estimated HBsAg prognostic value of artificial intelligence-based CT metric analysis has
seroprevalence for ethnic minorities to the established prevalence in not been much studied yet. We aimed to evaluate the comprehensive
the general population in order to guide future screening initiatives. prognosis through CT analysis using deep learning algorithm in
Method: Opportunistic outreach screenings using finger prick Vikia patients with chronic hepatitis B (CHB).
HBsAg tests were performed at municipal integration classes Method: Consecutive patients without hepatic decompensation
between 11/2017 and 03/2021. If tested positive, an appointment events who underwent contrast-enhanced abdomen CT for hepato-
was given immediately at the outpatient hepatology clinic for follow- cellular carcinoma (HCC) surveillance between January 2005 and
up and confirmation of HBsAg positivity in blood. A dedicated nurse June 2016 were included. CT images were processed in an automated
contacted identified patients via phone, social media or home visits analysis software program using convolutional neural network
to motivate them for further linkage to care. The latter was defined as (DeepCatch and MEDIP, MedicalIP, Seoul, Korea). We assessed the
having received medical care from a hepatologist, a blood test and an cumulative incidence (CI) of the occurrence of HCC, hepatic
abdominal ultrasound. decompensation, and diabetes mellitus (DM), and identified the
Results: A total of 521 persons with different ethnicities (Asia, significant predictors of each outcome. The optimal cutoff values
Middle-East and Africa) were serologically screened using POCT tests. related to each outcome was obtained using the minimal p value
The seroprevalence for HBsAg was 3.45% (18/521) and was signifi- approach method.
cantly higher compared to that of the general population (i.e. 0.66% in Results: A total of 3041 patients were included and retrospectively
2003 ( p < 0.0001)). All HBsAg-positive patients were linked to care reviewed. During the median follow-up period of 10.3 years, HCC
and assessed by a hepatologist. LTC for all ethnicities combined ( p < occurred in 141 patients, and a larger spleen volume was significantly
0.0001), for Sub-Saharan African patients ( p = 0.023) and Middle- correlated with HCC development ( p < 0.001). 103 patients experi-
Eastern patients ( p < 0.0001) was significantly higher compared to enced hepatic decompensation, and spleen volume was also
the previously observed rate of 34.38% (11/32 patients) using significantly associated with decompensation ( p < 0.001). DM devel-
venepunctures as a screening method, but without the commitment oped in 127 patients, and only the abdominal visceral fat area (VFA)
of dedicated nurse. Among the HBV infected patients, 22.22% (4/18), showed a significant association with DM development ( p = 0.002).
83.33% (15/18) and 22.22% (4/18) met criteria for treatment The optimal cutoff spleen volume was estimated to be 197 ml for HCC
indication, intrafamilial transmission risk and HCC surveillance development and 259 ml for the occurrence of decompensation. In
respectively. Despite COVID-19 pandemic, linkage to care remains addition, the optimal cutoff of abdominal VFA for DM development
high using POCT and through the commitment of a dedicated nurse. was predicted to be 7604 mm2. The estimated 5-year, 10-year, and 15-
However, the time frame between screening and the first hospital year CI of HCC occurrence with spleen volume >197 ml were 4.2%,
visit is significantly higher ( p = 0.0049) during the COVID-19 7.5%, and 9.5%, respectively, and were approximately two times
pandemic than in the pre-pandemic period. higher than in those of 1.7%, 2.8%, and 4.3% with spleen volume
≤197 ml ( p < 0.001). For hepatic decompensation, the estimated 5-

Figure: (abstract: THU417)

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POSTER PRESENTATIONS
year, 10-year, and 15-year CI were 2.8%, 6.7%, and 9.7%, respectively, THU419
with greater than 259 ml in spleen volume, compared with 1.9%, 3.2%, Prevalence rates and eligibility for antiviral treatment against
and 5.0% with less than 259 ml of spleen volume ( p = 0.001). In DM hepatitis B in Casamance, Senegal
development, the estimated 5-year, 10-year, and 15-year CI were 1.0%, Victor Arendt1, Mame Aisse Thioubou2, Kalilou Diallo2,
2.6%, and 5.8% with more than 7604 mm2 in abdominal VFA, Henri Goedertz3, Daouda Diouf4, Benjamin Sambou4, Chabi Bindia4,
significantly different from 0.6%, 1.4%, and 2.5% respectively below Ousseynou Cisse5, Salimata Camara4, Noel Manga2,
7604 mm2 of abdominal VFA ( p = 0.001). Esther CalvoLassoDelaVeiga1, Boubacar Diouf4. 1Centre Hospitalier de
Luxembourg, Infectious Diseases, Luxembourg, Luxembourg; 2Hôpital de
Conclusion: A larger spleen volume was significantly associated with
la Paix, Gastroenterology, Ziguinchor, Senegal; 3SANACCESS, Psychology,
HCC occurrence and hepatic decompensation, and a higher abdom-
Luxembourg, Luxembourg; 4Enda Santé, Epidemiology, Ziguinchor,
inal VFA was strongly correlated with DM development in patients
Senegal; 5Centre de Sante Silence, Medicine, Ziguinchor, Senegal
with CHB. Automatically measured spleen volume and abdominal
Email: [email protected]
VFA might be used as relevant prognostic biomarkers in CHB patients.
Background and aims: HBV infection is a major public health
THU418 problem in Casamance, southern Senegal. A cohort of HBV carriers
Analysis on the normal threshold of alanine aminotransferase has been set up within the framework of the CARES program. The
level based on liver pathology in patients with chronic hepatitis B objective of this study was to assess the prevalence of HBV in the
Airong Hu1, Suwen Jiang1, Xiaojun Shi1, Dedong Zhu2, Zheyun He3, region and the antiviral treatment needs of patients in this cohort
Lukan Zhang4, Chenqian Zhu4. 1HwaMei Hospital, University of Chinese based on current recommendations.
Academy of Sciences, Ningbo Institute of Liver Diseases, Ningbo, China; Method: Descriptive multicenter cohort study of patients followed in
2
HwaMei Hospital, University of Chinese Academy of Sciences, Liver four health facilities in the region (Bignona and Ziguinchor health
Oncology Department, Ningbo, China; 3HwaMei Hospital, University of centers, Regional and La Paix hospitals), carried out as part of the
Chinese Academy of Sciences, Liver Disease Department, Ningbo, China; CARES program from January 01, 2019 to December 31, 2021.
4
Medical School of Ningbo University, Graduate School, Ningbo, China Screening for HBsAg was performed with kits from Rapid Signal TM
Email: [email protected] HBsAg Serum/Plasma Dipstrip (Orgenics ltd Israel). Treatment
Background and aims: To comparatively analyze the liver pathology eligibility was assessed based on age, family history of severe HBV-
related disease, degree of fibrosis, Hbe antigen, viral load and
and clinical characteristics in chronic hepatitis B virus (HBV) infected
patients with normal alanine aminotransferase (ALT) of different transaminase levels according to WHO, EASL and the TREAT-B score.
Results: HBV prevalence rates were: 8, 8% in blood donors, 9, 7% in bus
upper limits of normal (ULN), and to explore the normal threshold of
drivers, 7, 7% in fishermen; 8, 5% in health care workers, 6% in women
ALT for initiating treatment.
Method: The clinical data of 667 chronic HBV infected patients who living with HIV (WLHIV), 5, 5% in pregnant women, 0% (0/88) in
children born to WLHIV. We included 1449 HBsAg positive patients.
underwent liver biopsy from January 2014 to December 2020 were
included in this study. The inclusion criteria were ALT <ULN and HBV The mean age was 35.6 years with a sex ratio (M/F) of 1, 37. The
predominant circumstances of screening were: blood donation (368
DNA positive (>30 IU/ml). According to the ULNs of ALT, the enrolled
cases), symptoms or medical consultation (306 cases), antenatal
patients were divided into ALT I group (male for <30 IU/L, female for
<19 IU/L), ALT II group (30 IU/L ≤male <35 IU/L, 19 IU/L ≤female <25 screening (167 cases), routine or occupational health visit (148 cases)
and a screening campaign (151 cases). To assess the need for
IU/L) and ALT III group (35 IU/L ≤male <40 IU/L, 25 IU/L ≤female <40
IU/L). The clinicopathological characteristics and their correlation, treatment we analyzed the available results of the following tests:
viral load (969/1449); transaminases and GGT (1153/1449); HBe
and the ALT cut-off value for significant liver pathological damage
antigen assay (846/1449), Fibroscan (830/1449), AST-platelet ratio
were analyzed.
Results: The constituent ratios of GS II (G ≥ 2 and/or S ≥ 2) in the index (609/1449), Fib-4 score (608/1449), history of cirrhosis or
hepatocellular carcinoma in first degree relatives (8/463). The
three groups were 26.05% (99/380), 32.03% (41/128) and 46.54% (74/
159), respectively. And there were significant differences in the mean complete panel of parameters was available in only 315 patients.
Ridit values of G and S and the constituent ratios of G II (≥G2), S II The proportion of eligible patients according to the different
recommendations was 6, 3% (WHO 2015), 8, 9% (WHO simplified),
(≥S2) and GS II among the three groups ( p < 0.001). There were
significant differences in the constituent ratios of gender and HBsAg 7, 6% (EASL 2017), 8% (TREAT-B).
Conclusion: The prevalence of HBV in Casamance remains high. The
staining positivity, and the levels of ALT, aspartate aminotransferase
proportion of HBV patients eligible for antiviral treatment ranges
(AST), APRI, LIF-5 among the three groups ( p < 0.01). The positively
correlated factor that affect the liver tissue damage was γ-glutamyl- from 6, 3 to 8, 9% with only small differences according to the
different consensus recommendations (WHO 2015, EASL 2017,
transferase level, and the negatively correlated factors were PLT,
albumin/globulin and HBV DNA levels. The ALT thresholds for G I TREAT-B).
(<G2) and G II, S I (<S2) and S II, GS I (<G2 + <S2) and GS II in total THU420
patients were 21.5 IU/L, 22.5 IU/L, and 25.6 IU/L, respectively. And
Comorbidities, and not viral load, are predictors of cirrhosis in
those of male patients were 25.6 IU/L, 23.5 IU/L and 25.6 IU/L,
AgHBe-negative chronic infection
respectively. Those of female patients were 17.5 IU/L, 22.5 IU/L and
Sara Archer1, Luís Maia1, Catarina Afonso2,3, Jose Manuel Ferreira1,
25.5 IU/L, respectively.
Teresa Moreira1, Marta Rocha1, Tiago Pereira Guedes1, Isabel Pedroto1.
Conclusion: There are statistically significant differences in the 1
Centro Hospitalar Universitário do Porto, Portugal; 2Instituto de
significant liver pathological damage in chronic HBV infected patients
Ciências Biomédicas Abel Salazar, Portugal; 3Instituto de Ciências
with normal ALT of different ULN. The normal threshold (diagnostic
Biomédicas Abel Salazar, Porto, Portugal
cut-off value) of ALT for judging significant liver pathological damage
Email: [email protected]
is recommended to be adjusted to 25 IU/L.
Background and aims: There is an ongoing debate about the
heterogeneity of the definition of HBeAg-negative chronic HBV
infection (formerly inactive carriers, IC), which patients to treat, and
how comorbidities can influence its natural course. The aim of our
study is to assess risk factors, including higher viral load (VL) and
increased ALT, for cirrhosis.

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 POSTER PRESENTATIONS
Method: This is a retrospective cohort of chronic HBV hepatitis utilities were higher in cHBV patients than in cHCV patients (except
patients with at least 2 consultations between 2010–2020 in a for advanced liver disease) and higher when determined based on
western center mediterranean terciary centre. Demographic and the EQ-5D-3L than when derived from a combination of all
clinical data were retrieved. Individuals with less than 1 year of instruments. Utility estimates decreased with disease progression,
follow-up, HCV or HIV co-infection and with insufficient data were with the development of cirrhosis having the largest impact while LT
excluded. Statistical analysis was performed using SPSS. As per EASL seems to allow for some recovery.
guidelines, upper limit of normal (ULN) of 40U/L for ALT was
considered.
Results: 635 patients were included, of which 340 as IC. From these,
53.5% were men with mean current age 56.16 ± 13.4 years, mean
follow-up of 10.14 ± 8 years, during which 4.1% developed cirrhosis.
Liver-related mortality was 0.9%. 14.5% patients had excessive alcohol
consumption; 12.4% diabetes, 15.9% arterial hypertension and 18.2%
dyslipidemia.
Risk factors for cirrhosis: diabetes (OR 4.8, p = 0.002), arterial
hypertension (OR 7.3, p = 0.000), dyslipidemia (OR 4.46, p = 0.004),
alcohol (OR 4.91, p = 0.002), ALT > ULN or VL > 2000 IU/ml (OR 5.32, p
= 0.005). On multivariate analysis including age and follow-up time,
none was an independent predictor.
When analysed separately, alcohol (OR 18.31, p = 0.031) predicted
cirrhosis in patients with both ALT < ULN and VL < 2000 IU/ml, while Figure: Results of the MAs by utility instrument and health state
in the others diabetes (OR 4.4, p = 0.028) and arterial hypertension Conclusion: There is a large body of available literature reporting on
(OR 5.4, p = 0.012) were the main predictors. This may be justified as utilities of patients living with cHCV, less in cHBV, but a paucity of
alcohol abuse has less influence in ALT values. studies in cHDV. The results show a large heterogeneity in reported
The cut-off of 2000 IU/ml for VL did not predict development of health state utilities, likely due to the variation in the methods used
cirrhosis in any group of patients. and health states considered. The most comprehensive set of health
Conclusion: In our cohort, comorbidities, and not VL, are predictors state utility estimates were derived using EQ-5D for cHCV and from a
of cirrhosis in IC. Treating HBV in these patients may not be as combination of instruments for cHBV. This is the first meta-analysis of
relevant as controlling comorbidities. Our results support EASL utilities in chronic viral hepatitis which could be used in future
current guidelines. economic evaluations.
THU421
A systematic literature review and meta-analysis of primary
sources reporting health state preference values in chronic
hepatitis B, C, and D Immune-mediated and cholestatic disease:
Ankita Kaushik1, Sarah Hofmann2, Mariajoão Janeiro2, Clinical aspects
Geoffrey Dusheiko3,4, Andrew Lloyd5, Filipa Aragão2,6. 1Gilead
Sciences, Inc., Foster City, California, United States; 2Maple Health Group,
New York, United States; 3University College London, Medical School, THU422
London, United Kingdom; 4King’s College Hospital, London, United Hepatitis B transmission in early life in very remote Aboriginal
Kingdom; 5Acaster Lloyd Consulting Ltd, London, United Kingdom; communities in northern Australia
6
Universidade NOVA de Lisboa, NOVA National School of Public Health, Richard Sullivan1,2,3, Jane Davies1,2, Paula Binks1, Melita McKinnon1,
Public Health Research Centre, Lisbon, Portugal Roslyn Dhurrkay1, Kelly Hosking1,4, Sarah Bukulatjpi5,
Email: [email protected] Stephen Locarnini6, Margaret Littlejohn6, Steven YC Tong1,7,
Background and aims: Chronic viral hepatitis is associated with Joshua Saul Davis1,8. 1Menzies School of Health Research, Charles
severe patient impairment and reduction in health-related quality of Darwin University, Darwin, Australia; 2Department of Infectious
life (HRQoL). This is also reflected in low patient health state Diseases, Royal Darwin Hospital, Darwin, Australia; 3Department of
preference values (utilities) for severe health states. Utilities for Infectious Diseases, Immunology and Sexual Health, St George and
health states are essential variables for cost effectiveness analyses for Sutherland Clinical School UNSW, Kogarah, Australia; 4Population and
treatments. This study aimed to derive utilities for health states in Primary Health Care, Top End Health Service Northern Territory, Darwin,
chronic hepatitis B (cHBV), C (cHCV) and D (cHDV) through a Australia; 5Miwatj Health Aboriginal Corporation, Northern Territory,
systematic literature review (SLR) and meta-analyses (MA). Australia; 6Victorian Infectious Diseases Reference Laboratory, Peter
Method: Electronic literature databases (EMBASE and MEDLINE) Doherty Institute for Infection and Immunity, Royal Melbourne Hospital
were searched for primary articles that reported health state utilities and University of Melbourne, Melbourne, Australia; 7Victorian Infectious
for cHBV, cHCV or cHDV. Health states evaluated include Metavir Disease Service, The Royal Melbourne Hospital and Doherty Department
fibrosis stages F0 to F4, decompensated cirrhosis (DC), hepatocellular University of Melbourne at the Peter Doherty Institute for Infection and
carcinoma (HCC), post-liver transplant (LT), post-LT in year (Y1), and Immunity, Melbourne, Australia; 8John Hunter Hospital, New Lambton
post-LT in year 2 and beyond (Y2+). MAs were performed with Heights, Australia
utilities based on EQ-5D-3L and based on a combination of Email: [email protected]
instruments, also including EQ-5D-5L, HUI3, HUI2, SF-6D, SF-36, Background and aims: Chronic hepatitis B is a public health concern
and standard gamble (SG), time trade-off (TTO) or visual analogue in Aboriginal communities of northern Australia with prevalence
scale (VAS) techniques. almost four times the non-Aboriginal population in the Northern
Results: The SLR identified 22 studies that derived utilities for cHBV Territory. Infection is suspected to occur in early life, however, the
and/or cHCV but none for cHDV. There was considerable heterogen- mode of transmission and vaccine effectiveness is not known in this
eity in the methods adopted for utility elicitation and in the health population. WHO has set a target for hepatitis B elimination by 2030;
states evaluated. Non-cirrhotic (NC; F0 to F3) and compensated elimination in this disproportionately affected population will
cirrhosis (CC; F4) were the most evaluated health states. Mean require understanding of transmission and vaccine effectiveness.

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POSTER PRESENTATIONS
Method: We conducted the study at four very remote communities. were observed between HBV patients transplanted for decompen-
We approached mothers who were Hepatitis B surface antigen sated cirrhosis and those for HCC. Almost all HBV patients were
(HBsAg) positive and gave birth between 1988 and 2013. We obtained treated with a combination therapy of HBIG and NA after LT and we
hepatitis B serology, immunisation and birth details. If both mother recorded only 2 cases of transitory HBV reactivation, with no
and child had hepatitis B viral DNA detected, we performed viral consequences on liver function.
whole genome sequencing.
Results: We included 20 mothers and 38 of their children. The
median age of the children was 8.8 years (IQR 5.7–13.0). Of 33
children with results available, 8 (24.2%, 95%CI 11.1–42.3) were anti-
hepatitis B core (anti-HBc) positive, 3 (9.1%, 95%CI 1.9–24.3) of whom
were also HBsAg positive. Hepatitis B immunoglobulin (HBIg) had
been given at birth in 29 (76.3%, 95%CI 59.8 − 88.6) children and 26
children (68.4%, 95%CI 51.3–82.5) were fully vaccinated. Of the 3
children who were HBsAg positive, all had received HBIg at birth and
two were fully vaccinated. Of the 5 who were anti-HBc positive and
HBsAg negative, 4 had received HBIg at birth and one was fully
vaccinated. Whole genome sequencing revealed one episode of
mother to child transmission.
Conclusion: Although uncommon, there is ongoing transmission of
hepatitis B in Aboriginal communities of northern Australia despite
vaccination, and is likely occurring by both vertical and horizontal
routes. Prevention will require ongoing investment to overcome the
many barriers experienced by this population in accessing care.

THU423
the changing scenario of HBV chronic related disease in the Conclusion: HBV still remains one of the most common indication to
transplant setting LT, both for end stage liver disease and hepatocellular carcinoma.
Sara Battistella1, Martina Gambato1, Umberto Cillo1, Alberto Zanetto1, Thanks to high barrier NAs the mortality in the waiting list is
Alessandro Vitale1, Enrico Gringeri1, Marco Senzolo1, Patrizia Burra1, decreased during the last years.
Francesco Paolo Russo1. 1University of Padova, Department of Surgery,
THU431
Oncology and Gastroenterology, Italy
Outcomes of pregnancy in patients with autoimmune hepatitis in
Email: [email protected]
the Netherlands
Background and aims: Hepatitis B virus (HBV) related chronic liver Susan Fischer1, Elsemieke de Vries1, Ynto de Boer2,
disease is one of the most common indication for liver transplant- Adriaan Van der Meer3, Robert De Man3, Johan Kuyvenhoven4,
ation (LT), for both decompensated cirrhosis and hepatocellular Michael Klemt-Kropp5, Tom Gevers6, E.T.T.L. Tjwa7, Edith Kuiper8,
carcinoma (HCC). Introduction of nucleos (t)ide analogues (NA) Marc A.M.T. Verhagen9, Philip W. Friederich10, Bart Van Hoek1. 1Leiden
significantly modified the natural history of the disease in the pre- University Medical Center (LUMC), Gastroenterology and Hepatology,
and post- transplant setting, preventing decompensation of liver Leiden, Netherlands; 2Amsterdam UMC, locatie VUmc, Gastroenterology
disease, disease recurrence and increasing post-LT patient and graft and Hepatology, Amsterdam, Netherlands; 3Erasmus MC,
survival. This study aimed to assess the evolution of admission and Gastroenterology and Hepatology, Rotterdam, Netherlands; 4Spaarne
management of patients affected by HBV-related liver disease in the Hospital Hoofddorp, Gastroenterology and Hepatology, Hoofddorp,
WL for LT relatively to the introduction and spreading of high barrier Netherlands; 5Noordwest Ziekenhuisgroep locatie Alkmaar,
NA and to evaluate overall long-term graft and patient survival after Gastroenterology and Hepatology, Alkmaar, Netherlands; 6Academic
LT. Hospital Maastricht, Gastroenterology and Hepatology, Maastricht,
Method: All adults with HBV listed for LT at Padua University Hospital Netherlands; 7Radboud University Medical Center, Gastroenterology and
between 01.2006 to 12.2020 were retrospectively evaluated. Patients Hepatology, Nijmegen, Netherlands; 8Maasstad Hospital,
were divided in two groups according to their indication to inclusion Gastroenterology and Hepatology, Rotterdam, Netherlands;
in the WL (decompensated cirrhosis group: patients listed with MELD 9
Diakonessenhuis Utrecht, Gastroenterology and Hepatology, Utrecht,
>15 with or without HCC; HCC group: patients with MELD <15 and Netherlands; 10Meander Medical Center, Gastroenterology and
presence of HCC). Patients were further divided according to the time Hepatology, Amersfoort, Netherlands
of inclusion in the WL (2006–2013 and 2014–2020). For each patient Email: [email protected]
we evaluated the antiviral treatment and HBV DNA at the time of
inclusion in WL and the type of prophylaxis after LT. Patient survival Background and aims: Data regarding the outcomes of pregnancy in
were calculated using Kaplan Meier curves and comparison between patients with autoimmune hepatitis (AIH) are limited. This study
different groups were performed using Log-Rank test. focuses on the effects of pregnancy in AIH patients and neonatal
Results: From 01.2006 to 12.2020 a total of 1502 patients included in outcomes.
the WL for LT, among them 186 patients were HBV infected. One Method: A retrospective multicenter cohort study was performed at
fourth of patients had HBV DNA detectable at the time of inclusion in the Leiden University Medical Centre (LUMC) in collaboration with nine
the WL and 86% were on antiviral treatment. Almost 60% of patients participating hospitals from the Dutch Autoimmune Hepatitis Study
were wait-listed for decompensated disease, 30% of them had HCC as Group in the Netherlands. Data concerning maternal and neonatal
well. Eventually 31 patients were excluded from the waiting list: 17 outcomes during and after pregnancy were collected from medical
for HCC progression, 3 for not liver related causes and 11 for stability records in AIH patients with pregnancy. Risk factors were identified
of the disease, principally after the introduction of high barrier NA using logistic regression analysis to examine the association of defined
treatment. A total of 29 patients died in the waiting list, mainly during risk variables with adverse maternal and neonatal outcomes.
the first period of the study, and 126 patients underwent LT with a Results: 93 pregnancies in 47 women resulted in 66 deliveries (71%)
median waiting time of 6 months. The overall survival after LT was with a live birth rate of 98.5%. Preterm birth was mentioned in 20% and
90% at 1 year and 80% at 5 years. No significative difference in survival 19% of the children were born dysmature. 34% of the neonates were
admitted to the hospital after birth. Flares of disease activity occurred in

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 POSTER PRESENTATIONS
4.5% during pregnancy, and in 26% of the postpartum episodes. The cirrhosis or obit. The role of SARS-CoV-2 seems relevant, however
absence of biochemical remission at conception was identified as risk other factors associated should be considered: mechanical ventila-
factor for the occurrence of postpartum flares (Odds ratio (OR) 6.8, 95% tion for a long time; high doses of vasopressors and possible severe
Confidence Interval (CI) 1.6–7.65). Flares in the year before conception hemodynamic instability; prolonged stay in the intensive care unit
were identified as a risk factor for the occurrence of gestational flares and the ketamine used.
(OR 21.6, CI 1.7–282.0) and were associated with the occurrence of post-
partum flares (p = 0.01). Maternal hypertensive disorders during THU433
pregnancy occurred in 15%. Women who were partially in remission Enhanced liver fibrosis score correlates with transient
were at higher risk for loss of biochemical remission after delivery (OR elastography in patients with treated autoimmune hepatitis
10.0, CI 1.5–67.0) and to develop hypertensive disorders during Anna Stoelinga1, Elsemieke de Vries1, Maarten Tushuizen1,
pregnancy (OR 10.3, CI 1.5–68.6). No risk factors were found for the Albert Stättermayer2, Xavier Verhelst3, Bart Van Hoek1. 1Leiden
occurrence of adverse neonatal outcomes. Cirrhosis was found a risk University Medical Center (LUMC), Gastroenterology and Hepatology,
factor for miscarriages (OR 3.4, CI 1.1–10.8). No other correlations Leiden, Netherlands; 2Medical University of Vienna, Wien, Austria;
3
between the presence of cirrhosis and adverse outcomes for both Ghent University Hospital, Gent, Belgium
mother and child were observed. Email: [email protected]
Conclusion: Pregnancy in women with AIH ended in childbirth in 71%.
Background and aims: Cirrhosis is an important prognostic factor for
There was a high incidence of spontaneous abortion, prematurity,
long-term survival of patients with autoimmune hepatitis (AIH).
dysmaturity compared to the general population. The rate of post-
Little is known about progression of fibrosis during adequate therapy.
partum flares of AIH was similar to previous literature. Absence of
The Enhanced Liver Fibrosis score (ELF-score) has not been validated
biochemical remission at conception and a flare in the year prior to
in patients with AIH. The aim of this study is to evaluate the
conception increases the risk of maternal complications during and
diagnostic accuracy of the ELF test for fibrosis compared to transient
after pregnancy. Lastly, cirrhosis was found a risk factor for miscarriages.
elastography (TE).
THU432 Method: Patients with AIH or AIH-variant syndrome, treated for a
Cholangiopathy after severe COVID-19: what do we know so far? minimum of 6 months at baseline (BL) were eligible for inclusion.
Serum samples of all patients were taken and TE was done
Valéria Ferreira de Almeida e Borges1, Helma Pinchemel Cotrim2,
simultaneously at BL and after one year. Patients were divided into
Marcelo Simão Ferreira3, José Humberto Caetano Marins1,
two groups: complete biochemical remission (CR) (group 1) and
Haroldo Luis Oliva Gomes Rocha1,
incomplete remission (group 2) at BL. ELF-scores and its components
Leonardo Augusto Dias Nascimento1, Mayra Machado Fleury Guedes1,
were calculated from the collected serum. We investigated if there is a
Julia Esteves Guerra1. 1Universidade Federal de Uberlândia, Uberlândia,
correlation between the ELF score and liver elastography for severe
Brazil; 2Universidade Federal da Bahia, Medicine School, Brazil;
3 fibrosis. Cut-off for cirrhosis (=F4 fibrosis) at TE was >16 kPa. A cut-off
Universidade Federal de Uberlândia, Medicine School, Brazil
for the ELF score was determined for cirrhosis in a receiver operator
Email: [email protected]
characteristics (ROC) curve analysis.
Background and aims: From 2001 to 2018, before the Covid-19 Results: A total of 66 patients in three academic hospitals in the
pandemic, at least 16 studies described a type of secondary sclerosing Netherlands, Belgium and Austria were included. 68.2% were female,
cholangitis (SSC) in critically ill patients. During the pandemic, mean age at inclusion was 51.20 years (±17.24), median treatment
similar cases of cholangiopathy were observed in patients with severe duration at inclusion was 6.50 years (IQR: 2.00–11.00). During follow-
Covid-19. The hypotheses suggested to explain this disease will be a up, two patients died (3%), two patients were lost-to-follow-up (3%).
liver ischemia related to micro thrombosis associated with SARS- Group 1 consisted of 35 patients (53.0%), of whom 16 (45.7%) had
CoV-2 or direct biliary epithelial infection. To describe the clinical moderate-severe fibrosis. Group 2 consisted of 31 patients (47.0%). 24
characteristics of cholangiopathy in patients who survived the ICU patients (77.4%) had none-mild fibrosis. ELF-score (9.46 vs 9.27, p =
period with severe Covid-19. 0.58) and liver stiffness (8.70 vs 7.10 kPa, p = 0.078) at BL did not differ
Method: Adult patients diagnosed with Covid-19, who presented significantly between the groups. Liver stiffness did not change after
severe cholestasis were included. All of them had prolonged stay in the one year irrespective of remission status.
ICU, needed for mechanical ventilation, high doses of vasopressors, There was a positive correlation between ELF-score and liver stiffness
ketamine use, and prone positioning. Criteria for SSC were elevated (rho = 0.48, p < 0.001). For F4 fibrosis, the area under the curve was
levels of alkaline phosphatase (ALP) and bilirubin; no previous history calculated as 0.83. The cut-off value was determined at 9.68.
of liver disease; magnetic resonance cholangiopancreatography sensitivity, specificity, positive and negative predictive value were
(MRCP) or endoscopic retrograde cholangiopancreatography (ERCP), 86.4%, 71.7%, 40.4% and 95.9%, respectively.
and or liver biopsy, which showed the biliary tract alterations. The
diagnosis of Covid-19 was with a positive PCR test in all cases.
Results: A total of 24 patients were include. Mean age was 57 ± 10 years
and 66% were male. All developed cholestasis, after a mean of 20 days.
The peak mean level of ALP was 1541 U/L, gamma-glutamyl transferase
2366U/L, aspartate aminotransferase 248, alanine aminotransferase
was 276 U/L, and total bilirubin 10 mg/dL. MRCP were performed in 75%
of cases, ERCP in 37% and cholangioscopy in one. The most relevant
finding was rarefaction of the intrahepatic bile ducts in all, and bacterial
cholangitis in two cases. Biliary casts were removed in seven of nine
cases who underwent ERCP. All patients presented elevated levels of
ALP, GGT and bilirubin after discharge, regardless of the ursodiol used.
During the mean follow-up of 205 days, 6 patients progressed to
cirrhosis and 7 (29%) to death. At follow-up, the most recent bilirubin
dosage was on average 19 mg/dL in the group that died and 3.7 mg/dL in
the group that survived (p < 0.001).
Conclusion: In this simple of 24 cases, patients with Covid-19
presented a severe cholestatic disease and with rapid progression to

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POSTER PRESENTATIONS
Conclusion: ELF-score shows good diagnostic accuracy in patients THU435
with AIH under immunosuppressive treatment irrespective of Acute hepatitis after COVID-19 vaccine: case series by the
remission status. A cut-off at 9.68 can rule out severe fibrosis in International autoimmune hepatitis group (IAIHG) and the
patients with AIH. Change in remission status did not significantly european reference network on hepatological diseases (ERN
change fibrosis with ELF-score or TE results. RARE-LIVER)
Greta Codoni3, Maria Alejandra Gracia Villamil4,
THU434 Albert Stättermayer5, Agustin Castiella6, Christoph Schramm7,8,
Rationale for evaluation of PLN-74809 treatment in participants Jan-Philipp Weltzsch7, Marcial Sebode7, Christine Bernsmeier9,
with primary sclerosing cholangitis in Phase 2a study INTEGRIS- Wikrom Karnsakul10, Ana Lleo11, Tom Gevers12, Limas Kupcinskas8,13,
PSC Nélia Hernandez14, Andreas Cerny2, Michele Ghielmetti15,
Eric Lefebvre1, Greg Cosgrove1, Simon Wong1, Erica Park2, Fiona Cilli1, Diego Vergani16, Giorgina Mieli-Vergani16, Jose Pinazo Bandera17,18,19,
Theresa Thuener1, Marzena Jurek1, Scott Turner1, Martin Decaris1, Maria Isabel Lucena20,21,22, Raul J. Andrade20,21,22, Yoh Zen16,
Johanna Schaub1. 1Pliant Therapeutics, Inc., South San Francisco, United Richard Taubert8,23. 1USI Università della Svizzera italiana, Lugano,
States; 2Pliant Therapeutics, Inc. (at time of study), South San Francisco, Switzerland; 2Epatocentro Ticino, Lugano, Switzerland; 3Università della
United States Svizzera Italiana, Facoltà di Scienze Biomediche, Lugano, Switzerland;
Email: [email protected] 4
Hospital Italiano de Buenos Aires, Argentina; 5Medical University of
Background and aims: Transforming growth factor beta (TGF-beta) Vienna, Wien, Austria; 6Donostia Unibertsitate Ospitalea, Donostia,
signalling is a key driver of liver fibrosis. In primary sclerosing Spain; 7University Medical Center Hamburg-Eppendorf, Hamburg,
cholangitis (PSC), integrins over-expressed on injured cholangiocytes Germany; 8European Reference Network on Hepatological Diseases (ERN
(alpha-v/beta-6) and myofibroblasts (alpha-v/beta-1) regulate TGF- RARE-LIVER); 9Centre for Gastrointestinal and Liver Diseases, Basel,
beta activity. PLN-74809 is an oral, once-daily, dual-selective Switzerland; 10The Johns Hopkins University School of Medicine,
inhibitor of integrins alpha-v/beta-6 and alpha-v/beta-1 in develop- Baltimore, United States; 11IRCCS Humanitas Research Hospital Milan,
ment for the treatment of PSC and idiopathic pulmonary fibrosis. It Milano, Italy; 12Maastricht University Medical Center, Maastricht,
has shown favourable tolerability in over 280 healthy participants, Netherlands; 13Lithuania University of Health Sciences, Kaunas,
reduced TGF-beta signalling and achieved high target engagement in Lithuania; 14Hospital de Clínicas, Facultad de Medicina, Montevideo,
human lungs. Pre-clinical evaluation of antifibrotic activity resulting Uruguay; 15Medical Practice, Mendrisio, Switzerland; 16King’s College
from dual integrin inhibition was performed to support clinical Hospital, United Kingdom; 17University Hospital, Málaga, Spain;
18
evaluation. IBIMA, Málaga, Spain; 19UMA, Málaga, Spain; 20Virgen de la Victoria
Method: PLN-74809 was administered orally for 6 weeks in BALBc. University Hospital-IBIMA, Málaga, Spain; 21University of Malaga,
Mdr2-/- mice with established fibrosis. A tool alpha-v/beta-6 and Málaga, Spain; 22CIBERehd, Málaga, Spain; 23Medizinische Hochschule
alpha-v/beta-1 inhibitor compound, PLN-75068, was tested thera- Hannover, Hannover, Germany
peutically in a diet-induced mouse model of biliary fibrosis using 3, Email: [email protected]
5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC). Hepatic collagen Background and aims: Autoimmune phenomena and clinically
was quantified by hydroxyproline (OHP) and collagen proportionate apparent autoimmune diseases, including autoimmune-like hepa-
area (CPA) and TGF-beta signalling by phosphorylated SMAD3 titis, have increasingly been reported after SARS-CoV-2 infection, and
( pSMAD3) levels. An ex vivo study evaluated the effects of 2-day after vaccination against it. It has been suggested that post-COVID19
treatment with PLN-74809 on the expression of profibrotic genes, vaccine hepatitis may be a novel clinical entity, urgently requiring
COL1A1 and COL1A2, in precision-cut liver slices (PCLivS) from tissue investigation of well characterized cases. Our international case
explants of participants with biliary fibrosis (n = 2 PSC; n = 2 primary collection aims at investigating in a standardized way, clinical,
biliary cholangitis [PBC]). A review of available blinded safety data serological and pathological features of a large number of patients
from the enrolling Phase 2a study in participants with PSC was with acute hepatitis after COVID-19 vaccination.
performed (NCT04480840). Method: Patients with acute hepatitis within 2 months from last
Results: PLN-74809 dose-dependently reduced OHP (up to ∼30%, p < vaccine dose and available liver biopsy, but without a history of
0.05), CPA (up to ∼50%, p < 0.05) and pSMAD3 (up to ∼40%, p < 0.001) autoimmune hepatitis, are included. Clinical data at diagnosis and
in the BALBc.Mdr2-/- mouse model, as well as COL1A1 and COL1A2 outcome after a follow-up of 6 months are collected. Histology and
gene expression (up to ∼30%, p = 0.0789) in PCLivS from tissue autoimmune serology are centrally reviewed/tested.
explants of participants with PSC and PBC. PLN-75068 reduced OHP Results: 42 patients included so far; 27 (65%) females; median age 59
(up to ∼20%, p < 0.05) in DDC-injured mice in a dose-dependent years (range 16–78). Vaccine type: 16 BNT162b2; 9 ChAdOx1 nCov-
manner. PLN-74809 was well tolerated in participants with PSC. Most 19; 6 mRNA-1273; 5 Gam-COVID-Vac; 1 BBIBP-CorV; 2 ChAdOx1
adverse events (AEs) were mild; none were severe. The most common nCov-19 + BNT162b2; 2 Gam-COVID-Vac + ChAdOx1 nCov-19; 1 Gam-
AE was mild headache. One participant experienced serious AEs at COVID-Vac + mRNA-1273. Locally tested serology was positive for
least 20 days after the last dose of study drug, deemed not related by anti-nuclear antibody (ANA) in 31 cases; anti-smooth muscle
the investigator. One participant prematurely discontinued due to antibody (ASMA) in 14, anti-mitochondrial antibody (AMA) in 3; 12
COVID-19. PLN-74809 pharmacokinetics in participants with PSC were ANA and ASMA-positive; none was anti-soluble liver antigen or
were consistent with those of healthy participants. anti-liver kidney microsomal antibody positive; 11 were seronega-
Conclusion: Pharmacological inhibition of integrins alpha-v/beta-6 tive. Mean IgG was 16.8 g/l (range: 6.6–34.4). Median time from
and alpha-v/beta-1 demonstrated antifibrotic activity in two models vaccination to hepatitis diagnosis: 24.6 days (IQR 10.7–38). 12 had
of biliary fibrosis and in PCLivS from participants with PSC or PBC. pre-existing extrahepatic autoimmune conditions.
Available safety findings from participants with PSC enrolled in the Central histological review of the first 7 cases showed isolated central
ongoing Phase 2a INTEGRIS-PSC study, continue to support the perivenulitis (n = 2) or mixed portal and lobular hepatitis with
favourable tolerability profile of PLN-74809. interface injury and confluent necrosis (n = 5; Figure). Aggregates of
plasma cells and eosinophils (>5 cells/hpf) were observed in 4 and 3
cases, respectively.

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 POSTER PRESENTATIONS
compared to patients without progression (non-progression cohort)
(median transplant-free survival:17 years vs. undefined; p = 0.021).

35/42 patients were treated with immunosuppressive drugs; 33 Conclusion: Our data indicate that implementation of a scheduled
steroids, 1 azathioprine, 1 azathioprine + steroids; all but one being ERCP program with interventions performed in predefined intervals
still on treatment. Mean follow-up is 5 months; one patient died of improves transplant-free survival in patients with PSC. Furthermore,
extrahepatic cause 7 months after the diagnosis of hepatitis. All we reveal that a progression in cholangiographic findings after the
treated patients responded satisfactorily. first ERCP procedure enables a prediction of the future disease
Conclusion: acute hepatitis arising after COVID-19 appears to be a activity and outcome.
heterogeneous condition: long-term follow-up will help under-
standing if in some cases the vaccine triggers autoimmune hepatitis THU437
or if it is a novel drug-induced nosological entity. Immune response and safety in standard and third dose SARS-
CoV-2 vaccination in patients with autoimmune hepatitis on
THU436 immunosupressive therapy, a prospective cohort study
Scheduled endoscopic program for patients with primary Kristin Jorgensen1,2, Adity Chopra3, Joseph Sexton4, Anne T Tveter4,
sclerosing cholangitis improves transplant-free survival and Johannes R. Hov2,5,6,7, Ingrid Jyssum4,7, Lise Sofie H. Nissen-Meyer3,
enables early risk stratification John T Vaage3,7, Silje W Syversen4, Guro L Goll4,
Burcin Özdirik1, Wilfried Veltzke-Schlieker1, Jule-Marie Nicklas1, Fridtjof Lund-Johansen3,8, Jørgen Jahnsen1,7. 1Akershus University
Hilmar Berger1, Daniel Schmidt1, Silke Leonhardt1, Andreas Adler1, Hospital, Dept. of Gastroenterology, Norway; 2Oslo University Hospital,
Tobias Müller1, Alexander Wree1, Frank Tacke1, Michael Sigal1. Norwegian PSC Research Centre; 3Oslo University Hospital, Department
1
Charité Universitätsmedizin Berlin, Department of Hepatology and of Immunology, Norway; 4Diakonhjemmet Hospital, Division of
Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Rheumatology and Research, Norway; 5Oslo University Hospital,
Mitte (CCM), Berlin, Germany Research Institute of Internal Medicine, Norway; 6Oslo University
Email: [email protected] Hospital, Section of Gastroenterology, Department of Transplantation
Medicine; 7University of Oslo, Institute of Clinical Medicine, Norway;
Background and aims: Primary sclerosing cholangitis (PSC) is 8
University of Oslo, ImmunoLingo Convergence Center
associated with biliary obstructions that can require endoscopic Email: [email protected]
retrograde cholangiopancreatography (ERCP). While beneficial short-
term effects of ERCP are well documented, follow-up interventional Background and aims: vaccines against SARS-COV-2 are proven
strategies are less defined and their long-term impact is debated. efficacious and safe in the general population. Data on vaccine
Here, we evaluated the outcome of a scheduled program that has response in patients with autoimmune hepatitis (AIH) are currently
been implemented at our tertiary liver center for over more than 20 lacking. The aim of this study was to evaluate immunogenicity and
years. safety following standard and three dose SARS-CoV-2 vaccination in
Method: Within our program, ERCPs were performed at regular and patients with AIH on immunosuppressive therapy.
pre-defined intervals to follow-up or treat previously detected biliary Method: this prospective, observational study included adult AIH
stenosis and/or to remove concrements. In this retrospective cohort patients and healthy controls, both groups receiving standard two
study, we evaluated the outcomes of this scheduled programmed dose SARS-CoV-2 vaccination. The patients were voluntarily allotted a
ERCP approach in comparison to patients, who received endoscopic third vaccine dose according to the national vaccine strategy.
interventions only on clinical demand. The primary end point was Antibodies to the receptor-binding domain (RBD) of SARS-CoV-2
transplantation-free survival. The secondary end points were spike proteins were analyzed in serum samples collected prior to, and
occurrence of hepatic decompensation, recurrent cholangitis epi- after vaccination, and serologic response was defined as >70 AU/ml.
sodes, development of hepatobiliary malignancies and endoscopy- Results: a total of 46 patients (median age 56 years [IQR 47–63], 32
related adverse events. [70%] women), and 1114 healthy controls (median age 43 years [IQR
Results: We included 268 consecutive patients with diagnosed PSC, 32–55], 854 [77%] women) were included in the study. All patients
135 receiving scheduled ERCP and 133 receiving on demand ERCP. had compensated liver disease (Child Pugh A), the median disease
The rates of transplant-free survival since initial diagnosis (median 27 duration was 6.2 years (IQR 4.2–9) and 80% received BNT 162b2 as
vs. 19 years; p = 0.027) and initial presentation (median 16 vs. 12 standard two-dose vaccine. After standard vaccination, 89% of
years; p = 0.001) were significantly higher in patients receiving patients compared to 99% of healthy controls were serologic
scheduled vs. on demand ERCP. Subgroup analysis revealed that responders, p = 0.005. Anti-RBD levels were significantly lower in
progression in cholangiographic findings between the 1st and 2nd patients (median 2184 AU/ml [IQR 245–8763]) than controls
ERCP ( progression cohort) was associated with a poorer outcome (3355 AU/ml [IQR 896 − 7849]), p = 0.005. Prednisolone and

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POSTER PRESENTATIONS
azathioprine combination therapy demonstrated the lowest response Separate Kaplan-Meier curves were generated for each of these
rate (80%), compared to azathioprine (94%) and prednisolone (100%) categories and analysed using Cox regression.
monotherapy (figure). The patients received the third vaccine dose Results: 744 patient order histories yielded 1138 person-years of
median 112 days (IQR 88–133) after the second dose. The serologic ordering data and 204 drop-out events, with an estimated 87%, 78%
response rate increased from 81% at time of receiving the third dose, and 69% of patients who continued to receive OCA deliveries at 6, 12
to 91%, measured 3–5 weeks post third vaccination. Likewise, the and 24 months respectively after their first Homecare order. Only 51%
overall anti-RBD levels increased from median 264 AU/ml [IQR 115– of patients had order histories indicating successful titration to 10 mg
6485]) to 6383 AU/ml [IQR 1480–9412]). After standard vaccination, OCA daily, with 43% never increasing beyond 5 mg. The remaining 6%
adverse events (AE) were reported in 30 (71%) of patients and in 191 had orders suggesting either mixed dosing, or 10 mg dosing for a
(78%) of 244 healthy controls with a comparable safety profile. period before returning to 5 mg doses. We observed marked
Following the third dose, 74% of patients reported AEs, without new separation between some dose order groups in terms of drop-out,
safety issues emerging. No serious AEs were reported. with the 5 mg only group most likely to drop out (69%, 56%, and 49%
remaining on treatment at 6, 12 and 24 months respectively). By
contrast, those who received 10 mg dosing (at any point) remained on
OCA at a rate of 99%, 93%, and 82% at 6, 12 and 24 months respectively.
The difference in retention was statistically significant (hazard ratio
of 10 mg vs 5 mg only dosing: 0.22, 95% CI 0.17, 0.30, p < 0.001). See
Figure. Moreover, these differences in retention rate remained
statistically significant on restricted analysis of those receiving OCA
for ≥6 months.

Conclusion: response rates as well as anti-RBD levels were lower in

AIH patients than healthy controls following standard vaccination,
with an attenuated serologic response in particular in patients on Figure: Proportion of patients continuing to receive OCA orders by time
combination therapy with azathioprine and prednisolone. Third dose since first Homecare order, separated by dose order history categories
vaccination was safe without new safety issues emerging and
resulted in an overall increased serologic response. Conclusion: Our findings suggest an association between dose order
history category and retention on treatment, prompting further study
THU438 into optimal systems of management and support for patients on
Analyses of obeticholic acid treatment retention in UK patients OCA. Conclusions about drop-out should be made with caution, as the
based on medicine delivery data analyses only consider product orders, disconnected from clinical
Carl Gibbons1, Subash Srinavasan1, Jaysal Bodhani2, Jing Li3, Li Chen3, characteristics.
Palak Trivedi4. 1Intercept Pharmaceuticals, United Kingdom; 2Intercept
Pharmaceuticals, Level 6, United Kingdom; 3Intercept Pharmaceuticals THU439
Inc, New York, United States; 4University of Birmingham, NIHR Real-world prevalence of pruritus with obeticholic acid: a
Birmingham Biomedical Research Centre, Birmingham, United Kingdom systematic literature review and meta-analysis
Email: [email protected] Patrick Horne1, Christina Hanson2, Tracy Mayne3, Leighland Feinman3.
1
University of Florida, Gainesville, United States; 2South Denver
Background and aims: Between 30–40% of patients with primary Gastroenterology, Englewood, United States; 3Intercept Pharmaceuticals
biliary cholangitis (PBC) inadequately respond to Ursodeoxycholic Inc, New York, United States
acid (UDCA) and are candidates for second-line therapy. Obeticholic Email: [email protected]
acid (OCA) is the only licensed second-line treatment in the UK,
however, compliance, treatment adherence and rates of drug Background and aims: Obeticholic acid (OCA) is the only approved
discontinuation have not been quantified at scale. 2nd line therapy for patients with primary biliary cholangitis (PBC)
Method: 6, 857 orders for OCA were examined, which were delivered with an inadequate response or intolerant to ursodeoxycholic acid
to 744 patients with PBC between 1 May 2017 and 1 Sept 2021. We (UDCA). High rates of pruritus observed in OCA trials have not been
constructed longitudinal datasets allowing study of patient dose observed in real-world studies. We performed a systematic review
order histories. Dropped-out status was assigned to patients against and meta-analysis to estimate real-world prevalence of pruritus and
which there had been no new orders for ≥6 months after the date associated OCA discontinuation compared to the POISE phase 3
covered by their most recent medicine delivery. Kaplan-Meier clinical trial.
estimates were then generated based on the cohort of 744 patients. Method: Systematic review and meta-analysis. We searched Embase
Additionally, to examine potential relationships between drop-out and MEDLINE for English-language publications and conference
and dose order history, patients were classified into one of 4 abstracts from real-world settings in patients with PBC treated with
categories: 1) 5 mg doses ordered only; 2) up-titrated to and OCA monotherapy or combined with UDCA. A fixed- or random-
remained on 10 mg doses; 3) up-titrated to 10 mg but later returned effects pooled estimate was performed based on heterogeneity.
to 5 mg doses; and 4) mixed 5 mg and 10 mg dosing patterns. POISE. We analyzed data from 209 patients with 1 year follow-up on
OCA in the double-blind and open-label phase of POISE. Patients were

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 POSTER PRESENTATIONS
censored if they exceeded the approved 10 mg dose. Pruritus was stage Primary Biliary Cholangitis (PBC), with functional imaging
assessed via visual-analogue scale, 5-D pruritus scale, Itch domain of studies demonstrating abnormalities of the central nervous system.
the PBC-40 scale, and standard adverse event assessment. We The aim of this study was to objectively assess performance in
compared prevalence of pruritus and discontinuations due to cognitive tasks, using CANTAB Neuropsychological Battery in PBC
pruritus in POISE to the real-world meta-analysis estimates via a patients and the differences between those with and without
chi-square goodness of fit test. cognitive symptoms.
Results: Eleven studies were included in the meta-analysis (total Method: Non-cirrhotic PBC patients were recruited from a single
patients = 1192). The random-effects pooled estimate of pruritus tertiary hospital; those with significant additional medical condi-
prevalence was 29% (95% CI, 24%–33%; Figure 1A); the fixed-effects tions were excluded. Participants completed PBC-40 questionnaires
pooled estimate of treatment discontinuation due to pruritus was 9% and CANTAB tasks (PAL, OTS, MTT, SWM, ERT, RTI, RVP) assessing
(95% CI, 8%–11%; Figure 1B). Real-world pruritus prevalence was working memory, executive function, emotional cognition, attention
significantly lower than in POISE (29% vs 62% in POISE; χ2 = 108.69; p and psychomotor speed. Analysis was performed against a normal
< 0.001); real-world treatment discontinuation was significantly population, with a z score of <-1.5 standard deviations considered a
higher than in POISE (9% vs. 4%; χ2 = 5.62; p < 0.02). significant deficit
Results: 38 PBC patients were recruited. Nearly a third of PBC patients
demonstrated significant cognitive deficits in memory tasks (PAL)
with more errors and fewer correct first attempt responses along with
reduced correct hits and slower response times in the emotional
cognition domain (ERT). PBC patients underperformed in 2 out of 3
executive function tasks (OTS;p = 0.00, SWM;p = 0.00, MTT;p = 0.42),
with fewer correct responses in the attention domain (RVP) and
slower responses to stimuli however they outperformed the
normative population in psychomotor speed domain (RTI). There
was, however, no significant difference in CANTAB performance
between cognitively symptomatic (n = 16) and asymptomatic (n = 22)
PBC patients when stratified by the PBC-40 cognitive domain. (Table)

Figure: Forest Plot of Pooled Real-world Prevalence of (A) Pruritus and (B)
Treatment Discontinuation due to Pruritus

Conclusion: The prevalence of pruritus in real-world data was

significantly lower than observed in POISE. Data collection in POISE,
with extensive repeated questions on itch, may have primed subjects
to report greater pruritus. The real-world discontinuation estimate of
9% was higher than reported in POISE, though still low. Experience
with other drugs indicates discontinuation can be higher in real-
world settings, in the absence of mechanisms and motivation in
clinical trials to maintain patients on therapy. Our observation of
significantly lower pruritus prevalence in the real-world vs clinical
trial setting may help providers calibrate treatment expectations
when considering OCA treatment.

THU440
Cognitive symptoms in non-cirrhotic primary biliary cholangitis Conclusion: Objective cognitive dysfunction was frequent in PBC
Naw April Phaw1, Aaron Wetten2,3, David Jones4,5, Jessica Dyson3, patients, with pronounced deficits observed in memory and
Amardeep Khanna6. 1Newcastle University, Translational and Clinical emotional domains. No significant differences in CANTAB perform-
Research Institute, Newcastle upon Tyne, United Kingdom; 2Newcastle ance was observed between cognitive symptomatic and non-
University, Translational and Clinical Research Institute; 3Freeman symptomatic patients suggesting behavioral adaption/variation may
Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust, influence the symptoms exhibited in PBC patients. The patterns of
Hepatology, Newcastle upon Tyne, United Kingdom; 4Newcastle abnormality integrated with functional imaging may shed light on
University, Liver Immunology, Newcastle upon Tyne, United Kingdom; the anatomical abnormality.
5
The Newcastle upon Tyne Hospitals NHS Foundation Trust, Hepatology,
Newcastle upon Tyne, United Kingdom; 6Nottingham University Hospitals
NHS TRUST, Hepatology Department, Nottingham, United Kingdom
Email: [email protected]
Background and aims: There is emerging evidence of cognitive
symptoms, such as memory loss and poor concentration even in early

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POSTER PRESENTATIONS
THU441
Screening and surveillance of biliary neoplasia based on brush
cytology in primary sclerosing cholangitis (PSC): prevalence and
outcomes
Martti Färkkilä1, Sonja Boyd2, Kalle Jokelainen1, Andrea Tenca1,
Lauri Puustinen1, Hannu Kautiainen3, Johanna Arola4,
Helena Isoniemi5. 1Helsinki University Hospital, Clinic of
Gastroenterology, Helsinki, Finland; 2Helsinki University Hospital, Clinic
of Gastroenterology, Helsinki, Finland; 3University of Eastern Finland,
Institute of Public Health and Clinical Nutrition, Kuopio, Finland;
4
Helsinki University Hospital, Pathology, Helsinki, Finland; 5Helsinki
University Hospital, Transplantation and Liver Surgery, Helsinki, Finland
Email: [email protected]
Background and aims: PSC is characterised with chronic inflamma-
tion of biliary epithelium leading to strictures in bile ducts and
secondarily to cirrhosis. Chronic inflammation is associated with the Conclusion: ERC with brush cytology is an accurate method to screen
increased risk for biliary dysplasia (BD) and cholangiocarcinoma and detect biliary neoplasia in PSC.
(CCA), with lifetime risk 10%. CCA is the most common cause of death
among PSC patients and up to half of CCAs are detected at the time of THU442
dg or within one year after. The current guidelines for surveillance for Impact of pruritus in primary sclerosing cholangitis (PSC): a
CCA in PSC are contradictory and the evidence for efficacy of multinational survey
surveillance is scarce. AGA guidelines recommend US, CT or MRI, Kris Kowdley1,2, Ricky Safer3, Rachel Gomel3, Joanne Hatchett3,
with or without Ca19-9 for surveillance of CCA, none of which are Martine Walmsley4, Julio Burman5, Sindee Weinbaum5,
suitable for early detection of biliary neoplasia. Kerrie Goldsmith6, MeeJ Kim7, Will Garner7, Andrew McKibben7,
We aimed to evaluate the role ERC with brush cytology (BC) in Elaine Chien7. 1Liver Institute Northwest, Seattle, WA, United States;
screening and surveillance of BD and to assess its prevalence and its 2
Elson. S. Floyd College of Medicine, Washington State University,
impact on patient outcome. Spokane, WA, United States; 3PSC Partners Seeking a Cure, Greenwood
Method: In total 989 patients were retrieved from Helsinki University Village, CO, United States; 4PSC Support, Oxford, United Kingdom; 5Hetz:
PSC registry referred for ERC: documentation of dg, MRCP/liver The Israeli Association for the Health of the Liver, Ramat Gan, Israel; 6PSC
histology suggestive for PSC or surveillance of PSC progression and/or Support Australia Inc, Melbourne, Australia; 7Mirum Pharmaceuticals
BD. We excluded 98 patients: age <18 years (n = 69) or >65 y (n = 19), Inc, Foster City, CA, United States
CCA detected at time of diagnosis or within one year (n = 7), serious Email: [email protected]
concomitant disease or malignancy, liver transplantation (LTx) before
f/u, n = 3. BC was systematically collected from intra-and extrahepatic Background and aims: Intense pruritus (itch) can be a debilitating
bile ducts, regardless of the presence of dominant strictures for complication of cholestatic liver diseases, including primary scleros-
detection of BD. Cytological evaluation from cytospin and cell-block ing cholangitis (PSC), and in some cases can be an indication for liver
slides was performed, using three-tiered criteria as benign, suspi- transplantation. Currently there are no clinically effective or approved
cious, or malignant (CCA). Suspicious cytology: any of the following: pharmacological therapies to treat cholestatic itch associated with
biphasic cell population, lack of polarity, nuclear moulding, nuclear PSC. The aim of this survey was to provide information about the
membrane irregularities, high nuclear-cytoplasm ratio, hyper/hypo- presentation and severity of cholestatic itch in PSC and its broader
chromacy and lack of cohesion. The screening and surveillance burden from the patient perspective.
strategy is presented in fig. Method: A multinational survey of patients with self-reported PSC
Results: Prevalence of BD and risk for CCA: Suspicion of dysplasia was was conducted. The 39-question web-based survey was focused on
detected ≥1 times in 91 patients (10%) during median f/u of 10 years, the impact of itch in patients with PSC, how itch severity affected
CCA in 25. If dysplasia was documented ≥3 times, the patient was quality of life (QoL), and therapeutic interventions used to address
referred for evaluation for LTx. itch. Severity of itch was quantified using a numerical rating scale (0
LiverTx: 22 patients were transplanted for suspicion of malignancy, for no itch, 10 for worst itch you can possibly imagine). The survey
58 for other indications. Out of the 58 patients with suspicion of was distributed to participants via Hetz, PSC Australia, PSC Partners,
dysplasia (≤2 times), but not transplanted, 11 (19%) developed CCA. and PSC Support. Responses were collected from June 2020 to Feb
800 patients without dysplasia, only 7 (0.9%) were diagnosed with 2021.
CCA. In patients transplanted for dysplasia, 91% were found to have Results: Of the 482 patients who responded, 91% had experienced
dysplasia in explant, in 3 CCA was detected at LTx. The sensitivity of BC itch due to PSC and 34% (164/482) were currently experiencing itch,
with suspicion of malignancy at least once to detect histologically with the median worst itch reported as a 6/10; 45% (74/164) reported
confirmed biliary neoplasia (transplantation/surgery) was 65% (52– the itch episode was at least 1 month in duration. Itch severity was
76%) and specificity 94% (93–96%) with OR 30. If patient had BC with associated with a higher degree of reported sleep disturbance and
suspicion of malignancy ≥3 times the sensitivity to detect histolo- worsening fatigue, with 63% of respondents indicating that evening
gically confirmed CCA was 100% (48% to 100%) and specificity 98% and night-time were the worst times of the day for itching. 50% (197/
(97–99%). 392) reported that itch led to disruption of day-to-day responsibil-
ities and lasted >30 days in 32% (62/197). 22% (88/392) reported
missing school or work. Itch was also associated with mood changes,
including but not limited to anxiety, irritability, and feelings of
hopelessness in more than half of patients (58%; 228/392). The most-
commonly used medicines to treat itch were antihistamines (46%),
UDCA (39%), Cholestyramine (39%), topical creams/ointments (28%),
and Rifampicin (19%). Half of the respondents (235/482) reported
using ≥2 medications but 75% (177/235) described only partial or no
relief with these interventions (Table).

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 POSTER PRESENTATIONS
0.78–0.87) and 94% (CI 0.91–0.98), respectively. In univariate analysis
AST (HR 1.58, CI 1.02–2.45), and IgG (HR 3.05, CI 1.1–8.4) were
significantly related to long-term outcomes in patients without
cirrhosis. In the multivariable model, cirrhosis at diagnosis (HR 4.39,
CI 2.73–7.07), baseline bilirubin (HR 2.41, CI 1.34–4.33), and older age
(HR 1.20, CI 1.04–1.38, unit = 10 years) were all independently
associated with poorer outcomes.
The predicted cumulative impact of time spent with elevated ALT
during follow-up was significant (HR 1.29, CI 1.11–1.50, unit = 10% of
time, Figure 1b. Patients that spent a greater amount of follow-up
time with elevated ALT values had an increased risk of experiencing
an event, and this was most marked in patients with cirrhosis.

Conclusion: Itch related to PSC has a major adverse impact on QoL

(eg, sleep, mood, fatigue), interferes with daily activities in a
substantial proportion of patients but remains inadequately treated
in most patients. These data highlight a major unmet need for the
development of safe and effective therapies for treatment of
cholestatic itch in patients with PSC.

THU443
A dynamic approach to modelling baseline disease status and ALT
elevation over follow-up on clinical-event free survival in
autoimmune hepatitis: a canadian multicentre cohort Conclusion: Patients with AIH are at increased risk of a clinical event
Christina Plagiannakos1,2, Gideon Hirschfield1,2, Ellina Lytvyak3, as the time spent with abnormal ALT values increases, especially
Surain Roberts4, Marwa Ismail1,2, Kattleya Tirona1, Andrew L. Mason3, those with cirrhosis at baseline. Persistent improvement in ALT values
Harry Janssen1,5, Aliya Gulamhusein1,2, Aldo J Montano-Loza3, is a logical treatment goal in AIH.
Bettina Hansen1,2. 1University Health Network, Toronto Centre for Liver
THU444
Disease, Toronto Western and General Hospital, Toronto, Canada;
2 Secondary sclerosing cholangitis following COVID-19 disease: a
University of Toronto, Institute of Health Policy, Management and
multicenter retrospective study
Evaluation, Toronto, Canada; 3University of Alberta, Department of
Medicine-Division of Gastroenterology and Liver, Edmonton, Canada; Peter Hunyady1, Lea Streller2, Darius Ruether3, Sara Reinartz Groba4,
4
Unity Health Toronto, St. Michael’s Hospital, Toronto, Canada; Dominik Bettinger5, Daniel Fitting6, Karim Hamesch7,
5
University of Toronto-St. George Campus, Department of Medicine, Jens Marquardt8, Victoria Mücke1, Fabian Finkelmeier1,
Toronto, Canada Asieb Sekandarzad5, Tobias Wengenmayer5, Ayoub Bounidane1,
Email: [email protected] Felicitas Weiss7, Kai-Henrick Peiffer1, Bernhard Schlevogt4,
Stefan Zeuzem1, Oliver Waidmann1, Marcus Hollenbach9,
Background and aims: Current and future treatments for auto- Martha M Kirstein8, Johannes Kluwe3, Fabian Kütting2,
immune hepatitis (AIH) target ALT as a biomarker of efficacy. In Marcus Mücke1. 1University Hospital Frankfurt; 2University Hospital
patients with AIH, we sought to model ALT response dynamically over Cologne; 3University Hospital Hamburg Eppendorf; 4University Hospital
long-term follow-up, to understand clinical associations with Münster; 5University Hospital Freiburg; 6University Hospital Würzburg;
clinical-event free survival (CEFS). 7
University Hospital Aachen; 8University Hospital Schleswig-Holstein
Method: Patients diagnosed with AIH (simplified score ≥6) who Campus Lübeck; 9University Hospital Leipzig
initiated treatment were included from the Canadian Network for Email: [email protected]
Autoimmune Liver Disease. AASLD sex-specific upper limits of
normal (ULN) defined ALT normalization and site-specific ULN were Background and aims: Secondary sclerosing cholangitis (SSC) is a
used for other biochemical markers. CEFS included the absence of a rare disease with poor prognosis. Cases of SSC have been reported
decompensation event, liver transplant, or death. Kaplan-Meier following coronavirus disease 2019 (COVID-19), COVID-SSC. Aim of
estimates and Cox proportional hazards dynamic time-varying this study was to compare COVID-SSC to SSC in critically ill patients
models adjusted for age at diagnosis, sex, cirrhosis at diagnosis, (SSC-CIP) and to assess factors influencing transplant-free survival.
baseline total bilirubin, and stratified by site were used; alpha = 0.05. Method: In this retrospective, multicenter study involving 127
Results: 579 patients with AIH initiated treatment between patients with SSC from 9 tertiary care centers in Germany, COVID-
November 1987 and June 2020, with a median follow-up time of SSC was compared to SSC-CIP and logistic regression analyses were
6.54 years [IQR 2.70–11.6] and an average of 9 visits [4.0–21]. Median performed investigating factors impacting transplant-free survival.
age at diagnosis was 48 years [31.0–59.4], 75.5% of patients were Results: Twenty-four patients had COVID-SSC, 77 patients SSC-CIP
female (n = 437) and 71.2% reported white ethnicity (n = 412). Median and 26 patients had other forms of SSC. COVID-SSC developed after a
baseline ALT was 15.7xULN [5.84–34.2], AST 10.5xULN [3.36–23.8], median of 91 days following COVID-19 diagnosis. All patients had
IgG 1.48xULN [1.12–1.93], total bilirubin 1.8xULN [0.68–6.25] and INR received extensive intensive care treatment (median days of
1.17 [1.05–1.34]. mechanical ventilation 48). Patients with COVID-SSC and SSC-CIP
Among the 21.2% (n = 123) of patients with cirrhosis at diagnosis, 40 were comparable in most of the clinical parameters and transplant-
had an event during follow-up, and of the 456 (78.7%) without free survival was not different from other forms of SSC ( p = 0.443 in
cirrhosis, 48 had an event. At 5-years of follow-up, the CEFS estimate log-rank test). In the overall cohort, the use of ursodeoxycholic acid
was 73% (CI 0.66–0.82) for patients with, and 92% (CI 0.90–0.95) for (UDCA, OR 0.36, 95%-CI 0.16–0.80, P = 0.013; P < 0.001 in log-rank
those without, cirrhosis (Figure 1a. The survival probability at 5 years test) and high serum albumin levels (OR 0.40, 95%-CI 0.17–0.96, P =
for patients with elevated and normal bilirubin values were 83% (CI 0.040) were independently associated with an increased transplant-
free survival, while the presence of liver cirrhosis (OR 2.52, 95%-CI

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POSTER PRESENTATIONS
1.01–6.25, P = 0.047) was associated with worse outcome. MDRO THU446
colonization or infection did not impact patients’ survival. Extrahepatic autoimmune diseases in autoimmune hepatitis:
effect on mortality
Rasmine Birn-Rydder1, Morten Daniel Jensen1, Peter Jepsen1,
Lisbet Groenbaek1,2. 1Aarhus University Hospital, Department of
Hepatology and Gastroenterology, Aarhus, Denmark; 2Regional Hospital
Horsens, Department of Medicine, Horsens, Denmark
Email: [email protected]
Background and aims: Autoimmune hepatitis (AIH) is a chronic
inflammatory liver disease associated with an increased prevalence
of extrahepatic autoimmune diseases and an increased mortality
Conclusion: COVID-SSC and CIP-SSC share the same clinical compared with the general population. The contribution of extra-
phenotype, course of the disease and risk factors for its development. hepatic autoimmune diseases to the increased mortality has not yet
UDCA may be a promising therapeutic option in SSC, though future been clarified. Our aim was to determine the effect of extrahepatic
prospective trials need to confirm our findings. autoimmune diseases on mortality in patients with AIH.
Method: This nationwide register-based cohort study included all
THU445 Danish patients diagnosed with AIH between 1995 and 2019. We
The efficacy of combined treatment of bezafibrate and examined the presence of extrahepatic autoimmune diseases
ursodeoxycholic acid was reduced in patients with primari concurrent with AIH in all included patients. We followed the
cholangitis at advanced stage patients until 30 April 2021 and calculated the cumulative mortality
Kosuke Matsumoto1, Junko Hirohara2, Toshiaki Nakano2, using the Kaplan-Meier estimator comparing AIH-patients with and
Atsushi Tanaka1. 1Teikyo University School of Medicine, Department of without extrahepatic autoimmune diseases. We estimated the effect
Medicine, Tokyo, Japan; 2Kansai Medical University, The Third of extrahepatic autoimmune diseases on mortality using Cox
Department of Internal Medicine, Osaka, Japan regression adjusted for age at AIH-diagnosis, calendar year of AIH-
Email: [email protected] diagnosis, sex, cirrhosis, and other comorbidities (cancer, chronic
obstructive pulmonary disease, and ischemic heart disease).
Background and aims: Bezafibrate (BZF) is a dual PPARs/PXR agonist Results: Our study included 2479 patients with AIH of whom 23.1%
with potent anti-cholestatic efficacy. Previously, we took advantage had one or more extrahepatic autoimmune diseases. The adjusted 10-
of a large-scale retrospective cohort of patients with primary biliary year cumulative mortality was 27.3% (95% confidence interval [CI]:
cholangitis (PBC) in Japan and demonstrated that a combination of 25.3–29.4) in patients with extrahepatic autoimmune diseases and
BZF and ursodeoxycholic acid (UDCA) was significantly associated 21.6% (95% CI: 19.9–23.6) in patients without. The adjusted mortality
with an improved liver transplantation (LT)-free survival in patients hazard ratio was 1.28 (95% CI: 1.10–1.49) in AIH patients with vs.
with PBC. Nevertheless, we found patients who deceased or without concurrent extrahepatic autoimmune diseases; it was 1.22
underwent LT in this cohort even with a combination treatment of (95% CI: 1.03–1.44) for patients with one extrahepatic autoimmune
UDCA and BZF. In the current study, we explored baseline covariates disease, and 1.59 (95% CI: 1.19–2.12) for those with more than one.
which were significantly associated with poor outcome, death or LT,
in patients treated with UDCA and BZF.
Method: The Japanese PBC cohort is established by the nation-wide
surveys, initiated in 1980 and updated every 3 years by the Intractable
Hepato-Biliary Diseases Study Group (Japan PBC Study Group). To
date, 9, 919 patients with PBC have been registered. Baseline
covariates included age, sex, presence of symptoms, serum levels of
bilirubin, alkaline phosphatase (ALP), and albumin. Primary outcome
(liver-related death or LT) was assessed using multivariable adjusted
Cox proportional hazard models.
Results: 1, 739 patients were excluded from the analysis due to
missing data in terms of outcome and final follow-up date. Among
the remaining 8, 180 patients, 889 patients (mean age at diagnosis
54.8yrs, 139 males (15.6%)) were treated with a combination of UDCA
and BZF and enrolled in the current study. During 9.9 ± 6.8 yrs of
mean observational period, 16 out of 889 (1.8%) reached primary end
point (death in 15, LT in 1). By the Cox proportional hazard model, low
albumin (<3.5 mg/dL) and high bilirubin (>1.5 mg/dL) at baseline
were significantly associated with death or LT; adjusted hazard ratio
(aHR) of low albumin was 5.511 (95% confidential interval 1.754–
17.315, p = 0.003), and aHR of high bilirubin was 9.986 (95% CI 3.097–
32.199, p < 0.001).
Conclusion: In patients with PBC at advanced stage who had low
albumin or high bilirubin at baseline, the risk for death or LT was
significantly increased compared to those with normal albumin or
bilirubin even with a combination treatment of UDCA and BZF.

Conclusion: Extrahepatic autoimmune diseases increased the mor-

tality in patients with AIH. Moreover, patients with multiple
extrahepatic autoimmune diseases had higher mortality than
patients with just one extrahepatic autoimmune disease.

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 POSTER PRESENTATIONS
THU447 Conclusion: Our analysis detects confidence in treatment as a novel
Confidence in treatment is contributing to quality of life in central determinant of HrQoL in patients with AILDs. This modifiable
patients with autoimmune liver diseases. The results of ERN-RARE and so far undepreciated factor should be further investigated in
Liver online survey order to improve care for patients with AILDs.
Ewa Wunsch1, Linda Krause2, Tom Gevers3,4, Christoph Schramm4,5,6,
Maciej K. Janik4,7, Marcin Krawczyk4,8,9, Natalie Uhlenbusch4,10, THU448
Bernd Löwe4,10, Ansgar W. Lohse4,11, Piotr Milkiewicz1,4,7. A pilot study of PBC symptom management with melatonin and
1
Pomeranian Medical University in Szczecin, Translational Medicine fenofibrate: the PIMBLE study
Group, Szczecin, Poland; 2University Medical Centre Hamburg- Beverly Rodrigues1, Steven Nicolaides1, Rohit Sawhney1,2,
Eppendorf, Institute of Medical Biometry and Epidemiology, Hamburg, Amanda Nicoll1,2, Stephen Bloom1,2. 1Eastern Health,
Germany; 3Maastricht University Medical Center, Department of Gastroenterology; 2Eastern Health Clinical School, Monash University,
Internal Medicine, Maastricht, Netherlands; 4RARE-LIVER European Australia
Reference Network; 5University Medical Centre Hamburg-Eppendorf, Email: [email protected]
Department of Medicine and Martin Zeitz Centre for Rare Diseases,
Background and aims: Primary biliary cholangitis (PBC) disease
Hamburg, Germany; 6Hamburg Center for Translational Immunology
progression is usually well controlled with ursodeoxycholic or
(HCTI), Hamburg, Germany; 7Medical University of Warsaw, Liver and
obeticolic acid. Bezafibrate has shown benefits in refractory disease
Internal Medicine Unit, Warsaw, Poland; 8Saarland University Medical
but is not available in Australia, and it is unknown if fenofibrate is
Center, Department of Medicine II, Homburg, Germany; 9Medical
similarly effective. Despite good biochemical response, the symptoms
University of Warsaw, Laboratory of Metabolic Liver Diseases, Warsaw,
of pruritus, fatigue and altered sleep often remain. Melatonin may
Poland; 10University Medical Centre Hamburg-Eppendorf, Department
improve fatigue as demonstrated in animal models. We studied the
of Psychosomatic Medicine and Psychotherapy, Hamburg, Germany;
11 short-term symptomatic and biochemical responses of PBC patients
University Medical Centre Hamburg-Eppendorf, Department of
to melatonin and fenofibrate therapy.
Medicine, Hamburg, Germany
Method: A randomised, cross-over 12-week intervention study
Email: [email protected]
examining symptoms and biochemistry in response to melatonin
Background and aims: Patients with autoimmune liver diseases and fenofibrate between 20th July 2020–15th November 2021 inclusive.
(AILDs) have been reported to have an impaired health-related Results: The interim results of 10 patients are shown in Table 1. Six
quality of life (HrQoL) in studies based on small sample sizes. The aim out of 10 patients completed both trial arms, patient 10 optionally
of this project was to investigate HrQoL in a large transnational cohort completed the melatonin arm only, and the remaining 3 are soon to
of patients with AILDs and to identify potentially modifiable factors complete arm 2 (n = 1 fenofibrate, n = 2 melatonin). Both agents were
in the context of impaired HrQoL. well tolerated overall; 3 patients had a mild rise in transaminases
Method: A cross-sectional online survey was conducted in patients (<5x upper limit of normal) post commencement of fenofibrate. ALP
with a diagnosis of autoimmune hepatitis (AIH), primary biliary improvement was seen in 6/8 on fenofibrate and 3/8 on melatonin,
cholangitis (PBC) or primary sclerosing cholangitis (PSC) from 15 with degree of improvement meeting Paris II criteria in all trialled
European countries. HrQoL was measured with EQ-5D-5L and EQ arms. Symptom improvement was seen in 6/8 on fenofibrate and 6/8
visual analogue scale (EQ VAS) and analysed in relationship to on melatonin.
demographic, psychosocial, disease- and treatment-related factors. A
PHQ-2 score larger than two indicated clinically relevant depression. Table 1: Descriptive analyses of clinical and biochemical responses to
Multivariable linear regression analyses were used to identify each trial arm
potentially modifiable factors associated with HrQoL and confidence Fenofibrate arm Melatonin arm

in treatment while adjusting for known confounders. Improved symptoms Improved symptoms

Results: A group of 1, 178 European patients (470 with AIH, 368 with Age
Abnormal
ALP Improved
Y/N MFIS: SF36: VAS
(itch) Improved
Y/N MFIS: SF36: VAS
(itch)
PBC and 317 with PSC, 79% female, mean age 48 ± 14 years) Patient (years) Gender (baseline) ALP (Y/N) ALP (Y/N)
MFIS SF36 VAS MFIS SF36 VAS
participated in the study. HrQoL was markedly impaired in all three
1 54.6 F N Y N/A Y N N N/A Y N
liver diseases (mean EQ-5D-5L = 0.75, mean EQ VAS = 68.9), particu- 2 68.8 F N Y N/A N/A N/A Y N/A N/A N/A
larly in patients with PBC (mean EQ-5D-5L = 0.73, mean EQ VAS = 3 65.8 F N Y Y N Y Y Y N Y
4 57.8 F N N Y N Y N Y Y Y
66.2). Clinically relevant depression was reported in 17% of the total 5 72.7 F N N Y N N N Y N N
6 60.6 F N P P P P Y N/A N N
sample. Depression, gender, age and advanced disease stage were 7 61.3 F Y Y Y N N P P P P
expectedly associated with HrQoL. Confidence in treatment was 8 55.1 M N Y P P P N N N Y
9 52.9 M N Y Y N N P P P P
identified as a modifiable factor strongly contributing to EQ-5D-5L in 10 45.2 F Y N/A N/A N/A N/A N Y N N

the entire cohort (reg. coef.: 0.12, 95%CI: 0.07 to 0.18, p < 0.001). PSC
or PBC diagnosis, advanced disease stage, treatment in non- Y = (Yes); N = (No); N/A = (not applicable or available); p = (pending)
transplant center and depression were negatively associated with
patients’ confidence in their treatment (Figure). Conclusion: This pilot study suggests that there is potential benefit in
these therapies for PBC and further studies evaluating their efficacy is
required.

THU449
Portal hypertension-associated clinical features in patients with
primary biliary cholangitis are of distinct prognostic value
Lukas Burghart1, Emina Halilbasic1, Philipp Schwabl1,
Benedikt Simbrunner1, Albert Stättermayer1, Oleksandr Petrenko1,
Bernhard Scheiner1, David JM Bauer1, Matthias Pinter1, Kaan Boztug1,
Mattias Mandorfer1, Michael Trauner1, Thomas Reiberger1. 1Medical
University of Vienna, Austria
Email: [email protected]
Background and aims: Primary biliary cholangitis (PBC) may
Figure: Factors associated with treatment confidence progress to cirrhosis and clinically significant portal hypertension

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POSTER PRESENTATIONS
(CSPH). This study assesses different features of CSPH and their THU450
distinct prognostic impact regarding decompensation and LTX-free The low incidence of HBV reactivation among anti-HBc+ subjects
survival in patients with PBC. on immunotherapy reduces the impact of suboptimal screening
Method: Patients with PBC were identified during a database query rate
of our digital patient reporting system. Laia Aceituno1, Juan Bañares1, Lourdes Ruiz1, Ana Callejo-Pérez2,
Results: A total of 333 PBC patients (mean age: 54.3 years, 86.8% Eva Muñoz-Couselo2, Carolina Ortiz-Velez2, Nely Díaz-Mejía2,
female, median follow-up: 5.8 years) were retrospectively assessed. Ana Barreira1,3, Maria-Josep Carreras4, Anna Farriols4, Maria Buti1,3,
Overall, 127 (38.1%) showed features of CSPH: 63 (18.9%) developed Mar Riveiro Barciela1,3. 1Hospital Vall Hebron, Liver Unit, Barcelona,
varices, 98 (29.4%) splenomegaly, 62 (18.6%) ascites and 20 (15.7%) Spain; 2Instituto de Oncología Vall d’Hebron (VHIO), Hospital
experienced acute variceal bleeding. Universitari Vall d’Hebron, Oncology Department, Barcelona; 3Centro de
Splenomegaly, portosystemic collaterals and esophageal varices were investigación biomédica en red de enfermedades hepáticas y digestivas,
associated with an increased 5-year (5Y) risk of decompensation Madrid; 4Hospital Vall Hebron, Pharmacy Department, Barcelona
(15.0%, 17.8% and 20.9%, respectively). Email: [email protected]
Patients without advanced chronic liver disease (ACLD) had a similar
5Y-transplant free survival (TFS) (96.6%) compared to patients with Background and aims: Immunotherapy with check-point inhibitors
compensated ACLD (cACLD) but without CSPH (96.9%). On the (CPIs) has become the pillar of treatment of many advanced cancers.
contrary, PBC patients with cACLD and CSPH (57.4%) or decompen- CPIs can reactivate Hepatitis B (HBV) in patients with chronic
sated ACLD (dACLD) (36.4%) had significantly decreased 5Y survival infection. However, there is scarce data on their possible impact on
rates. subjects with chronic hepatitis C or resolved HBV infection. To date,
During a subanalysis, the combination of LSM <15 kPa and platelets there is no evidence on awareness of Oncologists about the risk of
≥150 G/L indicated a negligible risk for decompensation (5Y 0.0%) prescribing CPIs for patients with viral hepatitis.
and for mortality (5Y 0.0%). Method: Retrospective-prospective study of all patients who began
Overall, 44 (13.2%) patients died, with 18 (40.9%) deaths attributed to Oncological immunotherapy between January 2019 and December
CSPH-related complications. 2020 in a University Hospital. Data on viral hepatitis screening prior
to the beginning of CPIs were collected retrospectively. In subjects
lacking information, serological tests were requested prospectively.
HBV reactivation was defined as the increase of 2 log of HBV-DNA
compared to baseline (HBsAg+ subjects) or reversed seroconversion
to HBsAg+ or detectable HBV-DNA (isolated antiHBc+).
Results: 595 subjects received CPIs: 364 (61.2%) male, mean age 64
years (IQR 57–72). Most prevalent cancers: lung (34.8%), urinary
(13.1%), melanoma (12.1%), gastrointestinal (11.6%), gynecological
(9.2%). CPIs: anti-PD1 (64.2%), anti-PD-L1 (19.2%), combined therapy
with anti-PD1 + anti-CTLA-4 (13.8%), anti-CTLA-4 alone (0.8%), others
(2.0%). Time between cancer diagnosis and CPI beginning was 13
months (IQR 3–33). Forty-three (7.2%) patients had underlying liver
disease, 15 (2.5%) of them cirrhosis and 16 (2.7%) hepatocellular
carcinoma. In 460 (77.3%) subjects anti-HCV was requested prior to
the beginning of immunotherapy, HBsAg in 459 (77.1%) and anti-HBc
in 332 (55.8%), complete screening (anti-HCV, HBsAg and anti-HBc)
in 325 (54.6%). In the remaining cases, serological tests were
completed prospectively in those alive, leading to diagnosis of 1
case of HCV, 1 HBsAg+ and 22 antiHBc+. Overall hepatitis prevalence
was: anti-HCV 3.6% (19/528), HBsAg 1.3% (7/528), anti-HBc 15.6% (74/
473). All anti-HCV positive subjects presented undetectable viral load
except two patients with hepatocellular carcinoma. Five out of the 7
HBsAg carriers received antiviral prophylaxis, leading to HBV
reactivation in 1case with previously unknown infection without
prophylaxis. Only 1 anti-HBc+ subject received antiviral prophylaxis
(HIV infection). Among the remaining anti-HBc+ individuals, just one
isolated case of HBV reactivation was observed (1.4%).
Conclusion: HBV and HCV screening prior to Oncological immuno-
therapy is suboptimal, especially regarding anti-HBc+. Though the
rate of HBV reactivation among anti-HBc+ subjects is very low, efforts
should be done to optimize viral hepatitis screening prior to
immunotherapy for selection of candidates to either antiviral
Conclusion: In PBC, features of CSPH may occur early and indicate an prophylaxis or periodical check-up.
increased risk for subsequent decompensation and mortality. Hence,
regular screening and on-time treatment for CSPH is crucial.
Combining LSM and platelets serves as a valuable preliminary
assessment, as LSM <15 kPa and platelets ≥150 G/L indicate an
excellent long-term outcome.

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 POSTER PRESENTATIONS
THU451 THU452
The ABCB4 variant c.711 increases liver injury in PBC but not in A multicentric study to estimate mortality and graft loss risk after
PSC: prospective analysis with a median follow-up of 7 years in liver transplantation (LT) in patients with recurrent primary
331 patients biliary cholangitis (PBC)
Beata Kruk1, Malgorzata Milkiewicz2, Piotr Milkiewicz3,4, Aldo J Montano-Loza1, Thierry Berney2, Christian Toso2,
Marcin Krawczyk1,5. 1Laboratory of Metabolic Liver Diseases, Giulia Magini2, Gideon Hirschfield3, Bettina Hansen3,
Department of General, Transplant and Liver Surgery, Medical University Andrew L. Mason1, Maryam Ebadi1, Frederik Nevens4,
of Warsaw, Warsaw, Poland; 2Department of Medical Biology, Natalie Van den Ende4, Debora Raquel Terrabuio5, Albert Parés6,
Pomeranian Medical University in Szczecin, Szczecin, Poland; 3Liver and Pablo Ruiz7, Alan Bonder8, Ellina Lytvyak1, Adriaan Van der Meer9,
Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland; Rozanne de Veer9, Annarosa Floreani10, Nora Cazzagon10,
4
Translational Medicine Group, Pomeranian Medical University in Stefania Casu11, Francesco Paolo Russo10, Mark Pedersen12,
Szczecin, Szczecin, Poland; 5Department of Medicine II, Saarland Marlyn J. Mayo12, Michael P. Manns13, Richard Taubert14,
University Medical Center, Saarland University, Homburg, Germany Theresa Kirchner13, Thomas Schiano15, Brandy Haydel15,
Email: [email protected] Xavier Verhelst16, Mercedes Robles-Díaz17, Miguel Jiménez-Pérez18,
Jérôme Dumortier19, Ansgar Lohse20, Christoph Schramm20,
Background and aims: Primary biliary cholangitis (PBC) and primary
Darius Ruether20, Benedetta Terziroli Beretta-Piccoli21,
sclerosing cholangitis (PSC) are two progressive chronic cholestatic
Maria Francesca Donato22, Christophe Corpechot23. 1University of
liver diseases. The ABCB4 gene encodes the hepatobiliary phospho-
Alberta, Canada; 2Geneva University Hospitals, Switzerland; 3Toronto
lipid transporter. Defects in the ABCB4 gene cause several cholestatic
Center for Liver Disease, Canada; 4Division Liver and Biliopancreatic
diseases (Stättermayer et al., J Hepatol. 2020). Here we aim to
Disorders, Belgium; 5University of São Paulo School of Medicine, Brazil;
investigate role of the ABCB4 genetic variant in patients with PBC 6
University of Barcelona, Spain; 7Liver Unit, Hospital Clínic, Spain; 8Beth
and PSC.
Israel Deaconess Medical Center, United States; 9Erasmus MC,
Method: We genotyped the ABCB4 c.711 polymorphism in a total of
Netherlands; 10University of Padova, Italy; 11Universitätsspital Bern,
331 patients with PBC and PSC who were prospectively recruited in
Switzerland; 12Southwestern University, United States; 13Hannover
our center from year 2005. The PBC cohort was composed 196
Medical School, Germany; 14Dept. Gastroenterology, Hepatology and
patients (173 females, median age 59 years, 49% with cirrhosis). The
Endocrinology, Hannover Medical School, Germany; 15Mount Sinai
PSC cohort was composed of 135 patients (96 males, median age 35
Medical Center, United States; 16Ghent University Hospital, Belgium;
years, 39% with cirrhosis). Clinical data were collected at least at two 17
University Hospital Virgen de la Victoria, Spain; 18Málaga Regional
time points: The follow-up ranged from 2 to 20 years (median: 7
Hospital, Spain; 19Croix Rousse Hospital and Edward Herriot Hospital,
years) The PBC-40 and Short Form (SF-36) questionnaires were used
France; 20University Medical Center Hamburg-Eppendorf, Germany;
for assessment health related quality of life. 21
Epatocentro Ticino, Switzerland; 22Fondazione IRCCS Maggiore
Results: Allele and genotype distributions of the ABCB4 variant in
Hospital Policlinico Milan, Italy; 23Saint-Antoine Hospital, France
patients with PBC and PSC cohort were consistent with Hardy-
Email: [email protected]
Weinberg equilibrium ( p >0.05). At baseline, the ABCB4 c.711 variant
was associated with an increased cirrhosis risk (OR = 1.84, p = 0.02) in Background and aims: Recurrent PBC (rPBC) developed in approxi-
the PBC cohort, the risk of cirrhosis was also modulated by patients mately 30% of patients, and negatively impacts graft and patient
gender ( p < 0.01). Carriers of heterozygote genotype showed signifi- survival after LT. Liver function tests and scores to evaluate response
cantly increased serum AST ( p = 0.02), GGTP ( p < 0.01) and ALP ( p < to ursodeoxycholic acid (UDCA) have been developed to monitor
0.01). Although we detected significant improvements in laboratory disease progression and evaluate the addition of second-line
findings (i.e., AST, ALT, ALP and GGTP) during the follow-up, a total of treatments before LT. We aimed to evaluate the utility of serum
22 patients developed new cirrhosis and this risk was significantly liver function tests and the GLOBE and UK-PBC scores to predict graft
modulated by the ABCB4 polymorphism (OR = 5.65, p = 0.04). On the and overall survival after LT in patients with rPBC.
other hand, the ABCB4 genotype did not affect life quality in either of Method: A total of 231 patients who had a liver biopsy-proven
the cohorts, did not modulate liver injury in patients with PSC did not diagnosis of rPBC after LT from 18 centers across Europe, North and
increase the odds of requiring transplantation (all p > 0.05). South America, were evaluated. The mean age at the time of rPBC was
Conclusion: The ABCB4 c.711 polymorphism might represent a 58 ± 10 years, and 206 patients (89%) were women. At the time of
common risk genetic factors for progressive liver injury in PBC. rPBC, 145 patients (63%) were receiving tacrolimus, and 78 (34%) with
Carriers of the c.711 ABCB4 might require more aggressive therapy to cyclosporine. The biochemical response was measured with alkaline
lower the progression of liver scarring. phosphatase (ALP) and bilirubin, and continuous prognostic (GLOBE
and UK-PBC scores) at 1-year after UDCA was started. Graft loss was
defined using a death-censored definition of graft failure and
therefore, graft loss did not include patients who died with a
functioning graft. Cox regression analysis was performed to deter-
mine associations between biochemical markers, scores and graft
loss and mortality.
Results: A total of 219 patients (95%) received treatment with UDCA
after rPBC diagnosis. During a median follow-up 9.16 ± 5.47 years, 47
patients (20%) had lost graft and 76 (33%) died. Graft survival after
rPBC was 92% and 85%, and overall survival was 87% and 76%, at 5-,
and 10-years, respectively. Use of tacrolimus or cyclosporine was not
associated with graft or overall survival. Serum ALP (HR 1.002, 95%
CI 1.001–1.004, p = 0.01), and bilirubin (HR 1.009, 95% CI 1.004–1.015,
p = 0.001) at 1-year after UDCA were associated with graft survival.
The GLOBE (HR 2.45, 95% CI 1.45–4.16, p < 0.001) and UK-score 5-year
formula (2.99, 95% CI 0.48–18.77, p < 0.001) at 1-year after UDCA
initiation were associated with graft survival. In addition, serum ALP
(HR 1.31, 95% CI 1.10–1.55, p = 0.002), and bilirubin (HR 1.008, 95% CI
1.004–1.012, p < 0.001) at 1-year after UDCA initiation were

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POSTER PRESENTATIONS
associated with overall survival. The GLOBE (HR 2.04, 95% CI 1.38– Results: At BL, serum COL4A1 and TSP-2 were moderately correlated
3.01, p < 0.001) and UK-score 5-year formula (1.94, 95% CI 0.37–10.05, with other serum markers, including ELF score, AST, ALP, and GGT
p < 0.001) at 1-year after UDCA were associated with overall survival. (Spearman correlations ρ = 0.38–0.74, all p < 0.001). YKL-40 demon-
Patients with an ALp > 2 × ULN (Figures 1a–b) and bilirubin >1 × ULN strated weaker but significant correlations to ALP, AST and ELF score
(Figures 1c–d) at 1-year of UDCA treatment had worse graft and (ρ = 0.24–0.54, p < 0.05). TSP-2 and COL4A1 were increased with
overall survival. Only two (1%) and 10 patients (4%) started second- fibrosis stage in PSC patients (both p < 0.001), but YKL-40 was
line treatment with obeticholic acid and fibrates, respectively. increased mainly in patients with cirrhosis (Figure). By W96, 44
patients (20%) developed a PSC-related clinical event (hepatic
decompensation, cholangiocarcinoma, ascending cholangitis, or
jaundice). Compared with patients without events (n = 175), those
with events had higher YKL-40 (median 42.5 vs 29.0 ng/ml, p =
0.001), COL4A1 (168.4 vs 121.1 ng/ml, p < 0.001) and TSP-2 (85.0 vs
50.4 pg/ml, p < 0.001) at BL. Among 176 non-cirrhotic patients at BL,
27 progressed to cirrhosis at W96. Compared with patients without
progression to cirrhosis (n = 149), those with progression had higher
BL levels of YKL-40 (OR = 1.91, p = 0.002), TSP-2 (OR = 4.24, p < 0.001),
and COL4A1 (OR = 8.24, p < 0.001). In addition, patients with
progression to cirrhosis had greater relative increases from BL to
W96 in YKL-40 (median 45.8% vs 11.8%, p < 0.001), COL4A1 (34.9% vs
− 3.4%, p = 0.0025) and TSP-2 (24.7% vs 0.1%, p < 0.001).

Figure: Graft and patient survival according to ALP and bilirubin at 1-year
of UDCA.

Conclusion: Patients with rPBC and disease activity as indicated by

standard PBC risk scores have impaired outcomes, supporting efforts
to treat recurrent disease in similar ways to pre-transplant PBC.

THU453
Associations between novel serum biomarkers chitinase-2-like
protein (YKL-40), type IV collagen, and thrombospondin-2 (TSP-2)
with fibrosis stage and clinical outcomes in patients with primary
sclerosing cholangitis (PSC)
Michael Trauner1, Andrew Muir2, Jun Xu3, Mina Khoshdeli3,
Bryan Downie3, Andrew Billin3, Chuhan Chung3, Robert Myers3,
Zachary Goodman4, Mitchell Shiffman5, Harry Janssen5,
Aldo J Montano-Loza6, Stephen Caldwell7, Velimir Luketic8,
Michael P. Manns9, Cynthia Levy10, Christopher Bowlus11. 1Medical
University of Vienna, Vienna, Austria; 2Duke Clinical Research Institute,
Durham, United States; 3Gilead Sciences. Inc., Foster City, United States;
4
Inova Fairfax Hospital, Falls Church, United States; 5Bon Secours Mercy
Health, Liver Institute of Virginia, United States; 6University of Alberta,
Edmonton, Canada; 7University of Virginia, Charlottesville, United
States; 8VCU Medical Center, Richmond, United States; 9University of
Miami, Hannover, Germany; 10University of Miami, Miami, United
States; 11University of California Davis, Davis, United States
Email: [email protected]
Background and aims: Primary sclerosing cholangitis (PSC) is a
chronic and progressive fibrotic liver disease associated with an
increased risk of liver-related complications and mortality. Non-
invasive biomarkers of fibrosis are needed for risk stratification and
monitoring of PSC patients. YKL-40, TSP-2, and type IV collagens (α-
subunit) are biomarkers of liver injury, inflammation, or extracellular
matrix turnover during hepatic fibrogenesis. Our study aimed to Figure: Associations between serum COL4A1, TSP-2, and YKL-40 and Ishak
evaluate associations between these biomarkers with fibrosis stage fibrosis stage
and PSC-related clinical events in a longitudinal study.
Conclusion: Serum levels of the novel fibrosis markers YKL-40, TSP-
Method: Serum biomarkers YKL-40, TSP-2, and COL4A1 were
2, and COL4A1 are associated with fibrosis stage, progression to
measured via ELISA at baseline (BL) and Week 96 (W96) in PSC
cirrhosis, and liver-related clinical events in patients with PSC. The
patients enrolled in a 96-week, phase 2 trial of simtuzumab
utility of these biomarkers for the staging of fibrosis, risk stratifica-
(NCT01672853). Since simtuzumab was ineffective in this trial, data
tion, and disease monitoring in PSC will be explored in additional
from the treatment and placebo groups were combined. Fibrosis was
studies.
staged according to the Ishak classification and biomarker values
were log-transformed. Odds ratios (OR) for associations between BL
biomarker values with progression to cirrhosis (Ishak 5–6) at W96
among non-cirrhotic patients (Ishak 0–4) at BL were calculated using
logistic regression models.

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 POSTER PRESENTATIONS
THU454 were correlated with all prognostic factors. Univariate analysis
MRCP+TM-derived biliary metrics are associated with disease showed that MRCP+ metrics representing duct diameter, dilatations,
severity and clinical outcomes in patients with primary sclerosing and the percentage of ducts with strictures and/or dilatations were
cholangitis associated with survival. According to the multivariate Cox regression
Nora Cazzagon1,2, Sanaa El Mouhadi3, Quentin Vanderbecq3, model, the median duct diameter was independently associated with
Carlos Ferreira4, Sara Lemoinne1, Christophe Corpechot1, adverse outcome-free survival over 5 years (HR 10.9, 95% CI 1.3–90.3,
Olivier Chazouillères1, Lionel Arrivè3. 1Assistance Publique-Hôpitaux p = 0.027) (Figure). Biliary tree volume was significantly higher in
de Paris, Sorbonne University, INSERM, Reference Center for patients with advanced disease as defined by the ANALI scores.
Inflammatory Biliary Diseases and Autoimmune Hepatitis and Saint-
Conclusion: MRCP+™ metrics demonstrated a significant correlation
Antoine Research Center (CRMR MIVB-H, ERN RARE-LIVER), Saint-
with biochemical, elastographic and radiological prognostic scores
Antoine Hospital, Paris, France, Paris, France; 2Department of Surgery,
and were predictive of patients’ outcomes highlighting its prognostic
Oncology and Gastroenterology, University of Padova, European
utility in PSC.
Reference Network on Hepatological Diseases (ERN RARE-LIVER),
Azienda Ospedale-Università Padova, Padova, Italy, Padova, Italy; THU455
3
Assistance Publique-Hôpitaux de Paris, Sorbonne University, Safety and efficacy of the farnesoid X receptor (FXR) agonist
Department of Radiology, Saint-Antoine Hospital, Paris, France, Paris, cilofexor in a proof-of-concept study in patients with
France; 4Perspectum Ltd, Oxford UK, Oxford, United Kingdom compensated cirrhosis due to primary sclerosing cholangitis
Email: [email protected] (PSC)
Background and aims: Patients with primary sclerosing cholangitis Cynthia Levy1, Stephen Caldwell2, Parvez Mantry3, Velimir Luketic4,
(PSC) have a variable, and often progressive disease course which is Charles Landis5, Jonathan Huang6, Edward Mena7,
associated with biliary and parenchymal changes. These changes are Rahul Maheshwari8, Kevin Rank9, Jun Xu10, Xiangyu Lu10,
typically assessed by magnetic resonance imaging (MRI), including Xiaomin Lu10, Chuhan Chung10, Robert Myers10, Kris Kowdley11.
1
magnetic resonance cholangiopancreatography (MRCP). Our aim was University of Miami Miller School, Miami, United States; 2University of
to study the association of novel quantitative MRCP metrics with Virginia School of Medicine, Charlottesville, United States; 3The Liver
prognostic scores and patient outcomes. Institute At Methodist Dallas, Dallas, United States; 4VCU School of
Method: We performed a retrospective study including 77 large-duct Medicine, Richmond, United States; 5University of Washington School of
PSC patients with baseline MRCP images, which were post-processed Medicine, Seattle, United States; 6University of Rochester School of
to obtain quantitative measures of bile ducts and biliary volume using Medicine and Dentistry, Rochester, United States; 7Pasadena Liver
MRCP+™ (Perspectum Ltd, Oxford). The participants’ ANALI scores, Center, Pasadena, United States; 8Piedmont Transplant Institute, Atlanta,
liver stiffness (measured by vibration controlled transient elastogra- United States; 9MNGI Digestive Health-Northeast Minneapolis Clinic,
phy) and biochemical indices were collected at baseline. Adverse Minneapolis, United States; 10Gilead Sciences, Inc., Foster City, United
outcome-free survival was measured as the absence of decompen- States; 11Liver Institute Northwest, Seattle, United States
sated cirrhosis and liver transplantation. The prognostic value of Email: [email protected]
MRCP+™ derived metrics was assessed by univariate analysis and
Background and aims: Cilofexor (CILO) is a nonsteroidal FXR agonist
multivariate Cox regression modelling. being evaluated in the phase 3 PRIMIS trial of non-cirrhotic patients
with PSC. The safety and efficacy of CILO in patients with cirrhosis is
unknown. This proof-of-concept, open-label study evaluated the
safety and efficacy of escalating doses of CILO in patients with PSC and
cirrhosis.
Method: Subjects with PSC and compensated cirrhosis were treated
with escalating doses of CILO for 12 weeks (30, 60, and 100 mg daily
for 4-week intervals). Safety, liver biochemistry, and serum markers
of fibrosis, cellular injury, and pharmacodynamic effects of CILO (bile
acids [BAs]) were evaluated.
Results: Among 19 subjects screened, 11 were enrolled and 10 (91%)
completed the study. The median age was 48 years, 55% were male,
55% had IBD, and 46% were on ursodeoxycholic acid. At baseline (BL),
median (IQR) laboratory parameters were: total bilirubin 1.1 mg/dL
(0.8, 1.5), albumin 4.0 g/dL (3.9, 4.6), INR 1.0 (0.9, 1.1), platelets 201 ×
103/μL (113, 218), ALP 510 U/L (269, 592), and GGT 344 U/L (208, 455).
BL ELF and liver stiffness by transient elastography were 10.4 (9.5,
12.6) and 18.0 kPa (8.5, 67.6), respectively. At week 12 (W12), liver
biochemistry tests improved relative to BL values including serum
ALP (median: −13% [IQR: −22, −9]; p = 0.006), GGT (−43% [−52, −31];
p = 0.002), ALT (−25% [−36, −7]; p = 0.012), and AST (−12% [−29, 7];
p = 0.32), and rebounded after 4 weeks of untreated follow-up
(Figure). Total bilirubin decreased at W12 relative to BL (−13% [−25,
0], p = 0.13), while albumin and INR remained stable. Among 10
subjects with detectable serum BAs at baseline (26.1 μM/L [19.7,
52.9]), median change in BAs at W12 was −18% (−23, 12; p = 0.73).
Results: During a total 386 patients-years, we recorded 16 cases of One patient discontinued treatment prematurely (subject decision).
decompensated cirrhosis, 2 liver transplantations and 5 liver-related While no treatment-emergent (TE) serious adverse events (AEs) or
deaths. At baseline, ∼50% of the patients were classified as being at deaths occurred in the study, Grade 2 or higher TEAEs occurred in 5
risk of developing disease complications based on radiological, subjects (45%). Pruritus was reported by 8 subjects (73%), the
elastographic, and biochemical prognostic scores. MRCP+™ metrics, majority (7 of 8) being Grade 1 or 2.
particularly those describing the severity of bile duct dilatations,

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POSTER PRESENTATIONS
p = 0.01; ELF: 1.5 vs 1.2, p = 0.02). Activities of daily living correlated
with LS (rho 0.26, p = 0.02) and ELF (rho 0.25, p = 0.03) with higher
scores in those with advanced fibrosis (LS: 1.5 vs 1.2, p = 0.01; ELF: 1.5
vs 1.3, p = 0.03).

Conclusion: In this proof-of-concept study of patients with compen-

sated cirrhosis due to PSC, escalating doses of CILO over 12 weeks
were well tolerated and improved markers of cholestasis and liver
biochemistry.

THU456
Association between patient-reported outcome measures and
surrogate markers of liver fibrosis in large-duct primary
sclerosing cholangitis
Emmanuel Selvaraj1,2,3, Jane D. Collier2, Emma Culver2,
J Michael Brady4,5, Adam Bailey2,3, Michael Pavlides1,2,3. 1University of
Oxford, Oxford Centre for Clinical Magnetic Resonance Research,
Radcliffe Department of Medicine, Oxford, United Kingdom; 2University Conclusion: SF-36 and PSC-PRO health domains showed significant
of Oxford, Translational Gastroenterology Unit, Nuffield Department of correlations with surrogate markers of liver fibrosis. Advanced
Medicine, Oxford, United Kingdom; 3NIHR Oxford Biomedical Research fibrosis appears to have a greater impact on the physical than
Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, mental components of both PROMs. Future antifibrotic drug trials in
United Kingdom; 4University of Oxford, Department of Oncology, Oxford, PSC should consider assessing the impact of drug on physical well-
United Kingdom; 5Perspectum Ltd., Oxford, United Kingdom being as one of the secondary end points.
Email: [email protected]
THU457
Background and aims: Liver fibrosis is the main driver of disease Association between patient-reported outcome measures and
progression in primary sclerosing cholangitis (PSC). Patient-reported severity of cholangiopathy in large-duct primary sclerosing
outcome measures (PROMs) are increasingly used as exploratory end cholangitis
points in clinical trials. The aim of this study was to investigate the Emmanuel Selvaraj1,2,3, Ahmed Ba-Ssalamah4, Sarah Poetter-Lang4,
impact of liver fibrosis on health-related quality of life (HrQoL) using Jane D. Collier2, Emma Culver2, J Michael Brady5,6, Adam Bailey2,3,
generic (SF-36) and disease-specific (PSC-PRO) tools. Michael Pavlides1,2,3. 1University of Oxford, Oxford Centre for Clinical
Method: Patients with large-duct PSC were invited to complete Magnetic Resonance Research, Radcliffe Department of Medicine,
HrQoL questionnaires in an outpatient setting. SF-36 and PSC-PRO Oxford, United Kingdom; 2University of Oxford, Translational
domains were scored out of a maximum of 100% and 5, respectively. Gastroenterology Unit, Nuffield Department of Medicine, Oxford, United
Mean scores were calculated for each health domain with lower SF- Kingdom; 3NIHR Oxford Biomedical Research Centre, Oxford University
36 and higher PSC-PRO scores representing poorer quality of life. Hospitals NHS Foundation Trust, Oxford, United Kingdom; 4Medical
Transient elastography liver stiffness (LS; Echosens, France), University of Vienna, Department of Biomedical Imaging and Image-
enhanced liver fibrosis (ELF; Siemens Healthineers, Germany) and Guided Therapy, Vienna, Austria; 5University of Oxford, Department of
LiverMultiScan-derived iron-corrected T1 (cT1; Perspectum, Oxford, Oncology, Oxford, United Kingdom; 6Perspectum Ltd., Oxford, United
UK) were obtained on the same day. Advanced fibrosis was defined as Kingdom
LS >9.6 kPa and ELF >9.8 according to published cut-offs in PSC. Email: [email protected]
Results: Eighty patients (68% male) with median age 42 years (range:
18–76) and median PSC duration 8 years (range: 1–25) completed Background and aims: Magnetic resonance cholangiopancreatogra-
both HrQoL questionnaires. Median cT1 was 760ms (range: 640– phy (MRCP) is used alongside serum alkaline phosphatase (ALP) to
1053), median LS was 6.9 kPa (range: 3.7–45.5) and median ELF was assess the severity of cholangiopathy in primary sclerosing cholan-
9.4 (range: 8.0–13.7). For the SF-36, median cT1 correlated with all gitis (PSC). Patient-reported outcome measures (PROMs) are increas-
health domains. Mental health (rho −0.37, p < 0.01), bodily pain (rho ingly used as exploratory end points in clinical trials. The aim of this
−0.31, p < 0.01) and physical functioning (rho −0.31, p < 0.01) showed study was to investigate the impact of ALP and the severity of
the strongest correlations. LS also correlated with all domains of SF- cholangiopathy on MRCP on health-related quality of life (HrQoL)
36 with bodily pain (rho −0.28, p = 0.02), social functioning (rho using generic (SF-36) and disease-specific (PSC-PRO) tools.
−0.27, p = 0.02) and physical functioning (rho −0.25, p = 0.03) Method: Patients with large-duct PSC were invited to complete
showing the strongest correlations, albeit weaker than median cT1. HrQoL questionnaires in an outpatient setting. SF-36 and PSC-PRO
ELF did not correlate with any of the SF-36 domains. SF-36 scores domains were scored out of a maximum of 100% and 5, respectively.
were lower in patients with advanced fibrosis defined by LS cut-off, Mean scores were calculated for each health domain with lower SF-
particularly for role physical (67% vs 85%, p < 0.01) and general health 36 and higher PSC-PRO scores representing poorer quality of life. 3D
(40% vs 54%, p < 0.01) domains (Figure 1). For the PSC-PRO, median MRCP and serum ALP were acquired on the same day. Two
cT1 did not correlate with any of the domains. Physical function radiologists reviewed MRCP images for the presence of dominant
correlated with LS (rho 0.30, p < 0.01) and ELF (rho 0.26, p = 0.02) stricture (DS) and measured the maximum intrahepatic bile duct
with higher scores in those with advanced fibrosis (LS: 1.5 vs 1.2, dilatation (IHBD) for Anali score. Images were analysed using a
quantitative biliary tool, MRCP+ (Perspectum, Oxford, UK) to compute

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 POSTER PRESENTATIONS
the intrahepatic sum of relative severity of dilatations dysplasia were assigned to the malignancy group. We determined a
(SumRelSevDilat). Patients were classified into high or low risk cut-off for detecting malignant polyps in ultrasound using a receiver
group for disease progression using ALP cut-off 1.5x upper limit operating characteristics curve.
normal (ULN) and the presence of DS. Results: From a cohort of 596 people with PSC at the University
Results: Eighty patients (68% male) with median age 42 years (range: Medical Center Hamburg-Eppendorf, 139 patients underwent chole-
18–76) and median PSC duration 8 years (range: 1–25) completed cystectomy. 77 patients underwent cholecystectomy for a suspected
both questionnaires. Median ALP was 150 IU/ml (range: 48–1180). DS underlying gallbladder pathology. In 37 of those patients (21 m, 16 f )
was reported in 25 (31%) patients. Maximum IHBD was ≤3 mm in 26 the detection of a polyp on imaging was the indication for surgery.
(33%), 4 mm in 19 (23%) and ≥5 mm in 35 (44%) patients. Median Additionally, 62 patients had their gallbladder removed in the
MRCP+−derived SumRelSevDilat was 7.0m−1 (range: 0.0–19.8). The context of other interventions such as liver transplantation. Looking
mean score for each health domain is shown in Figure 1 below. at all 139 cholecystectomy patients, ultrasound (sensitivity = 100%)
DS correlated with SF-36 bodily pain (rho −0.28, p = 0.02). Maximum was significantly more sensitive than MRI in detecting gallbladder
IHBD correlated with PSC-PRO physical function domain (rho 0.36, polyps (sensitivity = 35%) ( p < 0.001). MRI missed 3 of the 8 polyps
p < 0.01). SumRelSevDilat correlated with physical functioning (rho with malignant histology. In ultrasound, malignant polyps (n = 8,
−0.25, p = 0.04) and bodily pain (rho −0.26, p = 0.03) domains of SF- median size = 13 mm) were found to be significantly larger than non-
36, and the physical function (rho 0.26, p = 0.03) and activities of daily malignant polyps (n = 26, median size = 6.6 mm) ( p < 0.001).
living (rho 0.29, p = 0.01) domains of PSC-PRO. ALP correlated with Ultrasound was able to reliably detect a malignant polyp (area
bodily pain (rho −0.37, p < 0.01), general health (rho −0.26, p = 0.03), under the curve = 0.92, p < 0.001). At a cut-off value of 8 mm,
and energy/fatigue (rho −0.29, p = 0.01) domains of SF-36, and the sensitivity was 100% and specificity was 81%.
physical function (rho 0.30, p < 0.01) and emotional impact (rho 0.38,
p < 0.01) domains of PSC-PRO. Bodily pain score was lower in those
with DS compared to those without (74% vs 87%, p = 0.02). Both
physical functioning (80% vs 92%, p = 0.04) and bodily pain (78% vs
85%, p = 0.03) scores were lower in patients with ALP greater than
1.5x ULN.

Conclusion: In people with PSC, ultrasound is more sensitive in the

detection of gallbladder polyps than MRI. Based on the size of polyps,
Conclusion: The presence of DS, severity of intrahepatic biliary a reliable distinction can be made between malignant and benign
dilatations, and ALp >1.5x ULN have a significant impact on both findings: no malignant polyp was smaller than 8 mm. This validates
physical and mental health of patients with large-duct PSC. previously published data from the Mayo Clinic. Cholecystectomy
needs to be offered if a polyp of 8 mm or more is detected. Therefore,
THU458 ultrasound and MRI may be complementary methods for hepatobili-
Ultrasound for the diagnosis of gallbladder polyps in PSC: polyps ary malignancy surveillance in people with PSC. A multicentre
greater than 8 mm indicate malignancy validation of the data is ongoing.
Johannes Altenmüller1, Marcial Sebode2,3,
Christina Weiler-Normann2,4, Christiane Wiegard2, Ansgar Lohse2,3,5, THU459
Christoph Schramm2,3,4,5. 1University Medical Center Hamburg- Temporal changes in patient-reported outcome measures
Eppendorf, Hamburg, Germany; 2University Medical Center Hamburg- stratified by liver fibrosis severity in large-duct primary sclerosing
Eppendorf, Ist Department of Medicine, Hamburg, Germany; 3European cholangitis
Reference Network on Hepatological Diseases (ERN RARE-LIVER); Emmanuel Selvaraj1,2,3, Jane D. Collier2, Emma Culver2,
4
University Medical Center Hamburg-Eppendorf, Martin Zeitz Centre for J Michael Brady4,5, Adam Bailey2,3, Michael Pavlides1,2,3. 1University of
Rare Diseases, Hamburg, Germany; 5University Medical Center Oxford, Oxford Centre for Clinical Magnetic Resonance Research,
Hamburg-Eppendorf, Hamburg Center for Translational Immunology, Radcliffe Department of Medicine, Oxford, United Kingdom; 2University
Hamburg, Germany of Oxford, Translational Gastroenterology Unit, Nuffield Department of
Email: [email protected] Medicine, Oxford, United Kingdom; 3NIHR Oxford Biomedical Research
Centre, Oxford University Hospitals NHS Foundation Trust, Oxford,
Background and aims: The risk of gallbladder carcinoma is increased
United Kingdom; 4University of Oxford, Department of Oncology, Oxford,
in primary sclerosing cholangitis (PSC). Surveillance imaging every
United Kingdom; 5Perspectum Ltd., Oxford, United Kingdom
6–12 months is used for early diagnosis. The aim of the study is to
Email: [email protected]
assess the reliability of ultrasound and MRI in detecting gallbladder
polyps in people with PSC. Background and aims: Patient-reported outcome measures
Method: All patients with PSC and a history of cholecystectomy were (PROMs) are increasingly used as exploratory end points in clinical
included for the evaluation and comparison of the two imaging trials. The aim of this study was to evaluate the temporal relationship
methods, ultrasound and MRI for the detection of gallbladder polyps. between health-related quality of life (HrQoL) and liver fibrosis using
Data including gallbladder histology were gathered retrospectively generic (SF-36) and disease-specific (PSC-PRO) tools.
from the electronic medical records. Polyps with high-grade Method: Patients with large-duct PSC were invited to complete
HrQoL questionnaires in an outpatient setting at baseline (V1) and

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POSTER PRESENTATIONS
follow-up (V2) visits at least 12 months apart. Transient elastography Method: Patients with large-duct PSC attended study visits at
liver stiffness (LS; Echosens, France) measurements were recorded on baseline (V1) and follow-up (V2). Standardised liver T1 and T2*
the same day. SF-36 and PSC-PRO health domains were scored out of maps, transient elastography liver stiffness (LS; Echosens, France),
a maximum of 100% and 5, respectively. Mean scores were calculated enhanced liver fibrosis (ELF; Siemens Healthineers, Germany), and
for each domain with lower SF-36 and higher PSC-PRO scores blood tests were performed on the same day at each visit. MRI data
representing poorer quality of life. Advanced fibrosis (F3-6) was were analysed using LiverMultiScan to derive liver IQR cT1. The
defined based on published cutoff of LS >9.6kPa in PSC. Amsterdam-Oxford model (AOM) score was also calculated. Patients
Results: Fifty-five patients (64% male) with median age 45 years were classified into high-risk or low-risk groups for disease
(range: 20–77) and median PSC duration 11 years (range: 2–26) progression using baseline data according to published cut-offs in
attended both study visits. The median time between visits was 417 PSC: AOM >2, ELF >9.8 and LS >9.6 kPa. Mixed ANOVA models were
days (range: 362–582). The mean scores were numerically lower at used to examine the within-subject effect (time), between-subject
V2 than V1 in all the SF-36 domains but only three domains showed effect (high-risk or low-risk), and interaction between the two on
statistically significant difference: bodily pain (74% vs 83%, p < 0.01), changes in IQR cT1. The magnitude of effects (partial-ETA squared)
energy/fatigue (47% vs 57%, p < 0.0001), and mental summary score was defined as: 0.01 (small), 0.06 (medium), and 0.14 (large).
(66% vs 71%, p < 0.001). There were no differences in any of the PSC- Receiver operating characteristic curve (ROC) analyses were con-
PRO domains between the visits. When stratified by baseline LS ducted to assess the diagnostic performance of V1 and delta V1–V2
>9.6 kPa threshold (Figure 1), SF-36 physical functioning mean score measurements to identify the high-risk groups.
dropped in the F3-6 group but increased slightly in the F0-2 group Results: Fifty-five patients (64% male) with median age 45 years
(−9.0 ± 17% vs 0.4 ± 21%, p = 0.01). In the PSC-PRO, the emotional (range: 20–77) and median PSC duration 11 years (range: 2–26)
impact mean score increased in the F3-6 group but decreased in the attended both study visits. The median time between visits was 417
F0-2 group (0.6 ± 0.7 vs −0.1 ± 0.5, p < 0.01). There were no significant days (range: 362–582). IQR cT1 was higher in the high-risk groups
differences in mean scores in the other domains between the visits. compared to low-risk groups at either time points (AOM: p < 0.001;
ELF: p = 0.001; LS: p < 0.001). IQR cT1 increased over time in the high-
risk group and not in the low-risk group (AOM: p = 0.03; ELF: p = 0.04;
LS: p = 0.07). There was a significant interaction between time and
risk grouping on IQR cT1 when stratified by AOM (F = 15.3, p < 0.001;
partial-ETA squared = 0.23), ELF (F = 9.1, p < 0.01; partial-ETA squared
= 0.15) and LS (F = 7.2, p = 0.01; partial-ETA squared = 0.12). Delta V1–
V2 (AUC = 0.78, 95% CI: 0.61–0.95) numerically had a higher
diagnostic performance than V1 IQR cT1 (AUC = 0.75, 95% CI 0.61–
0.89; p < 0.001) to detect the AOM >2 group but was no better when
stratified by ELF and LS.

Conclusion: There was worsening of bodily pain, levels of energy and

mental health even within a year in patients with large-duct PSC.
Patients with advanced fibrosis reported lower physical functioning
and higher emotional impact of their disease compared to those
without advanced fibrosis. Changes in PROMs are related to liver
fibrosis and need to be considered in future antifibrotic drug trials. Conclusion: Patients who are at higher risk of death and/or liver
These findings, however, need to be interpreted in the context of transplantation (AOM >2) or with advanced fibrosis (ELF >9.8, LS
imposed restrictions during the Covid-19 pandemic which may have >9.6 kPa) are likely to have a progressively higher IQR cT1 over time.
had a significant psycho-social impact on patients. Single baseline measurements alone outperformed dynamic mea-
surements over two time points in detecting the high-risk group.
THU460 Further follow-up data points with repeated-measures analysis and
Temporal increase in interquartile range iron-corrected T1 in correlation with clinical outcomes are needed.
high-risk patients with large-duct primary sclerosing cholangitis
Emmanuel Selvaraj1,2,3, Jane D. Collier2, Emma Culver2, THU461
J Michael Brady4,5, Adam Bailey2,3, Michael Pavlides1,2,3. 1University of Seladelpar treatment of patients with primary biliary cholangitis
Oxford, Oxford Centre for Clinical Magnetic Resonance Research, (PBC) for 2 years improves the GLOBE PBC score and predicts
Radcliffe Department of Medicine, Oxford, United Kingdom; 2University improved transplant-free survival
of Oxford, Translational Gastroenterology Unit, Nuffield Department of Bettina Hansen1,2, Elaine Watkins3, Ke Yang3, Yun-Jung Choi3,
Medicine, Oxford, United Kingdom; 3NIHR Oxford Biomedical Research Charles McWherter3, Gideon Hirschfield4. 1Toronto Centre for Liver
Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, Disease, Toronto General Hospital, University Health Network, Toronto,
United Kingdom; 4University of Oxford, Department of Oncology, Oxford, Canada; 2Institute of Health Policy, Management and Evaluation
United Kingdom; 5Perspectum Ltd., Oxford, United Kingdom (IHPME), University of Toronto, Toronto, Canada; 3CymaBay
Email: [email protected] Therapeutics, Inc, Newark, United States; 4Toronto Centre for Liver
Disease, University of Toronto, Toronto, Canada
Background and aims: Median iron-corrected T1 (cT1) derived from Email: [email protected]
LiverMultiScan (Perspectum, Oxford, UK) correlates well with
histological liver fibrosis. Interquartile range (IQR) cT1 has been Background and aims: The GLOBE score is a validated risk
proposed to better reflect the patchy liver fibrosis in primary assessment tool providing an estimate of transplant-free survival
sclerosing cholangitis (PSC). The aim of this study was to investigate for patients with PBC. Seladelpar is a PPAR-delta agonist with anti-
the temporal changes in IQR cT1 in large-duct PSC. cholestatic, anti-inflammatory and anti-pruritic activity in PBC

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 POSTER PRESENTATIONS
patients. Our aim was to evaluate change in GLOBE score in patients suboptimal case-finding and case-ascertainment. Using administra-
with PBC treated with seladelpar for 2 years. tive databases to identify PSC in the population is not reliable.
Method: Eligible patients with PBC and an inadequate response or Guidelines recommend PSC patients should undergo a colonoscopy
intolerance to UDCA (alkaline phosphatase (ALP) ≥1.67xULN) were to rule out inflammatory bowel disease (IBD). Therefore, we aimed to
enrolled into an open-label one-year phase 2 study (EudraCT: 2016- evaluate the role of using an endoscopy database to improve PSC
002996-91) receiving daily oral 5 or 10 mg seladelpar. After 1 year, patient identification.
patients were eligible for an open label long-term study (EudraCT: Method: We used the Pentax medical endoscopy endoPRO iQ®
2017-003910-16). The change in GLOBE score following seladelpar database to identify adult (≥18 years) patients who had undergone a
treatment over 2 years and the resulting predictions of transplant- colonoscopy in the Calgary Health Zone [(CHZ) population ∼1.5
free survival were assessed. The contributions of alkaline phosphat- million]. We searched the endoscopy report database for one of the
ase, total bilirubin, albumin, and platelets to changes in GLOBE score following predefined texts: primary sclerosing cholangitis, PSC,
were examined. sclerosing cholangitis, between 2005 and 2019. The CHZ is a one-
Results: 101 patients entered the long-term study with available payer system providing medical care to all residents in the zone. All
GLOBE score and were evaluated: 94% female, mean (SD) age 57 (9.0) endoscopies performed in the CHZ are captured within a secure
years, duration of PBC 10 (6.6) years, and UDCA dose of 15 (3.7) mg/ Pentax medical database. We used the International Classifications of
kg/day. Mean baseline values were ALP 321 (165) U/L, bilirubin 0.8 Diseases (ICD) codes to identify patients with PSC in the following
(0.3) mg/dL, albumin 4.1 (0.3) mg/dL, platelets 237 (82) × 103/μL and administrative databases: inpatient, ambulatory, and physician
GLOBE score 0.390 (0.656). After treatment with seladelpar for 3 claims. Finally, for case-ascertainment, we conducted a validation
months, 1 year and 2 years the mean (SD) change from baseline in study using medical charts on all PSC patients identified in the
GLOBE score was −0.330 (0.321), −0.324 (0.281), and −0.417 (0.269), endoscopy database and a systematic random sample of patients
respectively. The observed early fall of GLOBE score within 3 months identified by the administrative databases but not by the endoscopy
was followed by a gradual decline through 2 years (Fig. 1A). The database (sample size = 207). In our validation study, we identified
improvements in GLOBE score for all patients and those completing patients with ulcerative colitis (UC), Crohn’s disease (CD), and
two years were comparable. The greatest changes in GLOBE score indeterminate colitis.
were attributable to changes in alkaline phosphatase values followed Results: During our study period, we identified 535 patients using
by those of total bilirubin (Fig. 1B). Seladelpar treatment led to the endoscopy database and 4, 544 patients in administrative
predicted changes in survival (Fig. 1C) at 3 months, 1 year and 2 years databases with a potential PSC diagnosis. Within the endoscopy
with hazard ratios of 0.72, 0.72 and 0.66 compared to baseline, database, we identified 406 PSC patients (male sex 59.4%) who had a
respectively. The improvements in GLOBE score were observed for confirmed PSC diagnosis using radiological modalities and/or a liver
nearly all patients completing 2 years treatment (47 of 50, Fig. 1D). biopsy. In this cohort, 1.5% (n = 6) patients were not identified in the
administrative databases. IBD was prevalent at 81.5% (n = 331) in our
cohort (UC 149 [36.7%], CD 146 [36.0%], and 36 [8.9%] indeterminate
colitis). In our validation study (n = 742 charts), 412 patients had a
confirmed PSC diagnosis. Using the endoscopy database alone to
identify PSC patients had sensitivity 98.5% (406/412), specificity
60.9% (201/330), positive predictive value (PPV) 75.9% (406/535), and
negative predictive value (NPV) 97.1% (201/207). Using multiple
previously recommended algorithms in the administrative databases
to identify PSC patients had a maximum PPV of 62% and sensitivity of
54%.
Conclusion: Using endoscopy databases to identify PSC patients is a
reliable, accurate and feasible method compared to using adminis-
trative databases. Our proposed method would lead to better case-
ascertainment and should improve the quality of future studies
evaluating the natural history of PSC.

THU463
The prevalence of primary biliary cholangitis (PBC) is on the rise: a
canadian population-based study
Bryce Tkachuk1, Fengjuan Yang2, Gideon Hirschfield3, Mark G Swain2,
Abdel-Aziz Shaheen2. 1University of Calgary, Medicine, Calgary,
Canada; 2University of Calgary, Calgary, Canada; 3University Health
Network, Toronto, Canada
Email: [email protected]
Conclusion: Seladelpar treatment over 2 years resulted in a sustained
Background and aims: Canada has one of the highest rates of
decrease in GLOBE score for patients with PBC that is associated with
primary biliary cholangitis (PBC) incidence and prevalence world-
a predicted improvement in transplant-free survival.
wide. Our group reported the natural history of PBC in Calgary
THU462 ( population ∼1.5 million) more than a decade ago. Significant
Validation of a novel method of identifying patients with Primary awareness and recent advancement of PBC management were
Sclerosing Cholangitis (PSC) in a canadian population reported. Therefore, we aimed to study the impact of these factors
on the natural history of PBC in a well-defined Canadian population
Harshil Patel1, Fengjuan Yang1, Mark G Swain1, Gideon Hirschfield2,
and evaluate the temporal trends of PBC incidence and prevalence.
Gilaad Kaplan1, Bettina Hansen2, Abdel-Aziz Shaheen1. 1University of
Method: We used population-based administrative data (inpatient,
Calgary, Calgary, Canada; 2University Health Network, Toronto, Canada
ambulatory care, and physician claims) and a previously validated
Email: [email protected]
International Classification of Diseases coding algorithm to identify
Background and aims: Studies describing the epidemiology of PBC patients in the Calgary Health Zone between 2003 and 2018. We
primary sclerosing cholangitis (PSC) have been limited due to applied the same validated methods that we implemented in our

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POSTER PRESENTATIONS
original study (Myers et al., 2009, study period: 1996–2002). We Results: 2763 AIH patients were included in the ColHai registry
conducted a validation study on incident cases to confirm the (Spanish registry for cholestasic and autoimmune disorders). Out of
performance of the used algorithm in order to identify definite PBC them, 13 patients with type 1-AIH were treated with rituximab in 8
patients (those who had at least two of the following criteria: positive different hospitals. The majority were women (10/13), median age 43
anti-mitochondrial antibody, cholestatic liver enzymes, and a years. At diagnosis 1 presented an acute severe hepatitis and 2 had
compatible liver biopsy). The positive predictive value (PPV) was liver cirrhosis. Time from diagnosis to beginning of rituximab was 20
78.2%, while PPV of the original algorithm was 73.1%. We used a months and to last follow-up 5 years. The reasons for biological
washout period of 2 years (2003–2004) to identify incident PBC therapy were: 4 difficult-to-manage AIH and 9 due to indication for
cases. We chose March 31st of each year as point prevalence. Temporal other concomitant autoimmune disorder (4 multiple sclerosis, 3
trends were evaluated using generalized linear models assuming a vasculitis and 2 rheumatoid arthritis). The majority (11/13) received a
Poisson distribution or a negative binomial distribution if over- 2-dose induction course followed by a new dose every 6 months.
dispersion is present. Rates were adjusted to the Canadian population After rituximab, at the 1-month follow-up an improvement of IgG
census of 2016. levels was observed ( p = 0.018) and a tendency towards decrease of
Results: Between 2005 and 2018, the overall age/sex annual AST/ALT. At month 6, the reduction in AST/ALT was statistically
incidence of PBC was 39.4 cases per million. Age-adjusted incidence significant ( p = 0.012 and p = 0.008). Eight out of 13 presented
rates were 60.7 per million in women versus 16.7 per million in men increased transaminases and IgG levels at the start of rituximab,
(incidence rate ratio [IRR] 3.68; 95% CI 2.98–4.54). The highest and 5/8 achieved biochemical response after rituximab therapy.
adjusted incidence was observed among the age group 60–79 years Treatment was well tolerated, without infusion reactions, though 3
(74.0 case per million). Age/sex-adjusted point prevalence rates of patients developed non-severe infectious complications. All patients
PBC increased from 295.8 to 500.0 per million between 2005 and but one were on corticoids at the beginning of rituximab and in 8/12
2018, p < 0.001. As expected, adjusted point prevalence rates were they could be tapered or discontinued. Moreover, in five of these
much higher among women than men (799.8 versus 169.0 per patients other immunosuppresants could be stopped due to the
million). We identified 520 incident cases during our study time positive impact of rituximab as shown in the figure. Despite initial
(female 78.7% [n = 409]). After a median follow-up of 6.8 years (IQR improvement, four patients presented flares of AIH during follow-up
3.9–10.6), 29 patients underwent transplantation (5.6%) and 81 that were successfully managed with new doses of ritixumab.
patients died (15.6%). The annual mortality rate was 8.1% (95% CI
9.8%–14.0%). The estimated 5- and 10-year survival rates were 90.7%
(87.5%–93.0%) and 77.4% (72.2%–81.7%), respectively. Survival was not
significantly different between men and women, p = 0.50.
Conclusion: In this well-defined cohort, we reported a significant
increase in the prevalence of PBC in a Canadian population.
Prevalence of PBC is higher among the older age group which could
reflect better case-identification and management.

THU464
Rituximab is a safe and effective treatment for patients with
autoimmune hepatitis: results from the Spanish registry for
cholestatic and autoimmune hepatitis
Ana Barreira1,2, Maria Carlota Londoño2,3,
Carmen Álvarez-Navascués4, Carlos Ferre Aracil5,
Indhira Perez Medrano6, Juan Turnes2,6, Diana Horta7,
Álvaro Díaz-González8, Fernando Diaz Fontela9,
Magdalena Salcedo2,9, Mar Riveiro Barciela2,10. 1Hospital Vall Hebron,
Liver Unit, Barcelona; 2Centro de investigación biomédica en red de
enfermedades hepáticas y digestivas; 3Hospital Clínic, Liver Unit,
Barcelona; 4Hospital Universitario Central de Asturias, Digestive Figure: Individual therapy at the beginning of rituximab (grey squares)
Department, Oviedo; 5Hospital Universitario Puerta de Hierro and drugs that were reduced or discontinued during follow-up (striped
Majadahonda, Digestive Department, Madrid; 6Complejo Hospitalario squares).
Universitario de Pontevedra, Digestive Department, Pontevedra;
7 Conclusion: Rituximab is a safe and effective treatment for AIH,
Hospital Universitari Mutua de Terrassa, Digestive Department,
leading to reduction of immunosuppression in a high proportion of
Barcelona; 8Hospital Universitario Marqués de Valdecilla. Instituto de
patients and improvement of transaminases and IgG levels.
Investigación Sanitaria Valdecilla., Digestive Department, Santander;
9
Hospital General Universitario Gregorio Marañón, Digestive
Department, Madrid; 10Hospital Vall Hebron, Liver Unit, Barcelona
Email: [email protected]
Background and aims: The evidence of second-line therapy for
autoimmune hepatitis (AIH) is relatively scarce, especially concerning
biological agents such as rituxumab. This study aims to evaluate the
efficacy and safety of rituximab in patients with autoimmune
hepatitis (AIH).
Method: multicenter retrospective study of all patients with AIH
from the ColHai registry who received rituximab from January 2015
to September 2021. Efficacy was assessed by improvement in
transaminases and Immunoglobulin (Ig) G or normalization (bio-
chemical response) and later development of flares; safety in terms of
adverse reactions, infectious and tumoral complications.

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 POSTER PRESENTATIONS
THU465 Conclusion: An increase in transaminase values after administration
Autoimmune hepatitis diagnosed after COVID-19 vaccination. of COVID-19 vaccine should be evaluated given the possibility of
Results from the spanish registry for autoimmune and cholestatic diagnosing autoimmune hepatitis.
hepatitis
Ana Barreira1,2, Mar Riveiro Barciela1,2, Agustin Castiella3, THU466
Álvaro Díaz-González4, Maria Carlota Londoño2,5, A prospective trial of a gluten free diet in primary sclerosing
Indhira Perez Medrano6, Judith Gómez-Camarero7, Marta Casado8, cholangitis with associated colitis
Carmen Del Pozo-Calzada9, María Dolores Antón Conejero2,10, Timur Liwinski1, Sina Hübener1, Lara Henze1, Peter Huebener1,
Magdalena Salcedo2,11. 1Hospital Universitario Vall de Hebrón, LIver Melina Heinemann1, Bettina Jagemann1, Marcus Tetzlaff1,
Unit; 2Instituto de Salud Carlos III., Centro de Investigación Biomédica en Guido Schachschal1, Thomas Rösch1, Erika Monguzzi2, Corinna Bang3,
Red de Enfemerdades Hepáticas y Digestivas (CIBERehd).; 3Hospital Andre Franke3, Ansgar W. Lohse1, Detlef Schuppan2,
Universitario de Donostia, Liver Unit; 4Hospital Universitario Marqués Christoph Schramm1. 1University Medical Center Hamburg-Eppendorf,
de Valdecilla. Instituto de Investigación Sanitaria Valdecilla (IDIVAL)., Hamburg, Germany; 2Universitätsmedizin der Johannes Gutenberg-
Servicio de Aparato Digestivo; 5Hospital Clínic Barcelona, Liver Unit; Universität Mainz, Mainz, Germany; 3University of Kiel, Kiel, Germany
6
Complejo Hospitalario Universitario de Pontevedra, Servicio de Aparato Email: [email protected]
Digestivo; 7Hospital Universitario de Burgos, Servicio de Aparato Background and aims: Primary sclerosing cholangitis (PSC) is a
Digestivo; 8Hospital Universitario de Torrecárdenas, Servicio de Aparato progressive autoimmune disease of the bile ducts associated with
Digestivo; 9Hospital Clínico Universitario de Valladolid, Servicio de inflammatory bowel disease. Several studies indicated that gluten
Aparato Digestivo; 10Hospital Universitario Dr. Peset, Valencia., Servicio restriction might ameliorate autoimmune liver disease and inflam-
de Aparato Digestivo; 11Hospital General Universitario Gregorio matory bowel disease (IBD) symptoms. We investigated whether
Marañón, Madrid, Hepatology and Liver Transplantation Unit patients with PSC with associated IBD can benefit from a diet free of
Email: [email protected] wheat and gluten (GFD) using a prospective multi-omics approach.
Background and aims: Universal vaccination has become the main Method: We performed a prospective clinical pilot study adminis-
strategy against the COVID-19 pandemic. The SARS-CoV-2 spike tering an eight-week GFD to PSC patients with non-advanced liver
protein used in the vaccines is believed to be responsible for disease and associated colitis without overt clinical activity. A clinical
stimulating the immune system, thus suggesting a possible associ- dietitian trained patients and controlled adherence to the interven-
ation between COVID-19 vaccines and the development of auto- tion by validated questionnaires and measuring gluten peptides in
immune diseases. To date, different events of probable autoimmune urine. The patients were evaluated at several time points, including
origin have been reported in association with the COVID-19 vaccine, endoscopy before and after the GFD period. We recorded multiple
including few cases of autoimmune hepatitis (AIH). The aim of this clinical parameters, dietary information, and biologically relevant
study was to describe the clinical and epidemiological characteristics parameters, including intestinal mucosal cytokine levels, intestinal
of a number of patients with AIH debut or reactivation after COVID-19 bulk RNA-Seq transcriptomics. The enteric fecal and mucosal
vaccination. microbiota were analyzed by sequencing the variable region V1/V2
Method: Multicenter, retrospective-prospective study, that included of the 16S rRNA gene and shotgun metagenomics.
subjects who have received one or two doses of any of the approved Results: In total, fifteen patients were enrolled and completed the
COVID-19 vaccines and later presented increased transaminases study. A decreased expression of proinflammatory mucosal cytokines
values due to AIH within the 90 days after vaccination. and chemokines such as IL6 ( p < 0.001), IL8 ( p < 0.001), CCL2 ( p =
Results: 23 patients from 9 Spanish academic hospitals were 0.042), and TNF-alpha ( p < 0.001) was observed after GFD. Moreover,
included. 17/23 were female, mean age 51 (±15) years. 19/23 patients the intestinal transcriptome indicated improvement of the gut
were biopsied and four were not, 3 of them had a previous diagnosis barrier, with an increase of pathways related to “adherens junction”
of AIH. Seven patients had another prior autoimmune disorder. ( p = 0.0471), “cell-substrate junction” ( p = 0.0262), “cell-substrate
COVID-19 vaccines: 12/23 Pfizer, 4 Moderna, 5 Astrazeneca and 2 adherens junction” ( p = 0.0233), and “focal junction” ( p = 0.0217). We
Janssen. In 14/23 patients the AIH episode happened after the second found mild to moderate changes in luminal microbiota composition
dose and in 9 after the first dose. Median time from the last dose of after GFD, including a decrease of Romboutsia ilealis (FC = −9.02, FDR
vaccine to AIH was 21 (11–36) days. Table 1 summarizes the analytical < 0.001). As expected from the short intervention period and the low
data of patients at the time of hepatitis. Antinuclear antibodies (ANA) disease activities, no statistically significant response was observed
≥1/80 was observed in 18/23 patients. Regarding the severity of regarding clinical parameters such as the endoscopic score ( p =
hepatitis, it was mild in the majority of patients (20/23), two patients 0.398) and patient-reported outcome measures. According to the
presented with fulminant hepatitis and in one subject it was severe. food frequency questionnaire, the macronutrient composition (other
All but one of the biopsied patients showed histological findings than gluten) did not change during eight weeks of diet.
compatible with AIH. The RUCAM to assess causality showed at least Conclusion: This is the first study to demonstrate that GFD may
possible association (≥4 points) in 11 patients. Simplified AIH Score improve intestinal inflammation and barrier function in patients with
showed at least probable AIH (≥6 points) in 16/23 patients. All PSC-IBD. This effect was linked to changes in the enteric microbiota
patients received treatment with corticosteroids and in 19 patients composition. This pilot study justifies subsequent studies in patients
immunosuppressive treatment with azathioprine was initiated. with more severe disease activity.

Figure: Analytical data of the patients at the time of hepatitis

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POSTER PRESENTATIONS
THU467
The international autoimmune hepatitis group retrospective
registry: quality assessment and analysis of clinical characteristics
and liver-related outcome
Charlotte Slooter1, Floris van den Brand1, Ana Lleo2,
Francesca Colapietro2, Marco Lenzi3, Paolo Muratori3, Nanda Kerkar4,
George Dalekos5, Kalliopi Zachou5, Maria Isabel Lucena6,
Mercedes Robles-Díaz6, Daniel E. Di Zeo-Sánchez6, Raul J. Andrade6,
Aldo J Montano-Loza7, Ellina Lytvyak7, Guilherme Macedo8,
Gerd Bouma1, Rodrigo Liberal8,9, Ynto de Boer1. 1Amsterdam
University Medical Center, Netherlands; 2Humanitas University, Italy;
3
University of Bologna, Italy; 4Golisano Children’s Hospital, University of
Rochester Medical Center, Rochester, United States; 5University Hospital
of Larissa, Greece; 6Vírgen de Victoria University Hospital, University of
Málaga, Spain; 7University of Alberta Hospital, Edmonton, Canada;
8
Centro Hospitalar Sao Joao, Porto, Portugal; 9King’s College, United
Kingdom
Email: [email protected]
Background and aims: The International Autoimmune hepatitis
(AIH) Group retrospective registry (IAIHG-RR) is a web-based Figure: Data captured in absolute numbers for a pre-defined set of 31 vari-
platform for large scale aetiological and therapeutic studies in ables in the IAIHG-RR (n = 2278).
paediatric and adult subjects enrolled with a diagnosis of AIH. This
study aimed to ascertain data quality and describe the clinical THU468
characteristics and outcomes of this cohort. Liver inflammation activity in autoimmune hepatitis patients
Method: This retrospective analysis included all patients with a with normal ALT and IgG levels
clinical diagnosis of AIH (n = 2278) from the IAIHG-RR entered Chuanwu Zhu1, Jiacheng Liu2, Jian Wang3, Huali Wang4, Yilin Liu2,
between December 2018 and September 2021. This registry contains Yiguang Li5, Li Zhu1, Weimao Ding6, Yuanwang Qiu5, Yongfeng Yang4,
data on clinical characteristics and liver-related outcomes from 37 Jie Li3, Rui Huang3, Chao Wu3. 1The Affiliated Infectious Diseases
centers in 7 countries. Quality assessment included cohort com- Hospital of Soochow University, Department of Infectious Diseases,
pleteness for 31 pre-defined variables, consistency and data was Suzhou, China; 2Nanjing Drum Tower Hospital Clinical College of
externally validated. Traditional Chinese and Western Medicine, Nanjing University of
Results: Completeness of individual data was 75.8% (range 3.0–100). Chinese Medicine, Department of Infectious Diseases, Nanjing, China;
3
Per center, completeness varied between 69.5% and 99.9%. Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing
Consistency of inclusion criteria and outlier analysis was nearly University Medical School, Department of Infectious Diseases, Nanjing,
100%. Among patients for whom a simplified AIH score was available, China; 4Nanjing Second Hospital, Nanjing University of Chinese
diagnosis was classified as possible in 27, 5%, probable in 25.0% and in Medicine, Department of Hepatology, Nanjing, China; 5The Fifth People’s
47.5% as definite. At diagnosis, 21.9% showed signs of cirrhosis and Hospital of Wuxi, Department of Infectious Diseases, Wuxi, China;
6
median Model for End-Stage Liver Disease (MELD) score was 11 Huai’an No. 4 People’s Hospital, Department of Hepatology, Huai’an,
[range 6–40]. Primary biliary cholangitis and primary sclerosing China
cholangitis were reported in 10.0% and 7.0%, respectively. Other Email: [email protected]
associated diseases were reported in 26.3%. For 1191 patients follow-
Background and aims: Serum alanine transaminase (ALT) and IgG
up and outcome data was available. With a median follow-up period
levels are considered as surrogate markers for histological activity in
of 12 [range 0–49] years 36.8% demonstrated signs of cirrhosis, 2.2%
autoimmune hepatitis (AIH). We assessed the inflammatory activity
were diagnosed with hepatocellular carcinoma and 10.6% underwent
in AIH patients with normal ALT and IgG levels.
liver transplantation. 172 patients died during the follow-up period at
Method: 257 AIH patients underwent liver biopsy (LB) were
a median age of 65 (range 15–94). In 49.7%, the cause of death was
retrospectively included from four medical centers. Liver inflamma-
reported liver-related. Liver transplantation and liver related death
tion and fibrosis were estimated by Scheuer scores. The definitions of
were both associated with signs of cirrhosis at baseline (hazard ratio
advanced inflammation and fibrosis were G ≥ 3 and S ≥ 3,
[HR] 1.90; p < 0.001), the MELD score at baseline (HR 1.09; p < 0.001)
respectively.
and with persistence of elevated aminotransferases at 6 months (HR
Results: 163 (63.3%) AIH patients had advanced inflammation, while
2.75; p < 0.001).
125 (48.6%) patients had advanced fibrosis. The proportion of
Conclusion: The IAIHG-RR represents world’s largest patient cohort advanced inflammation was 62.1% in patients with normal ALT and
with moderate-to-good quality of baseline and follow-up data with 55.6% in patients despite normal ALT and IgG. The proportion of
relevant number of liver-related adverse events. This study showed advanced inflammation was 44.0% in patients without advanced
that cirrhosis and MELD score at baseline and persistence of elevated fibrosis and was 81.8% in those with advanced fibrosis. Of patients
aminotransferases at 6 months are associated with liver transplant- with advanced fibrosis, 78.6% (33/42) of patients with normal ALT
ation and liver-related death. This registry is a suitable platform, presented advanced inflammation, which was 75.0% in patients with
which allows for patient selection for future therapeutic and normal ALT and IgG. Among patients without advanced fibrosis, the
aetiological studies. proportion of advanced inflammation was as high as 33.3% in those
with normal ALT and 31.3% in those despite normal ALT and IgG. Red
cell distribution width was independently associated with advanced
inflammation (OR: 1.521, 95%CI: 1.193–1.938, P = 0.001) in entire
patients.

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 POSTER PRESENTATIONS

Figure: Histological activity in relation to ALT and IgG levels in AIH

patients with or without advanced fibrosis

Conclusion: High proportion of advanced inflammation was found in

AIH patients despite normal ALT and IgG levels even for those without
advanced fibrosis. Though fibrosis can be ruled out by non-invasive
methods in AIH patients with normal ALT and IgG, LB is encouraged to
assess inflammatory activity.

THU469
Novel screening test for primary sclerosing cholangitis: the role of
serology, liver function tests, histology and radiology
Nina Barner-Rasmussen1, Nelli Sjöblom2, Hannu Kautiainen3,
Johanna Arola2, Martti Färkkilä1. 1University of Helsinki and Helsinki
University Hospital, Departement of Gastroenterology, Helsinki, Finland;
2
University of Helsinki and Helsinki University Hospital, Department of
Pathology, Helsinki, Finland; 3University of Eastern Finland, Institute of
Public Health and Clinical Nutrition, Kuopio, Finland
Email: [email protected]
Figure: Prognostic performance of HelPSCreening-score
Background and aims: Primary sclerosing cholangitis (PSC) is a
chronic cholestatic liver disease. There is no specific laboratory test Conclusion: We have created a novel scoring system to screen the
for surveillance or screening in PSC unlike in primary biliary probability of PSC using non-invasive tests. The HelPSCreening-score
cholangitis. At present, the screening of PSC is mainly based on may help target further investigations in patients with suspicion of
elevated alkaline phosphatase (ALP) in patients with inflammatory PSC.
bowel disease (IBD). However, ALP and gamma-glutamyl transferase
(GT) may be normal, even in advanced bile duct disease. The THU470
diagnosis is made by magnetic resonance cholangiopancreatography More than just an itch: impact of cholestatic pruritus in primary
(MRCP) or by endoscopic retrograde cholangiography (ERC). The biliary cholangitis (PBC) on health-related quality of life (HRQoL)
latest guidelines from Europe and America do not recommend liver Helen Smith1, James Fettiplace1, Robyn von Maltzahn1, Sugato Das2,
biopsy, apart from small-duct PSC or a suspicion of an overlap Megan McLaughlin3, David Jones4. 1GlaxoSmithKline, United Kingdom;
2
syndrome. We aim to produce a screening system to predict the GlaxoSmithKline, India; 3GlaxoSmithKline, United States; 4Newcastle
likelihood of PSC evaluating the role of laboratory tests, liver histology University, United Kingdom
and MRCP. Email: [email protected]
Method: We retrieved 395 PSC patients from the PSC registry of Background and aims: Pruritus associated with PBC affects sleep
Helsinki University Hospital who came for their 1st ERC to confirm and social and emotional wellbeing. Limited data exist on the impact
the diagnosis. 69 patients with suspicion of PSC who underwent ERC, of pruritus on health utility (a single value between 0 [death] and 1
liver biopsy and MRCP excluding PSC, served as controls (non-PSC [ perfect health]), commonly used in health technology assessments
patients). Liver histology was scored according to the Nakanuma to calculate quality-adjusted life years and compare different
classification from Herovici stained core needle biopsy specimens. conditions. A recent UK study explored EQ-5D utilities in a broad
MRCP before diagnosis was scored from the existing radiology report PBC population (Rice et al. Clin Gastroenterol Hepatol 2021;19:769–
as negative for PSC, finding suggestive for PSC, and clear findings for 76). Here, using data from the Phase 2b GLIMMER study ( post hoc)
PSC. We included demographics and eleven different laboratory tests investigating linerixibat for the treatment of pruritus in PBC
in the analysis. Area under the curve (AUC), positive prediction value, (NCT02966834), the impact of itch severity on health utility in PBC
likelihood ratio, sensitivity, specificity, and odds ratio (OR) were is explored and quantified for the first time.
calculated. Variables with highest OR were selected for multivariate Method: Patients in GLIMMER recorded itch twice daily on a 0–10
logistic regression, which was used to create the novel scoring numeric rating scale (NRS) and completed the EQ-5D-5L at study
system. entry, baseline (BL) and end of treatment. BL followed a.
Results: IBD, perinuclear anti-neutrophil cytoplasmic antibodies (P- 4-week single-blind placebo run-in. Patients were classed as having
ANCA) and ALP had the best predictive value. A score was assigned to mild (<4), moderate (≥4 to <7) or severe pruritus (≥7 to 10) based on
each statistically significant predictor. Presence of IBD and P-ANCA mean Worst Daily Itch NRS score in the 7 days prior to BL.
gives 2 points each and ALp >UNL 1 point. The optimal cut-off point Results: The GLIMMER population (N = 147) was 94% female with a
for the score was ≥3, with AUC of 0.83 (95%CI 0.78–0.88). If a patient mean (SD) age at BL of 55.8 (11.04) years. Most patients had moderate
got a score of 3 or higher, the probability of a true PSC diagnosis was pruritus (n = 76), with similar numbers with mild (n = 35) and severe
>90%. Adding liver histology or MRCP to the score did not add (n = 36) pruritus. At BL, alkaline phosphatase levels were higher with
predictive value. greater itch severity: mean (SD).
177 (115.4) and 249 (190.8) IU/L in patients with mild and severe itch,
respectively. Overall, mean (SD) BL utility was 0.69 (0.23), lower than
the general PBC population (Figure) and with a clear and notable
impact of pruritus severity on health utility. Thus, patients with mild
or moderate pruritus at BL had similar utilities (0.75 [0.17] and 0.76
[0.17], respectively), marginally lower than the general UK population

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POSTER PRESENTATIONS
(mean at age 55–64 years: 0.804). Patients with severe pruritus at BL 78 (29%) patients and flared in 28 (11%). The median time to
had notably worse utility (0.49 [0.28]), similar to patients with severe transaminases normalization was 15 months (IQR 7–27). Patients
Parkinson’s disease (0.47 [0.22]; Figure). Over the course of the study with IgGn were more frequently diagnosed with non-severe acute
health utility declined in the placebo group (−0.01) and increased AIH (NS-AIH; p = 0.001) and those with IgGe had lower prevalence of
across all linerixibat arms (0.04–0.05). Although improvements were positive anti-smooth muscle antibody (SMA, p = 0.001).
small (confidence intervals crossed zero), the directional change Immunosuppression was intensified in 13 (12%) patients with
supports a treatment effect of linerixibat. abnormal IgG, leading to normalization in 7 patients. 95 patients
had at least two liver stiffness measurements (LSM) available. After a
median follow-up of 4.5 years (IQR 3–8), LSM worsen in 12 (13%)
patients, improved in 23 (24%), and remained stable in 60 (63%). IgG
levels did not impact the evolution of LSM. 17 patients (6%) developed
cirrhosis, without differences between groups. The risk of cirrhosis
was higher in patients who normalized transaminases beyond month
15 after induction treatment (OR 3.42; CI95% 1.1–10.8) and in those
with LSM higher than 10.5 kPa at the time of transaminases
normalization (OR 6.13; CI95% 1.18–31.8).

Total (n = 266). IgGe (n = 78). IgGn (n = 160). IgGf (n = 28).

Age 64 (52–73) 63 (52–72) 63 (52–73) 67.1 (59–75)

AIH at diagnosis
Acute liver failure 3 (1) 2 (23) 0 1 (4)
Acute severe-AIH 43 (16) 18 (23) 20 (12) 5 (18)
Chronic AIH 80 (30) 26 (33) 43 (27) 11 (39)
NS-AIH 137 (52) 32 (41) 97 (61) 11 (39)
Cirrhosis at diagnosis 32 (12) 8 (10) 22 (14) 2 (7)
Conclusion: Pruritus ( particularly severe pruritus) has a significant (n, %)
negative impact on HRQoL and health utility. Presence and severity of ALT (UI/L) 584 (230–1204) 580 (390–1141) 622 (229–1264) 426 (161–1094)
Bilirubin (mg/dL) 2.2 (0.8–8) 2.1 (0.6–8) 2.4 (0.8–8) 1.3 (0.7–8.1)
itch should be evaluated in PBC and prioritised in treatment plans. INR 1.1 (1–1.3) 1.2 (1.03–1.44) 1.1 (1–1.24) 1.18 (1–1.24)
Funding: GSK (201000). ANA (n, %) 209 (80) 56 (75) 126 (80) 27 (100)
ASMA (n, %) 121 (46) 24 (32) 77 (49) 20 (71)
Anti-SLA (n, %) 5 (2) 1 (1) 2 (1) 1 (3)
THU471 IgG (mg/dL) 1954 (1405– 2033 (1462– 1740 (1300– 2800 (2200–
Isolated IgG elevation is not associated with worse outcome in 2560) 2520) 2290) 3330)
Cirrhosis follow-up 17 (6) 4 (5) 10 (6) 3 (11)
patients with autoimmune hepatitis (n, %)
Alvaro Diaz Gonzalez1, Lorena Carballo-Folgoso2,
Carmen Álvarez-Navascués2, Judith Gómez-Camarero3, Diana Horta4, Continuous variables are presented as median and IQR.
Beatriz Mateos Muñoz5, María Del Barrio1, Marina Cobreros1,
Sergio Rodriguez-Tajes6, Olivas Ignasi6, Indhira Perez Medrano7, Conclusion: Isolated IgG elevation in patients with persistently
Inmaculada Castello8, Alberto Gómez9, normal transaminase levels, did not impact the outcome of patients
Manuel Rodríguez-Perálvarez9,10, Javier Crespo1, with AIH.
Magdalena Salcedo11, Ana Barreira12, Mar Riveiro Barciela12,
Maria Carlota Londoño6. 1Marqués de Valdecilla University Hospital, THU472
Digestivo, Santander, Spain; 2Central University Hospital of Asturias, Linerixibat dose-response analysis of C4 concentrations as a
Oviedo, Spain; 3Burgos University Hospital, Burgos, Spain; 4Hospital quantitative approach to predict gastrointestinal tolerability
Universitari MútuaTerrassa, Terrassa, Spain; 5Hospital Ramón y Cajal, Fernando Carreño1, Rashmi Mehta2, Andrea Ribeiro3, Jon Collins2,
Madrid, Spain; 6Hospital Clínic de Barcelona, Barcelona, Spain; Brandon Swift2. 1GlaxoSmithKline, Upper Providence, PA, United States;
2
7
Complejo Hospitalario Universitario de Pontevedra, Digestivo, GlaxoSmithKline, Research Triangle Park, NC, United States;
3
Pontevedra, Spain; 8Consorci Hospital General Universitari de Valen ̀ cia, GlaxoSmithKline, Madrid, Spain
̀ cia, Spain; 9Hospital Universitario Reina Sofia, Córdoba, Spain;
Valen Email: [email protected]
10
University of Córdoba, IMIBIC, CIBERehd, Department of Hepatology Background and aims: Linerixibat is an ileal bile acid transporter
and Liver Transplantation, Córdoba, Spain; 11Gregorio Marañón (IBAT) inhibitor in Phase 3 development for the treatment of
Hospital, Madrid, Spain; 12Hospital Universitari Vall d’Hebron, cholestatic pruritus in primary biliary cholangitis (PBC). IBAT
Barcelona, Spain inhibition reduces bile acid (BA) reabsorption from the intestine,
Email: [email protected] reducing circulating systemic BA concentrations and pruritus but
Background and aims: The goal of treatment in patients with leading to excess BA in the colon with potential to cause diarrhoea.
autoimmune hepatitis (AIH) is biochemical remission, (normaliza- Linerixibat increases concentrations of 7-alpha-hydroxy-4-choles-
tion of transaminases and IgG). However, the clinical impact and the ten-3-one (C4), a prognostic biomarker for BA-induced diarrhoea.
management of isolated IgG elevation is unknown. We aimed to Here we evaluate the relationships between (1) linerixibat and serum
describe the outcome of AIH patients with persistently normal C4 concentrations; and (2) effect of C4 on probability of diarrhoea
transaminases attending to evolutionary changes in IgG levels. using the gastrointestinal symptoms rating scale (GSRS).
Method: Multicenter retrospective study of patients with AIH Method: Serum C4 data were included from healthy subjects in three
diagnosed at 10 referral centres in Spain. Only patients with Phase 1 studies (114985, 116511, 205808) and from patients with PBC
persistently normal transaminases after induction treatment were in two Phase 2 studies (177213, 201000 [GLIMMER]).
included in the study. Patients were divided according to IgG levels C4 concentrations over time were described by a k-PD indirect-
during the follow-up as: a) persistently normal (IgGn); b) persistently response model with a stimulatory effect of linerixibat on C4
elevated (IgGe); c) IgG flares (IgGf ). production. Weekly GSRS data were collected in GLIMMER, which
Results: Out of 1253 patients with AIH, 266 (21%) presented evaluated the impact of five linerixibat treatment regimens in
persistently normal transaminases during the follow-up. Baseline patients with PBC.
characteristics are shown in table 1. IgG was persistently elevated in Results: The k-PD model showed a saturable dose-response
relationship with C4 concentrations. The two BID linerixibat

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 POSTER PRESENTATIONS
regimens led to a 24% increase in C4 compared with the change from
baseline for a similar daily QD dose (i.e. 90 mg BID vs 180 mg QD).
Increased C4 concentrations trended with increased diarrhoea scores
in the GSRS tool. C4 concentrations ≥52 ng/ml were associated with a
62% increased probability of moderate-to-severe diarrhoea scores
compared with C4 concentrations <14 ng/ml, as observed in
participants in the placebo arm. Simulations showed increases of
9%, 17%, 20%, 19% and 23% in moderate-to-severe diarrhoea scores for
the 20 mg, 90 mg and 180 mg QD, and 40 mg and 90 mg BID doses,
respectively, after the first week of linerixibat dosing. This was
consistent with the rate of on-treatment diarrhoea adverse events by
treatment arm in GLIMMER ( placebo: 11%; 20 mg QD: 38%; 90 mg
QD: 65%; 180 mg QD: 67%; 40 mg BID: 52%; 90 mg BID: 68%).
Conclusion: Linerixibat led to dose-dependent increases in serum C4
concentrations that predicted an increased probability of moderate- Figure: Receiver operating characteristic curve demonstrating the ability
to-severe diarrhoea. The increase in diarrhoea scores highlights the of urinary PM8S to diagnose ICP at disease onset
trade-off between maximising the pharmacodynamic effect of
Conclusion: Urinary progesterone sulfate excretion appears useful
linerixibat on pruritus and increase in GSRS scores, which guided
diagnostically for ICP, which obviates the need for blood sampling.
dose selection for Phase 3.
Similarly, using the individual profile of urinary PMS may be helpful
Funding: GSK (114985, 116511, 205808, 177213, 201000)
to identify the subgroup of women for whom UDCA treatment is
THU473 beneficial, and may contribute to the variable clinical response to
Urinary sulfated progesterone metabolites are diagnostic markers UDCA treatment that complicates trials of its use in ICP.
for cholestatic pregnancy and markers of treatment response to
THU474
ursodeoxycholic acid
COVID-19 vaccine induced autoimmune hepatitis-a first case
Luiza Borges Manna1, Caroline Ovadia1, Jenna Sajous1, series from India
Anita Lövgren-Sandblom2, Hanns-Ulrich Marschall3,
Sowmya Iyengar1, Anand Kulkarni1, Goutham Reddy Katukuri2,
Catherine Williamson1. 1King’s College London, Women and Children’s
Mithun Sharma1, Nageshwar Reddy2, Nagaraja Rao Padaki1. 1AIG
Health, London, United Kingdom; 2Karolinska University Hospital
Hospital, Hepatology, Hyderabad, India; 2AIG Hospital, Gastroenterology,
Huddinge, Stockholm, Sweden; 3University of Gothenburg, Department
Hyderabad, India
of Molecular and Clinical Medicine, Gothenburg, Sweden
Email: [email protected]
Email: [email protected]
Background and aims: Liver injury is common in patients with
Background and aims: Serum concentrations of sulfated metabolites
coronavirus disease-2019 (COVID-19) infection. Recently, few studies
of progesterone are elevated in intrahepatic cholestasis of pregnancy
have reported the development of autoimmune hepatitis (AIH)
(ICP), and have been proposed as predictive and diagnostic
following COVID-19 vaccination. However, there is a lack of studies
biomarkers. Ursodeoxycholic acid (UDCA) treatment can alter
reporting the outcomes of AIH following ChAdOx1 (vector-based)
urinary excretion of progesterone sulfates. We aimed to determine
and BBV152 (inactivated virus) from India. Here we aimed to describe
whether urinary progesterone sulfate excretion is predictive or
the clinical profile of patients who developed AIH following COVID-19
diagnostic of ICP, and whether their levels are associated with
vaccination. The causal association is attributed based on the
UDCA treatment response.
temporal relationship in patients with no prior liver diseases.
Method: Urine was obtained from women with cholestatic and
Method: Patients presenting with deranged liver functions following
uncomplicated pregnancies throughout pregnancy and postpartum,
COVID-19 vaccination to hepatology clinic were included. Virus
including matched samples before and 1–2 weeks after commencing
infections were ruled out in all patients either by serology or viral
UDCA treatment. Urinary progesterone sulfates were measured by
quantification methods. We aimed to assess the demographics,
ultra performance liquid chromatography-mass spectrometry, and
clinical profile, and outcome of patients with vaccine-induced AIH
normalised according to creatinine levels (measured by colorimetric
(V-AIH) in the absence of known liver disease.
assay). Results were compared in Graphpad Prism by multiple t tests
Results: A total of 31 patients presented with altered liver chemistries
with Benjamini-Hochberg correction for multiple testing, Fisher’s
following vaccination. Seventeen patients were diagnosed with V-
exact test and logistic regression.
AIH (age-39.8 ± 11.4 years; males-70.4%). None of the patient had
Results: Urinary 5α-pregnan-3α, −20α-diol-3, 20-disulfate (PM2DiS),
history of alcohol overconsumption. Seventy six percent of patients
5β-pregnan-3α, 20α-diol-3, 20-disulfate (PM3DiS), 5β‐pregnan‐3α, ‐
had received ChAdOx1 and 23.53% had received BBV152 vaccine
20α‐diol‐3-sulfate (PM3S), 5α-pregnan-3α-S, 20-one (PM4S) and 5α-
(Table). Seventy six percent of patients following first dose of vaccine
pregnan-3β, 20β-diol-3-sulfate (PM8S) were higher in women with
and 23.5% following second dose of vaccine were diagnosed as V-AIH.
cholestatic than uncomplicated pregnancies; PM8S differentiated
Mean duration for development of symptoms after first dose was 25.7
well between the two groups (AUC 0.86, figure 1). UDCA treatment
days. Common symptom at presentation was jaundice in 82.3% of
was associated with significantly reduced PM2DiS and PM3DiS (from
patients. Antinuclear antibody was positive in 71% of patients and 17%
19.10 to 12.22, p = 0.032). Symptomatic response ( pruritus improve-
patients were negative for all serological markers of autoimmune
ment) with UDCA was predicted by the total disulfated progesterone
hepatitis but had elevated IgG levels. Fifty-nine percent of patients
metabolites (area under curve (AUC) = 0.80), whilst biochemical
required immunosuppression of which 41% percet of patients
response (fall in total serum bile acid concentration) was predicted by
received oral steroids, 17% patients received intravenous steroids for
urinary 5α-pregnan-3β-ol-20-one-sulfate (PM5S) and 5β-pregnan-
3 days followed by oral steroid, 12% patients received azathioprine.
3β-ol-20-one-sulfate (PM7S) (AUC = 0.81).
One patient succumbed to pneumonia with multiorgan failure by day
30. At 3 months, it was observed that only 17% patients needed
prolonged immunosuppression and had deranged liver functions
until last follow-up. Mean duration of recovery amongst rest of 76.4%
patients was 5.15 ± 3.1 weeks.

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POSTER PRESENTATIONS
Table: Clinical characteristics and outcome of V-AIH histopathological consensus criteria. Retrospective evaluation of
presence and timing of malignancy confirmed radiologically and
histologically through the MDM. UK national cancer registry data²
was used to determine the age and gender standardised incidence
ratios (SIR) for malignancy and non-hodgkin’s lymphoma (NHL) for
comparison.
Results: Of 105 IgG4-RD patients (median age 67; IQR 56–76 years,
male:female ratio 2.4:1), 21 (20%) developed malignancy (table 1),
with an SIR of 12.3 (95%CI 7.6–18.8).

Table 1:
Primary Observed
Cancer Cases
Lymphoma 7
Renal 2
Gastric 1
Biliary 2
Breast 1
Oesophagus 1
Thyroid 1
Pancreas 1
Prostate 2
Colon 2
Ovarian 1

One-third (7/21) had lymphoma. Most (6/7) were NHL B cell

lymphomas, SIR 93.6 (95%CI 34.2–203.7). 3 patients with lymphoma
had IgG4-related pancreato-biliary disease, 3 had IgG4-related head
and neck disease and 1 had IgG4-related renal disease. 3 lymphomas
were diagnosed prior, and 4 subsequent, to their IgG4-RD diagnosis.
The median time between lymphoma and IgG4-RD diagnosis was 4.4
years; (range −10.5–11.8 years). Of these, 1 had been exposed to an
immunomodulator, azathioprine, prior to lymphoma. Lymphoma
was successfully treated with R-CHOP chemotherapy in all cases.
Conclusion: We demonstrate an increased incidence of malignancy
in our IgG4-RD cohort with a striking incidence of NHL, which
otherwise accounts for <4% of annual UK new cancer diagnoses. There
are currently no cancer surveillance guidelines in IgG4-RD, and the
frequency of lymphoma makes us question the use of off-label
SD-standard deviation, CKD- chronic kidney disease, NAFLD- Non-alco- azathioprine as relapse prevention in this older male cohort.
holic fatty liver disease, ALT- alanine amino transferase, AST- aspartate
amino transferase, ALP- alkaline phosphatase, ANA-anti-nuclear antibody, References
ASMA- anti smooth muscle antibosy, Anti-LKM1- liver-kidney microsomal Huggett MT, et al. Type 1 Autoimmune Pancreatitis and IgG4-Related
antibody type 1, AMA-Anti mitochondrial antibody. Sclerosing Cholangitis Is Associated With Extrapancreatic Organ
Failure, Malignancy, and Mortality in a Prospective UK Cohort. Am.
Conclusion: COVID-19 vaccine can trigger autoimmune hepatitis.
J. Gastroenterology. 2014;109
Males are affected more often than females. Treatment with steroids Cancer Research UK-All cancer and Non-Hodgkin’s lymphoma incidence
has high success rate and significant proportion of patients have self- statistics comprising data from the National Cancer Registration and
limiting disease and may not require long term immunosuppression. Analysis Service, ISD Scotland, Welsh and the Northern Ireland Cancer
Registry-Accessed 22/11/2021 https://www.cancerresearchuk.org/
THU475 health-professional/cancer-statistics/statistics-by-cancer-type/non-
Lymphoma in IgG4-related disease: should we be concerned? hodgkin-lymphoma
Arif Hussenbux1,2, Rory Peters1,2, Charis Manganis1, Eve Fryer3,
Helen Bungay4, Joel David5, Emma Culver1. 1John Radcliffe Hospital, THU476
Gastroenterology, Oxford, United Kingdom; 2Authors contributed Measurement properties of the PBC-10 in a dutch population
equally; 3John Radcliffe Hospital, Histopathology, Oxford, United Maria van Hooff1, Rozanne de Veer1, Maren Harms1,
Kingdom; 4John Radcliffe Hospital, Radiology, Oxford, United Kingdom; Geraldine Da Silva1, José Willemse2, Herold Metselaar1,
5
John Radcliffe Hospital, Rheumatology, Oxford, United Kingdom Elaine Utomo3, Adriaan Van der Meer1. 1Erasmus University Medical
Email: [email protected] Center, Department of Gastroenterology and Hepatology, Rotterdam,
Netherlands; 2Dutch Liver Patients Association, Hoogland, Netherlands;
Background and aims: Immunoglobulin G4-Related Disease (IgG4- 3
Independent Researcher, Berkel en Rodenrijs, Netherlands
RD) is a systemic fibroinflammatory disorder, with a predilection for
Email: [email protected]
the pancreas and biliary tree. We have reported an association of
malignancy in our cohort of IgG4-related pancreato-biliary disease¹. Background and aims: Practice guidelines advice to evaluate the
We sought to assess the frequency and type of malignancy in our Health Related Quality of life (HRQoL) of all patients with primary
prospective cohort of IgG4-RD patients with radiological and biliary cholangitis (PBC). The PBC-40 has proven to be an adequate
histological evaluation through our monthly IgG4-RD multi-discip- PBC-specific HRQoL measure. However, as this measure can be time
linary meeting (MDM). consuming and thus less practical, the UK-PBC group developed the
Method: Patients diagnosed with IgG4-RD and discussed at the MDM PBC-10 as a shorter version for screening HRQoL in clinical practice.
between November 2016 and September 2021 were included, with The aim of this study was to assess the measurement properties of the
diagnosis based on established HISORt, CDC or Boston items selected for the PBC-10 in a Dutch PBC population.

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 POSTER PRESENTATIONS
Method: Our study group previously translated the PBC-40 into biliary cholangitis (PBC)-also carry gluco-regulatory disturbances is
Dutch and validated it in a Dutch population. Existing data of the unknown. We therefore investigated glucose and hormonal
Dutch PBC-40 questionnaire was used to assess patients responses on responses to an oral glucose tolerance test (OGTT) in patients with
the PBC-10 items. Internal consistency of the PBC-10 was assessed by biopsy-verified non-cirrhotic PBC and NAFLD and healthy controls.
Cronbach’s alpha. A value between 0.70 and 0.95 is considered as The data presented are early results from FALL, a prospective cohort
adequate. Content validity was assessed by determination of floor study.
and ceiling effects (i.e. >15%). Each PBC-10 item was correlated with Method: 23 participants have been included hereof 8 healthy
the total score of the corresponding original PBC-40 domain. controls (mean age 23, mean BMI 23 kg/m2), 9 patients with PBC
Results: In total, 177 patients with PBC were included. The mean (SD) (mean age 55, mean BMI 31 kg/m2) and 6 patients with NAFLD (mean
age was 61.1 (9.9) years and the majority of patients was female (n = age 38, mean BMI 31 kg/m2). None of the included patients had
164; 92.7%). Of the total 1770 items, 81 items (4.6%) were missing. The diabetes. In the PBC group, 3 had NAFLD. Blood samples were
PBC-10 showed a Cronbach’s alpha of 0.895. Floor and ceiling effects obtained at baseline (fasting) and 15, 30, 45, 60, 90 and 120 minutes
were observed in 7 and 3 items, respectively. Floor effects ranged during the OGTT. Glucose, c-peptide and insulin concentrations were
from 13.6% to 61.0%. All PBC-10 items were significantly correlated measured. A validated marker for hepatic insulin resistance (the
with the corresponding domains of the PBC-40 (Pearson correlations homeostasis model assessment of insulin resistance (HOMA-IR)) and
ranged from 0.711 to 0.912, p < 0.001 for all) (Table). the incremental area under curve (iAUC) for glucose, c-peptide and
insulin responses were calculated. Results are presented as means
(95% CI).
Results: Fasting glucose, c-peptide and insulin levels were signifi-
cantly increased in both PBC (glucose 5.6 mM (4.7–6.7), c-peptide
993 pM (556–1773), insulin 98 pM (33–298)) and NAFLD (glucose
5.7 mM (5.2–6.1), c-peptide 1334 pM (1036–1719), insulin 166 pM
(103–267)) compared with healthy (glucose 4.7 mM (3.9–5.6), c-
peptide 483 pM (268–869), insulin 43 pM (14–136)). Hepatic insulin
resistance (reflected by fasting HOMA-IR) was present in PBC (4.0
(1.2–13.9)) and NAFLD (7.0 (4.1–11.9)) but not in healthy individuals
(1.5 (0.4–5.4)). No significant difference in glucose levels was
observed between the groups ( p = 0.106). Beta-cell secretion (c-
peptide) was significantly increased in PBC ( p < 0.001) and NAFLD
( p < 0.001) suggesting that peripheral insulin resistance was present
in patients with PBC and NAFLD. Insulin responses (reflecting both
beta-cell secretion and hepatic insulin extraction) were numerically
higher in both PBC and NAFLD compared with healthy but only
reached statistical significance in NAFLD ( p = 0.002).
Conclusion: In a Dutch population, the PBC-10 showed an adequate
internal consistency and reflects the content of corresponding PBC-
40 domains. There were, however, substantial floor effects. The PBC-
10 may be considered in clinical practice as a screening tool for
patients with a profound impact of PBC on their HRQoL. However, the
Dutch PBC-10 may be less suitable to identify PBC patients with less
severe HRQoL impairment or to detect further improvement of their
HRQoL following intervention.

THU477
Gluco-regulatory disturbances in primary biliary cholangitis and
non-alcoholic fatty liver disease compared with healthy
individuals
Anne-Sofie Houlberg Jensen1,2, Henriette Ytting1,3,
Josephine Grandt1,2, Andreas Møller1, Mikkel Werge1, Elias Rashu1,
Liv Hetland1, Mira Thing1, Anders Junker1, Lise Hobolth1, Conclusion: Our data suggest that patients with PBC may have gluco-
Christian Mortensen1, Flemming Bendtsen1,4, Flemming Tofteng1, regulatory disturbances including both hepatic insulin resistance and
Mogens Vyberg5,6, Reza Serizawa5, Lise Lotte Gluud1, altered pancreatic endocrine function. Whether these impairments
Nicolai J Wewer Albrechtsen2,7,8. 1Hvidovre Hospital, Gastro Unit, reflect an obesity prone phenotype in PBC and NAFLD patients cannot
Hvidovre, Denmark; 2Novo Nordisk Foundation Center for Protein be concluded from the current data. Metabolic dysfunction of PBC
Research, København, Denmark; 3Rigshospitalet, European Reference may be underestimated and warrant further investigation.
Network on Hepatological Diseases (ERN-RARE-LIVER), København,
Denmark; 4The University of Copenhagen, Faculty of Health and Medical
Sciences, København, Denmark; 5Hvidovre Hospital, Department of
Pathology, Hvidovre, Denmark; 6Center for RNA Medicine, Aalborg,
Denmark; 7Rigshospitalet, Department of Clinical Biochemistry,
København, Denmark; 8The University of Copenhagen, Faculty of Health
and Medical Sciences, Department of Biomedical Sciences, København,
Denmark
Email: [email protected]
Background and aims: Gluco-regulatory disturbances such as
hepatic insulin resistance, hyperinsulinemia and pre-diabetes are
observed in individuals with non-alcoholic fatty liver disease
(NAFLD). Whether autoimmune liver diseases-herein primary

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POSTER PRESENTATIONS
THU478 Conclusion: Greater proportion of time spent out-of-range and
Proportion of time and degree to which liver biochemistries are greater divergence from normality on each liver biochemistry was
out-of-range predicts time to first occurrence of negative hepatic associated with significantly increased risk of hepatic decompensa-
outcomes in people with primary biliary cholangitis tion, liver transplant, or death in patients with PBC. These results
Timothy Ritter1, Christina Hanson2, Christopher C. Fernandes3, suggest that avoiding substantial time with out-of-range liver
Joanna MacEwan4, Xin Zhao4, Craig Parzynski4, Erik Ness5, biochemistries, potentially through greater utilization of effective
Gail Cawkwell5, Darren Wheeler5, Tracy Mayne5. 1GI Alliance, United first line and 2L therapies, may improve hepatic outcomes for
States; 2South Denver Gastroenterology, United States; 3TCU and patients with PBC.
UNTHSC School of Medicine, United States; 4Genesis Research, United
States; 5Intercept Pharmaceuticals Inc, United States THU479
Email: [email protected] Outcomes following immune checkpoint inhibitor re-challenge
in patients who developed grade 3 and 4 hepatotoxicity
Background and aims: Previous research has demonstrated a
Amy Hicks1, Ramu Chimakurthi1. 1Leeds Teaching Hospitals NHS Trust,
significant association between abnormal liver biochemistries at
Hepatology, Leeds, United Kingdom
one time point and the risk of death and liver transplant in patients
Email: [email protected]
with primary biliary cholangitis (PBC). We hypothesized that both
the proportion of time and degree to which liver biochemistries are Background and aims: Immune checkpoint inhibitors (ICI) are used
out-of-range, including normal values associated with adverse liver to treat a variety of cancers. Immune-related adverse events (irAEs)
health, predict time to first occurrence of negative hepatic outcomes. are not uncommon, with Grade 3 hepatitis in 1–2% of those treated
Method: Patients in the Optum Clinformatics database between July with single agents and ∼15% in those treated with Ipilimumab and
1, 2016 and December 31, 2020 were included if they were diagnosed Nivolumab combination (ESMO guidelines 2017). European and
with PBC by either ≥1 inpatient discharge claim with a PBC diagnosis American society guidelines recommend discontinuation of ICI after
or ≥2 outpatient claims with a primary PBC diagnosis on separate development of Grade 3 or 4 hepatitis. Re-challenge with single ICI
days and had >1 of each liver biochemistry available (ALP, TB, AST, ALT, can be considered in those who developed Grade 3 hepatitis on
and ALB). Patients with autoimmune hepatitis, HIV, gastric bypass, combination therapy. We reviewed our outcomes following re-
liver disease, hepatic decompensation, or use of second line (2L) challenge in those who developed Grade 3 and 4 hepatitis in our
treatment (obeticholic acid or fibrates) prior to PBC diagnosis were regional oncology centre.
excluded. Survival analysis with the proportion of time spent out-of- Method: Patients who received ICI from January 2018 to January
range as a time-dependent variable and a composite end point of 2022 were reviewed. Those who developed Grade 3 and 4
hepatic decompensation, liver transplant, or death was conducted. hepatotoxicity were identified by accessing their electronic health
Biochemistry values were carried forward until the next recorded record. We assessed the following outcomes in these patients: a)
value. Patients were censored at end of follow-up or initiation of 2L those who had re-challenge with ICI b) choice of ICI in re-challenged
treatment. c) whether they developed further hepatitis d) outcomes in those
Results: 2, 379 patients (85.3% female) were included. At baseline, who were not re-challenged.
mean age was 63 years; 11% had cirrhosis; 7% had NASH. During the Results: 1045 patients received ICIs over a 4-year period (807 single
follow-up period (mean 2.5 yrs), 73.8% received ursodeoxycholic acid agent and 238 Ipilimumab-Nivolumab combination). 54 patients
and 3.6% (N = 86) were censored at start of 2L treatment. Mean developed Grade 3 or 4 hepatitis. Of these, 22 (40.7%) were re-
number of measures per biochemistry ranged from 7.2–8.4. On challenged and their outcomes are shown in Table 1. All patients were
average patients spent 52.5%, 8.5%, 37.5%, and 20.7% of the follow-up off immunosuppression at the time of re-challenge. Contrary to
period over ULN for ALP, TB, AST, and/or ALT, respectively, and 19.1% existing guideline recommendations, 3 patients with Grade 4
under LLN for ALB. For each individual biochemistry the risk of hepatitis and 7 patients with Grade 3 hepatitis on single agent
negative hepatic events increased significantly with greater propor- were re-challenged with ICIs. 4 out of 11 (36%) developed further
tion of time out-of-range and greater divergence from desired values hepatitis (Grade ≥ 3) on re-challenge. Of note, all patients with
(Figure). For example, for a patient with all 5 years follow-up (i.e., recurrent hepatotoxicity developed this after only 1 cycle of re-
100% time) with ALB ≤0.9xLLN, the risk of an event was 271% higher treatment. ICI were discontinued permanently in the remaining 32
than that of a patient with ALB >0.9xLLN all 5 years (i.e., 0% time); patients. 15 had complete response to treatment, 8 had disease
104% higher for ALp >1.5x ULN; 124% for ALT >2xULN; 145% higher for progression and were switched to an alternative treatment, 6 patients
AST >1.5xULN; and 157% higher for TB >1x ULN. deteriorated and died (1 from irAE and 5 from disease progression), 1
is due for re-challenge soon, and 2 patients changed to an alternative
regimen due to the hepatitis.

Table 1: ICI re-challenge outcomes.

Initial hepatitis Recurrence of
grade (n = no. hepatitis and cycle
patients) Initial ICI Re-challenge ICI number (Cx)

Gr 3 = 19 Ipi and Nivo = 12 Nivo = 12 - 2 pts (17%):

- Gr 2 (C2)
- Gr 4 (C1)
Nivo = 3 Nivo = 3 - 1 pt (33%):
- Gr 4 (C1)
Pembro = 4 Pembro = 3 None
Ipi = 1 - 1 pt (100%):
- Gr 3 (C1)
Gr 4 = 3 Pembro = 2 Pembro = 2 - 2 pts (100%):
- Gr 3 (C1)
- Gr 3 (C1)
Ipi and Nivo = 1 Nivo = 1 None (Stopped due to
colitis after C2)

Figure: Hazard ratio of decompensation, transplant, or death for each add-

itional 10% of time out-of-range by biochemistry threshold Conclusion: Re-challenge with ICI following Grade 4 hepatitis
resulted in early irAE recurrence in our group. However, the vast
majority (>70%) re-challenged with ICIs after Grade 3 hepatitis on

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 POSTER PRESENTATIONS
single agent did not develop hepatitis recurrence. Nearly 50% of Results: 40 patients developed outcomes (liver transplantation or
patients are in remission and alive to this day despite cessation of ICI liver-related death). Interreader agreement between experienced
following Grade 3 and 4 hepatitis. Our numbers are small but will add radiologists was good (ICC = 0.82; 95%CI:0.74-0-87, and ICC = 0.81;
to a growing body of evidence in this field. 95%CI:0.70–0.87, respectively) and better than agreement for the pair
of experienced/less experienced radiologist (ICC = 0.48; 95%CI:0.05–
THU480 0.72). Agreement between radiologists from the three centers was
Development of a novel MRCP-score for patients with primary good (ICC = 0.76; 95%CI:0.57–0.89). Intrareader agreement was good
sclerosing cholangitis, and assessment of agreement and to excellent (ICC = 0.85–0.93). AUC for the MRCP-score was 0.83.
prognostic value Patients with MRCP-score 5–8 had 8.4 times higher risk (HR = 8.4;
Aristeidis Grigoriadis1,2, Kristina Ringe3, Johan Bengtsson4,5, 95%CI:3.9–18.3) for developing outcomes, and significantly worse
Erik Fridh Baubeta6, Cecilia Forsman7, Nafsika Korsavidou-Hult8, survival ( p < 0.000), compared to those with MRCP-score 0–4.
Fredrik Rorsman9, Emma Nilsson10, Nikolaos Kartalis2,11, Conclusion: This novel MRCP-score is reproducible and strongly
Annika Bergquist1,12. 1Karolinska Institutet, Medicine, Stockholm, associated to outcomes which indicates its value for the prognosis of
Sweden; 2Karolinska University Hospital, Radiology, Stockholm, Sweden; PSC-patients in clinical practice.
3
Hannover Medical School, Diagnostic and Interventional Radiology,
Hannover, Germany; 4Lund University, Department of Clinical Sciences/ THU481
Division of Radiology, Lund, Sweden; 5Skåne University Hospital, Center Right and left lobe biopsies by mini-laparoscopy reveals clinically
for Medical Imaging and Physiology, Lund, Sweden; 6Skåne University significant sampling error in staging and grading in AIH
Hospital, Diagnostic Radiology, Department of Translational Medicine, Johannes Hartl1, Marcial Sebode1, Malte Wehmeyer1,
Lund, Sweden; 7Uppsala University Hospital, Medical Imaging Centre, Sören Weidmann1, Christoph Schramm1, Ansgar Lohse1, Till Krech1,
Sweden; 8Uppsala University, Radiology and Nuclear Medicine, Sweden; Jörg Schrader1. 1University Hospital Hamburg-Eppendorf (UKE), First
9
Uppsala University Hospital, Gastroenterology and Hepatology, Department of Medicine, Hamburg, Germany
Sweden; 10Skåne University Hospital, Department of Clinical Sciences, Email: [email protected]
Lund, Sweden; 11Karolinska Institutet, Department of Clinical Science,
Background and aims: Liver diseases may affect the liver heteroge-
Intervention and Technology (CLINTEC), Stockholm, Sweden;
12 neously. Thus, not only diagnosis but also grading and staging of
Karolinska University Hospital, Hepatology, Stockholm, Sweden
inflammatory activity and fibrosis may largely depend on the area of
Email: [email protected]
liver biopsy. Hence, the aim of this study was to assess the added
Background and aims: MRCP is used for diagnosis and follow-up of benefit of double biopsy of both liver lobes during minilaparoscopy in
patients with primary sclerosing cholangitis (PSC). Interest in the patients with autoimmune liver disease.
prognostic value of MRCP is increasing. Aim of our study is to develop Method: We identified all patients with autoimmune hepatitis (AIH),
an MRCP-score based on cholangiographic findings previously primary biliary cholangitis (PBC), primary sclerosing cholangitis
associated to outcomes and assess its reproducibility and prognostic (PSC) or variant syndromes (AIH/PBC and AIH/PSC), who underwent a
value in PSC. double biopsy of both liver lobes via minilaparoscopy between 01/
Method: The MRCP-score was developed based on the extent and 2016–12/2020 in our prospectively maintained database. Differences
severity of cholangiographic changes of intrahepatic and extrahepatic in fibrosis stage and disease activity between liver lobes were
bile ducts (range 0–8) in coronal 3D-MRCP. In this ethics review- assessed by an experienced hepato-pathologist.
board approved retrospective, multicenter study, three pairs of Results: A total of 111 patients with AIH received a biopsy of both liver
radiologists (2 pairs of experienced, one pair of experienced and lobes (AIH: N = 83, AIH/PBC: N = 24, AIH/PSC: N = 4). Differences in
less experienced) from three tertiary centers, applied the score inflammatory activity as assessed by Ishaks`s modified activity index
independently on MRCP-examinations of 220 consecutive PSC (mHAI) were observed in 69 (62%) patients. In 41 (38%) patients the
patients (103, 52, and 65, respectively) from a prospectively collected difference was ≥2 points, in 12 patients (11%) ≥3 points. According to
PSC-cohort, with median follow-up of 7.4 years. Interreader and current EASL guidelines, starting/intensification of immunosuppres-
intrareader agreements were assessed with intraclass correlation sion should be discussed in patients with a mHAI of 4–5, as it was
coefficient (ICC). After consensus reading, the prognostic value of the reported to be associated with excess mortality, a mHAI ≥ 6 prompts
score was assessed with Cox-regression and outcome-free survival intensified immunosuppression in most cases. Thus, a mHAI 4–6
rates with Kaplan-Meier estimates. Area under the curve (AUC) was represents a most relevant range for guiding treatment decisions. 48%
calculated and 10-fold cross-validation was performed. of the AIH patients had a mHAI within this range. Importantly, in 21
patients (20%) a mHAI ≥ 4 was only observed in one liver lobe. Also, 17
(15%) patients demonstrated a mHAI ≥ 6 in only in one liver lobe.
Based on these observations, the number needed to double-biopsy to
identify clinically relevant differences in inflammatory activity was
only 5 patients. Differences of fibrosis stage were identified in 31/111
(28%) AIH patients. In 3/18 (17%) cirrhotic patients, histological
changes consistent with cirrhosis were only observed in one liver
lobe.
A biopsy of both liver lobes was performed in 16 PSC and 13 PBC
patients. Differences of fibrosis stage were observed in 1/16 and 3/13
patients, and differences in mHAI in 8/16 and 5/13 patients,
respectively. However, no treatment relevant difference was
identified.
No major adverse event occurred.
Conclusion: Obtaining a biopsy of the right and left liver lobe is a safe
procedure during minilaparoscopy that results in more accurate
staging and grading with direct therapeutic consequences in patients
with AIH.

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POSTER PRESENTATIONS
THU482 THU483
Should we seek complete liver tests normalization in primary Home-based exercise in patients with refractory fatigue
biliary cholangitis? Data from ColHai registry associated primary biliary cholangitis: final results from the
Álvaro Díaz-González1, Sergio Rodriguez-Tajes2, EXerCise Intervention in cholesTatic LivEr Disease (EXCITED)
Mercedes Vergara Gómez3, Emilio Fabrega1, Manuel Romero Gomez4, clinical trial
Agustin Albillos5, Judith Gómez- Camarero6, Diana Horta7, Alice Freer1, Felicity Williams1,2, Simon Durman1, Jennifer Hayden1,
Adolgo Gallego8, Montserrat Garcia-Retortillo9, Raul J. Andrade10, Matthew Armstrong1, Palak Trivedi1,3. 1University Hospital
Moises Diago11, Rosa M Morillas12, Manuel Hernández Guerra13, Birmingham NHS Foundation Trust, Liver Department, Birmingham,
Carlos Ferre Aracil14, Margarita Sala15, Elena Gómez Domínguez16, United Kingdom; 2University of Birmingham, Institute of Inflammation
Marina Berenguer17, Maria Carlota Londoño18, Grupo del Registro and Ageing, Birmingham; 3University of Birmingham, NIHR Birmingham
Col-Hai Enfermedades Autoinmunes y colestásicas19. 1Hospital Centre for Liver and Gastrointestinal Research, Birmingham, United
Marqués de Valdecilla; 2Hospital Clínic Barcelona; 3Hospital Kingdom
Universitario Parc Taulí; 4Hospital Universitario Virgen Del Rocío; Email: [email protected]
5
Hospital Universitario Ramón y Cajal; 6Hospital Universitario de
Background and aims: Debilitating, refractory fatigue is the most
Burgos; 7Hospital Mutua de Terrassa; 8Hospital de la Santa Creu i Sant
commonly reported symptom of primary biliary cholangitis (PBC),
Pau; 9Hospital del Mar; 10Universidad de Málaga; 11Hopsital
affecting 40–80% of patients ( pts). The pathogenesis is unknown, but
Universitario General de Valencia; 12Hospital Germans Trias i Pujol;
13 muscle bioenergetic abnormalities are proposed to contribute.
Hospital Universitario de Canarias; 14Hospital Universitario Puerta del
Herein, we present the results of a single-arm, open-label clinic
Hierro; 15Hospital Josep Trueta; 16Hospital Universitario Doce de
trial, to assess the efficacy and safety of a novel home-based exercise
Octubre; 17Hospital La Fe; 18Hospital Clínic Barcelona, Liver Unit,
program (HBEP) in pts with PBC and severe fatigue (NCT04265235).
Barcelona, Spain; 19AEEH, CIBEREHd
Method: A remotely-monitored, 12-week (wk) HBEP was delivered to
Email: [email protected]
patients with PBC and moderate-severe fatigue (PBC40 fatigue score
Background and aims: Response criteria to ursodeoxycholic acid >33; other causes excluded). This consisted of individualised body
(UDCA) treatment in patients with primary biliary cholangitis (PBC) weight resistance exercises completed at moderate intensity and
are based on the reduction of alkaline phosphatase (ALP), total weekly telephone health calls (first 6 wks only). Adherence was
bilirubin (TB), and aspartate aminotransferase (AST). However, recent monitored using GeneActiv wrist monitors. The primary efficacy
studies suggest that complete normalization of these tests result in outcome measure was the proportion of individuals attaining at least
better clinical outcomes. More studies are necessary to validate these a >5-point reduction in the PBC40 fatigue domain at wk 12. Key
data and to determine the need for increasing the strictness of UDCA secondary outcomes included assessment of the Fatigue Impact Scale
treatment-response criteria. Therefore, we sought to investigate the (FIS), other domains of the PBC-40, the Chronic Liver Disease
impact of TB, AST, ALP and gamma-glutamyl transferase (GGT) Questionnaire, (CLDQ), the Epworth Sleep Score (ESS), the Hospital
normalization after 12 months of UDCA treatment on patients’ Anxiety and Depression Scale (HADS), aerobic exercise capacity
survival. (incremental shuttle walk test [ISWT]; Duke Activity Status Index
Method: Retrospective analysis of 1154 patients with PBC patients [DASI]; metabolic equivalent of task [MET]), and functional capacity
included in the ColHai registry (Spanish registry for patients with (short physical performance battery [SPPB]) at 6 and 12wks. Full
autoimmune and cholestatic liver disease). Liver tests were categor- study protocol is available at BMJ Open Gastro (PMID33707216).
ized according to the upper limit of normal (ULN) for each center: 1) Results: In all, 31 pts were recruited. One individual withdrew prior
AST: <1, 1–1.5, >1.5; 2) ALP: <1, 1–1.5, 1.5–1.67, >1.67; 3) GGT: <1, 1–3, to wk12 due to unforeseen personal issues. The remaining thirty
3–5, >5; 4) TB: <0.6, 0.6–1.2, >1.2. participants (29 women, 1 man) completed the 12-wk HBEP: median
Results: Most of the patients were female (90%), with a median age of age 53yrs, ALP 1.9xULN, bilirubin 17 μmol/L, MELD 7, and baseline
55 years (range 46–63). 116 (10%) died during a median follow-up PBC40 fatigue score 41. The primary outcome was met by 26 pts
period of 10 years (range 6.7–15.7). In the univariate analysis AST < (87%); the median reduction in PBC40 fatigue score at wk12 was 11
ULN (HR 0.45; 95CI% 0.35–0.65), ALp < ULN (HR 0.51; 95CI% 0.34– points (interquartile range −9 to −13 (Fig). Significant reductions
0.78), GGT < ULN (HR 0.60; 95CI% 0.38–0.94) and TB <0.6 × ULN (HR were also observed in the FIS, score, ESS, HADS and the composite
0.35; 95CI% 0.24–0.52) were associated with a significantly lower PBC40 score (Fig), alongside individual symptom, cognition, emotion
mortality rate. There were no significant differences in survival and social domains, and the CLDQ (data not shown). Significant
between patients with ALp < ULN vs. <1.5 × ULN or those with GGT < changes were seen in METs (+0.46, p < 0.001) and SPPB (+1 point, p <
ULN vs. <3 × ULN (Figure). In the multivariate analysis, only TB < 0.6 × 0.001), with 28 pts (93%) achieving the maximum SPPB score at 12
ULN and ALp < 1.5 × ULN were independently associated with lower wks (vs. 43% at baseline; p < 0.001). No significant differences in ALP
mortality (HR 0.42; p < 0.01 and HR 0.57; p = 0.01, respectively). values or MELD score were observed from baseline to 12wks. No
significant adverse events were observed during the course of the
study.
Conclusion: A 12-wk individualised HBEP, incorporating resistance
and aerobic exercise, is safe, feasible, and significantly improves
fatigue, quality of life, and exercise/functional capacity in patients
with refractory fatigue associated with PBC. These findings warrant
validation through a longer duration randomised control trial.

Conclusion: ALP normalization was not better than the usual cut-off
of 1.5 × ULN to predict survival but decreasing TB to better than
normal levels (0.6 × ULN) significantly improved patients’ survival.

S334 Journal of Hepatology 2022 vol. 77(S1) | S119–S388

 POSTER PRESENTATIONS
inverse probability of treatment weighting (IPTW) was used to
balance groups. Logistic regression model was used to create weights
for the following key baseline confounders: age, sex, calendar year of
diagnosis, PBC duration, UDCA use, ALP, bilirubin and AST or ALT.
Weights were assigned to each patient. Cox-proportional hazards
models were run to establish the hazard ratio (HR) and 95%
confidence. A secondary analysis examined the impact of adding
cirrhosis to the model.
Results: Over the 6.3 years of follow-up, there were 16 events of
hepatic decompensation, liver transplant or death in 209 subjects in
the POISE arm (Incidence rate (IR) 18.0 per 1, 000 person-years; 95%
CI 10.7–28.6) and 212 events in 1381 patients (IR 35.5 per 1, 000
person-years; 95% CI 31.0–40.5) in the GLOBAL PBC external control
group. The IPTW HR = 0.42 (95% CI 0.21, 0.85; p = 0.02), indicating that
patients treated with OCA in a trial setting had significantly greater
event-free survival than patients in the Global PBC control group. The
Kaplan-Meier curve is shown in Figure. When cirrhosis was added to
the model, it was a significant predictor (HR = 0.26; 95% CI 0.21–0.43,
p < 0.01), and increased the effect size of treatment (HR = 0.35; 95% CI
THU484 0.17–0.71, p < 0.01). For patients with cirrhosis, HR = 0.38 (95% CI 0.12,
Long-term obeticholic acid (OCA) for primary biliary cholangitis 1.20) versus Global PBC controls; for patients without cirrhosis, HR =
(PBC) in a clinical trial improved event free survival (death, liver 0.34 (95% CI 0.14, 0.82). With widely overlapping confidence
transplant and hepatic decompensation) compared to external intervals, while cirrhosis significantly predicts time to events, it
controls from the GLOBAL PBC real-world database does not significantly affect treatment response.
Carla Fiorella Murillo Perez1, Femi Adekunle2, Tracy Mayne2,
Elizabeth Malecha2, Erik Ness2, Adriaan Van der Meer3,
Willem Lammers3, Palak Trivedi4, Pier Maria Battezzati5,
Frederik Nevens6, Kris Kowdley7, Tony Bruns8, Nora Cazzagon9,
Annarosa Floreani9, Andrew L. Mason10, Albert Pares11,
Maria Carlota Londoño11, Pietro Invernizzi12, Marco Carbone12,
Ana Lleo13, Marlyn J. Mayo14, George Dalekos15, Nikolaos Gatselis15,
Douglas Thorburn16, Xavier Verhelst17, Aliya Gulamhusein1,
Harry LA Janssen18, Michael Trauner19, Christopher Bowlus20,
Keith D. Lindor21, Christophe Corpechot22, Gideon Hirschfield23,
Bettina Hansen18. 1Toronto Centre for Liver Disease, Division of
Gastroenterology and Hepatology, Toronto General Hospital, Toronto,
Canada; 2Intercept Pharmaceuticals Inc; 3Erasmus MC University
Medical Center Rotterdam; 4University of Birmingham, United Kingdom;
5
Università degli Studi di Milano, Italy; 6University Hospital KU Leuven,
Belgium; 7Liver Institute Northwest, United States; 8University Hospital
RWTH Aachen, Germany; 9University of Padua, Italy; 10University of
Alberta, Canada; 11Liver Unit, Hospital Clinic Barcelona, Spain;
12
University of Milano-Bicocca, Italy; 13Humanitas University, Italy; 14UT
Southwestern, United States; 15University Hospital of Larissa, Greece;
16
The Royal Free Hospital, United Kingdom; 17Ghent University Hospital,
Belgium; 18Erasmus MC University Medical Center Rotterdam,
Conclusion: Patients treated with OCA in a trial setting demonstrated
Netherlands; 19Medical University of Vienna, Austria; 20University of
a statistically significant and clinically meaningful 58% reduction in
California Davis, United States; 21Arizona State University, United States;
22 relative risk of hepatic decompensation, LT or death compared to non-
Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris,
OCA treated patients in the GLOBAL PBC registry. Reduction in risk
Sorbonne University, France; 23Toronto Centre for Liver Disease,
was independent of cirrhosis. These results support the continued
University Health Network, University of Toronto, Canada
use of long-term OCA therapy to optimize prognosis of patients with
Email: [email protected]
PBC.
Background and aims: The POISE randomized double-blind (DB)
placebo-controlled trial and open label extension (OLE) demon- THU485
strated that obeticholic acid (OCA) reduced biomarkers associated Investigation of linerixibat 40mg BID for cholestatic pruritus of
with adverse clinical outcomes in patients with primary biliary primary biliary cholangitis (PBC); further data from the phase 2b
cholangitis (PBC). The objective of this analysis was to evaluate event- GLIMMER study to support the phase 3 GLISTEN study
free survival in OCA-treated patients in POISE (DB + OLE) compared to James Fettiplace1, Brandon Swift2, Shu Zhang2, Robyn von Maltzahn1,
non-OCA treated external controls. Megan McLaughlin2. 1GlaxoSmithKline, United Kingdom;
2
Method: The treatment arm included patients in the POISE study. GlaxoSmithKline, United States
External controls were OCA-naive patients from the GLOBAL PBC Email: [email protected]
registry who were diagnosed with PBC, treated or untreated with Background and aims: Reduction of pruritic bile acids in circulation
ursodeoxycholic acid (UDCA), with >1 year of follow-up. Study end is under investigation for the treatment of cholestatic pruritus in PBC.
point was time to first occurrence of hepatic decompensation, liver Due to lack of previously approved therapies, what constitutes a
transplant (LT) or death. As treatment was not assigned randomly, meaningful within-patient change in itch has not been determined.
baseline variables could influence both the chances of a clinical event The phase 2b GLIMMER study was a randomized, double-blind,
and of receiving treatment. To ensure a fair and balanced comparison, placebo-controlled, dose response study of linerixibat, a minimally

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POSTER PRESENTATIONS
absorbed ileal bile acid transporter inhibitor, in PBC patients with THU487
moderate to severe pruritus;12 weeks of treatment followed a 4- Post-COVID-19 cholangiopathy: does SARS-CoV-2 play a relevant
week placebo run-in (N = 147). Data from GLIMMER was reanalyzed role in histopathological findings?
to look at multiple potential itch responder definitions for the Valéria Ferreira de Almeida e Borges1,2, Helma Pinchemel Cotrim3,
linerixibat 40mg BID group, the phase 3 dose. Consistent with the Marcelo Costa Silva4, Liliana Sampaio Costa Mendes5,
mechanism of action, changes in total serum bile acids (TSBA) are also Francisco Guilherme Cancela Penna6,7,
reported. Antônio Ricardo Cardia Ferraz de Andrade3,
Method: Participants assessed itch daily using a 0–10 numeric rating Frederico Chaves Salomão8, Juliana Daud2,
scale. Proportion of responders were assessed using reductions in Luiz Antônio Rodrigues de Freitas3,9,10. 1Federal University of Bahia,
monthly itch scores (MIS) at week 16 compared to baseline. An Postgraduate Program in Medicine and Health, Brazil; 2Federal
empirical cumulative distribution function (eCDF) graph was gener- University of Uberlândia, Brazil; 3Federal University of Bahia, Medicine
ated for the percentage of participants with change from baseline in School, Brazil; 4Hospital e Clínica São Roque, Ipiaú, Brazil; 5Hospital de
MIS for the linerixibat 40mg BID (N = 23) and placebo (N = 36) groups. Base do Distrito Federal, Brasília-DF, Brazil; 6Federal University of Minas
Bile acid samples from GLIMMER were reanalyzed using an Gerais, Instituto Alfa de Gastroenterologia, Belo Horizonte, Brazil;
enzymatic assay that quantifies TSBA consistent with the Phase 2a 7
IPSEMG Hospital Governador Israel Pinheiro HGIP, Belo Horizonte,
study method (the original analysis summed specific bile acids Brazil; 8Centro Diagnóstico de Patologia, Uberlândia, Brazil; 9FIOCRUZ
utilizing a liquid chromatography tandem mass spectrometry Fundação Oswaldo Cruz, Pathology, Salvador, Brazil; 10Imagepat
method). Change from baseline in TSBA were analyzed using a Laboratory of Pathology, Salvador, Brazil
mixed model repeated measures analysis (MMRM). Email: [email protected]
Results: The eCDF curves showed clear separation of linerixibat 40
mg BID and placebo groups. The percentages of participants with an Background and aims: Cholangiopathy (CHP) occurs in critically ill
improvement from baseline in MIS at week 16 were greater in patients (CIP) after prolonged therapy in intensive care unit. Findings
linerixibat group than placebo group for a wide range of responder akin to those described in CIP were deemed a novel entity in patients
threshold values. The largest differences between the curves were with severe Covid-19. This study evaluates liver histopathological
observed between thresholds of −3 to −2, where the cumulative findings in patients with post Covid-19 cholangiopathy.
percentages were more than 20% greater in the linerixibat group than Method: Liver sections from 10 patients with post-Covid-19 CHP
the placebo group. were stained with hematoxylin and eosin and sirius red for fibrosis.
Linerixibat 40mg BID (n = 22) reduced mean TSBA from a baseline of Immunostaining for cytokeratin-7 was done in 7 cases to evaluate
18.6 μM (21.8) by −6.94 μM (17.5) [Mean (SD)] on average after 12- ductular proliferation and biliary metaplasia of hepatocytes.
weeks of treatment. A MMRM analysis resulted in a significant Semiquantitative analysis included portal changes (fibrosis, inflam-
decrease of 39% ( p = 0.0001) from baseline and 37% ( p = 0.0030) from mation, and biliary tree changes), and parenchymal alterations
placebo (n = 36) over the 12-week double-blind treatment period. (cholestasis, inflammation, hepatocellular lesions, and fibrosis).
Results: All 10 patients, 5 women and 5 men, mean age: 54 ± 11.29
years, were RT-PCR positive for Sars-CoV-2 infection, with respiratory
distress requiring mechanical ventilation, pronation, sedation and
vasoactive drugs. Median of liver enzymes closely before the biopsy
procedure were serum gamma-glutamyl transferase 925 U/L, alkaline
phosphatase 605 U/L, alanine aminotransferase 91 U/L, aspartate
aminotransferase 90 U/L and bilirubin 3 mg/dL. Imaging studies
revealed irregularities in the intrahepatic bile ducts. Biliary casts were
seen in 6 cases. Biopsies were performed 190 ± 16 days after the
molecular diagnosis of the infection. The median number of portal
tracts was 25 (15–32). Portal and periportal fibrosis were evidenced
in all cases, and septal fibrosis in 7. A mild to moderate inflammatory
infiltrate (mononuclear and neutrophilic with rare eosinophils) was
seen in all without interface activity. Moderate to severe ductular
proliferation was found in all, as well as bile duct dystrophy (irregular
contours, cytoplasmic vacuolization, loss of nuclear polarization,
nuclear pyknosis and cellular drop-out). Bile plugs were found in the
ductules in 6 cases. Mild swelling of endothelial cells of arterioles was
Conclusion: Consistent with inhibition of reuptake of bile acids, observed in 5 cases. In one case, a thrombus was found in a small
40 mg BID linerixibat resulted in significant reductions in total serum portal vein branch and in another a mild periductal fibrosis was
bile acids. The proportion of participants with change from baseline present. Ductopenia was not seen. Mild to severe parenchymal
in MIS at week 16 was greater in the linerixibat 40mg BID group than cholestasis was evidenced in 9 cases. One case had multiple small
placebo over a range of responder threshold values. Linerixibat 40 mg biliary infracts. Hepatocyte biliary metaplasia (CK7+ cells) was found
BID is being studied in the ongoing confirmatory phase 3 GLISTEN in all seven tested cases. Acinar inflammation, as well as hepatocyte
study (NCT04950127). Responder thresholds of 2, 3 and 4-point necrosis and apoptosis, were minimal and focal. One case showed
improvements in MIS compared to baseline are key secondary end multiple small biliary infarcts.
points of this phase 3 study.
Funding: GSK (study 201000)

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 POSTER PRESENTATIONS
did not impact steroid-free remission rates (52.4% vs. 66.7%, p = 0.47)
or low-dose steroid ( prednisolone 5mg or less) maintenance rates
(90% vs. 100%, p = 0.57). An AIH flare was documented in 29.4% of
patients over the study period, which did not differ by testing status
(40.0% vs 38.1%, p = 0.86). No significant differences in mean ALT, IgG
or TE were noted between groups from time of diagnosis to time of
censor. When stratified by testing status, no differences in TP-related
AEs were detected (16% vs. 25%, p = 0.30).
Conclusion: TP metabolite testing was not associated with improved
steroid-free remission, improvements in AIH disease activity, reduc-
tion in AIH flares or reduction in thiopurine-related adverse events.
Aiming for therapeutic metabolite levels did not improve steroid-free
remission rates. Metabolite testing may provide little utility in the
management of AIH patients on TPs and may result in increased
patient testing and healthcare resource burden.

THU489
Patient reported symptom burden in primary biliary cholangitis
and how to inform trial design
Aaron Wetten1,2, Claire Johnstone-hume2, Kathryn Houghton1,
Chris Mitchell3, David Jones1,2, Jessica Dyson1,2. 1Newcastle Freeman
Conclusion: The present findings are akin to those described in the Hospital, Liver unit, High Heaton, United Kingdom; 2Newcastle
CHP of CIP. Only Covid-19 patients requiring intensive care develop University, Translational and Clinical Research Institute, United
CHP. This suggests that the virus does not have a direct role in the CHP. Kingdom; 3PBC Foundation, United Kingdom
It is more likely that, as with CIP, hypoxemia due to arterial Email: [email protected]
hypotension and lung damage associated with vasoconstrictor and
Background and aims: Primary Biliary Cholangitis (PBC) is a chronic,
other drugs cause damage to the biliary tree.
cholestatic autoimmune liver disease. Symptoms of pruritus, fatigue
THU488 and ‘brain fog’ are common, and significantly impact quality of life.
Examining the role of thiopurine metabolite testing in the Current pruritus treatments are effective for some patients, but no
management of patients with autoimmune hepatitis therapies address fatigue or cognitive symptoms. This remains an
Andrew Roberts1, Declan Connoley1, Ryan Hirsch1, Gauri Mishra1, area of significant unmet need, reflected by the recent increase in
Marcus Robertson1, Sally Bell1, Dilip Ratnam1. 1Monash Health, clinical trials to identify new agents. This study explored the
Department of Gastroenterology and Hepatology, Clayton, Australia prevalence of PBC symptoms, patients’ priorities for their manage-
Email: [email protected] ment, what they consider a meaningful improvement in their
symptoms and how we should collect symptom data. These are
Background and aims: Thiopurines (TP) are widely used to maintain crucial questions to inform trial design in this area where patient-
steroid-free remission in autoimmune hepatitis (AIH), however there reported outcomes are key metrics for success.
is a lack of data examining the role of metabolite testing in the Method: An electronic survey was sent to members of the PBC
management of AIH. We evaluated whether metabolite monitoring Foundation (an international patient support group) in February
affected steroid-free remission and TP-attributed adverse event (AE) 2022 with responses collected over 6 weeks. The survey comprised 9
rates in our AIH patients. questions regarding: current/past symptom burden; nature/degree of
Method: We conducted a retrospective cohort study of adult patients symptom (fatigue, itch and brain fog) management that they would
with AIH treated with TPs at a metropolitan health network over a 10- consider a meaningful improvement, and their views on digital
year period (2011–2021). Baseline demographic and clinical data symptom assessment.
were recorded. Patients were stratified by metabolite testing status. Results: 599 surveys were completed. Symptom prevalence was
Time of censor was last clinical review. The primary outcome was high: 64% reporting current/past itch, 93% fatigue and 78% brain fog.
steroid-free remission status in patients who received metabolite ‘Any improvement being significant’ was the commonest category for
testing compared to those who had not. Secondary outcomes each symptom: brain fog 54%, fatigue 53% and itch 48% (Figure 1).
included mean reduction in ALT and IgG levels from diagnosis, rates When asked how a treatment should help reduce symptoms, ‘a
of AIH flares (defined as an increase in steroid dose or reintroduction treatment that made all day every day a little better’ was the most
of steroids in response to clinical or biochemical change), and TP- frequent response for brain fog (51%) and fatigue (47%), whilst 56% of
related AE rates. respondents with itch preferred a treatment that could be taken
Results: 109 AIH patients treated with TPs were included. Mean when ‘needed on really bad days’. 71% preferred symptom collection
follow-up time was 5.7 ± 6.6 years. Mean age was 54.5 ± 19.4 years, using an electronic device, 7% did not have a smartphone to use and
71.6% were female and 74.3% were Caucasian. 43 (39.4%) were anti- 3% would decline to participate.
smooth muscle antibody, 79 (72.4%) had typical AIH findings on
biopsy and 30 (27.5%) were cirrhotic. At time of diagnosis, the median
ALT was 666 (IQR 134–1148) U/L. At time of censor, 62 (56.9%)
patients remained on TPs with a mean azathioprine dose of 88.5 mg
and 6-mercaptopurine dose 32.1 mg in the metabolite tested group
vs. 78.8 mg ( p = 0.38) and 50 mg (p = 0.08) in the non-metabolite
tested group respectively.
Metabolite testing was performed in 44 (40.4%) patients. No
difference in steroid-free remission rate was detected between
patients who received TM testing compared to those who did not
(59.1% vs. 61.5%, p = 0.80). In these patients, achieving a therapeutic 6-
thioguanine level (defined as 225–450 pmol/8 × 108 erythrocytes)

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POSTER PRESENTATIONS
HADS depression score improved by 25.8% (95% CI 4.8, 46.8, p =
0.017). Significant improvements were seen in the PSS (15.2%), and
two PBC-40 domains (emotional symptoms by 16.3%, and social
symptoms by 11.8%) with a mean satisfaction score of 82/100. While
no significant improvements were observed in fatigue, interviews
revealed improved ability to cope with fatigue. In the 36/43
participants who completed the intervention, 25 (69%) adhered to
the program goal of completing the program at least 3x per week.
Enhancing group support was highlighted as a way to improve
adherence.
Conclusion: This 12-week intervention improved measures of
mental wellness and quality of life. High satisfaction and adherence
rates were observed. Future online mind-body online wellness
studies could explore strategies to optimize adherence and increase
the physical activity intervention, which may in turn result in a
Figure: What level of improvement in symptoms (itch, fatigue and brain greater impact on fatigue.
fog) are meaningful to patients
THU491
Conclusion: The prevalence of fatigue and brain fog were even higher Health-related quality of life in patients with primary sclerosing
than classically reported, demonstrating the unmet need. The cholangitis: a longitudinal population-based cohort study
majority of respondents felt that any symptom improvement would
Bregje Mol1, Kim van Munster1, Johannes Bogaards2, Rinse Weersma3,
be significant, with daily treatment for brain fog and fatigue being
Akin Inderson4, Joline de Groof1, Noortje Rossen1,
preferable. A ‘pill in the pocket’ approach to treating pruritus is not
Willemijn Ponsioen1, Maud Turkenburg1, Karel J. van Erpecum5,
currently utilised and is an interesting concept. Electronic symptom
Alexander Poen6, B.W. Marcel Spanier7, Ulrich Beuers1,
reporting was preferred by most patients and would standardise data
Cyriel Ponsioen1. 1Amsterdam UMC, Locatie AMC, Gastroenterology and
collection and facilitate care delivery. This cross-sectional data helps
Hepatology, Amsterdam, Netherlands; 2Amsterdam UMC, Locatie AMC,
us understand patient priorities’ when designing clinically relevant
Epidemiology and Data Science, Amsterdam, Netherlands; 3University
outcomes from drug trials and how to assess symptom burden and
Medical Center Groningen, Gastroenterology and Hepatology,
treatment efficacy in clinical practice.
Groningen, Netherlands; 4Leiden University Medical Center (LUMC),
Gastroenterology and Hepatology, Leiden, Netherlands; 5UMC Utrecht,
THU490
Gastroenterology and Hepatology, Utrecht, Netherlands; 6Isala Zwolle,
A randomized control trial evaluating the impact of a web-based
Gastroenterology and Hepatology, Zwolle, Netherlands; 7Rijnstate,
mind-body wellness intervention for patients with primary
Gastroenterology and Hepatology, Arnhem, Netherlands
biliary cholangitis
Email: [email protected]
Makayla Watt1, Ashley Hyde1, John Spence1, Gail Wright2,
Shauna Vander Well2, Emily Johnson1, Andrew L. Mason1, Background and aims: Data regarding health-related quality of life
Hin HIn Ko3, Edward Tam4, Puneeta Tandon1. 1University of Alberta, (HRQoL) in primary sclerosing cholangitis (PSC) is sparse and has
Edmonton, Canada; 2Canadian PBC Society, North York, Canada; 3The only been studied cross-sectionally in a disease which runs a
University of British Columbia, Vancouver, Canada; 4Dr. Edward Tam, fluctuating and unpredictable course. In this study we aim to
Vancouver, Canada describe HRQoL longitudinally by using repeated measurements in
Email: [email protected] a population-based cohort.
Method: Every three months from May 2017 up to August 2020
Background and aims: People with primary biliary cholangitis (PBC) patients received a digital questionnaire at home. These included the
experience significantly higher rates of mental distress, fatigue and
Short Form-36, EuroQol-5D-5L, 5-Dimension Itch, patient-based
impaired health related quality of life (HrQoL) as compared to the Simple Clinical Colitis Activity Index, and patient-based Harvey-
general population. Online mind-body wellness programming has Bradshaw Index. Data were compared with Dutch reference data and
improved mental wellness and decreased fatigue in a variety of a matched IBD disease-control from the population-based POBASIC
chronic disease populations, but limited data is available in PBC. We cohort. Mixed-effects modelling was performed to identify factors
previously conducted a pilot study of a novel online mind-body
associated with HRQoL.
wellness intervention in PBC that demonstrated high feasibility and Results: 328 patients completed 2576 questionnaires. A significant
acceptability, as well as promising exploratory efficacy. After refining reduction compared to the Dutch reference population of both the
the intervention using feedback from the pilot study, the current
physical component summary (46.4 versus 48.0, p = 0.018) and
study aimed to assess the efficacy of the online intervention. mental component summary (47.5 versus 50.5, p = 0.004) scores
Method: This was a sequential mixed-methods randomized control
measured by the SF-36 was found. HRQoL outcomes were signifi-
trial (RCT). Adult participants with PBC were randomized to receive cantly negatively associated with a coexisting active IBD which was
either standard of care (SOC) or SOC alongside a 12-week online not the case in case of quiescent IBD. Decreasing HRQoL scores were
mind-body intervention involving mindful movement, breathwork,
also negatively associated with increasing age, female sex, diagnosis
meditation, an acceptance and commitment therapy chronic disease of AIH overlap, end-stage liver disease, and the presence of itch. The
skills program, and tips from PBC physicians. The primary outcome
odds of reporting a clinically relevant reduction in EQ-5D score
was changes in the Hospital Anxiety and Depression Scale (HADS). showed seasonal variation, being lowest in summer (OR 0.48 (0.31–
Secondary outcomes evaluated fatigue, perceived stress, resilience, 0.74), p < 0.001). In patients with a liver transplant, HRQoL outcomes
HrQoL through the PBC-40, and physical functioning. ANCOVA was
were comparable to the Dutch general population.
used to determine between group differences. A qualitative descrip-
tive approach with semi-structured interviews was used to evaluate
study experiences.
Results: Of the 123 patients screened for the study, 87 were
randomized to the control (n = 44) and intervention (n = 43) groups
(mean age 59.8 ± 10.6 years; 98% female). The between-group HADS
total score improved by 20.0% (95% CI 4.7, 35.2, p = 0.011) and the

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 POSTER PRESENTATIONS
PCS MCS Background and aims: International registries have reported high
Estimate 95% CI Estimate 95% CI
mortality rates in patients with liver disease and coronavirus disease
2019 (COVID-19). However, the paucity and heterogeneity of data
Intercept 50.6 48.2 53.0 48.9 46.9. – 50.7
Female −2.8 −5.0 – −0.7 leaves the extent to which comorbidities contribute to excess COVID-
Age per 10 years (reference −0.1 −0.2 – −0.0 19 mortality in cirrhosis as controversial. This study thus aimed to
40y)
End-stage liver disease −4.3 −7.8 – −0.9 3.5 −0.0 – 6.7
control the influence of comorbidities through propensity score
AIH Overlap −3.7 −7.4 – 0.1 matching, enabling a controlled comparison of symptomatic pres-
IBD entation, disease progression and mortality of patients with COVID-
None (reference) (reference)
Ulcerative Colitis 2.3 −0.1 – 4.8 2.5 −0.0 – 4.8 19 and underlying cirrhosis to those without chronic liver disease.
Crohn’s Disease 3.3 0.2 – 6.4 −0.3 −3.8 – 2.8 Method: We used the multinational Lean European Open Survey on
IBD activity* −12.2 −16.7 – −7.6 −12.0 −18.9 – −5.9
Itch* −9.2 −12.2 – −6.2 −3.1 −6.9 – 0.3 SARS-CoV-2-infected patients (LEOSS) to identify patients with
cirrhosis. We compared symptoms, disease progression and mortal-
Table linear mixed-effects model SF-36. The intercept indicates the reference ity after propensity score matching (PSM) for age, sex, obesity,
value of the physical component summary (PCS) and mental component smoking status, and concomitant diseases. Mortality was further
summary (MCS) score for all patients without or before LT conditional on the compared with that of patients with another significant precipitator
reference value of the other variables included. The estimate of the listed
factors indicates the particular effect of each factor.
of acute-on-chronic liver failure, spontaneous bacterial peritonitis
*Itch and IBD activity are transformed to a 0 to 1 scale. 1 equals most severe (SBP).
complaints. Results: Among 7096 patients with SARS-CoV-2 infection eligible for
analysis, 70 (0.99%) had cirrhosis, and all were hospitalized. Risk
Conclusion: PSC patients report impaired HRQoL compared to the factors for severe COVID-19, such as diabetes, renal disease and
general population. After liver transplantation, HRQoL scores of PSC cardiovascular disease were more frequent in patients with
patients are at comparable levels as in the general population. HRQoL cirrhosis. Case fatality rate in patients with cirrhosis was 31.4% with
scores are associated with potentially modifiable factors such as itch the highest odds of death in patients older than 65 years (43.6%
and IBD activity, emphasizing the importance of adequate treatment. mortality; odds ratio [OR] 4.02; p = 0.018), Child-Pugh class C (57.1%;
OR 4.00; p = 0.026), and failure of two or more organs (81.8%; OR
19.93; p = 0.001). After PSM for demographics and comorbidity,
the COVID-19 case fatality of patients with cirrhosis was comparable
Cirrhosis and its complications: ACLF and to that of patients without (28.8% vs. 26.1%, p = 0.644) and similar
to 28-day mortality in a comparison group of patients with cirrhosis
Critical illness and SBP (33.3% vs. 31.5%; p = 1.000). In contrast, the number of
patients that initially reported no symptoms of COVID-19 was
significantly higher in patients with cirrhosis (37.5% vs. 10.5%; p <
THU493
0.001), yet more than half progressed into complicated or critical
COVID-19 in patients with cirrhosis: insights from the
disease phases.
multinational LEOSS registry
Conclusion: Although patients with cirrhosis and SARS-CoV-2
Jonathan Frederik Brozat1, Frank Hanses2, Martina Haselberger3, infection regularly present without any specific symptoms, the
Melanie Stecher4, Michael Dreher5, Lukas Tometten6, mortality in hospitalized SARS-CoV-2-infected patients with cirrho-
Maria Madeleine Rüthrich7, Janne Vehreschild8, Christian Trautwein1, sis is high. Propensity score matching suggests this can be largely
Stefan Borgmann9, Maria Vehreschild10, Carolin E. M. Jakob4, attributed to pre-existing comorbid conditions and extrahepatic
Andreas Stallmach11, Kai Wille12, Kerstin Hellwig13, Nora Isberner14, organ failure.
Philipp Reuken11, Fabian Geisler15, Jacob Nattermann16, Tony Bruns1.
1
University Hospital RWTH Aachen, Department of Gastroenterology, THU494
Digestive Diseases and Medical Intensive Care, Internal Medicine III, Serum metabolites on admission associate with the development
Aachen, Germany; 2University Hospital Regensburg, Emergency of nosocomial infections in inpatients with cirrhosis
Department, Regensburg, Germany; 3Klinikum Passau, Department of Jasmohan S Bajaj1, Jacqueline O’Leary2, Puneeta Tandon3,
Internal Medicine I, Passau, Germany; 4University of Cologne, Guadalupe Garcia-Tsao4, Patrick S. Kamath5, Paul J. Thuluvath6,
Department I of Internal Medicine, Faculty of Medicine and University Ram Subramanian7, Hugo E. Vargas8, Sara McGeorge1, Andrew Fagan1,
Hospital Cologne, Cologne, Germany; 5University Hospital RWTH Florence Wong9, Jennifer Lai10, Leroy Thacker1, Rajender Reddy11.
Aachen, Department of Pneumology and Intensive Care Medicine, 1
Virginia Commonwealth University and Richmond VAMC, GI, Richmond,
Internal Medicine V, Aachen, Germany; 6Hospital Ernst von Bergmann, United States; 2Dallas VAMC; 3University of Alberta; 4Yale University;
Potsdam, Germany; 7Jena University Hospital, Department of Internal 5
Mayo Clinic, Rochester; 6Mercy Medical Center; 7Emory university;
Medicine II, Jena, Germany; 8Goethe University Frankfurt, Department II 8
Mayo Clinic, Arizona; 9University of Toronto; 10UCSF; 11University of
of Internal Medicine, Hematology/Oncology, Frankfurt, Germany; Pennsylvania
9
Hospital Ingolstadt, Department of Infectious Diseases and Infection Email: [email protected]
Control, Ingolstadt, Germany; 10Goethe University Frankfurt,
Department of Internal Medicine, Infectious Diseases, Frankfurt, Background and aims: The inpatient course of patients with
Germany; 11Jena University Hospital, Department of Internal Medicine cirrhosis is complicated by a high rate of nosocomial infections (NI).
IV, Jena, Germany; 12Johannes Wesling Hospital Minden, Ruhr University These infections increase the need for intensive care, often lead to
Bochum, University Clinic for Haematology, Oncology, Haemostaseology acute on chronic liver failure (ACLF), and death and are challenging to
and Palliative Care, Minden, Germany; 13Catholic Hospital Bochum predict using clinical biomarkers. Better determination of a group
(St. Josef Hospital), Ruhr University Bochum, Department of Neurology, that develops NI on admission could prevent one of the leading
Bochum, Germany; 14University Hospital Würzburg, Department of causes of ACLF and death in cirrhosis. Aim: Determine predictors of NI
Internal Medicine II, Würzburg, Germany; 15Klinikum rechts der Isar der using serum metabolomics on admission in large cohort of inpatients
Technischen Universität München, Department of Internal Medicine II, with cirrhosis
München, Germany; 16UKB University of Bonn, Department of Internal
Medicine I, Bonn, Germany
Email: [email protected]

Journal of Hepatology 2022 vol. 77(S1) | S119–S388 S339

POSTER PRESENTATIONS
Method: We enrolled inpatients with cirrhosis admitted non- present study, we aimed to determine associations between
electively across 7 centres in North America and collected clinical neutrophil migration capacity and clinical outcome of patients with
data and infection status on admission. Serum was collected on liver cirrhosis and acute-on-chronic liver failure.
admission and analysed for LC/MS metabolomics. Hospital course, Method: Patients with compensated (n = 11) or acutely decompen-
including NI development, ICU, ACLF and death were analysed. sated liver cirrhosis (n = 84) or ACLF (n = 29) were recruited from a
Metabolomic analysis using ANCOVA adjusted for age, sex, admission prospective, monocentric cohort study. Neutrophils were isolated of
MELD, WBC, and albumin, rifaximin, infection status was performed. peripheral blood by magnetic beads. Neutrophil migration was
Also, we performed random forest analyses (RFA) for NI development. tracked during steady-state-, fMLP-, CXCL1-, or CXCL8-stimulated
Finally logistic regression with clinical variables and then additional conditions using time-lapse video microscopy and automated cell
metabolites to predict NI was performed. tracking. Proportion of migrating cells as well as average migration
Results: 602 patients (376 men, 231 admission infection) were speed was quantified. Regression analyses were used to determine
included. 101 (17%) developed NI 5 ± 2 days after admission. NI associations between neutrophil migration and clinical end points.
patients had more frequent admission infections and longer LOS. NIs Results: The percentage of migrating neutrophils was significantly
resulted in worse inpatient outcomes including ICU transfer, death, lower in patients with acute decompensation (81.32 ± 1.6%, P = 0.01)
and organ failures. Infection details: Most common initial infections or ACLF (76.63 ± 3.4%, P = 0.003) after fMLP-stimulation compared to
were SBP followed by UTI and respiratory tract from bacterial causes. healthy individuals (89.04 ± 0.8%). Moreover, CXCL8-stimulation was
On the other hand, NIs were more likely to be fungal (n = 39, p < less effective in neutrophils of patients with ACLF (77.56 ± 3.2%)
0.0001 vs admission infections); rest were bacterial. compared to healthy individuals (87.14 ± 2.0%, P = 0.04). Average
Metabolomics: 247 metabolites were significantly different between migration speed of neutrophils was reduced after both fMLP- and
patients with vs. without a NI using ANCOVA with a AUC of 0.83 CXCL8-stimulation in patients with acute decompensation (fMLP
(metabolites alone). The top 25 metabolites on RFA are shown in 15.23 ± 3.3 μm/min, P = 0.001; CXCL8 14.42 ± 0.3 μm/min, P = 0.048)
Table 1 and according to mean decrease accuracy (Figure). Logistic or ACLF (fMLP 14.91 ± 0.7 μm/min, P = 0.005; CXCL8 13.82 ± 0.4 μm/
regression: Higher MELD (OR 1.05, CI 1.02–1.09, p < 0.0001), admis- min, P = 0.008) compared to healthy individuals (fMLP 17.78 ±
sion infection (OR 3.54, CI 2.18–5.76, p < 0.0001) and admission WBC 0.5 μm/min, CXCL8 15.78 ± 0.5 μm/min). A low proportion of migrat-
(OR 1.05, CI 1.00–1.09, p = 0.04) were significant predictors with AUC ing neutrophils under steady-state or stimulated conditions was
of 0.74. Of the metabolites, ↓ 1-linolenoyl-GPC, 1-stearoyl-GPC and associated with the development of ACLF ( p < 0.05), sepsis ( p < 0.05),
and ↑ N-acetyltryptophan and N-acetyl isoputreanine added signifi- or the composite of ACLF, sepsis and death ( p < 0.01) within 7 days.
cantly to the clinical model (AUC 0.77, p = 0.05). Conclusion: Defective neutrophil migration under ex vivo steady-
state conditions or after stimulation with fMLP or CXCL8 is associated
with adverse outcomes in liver cirrhosis such as the development of
sepsis and ACLF. Hence, neutrophil migration analysis might provide
as a novel early warning sign for the development of severe
complications in liver cirrhosis patients.

THU496
Renal and circulatory effects of terlipressin in patients with
hepatorenal syndrome assessed by magnetic resonance imaging
Karen Vagner Danielsen1, Jens Hove1, Puria Nabilou1, Thit Kronborg1,
Signe Wiese1, Hartwig R. Siebner1, Søren Møller1,
Flemming Bendtsen1. 1Hvidovre University Hospital, Denmark
Email: [email protected]
Background and aims: Terlipressin improves renal function in about
40% of the patients with hepatorenal syndrome-acute kidney injury
(HRS-AKI), but the pathophysiological mechanisms are unclear and
the regional hemodynamic changes following terlipressin in patients
with HRS-AKI have not, to our knowledge, been studied
Method: Using cardiac- and phase contrast magnetic resonance-
Conclusion: NIs are seen in almost a fifth of hospitalized patients imaging (MRI) we assessed the cardiac function and renal, splanch-
with cirrhosis and are associated with poor outcomes. Admission nic, and peripheral flow changes after first bolus of 2 mg terlipressin
metabolites focused on spermidine, tryptophan, and phospholipid in 10 patients with HRS-AKI, six of whom also had acute-on-chronic
metabolism were independently associated with NI prediction with liver failure. The patients were prospectively followed, and creatinine
significant contribution over clinical factors. and mortality registered
Results: Cardiac output decreased by 15% following terlipressin ( p <
THU495 0.01). Despite a decrease in cardiac output, renal artery blood flow
Association of impaired neutrophil migration with adverse (RBF) increased by 23% ( p < 0.01) and RBF percentage of cardiac
outcomes in patients with liver cirrhosis output increased by 49% ( p = 0.01). Simultaneously, superior mes-
Mona-May Langer1,2, Stefanie Sichelschmidt1, Alina Bauschen1, enteric artery blood flow and femoral artery blood flow decreased by
Sabrina Guckenbiehl1, Lea Bornemann3, Matthias Gunzer3, 27% and 40%, respectively (both with p < 0.01). Mean arterial pressure
Christian M. Lange1,2. 1Essen University Hospital, Department for (MAP) and systemic vascular resistance increased by 13% and 32%,
Gastroenterology and Hepatology, Essen, Germany; 2Hospital of the respectively (both with p < 0.01). Baseline RBF correlated with
Ludwig Maximilian University (LMU), Medical Clinic and Polyclinic II, serum-creatinine ( p < 0.01), whereas changes in RBF or other
Munich, Germany; 3University Duisburg-Essen, Institute for cardiocirculatory variables did not correlate to changes in serum-
Experimental Immunology and Imaging, Essen, Germany creatinine after terlipressin
Email: [email protected] Conclusion: Terlipressin increases RBF, while reducing cardiac output
and alleviating splanchnic- and peripheral vasodilatation. These
Background and aims: Neutrophil granulocytes are important cells effects, together with an increase in MAP, seem to explain the benefits
of the first line defense against bacterial and fungal infections. In the of terlipressin for patients with HRS-AKI. MRI is a feasible, non-

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 POSTER PRESENTATIONS
invasive tool for assessing the cardiocirculatory effects of terlipressin; THU498
however, additional studies with larger sample sizes are needed to Low FT3 levels are associated with acute decompensation and
confirm these results. acute-on-chronic liver failure
Mona-May Langer1,2, Alina Bauschen1, Sabrina Guckenbiehl1,
THU497 G. Sebastian Hönes3, Denise Zwanziger3, Lars Christian Möller3,
SARS-CoV-2 infection in patients with underlying chronic liver Christian M. Lange1,2. 1University Hospital Essen, Department for
disease is associated with significantly greater risks of inpatient Gastroenterology and Hepatology, Essen, Germany; 2Hospital of the
hospitalization, intensive care unit admission, and overall Ludwig Maximilian University (LMU), Medical Clinic and Polyclinic II,
mortality Munich, Germany; 3University Hospital Essen, Department of
Robert Wong1, Yi Zhang2, Mae Thamer2. 1Stanford University School of Endocrinology, Diabetes and Metabolism and Division of Laboratory
Medicine, United States; 2Medical Technology and Practice Patterns Research, Essen, Germany
Institute, Bethesda, United States Email: [email protected]
Email: [email protected]
Background and aims: Thyroid hormones (TH) are important for
Background and aims: Patients with chronic liver disease (CLD) are regulation of hepatic lipolysis, gluconeogenesis, and immune-
hypothesized to have greater risk of developing liver decompensation metabolism, and may thereby impact the pathogenesis and severity
following COVID-19. However, it is unclear whether the increased of liver cirrhosis and acute-on-chronic liver failure (ACLF). Therefore,
risks of liver decompensation result in higher overall mortality in CLD we determined associations between TH, clinical stages of liver
patients with COVID-19 (CLD+COVID-19). We aim to evaluate cirrhosis including ACLF and TH targets in immune cells.
whether CLD+COVID-19 patients have higher rates of inpatient Method: From a prospective cohort study, patients with compen-
hospitalization, intensive care unit (ICU) admission, and overall sated liver cirrhosis (n = 163) or acute decompensation (n = 169) or
mortality compared to CLD patients without COVID-19 among one of ACLF (n = 36) were recruited. Thyroid-stimulating hormone (TSH),
the largest U.S. cohorts evaluating COVID-19 outcomes. free T3 (FT3) and free T4 (FT4) levels were determined by
Method: Using the Common Data Schema from COVID-19 Research immunoassays. Associations between TH and clinical parameters
Database, a large U.S. database containing over 72 million linked were assessed by regression analyses. T cells of healthy donors and
patients with both electronic health records and claims data, we patients were isolated from peripheral blood and characterized for
identified patients with CLD (hepatitis C, hepatitis B, alcoholic liver expression of TH target genes by RT-PCR.
disease, and non-alcoholic fatty liver disease/steatohepatitis) with Results: TSH concentration in patients with acute decompensation
COVID-19 (CLD+COVID-19) and without COVID-19. Patients were (2.81 ± 0.2 mU/l) was increased compared to patients with compen-
followed for at least 6 months until a censoring event (i.e. death) or sated liver cirrhosis (2.01 ± 0.1 mU/l, P = 0.03) and ACLF (2.18 ±
end of the study period (August 31, 2021). Outcomes assessed 0.34 mU/l, P = 0.42). Contrariwise FT3 levels were significantly
included need for inpatient hospitalization, ICU admission, and lower already in patients with acute decompensation (3.80 ±
overall mortality, and outcomes were compared between groups 0.06 pmol/l) compared to compensated liver cirrhosis (4.79 ±
with chi-square testing. Multivariate regression models evaluated 0.06 pmol/l, P < 0.0001), and even lower in those with ACLF (3.24 ±
whether COVID-19 was independently associated with greater risk of 0.15 pmol/l; compensated vs. ACLF P < 0.0001; acute decompensation
hospitalization, ICU admission, and overall mortality in CLD patients. vs. ACLF P < 0.01). Decreased FT3 concentrations were associated with
Results: Among 973, 634 adult patients with CLD (55.2% men, 44.8% infections in acute decompensated patients (3.45 ± 0.10 pmol/lwith
women, 28.9% age >65y, 40.4% age 45–64y, 30.7% age 18–44, 12.0% vs. 3.90 ± 0.07 pmol/lwithout infection, P = 0.0009), while FT3 con-
with cirrhosis), 3.5% had CLD+COVID-19 and 96.5% had CLD without centrations were not different in ACLF with (3.23 ± 0.24 pmol/l) or
COVID-19. Compared to CLD without COVID-19, CLD+COVID-19 without infections (3.25 ± 0.16 pmol/l, P = 0.8). FT3 concentrations
patients had significantly higher rates of hospitalization (25.7% vs. correlated inversely with CLIF-OF-, CLIF-C-AD/ACLF- and MELD-
9.2%, p < 0.01), ICU admission (15.5% vs. 4.9%, p < 0.01), and overall scores ( p < 0.0001). Furthermore, low FT3 levels ( p < 0.0001) as well
mortality (5.6% vs. 3.8%, p < 0.01). On adjusted multivariate regres- as a low FT3/FT4 ratio ( p < 0.001) were associated with mortality of
sion, when compared to CLD patients without COVID-19, patients liver cirrhosis patients. RT-PCR showed that T cells derived from
with CLD+COVID-19 had significantly greater risk of hospitalization healthy donors and patients with liver cirrhosis or ACLF did not
(OR 3.27, 95% CI 3.19–3.35, p < 0.01), ICU admission (OR 3.36, 95% CI express TH receptor β, but TH receptor α. Compared to T cells of
3.26–3.47), and overall mortality (OR 1.36, 95% CI 1.29–1.42). These healthy donors, expression of TH receptor α was significantly
findings were likely mediated by increased risks liver decompensa- decreased in T cells derived from patients with compensated liver
tion (HR 1.23, 95% CI 1.15–1.32, p < 0.01) and acute on chronic liver cirrhosis ( p = 0.02) and even more in T cells of patients with acute
failure (ACLF) (HR 7.32, 95% CI 6.40–8.38, p < 0.01) due to acute SARS- decompensation ( p = 0.001) or ACLF ( p = 0.009).
CoV-2 infection observed in CLD+COVID-19 compared to CLD without Conclusion: Acute decompensation complicated with infections as
COVID-19 patients. well as ACLF with or without infections is associated with profound
Conclusion: Among one of the largest cohorts evaluating COVID-19 alterations in the TH balance resembling low T3 syndrome. Strikingly,
outcomes in patients with underlying CLD, we observed that SARS- low FT3 level and decreased FT3/FT4 ratio are associated with
CoV-2 infection was associated with significantly greater risks of elevated mortality in patients with liver cirrhosis. Reduced TH
inpatient hospitalization, ICU admission, and overall mortality in receptor α expression suggests impaired TH signaling in T cells of
patients with CLD. The increased mortality observed in CLD patients patients with liver cirrhosis possibly contributing to reduced survival.
with COVID-19 is likely a result of the increased risks of liver Mechanism and functional consequences of these findings will be
decompensation and ACLF due to COVID-19. further explored in the new SFB-CRC/TR 296.

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POSTER PRESENTATIONS
THU499 THU500
Post hoc analyses of the ATTIRE trial suggest potential gender Can machines predict liver decompensation? Analysis of 1, 415
differences in response to albumin patients with liver cirrhosis recruited at three German referral
Margaret Hook1, Thais [email protected], Louise China1, centers
Alastair O’Brien1. 1UCL Institute for Liver and Digestive Health Upper 3rd Sophie Elisabeth Müller1, Cristina Ripoll2, Alexander Zipprich2,
Floor, University College London Division of Medicine, London, United Tony Bruns3, Paul Horn4, Marcin Krawczyk1, Frank Lammert1,
Kingdom Matthias Reichert1. 1Saarland University Medical Center, Saarland
Email: [email protected] University, Department of Medicine II, Homburg, Germany; 2University
Hospital Jena, Clinic for Internal Medicine IV, Jena, Germany; 3Aachen
Background and aims: Acute decompensation (AD) and acute-on-
University Hospital, Department of Medicine III, Aachen, Germany;
chronic Liver failure (ACLF) are characterised by increased systemic 4
University of Birmingham, Centre for Liver and Gastrointestinal
inflammation and immunosuppression. There are data supporting
Research, Institute of Immunology and Immunotherapy, Birmingham,
gender differences in the inflammatory response in health and
United Kingdom
differences in outcomes between genders in AD/ACLF. Post-hoc
Email: [email protected]
subgroup analyses of the neutral ATTIRE trial (Albumin To Prevent
Infection in Chronic Liver Failure) suggested a differential effect of Background and aims: Since decompensation of cirrhosis signifi-
targeted albumin infusions according to gender and so we investi- cantly increases mortality, early detection of patients at risk of
gated this in greater detail. worsening liver function is of paramount importance. Hence, we
Method: ATTIRE was a randomized, multicenter, open-label trial applied machine learning techniques to identify parameters predict-
involving 777 patients including 227 women, hospitalized with ing hepatic decompensation.
decompensated cirrhosis and serum albumin <30 g/L. Patients Method: Using Python, Keras, and Scikit-Learn, several machine
received standard of care or targeted albumin therapy (aiming for learning techniques including Decision Trees, Random Forests, Neural
serum albumin >30 g/L) for up to 14 days or discharge. Baseline Networks, and Support Vector Machines (SVM) were applied to the
clinical characteristics and patient outcomes were analysed using INCA trial database containing both pro- and retrospective data from
appropriate statistical tests in RStudio software. 1, 415 patients with cirrhosis from three German university hospitals
Results: Baseline characteristics, including MELD (Model for End- (Homburg, Halle, Jena). In addition to laboratory values and medical
Stage Liver Disease) score, age and cirrhosis aetiology were similar history, genetic data (including nucleotide-binding oligomerization
between genders apart from an elevated creatinine in men (70 (57– domain-containing protein 2 [NOD2] genotypes) were analyzed. The
94) vs 60 (48–77) μmol/L, p < 0.001). The volume of albumin infused models were trained and tested with an 85:15 split. After performing
did not differ between genders but resulting serum albumin values in hierarchical clustering on the numerical variables based on
the targeted albumin group were higher in women throughout the Spearman rank-order correlation using Ward’s minimum variance
trial treatment period ( p < 0.001). Women also had higher white cell method, we applied Permutation Feature Importance (PFI) to
counts (WCC) throughout the trial independent of treatment group evaluate the impact of features on the prediction of decompensation.
( p < 0.001) but not C-reactive protein values. Overall outcomes did Results: At the index date, 313 patients were permanently compen-
not differ between genders, although fewer events of renal dysfunc- sated, 354 patients had been decompensated before, and 748 patients
tion were seen in women (but not men) in the albumin treatment were currently decompensated. Overall, 825 patients could be
group compared to standard care (Chi-squared test (X² (1) = 6.85, p = followed up (median duration: 12 months, maximum: 55 months),
0.009). The incidence of serious adverse events with pulmonary of whom 46.5% decompensated during follow-up. SVM showed the
oedema or fluid overload was similar between treatment groups in best performance in predicting decompensation, achieving an
women, in contrast to men in which these were four times as common accuracy of 84.1% for the training and 77.7% for the test data set in
in the albumin group. retrospective assessment, and 78.4% and 73.8% in prospective
analysis. PFI revealed baseline levels of albumin and bilirubin as
Table: Outcomes and serious adverse events in ATTIRE according to gender well as minimum serum sodium concentrations as highest-ranking
and treatment group
parameters associated with former decompensation. The maximum
level of bilirubin and baseline levels of sodium and albumin were the
most accurate variables for prospective data. In addition to the
parameters of established scores such as MELD and Child-Pugh,
NOD2 genotype and parameters related to infections (e.g. inflamma-
tory markers and intake of antibiotics) were highly ranked.
Conclusion: Among tested machine learning models, SVM seems to
have the highest accuracy in predicting liver decompensation. In
addition to classical laboratory parameters, genetic factors and
infections were critical parameters for individual predictions by SVM.

THU501
LivR Well: a feasibility study for a home-based, multidisciplinary
liver optimization program for the first 28 days after an admission
for acute-on-chronic liver failure
Natalie Ngu1,2, Edward Saxby1, Patricia Anderson1, Lisa Stothers1,
Conclusion: Higher WCC levels in women irrespective of treatment Anita Figredo3, Thomas Worland1, Stephen Pianko1,2,
group might suggest a difference in the inflammatory response but William Sievert1, Benjamin Rogers2,3, Sally Bell1,2, Danny Liew2,
infection rates and overall outcomes were similar. The improved renal Suong Le1,2. 1Monash Health, Gastroenterology and Hepatology,
function in albumin-treated women without evidence of increased Melbourne, Australia; 2Monash University Clayton Campus, Faculty of
adverse events may relate to their increased rate of serum albumin Medicine, Nursing and Health Sciences, Clayton, Australia; 3Monash
increment, however, there was no mortality benefit according to Health, Hospital in the Home, Australia
gender. These findings may warrant further investigation. Email: [email protected]
Background and aims: Acute on chronic liver failure (ACLF) has a 28-
day mortality of 33.9% (1) and 30-day re-admission rate of 30% (2).

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 POSTER PRESENTATIONS
LivR Well is a multidisciplinary intervention aimed at reducing THU502
mortality and readmission through a home-based, liver optimisation Alcohol-associated hepatitis with acute-on-chronic liver failure
program after an ACLF episode. We assessed feasibility, safety, patient in a diverse cohort: lung and circulatory organ failures along with
acceptability and clinical impact. MELD 35 are predictive of mortality
Method: A prospective, feasibility study was conducted at an Stephanie Rutledge1, Rohit Nathani2, Erin Eschbach3, Lily Chu4,
Australian tertiary hospital from March to October 2021. ACLF was Parth Trivedi3, Thomas Schiano5, Leona Kim-Schluger5,
defined as an acute hepatic insult with serum bilirubin ≥50 umol/L Sander Florman5, Scott Friedman4, Gene Im5. 1Icahn School of
and International Normalized Ratio ≥1.5, complicated within 4 weeks Medicine at Mount Sinai, Division of Gastroenterology, Department of
by ascites and/or encephalopathy. Exclusions included end-of-life Medicine, New York, United States; 2Icahn School of Medicine at Mount
care, heart failure management and aged care residents. Participants Sinai Morningside-West, Department of Medicine, New York, United
received weekly medical review and oral nutritional supplementa- States; 3Icahn School of Medicine at Mount Sinai, Department of
tion. Home nursing, dietitian, physiotherapist, pharmacist, social Medicine, New York, United States; 4Icahn School of Medicine at Mount
worker, and neuropsychiatrist consultations were provided (Fig 1). Sinai, Division of Liver Diseases, Department of Medicine, New York,
The primary outcomes were adverse events/death. Secondary out- United States; 5Icahn School of Medicine at Mount Sinai, Recanati/Miller
comes were attrition, liver disease severity, healthcare utilization, Transplantation Institute, Division of Liver Diseases, Department of
and patient-reported outcomes. Medicine, New York, United States
Email: [email protected]
Background and aims: Severe alcohol-associated hepatitis (sAH)
without response to medical therapy is associated with unacceptably
high mortality, particularly with concomitant acute-on-chronic liver
failure (ACLF). Only a minority of these sAH-ACLF patients are eligible
for early liver transplantation (eLT) and the outcomes of declined
candidates are unknown. The aim of our study was to determine the
outcomes of declined eLT for sAH candidates and to examine
variables associated with outcomes in sAH-ACLF.
Results: We enrolled 32 patients; 31 patients completed the program. Method: We analysed a prospectively maintained database of sAH
The median age was 53 years (Interquartile range (IQR) 49–60); 75% patients ( probable or definite per NIAAA guidelines, MELD >20)
were male. The median Charlson Co-Morbidity Index score was 4 (IQR hospitalized at a LT centre from 1/2012–7/2021. All non-responders to
3–5.5). Excess alcohol was the most common etiology (72%). Baseline corticosteroids were presented at our transplant selection meeting.
median Model for End-Stage Liver Disease (MELD) score was 17 (IQR Patients declined for eLT for sAH and those accepted who died prior to
13–21). Baseline handgrip strength in 11/27 (41%) patients met sex- eLT were identified. The U.S. centralised National Death Index (NDI)
specific criteria for sarcopenia. Two patients died at 16 and 148 days was used to determine outcomes of patients lacking follow-up at our
from enrolment. The 28-day mortality was 3% and the 30-day centre.
readmission rate was 16%. LivR Well cost $4, 947 AUD compared to Results: Over 9.5 years, a total of 234 sAH patients were either
$16, 197 AUD for an inpatient ACLF admission. Median MELD score declined for eLT (n = 207) or accepted and died prior to eLT (n = 27).
improved at 28 days (17 vs. 15, p = 0.31). The Chronic Liver Disease Median time to eLT decision was 5 days (3–11). The cohort was young
Questionnaire showed improvement in ‘fatigue’ (p = 0.03) and and diverse: median age 44 years (35–53), nearly half were women
‘worry’ ( p = 0.05), at 28 days compared to baseline. Qualitative (108/234, 46%) with significant racial minority representation: 55%
interviews were undertaken in 24 participants with all reporting White, 26% Hispanic, 8% Black, 7% Asian, 3% unknown. Most of the
positive experience pertaining to interactions with clinicians. The cohort met EASL-CLIF criteria for ACLF (62%); 71% had ACLF grade 2 or
importance of health literacy (22/24) and patient autonomy (20/24) 3. Mean MELD score at the time of waitlisting decision was 33 (±8),
were emphasized in >80% of interviews. mean Maddrey’s discriminant function was 96 (±79), median CLIF-C
Conclusion: LivR Well was safe, feasible, acceptable, and cost- Organ Failure score (CLIF-C OFs) was 10 (9–12) and median CLIF-C
efficient with a reduction in 28-day mortality and 30-day readmis- ACLF score was 49 (43–55). Over a median follow-up of 494 days (17–
sion rates. We plan to conduct a randomized controlled trial of LivR 1291), 145/234 died (62%) Of patients with ACLF-3, 38/45 (84%) died
Well compared to standard care to evaluate cost-effectiveness and and median time to death was 8 days (3–18) versus 17 days (9–59) in
clinical impact on re-admission and mortality. ACLF-2, 78.5 days (22.5–228) in ACLF-1 and 71 days (19.5–210) in
1. Hernaez R, Kramer JR et al. Prevalence and short-term mortality of
patients without ACLF ( p = 0.001) (figure).
acute-on-chronic liver failure: A national cohort study from the USA. J
Hepatol. 2019;70 (4):639–47.
2. Moreau R, Jalan R et al. Acute-on-chronic liver failure is a distinct
syndrome that develops in patients with acute decompensation of
cirrhosis. Gastroenterology. 2013;144 (7):1426–37, 37.e1-9.

Figure: Kaplan-Meier survival by ACLF grade

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POSTER PRESENTATIONS
Of the components of CLIF-C OFs, lung (HR 3.9, 95% CI 1.4–11.3) and
circulatory scores (HR 3.13, 95% CI 1.6–6.2) were most predictive of
mortality. Liver (HR 2.5, 95% CI 1.4–4.6), brain (HR 2.4, 95% CI 1.5–3.8),
kidney (HR 1.6, 95% CI 1.2–2.2) and coagulation scores (HR 1.4, 95% CI
1.03–1.97) were also significantly associated. MELD >35 was
determined as the optimal threshold for predicting mortality (HR
3.1, 95% CI 1.7–5.6). Compared with a "static" bilirubin during
admission, a 10% bilirubin decrease had 66% lower mortality risk ( p =
0.01) and a 20% increase was associated with 200% higher mortality
( p = 0.05).
Conclusion: In a diverse, real-world cohort of patients with sAH
declined for eLT, we identified a high prevalence of ACLF with very
high short-term mortality. Lung and circulatory components of CLIF-
C OFs and MELD >35 at the time of waitlisting decision were most
predictive of mortality and may help guide clinical decision-making.

THU503
Bilirubin and its dynamics are independently associated with Figure: Kaplan-Meier 12-week survival estimates according to bilirubin at
mortality in patients with acute decompensation of cirrhosis admission.
Konstantin Kazankov1,2, Peter Holland-Fischer1,3,
Karen Louise Thomsen1,2, Rajiv Jalan1, Raj Mookerjee1. 1University Conclusion: In AD cirrhosis patients, bilirubin at admission is a
College London (UCL), Institute for Liver and Digestive Health, UCL strong independent predictor of mortality. A step-wise increase in
Medical School, Royal Free Hospital, Liver Failure Group, United mortality arises from bilirubin levels >12 mg/dL. Failure to improve
Kingdom; 2Aarhus University Hospital, Department of Hepatology and bilirubin during admission is an even stronger predictor of death. We
Gastroenterology, Denmark; 3Aalborg University Hospital, Department propose a more detailed analysis of bilirubin and its dynamics in
of Medical Gastroenterology, Denmark future studies, to generate new models for prognostication in AD
Email: [email protected] cirrhosis.

Background and aims: Patients with acute decompensation of THU504

cirrhosis (AD) are at high risk of mortality, and current practice is still Impact of predisposition and precipitants on the short-term
devoid of accurate parameters indicating poor outcome. In our AD prognosis among inpatients with chronic liver disease
cohort, we assessed the value of bilirubin alone and its dynamic Yan Zhang1, Guohong Deng2, Xian-Bo Wang3, Xin Zheng4,
changes to predict mortality. Yan Huang5, Jinjun Chen6, Zhong-Ji Meng7, Yanhang Gao8,
Method: We included patients with AD cirrhosis from a prospective Zhiping Qian9, Feng Liu10, Xiao-Bo Lu11,11, Yu Shi12, Yan Huadong13,
database in which clinical and biochemical data were registered. Zheng Yubao14, Hai Li1,1. 1Ren Ji Hospital, School of Medicine, Shanghai
Multivariate logistic regression and Kaplan-Meier analysis were used Jiao Tong University, Department of Gastroenterology, Shanghai, China;
for statistical analysis. Odds ratios (OR) were based on bilirubin 2
Southwest Hospital, Third Military Medical University (Army Medical
increments of 1.45 mg/dL (25 μmol/L). University), Department of Infectious Diseases, Chongqing, China;
Results: 519 patients were included, with alcohol (68%) as the 3
Beijing Ditan Hospital, Capital Medical University, Center of Integrative
predominant etiology. Main precipitants for AD were: harmful Medicine, Beijing, China; 4Institute of Infection and Immunology, Union
drinking (35%), infection (17%) and unknown (24%). 137 patients Hospital, Tongji Medical College, Huazhong University of Science and
had alcoholic hepatitis. 354 patients (67%) did not have ACLF on Technology, Department of Infectious Diseases, Wuhan, China; 5Hunan
admission or develop ACLF pre-discharge, whereas 24% had ACLF on Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South
admission, and 9% developed ACLF during hospitalization. Fifty-nine University, Department of Infectious Diseases, Changsha, China;
patients (11%) died within 4 weeks, and 118 (23%) within 12 weeks, 6
Nanfang Hospital, Southern Medical University, Hepatology Unit,
with the highest mortality in patients with ACLF on admission or Department of Infectious Diseases, Guangzhou, China; 7Taihe Hospital,
during hospitalization. Hubei University of Medicine, Department of Infectious Disease, Shiyan,
In multivariate analysis, admission bilirubin was associated with both China; 8The First Hospital of Jilin University, Department of Hepatology,
4- (OR 1.09 [CI 1.03–1.15]) and 12-week mortality (OR 1.08 [CI 1.03– Changchun, China; 9Department of Liver Intensive Care Unit, Shanghai
1.13]) adjusted for age, sodium, creatinine, INR, white cell count, CRP Public Health Clinical Centre, Fudan University, Shanghai, China;
and presence of alcoholic hepatitis and infection. Bilirubin levels 10
Tianjin Institute of Hepatology, Nankai University Second People’s
beyond 12 mg/dL, the liver failure threshold according to the CLIF- Hospital, Tianjin, China; 11Infectious Disease Center, The First Affiliated
Consortium ACLF-score, showed increasing 12-week mortality Hospital of Xinjiang Medical University, Urumqi, China; 12The State Key
(Figure, log-rank test p < 0.001). Laboratory for Diagnosis and Treatment of Infectious Diseases, The First
During admission (median 11 [IQR 7–20] days), 328 (63%) patients Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou,
decreased their bilirubin, whereas it increased or was unchanged in China; 13Department of Infectious Diseases, Hwamei Hospital, Ningbo,
190 (37%) patients. Lack of reduction in bilirubin was strongly China; 14Deparment of Infectious Diseases, The Third Affiliated Hospital
associated with death after 4 (OR 4.12 [CI 2.13–7.99]) and 12 weeks of Sun Yat-sen University, Guangzhou
(OR 2.77 [CI 1.65–4.64]) in multivariate analysis. Accordingly, 18% of Email: [email protected]
patients with a decrease in bilirubin died after 12 weeks vs. 35% in
those with an increase or no change. Background and aims: Little is known about the impact of
In patients with AD without ACLF, admission bilirubin lost its predisposition, especially the severity of liver fibrosis, and the type
association with death at 4 weeks (OR 0.96 [CI 0.75–1.24]) but of precipitants on the short-term prognosis in hospitalized patients
remained associated with 12-week mortality (OR 1.09 [CI 0.997– with chronic liver disease. We aimed to evaluated the risk of
1.20]) in multivariate analysis, especially for levels >17.5 mg/dL. In predisposition and precipitants on the short-term prognosis in
patients without ACLF at admission, bilirubin was independently hospitalized patients with chronic liver disease.
associated with ACLF development during hospitalization (OR 1.16 [CI Method: This study was performed in 3970 cirrhosis and other
1.07–1.26]). chronic liver disease patients hospitalized for acute decompensation

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 POSTER PRESENTATIONS

Figure: (abstract: THU504)

or acute liver injury from two prospective large multicenter studies in extrahepatic precipitants are suggested which could enhance
high-endemic HBV areas (NCT02457637 and NCT03641872). The disease management and decrease the mortality.
primary end point was a composite outcome comprised of death and
liver transplantation. We investigated the natural history of compos- THU505
ite outcome within 1 year and assessed the risk of predisposition, A study evaluating outcomes of a virtual specialist liver cirrhosis
precipitants for 90-day or 365-day composite outcome. clinic
Results: In 2826 patients with cirrhosis, 2306 admitted for classical Claudia Moore-Gillon1, Alex Cole1, Maria Bashyam1,
AD (including overt ascites, hepatic encephalopathy, gastrointestinal Mathew Vithayathil1, Rooshi Nathwani1,2, David Koeckerling2,
bleeding and bacterial infection) burden with high 90-day and 365- Sujit Mukherjee1,2, Benjamin H. Mullish1,2, Maud Lemoine1,2,
day composite outcome rate (24.7%, 33.0%), while 291 admitted Lucia Possamai1,2, Heather Lewis1,2, Nowlan Selvapatt1,2,
without classical AD but with jaundice (TB >5 mg/dl) showed Ameet Dhar1,2. 1Imperial College Healthcare NHS Trust, United
comparable high 90-day and 365-day composite outcome rate Kingdom; 2Imperial College London, United Kingdom
(26.1%, 33.0%). In 1144 patients without cirrhosis, 955 patients with Email: [email protected]
advanced fibrosis (FIB-4 >1.45) burdened with relatively high 90-day
Background and aims: Managing patients in a specialist cirrhosis
and 365-day composite outcome rate (8.7%, 9.9%) when compared to clinic improves survival. The COVID-19 pandemic necessitated the
those with mild or none fibrosis (2.2%, 2.2%). After adjusting age, transition to virtual clinics (VC). We aimed to evaluate the clinical
gender, TB, INR, Creatine and sodium, the severity of liver fibrosis in
impact of VC on survival, admission and decompensation rates in
non-cirrhosis had no impact of 90-day ( p = 0.222) and 365-day cirrhotic patients managed in a specialist service.
composite outcome ( p = 0.581). But the occurrence of cirrhosis
Method: We retrospectively analysed cirrhotic patients who had a
significantly increased the risk for 90-day (p < 0.001, OR = 2.45) and
specialised VC from March to June 2020. Clinical parameters were
365-day ( p < 0.001, OR = 3.09) composite outcome when compared collected at baseline and 6 months and compared with a cohort of
to non-cirrhosis. Moreover, in patients with cirrhosis and AD,
patients reviewed face to face (F2F) in the same specialist cirrhosis
previous decompensation independently increased the risk of 365- clinics from March to June 2019. Patients with COVID-19 were
day adverse outcomes by 1.39-fold ( p = 0.005) and 365-day compos-
excluded.
ite outcome by 1.85-fold ( p < 0.001), and the risk of 90-day and 365-
Results: 143 patients attended for VC, 129 for F2F review. Groups
day adverse outcomes in patients with extrahepatic precipitants was were matched for age, sex, aetiology, and Child Pugh grade (CP). There
significantly higher than that in patients with intrahepatic
was no difference at 6 months in survival, change in MELD/UKELD,
precipitants. decompensation or need for ambulatory review in all cirrhosis grades
Conclusion: The severity of liver fibrosis did not impact the 90-day combined or CP BandC subgroup alone ( p > 0.05) (Table 1). Fewer
and 365-day composite outcome in patients without cirrhosis, but patients were admitted in the VC vs the F2F group ( p = 0.01) but this
the occurrence of cirrhosis significantly increased the risk for 90-day was not validated in CP BandC subgroup ( p = 0.28). Fewer blood tests
and 365-day composite outcome. In cirrhosis, jaundice should be also were ordered for the VC group ( p = 0.0001). The VC group had longer
recognized as a kind of AD owing to its contribution to the delays for ultrasound HCC surveillance (<0.0001) without an increase
comparable high 90-day mortality. Moreover, in patients with in new HCC cases.
cirrhosis and AD, long-term surveillance monitoring in patients
with previous decompensation and intensive therapy targeting

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POSTER PRESENTATIONS
Table: Baseline Patient Demographics and 6 months’ outcome (*p < altered in chronic liver failure can yield superior prognostic accuracy
0.05, **p < 0.01) for short- and intermediate-term survival.
Method: We studied a multinational cohort of patients with chronic
VC (n = 143) F2F (n = 129)
liver failure of varying severity, including compensated cirrhosis (CC),
Age-yrs (range) 61 (30–85) 60 (32–84) AD and ACLF. Metabolomics analysis was performed by NMR
Gender-no (%) spectroscopy and revealed several metabolites that were significantly
Male 98/143 (69%) 93/129 (72%) associated with survival in univariate analyses. After checking
Main Aetiology-no (%)
intercorrelation of prognostic parameters by variance inflation
Alcoholic Liver Disease 90/143 (63%) 72/129 (56%)
Baseline Disease Severity factors (VIF), multivariable competing risk analysis was performed
CP A-no (%) 72/143 (50%) 59/129 (46%) with death as the event and liver transplantation as a competing risk
CP BandC-no (%) 71/143 (50%) 70/129 (54%) to identify independent predictors of survival. The performance of
MELD 10 11* the new prognostic model was compared to that of MELD using ROC
UKELD 50 51 analysis (DeLong test) for 3-month, 1-year and 2-year survival.
Outcomes at 6 months: Results: We included 423 patients (median age 58 years; 70% male;
Survival (all)-no (%) 138/143 (97%) 125/129 (97%) CC 54%/AD 35%/ACLF 11%; etiology alcohol 55%). Thirty-nine patients
CP BandC 67/71 (94%) 66/70 (94%) received liver transplantation, 160 patients died and 224 were
UKELD change (median) 0 0
censored. The risk of death (HR, 95%CI) increased with age (1.03,
CP BandC −1 0
New decomp (all)-no (%) 30/143 (21%) 25/129 (19.4%) 1.00–1.07), ln (creatinine) (1.88, 1.13–3.13), ln (bilirubin) (1.75, 1.31–
CP BandC 25/71 (35%) 23/70 (44%) 2.35), ornithine (0 vs. >0) (1.69, 1.06–2.69) and lower HDL-C (0.98,
Admissions (all)-no (%) 38/143 (27%) 53/129 (41%) 0.97–1.00). While the performance of this multivariable model was
** similar to that of MELD in the prediction of 3-month survival, it was
CP BandC 29/71 (41%) 35/70 (50%) superior to that of MELD for 1-year and 2-year survival (Table).
Ambulatory Review (all)-no (%) 15/143 (11%) 12/129 (9%)
CP BandC 11/71 (16%) 11/70 (16%)
Blood tests ordered-no (%) 110/143 (77%) 124/129 (96%)
90-day survival 1-year survival 2-year survival
**
CP BandC 54/71 (76%) 66/70 (94%) ** AUROC (95%CI)
Delay in HCC surveillance –months 3.0 ± 2.4 1.7 ± 2.7 ** Metabolomics- 0.88 (0.82–0.94) 0.90 (0.86–0.95) 0.87 (0.82–0.92)
CP BandC 2.2 ± 2.0 1.2 ± 1.8 ** based model
New HCC cases (all)- no (%) 2/143 (1%) 2/129 (2%) MELD 0.87 (0.82–0.93) 0.85 (0.80–0.90) 0.81 (0.76–0.87)
CP BandC 1/71 (1%) 1/70 (1%) p value (DeLong 0.934 0.006 0.004
test)

Conclusion: VC have not resulted in poorer clinical outcomes, even in

patients with decompensated cirrhosis. Access to ambulatory care Conclusion: A metabolomics-based prognostic model including age,
was still required. Fewer blood tests ordered and completed in the VC creatinine, bilirubin, ornithine and HDL-C showed superior accuracy
group did not result in adverse outcomes and this raises the for prediction of 1-year and 2-year survival as compared to MELD.
possibility of cost-saving. urther studies need to confirm the long- External validation is warranted to confirm our findings.
term clinical impact and cost-effectiveness of specialist VC in
management of cirrhotic patients. THU507
Uncovering monocyte transcription, functional and metabolic
THU506 signatures in recovery and non-recovery ACLF patients
A novel metabolomics-based prognostic model shows superior Rita Furtado Feio de Azevedo1, Hannelie Korf1, Markus Boesch1,
diagnostic accuracy than MELD in chronic liver failure Silvia Radenkovic1,2,3, Marie Wallays1, Lena Smets1,
Tobias Madl1,2, Jakob Kerbl-Knapp1, Florian Rainer3, Lukas Van Melkebeke1,4, Bart Ghesquière2,3, David Cassiman1,4,
Philipp Douschan3, Vanessa Stadlbauer3, Alexander Avian4, Philippe Meersseman5, Hannah Van Malenstein1,4,
Gunther Marsche5, Joan Claria6, Rudolf E. Stauber3. 1Medical Frederik Nevens1,4, Wim Laleman1,4, Jef Verbeek1,4,
University of Graz, Molecular Biology and Biochemistry, Graz, Austria; Schalk van der Merwe1,4. 1Laboratory Hepatology, KU Leuven,
2
BioTechMed-Graz, Graz, Austria; 3Medical University of Graz, CHROMETA Department, Leuven, Belgium; 2VIB Center for Cancer
Department of Internal Medicine, Graz, Austria; 4Medical University of Biology, Metabolomics Expertise Center, Center for Cancer Biology,
Graz, Institute for Medical Informatics, Statistics and Documentation, Leuven, Belgium; 3KU Leuven, Metabolomics Expertise Center,
Graz, Austria; 5Medical University of Graz, Division of Pharmacology, Department of Oncology, Leuven, Belgium; 4UZ Leuven, Department of
Graz, Austria; 6European Foundation for the study of chronic liver failure, Gastroenterology and Hepatology, Leuven, Belgium; 5UZ Leuven, KU
Barcelona, Spain Leuven, Department of Internal Medicine, Leuven, Belgium
Email: [email protected] Email: [email protected]
Background and aims: Chronic liver failure is associated with Background and aims: Cirrhosis is the end-result of a progressive
multiple metabolomic alterations that are related to its severity and chronic liver disease that may progress to the development of ascites,
pronounced in acute decompensation (AD) and more so in acute-on- variceal hemorrhage, encephalopathy and hepatic decompensation.
chronic liver failure (ACLF). We previously showed that high-density A precipitating event such as an infection can trigger a rapid
lipoprotein cholesterol (HDL-C) levels are reduced in patients with deterioration of liver function and result in organ failure: acute-on-
chronic liver failure, showing similar prognostic information as the chronic liver failure (ACLF). It is a devastating clinical entity with a
model for end-stage liver disease (MELD). In the present study we mortality exceeding 70% within a 28-day period in its most severe
aimed to determine whether a combination of metabolite parameters form. It is not known if these patients have infections due to a failure

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 POSTER PRESENTATIONS
of monocytes in dampening the production of pro-inflammatory system, Edwards Lifesciences) and blood gas parameters were
mediators, or whether they trigger a prolonged anti-inflammatory recorded.
response making these patients incapable to respond to a secondary Results: Thirty patients with ACLF [early group (EG, n = 15) and late
infection. Likewise, the functional and metabolic defects in ACLF are group (LG, n = 15)], aged 43.33 ± 10.1; 87% males, 70% alcoholics with
incompletely understood, and this information may be the key to mean MELD 37 ± 5, AARC 10 ± 1.61 and SOFA 14 ± 2.55 score were
restoring immune dysfunction. We aim to study the dynamics of enrolled. The median time to CRRT after onset of AKI was [44 ± 7.1 vs.
monocyte function during the course of ACLF progression and how 113.6 ± 40] hours and after initiation of vasopressors was [ (14.3 ±
this associates with disease outcome. 7.56) vs. (49.7 ± 17.8)] hours in EG vs. LG respectively ( p < 0.001). Only
Method: We performed paired transcriptional, functional and 36.7% had renal recovery and shock at day 7 (dialysis responders-DR),
metabolic analysis of CD14+CD16- monocytes at day 0 and 7 from majority in the EG [60% vs. 13.3%; p = 0.008]. A significant
ACLF patients to compare profiles in recovery vs non-recovery. ACLF improvement in SIRS, extravascular lung water (EVLW), pulmonary
patients with a CLIF-SOFA score of 2/3 with underlying chronic vascular permeability index, arterial lactate and ammonia was noted
alcoholic liver disease and no corticoid therapy were included in the in dialysis-responders (DR) compared to non-responders ( p < 0.05). A
study and were followed for 28 days after admission. significant decrease in the renal injury markers and increase in renal
Results: Transcriptomic analysis unraveled a distinct pattern repair markers [Figure] was noted in DR compared to non-
between ACLF non-recovery and recovery at baseline together with responders. Responders had lower 15-day mortality [18% vs. 58%;
expression differences between day 0 and 7 in each group. Non- HR 0.21, 0.05–0.96; P = 0.045]. Time to CRRT after initiation of
recovery monocytes showed an impaired phagocytic capacity, vasopressors [OR 0.93, 0.88–0.99] and SOFA score [OR 0.54, 0.32–
oxidative response and incapability of inducing CD4+T cell prolifer- 0.93] were independently associated with dialysis response. Each
ation and low capacity to trigger Tcell activation. Conversely, ACLF hour delay in CRRT initiation was associated with 7% decreased
patients that recovered showed an improvement in phagocytic and chances of renal recovery. The most frequent adverse event was
oxidative burst capacity from day 0 to 7, and despite being inefficient bleeding (40%) followed by hypotension (30%).
in triggering Tcell proliferation they featured an intact ability to
Conclusion: Only one in three patients of ACLF achieve renal recovery
induce T cell activation. In addition, monocyte metabolic profile of
with CRRT. Response to CRRT is associated with improvement in
recovery patients clustered separately from non-recovery ACLF
hemodynamics, systemic inflammation, endothelial and renal func-
patients at day 0. And, the monocyte metabolic profile clustered
tion. Each hour delay in CRRT after onset of shock and higher SOFA
separately day 0 from 7 on both groups.
score are associated with decreased chances of renal recovery and
Conclusion: The immune phenotype seen in monocytes from ACLF
worse outcomes in patients with ACLF.
patients that recover can effectively respond to an infectious
challenge. In stark contrast monocytes from non-recovery ACLF THU509
patients showed a functional impairment, which renders these Different clinical courses of acutely decompensated cirrhosis in
patients susceptible to new infections. hepatitis B virus high-endemic area: data from Chinese Acute-on-
Chronic Liver Failure (CATCH-LIFE) study
THU508
Early initiation of continuous renal replacement therapy Tongyu Wang1, Yu Shi2, Hai Li1. 1Shanghai, China; 2Hangzhou, China
improves renal outcomes and survival in patients with acute on Email: [email protected]
chronic liver failure-a prospective cohort study Background and aims: Cirrhotic patients with acute decompensa-
Rakhi Maiwall1, Ashini Hidam2, Sonia Kadyan1, Mansi Singh1, tion (AD) have different clinical course and pathophysiology base on
Anupam Kumar2, Rajendra Mathur3, Harshvardhan Tevethia1, the PREDICT study in a predominately alcohol-related etiologic
Hitesh Singh3, Siva Tez Pv3, Shiv Kumar Sarin1. 1ILBS, Hepatology, New population: pre-ACLF (acute-on-chronic liver failure), UDC (unstable
Delhi, India; 2ILBS, Clinical and Molecular Medicine, New Delhi, India; decompensated cirrhosis) and SDC (stable decompensated cirrhosis)
3
ILBS, Nephrology, New Delhi, India patients with different pathophysiology and prognosis. However, in
Email: [email protected] hepatitis B virus (HBV) high-endemic area, the characteristics of
these three subtypes are not well characterized. The aims of this
Background and aims: Systemic inflammatory response syndrome
(SIRS) is a driver of acute kidney injury (AKI) in patients with acute- study were to explore the characteristics and outcomes of different
clinical courses within 1 year.
on-chronic liver failure (ACLF). Early initiation of continuous renal
replacement therapy (CRRT) improves outcomes in patients with Method: We identified 2597 cirrhotic patients with AD from a
prospective multi-center cohort with 66.85% HBV-related etiology
acute liver failure, however there are no studies in patients with ACLF.
and explored the disease dynamics and prognosis within 1 year.
We aimed to investigate the impact of initiation strategy of CRRT on
AKI outcomes in patients with ACLF. Our primary outcome was to Clinical and biological parameters during hospitalization, 3-month
re-admission and outcomes during follow-up were collected. Pre-
evaluate predictors of renal recovery. Our secondary outcomes
included lactate and ammonia clearance, impact of CRRT on systemic ACLF was defined as patients developed ACLF within hospitalization.
Subgroup analysis was conducted based on etiology, prognostic
inflammation, endothelial function and adverse effects. Early
scores were recorded to predict outcomes in ACLF, UDC and SDC
initiation group (EG) was defined as initiation of CRRT within 24
hours of initiation of vasopressors (norepinephrine or terlipressin) patients, respectively.
Results: Totally, 2188 AD without ACLF at baseline were identified.
Method: Prospective cohort of ACLF patients admitted to the
intensive care unit. In all patients, urine and plasma samples were There are 184 (8.41%) pre-ACLF patients with 3-month and 1-year LT-
free mortality rates of 60.49% and 70.93%, respectively. 663 UDC
collected at baseline and 24 hours for analysing the impact of CRRT on
(27.38%) patients had at least one readmission within 3 month and
markers of inflammation, endothelial function, renal injury and
repair. Clinical, hemodynamic and lung parameters (VolumeView had no ACLF development during hospitalization, with 22.05% and

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POSTER PRESENTATIONS

Figure: (abstract: THU508)

35.27% mortality rates. 1232 (49.36%) SDC patients had neither significant differences between UDC and SDC group. Portal hyper-
readmission within 3 months nor ACLF development, with 3.42% 1- tension related complications including variceal haemorrhage and
year mortality. Systemic inflammation parameters including WBC, portal vein thrombosis proportion were significantly higher in UDC
CRP and PCT increased markedly in pre-ACLF group, while had no group than those in SDC group.

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 POSTER PRESENTATIONS
Metabolic state [measured REE (IC)/predicted REE (Harris-Benedict
equation)*100] was defined as hyper (>110%), hypo (<90%) and
normometabolic (90–110%).
Results: The clinical and metabolic characteristics are shown in table
1. Compared to HC, all 129 LC patients had increased REE and a state of
accelerated starvation (AS) [low RQ; low CHO; high FO]. Among LC,
vACLF had highest REE. Critical illness (sLC vs. vLC) worsens AS (RQ:
0.81vs.0.74) commensurate to incomplete macronutrient oxidation
(VCO2:185 vs.164) with a comparable REE. The prevalence of
hypermetabolism was higher in vACLF (38%); hypometabolism was
higher in vLC (45%). UN excretion and PO remained comparable.

Table 1: Age and BMI adjusted comparison of clinical and metabolic

characteristics
1 (HC) 2 (sLC) 3 (vLC) 4 (vACLF) Overall Intergroup-
Parameter (n−20) (n−46) (n−49) (n−34) p p

Age 28 ± 7.3 46.7 ± 9.3 47.1 ± 10.9 42.6 ± 9.6 <0.001 -

BMI 24.4 ± 3.3 24.5 ± 4.8 26.1 ± 4.6 26.1 ± 5.6 0.01 -
Etiology:n (%) - -
Ethanol 29 (63) 33 (67.3) 28 (82.4)
NASH 7 (15.2) 6 (12.2) 3 (8.8)
others 10 (21.7) 10 (20.4) 3 (8.8)
CTP 8.6 ± 1.2 12.8 ± 1.4 13.8 ± 1.9 - -
MELD 15.3 ± 5.8 29 ± 8.8 34.1 ± 5.8 - -
CLIF SOFA - 12.9 ± 3 15.2 ± 1.8 - -
REE 1393 ± 82 1581 ± 47 1528 ± 46 1760 ± 54 0.001 4 vs
all<0.005 1
vs 2-0.05
VO2 198.2 ± 13 229.3 ± 7.5 226 ± 7.3 263.2 ± 8.5 0.001 1 vs 3-0.01
2 vs 3-0.01
VCO2 180.8 ± 9.6 185.5 ± 5.6 164.3 ± 5.4 181.2 ± 6.4 0.039 2 vs 3-0.01
3 vs 4-0.04
RQ 0.95 ± 0.03 0.81 ± 0.02 0.74 ± 0.02 0.71 ± 0.02 0.001 1 vs all ; 4
vs all
<0.005
CHO 59.3 ± 7.9 27.7 ± 4.1 14.4 ± 5.2 18.9 ± 6.4 0.001 1 vs all
0.001 2vs
3-0.04
FO 27.4 ± 8.3 62.4 ± 4.3 71.3 ± 5.5 69.8 ± 6.8 0.001 1 vs all
0.001
Conclusion: The recently proposed different courses of hospitalized PO 13.4 ± 3.4 11.5 ± 1.9 14.3 ± 2.2 11.2 ± 2.8 0.72
UN 7.7 ± 2.1 8.5 ± 1.1 9.6 ± 1.3 7.9 ± 1.9 0.82
decompensated cirrhosis with AD are validated in a multi-center Metabolic state (%)
Normo 48 37 47 0.03 3 vs.4-0.01
large cohort. The systemic inflammation marked ACLF development Hypo 30 45 15
in cirrhotic AD patients during hospitalization, whereas severe portal Hyper 22 18 38

hypertension related complications are related to unstable episode of

decompensation exclusively, without apparent variation of systemic Data expressed in mean ± SE
inflammation. Developing a 90-day readmission prediction model for Conclusion: Accelerated starvation is the hallmark in LC, that
the rational management of patients with decompensated cirrhosis is worsens with critically illness. vACLF have highest energy expend-
necessary. iture. Critical illness does not augment energy demands in vLC
patients. This characterisation may help to redefine nutritional
THU510
targets in critically ill LC.
Characterization of energy and substrate metabolism in patients
with spontaneously breathing and mechanically ventilated THU511
patients with liver cirrhosis: an indirect calorimeter based study Extracorporeal membrane oxygenation, a valuable life-saving
Varsha Shasthry1, Jaya Benjamin1, Rakhi Maiwall2, Vandana Saluja3, treatment in liver transplanted patients
Prashant Mohan Agarwal3, Guresh Kumar4, Yogendrakumar Joshi1, Benjamin Buchard1,2, Sophie-Caroline Sacleux2,3, Samir Jaber4,
Shiv Kumar Sarin2. 1Institute of liver and biliary sciences, Clinical François Stéphan5, Alain Combes6, Elise Lemaître2, Marc Boudon2,3,7,
Nutrition, New Delhi, India; 2Institute of liver and biliary sciences, Audrey Coilly2,3,7, Faouzi Saliba2,3,7, Didier Samuel2,3,7,
Hepatology, New Delhi, India; 3Institute of liver and biliary sciences, Armand Abergel1, Philippe Ichai2,3. 1Chu Estaing, Medecine digestive et
Critical care anesthesia, New Delhi, India; 4Institute of liver and biliary hépatobiliaire, Clermont-Ferrand, France; 2Chb-Centre Hépato-Biliaire,
sciences, Biostatistics, New Delhi, India Liver Intensive Care Unit, Villejuif, France; 3DHU Hepatinov, Villejuif,
Email: [email protected] France; 4University Hospital Center Saint Eloi Hospital, Department of
Background and aims: Energy and substrate metabolism is Anesthesiology and Intensive Care, Montpellier, France; 5Hospital Marie
anomalous in liver cirrhosis (LC), which may be affected by critical Lannelongue, Département de réanimation adulte, Le Plessis-Robinson,
illness. Indirect calorimetry (IC) provides a precise insight into the France; 6University Hospitals Pitié Salpêtrier̀ e-Charles Foix,
same. Département de réanimation médicale, Paris, France; 7Université Paris-
Aim: To compare the resting energy expenditure (REE- Kcal/day), Saclay, INSERM Unité 1193, Villejuif
volumes (ml/min) of oxygen consumed (VO2) and carbon dioxide Email: [email protected]
released (VCO2), respiratory quotient (RQ-VCO2/VO2), percentage Background and aims: Despite a great improvement in post-liver
oxidation of carbohydrate (CHO), fat (FO) and protein (PO), between transplantation (LTx) survival over the last years, multiple organ
spontaneously breathing LC (sLC), ventilated LC (vLC), ventilated failure still accounts for 5% of deaths following surgery.
acute on chronic liver failure (vACLF) patients and healthy controls ExtraCorporeal Membrane Oxygenation (ECMO) is a salvage
(HC). therapy providing circulatory and/or ventilatory assistance.
Method: In 20 HC and 129 patients with LC [sLC: vLC: vACLF Outcomes following ECMO initiation remain uncertain. The proced-
(%)-36:38:26; all males], 24 hour urinary urea nitrogen (UN- g/day) ure itself can lead to bleeding and sepsis, especially in immunocom-
and IC (Quark RMR) was performed after 6 hrs of fasting; within 24 promised patients. Data on outcome and safety of ECMO after LTx are
hrs of intubation, following calibration and steady state attainment.

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POSTER PRESENTATIONS
scarce. The aim of this retrospective study was to assess both survival occurrence, predictors of development, diagnostic potential of
and safety under ECMO in post-LTx. biomarkers, antifungal prophylaxis with the outcome of IFI.
Method: We retrospectively reviewed all LTx patients undergoing Method: The demographic, clinical and laboratory characteristics of
veno-venous (VV) or arterio-venous (AV) ECMO between 2010 and ACLF patients, admitted to ILBS, developing IFI were studied
2020 in three LTx centers. We collected data about liver disease before retrospectively based on the APASL ACLF Research Consortium
transplantation, indication for ECMO, number of organ failure (AARC) data base. The diagnosis of IFI was based on revised
including Sequential Organ Failure Assessment (SOFA) score, out- definitions of invasive fungal disease from the European organization
comes and complications under ECMO. for research and treatment of cancer/Invasive fungal infections
Results: Twenty six transplanted patients were referred to an ECMO cooperative group and the national institute of allergy and infectious
centre. Five were contraindicated for ECMO as they were considered diseases mycoses study group (EORTC/MSG) consensus group. We
as too critically ill. ECMO was initiated in 21 out of 26 transplanted also measured the biomarkers in bronchoalveolar lavage (BAL) and
patients (80%). 13/21 (62%) had VA ECMO and 8/21 (38%) a VV ECMO. serum Galactomannan index (GMI).
Five patients underwent VA ECMO following cardiac arrest (n = 5). Results: Amongst 1670 ALCF patients, 320 (19.16%) had recent history
Others developed cardiogenic shock due to: Takotsubo syndrome of neutropenia, prolonged use of corticosteroids or immunosuppres-
(n = 2), infectious myocarditis (n = 2), refractory sepsis (n = 1), severe sive therapy, and sufficient clinical evidence consistent with IFD but
ischemia-reperfusion syndrome (n = 1), right ventricular failure no mycological evidence were classified as possible IFI. Sixty (3.6%)
secondary to pulmonary hypertension (n = 1) and unknown biven- patients who had host factors, clinical features, and mycological
tricular failure (n = 1). The main indication for VV ECMO was septic evidence consisting of direct test (cytology, direct microscopy, or
acute respiratory distress syndrome (ARDS) (n = 7). The other patient culture) and indirect test, positive Galactomannan assay, were
developed refractory transfusion-related acute lung injury. Median classified as probable IFI. Amongst the probable IFI group, the most
delay between LTx and ECMO was 10 days. Median duration of VA common site of infection was urinary tract (n = 42/60, 70%) followed
ECMO and VV ECMO until patient’s death or ECMO withdrawal was by respiratory (n = 12/60, 20%) and blood (n = 6/60, 10%). On
respectively 2 and 10 days. The survival rates at day 30, in patient univariate analysis, prior antibiotic use, high total leucocuyte count
treated with VA ECMO and VV ECMO, were 38.5% (5/13) and 37, 5% (3/ (TLC), acute renal failure, hemodialysis, diabetes mellitus, multiorgan
8) respectively (figure). In total, 11/13 (84.7%) patients died from failures, were predictors for development of IFI ( p < 0.05). On
multiorgan failure and 2 from brain death. One third of patients (7/ multivariate analysis, TLC >14.3 × 103/ml3, multiorgan failure, hemo-
21) presented bleeding during ECMO, mainly at the insertion site of dialysis and prior antibiotics use predicted the development of IFI ( p
cannulas (n = 5). Sepsis occurred in 4/21 patients. No liver graft < 0.05). IFI occurrence was associated with significantly high 30 and
dysfunction was observed in these patients treated with ECMO. The 90 day mortality ( p < 0.001). 68.4% patients with IFI in the first 7 days
30-days post-ECMO survival was significantly associated with SOFA of enrolment died as compared to 47.9% in control group (p = 0.002).
score at the initiation (14 in survivors vs. 16 in non-surviving patients, BAL GMI (cut-off >1) was positive in 38/60 (63.33%) and serum GMI
p = 0.03) and 24 hours after initiation of ECMO (12 in survivors vs. 18 was positive in 11/60, (18.33%). BAL GMI above 3.25 was a better
in non-surviving patients p = 0.04). predictor of IFI (sensitivity 72.7%, specificity 51.5%).
Conclusion: Invasive fungal infections cause high mortality in ACLF
100 patients. High TLC at admission, multiorgan failure, hemodialysis,
Veno-venous ECMO
prior antibiotics usage and high BAL GMI predict the development of
Veno-arterial ECMO
Percent survival

75 IFI. High vigilance, early diagnosis and initiation of anti-fungal

All ECMO therapy is essential to prevent mortality due to IFI in ACLF.
50
THU513
25 Outcomes in patients with cirrhosis and fungal infections: a
systematic review and meta-analysis with machine learning
0 Nipun Verma1, Shreya Singh2, Akash Roy3, Arun Valsan1,
0 5 10 20 30 Pratibha Garh1, Pranita Pradhan4, Meenu Singh5. 1Postgraduate
Days Institute of Medical Education and Reserach, Hepatology, Chandigarh,
Figure: Survival of transplanted patients during the first 30 days following India; 2Postgraduate Institute of Medical Education and Reserach,
ECMO initiation Microbiology, Chandigarh, India; 3Sanjay Gandhi Postgraduate Institute
of Medical Sciences, Hepatology, Lucknow, India; 4Postgraduate Institute
Conclusion: ECMO in liver transplanted patients should be con-
of Medical Education and Reserach, Pediatrics, Chandigarh, India;
sidered as a salvage treatment for refractory respiratory and/or 5
Postgraduate Institute of Medical Education and Reserach, Pediatrics,
circulatory failure. Our work reveals similar survival under ECMO
Chandigarh, India
compared to the general population.
Email: [email protected]
THU512 Background and aims: Fungal infections (FIs) are an emerging threat
Prevalence, profile and predictors of invasive fungal infections in in patients with cirrhosis. Due to the lack of systematic data, we
acute on chronic liver failure (ACLF): analysis of APASL-ACLF performed a comprehensive literature search to systematically
research consortium database evaluate the impact of FIs on mortality and contributory factors in
Pratibha Ramchandra Kale1, Ashok Choudhury2, Vikas Khillan1, cirrhosis patients.
Niharika Patel2, Sarin Shiv Kumar2. 1Institute of Liver and Biliary Method: PubMed, Embase, Ovid, and Web of Science were searched
Sciences, Clinical Microbiology, New Delhi, India; 2Institute of Liver and since their inception till Oct 30, 2020, for full-text articles describing
Biliary Sciences, Hepatology, New Delhi, India mortality in cirrhosis patients with FIs. Point and relative-risk
Email: [email protected] estimates of mortality were pooled on random-effects meta-analysis,
and their variation (I2) was explored on subgroups, meta-regression,
Background and aims: Acute-on-chronic liver failure (ACLF) causes
and machine learning (ML). Quality of studies was evaluated with the
immune dysregulation and increased susceptibility to fungal infec-
New-castle Ottawa scale and estimate’s asymmetry with a funnel plot
tions. We studied the epidemiology and risk factors associated with
and Eggers regression. (CRD42019142782)
invasive fungal infections (IFI) in ACLF. We correlated the timing of

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 POSTER PRESENTATIONS
Results: Of 4345, 34 studies (2134 patients) were included (good/fair/ THU514
poor quality: 12/21/1). The pooled mortality of patients with FIs was Impact of de presence of acute on chronic liver failure on morbi-
64.1% (95% CI: 55.4–72.0, I2: 87%, p < 0.01). Patients with proven, mortality after liver transplantation
probable, and proven + probable FIs had a mortality of 61.4%, 73.6%, Carlos Benitez1, Verónica Cambindo Santana1, Jorge Arnold1,2.
1
and 63.8%, respectively. Patients with acute-on-chronic liver failure Pontificia Universidad Catolica, Hepatologia, santiago, Chile; 2Pontificia
(ACLF: 76.6%) and intensive care unit admission (ICU: 70.4%) had a Universidad Católica de Chile, Gastroenterología
higher mortality than all-hospitalized patients (52.9%), p = 0.03 Email: [email protected]
(Figure 1). Significant variation in mortality estimates was identified
Background and aims: Acute over chronic liver failure (ACLF) implies
on geographic dimensions and site of infection. The highest mortality
was noted in pulmonary-FIs (79.4%), followed by peritoneal-FIs high short-term mortality. The impact of its presence at the time of
liver transplantation (LT) has been less studied.
(68.3%) and fungemia (55%). On meta-regression, MELD of cases was
Objectives: To evaluate the impact of ACLF on post-LT survival.
identified as a predictor of mortality; adjusted estimate: 64.5% (54.5–
83.9). The mortality among patients with FIs was 1.7 (1.4–2.1) and 2.9 Method: A retrospective registry of 263 liver recipients between 2013
and 2020 was evaluated; 197 patients met the inclusion criteria and
(1.8–4.9) times higher than bacterial infections and non-infected
controls. The relative risk persisted above 1.5 times in ICU-admitted their survival and complications were recorded at one year of follow-
up.
and ACLF patients as well. After adjusting for the proportion of
Results: The average age was 57.1 ± 10.5, men 55.3%, MELD Na 23.15 ±
bacterial infection in controls, the relative risk was 2.16 (1.85–2.53).
Asymmetry was evident in point-estimate and relative-risk estimates 9.76. The main etiologies were MAFLD (35.5%), alcohol (12.7%),
autoimmune hepatitis (9.6%), PBC (9.1%) and HCV (7.6%). 22.5% of the
of FIs. Three k-means clusters, 2 DBSCAN clusters, 8 GMM clusters,
and 5 outlier studies were detected on ML. On excluding these, the patients developed ACLF. One year survival of those transplanted
without ACLF, ACLF grade 1, grade 2, and grade 3 were 89.8%, 91.7%,
estimate’s heterogeneity was abolished (I2:0%, p = 0.68). Estimates
66.7%, and 66.7%, respectively ( p = 0.042). Survival of those without
did not vary as per the quality of the study.
ACLF and grade 1 vs grade 2 and 3 were 90% vs 66.7% ( p = 0.005)
(figure). Transplant patients with grade 2–3 ACLF had more post-LT
bacterial infections 59.3% vs 36.5% ( p = 0.024), a higher frequency of
mechanical ventilation 46.2% vs 19.4% ( p = 0.003) and renal replace-
ment therapy (RRT) (42.3% vs 11.6% ( p = <0.001). In the multivariate
analysis, the variables independently related to survival were the
requirement for mechanical ventilation before LT (OR 4.3, p = 0.026, CI
(1.19–15.62) and RRT post LT (OR 2.95. p = 0.39, CI (1.05–8.2).

Conclusion: The presence of ACLF grade 2 and 3 at the time of LT is

associated with marked reduction of one year patient survival.
1530/1600 (with space)

Conclusion: About 2/3rd cirrhosis patients with FIs die with the
highest risk of death among ACLF and ICU patients. FIs are more
serious than bacterial infections and warrant dedicated efforts in the
cirrhosis patients.

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POSTER PRESENTATIONS
THU516
Untargeted lipidomics differentiate ACLF precipitated by severe
alcoholic hepatitis
Florent Artru1,2, Stephen Atkinson1, Ewan Forrest3,
Francesca Trovato2, Nikhil Vergis1, Vishal C Patel2,4,5, Salma Mujib2,
Anna Cavazza2, Alexandros Pechlivanis1, Ellen Jerome2, Marc Zentar2,
Evangelos Triantafyllou1, Elaine Holmes1, Mark J W McPhail1,2,
Mark Thursz1. 1Imperial College London, London, United Kingdom;
2
Institute of Liver Studies, King’s College Hospital, London, United
Kingdom; 3UNiversity of Glasgow, Glasgow, United Kingdom; 4The Roger
Williams Institute of Hepatology London, Foundation For Liver Research,
London, United Kingdom; 5Institute of Liver Sciences, King’s College
London, Department of Inflammation Biology, School of Immunology
and Microbial Sciences, FoLSM, London, United Kingdom
Email: [email protected]
Background and aims: Severe alcoholic hepatitis (SAH) is a common
cause of acute on chronic liver failure (ACLF). Patients with SAH-ACLF
present intense systemic inflammation and immune dysfunction.
While lipids are involved in inflammatory and immune responses,
lipidomics is understudied in the setting of SAH-ACLF. We evaluated
whether specific changes in the blood lipidome are observed in ACLF
precipitated by SAH.
Method: Untargeted serum lipidomics was performed using
reversed phase ultra-performance liquid chromatography coupled
to mass spectrometry in patients with SAH participating in the
STOPAH trial (n = 154–46 with ACLF labelled SAH-ACLF) and with
cirrhosis (n = 74–21 with ACLF labelled Cirrh-ACLF). Serum lipidome
changes between patients with and without ACLF in SAH and
cirrhosis groups were evaluated by principal component analysis
(PCA) and orthogonal partial least squares discriminant analysis
(OPLS-DA).
Results: MELD score was higher in patients with SAH without ACLF
vs. cirrhotics without ACLF (20.7 vs. 11.3, p < 0.0001) but matched
between patients with SAH-ACLF vs. Cirrh-ACLF (26.1 vs. 24.7, p = 0.4).
PCA and OPLS-DA analyses were not able to accurately discriminate
between SAH with or without ACLF (OPLS-DA in positive mode R2Y =
Abstract withdrawn 0.14 Q2 = 0.06 CV-ANOVA p = 0.01 AUROC = 0.71 and negative mode
R2Y = 0.18 Q2 = 0.04 p = 0.22 AUROC = 0.62). Importantly, PCA and
OPLS-DA did accurately discriminate between SAH-ACLF and Cirrh-
ACLF (OPLS-DA in positive mode: R2Y = 0.78 Q2 = 0.49 CV-ANOVA
<0.0001 AUROC = 0.91; in negative mode: R2Y = 0.66 Q2 = 0.4 p <
0.0001 AUROC = 0.88) (Figure 1). The 10 metabolites showing the
greatest variable importance projection were included in multivari-
ate analyses adjusting for age, sex and MELD score. Two lipids in
positive mode (PE P-38:4, PE P-36:3) and negative mode (PC 41:5, LPC
14:0) disclosed independent associations with SAH-ACLF (Figure 1).
Using these lipids, we derived 2 scores relating to positive and
negative ionisation modes; both accurately discriminated SAH-ACLF
from Cirrh-ACLF with an AUROC of 0.86 (CI95% 0.73–0.93, p < 0.0001,
sensitivity 76% specificity 88%) and 0.82 (CI95% 0.68–0.90, p < 0.0001,
sensitivity 71% specificity 84%).

Figure: A. OPLS-DA in positive mode. B. ROC curve of OPLS-DA model in

positive mode. C. Univariate analyses of the lipids included in the 2-lipids
models in positive (PE-P38:4, PE-P36:3) and negative modes (PC41:5,
LPC14:0).

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 POSTER PRESENTATIONS
Conclusion: This lipidomic analysis of the STOPAH cohort demon- Method: VS-01 was infused in the peritoneal cavity of the patients
strates a specific lipidomic signature- mainly composed of species and removed by paracentesis after two ( part A) or three hours ( part
that are known to be involved in immune-modulatory functions and B). Patients received a single dose of 15, 30 or 45 ml/kg VS-01 (Part A;
liver repair-in patients with SAH-ACLF. These pathways require n = 9) or four consecutive doses of 34–42 ml/kg VS-01 (Part B; n = 3).
further exploration on their diagnostic and mechanistic role in the Metabolomic analysis was performed on plasma samples of patients
development of SAH-ACLF compared to other cause of ACLF. with ascites and covert hepatic encephalopathy (HE) using an
untargeted LC/MS analysis approach. Peak areas were extracted and
THU517 peak lists containing the mass features and identified compounds
Metabolomic analysis of organ failure marker compounds in were exported to MetaboAnalyst 5.0 for statistical analysis.
blood samples of patients with decompensated liver cirrhosis Results: In the whole dataset, 24 out of 65 highly upregulated OF
after administration of the novel drug VS-01 metabolites were detected. In part A of the study, we were able to
Frank Uschner1, Wenyi Gu1, Olaf Tyc1, Martin Schulz1, Philip Ferstl1, detect 19 OF metabolites in plasma samples, of which 11 showed a
Katharina Katharina Staufer2, Stoffers Philipp1, Hans-Peter Erasmus1, decreasing trend in the plasma samples of the patients up to 24 hours
Johannes Masseli1, Kai-Henrik Peiffer1, Fabian Finkelmeier1, after infusion of VS-01. In part B of the study, we could detect 10 OF
Anita Pathil-Warth1, Jörg Bojunga1, Stefan Zeuzem1, Meriam Kabbaj2, metabolites in plasma samples of which 7 metabolites showed a
Jonel Trebicka1,3. 1Department of Internal Medicine I, University decreasing trend during the infusion of VS-01 (Figure 1).
Hospital Frankfurt, Frankfurt, Germany; 2Versantis AG, Zurich, Conclusion: VS-01 is a novel drug, which is able to reduce
Switzerland; 3European Foundation for the Study of Chronic Liver metabolites that are associated with organ failures e.g. brain, liver
Failure, Barcelona, Spain and kidney failure. The current metabolic results support the future
Email: [email protected] development of VS-01 in patients with ACLF and organ failure.
Background and aims: Acute-on-chronic liver failure (ACLF) is
defined by the presence of organ dysfunctions and failures in
decompensated cirrhosis and is associated with high short-term
mortality. VS-01 is a novel intraperitoneal (i.p.) pH-gradient
liposomal infusion drug that enhances the clearance of ammonia
and other potentially harmful metabolites. This study analyzed
metabolite clusters already described to be involved in organ failure
(OF) of liver, brain and kidney in patients with liver cirrhosis (Moreau
et al. 2019) in the phase 1b clinical trial of VS-01 (Eudra no.: 2018-
004606-25).

Figure: (abstract: THU517): Heatmap of log2 (fold-change) reduced organ failure markers in plasma samples of study A shown per dosage (a) and study B
shown per marker compound (b) and per patient (c) after administration of VS-01 (red = high/Blue = low). *, FDR < 0.05.

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POSTER PRESENTATIONS
THU518 the patients. The infusion of VS-01 resulted in a decrease of several
Metabolomic analysis of bacterial infection markers in blood markers for bacterial infection in the blood of the patients (Figure 1).
samples of patients with decompensated liver cirrhosis infused In part A of the study, 6 metabolites related to bacterial infection
with the novel drug VS-01 showed a decreasing trend in plasma up to 24 hours after infusion of
Frank Uschner1, Olaf Tyc1, Wenyi Gu1, Martin Schulz1, Philip Ferstl1, VS-01. In part B of the study, 7 metabolites related to the infection-
Katharina Staufer2, Philipp Stoffers1, Hans-Peter Erasmus1, related ACLF cluster were detected in plasma samples, from which 4
Johannes Masseli1, Kai-Henrik Peiffer1, Fabian Finkelmeier1, showed a decreasing trend over time after infusion of VS-01
Anita Pathil-Warth1, Jörg Bojunga1, Stefan Zeuzem1, Meriam Kabbaj2, (Figure 1).
Jonel Trebicka1,3. 1Department of Internal Medicine I, University
Conclusion: Single and repeated i.p. administrations of the novel
Hospital Frankfurt, Frankfurt, Germany; 2Versantis AG, Zurich,
drug VS-01 was able to reduce the concentration of several
Switzerland; 3European Foundation for the Study of Chronic Liver
metabolites that are associated with the sepsis-related ACLF
Failure, Barcelona, Barcelona, Spain
metabolite cluster. These results support the future investigation of
Email: [email protected]
VS-01 in patients with ACLF and bacterial infection.
Background and aims: Bacterial infections are known as one
frequent precipitant event for the development of acute decompen- THU519
sation (AD) and its maximal-form acute-on-chronic liver failure Disturbances in sodium and chloride hemostasis predict outcome
(ACLF) (PREDICT study). VS-01 is a novel intraperitoneal (i.p.) pH- in stable and critically-ill patients with cirrhosis-not two sides of
gradient liposomal infusion drug that enhances the clearance of the same coin
ammonia and other metabolites associated to bacterial infection in Georg Semmler1,2, Bernhard Scheiner1,2, Rafael Paternostro1,2,
patients with ACLF. This study analyzed metabolites described to be Benedikt Simbrunner1,2, Lorenz Balcar1,2, Matthias Pinter1,2,
associated with bacterial infection in patients with liver cirrhosis Michael Trauner1, Mattias Mandorfer1,2, Christian Zauner1,
(Moreau et al. 2019) in the phase 1b clinical trial of VS-01 (Eudra no.: Thomas Reiberger1,2, Georg-Christian Funk3,4. 1Medical University of
2018-004606-25). Vienna, Division of Gastroenterology and Hepatology, Department of
Method: The novel drug VS-01 was infused in the peritoneal cavity Internal Medicine III, Wien, Austria; 2Medical University of Vienna,
and removed by paracentesis after two ( part A) or three hours ( part Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and
B). Patients received either a single dose (15, 30 or 45 ml/kg) VS-01 Hepatology, Department of Internal Medicine III, Wien, Austria; 3Klinik
(Part A; n = 9) or four consecutive doses of 34–42 ml/kg VS-01 (Part B; Ottakring, Department of Internal and Respiratory Medicine, Vienna,
n = 3). Metabolomic analysis was performed on blood samples of Austria; 4Karl-Landsteiner-Institute for Lung Research and Pulmonary
cirrhotic patients with ascites and covert hepatic encephalopathy Oncology, Vienna, Austria
(HE) using untargeted LC/MS analysis. Peak areas were extracted and Email: [email protected]
peak lists containing the mass features and identified compounds
Background and aims: Serum electrolyte disturbances are common
were exported to MetaboAnalyst 5.0 for statistical analysis.
in patients with cirrhosis. Hyponatremia has profound prognostic
Results: Overall, 10 out of 31 metabolites included in the metabolite
implications, and thus, has been incorporated in the 2016 update of
cluster of infection-related ACLF were identified in plasma samples of

Figure: (abstract: THU518): Heatmap of log2 (fold-change) reduced bacterial infection markers in plasma samples of study A shown per dosage (a) and
study B shown per marker compound (b) and per patient (c) after administration of VS-01 (red = high/Blue = low). *, FDR < 0.05.

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 POSTER PRESENTATIONS
the UNOS MELD. Changes in serum chloride (Cl) are thought to be THU520
interrelated, however, are less well studied in the context of cirrhosis. Sarcopenia assessed via computed tomography is associated with
We investigated the prognostic utility of Na- and Cl-changes on short-term outcomes and improves prognostic scores’
hepatic decompensation/liver-related death in patients with stable performance in critically ill patients with acute on chronic liver
advanced chronic liver disease (ACLD) as well as on ICU-mortality in failure
critically-ill patients with cirrhosis. Thomas Mangana Del Rio1, Fabio Becce1, Julien Vionnet1,
Method: 1256 patients with stable ACLD (defined by hepatic venous Alban Denys1, Antoine Schneider1, Alexandre Wetzel1,
pressure gradient (HVPG) ≥6 mmHg) undergoing HVPG measure- Darius Moradpour1, Jean-Daniel Chiche1, Florent Artru1,2. 1Lausanne
ment at the Vienna Hepatic Hemodynamic Lab between 2003–2020 University Hospital, Lausanne, Switzerland; 2King’s College Hospital,
were included in cohort I. 181 critically-ill patients with cirrhosis Institute of Liver Studies, London, United Kingdom
admitted to our ICU between 1993–2003 were recruited for cohort II. Email: [email protected]
Hypo-/hyper-Na (normal: 136–145 mmol/L) and hypo-/hyper-Cl
(normal: 98–107 mmol/L) were assessed. Background and aims: Prognostication of patients with cirrhosis and
acute-on-chronic liver failure (ACLF) relies on organ failure scores.
Results: Cohort I: 68% male patients with a mean UNOS MELD (i.e.,
excluding Na) of 12 ± 4 were included (CPS-A/B/C: 53%/35%/12%). Na Sarcopenia is associated with poor outcomes in patients with
cirrhosis but has not been investigated in critically ill patients with
and Cl levels were significantly interrelated (Spearman’s ρ = 0.54, p <
ACLF. We aimed to evaluate whether sarcopenia was associated with
0.001). Hypo-/hyper-Na was present in 25%/0% and hypo-/hyper-Cl in
15%/8%. Patients with hypo-Na (HR: 2.44 [95%CI:2.05–2.90], p < short-term outcome in this population.
Method: We retrospectively included all patients with cirrhosis and
0.001) and hypo-Cl (HR: 2.19 [95%CI: 1.74–2.77], p < 0.001) had an
increased risk for hepatic decompensation/liver-related death. When ACLF (as defined by EASL criteria) admitted to the intensive care unit
(ICU) of Lausanne University Hospital between January 2010 and
incorporating both variables in a model adjusting for age, HVPG,
December 2019, who had a recent CT (within 15 days from admission
albumin levels, and MELD score, hypo-Cl (aHR: 1.77 [95%CI:1.37–
2.29], p < 0.001) but not hypo-Na (aHR:1.10 (95%CI:0.88–1.38), p = to the ICU). L3 skeletal muscle index (L3SMI) was quantified by using
a deep learning-based method from a single axial CT image at the
0.40) remained independently associated with the outcome of
interest. As depicted in the Figure, the presence of hypo-Na, hypo- level of lumbar vertebra 3. Sarcopenia was defined by previously
Cl, none, or both identified patient groups with a distinct prognosis. published sex-specific cut-offs: 50 cm2/m2 in men and 39 cm2/m2 in
women.
Results: A total of 194 patients fulfilled the inclusion criteria. Their
characteristics at admission were the following: 26% were female,
median age was 62 years (IQR, 54–70 years), MELD 21 (13–28), CLIF-C
ACLF 79 (74–85), CLIF-C ACLF-lactate 83 (76–92). Sixty percent of
patients had ACLF grade 3, 34% grade 2 and 6% grade 1. Median 28-day
transplant-free survival (TFS) was 58% (95% CI, 51–65%). Median
L3SMI was 43 (37–51), with 59% of patients being sarcopenic. In
multivariate Cox-regression analyses at day 0 (D0), the three
independent variables associated with 28-day TFS were CLIF-C
ACLF-lactate (HR 1.06, 1.04–1.09, p < 0.0001), MELD score (HR 1.03,
1.01–1.07, p = 0.03) and sarcopenia (HR 2.1, 1.3–3.5, p = 0.003). At day
3 (D3), the two independent variables associated with 28-day TFS
were CLIF-C ACLF-lactate on day 3 (HR 1.08, 1.07–1.11, p < 0.0001) and
sarcopenia (HR 1.9, 1.2–3.1, p = 0.01). Based on the results of
multivariate analyses, we derived two scores (CLIF-C ACLF-lactate-
sarcopenia at D0 and D3, CCLS-D0 and CCLS-D3) with the aim of
improving prognostic stratification. For the prediction of 28-day TFS,
CCLS-D0 had an AUROC of 0.80 and outperformed CLIF-C ACLF-lactate
on day 0 (0.74, p = 0.004). Similarly, CCLS-D3 had an AUROC of 0.89
and outperformed CLIF-C ACLF-lactate on day 3 (0.86, p = 0.04)
(Figure 1).

Cohort II: 70% male patients had a mean UNOS MELD of 27 ± 9 at ICU
admission (92% with Child-Pugh-stage [CPS] C). Again, Na and Cl
levels were strongly correlated (Spearman’s ρ = 0.81, p < 0.001).
Hypo-/hyper-Na was present in 47%/7% and hypo-/hyper-Cl in 30%/
25%. ICU-mortality was 50% after a median of 6 (IQR:5–7) days. While
the effect of Na on ICU mortality was U-shaped in restricted cubic
spline analyses, it seemed to be rather linear for chloride with a worse
prognosis in patients with hypo-Cl as well as hypo- and hyper-Na. In
univariable logistic regression analyses, patients with hypo-Cl (OR:
2.65 [95%CI:1.30–5.53], p = 0.008), but not hypo-Na had a signifi-
cantly worse ICU survival, which was confirmed after adjusting for
hypo-Na and MELD (aOR Cl: 3.24 [95%CI: 1.31–8.23], p = 0.012).
Conclusion: Even though Na and Cl levels are strongly interrelated in
patients with stable ACLD/cirrhosis and critical illness, hypo-Cl rather
than hypo-Na is associated with a worse outcome.

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POSTER PRESENTATIONS
Conclusion: Sarcopenia, as assessed by CT-Scan is independently
associated with 28-day TFS in critically ill patients with cirrhosis and
ACLF. Adding sarcopenia to CLIF-C-ACLF-lactate score at D0 and D3
improved the performance of the scores. Sarcopenia is an important
parameter related to outcomes and should be evaluated in this
population.

THU521
Use of Tocilizumab in patients with stable chronic liver disease
and severe COVID-19 for prevention of decompensated cirrhosis, a
prospective, open-label, randomized controlled trial.
Luis Alejandro Rosales Renteria1,2, Hiram Jaramillo-Ramírez3,
Francisco Calderón-Mendieta3, Jesús Camacho-Escobedo1,
José Manuel Avendaño-Reyes2, Diana Laura López-Rubio1,
Adrián Sández Araiza1, Gisel Estefania Reyes-Higuera1,
Dulce Renée Soto-González1, Erikc Jesús Arzola-Renteria1. 1Mexicali
General Hospital, Internal Medicine, Mexicali, Mexico; 2Faculty Of
Medicine UABC, Mexicali, Mexico; 3Mexicali General Hospital, Mexicali, Conclusion: Tocilizumab reduced mortality in CLD patients with SC,
Mexico overall, in each stage of CTP classification, and reduced the risk of
Email: [email protected] developing both HRS-AKI and severe HE, but not other events.
Whether these results can be reproduced in patients without SC
Background and aims: Interleukin-6 (IL-6) is involved both in the warrants further research.
pathogenesis of severe COVID-19 (SC) and decompensated Chronic
Liver Disease (CLD). Tocilizumab, a monoclonal antibody used to THU522
block the IL-6 signal transduction pathway, has been proved to have Comprehensive immunophenotyping reveals profound
beneficial effects in the prognosis of patients with SC. However, alterations of T cell subsets in acute decompensation of liver
evidence of its effect on patients with CLD that develop SC is scarce. cirrhosis
We aimed to evaluate the efficacy of Tocilizumab on patients with Yasmina Chouik1,2, Fabienne Venet3,4, Morgane Gossez3,4,
CLD and SC in a tertiary care hospital from Mexico. Thibault Andrieu2, Marie-Laure Plissonnier2, Bordes Isabelle2,
Method: A single center, prospective, open-label, randomized Teresa Antonini1, Domitille Erard1, Miroslava Subic-Levrero1,
controlled trial, which included patients with CLD with either Francois Villeret1,2, Wafa Khamri5, Fabien Zoulim1,2,
compensated cirrhosis or stable decompensated cirrhosis (according Massimo Levrero1,2, Fanny Lebossé1,2. 1Hospices Civils of Lyon,
to EASL definition) that developed SC, and were admitted to our Hepatology Unit, Lyon, France; 2Cancer Research Center of Lyon INSERM
hospital in Mexicali, Mexico, from March 1, 2020, to December 31, U1052, Lyon, France; 3Hospices Civils of Lyon, Immunology Laboratory,
2021. General characteristics were obtained. The Primary Outcome Lyon, France; 4International Center for Infectiology Research, Lyon,
was overall mortality according to the absence or presence of France; 5Imperial College London, Liver Immunology Laboratory,
Tocilizumab administration (administered in the first 12 hours of London, United Kingdom
arrival according to hospital availability at an 8mg/kg single IV dose), Email: [email protected]
secondary outcomes were mortality according to each stage of CTP,
and development of acute decompensation (AD), defined as one or Background and aims: Bacterial infection is a frequent and life
more of the following : Acute Kidney Injury (AKI), Hepatorenal threatening event in acute decompensation (AD) of cirrhosis, with a
syndrome-AKI (HRS-AKI), Variceal Hemorrhage (VH), West Haven 1-month mortality rate of 20–30%. Septic risk is notably underpinned
(WH) grade III or IV Hepatic Encephalopathy (HE), Spontaneous by cirrhosis-associated immune dysfunction. Recent data suggest the
Bacterial Peritonitis (SBP) or Acute on Chronic Liver Failure (ACLF). A potential involvement of adaptive immune responses in cirrhosis-
value of p < 0.05 was significant. Exclusion criteria were age younger related immune dysfunction. We conducted a detailed analysis of
that 18 years and patients with unstable decompensated cirrhosis at circulating T cells in patients with AD compared to patients with
baseline. compensated cirrhosis (C) and healthy subjects (HS) in order to gain
Results: A total of 361 patients were included. They were classified insights in circulating adaptive immune cells alterations in cirrhosis.
according to the Child-Turcotte-Pugh (CTP) classification, and the Method: Thirty seven patients from a monocentric prospective study
Model for end-stage Liver Disease-Sodium (MELD-Na). Most patients (EmiC cohort, n = 97 patients) were selected for T cells phenotyping.
were classified as CTP B (216 patients, 59.8%). Median MELD-Na in the Clinical and biological samples were collected at hospital admission
intervention group was 22 vs 19 in control. 77 patients were and up to 6 months after inclusion. PBMC from HS were obtained
randomized to Tocilizumab, and 284 patients were not. With from the French Blood Bank. Phenotyping of circulating T cells was
regards to the primary outcome, 32.4% patients in the intervention conducted on frozen PBMC by spectral cytometry (26-color panel).
group died vs 53.8% patients in the control group, this difference was This panel enables the analysis of effector, memory and naïve T cells,
significant with a relative risk (RR) of 0.6, a 95% confidence interval regulatory T cells (Treg), T-helper (Th)1, Th2, Th17, Th17+1, Th22 CD4+
(CI) of (0.4–0.8), p < 0.001, and a number needed to treat (NNT) of 4.6 T cells, Tc1, Tc2, Tc17, Tc22 CD8+ T cells, gamma delta T cells and NKT
with a NNT 95% CI of (2.9–11.3). Secondary outcomes were significant cells. Activation, inhibition and death markers were also studied
for mortality reduction in the CTP subgroup for all grades of severity (CD38, HLA-DR, PD1, CD95). Unsupervised analysis was performed
and showed a lower risk of developing HRS- AKI (RR = 0.4, 95% CI using Qlucore™ and Cytobank™. Plasma cytokines were measured
[0.2–0.7], NNT 4.3, 95% NNT CI [2.8–9.1], p < 0.001) and WH III/IV HE by Simple Plex™ immunoassays on a microfluidic ProteinSimple®
(RR = 0.5, 95% CI [0.3–0.8], NNT 5.2, 95% NNT CI [3.1–14.7], p = 0.003). ELLA analyzer.
Results: Spectral cytometry analysis was performed in 7 HS, 10 C and
27 AD patients including 9 patients with Acute on Chronic Liver
Failure. Principal component analysis showed clear distinct T cells
features between HS, C and AD patients (Figure 1). T cell phenotyping
revealed progressive imbalance between type 1 and type 2 T cell
responses with a decrease of the Th1/Th2 and Th1/Treg ratios

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 POSTER PRESENTATIONS
throughout cirrhosis progression. T cells of patients with decompen- Cumulative incidence of all-cause readmission was 19% at 30 days,
sated cirrhosis displayed increased surface expression of both 36% at 90 days and 56% at 1 year. Fifty-four patients were readmitted
activation and death markers. In addition, circulating Th17 cells for emergent liver-related causes within 30 days after discharge. Early
significantly decreased in patients with bacterial infection (n = 12) readmission was associated to a higher 1-year mortality (47 vs 32%, p
and correlated with C-reactive protein and albumin levels. Increased = 0.037). Data collected both at admission (MELD-Na score, diabetes),
Th1/Th2 ratio was associated with the occurrence of nosocomial during hospitalization (development of ACLF, days spent in hospital)
infection (n = 6), while proportion of Th17 could significantly predict and at discharge (hemoglobin (Hb) value, MELD-Na score) were
6-month survival in AD patients. significantly associated with early readmission. Multivariable com-
peting risk regression analysis showed that Hb lower than 8.75 mg/dL
(sHR 2.38 [95%CI 1.22–4.64], p = 0.011), MELD-Na > 16 at discharge
(sHR 2.25 [95%CI 1.27–3.99], p = 0.005), and diabetes (sHR 1.74 [95%CI
1.02–2.99], p = 0.044) were independent predictors of early readmis-
sion. Cumulative incidence of early readmission was 8% (95% CI 4–14)
in patients without risk factors, 16% (95% CI 11–22) in those
presenting one risk factor and 35% (95% CI 23–47) in those presenting
2 or more risk factors ( p < 0.001). For instance, in patients with
MELD-Na>16 at discharge, the presence of Hb <8.75 g/dl doubles the
risk of early re-hospitalization (42% vs 21%, p = 0.031).
Conclusion: Besides the already documented MELD-Na and diabetes,
this study identifies a level of Hb <8.75 g/dl at discharge as a new
independent risk factor for liver-related early readmission, thus
contributing to identify the subgroup of high-risk patients to be
included in programs of transitional care after discharge.

THU524
Thrombospondin 1: an emerging key-role in the acute-on-chronic
liver failure pathogenesis
Hozeifa Mohamed Hassan1, Xi Liang1, Jiaojiao Xin1,2, Dongyan Shi1,2,
Keke Ren2, Qi Chen1, Jiang Li2, Peng Li2, Hui Yang2, Jinjin Luo2,
Jing Jiang1,2, Jun Li1,2. 1Taizhou Central Hospital (Taizhou University
Hospital), Precision Medicine Center, Taizhou, China; 2The First Affiliated
Conclusion: Alterations of circulating T cells subsets are associated Hospital, Zhejiang University School of Medicine, State Key Laboratory
with cirrhosis severity and clinical outcomes. These results underlie for Diagnosis and Treatment of Infectious Diseases, National Clinical
the role of T cells in cirrhosis-associated immune dysfunction. Research Center for Infectious Diseases, Collaborative Innovation Center
for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
THU523
Email: [email protected]
Low hemoglobin level predicts early hospital readmission in
patients with cirrhosis and acute decompensation Background and aims: Acute-on-chronic liver failure (ACLF) is a
Enrico Pompili1, Maurizio Baldassarre1,2, Giacomo Zaccherini1, clinical syndrome that develops in patients with chronic liver
Manuel Tufoni3, Giulia Iannone1, Dario Pratelli1, Clara De Venuto1, diseases following a precipitating event and associated with a high
Marco Domenicali1,4, Paolo Caraceni1,2,3. 1University of Bologna, mortality rate due to systemic multiorgan failure. In China, the most
Department of Medical and Surgical Sciences, Bologna, Italy; 2University common precipitating disorder is hepatic insult due to hepatitis b
of Bologna, Center for Applied Biomedical Research, Bologna, Italy; virus (HBV) reactivation. Although HBV-ACLF disease progress rapidly
3 with limited treatment options, the pathogenesis still unclear and
IRCSS Azienda Ospedaliero-Universitaria di Bologna, Division of
Medical Semiotics, Bologna, Italy; 4S. Maria delle Croci Hospital, AUSL there is a lack of effective biomarkers for early diagnosis and
della Romagna, Department of Internal Medicine, Ravenna, Italy prognosis of HBV-ACLF. Thrombospondin 1 (THBS1) was recognized
Email: [email protected] among the top significantly differentially expressed potential key
molecular biomarkers associated with HBV-ACLF disease progres-
Background and aims: Patients with decompensated cirrhosis are at sion, but the THBS1 key-role participation in ACLF is not clear. This
high risk of emergent hospitalizations leading to a very economic and study aimed to evaluate the biomarker probabilities of THBS1 in ACLF
social burden. This study aimed to determine the incidence of pathogenesis.
readmission up to 1 year after discharge from an index hospitaliza- Method: The biobanked peripheral blood mononuclear cells (PBMCs)
tion and to identify predictors of liver-related early readmission from 330 subjects with HBV-related etiologies, including HBV-ACLF,
(within 30 days). liver cirrhosis (LC), chronic hepatitis B (CHB) and normal controls
Method: We performed a secondary analysis in a prospectively (NC) from the Chinese Group on the Study of Severe Hepatitis B
collected cohort of patients admitted to hospital for acute decom- (COSSH) prospective multicenter cohort were subjected to transcrip-
pensation (AD) complicated or not by acute-on-chronic-liver-failure tome analyses (ACLF = 20; LC = 10; CHB = 10; NC = 15), and the
(ACLF). After discharge, patients were prospectively followed until findings were validated in humans and ACLF preclinical rat model.
death, liver transplantation or up to a maximum of 1 year for Substantially, a THBS1 knockout mice model was developed to
recording any emergent hospitalization and related cause. Laboratory validate the liver protection capabilities following drugs intoxication.
and clinical data at admission and discharge of the index hospital- Results: THBS1 was identified as the top significantly differentially
ization and the occurrence of nosocomial bacterial infection and ACLF expressed genes (DEGs) in PBMCs transcriptome, with most
were also collected. significant upregulation in ACLF, and qPCR (ACLF = 110; LC = 60;
Results: Of the 329 patients included in the analysis, 182 patients CHB = 60; NC = 45) verified the consistency of THBS1 expression with
were hospitalized during the 1-year follow-up (26% once, 15% twice, the ACLF disease severity. Moreover, the precision of THBS1
10% three times and 6% four or more times, leading to a total of 369 prediction abilities for ACLF short-term mortality were 0.8438 and
readmissions). The most frequent causes of readmission were hepatic 0.7778 at 28 and 90 days, respectively ( p < 0.05). THBS1 expression
encephalopathy (36%), ascites (22%) and bacterial infection (21%). patterns were significantly positively correlated with inflammatory-

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POSTER PRESENTATIONS
related cytokine gene (CCL2, IL-6, IL-1α, CXCL2, …etc.), and ACLF I and II but not in grade III. Furthermore, there was a significant
apoptosis-related genes (Bcl2 and Caspase-9). External validation in reduction in the incidence of infection in the BB group in ACLF grade I.
ACLF rat serum and liver tissues fortified the functional association
between THBS1, immune response and cellular apoptosis. THBS1
knockout improves mice survival, showed significant repressions of
major inflammatory cytokines (CCl2, IFNγ, IL-1β, …etc.), enhances
expression ( p <0.01) of several anti-inflammatory mediators (IL-10,
IL-4, IL-13, …etc.) and impedes hepatocellular apoptosis.
Conclusion: THBS1 might be considered as a new key-molecule in
severity prediction of ACLF, being a disease development-related
biomarker, promoting inflammatory responses and hepatocellular
apoptosis, thus facilitating timely intensive clinical interventions by
providing clinicians with potential new targets to improve the
diagnostic and therapeutic strategies for ACLF management.

THU525
Beta-blockers can reduce mortality in patients with acute-on-
chronic liver failure-a multi-center study
Anand Kulkarni1, Madhumita Premkumar2, Karan Kumar3,
Juned Khan4, Baqar Gora1, Sowmya Iyengar1, Mithun Sharma1,
Nageshwar Reddy1, Nagaraja Rao Padaki1. 1Asian Institute of
Gastroenterology, Hyderabad, India; 2Post Graduate Institute of Medical
Education and Research, Chandigarh, Chandigarh, India; 3Mahatma
Gandhi Hospital, Jaipur, Jaipur, India; 4Hopewell Hospital, Lucknow,
India
Email: [email protected]
Background and aims: Beta-blockers (BBs) can reduce the incidence
of complications in patients with cirrhosis and prolong survival. The
safety and efficacy of BBs in real-world settings in patients with ACLF Conclusion: Only 1 in 4 ACLF patients are suitable for beta-blocker
identified by the Asian Pacific Association for the Study of Liver therapy. Beta-blocker therapy can reduce mortality and lead to early
(APASL) criteria is unknown. Therefore, we aimed to assess the safety recompensation, especially in early grades of ACLF.
and efficacy of BB in patients with APASL defined ACLF.
Method: In this retrospective, multi-center study, patients with ACLF
with complete 30 days follow-up were included. The primary
objective was to compare day 30, 90, and 1-year mortality among
standard of care (SOC) and BB (+SOC) groups. The secondary
Cirrhosis and its complications: Experimental
objectives were: to compare the incidence of infection and variceal and pathophysiology.
bleed on days 30, 90, and one year among both the groups. We also
assessed the time to resolution of ACLF (recompensation).
Results: A total of 346 patients were included. Only 26% (n = 89) THU526
received BBs, while 74% (n = 257) received only SOC. Age and severity Increased platelet aggregation in decompensated cirrhosis
scores (MELD NA-SOC: 28.4 ± 5.21 vs. 27.88 ± 4.9 in BB; p = 0.3) were indicates higher risk of further decompensation and liver-related
similar in both groups. Alcohol was the most common cause of ACLF. mortality
Heart rate was higher and mean arterial pressure (MAP) lower in the Alberto Zanetto1, Elena Campello2, Cristiana Bulato2,
SOC group than in the BB group. The indication for BB was large high- Sabrina Gavasso2, Fabio Farinati1, Patrizia Burra1,
risk varices in 48.3% (43/89), history of acute variceal bleed in 40.4% Francesco Paolo Russo1, Paolo Simioni2, Marco Senzolo1.
(36/89), and 11.2% (10/89) were prophylactically started on BB to 1
Gastroenterology and Multivisceral Transplant Unit, Surgery, Oncology,
prevent further decompensation. Fifteen percent in SOC group and and Gastroenterology, Padova, Italy; 2Thrombotic and Hemorrhagic
12.35% in BB group were ACLF grade III patients. Though 9% of Diseases Unit, General Internal Medicine, Medicine, Padova, Italy
patients had a history of AVB in the SOC group, BB could not be added Email: [email protected]
either due to sepsis, low MAP, or kidney injury. The incidence of
mortality was 21% (54/257) in SOC group compared to only 8% (7/89) Background and aims: Studies on platelet aggregation in cirrhosis
in BB group at day 30 ( p = 0.005). Similarly, at day 90, mortality was are controversial because interpretation of platelet function is
37.2% (84/226) in SOC group compared to 17% (15/88) in BB group challenged by thrombocytopenia. In this two-part study, we
( p = 0.001). Mortality at one year was 48% (88/183) in SOC group investigated platelet aggregation in cirrhosis and its correlation
compared to 27% (18/66) in BB group ( p = 0.003). BB therapy could with development of liver-related events.
not reduce the incidence of infections or variceal bleed (Table). Method: Platelet aggregation was assessed by whole blood aggrego-
Complete resolution of ACLF (recompensation) was noted in 47% metry. To overcome the influence of platelet count, we calculated a
(121/257) of patients in SOC group and 73% (65/89) patients in BB “platelet aggregation/platelet count ratio” (PLT ratio) to compare
group ( p < 0.001). The mean time to recompensation was 2.66 ± 1.42 cirrhosis with thrombocytopenia and controls (60 chronic hepatitis
months in the SOC group compared to 2.3 ± 1.15 months in the BB and 45 healthy subjects) with normal platelet count (study part #1).
group (p = 0.07). Four percent in SOC group and 1% in BB group Then, we prospectively followed patients with cirrhosis and
underwent liver transplantation. Carvedilol was prescribed in 77.5% investigated predictors of hepatic decompensation, transplantation,
and propranolol in 22.5% of patients. Eight patients discontinued BB. and death (study part #2).
On subgroup analysis, BB reduced mortality in ACLF grades I and II but Results: 203 cirrhosis patients were prospectively recruited (77%
not in grade III. Recompensation was significantly better in those with decompensated; median MELD 14). PLT ratio was significantly higher
in cirrhosis than in chronic hepatitis and healthy subjects (0.44 vs.
0.25 and 0.26, respectively; p < 0.0001). Among patients with

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 POSTER PRESENTATIONS
cirrhosis, the ratio increased with disease severity (Child C > B > A) the study. In cirrhotic patients, portal hypertension was assessed by
and was particularly elevated in decompensated patients with severe hepatic venous pressure gradient (HVPG).
thrombocytopenia. During a 6-month follow-up, among decompen- Results: With increasing liver disease severity (Child-Pugh stage A vs.
sated patients, 65 had further decompensation, transplantation, or B vs. C) and compared to HS, CIR patients displayed higher RAS
died. As shown in the Figure, the relative risk of such events was 4- activity (renin, angiotensin-converting enzyme [ACE], aldosterone),
fold higher in patients with a baseline PLT ratio >1 than in those with a endothelial dysfunction (von Willebrand-factor [VWF] antigen) and
PLT ratio ≤0.45 (RR: 3.8, 95%CI: 2.3–6.2; p < 0.0001). On multivariate inflammation (C-reactive protein [CRP], interleukin-6 [IL-6]), along
analysis, PLT ratio (OR: 22.17, CI95%: 5.88–83.61; p < 0.0001) and with a dysregulated coagulation/fibrinolysis profile (D-dimer, pro-
MELD score (OR: 1.07, CI95%: 1.01–1.13; p = 0.03) were independently thrombin fragment F1, 2, plasminogen activity, antiplasmin activity).
predictive of outcome. Renin (i.e. RAS activity), VWF antigen (i.e. endothelial dysfunction),
coagulation parameters (D-dimer, prothrombin fragment F1, 2) and
parameters of inflammation (CRP, IL-6) were significantly elevated in
COVID-19 patients and increased from mCOV to aCOV.
In CIR patients, ACE activity was associated with IL-6 (ρ = 0.26; p =
0.003), independently linked to VWF antigen (aB: 0.10; p = 0.001) and
was inversely correlated with prothrombin fragment F1, 2 (aB: −0.03;
p = 0.023) and antiplasmin activity (aB: −0.58; p = 0.006).

Conclusion: Patients with cirrhosis, particularly when decompen-

sated, have increased platelet aggregation. Among decompensated
patients, those with PLT ratio >1 have an 80% probability of
progressing towards further decompensation, transplantation, or
liver-related death within 6 months.

THU527
Renin/angiotensin system-coagulation-inflammation axis Conclusion: RAS activity is considerably upregulated in Child-Pugh
abnormalities: a possible explanation for susceptibility to severe B/C cirrhosis and linked to endothelial dysfunction, abnormal
COVID-19 in cirrhosis coagulation profile and systemic inflammation. The cirrhosis-asso-
Lukas Hartl1,2, Mathias Jachs1,2, Benedikt Simbrunner1,2,3, ciated abnormalities of ACE (i.e. RAS activation), VWF antigen (i.e.
David JM Bauer1,2, Georg Semmler1,2, Daniela Gompelmann4, endothelial dysfunction), antiplasmin (i.e. coagulation dysregulation
Thomas Szekeres5, Peter Quehenberger5, Michael Trauner1, and increased plasmin) and IL-6 (i.e. increased inflammation) may
Mattias Mandorfer1,2, Bernhard Scheiner1,2, Thomas Reiberger1,2,3. explain the susceptibility for severe COVID-19.
1
Medical University of Vienna, Division of Gastroenterology and
Hepatology, Department of Medicine III, Vienna, Austria; 2Medical THU528
University of Vienna, Vienna Hepatic Hemodynamic Lab, Division of Improvement of hepatic and extrahepatic functions and anti-
Gastroenterology and Hepatology, Department of Medicine III, Vienna, inflammatory effects of nitazoxanide in disease models of LPS-
Austria; 3Medical University of Vienna, Christian Doppler Lab for Portal induced systemic inflammation and acute-on-chronic liver
Hypertension and Liver Fibrosis, Vienna, Austria; 4Medical University of failure
Vienna, Division of Pulmonology, Department of Internal Medicine II, Vanessa Legry1, Philippe Delataille1, Maryse Malysiak1, Valérie Daix1,
Vienna, Austria; 5Medical University of Vienna, Department of Simon Debaecker1, Bart Staels2, Remy Hanf1, Dean Hum1. 1GENFIT SA,
Laboratory Medicine, Vienna, Austria Loos, France; 2Univ. Lille, Inserm, CHU Lille and Institut Pasteur de Lille,
Email: [email protected] U1011-EGID, Lille, France
Email: [email protected]
Background and aims: Risk for severe coronavirus disease of 2019
(COVID-19) is increased among cirrhotic patients. Plasmin may Background and aims: Systemic inflammation (SI) is a hallmark of
aggravate COVID-19 by facilitation of cell entry of the virus. We multiple organ failures in Acute on Chronic Liver failure (ACLF).
investigated parameters of the renin/angiotensin system (RAS), Therefore, anti-inflammatory compounds may have the potential to
endothelial dysfunction, coagulation/fibrinolysis and inflammation alleviate ACLF, especially if they have immediate effects on the
in both cirrhotic patients and COVID-19 patients. inflammatory state. The FDA approved anti-parasitic drug, nitazox-
Method: 127 prospectively characterized cirrhotic patients (CIR), as anide (NTZ), is suspected to exert direct anti-inflammatory actions.
well as 9 patients with mild COVID-19 (mCOV), 11 patients with Our aim was to assess the efficacy of NTZ to rapidly counteract SI and
COVID-19 ARDS (aCOV) and 10 healthy subjects (HS) were included in improve hepatic and extra-hepatic functions after LPS challenge in
healthy and fibrotic rats.

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POSTER PRESENTATIONS
Method: Direct effects of NTZ on LPS-induced activation of human
differentiated THP1 macrophages were assessed in vitro. Single ip LPS
injection (1 mg/kg) was applied to healthy rats to induce a transient
increase in circulating cytokines at 1–3 hours. A single oral dose of
NTZ (100 mg/kg) was administered just before LPS injection and
blood samples were collected 3 h later before sacrifice.
To assess NTZ’s effects in an ACLF-model, a single ip LPS injection
(0.03 mg/kg-adapted dose to limit mortality) was administered to
rats with liver fibrosis induced by oral CCl4 administration for 15
weeks followed by 1-week CCl4 washout. Before the LPS challenge,
the rats received NTZ (50 mg/kg BID) or vehicle for 3 days. Plasma
samples were collected 24 h post-LPS.
Results: In THP1 macrophages, the active NTZ metabolite tizoxanide
blunted LPS-induced TNFα secretion (IC50 = 6 μM, Emax = 88%). In
healthy rats, NTZ reduced the LPS-induced rise in circulating
cytokines (619 vs 1782 pg/ml TNFα, p = 0.01; 17.5 vs 24.8 ng/ml IL6,
p = 0.06; 633 vs 834 pg/ml IL1b, p = 0.10; 4740 vs 6760 pg/ml IFNγ, p =
0.09) within 3 hours of treatment. In rats with CCl4-induced fibrosis
(F3-F4), NTZ treatment before LPS-induced ACLF reduced ALT (214 vs
919 U/l, p = 0.007), AST (355 vs 2072 U/l, p = 0.005) and total bilirubin
(3.7 vs 13.3 μmol/l, p = 0.02), resulting in hepatoprotective effects.
Moreover, NTZ treatment also prevented LPS-induced increases in
creatinine (48 vs 83 μmol/l, p = 0.009), urea (46 vs 140 mg/dl, p =
0.002) and cystatin C (1471 vs 2869 ng/ml, p = 0.02).
Conclusion: These results suggest that the rapid anti-inflammatory
effects of NTZ may participate in beneficial effects on hepatic and
extrahepatic functions in a disease model of ACLF.

THU529
In silico characterization of the interactome of hepatic
nonparenchymal cells reveals promising targets for antifibrotic
therapy
Oleksandr Petrenko1,2,3,4, Ksenia Brusilovskaya1,2,3,4,
Benedikt Hofer1,2,3,4, Philipp Königshofer1,2,3,4,
Benedikt Simbrunner1,2,3,4, Kaan Boztug1,2, Michael Trauner3,4,
Philipp Schwabl1,2,3,4, Thomas Reiberger1,2,3,4. 1Ludwig Boltzmann
Institute for Rare and Undiagnosed Diseases (LBI-RUD), Vienna, Austria;
2
CeMM Research Center for Molecular Medicine of the Austrian
Academy of Sciences, Vienna, Austria; 3Vienna Hepatic Hemodynamic
Lab (HEPEX), Division of Gastroenterology and Hepatology, Department Specifically, in cirrhosis, the endothelial cell-selective adhesion
of Internal Medicine III, Medical University of Vienna, Vienna, Austria; molecule (ESAM) and thrombospondin 1 (THBS) pathways were
4
Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, over-represented. Cirrhotic HSCs became a major source of ESAM,
Medical University of Vienna, Vienna, Austria especially directed towards endothelial cells. In healthy livers, THBS
Email: [email protected] participated in the cellular crosstalk between macrophages and other
immune cells. However, in cirrhosis, HSCs were linked to this THBS-
Background and aims: Advances in tissue dissociation and sequen-
based interaction with immune cells.
cing methodology allow functional characterization of non-paren-
Top drug-gene associations were identified based on the elements of
chymal liver cells (NPCs) on a single-cell resolution. Based on the
the cirrhotic NPC interactome with the highest network centrality
cellular expression of ligand-receptor pairs, the predicted molecular
score. The latter were represented mainly by extracellular matrix and
crosstalk in distinct cell populations can identify potential thera-
immunovascular signaling transcripts, such as collagens, laminins,
peutic targets.
and integrins (Figure-B, red vs. yellow indicating higher network
Method: We used published single-cell RNA sequencing (scRNA-seq;
centrality score).
MacParland-Nature Communications 2018; Ramachandran-Nature
We identified 59 drug candidates (8 approved drugs, 16 in clinical
2019) to predict in silico the interactome of hepatic non-parenchymal
trials, and 35 compounds with experimental evidence) with
cells (NPCs) from patients with healthy and fibrotic livers. After
predicted ESAM and THBS pathways activity.
filtering, integrating, and annotating the scRNA-seq datasets,
Conclusion: Prediction of the cellular and cell-matrix interactions
CellChat algorithms were used to build an interaction network
based on NPC scRNA-seq data represents a new bioinformatics
among both healthy and cirrhotic NPCs. Subsequently, Reactome
approach to identify potential therapeutic targets for liver fibrosis,
pathway analysis using predicted ligand-receptor pairs revealed key
such as ESAM and the THBS. An increased number of high-quality
pathways associated with cirrhosis. The PanDrugs platform was used
scRNA-seq datasets with clinical annotations will aid in the search for
to identify drug-gene associations.
new anti-fibrotic agents.
Results: We computed the cellular interactome among NPCs based
on both healthy and cirrhotic scRNA-seq datasets (Figure-A). In
cirrhosis (vs. healthy), the outgoing interactome of macrophages
primarily addressed endothelial and dendritic cells, and hepatic
stellate cells (HSCs) had significantly increased interactions, mainly
with endothelial and infiltrating immune cells.

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 POSTER PRESENTATIONS
THU530 THU531
Long-chain acylcarnitines promote leukocyte mitochondrial Reduced plasma extracellular vesicle CD5L content in patients
dysfunction: role in patients with acutely decompensated with acute-on-chronic liver failure: interplay with specialized
cirrhosis pro-resolving lipid mediators
Ingrid Wei Zhang1,2, Cristina López-Vicario1,2,3, Mireia Casulleras1,2, M. Belén Sánchez-Rodríguez1, Érica Téllez2, Mireia Casulleras1,
Marta Duran-Güell1,2, Roger Flores-Costa1,2, Paula Segalés3,4, Francesc Borras3, Vicente Arroyo4, Joan Clària1,4,5,
M. Carmen Garcia-Ruiz3,4,5, José Fernandez-Checa3,4,5, Maria-Rosa Sarrias2,6. 1Hospital Clínic-IDIBAPS, Biochemistry and
̀ iques August Pi i
Joan Clària1,2,3,6. 1Institut d’Investigacions Biomed Molecular Genetics Service, Spain; 2Innate Immunity Lab, IGTP, Spain;
Sunyer (IDIBAPS), Barcelona, Spain; 2European Foundation for the study 3
IVECAT, IGTP, Spain; 4European Foundation for the Study of Chronic Liver
of chronic liver failure, Barcelona, Spain; 3CIBER-Center for Biomedical Failure, Spain; 5Universitat de Barcelona, Department of Biomedical
Research Network, Madrid, Spain; 4Institut d’Investigacions Sciences, Spain; 6CIBERehd, Spain
Biomed̀ iques de Barcelona (IIBB-CSIC), Barcelona, Spain; 5Keck School of Email: [email protected]
Medicine of USC, Research center for ALPD, Los Angeles, United States;
6 Background and aims: Acute-on chronic liver failure (ACLF) is a
Universitat de Barcelona, Department of Biomedical Sciences,
syndrome that develops in patients with acutely decompensated
Barcelona, Spain
cirrhosis (AD). It is characterized by a systemic hyperinflammatory
Email: [email protected]
state, leading to multiple organ failure. Our objective was to analyze
Background and aims: Acute-on-chronic liver failure (ACLF) is macrophage anti-inflammatory protein CD5L in plasma extracellular
characterized by acute decompensation (AD) of cirrhosis, organ vesicles (EVs) and assess its as yet unknown relationship with lipid
failure (s) and high short-term mortality. The cytokinome of these mediators in ACLF.
patients revealed that exaggerated systemic inflammatory response Method: EVs, isolated by size exclusion chromatography from the
is an important driver of disease progression. Recently, it has been plasma of healthy subjects (HS) (n = 9) and patients with compen-
demonstrated that the elevated circulating levels of acylcarnitines sated cirrhosis (CC) (n = 8), AD (n = 13) and ACLF (n = 14), were
predict mortality in patients with AD and ACLF. Therefore, inflam- defined as positive for CD9, CD5L and CD63 and their size, number,
mation-associated mitochondrial dysfunction can be regarded as morphology and lipid mediator content were characterized by
another major contributor to disease progression. Here, we hypothe- nanoparticle tracking analysis, electron microscopy and liquid
size that acylcarnitines not only function as biomarkers of mito- chromatography with tandem mass spectrometry, respectively.
chondrial dysfunction but also exert biological effects on Plasma CD5L was quantified by enzyme-linked immunosorbent
mitochondria of circulating immune cells. In addition, as organ assay in 10 HS, 20 CC and 149 AD patients (69 with ACLF).
donors are scarce, we explore whether existing treatments such as Macrophage CD5L expression and the biosynthesis of specialized
human serum albumin (HSA) might modulate the effect of pro-resolving lipid mediators (SPMs) were characterized in vitro in
acylcarnitines on mitochondrial function. primary cells.
Method: Peripheral blood mononuclear leukocytes from healthy Results: Circulating EVs were significantly suppressed in cirrhosis,
subjects were isolated by Ficoll gradient and in vitro experiments regardless of severity, and showed considerable alterations in CD5L
were performed to assess mitochondrial function under treatment and lipid mediator content as the disease progressed. In AD patients,
with long- and medium-chain acylcarnitines, in the presence or levels of EV CD5L correlated best with those of the SPM resolvin E1
absence of HSA. We assessed mitochondrial membrane potential (RvE1). Analysis of total plasma supported these data and showed
(MMP) with the cationic dye JC-1 and mitochondrial respiration that, in ACLF, low CD5L levels were associated with circulatory ( p <
using Agilent Seahorse XF technology. This was complemented by 0.001), brain (p < 0.008) and respiratory (p < 0.05) failure (Mann-
electron microscopic evaluation of mitochondrial ultrastructure of Whitney test). Functional studies in macrophages indicated a positive
immune cells treated with acylcarnitines and expression analysis of feedback loop between CD5L and RvE1 biosynthesis.
genes involved in mitochondrial function and biogenesis. Conclusion: We have determined a significant alteration of circulat-
Results: Palmitoyl- and hexanoylcarnitine were increased in blood of ing EV contents in ACLF, with a loss of anti-inflammatory and pro-
patients with AD cirrhosis. In contrast to hexanoylcarnitine, the long- resolving molecules involved in the control of acute inflammation in
chain palmitoylcarnitine impaired maximal respiration of leukocyte this condition.
mitochondria and reduced MMP in peripheral mononuclear leuko-
cytes without affecting cell viability. Palmitoylcarnitine also down- THU532
regulated HMOX-1 gene expression in a concentration-dependent Peptidylglycine alpha-amidating monooxygenase and
manner, indicating impairment of cell antioxidant responses. The adrenomedullin measurements suggest cardio-circulatory
effect of palmitoylcarnitine on HMOX-1 expression was reversed by dysfunction in advanced cirrhosis
etomoxir, an inhibitor of the carnitine palmitoyltransferase 1A Søren Møller1, Andrei Voiosu1, Signe Wiese2, Janun Schulte3,
located at the outer mitochondrial membrane. Finally, HSA partially Paul Kaufmann3, Andreas Bergmann3, Emil Bartels4,
reversed the MMP-reducing effect, without being physically localized Jens Peter Goetze4. 1Hvidovre Hospital, Center of Functional and
to mitochondria. Diagnostic Imaging and Research, Department of Clinical Physiology and
Conclusion: Our results indicate that elevated circulating long-chain Nuclear Medicine 260, Hvidovre, Denmark; 2Hvidovre Hospital, Gastro
acylcarnitines in patients with AD are not only an epiphenomenon Unit, Hvidovre, Denmark; 3SpingoTec GmbH, Berlin, Germany;
4
but have the potential to actively promote mitochondrial dysfunction Rigshospitalet, Department of Clinical Biochemistry, Copenhagen,
in immune cells, thereby contributing to immune dysbalance in these Denmark
patients. Email: [email protected]
Background and aims: Peptidylglycine α-amidating monooxygenase
(PAM) is a processing enzyme involved in maturation of a plethora of
regulatory peptides. One product of PAM activity is adrenomedullin
(bio-ADM), which regulates vascular tone and endothelial integrity.
In this study, we aimed to examine PAM activity and bio-ADM
concentrations in patients with cirrhosis and explore the role of the
liver in net release of the two markers.
Method: We enrolled 48 patients with cirrhosis and 16 control
subjects. The patients were evenly distributed according to the Child-

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POSTER PRESENTATIONS
Turcotte class (16 patients in class A, 16 patients in class B, and 16 impairments by measuring biochemical and histological parameters
patients in class C). All underwent a complete hemodynamic (hematoxylin-eosin and sirius red), gene expression of inflammatory
examination with catheterization of the liver, renal, and femoral genes (qPCR) and serum cytokine levels (Luminex technology).
veins and corresponding arteries, from where blood was simultan- Results: As compared to CCl4-sham, CCl4 + CLP rats exhibited more
eously collected. PAM activity was determined in heparin plasma severe hypoalbuminemia and significantly higher serum levels of
with a new assay from PAM Theragnostics GmbH (Hennigsdorf, AST, GGT and bilirubin accompanied by increased liver expression of
Germany). Bio-ADM was measured in heparin plasma at a research inflammatory genes. CCl4 + CLP rats also showed increased serum
laboratory at SphingoTec GmbH (Hennigsdorf, Germany). creatinine and BUN levels and higher inflammatory gene expression.
Results: Patients with Child C cirrhosis displayed increased circulat- Of note, 33% of animals of this study group manifested acute tubular
ing PAM activity. PAM activity was similar across tissues and there necrosis. Compared to CCl4-sham, CCl4 + CLP rats showed circulatory
were no significant associations to ascites, esophageal varices, or (higher plasma renin activity), coagulation (higher INR) and brain
portal hypertension. We found associations of PAM activity to alanine (impaired neurological behavior test score) failures. Moreover, CCl4 +
aminotransferase (r = 0.30, p = 0.04), bilirubin (r = 0.47, p = 0.001) and CLP rats exhibited up-regulated expression of lung injury markers
INR (r = 0.42, p = 0.004). With respect to bio-ADM concentrations, and more exuberant systemic inflammation (higher levels of serum
there was a marked difference within the Child classes ( p < 0.0001) cytokines). Importantly, CCl4 + CLP rats had 25% mortality at 48 hours
and significant associations of circulating bio-ADM concentrations whilst CCl4-sham rats showed 100% survival.
and prothrombin time and serum albumin, ( p < 0.0001). We also
found a net release of bio-ADM across the liver (hepatic artery: 13.0
(8.7–21.0) vs. hepatic vein: 19.7 (12.7–29.6) pg/ml, n = 48, p < 0.001).
There was a release of bio-ADM across the lower limb (femoral artery:
12.6 (7.6–22.0) vs. femoral vein: 21.8 (13.5–29.2) pg/ml, n = 48, p <
0.001. Bio-ADM concentrations were increased in patients with
ascites (n = 26) compared to patients without (n = 22).
Conclusion: PAM activity is progressively increased in cirrhosis, but
without a net release across the studied organs. In contrast, bio-ADM
is released by the liver and relates to the severity of the disease. Given
the major expression of PAM in the heart, we propose that increased
PAM activity in cirrhosis may reflect a cardio-circulatory dysfunction
in advanced cirrhosis.

THU533
Combination of CCL4-induced decompensated cirrhosis with
acute polymicrobial peritonitis as an optimized experimental
model mimicking extrahepatic organ failures defined in ACLF
Roger Flores-Costa1,2, Albert Salvatella1, Bryan J Contreras1,2,
Marta Duran-Güell1,2, Mireia Casulleras1,2, Nico Kraus3, Sabine Klein3,
Cristina López-Vicario1,2, Ingrid Wei Zhang1,2,
Pierre-Emmanuel Rautou4, Javier Fernández2,5, Jonel Trebicka2,3,
Vicente Arroyo2, Joan Clària1,2,6. 1Hospital Clínic-IDIBAPS and Conclusion: The CCl4 + CLP model in rats reproduces the spectra of
CIBERehd, Biochemistry and Molecular Genetics Service, Barcelona, extra-hepatic organ impairments present in patients with ACLF and
Spain; 2European Foundation for the study of Chronic Liver Failure (EF- thus appears as an optimized experimental model to explore the
CLIF) and Grifols Chair, Barcelona, Spain; 3Goethe University Frankfurt, pathophysiology of this disease.
Department of Internal Medicine I, Frankfurt, Germany; 4Hôpital
Beaujon and INSERM, Centre de Recherche sur l’Inflammation, Paris, THU534
France; 5Hospital Clínic-IDIBAPS and CIBERehd, Liver ICU, Liver Unit, Thrombin-induced platelet activation across distinct stages of
Barcelona, Spain; 6University of Barcelona, Department of Biomedical portal hyperension and cirrhosis
Sciences, Barcelona, Spain Ksenia Brusilovskaya1,2,3, Benedikt Hofer1,2,3, Beate Eichelberger4,
Email: [email protected] Simon Panzer4, Benedikt Simbrunner1,2,3, Mattias Mandorfer1,2,
Background and aims: Acute-on-chronic liver failure (ACLF), which Thomas Gremmel5,6,7, Thomas Reiberger1,2,3. 1Medical University of
develops in patients with acutely decompensated cirrhosis, is Vienna, Division of Gastroenterology and Hepatology, Department of
characterized by multiple extrahepatic organ failures leading to Medicine III, Vienna, Austria; 2Medical University of Vienna, Vienna
high 28-day mortality. The investigation of ACLF pathophysiology is Hepatic Hemodynamic Lab (HEPEX), Division of Gastroenterology and
hampered by the lack of a proper animal model that reproduces the Hepatology, Department of Medicine III, Vienna, Austria; 3Medical
full spectra of extra-hepatic organ failures characteristic of this University of Vienna, Christian-Doppler laboratory for portal
disease. Since there is an unmet need for an animal model of ACLF, the hypertension and liver fibrosis, Vienna, Austria; 4Medical University of
current investigation explored the value of combining the well- Vienna, Department of blood group serology and transfusion medicine,
established model of chronic liver cirrhosis induced by carbon Vienna, Austria; 5Medical University of Vienna, Department of Internal
tetrachloride (CCl4) with the acute model of polymicrobial septic Medicine II, Vienna, Austria; 6Landesklinikum Mistelbach-Gänserndorf,
peritonitis induced by cecal ligation and puncture (CLP) as novel Department of Internal Medicine I, Cardiology and Intensive Care
experimental model of ACLF. Medicine, Mistelbach, Austria; 7Karl Landsteiner society, Institute of
Method: The study was performed in Sprague-Dawley rats induced antithrombotic therapy in cardiovascular disease, St. Poelten, Austria
to cirrhosis (n = 12) by CCl4 (i.p., 1 μL/g, 2 times/week). After Email: [email protected]
developing ascites, rats underwent CLP surgery (CCl4 + CLP group). Background and aims: Patients with advanced chronic liver disease
The study also included control (n = 6) and sham operated CCl4- (ACLD) often show thrombocytopenia; however, primary hemostasis
treated (CCl4-sham group) (n = 6) rats. Forty-eight hours after CLP or seems re-balanced by higher levels of von Willebrand factor (VWF).
sham surgery, functional tests and collection of blood and tissue Still, alterations in thrombin-induced platelet activation may put
samples were performed to assess tissue injury and organ ACLD patients at increased risk for both bleeding and

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 POSTER PRESENTATIONS
thromboembolic events. Therefore, we aimed to characterize platelet MFI [3.4–32.8] vs. B: 1.8 MFI [0.0–16.2], p < 0.01 vs. C: 0.0 MFI [0.0–
function in a thoroughly characterized ACLD patient cohort. 0.0], p < 0.001). Similarly, a decreased response to PAR-4 mediated
Method: 110 ALCD patients with portal hypertension (PH), i.e., a platelet activation was observed with increasing CPS stages (P-
hepatic venous pressure gradient (HVPG) ≥6 mmHg, were prospect- selectin: CPS A: 1159.0 MFI [332.8–2721.0] vs. B: 582.3 MFI [101.3–
ively included and stratified by Child-Pugh stage (CPS) and HVPG. 1236.0], p = 0.03 vs. C: 464.0 MFI [107.1–547.1], p = 0.02; GPIIb/IIIa:
Platelet surface P-selectin and activated glycoprotein IIb/IIIa (GPIIb/ CPS-A: 18.1 MFI [2.1–93.8] vs. B: 0.0 MFI [0.0–13.7], p < 0.01 vs. C: 0.0
IIIa) (mean fluorescent intensity, MFI) were assessed with flow MFI [0.0–0.0], p < 0.001). The severity of PH had no impact on
cytometry as sensitive parameters of platelet activation in unstimu- “baseline” activation (all p = ns). PAR-1 mediated platelet surface
lated and stimulated (agonists of the protease-activated receptors, expression of P-selectin was comparable across the HVPG strata 6–9
PAR-1 and PAR-4) conditions. vs. 10–19 vs. ≥20 mmHg ( p = ns), while activated GPIIb/IIIa was
significantly reduced in HVPG ≥20 group (HVPG 6–9: 20.8 MFI [7.5–
46.4] vs. HVPG ≥20: 0.5 MFI [0.0–20.8], p < 0.01). PAR-4 mediated
platelet activation was also reduced in the HVPG ≥20 mmHg group
(P-selectin: HVPG 6–9: 1775.0 MFI [668.6–3287.0] vs. HVPG
≥20 mmHg: 383.9 MFI [112.6–721.6], p < 0.001; GPIIb/IIIa: HVPG 6–
9: 36.1 MFI [8.0–141.1] vs. HVPG ≥20: 0.0 MFI [0.0–6.8], p < 0.001).
Conclusion: ACLD patients exhibit decreased thrombin-inducible
platelet activation when progressing to Child stages B and
C. Moreover, high risk PH (HVPG ≥20 mmHg) is associated with
impaired platelet activation upon stimulation. The impact of these
alterations on the risk of bleeding or thrombotic events remains to be
studied.

THU535
Exploring metabolic space of advanced chronic liver disease
regression
Yuly Mendoza1, Sofia Tsouka2, Jaime Bosch1, Annalisa Berzigotti1,
Mojgan Masoodi3. 1University Hospital Bern, Visceral Surgery and
Medicine; 2University hospital Bern, Institute of Clinical chemistry;
3
University hospital Bern, Institute of Clinical chemistry, Bern,
Switzerland
Email: [email protected]
Background and aims: Liver fibrosis is the main determinant of
clinical outcomes in advanced chronic liver disease (ACLD) of any
etiology. Regression of bridging fibrosis and cirrhosis can take place
after effective etiological treatment, but not in all cases, suggesting
that factors other than the etiology play a role in the modulation of
this important outcome. In patients achieving regression of ACLD,
liver function markedly improves, suggesting that several metabolic
pathways are influenced by regression of fibrosis. However, the
metabolic pathways associated with fibrosis regression in ACLD have
not been characterized. We hypothesize that thorough assessment of
liver metabolism could provide evidence-based data for better
characterization of cirrhosis patients with regression following
effective etiological treatment, thus providing a rational basis for
personalized interventions.
Method: We performed a case-control pilot study of 60 patients with
ACLD of different etiologies, 30 with histological and/or clinical
evidence of regression of ACLD (Regressors) and 30 without any
improvement (Non-regressors) after a minimum of 24 months of
successful etiological therapy. We used the combination of metabolic
modelling and metabolic profiling to define metabolic pathways and
associated signature that differentiate Regressors from Non-regres-
sors. We have developed a transcriptomics-driven metabolic model-
ling approach to assess the regression of ACLD. We further
investigated the associated metabolic signature using mass spec-
trometry-based metabolomics.
Results: Although Regressors and Non-regressors showed similar
profiles at baseline, our observation is pointing to fatty acid β-
oxidation and arachidonic acid metabolism (associated to inflamma-
Results: The level of “baseline” platelet activation was similar across tion and oxidative stress) as key metabolic pathways differentiating
CPS stages A, B, and C (unstimulated P-selectin expression: 0.0 MFI vs. Regressors from Non-regressors after therapy, suggesting that lipid
0.0 MFI vs. 0.0 MFI, p = ns; unstimulated GPIIb/IIIa expression: 0.0 MFI metabolism plays a central role in the modulation of the extracellular
vs. 0.0 MFI vs. 0.0 MFI, p = ns). PAR-1 mediated platelet activation was matrix in ACLD. In addition, Using Least Absolute Shrinkage and
significantly impaired in CPS-B and C patients (P-selectin: CPS-A: Selection Operator (LASSO) analyses, the Regressor phenotype was
2261.0 MFI [1815.0–2942.0] vs. B: 1793.0 MFI [1299.0–2523.0], p = predicted with 80% accuracy based on the levels of identified lipid
0.02 vs. C: 1577.0 MFI [1101.0–1926], p < 0.01; GPIIb/IIIa: CPS-A: 20.6 markers after etiologic therapy.

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POSTER PRESENTATIONS

Conclusion: Our histology and transcriptomics data show that the

cirrhotic liver has an exacerbated response to injury, possibly due to
Figure: Workflow for metabolic phenotyping. an increased susceptibility to ischemia which can compound with
other injuries to cause far greater damage. This could be a result of the
Conclusion: Our preliminary observations suggest several metabolic changes in the hepatic microvasculature that occur in cirrhosis, most
pathways that were associated with persistence or regression of ACLD notably capillarization of sinusoids and the formation of intrahepatic
after successful etiological therapy. These results allow proposing a vascular shunts.
metabolic signature of regression of fibrosis in ACLD.
THU537
THU536 The regulatory protein and gene expression profile of skeletal
Exacerbated response to patterned injury in the cirrhotic liver: muscle in chronic liver disease patients
potential susceptibility to ischemia
Sophie Allen1, Jonathan Quinlan1, Amritpal Dhaliwal2,
Benjamin Leaker1,2, Mozhdeh Sojoodi3, Kenneth K. Tanabe3, Thomas Nicholson2, Felicity Williams2, Matthew Armstrong3,
R. Rox Anderson2,4, Joshua Tam2,4. 1Massachusetts Institute of Ahmed Elsharkawy3, Simon Jones2, Carolyn Greig1, Janet Lord2,
Technology, Harvard-MIT Health Sciences and Technology, Cambridge, Gareth Lavery4, Leigh Breen1. 1University of Birmingham, School of
United States; 2Massachusetts General Hospital, Wellman Center for Sport, Exercise and Rehabilitation Sciences, Birmingham, United
Photomedicine, Boston, United States; 3Mass General Cancer Center, Kingdom; 2University of Birmingham, Institute of Inflammation and
Division of Surgical Oncology, Boston, United States; 4Harvard Medical Ageing, Birminghan, United Kingdom; 3University Hospitals
School, Department of Dermatology, Boston, United States Birmingham, Liver Unit, Birmingham, United Kingdom; 4Nottingham
Email: [email protected] Trent University, Department of Biosciences, Nottingham, United
Background and aims: The response to injury in the cirrhotic liver is Kingdom
an important factor in both the pathogenesis of cirrhosis and the Email: [email protected]
treatment of patients living with end stage liver disease. This study Background and aims: The molecular pathways which may
aimed to investigate the differences in the short-term tissue response underpin sarcopenia in Chronic Liver Disease (CLD) are largely
to a controlled injury between the healthy and cirrhotic liver. unclear. The aim of this study was to characterize the intracellular
Method: Healthy and cirrhotic rats underwent a laparotomy to signaling pathways that may underscore sarcopenia in CLD patients
expose the liver followed by treatment with a tunable ablative laser to of different etiologies and disease stages.
create a pattern of micro-injuries in the left lobe. The roughly 1cm2 Method: Muscle biopsy and blood samples were obtained from 9
treatment area contains over 100 uniformly spaced micro-injuries, non-cirrhotic non-alcoholic fatty liver disease patients (NAFLD; aged
each approximately 300um in diameter and 2 mm deep. Animals 61.1 ± 9.0), 12 decompensated alcoholic related end-stage liver
were euthanized 0hr, 2hr, 4hr, 6hr, 3d, 7d, and 14d after laser disease patients (ESLD;55.7 ± 5.7) and 12 healthy, age-matched
treatment. RNA samples from the 4hr timepoint were used for healthy controls (CON;55.7 ± 8.7). The protein content of skeletal
RNAseq transcriptome analysis. With DESeq2, a difference-in- muscle anabolic, catabolic and mitochondrial signaling intermedi-
differences statistical model was used to identify genes that ates was determined via western blot. The muscle transcriptome was
respond differently between the laser-treated cirrhotic and laser- analyzed using RNA-sequencing.
treated non-cirrhotic liver while controlling for the differences Results: Citrate synthase activity (∼43%) and the protein content of
between the untreated samples. Over-representation analysis and OXPHOS complex I was significantly lower (∼26%) in ESLD vs. CON ( p
gene set enrichment analysis were then used to identify biological < 0.01 for both), whereas OXPHOS complex IV was significantly lower
processes associated with the differential expression results. in ESLD vs. CON (71%; p < 0.01) and NAFLD (61%; p = 0.04). Total-
Results: In both cirrhotic and non-cirrhotic liver, the laser produced a mTOR protein was significantly lower in NAFLD (62%, p = 0.01) and
regular and uniform array of micro-injuries. These injuries com- ESLD (52%, p = 0.03) vs. CON. Myostatin protein content was
pletely healed within 7 days in the non-cirrhotic liver. In the cirrhotic significantly greater in NAFLD vs. CON (77%; p < 0.01) and ESLD
liver, TUNEL staining showed expanding zones of cell death between (70%; p < 0.01). Gene pathway analysis revealed a significant
the 4hr and 6hr timepoints, resulting in enlarged and haphazard enrichment in pathways related to oxidative stress in ESLD vs. CON.
injuries (see figure). Histology showed cells near blood vessels are A significant enrichment in genes related to senescence was evident
spared, particularly near the vascularized fibrous septa encapsulating in NAFLD vs. CON.
nodules. Evidence of these injuries could still be found at 14d.
Functional analysis of the differential expression data returned
enrichment of gene sets related to hypoxia, starvation, and
angiogenesis, as well as revealing suppression of a variety of
metabolic processes.

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 POSTER PRESENTATIONS
physiological markers of LSEC have been described, there is lack of
information regarding dysfunctional LSEC in chronic liver diseases
(CLD). Here, we aimed to decipher the molecular profile of
dysfunctional LSEC in different pathological situations to improve
the effectiveness of potential therapeutic agents.
Method: LSEC from three experimental rat models (bile duct ligation-
BDL, inhaled carbon tetrachloride-CCl4 and high fat glucose/fructose
diet-HFGFD) and their controls were isolated and sorted by flow
cytometry using cd11b to eliminate macrophages and cd32b to sort
dysfunctional (CD32−) LSEC. Full proteomic profile was performed
applying label free proteomics by nano-scale liquid chromatography
tandem mass spectrometry on an EvoSep ONE (EVOSEP) coupled on-
line to a TIMS Tof Pro (Bruker). Obtained data was processed and
analyzed with PEAKS software.
Conclusion: Collectively these findings highlight some similar but Results: The percentage of CD32− LSEC was different between
largely distinct signaling pathways that may underscore sarcopenia in groups. Of relevance is the comparison between HFGFD (early stage of
CLD patients across different etiologies and disease stages. CLD) with 16.9% CD32− LSEC and CCl4 (advanced stage) with only
6.0%, suggesting differences in the capillarization process.
THU538
Principal component analysis (PCA) revealed that CD32+ LSEC are
Proteomic analysis of dysfunctional liver sinusoidal endothelial
more similar between models and to healthy controls than to CD32−
cells reveals substantial differences in the most common
LSEC of their respective model (Fig A). Accordingly, the number of
experimental models of chronic liver disease
differentially expressed proteins vs. control LSEC is lower in CD32+
Mar Gil1, Carla Fuster1, Mikel Azkargorta2,3, Imma Raurell1,3, than in CD32− LSEC. Nevertheless, further PCA also clusters CD32+
Aurora Barbera1, Felix Elortza2,3, Joan Genesca1,3, Diana Hide1,3, LSEC in separate groups by models (Fig B) representing protein
María Martell1,3. 1Liver Diseases, Vall d’Hebron Institut de Recerca expression differences between them.
(VHIR), Liver Unit, Hospital Universitari Vall d’Hebron (HUVH), Vall Looking for similarities in the capillarization process, we found 51
d’Hebron Barcelona Hospital Campus, Universitat Autònoma de common proteins differentially expressed compared to controls in
Barcelona (UAB), Barcelona, Spain; 2Proteomics Platform, CIC bioGUNE, CD32− LSEC from the 3 models and 354 shared by at least 2 models.
BRTA (Basque Research and Technology Alliance), ProteoRed-ISCIII, Finally, heatmap representation of significantly differentially
Bizkaia Science and Technology Park, Derio, Spain; 3Centro de expressed proteins between models, both for CD32+ and CD32−
Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas LSEC, evidenced specific patterns for each model being CCl4 and
(CIBERehd), Madrid, Spain HFGFD more similar to each other than BDL (Fig C).
Email: [email protected] Conclusion: Substantial differences in dysfunctional LSEC from the
Background and aims: Therapies specifically aimed at liver three most common models of CLD were found, supporting the idea
sinusoidal endothelial cells (LSEC), first inducers of liver damage, that in different etiologies/disease stages, LSEC may harbor different
could help to slow down the entire pathological process. Although protein expression profiles. In deep analysis of deregulated proteins

Figure: (abstract: THU538)

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POSTER PRESENTATIONS
and pathways in each model will allow to better understand and use Conclusion: The results of this study show for the first time that that
the preclinical models in translational research and will facilitate the analbuminaemic animals have increased mortality, significantly
specific targeting of experimental drugs. increased liver injury and increased sensitivity to LPS. Chronic
Funded by Instituto de Salud Carlos III and European Union albumin administration partially reversed this, as well as reduces
EuroNanoMed III [AC18/00033]. gut translocation resulting in decreased TLR4 pathway activation and
improving the integrity of tight junctions. The data provide
THU539 mechanistic insight into the biological effect on albumin on gut-
Long-term albumin administration improves survival, reduces liver interactions.
TLR4 mediated hepatic inflammation and reduces gut
translocation in models of cirrhosis THU540
Alexandra Phillips1, Qianwen Zhao2, Abeba Habtesion1, The prevalence and prognostic significance of vitamin C
Fausto Andreola1, Nathan Davies1, Lindsey A Edwards3, deficiency in patients with cirrhosis: a prospective observational
Jane Macnaughtan1, Rajiv Jalan1. 1University College London, Institute cohort study
of liver and digestive health, United Kingdom; 2Sichuan University, Declan Connoley1, Phil Ha1, Joseph Nim1, Elaine Koh1, Ryan Hirsch1,
Department of Gastroenterology and Hepatology, West China Hospital, Marcus Robertson1. 1Monash Health, Department of Gastroenterology,
Chengdu Shi, China; 3Institute of Hepatology, King’s College Hospital, Melbourne, Australia
United Kingdom Email: [email protected]
Email: [email protected]
Background and aims: Malnutrition is a common comorbidity in
Background and aims: Long-term albumin administration reduces cirrhotic patients and confers a poorer prognosis. Vitamin C (VC) is a
mortality in patients with decompensated cirrhosis. The underlying micronutrient essential for human health. Vitamin C deficiency
mechanisms are unknown. The aims of this study were to investigate (VCD) can lead to scurvy and may impair immune and liver functions.
how the absence of endogenous albumin and albumin administration Although previously thought to be rare in developed countries, VCD
impacts liver injury, toll-like receptor 4 (TLR4) signalling and gut is now well described in patients with pneumonia, COVID19 and
translocation. upper gastrointestinal bleeding (UGIB). The prevalence and clinical
Method: 10 rodent groups: Naïve, cirrhosis (4-wk; bile-duct ligation significance of VCD in cirrhosis remains poorly studied.
(BDL)) and acute-on-chronic liver failure (ACLF) models (induced by Method: Patients with cirrhosis admitted to 3 metropolitan tertiary
lipopolysaccharide (LPS) 0.025 mg/kg intraperitoneal (i.p.) to BDL) ± centres in Australia were prospectively included over a 10-month
albumin infusion (1.5 g/kg ip; 2-wk) of analbuminaemic (NAR) and period in 2021. Fasting VC levels were collected on admission and we
wild-type (SD) rats. Plasma biochemistry and hepatic TUNEL staining. recorded demographic data and clinical outcomes. The primary
Hepatic TLR4 expression and pathways (hTLR4): qPCR and RT2 PCR outcomes were the prevalence of VCD (defined as VC level
profiler. Gut permeability: d-lactate and zonulin in plasma. Ileal <23 mcmol/L) and severe VCD (SVCD), defined as <11 mcmol/L.
integrity: western blot of tight junction proteins. Secondary outcomes included mortality, intensive care admission,
Results: ALT levels showed significant improvement after albumin length of stay (LOS) and rate of infection.
administration in SD BDL LPS group ( p = 0.01), and non-significant Results: 117 patients were included. Mean age was 57.1 ± 13.9 years,
improvement in SD BDL and NAR BDL LPS. Significant reduction in the 59.0% were male and 23.9% belonged to the lowest socioeconomic
liver of TUNEL positive areas in LPS groups with albumin adminis- decile. The most common aetiologies of cirrhosis were alcohol
tration ( p < 0.001). Coma-free survival increased from 62.5% to 80% (62.4%), viral hepatitis (24.0%) and non-alcoholic fatty liver disease
between NAR and SD animals exposed to LPS respectively, with 100% (18.8%). Median MELD score was 29 (IQR 22–36) and Child Pugh (CP)
survival in NAR animals exposed to LPS after albumin administration. grades were 12.8% A, 46.2% B and 41.0% C. Most patients (74.4%) were
hTLR4: NAR animals had greater hTLR4 expression, with all treatment hospitalised with complications of decompensated cirrhosis, includ-
groups showing a reduction of hTLR4 expression after albumin ing ascites (59.0%), encephalopathy (31.6%) and variceal bleeding
administration. hTLR4 gene array confirmed the activation of TLR4 (11.1%).
dependent pathways in the cirrhotic NAR animals, which was Median VC level was 34mcmol/L (IQR 16–55) and did not differ with
abrogated by albumin infusion. Markers of gut permeability: Plasma age, gender, or aetiology of cirrhosis. Increasing CP grade correlated
D-lactate showed a reduction in all treatment groups with albumin with significantly lower median VC levels (CP-A 46.0 mcmol/L vs. CP-
(see figure). Plasma zonulin decreased after albumin in NAR BDL B 36.5 mcmol/L and CP-C 20.5 mcmol/L, p = 0.026). The prevalence of
animals with and without LPS administration. Tight junction: ZO-1, VCD and SVCD were 39.3% and 17.1% respectively. SVCD was more
claudin-4 and occludin in ileum showed a reduction in NAR diseased prevalent in patients with a body mass index <25 (28.3% vs 13.0%, p =
animals compared to SD groups with albumin administration 0.036).
increasing tight junction protein abundance in all disease groups. In-hospital mortality was 12.8% and did not differ by VCD status,
however in the subgroup of patients presenting with UGIB, SVCD
Plasma D-lactate quantification correlated with significantly higher mortality (50% vs 4.1%, p = 0.045).
Bacteraemia was more frequent in patients with VCD (13.3% vs. 1.4%,
800
p = 0.014) and SVCD (26.3% vs 2.1%, p < 0.001), which remained
Plasma D-lactate (umol)

significant at multivariate analysis (OR for every 1mcmol/L increase

600
in VC, 0.91 (95% CI: 0.83–0.99), p = 0.037). Overall infection rates were
higher in patients with SVCD (40.0% vs. 27.8%) although this was non-
400
significant (p = 0.279). Median hospital LOS was 10 (IQR 6–18) days
and did not differ by VCD status.
200

0
N NA D DL
SD SD L L
B BD LB

N NA AM
SD SD M

D DL B

S S
N SA S

LB
R LB
B BD

LP LP
LP P

L
A

R RB
A

R RB A
L LL

A
SH
SH

L
D
SD

B
A

L
D

B
A

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 POSTER PRESENTATIONS

Figure: Cirrhosis (GS stain). A. Nodule showing HVs (arrows) draining into
septa with adjacent active GS+ buds. B. High mag. showing Wnt-GS in
ducts (arrows) and in new bud HC.

Conclusion: In cirrhotic livers, Wnt appears to migrate in intact HV

remnants to distal ductal regions, either by veno-portal approxima-
tion in collapsed tissue (PELs) or, where sinusoidal connections are
intact, by reversed sinusoidal blood flow aided by focal shunt-related
blood flow, as seen in other liver conditions. This explains how Wnt
Conclusion: VCD is common in hospitalised cirrhotic patients and
can be delivered from hepatic veins to the progenitor cell niche and
prevalence increases with severity of liver disease. VCD increases the
activate regeneration.
risk of infective complications and higher mortality was observed in
Wnt-GS is a useful surrogate marker for the location of Wnt, although
patients with UGIB and SVCD. Further studies are required to assess
confirmation with direct techniques is required. The patchy anatomic
the significance of VCD in cirrhosis and the impacts of VC
distribution of Wnt-GS suggests that Wnt concentration is focally
replacement.
suboptimal to support regeneration, justifying therapeutic trial
THU541 options.
Wnt as activator of regeneration in cirrhosis of human liver: tissue
THU542
collapse brings the Wnt source in hepatic veins to the site of the
The portal vein in patients with cirrhosis is not an extensively
progenitor cell niche
inflammatory or hypercoagulable vascular bed
IanR Wanless1, Ashley Stueck1. 1Dalhousie University, Anatomic
Ellen Driever1, Marta Magaz2, Jelle Adelmeijer1, Fanny Turon2,
Pathology, Halifax, Canada
Anna Baiges2, Pol Olivas2, Virginia Hernandez-Gea2, Annabel Blasi3,
Email: [email protected]
Juan Carlos Garcia Pagan2, Ton Lisman1. 1University Medical Center
Background and aims: Recent studies show that Wnt is secreted by Groningen, Department of Surgery, Groningen, Netherlands; 2Barcelona
hepatic vein endothelial cells (HV-EC). Glutamine synthetase (GS) Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de
activation in peri-venular hepatocytes (HC) of normal livers is ̀ iques August Pi i Sunyer (IDIBAPS); 3Hospital
Investigacions Biomed
considered a downstream event initiated by Wnt. Thus, we consider Clinic, Department of Anesthesiology, Barcelona, Spain
GS activation a surrogate histologic marker for Wnt and call it Wnt- Email: [email protected]
GS. Hepatic regeneration is also activated by the Wnt/beta-catenin
Background and aims: Portal vein thrombosis (PVT) is a common
pathway. We previously showed that human cirrhotic liver is
complication in patients with cirrhosis. Although we previously
repopulated by buds of new hepatocytes derived from distal bile
demonstrated that hypercoagulability is a reflection of severity of
ducts. GS expression was a prominent feature in ducts forming buds,
liver disease rather than a causal factor for PVT, other groups
which is consistent with a response to local exposure to secreted
demonstrated elevated levels of markers of inflammation and
Wnt. However, in normal livers, Wnt secreted from HV-EC affects a
activation of haemostasis in the portal vein (PV) compared to post-
thin rim of perivenular/zone 3 hepatocytes and is then washed
hepatic veins. However, many studies did not take clearance of these
toward the cava. In order to reach portal tracts and activate the bud
markers by the liver into account. We aimed to determine whether
sequence in cirrhosis, we hypothesize that some Wnt is distributed to
the PV in cirrhotic patients has particular proinflammatory or
the distal bile ducts by altered circulation. The aim is to identify the
hypercoagulable characteristics by comparing blood sampled in the
anatomic basis of this pathway in human cirrhosis.
PV, in the hepatic vein (HV), and in the peripheral circulation.
Method: Resected liver samples with chronic disease (n = 38) or
Method: Plasma samples from 52 cirrhotic patients with clinically
normal (2) were serially sectioned and stained with GS, CD34, and
significant portal hypertension receiving transjugular intrahepatic
CK19. Wnt-GS was semi-quantitated by location.
portosystemic shunt, were taken from the PV, HV, and jugular vein
Results: Perivenular Wnt-GS generally decreased with advancing
(JV). Plasma levels of markers of inflammation, endothelial damage
stage, associated with decreased HV number but also decreased Wnt-
and haemostasis were determined and compared between the three
GS per HV, likely because of damage to HV-EC and arterialization with
vascular beds.
washout. Stage 4A and 4B livers usually had occasional nodules with
Results: Inflammatory markers LPS and IL-6 were slightly, but
focal increase in Wnt-GS, likely because of retrograde flow. Active
significantly higher in the PV than in the HV and JV. The neutrophil
budding correlated with Wnt-GS, mostly in septal ducts and
extracellular trap markers cfDNA and MPO-DNA were similar
associated new hepatocytes, usually in stage 4A and 4B. Wnt-GS in
between the vascular beds. Endothelial marker VWF and markers
HC at nodular periphery were often seen to connect with intranod-
of haemostasis were modestly elevated in the PV. Levels of multiple
ular HVs but also appeared to be a response to Wnt-secreting HV
markers are lower in the HV compared to the PV and JV.
remnants that were deeply embedded in adjacent septa (see fig);
these HVs appear to be the main conduits allowing HV-derived Wnt
to be transported to small duct regions.

Journal of Hepatology 2022 vol. 77(S1) | S119–S388 S367

POSTER PRESENTATIONS
Table 1: Levels of markers of inflammation, endothelial damage and comparing cirrhotic to fibrotic environment, thus suggesting that
haemostasis, measured in plasma sampled from different vascular increased stiffness could induce EMT in HCC cells. HepG2 cells grown
beds. in the 3D cirrhotic group were also more resistant to doxorubicin
Portal vein Hepatic vein Jugular vein
treatment compared with those grown in the 3D fibrotic group or
‡‡ §§ grown in 2D. No differences were seen in drug distribution and
LPS (pg/ml) 162 [96–259]* 125 [68–233] 156 [66–251]
TNF-α (pg/ml) 12 [6–22.5] 11.7 [5.1–23.9] 11.9 [5.2–21.5] penetrations between the two different gel compositions, thus
‡‡ §
IL-6 (ng/ml) 16.5 [7–35.1]* 8.5 [5.5–32.5] 10.3 [5.4–34.7] further confirming that stiffness induced changes in the HCC
cfDNA (µg/ml) 1 [0.9–1.2] 1 [0.8–1.2] 1 [0.8–1.2]
MPO-DNA (AU) 0.2 [0.1–0.4] 0.1 [0.1–0.4] 0.2 [0.1–0.4]
phenotype that could explain a reduced response to chemother-
VWF (%) 339 [229–449]* 309 [218–456]
‡
301 [216–425]
§§
apeutics. This was then confirmed by an increased expression of the
TAT (µg/ml) 47.9 [29.8–47.9] 19.5 [7.2–35.6] 43.8 [12–117] drug resistance gene MDR1 in HepG2 cells grown in a cirrhotic gel,
‡ §
PAP (ng/ml) 1091 [556–4845]* 796 [535–1581] 867 [533–2146]
D-dimers (ng/ml) 3670 [2237–7205]* 2720 [1700–3662]
‡‡‡
3040 [1827–5330] compared to those grown in a fibrotic gel.
Conclusion: Increasing the stiffness of the liver markedly increases
‡
* Comparison between portal vein and peripheral vein; comparison between the formation of metastatic nodules, induces several markers of EMT
§
portal vein and hepatic vein; and comparison between hepatic vein and jugular and reduces response to chemotherapeutics in a biomimetic 3D
vein. *: p < 0.05; **: p < 0.001; ***: p < 0.0001.
model of HCC.
Conclusion: In contrast to published studies, we found only a slight THU545
prothrombotic environment in the PV. In previous studies, compari- Ascites reduction and anti-inflammatory effects after albumin
son of levels of markers in PV with an immediate post-hepatic infusion for the management of cirrhosis: evidence from an
vascular bed may have erroneously led to the conclusion that the animal model
portal circulation is hypercoagulable. Here we demonstrate that
Raquel Horrillo1, Anna Mestre1, Estefania Alcaraz1,
many markers are lowest in the HV compared to the PV and the
Guillermo Fernández Varo2, Wladimiro Jiménez2,3, Ricardo Gonzalo1,
systemic circulation, indicating that the low level of these markers in
Jordi Vidal1, Vicente Arroyo4, Joan Clària2,3,4, Todd Willis1,
the HV, at least in part, reflect clearance of those markers in the liver.
Montserrat Costa1. 1Grifols, Bioscience Research Group, Barcelona,
Spain; 2Hospital Clinic, IDIBAPS and CIBERehd, Barcelona, Spain;
THU543 3
University of Barcelona Medical School, Department of Biomedical
Effect of liver stiffness on hepatocellular carcinoma phenotype in
Sciences, Barcelona, Spain; 4EF Clif, EASL-CLIF Consortium and Grifols
a biometric 3D model
Chair, Barcelona, Spain
Carlemi Calitz1, Jaafar Khaled1, Jenny Rosenquist2, Maria Kopsida1, Email: [email protected]
Oliver Degerstedt3, Hans Lennernas3, Mårten Fryknäs4,
Ayan Samanta2, Femke Heindryckx1. 1Uppsala University, Medical Cell Background and aims: The prevention of mortality by long-term
Biology, Uppsala, Sweden; 2Uppsala University, Department of albumin treatment in decompensated cirrhotic patients with ascites
Chemistry-Ångström Laboratory, Polymer Chemistry, Uppsala, Sweden; is currently under investigation (PRECIOSA phase 3 trial,
3 NCT03451292). Albumin has non-oncotic functions such as binding,
Uppsala University, Department of Pharmaceutical Biosciences,
Uppsala, Sweden; 4Uppsala University, Department of Medical Sciences, antioxidant and immunomodulatory capacities which have been
Cancer Pharmacology and Computational Medicine, Uppsala, Sweden postulated to be related to beneficial effects of albumin administra-
Email: [email protected] tion in cirrhotic patients. However, the specific mechanisms of action
associated with albumin in liver cirrhosis are still under research. The
Background and aims: Hepatocellular carcinoma (HCC) usually
present study was aimed at evaluating the effect of therapeutic
occur in patients with an underlying chronic liver disease. The tumor albumin infusion in cirrhotic rats with ascites. Assessments included
micro-environment (TME) is therefore characterized by an increased were albumin binding capacity, inflammation biomarkers, and a
deposition of extracellular matrix proteins (ECM). The abundance of transcriptomic analysis.
ECM results in physical and biomechanical changes in the TME, Method: Male Wistar rats underwent chronic exposure to carbon
which could influence tumor behavior. The aim of our study was to
tetrachloride to induce cirrhosis. Two weeks after ascites develop-
determine how liver stiffness affects the HCC phenotype in a novel ment, rats were randomized to receive intravenously therapeutic
biomimetic 3D model to study tumor-stroma interactions. human albumin 1.5 g/Kg (Albutein®, Grifols; n = 20) or vehicle (0.9%
Method: HepG2 and Huh7 cells were grown in a 3D biomimetic saline; n = 16) on days 1 and 3. At day 4, ascites volume was assessed
hydrogel model with tuneable biomechanical properties for 21 days. and serum and tissue samples were collected for biochemical and
Matrix stiffness, epithelial-to-mesenchymal transitions (EMT), meta-
inflammatory markers determination (total protein, albumin, IL-2, IL-
static potential, drug sensitivity and overall survival was assessed and 18, TNF-alpha), albumin binding capacity (using a specific fluorescent
compared to current two-dimensional (2D) models, an in vivo HCC marker) and transcriptomic analysis (oxidative stress panel in liver
mouse model and clinical data. Tumour nodules were collected from
and Toll-Like Receptors (TLR) panel in liver, heart and kidney). Results
the culture medium and cells were extracted from the gels for were expressed as median [IQR].
subsequent RT-qPCR analyses.
Results: Therapeutic albumin infusion increased total protein and
Results: Cells were embedded in hydrogels mimicking the onset of a albumin levels (32 [27–34] g/L), compared to vehicle (22 [18–26] g/L;
fibrotic and cirrhotic TME, as determined by patient-derived data. p < 0.0001), 72 h after the initial administration. Human albumin
HepG2 and Huh7 cells grown in a stiffer matrix (resembling a
represented 41% of total albumin. Ascites volume was significantly
cirrhotic liver) increased proliferation and protein content, compared reduced after albumin infusion (2.0 [2.0–3.0] ml vs vehicle infused
to those grown in a less stiff matrix (resembling a fibrotic liver).
rats 13.5 [6.5–25.0] ml; p < 0.01). These changes were accompanied
HepG2 cells significantly decreased albumin synthesis in the cirrhotic by an increase of albumin binding capacity (treated 49.2 [43.3–55.8]
TME compared to the fibrotic TME, while Huh7 cells increased % vs vehicle 35.7 [33.3–43.4] %; p < 0.01) and a decrease of serum
albumin synthesis. While urea production in HepG2 cells decreased
proinflammatory cytokines IL-2 ( p < 0.01), IL-18 ( p < 0.01) and TNF-
over time, it increased in Huh7 cells in both conditions. Tumor alpha ( p < 0.05) in treated rats compared to vehicle. Furthermore,
nodules started to form spontaneously outside the 3D gels after 11 transcriptomic analysis in albumin-treated rats revealed an increase
days. The HepG2 tumour nodules appeared earlier in the medium in albumin gene expression in the liver, and an attenuation of
outside the cirrhotic gels and were significantly larger in size when transcriptomic changes associated with TLR signaling pathways
compared to those found in the medium outside a fibrotic gel. Cells
previously altered by cirrhosis induction in liver, heart and kidney.
derived from these tumor nodules showed an increased mRNA
expression of aSMA and SNAIL and decrease in E-cadherin when

S368 Journal of Hepatology 2022 vol. 77(S1) | S119–S388

 POSTER PRESENTATIONS
Conclusion: Albumin infusion resulted in increased albumin binding Conclusion: The presence of NOD2 mutations is not associated with
capacity that was accompanied by ascites mobilization and reduced hepatic or systemic hemodynamic abnormalities in patients with
systemic inflammation as observed by a decrease of cytokine levels cirrhosis, suggesting that other mechanisms leading to bacterial
and attenuation of transcriptomic changes in TLR signaling pathways. translocation predominate.
These results using an animal model are in agreement with the role of
albumin ameliorating liver disease complications. THU547
Demonstration of gut-barrier dysfunction and endotoxemia in
THU546 patients with cirrhosis presenting with acute variceal bleeding: a
Presence of NOD2 mutations is not associated with hepatic or proof of concept
systemic hemodynamic abnormalities of cirrhosis Rajat Bansal1, Samagra Agarwal1, Sanchit Sharma1,2, Kanav Kaushal1,2,
Robin Greinert1, Alexander Zipprich2, Anna Hauptmann3, Srikanth Gopi1, Deepak Gunjan1, Anoop Saraya1. 1All India Institute of
Markus Casper3, Frank Lammert3, Cristina Ripoll2. 1Martin-Luther Medical Sciences, Gastroenterology and Human Nutrition Unit, New
University Halle Wittenberg, Internal Medicine I, Halle, Germany; Delhi, India; 2John Radcliffe Hospital, Translational Gastroenterology
2
University Hospital Jena, Internal Medicine IV, Jena, Germany; Unit, Oxford, United Kingdom
3
Saarland University Medical Center, Internal Medicine II, Homburg, Email: [email protected]
Germany
Background and aims: Limited data exist on the demonstration of
Email: [email protected]
gut-barrier dysfunction and factors predisposing to this in patients
Background and aims: Presence of NOD2 Mutation has been with chronic liver disease (CLD) presenting with acute variceal
associated to infections in cirrhosis. This association is more bleeding (AVB). We studied the presence of this dysfunction in a
evident in compensated patients ( pts) (PMID: 30702490). prospectively.
According to the systemic inflammation hypothesis, bacterial recruited cohort of patients with AVB.
translocation is one of the main drivers of complications of end- Method: Consecutive patients with CLD presenting with AVB were
stage liver disease. The aim was to evaluate the association of NOD2 prospectively included, who underwent duodenal biopsy at the time
mutations with hepatic and systemic hemodynamics. of upper GI endoscopy. Gut-barrier dysfunction was demonstrated by
Method: The presence of NOD2 risk variants ( p.N289S, p.R702W, p. semi-quantitative immunohistochemical (IHC) expression of tight
G908R, c.3020insC, rs72796367) were evaluated in 825 pts (screen- junction proteins like claudin-2, claudin-4, zonulin-1, occludin and
ing in context of INCA trial: EudraCT 2013-001626-26). From these, junctional adhesion molecule-A (JAM-A) in both villi and crypt of
215 pts received a hepatic hemodynamic study and right heart duodenal biopsies. Endotoxemia was estimated indirectly using
catheterization. This cross-sectional study compared hepatic hemo- serum IgM anti-endotoxin assay and systemic inflammation was
dynamic and systemic hemodynamics according to NOD2 status. evaluated using serum interleukin-1 (IL-1) and tumor necrosis factor
Variables are described with median (IQR) or proportions. Mann alpha (TNF-alpha) levels. The expression was compared across
Whitney U or Chi-square test were applied. different Child-Pugh strata of liver disease and with a control group
Results: Two-hundred-fifteen pts were included [median age 59 (IQR of cirrhosis without AVB.
53–66); male 67%; 76% alcohol associated cirrhosis]. Most pts were Results: Patients with CLD presenting with AVB (n = 71) (Child A/B/C:
Child Pugh stage B (A 25%, B 64%, C 11%).Sixty-six pts (31%) carried a 25/30/16) and controls (n = 84) were recruited. Zonulin-1 protein
NOD2 risk variant, of which 64 were heterozygous pts. Although expression was elevated [H score at crypt: AVB: 9 (9-9) vs controls: 2
there was an increase in the proportion of NOD2 risk variants among (1–6), p < 0.001; H score at villi: AVB: 6 (6–9) vs controls: 2 (2–6), p <
Child Pugh stage C ( p = 0.05), no differences were observed in MELD 0.001] in patients with AVB. IgM endotoxin levels (AVB: 28.5 ±
score [wild-type: 13 (10–16); NOD2 variants 13 (10–18)]. No 9.9 MMU/ml vs controls: 87.4 ± 20.2 MMU/ml; p <0.001) were lower
significant differences in hepatic and systemic hemodynamics were while IL-1 (AVB: 1005 ± 82 pg/ml vs controls: 49 ± 14.4 pg/ml; p <
observed when comparing patients with and without NOD2 risk 0.001) were elevated in AVB cohort. No difference was seen in the IHC
variants (table 1). Analyses were repeated excluding patients who expression of any tight junction barrier proteins, IgM endotoxin, IL-1
were on prophylactic or therapeutic antibiotics, and again no and TNF-alpha levels across different strata of liver disease. No
association between hepatic or systemic hemodynamic parameters association was seen between the studied proteins expression with
and NOD2 risk variants could be observed. the aetiology, active alcohol consumption, hypotension at presenta-
tion, hepatic venous pressure gradient and presence of active
bleeding on endoscopy.
p
NOD2 wild-type NOD2 Variants value
HR (bpm) 74 (65–83) 78 (65–87) 0.405
MAP (mmHg) 83 (76–89) 83 (75–91) 0.961
CO (l/min) 5.56 (4.67–7.08) 5.97 (4.98–7.64) 0.183
CI (l/min/m2) 2.93 (2.47–3.52) 3.31 (2.59–3.95) 0.075
SVR (dyn·sec·cm−5) 1069 (840–1376) 1042 (747–1273) 0.219
SVRI (dyn·sec/cm5/ 2016 (1641–2490) 1814 (1473–2399) 0.315
m2)
PAP (mmHg) 16 (13–20) 17 (14–20) 0.285
PCWP (mmHg) 11 (7–15) 12 (8–15) 0.237
PVR (dyn·sec·cm−5) 75 (43–112) 65 (32–112) 0.542
VCI (mmHg) 8 (6–12) 8 (5–11) 0.395
WHVP (mmHg) 29 (23–32) 28 (23–35) 0.483
FHVP (mmHg) 12 (8–15) 12 (7–15) 0.982
HVPG (mmHg) 19 (15–22) 19 (15–23) 0.994

Journal of Hepatology 2022 vol. 77(S1) | S119–S388 S369

POSTER PRESENTATIONS
has been recognized in decompensated cirrhosis, where it contri-
butes to accelerate the disease course. However, less information is
available regarding inflammation in patients with compensated
cirrhosis. Our aims were to investigate i) whether systemic
inflammation is present in patients with compensated cirrhosis,
and if so, ii) whether its worsening associates with the development
of complications.
Method: This is a nested cohort study within the PREDESCI trial, a
double blind multicentre, RCT to evaluate the efficacy of beta-
blockers to prevent decompensation in patients with compensated
cirrhosis and clinically significant portal hypertension (HVPG
≥10 mmHg). Biomarkers were measured in blood at baseline and at
1-year follow-up. Development of complications of portal hyperten-
sion was registered during the study. A group of 35 healthy controls
was included for the specific purposes of this study.
Results: We included 201 patients with compensated cirrhosis, most
(56.2%) by chronic hepatitis C, that were followed-up for a median of
37 months (27–47). Decompensation occurred in 17.4% at a median of
24 months (13.6–31.4), being ascites the main cause of decompen-
sation (14.4%). Low-grade systemic inflammation was present at
baseline and at 1-year as shown by greater serum levels of IL-6, von
Willebrand factor (vWF) and CD163 at both time points in patients
compared to controls (Table). Compared to baseline, IL-6 increased
( p < 0.05) at 1-year in those patients that decompensated on follow-
Figure: Scattered boxplots showing Zonulin-1 expression in crypt and villi up. Fatty acid binding protein (FABP), used as marker of intestinal
between controls and AVB and different Child Pugh strata of AVB barrier function, was greater in patients compared to controls. Values
of TNFa, IL1b, IL8 LBP and CD14 were similar in patients and controls
Conclusion: While the gut-barrier dysfunction, endotoxemia and at all points. The macrophage activation marker, CD163, correlated ( p
systemic inflammation are upregulated in patients with cirrhosis
< 0.01) with HVPG at baseline (r = 0.27) and at 1-yr (r = 0.46).
with AVB, the extent of these changes may be independent of
aetiology and severity of liver disease, degree of portal hypertension
and severity of bleeding episode. Baseline 1-yr
P
Median IQR P Median IQR P intra
THU548
Worsening of low-grade systemic inflammation heralds IL-6 (pg/ Controls 1.6 1.01–2.6 <0.05 0.001
ml) (n = 30)
decompensation in patients with compensated cirrhosis Cirrhosis 2.3 1.3–3.6 Cirrhosis 2.93 1.29–5.16 0.02
Rubén Sánchez-Aldehuelo1, Càndid Villanueva2,3, Joan Genesca3,4, CD163
(n = 116)
Controls 258.74 210.7– <0.001
(n = 97)
<0.001
Juan Carlos Garcia Pagan3,5, Ana Brujats2, José Luis Calleja Panero3,6, (ng/ml) (n = 34) 362.4

Carlos Aracil7, Rafael Bañares3,8, Rosa M Morillas3,9, Maria Poca2,3, Cirrhosis

(n = 157)
857.72 605.5–1117 Cirrhosis
(n = 101)
820.35 524.2–
1087.1
0.76

Beatriz Peñas1,3, Salvador Augustin3,10, Juan Abraldes3,5,11, vWF (ng/ Controls 2.95 1.46–5.13 <0.001 0.005
ml) (n = 20)
Edilmar Alvarado-Tapias2,3, Ferran Torres12,13, Jaime Bosch3,5,14, Cirrhosis 6 3.61–9.81 Cirrhosis 4.79 2.78– 0.58
Agustin Albillos1,3. 1Ramon y Cajal University Hospital, Ramon y Cajal (n = 160) (n = 108) 9.18
FABP (ng/ Controls 0.31 0.19–0.50 <0.001 <0.001
Institute of Health Research (IRYCIS), University of Alcala, Madrid, Spain, ml) (n = 30)
Spain; 2Hospital of Santa Creu and Sant Pau, Autonomous University of Cirrhosis 0.72 0.52–1.04 Cirrhosis 0.73 0.419– 0.95
(n = 149) (n = 103) 1.01
Barcelona, Hospital Sant Pau Biomedical Research Institute (IIB Sant
Pau) Barcelona, Spain; 3Centre for Biomedical Research in Liver and P: controls vs cirrhosis. P intra: baseline vs 1-yr.
Digestive Diseases Network (CIBERehd); 4Liver Unit, Vall d’Hebron
UniversityHospital, Vall d’Hebron Research Institute (VHRI), Conclusion: Low-grade systemic inflammation is present in patients
Autonomous University of Barcelona, Barcelona, Spain; 5Barcelona with compensated cirrhosis. In this setting, worsening of systemic
Hepatic Haemodynamic Laboratory, Liver Unit, Institute of Digestive and inflammation herald cirrhosis decompensation.
Metabolic Diseases, August Pi i Sunyer Institute of Biomedical Research,
Hospital Clinic, Barcelona, Spain; 6Puerta de Hierro University Hospital, THU549
Puerta de Hierro Hospital Research Institute, Autonomous University of Patients with acutely decompensated cirrhosis present a distorted
Madrid, Madrid, Spain; 7Institute of Biomedical Research, Arnau de blood lipid landscape that affects the ability of albumin to
Vilanova University Hospital (IRBLleida), Lleida, Spain; 8Gregorio promote inlammation resolution
Marañon University General Hospital, Gregorio Marañon Sanitary Mireia Casulleras1,2, Roger Flores-Costa1,2, Marta Duran-Güell1,2,
Research Institute, Faculty of Medicine, Complutense University of Ingrid W. Zhang1,2, Cristina López-Vicario1,2, Anna Curto2,
Madrid, Spain; 9University Hospital Germans Trias i Pujol, Badalona, Javier Fernandez2,3, Vicente Arroyo2, Joan Clària1,2,4. 1Hospital Clínic-
Spain; 10Liver Unit, Vall d’Hebron University Hospital, Vall d’Hebron IDIBAPS, Biochemistry and Molecular Genetics Service, Barcelona, Spain;
2
Research Institute (VHRI), Autonomous University of Barcelona, EF-Clif, European Foundation for the Study of Chronic Liver Failure,
Barcelona, Spain; 11University of Alberta, Edmonton, Canada; 12Medical Barcelona, Spain; 3Hospital Clínic, Liver ICU, Liver Unit, Barcelona, Spain;
4
Statistics Core Facility, August Pi i Sunyer Biomedical Research Institute, University of Barcelona, Department of Biomedical Sciences, Barcelona,
Hospital Clinic, Barcelona; 13Biostatistics Unit, Faculty of Medicine, Spain
Autonomous University of Barcelona, Barcelona, Spain; 14Inselspital, Email: [email protected]
Bern University, Switzerland
Background and aims: Lipids, especially lipid mediators derived
Email: [email protected]
from polyunsaturated fatty acids (PUFA), play a critical role in the
Background and aims: Portal hypertension is a major driver of regulation of inflammatory and immune responses. In this investi-
progression and decompensation in cirrhosis. Systemic inflammation gation, we characterized the blood lipid profile in patients with

S370 Journal of Hepatology 2022 vol. 77(S1) | S119–S388

 POSTER PRESENTATIONS
acutely decompensated (AD) cirrhosis and explored how changes in 0.09–0.40)). miRNA expression was compared between ACLF/AD/
this profile might affect the composition of circulating albumin. In dCLD cohorts and HC/cCLD cohorts. Downregulation of miR-122, −24
addition, we investigated the effects of albumin on the release of and −30a and upregulation of miR-223, −27a and −29b was
PUFA-derived lipid mediators by peripheral leukocytes. associated with decompensated CLD states. MetaCore™ pathway
Method: Lipids and lipid mediators were measured by liquid analysis demonstrated an association between these miRNA and
chromatography-tandem. systemic inflammation (z = 188.35, p < 0.0001*). A model including
mass spectrometry in leukocyte incubations, plasma and albumin- miR-24 and −27a discriminated Pts with ACLF/AD/dCLD from cCLD/
enriched and albumin-depleted plasma fractions from 18 patients HC Pts (AUC 0.77 (95%CI 0.69–0.85)). Sensitivity analyses were
with AD and 10 healthy subjects. Lipid mediators were also measured performed excluding each group individually. Excluding the HC
in 41 patients with AD included in an albumin therapy trial. cohort reduced model performance (AUC 0.69 (95%CI 0.56–0.81)).
Results: The plasma lipidome associated with AD cirrhosis was However, subsequently excluding the 6 cCLD Pts who decompen-
characterized by generalized suppression of all lipid classes except sated the following year improved this (AUC 0.74 (95%CI 0.60–0.88).
FAs. The lipid profile of circulating albumin in AD patients was Only the detection of miR-200b discriminated 90-day TxFS across
dominated by reduced content of docosahexaenoic acid (DHA) CLD groups but did not remain significant when adjusted for MELD.
(omega-3-PUFA) and anti-inflammatory/pro-resolving lipid media- Subgroup analysis of Pts with; dCLD, alcohol related CLD (ARLD) and
tors (i.e. 15-hydroxyeicosatetraenoic (15-HETE) and 17-hydroxydo- ascites Pts demonstrated different miRNAs associated with 90-day
cosahexaenoic (17-HDHA). In addition, albumin from AD patients TxFS (miR-24 in dCLD, miR-220b in ARLD and no miRNA in ascites
was depleted in prostaglandins (PGs) (PGE2, PGD2 and PGF2α), Pts). Only the detection miR-200b in ARLD Pts remained significant
implying dysregulated degradation and higher circulatory content when adjusted for MELD (aOR 0.23 (95%CI 0.06–0.82).
of these pro-inflammatory lipid mediators. Incubation of leukocytes
with exogenous albumin reduced PG production while inducing 15-

Ascites grade
Lymphocytes
Haemoglobin

Neutrophils
Leucocytes

Monocytes

Creatinine
Ammonia

HE Grade

miR-103a

miR-451a
miR-16-2
Platelets

Bilirubin

Albumin

miR-29b
miR-122

miR-223

miR-27a

miR-30a

miR-150

miR-191

miR-23a

miR-26a
Sodium

Lactate

miR-24

miR-25
lipoxygenase expression and 15-HETE and 17-HDHA release. Finally,

MELD
CRP

INR

CP
pH
1.0
* * * * * * * * * * *
PGE2 and PGD2 levels were lower in AD patients receiving albumin Haemoglobin

Platelets * * * * * * * * * * * * * * * * * * * * * *
therapy whereas 15-HETE was increased after albumin treatment Leucocytes * * * * * * * * *
* * * * * * * * * *
compared to baseline.
Neutrophils

Lymphocytes * * * * * * * * * * * *
Conclusion: Our findings indicate that both blood and albumin lipid Monocytes * * * * * * * * * * * * *
CRP * * * * * * * * * * * * * *
landscape is severely disorganized in AD cirrhosis and that exogenous Ammonia * * * * * * * * *
albumin has potential to redirect leukocyte biosynthesis from pro- Bilirubin * * * *
* *
* * *
* * * *
* * * *
* * *
* *
*
*
*
*
* *
0.5

Albumin

inflammatory to pro-resolving lipid mediators. Sodium * * * * * * * * *

Creatinine * * * * * * *
* * * * * * * * * * * * * *
THU550
INR

pH * * * * * *
miRNA associated with systemic inflammation may have Lactate * * * * * * *
*
*
* * *
* *
* * * * * * *
prognostic utility in predicting decompensation in patients with
HE Grade

Ascites grade * * * * * * * * * * * * * 0

chronic liver disease CP

MELD
* * * *
* * * *
* * * * * *
* * * * * *
* * * * *
* * * *
* *
*
* *
* *
Oliver Tavabie1, Vishal C Patel2,3,4, Siamak Salehi1, Marilena Stamouli1, miR-122 * * * * * * * * * * * *
* * * * * *
Francesca Trovato1, Savannah Rivera1, Salma Mujib1, Ane Zamalloa1,
miR-223

miR-24 * * * * * * * * * * * * * * * * * *
Eleanor Corcoran1, Krishna Menon1, Andreas Prachalias1, miR-27a * * * * * *
* * * * * * * * * * * *
Michael Heneghan1, Kosh Agarwal1, Mark J W McPhail1,
miR-29b

miR-30a * * * * * * * * * * * * * * -0.5

Varuna Aluvihare1. 1King’s College Hospital, United Kingdom; 2King’s miR-103a *

*
* *
* *
* * *
*
*
* *
*
*
* *
* *
*
*
*
*
miR-150

College Hospital, Institute of Liver Studies and Transplantation, London, miR-16-2 * * * * * * * * * * * *

United Kingdom; 3Foundation For Liver Research, The Roger Williams miR-191

miR-23a *
* * *
*
* * *
* * * *
*
* * * * * *
Institute of Hepatology, London, United Kingdom; 4Institute of Liver miR-25 * * * * * * * * * * * *
* * * * * * * * * * * * * *
Sciences, King’s College London, Department of Inflammation Biology, miR-26a

miR-451a * * * * * * * * * * *
School of Immunology and Microbial Sciences, FoLSM, London, United
-1.0

Kingdom Figure: Correlation matrix of clinical and laboratory parameters with

miRNA expression in CLD Pts
Email: [email protected]
Background and aims: Chronic liver disease (CLD) is associated with Conclusion: miRNA associated with systemic inflammation discrim-
significant mortality and encompasses; acute-on-chronic liver failure inate Pts with and without decompensated CLD states. Whilst miRNA
(ACLF), acute decompensation (AD), chronic decompensation (dCLD) have limited prognostic value in predicting 90-day TxFS likely
and compensated CLD (cCLD). Transition between these states reflecting the impact of aetiology, disease phase and decompensation
impacts on patient (Pt) survival. Here we investigate miRNA manifestation, they may have prognostic utility in predicting future
expression across the spectrum of CLD to evaluate their prognostic decompensation.
utility.
Method: Plasma samples were provided by Pts and healthy controls
(HC). Pts sampled included ACLF, AD, cCLD, HC (each groups n = 20)
and dCLD (n = 94). ACLF and AD Pts were sampled within 72 hours of
admission. 90-day transplant-free survival (TxFS) across Pts with CLD
was 68.8%. 6 Pts in the cCLD group decompensated in the year post-
sampling. A panel of 21 miRNA developed from our previous studies
were analysed. Univariate and multivariate analyses were utilized to
identify miRNA associated with decompensated CLD states and 90-
day TxFS.
Results: Figure 1 demonstrates significant correlations of miRNA with
clinical and laboratory parameters across CLD groups. Notably, miR-
24 correlated with markers of systemic inflammation (CRP), liver
failure (bilirubin, INR, lactate and ascites) and CLD prognostic models
(Child-Pugh r (s) = 0.25 (95%CI 0.09–0.40), MELD r (s) = 0.25 (95%CI

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POSTER PRESENTATIONS
p = 0.09), ascites (HR = 3.45, CI95%:1.31, 9.03; p = 0.013) and tobacco
(HR = 2.29; CI95%:1.08, 4.87; p = 0.032) were independently asso-
Liver tumours: Therapy ciated with OS in patients with cHCC-CCA. Among patients with
cHCC-CCA, 25 patients treated with tyrosine kinase inhibitors were
compared with 54 patients with platinum-based chemotherapies.
THU566
Patients treated by tyrosine kinase inhibitors had a median overall
Systemic treatments with tyrosine kinase inhibitors and
survival of 7.28 months versus 12.1 months for patients treated with
platinum-based chemotherapy in patients with unresectable or
platinum-based chemotherapies ( p = 0.86) (Figure). After a robust
metastatic hepato-cholangiocarcinoma
double adjustment on tumor number and size, vascular invasion,
Elia Gigante1,2, Christian Hobeika3, Brigitte Le Bail4, Valérie Paradis5, ALBI, MELD and cirrhosis, treatment’s regimen had no influence on
David Tougeron6, Marie Lequoy7, Mohamed Bouattour8, overall survival (HR = 0.92, 95%CI = 0.27–3.15, P = 0.88) and progres-
Jean-Frédéric Blanc9, Nathalie Ganne-Carrié1, Henri Tran1, sion-free survival (HR = 1.24, 95%CI = 0.44–3.49, P = 0.67).
Clemence Hollande10, Manon Allaire11, Giuliana Amaddeo12,
Helene Regnault12, Paul Vigneron12, Maxime Ronot13, Laure Elkrief14,
Gontran Verset15, Eric Trepo15, Aziz Zaanan16, Marianne Ziol17,
Massih Ningarhari18, Julien Calderaro19, Julien Edeline20,
Jean Charles Nault1. 1Hôpital Avicenne, Service d’hépatologie, Bobigny,
France; 2Centre de recherche sur l’inflammation, Inserm, Université de
Paris, INSERM UMR 1149 « De l’inflammation au cancer », Paris, France,
Clichy, France; 3Hôpital de la Pitié Salpêtrier̀ e, Service de Chirurgie
Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique,
France; 4Hôpital Pellegrin-CHU Bordeaux, Service d’Anatomo-
Pathologie; 5Hôpital Beaujon, AP-HP, Service d’Anatomo-Pathologie,
France; 6CHU de Poitiers et Université de Poitiers, Service d’Hépato-
Gastroentérologie; 7Hôpital Saint-Antoine, AP-HP, Service d’hépatologie;
8
Hôpital Beaujon, AP-HP, Service d’hépatologie; 9Hôpital Haut-Lévêque,
CHU Bordeaux, Pessac and INSERM U1053, Université de Bordeaux,
Service d’hépato-gastroentérologie et d’oncologie digestive; 10Hôpital
Cochin, AP-HP, Paris, France, Service d’hépatologie; 11ôpital de la Pitié
Salpêtrier̀ e, AP-HP, Service d’hépatologie; 12Hôpital Mondor, AP-HP,
Paris, Service d’hépatologie; 13Hôpital Beaujon, AP-HP, Service de Conclusion: Systemic treatments with tyrosine kinase inhibitors or
radiologie; 14HC-UMUH 1, CHRU Tours, Service d’hépatologie; 15Erasme platinum-based chemotherapies have similar efficacy in first line of
Hospital, Brussels, Department of Gastroenterology and Digestive patients with unresectable/metastatic cHCC-CCA. The ALBI score
Oncology; 16Hôpital Européen Georges-Pompidou HEGP, AP-HP, Service predicts overall survival.
Hépato-gastro-entérologie et oncologie digestive; 17Hôpital Avicenne,
AP-HP, Service d’Anatomo-Pathologie; 18CHU Lille-Hôpital Huriez, THU567
Maladies de l’appareil digestif; 19Hôpital Mondor, AP-HP, Paris, Service The systemic inflammatory response identifies patients with
d’Anatomo-Pathologie; 20Centre Eugen ̀ e Marquis, Service d’oncologie adverse clinical outcome from immunotherapy in hepatocellular
Email: [email protected] carcinoma
Claudia Fulgenzi1,2, Ambreen Muhammed2, Sirish Dharmapuri3,
Background and aims: Although there is currently no validated Matthias Pinter4, Lorenz Balcar4, Bernhard Scheiner4,
systemic therapy for unresectable hepato-cholangiocarcinoma Thomas U. Marron3, Tomi Jun3, Anwaar Saeed5, Hannah Hildebrand5,
(cHCC-CCA), tyrosine kinase inhibitors and platinum-based chemo- Mahvish Muzaffar6, Musharraf Navaid6, Abdul Rafeh Naqash6,
therapy are frequently used in clinical practice. Our study has aim to Anuhya Gampa7, Umut Ozbek8, Jung-Yi Lin8, Ylenia Perone2,
describe the effectiveness of first-line systemic treatments in patients Bruno Vincenzi1, Marianna Siletta1, Anjana Pillai7, Yinghong Wang9,
with cHCC-CCA. Uqba Khan10, Yi-Hsiang Huang11, Dominik Bettinger12,
Method: Patients with histological diagnosis of unresectable or Yehia Abugabal13, Ahmed Kaseb13, Tiziana Pressiani14,
metastatic cHCC-CCA confirmed by a centralized review (WHO Nicola Personeni14,15, Lorenza Rimassa14,15, Naoshi Nishida16,
classification 2019) who received systemic treatment from 2009 to Luca Di Tommaso17, Masatoshi Kudo16, Arndt Vogel18,
2020 were included retrospectively in 11 centers. The outcomes of Francesco Mauri2, Alessio Cortellini2, Rohini Sharma2,
patients with cHCC-CCA were compared with patients with hepato- Antonio D’Alessio19,20, Celina Ang3, David J. Pinato2. 1Campus
cellular carcinoma (HCC) treated by sorafenib (n = 225) and with Biomedico, Medical Oncology, Roma, Italy; 2Imperial College London,
intrahepatic cholangiocarcinoma (iCCA, n = 94) treated mainly by Hammersmith Hospital, Surgery and Cancer, London, United Kingdom;
platinum using a frailty Cox model. The efficacy of tyrosine kinase 3
The Mount Sinai Hospital, Department of Medicine, Division of
inhibitors and platinum-based chemotherapies in patients with Hematology/Oncology, New York, United States; 4Medical University of
cHCC-CCA was assessed using a doubly robust estimator. Vienna, Department of Internal Medicine III, Division of
Results: A total of 83 patients with cHCC-CCAwere included and were Gastroenterology and Hepatology, Wien, Austria; 5University of Kansas,
predominantly male (72%), 67% of patients had extrahepatic Division of Medical Oncology, Department of Medicine, Westwood,
metastases and 31% macrovascular tumor invasion. Compared with United States; 6East Carolina University, Division of Hematology/
iCCA (n = 94) and HCC (n = 225), cHCC-CCA were more often Oncology, Greenville, United States; 7UChicago Medicine, Section of
developed on cirrhosis (55%) than iCCA (27%) but less frequently Gastroenterology, Hepatology and Nutrition, Chicago, United States;
than HCC (88%) ( p < 0.001). cHCC-CCA (66%) and HCC (30%) had 8
Icahn School of Medicine at Mount Sinai, Department of Population
extrahepatic metastases less frequently than iCCA (81%) ( p < 0.001). Health Science and Policy, New York, United States; 9The University of
Unadjusted overall survival was better in CCA (13 months) compared Texas MD Anderson Cancer Center, Department of Gastroenterology,
to cHCC-CCA (12 months) and HCC (9 months) ( p = 0.017). In Hepatology and Nutrition, Houston, United States; 10NY-Presbyterian
multivariate analysis after adjustment by a Cox frailty model, patients Hospital, Division of Hematology and Oncology, New York, United States;
with cHCC-CCA had the same survival than HCC and iCCA (HR = 1.5; 11
Veterans General Hospital, Division of Gastroenterology and
95% CI = 0.98, 2.3; p = 0.063). ALBI score (HR = 2.15; CI05%:1.23, 3.76; Hepatology, Institute of Clinical Medicine, National Yang Ming Chiao

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 POSTER PRESENTATIONS
Tung University School of Medicine, Taiwan; 12University of Freiburg, THU568
Department of Medicine II, Faculty of Medicine, Medical Center Combination of crafity score with alpha-fetoprotein response
University of Freiburg, Freiburg im Breisgau, Germany; 13The University predicts a favorable outcome of atezolizumab plus bevacizumab
of Texas MD Anderson Cancer Center, Department of Gastrointestinal for unresectable hepatocellular carcinoma
Medical Oncology, Houston, United States; 14IRCCS Humanitas Research Wei Teng1, Chen-Chun Lin1, Po-Ting Lin1, Yi-Chung Hsieh1,
Hospital, Medical Oncology and Hematology Unit, Humanitas Cancer Ming-Mo Ho2, Chia-Hsun Hsieh3, Chun-yen Lin1, Shi-Ming Lin1.
Center, Cascina Perseghetto, Italy; 15Humanitas University, Department 1
Linkou Chang Gung Memorial Hospital, Gastroenterology and
of Biomedical Sciences, Milan, Italy; 16Kindai University Hospital, Hepatology, Taoyuan, Taiwan; 2Linkou Chang Gung Memorial Hospital,
Department of Gastroenterology and Hepatology, Osakasayama, Japan; Medical Oncology, Taoyuan, Taiwan; 3Tucheng Hospital, Medical
17
IRCCS, Humanitas Research Hospital, Pathology Unit, Cascina Oncology, New Taipei City, Taiwan
Perseghetto, Italy; 18Hannover Medical Center, Department of Email: [email protected]
Gastroenterology, Hepatology and Endocrinology, Sharjah, United Arab
Emirates; 19Humanitas University, Department of Biomedical Sciences, Background and aims: Immune checkpoint inhibitors (ICIs) with
atezolizumab plus bevacizumab are promising agents for unresectable
Italy; 20Imperial College London, Department of Surgery and Cancer,
London, United Kingdom hepatocellular carcinoma (HCC). Recently, the CRAFITY score com-
posed of baseline alpha-fetoprotein (AFP) and CRP level is associated
Email: [email protected]
with survival and radiological response in patients with ICIs treatment.
Background and aims: Systemic inflammation is a hallmark of Therefore, we tries to propose an algorithm based on CRAFITY score
cancer, and it has a pivotal role in HCC development and progression. combining with on-treatment AFP response to guide treatment.
The role of systemic inflammation in influencing outcomes of Method: Seventy-two patients who received atezolizumab plus
patients treated with immunotherapy for HCC has not been fully bevacizumab regardless of as a first- or more than a second-line
elucidated. therapy for unresectable HCC in Chang Gung Memorial Hospital,
Method: We conducted a retrospective study including 362 patients Linkou Medical center were enrolled for analyses. Radiologic
receiving immune-checkpoint inhibitors (ICIs) across 3 continents, evaluation was based on modified Response Evaluation Criteria in
evaluating the influence of neutrophiles to lymphocytes ratio (NLR), Solid Tumors (mRECIST).
platelet to lymphocytes ratio (PLR) and prognostic nutritional index Results: Of 72 patients, the objective response rate (ORR) and disease
(PNI) on overall (OS), progression free survival (PFS) and radiologic control rate (DCR) were 23.4% and 57.8%, respectively. Twenty-five
responses. patients (34.7%) died during median 7.0 months follow-up duration.
Results: In our 362 patients treated with immunotherapy, median OS Multivariate analysis showed that low CRAFITY score (AFp <100 ng/
and PFS were 9 and 3.5 months respectively. Amongst tested ml or CRp <10 mg/l) and satisfactory AFP response at 6 weeks (≥75%
inflammatory biomarkers, patients with NLR ≥5 had shorter OS (7.7 decrease or ≤10% increase from baseline) were independent
vs 17.6 months, p < 0.0001), PFS (2.1 vs 3.8 months, p = 0.025) and factors associated with good OS (hazard ratio [HR] = 0.263, p = 0.041
lower ORR (12% vs 22%, p = 0.034), similarly, patients with PLR ≥300 and HR = 0.102, p = 0.004), PFS (HR = 0.681, p = 0.046 and HR = 0.326,
reported shorter OS (6.4 vs 16.5 months, p < 0.0001) and PFS (1.8 vs p = 0.008) and good responder (odds ratio [OR] = 4.354, p = 0.044 and
3.7 months, p = 0.0006). NLR emerged as independent prognostic OR = 6.406, p = 0.017). Patients were further divided into three
factors for OS in univariate and multivariate analysis (HR 1.95, 95%CI classes: low CRAFITY score (0–1 points) with satisfactory AFP
1.45–2.64, p < 0.001; HR 1.73, 95%CI 1.23–2.42, p = 0.002) and PLR response at 6 weeks (class I), either high CRAFITY score (2 points)
remained an independent prognostic factor for both OS and PFS in or unsatisfactory AFP response at 6 weeks (class II) and neither low
multivariate analysis (HR 1.60, 95%CI 1.6–2.40, p = 0.020; HR 1.99, 95% CRAFITY score nor satisfactory AFP response at 6 weeks (class III).
CI 1.11–3.49, p = 0.021). ORR was 41.7%, 15.4%, and 0% in class I, II and III patients, respectively
(overall p = 0.033). Patients in the class I had the longest overall
survival (OS) and progression-free survival (PFS), followed by class II
and class III (median OS: not reached vs. 8.6 vs. 4.3 months, log-rank
p < 0.001; median PFS: 5.9 vs. 4.7 vs. 2.7 months, log-rank p = 0.014).
Combination CRAFITY score and AFP response at 6 weeks with
AUROC predicts OS and tumor response to be 0.809 and 0.816,
respectively, superior to either CRAFITY score (0.771 and 0.767) or
AFP response at 6 weeks (0.725 and 0.729) alone.
Conclusion: The CAR (CRAFITY score and AFP-Response) classifica-
tion which combining CRAFITY score and AFP response at 6 weeks
Figure: OS by pre-treatment NLR provides a practical guidance for atezolizumab plus bevacizumab
therapy in unresectable HCC patients.
Conclusion: Systemic inflammation measured by NLR and PLR is an
independent negative prognostic factor in HCC patients undergoing THU569
ICI therapy. Further studies are required to understand the biological Survival of patients with advanced hepatocellular carcinoma
mechanisms underlying this association and to investigate the treated with sorafenib in France during 2009–2018: analysis of the
predictive significance of circulating inflammatory biomarkers in French hospital and claim database
HCC patients treated with ICIs. Jean-Pierre Bronowicki1, Julien Dupin2,
Alexandre Pissewoewoe Tanang2, Anika Gilbert-Marceau2,
Jean-Frédéric Blanc3, Pierre Nahon4, Caroline Laurendeau5,
Stéphane Bouée5, Mélina Gilberg6. 1CHRU Nancy, Hépato-
gastroentérologie, VANDOEUVRE LES NANCY, France; 2Roche, Boulogne-
Billancourt; 3CHU Bordeaux, Hépato-gastroentérologie, Bordeaux;
4
APHP Hôpital Avicenne, Hépatologie, Bobigny; 5CEMKA, Bourg La Reine,
France; 6Roche, Boulogne-Billancourt, France
Email: [email protected]
Background and aims: Hepatocellular carcinoma (HCC) is often
diagnosed at an advanced stage of the disease. Until 2017, sorafenib

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POSTER PRESENTATIONS
was the only systemic therapy indicated in advanced HCC as first-line prolonged hospital stay (<75. percentile). A multivariate logistic
therapy. This analysis describes the profile, overall survival (OS) and regression analysis was performed to identify factors influencing TO.
proxy of progression free survival (PFS) in patients with advanced Results: Of 283 patients, TO was achieved in 67 (24%) patients.
HCC treated with sorafenib in France. Multivariate analysis revealed that preoperative biliary drainage was
Method: This study was conducted using the French administrative associated with a decreased (OR = 0.405, 95% CI: 0.194–0.845, p =
healthcare claims database. All patients treated with sorafenib for 0.016) and left-sided-resection (OR = 1.899, 95% CI: 1.048–3.440, p =
HCC (identified by the ICD-10 code for hepatocellular carcinoma) as 0.035) with increased odds for TO. Overall survival (OS) and DFS
long-term illnesses or diagnosis-related group during hospitalization (disease-free survival) did not differ significantly between the
were included in the study between 2009 and 2018. The cause of the outcome groups (OS: p = 0.280, DFS: p = 0.735). However, there was
underlying chronic liver disease (CLD) was identified from ICD-10 a trend towards better overall survival, especially in the late course
codes and ATC codes of specific treatments. OS from sorafenib with TO. The differences in OS between the TO and no TO groups were
initiation was measured. PFS was defined on the proxy of the time statistically significant when analyzing patients with survival of at
from sorafenib initiation until treatment discontinuation or death. least 30 months ( p = 0.039, Figure 1).
The Kaplan-Meier method was used to estimate survival rates.
Results: 17, 680 newly treated HCC patients were identified. Their
mean age was 66.9 years (SD:10.3) and 87.6% were male. The most
frequent causes of underlying CLD were alcohol liver disease (54.8%)
and viral hepatitis (24.4%). The median OS from sorafenib initiation
was 8.4 months (95% CI = [8.2; 8.7]).
OS differed according to HCC etiologies:
Alcohol + (HCV or HBV) (1, 749 patients, 9.9%), 8.9 months [8.4;9.4]
Alcohol without viral hepatitis (7, 933 patients, 44.9%), 8.8 months
[8.4;9.1]
NASH/NAFLD without viral or alcohol hepatitis (403, 2.3%), 9.8
months [8.9;11.8]
Hepatitis B without alcohol hepatitis (655 patients, 3.7%), 5.9 months
[5.3;6.9]
Co-infection VHB/VHC without alcohol hepatitis (268 patients, 1.5%),
9.7 months [8.2;11.7]
Hepatitis C without alcohol hepatitis (1, 646 patients, 9.3%), 9.0
months [8.2;9.7]
No identified etiology (5, 026 patients, 28.4%), 7.7 months [7.3;8.1] Figure: Long-term survival of patients after major hepatectomy for perihi-
lar cholangiocarcinoma according to textbook outcome groups excluding
patients surviving less than 30 months.
The median survival decreased over the years: from 10.0 months in
2009 to 7.3 months in 2018. Conclusion: Our analysis proposed a uniform definition of TO after
The median proxy PFS was 3.5 months [3.3; 3.7]. Probability of MH for PHC. We identified left hepatectomy as an independent factor
sorafenib discontinuation or death before 12 months was 85%. positively influencing TO. In patients where both right- and left-sided
Conclusion: These results confirmed the high clinical burden of resections are feasible, this underlines the importance of a careful
treated HCC regardless of the cause of CLD. selection of patients who are scheduled for right hepatectomy.
OS in this real-world setting study is lower than in clinical trials and
THU571
consistent according to all etiologies.
Impact of body mass index in patients receiving atezolizumab
Earlier management adapted as well as the arrival of new treatments
plus bevacizumab for hepatocellular carcinoma
such as immunotherapy, will improve the prognosis of patients.
Mathew Vithayathil1, Antonio D’Alessio1,2, Arndt Weinmann3,
Peter Galle3, Claudia Angela Maria Fulgenzi1,4, Petros Fessas1,
THU570
Dominik Bettinger5, Bertram Bengsch5, Arndt Vogel6, Lorenz Balcar7,
Textbook outcome after major hepatectomy for perihilar
Bernhard Scheiner7, Mahvish Muzaffar8, Suneetha Amara8,
cholangiocarcinoma-definitions and influencing factors
Ambreen Muhammed1, Abdul Rafeh Naqash8, Nicola Personeni2,9,
Christian Benzing1, Lena Haiden1, Felix Krenzien1, Alexa Mieg1,
Tiziana Pressiani9, Antonella Cammarota2,9, Matthias Pinter7,
Annika Wolfsberger2, Cecilia Atik1, Nora Nevermann1,
Alessio Cortellini1,10, Lorenza Rimassa2,9, David J. Pinato1,11,
Uli Fehrenbach2, Wenzel Schöning1, Moritz Schmelzle1,
Rohini Sharma1. 1Imperial College London, United Kingdom;
Johann Pratschke1. 1Charité University Medicine Berlin, Department of 2
Humanitas University, Italy; 3Universitätsmedizin der Johannes
Surgery | Campus Charité Mitte and Campus Virchow Klinikum, Berlin,
Gutenberg-Universität Mainz, Mainz, Germany; 4Bio-Medico Campus
Germany; 2Charité University Medicine Berlin, Department of
University Hospital, Roma, Italy; 5University of Freiburg, Freiburg
Diagnostic and Interventional Radiology, Berlin, Germany
University Medical Center, Freiburg im Breisgau, Germany; 6Hannover
Email: [email protected]
Medical School, Hannover, Germany; 7Medical University of Vienna,
Background and aims: The concept of “textbook outcome” (TO) as Wien, Austria; 8East Carolina University, Greenville, United States;
9
composite quality measure depicting the ideal surgical outcome has Humanitas Research Hospital, Cascina Perseghetto, Italy; 10University
not yet been defined for patients undergoing major hepatectomy of L’Aquila, L’Aquila, Italy; 11University of Eastern Piedmont, Vercelli,
(MH) which remains the only curative therapy option for perihilar Italy
cholangiocarcinoma (PHC). This study aimed to propose a uniform Email: [email protected]
definition through a systematic literature review as well as to identify
Background and aims: Atezolizumab plus bevacizumab is the new
patient- or procedure-related factors influencing TO.
first line-treatment for unresectable hepatocellular carcinoma (HCC).
Method: In this retrospective study, we analyzed all patients
Body mass index (BMI) has demonstrated predictive value for
undergoing MH for PHC at our department between January 2005
response to immunotherapy in non-HCC cancer types. Our study
and August 2019. After conducting a systematic literature search, we
investigated the effect of BMI on safety and efficacy of real-life use of
defined TO as the absence of 90-day mortality and major complica-
atezolizumab plus bevacizumab.
tions, no hospital readmission within 90 days after discharge, and no

S374 Journal of Hepatology 2022 vol. 77(S1) | S119–S388

 POSTER PRESENTATIONS
Method: Sixty-four consecutive patients from seven centres receiv- Method: From December 2006 to January 2020, consecutive 309
ing atezolizumab plus bevacizumab were included in the retrospect- unresectable ICC patients were enrolled. Of them, 162 ICC patients
ive study. Overall survival (OS), progression-free survival (PFS), received chemotherapy as first-line treatment were retrospectively
overall response rate (ORR) and disease control rate (DCR) defined reviewed, and 123 patients had evaluable images for tumour
by RECIST v1.1 were measured in overweight (BMI ≥ 25) and non- response evaluation. Objective response rate (ORR) and overall
overweight (BMI < 25) patients. Treatment-related adverse events survival (OS) were assessed and factors associated with ORR and OS
(trAEs) were evaluated for each BMI cohort. were analysed.
Results: Baseline Child-Pugh class, Eastern Cooperative Oncology Results: Of the 162 ICC patients received chemotherapy as first-line
Group performance status and Barcelona Clinic Liver Cancer stage therapy, the mean age was 62 years old. Most patients were within
was similar between overweight (n = 36) and non-overweight Child-Pugh class A (61.7%) and Albumin-bilirubin (ALBI) grade 2/3
patients (n = 28). Underling non-alcoholic fatty liver disease was (67.3%). Of them, 106 (65.4%) received gemcitabine-based regimen,
more prevalent in overweight patients (27.8 vs. 7.1%; p = 0.04). while 56 (34.6%) patients received fluoropyrimidine-based regimen.
Overweight patients had a longer OS compared to non-overweight The ORR was 26.0% and disease control rate (DCR) was 48.0% in the
(median OS 11.6 vs. 7.5 months; p = 0.045) (Figure 1). BMI did not whole 123 ICC patients with evaluable images (including 32 partial
influence median PFS (6.9 vs. 3.0 months; p = 0.34), ORR (26.7% vs. responses, 27 stable diseases, and 64 progressive disease). HBV
25.0%; p = 0.90) and DCR (63.3% vs. 60.0%; p = 0.81). trAEs were infection (OR, 3.223; p = 0.032), gemcitabine-based regimen (OR,
comparable between the two groups (atezolizumab-related 44.4% vs. 4.714; p = 0.008) were the independent predictors of ORR. In general,
53.6%; p = 0.47 and bevacizumab-related 18.8% vs. 12.5%; p = 0.68). the median OS of the 162 ICC patients was 6.1 months. Presence of
cirrhosis, Albumin ≤3.5 g/dl, Child-Pugh B/C, ALBI grade 2/3, NLR ≧ 3,
and CA 19-9 ≧ 300 U/ml were independent risk factors associated
with OS. A novel ALBI‐based scoring system to predict OS was created,
the patients could be classified into 4 groups. Kaplan‐Meier analysis
showed that the new ALBI‐based model could significantly discrim-
inate OS between contiguous groups ( p < 0.001, Figure).
Noteworthily, patients without any risk factors had a promising
overall survival of 21.3 months.

Figure: Kaplan-Meier curve showing increased overall survival (months)

for overweight patients compared to non-overweight unresectable hepa-
tocellular carcinoma patients after atezolizumab plus bevacizumab
administration.

Conclusion: Higher BMI is associated with increased OS in HCC

patients receiving atezolizumab plus bevacizumab for unresectable
HCC, without an increase in trAEs. BMI may have a predictive role in
immunotherapy treatment response in HCC. Conclusion: Albumin-bilirubin grade is an important factor asso-
ciated with survival in unresectable ICC patients receiving chemo-
THU572 therapy. The new ALBI‐based model can be applied to select patients
Outcome predictors of gemcitabine-based or fluoropyrimidine- who can get the best benefit from chemotherapy.
based chemotherapy for unresectable intrahepatic Conflict of interest: The authors declared no conflicts of interest.
cholangiocarcinoma Funding: The work was partly supported by the Taipei Veterans
Chen-Ta Chi1,2, I-Cheng Lee1, Ming-Huang Chen3, Pei-Chang Lee1, General Hospital, Taipei, Taiwan (grant numbers V110A-004).
Yi-Ping Hung3, Ming-Chih Hou1, Yee Chao3, Yi-Hsiang Huang1,2.
1
Taipei Veterans General Hospital, Taipei, Taiwan, Division of THU573
Gastroenterology and Hepatology, Department of Medicine; 2National Transarterial radioembolisation in non resectable hepatocellular
Yang Ming Chiao Tung University, Taipei, Taiwan, Institute of Clinical carcinoma in curative strategies: a single centre experience
Medicine, School of Medicine; 3Taipei Veterans General Hospital, Taipei, Helene Regnault1, Clara Perrin2, Giuliana Amaddeo1, Sebastien Mulé1,
Taiwan, Department of Oncology Hicham Kobeiter1, Edouard Reizine1, Emmanuel Itti1,
Email: [email protected] Christophe Duvoux1, Alexis Laurent1, Vincent Leroy1,
Raffaele Brustia1, Daniele Sommacale1, Françoise Roudot-Thoraval1,
Background and aims: Intrahepatic cholangiocarcinoma (ICC) is a
Lerman Lionel1, Alain Luciani1, Julien Calderaro1, Julia Chalaye1,
highly aggressive malignancy, and the resectability rate for curative
Vania Tacher1, Athena Galletto3. 1Henri Mondor University Hospital,
surgical resection is low. Gemcitabine-based and fluoropyrimidine-
Hepatology, Créteil, France; 2Antoine Beclere University Hospital,
based chemotherapy are the mainstay treatments for Unresectable
Hepatology, Clamart, France; 3Henri Mondor University Hospital,
ICC, even though the survival is still far from satisfaction in real-world
Medical Imaging, Creteil, France
experience. This study aimed to assess outcomes and identify the
Email: [email protected]
prognostic factors for patients with unresectable ICC patients
receiving gemcitabine-based or fluoropyrimidine-based Background and aims: Transarterial radioembolisation (TARE) has
chemotherapy. the potential to be curative either directly (radiation segmentectomy)
or as neoadjuvant strategy before resection or transplantation.

Journal of Hepatology 2022 vol. 77(S1) | S119–S388 S375

POSTER PRESENTATIONS
However, its place remains largely debated. The aim of our study was THU574
to evaluate the outcome of initially non-operative patients after TARE Preliminary evidence of safety and tolerability of atezolizumab
in a single tertiary centre. plus bevacizumab in patients with hepatocellular carcinoma and
Method: This retrospective, observational study included all con- Child-Pugh A and B cirrhosis: a real-world study
secutive patients treated by TARE in our centre between october 2013 Antonio D’Alessio1,2, Arndt Weinmann3, Peter Galle3,
and june 2020. Clinical, biological and imaging data were collected at Vincent Gaillard4, Claudia Angela Maria Fulgenzi1,5,
baseline and every 3 months during follow-up. Tumour response was Dominik Bettinger6, Bertram Bengsch6, Arndt Vogel7, Lorenz Balcar8,
evaluated at 6 months according to Response Evaluation Criteria in Bernhard Scheiner8, Suneetha Amara9, Mahvish Muzaffar9,
Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST). The Abdul Rafeh Naqash9,10, Nicola Personeni2,11, Tiziana Pressiani11,
suitability of surgical treatment after downstaging was systematically Rohini Sharma1, Matthias Pinter8, Alessio Cortellini1,
discussed in a weekly tumour board. Lorenza Rimassa2,11, David J. Pinato1,12. 1Imperial College London,
Results: 128 patients (male = 90%, mean age 64 years) were included. Department of Surgery and Cancer, London, United Kingdom;
The majority (n = 88%) had cirrhosis (CPT A: 84%, CPT B: 16%) mainly 2
Humanitas University, Department of Biomedical Sciences, Italy;
due to viral hepatitis (21%), non-alcoholic steatohepatitis (18%) and 3
Johannes Gutenberg University of Mainz, Mainz, Germany;
4
alcohol (18%). HCC was classified as BCLC A: n = 14 (11%), BCLC B: n = F. Hoffmann-La Roche Ltd., Basel, Switzerland; 5Policlinico Universitario
50 (39%) and BCLC C: n = 64 (50%). The majority of patients had an Campus Bio-Medico, Division of Medical Oncology, Roma, Italy;
imaging infiltrative pattern: n = 52 (41%), a median diameter of 6
Department of Medicine II (Gastroenterology, Hepatology,
50 mm and portal vein invasion (n = 62, 49%) classified as VP1: n = 3, Endocrinology and Infectious Diseases), Freiburg University Medical
VP 2: n = 22, VP3: n = 28 and VP4: n = 9. Median AFP was 115. TARE Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany;
7
was the first-line therapy in 77 patients. TARE could be successfully Hannover Medical School, Hannover, Germany; 8Division of
applied in all patients. At 6 months, the rates of complete and partial Gastroenterology and Hepatology, Department of Internal Medicine III,
responses were 4 and 40% respectively, according to RECIST and 23 Medical University of Vienna, Vienna, Austria; 9Division of Hematology/
and 28% according to mRECIST. A downstaging was obtained in 50 Oncology, East Carolina University; 600 Moye Boulevard, Greenville, NC,
(39%) patients, whom 29 (23%) had access to a curative treatment 27834, USA; 10Medical Oncology/TSET Phase 1 program, Stephenson
(transplantation: n = 17 (13%), resection: n = 11 (9%) and ablation: n = Cancer Center, University of Oklahoma USA; 11IRCCS Humanitas
1) in a median time of 4.3 months. Absence of access to surgery was Research Hospital, Humanitas Cancer Center, Cascina Perseghetto, Italy;
due to general contra-indication (n = 10), progression (n = 5), refusal 12
Division of Oncology, Department of Translational Medicine,
(n = 4) and presence on waiting list (n = 2). Median overall survival of University of Piemonte Orientale, Novara, Italy
patients with or without downstaging were 50.1 months [8.6–78.8] Email: [email protected]
and 10.2 months [8.1–12.4] ( p < 0, 001) respectively. Progression free
survival (PFS) of patients with or without downstaging were 20.8 Background and aims: Atezolizumab plus bevacizumab (A+B) is new
months [14.8–26.8] and 5.4 months [4.7–6.1] ( p < 0, 001) respect- standard of care for first-line treatment of unresectable hepatocel-
ively. In patients who achieved downstating, PFS was higher in lular carcinoma (HCC). No evidence exists as to its use in routine
patients who had surgery (median not achieved). Two variables were clinical practice in patients with impaired liver function.
independently associated to downstaging: BCLC score ( p = 0, 049) Method: This retrospective, multi-centre observational study was
and ALBI score ( p = 0.042). conducted across 7 tertiary centres and collected 64 HCC patients
consecutively treated with A+B. Safety outcomes included treatment-
related adverse events (trAEs) graded according to CTCAE v5.0. We
also assessed overall survival (OS), progression-free survival (PFS),
overall response (ORR) and disease control rates (DCR) defined by
RECIST v1.1 in patients treated according to label.
Results: Fifty-four patients had Barcelona Clinic Liver Cancer (BCLC)-
C stage HCC (84%), mostly secondary to non-viral aetiology (n = 30;
47%) and Hepatitis C virus (n = 24; 37%). Forty-three patients (67%)
suffered from any trAE, of which 11 (17%) were G3 and 1 (2%) G4.
Compared to Child-Pugh A (n = 46, 72%), Child-Pugh B patients
showed comparable distribution of trAEs, with similar rates of
bevacizumab-related bleedings and atezolizumab-related AEs. In the
44 patients (69%) with a pre-treatment esophagogastroduodeno-
scopy, presence and grade of varices did not correlate with
gastrointestinal bleeding events. Median OS of patients treated in
first line was 12.7 months (95% CI, 7.6–12.7), while median PFS was
Conclusion: These results suggest that TARE could be an effective 6.97 months (95% CI, 2.8–11.3). ORR and DCR were respectively 29%
treatment leading to downstaging of 40% patients with unresectable and 67%, with no difference between patients with Child-Pugh A and
HCC, and allowed curative treatment in 57% of them. Combination of B cirrhosis.
TARE followed by curative treatment is associated with a 2 year- Conclusion: This study confirms reproducible efficacy and safety
survival of 70% vs 0% in patients with no downstaging. of A + B in routine practice. Child-Pugh B patients had similar
tolerability and radiologic response compared to Child-Pugh A
patients, warranting prospective evaluation of atezolizumab plus
bevacizumab in this treatment-deprived population.

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 POSTER PRESENTATIONS
THU575 THU576
Comparative effectiveness of treatment for early-stage Twenty-year trends in radiofrequency ablation for treatment-
intrahepatic cholangiocarcinoma naive hepatocellular carcinoma within the Milan criteria
Yi-Te Lee1, Amit Singal2, Marie Lauzon3, Michael Luu3, Se Young Jang1, Soo Young Park1, Yu Rim Lee1, Young Oh Kweon1,
Vatche Agopian1, Mazen Noureddin3, Tsuyoshi Todo3, Irene Kim3, Won Young Tak1, Won Kee Lee2, Sungmin Kim3. 1School of Medicine,
Kambiz Kosari3, Nicholas Nissen3, Gregory Gores4, Ju Dong Yang3. Kyungpook National University, Kyungpook National University
1
University of California, Los Angeles, Los Angeles, United States; Hospital, Internal Medicine, Daegu, Korea, Rep. of South; 2School of
2
University of Texas Southwestern Medical Center, United States; Medicine, Kyungpook National University, Medical Informatics;
3
Cedars-Sinai Medical Center, Los Angeles, United States; 4Mayo Clinic 3
University of Ulsan, Biomedical Engineering, Korea, Rep. of South
Rochester MN, Rochester, United States Email: [email protected]
Email: [email protected]
Background and aims: Radiofrequency ablation (RFA) is widely used
Background and aims: Incidence rates of intrahepatic cholangio- to treat hepatocellular carcinoma (HCC) because of its safety, cost
carcinoma (iCCA) continue to increase in western countries. Despite effectiveness, and liver function conservation. We examined tem-
increases in the detection of early-stage iCCA, comparative effective- poral trends in the long-term results of percutaneous RFA for
ness of treatment for early-stage iCCA remains unknown. treatment-naïve HCC within the Milan criteria and analysed factors
Method: We performed a retrospective cohort study using the affecting treatment outcomes.
National Cancer Database (NCDB),. Method: We retrospectively analysed 1, 099 HCC cases within the
which represents more than 70 percent of newly diagnosed cancer Milan criteria treated with percutaneous RFA from January 2000 to
cases nationwide. Patients diagnosed with single iCCA less than 3 cm December 2019 at a single tertiary hospital. The follow-up period
in size without lymph node or extrahepatic involvement between ranged from 0.3 to 247.9 months (median: 53.2 months). Overall
2004 and 2018 were analyzed. Multivariable cox regression was used survival, recurrence-free survival, and factors affecting survival and
to compare the efficacy of treatments. Propensity score matched progression were analysed. A trend test was performed to analyse the
analyses were performed to compare the outcome between resec- changing trends of subject characteristics and treatment outcome.
tion, liver transplant, and local ablation. Results: The overall and recurrence-free survival rates of patients
Results: 1093 patients received the following treatments: 464 (42%) improved in the later period. Viral hepatitis-related HCC decreased,
resection, 113 (10%) ablation, 62 (6%) transplant, and 454 (42%) other while alcohol- or non-alcoholic fatty liver disease-related
noncurative treatments including best supportive care. Overall HCC increased from the earlier to the later period (P for trend
median survival was 71.1 months (95% confidence interval [CI]: <0.001). Tumour size and alpha-fetoprotein levels decreased. Older
60.5–93.7), 48.0 months (95% CI: 33.1–52.1), 11.7 months (95% CI: age ( p < 0.001), Child-Pugh class B ( p < 0.001), the presence of
10.4–14.3) for resection, ablation, and other treatments, respectively. cirrhosis ( p < 0.001), non-viral aetiology ( p < 0.001), and large
Median survival was not reached in patients who received liver tumour size ( p = 0.001) were independent prognostic factors that
transplant (95% CI: 77.4-nonestimable). One, three, and five year predicted poor overall survival. Only large tumour size predicted local
survival were 89% (95% CI: 86%–92%), 68% (95% CI: 63%–73%), 56% tumour progression ( p < 0.001). Tumour location, such as subcap-
(95% CI: 51%–62%) for resection, 89% (95% CI: 83%–96%), 54% (95% CI: sular, subphrenic, or perivascular, was not a significant factor in
45%–66%), 33% (95% CI: 23%–47%) for ablation, 89% (95% CI: 81%– survival or local tumour progression.
98%), 73% (95% CI: 62%–86%), 68% (95% CI: 56%–83%) for liver Conclusion: Twenty-year outcomes of RFA showed excellent results
transplant, 49% (95% CI: 44%–55%), 20% (95% CI: 16%–25%), 13% (95% in treating early-stage HCC within the Milan criteria. Both subject
CI: 10%–17%) for other treatments ( p < 0.001) (Figure 1A). With characteristics and treatment outcomes of have changed over time.
surgical resection as a reference group, patients receiving liver Advances in technology and antiviral therapy have improved
transplant had improved overall survival (adjusted hazard ratio treatment outcomes.
[aHR]: 0.61, 95% CI: 0.38–1.00) while those who underwent ablation
(aHR: 1.32, 95% CI: 0.96–1.82) or other noncurative treatments (aHR: THU577
3.95, 95% CI: 3.24–4.82) had worse overall survival. Propensity score Incidence of hepatocellular carcinoma reduced in chronic
matched analyses showed a trend toward higher mortality with hepatitis B patients treated with entercavir plus Biejia-Ruangan:
ablation than resection (aHR: 1.46, 95% CI: 0.91–2.36) (Figure B) and extended follow-up of a multicenter, randomised, double-
reduced mortality with liver transplant compared to resection (aHR: blinded, placebo-controlled trial
0.37, 95% CI: 0.18–0.78) (Figure C). Dong Ji1, Yan Chen1, Zheng Dong1, Xiao-he Xiao1, Yongping Yang1.
1
Fifth Medical Center of Chinese PLA General Hospital, Senior
Department of Hepatology, Beijing, China
Email: [email protected]
Background and aims: Chronic hepatitis B virus (HBV) infection and
liver cirrhosis have been proven to be high-risk factors for
hepatocellular carcinoma (HCC), which is the fifth most common
tumour worldwide and the second most common cause of cancer-
related death in China. Over the past two decades, progress has been
made in treating fibrosis with traditional Chinese medicine due to
their multi-targeted molecular mechanism. In the present study, we
Conclusion: In early-stage iCCA patients, curative treatments are
aimed to compare incidence of HCC in chronic hepatitis B (CHB)
associated with improved survival. Surgical resection and liver
patients treated with entecavir (ETV) plus Biejia-Ruangan (BJRG)
transplantation are associated with improved survival compared to
versus entecavir (ETV) plus placebo.
ablation.
Method: In this study, we extended to followed up the participants of
a multicenter, randomised, double-blinded, placebo-controlled trial
(NCT01965418) after the end of the original trial. Originally, we had
randomised 1000 CHB patients in equal numbers (1:1) to receive
either ETV plus BJRG or ETV plus placebo treatment. The eligible
patients underwent paired biopsies at treatment baseline and week
72. Afterward, patients entered a long-term prospective

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POSTER PRESENTATIONS
observational open-label study, and were monitored at least every 12 DXR to cancer cells, with the double aim of enhancing its activity and
weeks. Surveillance for HCC was performed by ultrasonography and decreasing its off-target toxicity.
alpha-fetoprotein (AFP) at each visit. HCC was diagnosed by multi- Method: Two liposomal formulations were evaluated, i.e. atezolizu-
phase dynamic contrast-enhanced MRI. Intention-to-treat analysis mab-targeted liposomal DXR (Stealth ImmunoLiposomes,
was performed with the use of Kaplan-Meier curves and log-rank SIL_atezolizumab) and untargeted liposomal DXR (Stealth Liposomes,
test. The incidence of HCC was estimated with Cox proportional SL). The in vitro cytotoxicity of liposomal doxorubicin was evaluated
hazards regression models. after 72 h of treatment by means of the ATP assay on the three PD-L1
Results: Totally 1000 patients who received randomised treatment, expressing HCC cell lines Hu7, HepG2 and Hepa1–6 (Figure). In vivo
946 (94.6%) patients entered the open-label phase, and 872 (87.2%) efficacy was evaluated in a syngeneic HCC mouse model, obtained by
completed 84-month follow-up. Overall (during a median follow-up injecting the murine HCC cells Hepa1–6 in C57BL/6J immunocompe-
of 89.0 months), 23 (4.6%) in ETV plus BJRG group and 43 (8.6%) tent mice. SIL_atezolizumab and SL were administered e.v. once a week
patients in ETV plus placebo group developed HCC, cumulative HCC for 4 weeks. Tumor volumes were measured byan electronic caliper and
incidence was notably lower for ETV plus BJRG group than ETV plus collected and weighed at sacrifice for further analyses.
placebo group (HR 0.52, 95%CI 0.32–0.87, P = 0.001). one (0.2%) Results: Atezolizumab targeting increased the in vitro cytotoxic effect
patient in the ETV plus BJRG group and 13 (2.6%) patients in the of liposomal DXR in HepG2 and Hepa1–6 cells, showing significant
placebo group died. While there was no significant difference in non- lower IC50 values with respect to SL ( p < 0.01 and p < 0.05,
HCC events (e.g., colorectal, thyroid or pancreatic cancer, upper respectively). Both SL and SIL_atezolizumab decreased tumor
gastrointestinal bleeding, ascites, etc.) between the two groups (HR growth in vivo since tumor volumes measured at sacrifice were
0.47, 95%CI 0.12–1.89, P = 0.280). significantly lower in treated mice compared to controls ( p < 0.05). A
slight increase of survival was observed in SIL_atezolizumab treated
mice.
Conclusion: PD-L1-targeted liposomal doxorubicin is effective in
limiting HCC cells growth in vitro and in vivo. This approach could
open new avenues for HCC therapy, using two already approved two
drugs, joined in a novel combined formulation.

THU579
LiMAx faciliates patient selection prior radioembolization for
patients with hepatocellular carcinoma in liver cirrhosis
Catherine Leyh1, Niklas Heucke2, Clemens Schotten1,
Figure: Cumulative incidence of HCC and Non-HCC events in ETV plus
Matthias Buechter1, Lars Bechmann3, Marc Wichert4,
BJRG or ETV plus placebo groups
Alexander Dechene5, Ken Hermann6, Antonios Katsounas7,
Conclusion: Comparing to ETV plus placebo treatment, ETV plus Mustafa Özcürümez7, Dominik Heider8, Svenja Sydor7,9,
BJRG could further markedly reduce the incidence of HCC in chronic Johannes M. Ludwig6, Jens Theysohn6, Robert Damm10,
hepatitis B patients. Maciej Powerski10, Maciej Pech10, Ali Canbay7, Jochen Weigt2,
Verena Keitel-Anselmino1, Christian Lange1, Jan Best7, Paul Manka7.
THU578 1
University Hospital Essen, Department of Gastroenterology and
In vitro and in vivo preclinical efficacy of PD-L1-targeted Hepatology, Essen, Germany; 2Otto-von-Guericke University Hospital
liposomal doxorubicin as a combined therapy for the treatment of Magdeburg, Department of Gastroenterology, Hepatology and Infectious
hepatocellular carcinoma Diseases, Magdeburg, Germany; 3University Hospital
Daniela Gabbia1, Antonella Grigoletto2, Luana Cannella1, Knappschaftskrankenhaus Bochum, Deparetment of Internal Medicine,
Ilaria Zanotto1, Veronica Mazzucco1, Gianfranco Pasut2, Bochum, Germany; 4University Hospital Essen, Central Laboratory,
Sara De Martin1. 1University of Padova, Dept. of pharmaceutical and Essen, Germany; 5University Hospital Nürnberg, Nürnberg, Germany;
6
pharmacological sciences, Padova, Italy; 2University of Padova, Dept of University Hospital Essen, Radiology, Essen, Germany; 7University
pharmaceutical and pharmacological sciences, Padova, Italy Hospital Knappschaftskrankenhaus Bochum, Department of Internal
Email: [email protected] Medicine, Bochum, Germany; 8University Margurg, Marburg, Germany;
9
University Hospital Knappschaftskrankenhaus Bochum, Department of
Background and aims: Hepatocellular carcinoma (HCC), the primary
Internal Medicine, Bochum, Germany; 10Otto-von-Guericke University
malignancy of the liver and the outcome of chronic liver diseases of
Hospital Magdeburg, Radiology, Magdeburg, Germany
different etiologies, remains a global health challenge, due to the lack
Email: [email protected]
of effective therapeutic options. The aim of this study is to evaluate a
novel liposomal doxorubicin (DXR) formulation targeted with the Background and aims: LiMAx is a non-invasive test for liver function,
PD-L1 checkpoint inhibitor atezolizumab, for the selective delivery of measuring the maximum metabolic capacity for 13C-Methacetin by

Figure: (abstract: THU578): Anti-proliferative effect of liposomal doxorubicin and IC50 values after 72 h-treatment.

S378 Journal of Hepatology 2022 vol. 77(S1) | S119–S388

 POSTER PRESENTATIONS
the liver-specific enzyme CYP 450 1A2. Recently, radioembolization C. Median overall survival (OS) was not reached, and the 6-months
(RE) has demonstrated a non-inferior survival outcome compared to survival rate was 83.0%. The median follow-up duration was 6.4
systemic therapy for advanced hepatocellular carcinoma (HCC). months, and the median time to progression (TTP) was 6.8 months.
Therefore, current guidelines recommend RE for patients with Overall response rate (ORR) in 1st-line and later-line were 30.5 and
advanced HCC and preserved liver function who are unsuitable for 13.5%. Disease control rate (DCR) in 1st-line and later-line were 86.1%
transarterial chemoembolization (TACE) or systemic therapy. and 66.7%. Discontinuation of atez+bev due to disease progression
However, despite the excellent safety profile of RE, post-therapeutic was observed in 33 patients, while discontinuation due to adverse
hepatic decompensation remains a serious complication that is events was reported in 12 patients. In the 12 patients, lenvatinib (n =
difficult to be predicted by standard laboratory liver function 4), sorafenib-regorafenib (n = 1), cabozantinib (n = 3), and TACE (n =
parameters or imaging modalities. Our study investigates the 3) were performed after atez+bev. Three patients received multiple
potential of LiMAx for predicting post-interventional. therapies. Four of 12 (33%) patients received only supportive therapy.
Method: In total, 50 patients with HCC with or without liver cirrhosis In the 33 patients with disease progression, 5 patients (15%) received
and not amenable to conventional locoregional or systemic treat- only supportive therapy, and all 5 patients were pretreatment PS 1 or
ments were included in the study. The study was carried out in a two- modified ALBI 2b. Of the 33 patients, 2 were treated with HAIC, and
step fashion, including a retrospective and a prospective cohort. In 26 received other molecular targeted therapies after atez+bev.
both cohorts, LiMAx was carried out one day before RE (baseline). Sorafenib was administrated after atez+bev in 5 patients, and 2
Standard liver function parameters were assessed at baseline, day 28, patients showed SD. Regorafenib was started in 4 patients, and 2
and day 90 after RE. First, the relationship between baseline LiMAx patients showed SD. Lenvatinib was started in 12 patients, and ORR
and pre-and post-interventional liver function parameters was and DCR were 22% and 67%. Ramucirumab was administered in 3
analyzed in the retrospective cohort and subsequently validated in patients, and 1 patient showed SD. Cabozantinib was started in 14
the prospective cohort. Subsequently, the ideal cutoff for LiMAx to patients, and ORR and DCR were 14% and 80%. In total, 33 of 45 (73%)
predict post-interventional hepatic decompensation has been deter- patients who discontinued atez+bev received molecular targeted
mined in the prospective part of the study. therapy.
Results: We observed a significant correlation between baseline Conclusion: Discontinuation of atez+bev due to adverse events in
LiMAx and Bilirubin, Albumin, ALBI-Grade, and MELD Score, real-world practice was similar to the clinical trial, and all patients
especially at day 28 in the prospective cohort. Patients presenting with pretreatment PS 0 and modified ALBI 1 or 2a could receive post-
with Child-Pugh B Score 28 days after RE had a significantly lower atez+bev therapies after disease progression. The efficacy of molecu-
baseline LiMAx than those with a Child-Pugh A Score (223.5 μg/kg/h lar targeted agents after atez+bev would be different from the results
vs. 309 μg/kg/h, p = 0.0263). Using the ROC curve analysis, the of the past clinical trials without immunotherapy.
potential of LiMAx for predicting hepatic decompensation after RE
was determined and compared to MELD Score and ALBI Grade. LiMAx THU581
achieved an AUC of 0.8117. Patients with LiMAx values <238 μg/kg/h The LiMAx level before transarterial chemoembolization or
had a significantly higher risk of suffering hepatic decompensation radioembolization is a predictor for short-time survival in
after RE. patients with early stage HCC
Conclusion: Patients with low LiMAx values (<238 μg/kg/h) despite Janett Fischer1, Stella Wellhöner1, Sebastian Ebel2,
Child-Pugh A situation at baseline have a significantly increased risk Bettina Maiwald2,3, Steffen Strocka2,3, Tim-Ole Petersen2,3,
of hepatic decompensation after RE. Therefore, LiMAx can be used as Albrecht Boehlig1, Florian Gerhardt1, Rhea Veelken1, Timm Denecke2,
an additional tool to identify patients at high risk of post- Thomas Berg1, Florian van Bömmel1. 1Division of Hepatology,
interventional hepatic failure. Department of Medicine II, University Hospital Leipzig, Leipzig,
Germany; 2Department of Diagnostic and Interventional Radiology,
THU580 University Hospital Leipzig, Leipzig, Germany; 3Clinic for Diagnostic and
The efficacy of molecular targeted therapies after atezolizumab Interventional Radiology, St. Elisabeth and St. Barbara Hospital Halle,
plus bevacizumab in patients with unresectable hepatocellular Halle (Saale), Germany
carcinoma (HCC) in Japan Email: [email protected]
Kaoru Tsuchiya1, Yuka Hayakawa1, Yutaka Yasui1, Tatsuya Kakegawa1,
Background and aims: Transarterial chemoembolization (TACE) and
Mayu Higuchi1, Kenta Takaura1, Shohei Tanaka1, Chiaki Maeyashiki1,
transarterial radioembolization (TARE) are standard treatment
Shun Kaneko1, Nobuharu Tamaki1, Hiroyuki Nakanishi1,
strategies for patients with hepatocellular carcinoma (HCC). The
Masayuki Kurosaki1, Namiki Izumi1. 1Musashino Red Cross Hospital,
liver maximum capacity test (LiMAx) is a potential monitoring tool
Department of Gastroenterology and Hepatology, Japan
for post-interventional liver failure. The study aimed to investigate
Email: [email protected]
the correlation of LiMAx with patients’ response to TACE or TARE
Background and aims: In systemic therapy for unresectable HCC, 6 treatment and the severity of adverse events after therapy as well as
regimens (sorafenib, regorafenib, lenvatinib, ramucirumab, atezoli- short-term and overall survival.
zumab plus bevacizumab, and cabozantinib) have been approved in Method: In this study, 69 patients with TACE (n = 57) or TARE (n = 12)
Japan. Atezolizumab plus bevacizumab (atez+bev) is recommended treatment were enrolled. Liver function was assessed on the day
as 1st-line, and there is no established regimen after atez+bev. We before as well as at 4 weeks after TACE or TARE using the LiMAx test
investigated the efficacy of the other 5 regimens after atez+bev. and the well-established biochemical markers as well as MELD,
Method: A total of 76 patients who received atez+bev at our CHILD Pugh and ALBI scores. Adverse events were each recorded over
institution between Oct 2020 and Sep 2021 was enrolled. 4 weeks after the intervention. Survival was followed up until 3 years.
Tumor assessments in accordance with RECIST v1.1 were done using Results: A complete response to TACE/TARE and stable disease were
dynamic CT or MRI every 6–12 weeks. Clinical course, including the observed in 10.3% and 51.5% of patients, respectively, and progressive
efficacy of molecular targeted therapies after atez+bev was investi- disease in 38.2%. Mild adverse events developed in 48.5% of patients
gated retrospectively. whereas 14.7% suffered from severe complications such as ascites and
Results: The median age of the patients was 73 years. The median hepatic encephalopathy. LiMAx levels did not show a significant
ALBI score was −2.19, and 58% of the patients were modified ALBI association with the occurrence of adverse events, laboratory
grade 2b. Line of treatment was 1st (n = 41), 2nd (n = 19), 3rd (n = 7), 4th parameters, liver function-associated scores and tumor response.
(n = 5), 5th (n = 3), and 6th-line (n = 1). Forty-eight (63%) of the However, survival analysis showed significant lower 30-day and 60-
patients were BCLC stage B, and 28 patients were BCLC stage day survival rates for patients with LiMAx ≤150 μg/kg/h before

Journal of Hepatology 2022 vol. 77(S1) | S119–S388 S379

POSTER PRESENTATIONS
treatment compared to patients with LiMAx >150 μg/kg/h levels (30-
day: 86.7% ± 8.8% vs. 100%, p = 0.006; 60-days: 86.7% ± 8.8% vs. 98.1%
± 1.8%, p = 0.048). When the patients were divided into groups
according to the BCLC stage (BCLC A: n = 32, BLCL B: n = 29),
significant differences in survival rates were detected for early but
not for intermediate disease stage. The survival rates of patients with
BCLC A stage with LiMAx ≤150 μg/kg/h were significantly lower after
30 days (75.0% ± 15.3% vs. 100%, p = 0.011) and 90 days (62.5% ± 17.7%
vs. 95.8% ± 4.1%, p = 0.011) compared to those of patients with higher
LiMAx levels. This was even more pronounced after 180 days with
50.0% ± 17.7% vs. 95.8% ± 4.1%, ( p = 0.001) survival. Figure 1: Overall (A) and Disease-free survival (B) after curative resection
Conclusion: The LiMAx test identifies patients with early stage HCC for perihilar cholangiocarcinoma according to the proposed prognostic
and reduced short-time survival after transarterial treatment. score.

Conclusion: We proposed a simple scoring system that showed

THU582
highly significant correlations with the clinical outcome (DFS and
Implementation of a new prognostic scoring system after major
OS). This is of particular clinical significance since it allows a better
hepatectomy in curative intent for perihilar cholangiocarcinoma
risk stratification when compared to conventional scoring systems
Christian Benzing1, Thea-Charlotte Fritsch1, Lena Haiden1,
such as UICC and Bismuth stages.
Felix Krenzien1, Alexa Mieg1, Annika Wolfsberger1, Cecilia Atik1,
Nora Nevermann1, Uli Fehrenbach2, Wenzel Schöning1, THU583
Moritz Schmelzle1, Johann Pratschke1. 1Charité University Medicine The effect of discordance between preoperative imaging and
Berlin, Department of Surgery | Campus Charité Mitte and Campus postoperative pathology on the prognosis of hepatocellular
Virchow Klinikum, Berlin, Germany; 2Charité University Medicine Berlin, carcinoma
Department of Diagnostic and Interventional Radiology, Berlin, Germany Woo Sun Rou1, Byung Seok Lee2, Hyuk Soo Eun2, Seok Hyun Kim2,
Email: [email protected] Hong Jae Jeon2, In Sun Kwon3. 1Chungnam National University Sejong
Background and aims: Major hepatectomy (MH) is the only curative Hospital, Gastroenterology and Hepatology, Sejong-si, Korea, Rep. of
therapy option for patients with perihilar cholangiocarcinoma (PHC). South; 2Chungnam National University Hospital, Gastroenterology and
Despite recent advancements in adjuvant treatments and periopera- Hepatology, Daejeon city, Korea, Rep. of South; 3Chungnam National
tive management, recurrence rates are still high and overall prognosis University Hospital, Clinical Trial Center, Statistics Office, Biomedical
is poor. Current staging systems such as the American Joint Research Institute, Daejeon city, Korea, Rep. of South
Committee on Cancer (AJCC)/the Union for International Cancer Email: [email protected]
Control (UICC) or the Bismuth staging system fail to adequately depict Background ans aims: In patients who have undergone surgical
the patients’ risk profile in terms of tumor recurrence. The present resection, the discordance between preoperative imaging and
study seeks to establish a reliable scoring system that allows to postoperative pathological findings may be found. There was a
classify the risk of tumor recurrence for individual patients in order to report that the mismatch of the Milan criteria before and after liver
improve surveillance and adjuvant treatment programs. transplantation (LT) was reported to be 22.0–27.2% and had an effect
Method: In this retrospective study, all patients undergoing MH for on the survival rate. However, there is no studies about impact of this
PHC at our department between January 2005 and August 2018 were discordance in patients who have undergone surgical resection. In
retrospectively reviewed and analyzed. Demographic variables as this study, preoperative imaging and postoperative pathologic
well as perioperative, histopathological data and information on findings were compared for tumor size, number, vascular or biliary
recurrence and overall survival were collected. After excluding tract invasion, and lymph node (LN) metastasis. In addition, the
postoperative 90-day mortality (n = 38, 14%), an uni- and multivariate survival rate according to the discrepancy for each factor is compared,
logistic cox regression analysis was performed to identify factors and according to the number of discrepancies, the impact on HCC
associated with tumor recurrence. Subsequently, a score was prognosis is investigated.
assigned to each independent risk factor, which was summed up to Method: Among the 13, 838 patients with HCC extracted randomly
a prognostic score ranging from 0 to 3 was created. from the 2008–2016 national cohort of the Korean Central Cancer
Results: We included 232 patients in the analysis. Median age was 64 Registry, we selected the 2, 781 patients who had undergone surgical
years (33–86). The majority of patients had Bismuth-Corlette IV resection or LT. And we evaluated the concordance of tumor maximal
tumors (42%, n = 97) and UICC stage IIIb (41%, n = 93). Tumor-free diameter, tumor number, bile duct invasion, LN metastasis, and
resection margins (R0) were achieved in 160 patients (70%), 131 vascular invasion including portal vein (PV), hepatic vein (HV),
patients were lymph node negative (N0, 57%). The 1–3- and 5-year hepatic artery (HA) by comparing preoperative imaging findings with
disease-free survival (DFS) and overall survival (OS) rates were 77%, postoperative pathologic findings. In addition, the survival rate was
36% and 20% vs. 82%, 45% and 24%, respectively. Multivariate cox compared by Kaplan-Meier according to the number of discrepancies,
regression showed that R1-status (Hazard Ratio, HR = 1.525, (95% and further analyzed by Cox proportional hazards regression analysis.
Confidence interval, CI: 1.021–2.277), p = 0.039), V1 status (HR = Results: Vascular invasion including HA, HV and PV invasion had a
2.187, 95% CI: 1.378–3.470, p = 0.001), and N+ status (HR = 1.856, 95% poorer prognosis than the both negative group when either of the
CI = 1.272–2.709, p = 0.001) were independently associated with imaging findings or pathological findings were positive ( p = 0.001
tumor recurrence. When calculating the prognostic score, 82 patients and p < 0.001, respectively). In particular, PV invasion, when both
(35%) had a score of 0 points, 72 patients (31%) had a score of 1 point, findings were positive, was significantly worse prognosis ( p < 0.001).
32 patients (14%) had a score of 2, and 13 patients (6%) had a score of 3 Bile duct invasion had a poorer prognosis when pathological findings
points. Kaplan Meier analysis showed highly significant correlation of were positive than those that were not ( p = 0.001), and there was no
disease-free survival (DFS) and overall survival (OS) with the scoring difference in survival rate when pathologic findings were negative
system ( p < 0.001). even if bile duct invasion was suspected on imaging findings ( p =
0.911). When analyzing according to the number of mismatched
factors among seven factors, as the number of mismatched factors
increased, the prognosis of HCC patients was poor ( p < 0.001).
Multivariate analysis also showed that the number of discrepancies

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 POSTER PRESENTATIONS
(for all concordance, vs. 1 discrepancy HR 1.529, p = 0.001 or vs. 2 related, and 4 (13.3%) Tr-AE grade 3 of special interest. Table 1
discrepancy, HR 2.889, p < 0.001 or vs. 3 discrepancy, HR 3.986, p < describes the profile Tr-AE occurring in >10% of patients. Only 4
0.001, respectively), discrepancy in tumor diameter (HR 0.683, p = (13.3%) patients developed Tr-SAE, 3 (10%) Rego-related and 3 (10%)
0.003), and discrepancy in LN metastasis (HR 2.399, p = 0.001) were Nivo-related. Four patients discontinued the study due to physician
independent factors for the HCC prognosis. decision, 2 for progression, and 2 for AEs (one related to study
Conclusion: This study revealed for the first time that the more treatment). One patient had surgical resection after treatment
factors that did not match the preoperative imaging findings and the discontinuation and a complete necrosis was observed at pathology.
postoperative pathological findings is associated with the poorer
survival rate in patients undergoing surgical resection as independ- Table 1. Profile of Tr-AE occurring in >10% in the first 30 included patients.
ent predictive factor. Any Grade Grade 3
Adverse Events Patients, Patients, Patients, Patients,
THU584 n % n %
Early Nivolumab addition to Regorafenib in patients with Hand-foot-skin reaction 17 56.6 3 10.0

hepatocellular carcinoma progressing under 1st line therapy Asthenia 13 43.3 - -

Diarrhea 11 36.7 1 3.3
(GOING trial). Interim analysis and safety profile Decreased Appetite 9 30.0 - -
Marco Sanduzzi Zamparelli1, Ana M Matilla2, Jose Luis Lledó3, Arterial Hypertension 9 30.0 2 6.7
Sergio Muñoz Martinez1, Maria Varela4, Mercedes Iñarrairaegui5, Hypertransaminasaemia 9 30.0 1 3.3
Christie Perelló6, Beatriz Minguez7, Neus Llarch1, Hyperbilirubinaemia 6 20.0 1 3.3
Laura Marquez Perez8, Antonio Guerrero3, Gemma Iserte1, Aspartate Aminotransferase Increased 6 20.0 1 3.3

Andrés Castano-Garcia4, Laura Carrión8, Jordi Rimola9, Abdominal Pain 6 20.0 - -

Dysphonia 5 16.7 - -
Maria Ángeles García-Criado9, Gema Domenech10, Loreto Boix1,
Alanine Aminotransferase Increased 4 13.3 - -
Jordi Bruix1, María Reig1. 1Hospital Clinic of Barcelona, IDIBAPS. * None of these Tr-AE was grade 4- 5
CIBERehd, University of Barcelona, BCLC group. Liver Unit., Barcelona,
Spain; 2Hospital General Universitario Gregorio Marañón, CIBERehd,
Gastroenterology Department, Madrid, Spain; 3Hospital Universitario Conclusion: The sequential combination of Rego-Nivo has a
Ramón y Cajal, IRYCIS, CIBERehd, University of Alcalá, Gastroenterology manageable safety profile. Less than one third of the patients
and Hepatology Department, Madrid, Spain; 4Hospital Universitario developed grade 3/4 Tr-AE and there was no treatment-related
Central de Asturias, IUOPA, ISPA, Universidad de Oviedo., Liver Unit, death. Futility analysis allowed to continuing recruitment.
Gastroenterology Department, Oviedo, Spain; 5Clinica Universidad de
Navarra, IDISNA and CIBEREHD, Liver Unit and HPB Oncology Area, THU585
Pamplona, Spain; 6Hospital Universitario Puerta de Hierro, IDIPHISA, Impact of endobiliary radiofrequency ablation on survival of
CIBERehd, Gastroenterology Department. Hepatology Unit, Madrid, patients with advanced extrahepatic cholangiocarcinoma under
Spain; 7Valld’Hebron Institute of Research (VHIR), Vall d’Hebron systemic chemotherapy
Barcelona Hospital Campus.CIBERehd, Universitat Autònoma de Christian Möhring1, Maria Angeles Gonzalez-Carmona1,
Barcelona, Liver Unit, Hospital Universitari Vall d’Hebron, Liver Diseases Robert Mahn1, Taotao Zhou1, Alexandra Bartels1, Farsaneh Sadeghlar1,
Research Group, Barcelona, Spain; 8Hospital General Universitario Maximilian Bolch1, Annabelle Vogt1, Dominik Kaczmarek1,
Gregorio Marañón, Gastroenterology Department, Madrid, Spain; Dominik Heling1, Leona Dold1, Jacob Nattermann1, Vittorio Branchi2,
9
Hospital Clínic of Barcelona, IDIBAPS, University of Barcelona, BCLC Hanno Matthaei2, Steffen Manekeller2, Jörg Kalff2,
Group, Radiology Department, Barcelona, Spain; 10Medical Statistics Christian Strassburg1, Raphael Mohr1, Tobias Weismüller1. 1University
Core Facility, IDIBAPS-Hospital Clínic, Barcelona, Spain Hospital of Bonn, Germany, Internal Medicine I, Bonn, Germany;
2
Email: [email protected] University Hospital of Bonn, Germany, Department of Surgery, Bonn,
Germany
Background and aims: Regorafenib (Rego) improves survival in Email: [email protected]
patients with hepatocellular carcinoma (HCC) (RESORCE trial) while
Nivolumab (Nivo) is also safe and active in terms of radiologic Background and aims: Prognosis of patients with advanced
response (15–20% objective response) in second-line. The GOING trial extrahepatic cholangiocarcinoma is still poor. The current standard
(NCT04170556) is an investigator-initiated phase I/IIa study assessing first-line treatment is systemic chemotherapy with gemcitabine and
the safety of Rego plus Nivo in HCC patients who progress and tolerate a platinum derivate. Additionally, endobiliary radiofrequency abla-
sorafenib (Cohort A) or who discontinue atezolizumab plus bevaci- tion (eRFA) can be applied to treat biliary obstructions. The aim of this
zumab (Cohort B). study was to evaluate the additional benefit of scheduled regular
Method: Patients from cohort A receive Rego as monotherapy for the eRFA in a real-life patient cohort with advanced extrahepatic
first 2 cycles (starting dose 160 mg/day, 3 weeks on/1 week off and cholangiocarcinoma under standard systemic chemotherapy.
adjusted for adverse events [AEs]) and Nivo is added at day 1 of cycle Method: This is a single center retrospective analysis. All patients
3 (the first 10 patients at 3 mg/kg; since they did not present serious- with irresectable extrahepatic cholangiocarcinoma treated at
AE (SAE), the final dose is 240 mg every two weeks). Treatment University Hospital Bonn between 2010 and 2020 were eligible for
continues until unacceptable AEs, symptomatic tumor progression, inclusion. Patients were stratified according to treatment: standard
patient decision or death. Safety is measured by the rate of AEs, rate of systemic chemotherapy (n = 26) vs. combination of eRFA with
treatment related-AEs (Tr-AE), rate of AEs leading to treatment standard chemotherapy (n = 40). Overall survival (OS), progression
discontinuation and rate of death. Severity of AEs are evaluated free survival (PFS), feasibility and toxicity were analyzed using
according to CTCAE v.5.0. A futility analysis using the non-binding Lan univariate and multivariate approaches.
and DeMets beta-spending functions with a boundary of p = 0.814 is Results: Combined eRFA and chemotherapy resulted in significantly
mandated when 32.8% of cohort A has data of tumor assessment at longer median OS (17.3 vs. 8.6 months, p = 0.004) and PFS (12.9 vs. 5.7
least at week 16 by RECIST 1.1. months, p = 0.045) compared to the chemotherapy only group. While
Results: Fifty-one patients have been enrolled in cohort A as of May groups did not differ regarding age, sex, tumor stage and chemo-
15, 2021. The first 30 (BCLC-C 73%) were considered in this safety therapy treatment regimen, mean MELD was even higher (10.1 vs. 6.7,
analysis. All patients developed at least one AE, 29 (96.7%) had Tr-AEs p = 0.015) in the eRFA+CT group. The survival benefit of concomitant
of any grade and 10 (33.3%) had grade 3 (no grades 4 or 5 have been eRFA was more evident in the subgroup with locally advanced
reported). Ten (33.3%) patients had a Rego-related AE, 4 (13.3%) Nivo- tumors. Severe hematological toxicities (CTCAE grades 3–5) did not

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POSTER PRESENTATIONS
differ significantly between the groups. However, therapy-related responding to locoregional treatments is represented by systemic
cholangitis occurred more often in the combined treatment group ( p therapy, and sorafenib and lenvatinib, two tyrosine-kinase inhibitors
= 0.031). (TKIs) are currently the standard of care, providing modest but
Conclusion: Combination of eRFA and systemic chemotherapy was significant benefit on survival. Recently, the IMBrave-150 trial has
feasible, well-tolerated and could significantly prolong survival demostrated that the combination of with atezolizumab plus
compared to standard chemotherapy alone. Thus, eRFA should be bevacizumab (Atezo-Beva) is the best first-line systemic therapy for
considered during therapeutic decision making in advanced extra- HCC patients, showing a clear superiority compared to sorafenib.
hepatic cholangiocarcinoma. This study aimed at assessing the real-world potential feasibility of
the Atezo-Beva therapy in a large cohort of HCC patients treated with
THU586 TKIs.
Interleukin 10 and Interferon Gamma levels are elevated in Method: We retrospectively analysed 1448 patients diagnosed with
patients with hepatocellular carcinoma showing response to unresectable HCC not amenable/not responding to locoregional
treatment with atezolizumab and bevacizumab treatments, treated with TKIs (sorafenib 98%, lenvatinib 2%) and
Sabine Lieb2, Aaron Schindler2, Johannes Niemeyer2, Rhea Veelken2, followed-up from January 2010 to December 2020 by 24 Italian
Janett Fischer2, Rami Al-Sayegh2, Thomas Berg2, Florian van Bömmel2. centres. The percentage of patients potentially amenable to Atezo-
1
Leipzig University Medical Center, Division of Hepatology, Department Beva treatment (according to IMBrave-150 trial criteria) and the
of Medicine II, Leipzig, Germany; 2Leipzig University Medical Center, overall survival (OS) of eligible/non-eligible patients were assessed.
Division of Hepatology, Department of Medicine II, Leipzig, Germany Results: 423 (29.2%) of patients treated with TKIs were found to be
Email: [email protected] qualified for the Atezo-Beva therapy. Their median OS was 17.3
months (95% CI 19.7–14.9) while that of non-eligible patients was
Background and aims: The combination treatment of the PD-L1
13.1 months (95% CI 14.5–11.6) ( p = 0.038), likely due to better
inhibitor atezolizumab plus bevacizumab (atezo/bev) has become
baseline clinical characteristics (Table 1). The main exclusion causes
standard of care in first line therapy in advanced hepatocellular
were a Child-Pugh class >A (399 cases) and a performance status >1
carcinoma (HCC). However, prediction of treatment response is not
(187 cases). The proportion of eligible cases considering, as selection
well defined. Effector cytokines signalling (e.g. interferon gamma
criterion, PLT >50000 mmc (instead of >75000 mmc requested by the
(IFN-g) is supposed to drive clinical response to immune checkpoint
IMBrave trial) increased by 43 cases (+2.9%), while including Child-
blockade. We have analysed circulating cytokine pattern in patients
Pugh Class B7 it increased by 85 patients (+5.9%).
treated with atezo/bev.
Method: Thirty-three patients (31 male, mean age of 65 ± 11 (range
29–80) years) with advanced HCC (7 BCLC B, 26 BCLC C) treated at the Eligible populaon Non eligible populaon p
n. 423 n. 1025
University Cancer Center of Leipzig were retrospectively analysed.
Twenty-eight patients had liver cirrhosis (23 Child-Pugh A, 5 Child- Age (years) 0.198
Pugh B), two underwent liver transplantation, two showed no hepatic N, (%) 423 (100%) 1025 (100%)
disease and one had fatty liver disease. All together 136 cycles (mean Median (range) 69 (33-90) 69 (21-92)
4.12, range 1–16 cycles) atezo/bev were applied to the patients.
Tomography imaging was performed after 3 to 4 cycles of atezo/bev Sex 0.679
and evaluated according to mRECIST criteria. A cytokine panel N, % 423 (100%) 1025 (100%)
including interleukin (IL)-1beta, interferon (IFN) alpha2, IFN-g, TNF M 344 (81%) 843 (82%)
F 79 (19%) 182 (18%)
alpha, IL-6, IL-8, IL-10, IL-12p70, Monocyte chemotactic protein 1
(MCP-1), IL-17A, IL-18, IL-23 and IL-33 was measured at baseline and Child-Pugh Class <0.001
correlated with treatment outcomes. N (%) 423 (100%) 916 (89%)
Results: The mean overall survival was 7 ± 5.3 (range 0–17) months. A 423 (100%) 478 (52%)
At the end of observation, 13 Patient showed stable disease (SD), 2 B1 0 (0%) 417 (46%)
partial response (PR), 1 patient complete response (CR), 2 progressive C 0 (0%) 21 (2%)
disease (PD) and 15 patients died. Patients showing either CR, PR or
SD at month 3 of treatment had higher mean baseline levels of IFN-g BCLC 0.007
N (%) 423 (100%) 966 (94%)
and IL-10 in comparison to patients with PD (IFN-g: 8.0 ± 5.48 (range
0 4 (1%) 1 (0%)
4.18–18.96) vs. 4.6 ± 0.87 (range 4.18–6.79), p < 0.001) and IL-10 A 56 (13%) 117 (12%)
(11.19 ± 9.6 (range 4.07–33.64) vs. 5, 74 ± 2, 05 (range 4.07–11.04), p < B 80 (19%) 153 (16%)
0, 001). At month six of treatment, patients with either CR, PR or SD C 283 (67%) 663 (69%)
still presented higher mean baseline levels of IFN-g in comparison to D 0 (0%) 32 (3%)
patients with PD (8.74 ± 6.01 (range 4.18–18.96) vs. 4.18 ± 0.0, p =
0.026). There was no association of other cytokine levels measured MELD Score <0.001
N (%) 423 (100%) 900 (88%)
with response to atezo/bev.
Median (range) 8 (6-23) 9 (6-31)
Conclusion: Response to atezo/bev in the treatment of HCC may
depend on IFN gamma and IL-10 signalling. The value of these cytokines Alpha-fetoprotein 0.036
as response predictors needs to be evaluated in a larger cohort. N (%) 391 (92%) 828 (81%)
≤10 ng/ml 131 (31%) 218 (26%)
THU587 11-200 ng/ml 125 (30%) 293 (35%)
Potential faesability of atezolizumab-bevacizumab therapy in >200 ng/ml 135 (32%) 316 (38%)
patients with hepatocellular carcinoma: a real-world analysis
ECOG (Performance <0.001
Benedetta Stefanini1,2, Laura Bucci1, Valentina Santi1,
Status)
Nicola Reggidori1, Davide Rampoldi1, Lorenzo Lani1, Franco Trevisani1. N (%) 423 (100%) 959 (93.6%)
1
S. Orsola-Malpighi Polyclinic, Division of Medical Semeiotics, Bologna, 0-1 423 (100%) 832 (87%)
Italy; 2Bologna, Semeiotica Medica, Bologna, Italy >1 0 (0%) 127 (13%)
Email: [email protected]
Background and aims: Option treatments for patients with
1
In Child-Pugh class B 258 (62%) patients showed a score of 7 (B7)
Figure 1. Characteristic of eligible population and not eligible population
unresectable hepatocellular carcinoma (HCC) not amenable/

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 POSTER PRESENTATIONS
Conclusion: Real world data indicate that no more than one-third Method: From an international consortium of 13 tertiary-care
of HCC patients treated with TKIs are potentially eligible for referral centres, we screened 604 HCC patients treated with ICIs,
Atezo-Beva therapy. These patients have a better OS than non- including only those who experienced PD by data cut-off. We
eligible ones, owing to a better baseline clinical profile. Therefore, evaluated post-progression survival (PPS) according to treatment
TKIs will remain the front-line approach for most of the HCC strategy at PD and verified its relationship with radiologic patterns of
patients qualified for systemic therapy, due to the stringent progression: intrahepatic growth (IHG), new intrahepatic lesion
selection criteria dictated by immunotherapy trials and the use of (NIH), extrahepatic growth (EHG), new extrahepatic lesion (NEH)
TKIs currently extended to Child-Pugh B patients. However, and new vascular invasion (nVI).
further prospective studies in real life may broaden Atezo-Beva Results: 364 (60.3%) patients had PD during observation, mostly
indications. following PD-1/PD-L1 monotherapy (80%). Median PPS was 5.3
months (95%CI: 4.4–6.9; 271 events). At data cut-off, 165 patients
THU588 (45%) received no post-progression anticancer therapy. Both IHG (HR
Progression patterns and therapeutic sequencing following 1.64 [95%CI:1.21–2.22]; p = 0.0013) and nVI (HR 2.15 [95%CI:1.38–
immune checkpoint inhibition for HCC: an observational study 3.35]; p = 0.0007) at PD were significantly associated with shorter
Thomas Talbot1, Antonio D’Alessio1,2, Matthias Pinter3, PPS. Continuation of ICI therapy beyond PD occurred in 64 patients
Lorenz Balcar3, Bernhard Scheiner3, Thomas Marron4, Tomi Jun5, (17.6%). Multivariate models adjusted for progression patterns,
Sirish Dharmapuri4, Celina Ang4, Anwaar Saeed6, treatment line, and ALBI grade and ECOG-PS at PD confirmed
Hannah Hildebrand6, Mahvish Muzaffar7, receipt of ICI beyond PD with (HR 0.17, 95%CI 0.09–0.32; p <
Claudia Angela Maria Fulgenzi1,8, Suneetha Amara7, 0.0001), or without subsequent TKI (HR 0.39, 95%CI 0.26–0.58; p <
Abdul Rafeh Naqash7,9, Anuhya Gampa10, Anjana Pillai10, 0.0001) as predictors of prolonged PPS compared to no anticancer
Yinghong Wang11, Uqba Khan12, Pei-Chang Lee13, therapy.
Yi-Hsiang Huang13,14, Bertram Bengsch15, Dominik Bettinger15, Conclusion: ICI-TKI sequencing is a consolidated option in advanced
Yehia Abugabal16, Ahmed Kaseb16, Tiziana Pressiani17, HCC, with poorer prognosis predicted by nVI and IHG. Despite lack of
Nicola Personeni2,17, Lorenza Rimassa2,17, Naoshi Nishida18, recommendation, continuation of ICI beyond progression in HCC is
Masatoshi Kudo18, Arndt Weinmann19, Peter Galle19, adopted in clinical practice: efforts should be made to identify
Ambreen Muhammed1, Alessio Cortellini1, Arndt Vogel20, patients who benefit from this approach.
David J. Pinato1,21. 1Imperial College London, Department of Surgery and
Cancer; 2Humanitas University, Department of Biomedical Sciences; THU590
3
Medical University of Vienna, Department of Internal Medicine III; GALAD score correlates with therapy response for transarterial
4
Tisch Cancer Institute, Mount Sinai Hospital, Department of Medicine, and systemic therapies in patients with hepatocellular carcinoma
United States; 5Sema4, Stamford, CT, United States; 6Kansas University Anne Olbrich1, Johannes Niemeyer1, Hendrik Seifert1, Olga Gros2,
Cancer Center, Division of Medical Oncology, United States; 7East Florian Lordick3, Dirk Forstmeyer3, Daniel Seehofer4, Robert Sucher4,
Carolina University, Division of Hematology/Oncology, United States; Sebastian Rademacher4, Timm Denecke5, Sebastian Ebel5,
8
University Campus Bio-Medico, Department of Medical Oncology, Italy; Nicolas Linder5, Madlen Matz-Soja1,6, Thomas Berg1,
9
National Cancer Institute, Division of Cancer Treatment and Diagnosis, Florian van Bömmel1. 1Leipzig University Medical Center, Department of
Bethesda, Maryland, United States; 10The University of Chicago Medicine II, Division of Hepatology, Leipzig, Germany; 2Helios Clinic
Medicine, Section of Gastroenterology, Hepatology and Nutrition, Köthen, Department of Anesthesia and Intensive Care, Köthen, Germany;
3
Chicago, United States; 11The University of Texas MD Anderson Cancer, Leipzig University Medical Center, University Cancer Center Leipzig
Department of Gastroenterology, Hepatology and Nutrition, United (UCCL), Leipzig, Germany; 4Leipzig University Medical Center,
States; 12Weill Cornell Medicine/New York Presbyterian Hospital, Department of Visceral, Vascular, Thoracic and Transplant Surgery,
Division of Hematology and Oncology, United States; 13Taipei Veterans Leipzig, Germany; 5Leipzig University Medical Center, Department of
General Hospital, Division of Gastroenterology and Hepatology, Diagnostic and Interventional Radiology, Leipzig, Germany; 6University
Department of Medicine, Taiwan; 14National Yang Ming Chiao Tung of Leipzig, Rudolf-Schönheimer-Institute for Biochemistry, Leipzig,
University School of Medicine, Institute of Clinical Medicine, Taiwan; Germany
15
Medical Center University of Freiburg, Department of Medicine II, Email: [email protected]
Faculty of Medicine, Germany; 16The University of Texas MD Anderson
Background and aims: The GALAD score is a biomarker-based
Cancer Center, Dept of Gastrointestinal Medical Oncology, United States;
17 scoring system used for prediction of early hepatocellular carcinoma
Humanitas Cancer Center, IRCCS Humanitas Research Hospital,
(HCC) in patients with chronic liver disease. It consists of the two risk
Medical Oncology and Hematology Unit, Italy; 18Kindai University
factors gender (G) and age (A) and levels of AFP-L3 (L), AFP (A), and
Faculty of Medicine, Department of Gastroenterology and Hepatology,
DCP (D). So far, a possible association of baseline GALAD score and
Osaka, Japan; 19University Medical Center of the Johannes Gutenberg-
therapy response was not investigated. For patients with advanced
University Mainz, 1st Department of Internal Medicine,
HCC, loco-regional treatment approaches, such as transarterial
Gastroenterology and Hepatology, Germany; 20Hannover Medical
chemoembolization (TACE) and transarterial radioembolization
School, Department of Gastroenterology, Hepatology and Endocrinology,
(TARE) as well as systemic therapies are available, but response to
Germany; 21University of Piemonte Orientale “A. Avogadro,” Division of
these therapies is highly variable. The study aim is to assess the value
Oncology, Department of Translational Medicine, Italy
of the GALAD model as a response marker to these treatment
Email: [email protected]
approaches.
Background and aims: Different approaches are available after Method: In a retrospective German single-center study, 238 patients
progression of disease (PD) while on treatment with immune with HCC treated with either TARE or TACE or systemic drugs were
checkpoint inhibitors (ICI) for hepatocellular carcinoma (HCC), enrolled. Serum samples at baseline were analyzed to evaluate the
including continuation of ICI, switching to tyrosine kinase inhibitors prognostic performance of the GALAD score. Treatment efficacy was
(TKIs) and cessation of therapy. Little is known about progression evaluated by mRECIST criteria based on magnet resonance imaging
patterns and their relationship with optimal sequencing and survival (MRI) three months (10–14 weeks) after intervention.
outcomes post-ICI. Results: In our patient cohort (n = 238) the mean GALAD score at
baseline was 3.96 [range, −5.19–17.89]. Baseline GALAD scores were

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POSTER PRESENTATIONS
significantly higher in patients in BCLC stage B or C/D as compared to chemotherapy (fludarabine 25 mg/m2/day and cyclophosphamide
stages A. 500 mg/m2/day for 3 consecutive days. Ascending dose levels of
At baseline, mean GALAD scores were significantly higher in the SCG101 at 1 × 107/kg to 2 × 108/kg TCR-transduced T cells were
refractoriness group compared to response group (5.66 versus 2.49; permitted according to protocol and safety assessment including
p < 0.001; Fig.). Regarding the different therapy options, the GALAD dose-limiting toxicity (DLT) was adjudicated by a Safety Review
score showed a significant discrimination between the refractory and Committee.
responder in the transarterial therapy group ( p < 0.001) as well as in Results: As of Feb 28th, 2022, three HLA-A*02:01+ patients have been
the systemic treatment group ( p = 0.01). enrolled: subjects ST1301 and ST1401 received 5 × 107/kg TCR-T cells,
subject ST1204 received 1 × 108/kg. Transduced T cells were detect-
able in peripheral blood of all three patients up to last visit. Two
patients, ST1301 and ST1204 showed a rapid HBsAg reduction of >1.7
log within 28 days after infusion and sustained with continuous
decline thereafter. The HBsAg drop was correlated with a transient
ALT/AST flare without significant change of other liver function
markers including albumin, bilirubin, etc. Tumor response assess-
ment by mRECIST showed that these two patients had stable disease
(SD) with target lesion reduction of 14.5% and 6.2%, respectively, and
maintained SD up to last visit (96+ and 55+ days). Patient ST1401 had
a transient HBsAg drop of ∼0.2 log from day 1–4 post treatment and
was diagnosed with progressive disease (PD) at day 28. For all
patients, no DLT or drug-related serious adverse events (SAEs) have
been observed to date. Drug-related adverse events were typical for a
T-cell therapy associated cytokine-release syndrome and transient or
reversible after treatment.
Conclusion: Systemic SCG101 TCR-T cell therapy was well tolerated
and showed promising early signs of clinical efficacy in advanced
HBV-related HCC patients who have exhausted available targeted and
immunotherapy options. Early and sustained HBsAg reduction
demonstrates encouraging antiviral activity with target engagement
Using ROC analyses the GALAD score for response of transarterial or of SCG101 and might serve as a potential predictive marker of
systemic treatment showed higher AUC (AUC = 0.704; p < 0.001) than antitumor efficacy. Preliminary data support further systematic
the individual biomarkers AFP, AFP-L3, and DCP in the overall cohort clinical evaluation.
(AUC = 0.685, 0.629 and 0.645, respectively).
Conclusion: The GALAD model is a potent predictor of tumor THU592
response to transarterial and systemic treatment in HCC at baseline. Current trends and in-hospital mortality of transarterial
chemoembolization (TACE) in Germany: a systematic analysis of
THU591 hospital discharge data between 2010 and 2019.
Antiviral and antitumor activity of SCG101, an autologous HBV- Sven H Loosen1, Sarah Krieg1, Tobias Eßing1, Andreas Krieg2,
specific T cell receptor engineered T cell (TCR-T) therapy in HBV- Christoph Roderburg1, Tom Lüdde2. 1University Hospital Düsseldorf,
related advanced hepatocellular carcinoma (HCC) patients after Clinic for Gastroenterology, Hepatology and Infectious Diseases,
receiving ≥2 prior lines of systemic therapies Düsseldorf, Germany; 2University Hospital Düsseldorf, Department of
Shunda Du1, Yuhong Zhou2, Xiujuan Qu3, Wei Wu4, Ke Zhang5, Surgery (A), Düsseldorf, Germany
Xueshuai Wan1, Wei Li2, Dongmei Quan4, Karin Wisskirchen6,7, Email: [email protected]
Ulrike Protzer6,7, Yun Peng Liu3. 1Peking Union Medical College Background and aims: Transarterial chemoembolization (TACE)
Hospital, Liver Surgery, Beijing, China; 2Zhongshan Hospital, Fudan represents a standard of care for intermediate-stage hepatocellular
University, Medical Oncology, Shanghai, China; 3The First Hospital of carcinoma (HCC) and is also increasingly performed in patients with
China Medical University, Medical Oncology, Shenyang, China; 4The cholangiocarcinoma (CCA) or liver metastases. Recently, newer
Sixth People’s Hospital of Shenyang, Hepatobiliary Surgery, Shenyang, particle-based TACE procedures have been introduced but compre-
China; 5SCG Cell Therapy, Shanghai, China; 6Technical University of hensive data on clinical trends of TACE as well as its in-hospital
Munich, Institute of Virology, Munich, Germany; 7Helmholtz Munich, mortality in Germany are missing. A systematic evaluation of existing
Institute of Virology, Munich, Germany data sets and their careful interpretation can support a rational
Email: [email protected] discussion aiming at further optimizing framework conditions of
Background and aims: Adoptive cell therapy with TCR-T cells TACE.
targeting HBV antigens represents an innovative approach for Method: Based on standardized hospital discharge data provided by
treatment of HBV-related HCC. SCG101 is a first-in-class genetically the German Federal Statistical Office, we systematically evaluate
modified autologous TCR-T with a natural high-avidity TCR directed current clinical developments, associated post-interventional com-
towards the HLA-A*02-restricted HBsAg peptide S20–28. We here plications as well as in-hospital mortality of TACE in Germany
report first results from an ongoing pilot, investigator-initiated trial between 2010 and 2019.
(IIT) conducted to evaluate the safety as well as the antiviral and Results: A total of 49, 595 individual cases undergoing TACE were
antitumor activity of SCG101. identified within the observation period. The overall in-hospital
Method: Patients with HBV-related HCC (HBsAg positive, HBeAg mortality was 1.00% and significantly higher in females compared to
negative and HBV DNA ≤2 × 103 IU/ml), who are HLA-A*02 positive males (1.12% vs. 0.93%; p < 0.001). We identified several post-
and have received at least two lines of systemic therapy including interventional complications such as liver failure (51.49%), sepsis
small-molecule tyrosine kinase inhibitors and PD-1 checkpoint (33.87%), renal failure (23.9%) and liver abscess (15.87%), which were
inhibitors were eligible. Following leukapheresis, SCG101 TCR-T associated with a significantly increased in-hospital mortality.
cells were manufactured using an automated closed system. Prior Moreover, in-hospital mortality significantly differed between the
to intravenous infusion of SCG101, patients receive lymphodepleting underlying indication for TACE (HCC: 0.83%, liver metastases: 1.22%,

S384 Journal of Hepatology 2022 vol. 77(S1) | S119–S388

 POSTER PRESENTATIONS
and CCA: 1.40%) as well as between different embolization agents THU594
(liquid embolization: 0.80%, loaded microspheres: 0.92%, spherical The influence of fasting on tumor-targeted drug delivery
particles: 1.54% and non-spherical particles: 2.84%), for which we Svea Becker1, Diana Möckel2, Ilaria Biancacci2, Jan-Niklas May2,
observed large geographic differences in their frequency of use. Qingbi Wang1, Huan Sun1, Marek Weiler2, Twan Lammers2,
Finally, in-hospital mortality was significantly increased in centers Maximilian Hatting1, Christian Trautwein1. 1Medical Department III,
with a low annual TACE case volume (<15 TACE/year: 2.08% vs. >275 Universitätsklinikum Aachen, Aachen, Germany; 2Experimentelle
TACE/year: 0.45%). Molekulare Bildgebung, RWTH Aachen, Aachen, Germany
Conclusion: We identified a variety of factors such as post- Email: [email protected]
interventional complications, the embolization method used as
well as the hospitals’ annual case volume, which are associated Background and aims: Hepatocellular carcinoma is increasing in
industrialized countries. Disease progression is accelerated by a
with an increased in-hospital mortality following TACE. These data
number of risk factors, although it can be reduced to some extent by
might help to further reduce mortality of this routinely performed
local-ablative procedure in the future. using intermittent fasting. Tumorous cells are stressed by regular
food deprivation because they are constantly proliferating. Fasting
THU593 has also been established in recent clinical research to be a new
Pre-treatment cross-talk between the tumoural and peripheral therapeutic before tumor therapy leading to maintenance and repair
immune system predicts response to checkpoint inhibition in processes such as autophagy. As a result, tumor therapy can be more
advanced HCC: a single-cell study precise and patients can show a higher survival rate.
Sarah Cappuyns1,2,3,4, Gino Philips2,3, Vincent Vandecaveye5,6, Here, we aimed to show how fasting induces changes in the tumor
Chris Verslype1,7, Eric Van Cutsem1,7, Diether Lambrechts2,3, microenvironment facilitating tumor-targeted drug delivery.
Jeroen Dekervel1,7. 1Digestive Oncology, Department of Method: We used a well-established syngeneic tumor model with
Gastroenterology, University Hospitals Leuven, Leuven, Belgium; the murine liver hepatoma cell line Hep-55.1C. The tumor was
2
Laboratory for Translational Genetics, Department of Human Genetics, implanted subcutaneously and grew over 3.5 weeks. During tumor
KU Leuven, Leuven, Belgium; 3VIB Center for Cancer Biology, Leuven, growth, the mice were either fasted intermittently every 12 h (IF),
Belgium; 4Mount Sinai Liver Cancer Program, Divisions of Liver Diseases, once overnight after 20 d for 12 h (STF), or fed ad libitum (a.l.). After 21
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, d, DSPE-Cy7 labeled liposomes were injected i.v. and the biodistribu-
New York, United States; 5Radiology Department, University Hospitals tion of the nanoparticles was observed longitudinally up to 72 h p.i.
Leuven, Leuven, Belgium; 6Laboratory of Translational MRI, Department via hybrid computed- and fluorescence tomography (CT-FLT).
of Imaging and Pathology, KU Leuven, Leuven, Belgium; 7Laboratory of Results: Our analysis demonstrates that mice in the a.l. group have
Clinical Digestive Oncology, Department of Oncology, KU Leuven, Leuven, little to no liposome-signal in the tumor but have substantial levels of
Belgium uptake in reticuloendothelial system organs (RES). The STF group has
Email: [email protected] tumor signals, but the RES-organs still have significant signals. The IF
mice had the most signal in the tumor, while the RES-organs had
Background and aims: Checkpoint inhibitors have radically changed fewer liposome signals detected by the CT-FLT.
the treatment of advanced hepatocellular carcinoma (aHCC), albeit In addition, intermittent fasting alters the microenvironment of
that only a subset of patients achieve durable disease control. We tumors. Collagen1A1 levels in the IF group were considerably lower.
aimed to characterize both the tumoural and peripheral immune This was accompanied by a considerable rise in the number of vessels
system of aHCC using single-cell sequencing technology and identify that were positive for Lectin. In these tests, there was no difference
features associated with response and/or resistance to immunother- between STF and a.l. mice.
apy targeting the PD (L)1 axis. Conclusion: Our findings show that intermittent fasting prior to
Method: Patients with aHCC were prospectively enrolled prior to tumor therapy improves the likelihood of a more precise and direct
initiation of systemic therapy. Clinical response was defined as delivery method. Fasting softens the tissue and increases blood flow,
mRECIST objective response or durable stable disease. Pre-treatment making it easier to deliver (nano-)therapeutics into the tumor
tissue biopsies (n = 31) and both pre- and on-treatment peripheral through the bloodstream.
immune cell samples (n = 58) were subjected to simultaneous single-
cell transcriptome, T-cell receptor (TCR) and proteome sequencing, THU595
resulting in data from 377 975 single cells. CXCR2 inhibition sensitises NASH-HCC to immunotherapy
Results: PD1 and PDL1 were expressed in tumour-infiltrating T-cells Jack Leslie1, John B. G. Mackey2, Thomas Jamieson2, Helen L. Reeves1,
versus myeloid cells and tumour cells, respectively. Myeloid cells Josep M. Llovet3, Carlin Leo2, Thomas G Bird2, Owen Sansom2,
from tumours responding to immunotherapy expressed significantly Derek A Mann1. 1Newcastle University Medical School, United Kingdom;
higher levels of PDL1 at baseline ( p = 0.014), driven by pro- 2
Beatson Institute for Cancer Research, Bearsden, United Kingdom;
inflammatory PDL1-expressing CXCL10+ macrophages involved in 3 ̀ iques August Pi i Sunyer (IDIBAPS),
Institut d’Investigacions Biomed
T-cell recruitment. In contrast, non-responding tumours were Barcelona, Spain
infiltrated by immature ‘monocyte-like’ CX3CR1+ and CCR2+ macro- Email: [email protected]
phages ( p = 0.009 and p = 0.01, respectively). Responding tumours
were also characterized by a more clonal baseline TCR repertoire ( p = Background and aims: Non-alcoholic steatohepatitis (NASH) is
0.007) and a higher degree of TCR sharing (p = 0.008) with peripheral increasingly a major underlying cause of hepatocellular carcinoma
blood that decreased significantly on-treatment ( p = 0.026). In (HCC). Immunotherapy offers great promise for HCC therapy;
peripheral T-cells, TCRs shared between tumour and blood displayed however, recent published data suggests that NASH is the cause of
a higher TCR clonality ( p = 0.003), while in the tumour they were immune changes that negatively impacts on the efficacy of
present in recently activated CD8+ effector T-cells, characterized by conventional immune checkpoint inhibition (ICI). Here we aimed to
high levels of cytotoxic markers. sensitise NASH-HCC to anti-PD1 therapy by targeting neutrophils
Conclusion: Response to checkpoint inhibition in aHCC is driven by using a CXCR2 small molecule inhibitor (AstraZeneca-AZD5069).
the pre-treatment presence of clonally expanded, recently activated Method: Neutrophil infiltration was characterised in multiple models
cytotoxic CD8+ effector T-cells, infiltrating from peripheral blood and of murine HCC and in human patient biopsies. Late-stage interven-
supported by a pro-inflammatory tumoural myeloid component. tion with anti-PD1 and/or AZD5069 was performed in two NASH-
HCC models (orthotopic and autochthonous). The tumour micro-
environment was characterised by a combination of immunohisto-
chemistry, flow cytometry and RNA-seq.

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POSTER PRESENTATIONS
Results: CXCR2+ neutrophils were found to be highly represented in THU596
both murine and human NASH-HCC. In models of NASH-HCC lacking Combination of systemic immune-inflammation index and
response to ICI, the combination of AZD5069 with anti-PD1 albumin-bilirubin score predict prognosis of sequential therapy
effectively suppressed tumour burden and extended survival (Fig with sorafenib and regorafenib in unresectable hepatocellular
1). The combination therapy increased intratumoral CD103+XCR1+ carcinoma
dendritic cells and CD8+ T cells that are associated with anti-tumoral Tai-An Cheng1, Wei Teng2, Po-Ting Lin3, Chen-Chun Lin3,
immunity. The therapeutic effect was lost upon genetic impairment Chun-yen Lin3, Shi-Ming Lin3. 1Chang Gung Memorial Hospital,
of dendritic cells or antibody mediated depletion of CD8+ T cells. Taiwan; 2Chang Gung University, Taiwan; 3Taipei Chang Gung Memorial
Combination therapy resulted in an unexpected increase in tumour- Hospital, Taiwan
associated neutrophils (TANs). These TANs were found to be Email: [email protected]
proliferative and by the use of image mass cytometry to be located
Background and aims: Sequential therapy with sorafenib and
within immunological hubs in direct contact antigen presenting cells
and CD8+ T cells. These immune hubs were enriched for the cytotoxic regorafenib had shown promising results to improve outcomes for
unresectable hepatocellular carcinoma (uHCC) patients. Although
anti-tumoural protease granzyme B which was found at increased
levels in tumours co-treated with CXCR2 antagonist and anti-PD1 there have been several reports regarding the efficacy of sequential
therapy in real-world, the role of specific inflammation markers for
compared with monotherapy groups.
predicting the prognosis are still unclear. This study aimed to
investigate prognostic value of systemic inflammatory markers in
patients with HCC who received sorafenib-regorafenib sequential
therapy.
Method: A total of 122 uHCC patients who received sorafenib-
regorafenib sequential therapy from August 2016 to August 2021
were retrospectively enrolled for analysis. Treatment response was
evaluated by modified Response Evaluation Criteria in Solid Tumors
(mRECIST) criteria. The pre-treatment host factors, tumor status,
biochemistry markers and inflammatory index (NLR, PLR, MLR, SII,
SIRI, ILIS) were collected. Progression-free survival (PFS) and overall
survival (OS) were assessed using the Kaplan-Meier survival curves.
The Cox regression model was used to identify independent
predictors of PFS and OS.
Results: Among the 122 patients, the median age was 66 years old
and 84% were male gender. Regorafenib was used as the second and
third lines of therapy in 97 (80%) and 25 (20%) patients respectively.
Most patients were Child-Pugh A (96%), ABLI grade II (52%) and BCLC
stage C (73%) at baseline. The overall response rate (ORR) and disease
control rate (DCR) was 7.4% and 46.7%, respectively. The median OS
from the initiation of sorafenib was 39.4 (95%CI: 32.9–45.8) and the
median PFS after sorafenib was 3.4 (95%CI: 3.0–3.8) months.
Multivariate Cox regression analysis showed that baseline ALBI
grade I and systemic inflammatory index (SII) <330 were independ-
ent factors associated with good OS (hazard ratio [HR] = 0.655, p =
0.031 and HR = 0.570, p = 0.039) and PFS (HR = 0.725, p = 0.040 and
HR = 0.341, p = 0.016). We further stratified our patients into 3 risks
group (A: SII ≤330 and ALBI grade I, B: SII >330 or ALBI grade II/III, C:
SII >330 and ALBI grade II/III). The combination of SII ≤330 and ALBI
grade I showed the best OS (A vs. B vs. C = NR vs. 17.9 vs. 7.5 months,
log-rank p = 0.003) and PFS (A vs. B vs. C = NR vs. 3.7 vs. 2.9 months,
TANs in combination-treated tumours displayed a switch from a pro- log-rank p = 0.001) than other two groups.
tumour to anti-tumour progenitor-like neutrophil phenotype,
closing resembling a recently characterised acute-inflammatory
immature-Ly6GInt neutrophil population isolated from lipopolysac-
charide- (LPS)-treated mice. Intravenous infusion of these neutro-
phils into orthotopic tumour bearing mice, sensitised to anti-PD1
therapy, promoting dendritic cell and CD8+ T cell recruitment and
activation.
Conclusion: CXCR2-inhibition induces multi-cellular reprogram-
ming of the tumour immune microenvironment that promotes ICI
treatment of HCC in the context of NASH.

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 POSTER PRESENTATIONS
Conclusion: The combination of baseline ALBI grade and SII index its usefulness as a predictive marker of early therapeutic effect after
can be used as a promising prognostic tool to predict prognosis of the administration of AB.
uHCC patients receiving sorafenib-regorafenib sequential therapy. Method: Twenty-five patients who received AB for unresectable HCC
were included. The initial treatment response after the administra-
THU597 tion of AB was reported using Response Evaluation Criteria in Solid
Induce the endogenous tumor suppressor miR-34a by small Tumors (RECIST) after 8–12 weeks. The treatment response was
molecules to inhibit liver metastasis evaluated every 8–12 weeks thereafter. CEUS was performed before
Dayana Yaish1, Tomer Friehmann1, Alexander Plotnikov2, Shira Levi1, administration and early after administration (3–7 days), and TIC
Hilla Giladi1, Amnon Peled1, Haim Barr2, Eithan Galun1. 1Hadassah analysis was performed using the arterial phase for 2 minutes after
University Hospital-Ein Kerem, Goldyne Savad Institute of Gene and Cell injection of the contrast medium. The time to peak (TTP) and the
Therapy, Jerusalem, Israel; 2Weizmann Institute of Science, The Nancy slope of wash-in (Slope) indicators were used for TIC analysis.
and Stephen Grand Israel National Center for Personalized Medicine, Results: The baseline characteristics of 25 patients were 69 (44–81)
Rehovot, Israel years old, 20 males, the maximum intrahepatic tumor diameter 64
Email: [email protected] (21–112) mm, and BCLC stage C 45%. The treatment response was
Complete Response 1 case, Partial Response 7 cases, Stable Disease 11
Background and aims: Metastasis originating from different cancers,
cases, and PD 6 cases.
are commonly spreading to the liver, and as such, are a common cause
Patients with prolonged TTP and decreased Slope were 36% using CEUS
of death. Recent evidences have indicated the role of microRNAs
at 3–7 days, and all cases achieved disease control based on the initial CT
(miRs) in modulating the metastatic process. There are specific miRs
after 8–12 weeks. There was a significant difference in the median
that exhibit tumor-suppressive activity by targeting cancer driver
progression-free survivals (PFSs) between patients with and without
genes. MiR-34a is a well-known tumor suppressor and anti-
prolonged TTP and decreased Slope (p = 0.0051). There was a significant
metastatic miR. We hypothesize that induction of endogenous
difference in the median PFSs between patients with and without
expression and secretion of miR-34a, could be a new strategy for
decreased α-fetoprotein (AFP) levels (p = 0.019). There was also a
metastasis therapy.
significant difference in the median PFSs between patients with and
Method: We performed high throughput screening of synthetic small
without decreased neutrophil-to-lymphocyte ratio (NLR) (p = 0.038).
molecule libraries searching for compounds that induce miR-34a
PFS stratification was possible by the number of positive numbers
promoter activity and secretion. The compounds were initially tested
among the 3 early markers (TTP prolongation and Slope decrease/AFP
for their ability to induce EGFP on HepG2 cells carrying a miR-34a-
decrease/NLR decrease) (0/1 vs. 2/3 8.6 vs. 33 weeks, p < 0.001).
promoter-EGFP reporter. Compounds that induced EGFP levels were
tested further for their effect on miR-34a secretion using qRT-PCR
analysis performed on RNA extracted from the cell’s media.
Results: We identified 6 compounds which induced miR-34a
promoter activity. However, only 2 out of these 6 compounds
induced miR-34a secretion. Searching databases for predicted
activities of these 2 compounds, revealed that both may repress
Cyclin Dependent Kinase 5 (CDK5). We therefore, examined the
activity of known CDK5 repressors, Dinaciclib and Flavopiridol. Both
molecules induced miR-34a promoter activity and secretion.

Conclusion: Early evaluation using CEUS may be useful in predicting

the therapeutic effect in patients treated with Atezolizumab and
Conclusion: small molecule induction of miR-34a is a therapeutic Bevacizumab for unresectable HCC.
approach against liver metastasis.
THU599
THU598 Efficacy and safety of Atezolizumab plus Bevacizumab-based
Prediction of treatment response using contrast-enhanced sequential treatment for unresectable hepatocellular carcinoma:
ultrasonography in patients treated with Atezolizumab and a simulation model
Bevacizumab for unresectable hepatocellular carcinoma Ciro Celsa1, Giuseppe Cabibbo1, Salvatore Battaglia2, Paolo Giuffrida1,
Hitomi Takada1, Shinya Maekawa1, Nobuyuki Enomoto1. 1University of Giacomo Emanuele Maria Rizzo1, Mauro Grova1, Marco Giacchetto1,
Yamanashi, Gastroenterology and Hepatology, Chuo, Japan Gabriele Rancatore1, Caterina Stornello1, Maria Vittoria Grassini1,
Email: [email protected] Giuseppe Badalamenti3, Marco Enea1, Antonio Craxi1, Vito Di Marco1,
Calogero Camma1. 1Section of Gastroenterology and Hepatology,
Background and aims: Atezolizumab plus Bevacizumab therapy
(AB) was approved for unresectable hepatocellular carcinoma in
2020. However, the prediction of treatment response that can be
easily used in clinical practice is still unknown. In this study, we
performed Time-intensity curve (TIC) analyses using the arterial
phase of contrast-enhanced ultrasonography (CEUS), and examined

Journal of Hepatology 2022 vol. 77(S1) | S119–S388 S387

POSTER PRESENTATIONS
Department of Health Promotion, Mother and Child Care, Internal THU600
Medicine and Medical Specialties, PROMISE, University of Palermo, Italy; Risk factors for hepatic encephalopathy in hepatocellular
2
Department of Economics, Business and Statistics (SEAS), University of carcinoma after sorafenib or lenvatinib treatment: a real-world
Palermo, Department of Economics, Business and Statistics (SEAS), study
University of Palermo, Italy; 3Department of Surgical, Oncological and Bowen Chen1,2, Linzhi Zhang2,3, Jiamin Cheng2, Xu Yang4, Jin Lei2,5,
Oral Sciences (Di.Chir.On.S.), University of Palermo, Department of Tong Wu2, Tao Yan2, Yinyin Li2, Yinying Lu1,2. 1Peking University 302
Surgical, Oncological and Oral Sciences (Di.Chir.On.S.), University of Clinical Medical School, Beijing, China; 2The 5th Medical Centre of the
Palermo, Italy PLA General Hospital, Beijing, China; 3Tianjin Medical University Cancer
Email: [email protected] Institute and Hospital, Tianjin, China; 4Peking Union Medical College
Background and aims: Systemic therapies for unresectable hepato- Hospital. Chinese Academy of Medical Sciences and Peking Union
Medical College, Department of Liver Surgery, State Key Laboratory of
cellular carcinoma (HCC) have rapidly increased in numbers over
recent years and they should be combined in a rationale sequence to Complex Severe and Rare Diseases, Beijing, China; 5Guizhou Medical
University, Guiyang, China
offer the best net health benefit. Atezolizumab plus Bevacizumab
Email: [email protected]
now represents the standard of care for first-line treatment, but
efficacy and safety of subsequent treatment lines still remain Background and aims: This study aimed to investigate the incidence
unknown. According to hepatological and oncological guidelines, rate and risk factors for hepatic encephalopathy (HE) among
Sorafenib could be an option for second-line treatment after first-line unresectable hepatocellular carcinoma (uHCC) patients with liver
Atezolizumab plus Bevacizumab and Cabozantinib is the only cirrhosis who received sorafenib (SOR) or lenvatinib (LEN) treatment.
systemic agent tested as third-line treatment. The aim was to Method: uHCC patients with cirrhosis who received SOR or LEN
estimate the overall survival (OS) of the sequence of Atezolizumab treatment from September 2014 to February 2021 were continually
plus Bevacizumab (first-line) followed by Sorafenib (second-line) recruited in our single-centre retrospective study. Hepatic
followed by Cabozantinib (third-line). Encephalopathy Scoring Algorism was used to evaluate occurrence
Method: A Markov model (Figure 1) was constructed to estimate the and grade of HE during treatment and logistic regression models
OS of the sequence Atezolizumab plus Bevacizumab (first-line) were used to further explore risk factors for HE.
followed by Sorafenib (second-line) followed by Cabozantinib (third- Results: 214 patients were enrolled in SOR group, while the other 240
line). The probability of transition between states (first-line treat- patients were in LEN group, with no statistical difference in baseline
ment, HCC progressions and death) was derived from published characteristics. At time of data cut-off (2021–12), the incidence of HE
randomized controlled trials (RCTs). The proportion of patients who in SOR group (4.2%, 95%CI: 2%–7%) was significantly lower than that
did not receive subsequent lines of therapy due to death was in LEN group (11.3%, 95%CI: 7%–15%) ( p = 0.006). Alcohol-related
considered when estimating survival. OS was the main outcome. cirrhosis [OR: 5.857 (95%CI: 1.519–22.591)], Child-Pugh Score >7 [OR:
Rates of severe adverse events (SAEs) (defined as ≥grade 3 adverse 3.023 (95%CI: 1.135–8.053) ], blood ammonia ≥38.65 μmol/L [OR:
events) were calculated. 4.693 (95%CI: 1.782–12.358) ], total bile acid ≥29.5 μmol/L [OR:
11.047 (95%CI: 4.414–27.650)], LEN treatment [OR: 6.162 (95%CI:
2.258–16.818)] and duration of treatment ≥5.6 months [OR: 4.350
(95%CI: 1.701–11.126)] were confirmed as risk factors for HE
occurrence during tyrosine kinase inhibitors treatment.

Table 1: Occurrence of Hepatic Encephalopathy.

SOR Group LEN Group P
Variables (n = 214, %) (n = 240, %) value
Cases of HE 9 (4.2%) 27 (11.3%) 0.006
Grade of HE
1 0 (0%) 1 (0.4%) ——
2 3 (1.4%) 14 (5.8%) ——
3 5 (2.3%) 4 (1.7%) ——
4 1 (0.5%) 7 (2.9%) ——
Unknown 0 (0%) 1 (0.4%) ——
Therapeutic Effect
Results: The estimated median OS of the sequential strategy is 28 of HE
Cure 8 (3.7%) 20 (8.3%) ——
months (95% Confidence Interval 27–29 months). Rate of SAEs is
Void 1 (0.5%) 7 (2.9%) ——
67.5%. Discontinuation 5 (2.3%) 18 (7.5%) ——
Conclusion: This simulation model provides a forecast of the of SOR/LEN
outcomes of the next available sequential systemic treatment of Treatment
patients with HCC. The sequence including first-line Atezolizumab
plus Bevacizumab followed by second-line Sorafenib followed by ——: not applicable
third-line Cabozantinib leads to a median OS of more than two years, HE: hepatic encephalopathy, SOR: sorafenib, LEN: lenvatinib.
with about two thirds of patients experiencing SAEs. Prospective real- Conclusion: uHCC patients with cirrhosis who receive LEN are more
world studies are needed to substantiate the net health benefit of this likely to develop HE than SOR, with alcohol-related cirrhosis, Child-
sequence. Pugh Score, serum ammonia, total bile acid, and duration of
treatment to be risk factors for HE.

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POSTER PRESENTATIONS JOURNAL OF
HEPATOLOGY

Friday 24 June and immunohistochemistry staining of CK19 revealed that OCA

treatment enhanced ductular reaction induced by BDL, and the
immunofluorescence staining of CK19 and Ki67 also proved this.
Immunoblots analysis of PCNA and immunohistochemistry staining
of Ki67 revealed that OCA treatment weakened liver regeneration. RT-
PCR analysis of liver nonparenchymal cells revealed that OCA
Acute liver failure and drug induced liver injury increased the expression of integrin αvβ3 receptors in BDL mice,
which is OPN targeted.
Conclusion: OCA aggravated the degree of liver injury and fibrosis in
FRI001 obstructive cholestasis probably associated an apparent increase of
Obeticholic acid exacerbates the liver fibrosis of bile duct ligation OPN in serum and liver. OPN may be a biomarker of liver toxicity
model by inducing the liver expression of osteopontin caused by OCA.
Jie Wang1, Yuan Zihang1, Yingying Miao1, Haoran Zhang1,
Qipeng Wu1, Xinliang Huang1, Luyong Zhang1,2, Q. W. Yu1, FRI002
Zhenzhou Jiang1,3,4. 1China Pharmaceutical University, New Drug A report on the Australian Drug Induced Liver Injury Network:
Screening Center, Jiangsu Center for Pharmacodynamics Research and AusDILIN
Evaluation, Nanjing, China; 2Guangdong Pharmaceutical University, Beverly Rodrigues1, Stephen Bloom1,2, Rohit Sawhney1,2,
Center for Drug Research and Development, Guangdong, China; 3China Geoffrey Haar1,3, Maria Bishara1, Ayushi Chauhan1, Paul Gow4,
Pharmaceutical University, Key Laboratory of Drug Quality Control and Simone Strasser5, Alan Wigg6, Karl Vaz4, Fadak Mohammadi6,
Pharmacovigilance, Nanjing, China; 4China Pharmaceutical University, Amanda Nicoll1,2. 1Eastern Health, Gastroenterology, Australia; 2Eastern
State Key Laboratory of Natural Medicines, Nanjing, China Health Clinical School, Monash University, Australia; 3Eastern Health,
Email: [email protected] Pharmacy, Australia; 4Austin Health, Gastroenterology, Australia; 5Royal
Background and aims: Liver fibrosis is a dynamic process character- Prince Alfred Hospital, Gastroenterology, Australia; 6Flinders Medical
ized by the deposition of the accumulated extracellular matrix (ECM). Centre, Gastroenterology, Australia
To date, there are still no therapeutic medications approved for Email: [email protected]
fibrosis or cirrhosis. Osteopontin (OPN) is a phosphoglycoprotein of Background and aims: Drug induced liver injury (DILI) may vary in
ECM, and has been reported to drive ductular reaction (DR) and the different regions due to population and prescribing differences. Data
formation of periportal scarring. Obeticholic acid (OCA) is approved on DILI in Australia is limited but is necessary to inform local
for Primary Biliary Cholangitis (PBC), and OCA has been shown to management. We present prospectively collected data from seven-
improve the fibrosis in NASH patients evaluated in REGENERATE teen Australian liver centres in a new collaboration named AusDILIN.
study. But the applications of OCA are limited due to its side effects. Method: A prospective multicentre clinical audit was conducted on
The main objective of this study is to investigate the impact of OCA on reported DILI patients between June 2018 to November 2021
liver diseases. inclusive (41 months).
Method: The bile duct ligation model was used to evaluate the effect Results: Data on 150 patients was obtained, and showed the
on fibrosis of OCA assessed by assessment of blood markers of liver commonest causes were: amoxicillin/clavulanic acid (n = 26, 17%),
injury, pathological section, western blotting, RT-PCR, immunohis- statins (n = 15, 10%) and cephalosporins (n = 12, 8%). Remdesivir was
tochemistry and immunofluorescence stainging. OPN and Thr-OPN the identified causative agent in 5 (3%) of cases. Sixteen (11%) of
were detected by ELISA. The primary mouse cholangiocytes and patients were icteric on presentation. The median duration to onset
human intrahepatic bile epithelium cells were chosen to investigate and recovery was 3 ± 7.4 weeks, and 8 ± 12.9 weeks, respectively. One
in vitro. hundred and twelve (75%) were managed as inpatients. Forty-seven
Results: Compared to control, OCA treatment (40 mg/kg) aggravated (31%) received some form of treatment; 11 (7%) were managed with
BDL induced liver injury and liver fibrosis in mice, demonstrated by ursodeoxycholic acid and 23 (15%) with corticosteroid monotherapy
significantly increase in serum ALT, AST, ALP, TGF-β1, hepatic respectively, although 2 (1%) and 1 (1%) were already on these
hydroxyproline, Masson Trichrome, H&E, and Sirius red staining as treatments long-term for chronic conditions. Of the 11 (7%) of
well as immunohistochemistry staining of α-SMA. The serum and patients with unresolving DILI, 4 (3%) were considered for liver
liver content of OPN and its another active form, thrombin-cleaved transplant. Two (1%) of these were successfully transplanted and 1
OPN (Thr-OPN), were obviously increased in OCA-treated BDL mice. (1%) died, with the overall cohort death rate being 4 patients (3%).
Interestingly, there was also a significant increase in the content of Fifty patients (33%) were lost to follow up. The DILI persisted beyond 3
Thr-OPN in the liver of OCA-treated sham mice. Next we examined and 6 months in 30 (45%) and 10 (7%) of cases, respectively.
the downstram effects of OPN in liver disease. Immunoblots analysis

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 © 2022 All rights reserved.
POSTER PRESENTATIONS
existing liver disease, age, sex, albumin, obesity, diabetes mellitus,
Table 1: Baseline characteristics of AusDILIN cohort cardiovascular disease, lung disease and malignancy.
Results: 900 patients (52.4% male) were included with 32.2% aged
Median age (years) 56.37 ± 0.44 [18–94]
Gender (M: F, n, %) 80 (53%): 70 (47%) 18–39 years, 39.7% 40–69 years, and 28.1% ≥70 years age strata,
Ethnicity (n, %) Caucasian/European 114 (76%) respectively. Frequency of comorbidities, median D-dimer and
SE Asian/Arabic 31 (21%) C-reactive protein increased with age.
African 2 (1%) After SARS-CoV-2 infection, parameters of hepatocellular (aspartate
Unknown 3 (2%) aminotransferase [AST]/alanine-aminotransferase [ALT]) and chole-
Pattern of liver injury (n, %) Hepatitic: Cholestatic 54 (36%): 44 static liver injury (alkaline phosphatase [ALP]/gamma-glutamyl
(29%) transferase [GGT]) all significantly increased. AST/ALT and ALP/GGT
Mixed: Unknown 51 (34%): 1 were elevated in 40.3% (n = 262/650) and 45.0% (n = 287/638) of
(1%)
patients, respectively. The rates of COVID-19-associated liver injury
Treatment offered (n, %) CS monotherapy 23 (15%)
UDCA monotherapy 11 (7%) and median levels of liver chemistries were highest in patients aged
CS plus UDCA 5 (3%) 40–69 (18–39 years: 8.5% vs. 40–69 years: 16.0% vs. ≥70 years: 4.6%;
combination therapy p < 0.001).
CS plus IM 4 (3%) Elevated AST after the first SARS-CoV-2 PCR test was associated with
combination therapy the requirement for hospital admission, ICU admission and intub-
NAC infusion 2 (1%) ation throughout all age strata and with a higher frequency of death
Clinical outcomes (n, %) Self-resolved or 87 (58%) and liver-related death in patients aged 40–69. Elevated AST and total
resolving bilirubin (BIL) at the time of first positive SARS-CoV-2 PCR test
Unknown or lost to 50 (33%)
independently predicted of mortality in the overall cohort (AST: aHR:
follow up
Persistent or 11 (7%) 1.47; 95%CI: 1.01–2.14; p = 0.043/BIL: aHR: 2.20; 95%CI: 1.22–3.98;
progressed p = 0.009) and in patients aged 40–69 years (AST: aHR: 1.78; 95%CI:
Death (DILI ALF) 4 (3%) 1.04–3.06; p = 0.037/BIL: aHR: 2.18; 95%CI: 1.15–4.13; p = 0.017).
Considered for LTx (n, %) 4 (3%)
Transplanted 2 (1%)
Resolved 1 (1%)
Death 1 (1%)

HTN = hypertension, Chol = cholesterol, DM = diabetes mellitus,

CS = corticosteroids, UDCA = Ursodeoxycholic acid, IM = immunomodulator,
NAC = N-acetyl cysteine, LTx = liver transplant, ALF = acute liver failure.

Conclusion: DILI is a significant cause of morbidity and mortality in

Australia, with a high proportion suffering persistent liver injury, and
with the role of treatment remaining undetermined and requiring
further study.

FRI003 Conclusion: A considerable proportion of COVID-19 patients show

Incidence, phenotype and prognostic relevance of COVID-19- abnormal liver chemistries. The subgroup of patients aged 40–69
related liver injury across different age strata years was at particularly high risk for COVID-19-related liver injury;
Lukas Hartl1,2, Katharina Haslinger1,2, Martin Angerer1,2, elevated ALT was predictive of liver-related mortality. AST and BIL at
Mathias Jachs1,2, Benedikt Simbrunner1,2,3, David J. M. Bauer1,2, the time of first positive SARS-CoV-2 PCR were independent
Bernhard Scheiner1,2, Ernst Eigenbauer4, Robert Strassl5, predictors of mortality in the overall group, and particularly in
Monika Breuer5, Oliver Kimberger6, Daniel Laxar6, Michael Trauner1, patients aged 40–69 years.
Mattias Mandorfer1,2, Thomas Reiberger1,2,3. 1Medical University of
Vienna, Division of Gastroenterology and Hepatology, Department of FRI004
Medicine III, Vienna, Austria; 2Medical University of Vienna, Vienna Two different types of COVID-19 vaccines and serial liver
Hepatic Hemodynamic Lab, Division of Gastroenterology and biochemistries
Hepatology, Department of Medicine III, Vienna, Austria; 3Medical Grace Lai-Hung Wong1, Vicki Wing-Ki Hui1, Terry Cheuk-Fung Yip1,
University of Vienna, Christian Doppler Lab for Portal Hypertension and Yee-Kit Tse1, Vincent Wai-Sun Wong1. 1The Chinese University of Hong
Liver Fibrosis, Vienna, Austria; 4Medical University of Vienna, IT-Systems Kong, Medical Data Analytic Centre (MDAC), Hong Kong
and Communications, Vienna, Austria; 5Medical University of Vienna, Email: [email protected]
Department of Laboratory Medicine, Division of Clinical Virology,
Background and aims: A handful of vaccines against COVID-19 have
Vienna, Austria; 6Medical University of Vienna, Department of
been approved around the world. These vaccines have excellent
Anaesthesia, Intensive Care Medicine and Pain Medicine, Vienna, Austria
safety profiles with few reported side effects. Data concerning the
Email: [email protected]
liver safety of COVID-19 vaccines are lacking. We aimed to report the
Background and aims: Severe acute respiratory distress syndrome- serial liver biochemistries of people before and after receiving COVID-
coronavirus-2 (SARS-CoV-2) caused the pandemic of coronavirus 19 vaccines.
disease of 2019 (COVID-19). Variable abnormalities in liver chemis- Method: This was a territory-wide retrospective observational cohort
tries have been reported in COVID-19 patients. We assessed the study in Hong Kong. We identified subjects who had received any of
prevalence rates and trajectories of elevated liver enzymes after the two COVID-19 vaccines approved in Hong Kong-CoronaVac (the
SARS-CoV-2 infection, as well as their prognostic values across inactivated virus technology platform by Sinovac Biotech (Hong
different age strata in a large cohort of COVID-19 patients. Kong) Limited) and Comirnaty (mRNA technology platform by Fosun
Method: Patients with a positive SARS-CoV-2 PCR result between 03/ Pharma in collaboration with the German drug manufacturer
2020–07/2021 at the Vienna General Hospital were included in this BioNTech, the BNT162b2 mRNA vaccine). Serial liver biochemistries
study. Patients were stratified for age (i.e. 18–39 vs. 40–69 vs. ≥70 at least 3 months before and after the COVID-19 vaccines were
years). Multivariate Cox regression analyses were adjusted for pre- reported, in subjects with or without chronic hepatitis B or C.

S390 Journal of Hepatology 2022 vol. 77(S1) | S389–S664

 POSTER PRESENTATIONS

Figure: Serial liver biochemistries before and after COVID-19 vaccine.

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S391

POSTER PRESENTATIONS
Results: 851 subjects (513 received CoronaVac and 338 received normalization was 110 (20–265) days for patients with cholangitic
Comirnaty; 56.2% male, median age 52 years old; 6.8% chronic profile without corticosteroids, 120 (18–221) days for patients with
hepatitis B or C) were included. Majority (87%) subjects had normal cholangitic profile with corticosteroids and 54 (29–79) days for non
ALT (1–2 × ULN: 10.8/%; >2 × ULN: 2.4%), total bilirubin (1–2 × ULN: cholangitic patients (Figure 1).
3.3%; >2 × ULN: 0%) and ALP (1–2 × ULN: 5.4%; >2 × ULN: 0.5%) before
or at the time of receiving COVID-19 vaccines; these parameters
remained stable for up to 3 months after the vaccination-ALT (1–2 ×
ULN: 11.6%; >2 × ULN: 2.1%), total bilirubin (1–2 × ULN: 3.7%; >2 ×
ULN: 0%) and ALP (1–2 × ULN: 5.4%; >2 × ULN: 0.8%) at or after the
time of receiving COVID-19 vaccines. While patients with chronic
viral hepatitis had higher ALT and ALP than those without chronic
viral hepatitis at most of the times, these parameters remained
normal (ALT: median 24 to 26 U/L vs. 20 to 21 U/L; ALP: median 88 to
90 U/L vs. 80 U/L). Similar serial liver biochemistries were observed in
subjects who received CoronaVac and Comirnaty vaccine.
Conclusion: Both types of COVID-19 vaccines have very favourable
liver safety profile in people with or without chronic viral hepatitis.
Grant support: This work was supported by the Health and Medical
Research Fund (HMRF)-Food and Health Bureau Commissioned
Research on COVID-19 (Reference no.: COVID1903002) awarded to
Grace Wong.

FRI005 Figure: ALT normalisation interval according to cholangitic histological

Role of liver biopsy in management of immune checkpoint profile and corticosteroids treatment
inhibitors hepatitis: a single-center retrospective study
Conclusion: In ICI-DILI, liver biopsy must not delay patient care but
Kennie Marcin1, Lucia Parlati1, Benoit Terris2, Clemence Hollande1,
may be useful in identifying patients with a cholangitic profile who
Anais Vallet Pichard1, Helene Fontaine1, Marion Cororuge1,
have a poorer response to corticosteroids. Corticosteroids could be
Loriane Lair Mehiri1, Vincent Mallet1, Philippe Sogni1, Stanislas Pol1.
1 reserved to patients who do not improve after ICI withdrawal.
AP-HP.Centre-Université de Paris, Groupe Hospitalier Cochin Port Royal,
DMU Cancérologie et spécialités médico-chirurgicales, Service FRI006
d’Hépatologie, Paris, France, France; 2AP-HP.Centre-Université de Paris, Immune checkpoint inhibitors induced liver injury: an
Groupe Hospitalier Cochin Port Royal, Service de Pathologie, Paris, France observational study
Email: [email protected] Lina Hountondji1, Pascale Palassin2, Stéphanie Faure1, Sarah Iltache1,
Background and aims: Immune check point inhibitors drug Marie Dupuy3, Georges-Philippe Pageaux1, Jean Luc Faillie2,
induced-liver injury (ICI-DILI) may be associated with chemotherapy Candice Lesage4, Elodie Negre5, Eric Assenat3, Patricia Rullier6,
dose reduction and cancer progression. It is unclear whether liver Valérian Rivet3, Xavier Quantin7, Alexandre Maria6, Lucy Meunier1.
1
biopsy modifies, or not, the management of ICI-DILI. CHU Montpellier, Hepatology, Montpellier, France; 2CHU Montpellier,
The aim of this study was to explore the impact of liver biopsy on the Pharmacology, Montpellier, France; 3CHU Montpellier, Oncology,
clinical management and the response to corticosteroids according to Montpellier, France; 4CHU Montpellier, Dermatology, Montpellier,
histological findings. France; 5CHU Montpellier, Pneumology, Montpellier, France; 6CHU
Method: We conducted a retrospective, single-center study to Montpellier, Internal Medicine and Multi-Organic Diseases, Montpellier,
evaluate the biochemical, histological and clinical data of 28 patients France; 7Montpellier Cancer Institute, Medical Oncology, Montpellier,
with ICI-DILI who underwent liver biopsy (June 2015 to January France
2021) in a teaching hospital in France. The severity of liver injury was Email: [email protected]
graded according to Common Terminology Criteria for Adverse Background and aims: Immune checkpoint inhibitors (ICI), target-
Events version 5.0 guidelines. ing programmed cell death 1 (PD-1), its ligand (PD-L1) and anti-
Results: Of the 28 patients (median [interquartile range] age 55 [23– cytotoxic T lymphocyte-associated protein 4 (CTLA-4) changed the
80] years, 36% males), 13 patients (46%) had anti PD1 monotherapy, 6 landscape of cancer therapy. Liver toxicity is occurring up to 16% in
patients (21%) anti PD1/anti CTLA4 combination therapy and 9 patients treated with ICI. International guidelines recommend
patients (32%) other immunotherapy. ICI-DILI occurred later in the pausing immunotherapy and administering corticotherapy, regard-
other immunotherapy group than in the anti PD1 monotherapy and less of the hepatitis phenotype. The aim of our study is to describe the
anti PD1/anti CTLA4 combination therapy groups (18.6 injections [1– different phenotypes of ICI induced hepatitis and to assess their
60] vs 4 [1–28] and 3 [1–4] respectively, p = 0.047). The type of ICI did evolution.
not influence the severity of the histological profile of the hepatitis, Method: We conduct an observational study in patients with
but patients receiving anti PD1/anti CTLA4 combination therapy had immune-mediated hepatitis due to ICI and submitted to the
a tendency to more severe hepatitis in comparison to anti PD1 and «ToxImmun» multidisciplinary meeting in Montpellier between
other immunotherapy (83% of grade 3–4 hepatitis vs 61% and 57% December 2018 and October 2021. Data were collected at diagnosis,
respectively, p = 0.095). We did not observe any severe liver injury in week 1, 2 and 4, and once a week until hepatitis recovery. Data
our cohort. Corticosteroids were introduced in 6 (100%) patients of regarding cancer, hepatitis treatments, and ICI rechallenge were
the anti PD1/anti CTLA4 combination therapy group, 7 (54%) patients collected. The hepatitis phenotype is defined by the ratio of serum
of the anti PD1 monotherapy group and 4 (44%) patients under other ALT and ALP [R value = (ALT/ULN)/(ALP/ULN)], and categorized as
therapy. All patients had a favourable clinical evolution after ICI cholestatic (R ≤ 2), hepatocellular (R ≥ 5), or mixed (2 < R < 5).
withdrawal with no significative difference in the ALT normalization Results: Of the 389 patients presented, hepatitis accounted for 14.7%
interval depending on the introduction of corticosteroids. The of toxicities due to ICI (n = 57), 52 patients were included. 52.8% were
response to corticosteroids was similar according to the type of ICI men (n = 28) and the median age was 66 (range 23–87). PD-1
and to the histological findings except for the cholangitic profile inhibitor was the most prescribed ICI class (n = 48, 92.3%), alone (n =
which seems to have a poorer response. The interval for ALT 31, 59.6%), or with CTLA-4 inhibitor (n = 17, 32.7%). Hepatitis

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 POSTER PRESENTATIONS

Figure: (abstract: FRI006)

phenotype was cholestatic in 40.4% (n = 21), hepatocellular in 30.8% Sorbonne.Université, Hôpitaux Universitaires Pitié Salpêtrier̀ e-Charles
(n = 16), and mixed in 28.8% (n = 15). Hepatitis were predominantly Foix, DMU PRIME, Pharmacie à Usage Intérieur, France, France; 4AP-HP.
grade 3, according to the CTCAE system (71.2%, n = 37). No case of Centre-Université de Paris, Groupe Hospitalier Cochin Port Royal, DMU
severe acute hepatitis has been reported. Liver biopsy was performed BIOPHYGEN, Service de Virologie, Paris, France; 5AP-HP.Centre-
in 38.5% (n = 20). Biliary stenosis occurred in 6 patients (28.6%). An Université de Paris, Groupe Hospitalier Cochin Port Royal, DMU PRIM,
extra-hepatic irAE was reported in 46.2% (n = 24). Most patients were Service d’Information Médicale, Paris, France; 6AP-HP.Sorbonne.
treated with corticosteroids (76.9%, n = 40) and ursodeoxycholic acid Université, Hôpitaux Universitaires Pitié Salpêtrier̀ e-Charles Foix, DMU
(UDCA) was in 32.7% (n = 17) patients. ICI was resumed in 46.2% (n = ESPRIT, Département d’Information Médicale, France; 7AP-HP.Centre-
24), 70.8% received the same ICI (n = 17) and 95.8% received a single Université de Paris, Groupe Hospitalier Cochin Port Royal, DMU PRIME,
ICI (n = 23). The rate of hepatitis recurrence after treatment Pharmacie clinique, Paris, France; 8AP-HP.Sorbonne.Université, Hôpitaux
reintroduction was 37.5% (n = 9). 10 patients died (19.2%), unrelated Universitaires Pitié Salpêtrier̀ e-Charles Foix, DMU PRIME, Pharmacie à
to ICI. Usage Intérieur, France; 9AP-HP.Sorbonne.Université, Hôpitaux
Conclusion: The frequency of ICI related hepatitis is about 14.7% in Universitaires Pitié Salpêtrier̀ e-Charles Foix, DMU SAPERE, Service
our study. This result is consistent with the literature. Future studies d’Hépatogastroentérologie, Paris France; 10AP-HP.Sorbonne.Université,
should be considered to adapt the treatment to the hepatitis Hôpitaux Universitaires Pitié Salpêtrier̀ e-Charles Foix, DMU ORPHE,
phenotype, particularly in the case of cholestatic pattern, by Service d’oncologie médicale, France; 11AP-HP.Centre-Université de
specifying the place of UDCA. Paris, Groupe Hospitalier Cochin Port Royal, DMU Cancérologie et
spécialités médico-chirurgicales, Service de Cancérologie, Paris, France;
FRI007 12
AP-HP.Centre-Université de Paris, Groupe Hospitalier Cochin Port
Liver toxicities of immune checkpoints inhibitors for cancer: a Royal, DMU Cancérologie et spécialités médico-chirurgicales, Service
multicenter retrospective study d’Hépatologie, Paris, France
Lucia Parlati1, Mehdi Sakka2, Agnès Bellanger3, Jean François Meritet4, Email: [email protected]
Samir Bouam5, Aurelia Retbi6, Pierre Rufat6,
Dominique Bonnefont-Rousselot2, Rui Batista7, Patrick Tilleul8, Background and aims: There are uncertainties on the clinical
significance of liver toxicities of immune checkpoint inhibitors
Dominique Thabut9, Jean-Philippe Spano10, Francois Goldwasser11,
(ICI). The aim of our study was to compare liver toxicities under ICI
Philippe Sogni12, Stanislas Pol12, Vincent Mallet12. 1AP-HP.Centre-
Université de Paris, Groupe Hospitalier Cochin Port Royal, DMU and conventional chemotherapy.
Method: We conducted a retrospective, longitudinal cohort study
Cancérologie et spécialités médico-chirurgicales, Service d’Hépatologie,
Paris, France, PARIS 14E ARRONDISSEMENT, France; 2AP-HP.Sorbonne. among cancer patients who received systemic chemotherapy with or
without ICI between January 1, 2010, and December 31, 2019, in two
Université, Hôpitaux Universitaires Pitié Salpêtrier̀ e-Charles Foix, DMU
teaching hospitals of Assistance Publique-Hôpitaux de Paris (France).
BioGeM, Service de Biochimie Métabolique, Paris, France; 3AP-HP.
We measured the incidence of grade 3–4 liver injury after ICI or

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S393

POSTER PRESENTATIONS

Figure: (abstract: FRI007): Cumulative incidences of liver injury after systemic chemotherapy in a multicenter, retrospective, cohort of cancer patients (N =
22, 206).

conventional chemotherapy, the adjusted hazard ratios [aHR (95% University Feinberg School of Medicine, Chicago, United States;
2
CI)] for hepatocellular injury, cholestasis and jaundice and investi- UT Southwestern Medical Center, Dallas, United States; 3Virginia
gated the management and outcome of patients with ICI drug- Commonwealth University Medical Center, Richmond, United States;
4
induced liver injury (ICI-DILI). Mayo Clinic, Phoenix, United States; 5Medical University of South
Results: The sample comprised 22, 206 patients (median [interquar- Carolina, Columbia, United States; 6Baylor College of Medicine, Houston,
tile range] age 63 [52–72] years, 54.4% males), including 953 (4.3%) United States; 7University of Washington Medicine, Seattle, United
with ICI. The incidence of grade 3–4 liver injury was 209 (21.9%) and States; 8University of California San Francisco, San Francisco, United
5, 765 (27.1%) for patients treated with and without ICI, respectively States; 9Medical University of South Carolina, Columbia
( p < 0.001). ICI patients were at risk [aHR 1.46 (1.23–1.75) P < 0.001] Email: [email protected]
for cholestasis without [aHR 0.96 (0.60–1.53) P = 0.860] jaundice. ICI
Background and aims: Autoimmune hepatitis (AIH) is a common
patients were not [aHR 1.12 (0.86–1.45), P = 0.401] at risk for
cause of acute liver failure (ALF). Treatment includes steroids in those
hepatocellular injury. Grade 3–4 liver injury was attributed to ICI-
with acute liver injury (ALI) and liver transplantation (LT) in those
DILI in 26 (2.7%) patients. Grade 4 transaminase and serum bilirubin
who fail to respond or develop ALF. The aim of this study is to better
elevations concerned 6 (0.6%) and 1 (0.1%) ICI-DILI patient,
characterize the clinical and laboratory data of patients presenting
respectively. All patients with ICI DILI had ICI withdrawal, and 11
with ALI or ALF secondary to AIH and to identify a combination of
(42.3%) died thereafter with cancer progression. ICI reintroduction
clinical variables that predict 21-day transplant-free survival (TFS).
after ICI-DILI was a rare (n = 7; 26.9%) event and was infrequently (n =
Method: The study included hospitalized adults presenting with ALI
1) associated with recurrent liver injury.
or ALF enrolled in the Acute Liver Failure Study Group Registry
Conclusion: Patients treated with ICI were at lower risk of clinically
between 1998 and 2019 from 32 centers within the United States.
significant liver injury than patients treated with conventional
A review panel adjudicated the etiology of all cases and those iden-
chemotherapy. There may be potential gains from refraining ICI
tified as AIH were reviewed. ALI was defined as international normal-
dose reduction in patients with ICI-associated liver injury.
ized ratio (INR) ≥2.0 without encephalopathy and ALF as any degree
FRI008 of encephalopathy with INR ≥1.5. Laboratory and clinical data were
Acute severe presentation of autoimmune hepatitis: a 20-year reviewed, and variables significantly associated with 21-
retrospective review of the United States day TFS were used to develop a multivariable logistic regression
model.
Thomas Enke1, Daniel Ganger1, Jody Rule2, Richard Stravitz3,
Results: A total of 244 of 3364 cases were identified as AIH and
Jorge Rakela4, Adrian Reuben5, Norman Sussman6, Anne Larson7,
reviewed. 161 patients (66%) were diagnosed with ALF and 83 with
Shannan Tujios2, Nathan Bass8, Sherry Livingston9,
ALI (34%). At 21 days, 116 patients (48%) had undergone LT, 69 (28%)
Valerie Durkalski-Mauldin9, William M. Lee2. 1Northwestern
had TFS and 59 (24%) had died. Patients presenting with ALI had a
higher TFS rate (53%) than patients presenting with ALF (16%). Most
presenting with ALI received steroids (73%) and were more likely to
have TFS (66%) than those who did not receive steroids

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 POSTER PRESENTATIONS
(18%). Administration of steroids in those with ALI, admission values These subgroups displayed differential gene expression upon cocktail
of bilirubin, INR, albumin and platelet count were significantly asso- treatment, and xenobiotic metabolism-related specialization.
ciated with improved TFS and a diagnosis of ALF in those who Furthermore, lipid accumulation was found to increase transcrip-
received steroids was associated with worse TFS in a multivariable tional variability in two subgroups of hepatocytes, and to differen-
logistic regression analysis. The resulting model predicted TFS with a tially affect the expression of genes involved in lipid metabolism. In
C-statistic of 0.94. particular, intracellular fat accumulation was shown to diminish the
drug-related metabolic capacity of hepatocytes.
Table 1: Variables associated with 21-day transplant free survival
Multivariate model
Predictor Adjusted odds ratio 95% CIa
Bilirubin 0.04 (0.01, 0.15)
INRb 0.30 (0.16, 0.56)
Platelet count 1.06 (1.01, 1.10)
Albumin 3.10 (1.34, 7.16)
Steroid use with ALIc 31.19 (3.35, 290.05)
Steroid use with ALFd 1.62 (0.57, 4.58)
ALF without steroid use 0.78 (0.11, 5.51)
ALF with steroid use 0.041 (0.01, 0.171)
a
CI = confidence interval.
b
INR = international normalized ratio.
c
ALI = acute liver injury.
d
ALF = acute liver failure during hospitalization. Figure: Graphical abstract summarizing the hypothesis stated.
Conclusion: Acute severe presentations of AIH are associated with a Conclusion: Our results demonstrate that, upon a metabolic
high mortality. Steroids remain a cornerstone of treatment and nearly challenge such as exposure to drugs or intracellular fat accumulation,
half of patients will require LT. Early identification of those needing LT hepatocyte subgroups exhibit heterogeneous transcriptomic
is critical to prevent delays in listing. We developed a model responses.
specifically for AIH that may be helpful in predicting 21-day TFS
and early identification of patients in need for expedited LT References
evaluation. Further assessment of model performance and inde- 1. Richter M. L. et al. (2021). Nat Commun.
pendent model validation are future work. 2. Kamies R. and Martinez-Jimenez C. P. (2020). Mamm Genome.
3. Xiong X. et al. (2019). Molecular Cell.
4. Park S. R. et al. (2020). American Journal of Physiology-Endocrinology
FRI009 and Metabolism.
Single-cell metabolic profiling of primary human hepatocytes 5. Turpault S. et al. (2009). Br J Clin Pharmacol.
shows heterogenous responses to drug metabolism
Eva Sofía Sánchez Quant1, Maria Richter1, Celia Martinez Jimenez1,2, FRI010
Maria Colome Tatche3,4,5. 1Helmholtz Zentrum Munich, Helmholtz Management of severe, steroid-resistant and steroid-refractory
Pioneer Campus, Munich, Germany; 2Technical University Munich, hepatotoxicity in patients treated with checkpoint inhibitor
Faculty of Medicine, Munich, Germany; 3Helmholtz Zentrum Munich, immunotherapy
Institute of Computational Biology, Munich, Germany; 4Ludwig Nashla Hamdan1, Marco Iafolla2, Yada Kanjanapan2, Marcus Butler2,
Maximilian University of Munich, Biomedical Center (BMC), Lillian Siu2, Philippe Bedard2, Kendra Ross2, Keyur Patel1,
Physiological Chemistry, Munich, Germany; 5Technical University Anna Spreafico2, Jordan Feld1, Morven Cunningham1. 1University
Munich, TUM School of Life Sciences Weihenstephan, Munich, Germany Health Network, Toronto Centre for Liver Disease, Toronto, Canada;
2
Email: [email protected] University Health Network, Princess Margaret Cancer Centre, Toronto,
Canada
Background and aims: Drugs are primarily metabolized by
Email: [email protected]
hepatocytes in the liver, and primary human hepatocytes (PHHs)
are the gold standard model for the assessment of drug efficacy, Background and aims: Checkpoint inhibitor immunotherapy (ICI)
safety and toxicity in the early phases of drug development. Classic has revolutionized cancer care and is increasingly used in a range of
approaches assume that all hepatocytes in culture are homogeneous primary malignancies. Treatment is associated with immune-related
and share a similar metabolic profile. However, advances in single- toxicities which may require ICI discontinuation and immunosup-
cell genomics have shown the relevance of cellular heterogeneity in pressive therapies (IST). Management of severe ICI hepatotoxicity is
health and disease conditions.1,2 Recently, single-cell RNA sequencing not well defined, especially for patients who respond poorly to initial
has shown that intrahepatic lipid accumulation in Non-alcoholic fatty corticosteroids. We sought to better understand management of
liver disease (NAFLD) affects the transcriptomic profile of parenchy- severe ICI hepatotoxicity and responses to IST.
mal and non-parenchymal liver cells.3,4 The aim of this study is to Method: Patients receiving ICI in early phase clinical trials at Princess
investigate the metabolic capacity of individual human hepatocytes Margaret Cancer Centre, or treated at the Toronto Centre for Liver
in vitro, and assess whether the chronic accumulation of lipids Disease for ICI hepatotoxicity, were included. Patients with CTCAE
enhances cellular heterogeneity. Grade (G)3/4 ICI hepatotoxicity (ALT >5 × ULN) were identified and
Method: PHHs isolated from four donors were incubated with a clinical records reviewed for management and outcomes.
phenotyping 5-probe cocktail (Sanofi-Aventis5) using the so-called Results: From Aug 2012-Oct 2021, 25 patients with G3/4 ICI
“cocktail approach.” In order to mimic the hepatic steatosis occurring hepatotoxicity were identified. Most (17; 68%) had metastatic
in NAFLD, hepatocytes were loaded with free fatty acids, resulting in melanoma. Eleven received anti-CTLA-4/PD-1; 9 anti-PD-1, and 5
intracellular lipid accumulation. Subsequently, cells were incubated anti-CTLA-4 monotherapy. All patients initially received corticoster-
with the five-drug cocktail. After 72 h in culture, hepatocytes were oids for hepatotoxicity (1–2 mg/kg/day prednisone equivalent).
collected and single-cell RNA-sequencing was performed using a Figure 1 shows response to corticosteroids and sequence of
droplet-based approach. additional IST. 13 patients (52%) were steroid-refractory (no response
Results: Four subgroups of hepatocytes were identified consistently, after 48–72 hours) or steroid-resistant (rebound ALT upon steroid
independently of the treatment condition, and across all four donors.

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POSTER PRESENTATIONS

Figure: (abstract: FRI010)

taper). Ten received steroid dose escalation (up to 2 mg/kg/day) with in peripheral blood mononuclear cells from NAFLD, with or without
sustained response in five (50%). Eight (32%) received 2nd line IST significant liver fibrosis, and DILI patients.
with mycophenolate (MMF) for steroid resistant/refractory hepato- Results: There was an increase in iNKT cells in NAFLD patients
toxicity, after median 17.5 days of steroid treatment (IQR 9–21). Four compared to DILI or control subjects ( p = 0.035 and p = 0.031,
(50%; 16% of total cohort) did not respond to MMF and required 3rd respectively). Regarding the cellular activation profile, NAFLD with
line IST (Tacrolimus; dose targeting trough level of 4–6). Age, sex, significant liver fibrosis (F ≥ 2) displayed higher levels of CD69 + iNKT
liver metastases, prior ICI exposure or peak ALT did not predict need cells compared to NAFLD with none or mild liver fibrosis (F ≤ 1) ( p =
for 2nd or 3rd line IST. ALT normalized in all, after median 14 days 0.040) and control patients ( p = 0.031). CD69 + iNKT positively
(IQR 10–27). Patients on corticosteroid alone had shorter total time correlated with insulin resistance, liver fibrosis indexes FIB4 and
on IST than those with additional IST (median 86 days, IQR 41–123) vs APRI, and AST levels. DILI patients showed an increase in CD69+ and
113 days (85–235), p = 0.03). In those given additional IST, rate of ALT HLA-DR+ in both CD4+ and CD8+ T cells, detecting the most relevant
improvement tended to be faster with Tacrolimus than MMF (25.5 IU/ difference in the case of CD69 + CD8+ T cells.
day (IQR 22–29.5) vs 10.5 IU/day (IQR −3 to 29.5), p = ns in this small
cohort). IST-related adverse events occurred in two patients
(vertebral fracture; hyperglycaemia). Over median follow up of 30.6
months (range 2.3–81.5), 12 patients died. No patients died of
complications of hepatotoxicity.
Conclusion: Up to a third of patients with severe (G3/4) ICI
hepatotoxicity may not respond adequately to corticosteroids and
require additional IST. MMF is not consistently effective as 2nd line
IST. To expedite resolution and minimize IST exposure, Tacrolimus
should be considered 2nd line IST alternative. These results will assist
development of treatment algorithms for severe ICI hepatotoxicity,
for further prospective evaluation.

FRI011
Activation marker CD69 differentiates non-alcoholic
steatohepatitis from drug-induced liver injury
Estefanía Caballano-Infantes1, Alberto Garcia Garcia1,
Carlos Lopez-Gomez1, A. Cueto2, Mercedes Robles-Díaz3,
Aida Ortega-Alonso1, F. Martin-Reyes1, Ismael Alvarez-Alvarez2,
Isabel Arranz-Salas4, Francisco Ruiz-Cabello5, Maria Isabel Lucena2,6,
Conclusion: CD69 + iNKT may be a biomarker to assess liver fibrosis
Eduardo García-Fuentes1, Raul J. Andrade1,3, Miren Garcia Cortes1.
1 progression in NAFLD. CD69 + CD8+ T cells were identified as a
IBIMA, Servicio de Aparato Digestivo, Hospital Universitario Virgen de la
potential distinctive biomarker for distinguishing DILI from NAFLD.
Victoria, IBIMA, UMA, Malaga, Spain, Málaga, Spain; 2UMA,
These results support the involvement of the immune system on
Departamento de Farmacologia, Málaga, Spain; 3UMA, Departamento
NAFLD with significant liver fibrosis and DILI development.
de Medicina, Málaga, Spain; 4IBIMA, Servicio de Anatomía Patológica,
Málaga, Spain; 5Hospital Universitario Virgen de las Nieves/UGR, FRI012
Servicio de Análisis Clínicos e Inmunología/Departamento de Natural antibodies are required for necrotic cell debris clearance
Bioquímica y Biología Molecular II/Inmunología, Facultad de Medicina, and liver repair during necrotic liver injury
Granada, Spain; 6IBIMA, Málaga, Spain Matheus Mattos1, Sofie Vandendriessche1, Sara Schuermans1,
Email: [email protected] Romy Mittenzwei2, Ari Waisman2, Pedro Elias Marques1. 1Rega
Background and aims: Activation of the immune system is involved Institute Ku Leuven, Leuven, Belgium; 2Institute for Molecular Medicine,
in both non-alcoholic fatty liver disease (NAFLD) and idiosyncratic University Medical Center of the Johannes Gutenberg-University Mainz,
drug-induced liver injury (DILI). We aimed to identify activation Mainz, Germany
markers in invariant natural killer T (iNKT) and CD4/CD8+ T cells to Email: [email protected]
better understand the pathophysiology of these disorders.
Method: We analyzed the activation profile (CD69, CD25 and HLA- This abstract is under embargo until Thursday 23 June 2022,
DR) and NKG2D on iNKT cells, and CD4/CD8 T cells by flow cytometry 13:30 BST. It will be made publicly available on the congress
website once the embargo has lifted.
S396 Journal of Hepatology 2022 vol. 77(S1) | S389–S664
 POSTER PRESENTATIONS
Method: We used the Caco-2 human colorectal adenocarcinoma cell
line to represent gut and the human hepatic HepaRG line to represent
liver. Caco2 cells were incubated with 0, 5,10 and 20 mM of APAP for 24
hours. Supernatant was transferred onto fresh HepaRG cells for a further
24 hours. Cell cultures were monitored in real time using the ECIS Zθ, an
impedance based cellular assay, using multiple frequencies to measure
tight junctions, adhesion (4 kHz) and cell membrane integrity (64 kHz).
Viability was assessed using PrestoBlue, to monitor cell metabolism,
and Promega Celltiter glo for a measure of total ATP. Percentage of APAP
metabolized by Caco2 cells was measured using LC-MS/MS. IL-8, IL-1b,
IL-6, IL-10, TNF, and IL-12p70 were measured using the CBA Human
Inflammatory Cytokines kit flow-cytometry bead assay.
Results: ECIS measurements showed an increase in tight junctions/
adhesion in a concentration dependent manner on Caco2 cells. In
contrast to previously published work,1 when using Caco2 precondi-
tioned media, toxicity to HepaRG cells was mitigated with no loss of
tight junctions. LC-MS/MS showed that Caco2 cells metabolize 64–
68% of total APAP without any adverse effect on their viability. IL-6
and IL-8 produced by HepaRG cells was appropriately reduced
suggesting an anti-inflammatory effect of APAP.
Conclusion: We have shown that intestinal cells are capable of
removing 2/3 APAP within the intestinal barrier with no compromise
of viability or tight junctions mitigating toxicity to hepatic cells.
Based on these observations, the intestine is an effective barrier
protecting the liver from APAP hepatotoxicity therefore parenteral
administration of APAP should be avoided and if no other option
intravenous dose should be adjusted accordingly.
Reference
1. Gamal Treskes et al. 2017. Low-dose acetaminophen induces early
disruption of cell-cell tight junctions in human hepatic cells and
mouse liver.

FRI014
A new score to predict mortality at baseline in patients not
fulfilling KCH criteria for non acetaminophen induced liver
failure-The "SAFE" score (Severity of ALF in emergency)
Harshvardhan Tevethia1, Rakhi Maiwall1, Shalini Thapar2, Roshan Koul3,
Prashant Mohan Agarwal4, Guresh Kumar5, Ashok Choudhury1,
Shiv Kumar Sarin6. 1Institute of Liver and Biliary Sciences, Hepatology,
Delhi, India; 2Institute of Liver and Biliary Sciences, Radiology, Delhi, India;
3
Institute of Liver and Biliary Sciences, Neurology, Delhi, India; 4Institute of
Liver and Biliary Sciences, Critical Care, Delhi, India; 5Institute of Liver and
Biliary Sciences, Biostatistics, Delhi, India; 6Institute of Liver and Biliary
Sciences, Hepatology, Delhi, India
Email: [email protected]
FRI013
Human paracetamol hepatotoxicity is mitigated by the gut-liver Background and aims: Prognostic scores in ALF such as King’s
axis in vitro College Hospital (KCH) Score have limited sensitivity in stratifying
Katie Morgan1, Martin Vandeputte1, Kay Samuel2, Steven Morley1, patients for liver transplant especially related to non-acetaminophen
Natalie Homer3, Martin Waterfall4, Jonathan Fallowfield1,5, etiology, leading to delayed listing and poor outcomes. The MELD
Peter Hayes1, John Plevris1. 1University of Edinburgh, Hepatology Dept, score also has limitations with the use of creatinine which is not a
Edinburgh, United Kingdom; 2Scottish National Blood Transfusion true representative of liver injury. We studied ALF patients not
Service, The Jack Copland Centre 52 Research Avenue North, Edinburgh, fulfilling KCH criteria; for their clinical course, outcomes, liver
United Kingdom; 3University of Edinburgh, Mass spectrometry core, volume, markers of cerebral edema like Optic Nerve Sheath
Edinburgh, United Kingdom; 4University of Edinburgh, Flow Cytometry Diameter (ONSD) to develop a new score to predict mortality at
Core Facility, Edinburgh, United Kingdom; 5University of Edinburgh, baseline.
Centre for Inflammation Research, Edinburgh, United Kingdom Method: Patients diagnosed to have ALF and not fulfilling KCH
Email: [email protected] criteria at admission were enrolled and electronic data was retrieved
[from June 2010 to May 2021] from the HIS using a predefined format.
Background and aims: The gut liver axis is a bidirectional system
All patients underwent CT imaging (Non contrast) of both Brain and
communicating via signals from the microbiome, immune system,
abdomen at admission. The Liver volume was calculated (CT) along
dietary and genetic influences. We have previously shown in vitro
with changes of cerebral edema were recorded. Baseline parameters
that APAP disrupts tight junctions in hepatic HepaRG cells in a
were correlated along with predictors of outcome, need for liver
concentration dependant manner.1 The aim of this study, was to
transplant, KCH and MELD scores. Cox regression analysis was done at
develop a model of enterohepatic circulation of paracetamol (APAP)
baseline for prediction of mortality.
in vitro and establish whether intestinal barrier has a hepato-
Results: A total of 75 patients were screened of which 49 (65.5%)
protective effect in the context of APAP toxicity.
patients did not fulfil the KCH criteria [mean age 33.24 ± 15.5 years,

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POSTER PRESENTATIONS

Figure: (abstract: FRI013)

males 59.2%]. The all-cause mortality in patients not meeting the KCH
criteria was 44.8%. The most common etiology was hepatitis E (34.7%)
followed by indeterminate etiology (28.6%). On the CT imaging of the
brain, cerebral edema was seen in 34% patients; with significantly
lower liver volume in the ALF non-survivors than survivors (765 ±
465 cm3 vs 1265 ± 346 cm3 p < 0.04). On univariate analysis Grade >3
Hepatic encephalopathy (HE), ONSD (both right/left eye) >5 mm,
jaundice to HE duration >9 days and liver volume <980 cm3 were
found to be significant. On multivariate analysis, HE grade 3 (OR-
7.671, 95% C.I- 0.912–64.55), ONSD > 5 mm (OR- 22.14 95% C.I- 1.943–
252.423), jaundice to encephalopathy >9 days (O.R- 24.82 95% C.I-
2.293–268.65) were found to be significant. We developed the “SAFE”
score using these variables. A score of 5, gave the AUROC value of 90.9
with p < 0.01 (95% CI-82.9–98) with a sensitivity of 90%, specificity of
71%, positive and negative predictive values of 82% and 73%
respectively with Youden index at 50%. On comparison with KCH
(50, 95% C.I-33.6–64.4) and MELD score (65.9, 95% C.I -50–81.9) the
SAFE score was significantly better at predicting mortality in ALF
patients at baseline. Conclusion: In patients not fulfilling the KCH criteria, the newly
developed SAFE score was significantly better in predicting worse
outcomes . Its variables indicate the presence of cerebral edema and
low liver volume as the main causes of mortality in these subset of
patients. Application of the SAFE score should be validated and a
routine use of CT brain and liver be practiced for better stratification
of ALF patients at baseline.

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 POSTER PRESENTATIONS
FRI015 staining, ALT and pro-inflammatory panel of cytokines), fibrosis
Ten-year single center experience in hepatotoxicity due to (Sirius red staining, a-smooth muscle actin, collagen and fibronectin)
mushroom poisoning and metabolic (BAs, cholesterol, triglyceride, glucose tolerance test
Ozan Sarikaya1, Ilker Turan1, Fulya Günsar1, Aysenur Arslan2, (GTT) and fasting blood sugar (FBS)) profiles. In addition, ICS were
Nilay Daniş3, Ferit Çelik1, Galip Ersoz1, Sezgin Ulukaya4, assessed for NTCP and membrane injury of surfactant D (SP-D) and
Murat Zeytunlu5, Omer Ozutemiz1, Ulus Akarca1, Zeki Karasu1. 1Ege the receptor for advanced glycation end-products (RAGE). BAs
University, Medical Faculty, Gastroenterology, Izmir, Turkey; 2Ege trafficking were assessed in ICS and their impact on proliferation
University, Medical Faculty, Internal Medicine, Izmir, Turkey; 3Karabuk and apoptosis were evaluated.
University, Gastroenterology, Karabuk, Turkey; 4Ege University, Medical Results: Compared to WT mice, CCl4-induced ALI and was worsened
Faculty, Anesteziology, Izmir, Turkey; 5Ege University, Medical Faculty, in the histopathology outcome. In addition, serum showed elevated
General Surgery, Izmir, Turkey levels of BAs (3-fold; P = 0.002) associated with increased RAGE, TNF-
Email: [email protected] a, MCP-1, INF-γ, IL-1, IL-6 and IL-8 ( p < 0.01). Moreover, CCl4-induced
ALI showed elevated serum levels in liver enzymes, lipids, glucose
Background and aims: Mushroom poisoning is quite common in and metabolic markers ( p < 0.01). ICS showed high expressions of
Turkey. It can cause acute liver injury and acute liver failure (ALF) aSMA and were correlated with elevated expressions of NTCP. ICS BAs
requiring liver transplantation. We investigated the outcomes of intracellular concentrations were increased (2-fold) with increased
patients with acute hepatotoxicity due to mushroom poisoning in our SP-D (1.2-fold) as well as elevation in their apoptotic rate (2.1-fold) in
cohort. the ALI mice model.
Method: We retrospectively evaluated the characteristics of patients Conclusion: NTCP modulatory expressions on ICS could be an
with liver toxicity due to mushroom poisoning. We also investigated important step in the pathogenesis of ALI. Antagonizing BAs uptake
parameters related to mortality or liver transplantation. may suggest a therapeutic strategy in improving liver-gut axis.
Results: Thirty patients (17/13: F/M, median age 50.4 (22–73)) were
included in the study. Twenty-seven patients presented with nausea FRI017
and vomiting. In addition, fourteen patients had abdominal pain and The association between chronic Colchicine use and incident
sixteen had diarrhea. These patients were admitted to our intensive decompensated cirrhosis
care unit within an average of 2.5 days (6 hours–8 days) after eating Michal Carmiel1,2, Fadi Hassan2,3, Vered Rosenberg4,
mushrooms from the countryside. In 15 patients (fourteen at Gabriel Chodik4,5, Mohammad Naffaa2,3. 1Galilee Medical Center, Liver
admission, one during hospitalization), INR increased >1.5, acute Unit, Nahariya, Israel; 2Bar-Ilan University, The Azrieli Faculty of
liver failure developed in 4 patients (two patients at admission, Medicine, Safed, Israel; 3Galilee Medical Center, Rheumatology Unit,
hepatic encephalopathy developed in two patients during follow- Nahariya, Israel; 4Maccabi Healthcare Services, Epidemiology and
up). The peak levels of ALT, AST and total bilirubin were 2109 ± Database Research, Tel Aviv, Israel; 5Tel-Aviv University, Sackler Faculty of
1963 U/l, 1828 ± 1675 U/L, 4.92 (0.1–28.56 mg/dl), respectively. In Medicine, Tel Aviv, Israel
hospital follow-up, the highest INR levels were found to be an average Email: [email protected]
of 2.29 (±1.56). All patients were treated with N-acetylcysteine (NAC).
Seven patients were treated with penicillin G, six patients with Background and aims: Colchicine (COL) is an anti-inflammatory
silymarin, and two patients with both penicillin G and silymarin. agent, prescribed as a chronic treatment in some medical conditions.
Eight patients underwent plasmapheresis (median 6 times). Two of Although high doses inhibits microtubule formation resulting in
the four patients with ALF underwent emergency liver transplant- mitotic arrest and hepatotoxicit, in clinical practice COL is considered
ation, and one patient died 72 days after transplantation. One patient safe due to relatively low doses. In this study, we examined the
who developed ALF recovered with medical treatment, while the association between chronic use of COL and the incidence of
other patient who could not be transplanted died. In multivariate decompensated cirrhosis event.
analysis, INR and chlorine levels at hospital admission were found to Method: A cohort study using computerized database of 2.3-million
be statistically significant factors for death and liver transplantation. member Maccabi Healthcare Services in Israel. All patients ≥18 y/o
(respectively; OR: 17.8 and p: 0.04 and OR: 0.54 and p: 0.04) who initiated COL between Jan. 1 2000 and Dec. 31 2018 were
Conclusion: In our cohort, the mortality rate of mushroom liver included. Patients were followed until first event of decompensated
toxicity was 10%. High INR levels and detection of hypochloremia cirrhosis (DC), leaving MHS, death or Dec. 31 2019. Excluded: patients
have been associated with serious outcomes such as liver transplant- with a diagnosis of cirrhosis, chronic HBV, HCV, alcoholic or biliary
ation or mortality, and these parameters may be predictive of urgent disease at beseline, patients who developed an event within 12
liver transplantation. months of follow-up, patients treated <30 days, and patients treated
with a mean daily treatment >3 mg/day. COL exposure was evaluated
FRI016 as the Proportion of Months Covered with drug (PMC) and by Mean
CCl4-induced acute liver injury in C57/BL mice model showed Daily Dose (MDD). The PMC was categorized as follows: <20%, 20–
elevated expressions of Na+ taurocholate cotransporting 40%, 40–60%, 60–80%, >80%. Cox regression models were used to
polypeptide on intestinal stellate cells calculate the hazard ratios (HR) and confidence intervals (CI) for the
Johnny Amer1, Reem Sbieh1, Ahmed Salhab1, Rifaat Safadi1. 1Hadassah development of DC.
Hebrew University Hospital, Liver Unit, Jerusalem, Israel Results: A total of 21773 eligible patients initiated COL during study
Email: [email protected] period. During follow-up, 129 incident cases of DC were identified
(68.5/100, 000 person-years, mean follow-up 8.65 ± 5.53 years). In
Background and aims: The Na+ taurocholate cotransporting poly- univariate analysis: COL PMC as well as older age, Familial
peptide (NTCP/SLC10A1) is believed to be pivotal for hepatic uptake Mediterranean Fever (FMF), HbA1c ≥ 6.5, BMI > 40 and Fib-4 > 1.45
of conjugated bile acids. In the case of acute liver injury (ALI), NTCP is at baseline were associated with an event of DC. In multivariate
downregulated leading to hepatic and biliary injury, driving analysis: FMF, BMI > 40, FIB-4 > 1.45 and COL PMC were all signifi-
inflammatory and fibrotic processes. Several studies linked ALI to cantly associated with incident of DC. The highest risk for developing
cause intestinal mucosa damaged. In this study, we aimed to evaluate DC (HR 3.68, 95% CI 2.23–6.07) was in ‘60–80%’ PMC group.
whether bile acid (BAs) trafficking interfere with intestinal stellate Restricting analysis to patients treated for >12 and >60 months, the
cells in an ALI of CCl4 mice model. risk for DC in the PMC group ‘60–80%’ was higher, (HR 4.56, 95% CI
Method: C57/BL mice were i.p injected (1X) with CCl4 (xxx) to induce 2.74–7.58) and (HR 6.69, 95% CI 3.56–12.56), respectively. Patients
ALI. Livers, intestinal stellate cells (ICS) isolated form intestine and
serum were obtained from mice and assessed for inflammatory (H&E

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POSTER PRESENTATIONS

Figure: (abstract: FRI017): Kaplan-Meier analysis for cumulative hazard risk for cirrhosis decompensation related to PMC (%).

with COL PMC ‘60–80%’ had the highest cumulative hazard risk for DC of AP2 on CCL2-driven chemotaxis was examined in vitro in mouse
(Kaplan-Meier analysis, LogRank = 47.192, p < 0.001). RAW 264.7 macrophages and human THP-1 monocytes using
Conclusion: Chronic colchicine use is associated with incident DC in transwell assays, and in vivo in an acute carbon tetrachloride
a cohort of new COL users. induced liver injury mouse model. To assess intrahepatic monocyte
infiltration in vivo, liver tissues were mechanically dissociated using
FRI018 Tissue Grinder, and cell population such as CD45+ leukocytes,
Inhibition of C-C motif chemokine receptor 2 (CCR2) using a novel resident and monocytes-derived macrophages (MoMFs) (CD11b+/++
in silico designed peptide attenuates macrophage migration in and F4/80+/++), and T-cells (CD3+) were analyzed using flow
vitro and intrahepatic monocyte recruitment in vivo cytometry. Furthermore, effects of AP2 on disease progression
Eline Geervliet1,2, Ralf Weiskirchen2, Ruchi Bansal1,3. 1University of (inflammatory and fibrosis markers) were assessed using immuno-
Twente, Medical Cell Biophysics, Enschede, Netherlands; 2RWTH Aachen, histochemistry. The effects of AP2 were compared with CVC in vitro
Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and in vivo.
and Clinical Chemistry, Aachen, Germany; 3University of Twente, Results: AP2 ( p < 0.01) and CVC ( p < 0.05) showed favorable
Translational Liver Research, Netherlands inhibition of CCL2-driven macrophage/monocyte chemotaxis. In
Email: [email protected] vivo, flow cytometric analysis revealed that a decrease in the
population of CD45+ cells and CD11b++F4/80+ MoMFs and (activated)
Background and aims: Acute liver injury is a highly prevalent and a
life-threatening disease. Hepatocyte injury induces activation of CD11b++/F4/80++ KCs, while CD3+ T cells in CVC and AP2 treated
mice were comparable to that of healthy controls.
liver-resident Kupffer cells (KCs) and consequently activation of
hepatic stellate cells (HSCs). Hepatocytes, HSCs and KCs secrete C-C Immunohistochemical analysis evidenced decreased expression of
fibrosis markers (collagen-I and alpha-smooth muscle actin) and an
motif chemokine ligand 2 (CCL2) and trigger the recruitment of C-C
increase in Ki-67 positive hepatocytes in the AP2 treated mouse
motif chemokine receptor 2 (CCR2) expressing circulating mono-
cytes. This results in chronic liver inflammation that further livers. Our data shows effective amelioration of inflammation and
fibrosis by inhibition of CCR2 using CCR2-antagonizing peptide. SPRi
progresses to liver fibrosis, cirrhosis and/or hepatocellular carcinoma.
Blocking the CCR2, using a small molecule CCR2/CCR5 inhibitor and in vitro peptide binding studies are ongoing alongside with more
in vivo analysis. The peptide will be evaluated further in a non-
cenicriviroc (CVC), has already been proven effective in vitro, in vivo,
alcoholic steatohepatitis (NASH) mouse model.
and in phase-I and -IIb clinical trials. However, small molecules often
have limitations i.e. poor pharmacokinetics and lack of receptor Conclusion: Our CCR2-antagonizing peptide inhibited migration of
macrophages/monocytes in vitro and ameliorated inflammation and
specificity. We designed a CCR2 antagonizing peptide (AP2) with
improved pharmacokinetics, and high receptor specificity to reduce fibrosis in vivo in an acute liver injury mouse model.
monocyte infiltration and disease progression in acute liver injury.
Method: Receptor binding affinity of the AP2 was characterized using
surface plasmon resonance imaging (SPRi) in situ and in vitro. Efficacy

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 POSTER PRESENTATIONS

Figure: (abstract: FRI018)

FRI019 damage following a single dose of carbon tetrachloride (CCL4) injury

Murine intrahepatic regulatory t cells modulate acute liver was investigated 24 hours later in both models.
inflammation by promoting a protective and restorative Results: Quantification of Foxp3+CD4+ cells among different tissues
microenvironment showed that the liver exhibited the lowest abundance of Tregs.
Ada Kurt1, Karoline Strobl2, Tonika Chester1, Gabriel Osborn1, Analysis in homeostatic conditions revealed that, although intrahe-
Paula Ruiz1, Elizabeth H. Gray1, Alberto Sanchez-Fueyo1, patic Tregs exhibited the core transcriptional Treg signature, they
Marc Martinez-Llordella1. 1King’s College London, Department of expressed a distinct transcriptional profile. This was characterized by
Inflammation Biology, London, United Kingdom; 2Medical University of reduced CD25 expression and increased levels of pro-inflammatory
Vienna, Institute for Cancer Research, Vienna, Austria Th1 transcripts IL1b and IFNγ. Depletion of Tregs showed that Tregs
Email: [email protected] effectively reduced the magnitude of systemic and intra-hepatic
inflammatory responses following CCL4 injury, but they were not
Background and aims: CD4+CD25+Foxp3+ regulatory T cells (Tregs) directly involved in ameliorating hepatocyte necrosis. In contrast, the
exert powerful immunomodulatory effects that are essential to administration of IL-2c markedly increased the number of intra-
maintain immune homeostasis and prevent the development of hepatic Tregs and significantly ameliorated liver damage following
immune-mediated diseases. In addition to their immunomodulatory CCl4 administration. The cytoprotective effect observed in response
role, recent studies have identified that depending on the tissue to IL-2c was associated with the increased expression by Tregs of
compartment they migrate to or reside in, Tregs acquire tissue- markers known to regulate their suppressive function.
specific features and develop cytoprotective and regenerative func-
tions. The liver is an organ known to be deprived in IL-2, a cytokine
that is essential for the adequate function and survival of Tregs. The
extent to which this affects intra-hepatic Treg phenotype and the
capacity of these cells to modulate liver damage has not been
adequately investigated. In this study, we aimed to explore the
phenotypic and functional diversity of liver resident Tregs during
homeostasis. Additionally, we investigated their role in ameliorating
liver inflammation and tissue damage by depleting Tregs and
increasing their pool by exogenous IL-2 complex (IL-2c) administra-
tion in murine models.
Method: Flow cytometry phenotyping and microarray analysis was
performed on Foxp3-YFP intrahepatic and splenic Tregs in homeo-
static conditions and with the administration of IL-2c for 3
consecutive days. Tregs were depleted in Foxp3-DTR mice by
intraperitoneal (i.p) injection of 1μg diphtheria toxin and IL-2c
were administered i.p. to wild-type C57BL/6 mice. The extent of liver

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POSTER PRESENTATIONS
Conclusion: Our results offer insight into the transcriptome and Table: Characteristics of patients treated vs not treated with steroids
complex immune network of intrahepatic Tregs and how their
number and phenotype may affect their ability to modulate liver
inflammation. Strategies capable of selectively increasing the pool of
intra-hepatic Tregs could constitute effective therapies in inflamma-
tory liver diseases.

FRI020
Place of steroids and prognosis factors for grade = 3 immune-
checkpoint inhibitors induced hepatitis: a 6-year prospective
study
Eleonora De Martin1, Alina Lutu1, Ariane Laparra-Ramakichenin2,
Nicolas Golse1, Astrid Laurent Bellue3, Caroline Robert2,
Olivier Lambotte4, Audrey Coilly1, Ilias Kounis1, Edoardo Poli1,
Lea Duhaut1, Olivier Rosmorduc1, Catherine Guettier3,
Jean-Marie Michot2, Didier Samuel1. 1Hôpital Paul Brousse, Centre
Hépato-Biliaire, Villejuif, France; 2Institut Gustave Roussy; 3Hôpital
Bicetre, Anatomo-pathologie, France; 4Hôpital Bicetre, Medecine interne
et Immunologie clinique
Email: [email protected]
Background and aims: The management of liver toxicity of immune
checkpoint inhibitors (ICI) and the role of steroids is controversial.
This study aimed to provide a report of a well characterized cohort of Conclusion: Grade ≥3 ICI-induced hepatitis was non-severe in the
patients with ICI-induced hepatitis and their management. majority of cases. Steroid therapy was introduced in only half of the
Method: In this prospective cohort study, patients treated with ICI for patients and was associated with higher ALT and bilirubin level. New
metastatic cancer and referred to hepatology unit for grade ≥3 cut off to indicate the use of steroid therapy is needed.
hepatitis (06/2015–09/2021) were evaluated and the ones with ICI-
induced hepatitis, after exhaustive causal investigations, were FRI021
included. The decision to introduce steroids and/or ursodeoxycholic The role of macrophage ETS Proto-oncogene 2 in acute-on-
acid (UDCA) was at physician discretion (oncologist/hepatologist). chronic liver failure
Results: Among 64 included patients, 29 (45%) female, median age 61 Lulu He1, Qun Cai1, Xi Liang2, Jiaojiao Xin1, Jing Jiang1, Dongyan Shi1,
(33–83) yrs, the most common cancers were metastatic melanoma Keke Ren1, Yun Li3, Jiaxian Chen1, Jinjin Luo1, Jiaqi Li1, Peng Li1, Jun Li1.
(n = 30), renal cancer (n = 12) and epidermoid carcinoma (n = 6). The 1
The First Affiliated Hospital, Zhejiang University School of Medicine,
ICI administered were anti-PD1 (n = 29), anti-PDL1 (n = 9), anti-CTL4 China; 2Taizhou Central Hospital (Taizhou University Hospital), Precision
(n = 5), anti-PD1+anti-CTL4 (n = 21) and ICI+chemotherapy (ex. Medicine Center, Taizhou, China; 3Zhejiang University School of
carboplatin, anti-EGFR) (n = 21). 20% of patients were previously Medicine, Institute of Pharmaceutical Biotechnology and the First
exposed to another ICI. Median time between ICI introduction and Affiliated Hospital Department of Radiation Oncology, Hangzhou, China
first increase of liver tests (LFTs) was 1.80 (0.82–3.42) months and Email: [email protected]
between ICI introduction and peak of LFTs was 2.67 (1.43–5.17)
months, median number of doses was 2 (1.75–4). Forty (62%) patients Background and aims: Acute-on-chronic liver failure (ACLF) is a
had grade 3 and 24 (38%) grade 4 hepatitis, 33% were symptomatic. At critical disease caused by acute aggravation of chronic liver disease, with
peak median (IQR) LFTs were AST 481 (280–780) IU/l, ALT 320 (164– poor prognosis and high mortality. The detailed mechanism of ACLF
549) IU/l, total bilirubin 14.5 (10–28) μmol/l, conjugated 8.85 (5.32– remains unclear. The purpose of this study was to investigate the value
19.2) μmol/l, GGT 366 (150–800) IU/l, ALP301 (134–513) IU/l, only 2 of macrophage ETS Proto-oncogene 2 (ETS2) as a prognostic marker in
patients had increased INR. Median IgG were 10.0 (7.8–12.3) g/L, ANA ACLF, and its role in mouse liver failure model induced by D-GalN/LPS.
was positive in 49% and ASMA in 3.5% of patients. The diagnosis was Method: In this study, peripheral blood monocytes from 50 patients
histologically confirmed in 91% of patients. Seven patients underwent with ACLF, 19 patients with chronic liver disease and 14 healthy
biliMRI and 3 had cholangitis. No differences were found between persons were collected for RNA-SEQ sequencing analysis. ACLF
patients with grade 3 or 4 hepatitis regarding type of cancer, type of patients were divided into ETS2-high and ETS2-low expression
ICI, number of doses, interval between ICI and peak of LFTs. Steroids group, and the differentially expressed genes between two groups
were introduced in 32 (50%) patients and UDCA was used in 27% of were analysed. AAV9-ETS2-shRNA were injected to knockdown ETS2
patients. Doses of steroids were 0.5, 1 and 2 mg/kg/day in 8, 21 and 2 in vivo. And then acute liver failure model of D-GalN/LPS was
patients (not known in 1), respectively. Four patients didn’t improve, constructed. Serum biochemical indicators and the expression of
1 required increase of steroids, 3 a second immunosuppressive drug, inflammatory factors was detected by qPCR and ELISA. HE staining
1 multiple drugs and died of liver failure. Use of steroids was and TUNEL staining were used to observe the inflammatory
associated with higher AST ( p = 0.041), ALT ( p = 0.041), total and infiltration and necrosis. Immunohistochemistry was used to detect
conjugated bilirubin ( p < 0.01 and 0.025) but not with type of ICI, the expression of high mobility group box 1 (HMGB1). In vitro,
number of doses, interval between ICI introduction and LFTs increase. CRISPR-Cas9 was used to knockout ETS2 in RAW264.7 cells. The
Among grade 4 patients, 8 (33%) improved without steroids. changes of inflammatory factors and related signalling pathways
were detected with the intervention of HMGB1.
Results: The mRNA expression of ETS2 in peripheral blood of ACLF
group was significantly increased compared with other groups.
People who died within 28 days and 90 days showed increased
expression of ETS2 compared with people who survived. The
activation of innate immune and the suppression of adaptive
immune were observed in ETS2- high expression group. In vivo
experimental results showed that, ETS2 knockdown increased the
liver function impairment and the expression of inflammatory factors

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 POSTER PRESENTATIONS

Figure: (abstract: FRI021)

significantly in acute liver failure model. The inflammatory infiltra- Era 2 (2006–12) and Era 3 (2013–21) and paracetamol (APAP) and
tion and necrosis in liver tissue were significantly increased, and the non-APAP aetiologies. ALF was assigned in those with hepatic
expression of HMGB1 in liver tissue was significantly increased. In encephalopathy (HE) and ALI in those without. Severity of illness
vitro results showed that D-GalN could induce HMGB1 release from was assessed by presence of HE and laboratory measures. Data is
hepatocytes. Knockout of ETS2 in RAW264.7 significantly increased expressed as n (%) or median (IQR). Data underwent univariate and
the expression of HMGB1-induced inflammatory factors, and multivariate analysis including logistic regression for the primary
increased NF-kappa B phosphorylation. outcome of hospital survival.
Conclusion: ETS2 was a prognostic marker in ACLF and associated Results: The study cohort comprised 1752 patients (median age 36
with the activation of innate immune. ETS2 alleviates HMGB1 (27–48) years, 60% female, 56% APAP), of whom 1177 (68%) had/
induced macrophage inflammation by decreasing NF-kappa B developed ALF. Mortality was 4% in those with ALI and 36% in ALF ( p
activity. Knockdown ETS2 in vivo can increase inflammatory response < 0.001). Era 1 comprised 628 patients, Era 2: 577 and Era 3: 547. Over
and further aggravate hepatocyte injury. the study period the proportion with HE grade 3 on admission rose
from 50% to 61% ( p < 0.001), and in both APAP and non-APAP cases
FRI022 measures of liver injury increased: admission INR: APAP 3.3 (2.4–4.9)
Novel strategies required to further improve outcomes in acute in Era 1 to 5.6 (3.6–9.1) in Era 3, non-APAP 2.4 (1.6–4.3) to 3.0 (2.1–
liver failure 4.9) both p < 0.001). Survival in ALF rose from 53% in Era 1 to 70% in
William Bernal1, Mark J. W. McPhail1, Anshuman Singh1, Era 2 ( p < 0.001), plateauing at 71% Era 3. In parallel there was a fall in
Brian J. Hogan1, Tasneem Pirani1, Sameer Patel1, Robert Loveridge1, use of LT from 30% of ALF cases in Era 1 to 22% in Era 3 ( p < 0.001). This
Christopher Willars1, Michael Heneghan2, Varuna Aluvihare2, was seen in both APAP (22% to 13%, p < 0.001) and non-APAP (41% to
Parthi Srinivasan3, Andreas Prachalias3, Georg Auzinger1, 31%, p < 0.001) cases. 343 patients underwent LT: post-LT survival
Nigel Heaton3, Julia Wendon1. 1Institute of Liver Studies, King’s College increased from 72% in Era 1 to 91% in Era 2 and Era 3 ( p < 0.001).
Hospital, Liver Intensive Therapy Unit, London, United Kingdom; Transplant-free survival (TFS) rose from 54% in Era 1 to 70% in Era 3
2
Institute of Liver Studies, King’s College Hospital, Hepatology, London, for APAP and from 29% to 59% in non-APAP cases (both p < 0.001).
United Kingdom; 3Institute of Liver Studies, King’s College Hospital, Liver Non-significant increases in TFS were seen when Eras 2 and 3 were
Transplantation Surgery, London, United Kingdom compared (APAP 66% vs. 70% p = 0.47, non-APAP 50% vs 59% p = 0.14).
Email: [email protected] On multivariate analysis adjusting for age, aetiology and illness
severity, Era was associated with improved overall survival: Era 1 to
Background and aims: Care for patients with Acute liver injury (ALI)
Era 2 (Adjusted Odds Ratio 4.1 (95% CI 2.9–5.9)) and Era 3 (4.7
and Failure (ALF) has advanced significantly in recent years through
(3.2–6.9), but there was no difference in between Era 2 and 3 (1.1
critical care medical therapy and the targeted use of liver transplant-
(0.78–1.6).
ation (LT). Case series have shown changes in the character of illness
Conclusion: Survival for patients with ALF has markedly improved
and its outcomes from the 1970 to early 2000s but the current
over the last 20 years, despite an increase in illness severity. Patient
outcomes are poorly characterised. We examined the changing
survival after LT is high, but its use has fallen, particularly in APAP ALF.
treatment and outcomes of a large cohort of patients with ALF and ALI
TFS has progressively improved but outcomes in non-APAP ALF
admitted to a single specialist ICU.
remain inferior. However, overall survival has now plateaued
Method: consecutive patients with acute liver disease admitted over
suggesting a need for new medical therapies and/or a re-evaluation
the period 1999–2021 were studied, classified in Era 1 (1999–2005),
of the use of transplantation.

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POSTER PRESENTATIONS
FRI023
Human liver biopsies from people with hemophilia A who
received factor VIII gene transfer with valoctocogene
roxaparvovec (AAV5-hFVIII-SQ) show unremarkable
histopathology and reveal interindividual variability in transgene
production
Sylvia Fong1, Bridget Yates1, Choong-Ryoul Sihn1, Aras Mattis2,3,
Nina Mitchell1, Su Liu1, Chris Russell1, Benjamin Kim1,
Adebayo Lawal1, Savita Rangarajan4, Will Lester5, Stuart Bunting1,
Glenn Pierce6, K. John Pasi7, Wing Yen Wong1. 1BioMarin
Pharmaceutical Inc, Novato, United States; 2University of California
San Francisco, Department of Pathology, San Francisco, United States;
3
University of California San Francisco, Liver Center, San Francisco,
United States; 4University Hospital Southampton, Southampton, United
Kingdom; 5University Hospitals Birmingham, Birmingham, United
Kingdom; 6Voyager Therapeutics, Cambridge, United States; 7Barts and
the London School of Medicine and Dentistry, London, United Kingdom
Email: [email protected]
Background and aims: Hemophilia A is an X-linked bleeding
disorder caused by deficiency in factor VIII (FVIII), a cofactor in the Figure: Cross species comparison of valoctocogene roxaparvovec transduc-
tion. In situ hybridization of hFVIII-SQ vector DNA (brown foci) in mouse,
intrinsic pathway of the coagulation cascade. Factor VIII is made
monkey, and human liver samples.
predominantly in liver sinusoidal endothelial cells but gene therapy
efforts using adeno-associated viruses (AAV) have targeted heterol- Conclusion: Overall, our results showed that liver histopathology
ogous expression in hepatocytes. Factor VIII gene transfer with a was unremarkable following AAV5-hFVIII-SQ administration and that
single intravenous infusion of valoctocogene roxaparvovec (AAV5- persistent episomal vector structures were formed. This work
hFVIII-SQ) has been shown to confer clinical benefit through at least 5 elucidates several potential mechanisms that may mediate inter-
years in people with severe hemophilia A. Molecular mechanisms individual variability in FVIII production and advances our under-
underlying sustained AAV5-hFVIII-SQ-derived FVIII expression in standing of inter-species translatability.
hepatocytes have not been studied in humans.
Method: In a substudy of the phase 1/2 clinical trial (NCT02576795), FRI024
liver biopsy samples were collected from five participants 2.6–4.1 Liver toxicity associated to novel cyclin-dependent kinase
years after AAV5-hFVIII-SQ gene transfer. The objectives of the inhibitor ribociclib in a cohort of advanced breast cancer patients
substudy were to examine effects on liver histopathology, determine Miki Scaravaglio1, Antonio Ciaccio1, Alice Laffusa1, Martina Lucà1,
the transduction pattern and percentage of hepatocytes transduced Salvatore Longo2, Martina Manna1, Claudia Maggioni3,
with AAV5-hFVIII-SQ genomes, characterize and quantify episomal Francesca Riva3, Federica Cicchiello3, Marina Elena Cazzaniga4,
forms of vector DNA, and quantify transgene expression (hFVIII-SQ Diego Cortinovis3, Pietro Invernizzi1. 1Division of Gastroenterology,
RNA and hFVIII-SQ protein). Separately, we compared patterns and Department of Medicine and Surgery, University of Milano-Bicocca, San
efficiencies of hepatocyte transduction in mice, monkeys, and Gerardo Hospital, Monza, Italy, Monza, Italy; 2Gastroenterology,
humans who had all received AAV5-hFVIII-SQ to assess translatability Hepatology and Nutrition Division, Department of Life, Health and
of preclinical findings. Environmental Sciences, University of L’Aquila, L’Aquila, Italy, Monza,
Results: Histopathological examination of human samples revealed Italy; 3Division of Medical Oncology, Department of Medicine and
no dysplasia, architectural distortion, fibrosis or chronic inflamma- Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza,
tion. No endoplasmic reticulum stress was detected in hepatocytes Italy, Monza, Italy; 4Department of Medical Oncology & Phase 1
expressing hFVIII-SQ protein. Hepatocytes stained positive for vector Research, University of Milano-Bicocca, San Gerardo Hospital, Monza,
genomes, and the number of transduced cells increased with AAV5- Italy, Monza, Italy
hFVIII-SQ dose. Molecular analysis demonstrated the presence of Email: [email protected]
stable full-length circular episomal genomes that are associated with
Background and aims: Three cyclin-dependent kinase 4/6 inhibitors
long-term expression. Interindividual differences in transgene
(CKIs) have shown to significantly improve the progression-free
expression were noted despite the successful administration of
survival in patients with hormone receptor (HR)-positive, human
identical vector doses. Variability may be related to host-mediated
epidermal growth factor receptor 2 (HER2)-negative advanced breast
post-transduction mechanisms of vector transcription, hFVIII-SQ
cancer (ABC). Among them, ribociclib has recently proved an overall
protein translation, and secretion. Higher levels of vector genomes
survival benefit, emerging as a first-class option. Nevertheless,
were detected in the livers of humans and monkeys than in mice;
clinically significant drug induced liver injury (DILI) has been
however, transcription of the vector DNA into RNA occurred more
reported, leading to temporary or definitive withdrawal of anti-
efficiently in mice.
neoplastic therapy with related concerns about liver and oncologic
outcomes. In a previous analysis of this cohort (manuscript in
preparation) we found a significant higher risk of DILI with ribociclib
compared to others CKIs. We aimed to assess characteristics and
predictors of ribociclib-induced liver toxicity.
Method: All consecutive patients with ABC evaluated between June
2017 and December 2021 at the Oncology Unit of San Gerardo
University Hospital, Monza, and received ribociclib for at least a
complete cycle of 28 days were included in this retrospective study.
Patients with hepatocellular carcinoma and/or chronic advanced liver
disease were excluded.

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 POSTER PRESENTATIONS
Results: Of 122 ABC patients treated with CKIs, 43 received ribociclib FRI025
and were included in the analysis, with a median treatment time of 15 Exogenous fibroblast growth factor 7 improved hepatocyte
months (interquartile range [IQR], 3.5 to 26.5). After a median follow- regeneration and ameliorated CCl4-induced acute liver injury in
up time of 21 months (IQR, 15.5 to 30.5) an elevation of liver enzymes vivo
of any grade was reported in 13 out of 43 patients (30.2%) and 6 Eline Geervliet1,2, Ruchi Bansal1. 1University of Twente, Medical Cell
patients (14%) had a DILI, as defined by an ALT >5 × upper limit of Biophysics, Enschede, Netherlands; 2RWTH Aachen, Institute of
normal (ULN) and/or ALp >2 × ULN. DILI episodes occurred after a Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical
median of 6 months (IQR, 3 to 8) from treatment start and all of them Chemistry, Aachen, Germany
had a hepatocellular pattern. A single case of DILI with autoimmune Email: [email protected]
features was described. Of 6 DILI patients, 1 (17%) underwent
Background and aims: During acute and chronic liver injury,
temporary and 5 (83%) definitive treatment interruption, achieving
hepatocyte damage instigates activation of inflammatory responses
liver enzymes normalization within a median of 13 weeks (IQR, 7 to
24). Overall, the occurrence of DILI accounted for over a quarter of the and ultimately fibrosis. Fibroblast growth factor-7 (FGF7), that binds
specifically to FGFR2b (highly expressed on hepatocytes and liver
total number of treatment discontinuations. No acute liver failure was
reported. Fourteen of 43 patients (33%) died during the study period, progenitor cells), plays an important role in cholangiocytes/hepato-
cytes proliferation and liver regeneration as shown in a mouse model
none of liver-related cause. Baseline steatosis (RR 13.3, CI 4.5–39.6,
of cholangitis and biliary fibrosis, and partial hepatectomy.
p < 0.01) and dyslipidemia (RR 3.3, CI 0.8–13.9, p = 0.05) were
associated with a significant higher risk of DILI. No associations Unfortunately, during acute and chronic liver disease this ligand is
insufficiently expressed resulting in lack of hepatocyte survival, and
were found when assessing previous exposure to antineoplastic
treatments including endocrine agents, concomitant medications, progression of liver disease. On the other hand, FGFR2b is
upregulated during acute and chronic liver disease making it an
presence of liver metastases, and fibrosis-4 index (FIB-4) at baseline.
excellent therapeutic target. In this research, we aim to target FGFR2b
Conclusion: Ribociclib is associated with a significant risk of DILI,
turning in a relevant rate of antineoplastic treatment discontinuation with its natural highly specific ligand FGF7 to improve survival and
proliferation of hepatocytes, differentiation of liver progenitor cells,
in ABC patients. Once confirmed in larger prospective studies,
baseline assessment of steatosis and dyslipidemia should be and thereby ameliorating liver disease progression in carbon
warranted to assist pre-treatment risk stratification. tetrachloride (CCl4)-induced acute liver injury mouse model.
Method: Acute liver injury was induced by a single injection of CCl4.
Mice were subsequently treated with vehicle or 1 μg/kg FGF7 twice a
day for two days. After treatment, the mice were sacrificed, and the
organs were harvested for further analysis. Hepatocyte survival and
proliferation, inflammation and fibrosis were evaluated by immuno-
histochemical staining, and gene and protein expression.
Results: Exogenous FGF7 increased liver- and spleen-to-body weight
ratio while significantly decreased the liver-to-spleen weight ratio.
Immunohistochemical analysis of liver sections showed increased

Figure 1: (abstract: FRI025): Representative microscopic images (10x) and quantitative analysis of liver sections of control (healthy, n = 5), CCl4 (n = 5) and
FGF7 (n = 5) treated mice stained with Ki67 ( proliferation marker), F4/80 (macrophage marker) and Collagen-I (fibrosis marker). *p < 0.05 and **p < 0.01
denotes significance.

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POSTER PRESENTATIONS
proliferation as determined by Ki67 expression. Furthermore, FRI027
macrophage/inflammation marker, F4/80 and fibrosis marker, colla- Trends in liver transplantation for acute liver failure. A Spanish
gen-I were significantly decreased upon treatment, see Figure 1. Gene multicenter study
expression analysis of proliferation, inflammation and fibrosis Isabel Conde1,2, Victoria Aguilera Sancho1,2,3, Sara Martinez4,
markers followed the similar trend. Extensive protein analysis of Tommaso Di Maira1, Maria Senosiáin5, Rosa María Martín Mateos6,6,
hepatocyte survival pathways will be investigated using Western blot. Carolina Almohalla7, Maria Luisa Gonzalez Dieguez8,
Conclusion: Our results show that exogenous administration of FGF7 Sara Lorente Perez4, Alejandra Otero9, Maria Rodriguez10,
induces hepatocyte survival and leads to amelioration of inflamma- Jose Ignacio Herrero11, Isabel Campos-Varela12, Ainhoa Fernandez13,
tory response and fibrosis in acute liver injury. Our study demon- Marina Berenguer1. 1La Fe University and Polytechnic Hospital,
strates that FGF7, FGF7 derivatives or nano-engineered FGF7 may Valen ̀ cia, Spain; 2Instituto de Investigación Sanitaria La Fe de Valencia,
benefit patients with hepatic dysfunction. Valeǹ cia, Spain; 3ISCIII, CIBERehd, Valencia, Spain; 4Hospital Clinico
Universitario Lozano Blesa, Zaragoza, Spain; 5Hospital Universitario
FRI026 Cruces, Barakaldo, Spain; 6Hospital Ramón y Cajal, Madrid, Spain; 7Rio
Three COVID-19 medications-remdesivir, molnupiravir and Hortega University Hospital, Valladolid, Spain; 8Central University
ritonavir-boosted nirmatrelvir-and serial liver biochemistries in Hospital of Asturias, Oviedo, Spain; 9Hospital Universitario da Coruña
22, 456 subjects (CHUAC), A Coruña, Spain; 10General University Hospital of Alicantet,
Grace Lai-Hung Wong1, Vicki Wing-Ki Hui1, Terry Cheuk-Fung Yip1, Alacant, Spain; 11Clínica Universidad de Navarra, Madrid, Spain; 12La
Yee-Kit Tse1, Vincent Wai-Sun Wong1. 1The Chinese University of Hong Vall d’Hebron, Barcelona, Spain; 13Gregorio Marañón Hospital, Madrid,
Kong, Medical Data Analytic Centre (MDAC) and Department of Spain
Medicine and Therapeutics, Hong Kong Email: [email protected]
Email: [email protected]
Background and aims: ALF is a critical illness with high morbi-
Background and aims: Several medications as treatment for COVID- mortality. LT has improved outcome. Aims: to asses if there have been
19 have been approved around the world. These medications have changes in aetiology, profile and outcomes of patients LT due to ALF in
generally good safety profiles, while data concerning the liver safety a Spanish multicenter cohort and to identify factors associated with
of these COVID-19 medications and risk of drug-induced liver injury mortality.
(DILI) are lacking. We aimed to report the serial liver biochemistries Method: Retrospective study of LT due to ALF cohort from 11
of people before and after receiving COVID-19 medications. hospitals between 2001 and 2020. Baseline features, comorbidities,
Method: This was a territory-wide retrospective observational cohort biochemical data, acute complications, early and late outcomes were
study in Hong Kong. We identified subjects who had received any of recorded.
the three COVID-19 medications approved in Hong Kong-remdesivir, Results: 218 adults LT due to ALF (2001–2020). The cohort was
molnupiravir and ritonavir-boosted nirmatrelvir. Serial liver bio- subdivided in 4 time-groups (G1:2001–2005; G2:2006–2010;
chemistries at least three months before and one month after the G3:2011–2015; G4:2016–2020). The number of ALF LT remained
COVID-19 medications were reported. stable (G2: 2.5%, G3:2.2%. G4:2.7%.). Median age: 41 yrs, 62%women,
Results: 22, 456 subjects (5, 370 received remdesivir, 13, 127 received AHT 11.5%, diabetes 3.7%, dyslipidaemia 8.3%, MELD 34 (29.5–38.1),
molnupiravir and 4, 510 received ritonavir-boosted nirmatrelvir; 551 83.5% caucasic. Main LT indications were viral (26.2%), cryptogenic
subjects had received more than one medication) of whom 48.3% (26.1%), autoimmune (22.5%), and DILI (17%). 87% meet King’s College
male, median age 77 years old, were included. Majority (98.7%) criteria. 38% had severe encephalopathy, 22% renal impairment (RI)
subjects had normal ALT (1–2 × ULN: 0.9/%; >2 × ULN: 0.4%) and total with haemodialysis, 23% required mechanical ventilation (MV). There
bilirubin (normal 91.3%; 1–2 × ULN: 7.2%; >2 × ULN: 1.5%) before or at was a trend towards an increase of LT for autoimmune (21%, 21%, 31%,
the time of receiving COVID-19 medications. These parameters 29% in G1–4 respectively, p = 0.88) and DILI (12.5%, 14%, 18%, 21% in
remained stable for up to one month after the treatment-ALT G1–4, p = 0.72). Women seem more susceptible to ALF TH over time
(normal 97.7%; 1–2 × ULN: 1.5%; >2 × ULN: 0.8%) and total bilirubin (58%, 53.5%, 65.6% and 67% in G1–4, p = 0.4). Complications in the
(normal 90.3%; 1–2 × ULN: 7.9%; >2 × ULN: 1.8%). Similar serial liver early post-LT period were infections (58.7%), RI (25%) and primary
biochemistries were observed in subjects who received remdesivir, dysfunction (24%). Late post-LT complications were AHT (30%), RI
molnupiravir and ritonavir-boosted nirmatrelvir. (20%) and diabetes (17%). 27% of patients died. Main causes of death
Conclusion: Three registered COVID-19 medications (remdesivir, were infections (41.5%) and liver-related (20%). Survival was 85%, 81%
molnupiravir and ritonavir-boosted nirmatrelvir) vaccines have very and 70% at 1, 5 and 10 years. Diabetes, MV, ascites and creatinine were
favourable liver safety profile in people. independently associated with poorer survival (HR 4.05, p = 0.054;
Grant support: This work was supported by the Health and Medical HR 2.74, p = 0.037; HR 2.48, p = 0.048 and HR 1.47, p = 0.007,
Research Fund (HMRF)-Food and Health Bureau Commissioned respectively).
Research on COVID-19 (Reference no.: COVID1903002) awarded to Conclusion: LT for ALF remained stable in the last years in Spain.
Grace Wong. Autoimmune and DILI seem to increase over time, being women
more susceptible to ALF TH. Patients with diabetes, ascites, high
creatinine levels, and MV were associated with poor outcomes after
LT.

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 POSTER PRESENTATIONS

Figure: (abstract: FRI026): Serial liver biochemistries before and after COVID-19 medications.

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POSTER PRESENTATIONS
FRI028 increase in the hospital stay. DILI was a relevant complication.
Hepatobiliary disease after bone marrow transplant Allogeneic haploidentical BMT was the most associated with C-
Maria Dezan1,2, Marco Salvino3,4, Alessandro Almeida3,5, Hugo Silva6, HEPBILI.
Lourianne Cavalcante7,8, Helma Pinchemel Cotrim8, Andre Lyra7,8.
1
Hospital São Rafael, Gastroenterology and Hepatology, Salvador, Brazil; FRI029
2
Federal University of Bahia, Programa de Pós Graduação em Medicina e FOXA2 prevents hyperbilirubinemia through maintaining apical
Saúde, Salvador, Brazil; 3Hospital São Rafael, Hematology, Salvador, MRP2 expression in acute liver failure
Brazil; 4Hospital Universitário Professor Edgard Santos-HUPES, Sai Wang1, Rilu Feng2, Shanshan Wang3, Hui Liu4, Chen Shao4,
Hematology, Salvador, Brazil; 5Hospital Universitário Professor Edgard Yujia Li1, Frederik Link1, Stefan Munker5, Roman Liebe6,
Santos-HUPES, Hematology, Salvador; 6Hospital Sao Rafael, Hematology, Christoph Meyer1, Elke Burgermeister2, Matthias Ebert2,
Salvador, Brazil; 7Hospital São Rafael, Gastroenterology and Hepatology, Steven Dooley2, Huiguo Ding7, Honglei Weng2. 1Medical Faculty
Salvador, Brazil; 8Hospital Universitário Professor Edgard Santos-HUPES, Mannheim, Heidelberg University, Department of Medicine II,
Gastroenterology and Hepatology, Salvador, Brazil Mannheim, Germany; 2Medical Faculty Mannheim, Heidelberg
Email: [email protected] University, Department of Medicine II, Mannheim, Germany; 3Beijing
You’an Hospital, Capital Medical University, Beijing Institute of
Background and aims: Post-bone marrow transplantation (BMT) Hepatology, Beijing, China; 4Beijing You’an Hospital, Affiliated with
hepatobiliary complications (C-HEPBILI) may occur in up to 80% of Capital Medical University, Department of Pathology, Beijing, China;
the cases. We evaluated the frequency and clinical characteristics of 5
University Hospital, LMU Munich, Department of Medicine II,
C-HEPBILI in patients undergoing BMT at a referral center. Mannheim, Germany; 6Saarland University Medical Center, Saarland
Method: This is a cross-sectional study that analyzed patient data University, Department of Medicine II, Germany; 7Beijing You’an
from 2017 to 2021, including demographics, the period between BMT Hospital, Affiliated with Capital Medical University, Department of
and C-HEPBILI diagnosis, outcome, and length of hospital stay. Drug- Gastroenterology and Hepatology, China
induced liver disease (DILI), sepsis-associated liver injury (SALI), Email: [email protected]
sinusoidal obstruction syndrome (SOS), graft versus host disease
(GVHD), hypoxic hepatitis (HH), and fulminant hepatitis (FH), among Background and aims: Multidrug resistance protein 2 (MRP2) is a
others, were evaluated. We diagnosed DILI according to EASL bottleneck in bilirubin excretion. Its loss is sufficient to induce
guidelines. For SALI, we considered the infectious context and a hyperbilirubinemia, a prevailing characteristic of acute liver failure
total bilirubin ≥2 mg/dL and ALP or ALT ≥2 × ULN. We used the EBMT, (ALF), that is closely associated with clinical outcome. This study
Seattle, and Baltimore criteria to diagnose SOS and considered scrutinizes the transcriptional regulation of MRP2 under different
hepatic GVHD when patients had skin and or intestinal GVHD and pathophysiological conditions.
increased liver enzymes that improved after treatment. For altera- Method: Thirty-six patients, 14 with quiescent liver cirrhosis and 22
tions that did not meet the previous criteria, we defined liver with ALF, were enrolled. Hepatic MRP2, FXR, and FOXA2 expression
enzymes elevation as an increase ≥1.5 ULN, named this condition were examined by immunohistochemistry. Clinicopathologic associ-
isolated liver enzymes elevation (ILEE), and linked them to a possible ation was analysed. MRP2 regulatory mechanisms were investigated
etiology whenever clinically pertinent. in primary hepatocytes, Fxr−/− mice and LPS-treated mouse model.å
Results: Thus far, the study comprised 297 patients, 52% men. The Results: In normal hepatocytes, homeostatic MRP2 transcription is
mean age of the total population and the C-HEPBILI patients was 49.6 mediated by the nuclear receptor FXR/RXR complex. Fxr−/− mice lack
(±14.1) and 48.7 (±13.6) years, respectively; 164 of 297 patients (55%) apical MRP2 expression and rapidly progress into hyperbilirubine-
had C-HEPBILI; 91 of them (55%) were women. Table 1 describes all mia. In ALF patients, hepatic FXR expression is undetectable, however,
detected C-HEPBILI. Most patients had ILEE that probably was the patients without infection maintain apical MRP2 expression and
associated with drugs or infection. We analyzed 201 autologous, 47 do not suffer from hyperbilirubinemia. These patients express robust
allogeneic haploidentical, and 49 allogeneic full-match BMT; C- FOXA2 in hepatocytes. FOXA2 upregulates MRP2 transcription
HEPBILI occurred in 53%, 74%, and 47% of the cases, respectively, and through binding to its promoter. Physiologically, nuclear FOXA2
was more frequent among patients with acute lymphoid leukemia. translocation is inhibited by insulin. In ALF, high levels of glucagon
DILI occurred in 15% of patients with C-HEPBILI (44% had cholestatic and TNF-α induce FOXA2 expression and nuclear translocation in
DILI pattern, 44%, hepatocellular, and 12% mixed). The commonest hepatocytes. Impressively, ALF patients with sepsis express few
conditioning regimens among patients with DILI used Melphalan. FOXA2, lose MRP2 expression, and show severe hyperbilirubinemia.
Nine out of 15 SOS patients died. The mean post-BMT hospital stay In this case, LPS inhibits FXR expression, induces FOXA2 nuclear
among C-HEPBILI patients was 25.8 days, while patients without exclusion, and thus destroys the compensatory MRP2 upregulation.
these complications stayed for 17.9 days (mean). Twenty-two of 27 In both Fxr−/− and LPS-treated mice, ectopic FOXA2 expression
deaths occurred in C-HEPBILI patients, especially among SALI restored apical MRP2 expression and serum bilirubin levels.
subjects. Conclusion: Upregulation of FOXA2 to maintain MRP2 is an efficient
strategy to prevent hyperbilirubinemia.
Table 1: C-HEPBILI frequency in BMT patients*
Total C-HEPBILI
Population Population
N (N = 297) (N = 164)
ILEE 120 40, 4% 73, 1%
DILI 25 8, 4% 15, 2%
SOS 15 5, 1% 9, 1%
HH 6 2, 0% 3, 6%
SALI 5 1, 7% 3, 0%
FH 2 0, 7% 1, 2%
GVHD 1 0, 3% 0, 6%

*Some patients progressed with more than one C-HEPBILI.

Conclusion: C-HEPBILI is frequent after BMT, is more common in

women, and is associated with considerable morbidity, as well as an

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 POSTER PRESENTATIONS
split of half the data and predicting on held-out samples. All genetic
association testing focuses on subjects of European ancestry due to
NAFLD: Diagnostics and non-invasive population stratification concerns and considers 10 genotype
assessment principal components, age, and sex as covariates.
Results: Predictions of gene expression are improved with the ML
biopsy embeddings relative to the standard histological endpoints
FRI030 (A). While the I148M variant is enriched in this cohort relative to the
Machine learning encoding of liver biopsy images enables general population (allele frequency G = 0.46 vs G = 0.22 in gnomAD
prediction of molecular measurements in a NASH F3/F4 fibrosis EUR samples), we do not observe any association between patholo-
clinical cohort gist or quantitative microscopy measurement and I148M genotype
Michael D. Bereket1, Francesco Paolo Casale1, Rohit Loomba2, ( p > 0.05). Similarly, genotype predictions from these measurements
Arun Sanyal3, Stephen Harrison4, Zobair Younossi5, Catherine Jia6, are not significantly associated with the I148M genotype. However,
David Lopez6, Li Li6, Robert Myers6, David Breckinridge6, genotype predictions using the self-supervised ML biopsy embed-
Andrew Billin6, Eilon Sharon1, Matthew Albert1, dings are significantly associated with I148M genotype in the held
Theofanis Karaletsos1, Daphne Koller1. 1Insitro, South San Francisco, out samples ( p = 4E-9, n = 378; B). Tiles that influence these genotype
United States; 2University of California San Diego, La Jolla, United States; predictions are visualized in C.
3
Virginia Commonwealth University, Richmond, United States; Conclusion: ML models of H&E biopsy images identify histological
4
University of Oxford, Radcliffe Department of Medicine, United features that improve predictions of molecular endpoints relative to
Kingdom; 5Inova Fairfax Medical Campus, Falls Church, United States; standard histological readouts. Notably, we identify a histological
6
Gilead Sciences, Inc., Foster City, United States phenotype associated with PNPLA3 I148M genotype in F3/F4 fibrosis
Email: [email protected] NASH patients that is not captured by standard histological end-
points. This result supports the potential for ML models to provide
Background and aims: Machine learning (ML) models of biopsy
orthogonal characterizations of histological state, enabling novel
images have the potential to improve the characterization of liver
insights on the interplay of clinical phenotypes, transcriptomic state,
state by identifying biologically relevant phenotypes that are not
and genetic backgrounds in NASH patients.
captured by standard histological endpoints. To explore this
possibility, we develop and compare ML models that predict FRI031
transcriptomic and genetic endpoints based on standard histology Validation of AI-assisted method of liver fat measurement in
readouts or ML derived histological features. We focus our genetic adults with type 2 diabetes
analysis on the PNPLA3 I148M genotype, which has been robustly
Athena Dworakowski1, Wenjie Pang1, Sherif Boulos1, Sofie De Meyer1,
linked to NAFLD/NASH risk through GWAS studies (Romeo et al,
Jian Yeo2, Gaurav Gulsin2, Abhishek Dattani2, Emer Brady2,
2008; Anstee et al, 2020).
Joanna Bilak2, Sarah Ayton2, Alastair Moss2, Michael House3,
Method: Pathologist scores (NASH CRN and Ishak fibrosis scores),
Tim St Pierre3, Gerry McCann2. 1Resonance Health, Burswood,
quantitative microscopy measurements (alpha-SMA, collagen, and
Australia; 2University of Leicester, Department of Cardiovascular
fat content), H&E-stained biopsy images, liver bulk RNA-seq, and
Sciences, United Kingdom; 3The University of Western Australia, School
PNPLA3 I148M genotypes are curated from the STELLAR3, STELLAR4,
of Physics, Crawley, Australia
and ATLAS clinical trial F3/F4 fibrosis cohorts. We use self-supervised
Email: [email protected]
ML methods (trained with no clinician annotations) to generate
quantitative embeddings that represent histological phenotypes. We Background and aims: Type 2 diabetes (T2D) is strongly associated
fit generalized linear models to predict the molecular endpoints from with the development of non-alcoholic fatty liver disease (NAFLD),
the standard and ML-derived biopsy features, training on a random which is an emerging independent risk factor for cardiovascular

Figure: (abstract: FRI030)

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POSTER PRESENTATIONS
dysfunction. Hepafat-AI® is a software device developed using FRI032
artificial neural networks (ANN) and provides rapid (less than one Identifying advanced liver disease in asymptomatic patients in
minute) automated liver fat quantification from magnetic resonance primary care: an evaluation of patient outcomes 24 months after
images without the need for labour-intensive manual image analysis. implementing a primary care liver pathway and community liver
The aims of this study were to compare HepaFat-AI against the service
histologically validated HepaFat-Scan® technique as a reference Tina Reinson1, Chris Byrne2, Mead Mathews3, Janisha Patel4.
standard in a cohort of asymptomatic adults with T2D. 1
University of Southampton, Primary Care, Population Sciences and
Method: One hundred and thirty-three adults (97% T2D, mean age Medical Education, Southampton, United Kingdom; 2University of
62.6 ± 7.6 years, 60% male) underwent magnetic resonance imaging Southampton, Human Development and Health, Southampton;
3
(MRI) of the liver and heart. Nineteen were excluded due to incorrect St Mary’s Surgery, Southampton, United Kingdom; 4University Hospital
imaging parameters or breathing artifacts, leaving a sample of 114 Southampton, Hepatology, Southampton
subjects. Volumetric liver fat fraction (VLFF) was analysed twice, first Email: [email protected]
manually with HepaFat-Scan based on the 3-point Dixon principle
and then automatically processed using HepaFat-AI. HepaFat-AI was Background and aims: In 2019, Southampton Clinical
previously trained on 889 individual HepaFat-Scan datasets from Commissioning Group implemented a liver guidance pathway and
both 1.5 T and 3 T scanners and generates a report comprising VLFF community liver service to help early detection and reduce the
measurements, proton density fat fraction (PDFF), and steatosis number of deaths from liver disease. The liver guidance pathway
grade. Bland-Altman analysis was performed to determine the 95% supports primary care clinicians identify patients at risk of liver
limits of agreement between the two methods of measuring VLFF. disease to access early intervention before developing to advanced
The diagnostic performance of HepaFat-AI for predicting HepaFat- liver disease. The community liver service provides vibration
Scan steatosis grade 1 or above was also analysed in terms of controlled transient elastography (VCTE) assessment to patients
sensitivity, specificity, and accuracy. who, after following the liver guidance pathway, have been identified
Results: Bland-Altman analysis showed that on average HepaFat-AI as having severe liver fibrosis. This study aims to evaluate the patient
yields slightly higher VLFF results with a bias of +0.42 (95%CI 0.10– outcomes 24 months after implementing the liver pathway and VCTE
0.74)%VLFF against HepaFat-Scan. The 95% limits of agreement service.
between the two methods were -3.02 and +3.85%VLFF. The sensitivity Method: All patients referred to the Southampton community liver
and specificity of HepaFat-AI for predicting HepaFat-Scan determined service between January 2019 and December 2020. Demographics
steatosis grade of 1 or above were 0.97 (95% CI 0.84–0.99) and 0.88 recorded included: Age, sex, body mass index (BMI), alcohol
(95% CI 0.64–0.99) respectively. With HepaFat-Scan as the reference consumption (high or low), VCTE reading (kPa), diagnosis (alcohol
standard, HepaFat-AI had an accuracy of 0.90 (95% CI 84–95) for related liver disease, non-alcoholic fatty liver disease or both) and
grading steatosis above or below the grade 0/1 boundary. patient outcomes (stay in primary care or refer to secondary care for
Conclusion: HepaFat-AI provides a rapid and automated liver fat clinical management).
quantification analysis of MR images which has important implica- Results: 527/632 patients referred to the community liver service
tions for cost and may provide a fast alternative point-of-care testing received a VCTE assessment.16.6% (n = 105) did not attend their
for patients. The adoption of ANNs in clinical settings has the appointment and for 0.9% (n = 5), no valid VCTE reading was obtained.
potential to enhance diagnostic efficiency and medical intervention The median (IQR) age of patients was 58 (46–65) years, 58.6% were
for T2D adults with liver disease. male; median (IQR) BMI was 30.5 (27.1–35.1) kg/m2 and alcohol

Figure: (abstract: FRI031): (A) VLFF from manual processing (HepaFat-Scan) vs automated processing (HepaFat-AI) with line of equivalence. (B) Bland-
Altman plot showing the differences between the HepaFat-AI and HepaFat-Scan VLFF measurements. The solid line shows the mean difference and the
dashed lines show the upper and lower 95% limits of agreement between the two methods.

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 POSTER PRESENTATIONS
consumption in 23.9% (n = 126) was graded as high (defined as FRI033
drinking more than the UK recommended alcohol guidelines). Mean Predictive survival-time modelling of Non-Alcoholic
(SD) VCTE was 9.5 (9.2) kPa, of whom 8% (n = 42) had a reading of Steatohepatitis (NASH) fast progressors using real-world evidence
>20.0 kPa. 77.4% (n = 408) were diagnosed with non-alcoholic fatty Nils Svangård1, Christen Gray2, Ally Taylor3, Taylor Cohen4,
liver disease (NAFLD); 15.7% (n = 83) with alcohol related liver disease Bret Sellman4, Claire Donoghue2, Faisal Khan5, Christopher Rhodes6,
(ARLD) and 6.8% (n = 36) with both NAFLD and ARLD. 27.9% (n = 147) Philip Ambery7, Shameer Khader5, John Dillon3. 1AstraZeneca, Data
of patients were found to have a liver fibrosis stage of F3/F4 (9.7 kPa– Science & Artificial Intelligence, Sweden; 2AstraZeneca, Data Science &
13.5 kPa/>13.6 kPa) and were referred to secondary care. 71.0% (n = Artificial Intelligence, Cambridge, United Kingdom; 3University of
374) had a liver fibrosis stage of F0-F2 (between 3.0 kPa and 9.6 kPa) Dundee, United Kingdom; 4AstraZeneca, Microbiome Discovery,
and were referred back to primary care for repeat VCTE assessment in Gaithersburg, United States; 5AstraZeneca, Data Science & Artificial
3 years time. Intelligence, Gaithersburg, United States; 6AstraZeneca, Early CVRM,
Gaithersburg, United States; 7AstraZeneca, Clinical Metabolism,
Gothenburg, Sweden
Email: [email protected]
Background and aims: Evidence suggests that a subset of patients
with Non-Alcoholic Fatty Liver Disease (NAFLD) may progress faster
to end stage liver disease via Non-alcoholic Steatohepatitis (NASH).
There is a need for methods to identify such sub-populations of fast
progressors in order to improve patient care and enable more
effective clinical trials. Prior machine learning based approaches to
identify progressors, e.g. using binary prediction of progression types,
did not consider censored events due to death, transfer out of data
source, or end of study period, which can reduce accuracy of the
results. The aim of this study is to develop a machine learning
survival-time prediction model that can identify NAFLD and NASH
patients at risk of fast progression to end stage liver disease based on
real-world data, taking censoring of events into account.
Method: We retrospectively evaluated patients in Optum®
Clinformatics® Data Mart (de-identified US electronic health
records, 2007–2021) aged ≥18 with the index-time being the first
diagnosis of NAFLD or NASH based on ICD- codes with no prior liver
disease. Progression time was defined as the time between index date
and the first hard endpoint of NASH or censored at death, transfer out
of data source, or end of study period. Progression times were
Figure: Summary of patient pathway through the community-based liver predicted using a machine learning survival-time model robust to
scanning service. missing data, trained on sparse data and 80% of the subjects. Model
performance was evaluated using the cumulative dynamic area-
Conclusion: 8% asymptomatic patients identified as having advanced under-the-curve on the remaining subjects and compared with five
liver disease/cirrhosis and ∼20% identified as being at risk of single biomarker baseline models. The most important features were
developing progressive liver fibrosis, are now being monitored by visualized using Shapley Additive exPlanations (SHAP).
secondary care. The remaining patients (71%) are being monitored in Results: A final cohort of 260, 180 patients matched the inclusion and
primary care and will be referred for repeat VCTE assessment in 3 exclusion criteria, 3% of the patients had a severe endpoint observed,
years time. This evaluation demonstrates the usefulness of providing and the median progression time for these patients was 14 months.
primary care clinicians with a liver guidance pathway with access to The predictive model had an average cumulative dynamic AUC of 0.76
VCTE assessment, a service that is still predominantly only accessible for predicting progression times from index to the end of the study
in secondary care. period, compared with 0.64 for the best performing baseline model,
Acknowledgements: Lucie Lleshi, NHS Southampton Clinical the AST/ALT ratio.
Commissioning Group. Conclusion: The predictive survival-time model outperforms indi-
vidual biomarkers at characterizing NASH fast progressors both at
index time and continuously until the time of event. Future research
of the model should include validation in other datasets, including
patients in a range of geographic regions, of different ethnicities and
with biopsy confirmed NASH.

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POSTER PRESENTATIONS

Figure: (abstract: FRI033)

FRI034 Cohen’s d with correction for paired samples estimated the effect size
Online education significantly improved gastroenterologists’ of the education on number of correct responses (<0.20 modest,
knowledge of the diagnostic and monitoring techniques used in 0.20–0.49 small, 0.59–0.79 moderate, ≥0.80 large). Data were
liver fibrosis collected from 04/01/21 to 09/03/21.
James White1, Elaine Bell1, Briana Betz2, Jörn Schattenberg3. Results: Results showed significant overall improvement in average
1
Medscape Global Education, London, United Kingdom; 2Medscape LLC, percentage of correct responses for gastroenterologists (45% pre- to
New York, United States; 3University Medical Center Mainz, 63% post-education, p < 0.001, Cohen’s d = 0.56). The percentage of
I. Department of Medicine , Mainz, Germany gastroenterologists that answered all questions correctly improved
Email: [email protected] from 9% pre-, to 30% post-education.
Whilst 23% improved and 27% reinforced their knowledge regarding
Background and aims: Non-alcoholic steatohepatitis is a leading which set of markers is included in the Enhanced Liver Fibrosis (ELF)
cause of liver fibrosis. Progression of liver fibrosis to advanced stages score, 50% of gastroenterologists still lack this information after
is linked to severe outcomes and increased healthcare costs. Non- education (p < 0.001).
invasive techniques, including biomarkers and elastography, improve Post-activity, 41% of gastroenterologists had a measurable increase in
the diagnosis and monitoring of liver fibrosis. Unmet educational confidence in using non-invasive techniques in clinical practice to
needs are one barrier in the use of non-invasive techniques. We identify patients with advanced fibrosis ( p < 0.001), with an average
assessed whether online continuing medical education (CME) could confidence shift of 58%.
improve physicians’ knowledge and confidence of appropriate Conclusion: Participation in an online chapterised video activity
diagnostic and monitoring techniques in liver fibrosis. significantly improved physicians’ knowledge and confidence of
Method: Gastroenterologists (n = 220) participated in a chapterised appropriate diagnostic and monitoring techniques in liver fibrosis.
video activity entitled “Evolution of Diagnosis and Monitoring for Despite this, further education regarding the markers included in the
Liver Fibrosis” which covered guideline recommendations, identifi- ELF score is needed for gastroenterologists.
cation of patients at risk of progression, and non-invasive pathways
for identifying advanced fibrosis. Educational effect was assessed
using a repeated-pair design with pre-/post-assessment. 3 multiple
choice questions assessed knowledge and 1 question, rated on a
Likert-type scale, assessed confidence. A paired samples t-test was
conducted for significance testing on overall average number of
correct responses and for confidence rating, and a McNemar’s test
was conducted at the question level (5% significance level, p < 0.05).

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 POSTER PRESENTATIONS
FRI035 broad, unselected population of healthcare-seeking individuals in
Health outcomes and risk assessment in chronic liver disease Sweden. Furthermore, HERALD will utilize clinical and non-clinical
(HERALD): a large Swedish research platform information to characterize patients with different risk profiles and to
Emilie Toresson Grip1,2, Oskar Ström1,2, Hannes Hagström1,3,4. estimate long-term societal burden associated with severe liver
1 outcomes in clinical practice over a 20-year period.
Karolinska Institutet, Department of Medicine Huddinge, Sweden;
2
Quantify Research AB, Stockholm, Sweden; 3Karolinska University
Hospital, Division of Hepatology, Department of Upper GI Diseases, FRI036
Stockholm, Sweden; 4Karolinska Institutet, Clinical Epidemiology Impact of alcohol use on the diagnostic performance of serum-
Division, Department of Medicine Solna, Stockholm, Sweden based indices for fatty liver disease
Email: [email protected] Oscar Danielsson1, Markku Nissinen1, Katja Pahkala2,3,4,
Terho Lehtimäki5,6, Olli Raitakari2,3,7, Fredrik Åberg8. 1Clinic of
Background and aims: The ‘HEalth outcomes and Risk Assessment Gastroenterology, Helsinki University Central Hospital and University of
in chronic Liver Disease’ (HERALD) study is a multi-stakeholder Helsinki, Helsinki, Finland, Finland; 2Centre for Population Health
Swedish research-platform linking national and regional registries to Research, University of Turku and Turku University Hospital, Turku,
investigate the epidemiology and risk factors of liver outcomes, Finland, Finland; 3Research Centre of Applied and Preventive
resource-use and costs, in patients with chronic liver diagnoses (CLD) Cardiovascular Medicine, University of Turku, Turku, Finland, Finland;
or liver-related laboratory tests. HERALD is also planned to include 4
Paavo Nurmi Centre, Unit of Health and Physical Activity, University of
data from the National Diabetes Register and other countries during Turku, Turku, Finland, Finland; 5Department of Clinical Chemistry,
2022, and is open to international collaboration. Fimlab ltd., Finland, Finland; 6Faculty of Medicine and Health
Method: A CLD cohort will consist of all patients ≥18 years with ≥1 Technology, Finnish Cardiovascular Research Center-Tampere, Tampere
CLD diagnosis (ICD-10) in the Swedish Patient Register, or primary University, Tampere, Finland, Finland; 7Department of Clinical
care from the Stockholm region. A Fib-4 cohort will consist of patients Physiology and Nuclear Medicine, Turku University Hospital, Turku,
with laboratory tests (AST, ALT and platelets), required for estimating Finland, Finland; 8Transplantation and Liver Surgery, Helsinki University
the non-invasive Fibrosis-4 (Fib-4) score in all care settings in Central Hospital and University of Helsinki, Finland
Stockholm. All patients will be linked with longitudinal data on Email: [email protected]
diagnoses, comorbidities, healthcare utilization, prescribed medi-
cines, mortality, work absence, socioeconomic status and demo- Background and aims: Non-alcoholic fatty liver disease (NAFLD) and
graphics. For a subset, other laboratory data and data on transient alcohol-related liver disease (ARLD) frequently co-exist, and recently
elastography (FibroScan) are extracted from electronic health records proposed diagnostic criteria for metabolic-dysfunction associated
(EHR) and FibroScan-devices, respectively. High-risk subgroups and fatty liver disease (MAFLD) have removed strict cut offs for alcohol
costs will be compared with matched controls from the general use. While several indices exist for detection of NAFLD, there is
population. paucity of study on how alcohol use possibly impact their diagnostic
Results: A feasibility study was completed in 2020 and ethical performance. We analysed the effect of various level of alcohol use on
approval for HERALD was granted in August, 2020. During 2001– the performance of several indices for detecting fatty liver disease
2019, the number of patients with NAFLD was 16, 285, with at least (FLD).
46, 122 patient years of follow-up. The number of patients with Method: From the Cardiovascular Risk in Young Finns study, we
chronic HCV, AIH or PBC were n = 53, 602, n = 5, 337 and n = 5, 247, included participants who underwent abdominal ultrasound (US) in
respectively. 200, 000 to 300, 000 patients with CLD are expected, 2010–2012 for detection of FLD and had serum analyses available
partly overlapping with the ∼270, 000 patients expected in the Fib-4 from the same time for calculation of the Fatty Liver Index (FLI),
cohort. Hepatic Steatosis Index (HSI) and Lipid Accumulation Product (LAP).
Alcohol use was assessed by questionnaires. Predictive performance
for FLD was assessed by AUROC, logistic regression, sensitivity,
specificity, and positive and negative predictive values (PPV and NPV)
according to alcohol consumption.
Results: Study comprised 1426 individuals (mean age 42.1 years,
42.6% males, mean BMI 26.3 kg/m², mean alcohol use 9.4 g/day), of
which 234 (16%) had FLD by US. High risk index-scores were observed
in 27.2%, 24.7% and 54.8% (FLI, HSI and LAP, respectively) of the study
population. When daily alcohol consumption was <50 grams, all
indices discriminated FLD with AUROCs of 0.82–0.88. Among heavy
drinkers (>50 g/day), AUROCs were 0.61–0.66. Alcohol use correlated
weakly with both FLI (r = 0.09) and LAP scores (r = 0.16, both p-values
<0.001), no significant correlation for HSI.

Conclusion: This study is the result of a research collaboration

between academia and analytical and pharmaceutical industry.
HERALD will be the largest data collection to date to estimate a
contemporary prevalence of liver disease and advanced fibrosis in a

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POSTER PRESENTATIONS
however, limited data characterize its association with outcomes.
We conducted a systematic review and pooled analysis of individual
participant data from published studies and additional identified
cohorts to evaluate the association between liver stiffness on MRE
and liver-related outcomes.
Method: A systematic search identified 6 cohorts of adults at risk for
NAFLD who underwent MRE and were assessed for liver-related
outcomes. In a pooled analysis, logistic regression and Cox propor-
tional hazards models were used to assess the association between
liver stiffness on MRE and liver-related outcomes including a
composite primary outcome defined as varices needing treatment,
ascites and hepatic encephalopathy. Secondary outcomes included
hepatocellular carcinoma (HCC) and death. Cumulative incidence
curves evaluated time to first event for the primary outcome.
Results: Our pooled analysis included 2275 patients (54% women)
with a mean age 57.5 (±15) years and mean MRE at baseline of 4.01
(±2.17) kPa. A total of 948 events occurred in 458 participants. Each
1 kPa increase in liver stiffness was associated with OR = 1.22 (95%
CI:1.16–1.29, p < 0.001) increased odds of the primary outcomes at
baseline. Among 1983 patients with a median (IQR) of 3 (4.14) years
of follow up time the 1- and 3-year risk of the primary outcome was
0.6% and 1.5% for MRE <5 kPa, 7.2% and 16.6% for 5–8 kPa and 8.5% and
18.8% for MRE >8 kPa respectively (Figure). The hazard ratio (HR) for
Conclusion: With alcohol consumption below 50 g/day, FLI, HSI and the primary outcome, HCC and death for MRE 5–8 kPa were HR = 11.9
LAP perform well for detection of FLD, all with comparable (95% CI:7.58–18.96, p < 0.001), HR = 14.8 (95%CI:5.53–39.6, p < 0.001)
performance. With higher alcohol consumption, their diagnostic and HR = 2.37 (95%CI:1.68–3.34, p < 0.001) respectively and for >8 kPa
performance is reduced substantially. HR = 17.3 (95% CI:10.1–29.7, p < 0.001), HR = 23.3 (95%CI:7.94–68.2,
p < 0.001) and HR = 4.84 (95%CI:3.22–7.27, p < 0.001) respectively,
FRI037 compared to <5 kPa. The MEFIB index defined as positive when MRE
Liver stiffness on magnetic resonance elastography and liver- ≥3.3 kPa and FIB-4 ≥1.6 had a strong association with the primary
related outcomes in nonalcoholic fatty liver disease: a systematic outcome HR = 21.8 (95% CI:11.0–43.2, p < 0.001) and excellent
review and meta-analysis of individual participants negative predictive value for hepatic decompensation (Figure).
Veeral Ajmera1, Kun Yang1, Beom Kyung Kim1, Abdul Majzoub2, Conclusion: Liver stiffness assessed by MRE is associated with liver-
Nobuharu Tamaki3, Atsushi Nakajima4, Ramazan Idilman5, related outcomes and death and the combination of MRE and FIB-4
Mesut Gumussoy5, Digdem Kuru Öz5, Ayse Erden5, Natalie Quach6, has excellent negative predictive value for hepatic decompensation.
Xin Tu6, Xinlian Zhang6, Mazen Noureddin7, Alina Allen8,
Rohit Loomba6. 1University of California San Diego; 2Conemaugh
Memorial Medical Center; 3Musashino Red Cross Hospital, Japan;
4
Yokohama City University Medical Center; 5Ankara University, Turkey;
6
University of California San Diego, United States; 7Cedars Sinai Medical
Center, United States; 8Mayo Clinic, United States
Email: [email protected]
Background and aims: Magnetic resonance elastography (MRE) is a
reproducible, accurate, continuous biomarker of liver fibrosis,

Figure: (abstract: FRI037): Cumulative incidence curves for primary outcome by (a) MRE <5 kPa vs 5–8 kPa and >8 kPa and (b) MEFIB Index.

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 POSTER PRESENTATIONS
FRI038 categories (≤26, 27–34, ≥35). In patients with BMI ≥35 (n = 114), any
Utilising features of metabolic syndrome to cost-effectively one feature of metabolic syndrome is a strong enough predictor of
improve metabolic dysfunction-associated fatty liver disease USS steatosis that MAFLD can be diagnosed and managed in the
diagnosis rates community, and USS and liver clinic can be avoided ( p < 0.003, Sen =
Cassandra Baiano1, Jennifer Nobes1, Iain Macpherson1, 85%, PPV = 91%). In BMI 27–34 (n = 275), glucose impairment is a
Callum Livingstone1, Madeleine Caven1, Paul Brennan1, Ellie Dow2, strong enough predictor of USS steatosis that MAFLD can be
John Dillon1. 1School of Medicine-University of Dundee, United diagnosed and managed in the community, and USS and liver clinic
Kingdom; 2NHS Tayside, United Kingdom can be avoided ( p < 0.007, Sen = 35%, PPV = 89%). In patients with a
Email: [email protected] high NAFLD fibrosis score or BMI ≤26 (n = 257), both ultrasound and
liver clinic are still required for assessment.
Background and aims: The international consensus currently The expert liver team reviewed a sub-cohort of 144/646 patients and
defines Metabolic Dysfunction-associated Fatty Liver Disease found that new MAFLD diagnostic pathways based on this stratifica-
(MAFLD) as obesity, multiple metabolic risk factors, or type 2 tion produce the correct MAFLD diagnosis or a fail-safe next step in
diabetes mellitus plus hepatic steatosis on imaging. To facilitate the 96% (n = 138) of cases. The new pathways offer a savings of £36.22 for
diagnosis of liver diseases, like MAFLD, in the community, an every £1 spent.
algorithm-based diagnostic tool (intelligent liver function testing, Conclusion: New MAFLD diagnostic pathways that stratify patients
iLFT) that uses biochemical tests and clinical information has been by BMI and include features of metabolic syndrome to predict fatty
developed. 22% of iLFT results are initially descriptive (i.e. isolated infiltration on USS could cost-effectively increase MAFLD diagnosis in
raised ALT) with no definitive aetiology but are identified as MAFLD the community and reduce referral to USS by 26% while reducing
after costly, prolonged investigations. This study aimed to identify referral to liver clinic by 24% (Sen = 100%, PPV = 98%).
whether features of the metabolic syndrome could be used to cost-
effectively increase MAFLD diagnosis in the community while FRI039
decreasing the need for imaging or liver clinic attendance. Non-invasive assessment of type VII collagen degradation is
Method: A retrospective analysis of iLFT patients from 2018 to 2020 related to NAFLD activity but not fibrosis stage
was conducted. Medical records were used to identify BMI, features of Mette Juul Nielsen1, Peder Frederiksen1, Morten Karsdal1,
metabolic syndrome, and steatosis on ultrasound scan (USS). Logistic Diana Leeming1, Jörn Schattenberg2. 1Nordic Bioscience A/S, Herlev,
regression analyses assessed which features of metabolic syndrome Denmark; 2University Medical Centre of the Johannes Gutenberg-
could predict USS steatosis. New MAFLD diagnostic pathways within University Mainz, Mainz, Germany
iLFT were modelled with a cost-benefit analysis. Email: [email protected]
Results: 2720/6791 patients had no cause for deranged liver function
tests identified by iLFT or had suspected MAFLD, of which 646 had Background and aims: Type VII collagen is an anchoring fibril
sufficient health data for analysis. collagen crucial for the function and stability of the extracellular
While glucose impairment is the only statistically significant feature matrix (ECM) by linking basement membrane and interstitial matrix
to predict USS steatosis across BMIs ( p < 0.000, Sen = 41%, PPV = 88%), collagens together. Remodeling of the basement membrane is
prediction can be optimised by stratifying patients into three BMI observed in early stage pericellular fibrosis, whereas accumulation

Figure: (abstract: FRI038)

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S415

POSTER PRESENTATIONS
of interstitial matrix collagens is observed during advanced fibrosis. Health Sciences, Calgary, Canada; 18Cedars-Sinai Medical Center,
The role of type VII collagen in liver fibrosis is unknown. The aim of Division of Gastroenterology and Hepatology, Department of Medicine,
this study was to investigate the role of type VII collagen using a Los Angeles, United States; 19Pitié Salpêtrier̀ e Hospitals , Sorbonne
collagen neoepitope technology in relation to fibrosis development in Université, Institute of Cardiometabolism and Nutrition, Paris, France;
20
NAFLD patients. University of California San Diego, Department of Pathology, La Jolla,
Method: Degradation of type VII collagen was assessed by the novel United States; 21Inova Health System, Betty and Guy Beatty Center for
neoepitope marker, C7M, developed by Nordic Bioscience A/S, in Integrated Research, Falls Church, United States; 22Inova Fairfax Medical
serum samples from 140 NAFLD patients with biopsy confirmed liver Campus, Department of Medicine, Center for Liver Diseases, Falls Church,
fibrosis F0-F4 and NAS 0–7 in a cross-sectional study design. United States; 23University of Oxford, Radcliffe Department of Medicine,
Histopathological staging of fibrosis, steatosis, hepatocyte ballooning Oxford, United Kingdom; 24Pinnacle Clinical Research, Medical Director,
and lobular inflammation was scored according to the Kleiner scoring San Antonio, United States; 25University of California San Diego, NAFLD
system. Research Center, Department of Medicine, La Jolla, United States
Results: Patients had median age of 53.5 (IQR 43–60) years and Email: [email protected]
median BMI of 32.2 kg/m2 (IQR 29.0–36.1) of which 74 (53%) were
Background and aims: In clinical trials of non-alcoholic steatohe-
male ( p = 0.499). Serum C7M significantly correlated with the NAS (r
patitis (NASH), the Non-alcoholic Steatohepatitis Clinical Research
= 0.255; p = 0.003), the grade of hepatocyte ballooning (r = 0.278; p =
Network (NASH CRN) histologic scoring system is the current gold
0.001), and steatosis (r = 0.285; p < 0.001), but not the degree of
standard histology assessment but has demonstrated intra- and
lobular inflammation (r = 0.161; p = 0.065) or the histological fibrosis
inter-observer variability. An expert panel determined in a prior
stage (r = −0.005; p = 0.962). C7M was significantly elevated in
Research and Development/University of California Los Angeles
patients with NAS ≥3 compared to NAS ≤2 ( p < 0.001). A 30% and
(RAND/UCLA) process that existing histologic scoring systems do
18% increase in C7M was observed from hepatocyte ballooning grade
not fully capture NASH disease activity and fibrosis. We evaluated the
0 to 1–2 ( p = 0.001) and from steatosis grade 0–1 to 2–3 ( p = 0.004),
intra- and inter-rater reliability of histologic disease activity
respectively. In the same cohort, the levels of the fibrogenic collagen
measures and correlated these measures with a disease activity
marker, PRO-C3, was increased in the population with advanced vs
visual analogue scale (VAS) to propose an exploratory expanded non-
early fibrosis ( p < 0.0001), as well as in patients with steatosis ( p =
alcoholic fatty liver disease (NAFLD) activity score (NAS) index
0.0001), hepatocyte ballooning ( p = 0.0001), and lobular inflamma-
comprising optimized items.
tion ( p < 0.0001).
Method: Four liver pathologists assessed 40 liver biopsies represent-
Conclusion: Degradation of type VII collagen may be an early
ing the full spectrum of NAFLD. These central readers were blinded to
indicator of increased protease activity, related to linkage disruption
clinical information, completed standardized training, and scored
of the ECM structure between basement membrane and interstitial
each histologic measure twice, with ≥2 weeks between each
matrix collagens in liver fibrosis development in patients with
assessment. Scored measures included existing histologic indices,
NAFLD.
the component items of these indices, and additional items identified
FRI040 in the prior RAND/UCLA study. Reliability was assessed using intra-
Reliability of histologic disease activity measures in non-alcoholic class correlation coefficients (ICCs).
fatty liver disease (NAFLD) and development of an expanded Results: The ICCs for existing NAFLD activity indices demonstrated
NAFLD activity score substantial to almost perfect intra-rater reliability (ICC, 0.80–0.85)
and moderate to substantial inter-rater reliability (ICC, 0.60–0.72).
Rish Pai1, Vipul Jairath2,3,4, Malcolm Hogan4, Guangyong Zou3,4,5,
Ballooning degeneration items (ICC, 0.68–0.79), including those that
Oyedele Adeyi6, Quentin Anstee7,8, Bashar Aqel9, Cynthia Behling10,11,
extended scores from 0 to 2 to 0–4, and steatosis items (ICC, 0.72–
Elizabeth Carey9, Andrew Clouston12, Kathleen Corey13,14,
0.80) had substantial inter-rater reliability. Fibrosis measures demon-
Brian Feagan2,3,4, David E. Kleiner15, Christopher Ma4,16,17,
strated substantial to almost perfect inter-rater agreement (ICC, 0.70–
Stefanie McFarlane4, Mazen Noureddin18, Vlad Ratziu19,
0.87). Items for ballooning degeneration and Mallory-Denk bodies
Mark Valasek20, Zobair Younossi21,22, Stephen Harrison23,24,
(MDBs) had large correlations with the disease activity VAS (r = 0.66–
Rohit Loomba25. 1Mayo Clinic Arizona, Department of Laboratory
0.96) and were used to develop an expanded NAS (intra-rater ICC,
Medicine & Pathology, Scottsdale, United States; 2University of Western
0.90; inter-rater ICC, 0.80). Steatosis items were poorly correlated
Ontario, Department of Medicine, Division of Gastroenterology, London,
with the disease activity VAS (r = −0.02 to 0.12).
Canada; 3University of Western Ontario, Department of Epidemiology
Conclusion: Histologic indices, including the expanded NAS, had
and Biostatistics, London, Canada; 4Alimentiv Inc., London, Canada;
5 almost perfect intra-rater reliability and moderate to substantial
Robarts Research Institute, Schulich School of Medicine and Dentistry,
inter-rater reliability. Ballooning degeneration and MDBs were used
University of Western Ontario, London, Canada; 6University of
for the expanded NAS based on their strong correlations with disease
Minnesota Medical School, Department of Laboratory Medicine and
activity. Future evaluation of the responsiveness of these measures is
Pathology, Minneapolis, United States; 7Translational & Clinical Research
needed.
Institute, Newcastle University, Faculty of Medical Sciences, Newcastle
upon Tyne, United Kingdom; 8Newcastle NIHR Biomedical Research FRI041
Center, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle Evaluating future risk of NAFLD fibrosis in adolescents: prediction
upon Tyne, United Kingdom; 9Mayo Clinic Arizona, Division of and decision curve analysis
Gastroenterology and Hepatology, Phoenix, United States; 10Pacific Rim
Kushala Abeysekera1,2, Julian Hamilton-Shield1, James Orr2,
Pathology, San Diego, United States; 11University of California San Diego,
Fiona Gordon2, Laura Howe1, Jon Heron1, Matthew Hickman1.
Department of Pediatrics, La Jolla, United States; 12University of 1
University of Bristol, United Kingdom; 2Bristol Royal Infirmary
Queensland, Faculty of Medicine and Biomedical Sciences, Saint Lucia,
Email: [email protected]
Australia; 13Massachusetts General Hospital, Division of
Gastroenterology, Boston, United States; 14Harvard Medical School, Background and aims: Elevated body mass index (BMI) is the major
Boston, United States; 15Center for Cancer Research, National Cancer risk factor for nonalcoholic fatty liver disease (NAFLD) development.
Institute, Laboratory of Pathology, Bethesda, United States; 16Cumming Using data from the Avon Longitudinal Study of Parents and Children
School of Medicine U C, Division of Gastroenterology & Hepatology, (ALSPAC), we sought to investigate whether other variables from
Calgary, Canada; 17University of Calgary, Department of Community adolescence could improve prediction of future NAFLD fibrosis risk at
24 years, above BMI.

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 POSTER PRESENTATIONS
Method: Aged 24 years, 4018 ALSPAC participants had transient FRI042
elastography (TE) using Echosens 502 Touch. 513 participants with Quantification of hepatic steatosis in patients with non-alcoholic
harmful alcohol consumption were excluded. 2.7% had ≥F2 equiva- fatty liver disease: comparison of sound speed, attenuation
lent fibrosis. Logistic regression models examined which factors that coefficient and continuous CAP measurements with MRI-PDFF
were measured at age 17 were predictive of NAFLD fibrosis in young Rémi Collin1, Benjamin Buchard1, Benoît Magnin2, Carine Nicolas1,
adults. Predictors included sex, BMI, central adiposity, lipid profile, Constance Gaillard2, Armand Abergel1. 1Centre Hospitalier
blood pressure, liver function tests, homeostatic model assessment Universitaire Estaing de Clermont-Ferrand, Department of Hepatology
for insulin resistance (HOMA-IR), and steatosis at 17 years (based on and Gastroenterology, Clermont-Ferrand, France; 2Centre Hospitalier
ultrasound). A model including all these variables reflected “standard Universitaire Estaing de Clermont-Ferrand, Department of Radiology,
of care” (SoC). Models were compared using area under the receiver Clermont-Ferrand, France
operator curve (AUROC) and Bayesian Information Criterion (BIC), Email: [email protected]
analysis, which penalises model complexity. Models were tested in
participants with overweight and obese standardised BMIs (BMI SDS) Background and aims: Non-alcoholic fatty liver disease (NAFLD) is
becoming a major health problem, resulting in hepatic, metabolic and
centiles at the 17-year time point. A decision curve analysis (DCA) was
performed to evaluate the clinical utility of models at 17-years cardio-vascular morbidity. Our study aims at evaluating new
ultrasonographic tools to detect and measure hepatic steatosis.
predicting NAFLD fibrosis at a threshold probability of 0.1. Datasets
Method: After local approval and patient consent, we included 73
were imputed up to the number of available TE outcomes.
Results: In adolescents with overweight/obese BMI SDS centiles, the patients addressed to a hepatology consultation for NAFLD suspicion
or follow-up. They underwent ultrasonographic measurement of
SoC model had the highest AUROC (AUROC 0.84 [SD 0.03]). However
following BIC analysis, BMI SDS at 17 years was the best predictor of liver sound speed estimation (SSE) and attenuation coefficient (AC)
using Aixplorer MACH 30 (Supersonic Imagine, France), and
NAFLD fibrosis at 24 years. A DCA examining overweight/obese
continuous Controlled Attenuation Parameter (cCAP) using
adolescent participants demonstrated the model that had greatest
net benefit, above a treat all assumption, was the SoC model although Fibroscan (Echosens, France). Hepatic steatosis was then classified
according to MRI proton density fat fraction (PDFF). Receiver
the net benefit was marginal (0.0054 [IQR 0.0034–0.0075]). This was
equivalent to 5 more NAFLD fibrosis cases being detected per 1000 operating curve (ROC) analysis was performed to evaluate the
patients. diagnostic performance in the diagnosis of steatosis.
Results: Our 73 patients (35 males and 38 females) had high mean
Conclusion: SoC measurements are not superior to BMI SDS in
adolescence at predicting NAFLD fibrosis development in young age, BMI, weight, and waist circumference, respectively 60 years,
29.4 kg/m2, 85 kg and 104 cm. 67% had a metabolic syndrome and
adulthood. Additional SoC measurements provide incremental but
small benefit in detecting true positive fibrosis cases. Thus, with the 15% significant liver fibrosis. According to PDFF, 18 (24.7%) patients
agenda of reducing long term morbidity and mortality associated had no steatosis (PDFF <6.5%, S0), 30 (41.1%) suffered from mild
with fibrosis, providing targeted interventions to overweight and steatosis (6.5 <PDFF <16.5%, S1), 8 (10.9%) from moderate steatosis
obese adolescents is important to prevent progression to fibrosis. (16.5 <PDFF <22%, S2), and 17 (23.3%) from severe steatosis (PDFF
>22%, S3). SSE, AC and cCAP correlate with PDFF, with respective
Spearman correlation coefficient of −0.50, 0.51 and 0.65 ( p < 0.01).

Figure: (abstract: FRI041): Decision curve analysis of different models to predict NAFLD Fibrosis at 24 years in 17 years with overweight or obese BMI
centiles.

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S417

POSTER PRESENTATIONS
Mean SSE, AC and cCAP values significantly differ between non- dates between June and July 2021 and results sent to patients’ GPs.
steatotic and steatotic patients (S1–S3). SSE values also differs Patients with liver stiffness measurements (LSM) >8.2 kPa were
between S1 and S2–S3 steatosis ( p = 0.04). An SSE threshold of referred to a specialist Hepatology clinic for follow up.
1524 m/s had a sensitivity of 69% and a specificity of 74% for the Results: The median age was 63 years (range 27–84). 88% of patients
diagnosis of steatosis (S1–S3). The corresponding area under the ROC had T2DM and 53% had a BMI >30. The median CAP score was 291 dB/
curve (AUC) was 0.77 (95% CI 0.66–0.88, p < 0.01). An AC threshold of m (range 160–400), and 45% of patients had a CAP score ≥300 dB/m.
0.41 dB/cm/MHz had a sensitivity of 91% and a specificity of 79% for The median LSM was 5.8 kPa. 31% of patients had LSM ≥7.1 kPa, 15%
the diagnosis of steatosis (S1-S3). The corresponding AUC was 0.91 had LSM ≥9.1 kPa and 6.7% had LSM ≥12.5 kPa. Only 19% of patients
(95% CI 0.84–0.98, p < 0.01). An cCAP threshold of 263 dB/m had a had both a normal CAP and LSM.
sensitivity of 82% and a specificity of 78% for the diagnosis of steatosis Conclusion: This is the first study to assess VCTE screening for
(S1–S3). The corresponding AUC was 0.92 (95% CI 0.86–0.98, p < hepatic fibrosis beyond traditional healthcare settings, and demon-
0.01). The EASL-suggested threshold of 275 dB/m has a sensitivity of strates that community-based risk-stratified screening leads to
75% and a specificity of 94%. earlier identification of patients with liver fibrosis. Community
pharmacy is a readily accessible healthcare setting in which access
to non-invasive assessments of liver fibrosis outside of the hospital
setting could be offered with potential significant cost savings to the
healthcare system.

FRI044
Non-alcoholic fatty liver disease in patients with type-2 diabetes
mellitus in Greenland
Rasmus Hvidbjerg Gantzel1,2, Abdullah Ghassan Farik Muhammad1,3,
Frederik Orm Hansen1,3, Karsten Fleischer Rex3,
Gerda Elisabeth Villadsen1, Henning Grønbæk1,2,
Michael Lynge Pedersen3,4. 1Aarhus University Hospital, Department of
Hepatology and Gastroenterology, Århus N, Denmark; 2Aarhus
University, Department of Clinical Medicine, Århus N, Denmark; 3Steno
Diabetes Center Greenland, Nuuk, Greenland; 4Institute of Nursing and
Health Science, Greenland Center for Health Research, Nuuk, Greenland
Email: [email protected]
Background and aims: Non-alcoholic fatty liver disease (NAFLD) is
Conclusion: SSE and AC, simultaneously measured using Aixplorer the liver manifestation of the metabolic syndrome with a close
MACH 30 system, demonstrate their reliability to detect liver relation to type-2 diabetes mellitus (T2DM). The prevalence of T2DM
steatosis. AC has high sensitivity for all-grade steatosis detection, is increasing in the Greenlandic population. However, due to genetic
with AUC >0.90, despite having more than 40% of our patients variants, diabetic complications may occur less frequently in
suffering from mild steatosis (S1). Greenlanders than non-Greenlanders. We aimed to characterize the
To be noted that mean SSE values significantly differ between S1 and prevalence and severity of NAFLD in patients with T2DM in
S2–S3 patients, maybe allowing for future ultrasonographic steatosis Greenland.
grading. Method: We included 1619 patients with T2DM living in Greenland
cCAP has good overall performances, but optimal thresholds are yet to in a register-based cross-sectional study. 1436 patients were born in
be determined, and is not able to distinguish between different Greenland and 183 were born in Denmark. In the absence of
grades of steatosis. histopathology and radiological data, we used alanine aminotrans-
ferase (ALAT) as surrogate marker of steatosis and estimated the
FRI043 degree of liver fibrosis with the FIB-4 score. Linear regression
Community NAFLD screening programme in patients with type 2 analyses were performed to assess associations between steatosis
diabetes mellitus indicates high burden of undiagnosed liver and the severity of the metabolic syndrome. A diagnosis of metabolic
disease syndrome required ≥3 of the criteria: T2DM, BMI >30 kg/m2,
Emma McCormick1, Noelle Cullen1, Suzanne Norris1, triglycerides >1.7 mmol/l or antilipidemic treatment, HDL <1.0/
Oonagh O’Hagan2. 1St James’s Hospital, Hepatology, Dublin, Ireland; 1.3 mmol/l for men/women or antilipidemic treatment, and sys-
2 tolic/diastolic blood pressure >130/85 mmHg or antihypertensive
Meaghers Pharmacy Group, Dublin, Ireland
Email: [email protected] treatment.
Results: Despite higher BMI and plasma lipid levels, Greenlanders
Background and aims: NAFLD is the most common liver disease in
had a better glycemic control with lower HbA1c and a lower
Western countries, affecting 1 in 4 adults, with prevalence mirroring proportion on anti-diabetic treatments compared with Danes. The
that of obesity and T2DM. The presence of hepatic fibrosis is an median ALAT was similar, though ALAT was elevated in a larger
important predictor of premature mortality and liver-related mor-
proportion of Greenlanders (21%) compared with Danes (11%). The
bidity and mortality. Vibration-controlled transient elastography median ALAT was statistically significantly higher in Greenlanders
(VCTE) is a validated non-invasive test with NPV >90% for detection
with metabolic syndrome compared with Greenlanders without
of advanced fibrosis/cirrhosis, but is largely confined to specialist metabolic syndrome (51 vs. 39 U/L, p < 0.001). Further, ALAT
centres. The lack of optimised public health screening strategies to increased with 8.0% (95% CI: 5.2–10.9, p < 0.001) for each metabolic
detect liver fibrosis in adults remains a healthcare challenge.
syndrome criteria fulfilled. The Danes had a higher FIB-4 score than
The aim of this study was to assess the feasibility of VCTE as a Greenlanders (median 0.97 vs. 0.91, p = 0.048). 84% of Greenlanders
screening method to detect hepatic fibrosis in patients with and 80% of Danes had a FIB-4 score <1.45 with a very low risk of
identified risk factors for NAFLD in a community healthcare setting. significant fibrosis, while 13% of Greenlanders and 18% of Danes had a
Method: 206 patients (94 male, 112 female,) with risk factors for FIB-4 score of 1.45–2.67 with an intermediate risk of fibrosis. Only 2%
NAFLD were identified via dispensing records in community
in both ethnic groups had a FIB-4 score >2.67 suggesting advanced
pharmacies and invited to register for VCTE appointment. VCTE fibrosis.
assessments were performed in 4 community pharmacies over 14

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 POSTER PRESENTATIONS
Conclusion: ALAT elevations are more frequent in Greenlanders than signature will be retrospectively tested and extended to histology
in Danes with T2DM, and ALAT increases with 8.0% for each metabolic analysis.
syndrome criteria fulfilled. Accordingly, ALAT may be a useful and
easily accessible tool to monitor NAFLD in patients with T2DM in FRI046
Greenland. The median FIB-4 score is lower in Greenlanders Enchanced Liver Fibrosis test in predicting severe liver-related
compared with Danes, suggesting a lower degree of liver fibrosis. outcomes in the general population
These findings need further evaluations preferably including com- Kustaa Saarinen1,2, Martti Färkkilä1,2, Antti Jula3, Iris Erlund3,
parisons with histopathology. Terhi Vihervaara3, Annamari Lundqvist3, Fredrik Åberg4. 1Helsinki
University Hospital, Abdominal Center, Helsinki, Finland; 2University of
FRI045 Helsinki, Helsinki, Finland; 3Finnish Institute for Health and Welfare,
A baseline signature of metabolites involving the gut-liver axis Helsinki, Finland; 4Helsinki University Hospital, Transplantation and
predicts MRI-PDFF response to FASN inhibitor TVB-2640: results Liver Surgery Clinic, Finland
from the FASCINATE-1 study Email: [email protected]
Rohit Loomba1, Marie O’Farrell2, Eduardo Martins2,
Background and aims: Liver fibrosis is the most important
Katharine Grimmer2, Alithea Zetter2, Cristina Alonso3,
prognostic factor for liver-related morbidity and mortality in liver
Ibon Martínez-Arranz3, George Kemble2, Stephen Harrison4. 1UC San
diseases in population including non-alcoholic fatty liver disease and
Diego School of Medicine, Dept of Gastroenterology, La Jolla; 2Sagimet
alcohol-related liver disease. Existing methods for liver fibrosis
Biosciences, San Mateo, United States; 3OWL Metabolomics, Derio,
assessment are either not suitable or show suboptimal performance
Spain; 4Pinnacle Clinical Research, San Antonio, United States
for fibrosis screening in unselected populations. The Enhanced Liver
Email: [email protected]
Fibrosis (ELF) test, a composite score based on three serum-based
Background and aims: TVB-2640 is a potent FASN inhibitor in Ph2b markers of matrix turnover tissue inhibitor metalloproteinase 1
development for NASH. FASN is an attractive target because de novo (TIMP-1), human procollagen type III amino terminal propeptide
lipogenesis drives steatosis, causes lipotoxicity, and is necessary for (PIIINP) and hyaluronic acid (HA) can detect advanced fibrosis and
fibrogenesis. A 12 wk Ph2a study FASCINATE-1 was completed and predict liver-related outcomes in various types of chronic liver
met its primary endpoint. TVB-2640 reduced liver fat by 28.1% ( p = diseases, but studies in large general population cohorts are lacking.
0.001) at 50 mg with a 61% MRI-PDFF response rate (decrease >30%, p We evaluated the performance of the ELF test in predicting liver
= 0.001), and decreased biomarkers including ALT, PRO-C3, PIIINP, CK- related outcomes at the population level.
18 and lipotoxins. NASH clinical studies are often confounded by high Method: ELF was measured at baseline from frozen serum samples of
pbo but relatively low drug response rates. The objective of this work adult (age >30 years) participants of the Finnish Health 2000 study, a
was to identify predictive biomarkers of MRI-PDFF response using population-based epidemiological survey conducted in year 2000–
metabolomic and SNP profiling of baseline blood samples from 2001. Subjects with baseline liver disease were excluded. Data were
patients in FASCINATE-1. linked with national healthcare registers for hospitalization, cancer
Method: Metabolomic plasma profiling of ∼460 species was and death related to severe liver disease.
performed on the OWL platform for pbo, 25 mg, 50 mg. Two Results: The cohort comprised 6040 individuals (46% men, mean age
machine learning approaches, Random Forest (RF) and Support 52.7 ± 15 years, BMI 26.9 kg/m2, median alcohol use 74.9 g/week, 10%
Vector Machine were applied to baseline data. Using% change in MRI- with diabetes). ELF was <9.8 in 5243 (87%), 9.8–11.3 in 741 (12%), and
PDFF as a continuous variable, a signature was developed using 50% of ≥11.3 in 56 (0, 9%). During a median follow-up of 13.1 years, 67 severe
samples and tested using the other 50% with extensive cross- liver-related outcomes occurred. By age- and sex-adjusted Cox
validation for sample size. Genotyping of SNPs relevant to NAFLD was regression, hazards ratios (HRs) for liver outcomes were 6.44 (95%CI
completed for 19 patients to date (6 pbo, 13 on 50 mg, 79% Hispanic). 3.37–12.29) with ELF 9.8–11.3, and 24.37 (95% CI 8.55–69.50) with
Correlative analysis included metabolomics, genomics and other ELF ≥11.3, compared to ELF <9.8. Corresponding cumulative Aalen-
NASH biomarkers. Johansen incidences are shown in the figure. The C-statistic of ELF for
Results: A 6-metabolite signature was identified that enriches for predicting liver outcomes was 0.82 (95% CI 0.72–0.91) at 5 years and
MRI-PDFF response to TVB-2640. This showed 79% accuracy, 88% 0.73 (0.65–0.81) at 10 years.
positive predictive value and 63% negative predictive value by the RF
method. The components are ursodeoxycholic acid, glycoursodeoxy-
cholic acid, DL-2-Aminocaprylic acid, Sarcosine, D (-)-2-
Aminobutyric acid and phosphatidyl choline (O-18:0/22:4). The
composition of several bile acid derivatives suggests a role for the gut
liver axis in TVB-2640 response. Overall, secondary bile acids
increased after 12 wk of TVB-2640 across several classes and 9/10
species tested although not statistically significant. Analysis of pbo
and independent validation is ongoing to refine this signature.
SNP analysis showed allele variants in PNPLA3 rs738409, TMF6SF2
rs58542926 and MBOAT7 rs641738 in 68%, 16% and 53% of patients
respectively, consistent with literature. MRI-PDFF responders
included patients with wild type, hetero- or homozygous PNPLA3
rs738409. The effect of PNPLA3 genotype on baseline metabolomic
profile will be assessed. Additional predictive signatures are under
development using a combination of metabolomics and genomic
profiling.
Conclusion: TVB-2640 decreased liver fat and markers of inflamma-
tion, lipotoxicity and fibrosis. Plasma metabolomics identified a
baseline predictive signature of MRI-PDFF response to FASN
inhibition, which indicates a role for the gut-liver axis. The Ph2b
FASCINATE-2 study will incorporate microbiome analysis and the

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POSTER PRESENTATIONS
Conclusion: The ELF test predicts severe liver-related outcomes in FRI048
the general population. The ELF test could thus be used for initial The combination of the ELF and FIB-4 scores have high predictive
stratification of the population regarding risk for future liver disease. performance for significant fibrosis in patients with NAFLD
Zobair Younossi1,2, Sean Felix2, Thomas Jeffers2, Elena Younossi2,
FRI047 Fatema Nader3, Andrei Racila1,2, Brian Lam2, Maria Stepanova3. 1Inova
Radiowater perfusion PET of the liver, and its value as a biomarker Health System, Medicine Service Line, Falls Church, United States; 2Betty
to discriminate between NAFLD and NASH, and activity and and Guy Beatty Center for Integrated Research, IHS, Falls Church, United
fibrosis grade States; 3Center for Outcomes Research in Liver Disease, Washington DC,
Olof Eriksson1, Kerstin Heurling1, Paul Hockings1, Edvin Johansson1, United States
Alkwin Wanders2, Håkan Ahlström1, Lars Johansson1, Johan Vessby3, Email: [email protected]
Fredrik Rorsman3, Mark Lubberink4. 1Antaros Medical AB, Sweden;
2
Aalborg University Hospital, Aalborg, Denmark; 3Uppsala University Background and aims: Patients with nonalcoholic fatty liver disease
Hospital, Sweden; 4Uppsala University Hospital, Uppsala, Sweden (NAFLD) and fibrosis of stage 2 or greater (clinically significant
Email: [email protected] fibrosis) are at risk for adverse outcomes, and are commonly
considered to be candidates for clinical trials. Although non-invasive
Background and aims: The lack of non-invasive, biopsy free and tests (NITs) for fibrosis have good negative predictive value (NPV),
repeatable assessments for fibrosis and activity stage in NAFL and they tend to have suboptimal positive predictive value (PPV) for
NASH is a significant hurdle in respect to clinical diagnosis and determining significant fibrosis. Our aim was to use a combination of
evaluation of novel interventions. Radiowater PET has been shown to two NITs to rule in and to rule out significant fibrosis among patients
be a sensitive technique to quantify blood flow and identify perfusion with NAFLD.
defects in e.g. cardiology and neurology. We hypothesized that Method: Data were collected from patients with confirmed NAFLD
pathological changes in liver perfusion and arterial and portal blood diagnosis. Serum and liver biopsies were obtained for all patients. The
flow could be detected by radiowater PET. The aim of this clinical Enhanced Liver Fibrosis (ELF) and FIB-4 NITs were calculated. Liver
study was to assess the value of radiowater PET for distinguishing biopsies were read by a single hepatologist and scored according to
between NAFL and NASH, as well as predicting activity and fibrosis the NASH CRN criteria, from stage 0 (no fibrosis) to 4 (cirrhosis).
grade in direct comparison with established biomarkers. Significant fibrosis stage was defined as stage F2–F4.
Method: A subset of patients with suspected NAFL/NASH (N = 30) Results: There were 463 NAFLD patients included: 48 ± 13 years old,
recruited within the NASH AM-02 study was examined by radiowater 31% male, 35% type 2 diabetes. Of included patients, 39% had
PET/MRI, as well as transient elastography (FibroScan), in addition to significant fibrosis; mean ELF score was 9.0 ± 1.2, mean FIB-4 score
sampling for established biomarkers of liver fibrosis. NAFL/NASH was 1.22 ± 1.05. Patients with significant fibrosis were older, more
diagnosis as well as activity and fibrosis grade were verified by commonly male, had lower BMI but more components of metabolic
hepatic biopsy. Dynamic radiowater PET data of the liver was used to syndrome (type 2 diabetes, hypertension, hyperlipidemia), higher
assess total hepatic blood flow, portal vein flow, hepatic arterial flow ELF and FIB-4 scores ( p < 0.0001). The performance of the two NITs in
and portal flow fraction. The ROC AUC, the Youden cut-off and identifying NAFLD patients with significant fibrosis was as follows:
sensitivity/specificity were calculated for discrimination between (a) AUC (95% CI) = 0.78 (0.74–0.82) for ELF, 0.79 (0.75–0.83) for FIB-4. A
NAFL vs NASH, (b) activity grade 0–1 vs 2–4 and (c) fibrosis grade 0–1 combination of ELF score ≥9.8 and FIB-4 ≥1.96 returned PPV of 95%
vs 2–4. The correlation between parameters and activity grade 0–4 which can reliably rule in significant fibrosis (sensitivity 22%,
and fibrosis grade 0–4 was estimated by Spearmań s correlation specificity >99%), while an ELF score ≥7.7 and FIB-4 ≥0.30 had NPV
coefficient. of 95% which can be used to rule out significant fibrosis (sensitivity
Results: In total 30 patients were examined in this sub-study and 98%, specificity 22%); based on the latter, a rule to rule out significant
diagnosed with NAFL (n = 11) or NASH (n = 19), fibrosis grade 0–1 (n = fibrosis could be rewritten as follows: ELF <7.7 or FIB-4 <0.30.
17) or 2–4 (n = 13) and activity grade 0–1 (n = 11) or 2–4 (n = 19). The Conclusion: The combination of ELF and FIB-4 can provide an easy
ROC UAS as well as the Spearmań s correlation coefficient for each algorithm with both high NPV and high PPV to rule out or rule in
parameter is reported in Table 1. significant fibrosis in NAFLD. These data can be used to risk-stratify
Conclusion: Radiowater PET has similar value as biomarker for NAFLD patients in clinical practice as well as identify those who could
distinguishing between NAFL/NASH and identifying activity grade, be candidates for clinical trials.
but not fibrosis grade, as transient elastography and established
plasma markers.

Table 1: (abstract: FRI047).

PET Portal Liver
PET Total vein blood PET Portal stiffness
blood flow flow [ml/g/ vein flow Fibroscan
[ml/g/min] min] fraction [1/1] [kPa] CK18 M30 ALT AST
1
ROC AUC (Youden cut-off), p-value
NAFL vs NASH, and 0.71 (<0.771)* 0.73 (<0.63)* 0.70 (<0.868)* 0.74 (>5.4)* 0.76 (>186)** 0.66 (>0.73) 0.58 (>0.63)
Activity grade 0–1 vs 2–4
Fibrosis grade 0–1 vs 2–4 0.66 (<0.692) 0.68 (<0.612) 0.61 (<0.888) 0.84 (>6.4)** 0.37 (<353) 0.64 (>0.8) 0.66 (>0.74)
Spearman’s correlation coefficient, p-value
Activity grade 0–4 −0.40** −0.42** −0.29 0.37* 0.42** 0.27 0.17
Fibrosis grade 0–4 −0.41** −0.45** −0.27 0.68*** 0.31 0.37** 0.41**
1
p-value for testing if variable is able to predict group, i.e. p-value for testing OR differ from 1. *p < 0.1, **p < 0.05, ***p < 0.0001.

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 POSTER PRESENTATIONS
FRI049 FRI050
Association of the biological age and the level of global LEARN algorithm: a novel option for predicting non-alcoholic
deoxyribonucleic acid methylation with metabolic parameters in steatohepatitis
patients with non-alcoholic fatty liver disease Gang Li1, Tian-lei Zheng2, Xiaoling Chi3, Yong-Fen Zhu4, Jinjun Chen5,
Olena Kolesnikova1, Anastasiia Radchenko1, Valentina Galchinskaya2. Liang Xu6, Jun-Ping Shi7, Xiaodong Wang8, Wei-Guo Zhao2,
1
L.T. Mala Therapy National Institute of the National Academy of Medical Chris Byrne9, Giovanni Targher10, Rafael Rios1, Ou-Yang Huang1,
Sciences of Ukraine, Department of Study of Aging Processes and Liangjie Tang1, Shi-Jin Zhang2, Shi Geng2, Huanming Xiao3,
Prevention of Metabolic-Associated Diseases, Kharkiv, Ukraine; 2L.T. Sui-Dan Chen11, Rui Zhang12, Ming-Hua Zheng1. 1the First Affiliated
Mala Therapy National Institute of the National Academy of Medical Hospital of Wenzhou Medical University, Wenzhou, China, NAFLD
Sciences of Ukraine, Laboratory of Immuno-Biochemical and Molecular- Research Center, Department of Hepatology, Wenzhou, China; 2The
Genetics Researches, Kharkiv, Ukraine Affiliated Hospital of Xuzhou Medical University, Artificial Intelligence
Email: [email protected] Unit, Department of Medical Equipment, Xuzhou, China; 3Guangdong
Provincial Hospital of Chinese Medicine, the Second Affiliated Hospital of
Background and aims: Changes in the metabolic phenotype occur
Guangzhou University of Chinese Medicine, Department of Hepatology,
with age in patients with non-alcoholic fatty liver disease (NAFLD),
Guangzhou, China; 4Sir Run Run Shaw Hospital, Affiliated with School of
however, the time of their occurrence and the connection with the
Medicine, Department of Hepatology and Infection, Hangzhou, China;
processes and markers of aging remain not fully understood. Our aim 5
Nanfang Hospital, Southern Medical University, Guangzhou, China,
was to establish the relationship between biological age (BA) and the
Hepatology Unit, Zengcheng Branch, Nanfang Hospital, Southern
global methylation level (GML) with metabolic parameters in
Medical University, Hepatology Unit, Department of Infectious Diseases,
patients with NAFLD.
Guangzhou, China; 6Tianjin Second People’s Hospital, Department of
Method: Our study included 106 patients with NAFLD with a mean
Hepatology, Tianjin, China; 7Hangzhou Normal University Affiliated
age of 51.4 ± 8.9 years (62.3% women). All patients were divided into
Hospital, Department of Liver Diseases, Hangzhou, China; 8the First
groups according to age: group 1-young patients (<45 years), group
Affiliated Hospital of Wenzhou Medical University, Key Laboratory of
2-middle-aged (45–59 years), group 3-the elderly (>60 years). The
Diagnosis and Treatment for The Development of Chronic Liver Disease
diagnosis of NAFLD was based on the fatty liver index and fibrosis-4
in Zhejiang Province, Wenzhou, China; 9University Hospital
index. Anthropometric and biochemical parameters were deter-
Southampton, Southampton General Hospital, Southampton National
mined in all patients. The GML that is the content of 5-methylcytosine
Institute for Health Research Biomedical Research Centre, Southampton,
in the DNA of mononuclear blood cells was detected with ELISA as a
United Kingdom; 10University and Azienda Ospedaliera Universitaria
marker of aging. BA was calculated according to the method of A.G.
Integrata of Verona, Verona, Italy, Section of Endocrinology, Diabetes and
Gorelkin, B. B. Pinkhasov.
Metabolism, Department of Medicine, Verona, Italy; 11the First Affiliated
Results: Analysis of anthropometric, lipid profile and liver para-
Hospital of Wenzhou Medical University, Department of Pathology,
meters in patients with NAFLD depending on age revealed significant
Wenzhou, China; 12the First Affiliated Hospital of Wenzhou Medical
differences in the level of triglycerides (TG) ( p = 0.043), BA ( p = 0.002)
University, Department of Nutrition, Wenzhou, China
between groups 1 and 2, and in BA ( p = 0.002) between groups 1 and
Email: [email protected]
3. There was a significantly higher proportion of young patients with
an increased percentage of body fat (FAT) (χ2 = 4.011; p = 0.045) Background and aims: There is an unmet need for accurate non-
compared to middle-aged patients. Correlation analysis in group 1 invasive methods to diagnose non-alcoholic steatohepatitis (NASH).
showed a positive association between calendar age (CA) and visceral Since impedance-based measurements of body composition are
fat (VIS) ( p = 0.023) and negative one between CA and alkaline simple, repeatable and have a strong association with non-alcoholic
phosphatase (AP) ( p = 0.017), BA was associated with VIS ( p = 0.016), fatty liver disease (NAFLD) severity, we aimed to develop a novel and
and the GML-with ALT ( p = 0.036). In group 2 there was no fully automatic machine learning algorithm, consisting of a deep
relationship between CA and the observed parameters, while BA neural network based on impedance-based measurements of body
was positively associated with FAT ( p = 0.012), VIS ( p = 0.002), composition to identify NASH (the LEARN algorithm, bioeLectrical
aspartate aminotransferase (AST) ( p = 0.045), TG ( p = 0.019), very impEdance Analysis foR Nash).
low-density lipoprotein cholesterol (VLDL-C) ( p = 0.019) and had a Method: 1, 259 consecutive subjects with suspected NAFLD aged 12–
negative relationship with the percentage of skeletal muscle (MUS) 75 years were screened from six medical centers across China from
( p = 0.021) and AP ( p = 0.042). The GML in this group was associated 2016 to 2021. 766 patients with biopsy-proven NAFLD were included
with body mass index (BMI) ( p = 0.040), TG ( p = 0.002), VLDL-C ( p = in the final analysis. Patients were randomly divided into the training
0.003). In group 3, CA had a direct association with VIS ( p = 0.021) and and validation groups, in a ratio of 4:1. The LEARN algorithm (utilizing
a reverse one with total cholesterol (TC) ( p = 0.005), BA was not impedance-based measurements of body composition along with
associated with indicators that were not used for calculation, the GML age, sex, history of hypertension and diabetes) was developed in the
was directly related to hip circumference (HC) ( p = 0.035) and AP training group to identify NASH, and subsequently, tested in the
level (p = 0.011). validation group.
Conclusion: BA has been associated with anthropometric, lipid and Results: The LEARN algorithm showed good discriminatory ability for
liver parameters in middle-aged patients with NAFLD. The GML has identifying NASH in both the training and validation groups (AUROC:
been related to the levels of HC, BMI, TG, VLDL-C, ALT, AP, mainly in 0.81, 95%CI 0.77–0.84 and 0.80, 0.73–0.87, respectively). This
middle-aged patients with NAFLD, which may be associated with algorithm performed better than serum cytokeratin-18 neoepitope
more pronounced changes in the metabolic profiles of this age group. M30 level or other non-invasive NASH scores (including HAIR, ION,
The data obtained can be useful for the prevention of accelerated NICE) for identifying NASH ( p-value <0.001). Additionally, even in a
aging rates in patients with NAFLD. condition of partial missing the data of body composition, LEARN
algorithm performed well in identifying NASH (AUROC: 0.82, 95%CI
0.72–0.92). Subgroup analysis showed that the LEARN algorithm
performed well in different subgroups.

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S421

POSTER PRESENTATIONS
Key words: NAFLD, significant fibrosis, MEFIB, FAST, MAST, diagnosis,
validation

FRI052
MRI assessment (cT1) with LiverMultiScan following VCTE
improves the diagnostic yield for high-risk NASH
Naim Alkhouri1, Andrea Dennis2, Atsushi Nakajima3,
Stephen Harrison4, David J. Breen5, Daniel Cuthbertson6,
Mazen Noureddin7. 1Arizona Liver Health, Chandler, United States;
2
Perspectum, United Kingdom; 3Department of Gastroenterology and
Hepatology, Yokohama City University School of Medicine, Japan;
4
Division of Cardiovascular Medicine, Department of Medicine,
University of Oxford, Oxford, United Kingdom; 5University of
Southampton, United Kingdom; 6Institute of Ageing & Chronic Disease,
Faculty of Health & Life Sciences, University of Liverpool, United
Kingdom; 7Karsh Division of Gastroenterology and Hepatology,
Comprehensive Transplant Center, Cedars Sinai Medical Center, Los
Angeles, CA, USA, United States
Email: [email protected]
Background and aims: In the diagnostic pathway for NAFLD, EASL
recommends the use of non-invasive tests (NITs) for assessing
Conclusion: The LEARN algorithm, utilizing simple easily obtained fibrosis. However, NASH, independently of fibrosis stage, is also
measures, provides a fully automated, simple, non-invasive method associated with poor outcomes and thus high costs of care.
for identifying NASH. Accordingly, recent EASL and NICE guidance recommend diagnosis
Keywords: NAFLD, NASH, LEARN algorithm, body composition. and management of this patient group. As an MRI-derived measure,
cT1 is an excellent biomarker to diagnose NASH, shown to predict
FRI051 clinical outcomes, and has become a leading NIT for stratifying
Head to head comparison between MEFIB versus MAST for patients based on high-disease risk. We compared a clinical pathway
identification of high-risk patients with NAFLD using cT1 for stratifying high-risk NASH to the current recommen-
Beom Kyung Kim1,2, Nobuharu Tamaki1,3, Jinho Jung1, Nancy Sutter1, dation using NITs for advanced fibrosis only, to explore diagnostic
Claude Sirlin1, Atsushi Nakajima4, Rohit Loomba1. 1University of accuracy and appropriate further referral to specialist care.
California San Diego; 2Yonsei University College of Medicine; Method: We studied NAFLD patients who had undergone NITs; liver
3
Musashino Red Cross Hospital; 4Yokohama City University Graduate stiffness (kPa) from vibration controlled transient elastography
School of Medicine (VCTE, FibroScan®), and MRI-derived cT1 (ms) with
Email: [email protected] LiverMultiScan®. All had liver fat ≥5% (LiverMultiScan® PDFF) and
had histologically confirmed NAFLD with liver biopsy. We compared
Background and aims: Nonalcoholic fatty liver disease (NAFLD)
two diagnostic approaches: (1) Utilising VCTE results only, to exclude
patients with ≥stage 2 fibrosis are at an increased risk for developing
low risk individuals and identify those with advanced fibrosis
liver-related morbidity and mortality. We performed a head-to-head
suitable for onward referral; (2) VCTE followed by cT1 (for NASH
comparison to evaluate the diagnostic test accuracy and predictive
risk stratification). We assessed the number of failed and indeter-
performance of MAST (magnetic resonance imaging-aspartate
minate results,% positive predictor value (PPV) for high-risk NASH
aminotransferase) versus MEFIB (the combination of magnetic
cases correctly identified, and number referred onto specialist care.
resonance elastography [MRE] and FIB-4).
Correct identification of fibrosis was based on F≥3; “high-risk NASH”
Method: NAFLD patients with a liver biopsy and MRE were analyzed
was NAS≥4 and F≥2; established (EASL guidelines) VCTE thresholds
from two prospective cohorts, the University of California San Diego
were <8 kPa rule out and ≥12 kPa rule in; cT1 threshold was ≥875 ms.
(n = 414) and Yokohama City University (n = 314). Diagnostic perfor-
Results: Using data from N = 121 patients (60 yrs., 40% female, 59%
mances for significant fibrosis (stage ≥2) were assessed using area
BMI ≥27 kg/m2). The second pathway (VCTE followed by cT1)
under receiver operating characteristic curves (AUROCs).
increased the PPV for high-risk NASH from 62% (43/69 with
Results: The mean age was 55.3 years and 48.1% were male.
VCTE≥8 kPa) to 75% (24/32 with cT1 ≥875 ms) and reduced
Significant fibrosis was observed in 46.4%. MEFIB was superior than
subsequent referrals from 95 to 69 individuals. This was driven by
MAST with AUROCs of categorized MEFIB (rule-in, intermediate, and
better stratification of failed or indeterminate cases, and greater
rule-out) and MAST (>0.242, 0.165∼0.242, and <0.165) being 0.889
specificity for the identification of those with high-risk NASH by
(95% confidence interval [CI] 0.864∼0.914) and 0.769 (95% CI
incorporating cT1 (Figure 1).
0.733∼0.805), respectively ( p < 0.001). Positive predictive value for
significant fibrosis of MEFIB rule-in criteria was significantly higher,
compared to MAST >0.242 (94.2% versus 88.2%, respectively; p =
0.031). Negative predictive value for significant fibrosis of MEFIB rule-
out criteria was also significantly higher, compared to MAST <0.165
(89.8% versus 73.3%, respectively; p < 0.001). When MAST was
analyzed as a continuous variable, its AUROC improved to 0.890
(95% CI 0.866∼0.914).
Conclusion: For the identification of high-risk patients with NAFLD,
MEFIB is significantly superior to categorized MAST. As continuous
MAST score had high AUROC, the optimal cutoffs should be modified.
Conversely, MEFIB, as a simple and easy algorithm, has practical
advantages with a more reliable diagnostic performance as well as a
better rule-in/-out ability.

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 POSTER PRESENTATIONS
Conclusion: Investigating suspected advanced fibrosis using positive Conclusion: The G/G genotype in PNPLA3 is associated with an
NIT results, with combined TE and MRI assessment of cT1 increased increased risk of progression to cirrhosis in NAFLD. This was confined
the diagnostic accuracy of high-risk NASH by 21% and reduced liver to patients without advanced fibrosis at baseline. Our results suggest
biopsy by 28%. Screening tests based on NITs for fibrosis alone are that assessment of PNPLA3 genotype can be of clinical relevance in
inadequate for risk stratification and diagnosis of NASH. Inclusion of non-cirrhotic patients with NAFLD to individualize monitoring and
MRI-assessed cT1 in NAFLD/NASH clinical diagnostic pathways therapeutic strategies.
improves diagnostic accuracy and reduces the need for biopsy and
for specialist referral, which would result in downstream cost savings. FRI054
Hepatic expression of secreted calcium-binding protein 2 by
FRI053 hepatic stellate cells is associated with human non-alcoholic fatty
The PNPLA3 (rs738409) G/G-genotype is associated with presence liver disease progression
of NASH and increased long-term risk of cirrhosis in NAFLD Frederik Larsen1, Mike Terkelsen1, Sofie Bendixen1, Daniel Hansen1,
Magnus Holmer1, Robin Zenlander1, Axel Wester1, Mattias Ekstedt2, Charlotte Wernberg2, Mette Lauridsen2, Tina Di Caterino3,
Patrik Nasr2, Stergios Kechagias2, Stefano Romeo3, Per Stal1, Fabio Avolio1, Majken Siersbæk1, Vineesh Indira Chandran1,
Hannes Hagström1. 1Karolinska Institutet, Department of Medicine, Jonas Graversen1, Aleksander Krag1,3, Lars Groentved1,
Huddinge, Stockholm, Sweden; 2Linköping University, Division of Kim Ravnskjaer1. 1University of Southern Denmark, Odense, Denmark;
2
Diagnostics and Specialist Medicine, Department of Health, Medicine Sydvestjysk Sygehus, Esbjerg, Denmark; 3Odense University Hospital,
and Caring Sciences, Linköping, Sweden; 3University of Gothenburg, Odense, Denmark
Department of Clinical and Molecular Medicine, Gothenburg, Sweden Email: [email protected]
Email: [email protected]
Background and aims: Non-alcoholic fatty liver disease (NAFLD) and
Background and aims: Mutations in several genes are linked to a its progressive form, non-alcoholic steatohepatitis (NASH), is the
worse histopathological profile in patients with nonalcoholic fatty hepatic manifestation of obesity-induced metabolic syndrome.
liver disease (NAFLD). It is unclear if these genotypes impact long- Activated Hepatic stellate cells (aHSCs) play a pivotal role in hepatic
term outcomes. Here, we investigated the prognostic importance of fibrosis, a defining process of NAFLD pathogenesis. Thus, secreted
PNPLA3, TM6SF2, MBOAT7 and GCKR genotypes on the development aHSC-specific proteins may hold promise as non-invasive biomarkers
of cirrhosis, liver related events (LRE) and all-cause mortality in a for diagnosis of NASH. Histological assessment of liver biopsies is the
well-defined cohort of patients with NAFLD. golden standard in diagnosis of NASH. Liver biopsy, however, is
Method: DNA samples were collected from 546 patients with NAFLD. associated with risk for the patient and does not fully capture the
Presence of advanced fibrosis was established through liver biopsy tissue heterogeneity of the fibrotic liver.
(stage 3–4) or elastography (≥15 kPa), while presence of nonalcoholic Method: RNA sequencing was performed on liver needle biopsies
steatohepatitis (NASH) was defined only by histology. A total of 5396 from a histopathological characterized severely obese (BMI >35)
controls matched by age, sex and municipality were identified from discovery cohort (n = 30). Bioinformatical analysis was used to
the Swedish population. Outcome of cirrhosis, LRE and overall identify potential biomarkers and their hepatocellular origin.
mortality were collected from national registries. Cox regression Detection of mRNA in liver tissue and protein levels in plasma was
models were used to estimate adjusted hazard ratios (aHR) for these performed using single molecule fluorescence in situ hybridization
outcomes. (smFISH) and ELISA, respectively.
Results: In patients with NAFLD, the G/G genotype of PNPLA3 Results: Hepatic expression of secreted modular calcium-binding
(rs738409) was associated with a higher prevalence of NASH at the protein 2 (SMOC2) was upregulated in NASH patients compared to
time of biopsy (OR 3.67 [95% CI = 1.66–8.08]), but not with advanced healthy obese patients ( padj <0.001). Single-cell RNA sequencing
fibrosis (OR 1.81 [95% CI = 0.79–4.14]). In NAFLD subjects without data indicated hepatic SMOC2 expression by quiescent and aHSCs
advanced fibrosis at baseline, the G/G genotype was associated with a exclusively, which was validated using smFISH. Moreover, plasma
higher risk of developing cirrhosis and LRE (aHR 2.41 [95% CI = 1.02– [SMOC2] was elevated in NASH patients compared to healthy obese
5.71], Figure 1) after adjustments for age, sex, body mass index and patients ( p <0.001) with a predictive accuracy of AUROC 0.88
type 2 diabetes during a median follow-up of 18.1 years. However, no (steatosis activity score >2).
increased risk was found for patients with advanced fibrosis at Conclusion: Plasma [SMOC2] shows promise as a non-invasive
baseline (aHR 0.67, [95% CI = 0.13–3.43]). Compared to controls, biomarker for diagnosis of NASH. Linkage of plasma [SMOC2] to
NAFLD cases had a higher rate of developing cirrhosis and the aHSCs, moreover, may directly reflect key cellular changes associated
increased risk correlated to PNPLA3 and GCKR genotypes. Mortality with NASH progression.
was not affected by any genetic variant.

Figure 1: Kaplan-Meier estimate of cirrhosis and LRE-free time in patients

with NAFLD without advanced fibrosis at baseline. LRE = Liver related
events.

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POSTER PRESENTATIONS
FRI055 factors were indicated as important facilitating factors: ease of use
Clinicians’ perspectives on barriers and facilitators for the and quick measurement process, evidence showing better perform-
adoption of non-invasive liver tests: a mixed-method study ance compared to other available tests, local champions (clinicians
Yasaman Vali1, Roel Eijk2, Timothy Hicks3, Will Jones3, Jana Suklan3, with special interest in and knowledge about the new test), proper
Vlad Ratziu4, Adriaan G. Holleboom5, Miranda Langendam1, functional payment system and existence of resources in academic
Quentin Anstee6, Patrick Bossuyt1. 1Amsterdam UMC, University of hospitals.
Amsterdam, Department of Epidemiology and Data Science, Amsterdam, Conclusion: Adoption of new diagnostic NAFLD tests is a complex
Netherlands; 2Athena Institute, VU University Amsterdam, Faculty of process and can be promoted or restricted by several factors, such as
Science, Amsterdam, Netherlands; 3NIHR Newcastle In Vitro Diagnostics robust evidence, practical guidelines, a proper payment system, and
Co-Operative, Newcastle University, Newcastle upon Tyne, United local champions. As this study was restricted to clinicians, future
Kingdom; 4University Paris-Diderot, Assistance Publique-Hôpitaux de studies could explore other stakeholders’ perspectives necessary to
Paris, hôpital Beaujon, Paris, France; 5Amsterdam University Medical improve the adoption of new biomarker-based NITs into clinical
Centres, Department of Internal and Vascular Medicine, Amsterdam, practice.
Netherlands; 6Newcastle University, The Newcastle Liver Research
Group, Translational & Clinical Research Institute, Faculty of Medical FRI056
Sciences, Newcastle upon Tyne, United Kingdom Ectopic fat deposition in the liver and pancreas and the presence
Email: [email protected] of excess visceral adipose tissue significantly increase
hospitalisation risk following COVID-19
Background and aims: Multiple non-invasive tests (NITs) have been Tom Waddell1,2, Adriana Roca-Fernandez2, John McGonigle2,
developed to evaluate NAFLD patients. However, the availability of Arun Jandor2, Valentina Carapella2, Helena Thomaides-Brears2,
NITs varies from country to country, and little is known about their Andrea Dennis2, John Michael Brady2, Rajarshi Banerjee2. 1The
implementation and adoption in clinical practice. This study aimed to University of Oxford, Department of Engineering Science, Oxford, United
explore clinicians’ perspectives on barriers and facilitators that Kingdom; 2Perspectum Ltd, Oxford, United Kingdom
influence the adoption of NITs. Email: [email protected]
Method: This cross-sectional study was performed using an
exploratory mixed-methods approach. Twenty-seven clinicians Background and aims: In patients with COVID-19, obesity may
from different countries, with a wide age range (from 30 to 63), increase risk of hospitalisation, use of mechanical ventilation and
specialties, and years of experience, were purposefully sampled. All patient mortality. High liver fat, body mass index (BMI) and male sex
participants filled in a questionnaire; 16 of those participated in a are significant predictors of hospitalisation risk following COVID-19.
follow-up semi-structured interviews. Qualitative and quantitative However, BMI is a poor indicator of body fat distribution. Here, we
data were collected and summarized using the recently published studied ectopic fat accumulation within the liver and pancreas and
Non-adoption, Abandonment, Scale-up, Spread, and Sustainability body composition through multiparametric magnetic resonance
(NASSS) framework for new medical technologies in healthcare (mpMR) and compared participants with and without hospitalisation
organizations on seven domains: 1) the condition, 2) the technology, for COVID-19.
3) the value proposition, 4) the adopters, 5) the organization, 6) the Method: Participants with laboratory-confirmed or clinically sus-
wider system, and 7) embedding and adaptation over time (see pected SARS-CoV-2 infection were recruited to the COVERSCAN study
Figure 1). (NCT04369807; median time from initial symptoms = 177 days) and
underwent a multi-organ mpMR scan (CoverScan, Perspectum Ltd).
Measures of liver and pancreatic fat (PDFF), liver fibroinflammation
(cT1) and body composition [visceral adipose tissue (VAT), subcuta-
neous adipose tissue (SAT), skeletal muscle index (SMI)] were
analysed. Differences between participants hospitalised (n = 59)
and not hospitalised (n = 348) for COVID-19 were assessed using
Wilcoxon signed-rank tests. Univariate and multivariate analyses
were performed on all biomarkers to assess the hospitalisation risk.
Data presented are median values.
Results: Approximately 6-months after initial symptoms, partici-
pants hospitalised following COVID-19 had significantly elevated
pancreatic fat (3.8% vs 2.8%, p < 0.01), liver fat (3.8% vs 2.4%, p < 0.01)
and liver cT1 (735 ms vs 706 ms, p < 0.01) compared to those who
convalesced at home. Though hospitalised participants had a
significantly elevated BMI (27 kg/m2 vs 25 kg/m2, p = 0.014), it was
VAT, but not SAT, that was significantly elevated (132 cm2 vs 86 cm2, p
< 0.01). Univariate analysis revealed that male sex, advanced age and
elevated BMI, VAT, pancreatic fat, liver fat, and liver cT1 were all
significantly predictive of hospitalisation following COVID-19. In
multivariate analysis, only age remained significantly predictive of
hospitalisation. In hospitalised people with obesity (≥30 kg/m2), VAT,
Figure: NASSS (Non-adoption, Abandonments, Scale-Up, Spread, and liver cT1 and liver fat, but not BMI nor pancreatic fat, remained
Sustainability) framework and the main barriers (−) and facilitators (+) of significantly elevated [VAT: 220 cm2 vs 152 cm2, p = 0.01 (Figure 1);
NAFLD tests’ adoption in each domain. liver fat: 9.9% vs 4.2%, p = 0.003; liver cT1: 782 ms vs 742 ms, p =
0.012].
Results: Several influencing factors were reported in different
domains of the NASSS framework (see Figure 1). Among those,
insufficient knowledge and limited awareness, impractical practice
guidelines not yet built upon robust evidence for specific patient
populations and care settings, need for extra training to perform the
tests, difficult interpretation, and absence of sufficient reimburse-
ment systems were perceived as the most important barriers. Other

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 POSTER PRESENTATIONS
DA score plot, two metabolomics profiles were identified, signifi-
cantly different, in the two groups (R2 = 0.98, p < 0.001). The
metabolites profiles are presented in figure 1. By comparing PAT
scores of patients with simple steatosis (NAFL) (n:61, 19 with ED),
NASH (n:29, 12 with ED), and NASH-cirrhosis (n:17, 9 with ED) no
significant difference was observed ( p = 0.34), suggesting that CVD
risk is not associated with the degree of liver disease. Moreover, the
clinical and genetic parameters associated to ED were type 2 diabetes,
MS and BMI (directly) and TM6SF2 dominant model (CC + CT)
(inversely) at the univariate and only MS at a multivariate analysis.

Conclusion: mpMR revealed significantly elevated visceral and

ectopic fat deposition within the liver and pancreas in hospitalised
participants following COVID-19. In obese participants, BMI was not
significantly different in hospitalised, and non-hospitalised patients,
whereas visceral fat, liver fibroinflammation and liver fat were
significantly elevated. Our work highlights body fat distribution an
important consideration for COVID-19 risk profiling, which cannot be
sufficiently evaluated based on BMI alone.
Figure: Metabolomic profiles of NAFLD patients with and without ED.
Panel A: Impaired Metabolites. Panel B Volcano plot of impaired
FRI057
metabolites.
Genomic and metabolomic profiles and their correlations with
preclinical signs of endothelial dysfunction measured by Conclusion: NAFLD patients with and without ED exhibit significant
peripheral arterial tonometry in non-alcoholic fatty liver disease differences in their metabolomics profiles, demonstrating that they
Mario Masarone1, Jacopo Troisi2,3, Benedetta Maria Motta1, could be a useful early diagnostic tool for assessing CVD risk and
Martina Lombardi2,3, Pietro Torre1, Roberta Sciorio1, Marco Aquino1, providing an in-depth understanding of its underlying mechanisms.
Marcello Persico1. 1University of Salerno, Internal Medicine and Among the NAFLD associated SNPs, only TM6SF2 mutation was
Hepatology Unit, Department of Medicine, Surgery and correlated to a reduced prevalence of ED, but the only independent
Odontostomatology “Scuola Medica Salernitana”, Baronissi (Salerno), factor for ED was MS presence.
Italy; 2Theoreo srl, Montecorvino Pugliano (Salerno), Italy; 3University of
Salerno, Department of Chemistry and Biology, “A. Zambelli”, Fisciano FRI058
(Salerno), Italy Determinants of liver stiffness measurements in patients with
Email: [email protected] NAFLD-an individual patient data meta-analysis
Ferenc Mozes1, Emmanuel Selvaraj2,3, Arjun Jayaswal3,
Background and aims: NAFLD is associated with insulin resistance,
Jerome Boursier4, Céline Fournier5, Elisabetta Bugianesi6,
metabolic syndrome (MS) and diabetes and it is an independent CVD
Ramy Younes7, Salvatore Petta8, Sanjiv Mahadeva9,
risk factor. Endothelial Dysfunction (ED) plays a central role in the
Wah-Kheong Chan9, Peter Eddowes10, Philip N. Newsome11,
pathogenesis of CVD. Preclinical ED can be detected by vascular
Gideon Hirschfield12, Vincent Wai-Sun Wong13,
reactivity studies, such as Peripheral Arterial Tonometry (PAT).
Victor de Lédinghen14, Jeremy Cobbold2, Won Kim15,
Genome Wide Studies (GWAS) identified Single Nucleotide
Myoung Seok Lee16, Cristophe Cassinotto17, Geraldine Ooi18,
Polymorphisms (SNPs) associated to NAFLD progression. Some of
Atsushi Nakajima19, Masato Yoneda19, Ming-Hua Zheng20,
them (ie TM6SF2) have been postulated to influence CVD risk. The use
Andreas Geier21, Theresa Tuthill22, M. Julia Brosnan22,
of specific biomarkers related to ED presence in NAFLD may allow an
Quentin Anstee23, Stephen Harrison3, Patrick Bossuyt24,
early identification of CVD risk and provide crucial insights into its
Michael Pavlides2,3. 1University of Oxford, Oxford Centre for Magnetic
pathophysiology. This could be addressed through untargeted
Resonance (OCMR), Oxford, United Kingdom; 2University of Oxford,
metabolomics and genomic approaches. Aims: to identify metabo-
Translational Gastroenterology Unit, Oxford, United Kingdom;
lomics signatures able to discriminate the presence of ED by 3
University of Oxford, Oxford Centre for Magnetic Resonance (OCMR),
combining data provided by metabolomics analyses with those
Oxford, United Kingdom; 4Universite d’Angers, Laboratoire HIFIH,
from PAT, and to correlate them with anthropometric, laboratory and
Angers, France; 5Echosens, Paris, France; 6University of Turin,
genomic profiles of NAFLD subjects.
Department of Medical Sciences, Turin, Italy; 7Boehringer Ingelheim,
Method: Serum was collected from 107 subjects with biopsy-proven
Ingelheim am Rhein, Germany; 8University of Palermo, Section of
NAFLD (55.9% NAFL; 26.6% NASH; 17.5% NASH-Cirrhosis) without
Gastroenterology and Hepatology, PROMISE, Palermo, Italy; 9University
clinically evident CVD. Metabolomics analysis was performed by
of Malaya, Gastroenterology and Hepatology Unit, Department of
mass spectrometry. The resulting profiles were correlated with PAT
Medicine, Faculty of Medicine, Malaysia; 10Nottingham University
scores, revealed by an EndoPAT-2000 device, and with genomic
Hospitals NHS Trust and University of Nottingham, National Institute for
profiles of 4 SNPs of NAFLD (PNAPL3; TM6SF2; GKR; MBOAT).
Health Research Nottingham Biomedical Research Centre, Nottingham,
Results: Class separation in metabolomics profiles between patients
United Kingdom; 11University Hospitals Birmingham NHS Foundation
with and without ED (EndoPAT cut-off = 0.51) was obtained through a
“Partial Least Square Discriminant Analysis” (PLS-DA), which was also
used to identify the discriminating metabolites. According to the PLS-

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POSTER PRESENTATIONS
Trust and the University of Birmingham, National Institute for Health Conclusion: Our data confirm that fibrosis is the main determinant of
Research Biomedical Research Centre , Birmingham, United Kingdom; LSM in patients with NAFLD, with BMI, GGT and AST explaining most
12
University Health Network, Toronto Centre for Liver Disease, Toronto, of the remaining variance. However, LSM was less dependent on
Canada; 13The Chinese University of Hong Kong, Department of Medicine fibrosis stage in younger patients-a result that deserves further
and Therapeutics, Hong Kong, Hong Kong; 14Bordeaux University exploration. Our findings should be taken into account when
Hospital, Centre d’Investigation de la Fibrose Hépatique, Hôpital Haut- interpreting LSM results from these patients.
Lévêque, Bordeaux, France; 15Seoul National University College of
Medicine, Division of Gastroenterology and Hepatology, Department of FRI059
Internal Medicine, Seoul, Korea, Rep. of South; 16Seoul National Knowledge of liver fibrosis stage among adults with non-
University College of Medicine, Department of Radiology, Seoul, Korea, alcoholic fatty liver disease/non-alcoholic steatohepatitis
Rep. of South; 17University Hospital of Montpellier, Department of improves adherence to life style changes
Diagnostic and Interventional Radiology, Saint-Eloi Hospital, Carrieri Patrizia1, Abbas Mourad1, Fabienne Marcellin2,
Montpellier, France; 18Monash University, Centre for Obesity Research José Luis Calleja Panero3, Camelia Protopopescu1, Jeffrey Lazarus4,5.
1
and Education, Department of Surgery, Melbourne, Australia; Aix Marseille Univ, Inserm, IRD, SESSTIM, Sciences Economiques &
19 Sociales de la Santé & Traitement de l’Information Médicale, ISSPAM,
Yokohama City University, Department of Gastroenterology and
Hepatology, Yokohama, Japan; 20The First Affiliated Hospital of Wenzhou Marseille, France; 2Aix Marseille Univ, Inserm, IRD, SESSTIM, Sciences
Medical University, NAFLD Research Center, Department of Hepatology, Economiques & Sociales de la Santé & Traitement de l’Information
Wenzhou, China; 21University of Wurzburg, Division of Hepatology, Médicale, ISSPAM, Marseille, France; 3Department of Gastroenterology,
Wurzburgh, Germany; 22Pfizer Inc, Internal Medicine Research Unit, Hospital Universitario Puerta de Hierro de Majadahonda, Madrid, Spain;
4
Cambridge, United States; 23Newcastle University, Translational and Barcelona Institute for Global Health (ISGlobal), Hospital Clínic,
Clinical Research Institute, Faculty of Medical Sciences, Newcastle upon University of Barcelona, Barcelona, Spain; 5University of Barcelona,
Tyne, United Kingdom; 24University of Amsterdam, Department of Faculty of Medicine, Barcelona, Spain
Epidemiology and Data Science, Amsterdam UMC, Amsterdam, Email: [email protected]
Netherlands Background and aims: Non-alcoholic fatty liver disease (NAFLD)
Email: [email protected]
continues to rise in many countries, paralleling the epidemic of
Background and aims: Liver stiffness measurements (LSM) per- obesity worldwide. NAFLD can evolve into non-alcoholic steatohe-
formed with FibroScan are used in the clinical assessment of patients patitis (NASH) depending on age, lifestyle, and metabolic risk factors.
with non-alcoholic fatty liver disease (NAFLD). Fibrosis is the main Both diseases are managed with lifestyle interventions, but unaware-
determinant of LSM, but the contribution from other determinants ness of liver disease severity may compromise adherence. An
and how they vary in patient subgroups is less well studied. Our aim international survey of people living with NAFLD/NASH was
was to describe the dependence of LSM on histological, demographic conducted for the first time to identify correlates of a lack of
and laboratory parameters. knowledge about fibrosis status, and to assess whether this
Method: Data sets including LSM, demographics, histology- and lab unawareness was associated with poor adherence to lifestyle
parameters were reported in 2768 patients. Parameters with changes.
correlation r >0.15 with LSM were selected as possible determinants Method: We recruited 1411 adults living with NAFLD/NASH in
of LSM in the entire patient group. Linear regression models were Canada, France, Germany, Italy, Spain, and the United Kingdom who
built by adding one predictor at a time to a base model including the were registered on the online patient community platform Carenity.
log-transformed LSM and fibrosis stages as indicator variables. Partial Weighted binary and multinomial logistic regressions were per-
R2 values were compared to evaluate the contribution of each formed to estimate the effect of explanatory variables on unaware-
variable in explaining the variability of log-transformed LSM. A ness of fibrosis stage and poor adherence to lifestyle changes,
separate analysis evaluated the interaction between age and fibrosis respectively, in univariable and multivariable analyses.
stage. Results: In the study group, men accounted for 54.1%, 15.5% of the
Results: NASH CRN fibrosis stage, lobular inflammation and participants had obesity, and 75.3% of NAFLD patients reported being
ballooning grades, age, aspartate aminotransferase (AST), platelet in an early fibrosis stage. Of the total, 59.2% were unaware of their
count (Plt), gamma-glutamyltransferase (GGT), BMI and presence of fibrosis stage, and 34.4% reported non-adherence to lifestyle changes.
T2DM correlated with LSM with r >0.15. Mean age was 51 years, mean After multiple adjustments (Figure 1), older people were found to be
BMI was 30 kg/m2, 41% of patients had T2DM. Fibrosis stage at more risk of not knowing their fibrosis stage. Individuals who were
explained most of the variance (R2 = 0.411) in log-transformed LSM, aware of their fibrosis stage were more likely to have discussed their
followed by BMI ( partial R2 = 0.051), GGT ( partial R2 = 0.023), and AST liver tests with their physicians throughout the previous year (AOR =
( partial R2 = 0.022) (see Table). Furthermore, including an interaction 0.24; 95%CI: 0.16–0.36), and to have been diagnosed throughout the 5
term between fibrosis stage and age explained log-transformed LSM years preceding the survey (AOR = 0.59; 95%CI: 0.38–0.91).
better than only considering the main effect of fibrosis stage (F- Individuals with a body mass index (BMI) ≥35 were over twice as
statistic = 3.171, p = 0.007). likely to not know their fibrosis stage (AOR = 2.26; 95%CI: 1.37–3.40).
Unawareness about fibrosis stage was significantly associated with
poor adherence to lifestyle changes (AOR = 1.70; 95%CI: 1.14–2.41).
Partial Individuals with obesity (BMI ≥30) had a threefold higher risk of
Model predictors R2 having poor adherence to lifestyle changes (AOR = 3.12; 95%CI: 1.74–
5.60). People reporting having received support from nurses and
Age 0.0018
BMI 0.0514 other health staff were more likely to be adherent to lifestyle changes
Plt 0.0068 (AOR = 0.37; 95%CI: 0.25–0.54).
AST 0.0221
GGT 0.0232
T2DM 0.0183
Ballooning grade 0.0119
Lobular inflammation grade 0.0132

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 POSTER PRESENTATIONS
19
Ruane Medical and Liver Health Institute, Los Angeles, CA, United
States; 20Bon Secours Mercy Health, Richmond, VA, United States;
21
Royal Prince Alfred Hospital and The University of Sydney, New South
Wales, Australia, Australia; 22Department of Medicine and Therapeutics,
The Chinese University of Hong Kong, Hong Kong, Hong Kong; 23NAFLD
Research Center, University of California at San Diego, La Jolla, CA, United
States
Email: [email protected]
Background and aims: The MAST Risk score is a noninvasive tool
that includes AST and MRI-based assessments of liver stiffness (LS) by
elastography (MRE) and steatosis by proton density fat fraction (MRI-
PDFF), for the identification of patients at risk of progressive NASH.
Our aims were to evaluate the effects of cilofexor (CILO) and
firsocostat (FIR) on MAST, and associations between treatment-
induced changes in MAST with histologic and noninvasive test (NIT)
responses in patients with advanced fibrosis due to NASH.
Method: NASH patients with histologically-confirmed, advanced
fibrosis (NASH CRN F3–F4) in the phase 2b ATLAS trial were treated
with regimens including CILO 30 mg (n = 40), FIR 20 mg (n = 40), CILO
+ FIR (n = 78), or placebo (n = 39), once daily for 48 weeks (W48).
Liver histology was evaluated by a central reader and a machine
learning (ML) approach (PathAI; Boston, MA). Endpoints included a
≥1-stage improvement in fibrosis without worsening of NASH
( primary endpoint [PE]), ≥2-pt reduction in NAFLD Activity Score
Conclusion: As fibrosis stage is becoming the main predictor of (NAS response [NAS-R]), and LS by vibration-controlled transient
NAFLD progression, patients’ knowledge of their fibrosis stage should elastography (VCTE) and ELF responses (ELF-R), defined as ≥25% and
become a priority to improve liver health. Given the seriousness of ≥0.5-unit reductions from baseline (BL) to W48, respectively.
NASH-related morbidity and mortality, improving patient-provider Changes in MAST were evaluated using Wilcoxon rank sum and
communication, especially for people with obesity, about liver Fisher’s exact tests.
fibrosis stage, its associated risks, and how to mitigate them, is Results: At BL, 56% of patients had cirrhosis (F4); median MAST Risk
essential. Training healthcare professionals and promoting patient score was higher in those with F4 vs F3 fibrosis (0.36 vs 0.24; p =
educational programs to support behavior changes should also be 0.003). Across study groups, BL MAST was significantly correlated
included in the liver health agenda. with ELF score (ρ = 0.53), LS by VCTE (ρ = 0.48), hepatic collagen
content (ρ = 0.37) and α-SMA expression by morphometry (ρ = 0.26),
FRI060 serum bile acids (ρ = 0.44), ML NASH CRN fibrosis score (ρ = 0.39), and
The MRI and AST (MAST) score is correlated with noninvasive and proportionate areas of NASH CRN F4 (ρ = 0.38), portal inflammation
histologic markers of fibrosis in patients with advanced fibrosis (ρ = 0.36), and hepatocellular ballooning (ρ = 0.27; all p < 0.05), but
due to NASH not proportionate areas of steatosis or lobular inflammation.
Mazen Noureddin1, Kris V. Kowdley2, Anita Kohli3, Aasim Sheikh4, Compared with placebo (median change in MAST from BL to W48:
Guy Neff5, Bal Raj Bhandari6, Nadege Gunn7, Stephen Caldwell8, −0.04), greater improvements in MAST at W48 were observed with
Zachary Goodman9, Dora Ding10, Lily Ma10, Jay Chuang10, FIR (−0.23; p = 0.03); differences with CILO (-0.06, p = 0.46) and CILO
Ryan Huss10, Chuhan Chung10, Robert Myers10, Keyur Patel11, +FIR (−0.05; p = 0.68) were not statistically significant. Compared to
Brian Borg12, Reem Ghalib13, John Poulos14, Ziad H. Younes15, non-responders, greater improvements in MAST from BL to W48
Magdy Elkhashab16, Tarek Hassanein17, Rajalakshmi Iyer18, were observed in patients with NAS-R and LS by VCTE-response, but
Peter Ruane19, Mitchell Shiffman20, Simone Strasser21, not ELF or PE response (Figure).
Vincent Wai-Sun Wong22, Rohit Loomba23, Naim Alkhouri3. 1Fatty
Liver Program, Cedars-Sinai Medical Center, Los Angeles, CA, United
States; 2Liver Institute Northwest, Seattle, WA, United States; 3Arizona
Liver Health, Chandler, AZ, United States; 4GI Specialists of Georgia,
Marietta, GA, United States; 5Covenant Research, LLC, Sarasota, FL,
United States; 6Delta Research Partners, LLC, Bastrop, LA, United States;
7
Pinnacle Clinical Research, Austin, TX, United States; 8University of
Virginia, Charlottesville, VA, United States; 9Inova Fairfax Hospital, Falls
Church, VA, United States; 10Gilead Sciences Inc., Foster City, CA, United
States; 11University of Toronto, Toronto, ON, Canada, Canada; 12Southern
Therapy and Advanced Research, Jackson, MS, United States; 13Texas
Clinical Research Institute, Arlington, TX, United States; 14Cumberland
Research Associates, Fayetteville, NC, United States; 15Gastro One,
Germantown, TN, United States; 16Toronto Liver Centre, Toronto, ON, Figure: Change in MAST Risk Score by Histologic and Noninvasive Test
Canada, Canada; 17Southern California Research Center, Coronado, CA, Response at Week 48.
United States; 18Iowa Digestive Disease Center, Clive, IA, United States;
Conclusion: In patients with advanced fibrosis due to NASH, the
MAST Risk score is correlated with noninvasive and histologic
measures of fibrosis and may be a useful marker of treatment
response beyond conventional histologic methods.

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POSTER PRESENTATIONS
FRI061 FRI062
Independent determinants of CAP values in healthy individuals Performance of liver-related clinical scores in the SAPHIR study
with dysmetabolism Lorenz Balcar1,2, Georg Semmler1,2,3, Stephan Zandanell1,
Cristiana Bianco1, Serena Pelusi1, Eleonora Giacopuzzi Grigoli2, David Niederseer4, Sophie Gensluckner1, Alexandra Feldman1,
Luigi Santoro1, Francesco Malvestiti1,3, Melissa Tomasi1, Ilaria Marini1, Christian Datz3, Bernhard Paulweber1, Elmar Aigner1. 1Paracelsus
Sara Margarita1, Rossana Carpani1, Daniele Prati1, Luca Valenti1,3. Medical University of Salzburg, First Department of Medicine, Salzburg,
1
Precision Medicine, Department of Transfusion Medicine and Austria; 2Medical University of Vienna, Division of Gastroenterology and
Hematology-Fondazione IRCCS Ca’ Granda Ospedale Maggiore Hepatology, Department of Internal Medicine III, Vienna, Austria;
Policlinico; 2Università degli Studi di Milano; 3Università degli Studi di 3
General Hospital Oberndorf, Department of Internal Medicine,
Milano, Department of Pathophysiology and Transplantation Oberndorf bei Salzburg, Austria; 4University Hospital Zurich,
Email: [email protected] Department of Cardiology, Zurich, Switzerland
Email: [email protected]
Background and aims: Controlled attenuation parameter (CAP)
values determined during vibration controlled transient elastography Background and aims: There are several established clinical scores
correlate with hepatic fat content and can non-invasively assess the for patients with chronic liver diseases; however, the prognostic
presence of fatty liver with moderate accuracy. Aim of the study was value of these scores in the general population is unclear. Therefore,
to examine the clinical and metabolic determinants of CAP in a cohort our study aimed to evaluate the value of liver-related risk-scores in a
of apparently healthy individuals with dysmetabolism. population-based cohort with a 20-year follow-up.
Method: We assessed CAP in 953 consecutive blood donors with ≥3 Method: We included participants from the SAPHIR study from the
dysmetbolism features (hypertension, hyperglicemia, overweight/ city of Salzburg, Austria. We calculated Cox regression models for (i)
obesity, low HDL/high tryglicerides), who participated in a primary overall mortality, (ii) malignancy-related-, (iii) major adverse
prevention program (LIVER-BIBLE cohort up to July 2021). CAP cardiovascular (CV)-, and (iv) composite CV events (minor/major
determinants were assessed by generalized linear models. adverse CV events).
Results: Mean age was 53.9 ± 6.3 yrs, BMI 28.5 ± 3.0 Kg/m2, 158 Results: Overall, 1646 patients were included (mean age 52 ± 6 years;
(16.6%) participants were females, 35 (3.7%) diabetics, 704 (73.9%) 63% male). Mean BMI was 27 ± 4 kg*m−2 and 15% of patients had
had hypertension and 383 (40.2%) dyslipidemia, 463 (48.6%) had metabolic syndrome (MetS) at baseline. Mean Framingham risk score
fatty liver (CAp >275 db/m), and 17 (1.8%) liver stiffness measurement (FRS) was 12 ± 4 points, indicating an intermediate risk for develop-
(LSM) ≥8 kPa. CAP correlated with LSM ( p < 10−16). CAP was ing CV diseases within 10 years. Median follow-up was 18.7 years
associated with older age ( p = 0.02), higher BMI, abdominal circum- (IQR: 15.4–20.5).
ference, glucose, insulin, ferritin ( p < 0.01 for all), and lower HDL ( p = In univariable analyses, APRI was associated with overall mortality
0.03). No consistent association with CRP, hypertension, diet or (hazard ratio [HR]: 5.01 [95% confidence interval (95%CI): 1.27–
lifestyle factors was detected, except for alcohol consumption ( p = 19.78)]; p = 0.021), as was FIB-4 (HR: 1.53 [95%CI: 1.18–1.99]; p =
0.003). At multivariable analysis (Table), abdominal circumference 0.002), the MetS (HR: 1.28 [95%CI: 1.11–1.49]; p < 0.001), the Forns-
was the main determinant of CAP ( p < 10−9), with insulin ( p < 10−6), (HR: 1.24 [95%CI: 1.08–1.42]; p = 0.002), and the FLI- (HR: 1.03 [95%
HbA1c ( p = 0.006), ferritin ( p = 0.04) and HDL levels ( p = 0.04). CI: 1.01–1.04]; p = 0.002), but not the BARD-score (HR: 1.16 [95%CI:
Independent determinants of CAP ≥275 dB/m were confirmed to be 0.97–1.38]; p = 0.097). The FLI-score (HR: 1.02 [95%CI: 1.01–1.03]; p =
abdominal circumference ( p < 10−5), insulin ( p = 0.0003), HDL, 0.006) and the MetS (HR: 1.17 [95%CI: 1.07–1.28]; p < 0.001) were
HbA1c, BMI and alcohol consumption ( p < 0.05 for all). Fatty liver univariably associated with malignant events. For major adverse CV
index predicted CAP ≥275 dB/m with low-moderate accuracy events, results were similar (FLI-score: HR: 1.03 [95%CI: 1.02–1.05]; p
(AUROC = 0.70), whereas ALT with low accuracy (AUROC = 0.60). In < 0.001; MetS: HR: 1.50 [95%CI: 1.31–1.73]; p < 0.001). Furthermore,
the subset of the latest 352 enrolled participants for whom the the Forns- (HR: 1.13 [95%CI: 1.04–1.23]; p = 0.005), as well as the FLI-
information was available, we found an independent association score (HR: 1.03 [95%CI: 1.02–1.04]; p < 0.001) and the MetS (HR: 1.32
between CAP and lower TSH levels (estimate −5.06 ± 2.22, p = 0.02). [1.21–1.43]; p < 0.001) were associated with a combined CV endpoint.
In multivariable analyses including age, BMI, mean arterial pressure,
FRS, and respective scores significantly associated in univariable
analyses, none of the scores remained independently associated with
overall mortality and malignant outcomes. Interestingly, the MetS
remained independently associated with major adverse CV events
(aHR: 1.36 [95%CI: 1.11–1.65]; p = 0.003) and the FLI-score for
combined CV endpoints (aHR: 1.02 [1.01–1.04]; p = 0.010).
Conclusion: While specific liver-related scores (i.e., FIB-4, APRI) are
strongly associated with outcomes in liver diseased patients, their
prognostic value is limited in the general population. Most of the
scores of interest were univariably associated with overall mortality;
Figure: Independent predictors of CAP values in the LIVER-BIBLE cohort. however, these associations vanished when adjusting for other
F: female; BMI: body mass index; HbA1c: glycate hemoglobin; TSH: variables. Importantly, the MetS as well as the FLI-score showed
thyroid stimulating hormone; SE: standard error. independent associations with CV events, suggesting a strong
Conclusion: In healthy individuals with dysmetabolism, CAP values correlation of fatty liver disease and rate of CV outcomes in the
were most strongly associated with the severity of hyperinsulinemia general population.
and abdominal adiposity. The association between activation of the
pituitary-thyroid axis and fatty liver is being evaluated in the whole
updated cohort.

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 POSTER PRESENTATIONS
FRI063 patients with NAFLD enrolled in clinical trials and in patients seen in a
Correlations of 2D-Shear wave and transient elastography liver real-life hepatology clinic.
stiffness measurements in patients with non-alcoholic fatty liver Method: Data collected from two non-overlapping samples of NAFLD
disease patients were used in this study (Group 1: real world hepatology
Dimitrios Karagiannakis1, Georgios Markakis1, Dimitra Lakiotaki1, practice, Group 2: enrollees from NASH Clinical trials). Both groups
Elisavet Michailidou1, Paraskevi Fytili1, Evangelos Cholongitas1, were matched according to presence of advanced fibrosis. Clinical
Ioannis Vlachogiannakos1, George Papatheodoridis1. 1Laiko General data, liver biopsy, and serum were collected for each included patient.
Hospital, Medical School, National and Kapodistrian University of ELF scores were calculated using an ADVIA Centaur XP analyzer. Liver
Athens, Greece biopsies were scored by a single hepatopathologist 0–4 using CRN
Email: [email protected] criteria; advanced fibrosis was defined as stage 3 (bridging fibrosis) or
4 (compensated cirrhosis). Performance of ELF for predicting
Background and aim: The performance of transient elastography advanced fibrosis was assessed in both groups.
(TE) has been widely assessed, while 2D-shear wave elastography Results: A total of 1, 379 subjects were available [Group 1: N = 467,
(2D-SWE) is a newer elastographic technique. The aim of the study age 48 ± 13 years old, 31% male, 35% type 2 diabetes, 24.6% advanced
was to investigate if liver stiffness measurements (LSM) of 2D-SWE fibrosis, mean (SD) ELF score was 9.0 ± 1.2; based on published
are correlated with LSM of TE for the evaluation of liver fibrosis in cutoffs, 78% had ELF <9.8 (low-risk), 17% 9.8 ≤ ELF <11.3 (moderate
patients with non-alcoholic fatty liver disease (NAFLD). risk), and 5% ELF ≥11.3 (high-risk), Group 2: N = 912, age 54 ± 11 years
Methods: In total, 552 consecutive patients with NAFLD were old, 43% male, 55% type 2 diabetes, 26% advanced fibrosis; mean (SD)
included [median age: 55 (range:19–87) years, Males: 288 (52.5%)]. ELF 9.6 ± 1.0 including 61% with low-risk, 33% moderate risk, 6% high-
Mean waist circumference was 105 ± 13 cm and median BMI 28.7 risk ELF scores]. Area under the ROC curve (AUC) (95%) for predicting
(17.3–79.7) kg/m2 [Normal BMI (<25): 94 (17%), Overweight (BMI = advanced fibrosis by ELF was 0.81 (0.77–0.85) in Group 1. The cutoff
25–30): 94 (17%), Obese (ΒΜΙ > 30): 192 (34.8%)]. Liver fibrosis was of ELF ≥9.8 returned sensitivity 57% (47%–66%), specificity 89% (86%–
assessed by TE (M/XL probe) and 2D-SWE at the same time. CAP was 92%), positive predictive value (PPV) 63% (54%–70%), negative
performed for the estimation of the degree of liver steatosis. predictive value (NPV) 86% (83%–89%); in addition, the cut-off of
Results: Median LSM of TE was 5.5 (2.8–75) kPa and of 2D-SWE 62 ELF ≥11.3 returned specificity 99% (98%–100%), sensitivity 19% (12%–
(3.7–46.2) kPa. TE (and CAP) and 2D-SWE were not feasible in 18 28%), PPV 88% (69%–96%), NPV 79% (77%–80%). In Group 2, ELF had
(3.3%) and 26 (4.7%) patients respectively. Mean CAP value was 290 ± AUC (95% CI) = 0.80 (0.77–0.82) for predicting advanced fibrosis
54 db/m. One hundred and twenty eight patients (23.2%) had mild which was identical to that seen in Group 1. The cutoff of ELF ≥9.8
steatosis (CAP < 250 db/m) and 406 (73.6%) had moderate/severe returned sensitivity 74% (68%–79%), specificity 74% (70%–77%),
steatosis (CAP≥250 db/m). LSMs by TE and 2D-SWE were correlated positive predictive value (PPV) 50% (45%–55%), negative predictive
in normal BMI (r: 0.774; p < 0.001), overweight (r:0.774; p < 0.001) value (NPV) 89% (86%–91%); in addition, the cut-off of ELF ≥11.3
and obese (r: 0.75; p < 0.001) patients, as well as in patients with CAP returned specificity 98% (97%–99%), sensitivity 17% (12%–22%), PPV
≤250 db/m (r = 0.63; p < 0.001) and CAp >250 db/m (r = 0.743; p < 77% (66%–89%), NPV 77% (74%–80%).
0.001). According to TE measurements, patients were sub-classified Conclusion: The non-invasive serum-based ELF test performs well in
to those without moderate fibrosis (F0–F1; LSM by TE <7 kPa; n = 388 identifying high risk NAFLD patients in both real-life and clinical trial
or 70.3%), moderate/severe fibrosis (F2/F3; LSM:7–13 kPa; n = 117/ settings.
19.3%) and cirrhosis (F4; LSM>13 kPa; n = 57/10.3%). A significant
correlation between TE and 2D-SWE was found in all these subgroups FRI065
(r:0.458; r:0.624; r:0.696, respectively; all p < 0.001). The accuracy of Machine learning using simple non-invasive tests of fibrosis and
2D-SWE for detecting patients with moderate/severe fibrosis B-mode ultrasound for the prediction of adverse liver-related
diagnosed by TE was 89.7% (LSM cut-off 6.87 kPa: 87% sensitivity, outcomes in NAFLD
81.2% specificity for discrimination between moderate/severe (F2/F3) Heather M. Kosick1,2, Chris McIntosh3,4, Mina Fakhriyehasl3,
and no moderate fibrosis (F0–F1). The accuracy of 2D-SWE for Chinmay Bera5, Oyedele Adeyi6, Kartik Jhaveri3, Keyur Patel5.
diagnosing patients with cirrhosis diagnosed by TE was 99.1% (LSM 1
University of Toronto, Toronto, Canada; 2University Health Network,
cut-off 12.16 kPa: 90.4% sensitivity, 95.9% specificity). Toronto, Canada; 3University Health Network, Joint Department of
Conclusion: LSMs by 2D-SWE correlate with those of TE and Medical Imaging, Toronto, Canada; 4University Health Network, Peter
therefore 2D-SWE can reliably substitute TE in the evaluation of Munk Cardiac Centre and Joint Department of Medical Imaging, Canada;
liver fibrosis in patients with NAFLD. Similar LSM cut-off values of TE 5
University Health Network, Gastroenterology & Hepatology, Toronto,
and 2d-SWE can be applied in order to classify NAFLD patients into Canada; 6University of Minnesota, Department of Laboratory Medicine
fibrosis stages. and Pathology, Minneapolis, United States
Email: [email protected]
FRI064
Performance of the Enhanced Liver Fibrosis (ELF) test in real Background and aims: Advanced fibrosis (F3–4) in non-alcoholic
world practice versus clinical trials of non-alcoholic fatty liver disease (NAFLD) increases the risk of adverse liver-related
steatohepatitis outcomes. Serum-based non-invasive tests (NIT) alone are still not
Maria Stepanova1,2,3,4, Sean Felix2,3, Thomas Jeffers2,3, yet able to reliably predict NAFLD outcomes. Our aims were to explore
Elena Younossi2,3, Brian Lam2,3, Linda Henry1,2,3,4, the role of machine learning (ML) algorithms based on simple NIT
Zobair Younossi1,2,3. 1Inova Health System, Medicine Service Line; combined with B-mode ultrasound (US), for prediction of adverse
2
Betty and Guy Beatty Center for Integrated Research, IHS; 3Inova Health liver-related outcomes.
System, Center for Liver Disease, Department of Medicine; 4Center for Method: Retrospective observational single center cohort study
Outcomes Research in Liver Disease which included NAFLD patients with biopsy between 2010–2018.
Email: [email protected] Demographics, anthropometric measurements, clinical outcomes,
NIT, including FIB-4 and NFS, and US data, including liver/spleen size,
Background and aims: The ELF score is calculated using three direct steatosis, and features of advanced liver disease, were collected. ML
markers of fibrosis [hyaluronic acid (HA), amino-terminal propeptide algorithms were generated using the random forest technique to
of type III collagen (PIIINP), tissue inhibitor of matrix metalloprotei- create predictive models for each clinical outcome, including hepatic
nase 1 (TIMP-1)]. In NAFLD, advanced stage of fibrosis is the most decompensation, hepatocellular carcinoma (HCC), liver transplant,
important predictor of long-term clinical outcomes. Our aim was to all-cause and liver-related mortality.
assess performance of ELF for identification of advanced fibrosis in

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POSTER PRESENTATIONS
Results: 389 NAFLD patients were included with F3–4 prevalence biopsy/endoscopy). 6/20 (30%) patients with advanced disease have
48.6%, 54.5% male, mean age 48.5±13.2 years, diabetes in 30.1%, and died- 2/20 liver related deaths (hepatocellular carcinoma (HCC) and
BMI 32.4 ± 7.0 kg/m2. Overall, 51 (13.1%) patients had an adverse liver- decompensated cirrhosis); 1 patient diagnosed with HCC was treated
related outcome over median 3.14 years, and included hepatic with curative transarterial chemoembolisation; 3 patients had
decompensation in 9.5%, HCC 4.1%, liver transplant 5.4%, mortality varices on OGD (2 started on carvedilol for primary prophylaxis);
2.6% and liver-related mortality 2.1%. AUC measures for the ML 12 remain under follow up. In all patients with LSM >8 kPa (n = 25): 8/
predictive models were: hepatic decompensation 0.958, HCC 0.770, 25 (32%) died (3/8 from COVID-19); 24% (6) LSM improved, 8% (2) LSM
liver transplant 0.931, all-cause mortality 0.831, and liver-related deteriorated; 32% (8/25) lost weight. No patients missed by the
mortality 0.859. ML feature importance for predictive variables was pathway presented with decompensated disease. Serial FIB-4 at
determined for each outcome. FIB-4, AST:ALT ratio, and age had the annual screening 2019–2021: 4 patients new raised Fib-4 scores-1
greatest feature importance for NIT and clinical variables respectively. DNA, 1 TE is awaited, 1 LSM <8 kPa (discharged), 1 advanced disease
US-based parameters did not have significant feature importance for (LSM 17.1 kPa).
liver-related outcomes compared to clinical or biochemical features. Conclusion: Incorporation of a two-tiered liver fibrosis assessment
into primary care annual diabetic screening significantly improves
identification of advanced liver disease and no patients have
presented with advanced disease out-with the pathway. It allows
for early detection and interventions against the complications
associated with advanced liver disease. Mortality in patients with
advanced liver disease remains high. Referrals for TE and into
secondary care dramatically reduce after the initial year of case
finding.

FRI067
New scoring system using MRI with AST for the non-invasive
identification of patients with non-alcoholic steatohepatitis with
significant activity and fibrosis
Kento Imajo1,2, Yusuke Saigusa3, Takashi Kobayashi1, Koki Nagai2,
Shinya Nishida2, Nobuyoshi Kawamura2, Michihiro Iwaki1,
Yasushi Honda1, Takaomi Kessoku1, Yuji Ogawa4, Hiroyuki Kirikoshi5,
Figure: Feature Importance Box Plot for Machine Learning Algorithm
Prediction of Hepatic Decompensation. Satoshi Yasuda6, Hidenori Toyoda6, Hideki Hayashi7, Hiroyoshi Doi2,
Shigehiro Kokubu2, Daisuke Utsunomiya8, Hirokazu Takahashi9,
Conclusion: ML models based on readily available clinical, biochem- Shinichi Aishima10, Satoru Saito1, Masato Yoneda1, Atsushi Nakajima1.
1
ical, and US-based variables were able to accurately predict adverse Yokohama City University Graduate School of Medicine, Department of
liver-related outcomes in a tertiary cohort of biopsy-proven NAFLD Gastroenterology and Hepatology, Yokohama, Japan; 2Shin-yurigaoka
patients. Age, AST:ALT ratio, and FIB-4, but not US-based parameters, General Hospital, Department of Gastroenterology, Kawasaki, Japan;
3
contributed significantly to ML predictive models for clinical Yokohama City University Graduate School of Medicine, Department of
outcomes. Biostatistics, Yokohama, Japan; 4National Hospital Organization
Yokohama Medical Center, Department of Gastroenterology, Yokohama;
FRI066 5
Yokohama City University Hospital, Department of Clinical Laboratory,
Incorporating a two-tiered liver fibrosis assessment into annual Yokohama, Japan; 6Ogaki Municipal Hospital, Department of
diabetes review in primary care-3 year follow up study Gastroenterology and Hepatology, Ogaki, Japan; 7Gifu City Hospital,
Rajan Bhandari1, Dina Mansour1. 1Q E hospital Gateshead, United Department of Gastroenterology and Hepatology, Japan; 8Yokohama City
Kingdom University Graduate School of Medicine, Department of Radiology,
Email: [email protected] Yokohama, Japan; 9Saga University, Division of Metabolism and
Background and aims: We previously presented the outcome of a Endocrinology, Saga, Japan; 10Saga University, Department of Pathology
pathway incorporating 2-tiered fibrosis assessment into annual & Microbiology, Saga, Japan
diabetic reviews in primary care. This 3 year follow up study looks at Email: [email protected]
Outcomes in patients referred into secondary care with moderate- Background and aims: Clinical trials enroll patients with elevated
advanced fibrosis non-alcoholic fatty liver disease (NAFLD) activity score (NAS≥4) and
Ongoing service delivery requirements after the first year of case significant fibrosis (F≥2); however, screening failure rates are often
finding high following biopsy. We aimed to develop a new score to identify
Effectiveness of the pathway in detecting patients with advanced non-alcoholic steatohepatitis (NASH) with NAS≥4 and F≥2 using
disease, by looking at the number of patients missed in the pathway magnetic resonance imaging (MRI).
presenting with advanced disease. Method: We undertook a prospective primary study of 176 patients
Method: All patients aged >35 years with T2DM attending annual and a retrospective validation study of 169 patients with liver biopsy
review at two primary care practices in North East England between proven NAFLD at three liver centers. Liver stiffness measurement
April 2018 and September 2019 (n = 467) had a Fib-4 requested, (LSM) by magnetic resonance elastography (MRE), proton density fat
followed by transient elastography (TE) if the Fib-4 was above the fraction (PDFF) measured by MRI, and aspartate aminotransferase
high sensitivity threshold. Those with a liver stiffness >8 kPa were (AST) were combined to develop a simple index (MRI with AST;
reviewed in secondary care. This pathway was continued in both MRAST score) for NASH with NAS≥4 and F≥2, as in FibroScan-AST
practices after the end of the initial study period. We reviewed the (FAST) score (One-step strategy).
outcomes of all patients referred to secondary care; the number of Results: MRAST score was generally equivalent to FAST (an area under
patients referred in the subsequent years with ongoing case-finding; the ROC curve (AUROC) = 0.780) for the detection of NASH with
and any patients missed from initial screening presenting with NAS≥4 and F≥2 with an AUROC of 0.756, with consistent results in
decompensated/symptomatic disease. the validation cohort (AUROC = 0.812 [MRAST] vs 0.779 [FAST]). We
Results: Of 467 patients in the initial study, 58 were referred for TE, then examined a two-step strategy, VCTE-LSM or MRE-LSM as first-
25 had a LSM>8 kPa and 20 had advanced disease (on imaging/ step, following CAP+AST or PDFF+AST as second-step. When used as

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 POSTER PRESENTATIONS
the rule-in criteria, the positive predictive value (PPV) was 71.6% for 3 weeks. H&E and MT-stained images were digitised and uploaded
FAST, 74.2% for MRAST, 82.6% for F-CAST, and 78.1% for M-PAST in onto a WSI platform, and the assisted reads included an additional
combined cohort. When used as the rule-out criteria, negative SHG image with qFibrosis stage and continuous values. 3 pathologists
predictive value (NPV) was 85.2% for FAST, 88.8% for MRAST, 85.3% for participated in this study, with experiences ranging from 5 to 40
F-CAST, and 87.3% for M-PAST. Indeterminate patients by the FAST, years.
MRAST, F-CAST and M-PAST were 48.5%, 49.9%, 32.5% and 28.1%, Results: The qFibrosis AI tool has been validated in studies, showing
respectively. >95% agreement. When assisted by the qFibrosis AI tool, the
concordance rate between pathologists improved to near perfect
agreement, with 0.82 linear weighted kappa, as compared to 0.72 for
the unassisted review. Mean overall percentage agreement between
pathologists improved from 89.38% to 92.93% ( p = 0.032). Mean
linear weighted kappa for intra-observer agreement is also higher,
achieving 0.91 kappa compared to 0.79 for unassisted reads. The
effect of AI assistance on fibrosis assessment consistency was
examined by reviewing the percentage of patients who remained
staged between F1-F3 after the initial reads. Using qFibrosis, 95.3% of
the patients were retained versus 82% for the unassisted review.

Table: Mean percentage agreement and weighted kappa (linear) for

assisted and unassisted reads.
Unassisted Assisted
Inter-observer Mean Percentage Agreement 89.38% 92.92%
Mean Weighted Kappa (Linear) 0.7157 0.8163
Intra-observer Mean Percentage Agreement 92.08% 96.46%
Mean Weighted Kappa (Linear) 0.7861 0.9081

Conclusion: qFibrosis as an AI assistive tool can improve inter-

pathologist weighted kappa to near perfect agreement with 93%
agreement and 95% retention rate. qFibrosis has been well validated
Conclusion: MRAST has equal diagnostic accuracy with FAST for and enable pathologists with varying experience to establish similar
NASH with NAS≥4 and F≥2. In addition, our results supported the performance in fibrosis evaluation. This has important implications
higher utility of a two-step strategy using F-CAST and M-PAST over in the development of drugs for NASH treatment.
one-step method (FAST and MRAST) for detecting NASH with NAS>4
+F > 2. FRI069
PRO-C3 based sequential algorithm can screen high-risk NASH
FRI068
and severe fibrosis in asian NAFLD population
Impact of artificial intelligence assistive tool on the
histopathologic review of fibrosis in non-alcoholic steatohepatitis Liang-Jie Tang1, Gang Li1, Mohammed Eslam2, Pei-Wu Zhu3,
patients Sui-Dan Chen4, Howard Ho-Wai Leung5, Ou-Yang Huang1,
Grace Lai-Hung Wong6,7, Yu-Jie Zhou8, Morten Karsdal9,
Aileen Wee1, Wei Qiang Leow2, Gwyneth Soon3, Elaine Chng4,
Diana Leeming9, Chris Byrne10, Giovanni Targher11, Jacob George2,
Dean Tai4, Yayun Ren4, Jia Ling Chong4, Yee Chen Ng4, Feng Liu5,
Vincent Wai-Sun Wong6,7, Ming-Hua Zheng1,12,13. 1The First Affiliated
Lai Wei6, Arun Sanyal7. 1Department of Pathology, Yong Loo Lin School of
Hospital of Wenzhou Medical University, NAFLD Research Center,
Medicine, National University of Singapore, Singapore; 2Department of
Department of Hepatology, Wenzhou, China; 2Westmead Hospital,
Anatomical Pathology, Singapore General Hospital, Singapore and Duke-
Westmead, and University of Sydney, Storr Liver Centre, Westmead
NUS Medical School, Singapore; 3Department of Pathology, National
Institute for Medical Research, Sydney, Australia; 3The First Affiliated
University Hospital, Singapore; 4HistoIndex Pte. Ltd., Singapore; 5Peking
Hospital of Wenzhou Medical University, Department of Laboratory
University People’s Hospital, Peking University Hepatology Institute,
Medicine, Wenzhou, China; 4The First Affiliated Hospital of Wenzhou
Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver
Medical University, Department of Pathology, Wenzhou, China; 5The
Diseases, Beijing, China; 6Hepatopancreatobiliary Center, Beijing
Chinese University of Hong Kong, Department of Anatomical and Cellular
Tsinghua Changgung Hospital, Tsinghua University, Beijing, China;
7 Pathology, Hong Kong, China; 6The Chinese University of Hong Kong,
Virginia Commonwealth University, Richmond, Virginia, USA
Department of Medicine and Therapeutics, Hong Kong, China; 7The
Email: [email protected]
Chinese University of Hong Kong, State Key Laboratory of Digestive
Background and aims: Inter-observer variability for categorical Disease, Hong Kong, China; 8Shanghai Jiao Tong University, Division of
scores of liver fibrosis among pathologists ranges from fair to Gastroenterology and Hepatology, Key Laboratory of Gastroenterology
moderate weighted kappa. Artificial intelligence (AI) and advances and Hepatology, Shanghai, China; 9Nordic Bioscience Biomarkers and
in digitised whole-slide images (WSI) facilitated the use of an AI- Research A/S, Herlev, Denmark; 10University Hospital Southampton,
assistive tool in pathology to improve histopathologic interpretation. Southampton General Hospital, Southampton National Institute for
Second harmonic generation/two-photon excitation fluorescence Health Research Biomedical Research Centre, Southampton, United
(SHG/TPEF) microscopy with AI can provide standardised evaluation. Kingdom; 11University and Azienda Ospedaliera Universitaria Integrata
This pilot study aims to explore the impact of AI tools on the overall of Verona, Section of Endocrinology, Diabetes and Metabolism,
agreement on fibrosis assessment between pathologists. Department of Medicine, Verona, Italy; 12Wenzhou Medical University,
Method: Unstained sections of liver biopsies from 50 non-treated Institute of Hepatology, Wenzhou, China; 13Key Laboratory of Diagnosis
patients with NASH (F0–F4) were taken from Peking University and Treatment for the Development of Chronic Liver Disease in Zhejiang
People’s Hospital and fibrosis was quantitated using SHG/TPEF Province, Wenzhou, China
microscopy (qFibrosis). To evaluate performance metrics for assisted Email: [email protected]
and unassisted reads, pathologists interpreted images in both
Background and aims: With non-alcoholic fatty liver disease
modalities in 2 sessions separated by a wash-out period of at least
(NAFLD) incidence and prevalence increasing, there is an urgent

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S431

POSTER PRESENTATIONS
need for non-invasive diagnostic tests to accurately screen high-risk FRI070
patients for liver inflammation and fibrosis. We evaluated the Real-world use of the FIB-4 calculator in primary care workflows
diagnostic performance of a new sequential algorithm for assessing to screen for advanced non-alcoholic fatty liver disease in a large
liver inflammation and fibrosis in NAFLD. US health system
Method: Data from two prospective Asian cohorts (327 biopsy- George Therapondos1, Anna Thomas2, Douglas T. Dieterich3,
confirmed patients with NAFLD [262 from Wenzhou, 65 from Hong Nigel Girgrah1, Philip Oravetz4. 1Ochsner Health, Multiorgan
Kong]) were studied. The area under the receiver operating Transplant, New Orleans, United States; 2NASHNET; 3Icahn School of
characteristic curve (AUROC) was used to test the diagnostic Medicine, Department of Medicine, New York, United States; 4Ochsner
performances of FAST, ADAPT, Agile 3+ and Agile 4, and for Health, Population Health, New Orleans, United States
comparison with other widely used non-invasive fibrosis scores. Email: [email protected]
Results: For progressive non-alcoholic steatohepatitis (NASH)
Background and aims: Non-alcoholic fatty liver disease (NAFLD)
patients (NASH + NAFLD activity score (NAS) ≥4 + F ≥2), the AUROC
of FAST score was 0.801 (95% confidence interval (CI): 0.739–0.863), affects about 25% of the global population. Early identification is
needed to appropriately direct patients to expected new therapies.
and the negative predictive value (NPV) was 0.951. For advanced
fibrosis (F3) and cirrhosis (F4), the AUROC of ADAPT, Agile 3+ and Ochsner Health is a large health system located in Louisiana, USA. The
FIB-4 calculation was integrated into the Ochsner Health electronic
Agile 4 were 0.879 (95% CI: 0.825–0.933), 0.805 (95% CI: 0.725–0.886)
health record (EHR) to better understand the burden of disease and
and 0.943 (95% CI: 0.892–0.994), and the NPV was 0.972 and 0.992,
respectively. A new sequential algorithm of ADAPT + Agile 4 combin- real-world implications of its use for NAFLD.
Method: The FIB-4 calculation was integrated within the EPIC EHR in
ation was better than other combinations (AUROC = 0.88, 95% CI:
0.824–0.935). This new combination algorithm approach can more Summer 2021 but is not yet available for use by primary care
providers. The data presented here are aggregated for exploratory
accurately screen out high-risk patients (i.e. the number of true
analyses to understand the impact of its use in primary care. The
positive (TP) groups has increased from 21%, 26%, and 31% to 32%),
while reducing the number of patients requiring liver biopsy following FIB-4 cut offs were used: if FIB-4 ≥2.67, then high-risk; if
FIB-4 from 1.0-2.67 and below 35 years or 1.3–2.67 and 35 to 65 years,
(including false positive (FP)), false negative (FN) and indeterminate
groups from 29% and 26% to 20%) (Figure). At the same time, in all or 2.0–2.67 and above 65 years, then medium risk; if FIB-4 <1.0 and
subgroup analyses (stratifying by sex, age, diabetes, NAS, BMI and below 35 years or <1.3 and 35 to 65 years or below 2.0 and over 65
years, then low risk. Data from 2016–2021 were aggregated and a
ALT), ADAPT + Agile 4 had good diagnostic performance.
provider-facing dashboard was generated to show patient demo-
graphics, comorbidities and FIB-4 scores.
Results: Out of 606, 906 patients, FIB-4 scores were able to be
calculated in 283, 880 (46.77%) of these patients. Average age was
52.4 years (60.23% male, 29.71% female). 53.05% identified as White/
Caucasian, 37.22% as African American/Black, 0.50% as Asian, and
3.50% as Hispanic or Latino. Prevalence of comorbidities was as
follows: obesity (43.45%), diabetes (26.01%), hypertension (24.16%),
heart disease (21.83%), hypercholesterolemia/hyperlipidemia
(16.21%), and renal disease (9.27%). 60.51% of the total population
had two or more comorbidities. Rates of comorbidities amongst the
50 lowest income zip codes in Louisiana were significantly higher
than the general population.
20, 013 patients were classified as high-risk for advanced liver
fibrosis, and 55, 265 were classified as medium risk. However, only
2.46% of the total population had been referred to hepatology. This
trend remained true across multiple subpopulations, including
patients with obesity (11.45% were medium/high-risk, 2.35% actually
referred), diabetes (9.75% were medium/high-risk, 3.25% referred),
heart disease (8.92% were medium/high-risk, 3.24% referred),
hypercholesterolemia/hyperlipidemia (6.57% were medium/high-
risk, 4.65% referred) and hypertension (9.39% were medium/high-
risk, 3.23% referred).
Conclusion: The gap in patients classified as medium and high-risk
to the actual rate of referral to hepatology suggests that many patients
at-risk for NAFLD are not being identified. This study identified 75,
278 patients who need further hepatology investigation. The
implications of this large number of NAFLD patients on the delivery
of liver services needs to be further investigated. Additional analysis
is needed to understand the impact of health disparities on NAFLD
patients.

Conclusion: The new sequential algorithm reliably assesses inflam-

mation and fibrosis in NAFLD patients, making it easier to exclude
low-risk patients and recommending high-risk patients for referral
treatment, while reducing the need for liver biopsy.

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 POSTER PRESENTATIONS
FRI071 chronic liver disease (cACLD) as 10 kPa and 15 kPa. Baveno seven
In silico identification and validation of plasma Ficolin-2 (FCN-2) suggested lowering the cACLD cut-off for NAFLD, though it is
as non-invasive biomarker of fibrosis in Non-alcoholic Fatty Liver supported by scanty data. We aimed to identify the LS cut-off for
Disease (NAFLD) cACLD in people with non-alcoholic fatty liver disease (NAFLD).
Pablo J. Giraudi1, Noel Salvoza1,2,3, Natalia Rosso1, Claudio Tiribelli1, Method: Included 330 patients with biopsy proved NAFLD (male 173
Deborah Bonazza4, Biagio Casagranda5, Nicolo de Manzini5,6, [52.4%]; age, median [interquartile range] 39 [33–47] years; body
Michela Giurucin5, Silvia Palmisano6,7. 1Fondazione Italiana Fegato mass index 32.6 (25.6–44.4) kg/m2); diabetes 102 (30.9%). All the LS
Onlus, Basovizza, Italy; 2University of Trieste, Trieste, Italy; 3Philippine measurements were done by a single operator, after overnight fasting
Council for Health Research and Development, Taguig, Philippines; using a standard measurement technique. All the LS measurements
4
Cattinara Hospital, Surgical Pathology Unit, Trieste, Italy; 5Cattinara were done within four weeks of liver biopsy.
Hospital, Surgical Clinic Division, Trieste, Italy; 6University of Trieste, Results: Liver biopsy revealed ≥F3 fibrosis, i.e., cACLD, in 70 (21.2%).
Department of Medical, Surgical and Health Sciences, Trieste, Italy; Measured LS were <10, 10 to <15 and ≥15 kPa in 230 (69.7%), 46
7 (13.9%) and 54 (16.4%), respectively. Baveno six criteria achieved a
Cattinara Hospital, Trieste, Italy
Email: [email protected] sensitivity (rule out) and specificity (rule-in) of 72.9% and 93% for
cACLD. The area under receiver operator characteristic (AUROC) curve
Background and aims: Non-alcoholic fatty liver disease (NAFLD)
of LSM for predicting cACLD was 0.862 (0.810–0.914). The LS <8, 8 to
covers a spectrum of diseases from simple steatosis (SS) to non-
13, and >13 kPa were present in 182 (55.2%), 82 (24.8%) and 66
alcoholic steatohepatitis (NASH), with a significant risk of progressing (20.0%), respectively. A new cut-off at 8 KPa and 13 KPa showed
to fibrosis. Fibrosis is considered as the most important predictive
sensitivity and specificity of 90% each. Univariate analysis identified
factor in the prognosis and mortality of NAFLD patients. Liver biopsy age, diabetes, and LS as independent predictors of cACLD, but platelet
is widely accepted as the gold standard for its diagnosis and reliable
count and albumin were not statistically significant. On multivariate
non-invasive methods are unavailable. We investigated the diagnos-
analysis, only LS (OR, 1.201, 95% CI, 1.139–1.267) and diabetes (OR,
tic performance of plasma Ficolin-2 (FCN-2), identified by an in silico 2.592, 95% CI, 1.298–5.179) were independent predictors of cACLD.
approach for the diagnosis of fibrosis in NAFLD.
The AUROC for the model with LSM and diabetes was 0.863
Method: For the in silico analysis, a biological network was built to compared with 0.862 for LSM alone (Delong test, P = 0.934). The
identify proteins related to fibrogenesis using molecular databases AUROC for predicting cACLD with BMI <25 kg/m2 and ≥25 kg/m2 was
and bioinformatic tools. Of the several markers identified, FCN-2 met
0.945 (0.886–1.000) and 0.844 (0.784–0.904), respectively.
the criteria as one of the most interesting candidates that follows the Conclusion:LS cut-offs set at <8 and >13 kPa perform better to
fibrotic process aside from being secreted in the plasma. For the
diagnose cACLD than the Baveno 6 criteria. The presence of diabetes
validation phase, 76 morbidly obese (MO) subjects with biopsy-
and body mass index needs to be accounted for while interpreting the
proven NAFLD were stratified according to fibrosis stage (minimal F0- cut-offs.
F1, n = 43; moderate-advanced F2-F3-F4, n = 33). Plasma FCN-2 levels
were determined by enzyme-linked immunoabsorbent assay and the FRI073
diagnostic performance was assessed. High prevalence of multi-organ steatosis and fibroinflammation,
Results: Although FCN-2 did not differentiate the steatosis stage of identified by multi-parametric magnetic resonance imaging, in
NAFLD, plasma FCN-2 levels significantly decreased when liver people with type 2 diabetes
damage progresses from minimal to moderate/advanced fibrosis ( p Nicole Eichert1, Karyna Gibbons2, Azlinda Hamid3,
< 0.0001). Interestingly, FCN-2 levels correlated inversely with Vashist Deelchand4, Jinny Woolgar1, Rob Suriano1,
lobular inflammation ( p = 0.0002) and portal inflammation ( p = Helena Thomaides-Brears1, Rajarshi Banerjee1, Graham Kemp5,
0.0007) histological features of NAFLD. When stratified according to Sarah Ali4, Gaya Thanabalasingham2, Daniel Cuthbertson3,5.
sex, the FCN-2 plasma levels are similar between males and females. 1
Perspectum Ltd., Oxford, United Kingdom; 2Oxford University Hospitals
The diagnostic performance of plasma FCN-2 in detecting F≥2 fibrosis NHS Foundation Trust, Oxford Centre for Diabetes, Endocrinology and
was higher than those of other current fibrosis’ indexes (FORNS, FIB- Metabolism; 3Liverpool University Hospitals NHS Foundation Trust,
4) (AUROC 0.76, 0.72, and 0.67, respectively). Furthermore, when University Hospital Aintree, United Kingdom; 4Royal Free London NHS
combined with other tests (GGT and APRI), the score index yield an Foundation Trust, United Kingdom; 5University of Liverpool, United
excellent discrimination power with AUC of 0.80 in identifying Kingdom
advanced fibrosis. Email: [email protected]
Conclusion: Plasma FCN-2 can be used as potential biomarker for
discriminating moderate/advanced from minimal fibrosis in the Background and aims: Type 2 diabetes (T2D) is a multi-system
context of NAFLD. Validation in larger cohorts will be required for its disease characterized by a high prevalence of micro- and macro-
clinical utility. The use of FCN-2 alone or in combination with other vascular complications, like diabetic nephropathy and cardiovascular
tests may provide an alternative to minimize the need for biopsies to disease, and co-morbidities, like metabolic-associated fatty liver
detect fibrosis in NAFLD patients. disease. These are often only detected at a late stage, particularly
when they become clinically manifest. Early detection provides a
FRI072 window to potentially prevent and reverse disease progression, and
A lower cut-off of liver stiffness measurement (8/13) kPa performs improve outcomes. The aim of this study was to provide compre-
better than Baveno 6 criteria for advanced chronic liver disease in hensive assessment of multi-organ health and pre-clinical detection
patients with non-alcoholic fatty liver disease of diabetes-related organ damage with a single, efficient, 30 min non-
Sagnik Biswas1, Manas Vaishnav1, Piyush Pathak1, Himanshu Narang1, contrast magnetic resonance imaging (MRI) scan in patients with
Shubham Mehta1, Amit Goel2, Shalimar1. 1All India Institute of Medical T2D.
Sciences, New Delhi, Gastroenterology and Human Nutrition, New Delhi, Method: Overall, 138 adults with T2D [62 yr (54–70); 60% male; BMI
India; 2Sanjay Gandhi Post Graduate Institute of Medical Sciences, of 31 kg/m2 (28–35); HBa1c 60 mmol/L (51–70); 92% on metformin,
Gastroenterology, Lucknow, India T2D duration 11 yr (6–11)] were recruited to the MODIFY study
Email: [email protected] (NCT04114682). MRI data were acquired to derive organ-specific
measures of size, fat deposition, fibroinflammation, body compos-
Background and aims: Patients with ≥F3 fibrosis are grouped as ition (visceral adipose tissue, VAT; subcutaneous adipose tissue, SAT;
compensated advanced chronic liver disease (cACLD). Baveno six
skeletal muscle index, SMI) and aortic distensibility (CoverScan®,
consensus recommended the rule in and out liver stiffness Perspectum Ltd.). Normative values of MRI metrics were based on 92
measurement (LSM) cut-offs for diagnosing compensated advanced

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POSTER PRESENTATIONS
healthy volunteers [44 yr (32–53); 66% male; BMI 23 kg/m2 (21–25)] applied. Soluble TREM2 in plasma was measured by quantitative
and published literature, and the prevalence of abnormalities for each immunoassay. Since patients with low fibrosis score are not eligible
organ was assessed using Fisher’s exact tests. Statistical significance for clinical trials, we excluded patients with LSM <8.0. At risk NASH
of co-prevalence was assessed by simulation assuming that values was defined as patients with non-alcoholic fatty liver disease
were independently binomially distributed. (NAFLD) activity score (NAS) ≥4.
Results: In this cohort of established T2D patients, characterised by Results: Plasma TREM2 levels were significantly elevated in the
abnormal body composition (high SAT and VAT, low SMI), there was a derivation cohort in at-risk NASH patients with NAS≥4 as compared
high prevalence of multi-organ abnormality (86% with at least 2 with NAS<4 subjects, with an area under the receiver operating
organs affected). There was evidence of fatty infiltration and/or characteristics curve (AUROC) 0.92 (95% CI: 0.84–0.99). Plasma
fibroinflammatory changes in the liver (72% of patients), co-occurring TREM2 level was 2.1-fold increased in at-risk NASH patients and a
with abnormality in pancreas (38%), spleen (44%), kidney (64%), and strong diagnostic accuracy was confirmed in the validation cohort
aorta (71%). High-risk non-alcoholic steatohepatitis (NASH) was with an AUROC 0.83 (95% CI: 0.77–0.89, p < 0.0001). TREM2 level was
significantly more prevalent in the obese ( p < 0.005). Prevalence of associated with histologic features i.e., steatosis, lobular inflamma-
low SMI and elevated pancreatic fat were associated with duration of tion, and ballooning ( p < 0.0001) but not fibrosis. Clinical cut-offs for
T2D ( p < 0.05). Aortic stiffness was significantly associated with rule-in and rule-out (90% sensitivity and 90% specificity) were settled
organ steatosis (p < 0.05, Figure). and TREM2 values <38 ng/ml was found to be the optimal rule-out
cut-off (sensitivity 90%, specificity 51%) whereas TREM2 level >65 ng/
ml was the optimal rule-in cut off for at-risk NASH (sensitivity 89.9%
and specificity 52%).

Figure: Left: Co-prevalence of organ abnormality in T2D patients with

liver abnormality. Right: Co-prevalence of all abnormalities; pairs with co-
prevalence exceeding the significance threshold for association indicated
by numeric values.

Conclusion: Elevated levels of fat and fibroinflammation were highly

prevalent in the liver, pancreas, spleen, and kidney with evidence of
atherosclerosis and sarcopenia in most patients with T2D. The use of
glucose-lowering therapies associated with weight loss, such as GLP-
1 receptor agonists and SGLT2 inhibitors, are likely to have a beneficial Conclusion: Plasma TREM2 is a promising novel blood-based single
effect on mobilising ectopic fat. biomarker that can rule out or rule in presence of NASH with high
accuracy.
FRI074
Plasma TREM2, a novel non-invasive biomarker for diagnosis of FRI075
NASH in NAFLD patients with elevated liver stiffness Unbiased clustering of exhaled breath profiles in metabolic
Charlotte Wernberg1,2, Vineesh Indira Chandran3, Mette Lauridsen2, dysfunction-associated fatty liver disease identifies a patient
Frederik Larsen4, Maria Kløjgaard Skytthe3, Camilla Dalby Hansen1, phenotype at higher risk of disease progression
Majken Siersbæk4, Tina Di Caterino5, Sönke Detlefsen5, Rohit Sinha1, Paul Brinkman2, Khalida Ann Lockman1, Alan Jaap3,
Yaseelan Palarasah3, Kim Ravnskjaer4, Lars Groentved4, Peter Hayes1, John Plevris1. 1Hepatology Laboratory and Centre of Liver
Søren Kragh Moestrup3, Maja Thiele1, Jonas Graversen3, and Digestive Diseases, The University of Edinburgh, Edinburgh, United
Aleksander Krag1. 1Odense University Hospital, Centre for Liver Kingdom; 2UMC Amsterdam, The Department of Respiratory Medicine,
Research, Department of Gastroenterology and Hepatology, Odense, Amsterdam, Netherlands; 3Edinburgh Centre for Endocrinology &
Denmark; 2University Hospital of South Denmark, Department of Diabetes, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
Gastroenterology and Hepatology, Esbjerg, Denmark; 3, Department of Email: [email protected]
Molecular Medicine, Odense C; 4University of Southern Denmark,
Department of Biochemistry and Molecular Biology, Odense, Denmark; Background and aims: Human breath contains numerous volatile
5
Odense University Hospital, Department of Clinical Pathology, Odense, compounds which reflect the metabolic activity. Electronic nose
Denmark (eNose) technology can distinguish metabolic dysfunction-asso-
Email: [email protected] ciated fatty liver disease (MAFLD) from healthy with reasonable
confidence [1, 2]. We hypothesised breath prints obtained from eNose
Background and aims: Non-invasive markers of non-alcoholic could identify patient subgroups at higher risk for progression within
steatohepatitis (NASH) is still an unmet clinical need, but also the MAFLD spectrum.
represent a key barrier in NASH clinical trials. Here we investigate the Method: The study was a prospective single-centre cohort study
diagnostic accuracy of soluble plasma Triggering Receptor Expressed (ClinicalTrials.gov: NCT02950610). eNose is a custom-made device
on Myeloid cells 2 ( plasma TREM2) as a circulating biomarker for made up of five-sensor arrays, each containing four sensors,
NASH in patients with NAFLD and elevated liver stiffness. previously validated in respiratory and liver disease [1, 3]. eNose on
Method: A cross-sectional design with a derivation (n = 48) and a the exhaled breath was performed on well characterised MAFLD
validation cohort (n = 170) among patient with suspected NAFLD, a patients (n = 60)-Child’s A MAFLD cirrhotics (n = 30) and non-
valid liver biopsy and liver stiffness measure (LSM) >7.9 kPa, was

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 POSTER PRESENTATIONS
cirrhotic MAFLD (n = 30), previously described [1]. Data were associated with early liver injury, repair mechanisms and pericellular
analysed using R studio (v 2.3.2) and SPSS 21. An unbiased machine fibrosis. The aim of this study was to investigate changes in
learning clustering technique was applied. First hierarchical ward biomarkers targeting two distinct epitopes reflecting BM remodeling
clustering, combined with similarity profile analysis, was used to of type IV collagen (PRO-C4 and C4M) after bariatric surgery (BS) as
assess the number of significant cluster groups. Between-cluster well as in relation to baseline liver histology.
comparisons and Games-Howell post hoc analyses of clinical Method: 60 weight stable patients with severe obesity (BMI >35 kg/
variables at baseline were performed using the Kruskal-Wallis test m2) were examined at baseline and 12 months after BS-induced
for continuous data and the chi-square test for categorical data. weight loss. Liver biopsies were performed during BS. Serological
Results: Data reduction to 3 principal components (PCs) explained levels of PRO-C4 and C4M were measured using competitive ELISAs
97.8% of the total variance. Three groups of patients with MAFLD and change from baseline to 12-months follow-up were evaluated
disease were delineated solely based on their exhaled breath profiles. using a linear mixed effect model adjusted for type of surgery. Linear
Three clusters were identified; cluster 1 consists of 23 patients, regression models adjusted for age, sex, BMI and type 2 diabetes were
cluster 2 consists of 24 patients, and cluster 3 consists of 13 patients. used to evaluate the association of PRO-C4 and C4M with hepatocyte
The clusters were comparable in clinical phenotyping. Cluster 2 was ballooning, steatosis, lobular inflammation and fibrosis at baseline.
identified as a higher risk group with significant differences in serum Results: The cohort consisted of 56.7% females with a mean age of 46
hyaluronic acid levels ( p = 0.001), endoscopic evidence for portal and BMI of 49.0 kg/m2. 66.7% of the patients were F2. Interestingly,
hypertension ( p = 0.003) and exhaled breath concentration of baseline levels of both PRO-C4 and C4M decreased with increasing
dimethyl sulphide ( p = 0.041) and D-limonene ( p = 0.015). hepatocyte ballooning ( p < 0.0001) and PRO-C4 decreased with
increasing lobular inflammation ( p = 0.022), while this association
was borderline significant for C4M ( p = 0.055). No significant
associations were observed for collagen type IV remodeling with
liver steatosis or fibrosis at baseline. Furthermore, median PRO-C4
and C4M levels decreased significantly from baseline to 12-months
post BS by 21% ( p = 0.01) and 14% ( p < 0.001), respectively.
Conclusion: Hepatocytes are embedded in the BM, and changes in
hepatocyte health is reflected by remodeling of the adjacent ECM.
This study shows that BM remodeling is associated with liver
histopathology. Consequently, serological biomarkers of type IV
collagen remodeling could be used as markers of treatment efficacy
in NAFLD patients.

FRI077
A re-appraisal of the diagnostic performance of ultrasonography
for fatty liver disease
Chul-min Lee1, Eileen Yoon2, Jonghyun Lee3, Mi Mi Kim1,
Bo-Kyeong Kang1, Dae Won Jun2, Hyunwoo Oh4, Hyo Young Lee4,
Sang Bong Ahn5, Joo Hyun Sohn6, Huiyul Park7. 1Hanyang University
College of Medicine, Department of Radiology, Seoul, Korea, Rep. of
South; 2Hanyang University College of Medicine, Department of
Conclusion: This study shows that unbiased clustering of exhaled Medicine, Seoul, Korea, Rep. of South; 3Hanyang University College of
breath profiles captured using eNose technology identifies three Engineering, Department of Medical and Digital Engineering, Seoul,
phenotypes within the MAFLD spectrum. One of the three clusters Korea, Rep. of South; 4Uijeongbu Eulji Medical Center, Department of
included most patients with more advanced liver disease. These Medicine, Gyeonggi-do, Korea, Rep. of South; 5Nowon Eulji Medical
results warrant prospective studies on the potential of exhaled breath Center, Eulji University School of Medicine, Department of Medicine,
fingerprinting using eNose technology as point-of-care diagnostics in Seoul, Korea, Rep. of South; 6Hanyang University Guri Hospital,
the surveillance of patients with established metabolic dysfunction- Department of Medicine, Gyeonggi-do, Korea, Rep. of South; 7Uijeongbu
associated fatty liver disease. Eulji Medical Center, Department of Family Medicine, Gyeonggi-do,
Korea, Rep. of South
FRI076 Email: [email protected]
The pericellular basement of the hepatocytes is highly affected by
Background and aims: Previous studies showed that ultrasonog-
bariatric surgery in obese patients with non-alcoholic fatty liver
raphy (USG) has high specificity but low sensitivity for diagnosing
disease
fatty liver. Especially, the diagnostic performance of USG for mild
Ida Lønsmann Lønsmann1,2, Pierre Bel Lassen3,4, Diana Leeming2, fatty is low. We tried to re-appraisal the diagnostic performance of
Morten Karsdal2, Mette Juul Nielsen2, Karine Clément3,4. 1University USG for fatty liver disease at this point.
of Southern Denmark, Faculty of Health Research, Odense, Denmark; Method: We performed a retrospective, multi-nation, multi-center,
2
Nordic Bioscience A/S, Biomarkers and Research, Herlev, Denmark; cross-sectional, and observational study. We included subjects who
3
Sorbonne Université, INSERM, Paris, France; 4Assistance Publique underwent both the USG and magnetic resonance proton density fat
Hôpitaux de Paris, Nutrition Department, Paris, France fraction (MR PDFF) within the six-month interval. The diagnostic
Email: [email protected] performance of USG for fatty liver was evaluated as MR PDFF
Background and aims: Bariatric surgery decreases the severity of reference standard using sensitivity, specificity, positive and negative
non-alcoholic fatty liver disease (NAFLD) in patients with severe predictive value (PPV and NPV), diagnostic accuracy, and area under
obesity by improving liver histology and liver function tests. the receiver operating characteristics curve (AUC).
Nevertheless, there is a need for non-invasive biomarkers for Results: We included a total of 5056 subjects in this study. The USG
monitoring treatment efficacy in NAFLD. The extracellular matrix showed a sensitivity of 89.1%, specificity of 81.0%, and AUC of 0.850 for
(ECM) of the liver is subject to major changes during disease diagnosing any fatty liver (MR PDFF ≥6.5%). Furthermore, the
progression. The ECM basement membrane (BM) consists of mainly sensitivity, specificity, and AUC of USG for diagnosing mild fatty
type IV collagen produced by hepatocytes. Changes in BM has been liver (6.5%≤MR PDFF ≤14%) were 83.4%, 81.0%, and 0.822,

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POSTER PRESENTATIONS
respectively. The mean hepatic fat contents on MR PDFF were Conclusion: Screening for fibrotic-NASH in T2D persons over the age
significantly different according to the USG fatty liver grading ( p < of 55 as well as younger patients (over 40 years) is cost effective in
0.05). There was acceptable inter-institution variability of USG for European countries. Given the increasing burden of NAFLD/NASH and
diagnosing fatty liver among six centers. the expected approved medications, we recommend screening
Conclusion: The USG showed good diagnostic performances for any patients with T2D for fibrotic-NASH in Europe.
fatty liver and mild fatty liver, higher than previously known.
FRI079
FRI078 Free Light Chains as a potential biomarker of inflammation and
Cost utility analysis for screening for fibrotic NASH in the type 2 fibrosis in non-alcoholic steatohepatitis
population from European countries Antonio Liguori1,2, Umberto Basile2,3, Cecilia Napodano2,3,
Mazen Noureddin1, Manuel Romero Gomez2,3, Calum Jones4, Lidia Tomasello1,2, Fabrizio Mancuso1,2, Luca Di Gialleonardo1,2,
Kristen Shea5, Douglas T. Dieterich6, Jörn Schattenberg7, Giuseppe Marrone1,2, Marco Biolato1,2, Antonio Gasbarrini1,2,
Emmanuel Tsochatzis8,9, Elisabetta Bugianesi10, Vlad Ratziu11. Gian Ludovico Rapaccini1,2, Antonio Grieco1,2, Luca Miele1,2.
1 1
Cedars-Sinai Medical Center, Division of Digestive and Liver Diseases, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Dipartimento
Department of Medicine, Los Angeles, United States; 2Virgen del Rocío Scienze Mediche e Chirurgiche, Roma, Italy; 2Università Cattolica del
University Hospital, Digestive Diseases Department, Seville, Spain; Sacro Cuore, Roma, Italy; 3Fondazione Policlinico Universitario A
3
University of Seville, Institute of Biomedicine of Seville, Seville, Spain; Gemelli, IRCCS, Dipartimento Scienze di laboratorio e infettivologiche,
4
Mtech Access, Bicester, Oxfordshire, United Kingdom; 5NASHNET, Roma, Italy
New York, United States; 6Icahn School of Medicine at Mount Sinai, Email: [email protected]
New York, United States; 7University Medical Centre Mainz, Department
Background and aims: Non-alcoholic fatty liver disease (NAFLD) is
of Medicine, Mainz, Germany; 8UCL Institute for Liver and Digestive
the most common chronic liver disease worldwide. Almost 20-30% of
Health, London, United Kingdom; 9Royal Free Hospital, London, United
NAFLD patient develop steatohepatitis (NASH) characterized by
Kingdom; 10University of Torino, Division of Gastroenterology,
hepatocyte ballooning, lobular inflammation and progressive fibro-
Department of Medical Sciences, Torino, Italy; 11Hospital Pitié
sis. Inflammation process in NASH is known to be associated with
Salpêtrier̀ e, Paris, France
overexpression of pro-inflammatory biomarkers (IL1-beta, IL6, TNF-
Email: [email protected]
alfa).
Background and aims: The American Association for the Study of Polyclonal free light chains (FLC) reflect B cell activation and could
Liver Disease does not recommend screening for non-steatohepatitis give insight into the activity of the adaptive immune system in a
(NASH) among patients with type 2 diabetes (T2DM) while the variety of inflammatory conditions. The aim of this study is to
European Association of the liver (EASL) recommends screenings. evaluate the potential role of FLC as biomarker of inflammation and
Both organizations have called for cost effective analysis (CEA) which fibrosis in NAFLD/NASH.
has been recently published from the US population. Our aim was to Method: We enrolled 187 patients with metabolic liver disease at
assess the value of screening for NASH with significant fibrosis Liver Outpatient clinic at Policlinico A. Gemelli: 48 with NAFLD, 85
(fibrotic NASH) in five separate European populations. with NASH and 54 with cirrhosis. Diagnosis of NASH was histologi-
Method: We performed cost-utility analyses of four separate fibrotic- cally assessed. Medical and pharmacological anamnesis, anthropo-
NASH screening strategies using third-party, public sector payer metric measurements and laboratory tests (FLC included, lambda and
perspectives for five European countries, each for two separate kappa) were obtained for all patients.
hypothetical populations initially aged 55 years with either T2DM Results: Total FLC (lambda + kappa) were significantly higher in
and fibrotic-NASH, or fibrotic-NASH and no T2DM, and compared it to patients with cirrhosis than in patients with NAFLD or NASH (125.2 vs
the strategy of not screening these populations for fibrotic-NASH. 32.7 mg/L p < 0.01). Total FLC, lambda and kappa were higher in NASH
Screening methods involved combinations of Fibrosis-4 (FIB-4) patients than in NAFLD although non significantly (respectively 34.5
followed by Fibroscan® or liver biopsy for detecting fibrotic NASH vs 32.4 mg/L p = 0.2, 15.0 vs 13.2 mg/L p = 0.2, 19.9 vs 19.1 mg/L p =
indicated per recent EASL guidelines. An incremental cost-effective- 0.8). In patients with NASH, total FLC are higher in patients with
ness ratio (ICER) of ≤50, 000 local currency units per incremental advanced fibrosis (F >2, 39.0 vs 30.3, p = 0.03). Total FLC are associated
quality-adjusted life year was considered cost-effective. to advanced fibrosis independently from age, sex, BMI and diabetes
Results: When screening T2DM+ fibrotic-NASH patients aged 55 (OR1.04, CI 1.00-1.08, p = 0.04).
years first with FIB-4 followed by Fibroscan®, and then treating Conclusion: In this study we highlight that FLC concentration is
detected fibrotic NASH patients with an intensive lifestyle interven- significantly higher in patients with cirrhosis than in patients with
tion, this is shown to be a cost-effective strategy in all of the country- NAFLD or NASH. In NASH patients, advanced fibrosis is associated
specific analyses when compared to not screening these patients with higher serum concentration of total FLC. Serum FLC may
(Figure 1). These outcomes hold steady both in the base case represent a useful tool in grading and staging non-alcoholic fatty liver
assessment and in the sensitivity analyses of the model. Screening disease.
approaches involving liver biopsy were found non cost-effective in all
studied countries. The results have not changed when we assessed
the analysis starting screening at age 40.

Figure: Base case results when screening T2DM+ Fibrotic NASH patients
aged 55 years

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 POSTER PRESENTATIONS
FRI080 Rapid changes in NITs were observed within a week of commencing
12-week very low calorie diet in NAFLD induces rapid VLCD. Significant weight-loss associated improvements in markers of
improvements in biomarkers of necro-apoptosis and fibrogenesis NASH-associated necrosis/apoptosis (CK18-M65), and some but not
of a magnitude comparable to those seen in phase 2 drug trials all markers of fibrogenesis (PIIINP, ELF) were present at week-12.
Jadine Scragg1,2,3,4, Ida Villesen5, Diana Leeming5, Olivier Govaere6, These were of a magnitude similar to those reported in Phase 2 drug
Guy Taylor1, Stuart Mcpherson2,6,7, Kate Hallsworth2,6,7, trials. Changes occurred too rapidly to reflect a drop in hepatic fibrosis
Morten Karsdal5, Quentin Anstee2,6,7. 1Newcastle University, stage, suggesting that NITs are sensitive to changes in disease activity
Population Health Sciences, Newcastle upon Tyne, United Kingdom; and fibrogenesis that precede fibrosis resolution.
2
Newcastle Upon Tyne Hospitals NHS Foundation, Newcastle NIHR
Biomedical Research Centre, Newcastle upon Tyne, United Kingdom; FRI081
3
University of Oxford, Nuffield Department of Primary Care Health Signature of circulating hepatic proteins detects fibrosing-
Sciences, Oxford, United Kingdom; 4University of Oxford, NIHR Oxford steatohepatitis in progressive non-alcoholic fatty liver disease
Biomedical Research Centre, Oxford, United Kingdom; 5Nordic Olivier Govaere1, Megan Hasoon2, Leigh Alexander3, Simon Cockell2,
Bioscience Biomarkers and Research A/S, Herlev, Denmark; 6Newcastle Dina Tiniakos1, Jerome Boursier4, Elisabetta Bugianesi5, Vlad Ratziu6,
University, Translational and Clinical Research Institute, Newcastle upon Ann K. Daly1, Quentin Anstee1. 1Newcastle University, Translational and
Tyne, United Kingdom; 7Newcastle Upon Tyne Hospitals NHS Foundation Clinical Research Institute, Faculty of Medical Sciences, United Kingdom;
2
Trust, Liver Unit, Newcastle upon Tyne, United Kingdom Newcastle University, Bioinformatics Support Unit, Faculty of Medical
Email: [email protected] Sciences, United Kingdom; 3SomaLogic, Inc., United States; 4Angers
University Hospital, Hepatology Department, France; 5University of
Background and aims: Nonalcoholic fatty liver disease (NAFLD) is Turin, Department of Medical Sciences, Division of Gastro-Hepatology, A.
associated with inflammation and hepatocellular death, leading to O. Città della Salute e della Scienza di Torino, Italy; 6Sorbonne University,
activation of fibroblasts and progressive hepatic fibrosis-the single Assistance Publique-Hôpitaux de Paris, Hôpital Pitié Salpêtrier̀ e, France
most important factor determining liver-related clinical outcomes Email: [email protected]
and mortality. A range of non-invasive biomarker tests (NITs) are used
in drug trials to measure biological response to therapy including Background and aims: Non-alcoholic fatty liver disease (NAFLD) is
routine biochemistry (ALT, AST), markers of necrosis/apoptosis considered as the hepatic manifestation of the metabolic syndrome
(CK18-M65), and fibrosis (ELF, PRO-C3, and Fibroscan (VCTE)). and changes in circulating blood proteins have been associated with
Although sustained weight loss >10% has been shown to improve advanced NAFLD. Yet, it is still unclear which proteins originate from
histological fibrosis, little is known about its acute effects on NITs. the liver and how these alter during disease progression.
Method: 26 non-cirrhotic NAFLD patients were prescribed a 12-week Method: The cohort comprised 256 patients from the European
very low calorie diet (VLCD) (800kcal/day). Fasted blood samples NAFLD Registry with histologically proven NAFLD identified at four
were taken at weeks 0, 1, 3, 5, 7, 9 and 12 and VCTE measured at weeks specialist centres. The histological semi-quantitative NASH CRN
0 and 12. Routine labs as well as hyaluronic acid (HA), TIMP-1, PIIINP, system was used to score the biopsies. 191 plasma and 65 serum
PRO-C3, PRO-C4, PRO-C5, CK18-M65 were serially measured and ELF, samples were processed for proteomics analysis using the
ADAPT and FIB4 scores calculated. Patients were stratified by weight SomaScan™ platform. In a subset of 51 cases, snap-frozen liver
loss at 12 weeks into <5%, 5–7% and >7% of initial body weight and NIT biopsies underwent high-throughput RNA sequencing (RNAseq).
change from baseline assessed. Integrative analysis of these data with publicly available single-cell
Results: After 12-weeks VLCD, 4 patients had lost <5%, 4 had lost 5– RNAseq data was used to identify cell of origin. Binary logistic
7% weight and 18 had lost >7% body weight. No significant difference modelling was implemented to predict disease activity.
in NIT values were evident between weight loss groups at baseline. Results: Comparing patients with advanced fibrosis (F3–4) to mild
Rapid reductions in multiple collagen biomarkers were apparent disease (F0–2) in the discovery cohort of 191 plasma samples
after a week of VLCD. At 12-weeks, significant reductions in ELF identified 156 differentially expressed proteins, while stratifying
(ANOVA p = 0.040, −5.3 ± 1.8% at >7% weight loss), driven by PIIINP based on a NAFLD Activity Score (NAS) ≥4 identified 79 proteins. Of
(ANOVA p = 0.004, −23.7 ± 3.9% at >7% weight loss), and CK18-M65 these, 34 proteins were common to both analyses, including
(ANOVA p = 0.023, −43.5 ± 7.6% at >7% weight loss) were seen in AKR1B10, APOF, THBS2 and TREM2. To determinate which proteins
patients who lost >7% weight. Similar trends were observed in ALT, originate from the liver, we performed a correlation analysis between
AST, PRO-C3, and ADAPT but no difference was seen in FIB4 or VCTE. plasma proteins identified by the F3-4/NAS≥4 analyses and mRNA
within 51 patients, finding 40 proteins/mRNAs reaching the signifi-
cance threshold. Deconvolution by single-cell RNAseq data indicated
the different hepatic cellular changes during disease progression,
such as AKR1B10, APOF and GDF15 to originate from epithelial cells,
ADAMTSL2 and THBS2 from fibroblasts and TREM2 from macro-
phages. Finally, to assess potential utility within a non-invasive
diagnostic pathway to detect fibrosing-steatohepatitis defined as the
presence of NASH, NAS≥4 and F≥2, we performed logistic regression
analysis. Backward elimination of variables identified a composite
model that could predict NASH+NAS≥4+F≥2 with an Area Under the
Curve of 0.878 based on markers including circulating ADAMTSL2,
AKR1B10, CFHR4 and TREM2. Performance of the model was
validated in a cohort of 65 serum samples with an AUC = 0.851
compared to 0.678 for the FIB4 score.
Conclusion: We showed that circulating proteomic changes reflect
grade of steatohepatitis and stage of fibrosis that may be used to
assess disease severity.

Conclusion: A 12-week VLCD intervention induced significant

weight loss of a level reported to reduce hepatic fibrosis if sustained.

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POSTER PRESENTATIONS
FRI082 subjects with NAFLD. Since metabolic dysfunction-associated fatty
Peripheral blood mononuclear cells mitochondrial copy number liver disease (MAFLD) has been proposed as a new category of fatty
and adenosine triphosphate inhibition test in non-alcoholic fatty liver disease, we aimed to compare the diagnostic performance of
liver disease FIB-4 and NFS in subjects with MAFLD and in various subgroups.
Eileen Yoon1, Dae Won Jun1, Sang Bong Ahn2, Huiyul Park3, Method: This study was designed as cross-sectional study. Data from
Hyo Young Lee4, Hyunwoo Oh4, Chul-min Lee5, Mi Mi Kim5, 6, 775 subjects who underwent magnetic resonance elastography
Bo-Kyeong Kang5, Joo Hyun Sohn6. 1Hanyang University College of (MRE) and abdominal ultrasonography at the same time during a
Medicine, Department of Medicine, Seoul, Korea, Rep. of South; 2Nowon health check-up at 13 various health check-up centers were
Eulji Medical Center, Eulji University School of Medicine, Department of retrospectively reviewed. Advanced fibrosis was defined as an MRE
Medicine, Seoul, Korea, Rep. of South; 3Uijeongbu Eulji Medical Center, value of ≥3.6 kPa.
Department of Family Medicine, Gyeonggi-do, Korea, Rep. of South; Results: The area under the receiver operating characteristic curves
4 (AUROCs) of FIB-4 and NFS for diagnosing advanced fibrosis were
Uijeongbu Eulji Medical Center, Department of Medicine, Gyeonggi-do,
Korea, Rep. of South; 5Hanyang University College of Medicine, similar in subjects with MAFLD. However, the AUROC of NFS was
Department of Radiology, Seoul, Korea, Rep. of South; 6Hanyang lower than that of FIB-4 in the diabetic subgroup of MAFLD (0.809 in
University Guri Hospital, Hanyang University College of Medicine, FIB-4 vs. 0.717 in NFS, p = 0.002). The performances of both FIB-4 and
Department of Medicine, Gyeonggi-do, Korea, Rep. of South NFS were poor in the subgroup of MAFLD with significant alcohol
Email: [email protected] intake.
Conclusion: The overall diagnostic performance of FIB-4 and NFS for
Background and aims: Non-alcoholic fatty liver disease (NAFLD) is diagnosing advanced fibrosis did not differ among subjects with
known to be associated with mitochondrial dysfunction. The purpose MAFLD. However, the performance of NFS was lower in the diabetes
of this study was to develop biomarkers for the assessment of subgroup of MAFLD. The diagnostic performance of FIB-4 was better
mitochondrial dysfunction in patients with NAFLD. for fibrosis in various subgroups of MAFLD.
Method: Mitochondrion-associated transcriptome analysis was
performed from the NAFLD and healthy control liver. Peripheral FRI084
blood mononuclear cells obtained from 88 patients with NAFLD and Assessing the applicability of non-invasive diagnostic tests (NITs)
healthy controls were used to measure mitochondrial DNA (mtDNA) in non-alcoholic fatty liver disease: an international qualitative
copy number. Mitochondrial inhibition substrate test (ATP assay) was study
performed in HepG2 cells using patients’ serum. Cellular ATP Maja Thiele1, Sophie Péloquin2, Luca Valenti3, Patrice Lazure4,
concentration was measured in patient serum was applied at the Mounia Heddad Masson5, Alina Allen6, Jeffrey Lazarus7,
same quantity as the media. Mazen Noureddin8, Mary Rinella9, Frank Tacke10, Suzanne Murray2,
Results: Hepatic mRNA transcriptome analysis showed that patients Emmanuel Tsochatzis11. 1Center for Liver Research, Odense University
with NAFLD exhibited upregulated expression of genes related to Hospital and University of Southern Denmark, Odense, Denmark;
mitochondrial tricarboxylic acid (TCA) cycle (E2F1, E2F2, and ORC6) 2
AXDEV Group Inc., Canada; 3Università degli Studi di Milano,
and those related to the mitochondrial envelope (E2F1, MAPK4, and Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan,
CYP2K6) compared to healthy controls. Gene set enrichment analysis Italy; 4AXDEV Group Inc.; 5EASL, Geneva, Switzerland; 6Mayo Clinic,
revealed upregulated expression of genes related to the pathways of Rochester, MN, United States; 7Barcelona Institute for Global Health
TCA cycle and DNA replication in patients with NAFLD as compared to (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain;
that in healthy controls. The mtDNA copy number in the peripheral 8
Cedars Sinai Medical Center, Los Angeles, CA, United States;
blood mononuclear cells was 1.28-fold lower in patients with NAFLD 9
Northwestern University Feinberg School of Medicine, Chicago, IL,
than in healthy controls ( p < 0.0001). Cellular adenosine triphos- United States; 10Charité Universitätsmedizin Berlin, Dept. of Hepatology
phate (ATP) concentration decreased 1.2-fold times in NAFLD patients and Gastroenterology, Berlin, Germany; 11UCL Institute for Liver and
than in healthy controls (p < 0.0001). The mtDNA copy number and Digestive Health, Royal Free Hospital and UCL, London, United Kingdom
ATP inhibition test showed negative correlation with degree of Email: [email protected]
hepatic steatosis. And ATP concentration showed positive correlation
with mtDNA copy number. Background and aims: The use of non-invasive tests (NITs) in the
Conclusion: Peripheral blood mononuclear cells mitochondrial copy field of non-alcoholic fatty liver disease (NAFLD), non-alcoholic
number and ATP inhibition test can be used biomarkers for the steatohepatitis (NASH), and advanced fibrosis has the potential to
assessment of mitochondrial dysfunction in patients with NAFLD. improve patient care by simplifying the diagnostic process, providing
comprehensive data, and reducing the need for biopsies. We assessed
FRI083 the challenges to implementation of NITs in Germany, Italy, the
Comparison of diagnostic performance between FIB-4 and NFS in United Kingdom, and the United States.
metabolic-associated fatty liver disease era Method: We conducted a two-phase qualitative assessment consist-
Dae Won Jun1, Eileen Yoon1, Sang Bong Ahn2, Huiyul Park3, ing of interviews (n = 29) followed by an expert workgroup discussion
Hyo Young Lee4, Hyunwoo Oh4, Joo Hyun Sohn5, Bo-Kyeong Kang6, (n = 8). Interviews allowed for exploration of challenges with
Mi Mi Kim6, Chul-min Lee6. 1Hanyang University College of Medicine, diabetologists, hepatologists, primary care providers (PCPs), patient
Department of Medicine, Seoul, Korea, Rep. of South; 2Nowon Eulji advocates, clinical/basic researchers, and healthcare administrators/
Medical Center, Eulji University School of Medicine, Department of payers. The expert working group discussion included internationally
Medicine, Seoul, Korea, Rep. of South; 3Uijeongbu Eulji Medical Center, recognized clinicians and researchers in NAFLD and liver fibrosis from
Department of Family Medicine, Gyeonggi-do, Korea, Rep. of South; the four selected countries. They were asked to review, validate, and
4 expand on the identified challenges and collaboratively discuss
Uijeongbu Eulji Medical Center, Department of Medicine, Gyeonggi-do,
Korea, Rep. of South; 5Hanyang University Guri Hospital, Hanyang potential solutions. Transcripts from both phases were analyzed
University College of Medicine, Department of Medicine, Gyeonggi-do, thematically.
Korea, Rep. of South; 6Hanyang University College of Medicine, Results: The main challenges related to the implementation of NITs
Department of Radiology, Seoul, Korea, Rep. of South are shown in Figure 1. First, we identified a lack of awareness about
Email: [email protected] NITs and the importance of early detection of NAFLD, NASH, and
advanced fibrosis among PCPs and diabetologists. Second, respon-
Background and aims: Fibrosis-4 index (FIB-4) and non-alcoholic dents described a need for NITs with more specificity and for their
fatty liver disease (NAFLD) fibrosis score (NFS) are the two most automation to build effective and efficient referral pathways. Some
widely used non-invasive tools for screening of advanced fibrosis in

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 POSTER PRESENTATIONS
first phase participants reported that, in the absence of available 1.41 for "false" lobular inflammation such as isolated ducts or
therapeutic agents, there was no need for novel diagnostic tools. In microscopic necrosis, 1.08 for ballooning and 787 for balloon mimics
the opinion of experts, more effort should be made to demonstrate made by 4 hepatopathologists familiar with the NAS scoring system.
the impact of early diagnosis through NITs. This would help in The predictive ML model established topographical probability maps
enhancing patient motivation for improved metabolic health, for lobular, total inflammation, and hepatocellular ballooning.
slowing or halting disease progression and establishing surveillance Confidence thresholds are defined to identify histological features
for the timely detection or prevention of liver related complications. of interest, which are then quantified by several continuous and
Liver disease was reported to be of low priority among non- normalized parameters (biopsy area ration, density count, and
hepatologists. This challenge is unlikely to change unless the cost- 200XFOV normalized count).
effectiveness of the more costly NITs and their impact on patient Results: The Lobular Inflammation composite score exhibits moder-
outcomes can be demonstrated. ate correlation with the histological grades. Significant disagreement
in the assessment of grade 1 lobular inflammation is driven by
“confusion” with portal inflammatory features which degrades the
specificity between grades 1 and 2 ( p = 0.187). The mean values of the
Ballooning Density correlate with the histological assessment, but p-
values between grades are poor. The mediocre performance of the ML
model is driven by the lack of agreement in the annotations provided
by pathologists. The steatosis proportion area is in fair agreement
with steatosis grades. Disagreement is driven by the fact that the
NASH-CRN criteria is based on percent hepatocytes with fat rather
than fat area ratio (in full tissue area).

Conclusion: The results of this qualitative study should inform the

development of awareness campaigns and targeted educational
interventions focused on diagnosis and risk stratification with NITs.
This will facilitate early diagnosis and care and help to raise NAFLD as
a public health issue.

FRI085 Conclusion: As reported by other teams, liver biopsy Digital

Evaluation of the performance of a novel digital pathology Pathology methods based on supervised ML and annotation provided
method for the continuous quantification of steatosis, ballooning by pathologists (H&E stains, Inflammation, Ballooning) result in
and inflammation in liver biopsies and its correlation with NASH- continuous quantification methods of moderate performance.
CRN scores in patients with NASH
FRI086
Louis Petitjean1, Li Chen1,2, Aras Mattis3, Mojgan Hosseini4,
Can combination of M2BPGi and APRI help endocrinologists refer
Michael Goedken5, Cynthia Behling4, Arun Sanyal6,
patients with advanced hepatic fibrosis to hepatologists?
Mathieu Petitjean1. 1PharmaNest, Princeton, United States;
2
PharmaNest Inc, Princeton, United States; 3University of California Mi Mi Kim1, Bo-Kyeong Kang1, Chul-min Lee1, Huiyul Park2,
San Francisco, San Francisco, United States; 4University of California San Hyo Young Lee3, Hyunwoo Oh3, Sang Bong Ahn4, Dae Won Jun5,
Diego, La Jolla, United States; 5Rutgers University, New Brunswick, Eileen Yoon5, Joo Hyun Sohn6. 1Hanyang University College of
United States; 6Virginia Commonwealth University, Richmond, United Medicine, Department of Radiology, Seoul, Korea, Rep. of South;
2
States Uijeongbu Eulji Medical Center, Department of Family Medicine,
Email: [email protected] Gyeonggi-do, Korea, Rep. of South; 3Uijeongbu Eulji Medical Center,
Department of Medicine, Gyeonggi-do, Korea, Rep. of South; 4Nowon
Background and aims: We have previously shown that the Eulji Medical Center, Eulji University School of Medicine, Department of
Phenotypic Fibrosis Composite Score calculated by the FibroNest Medicine, Seoul, Korea, Rep. of South; 5Hanyang University College of
Quantitative Image analysis and AI methods correlate with the NASH- Medicine, Department of Medicine, Seoul, Korea, Rep. of South;
CRN histological fibrosis stages and steatosis grades established from 6
Hanyang University Guri Hospital, Hanyang University College of
collagen-stained histology slides. Here, we report the performance of Medicine, Department of Medicine, Gyeonggi-do, Korea, Rep. of South
the FibroNest method to quantify Ballooning, Inflammation and Email: [email protected]
Steatosis from digital images of H&E human liver biopsy sections.
Method: This retrospective study comprised a cohort of 87 patients Background and aims: Although the non-invasive tests (NITs, ex.
with NASH diagnosed by histologic assessment of liver biopsy FIB-4, NAFLD fibrosis score (NFS), AST to platelet ratio index (APRI))
according to NASH-CRN criteria with Lobular Inflammation grades are widely used to diagnose advanced hepatic fibrosis, there is a
of 0 (N = 7), 1 (68), and 2 (12), hepatocyte ballooning grades of 0 (N = considerable intermediate zone and diagnostic performance
31), 1 (43) and 2 (13), and steatosis grades of 0 (N = 2), 1 (40), 2 (30) decreased in diabetes subjects. The purpose of this study is to
and 3 (14). Formalin-fixed, paraffin embedded biopsy sections were figure out whether combination of M2BPGi with various NITs can
H&E stained and imaged with an Operio CS2 scanner at 20X in white help endocrinologist screening for advanced hepatic fibrosis in clinic.
light. Quantitative image analysis was performed by FibroNest™ to Method: A total of 1, 129 subjects visiting endocrinology clinic of
extract individual features of inflammation (stained nuclei) and tertiary hospital and performed M2BPGi were included (mean age:
tissue texture quantitative layers from the calibrated and normalized 53.7 ± 14.8 years). NFS, FIB-4, and APRI were calculated for all
images. A subset of 21 representative images was used to develop a subjects. Advanced fibrosis was defined by transient elastography
machine learning (ML) predictive model using 2.3 K annotations for (TE≥8.0 kPa). Sensitivity analysis was also performed.
lobular inflammation, 5.62 K for portal and periportal inflammation, Results: This study included 426 (37.7%) were diabetes and 703
(62.3%) were non-diabetes who visited the endocrinology

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POSTER PRESENTATIONS
department. Mean age was 53.7 ± 14.8 years. Diagnostic performance Results: NAFLD was diagnosed in 92 of 576 (16%) adolescents (52%
of predicting advanced hepatic fibrosis was highest in APRI (the area male). Adolescents with NAFLD had higher body mass index (BMI),
under the receiver operating characteristics curve (AUROC) = 0.811), waist circumference, suprailiac skinfold thickness, alanine amino-
followed by M2BPGi (0.720) and FIB-4 (0.718). M2BPGi at a cutoff of transferase (ALT), gamma glutamyl transpeptidase, triglycerides, total
0.8 showed similar diagnostic performance to lower cutoff of other and low density lipoprotein cholesterol, leptin and Homeostasis
NITs (sensitivity: 72.9% in M2BPGi vs. 77.4–82.8% in other NITs; Model Assessment for Insulin Resistance (HOMA-IR), but lower high
specificity: 57.3% vs. 43.1–65.9%). Diagnostic performance of APRI in density lipoprotein cholesterol and adiponectin levels compared
diabetes was comparable to non-diabetes group (0.832 vs. 0.811, P = with those without NAFLD ( p < 0.05 for all). Birth weight, gestational
0.393). When the combination of M2BPGi (cutoff of 0.8) and APRI age, IUGR, SGA and LGA were not associated with NAFLD. Using
(cutoff of 0.5 and 1.5), the sensitivity and specificity for advanced multivariable logistic regression analysis, low-stable HC trajectory
hepatic fibrosis were 67.4% and 80.4% in endocrinology clinic and group 1 (OR 3.54; 95% CI, 1.21–10.35, p = 0.02), suprailiac skinfold
68.9% and 79.2% in diabetic subjects, respectively. thickness (OR 1.09, 95% CI 1.05–1.13, p < 0.001), ALT (OR 1.03, 95% CI
Conclusion: Combination of M2BPGi and APRI can help screening for 1.01–1.06, p = 0.02) and leptin (OR 1.03, 95% 1.02–1.05, p = 0.001)
advanced hepatic fibrosis in endocrinology clinic. were associated with NAFLD.
Conclusion: The low-stable HC trajectory associated with a persisting
FRI087 small HC through pregnancy, but not birth characteristics, was
The relationship between foetal head circumference growth associated with increased risk of subsequent NAFLD in adolescents.
trajectories and nonalcoholic fatty liver disease in adolescents The association of a low foetal HC trajectory with NAFLD in
Jeffrey Lee1, Ashish Yadav2, Trevor Mori2, Rae-Chi Huang3, adolescence supports the Developmental Origins of Health and
Leon Adams4, Lawrence J. Beilin2, Elizabeth McKinnon3, John Olynyk1, Disease (DOHaD) hypothesis linking early life events with subse-
Oyekoya Ayonrinde1. 1Fiona Stanley Hospital; 2The University of quent disease.
Western Australia; 3Telethon Kids Institute; 4Sir Charles Gairdner
Hospital FRI088
Email: [email protected] Liver stiffness assessed by transient elastography predicts clinical
events in patients with T2DM and NAFLD
Background and aims: Intrauterine and childhood factors are Jesús Rivera1, Monica Pons1, Alejandra Planas2, Rafael Simo Canonge2,
associated with nonalcoholic fatty liver disease (NAFLD) in adoles- Jordi Bañeras3, Ignacio Ferreira3, Joan Genesca1, Juan Manuel Pericàs1.
cents and adults. Previous studies have associated intrauterine 1
Vall d’Hebron Hospital Universitari, Liver Unit, Barcelona, Spain; 2Vall
growth restriction (IUGR), small for gestational age (SGA) and d’Hebron Hospital Universitari, Diabetes and Metabolism Research Unit,
intrauterine exposures such as smoking in pregnancy, and gestational Spain; 3Vall d’Hebron Hospital Universitari, Cardiology Department,
weight gain, with NAFLD in offspring. Maternal factors and Spain
intrauterine influences determine foetal growth patterns and birth Email: [email protected]
weight. Serially measured foetal head circumference (HC) provide a
useful measure of foetal growth patterns and IUGR. We aimed to Background and aims: Non-alcoholic fatty liver disease (NAFLD) and
examine associations between foetal HC growth trajectories and type 2 diabetes (T2DM) are intimately related entities. T2DM is a
subsequent NAFLD during adolescence. major predictor of cardiovascular events (CVE) in NAFLD patients,
Method: Repeated antenatal ultrasound with foetal morphometry whereas the role of NAFLD on CVE in T2DM as well as the impact of
was measured in 1440 pregnant women (Gen1) in the Raine Study, T2DM on liver-related events (LRE) in NAFLD remain poorly known.
between 16 weeks gestation and delivery. Using standard deviation The aim of this study was to evaluate the role of NAFLD on the onset of
scores or z-scores for the HC measurements, five foetal HC clinical outcomes among T2DM patients.
trajectories were developed (Figure 1). Offspring (Gen2) birth Method: Prospective cohort with case-control analysis comprising
weight was recorded and IUGR, SGA and large for gestational age 200 T2DM subjects with no history of CV disease (CVD) and 60 non-
(LGA) were determined for the live-born neonates. As part of the 17- diabetic subjects matched by age with available transient elasto-
year follow up of the Gen2 cohort, lifestyle questionnaires, graphy (TE) data. Patients were selected from the Outpatient Diabetes
anthropometry, blood tests and liver ultrasound, were performed. A Clinic of Vall d’Hebron Hospital and the Primary Healthcare centres
subset of 576 adolescents had both liver ultrasound and foetal within its catchment area (North Barcelona). Overall clinical events
ultrasound HC trajectories data. (CE) were composed by CVE (coronary, cerebrovascular or peripheral
arteriopathy), LRE (liver decompensation or hepatocellular carcin-
oma) and all-cause mortality. NAFLD was defined as Controlled
Attenuation Parameter (CAP) ≥275 dB/m and/or Fatty liver index (FLI)
≥60 after exclusion of the other liver diseases and alcohol
consumption over 30 gr/day in males and 20 gr/day in females. A
value of coronary arterial calcium score (CACs) ≥400 Agatston units
(AU) was considered indicative of high risk of CVD. Cox regression
analysis to predict CE was performed.
Results: Overall, 34 (18.2%) T2DM patients presented any CE vs 4
(7.0%) controls ( p 0.042) during a median follow-up of 5.6 years.
Among patients with T2DM and NAFLD (n = 134), 21 (28.4%) CVE
were reported, being coronary events the most frequent outcome (11/
134; 8.2%). One subject (0.7%) presented LRE and 8 (6%) patients died,
25% of which due to CVD and 37.5% each for malignancy and
infectious diseases. T2DM-NAFLD patients with CE showed higher
rates of diabetes complications (42.9% vs 22.1%; p 0.04 and 61.9% vs
34.2%; p 0.017 for diabetic retinopathy and nephropathy, respect-
ively), high-risk CVD (CACs ≥400 52.6% vs 19.3%, p 0.002) and higher
Figure: Head Circumference trajectory groups: 1 Low-stable, 2 Average- median liver stiffness (6.7 vs 5.4 kPa, p 0.007) than those without CE.
falling, 3 Low-rising, 4 Average-stable, 5 High-stable. SDS-standard devi- No differences were found between groups in terms of T2DM control
ation scores, Dotted lines represent 95% confidence intervals, Percentages (fasting glucose; HbA1c) or metabolic syndrome determinants rates
represent individual group membership.

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 POSTER PRESENTATIONS
(high blood pressure or obesity). In Cox analysis, development of
clinical events among T2DM-NAFLD patients was associated with a
higher liver stiffness (HR = 1.05; 95%CI 1.01–1.09, p 0.003) and male
gender HR = 4.02; 95%CI 1.29–12.50, p 0.016). No statistical associ-
ation was found for diabetes complications or CACs ≥400.

HR (95%CI) for LF-Fib half-stage improvement (0.15 score) in the

Conclusion: Our results suggest that severity of NAFLD is associated group with BMI improvement of ≥10% was 1.78 (0.38–8.39) vs 0.56
with clinical events in patients with T2DM independently of CV (0.12–2.64) in the group that not achieved a BMI improvement of
disease or T2DM complications. TE might help stratifying T2DM ≥10% (logrank probability level = 0.37).
patients with NAFLD at higher risk of developing clinical events and Conclusion: LF-Fib improvement of half-stage was significantly more
therefore shall be recommended in all T2DM patients. prevalent in patients that achieved ALT decrease ≥50% from baseline
and a trend was observed in patients that had ≥10% decrease in BMI
FRI089 from baseline. LF-Fib correlates with clinical endpoints and, therefore
Repeated noninvasive liver biopsy surrogate LIVERFASt correlates can be used for long-term monitoring of MAFLD patients.
with BMI and liver enzyme improvements
Marie Decraecker1, Hiriart Jean-Baptiste1, Marie Irles-Depe1, FRI090
Faiza Chermak1, Juliette Foucher1, Victor de Lédinghen1. 1CHU Increased liver stiffness on vibration controlled transient
BORDEAUX, Pessac, France elastography (Fibroscan) as a predictor of all-cause mortality in
Email: [email protected] people with fatty liver disease
Michael Braude1,2, Ammar Majeed2,3, Stuart Roberts2,3,
Background and aims: MAFLD-related morbi-mortality is increasing Stephen Bloom2,4, Paul Gow5,6, Anouk Dev1,2, William Sievert1,2,
worldwide due to epidemics of obesity and type 2 diabetes (T2D). William Kemp2,3. 1Monash Health-Clayton Hospital Main Entrance,
LIVERFASt (LF, Fibronostics, US) is a new point-of-care proprietary Gastroenterology and Hepatology, Clayton, Australia; 2Monash
technology to assess quantitatively (score from 0.00 to 1.00) liver University Clayton Campus, Clayton, Australia; 3The Alfred, Melbourne,
fibrosis (LF-Fib) in MAFLD pts, with prognostic value for liver-related Australia; 4Eastern Health, Box Hill, Australia; 5Austin Hospital,
events and overall mortality (Hepatology Suppl.2021). Heidelberg, Australia; 6Melbourne University-Swanston St, Parkville,
To assess repeated LF-Fib performance for liver fibrosis regression Australia
rate (LFR) reflected with significant improvement in clinical end- Email: [email protected]
points, body mass index BMI≥10% and liver enzymes ALT ≥50% from
baseline. Background and aims: Fatty liver disease, which is often asymp-
Method: Pts with repeated LF-Fib were prospectively included. tomatic and progressive, is a multi-system, condition which is
Significant improvements in clinical endpoints were: BMI decrease of becoming the leading cause of liver-related morbidity, mortality,
≥10% and ALT decrease ≥50% from baseline. Half fibrosis stage and liver transplant. Ascertaining liver disease severity is therefore
improvement was considered with each 0.15 of LF-Fib score. Statistics important to guide management and prognosis. Several studies have
were descriptive and FPR time dependent using hazard ratios HR shown a correlation between mortality and progressive liver fibrosis
(95%CI). on both histopathology and blood-based fibrosis predictive tests. We
Results: 500 MAFLD patients from a tertiary center were pre- aimed to assess vibration-controlled transient elastography (VCTE) as
included with LF-Fib at baseline and 401 were included with at least a predictor of mortality.
one repeated LF-Fib during follow up; 87 pts had 7 repeated LF-Fib Method: VCTE studies for a primary indication of non-alcoholic fatty
during 9.9 years follow up. 44.3% were female, median (range) age 56 liver disease (NAFLD) were collated from consecutive outpatients
(21–77) yrs, distribution of fibrosis 45%F0, 29%F1, 6%F2, 12%F3 and 8% across 4 Australian tertiary referral centres between July 2008 and
F4, respectively. 13/401 (3.24%) regressed liver fibrosis as per LF-Fib April 2019. Patients with VCTE data were linked to Victorian Death
≥0.15 from baseline score. 109 (27.2%) patients had an ALT regression Index (VDI) and the Victorian Admitted Electronic Dataset (VAED) via
of ≥50% from baseline during FU. 75 (18.7%) experienced an the Centre for Victorian Data Linkage (CVDL). Comorbidity data was
improvement in BMI ≥10% during FU. Median LF-FIB was 0.27 and derived from International Classification of Diseases 10th Revision
median (range) FU between baseline and last repeated LF-Fib was (ICD-10) coding within the VAED. Cause of death (COD) was analysed
3.57 yrs (3–9.9). using descriptive statistics. Liver stiffness measurement (LSM, kPa)
Occurrence of half-stage liver fibrosis improvement as per LF-Fib was was analysed as a predictor of all-cause mortality using Cox-
more probable among those that achieved ALT regression of ≥50% proportional regression analysis with multivariable adjustment for
from baseline: Cox Mantel Hazard Ratios [HR (95%CI)] 3.47 (1.08– age, gender, and comorbidities, including the Charlson Comorbidity
11.19) versus 0.29 (0.09–0.93) in those without ≥50% ALT decrease Index (CCI).
(logrank probability level 0.02) (Figure 1). Results: A total of 7079 individual VCTE records were identified, 6341
of which were matched via data linkage, and 5857 were represented
in the VAED. The median follow-up period from VCTE to death/
censorship was 3.6 (IQR 2.1–5.5, range 0.2–11.0) years. Mean age at
VCTE across the 7079-patient cohort was 55.4 ± 13.6 years, median
LSM was 6.1 kPa (IQR 4.7–9.3) and mean controlled attenuation

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S441

POSTER PRESENTATIONS
parameter (CAP) (n = 3789) was 287.7 ± 68.7 db/m. In the linked available magnetic resonance imaging (MRI) for the detection of
cohort of 6341 patients, 217 deaths occurred during follow-up. NASH with fibrosis.
Median age of death was 72.3-years (IQR 64.4-79.0). Sepsis (n = 41, Method: We performed a cross-sectional international study that
LSM 12.0 kpa, IQR 5.8–20.2), followed by decompensated liver included subjects with NAFLD from three countries evaluated
disease (n = 33, LSM 32.2, IQR 18.8–49.1) and non-gastrointestinal between 2017 and 2021. The training cohort included 138 consecu-
malignancy (n = 25, LSM 13.9, IQR 6.2–23.9) were the most common tive patients with contemporaneous MRI and biopsy-proven NAFLD
primary COD, accounting for 18.9%, 15.2%, and 11.5% of deaths from Spain and Portugal and a validation cohort of 44 patients from
respectively. Hepatocellular carcinoma (HCC) was either a primary or USA. Patients with Fibrosis-4 index >4.63 and NAFLD fibrosis score
comorbid COD in 8.8% (n = 19, LSM 22.8 kPa, IQR 11.7–31.5) of >1.57 were excluded due to high pretest probability of cirrhosis (98%
individuals. CAP was not associated with mortality in univariable specificity). Disease severity was estimated using the histology
analysis (HR = 1.00, CI 1.0–1.0, p = 0.488). In a multivariable analysis, NAFLD activity score (NAS), defining NASH as NAS≥4 and significant
n = 5857 records, increased LSM (HR 1.02, CI 1.01–1.03, p < 0.001), fibrosis as F≥2. Performance parameters of sensitivity, specificity,
increased CCI (HR 1.32, CI 1.27–1.38, p < 0.001) and advanced age (HR positive predictive value (PPV) and negative predictive value (NPV)
1.05, CI 1.03–1.07, p < 0.001), but not gender, were associated with were calculated.
increased mortality. Results: NASH was diagnosed on liver biopsy in 53% of the European
and 59% of the US cohorts, while significant fibrosis was found in 50%
and 82% patients in the two cohorts, respectively. In the training
cohort, MRI-Proton Density Fat Fraction (MRI-PDFF; OR: 1.57; 95%CI
1.31–1.86) and MRI-determined waist circumference (WC; OR: 1.004;
95%CI 1.001–1.007) were imaging biomarkers independently asso-
ciated with NASH (adjusted for sex, age, height and liver fibrosis). A
median MRI-PDFF >11% combined with a WC >96 cm in women and
>107 cm in men, showed 86% sensitivity, 88% specificity, 89% PPV and
84% NPV for the diagnosis of NASH. Among patients that were above
these cut-offs, 90% had fibrosis and 63% demonstrated significant
fibrosis. In the validation cohort, the combined image biomarkers had
82% sensitivity, 83% specificity, 86% PPV, and 79% NPV for the
diagnosis of NASH. All selected patients had fibrosis, including 81%
with significant fibrosis.

Figure: Kaplan-Meier survival curves based on LSM (kPa).

Conclusion: LSM based on VCTE is independently associated with

all-cause mortality in fatty liver disease.

FRI091
Magnetic resonance imaging-based biomarker accurately
identifies patients with nonalcoholic steatohepatitis and
significant liver fibrosis: a multicentre, international, validation
study
David Marti-Aguado1, Joud Arnouk2, Jaideep Behari2,
Alessandro Furlan3, Ramon Bataller2, Maria Manuela Franca4,
Ana Gallen5, Victor Merino1, Clara Alfaro-Cervello6, Judith Pérez7, Conclusion: An MRI-based composite biomarker of PDFF+WC
Salvador Benlloch5, Victoria Aguilera Sancho8, identified patients with NASH and liver fibrosis with high specificity
Desamparados Escudero-García1, Ana Jimenez-Pastor9, and PPV. This finding offers clinical utility in the management of
Angel Alberich-Bayarri9, Miguel Serra1, Luis Marti-Bonmati9. 1Clinic NAFLD and patient selection for NASH clinical trials.
University Hospital, Valencia, Spain, Department of Gastroenterology
and Hepatology, Valencia, Spain; 2University of Pittsburgh Medical FRI092
Center (UPMC), Hepatology Department, United States; 3University of Diagnostic accuracy of MRE for staging hepatic fibrosis in patients
Pittsburgh Medical Center (UPMC), Radiology Department, Pittsburgh, with NAFLD
United States; 4Centro Hospitalar Universitário do Porto, Radiology
Carmen Lara Romero1,2, Jia-xu Liang3, Isabel Fernández-Lizaranzu4,
Department, Porto, Portugal; 5Hospital Arnau Villanova, Hepatology
Javier Ampuero1,2, Javier Castell3, Manuel Romero Gomez1,2. 1Hospital
Department, Valencia, Spain; 6Clinic University Hospital, Pathology
Universitario Virgen del Rocío, Department of Digestive and Liver
Department, Valencia, Spain; 7Hospital Universitario y Politécnico La Fe,
Diseases; 2Institute of Biomedicine of Seville, Seville, Spain; 3Hospital
Pathology Department, Valencia, Spain; 8Universitario i Politecnic de La
Universitario Virgen del Rocío, Department of Radiology; 4Universidad
Fe, Hepatology Department, Valencia, Spain; 9Universitario i Politecnic
de Sevilla, Interdisciplinar Physics Group, Seville, Spain
de La Fe , Radiology Department, Valencia, Spain
Email: [email protected]
Email: [email protected]
Background and aims: To evaluate the diagnostic accuracy of
Background and aims: Liver fibrosis is the only histological feature
magnetic resonance elastography (MRE) instaging hepatic fibrosis
predictive of nonalcoholic steatohepatitis (NASH) progression to
in patients with histologically confirmed nonalcoholic fatty liver
cirrhosis and liver-related complications. Currently, the FDA requires
disease (NAFLD) and analyze possible confounding factors of MRE.
the inclusion of patients with biopsy-proven NASH-related fibrosis
Method: 54 subjects were prospectively enrolled. Liver stiffness
for therapeutic trials. We aimed to assess the accuracy of simple and
measured by MRE and by transient elastography (Fibroscan ®) was
correlated with the grade of fibrosis determined by liver biopsy.

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 POSTER PRESENTATIONS
Patients in our cohort were classified according to the cut-off values FRI093
obtained from another Meta-analysis of individual patient data Aldafermin quantitatively improves inflammation in a 24-week
(2.61 kpa for F1, 2.97 kpa for F2, 3.62 kpa for F3, 4.69 kpa for F4). We clinical trial in patients with nonalcoholic steatohepatitis
also made an analysis to identify those variables that could Tian Lan1, Luong Ruiz1, Wenhui Liu1, Amir Ashique1, Harry Chen1,
underestimate (MRE result lower than biopsy result), overestimate Jiping Zha2, Alex DePaoli1, Igor Mikaelian1, Cynthia Guy3,
(MRE result higher than biopsy results) or achieve concordance (MRE Eugenia Henry4, Corinne Foo-Atkins4, William Chang4, Hsiao Lieu4.
result consistent with biopsy result). 1
NGM Biopharmaceuticals Inc., Translational Science, South
ANOVA, Kruskal-Wallis test were used for continuous variables and San Francisco, United States; 2Adagene Inc., Clinical Development, San
chi-square test or Fisher’s exact test for categorical variables. ROC Diego, United States; 3Duke University Medical Center, Pathology,
(receiver operator characteristic) curves for diagnostic accuracy were Durham, United States; 4NGM Biopharmaceuticals Inc., Clinical
evaluated, and Spearman’s correlation was performed to compare Research, South San Francisco, United States
histologic liver fibrosis with MRE elastography and Fibroscan. Email: [email protected]
Results: The area under the ROC curve (AUROC) of MRE for ≥F2 was
0.886 vs Fibroscan AUROC 0.842 ( p = 0.48). MRE AUROC for F3 was Background and aims: Pathologist-based scores are the standard for
0.887 vs Fibroscan AUROC 0.820 ( p = 0.27). Spearman’s correlation assessing efficacy in nonalcoholic steatohepatitis (NASH) clinical
coefficient of liver fibrosis and Fibroscan was 0.651 ( p < 0.0001) trials, but are limited by variability in interpretation and insensitivity
whereas correlation coefficient of liver fibrosis and MRE elastography to small changes, especially for lobular inflammation. Lobular
was 0.704 ( p < 0.0001). inflammation scores reflect the number of inflammatory foci per
Variables that could overestimate MRE accuracy were AST ( p = microscopic field, which are in part contributed by macrophages.
0.0005), ALT ( p = 0.0032) and inflammation activity ( p = 0.008). BMI, Samples from a Phase 2 clinical trial with aldafermin (NGM282), an
weight, or DM did not affect diagnostic accuracy ( p = 0.732, p = 0.816, engineered fibroblast growth factor 19 analogue, were used to
p = 0.521, respectively). develop and test novel image analysis readouts for liver inflammation
based on CD68, a macrophage lysosomal marker.
Method: Liver biopsies were from a 24-week clinical trial with
aldafermin: NCT02443116 (Cohort 4, placebo (PBO), n = 18; 1-mg
NGM282, n = 47). Biopsies and blood for non-invasive biomarkers
were collected at baseline and at the end of treatment. A 6-plex
immunohistochemistry (IHC) panel that included CD68 was devel-
oped to enable two image analysis endpoints: (1) “Type 1 macro-
phages” (M1 s) based on CD68 expression and cell shape; and (2)
“Macrophage foci” to account for focal accumulations of M1 s.
Results: NGM282 decreased lobular inflammation measured by the
NASH Clinical Research Network (CRN) criteria ( p = 0.02) and the
inflammation measured by the IHC macrophage foci (PBO vs. 1-mg,
−0.39% vs. −1.41%, p = 0.04). The decrease of M1 s did not reach
statistical significance in this relatively small study ( p = 0.18).
Inflammation reads by CRN criteria and by image analysis did not
correlate robustly with the circulating biomarkers, including AST and
ALT (r-squared ≈ 0.2).

Conclusion: MRE is an effective, non-invasive method for detecting/

staging hepatic fibrosis in NAFLD. Although we did not reach
statistical significance, MRE showed a higher diagnostic accuracy
than transient elastography in discriminating significant and
advanced fibrosis. The liver inflammation grade may affect the
diagnostic accuracy of MRE in staging hepatic fibrosis in NAFLD Conclusion: Quantified IHC readouts can identify histological
patients, but BMI or DM did not. changes in an automated manner. These histological endpoints do
not correlate well with current circulating biomarkers.

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POSTER PRESENTATIONS
FRI094
Clinical and economic evaluation of community-based
preventative screening strategies for non-alcoholic fatty liver
disease in people with Type-2 diabetes melllitus
Roberta Forlano1, Tijana Stanic2, Sahan Jayawardana2,
Benjamin H. Mullish1, Michael Yee1, Mark Thursz1, Elias Mossialos2,3,
Pinelopi Manousou1. 1Department of Metabolism, Digestion and
Reproduction, Imperial college London, London, UK, United Kingdom;
2
Department of Health Policy, London School of Economics and Political
Science, London, UK, United Kingdom; 3Centre for Health Policy, The
Institute of Global Health Innovation, Imperial College London, London,
UK
Email: [email protected]
Background and aims: The exact prevalence of Non Alcoholic Fatty
Liver Disease (NAFLD) in type 2 diabetes (T2DM) is unknown. We
aimed to determine the prevalence and develop a risk stratification
and cost analysis for a screening policy in T2DM in primary care. We
compared the cost-effectiveness of 5 screening strategies vs standard
of care (SoC).
Method: Consecutive T2DM patients underwent blood tests, ultra-
sound (US) and liver stiffness measurement (LSM). Significant Conclusion: Screening for NAFLD in T2DM improved diagnostic
fibrosis and advanced fibrosis were defined by LSM≥8.1 kPa and outcomes and was cost-effective in all evaluated scenarios within
≥12.1 kPa. Diagnosis of cirrhosis was clinical, histological or radio- NICE’s cost-effectiveness threshold. Fibroscan followed by BIMAST
logical. Markov model included 3 health states: NMD-: no NAFLD; was the screening strategy associated with the greatest clinical gains.
NMD+: NAFLD with LSM≤8 kPa; significant liver disease (SLD:
LSM≥8.1 kPa); compensated cirrhosis (CC) (Fig 1). FRI095
The probability of progressing was assumed reduced for those at risk Confounding factors in diagnostic performance of magnetic
of NAFLD (NMD+) or diagnosed with SLD (SLD+) compared to those at resonance elastography for staging liver fibrosis in patients with
lower risk (NMD−), or with undiagnosed disease (SLD−). The effect of non-alcoholic fatty liver disease: an individual patient data meta-
earlier identification, diagnosis and treatment was based on the analysis
reduction of transition probabilities for NMD+/SLD+ vs NMD−/SLD−. JiaXu Liang1,2,3, Javier Ampuero1,2, Kento Imajo4, Mazen Noureddin5,
The base-case analysis was conducted over a lifetime horizon and Jaideep Behari6, Dae Ho Lee7, Richard L. Ehman8, Juan R. Lacalle9,
generated the cost per quality-adjusted life year (QALY) gained. We Javier Castell10, Ferenc Mozes11, Michael Pavlides11,12,
calculated average cost-effectiveness and the incremental cost- Quentin Anstee13, Stephen Harrison11, Manuel Romero Gomez1,2.
1
effectiveness ratio (ICER) vs SoC. Life expectancy, lifetime costs, and Virgen del Rocío University Hospital, Digestive Diseases Unit, Seville,
number of correct diagnoses were estimated. A cost-effectiveness Spain; 2Institute of Biomedicine of Seville (HUVR/CSIC/US), Seville, Spain,
threshold was set at £20, 000/QALY gained, as per NICE. University of Seville, Seville, Spain; 3People’s Hospital of Zhengzhou,
Results: Of 300 patients enrolled, 287 were included; 13 withdrew: Radiology, Zhengzhou, China; 4Yokohama City University Graduate
184 (73%) had NAFLD, 28 (10%) other causes of liver disease (alcohol, School of Medicine, Department of Gastroenterology, Yokohama, Japan;
5
HBV) and 75 (26%) no liver disease. Significant fibrosis and advanced Cedars-Sinai Medical Center, Fatty Liver Program, Karsh Division of
fibrosis due to NAFLD were 17% (50/287) and 11% (31/287) Digestive and Liver Diseases, Comprehensive Transplant Program, Los
respectively. The prevalence of cirrhosis was 3% (8/287). Based on Angeles, CA, United States; 6University of Pittsburgh Medical Center,
predictors of significant fibrosis, the BIMAST score (BMI and AST) Department of Medicine, Division of Gastroenterology, Hepatology and
performed better for diagnosing significant (AUROC 0.81, p < 0.0001) Nutrition, Center for Liver Diseases, Pittsburgh, United States; 7Gachon
and advanced fibrosis (AUROC 0.84, p < 0.0001) (Fig 2). Five screening University Gil Medical Center, Gachon University College of Medicine,
strategies were compared: 1) US + liver function tests (LFTs), 2) FIB-4, Departments of Internal Medicine, Incheon, Korea, Rep. of South; 8Mayo
3) NAFLD fibrosis score, 4) BIMAST score, 5) fibroscan. In a Markov Clinic College of Medicine, Department of Diagnostic Radiology,
model, NAFLD screening improved the rate of correct diagnoses by 8– Rochester, United States; 9University of Seville, Biostatistics Unit,
15%, with an exception of the NAFLD fibrosis score strategy, which led Department of Preventive Medicine and Public Health, Seville, Spain;
10
to a 2% decrease in correct diagnoses. All screening strategies were Virgen del Rocío University Hospital, Radiology, Seville, Spain;
11
associated with QALY gains, ranging from 121–148 years, with Radcliffe Department of Medicine, University of Oxford, Oxford Centre
fibroscan resulting in the most substantial gains. In all screening for Clinical Magnetic Resonance Research, Division of Cardiovascular
strategies, ICER compared to SoC was between £1, 970 (BIMAST score) Medicine, United Kingdom; 12University of Oxford, Translational
and £2, 480 (fibroscan) per QALY gained (Tab 1). Gastroenterology Unit, United Kingdom; 13Faculty of Medical Sciences,
Newcastle University, Translational and Clinical Research Institute,
Newcastle upon Tyne, United Kingdom
Email: [email protected]
Background and aims: We conducted an individual patient data
meta-analysis to assess potential confounding factors influencing
diagnostic accuracy of magnetic resonance elastography in staging
liver fibrosis and to determine specific diagnostic cutoff values in
patients with non-alcoholic fatty liver disease.
Method: A review of the literature identified studies containing MRE
data for grading liver fibrosis in NAFLD patients with liver biopsy as
reference standards. The original database was obtained in Excel form
the corresponding authors. Pooled diagnostic cutoff value for the

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 POSTER PRESENTATIONS
various fibrosis stages were determined in a two-stage meta-analysis NASH and AF vs patients with MF, (161.86 ± 115 vs 90.6 ± 56, p = 0.04,
as the primary outcome. Multilevel modelling methods were used to 15.9 ± 8.6 vs 10 ± 1.48, p = 0.02). 42% of patients with MF had APRI<0.5
analyses potential confounding factors influencing diagnostic accur- and 57% had APRI between 0.5–1. No patient with MF had APRI>0.5.
acy of MRE in staging liver fibrosis. Likewise, 50% of patients with AF had APRI >0.5, and 50% of them, had
Results: 6 independent cohorts comprising 483 patients were APRI >1.5 ( p = 0.026). All patients with APRI >1 and LS >12.1 kPa had
included in the meta-analysis, yielding liver stiffness cutoffs of AF, and only 29% of patients with AF did not meet both criteria ( p =
2.77 kPa (area under the receiver operating characteristic curve 0·86 0.037). In addition, all patients with APRI>1.5 and GGT>115.6 IU/ml
[0·83–0·89]) for any fibrosis (≥F1), 3.09 kPa (0·90 [0·87–0·92]) for had AF, compared to 29% of patients with AF who did not meet both
significant fibrosis (≥F2), 3.41 kPa (0·93 [0·91–0·96]) for advanced analytical criteria ( p = 0.037).
fibrosis (≥F3) and 4.10 kPa (0·91 [0·88–0·93]) for cirrhosis (F4).
Notably, cases with mild fibrosis stage (F0–1) with moderate to
severe inflammatory activity (A3–4) had exhibited greater stiffness VARIABLE RESULTS (n = 40)
than matched cases of the same fibrosis stage with none to mild
AGE 59.78 ± 8.5
inflammation activity. Similarly, higher liver inflammatory activity SEX (%) MALE 20 (50%)
was an independent variable predicting reduced diagnostic accuracy FEMALE 20 (50%)
of MRE [OR (95% CI) = 0.404 (0.220–0.740), p < 0.01], whereas AHT (%) 30 (75%)
steatosis degree, BMI, ALT, and AST did not affect the diagnostic DYSLIPIDEMIA (%) 25 (62.5%)
accuracy of MRE (Table). DIABETES (%) 27 (67.5%)
OBESITY (%) 40 (100%)
Table: GLMM (generalized linear mixed model) explore variables associated AST 47.4 ± 28.2 U/L
with prediction failure ALT 56.1 ± 33.5 U/L
GGT 115.6 ± 88 U/L
HEMOGLOBIN A1c 6.5 ± 1.27%
CHOLESTEROL 202 ± 33.4 mg/dL
TRIGLYCERIDES 190.4 ± 95 mg/dL
ADVANCED FIBROSIS (%) 14 (35%)
LIVER STIFFNESS (kPa) 12.1 ± 5.8 kPa
CAP (n = 23) 334.4 ± 32.4
FIB-4 (%) <1.33 13 (32.5%)
1.33–2.66 22 (55%)
>2.66 5 (12.5%)
FIB-4 1.8 ± 1.04
APRI (%) <0.5 18 (45%)
0.5–1.5 19 (47.5%)
Conclusion: MRE has excellent diagnostic performance for deter- >1.5 3 (7.5%)
mining significant, advanced fibrosis and cirrhosis in patients with APRI 0.66 ± 0.49
NAFLD. Accuracy was not influenced by anthropometric, biochemical,
or steatosis degree, but could be influenced by high inflammatory Conclusion: Most patients with MAFLD and RH >8 kPa have NASH,
activity. one-third of them have AF. Increased GGT, APRI index, and LS were
associated with a higher probability of having NASH with AF. LS and
FRI096
APRI combination or APRI and GGT combination, can identify patients
Is it possible to identify nonalcoholic steatohepatitis and the
with NASH and FA. Therefore, it seems possible to identify patients
associated degree of fibrosis by noninvasive methods in patients
with MAFLD and high risk of NASH and NASH with AF with non-
with MAFLD?
invasive methods. Nevertheless, further prospective studies are
José López González1, Marta Casado1, Teresa Maria Jordan Madrid1, needed to confirm these preliminary results.
Almudena Porcel Martin1, José Luis Vega Sáenz1. 1Torrecárdenas
University Hospital, Almería, Spain FRI097
Email: [email protected] The potential role of fatigue in identifying patients with NASH and
Background and aims: Non-alcoholic steatohepatitis (NASH) is a advanced fibrosis who experience disease progression
chronic and progressive form of metabolic associated fatty liver Zobair Younossi1,2,3, Maria Stepanova1,2,4, Robert Myers5,
disease (MAFLD). NASH diagnosis requires histological evaluation Reem Al Shabeeb3, Issah Younossi4, Linda Henry1,2,4. 1Inova Health
after liver biopsy. Therefore, it is necessary to develop non-invasive System, Medicine Service Line, Falls Church, United States; 2Betty and
diagnostic alternatives to identify NASH and the associated degree of Guy Beatty Center for Integrated Research, IHS, Falls Church, United
fibrosis. The aim of this study is to analyze the presence of NASH and States; 3Center for Liver Diseases, Department of Medicine, Falls Church,
NASH with advanced fibrosis (AF) in patients with MAFLD and United States; 4Center for Outcomes Research in Liver Disease,
increased liver stiffness (LS), and to identify those associated factors Washington DC, United States; 5Gilead Sciences, Inc., Foster City, United
with AF. States
Method: We included a prospective cohort of all patients with clinical Email: [email protected]
and ultrasound diagnosis of MAFLD, treated in our department since
Background and aims: Fatigue is common in patients with advanced
January 2019, with LS >8 kPa, measured by transient elastography.
liver disease. We aimed to investigate the association of fatigue with
Presence of NASH and the degree of fibrosis, were evaluated after
the risk of progression among patients with NASH and advanced
histological analysis of a liver biopsy. Epidemiological, clinical,
fibrosis.
analytical, elastographic and histological variables were collected.
Method: In this post hoc cohort study, enrolled subjects were
Patients were classified according to the presence of AF in the liver
required to have a liver biopsy consistent with NASH and bridging
specimen (grade 3–4) or mild fibrosis (MF) (grade 1–2 or absence).
fibrosis (F3) or compensated cirrhosis (F4), and were followed up for
Results: Our study included 40 patients, whose characteristics are
up to two years. Fatigue was quantified using the fatigue domain of
shown in Table 1. Histological analysis demonstrated NASH in 36
the CLDQ-NASH instrument completed by subjects at baseline (score
patients (90%), 14 patients with AF (35%), and two of them with F4
range 1–7, lower score indicates worse fatigue). Cox proportional
grade fibrosis. GGT and LS were significantly higher in patients with
hazard model was used to determine the relationship between the

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POSTER PRESENTATIONS
baseline fatigue score and the time to liver-related clinical events measured, and its square root is used as an exploratory marker SQRT
( progression to histologic cirrhosis for F3, developing hepatic (A%). Each digital image was evaluated for quality along 20
decompensation for F4). dimensions (tissue processing, staining, and scanning) to generate a
Results: There were 1679 advanced NASH patients (N = 802 F3 and Digital Biopsy Adequacy Score (DBA).
877 patients F4, age 58 ± 9 years, 40% male, 74% type 2 diabetes). Results: Patients with biopsies with a DBA lower than 5 (non-
During median follow-up of 16 months (IQR 14–18 month, max 26 adequate, ∼10% of the cohort) were not included in the results.
months), 123 (15%) of F3 patients and 31 (3.5%) F4 patients Groups sizes ranged from 27 to 45 patient per group. The
experienced liver-related clinical events. The mean baseline CLDQ- quantification of the antifibrotic effect of the treatments was
NASH fatigue score was 4.77 ± 1.36 in F3 and 4.56 ± 1.44 in F4. In both similar using the mean change from baseline of the Ph-FCS and
F3 and F4 cohorts, patients with liver-related events in follow-up had MRE. SQRT (A%) was highly correlated to PDFF (R^2 = 0.660, N = 334)
higher baseline AST, lower platelet count, and elevated non-invasive and demonstrated same anti-steatotic effects as PDFF for each group
test scores for fibrosis (APRI, FIB-4, ELF, Fibrotest, NAFLD Fibrosis (Fig. A). Responders were identified with a relative reduction from
Score) in comparison to patients who remained stable in follow-up baseline of MRE, Ph-FCS, PDFF and SQRT (A%) of ≥15%, ≥25%, ≥30%
(all p < 0.01). Their baseline fatigue scores were also significantly and ≥30% respectively, and with a 1-unit reduction for the
lower: 4.47 ± 1.36 in progressed F3 vs. 4.83 ± 1.35 in stable F3 ( p = histological stage. The agreement between quantitative digital
0.0091); 3.74 ± 1.31 in progressed F4 vs. 4.59 ± 1.43 in stable F4 ( p = pathology and imaging methods is illustrated in Fig. B, C.
0.0011). In multivariate analysis, the association of lower fatigue
scores (more fatigue) with the risk of liver-related events was
significant: hazard ratio (HR) per 1 fatigue point = 0.84 (0.75–0.93), p
= 0.0012, in all patients; HR = 0.85 (0.75–0.96), p = 0.0088, in F3; HR =
0.67 (0.53–0.85), p = 0.0014, in F4. These associations remained
significant after adjustment for clinico-demographic confounders:
adjusted HR = 0.79 (0.70–0.89), 0.85 (0.74–0.97), and 0.62 (0.48–
0.81), respectively (all p < 0.02).
Conclusion: Lower baseline fatigue scores were associated with
adverse clinical events in patients with advanced NASH. A combin-
ation of baseline clinical and fatigue parameters can inform clinicians
of which patients with advanced fibrosis due to NASH are at risk of
Conclusion: Combined to AI algorithms, quantitative digital path-
adverse clinical outcomes.
ology image analysis generates continuous scores that enhance
FRI029 conventional histological staging methods. They detect the antifi-
Novel digital pathology quantitative image analysis and AI brotic and anti-steatosis effect of treatment such as PGBF with a
method detects the treatment effects of NASH drug candidates performance that benchmarks imaging-based measurements.
with a performance that benchmarks imaging-based
measurements FRI099
Translational fibrosis phenotypes between the 3D human NASH
Li Chen1, Elizabeth Brown2, Anne Minnich2, Vipul Baxi2,
spheroidal model and clinical NASH samples
Dimple Pandya2, Shuyan Du2, Edgar Charles2, Zachary Goodman3,
Louis Petitjean1, Simon Ströbel2, Li Chen1,3, Francisco Verdeguer2,4,
Mathieu Petitjean1, Arun Sanyal4. 1PharmaNest, Inc, Princeton, United
States; 2Bristol Myers Squibb, Princeton; 3Inova Health Systems, Falls Radina Kostadinova2, Arun Sanyal5. 1PharmaNest, Inc, Princeton,
Church, United States; 4Virginia Commonwealth University, Richmond, United States; 2InSphero AG, Shlieren, Switzerland; 3PharmaNest Inc,
Princeton, United States; 4University of Zurich, Zürich, Switzerland;
United States 5
Email: [email protected] Virginia Commonwealth University, Richmond, United States
Email: [email protected]
Background and aims: Manual histological evaluation of liver biopsy
is the gold standard method for fibrosis and steatosis staging in Non- Background and aims: The use of 3D human spheroidal model for
Alcoholic Steatohepatitis (NASH), but it is limited by its inter and efficacy testing of anti-fibrotic compounds for Non-Alcoholic
intra-reader variability. Quantitative Digital Pathology image analysis Steatohepatitis (NASH) has led to the need to understand the
and AI (FibroNest™) as well as quantitative MRI signal analysis relevance of the fibrosis histological phenotypes and their clinical
translational relevance. Here, a novel digital pathology quantitative
methods have the potential to overcome the current limitation of
standards. This exploratory post-hoc analysis compared FibroNest image analysis and AI platform, FibroNestTM, was used to measure
digital pathology scoring methods with NASH-CRN categorical stages quantifiable Fibrosis Traits (qFTs) in 3D human NASH models and
natural cohort of patients diagnosed with NASH.
and imaging-based scores in patients with NASH from the phase 2b
FALCON1 study (NCT348699). Method: 3D liver tissues were either treated for 10 days with free
fatty acids and LPS or not to generate NASH (n = 14 tissues) and lean
Method: Eligible adults were 18–75 years of age (N = 197) with NASH
diagnosed by histologic assessment of liver biopsy according to NASH (n = 17 tissues) conditions respectively. The clinical cohort was
CRN criteria and stage 3 fibrosis. During the 48-week double-blind retrospective and consisted of 104 patients with NASH diagnosed
by histologic assessment of liver biopsy according to NASH CRN
treatment period, patient received 10 mg, 20 mg, or 40 mg PGBF
subcutaneous or placebo once weekly. Liver biopsies were obtained criteria by pathologists F0 (26), F1 (24), F2 (28), F3 (20), F4 (6). 4 μm
FFPE spheroid and liver biopsies sections were stained with Picro
six months before or during screening and at week 24. Most patients
underwent imaging resulting in Mean Liver Stiffness (MRE) and Sirus Red, and scanned (40X and 20X) with bright-light whole slide
Mean Proton Density Fat Fraction (MRI-PDFF) measurements. imaging scanners. FibroNestTM, was used to quantify the fibrosis
Formalin-fixed, paraffin embedded sections of the liver biopsies histological phenotype including 32 traits for collagen content, fiber
where stained with Masson Trichrome and imaged at 40X. morphometry, and architecture, generating 315 qFT. Principal qFTs
Quantitative image analysis was performed to extract single-fiber were automatically detected to best describe the progression of the
quantitative traits (qFTs, N = 315) from the fibrosis histological fibrosis in both models. A Venn diagram approach was used to
phenotype. A previously validated selection of principal qFTs were identify those traits that describe histological fibrosis severity in both
normalized and combined into a fibrosis severity score (Ph-FCS, 1 to models.
10). The non-fibrotic/scar parenchymal tissue area fat ratio (A%) is Results: The Venn Diagram identifies 97 shared traits between the
two fibrosis progression models. qFTs are normalized to their initial

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 POSTER PRESENTATIONS

Figure: (abstract: FRI099)

value and their folds describe relative levels of progression bench- Method: Using the electronic health records (EHRs), patients seen at
marked from a model to another. 10 traits described collagen features PCP and ENDO clinics were screened for the presence of NASH risk
such as collagen area ratio, assembled/fine collagen fibers area ratio, factors. Patients with a diagnosis of type 2 diabetes or those with >2
and density area ratio (Figure). 61 traits described common other components of metabolic syndrome (hypertension, hyperlip-
morphometric features, such as the proportion of long collagen idemia, or obesity) were eligible for the second round of assessment
fibers, the mean fiber skeleton length, and the mean fiber area. 26 using FIB-4. Patients with FIB-4 score ≥1.45 were referred to a
traits described common architectural features. The 3D human NASH hepatology practice for transient elastography (TE) by FibroScan™
spheroidal model cannot be directly associated to a specific NASH (Echosens, Paris, France: liver stiffness [LSM] and fat assessment by
CRN score, but specific qFTs can be associated with either F2 or F3 controlled attenuation parameter [CAP]), shear-wave elastography
stages using their fold values. (SWE) by ACUSON Sequoia Ultrasound System (Siemens
Conclusion: We identified 97 histological traits of fibrosis severity Healthineers, Erlangen, Germany: LSM by Point Shear Wave
phenotype that can be translated from the 3D NASH spheroid model Elastography [pSWE] and ultrasound-derived fat fraction [UDFF]),
to clinical F2 or F3 NASH CRN stages. These traits will be used to and the Enhanced Liver Fibrosis (ELF) Test (Siemens Healthineers,
evaluate the anti-fibrotic compounds effect in 3D NASH model to Tarrytown, NY, USA).
predict their effect in human. Results: 13, 953 patients were screened (53% from ENDO practices,
47% from PCP). Of those, 4, 269 (30%) met the criteria for the second
FRI100 round of screening with FIB-4: 1, 286 (30%) agreed to enroll. Based on
Shear wave elastography, transient elastography and enhanced the FIB-4 risk cut-off, 328 (25%) patients were considered eligible for
liver fibrosis test use in the assessment of non-alcoholic fatty liver linkage to hepatology care, of whom 177 (53%) agreed to undergo
disease (NAFLD) in real- world practices linkage assessment. Patients who underwent linkage assessment
Sean Felix1, Elena Younossi1,2, Thomas Jeffers2, Evis Hudson3, were 67 ± 10 years of age, 52% male, 61% white, 23% black, 4%
Nagashree Gundu Rao3, Z. Chris3, Amish Gandhi3, Hispanic, and 8% Asian, mean BMI was 31.6 ± 6.4 kg/m2, 90% had
Maria Castillo-Catoni3, Maria Ramirez3, Mehreen Husain3, clinical history of hyperlipidemia, 79% hypertension, 62% type 2
Evangeline Delgado3, Ambika Baru3, Merica Shrestha3, diabetes, and 23% reported having coronary artery or cardiovascular
Romona Satchi3, Yemsrach Gami3, Pegah Golabi3, Andrei Racila4, disease. Mean (SD) FIB-4 score: 1.95 ± 0.74; ELF score: 9.55 ± 0.83,
Fatema Nader5, Maria Stepanova3,5, Zobair Younossi3. 1Inova Fairfax LSM by TE: 7.0 ± 4.0 kPa, CAP 287 ± 64 dB/m, LSM by SWE: 3.98 ±
Medical Campus, Department of Medicine, Falls Church, United States; 1.55 kPa, UDFF: 13.4 ± 8.6%, and FAST score: 0.25 ± 0.24. Of these
2
Inova Fairfax Hospital, Falls Church, United States; 3Inova Health patients, based on published or recommended by manufacturers cut-
System, Medicine Service Line, Falls Church, United States; 4Inova Fairfax offs, 3% were considered high-risk by ELF, 17% by TE, and 8% by SWE;
Medical Campus, Falls Church, United States; 5Center for Outcomes and additional 64% by ELF, 68% by TE, and 84% by SWE were
Research in Liver Diseases, Washington, United States considered low-risk. The correlations among the two stiffness
Email: [email protected] measures (TE and SWE) and ELF were significant: Spearman’s rho =
+0.51 ( p < 0.0001) between stiffness by TE and SWE; +0.40 ( p <
Background and aims: Risk stratification of NAFLD patients using
non-invasive tests can be challenging. In this context, correlation of 0.0001) between stiffness by SWE and ELF; +0.25 ( p = 0.0028)
between stiffness by TE and ELF.
different radiologic and blood-based NITs to each other can be
clinically informative. We aimed to assess the correlation of different Conclusion: High-risk NASH patients can be identified by applying a
NITs to identify high-risk NAFLD/NASH patients seen at real-world simple clinical algorithm using electronic heath records and point-of-
care NITs.
primary care provider (PCP) and endocrinology (ENDO) practices and
link them to a GI or hepatology practice for specialized care.

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POSTER PRESENTATIONS
FRI101 Haţieganu University of Medicine and Pharmacy, Department of Medical
Diagnostic performance of AGILE 3+ score for identification of Imaging, Romania; 7University of Palermo, Department of
advanced fibrosis and prediction of liver-related events in Gastroenterology and Hepatology Promise, Palermo, Italy; 8Saiseikai
patients with non-alcoholic fatty liver disease Suita Hospital, Department of Gastroenterology and Hepatology, Suita,
Grazia Pennisi1, Ciro Celsa1, Marco Enea1, Alessandra Pandolfo2, Japan; 9University of Malaya, Gastroenterology and Hepatology Unit,
Michela Antonucci3, Carlo Ciccioli1, Giuseppe Infantino1, Department of Medicine, Faculty of Medicine, Kuala Lumpur, Malaysia;
10
Claudia La Mantia1, Stefanie Parisi1, Adele Tulone1, Vito Di Marco1, University Health Network, Toronto Centre for Liver Disease, Toronto,
Antonio Craxi1, Calogero Camma1, Salvatore Petta1. 1Section of Canada; 11Nottingham University Hospitals NHS Trust and University of
Gastroenterology and Hepatology, Department of Health Promotion, Nottingham, National Institute for Health Research Nottingham
Mother and Child Care, Internal Medicine and Medical Specialties Biomedical Research Centre, Nottingham, United Kingdom; 12University
(PROMISE), University of Palermo, Italy; 2University of Palermo; Hospitals Birmingham NHS Foundation Trust and the University of
3 Birmingham, National Institute for Health Research Biomedical Research
University of Palermo, Dipartimento di Biomedicina, Neuroscienze e
Diagnostica avanzata (BIND) Centre , Birmingham, United Kingdom; 13The Chinese University of Hong
Email: [email protected] Kong, Department of Medicine and Therapeutics, Hong Kong, Hong
Kong; 14Bordeaux University Hospital, Centre d’Investigation de la
Background and aims: We aimed to assess the diagnostic accuracy of
Fibrose Hépatique, Hôpital Haut-Lévêque, Bordeaux, France;
AGILE 3+, a recently developed score based on the combination of 15
University of Oxford, Translational Gastroenterology Unit, Oxford,
AST/ALT ratio, platelet count, diabetes status, sex, age and LSM, United Kingdom; 16Aichi Medical University, Aichi, Japan; 17Koseikai
respect to FIB-4 and LSM, for the diagnosis of advanced fibrosis and
Takeda Hospital, Kyoto, Japan; 18University Medical Centre Mainz,
for the prediction of liver-related events (LRE) occurrence in patients Mainz, Germany; 19University Medical Center of the Johannes
with non-alcoholic fatty liver disease (NAFLD).
Gutenberg-University, Mainz, Germany; 20Seoul Metropolitan
Method: 614 consecutive patients with biopsy-proven NAFLD or
Government Boramae Medical Center, Division of Gastroenterology and
clinical diagnosis of NAFLD-related compensated cirrhosis were Hepatology, Department of Internal Medicine, Seoul National University
enrolled. LRE were recorded during follow-up. FIB-4, LSM by TE and
College of Medicine, Seoul, Korea, Rep. of South; 21Seoul Metropolitan
AGILE 3+ were measured. The diagnostic performance of noninvasive Government Boramae Medical Center, Department of Radiology, Seoul
criteria for advanced fibrosis and for the prediction of LRE was National University College of Medicine, Seoul, Korea, Rep. of South;
assessed by AUROC curve and by decision curve analysis (DCA). 22
University of Nottingham, Nottingham Digestive Diseases Centre,
Results: In patients with biopsy-proven NAFLD (n = 520), LSM and Translational Medical Sciences, School of Medicine, Nottingham, United
AGILE 3+ had higher AUROC than FIB-4 (0.88 for LSM and AGILE 3+ vs
Kingdom; 23University Hospital of Montpellier, Department of
0.78 for FIB-4; p < 0.001) for advanced fibrosis, and AGILE 3+
Diagnostic and Interventional Radiology, Saint-Eloi Hospital,
exhibited the lower rate of indeterminate area of the test (25.2% for
Montpellier, France; 24AIIMS, Department of Surgical Disciplines, New
FIB-4, vs 13.1% for LSM, vs 8.3% for AGILE 3+). In the entire cohort
Delhi, India; 25Monash University, Centre for Obesity Research and
AGILE 3+ had significantly higher AUC for predicting LRE respect to
Education, Department of Surgery, Melbourne, Australia; 26Yokohama
LSM (36-month AUROC 0.95 vs 0.93, p = 0.008; 60-month 0.95 vs
City University, Department of Gastroenterology and Hepatology,
0.92, p = 0.006; 96-month 0.97 vs 0.95, p = 0.001). DCA showed that
Yokohama, Japan; 27The First Affiliated Hospital of Wenzhou Medical
all scores had modest net benefit for ruling-out advanced fibrosis at
University, NAFLD Research Center, Department of Hepatology,
the risk threshold of 5%–10% of missing advanced fibrosis. At the risk
Wenzhou, China; 28Echosens, Paris, France; 29University Hospital
threshold of 5% of false negative or false positive LRE at 36-, 60-, 96-
Würzburg, Division of Hepatology, Wurzburg, Germany; 30Pfizer, Inc.,
and 120-month, AGILE 3+ outperformed both FIB-4 and LSM for
Cambridge, MA, United States; 31Newcastle University, Newcastle upon
ruling-out LRE.
Tyne Hospitals NHS Foundation Trust, NUTCRI, Framlington, United
Conclusion: AGILE 3+, according to resource availability, clinical
Kingdom
setting and the risk scenarios is an accurate and valid alternative to
Email: [email protected]
FIB-4 and LSM for the noninvasive assessment of disease severity and
prognosis in NAFLD patients. Background and aims: Screening for non-alcoholic steatohepatitis
with cirrhosis (NASH+F4), identified by regulators as an unmet
FRI102 medical need, is done by liver biopsy. Given the low prevalence of the
Diagnostic accuracy of non-invasive tests for cirrhotic NASH-an condition in typical clinical populations, risk stratification using non-
individual participant data meta-analysis invasive tests (NITs) is desirable to reduce the number of unnecessary
Ferenc Mozes1, Jenny Lee2, Yasaman Vali2, Emmanuel Selvaraj1, liver biopsies. The aim of this study was to evaluate the diagnostic
Arjun Jayaswal1, Jerome Boursier3, Elisabetta Bugianesi4, performance of vibration-controlled transient elastography (LSM-
Ramy Younes5, Monica Lupsor-Platon6, Salvatore Petta7, VCTE), fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) as
Toshihide Shima8, Takeshi Okanoue8, Sanjiv Mahadeva9, screening tests for NASH+F4.
Wah-Kheong Chan9, Gideon Hirschfield10, Peter Eddowes11, Method: This was an individual participant data meta-analysis of
Philip N. Newsome12, Vincent Wai-Sun Wong13, studies evaluating NITs against liver histology. NASH was defined as
Victor de Lédinghen14, Jeremy Cobbold15, Yoshio Sumida16, NAS>4 with at least grade 1 in each of the components. Diagnostic
Akira Okajima17, Jörn Schattenberg18, Christian Labenz19, Won Kim20, accuracy was assessed by the area under the receiver operating curve
Myoung Seok Lee21, Guruprasad Aithal22, (AUROC). The relationship between NIT cut-off and screen failure rate
Naaventhan Palaniyappan22, Cristophe Cassinotto23, (SFR) and the number of patients that needed to be tested (NNT) to
Sandeep Aggarwal24, Harshit Garg24, Geraldine Ooi25, identify 1 positive case was explored visually. We report on cut-offs
Atsushi Nakajima26, Masato Yoneda26, Ming-Hua Zheng27, that achieved 90% sensitivity, 90% specificity and maximised the
Céline Fournier28, Andreas Geier29, Theresa Tuthill30, Carla Yunis30, Youden-index as well as cut-offs that achieved screen failure rate of
Quentin Anstee31, Stephen Harrison1, Patrick Bossuyt2, 50% and 60%. Sequential combinations of serum NITs followed by
Michael Pavlides1. 1University of Oxford, RDM Cardiovascular Medicine, LSM-VCTE were also evaluated.
Oxford, United Kingdom; 2University of Amsterdam, Department of Results: We included 2738 individual patient data from 25 primary
Epidemiology and Data Science, Amsterdam UMC, Amsterdam, studies (43% female, median age 52 years, median BMI 29 kg/m2; 41%
Netherlands; 3CHU Angers, Angers, France; 4University of Turin, had type 2 diabetes; 57% had NASH, 6% had NASH + F4). LSM-VCTE
Department of Medical Sciences, Division of Gastroenterology, Turin, had AUROC = 0.90, higher than 0.80 for FIB-4 and 0.78 for NFS (both
Italy; 5Boehringer Ingelheim, Binger Strasse 173, Germany; 6Iuliu p < 0.001). Cut-offs for 90% sensitivity, 90% specificity and maximum

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 POSTER PRESENTATIONS
Youden-index were 10.2 kPa (Sp 76%, SFR 80%, NNT = 18), 14.6 (Se Method: TARGET-NASH is a longitudinal study of patients managed
68%, SFR 69%, NNT = 24), and 10.4 kPa (Se 89%, Sp 77%, SFR 79%, NNT for NAFLD in usual clinical practice. Data from patients enrolled in the
= 18) for LSM-VCTE; 1.16 (Sp 52%, SFR 89%, NNT = 18), 2.73 (Se 41%, US with ≥3 ALT measures were included. Liver transplant, cholecyst-
SFR 79%, NNT = 39) and 1.35 (Se 88%, Sp 61%, SFR 87%, NNT = 18) for itis, liver cancer, sepsis were excluded. ALT categories: normal (≤30 U/
FIB-4; − 1.637 (So 53%, SFR 89%, NNT = 18), 0.473 (Se 32%, SFR 82%, L), slightly high (1–2X normal), high (2–3X normal), very high (>3X
NNT = 50) and −0.878 (Se 77%, Sp 69%, SFR 86%, NNT = 21) for NFS normal). Using available data, the transition between ALT categories
(Figure 1). A cut-off combination of FIB4 1.16 or NFS −1.637 followed was modelled using a recurrent neural network. 80%–20% data split
by LSM VCTE of 16 kPa yielded Se 59%, Sp 93%, SFR 62%, and NNT = 27 into training-testing approach was utilized to fit the model and assess
and only 10% of the entire patient group would have to undergo liver accuracy. Age, sex, body mass index (BMI), race/ethnicity, ALT date,
biopsy while also reducing the number of LSM-VCTE exams to 51%. hypertension, diabetes, cardiovascular disease and statin use were
identified a priori.
Results: 3, 664 adult patients were followed over a median of 38.2
months (range: 1.7–87) with 3.9 months (range: 0.5–54.2) between
ALT measures. Median age: 59; non-Hispanic (85%), White (76%), BMI
32 kg/m2, history of hypertension (74%), type 2 diabetes (54%),
cardiovascular disease (22%), statin use (46%); diagnosed with NASH
(44.3%), cirrhosis (40.4%), NAFLD (15.3%). Patients in higher ALT
categories at baseline were younger with a greater percentage of
Hispanic or Latino participants vs. lower ALT categories. At baseline,
33%, 38%, 15%, 14% of patients had normal ALT, slightly high, high, very
high ALT levels, respectively. In the unadjusted model, 39% with
normal ALT at baseline remained in that category during follow up.
Among those with slightly high ALT at baseline, 18% remained within
that stratum; 5% and 18% of those with high and very high ALT,
respectively, at baseline remained in the same strata. Probability of
transitioning from normal or slightly high to very high ALT level was
2% and 6%, respectively, suggesting that transition from low to high
ALT levels is uncommon. Risk of transition was higher in NH Whites
(24%) and Hispanics (24%), followed by NH Black (21%), Asians (19%).
Statin use did not influence transition. Accuracy of the neural
network on training and testing data sets was 99% and 82%,
respectively. Accuracy of the testing data set improved when limiting
to phenotype at baseline: 89% (NAFLD), 84% (NASH), 84% (cirrhosis).

Conclusion: Only LSM-VCTE achieved SFR of 50% and 60% which was
at the cost of high NNT. Sequential combinations can achieve similar
diagnostic accuracy while potentially reducing the number of LSM-
VCTE exams and biopsies being performed, which could have
favorable cost implications.

FRI103
Longitudinal ALT trajectories are generally stable among patients Conclusion: Longitudinal ALT trajectories remained relatively stable
with non-alcoholic fatty liver disease (NAFLD): an investigation among patients with NAFLD. Understanding the course of ALT
using artificial recurrent neural networks fluctuations is important for helping to differentiate natural variation
Michael Fried1, Breda Munoz1, Jamie Wu1, Kenneth Cusi2, from potential hepatotoxic or beneficial effects of therapeutics. Next
Vincent Wai-Sun Wong3, Peter Mesenbrink4, Marcos Pedrosa4, steps include exploration of ALT trends associated with probability of
Andrea Mospan1, Miriam Vos5, Rohit Loomba6, Arun Sanyal7. 1Target clinical outcomes.
RWE, Durham, United States; 2University of Florida, Gainsville, United
States; 3The Chinese University of Hong Kong, Hong Kong, China;
4
Novartis, East Hanover, United States; 5Emory University, Atlanta,
United States; 6University of California at San Diego, San Diego, United
States; 7Virginia Commonwealth University Medical Center, Richmond,
United States
Email: [email protected]
Background and aims: Serum alanine aminotransferase (ALT) is a
biomarker used to monitor liver injury. Little is known about ALT
fluctuations over short intervals or the influence of patient
characteristics on ALT trajectory in patients with NAFLD. This study
modelled longitudinal variability in ALT and estimated the probability
of a patient transitioning from their baseline level.

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POSTER PRESENTATIONS
FRI104 Conclusion: The adult-based GRS for hepatic fat was associated with
An adult-based genetic risk score for hepatic fat associates with liver fat content, liver enzymes and lipid profiles, but was not
liver and lipid traits in Danish children and adolescents associated with adiposity and other metabolic traits in children and
Yun Huang1, Sara Stinson1, Helene Bæk Juel1, Morten Lund2,3, adolescents. The GRS could serve as a predictor of the risk for hepatic
Louise Aas Holm1,3, Cilius Esmann Fonvig1,3,4, Niels Grarup1, steatosis in addition to clinical risk factors and could be used for early
Oluf Pedersen1, Michael Michael Christiansen2,5, Aleksander Krag6,7, preventative initiatives.
Stefan Stender8, Jens-Christian Holm1,3,9, Torben Hansen1. 1University
of Copenhagen, The Novo Nordisk Foundation Center for Basic Metabolic FRI105
Research, København, Denmark; 2University of Copenhagen, Identification of new potential biomarkers to follow
Department of Biomedical Sciences, Denmark; 3Copenhagen University steatohepatitis in patients with non-alcoholic/metabolic-
Holbæk Hospital, Department of Pediatrics; 4Kolding Hospital a part of associated fatty liver disease
Lillebælt Hospital, Department of Pediatrics; 5Statens Serum Institute, Douglas Maya1,2,3, Rocío Gallego-Durán1,2,3,
Department for Congenital Disorders; 6Odense University Hospital, María del Rosario García-Lozano1,2, Rocio Munoz Hernandez1,3,4,
Department of Gastroenterology and Hepatology; 7University of Angela Rojas Alvarez-Ossorio1,2,3, Antonio Gil-Gomez1,2,3,
Southern Denmark, Institute of Clinical Research; 8Rigshospitalet, Javier Ampuero1,2,3,4, Manuel Romero Gomez1,2,3,4. 1Institute of
Department of Clinical Biochemistry; 9University of Copenhagen, Faculty Biomedicine of Seville, Hepatic, Digestive and Inflammatory Diseases,
of Health and Medical Sciences Sevilla, Spain; 2Centro de Investigación Biomédica en Red en el Área
Email: [email protected] temática de Enfermedades Hepáticas, Spain; 3Hospital Universitario
Virgen del Rocío, Gastroenterology and Hepatology, Sevilla, Spain;
Background and aims: Several genetic variants that associate with 4
Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain
hepatic fat content in adults have been identified in genome-wide Email: [email protected]
association studies. Their effects in children and adolescents remain
unclear. The aims of this study were to test the effect of genetic Background and aims: To integrate different liver gene-expression
variants known to associate with hepatic fat in adults, individually datasets to identify novel potential serological biomarkers to follow-
and combined as a genetic risk score (GRS), with cardiometabolic up steatohepatitis in NAFLD patients.
traits, and to investigate the predictive ability of the GRS for hepatic Method: Initial candidates were obtained by comparing the gene
steatosis in children and adolescents. expression of paired liver biopsies coming from NAFLD patients that
Method: Children and adolescents with overweight/obesity from an were able (n = 20) or not (n = 17) to resolve steatohepatitis at the end
obesity clinic cohort (n = 1, 843, median age 11.7 years, body mass of a dietary or a surgical intervention of 1 year (section 1). Association
index standard deviation score [BMI SDS] 2.85, 45.2% male) and a of candidates to steatohepatitis was initially explored in 6 microarray
population-based cohort of children and adolescents (n = 2, 271, gene expression datasets (n = 317) in which patients were classified
median age 11.6 years, BMI SDS 0.26, 40.1% male) were included. as NASH or No NASH according to the SAF score and analysed as a
Anthropometrics and biochemical parameters were measured in single cohort after batch normalization. Selected candidates were
both cohorts. Liver fat content was measured by magnetic resonance filtered through a series of public datasets to retain exclusively
spectroscopy in 539 individuals. We calculated a weighted GRS based secreted proteins able to reach the bloodstream. Candidates were
on eight genetic variants known to associate with hepatic fat content validated independently in three additional RNA-seq additional
in adults. Associations of individual genetic variants and the GRS with datasets in which patients with Bland Steatosis (SS) were compared
cardiometabolic traits were tested using multiple linear and logistic against patients with steatohepatitis (NASH (Cohort 1: N = 3115 SS/16
regression models. Receiver operating characteristic (ROC) curve NASH) (Cohort 2 N = 67 23 SS/44 NASH) (Cohort 3 N = 99 51 SS/47
analysis was performed on models based on risk factors for hepatic NASH)) introducing age (Cohorts 2 and 3) and sex as covariables in
steatosis, defined as hepatic fat ≥5%, and area under the curve (AUC) the analysis (all 3). These candidates were further explored in a
was calculated to evaluate model performance. recently published gene expression (Govaere et al. 2020) in which 163
Results: Variants in PNPLA3, TM6SF2, GPAM, and GCKR were NASH patients were stratified by fibrosis stage (F0–F1 n = 34; F2 n =
significantly associated with higher liver fat content ( p < 0.01) and 53; F3 n = 54; F4 n = 12) and compared against patients with bland
with distinct patterns of circulating lipids. The GRS was associated steatosis with no or mild fibrosis (SS n = 51).
with higher liver fat content and alanine transaminase (ALT), as well Results: Paired liver biopsy analysis identified 1363 genes that
as lower LDL-cholesterol and triglycerides in the obesity clinic and significantly change their behaviour specifically in patients achieving
population-based cohorts. The GRS was not associated with adiposity NASH resolution. 61 or them showed a positive or a negative
or other metabolic traits. The GRS was associated with higher association to steatohepatitis in the integrative multiarray compari-
prevalence of hepatic steatosis (odds ratio [OR] per 1-unit GRS- son in the microarray multicohort dataset. 22 of them are secreted
increase: 2.18, p = 1E-8), and with lower prevalence of dyslipidemia and can reach the bloodstream. Only one of them, IL-32, replicated its
(OR 0.90, p = 0.02). A prediction model for hepatic steatosis including behaviour in the microarray cohort (Fold Change (FC): 1.43, p-value
GRS alone yielded cross-validated AUC of 0.76 (95% CI 0.69–0.83). The 1.3 × 10−9, FDR:1.3 × 10−6) and in all three RNA-seq analysis (Cohort 1
addition of the GRS to a model containing clinical risk factors for FC: 2.47, p-value 6.2 × 10−4 FDR 1.0 × 10−2; Cohort 2: FC: 1.59, p-value
hepatic steatosis (BMI SDS, ALT, homeostatic model assessment of 8.3 × 10−5, FDR: 9.7 × 10−2; Cohort 3 FC: 2.11, p-value 1.15 × 10−7, FDR:
insulin resistance [HOMA-IR]) increased AUC slightly from 0.87 (95% 3.2 × 10−6). This protein also replicated its behaviour in the last
CI 0.82–0.92) to 0.89 (95% CI 0.84–0.94). dataset independently from fibrosis stage (NASH F0-F1 vs NAFL FC:
1.64, p-value: 3.78 × 10−6, q-value: 9.99 × 10−4) (NASH F2 vs NAFL FC:
1.69, p-value: 5.62 × 10−5, q-value: 2.90 × 10−2) (NASH F3 vs NAFL
FC: 2.03, p-value: 4.81 × 10−8, q-value: 8.52 × 10−6) (NASH F4 vs NAFL
FC: 2.16, p-value: 4.80 × 10−5, q-value: 1.83 × 10−3).

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 POSTER PRESENTATIONS
4 underwent MRE. Two out of six, four out of six and one out of three
patients in each arm showed MRE>2.99 kPa (significant fibrosis) in
five patients MRE was not valid. Estimated cost for NAFLD patient
referral to the liver unit was approximately €570, 78 (Sánchez-
Torrijos et al. REED 2019), VCTE €120 and CFS €0.59 per patient with
T2DM: cost in Arm A was €31, 392.9; cost in Arm B was €24, 90053
and in Arm C was €16, 215.12

Conclusion: The prevalence of advanced fibrosis in a diabetic cohort

reached 7.3% confirmed by transient elastography and MRE. A
Conclusion: IL-32 expression in the liver shows the most robust and
stepwise algorithm in the management of patients with type 2
dynamic association to steatohepatitis and might constitute a useful
diabetes with combined score and VCTE was cost-effective, allowing
biomarker for its detection and follow-up in patients.
to save 50% of the budget compared to the standard of care.
FRI106 Acknowledgement: Unrestricted grant from Gilead Sciences.
NASH patient’s itinerary: Comparison of strategies for screening,
FRI107
referring and management
Peformance of fibrometer-derived biomarker panels for
Manuel Romero Gomez1,2,3, Yolanda Sánchez2,4, Silvia García Rey2,4, assessment of fibrosis stage in NAFLD: NIMBLE stage 1 and the
Francisco Javier Atienza Martín5, Pablo Remon6, NASH CRN collaborative Study
Carmen Lara Romero2,6, María C. Roque-Cuéllar2,4,
Rohit Loomba1, Sudha Shankar2, Katherine Yates3, Clayton Dehn4,
Inmaculada Dominguez7, Ioanna-Panagiota Kalafati8, Sabine Kahl9,
James Bolognese5, Brent Tetri6, Kris Kowdley7, Raj Vuppalanchi8,
Pedro Pablo García-Luna7,10, Jörn Schattenberg11, Michael Roden12,
Cynthia Guy9, James Tonascia3, Anthony Samir10, Claude Sirlin11,
George Dedoussis8, Jeffrey Lazarus13. 1Digestive Diseases Department,
Sarah Sherlock12, Kathryn Fowler11, Helen Heymann13,
Virgen del Rocío University Hospital; 2Institute of Biomedicine of Seville;
3 Tania Kamphaus13, Roberto Calle14, Arun Sanyal15. 1University of
CIBERehd; 4Virgen del Rocío University Hospital; 5Centro de Salud El
California at San Diego, San Diego, United States; 2Astrazeneca, United
Porvenir, Seville, Spain; 6Endocrinology and Nutrition Department,
States; 3Johns Hopkins University, Bloomberg School of Public Health,
Virgen del Rocío University Hospital; 7Clinical Biochemistry Department,
United States; 4P-value LLC, United States; 5Cytel, United States; 6Saint
Virgen del Rocío University Hospital; 8Harokopio University Athens;
9 Louis University, Department of Gastroenterology and Hepatology,
Deutsches Diabetes-Zentrum; 10University of Seville; 11University
United States; 7Liver Institute Northwest, United States; 8Indiana
Medical Center Mainz; 12German Diabetes Center; 13Barcelona Institute
University, Division of Gastroenterology and Hepatology, United States;
for Global Health (ISGlobal), Hospital Clínic, University of Barcelona 9
Duke University, Department of Pathology, United States;
Email: [email protected] 10
Massachusets General Hospital, Department of Radiology, United
Background and aims: Non-alcoholic fatty liver disease (NAFLD) is a States; 11University of California at San Diego, Department of Radiology,
highly prevalent, underdiagnosed, health system burden and impacts United States; 12Pfizer, United States; 13Foundation for the National
on quality of life including comorbidities in the affected population. Institutes of Health (FNIH), United States; 14Regeneron Pharmaceuticals,
Cost-effective strategies focusing on clinical pathways to detect and United States; 15Virginal Commonwealth University, Division of
refer patients to care are needed. The aim of this study is to build a Gastroenterology, Hepatology and Nutrition, Department of Internal
stepwise algorithm combining non-invasive freely available methods Medicine, United States
(FIB-4, NFS, HFS alone or combined) and vibration-controlled Email: [email protected]
transient elastography (VCTE) in diabetic patients from primary
Background and aims: The intent of the current collaborative study
care and endocrinology units.
between NIMBLE & the NASH CRN was to further evaluate the
Method: One-hundred sixty-four diabetes patients were recruited
performance of Fibrometer-based biomarker panels, including those
from January 2021 to February 2022 and randomized to one of three
developed for NAFLD or other liver diseases, with & without VCTE for
arms: Arm A (n = 55) patients referred following standard of care;
identification of fibrosis strata in those with NAFLD. This cross-
Arm B (n = 55) patients referred due to altered combined fibrosis
sectional study evaluated the diagnostic-test performance character-
score (CFS) (FIB4>1.3 or NFS >−1.456 or HFS>0.12); and Arm C (n = 54)
istics of four Fibrometer-based biomarker panels for assessing
patients referred due to HFS>0.12 or VCTE>8 KPa. Patients at risk of
fibrosis in a well-characterized cohort of patients with biopsy-
NAFLD-fibrosis (VCTE>8 kPa) underwent magnetic resonance elasto-
confirmed NAFLD with description of sensitivity & specificity at
graphy (MRE).
Youden’s cutoff for their intended diagnostic use in a large, multi-
Results: Age average was 55 ± 10 y, 54.3% males, and 66.5% obese
center US cohort of patients with NAFLD/NASH.
(BMI>30 Kg/m2). Transient elastography >8 kP was found in 35/164
Method: The performance of Fibrometer Virus (FM-VIRUS),
(21.3%); >10 kPa 22/164 (13.4%) and >15 kPa 12/164 (7.3%). No Cirrhometer Virus (CM-VIRUS), Fibrometer NAFLD (FM-NAFLD) &
statistical differences were seen among these three arms in Fibrometer VCTE-Light (FM-VCTE-Light) was evaluated for the
biochemical, anthropometric or clinical features. All patients from assessment of fibrosis. Blood-based parameters were tested from
Arm A were referred and 12/55 showed VCTE>8 kPa and 7 underwent aliquots of the same blood sample from each patient obtained within
MRE. In Arm B, 36 patients were referred and 10/36 showed 90 days of a liver biopsy demonstrating NAFLD of varying activity &
VCTE>8 kPa and 9 underwent MRE. In Arm C, 17 were referred and

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POSTER PRESENTATIONS
stages (Stages 0–4). VCTE measurements were performed in a UMC, Amsterdam, Netherlands; 3Centre Hospitalier Universitaire
subgroup of trial participants within this time window. In order to d’Angers, Service d’Hepato-Gastroenterologie et Oncologie Digestive,
minimize spectrum bias, the cohort was selected a priori to have a Angers, France; 4University of Turin, Division of Gastroenterology and
similar distribution of fibrosis stages across its entire range. The Hepatology, Department of Medical Sciences, Turin, Italy; 5Boehringer
primary hypothesis was that the AUROC for each panel for its Ingelheim, Ingelheim, Germany; 6Iuliu Haţieganu University of Medicine
intended use was numerically >0.7 & significantly superior to 0.5. The and Pharmacy, Department of Medical Imaging, Regional Institute of
secondary hypothesis was that the AUROC for each panel for fibrosis Gastroenterology and Hepatology “Prof.Dr. Octavian Fodor,” Cluj
was significantly greater than that for FIB-4 (as the common Napoca, Romania; 7University of Palermo, Section of Gastroenterology
reference). and Hepatology, PROMISE, Palermo, Italy; 8Saiseikai Suita Hospital,
Results: 1073 patients with biopsy-proven NAFLD including NAFL (n Department of Gastroenterology and Hepatology, Suita, Japan;
9
= 220) & NASH (n = 853) were evaluated. The number of patients with University of Malaya, Gastroenterology and Hepatology Unit,
fibrosis stages 0, 1, 2, 3 & 4 were 222, 114, 262, 277 & 198, respectively. Department of Medicine, Faculty of Medicine, Kuala Lumpur, Malaysia;
10
The dataset for Fibrometer VCTE-Light was smaller as VCTE data were University Health Network, Toronto Centre for Liver Disease, Toronto,
available in only 393 patients. The AUROCs, Youden’s cutoff with its Canada; 11Nottingham University Hospitals NHS Trust and University of
sensitivity/specificity are provided below: All 4 panels met criteria for Nottingham, National Institute for Health Research Nottingham
intended use for diagnosis of fibrosis stage ≥2, advanced fibrosis, & Biomedical Research Centre, Nottingham, United Kingdom; 12National
cirrhosis. Compared to FIB-4, FM-VIRUS & FM-NAFLD met criteria for Institute for Health Research Biomedical Research Centre at University
diagnosis of advanced fibrosis but not for fibrosis stage ≥2 or Hospitals Birmingham NHS Foundation Trust and the University of
cirrhosis, while CM-VIRUS was not superior to FIB-4 for any of the Birmingham, Birmingham, United Kingdom; 13The Chinese University of
intended uses. In contrast, FM-VCTE-Light was significantly superior Hong Kong, Department of Medicine and Therapeutics, Hong Kong, Hong
to FIB-4 for all three intended uses. Kong; 14Bordeaux University Hospital, Centre d’Investigation de la
Fibrose Hépatique, Hôpital Haut-Lévêque, Pessac, France; 15University of
Oxford, Translational Gastroenterology Unit, Oxford, United Kingdom;
16
Aichi Medical University, Division of Hepatology and Pancreatology,
Department of Internal Medicine, Aichi, Japan; 17University Medical
Center of the Johannes Gutenberg-University, Metabolic Liver Research
Program, I. Department of Medicine, Mainz, Germany; 18University
Medical Center of the Johannes Gutenberg-University, Mainz,
I. Department of Medicine, Mainz, Germany; 19Seoul Metropolitan
Government Boramae Medical Center, Division of Gastroenterology and
Hepatology, Department of Internal Medicine, Seoul National University
College of Medicine, Seoul, Korea, Rep. of South; 20Seoul Metropolitan
Government Boramae Medical Center, Department of Radiology, Seoul
National University College of Medicine, Seoul, Korea, Rep. of South;
21
University of Nottingham, Nottingham Digestive Diseases Centre,
Translational Medical Sciences, School of Medicine, Nottingham, United
Kingdom; 22University Hospital of Montpellier, Department of
Diagnostic and Interventional Radiology, Saint-Eloi Hospital,
Montpellier, France; 23AIIMS, Department of Surgical Disciplines, New
Delhi, India; 24Monash University, Centre for Obesity Research and
Conclusion: FM-VCTE-Light consistently outperformed FIB-4 for Education, Department of Surgery, Melbourne, Australia; 25Yokohama
stratification of fibrosis across a spectrum of fibrosis stages. FM-VIRUS City University, Department of Gastroenterology and Hepatology,
& FM-NAFLD appear to be better than FIB-4 for detecting advanced Yokohama, Japan; 26the First Affiliated Hospital of Wenzhou Medical
fibrosis but not for other fibrosis stages. These data will be helpful in University, NAFLD Research Center, Department of Hepatology,
informing trial design for future studies using these Fibrometer- Wenzhou, China; 27Echosens, Paris, France; 28University of Vienna,
based non-invasive tools across various intended use populations. Vienna, Austria; 29University Hospital Würzburg, Division of Hepatology,
Würzburg, Germany; 30Pfizer, Cambridge, United States; 31Newcastle
FRI108 University, Translational and Clinical Research Institute, Faculty of
Diagnostic accuracy of non-invasive tests for fibrotic NASH-An Medical Sciences, Newcastle, United Kingdom
individual participant data meta-analysis Email: [email protected]
Ferenc Mozes1, Jenny Lee2, Yasaman Vali2, Emmanuel Selvaraj1, Background and aims: Histological assessment to confirm non-
Arjun Jayaswal1, Jerome Boursier3, Elisabetta Bugianesi4, alcoholic steatohepatitis with significant fibrosis (NASH+F2–3) is
Ramy Younes5, Monica Lupsor-Platon6, Salvatore Petta7, needed prior to enrolment in clinical trials. Non-invasive testing (NIT)
Toshihide Shima8, Takeshi Okanoue8, Sanjiv Mahadeva9, strategies to identify those with high risk for the target condition are
Wah-Kheong Chan9, Gideon Hirschfield10, Peter Eddowes11, needed to reduce screen failure rates (SFR). Our aim was to evaluate
Philip N. Newsome12, Vincent Wai-Sun Wong13, liver stiffness measurements by vibration-controlled transient
Victor de Lédinghen14, Jeremy Cobbold15, Yoshio Sumida16, elastography (LSM-VCTE), alone or in combination with the
Akira Okajima16, Jörn Schattenberg17, Christian Labenz18, Won Kim19, fibrosis-4 score (FIB-4) and the NAFLD fibrosis score (NFS) in such
Myoung Seok Lee20, Guruprasad Aithal21, screening strategies.
Naaventhan Palaniyappan21, Cristophe Cassinotto22, Method: This was an individual participant data meta-analysis of
Sandeep Aggarwal23, Harshit Garg23, Geraldine Ooi24, studies evaluating LSM-VCTE against liver histology. The target
Atsushi Nakajima25, Masato Yoneda25, Ming-Hua Zheng26, condition was NASH+F2–3. NASH was defined as NAS≥4 with at
Céline Fournier27, Michael Trauner28, Andreas Geier29, least grade 1 in each of the components. Upper and lower cut-offs
Theresa Tuthill30, Carla Yunis30, Quentin Anstee31, Stephen Harrison1, were used, with patients with NIT cut-offs between these two
Patrick Bossuyt2, Michael Pavlides1. 1University of Oxford, RDM thresholds being selected for liver biopsy. Diagnostic performance
Cardiovascular Medicine, Oxford, United Kingdom; 2University of was tested over a range of lower and upper NIT thresholds for single
Amsterdam, Department of Epidemiology and Data Science, Amsterdam NITs, and sequential combinations of serum NITs and LSM-VCTE.

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 POSTER PRESENTATIONS
Sensitivity (Se), specificity (Sp), SFR, and number of patients that (cT1), has previously been shown to predict clinical outcomes. With
need to be tested to identify one true positive case (NNT) are this study we investigate the association of increasing cT1 thresholds
reported. with clinical outcomes.
Results: We included 2738 individual patient data from 25 primary Method: Imaging and outcomes data were collected at two tertiary
studies (43% female, median age 52 years, median BMI 29 kg/m2; 41% centers in the UK between May 2011 and July 2017 from patients
had type 2 diabetes; 57% had NASH, 28% had NASH+F2–3). Threshold referred to clinically indicated biopsy or known liver cirrhosis
combinations and corresponding SFR and NNT for single NIT diagnosis. Clinical outcomes data were collected as a composite
strategies are shown in Figure 1. Visual inspection of the SFR and endpoint comprising ascites, variceal bleeding, hepatic encephalop-
NNT distributions showed that increasing the upper NIT thresholds athy, hepatocellular carcinoma (HCC), liver transplantation and
above 20 kPa, 3.0 and 1.0 for LSM-VCTE, FIB-4 and NFS, respectively, mortality, more details described by Jayaswal et al. Liver Intl (2020)
does not improve diagnostic performance, so these were chosen as and in NCT01543646. Cox proportional hazard analysis was used to
upper cut-offs. LSM-VCTE thresholds of 6 kPa and 20 kPa (Se 80%, Sp calculate hazard ratios (HRs) for the continuous and grouped
44%, SFR 64%, NNT 4) had higher sensitivity, higher SFR and lower variables. Probability of clinical outcome for cT1 as a continuous
NNT, than thresholds 10 kPa and 20 kPa (Se 39%, Sp 83%, SFR 53%, NNT variable was used as reference and the HRs for each cut-off were used
9). FIB-4 thresholds 0.7 and 3.0 (Se 73%, Sp 33%, SFR 67%, NNT 6), only as scaling factors.
differed in sensitivity and specificity from thresholds 1.0 and 3.0 (Se Results: 182 patients, including 54% with NAFLD, with 620 years
58%, Sp 53%, SFR 67%, NNT 6). NFS thresholds −3.0 and 1.0 (Se 79%, Sp follow up were included in the analysis where 13 patients had liver
34%, SFR 68%, NNT 5), and −2.6 and 1.0 (Se 73%, Sp 43%, SFR 66%, NNT event occurrences, suggesting the overall risk of complications of 7%
5) had similar diagnostic performances. within the <72 months follow-up time. The events were ascites (5),
variceal bleeding (1), hepatic encephalopathy (2), HCC (3) and
mortality (9), with some patients having multiple events. cT1 had a
0.7% increased risk of clinical event for every 1 ms increase in cT1 (HR
= 1.007, 95% CI: 1.003–1.011, p = 0.0010), which is equivalent to 91%
increase of risk per 100 ms (HR 1.91). Patients with cT1 greater than
875 ms had 3.42 [95% CI: 1.05–11.11, p < 0.05] times higher risk to
experience an event before those with cT1 below or equal to 875 ms.
The cumulative probability of clinical events over time was higher for
patients with cT1 of greater than 875 ms, compared to those with
intermediate (800–875 ms) and low (<800 ms) cT1 (Fig. 1).

Sequential combinations of NITs could perform similarly to single

NITs, with fewer individuals needing LSM-VCTE and liver biopsy. FIB-
4 with cut-offs 0.7 and 4.63 followed by LSM-VCTE with cut-offs 6
and 20 kPa had Se 68%, Sp 59%, SFR 60%, NNT 5. NFS with cut-offs
−3.272 and 1.766 followed by LSM-VCTE with cut-offs 6 and 20 kPa
had Se 70%, Sp 56%, SFR 62%, NNT 5.
Conclusion: The major benefit of employing a sequential testing
strategy was the reduced number of liver biopsies. Additionally, we
noticed no further gain in diagnostic accuracy for the upper threshold
of NITs above a certain level, suggesting that a judicious choice of Conclusion: This study demonstrates that cT1 above 875 ms is not
thresholds can lead to a reduction in testing costs. only able to identify high-risk NASH patients, but also predicts who is
at higher risk for clinical events by evaluating patient health records
FRI109 and clinical outcomes. These results show the potential impact non-
Multiparametric MRI biomarker corrected T1 as a prognostic invasive mpMRI biomarkers can have to inform public health
marker in chronic liver disease strategies and mitigate the impact of the growing burden of NAFLD.
Naim Alkhouri1, Cayden Beyer2, Anneli Andersson2,
Elizabeth Shumbayawonda2, Michael Pavlides3, Arjun Jayaswal3,
Matt Kelly2, Stephen Harrison3. 1Arizona Liver Health, Fatty Liver
Program, Chandler, United States; 2Perspectum, Innovation, United
Kingdom; 3Oxford Centre for Magnetic Resonance (OCMR), Headington,
United Kingdom
Email: [email protected]
Background and aims: Liver biopsy is an imperfect reference test for
non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steato-
hepatitis (NASH), due to its invasive nature, 2.4% major complication
rate, high intra- and inter-reader variability and sampling error. The
utility of non-invasive technologies (NITs) as alternative tools for
NASH prognosis are assessed by their ability to predict clinical
outcomes. Non-invasive multiparametric magnetic resonance
imaging (mpMRI) with LiverMultiScan, and specifically corrected T1

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POSTER PRESENTATIONS
FRI110 Conclusion: SWE demonstrated good RDCDDDO, with slightly higher
Results of the Non-invasive Biomarkers of Metabolic Liver Disease RDCDDDO observed for VCTE. Considerably higher SWE variability is
(NIMBLE) study 1.1 on the reproducibility and repeatability of observed with measurements on different vendor platforms. These
shear-wave and transient elastography in non-alcoholic fatty liver estimates are likely to inform ultrasound-based NIT qualification by
disease (1) defining expected variability, (2) establishing that serial examin-
Theodore Pierce1,2, Arinc Ozturk1,2, Sarah Sherlock3, ation variability is lower when performed on the same vendor
Guilherme Cunha4, Xiaohong Wang5, Qian Li1,2, Marian Martin1, platform, and (3) informing future clinical trial design, including
Hannah Edenbaum1, Kathleen Corey2,5, Yesenia Covarrubias4, NIMBLE stage 2.
Sudha Shankar6, Helen Heymann7, Tania Kamphaus7, Roberto Calle8,
Nancy Obuchowski9, Arun Sanyal10, Rohit Loomba4, Claude Sirlin4, FRI111
Kathryn Fowler4, Anthony Samir1,2. 1Massachusetts General Hospital, Independent association of physical activity with nonalcoholic
Radiology, Boston, United States; 2Harvard Medical School, Boston, MA; fatty liver disease and alanine aminotransferase levels
3
Pfizer; 4University of California San Diego, La Jolla; 5Massachusetts Jun Kyu Lee1. 1Dongguk University Ilsan Hospital, Internal Medicine,
General Hospital, Fatty Liver Clinic; 6AstraZeneca; 7Foundation for the Goyang, Korea, Rep. of South
National Institutes of Health (FNIH), North Bethesda, United States; Email: [email protected]
8
Regeneron, United States; 9Cleveland Clinic; 10Virginia Commonwealth Background and aims: The aim of the current study was to examine
University the independent association of physical activity with nonalcoholic
Email: [email protected] fatty liver disease (NAFLD) and aminotransferases while adjusting for
Background and aims: The regulatory qualification of non-invasive obesity and diet.
tests (NITs) for liver fibrosis severity assessment is a major unmet Method: A data from 32, 391 participants aged ≥20 years in the Korea
need in non-alcoholic fatty liver disease (NAFLD). Ultrasound-based National Health and Nutrition Examination Surveys (KNHANES) was
methods such as shear-wave elastography (SWE) and vibration- analyzed by logistic regression models and general linear models.
controlled transient elastography (VCTE) have the potential, through Physical activity was assessed from the questionnaire by health-
repeated use, to assess disease response and progression. However, enhancing physical activity (HEPA).
this application has been limited by a paucity of reproducibility data Results: The physical activity was negatively associated with NAFLD
across device manufacturers in the population at risk. The aim of this after adjustment for multiple factors with an odds ratio of 0.66 (95%
study from the imaging workstream of the FNIH NIMBLE consortium CI, 0.57–0.76) comparing the most active (HEPA active) and the least
(NCT04828551), was to address this knowledge gap and contribute to active (inactive) participants. Among the participants with NAFLD,
the evidence needed for qualification of ultrasound-based methods. physical activity also showed an independent negative association
Method: A prospective two-center study of adults with suspected or with alanine aminotransferase (ALT) levels but not with aspartate
established NAFLD stratified by FIB-4 (≤1.3, >1.3 < 2.67, ≥2.67) to aminotransferase levels. These independent associations were not
reduce spectrum bias was performed. Each participant underwent 6 observed when comparing the minimally active and inactive
examinations on different ultrasound systems and VCTE on two days, participants.
each day by a different operator, less than a week apart. Sonographers
and clinical investigators were blinded and a pre-specified data chain
of custody was maintained. For uniformity, VCTE and SWE measure-
ments were reported and analyzed in units of meters per second by
an independent statistician. The primary end point was pooled
different-day, different-operator reproducibility coefficient
(RDCDDDO). Secondary endpoints included scanner-specific
RDCDDDO, same-day/same-operator repeatability coefficient
(RCSDSO), and between-vendor RDCSDSO. The study was powered to
detect a 95% RDCDDDO upper bound (UB95%) of ≤35%.
Results: 40 participants (mean age 60 years, 60% female) with low
(17), intermediate (15), and high (8) FIB-4 scores were recruited.
Mean body mass index was 30.9 kg/m2. RDCDDDO was 30.7% (UB95%
34.4%) for SWE and 35.6% (UB95% 43.9%) for VCTE. SWE vendor-
specific RDCDDDO varied from 24.2%–34.3%. RCSDSO was 21.0% for SWE Fig. 1. Flow diagram of participant inclusion and exclusion in the current
(13.9%–35.0%, by scanner) and 19.6% for VCTE. Between-vendor study using data from Korea National Health and Nutrition Examination
RDCSDSO was 52.7% (UB95% 64.7%). Surveys (KNHANES IV, V and VI).

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 POSTER PRESENTATIONS
and may suffice. The Quantitative Imaging Biomarker Alliance (QIBA)
has considered this question as part of their efforts to provide
guidelines on how MRE exams should be acquired and analyzed. Data
from drug development clinical trials are in many ways ideal to study
this kind of question, given that typically such studies are conducted
at large numbers of clinical sites using a wide variety of MR scanners
of different styles and field strengths, from different MR scanner
vendors. Hence, we undertook an analysis of MRE baseline and screen
failure imaging data from a clinical trial testing a potential new
treatment drug for NASH (NCT03439254; in progress) to determine
whether liver stiffness values differed as to whether weighted, or
simple means were used to generate final liver stiffness values for
each exam.
Method: 308 baseline and screen failure MRE exams were obtained
between October 2017 and December 2019 from 49 imaging sites
worldwide. 19 MR scanner styles were represented, including 1.5 T
and 3 T scanners from GE, Siemens, and Philips, with each exam using
either a 2D GRE or a 2D SE-EPI pulse sequence. After exclusion of 13/
308 (4.2%) of exams that were not analyzable, and 6/308 (1.9%) of
exams for which incorrect images were acquired, 289/308 (93.8%) of
exams were included in this analysis. Weighted and simple liver
stiffness means were calculated, and compared using regression,
Bland Altman, and Student t test analyses.
Results: Weighted liver stiffness means were not different from
simple means (5.51 ± 1.97 kPa vs. 5.50 ± 1.94 kPa, respectively; p =
0.11). On regression analysis, slope was 0.986, intercept was 0.07 kPa,
and the R2 value was 0.995. On Bland Altman analysis, weighted and
simple means differed by 0.01 ± 0.14 kPa. This difference is small
compared to typical variability due to inter-scanner reproducibility,
and is not clinically meaningful.

Fig. 2: Adjusted weighted means of ALT (upper) and AST (lower) by the
physical activity level among participants with NAFLD (n = 6, 968).

Conclusion: Physical activity is independently associated with the

degree of hepatocellular injury in patients with NAFLD as well as the
risk of NAFLD in the general population. Sufficiently active physical
activity greater than a minimally active level may be needed to lower
the risk of NAFLD and ALT levels.
Conclusion: In a multi-center NASH clinical trial in which sites were
FRI112 trained and site protocols qualified by a central analysis center before
In a nonalcoholic steatohepatitis (NASH) clinical trial, baseline study exams were acquired, no difference was observed between
and screen failure magnetic resonance elastography (MRE) liver baseline weighted and simple mean MRE liver stiffness values across
stiffness values calculated as weighted means were not different four acquired slices. This data will help inform ongoing work by QIBA
from values calculated as simple means in qualifying MRE liver stiffness as a quantitative imaging biomarker
Michael Middleton1,2, Mark Becker3, Walter Henderson1, of hepatic fibrosis.
Claude Sirlin1. 1University of California, San Diego, Radiology, San Diego,
FRI113
United States; 2Quantix Bio, Lewes, United States; 3Intercept
Influence of pregnancy on NAFLD-associated lipidomic signatures
Pharmaceuticals, Inc., San Diego, United States
Tatyana Kushner1, Ibon Martínez-Arranz2, Marco Arrese3,
Email: [email protected]
Mazen Noureddin4, Rhoda Sperling1, Keith Sigel1, Scott Friedman1,
Background and aims: Magnetic resonance elastography (MRE) liver Pablo Ortiz2, Cristina Alonso2. 1Icahn School of Medicine at Mount
stiffness, a quantitative imaging biomarker of hepatic fibrosis, is Sinai; 2OWL Metabolomics, Spain; 3Pontificia Universidad Catolica de
commonly used in nonalcoholic steatohepatitis (NASH) clinical Chile; 4Cedars Sinai
treatment trials. Typically, four images are acquired through the Email: [email protected]
liver, and means of liver stiffness, weighted based on region-of-
Background and aims: Although NAFLD-associated lipidomic
interest size are calculated to generate a single representative liver
signatures have been defined in the general population, there is
stiffness value for each exam. This is an appropriate method to use in
limited data on the influence of pregnancy on NAFLD-associated
clinical trials, but anecdotally it has been suggested that obtaining
simple, rather than weighted means for routine clinical care is easier

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POSTER PRESENTATIONS
lipidomic changes. In this study, we elucidate the deregulated Conclusion: Our findings suggest that NAFLD associated lipidomic
lipidomic serum landscape of pregnant women with NAFLD. signatures may be significantly impacted by pregnancy. NAFLD in
Method: We prospectively screened for NAFLD at 18–22 weeks pregnancy appears to be associated with a depletion in serum
gestation in pregnant women. Pregnant woman with NAFLD (n = 6) triglycerides and ceramides. Further workup should evaluate
and without NAFLD (n = 7) were matched 1:1 with retrospectively pregnancy-trimester specific changes as well as the role these lipid
collected cases from non-pregnant woman with and without NAFLD changes may play on NAFLD-associated adverse pregnancy outcomes
(n = 13) based on age-, BMI- and disease-stage. Lipidomic analysis of such as gestational diabetes or effects on the newborn.
serum samples collected under fasting conditions was performed
using ultra-high performance liquid chromatography-mass spec- FRI114
trometry, covering lipid species across classes of glycerolipids, Plasma sgp130 is an independent predictor of non-alcoholic fatty
glycerophospholipids ( phosphatidylinositol, acyl- and ether-linked liver disease severity
phosphatidylethanolamine (PE) and phosphatidylcholine (PC)), Aysim Gunes1,2,3, Laurent Bilodeau4, Catherine Huet4,
sphingolipids (ceramides, monohexosylceramides and sphingomye- Assia Belblidia4, Cindy Baldwin1, Jeanne-Marie Giard5,
lins), fatty acids and sterols (cholesteryl esters, steroids and bile Laurent Biertho6,7, Annie Lafortune6,7, Christian Couture6,8,
acids). Lipidomic profiles in pregnant females with vs. without NAFLD Bich N. Guyen9, Eithan Galun10, Chantal Bemeur11,12, Marc Bilodeau12,
and in pregnant females vs. non-pregnant matched female controls Mathieu Laplante3,6,13, An Tang4, May Faraj1,3,11, Jennifer Estall1,2,3.
1
were compared. Institut de recherches cliniques de Montréal (IRCM), Montréal, Canada;
2
Results: Pregnant women with NAFLD had higher PE, lysoPE and McGill University, Division of Experimental Medicine, Montréal,
lower ceramides compared to non-pregnant women with NAFLD (see Canada; 3Montreal Diabetes Research Centre, Canada; 4Hôtel Dieu de
Figure). Pregnant women with NAFLD had lower triglycerides Montréal-CHUM, Département de radiologie, Montréal, Canada; 5Hôtel
compared to non-NAFLD pregnant women; non-pregnant females Dieu de Montréal-CHUM, Département d’hépatologie, Montréal,
with NAFLD had higher triglycerides compared to non-pregnant Canada; 6University Institute of Cardiology and Respirology of Quebec,
females without NAFLD. Pregnant women without NAFLD were Québec, Canada; 7Laval University, Département de chirurgie, Québec,
significantly more likely to have lower saturated (SFA), monounsatu- Canada; 8Department of Molecular Biology, Medical Biochemistry and
rated (MUFA), and polyunsaturated fatty acids (PUFA) (p < 0.05), but Pathology, Québec, Canada; 9University of Montreal, Département de
have significantly higher triglyceride levels than non-pregnant pathologie et biologie cellulaire, Montréal, Canada; 10Goldyne Savad
women with NAFLD ( p < 0.05). Non-NAFLD pregnant women also Institute of Gene Therapy, Israel; 11University of Montreal, Département
had lower ceramides and ether linked-lysoPC compared to non- de nutrition, Montréal, Canada; 12Research Center Du Chum, Labo
pregnant women. HépatoNeuro, Montréal, Canada; 13Laval University, Centre de recherche
sur le cancer de l’Université Laval, Québec, Canada
Email: [email protected]
Background and aims: Nonalcoholic steatohepatitis (NASH) is a
metabolic disease associated with liver failure and cancer.
Monitoring of advancing NASH is challenging. Since liver inflamma-
tion is a main driver of fibrosis, we investigated relationships between
circulating components of the interleukin-6 signaling pathway (IL-6,
sIL-6R and sgp130) and liver pathology in subjects with NAFLD and
NASH.
Method: Predictive performance of plasma IL-6, sIL-6R and sgp130
were investigated in two independent cohorts: 1) patients with
biopsy-confirmed NASH (n = 49), where magnetic resonance spec-
troscopy (MRS), imaging (MRI) and elastography (MRE) assessed liver
fat, volume and stiffness; and 2) patients with morbid obesity (n =
245) undergoing bariatric surgery where histological staging of
steatosis, activity, and fibrosis assessed NASH severity. Correlations
were evaluated between IL-6, sIL-6R, sgp130 and anthropomorphic
characteristics, plasma markers of metabolic disease or liver
pathology.
Results: In patients with NASH, plasma IL-6 and sgp130 strongly
correlated with liver stiffness, which for sgp130 was independent of
age, sex, BMI, diabetes, hyperlipidemia, hypertension or history of
HCC. Plasma sgp130 was the strongest predictor of liver stiffness
compared to common biomarkers and risk scores. Plasma sIL-6R
correlated with liver volume independent of age, sex, and BMI. In
stepwise regression analysis, plasma sgp130 followed by NAFLD
fibrosis score and plasma globulin, predicted up to 74% of liver
stiffness. In patients with morbid obesity, circulating sgp130
correlated with advanced liver fibrosis.

Figure: Heatmaps of lipidomic profiles in pregnant women (with and

without NAFLD) compared to non-pregnant controls (with and without
NAFLD).

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 POSTER PRESENTATIONS
fibrosis and cirrhosis in pure MAFLD. However, FIB4 performed less
well for the prediction of cirrhosis in patients with MAFLD-ALD
compared to pure MAFLD (AUROC 0.83 vs 0.94, p = 0.005), while the
other scores performed similarly.

Table: Comparison of the diagnostic performance of non-invasive

fibrosis scores in MAFLD
Non-invasive Sensitivity Specificity
score AUROC 95% CI Cut-offs (%) (%)
Advanced fibrosis
FIB4 0.88 0.83–0.93 1.3 79 75
2.67 49 98
Figure: Advanced NASH is associated with liver failure and cancer; NFS 0.74* 0.66–0.81 −1.455 90 29
however, its detection in early stages is limited due to lack of non-invasive 0.676 43 89
biomarkers. Interleukin-6 is an important player in NAFLD at all stages, APRI 0.78* 0.72–0.84 0.5 68 72
involving multiple signaling mediators that circulate in blood. In biopsy- 1.5 12 97
confirmed NASH, plasma sgp130 was the best predictor of liver stiffness BARD 0.73* 0.66–0.8 2 84 43
and sIL-6R correlated with liver volume (MRI/MRE). In a second popula- 4 42 90
tion, high sgp130 was detected in subjects with advanced fibrosis (hist- Cirrhosis
ology). Circulating sgp130 may be a sensitive biomarker across all stages FIB4 0.94 0.92–0.97 1.3 92 72
of NASH linked to metabolic disease independent of sex, age and BMI in 2.67 67 97
progressive NAFLD. NFS 0.82* 0.73–0.91 −1.455 94 28
0.676 64 89
Conclusion: Levels of circulating sgp130 can predict progressing APRI 0.8* 0.73–0.87 0.5 76 69
NASH and may be used alone or in combination with other 1.5 16 97
biomarkers as a non-invasive measure of liver disease severity. BARD 0.79* 0.71–0.86 2 91 41
4 50 88
FRI115
*p < 0.05 significantly different to FIB4.
FIB-4 outperforms other serum non-invasive fibrosis tests in
metabolic associated fatty liver disease
Conclusion: FIB4 performs better than other serum non-invasive
Nikoletta Maria Tagkou1, Giulia Magini1,2, Laurent Spahr1,
tests for the prediction of advanced fibrosis and cirrhosis in MAFLD
Francesco Negro1,3, Jean-Louis Frossard1, Nicolas Goossens1,2.
1 ̀ e (HUG), Division of Gastroenterology patients, however its performance for the prediction of cirrhosis is
Hôpitaux Universitaires de Genev
̀ e, Switzerland; 2Hôpitaux Universitaires de reduced in the presence of alcohol abuse.
and Hepatology, Genev
Genev̀ e (HUG), Division of Transplantation, Genev ̀ e, Switzerland;
FRI116
3
Hôpitaux Universitaires de Genev̀ e (HUG), Division of Clinical
̀ e, Switzerland Presence of auto-antibodies has no impact on histological
Pathology, Genev
parameters in non-alcoholic fatty liver disease
Email: [email protected]
Ajeet Singh Bhadoria1, Kavita Jain2, Archana Rastogi2,
Background and aims: Metabolic associated fatty liver disease Chhagan Bihari2. 1All India Institute of Medical Science Rishikesh,
(MAFLD) is a recently proposed terminology to replace non-alcoholic Community and Family Medicine, Rishikesh, India; 2Institute of Liver and
fatty liver disease (NAFLD) but non-invasive fibrosis scores have not Biliary Sciences, New Delhi, India
been validated in this population. Additionally, MAFLD definition Email: [email protected]
broadens the disease spectrum by including the overlap with alcohol
related liver disease (MAFLD-ALD). We therefore aimed to determine Background and aims: Presence of auto-antibodies have been
the diagnostic performance of non-invasive fibrosis scores in MAFLD documented with liver diseases like viral hepatitis, drug induced
and whether the coexistence of alcohol abuse affects their hepatitis and non-alcoholic fatty liver disease (NAFLD). However,
performance. significance and impact of these autoantibodies on histological
Method: We retrospectively collected data of 409 consecutive MAFLD severity of NAFLD yet needs to be explored. Previous reports on
patients undergoing liver biopsy at our institution from 2007 to 2021. association of autoantibodies with histological severity in other
We stratified our patients by excessive alcohol consumption defined cohorts have revealed inconsistent results. Therefore, this study was
as >20 g/day in females and >30 g/day in males. The following scores undertaken to document the impact of auto-antibodies on histo-
were calculated with previously published cutoffs: NFS, FIB4, APRI logical parameters of NAFLD.
and BARD. Advanced fibrosis was considered as F3–4 and cirrhosis as Method: All cases with histological diagnosis of NAFLD during Jan
F4 fibrosis on liver biopsy. Diagnostic performance was assessed by 2016–Jan 2021 were included in the study. Laboratory parameters
analysis of the area under receiver operating characteristic curve were recorded and histological assessment was done utilizing Ishak’s
(AUROC) and sensitivity/specificity calculations. modified system. Positivity of autoimmune markers was defined as
Results: Among 409 patients, 277 (66.4%) had pure MAFLD and 132 presence of either Anti-nuclear Antibody (ANA; titre of >1:80), anti-
(31.7%) had MAFLD-ALD. Baseline characteristics in pure MAFLD vs smooth muscle antibodies (ASMA), or anti-liver-kidney-microsomal
MAFLD-ALD were: age (51.2 vs 58.2, p < 0.001), male sex (49.5 vs antibodies (LKM-1; titre of >1:40). Demographic, biochemical,
87.9%, p < 0.001), BMI (36.9 vs 30.4 kg/m2, p < 0.001), diabetes (51.1 vs serologic and histological characteristics were compared between
69.2%, p = 0.001), advanced fibrosis (27.7 vs 71.2%), cirrhosis (17.5 vs cases with and without any antibody positivity. Serum levels of CK18-
63.6%), NASH (37.3 vs 32.6%, p = 0.406) and median steatosis M30 and PIIINP were evaluated by ELISA to assess the subtle changes
proportion (50 vs 30%, p < 0.001). In pure MAFLD, the AUROCs of in necro-inflammatory activity and fibrosis.
FIB4, NFS, APRI, and BARD for advanced fibrosis were 0.88, 0.74, 0.78 Results: Out of 1149 NAFLD cases screened, complete autoantibody
and 0.73, respectively (Table). The same AUROCs for predicting status was known for 683 cases. Autoantibodies were present in 281/
cirrhosis were 0.94, 0.82, 0.8 and 0.79, respectively. When comparing 683 (41.1%, 95% CI 37.4–44.9) patients. ANA, ASMA, ANA plus ASMA
the AUROCs, FIB4 performed significantly better than the other non- was seen in 20.9% (95% CI 17.9–24.2), 14.5% (95% CI 11.9–17.4) and
invasive scores ( p < 0.001) for the prediction of both advanced 5.7% (95% CI 4.1–7.7) cases, respectively. LKM-1 was not seen in any
case. No significant difference was noted between the two groups in

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POSTER PRESENTATIONS
terms of age, gender, body mass index, platelet levels, serum IgG, liver S3: >66%) for PDFF resulted in gross misclassification of especially
function parameters, ferritin, fasting glucose, fasting insulin, and those patients with histological steatosis above grade S1 (kappa =
HbA1c and lipid profile ( p > 0.05). No significant difference was noted 0.32; Fig. B-C). Median PDFF values corresponding to each steatosis
in histological parameters between the groups. However, mean CK18- grade were 2.2% for S0, 8.0% for S1, 18.9% for S2, and 25.2% for S3.
M30 and PIIINP showed a rising trend with NAFL, NASH, NASH+AIH
(χ2 trend p < 0.001). Mean CK18-M30 between cases with negative
autoantibody, ANA positivity, ASMA positivity and combined posi-
tivity of autoantibody were 178.2 ± 81.8, 161.6 ± 63.7, 153.2 ± 70.3 and
169.8 ± 42.9, respectively ( p = 0.57).
Conclusion: Auto antibodies were present in more than one third of
NAFLD cases, with ANA positivity in one fifth and presence of ASMA
in more than one in ten cases. No significant necro-inflammatory
activity or fibrosis was seen with presence of auto-antibodies.
However, CK-18-M30 and PIIINP showed a significant rising trend
from NAFL to NASH to NASH+AIH.
Conclusion: Histological and PDFF measurements of liver fat are
FRI117 fundamentally different. While they are in reasonable agreement at
Marked underestimation of liver fat content as measured by levels around the diagnostic threshold for NAFLD (∼5%), histological
magnetic resonance versus histology—a systematic review and steatosis far surpasses PDFF in patients with moderate-to-severe fatty
meta-analysis liver. This difference should be acknowledged in guidelines for NAFLD
Sami Qadri1,2, Kimmo Porthan1,2, Anne Juuti3, Anne Penttilä3, to prevent misjudgement of the clinical status or treatment effect in
Juhani Dabek1,2, Tiina E. Lehtimäki4, Wenla Seppänen4, patient care.
Johanna Arola5, Perttu Arkkila6, Hannele Yki-Järvinen1,2. 1University
of Helsinki and Helsinki University Hospital, Department of Medicine, FRI118
Helsinki, Finland; 2Minerva Foundation Institute for Medical Research, Disease severity assessment of metabolic dysfunction-associated
Helsinki, Finland; 3University of Helsinki and Helsinki University fatty liver disease in Taiwan
Hospital, Department of Gastrointestinal Surgery, Abdominal Centre, Jee-Fu Huang1,2,3, Pei-Chien Tsai1, Ching-I Huang1,3, Ming-Lun Yeh1,3,
Helsinki, Finland; 4Helsinki University Hospital, HUS Medical Imaging Chung-Feng Huang1,3, Chia-Yen Dai1,3, Ming-Lung Yu1,3,
Centre, Helsinki, Finland; 5University of Helsinki and Helsinki University Wan-Long Chuang1,3. 1Kaohsiung Medical University Hospital,
Hospital, Department of Pathology, Helsinki, Finland; 6Helsinki Hepatobiliary Division, Department of Internal Medicine, Kaohsiung,
University Hospital and University of Helsinki, Department of Taiwan; 2Kaohsiung Medical University Hospital, Hepatitis Center,
Gastroenterology, Abdominal Centre, Helsinki, Finland Kaohsiung, Taiwan; 3Kaohsiung Medical University, Faculty of Internal
Email: [email protected] Medicine, College of Medicine, Kaohsiung, Taiwan
Email: [email protected]
Background and aims: Magnetic resonance spectroscopy (MRS) and
imaging (MRI) measure liver fat via the proton density fat fraction Background and aims: Disease severity in metabolic dysfunction-
(PDFF), which reflects the tissue volume fraction of hepatic associated fatty liver disease (MAFLD) has rarely been investigated in
triacylglycerols. Intuitively, PDFF would be predicted to give lower Asians. The study aimed to assess the fibrosis stages of MAFLD in a
values of steatosis compared to histology, which estimates the community-based cohort in Taiwan. We also aimed to compare the
percentage of lipid droplet-laden hepatocytes out of all hepatocytes. differences of features between different definitions as well as the
We conducted a systematic review and meta-analysis of patient-level interaction between metabolic factors and viral factors.
data to characterise the linearity and agreement between PDFF and Method: The retrospective case-control study was performed in
histological steatosis across the full spectrum of fatty liver. adult subjects participating liver disease screening in Southern
Method: Following the PRISMA guideline, we searched PubMed, Taiwan. The items of liver disease screening included HBsAg, anti-
Scopus, Web of Science, and the Cochrane Library until February 20, HCV, transaminases, and metabolic profiles in a voluntary basis.
2022, to identify all studies showing data on histological macro- Abdominal sonography was performed for those who had viral
vesicular steatosis percentage and MRS/MRI-PDFF in adults with hepatitis or elevated transaminase levels. According to the MAFLD
non-alcoholic fatty liver disease (NAFLD) or in living liver donor diagnostic criteria we stratified the subjects into: group A for type 2
candidates. We invited authors to submit individual patient data for diabetes, group B for BMI>23 kg/m2, and group C of BMI≤23 kg/m2
pooled analysis. Linearity between PDFF and histological steatosis subjects who carried at least 2 metabolic items, respectively. Disease
was assessed using Pearson’s correlation, linear regression, and severity was assessed by non-invasive Fibrosis-4 (FIB-4) Index.
mixed-effects models. Agreement was assessed using Bland-Altman Advanced fibrosis was defined as FIB-4 value>3.25.
analysis and intraclass correlation coefficient (ICC) for continuous Results: From 2009 to 2020, there’re 5, 180 subjects who had fatty
data and Cohen’s kappa for graded classification. Risk-of-bias was liver index (FLI)>60 and has fatty liver on sonography. We recruited 1,
assessed using QUADAS-2. 948 subjects (mean age = 51.5 ± 13.4 years, females 52.1%) who met
Results: The eligible studies numbered 11 (3 with MRI-PDFF and 8 the diagnostic criteria of MAFLD and had completed results for
with MRS-PDFF; N = 755). The relationship between PDFF and fibrosis assessment. The study pool included 1, 470 (75.5%) NBNC
histological steatosis was highly linear (r = 0.82, p < 0.0001), and NAFLD subjects and 478 subjects possessing concomitant liver
their values were fairly similar at low levels of liver fat (<5–10%). diseases such as viral hepatitis infections and alcoholism. There
However, the higher the liver fat, the more PDFF underestimated were 395 (20.3%) of Gr A, 1, 818 (93.3%) of Gr B, and 44 (2.3%) subjects
steatosis as compared to histology (Fig. A). On the average, of Gr C, respectively. Advanced fibrosis on FIB-4 was observed in 79
histological steatosis was 2.7-fold higher than PDFF, and the fractional (4.1%) subjects. The subjects of Gr C had a significantly higher
underestimation by PDFF tended to increase from low to high levels percentage (20.5%, 9/44) of advanced fibrosis than Gr A (4.1%, 16/395)
of liver fat. A histological steatosis of 100% corresponded to an average and Gr B (3.6%, 65/1, 818) ( p < 0.001). Excluding those who had
PDFF of 33% (Fig. A). The ICC for absolute agreement between the concomitant liver diseases, the subjects of Gr C still had a significantly
measures was 0.43, denoting poor reliability, and for consistency higher percentage (15%) of advanced fibrosis than Gr A (1.8%) and Gr
between the measures 0.52, denoting moderate reliability. Use of the B (1.4%) ( p = 0.003). Multivariate regression analysis demonstrated
common NAFLD grading of steatosis (S0: <5%; S1: 5–33%; S2: 34–66%; that HBV/HCV co-infection (OR = 16.74, 95% CI = 4.62–60.67, P <

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 POSTER PRESENTATIONS
0.001), HCV infection (OR = 8.83 95% CI = 4.79–16.30, P < 0.001), Gr C
(OR = 6.94, 95% CI = 2.65–18.15, P < 0.001), and age (OR = 1.08, 95% CI
= 1.05–1.11, P < 0.001) were significant factors for predicting the
subjects with advanced fibrosis.
Conclusion: Lean MAFLD Taiwanese subjects carrying metabolic
abnormalities had a higher chance of advanced fibrosis than others in
a community-based setting.

FRI119
Optical analysis of liver magnetic resonance images (MRI) 3 T to
detect steatohepatitis features: the program DeMILI 3.0.
Isabel Fernández-Lizaranzu1,2, Emilio Gomez-Gonzalez2,
Sheila Gato Zambrano1, Rocío Montero-Vallejo1,
Enrique Claudio Fernandez3, Juan Carlos Diaz Martin3,
Rebeca Sigüenza4, Rocío Aller4, Maria Angeles Martin Prats5,
Manuel Romero Gomez6. 1Institute of Biomedicine of Seville, Seville,
Spain; 2Universidad de Sevilla, Higher Technical School of Engineering
(ETSI), Group of Interdisciplinary Physics (GFI), Seville, Spain; 3Virgen del
Rocio University Hospital, Department of Radiology, Spain; 4Hospital
Clínico Universitario de Valladolid, Spain; 5Universidad de Sevilla,
Department of Electronic Engineering, Spain; 6Institute of Biomedicine of
Figure: ROC curves of LRs (v1 and v2) for training and validation subsets.
Seville, Seville, Spain
Email: [email protected] Conclusion: Initial results with limited cohorts show that DeMILI 3.0
detects steatohepatitis in patients with NAFLD with a diagnosis
Background and aims: DeMILI in MRI 1.5 T has been proved as useful
accuracy of 0.73 (DeMILI 3.0-v1). Validation cohorts include patients
to detect steatohepatitis in patients with non-alcoholic fatty liver
from other center than training. DeMILI 3.0-v1 yields results close to
disease (NAFLD) (Gallego-Durán et al. Sci Rep 2016). The aim of this
DeMILI using 1.5 T MRI.
study was to evaluate the potential of optical processing methods
applied to non-enhanced contrast liver 3 T MRI to predict steatohe- FRI120
patitis in NAFLD patients. The fibrosis-4 cut-off value for significant fibrosis is dependent on
Method: Seventy-nine biopsy-proven NAFLD patients recruited the type of non-alcoholic fatty liver disease patients
between October 2019 and December 2021 at ‘Virgen del Rocío’
Leen Heyens1,2,3, Wouter Robaeys1,2, Christophe Van Steenkiste4,5,
University Hospital (HUVR, n = 68) and Valladolid Clinical University
Sven Francque5,6, Geert Robaeys1,2,7. 1Hasselt University, Faculty of Life
Hospital (HCUV, n = 11). Main characteristics: 50.6 % female, 21.5%
Sciences and Medicine, Hasselt, Belgium; 2Ziekenhuis Oost-Limburg,
<45 years old and 32.9% >65 years old, 55.6% showed steatohepatitis
Gastro-enterology and Hepatology, Genk, Belgium; 3Maastricht
in the liver biopsy. 3.0 T MRI was conducted using a whole-body
University, Faculty of Health, Medicine and Life Sciences, Maastricht,
Philips® scanner without contrast medium. 3 different sequences
Netherlands; 4Maria Middelares, Gastro-enterology and Hepatology,
were performed in axial plane: SSFSE-T2 (Single Shot Fast Spin Echo
Gent, Belgium; 5University of Antwerp, Gastro-enterology and
T2-weighted), FAST-STIR (Fast Short inversion Time Inversion
Hepatology, Antwerpen, Belgium; 6Antwerp University Hospital, Gastro-
Recovery) and DYNAMIC. The entire liver was imaged and 6
enterology and Hepatology, Edegem, Belgium; 7UZ Leuven Gasthuisberg
consecutive slices, per each sequence, were manually selected
Campus, Gastro-enterology, Leuven, Belgium
covering the whole organ. 84 physical and mathematical feature
Email: [email protected]
descriptors (estimators) were computed from every image. Principal
Component Analysis was performed to extract the main estimators Background and aims: Non-alcoholic fatty liver disease (NAFLD) has
related to steatohepatitis and two logistic regressions (LR) were built: become the most frequent cause of chronic liver disease. The fibrosis
The first one (DeMILI 3.0-v1) used estimators E63, E12 and E21, n = 43 stage has been identified as the most important predictor of
HUVR patients for training, and n = 36 patients (25 HUVR + 11 HCUV) prognosis. The Fibrosis-4 (FIB-4) is an easy-to-use non-invasive
for validation. The second LR (DeMILI 3.0-v2) was built with score to predict fibrosis based on routine blood parameters. However,
estimators E70, E12 and E21 and the same cohort in different we previously showed that the 1.3 FIB-4 cut-off value had a low
subsets: training n = 64 from HUVR, and validation n = 15 (4 HUVR + performance to detect significant fibrosis (≥F2) in a primary care (PC)
11 HCUV). Receiver operating characteristic (ROC) curves were population. We aimed to determine whether NAFLD-group-specific
obtained. optimal FIB-4 cut-off values can be determined to identify patients
Results: ROC curves for DeMILI 3.0-v1 and DeMILI 3.0-v2 are shown with a high likelihood of ≥F2, considered an at-risk population to be
in Figure 1. The area under the ROC curves (AUROC) obtained were: i) referred for further management.
for DeMILI 3.0-v1, AUROC = 0.7378 for training set and AUROC = Method: In a prospective study in the Belgian regions of Limburg,
0.7307 for validation set, and ii) for DeMILI 3.0-v2, AUROC = 0.7958 East-Flanders, and Antwerp, patients were screened in seven PC
for training set and AUROC = 0.6071 for validation set. practices. Type 2 diabetes mellitus patients (T2DM) were screened in
the hospital of Ziekenhuis Oost-Limburg. As a proxy of the fibrosis
stage, liver stiffness was determined using Vibration Controlled
Transient Elastography (VCTE) by FibroScan® (Echosens, France) and
used as the reference method. The FIB-4 was calculated based on
recent laboratory data from the electronic patient file. The Youden
Index (J) was used to determine the optimal cut-off value for
detecting ≥F2 (>7.9 kPa for the M-probe and >7.2 kPa for the XL-
probe) in three populations: PC (unselected all-comers), T2DM
screened in PC (T2DM-PC, PC subgroup), T2DM screened in a hospital
(T2DM-H).

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POSTER PRESENTATIONS
Results: Of the 816 (424 (52.0%) PC, 103 (12.6%) T2DM PC, and 289 physicians to gauge the risk of NAFLD in volunteers, using two
(35.4%) T2DM-H) screened patients, 534 (65.4%) had FIB-4 values and variables (GGT and waist circumference), with high sensitivity and
no other causes of steatosis but NAFLD. Of these, 275 (51.5%) were acceptable specificity (E score sensitivity 90%, specificity 45%, CAP
male, median age was 63 (26–71) years, median BMI 29.8 (26.2– score sensitivity 85.5%, specificity 81.9%).
33.46) kg/m2, median waist circumference 104.0 (97.0–113.0) cm for
men and 98.0 (86.1–110.0) cm for women, and 276 (51.9%) had T2DM.
The number of patients with ≥F2 was 30 (11.8%), 20 (30.3%), and 96
(45.7%) for the PC, T2DM-PC, and T2DM-H cohorts. Using logistic
regression, both FIB-4 ( p < 0.05) and the type of NAFLD-group
significantly ( p < 0.05) contributed to ≥F2. The area under the
operating curve (AUROC) of the model was 0.76 compared to an
AUROC of 0.61 using only FIB-4. The maximum J was 0.40461 and
corresponded to a sensitivity of 0.61 and specificity of 0.80. Using the
linear predictor, the optimal cut-off value per population was 4.3 for
the PC cohort, 2.3 for the T2DM-PC, and 0.66 for the T2DM-H cohort.
These cut-off values were not influenced by age or the grade of
steatosis as measured by controlled attenuation parameter (CAP).
Conclusion: The optimal cut-off value of the FIB-4 score for detecting
NAFLD-associated significant fibrosis depends on the patient groups’
characteristics, potentially resulting from the different prevalence of
the condition in the respective groups. However, the cut-off values
were not influenced by age or the severity of the steatosis.

FRI121
Developing an algorithm to predict NAFLD in clinical trial
volunteers-interim report NCT04873258
Jörg Täubel1,2,3, Dominic Pimenta4, Aviva Petrie5, Lydia Sulaiman6,
Ulrike Lorch3, Kevin Moore5. 1St George’s University of London, United
Kingdom; 2Richmond Research Institute, London, United Kingdom;
3
Richmond Pharmacology, United Kingdom; 4Richmond Research
Institute, London, United Kingdom; 5University College London, United Figure: Prototype NAFLD clinical tool (Alpha).
Kingdom; 6King’s College London, United Kingdom Conclusion: Our early interim analysis shows promising results,
Email: [email protected] sufficient to prototype a clinical tool with high sensitivity and
Background and aims: Non-alcoholic fatty liver disease (NAFLD) acceptable specificity for screening out individuals in clinical trials at
affects around 1 in 4 of the global adult population, and ranges in high probability of occult NAFLD and/or fibrosis. Future work to
severity from benign fatty liver infiltration, to hepatitis, cirrhosis and develop the underlying model, advance machine learning models to
hepatocellular carcinoma. NAFLD has important implications for further improve performance, and deliver to clinic is underway.
clinical trial volunteers as an occult co-morbidity. NAFLD may
modulate drug metabolism, and studies have suggested that Grade FRI122
III/IV liver reactions are 4x commoner in healthy volunteers with Correlation of ultrasound derived fat fraction (UDFF) with MRI
probable NAFLD than without. We therefore aimed to develop a non- (PDFF): possibilities and analysis of confounding factors
invasive tool, utilizing new technology, to predict NAFLD in this Reinhard Kubale1,2, Marcin Krawczyk3,4, Paul Lessenich1,
population. This is our interim report (NCT04873258) Arno Bücker1, Aaron Engel5, Andrzej Milkowski5,
Method: This is an ongoing observational cross-sectional study Guenther Schneider2. 1Saarland University Hospital, Homburg,
design. Volunteers attend the unit for a single day of biomarker Germany; 2Saarland University, Saarbrücken, Germany; 3Saarland
assessment, including bioimpedance vector analysis (%visceral fat, University Hospital, Department of Internal Medicine II-
total body fat% and skeletal muscle %), anthropometric measurement Gastroenterology, Hepatology, Endocrinology, Diabetology, and
(BMI, waist circumference), and lab bloods. A FibroScan is performed Nutritional Medicine, Homburg, Germany; 4Innere II, Homburg/Saar,
as a pragmatic gold standard ‘outcome’ for NAFLD, and E (fibrosis) Germany; 5Siemens Healthineers, Forchheim, Germany
and CAP (steatosis) scores are recorded. Traditional multivariate Email: [email protected]
linear and logistic regression is performed, correlating biomarkers Background and aims: Ultrasound derived Fat fraction (UDFF) is a
with linear E and CAP scores, and ‘significant’ disease (≥F2, E >7.5 kPa quantitative sonographic method based on a combination of
and ≥S2, CAp >260 dB) respectively. Alongside this machine learning attenuation and backscatter coefficients. Aim of the study was to
models are trained (Python {sklearn, TensorFlow}) and performance evaluate feasibility and correctness in correlation with MRI (PDFF:
compared. Proton density fat fraction) and to analyze confounding factors.
Results: Interim results: 290 individuals (of extended target 1500) Method: Examinations were done with 2 US-machines (Sequoia and
with demographics as follows; 61% male, 51.5% Caucasian, average S2000: Siemens) with 5C1, DAX and 6C1 transducers with an
age of 39.4 years, 40% of the cohort had diabetes. The overall algorithm based on a phantom corrected combination of attenuation
prevalence of significant fibrosis (E score ≥7.5 kPa) was 11.4% and the (AC) and backscatter coefficient (BSC). Measurements of a ROI of
prevalence of significant steatosis (CAP ≥260 dB) was 35.6%. A logistic 9 cm2 were correlated with MRI PDFF values of the whole liver and a
regression model was trained for E and CAP scores, identifying key ROI in the right liver lobe (RLL) in the same position (Vida, Siemens-
features in the dataset as waist circumference and GGT. A prototype LiverLab®). To test the reproducibility we examined in a pilot study
clinical score was derived, with an AUC of 0.81 for E and 0.89 for CAP 20 patients with two UDFF-measurements on different days. The
scores. Machine learning models were compared, with the best effect of fasting state was tested by performing UDFF before, 1, 3 and 5
performing model being Gaussian Naïve Bayes for E (AUC 0.82) and hours after a standard meal. The main study consists of 194
Decision Tree for CAP (0.79). A clinical tool based on a score derived
from logistic regression coefficients was created (Figure) for use by

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 POSTER PRESENTATIONS

Figure: (abstract: FRI122): Comparison of Multiparametric Assessment of UDFF with PDFF in patients with 2, 1 % and 26%.

consecutive patients (112 male, 82 female), who received a liver MRI FRI123
for clinical reasons. ELF to identify NASH and fibrosis in non-alcohol related fatty liver
Results: In the pilot study (Study I) PDFF of the whole liver (10.3 ± disease
9.4%), was significantly higher than in the corresponding ROI (8.65 ± Richard Parker1, Peter Eddowes2, Natasha McDonald3,
9.6%). The correlation of PDFF-measurements with scan heads (5C1, Philip N. Newsome2, Gideon Hirschfield4, Jonathan Fallowfield3,
DAX, 6C1) were r = 0.94/0.91 and 0.85. Repeated measurements Ian Rowe5. 1Leeds Teaching Hospital Trust, Leeds Liver Unit, Leeds,
showed values of r = 0.99/0.97 and 0.89 with best reproducibility of United Kingdom; 2University of Birmingham, Centre for Liver Research,
the DAX. Measurements before, 1, 3 and 5 hours after meal showed no Birmingham, United Kingdom; 3MRC/University of Edinburgh Centre for
significant differences between the time points (Friedmann-Test). Inflammation Research, Queen’s Medical Research Institute, Edinburgh,
The main study shows a significant difference in PDFF-measurement Edinburgh, United Kingdom; 4University of Toronto, Division of
of the whole liver (11.6 ± 9.1%) and the ROI (8.9 ± 9.5%). Although AC Gastroenterology, Toronto, Canada; 5University of Leeds, Leeds Institute
and BSC are not linear related to PDFF the model with both for Medical Research, Leeds, United Kingdom
parameters shows a significant correlation between UDFF and PDFF Email: [email protected]
of the whole liver and the corresponding ROI and Voxel for all patients
r = 0.80/0.7 and 0.6 (6C1). Bland-Altmann shows, that main con- Background and aims: The current paradigm for eligibility for trials
founding factors are severe liver cirrhosis with a small RLL, in NAFLD requires the presence of NASH and fibrosis of particular
chemotherapy/lipiodol application, sarcoidosis and amyloidosis. severity. We examined whether the ELF score could be repurposed to
Problems in MRI arose in severe Hemochromatosis, patients over predict both NASH and fibrosis.
150 kg due to artifacts. Method: A cohort of 240 patients with biopsy-proven NAFLD was
Conclusion: UDFF shows a strong positive correlation with PDFF. used. Treatment threshold was NAS ≥4 (as per the FLIP algorithm)
Confounding factors could be identified hypothetically allowing for and fibrosis grade of greater than 2. The cohort was split 60:40 into
improvement in the future. UDFF could be a screening tool for early modelling and validation groups. Internal validation of modelling
diagnosis of NAFLD and a biomarker for therapy control. was done using 2000 bootstrapped samples. Test performance was
evaluated with AUROC analysis. Low and high cut-offs at 90%
sensitivity or specificity respectively were calculated in the modelling
cohort, and negative and positive predictive values (NPV, PPV) and
positive and negative diagnostic likelihood ratios (PDLR, NDLR)

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POSTER PRESENTATIONS
calculated. The model was calibrated graphically in the validation
cohort and test performance confirmed. All statistical tests were done
in R using pROC, rms and ggplot2 packages.
Results: The average age of the cohort was 55 years, 117 (66%) were
male. All components of the ELF score correlated with NAS and were
significantly different between patients with NAS <4 or ≥4. A model
(‘ELF-t’) that included all of the ELF parameters (HA, P3P and TIMP-1)
performed best to identify cases suitable for trials or treatment
(AUROC 0.74). At a low cut-off ELF-t had a NPV of 91% and the high
cut-off gave a PPV of 92%. NDLR was 0.27 (0.12–0.607), PDLR 2.47
(1.15–5.31). Calibration was good in the validation cohort with similar
test performance (AUC 0.79, NPV 91%, PPV 93%).
Conclusion: The constituent markers of the ELF test can be
repurposed to assess the likelihood of NAFLD with sufficient activity
and scarring to meet common eligibility criteria for clinical trials,
which are likely to translate into a paradigm for treatment as new
drugs come to market. This provides a non-invasive method for
assessing patients as an alternative to liver biopsy.

FRI124
Performance of the Steatosis-Associated Fibrosis Estimator (SAFE)
to predict F2 fibrosis and higher in a cohort of South Korean
patients with non-alcoholic fatty liver disease (NAFLD)
Vivek Charu1, Allison Kwong1, Ajitha Mannalithara1, Eileen Yoon2, Conclusion: In a cohort of Korean adults with NAFLD, the SAFE score
Dae Won Jun2, W. Ray Kim1. 1Stanford University School of Medicine, performs better than FIB-4 or NFS to predict F2 fibrosis or higher
Stanford, United States; 2Hanyang University College of Medicine, Korea, based on FibroScan measurement. A SAFE threshold of greater than
Rep. of South 100 has reasonable, but not perfect, negative predictive value for
Email: [email protected] identifying F2 fibrosis or greater in this cohort (0.88). Evaluating the
Background and aims: The Steatosis-Associated Fibrosis Estimator performance of the SAFE score in additional diverse cohorts is
(SAFE) score is a recently developed scoring system to categorize essential to assess its utility in identifying patients at low risk of
NAFLD patients by their risk of having significant liver fibrosis (F2 or having clinically significant fibrosis.
higher). Here we evaluate the performance of the SAFE score in
predicting F2 fibrosis based on transient elastography (FibroScan) FRI125
measurements in a cohort of South Korean patients with NAFLD. FIB-4 combined with positron emission tomography biomarkers
Method: We identified a cohort of adult patients with a clinical detects fibrotic NASH
diagnosis of NAFLD who underwent FIbroScan at Hanyang University Sean Romeo1, Connie Chan2, Blake Shaw3, Karen Matsukuma4,
from 2020 to 2022. Using the available laboratory information, we Michael Corwin5, Victoria Lyo6, Shuai Chen3, Guobao Wang5,
calculated SAFE, Fibrosis-4 (FIB-4) and the NAFLD fibrosis score (NFS) Souvik Sarkar1,7. 1University of California, Davis, Internal Medicine/
for each patient. Our outcome of interest was F2 fibrosis or higher, and Gastroenterology and Hepatology, United States; 2UC Davis School of
a FibroScan threshold of greater than 7 kPa was used. We computed Medicine, Sacramento, United States; 3University of California, Davis,
the area under the receiver operating curves (AUROC) to quantify the Public Health Sciences/Biostatistics, United States; 4University of
performance of each non-invasive score to predict F2 fibrosis or California, Davis, Pathology and Laboratory Medicine, United States;
5
greater. We calculated the sensitivity, specificity, positive predictive University of California, Davis, Radiology, United States; 6University of
value and negative predictive values of the SAFE score using an California, Davis, Surgery, United States; 7Florida Research Institute,
apriori determined threshold of greater than or equal to 100. Lakewood Ranch, United States
Results: We identified 749 patients with a clinical diagnosis of NAFLD Email: [email protected]
who underwent FibroScan testing with clinical/laboratory data to Background and aims: Non-alcoholic steatohepatitis (NASH) is a
generate SAFE, FIB-4 and NFS scores (Table). SAFE, FIB-4 and NFS were severe form of non-alcoholic fatty liver disease (NAFLD) that is
strongly correlated with each other in this cohort ( pairwise associated with liver cirrhosis and hepatocellular cancer. Methods for
Spearman’s correlations: SAFE-FIB4: 0.83; SAFE-NFS: 0.80; FIB4- diagnosing NASH without liver biopsy are limited, therefore
NFS: 0.84). We estimated the AUROC for each fibrosis estimator presenting an urgency to noninvasively detect NASH by character-
(Table), and found that the AUROC for the SAFE score (0.76) was izing features: steatosis, inflammation, and fibrosis. We combined the
significantly higher than that for FIB-4 (0.64) and NFS (0.63) ( p- well-established non-invasive fibrosis-4 (FIB-4) measurement with a
values for DeLong’s tests: SAFE-FIB4, <2.2e-16; SAFE-NFS, 6.352e-16). recent 18F-fluorodeoxyglucose (FDG) positron emission tomography/
FIB-4 and NFS scores had similar AUROC (0.64 and 0.63, p-value for computed tomography (PET/CT) imaging approach for NASH to
DeLong’s test: 0.5822). Using a threshold for the SAFE score of greater elucidate imaging determinant of fibrotic NASH.
than 100 to identify high-risk patients would result in a sensitivity of Method: The study was approved by the institutional review board.
0.66 (95%CI: 0.58–0.73), specificity of 0.74 (95%CI: 0.70–0.78), Patients ≥18 years with NAFLD who had undergone liver biopsy were
positive predictive value of 0.42 (95%CI: 0.36–0.48) and negative enrolled. FDG transport rate (K1) by dynamic PET and CT Hounsfield
predictive value of 0.88 (95%CI: 0.85–0.91) for predicting F2 fibrosis units (CTHU) were determined from liver regions-of-interest (ROI) as
or higher based on FibroScan measurements. previously defined, while FIB-4 was calculated from serum by an
established criterion. Liver biopsies were scored per NASH-CRN
(Clinical Research Network) criteria. Fibrotic NASH was defined as
NAFLD activity score (NAS) ≥4 with Kleiner fibrosis stage ≥2. Severe
fibrotic NASH was defined as NAS ≥5, plus fibrosis stage ≥3.
Correlations among parameters were calculated using the

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 POSTER PRESENTATIONS
Spearman correlation. Receiver operating characteristics (ROC) (APRI). Participants were divided into four groups according to MMA
analyses were performed with cut-off selected based on Youden’s levels (<120, 120–175, 175–250 or >250 (nmol/L)).
Index, where FIB-4, K1 and CTHU were combined using logistic Results: The prevalence of MAFLD was 38.3, 40.6, 42.1 and 39.8% ( p =
regression. 0.068) and the prevalence of participants with advanced fibrosis risk
Results: Of 45 enrolled patients, 31 were female, 54 ± 13 years, and was 2.0, 3.5, 5.6, 10.6% ( p < 0.001) in four consecutive MMA groups.
BMI 34.0 ± 5.7 kg/m2; 16% of patients had inflammation >3, while 58% Compared with participants with lower MMA levels, higher MMA
had NAS >4 and 29% with fibrosis ≥3. FIB-4 correlated with fibrosis levels had a higher prevalence of diabetes, hypertension and
significantly (r = 0.58, p < 0.001), as expected, but not with NAS (r = dyslipidaemia, increased ALT, and decreased vitamin B12, RBC and
0.2, p = 0.178). K1 and CTHU showed significant correlations with NAS. platelet counts. Higher MMA levels were not independently
As shown prior, the dual-variate model of K1+CTHU could detect associated with NAFLD ( p for trend: 0.997). MMA>250 nmol/L
clinical NASH but not fibrotic NASH. When FIB-4 score was combined independently increased the risk of advanced fibrosis by one fold in
in the model it was able to detect fibrotic NASH with an AUC of 0.781 MAFLD patients (OR 95% confidence interval:2.05 (1.37, 3.08)), but
(Figure 1) and severe fibrotic NASH with an AUC of 0.845. The triple not in non-MAFLD participants (OR 95%CI:1.81 (0.93, 3.54)). The
variate model of 1.46001*K1–0.04009*CTHU + 1.27309*FIB-4 association between MMA and fibrosis was consistent among
≥1.574408, was able to predict fibrotic NASH with a sensitivity of different subgroups stratified by alcohol intake, BMI, blood glucose,
83% and a specificity of 64%. While 3.27447*K1 + 0.00597*CTHU + pressure or lipids ( p for interaction >0.05). The area under the
0.99330*FIB-4 ≥−1.296305 predicted severe fibrotic NASH with a receiver operator characteristics curve (ROC AUC) of MMA in
sensitivity of 91% and specificity 68%. detecting fibrosis in MAFLD was 0.658 (0.658, 0.658), which was
higher than that of C-reactive protein 0.540 (0.540, 0.540) ( p < 0.001).
Conclusion: MMA was independently associated with advanced
fibrosis risks in MAFLD, and this association was unaltered in
subgroups stratified by different metabolic profiles or lifestyles.
This finding indicated a possibility of using MMA as a novel candidate
non-invasive biomarker and therapeutic target for fibrosis in MAFLD.

Fibrosis

FRI146
Hepatic angiocrine HGF attenuates liver fibrogenesis via
modulation of PDK1/AKT axis
Jianye Wang1, Sarah Schulze1, Victor Olsavszky2, Kai Schledzewski2,
Cyrill Géraud2, Helmut Friess1, Norbert Hueser1, Daniel Hartmann1.
1
Klinikum rechts der Isar der Technischen Universität München,
München, Germany; 2Medical Faculty Mannheim, Heidelberg University,
Mannheim, Germany
Email: [email protected]
Background and aims: Hepatocyte growth factor (HGF) is a complete
hepatic mitogen and is believed to play a role in liver fibrogenesis and
hepatocarcinogenesis. Liver sinusoidal endothelial cells (LSEC) can
recruit inflammatory cells by releasing angiocrine signals to produce
Conclusion: Combination of non-invasive serum and imaging tests HGF in the process of liver fibrosis and cirrhosis, but the precise
enabled detection of clinical fibrotic NASH. Studies in larger and contributions of HGF from LSEC to liver fibrosis remain elucidated.
diverse cohorts will enable establishing this tool for determination of Method: To investigate the effects of hepatic angiocrine HGF on liver
clinical changes in NAFLD patients. fibrogenesis, Stab2-Cretg HGFfl/fl (HGFLSEC-KO) mice, in which HGF is
specifically switched off in LSEC, were used. Carbon tetrachloride
FRI126 (CCl4) injection was performed in these mice and the kinetics of the
Mitochondria-derived methylmalonic acid is associated with ratio of liver to body weight, immunohistochemistry for liver fibrosis,
advanced fibrosis risks in metabolic dysfunction-associated fatty Western blot and RT-PCR for fibrotic markers, HGF/c-MET signaling
liver disease (MAFLD): results from the NHANES 1999–2004 pathways and cell cycle-associated genes were determined after
Qi Huang1, Li Li1, Linjian Yang1, Linong Ji1, Xiantong Zou1. 1Peking initiation of cirrhosis.
University People’s Hospital, China Results: We found that HGFLSEC-KO mice showed no difference in the
Email: [email protected] liver-to-body-weight ratio compared to the control group after early-
stage CCl4 treatment. After fibrogenesis, HGFLSEC-KO mice had a higher
Background and aims: Methylmalonic acid (MMA) is related to
expression of collagen 1A1 and alpha-SMA and the proliferation of
mitochondrial dysfunction, which is a key process of fatty liver
hepatocytes was significantly impaired in HGFLSEC-KO mice. In
disease. This study aimed to investigate the association between
addition, the LSEC-specific HGF deficiency reduced the c-met level
MMA and metabolic dysfunction-associated fatty liver disease
and thus deactivated the PDK1 (3-phosphoinositide-dependent
(MAFLD) using large epidemiological data.
protein kinase-1)/Akt pathway while hepatic angiocrine HGF did
Method: We included 12, 494 individuals from the National Health
not alter immune cell infiltration.
and Nutrition Examination Survey (NHANES) 1999–2004. MAFLD
Conclusion: The hepatic angiocrine HGF signaling pathway plays a
was diagnosed with Fatty Liver Index (FLI) ≥60 or USFLI≥30, and
crucial role in the early stages of liver fibrogenesis. The hepatic
participants with advanced fibrosis risks were identified with
angiocrine HGF signaling pathway is essential not only for liver
elevated non-alcoholic fatty liver disease fibrosis score (NFS),
fibrosis-4 (FIB4) or aspartate aminotransferase (AST): platelet ratio

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POSTER PRESENTATIONS
recovery during fibrogenesis, but also for the growth of the liver and Conclusion: This nanogel platform and the presented delivered drug
even the entire organism. conjugate AL/NP may serve as a novel, highly effective tool to treat
Key words: hepatocyte growth factor (HGF), liver sinusoidal liver fibrosis and possibly other diseases that are dominated by M2-
endothelial cells (LSEC), hepatocytes, liver, fibrogenesis, liver type macrophages.
cirrhosis
FRI148
FRI147 Preclinical evaluation of the calpain inhibitor BLD-3051 as a
Bisphosphonate-loaded nanogels attentuate liver fibrosis by therapeutic strategy for liver fibrosis
repolarization of M2-type macrophages C. Wong1, J.-X. Huang1, W. Yu1, P. Ibrahim1, Ravi Rajagopalan1. 1Blade
Leonard Kaps1, Anne Huppertsberg2, Niklas Choteschovsky1, Therapeutics, Inc, South San Francisco, United States
Adrian Klefenz1, Feyza Durak3, Barbara Schoers3, Mustafa Diken3, Email: [email protected]
Emma Eichler1, Sebastian Rosigkeit1, Sascha Schmitt2, Christian Leps4,
Background and aims: Calpains are a family of non-lysosomal
Friedrich Foerster1, Ernesto Bockamp1, Bruno Degeest5,
intracellular calcium-dependent cysteine proteases that perform
Federico Marini6, Kaloian Koynov7, Stefan Tenzer4, Detlef Schuppan1,
limited proteolytic cleavage of its substrates that in turn modulate a
Lutz Nuhn7. 1University Medical Center Mainz, Institute of Translational
variety of signaling pathways controlling phenotypic effects like cell
Immunology and Research Center for Immune Therapy, Mianz, Germany;
2 proliferation, migration, differentiation, and apoptosis. Elevated
Max Planck Institute for Polymer Research, Mainz, Germany;
3 dimeric calpain activity levels are implicated in a variety of disease
University Medical Center Mainz, TRON-Translational Oncology, Mainz,
pathologies including fibrotic diseases. Additionally, calpain knock-
Germany; 4University Medical Center Mainz, Institute of Immunology,
outs and small molecule dimeric calpain inhibitors are efficacious in
Mainz, Germany; 5Ghent University, Department of Pharmaceutics and
animal models of fibrosis. We have generated multiple calpain
Cancer Research Institute Ghent (CRIG), Belgium, Belgium; 6University
inhibitors with significantly improved potency, protease selectivity,
Medical Center Mainz, Institute of Medical Biostatistics, Epidemiology
and ADMET properties that may represent important new anti-
and Informatics, Mainz, Germany; 7Max Planck Institute for Polymer
fibrotic agents. Here, we describe the properties of BLD-3051, a small
Research, Mainz
molecule dimeric calpain inhibitor and characterize its activity in a
Email: [email protected]
therapeutic model of liver fibrosis.
Background and aims: In liver fibrosis, M2-type macrophages Method: 8-week-old C57BL/6 mice were fed a choline-deficient, L-
promote the replacement of functional parenchyma by collagen- amino acid, high fat diet (CDAHFD) for the entire 10-week study
rich scar tissue. Bisphosphonates impaired the polarization towards duration. Oral gavage dosing of BLD-3051 was initiated on week 5 of
M2-type macrophages and demonstrated an anti-fibrotic/-tumor CDAHFD and continued for 6 weeks. Once daily (QD) doses of 60 and
effect in murine models of mesothelioma and liver cancer [V. JD et al., 200 mg/kg and twice daily (BID) doses of 30 and 100 mg/kg were
Br J Cancer. 2010; T. L. Rogers et al., J Transl Med. 2011]. But, evaluated. Body and liver weight and liver enzyme panel data were
pharmacokinetics of bisphosphonates are poor for liver targeting as collected. Histopathology by modified NAFLD activity score (NAS) and
they are rapidly excreted by the kidneys after intravenous (iv) liver hydroxy-proline levels were used to assess anti-fibrotic efficacy.
application. Here, we aimed to treat liver fibrosis by repolarizing liver Results: BLD-3051 reduced NAS scores and liver hydroxy-proline
M2-type macrophages towards an antifibrotic M1-type via a levels in a dose-dependent manner with BID dosing being more
biocompatible, pH-degradable, nanogel carrier system conjugated efficacious. The lowering of NAS by BLD-3051 is largely driven by an
to the bisphosphonate alendronate (AL). anti-fibrotic effect.
Method: In primary murine macrophages, AL/NP (∼30 μM AL)
induced no cytotoxic effect and repolarized M2-type polarized
macrophages towards a M1-type, increasing the expression of the
M1-type related markers TNF-α, CCL-2 and downregulated the M2-
type markers IL-10 and chitinase YM-1 on the transcript and protein
level as determined via qPCR and flowcytometry (FACS).
Results: After iv injection in CCl4 fibrotic Balb/c mice, more than 80%
of near-infrared fluorescence labeled (CS800)-AL/NP rapidly accu-
mulated in the liver, whereas CS800-AL were instantly cleared via the Conclusion: BLD-3051 is a potent, selective, orally bioavailable
kidneys. On the cellular level, CS800-AL/NP were effectively engulfed calpain inhibitor that when dosed therapeutically shows robust
by non-parenchymal cells (e.g. liver macrophages), while the AL/NP’s anti-fibrotic effects against multiple endpoints in a CDAHFD induced
uptake was significantly lower in parenchymal cells (hepatocytes) as model of liver fibrosis. BLD-3051 is currently in preclinical
determined by FACS. CS800-AL/NP were well tolerated and showed development.
no overt toxicity. For fibrosis induction, Balb/c mice were gavaged
with CCl4 for 5 weeks. At week 4, mice received two iv injections of
AL/NP (∼2 mg/kg or 4 mg/kg AL) per week while control groups
received equal concentrations of AL or NP, respectively. At the end of
week 5, mice were sacrificed and liver collagen and the surrogate
marker α-SMA were significantly reduced to physiological levels in
AL/NP treated vs. control mice as determined by HYP quantification,
Sirius Red readout and immunohistochemistry, while free AL and NP
had no significant effect. Transcriptomic and proteomic data from
total liver tissue of AL/NP (∼4 mg/kg AL) treated vs. control mice (n =
3) revealed an upregulation of proinflammatory pathways and an
enrichment of M1-type macrophages related genes in the treated
mice, suggesting that AL/NP treatment triggers a switch from M2- to
M1-type macrophages. In addition, we showed a downregulation of
the M2-type markers YM-1, CD206 and IL-10 in the treated vs. control
fibrotic liver both on the transcript and protein expression level.

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 POSTER PRESENTATIONS
FRI149 by lysosomal proteases, cathepsins, in liver fibrosis, our knowledge of
Experimental fibrosis alters matrix-bound vesicles cargo that do their specific targets and signaling networks remains limited. Thus,
not revert after histologic recovery the aim of this study was to analyse cathepsin D (CtsD) cell-specific
Toshifumi Sato1,2, Bashar Matour3, Jiang Li2, Michael Merchant4, role in hepatocytes during liver fibrosis.
Daniel Wilkey4, Kenichi Ikejima1, Stephen Badylak3,5, Method: To study the cell-specific role of CtsD we generated a novel
George Hussey5,6, Melanie Scott3,7, Gavin Arteel2,7. 1Juntendo knock-out mouse strain by breeding Albumin Cre (hepatocytes) mice
University Hospital, Gastroenterology, Bunkyo City, Japan; 2University of with CtsD floxed mice. CtsD cell-specific deletion was confirmed by
Pittsburgh-Department of Medicine, Gastroenterology, Pittsburgh, CtsD WB in primary mouse hepatocytes and dual IF (F4/80-CtsD) in
United States; 3University of Pittsburgh, Surgery, Pittsburgh, United liver sections. Fibrosis was established using bile duct ligation (BDL)
States; 4University of Louisville, Medicine, Louisville, United States; for 14 days or chronic administration of CCl4 (0.5 μl/g) twice a week
5
University of Pittsburgh, McGowan Institute for Regenerative Research, for 8 weeks in CtsDF/F and CtsDΔHep mice. Liver damage was
Pittsburgh, United States; 6University of Pittsburgh, Pathology, determined by serum ALT and H&E staining in liver sections. CtsD
Pittsburgh, United States; 7Pittsburgh Liver Research Center, University was assessed by enzymatic activity assay and RTPCR. Fibrosis was
of Pittsburgh, Pittsburgh, United States analysed by Sirius Red staining α-SMA IHP and α-SMA, Col1A1 and
Email: [email protected] TGF-beta RTPCR. Liver inflammation was determined by NIMP and
F4/80 IHP and TNF-α, CCL2 and CCL3 RTPCR.
Background and aims: Although it is now understood that hepatic
Results: First we determined CtsD expression in mouse fibrotic livers,
fibrosis can resolve, potential therapies to enhance fibrosis resolution demonstrating CtsD presence in hepatocytes and macrophages. CtsD
are lacking. MBV are nanometer-sized vesicles bound within the ECM
cell-specific deletion in hepatocytes was validated by CtsD WB in
collagen network. Changes in MBV cargo may contribute, at least in primary mouse hepatocytes and dual IF (F4/80-CtsD) in liver section
part, to the phenotypic changes driven by fibrosis and recovery.
from CtsDF/F and CtsDΔHep mice. Of note, CtsD expression remained
Method: Fibrosis was induced by injecting male C57BI/6J mice with
unaffected in liver non-parenchymal cells. In addition, adult
CCl4 (1 ml/kg 2 × /wk 4wks); animals were sacrificed 1–28 days later. unchallenged CtsDΔHep mice displayed normal liver damage deter-
Liver injury and fibrosis was monitored by clinical chemistry,
mined by ALT and H&E staining in liver sections. Next, fibrosis was
histology and gene expression. MBV were extracted from the livers established for 14d using BDL. CtsD deletion in CtsDΔHep livers was
of mice and the trypsinized MBV proteome cargo was analyzed by LC- confirmed by CtsD activity assay and gene expression. CtsD deletion
MS/MS analysis using a Proxeon EASY-nLC 1000 UHPLC and
in hepatocytes, did not affect liver damaged (ALT) and liver fibrosis as
nanoelectrospray ionization into an Orbitrap Elite mass spectrometer. determined by Sirius red staining, α-SMA IHP and hepatic α-SMA,
Feature data were extracted and analyzed using Proteome Discoverer
Col1A1 and TGF-beta gene expression. Furthermore, liver inflamma-
v2.4. Hierarchical clustering of significantly-changed MBV proteins
tion was also not significantly affected in CtsDΔHep mice after BDL as
was performed using StringDB and KEGG classification. To investigate assessed by NIMP and F4/80 IHP and TNF-α, CCL2 and CCL3 gene
the effect of MBV on the recovery of liver fibrosis, normal MBV from
expression. In agreement, no significant changes in liver damage,
porcine urinary bladder (30 mg/mouse i.p.) were injected for up to 2 fibrosis and inflammation were observed after chronic CCl4 admin-
weeks after cessation of CCl4.
istration between CtsDF/F and CtsDΔHep mice supporting our results in
Results: Fibrosis caused by CCl4 rapidly resolved after cessation,
the BDL model.
reverting to almost normal histology and expression after 28 d Conclusion: CtsD expressed in hepatocytes does not play an essential
recovery. The amount and type of proteins associated with the MBV
contribution to liver fibrosis development after cholestatic-induced
tended to decrease in fibrosis, which was not reversed even after liver injury.
fibrosis recovery. StringDB and KEGG analysis indicated that the
proteins lost in fibrosis/recovery were predominantly RNA-binding FRI151
proteins associated with the ribosome, which may also impact the The therapeutic potential of alpha v integrins in liver fibrosis
RNA cargo of the MBV. Some mice injected with normal MBV Syedia Rahman1,2,3, Guruprasad Aithal1,3, Jane Grove1,3, K. Tao Pun4,
accelerated the fibrotic resolution. James Roper4, Andrew Bennett1,2,3. 1NIHR Nottingham Biomedical
Conclusion: Liver MBV alter their protein cargo in response to Research Centre, Nottingham University Hospitals NHS Trust and
experimental fibrosis. Importantly, these changes do not revert to University of Nottingham, Nottingham, United Kingdom; 2FRAME
baseline levels even after almost complete histological recovery of Alternatives Laboratory University of Nottingham Medical School, Life
fibrosis. These data suggest MBV may be a novel prospect for Sciences, Nottingham, United Kingdom; 3Nottingham Digestive Diseases
mechanistic insight into hepatic disease progression and recovery. Centre, Medicine, Nottingham, United Kingdom; 4GlaxoSmithKline,
Novel Human Genetics Research Unit, United Kingdom
FRI150
Email: [email protected]
Hepatocyte cell-specific deletion of cathepsin D does not affect
liver inflammation and fibrosis during cholestatic-induced liver Background and aims: Hepatic stellate cells (HSC) are the primary
fibrosis effector cells in liver fibrosis and they secrete inactive transforming
Maria Fernandez-Fernandez1,2, Paloma Ruiz-Blazquez2,3, growth factor beta (TGFbeta) which, when activated through proteins
Valeria Pistorio3,4, Susana Núñez2,5, M. Carmen Garcia-Ruiz2,5,6,7, known as alpha v integrins, contributes to liver fibrosis. These
José Fernandez-Checa2,5,6,7, Anna Moles2,3,6. 1Institute of Biomedical integrins are composed of beta 1, 3, 5, 6 and 8 subunits. Specific
Research of Barcelona (IIBB-CSIC), Experimental Pathology, Barcelona, inhibitors which target alpha v integrins and their particular beta
Spain; 2CiberEHD, Spain; 3Institute of Biomedical Research of Barcelona subunit have shown to reduce fibrosis progression in mouse models
(IIBB-CSIC), Experimental Pathology, Barcelona, Spain; 4University of but their role has not been explored in human liver disease. We aimed
Naples Federico II, Italy; 5Institute of Biomedical Research of Barcelona to assess integrin expression on activated human HSCs and the level
(IIBB-CSIC), Cell Death and Proliferation, Barcelona, Spain; 6IDIBAPS, of integrin expression in human liver samples from patients with
Barcelona, Spain; 7USC Research Center for ALPD, United States varying degrees of fibrosis. Subtype selective integrin inhibitors were
Email: [email protected] tested to determine their capability to inhibit HSC activation and
their effect on TGFbeta activity. This has previously never been
Background and aims: During liver fibrosis proteolytic activity is performed before using human samples.
regulated in a timely manner in infiltrating and liver-resident cells Method: HSCs were isolated from healthy individuals, integrin gene
depending on the cellular demands and controls not only matrix and protein expression was measured using qPCR and western blot.
turnover but also, the activation and repression of growth factors and Tissue expression of integrins on fibrotic human liver tissue was
chemokines. Despite our growing understanding of the roles played

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S465

POSTER PRESENTATIONS
examined using a novel technique known as RNAscope®. To assess FRI152
TGFbeta activity in HSCs, HSCs were co-cultured with mink lung Dual inhibition of integrins alpha-v/beta-6 and alpha-v/beta-1
epithelial TGFbeta reporter cells which were used to detect levels of decreases portal pressure and liver fibrosis in rats with biliary
active TGFbeta. cirrhosis
Results: There was gene and protein expression of alpha v, beta 1, 3 Philipp Königshofer1,2,3,4,5, Johanna Schaub6,
and 5 integrins with the exception of beta 6 on activated human Ksenia Brusilovskaya1,2,3,4,5, Benedikt Hofer1,2,3,
HSCs. There was high gene expression of alpha v, beta 1, 3, 5 and 8, Benedikt Simbrunner1,2,3,4,5, Oleksandr Petrenko1,2,3,4,5,
normalized to beta-actin. We show, for the first time, an identical Hubert Scharnagl7, Tatjana Stojakovic7, Philipp Schwabl1,2,3,4,5,
pattern of integrin expression observed in fibrotic human liver tissue Eric Lefebvre6, Scott Turner6, Thomas Reiberger1,2,3,4,5. 1Medical
which showed increased expression compared to healthy controls. In University of Vienna, Division of Gastroenterology and Hepatology,
co-culture assays, antibodies to alpha v, beta 1 and beta 3 integrins Vienna, Austria; 2Medical University of Vienna, Vienna Experimental
inhibited the increase in active TGFbeta, while antibodies to beta 5 Hepatic Hemodynamic Lab (HEPEX), Vienna, Austria; 3Medical
and beta 6 integrins did not have any effect. From the subtype University of Vienna, Christian Doppler Laboratory for Portal
selective compounds tested, a beta 1 inhibitor, prevented the TGFbeta Hypertension and Liver Fibrosis, Vienna, Austria; 4Ludwig Boltzmann
increase in a dose-dependent manner while a beta 6 inhibitor did Institute for Rare and Undiagnosed Diseases (LBI-RUD), Vienna, Austria;
not. 5
CeMM Research Center for Molecular Medicine of the Austrian
Academy of Sciences, Vienna, Austria; 6Pliant Therapeutics, Inc., South
San Francisco, United States; 7University Hospital Graz, Clinical Institute
of Medical and Chemical Laboratory Diagnostics, Graz, Austria
Email: [email protected]
Background and aims: Transforming growth factor-beta (TGF-beta)
signalling is a key driver of liver fibrosis. In primary sclerosing
cholangitis (PSC), integrins overexpressed on injured cholangiocytes
(alpha-v/beta-6) and myofibroblasts (alpha-v/beta-1) regulate TGF-
beta activity; they bind and activate latent TGF-beta thereby
promoting liver fibrosis. We investigated the effects of PLN-75068,
a tool alpha-v/beta-6 and alpha-v/beta-1 inhibitor compound, on
liver fibrosis and portal hypertension in rats with cholestatic biliary
cirrhosis.
Method: Male Sprague Dawley rats underwent bile duct ligation
(BDL) or sham operation (SHAM). Two weeks post-surgery, BDL rats
received PLN-75068 100 mg/kg (BDL-LOW), 300 mg/kg (BDL-HIGH),
riociguat ([RIO], BDL-RIO; positive control) 0.5 mg/kg or vehicle
([VEH], BDL-VEH), and SHAM rats received VEH (SHAM-VEH) twice
daily via oral gavage for 2 weeks. Portal pressure (PP), mean arterial
pressure (MAP), heart rate and splanchnic/portal blood flow were
measured at end of treatment. Alanine transaminase (ALT), aspartate
transaminase (AST), alkaline phosphatase (ALP) and bilirubin (BIL)
were assessed. Fibrosis was quantified by automated morphometry of
Conclusion: In activated HSCs, there was gene and protein expression
collagen proportionate area (CPA) on Picro-Sirius red-stained full
of integrins beta 1, 3 and 5 with similar integrins expressed on fibrotic
liver lobe sections and assessment of hydroxyproline (HP).
human liver tissue, not reported previously. A beta 1 integrin
Results: Cirrhotic vehicle control rats (BDL-VEH) showed signifi-
inhibitor compound successfully inhibited TGFbeta activation in a
cantly higher values of PP (12.2 ± 1.9 vs 6.8 ± 0.9 mmHg; p < 0.001)
dose-dependent manner. This shows the exciting potential of beta 1
and CPA (13.8 ± 4.3 vs 1.1 ± 0.2%; p < 0.001) compared with SHAM-
integrin specifically being a successful treatment target for liver
VEH. Elevated PP in BDL rats was lowered with treatment: BDL-LOW
fibrosis.
(−10%; p = 0.009), BDL-HIGH (−9%; p = 0.26) and BDL-RIO (−10%; p =
0.02). MAP was significantly reduced in all treated groups (BDL-LOW:
−22%; BDL-HIGH: −27%; BDL-RIO: −24%; all p < 0.001) vs BDL-VEH.
CPA was decreased with treatment: BDL-LOW (−28%; p = 0.04), BDL-
HIGH (−41%; p = 0.003) and BDL-RIO (−29%; p = 0.03) compared with
BDL-VEH (Figure). HP levels were comparable across all BDL rats
(VEH: 489 ± 163 ug/g; LOW: 508 ± 111 ug/g; HIGH: 473 ± 114 ug/g;
RIO: 476 ± 174 ug/g). ALT was significantly lower with treatment:
BDL-LOW (63 ± 10 U/L; −26%), BDL-HIGH (58 ± 12 U/L; −32%) and
BDL-RIO (59 ± 9 U/L; −31%) all p < 0.001, compared with BDL-VEH
(85 ± 17 U/L). Treatment with RIO significantly reduced AST ( p =
0.03), but ALP and BIL remained unchanged in all treated animals
compared with BDL-VEH. Weight loss was observed in BDL-HIGH but
was not statistically significant.

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 POSTER PRESENTATIONS
expression level is positively correlated with patients’ survival. PSMP
deficiency (Psmp −/−) resulted in a marked amelioration of hepatic
fibrosis, but promoted liver tumor growth in mice. Damage-
associated molecular patterns molecules HMGB-1 and IL-33 signifi-
cantly induced hepatocytes to produce PSMP. In CCl4-induced hepatic
injury, the infiltration of CCR2+ monocytes and macrophages into the
liver is significantly decreased in Psmp −/− mice. In HCC, knockout of
PSMP can inhibit the infiltration of tumor-infiltrating CD8+ lympho-
cytes and promote M2-polarization of tumor-associated macro-
phages (TAMs) in mice. At the cellular level, we found that PSMP can
directly promote the M1 polarization of bone marrow-derived
macrophages and the activation of LX-2 cells, and also inhibit the
proliferation and migration of HCC cells.

Conclusion: In rats with biliary cirrhosis, dual alpha-v/beta-6 and

alpha-v/beta-1 inhibition by PLN-75068 ameliorated portal hyper-
tension, exerted dose-dependent anti-fibrotic effects as assessed by
CPA and significantly reduced ALT levels. A multinational Phase 2a
evaluation of PLN-74809 in participants with PSC is ongoing
(INTEGRIS-PSC; EudraCT: 2020–001428-33; NCT04480840).
Conclusion: In conclusion, PSMP can promote liver fibrosis, while
FRI153
inhibit liver carcinogenesis. These results indicate that PSMP may
Dual roles of PSMP/MSMP in the progression of hepatic fibrosis
play different or even opposite functions in different stages of liver
and hepatocellular carcinoma
disease, suggesting that PSMP is a potential target for the treatment
Shaoping She1, Liying Ren2, Pu Chen1, Dongbo Chen1, of chronic liver disease and HCC.
Hongsong Chen1. 1Peking University People’s Hospital, Peking
University Hepatology Institute, Beijing Key Laboratory of Hepatitis C FRI154
and Immunotherapy for Liver Diseases, Beijing, China; 2Affiliated NKT cells promote both type 1 and type 2 inflammatory responses
Hospital of Guilin Medical University, Laboratory of Hepatobiliary and in the non-obese diabetic inflammation and fibrosis (NIF) mouse
Pancreatic Surgery, Guilin, China model
Email: [email protected] Julia Nilsson1,2, Maria Hörnberg1, Kajsa Linde1, Dan Holmberg1,2,
Background and aims: Chemokines are a family of cytokines that Sofia Mayans1. 1InfiCure Bio AB, Umeå, Sweden; 2Lund University,
orchestrate the migration and positioning of immune cells within Experimental Medical Science, Malmö, Sweden
tissues and are critical for the function of the immune system. PC3 Email: [email protected]
secreted microprotein (PSMP) or microprotamine (MSMP) is a novel Background and aims: Sterile liver inflammation and fibrosis are
chemotactic cytokine discovered through genome-wide bioinfor- associated with many liver disorders of different etiologies. Both type
matics analysis and chemoattractant platform screening, which can 1 and type 2 inflammatory responses have been reported to
act as a CCR2 ligand to recruit peripheral blood monocytes and contribute to liver pathology and the mechanisms controlling the
lymphocytes. CCR2 participates in liver pathology, including acute balance between these responses are largely unknown. Here we use
liver injury, chronic hepatitis, fibrosis/cirrhosis and tumor progres- the non-obese diabetic inflammation and fibrosis (NIF) mouse model
sion, by mediating the recruitment of immune cells to inflammation for chronic liver inflammation and fibrosis to investigate the role of
and tumor sites. In the present study, we investigated the expression NKT cells in the different phases of sterile liver inflammation.
and role of PSMP in liver fibrosis/cirrhosis and hepatocellular Method: Transgenic mice overexpressing a NKT cell population in the
carcinoma (HCC). presence or absence of an adaptive immune system was analyzed and
Method: PSMP expression was studied in patients and murine the role of this population in the generation of chronic liver
models of fibrosis/cirrhosis and HCC. The role of PSMP in vivo was inflammation and fibrosis was examined.
evaluated in PSMP gene knockout mice. The direct effects of PSMP on Results: We demonstrate that transgenic NKT cells, when developing
macrophages, hepatic stellate cells and tumor cells were studied in in an immunodeficient Rag2 −/− genetic background (the NIF mouse),
vitro. expresses a mixed Th1/Th2 cytokine profile, which induces IL-1β
Results: In this study, we found that PSMP is highly expressed in production through the NLRP3 pathway that initially result in the
fibrotic/cirrhotic tissues from patients with multiple etiologies. PSMP development of chronic liver inflammation. This phase is followed by
is also overexpressed in human liver cancer-adjacent tissues, and its the development of a type 2 inflammatory response including the

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POSTER PRESENTATIONS
expression of the IL-33 alarmin, production of anti-inflammatory/ imaged and assessed using qFibrosis system, and generated a total of
profibrotic cytokines, the activation of the TGFβ pathway, and 33 and 156 collagen parameters from liver tissue and tumor part,
recruitment of activated hepatic stellate cells (HSC) which results in respectively. We used these collagen parameters to build two models,
the development of liver fibrosis. This process is controlled by the PVT-index and Meta-index, to differentiate the patient’s clinical
adaptive immune system since littermate controls carrying one outcome of PVT and Meta, respectively. The models were validated
functional Rag2 allele and developing a normal adaptive immune using leave-one-out method.
system, fail to develop chronic liver inflammation and fibrosis. Results: Both developing PVT and metastasis were significant
indicators for poor prognosis. Seven parameters were selected from
the parameters of liver tissue and tumor part to build the PVT-index
and Meta-index, respectively. The PVT-index well differentiates
patients developing PVT ( p < 0.001 for training, p = 0.030 for
validation, Figure), and the Meta-index also well differentiate
patients developing metastasis during follow-up ( p < 0.001 for
training, p = 0.024 for validation, Figure).

Conclusion: Our data illustrates how plasticity in NKT cells can drive
an initial type 1 inflammatory response and promote the transition
into a type 2 inflammatory response thus overlapping key cellular
and molecular events characterizing human liver diseases such as e.g.
NAFLD/NASH. Further, the data suggests that this process is
controlled by some component (s) of the adaptive immune system.
The observed mechanistic overlap with human liver disease suggest
that the NIF mouse model represents a unique tool for drug efficacy
tests in liver inflammation and/or fibrosis with large translational
Conclusion: Prognostic estimation models consist of collagen
potential as illustrated in the figure.
parameters in qFibrosis system could be built to predict HCC patient’s
FRI155 clinical outcomes of developing PVT and Meta during follow-up after
Using qFibrosis analysis to predict disease and survival outcome radical treatment. Our results demonstrated the potentials of using
of patients with hepatocellular carcinoma after curative qFibrosis system to transform the histopathological features into
treatment quantifiable data that could be used to correlate with patient
Chih-Yang Hsiao1,2, Dean Tai3, Yayun Ren3, Kai-Wen Huang1,2. outcome as other clinical biomarkers.
1
National Taiwan University Hospital, Department of Surgery, Taipei,
FRI156
Taiwan; 2National Taiwan University, Graduate Institute of Clinical
Multi-target engagement effect of a novel long-acting Glucagon/
Medicine, College of Medicine, Taipei, Taiwan; 3HistoIndex Pte Ltd,
GIP/GLP-1 triple agonist, HM15211, in animal model of NASH/
Research, Singapore, Singapore
fibrosis
Email: [email protected]
Jong Suk Lee1, Jung Kuk Kim1, Seonmyeong Lee1, Yohan Kim1,
Background and aims: Stromal remodelling in tumor microenvir- Jaehyuk Choi1, Hyunjoo Kwon1, Eun Jin Park1, Sung Min Bae1,
onment plays an important role in cancer progression. It is featured Sang Hyun Lee1, In Young Choi1. 1Hanmi Pharm.Co., Ltd., Seoul, Korea,
by collagen realignment in the stromal compartment, collagen fibers Rep. of South
and basal membrane. There remains a lack of studies addressing the Email: [email protected]
stromal background and fibrosis features and its prognostic value in
Background and aims: Although its benefits were confirmed for
liver cancer. qFibrosis is a system of second harmonic generation and
NASH resolution, semaglutide failed to improve fibrosis in human.
two photon emission (SHG/TPE) microscopy which can identify,
Recently, benefits of glucagon and GIP in addition to GLP-1 have been
quantify and visualize the fibrosis features from biopsy samples.
suggested beyond metabolism such as fibrosis. Thus, optimal use of
qFibrosis has been validated for its application in diagnosis and
these incretins simultaneously could be a promising strategy for
prognosis of hepatitis B and non-alcoholic steatohepatitis. In this
NASH and fibrosis treatment. For this purpose, a novel long-acting
study, we aim to establish a prognostic estimation model by using
Glucagon/GIP/GLP-1 triple agonist, HM15211, was developed. Here,
qFibrosis analysis in liver cancer.
beneficial effect of HM15211 via multi-target engagement was
Method: Total of 198 patients with HCC underwent curative tumor
evaluated in animal models of NASH/fibrosis.
resection were included. Their disease status, survival time, and
Method: AMLN-diet induced NASH mice and CDA-HFD induced
clinical outcomes of whether portal vein thrombosis (PVT) and
nash.fibrosis mice were administered either with HM15211 or
metastasis (Meta) developed during follow-up after surgery were
acylated GLP-1, GLP-1/GIP, or GLP-1/Glucagon agonist. Choline-
analyzed. Liver tissue and liver tumor from the 198 patients were
deficient, L-amino acid-defined, and high fat diet (CDA-HFD)

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 POSTER PRESENTATIONS
induced NASH and fibrosis mice were also utilized. After treatment HM15211. TGF-beta-induced collagen production was also reduced in
for 8 ∼ 12 weeks, histologic analysis including NAFLD Activity Score LX2 cell. Based on in vitro results, observed benefits in TAA mice
(NAS) and hepatic hydroxyproline (HP) were determined. Liver might primarily results from direct anti-inflammatory and -fibrotic
transcriptome analysis was performed to investigate differentially effects of HM15211.
expressed genes (DEGs) for diverse biological pathways. Conclusion: HM15211 markedly improved liver inflammation and
Results: In AMLN mice, HM15211 treatment led to greater reduction fibrosis in TAA mice, and related MoAs were elaborated by in vitro
in each component and composite NAS (6.1, 4.9, 3.6, 4.9, 2.0 for studies. Together with previous results, generalized anti-inflamma-
vehicle, acylated GLP-1, GLP-1/GIP, GLP-1/Glucagon, HM15211) than tory and -fibrotic effects of HM15211 were corroborated. Thus,
incretin analogs, and more NASH resolution achievement were HM15211 could be a novel therapeutic option for fibrosis due to
confirmed for HM15211. In CDA-HFD mice, HM15211 treatment was NASH. Human study is ongoing to assess the clinical relevance of
consistently associated with greater reduction of NAS than incretin these findings.
analogs. More reduction in hepatic HP and collagen contents (−4.2,
−10.0, 7.1, and −26.5% vs. vehicle for acylated GLP-1, acylated GLP-1/ FRI158
GIP, acylated GLP-1/Glucagon, and HM15211) than incretin analogs Loss of bile salt export pump (BSEP/ABCB11) protects mice from
were confirmed, indicating potential benefits of HM15211 for liver development of carbon tetrachloride (CCl4) induced hepatic
fibrosis. To understand underlying mechanisms for improved fibrosis
therapeutic effects of HM15211 on NASH and fibrosis, DEG analysis Claudia Fuchs1, Emmanuel Dauda Dixon1, Philipp Königshofer1,2,3,4,5,
was performed and compared to acylated GLP-1, HM15211 treatment Veronika Mlitz1, Hubert Scharnagl6, Tatjana Stojakovic7,
was associated with more favourable DEG signature in diverse Thomas Reiberger1,2,3,4,5, Michael Trauner1. 1Medical University of
pathways including bile acid metabolism, inflammation and fibrosis Vienna, Division of Gastroenterology and Hepatology, Internal Medicine
in addition to lipid metabolism, highlighting its multi-targeting MoA III, Vienna, Austria; 2Medical University of Vienna, Vienna Experimental
for the treatment of NASH and fibrosis. Hepatic Hemodynamic lab (HEPEX); 3Medical University of Vienna,
Conclusion: In NASH/fibrosis animal models, more therapeutic Christian Doppler laboratory for Portal Hypertension and Liver Fibrosis;
4
benefits of HM15211 over other incretins were demonstrated. , Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases (LBI-
Notably, DEG analysis supports the basis for multi-target engagement RUD); 5CeMM Research Center for Molecular Medicine of the Austrian
effects of HM15211. Thus, HM15211 might be a novel therapeutic Academy of Sciences; 6Medical University of Graz, Clinical Institute of
option for NASH and fibrosis. Human study is ongoing to assess the Medical and Chemical Laboratory Diagnostics; 7University Hospital
clinical relevance of these findings. Graz, Clinical Institute of Medical and Chemical Laboratory Diagnostics
Email: [email protected]
FRI157
Direct anti-inflammatory and anti-fibrotic effects of a novel long- Background and aims: Loss of BSEP/ABCB11 was shown to protect
acting Glucagon/GIP/GLP-1 triple agonist, HM15211, in mice from acquired cholestasis due to preconditioning with a
thioacetamide-induced mouse model of liver injury and fibrosis hydrophilic bile acid (BA) pool, with tetrahydroxylated BAs as the
most prominent species. In this study we aimed to investigate
Jung Kuk Kim1, Jong Suk Lee1, Yohan Kim1, Seonmyeong Lee1,
whether loss of BSEP and subsequent increase in hydroxylation/
Jaehyuk Choi1, Hyunjoo Kwon1, Eun Jin Park1, Sung Min Bae1,
detoxification of BAs protects mice from development of carbon
Dae Jin Kim1, Sang Hyun Lee1, In Young Choi1. 1Hanmi Pharm.Co., Ltd.
tetrachloride (CCl4) induced hepatic fibrosis.
Email: [email protected]
Method: BSEP WT and KO mice were injected every other day with
Background and aims: HM15211 is a novel long-acting triple agonist CCl4 for 8 weeks as model of hepatic fibrosis. In vitro, the hepatic
consisting of rationally designed Glucagon/GIP/GLP-1 triple agonist stellate cell line LX2 was challenged with TGF-beta with and without
conjugated to human IgG FC fragment via short PEG linker. cotreatment of tetrahydroxylated BAs. RNA profiling was performed
Previously, therapeutic benefits of HM15211 were demonstrated in by RT-PCR. Liver histology/immunohistochemistry (IHC), immuno-
diet-induced animal models of NASH and/or fibrosis. Here, we fluorescence (IF) and immunoblot were assessed.
evaluate direct anti-inflammatory and -fibrotic effects of HM15211 in Results: In contrast to WT mice, serum parameter ALT and AST were
TAA (thioacetamide)-induced liver injury and severe fibrosis mouse, not elevated in BSEP KO mice by CCl4 injection. In line, mRNA
and investigate underlying MoA. expression of inflammatory markers Cxcl1, Cxcl2, Ccl2, Ccl5 remained
Method: To induce liver injury and liver fibrosis, escalating doses of unchanged in BSEP KO mice injected with CCl4, while in WT CCl4 mice
dose of TAA was injected to mouse for 12 weeks. HM15211 was these markers were significantly increased (3fold, 20fold, 20fold,
administered during last 10 weeks. Hepatic hydroxyproline (HP) 2fold, respectively). Accordingly, numbers of MAC-2 positive cells
contents were measured and Sirius red staining was conducted. qPCR were significantly lower in BSEP KO CCl4 injected mice when
was performed to evaluate relevant marker gene expression. compared to CCl4 WT mice. Fibrotic markers Col1a1, Col1a2 as well
Multiplex assay was performed to measure blood level of pro- as Sirius red were significantly reduced in BSEP KO CCl4 mice
inflammatory cytokines. For mechanistic study, THP-1 cell and LX2 compared to WT CCl4 mice (by 40%, 60%, 65% respectively).
cell were used. Accordingly, alpha-SMA (marker of activated hepatic stellate cells)
Results: HM15211 treatment significantly reduced HP content (−51% (IF) remained at basal levels in BSEP KO CCl4 mice. Mechanistically,
vs. Veh., p < 0.01), Sirius red positive area (−65% vs. Veh., p < 0.001), we could demonstrate that hepatic protein expression of pJNK
and fibrosis score (0.7 for HM15211 vs. 3.0 for Veh., p < 0.001) in TAA (known to be involved in development of CCl4 induced hepatic
mice. Considering baseline fibrosis score at week 2 (1.0), HM15211 fibrosis) was reduced in BSEP KO CCl4 mice in comparison to
could confer both potential reversal effect on pre-existing fibrosis and challenged WT mice. In vitro, activated phenotype of LX2 cells was
prevention effect on fibrogenesis. Consistently, expression of hepatic ameliorated with treatment of tetrahydroxylated BAs, as reflected by
marker genes for fibrosis (i.e. collagen) and inflammation (i.e. F4/80 significant reductions of alpha-SMA and Col1a1 gene expression.
and TNF-alpha) were significantly reduced in HM15211-treated Conclusion: Loss of BSEP and subsequent hydroxylation of the bile
group. Furthermore, multiplex analysis revealed that HM15211 pool protects mice from CCl4 induced hepatic fibrosis via suppression
treatment was associated with robust reduction across pro-inflam- of hepatic pJNK signalling and attenuation of HSC activation.
matory cytokines such as TNF-alpha, IL-1beta, IL-6, and etc.
Significant reduction in blood level of liver enzymes was also
confirmed. Mechanistically, PMA/LPS-induced THP-1 cell adhesion
and subsequent cytokine secretion were significantly attenuated by

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POSTER PRESENTATIONS
FRI159 FRI160
Large-scale multicenter study for the clinical utility of the non- Multispectral analysis of liver biopsies from patients with chronic
invasive biomarkers Gas6 and soluble Axl in hepatocellular hepatitis C reveals unique macrophage phenotypes and spatial
carcinoma, liver fibrosis and end-stage liver disease interactions associated with fibrosis progression
Katharina Staufer1,2, Heidemarie Huber3, Omar Saldarriaga1, Santhoshi Krishnan2, Morgan Oneka2,
Jasmin Zessner-Spitzenberg3, Rudolf E. Stauber4, Armin Finkenstedt5, Arvind Rao3, Joseph Gosnell1, Daniel Millian1, Timothy Wanninger1,
Heike Bantel6, Thomas Weiss7, Markus Huber8, Patrick Starlinger9, Jingjing Jiao4, Laura Beretta4, Heather Stevenson1. 1University of Texas
Thomas Grünberger9,10,11, Thomas Reiberger2, Susanne Sebens12, Medical Branch, Department of Pathology, Galveston, United States;
Gail McIntyre13, Ray Tabibiazar13, Amato Giaccia13, Heinz Zoller5, 2
Rice University, Department of Electrical and Computer Engineering,
Michael Trauner2, Wolfgang Mikulits3. 1Medical University of Vienna, Houston, United States; 3University of Michigan, Department of
Department of General Surgery, Division of Transplantation, Wien, Computational Medicine and Bioinformatics, Ann Arbor, United States;
Austria; 2Medical University of Vienna, Department of Internal Medicine 4
University of Texas MD Anderson Cancer Center, Department of
III, Division of Gastroenterology & Hepatology, Wien, Austria; 3Medical Molecular and Cellular Oncology, Houston, United States
University of Vienna, Department of Medicine I, Division: Institute of Email: [email protected]
Cancer Research, Comprehensive Cancer Center Vienna, Vienna, Austria;
4 Background and aims: Despite availability of direct-acting antivirals,
Medical University of Graz, Division of Gastroenterology and
viral hepatitis C (HCV) still impacts ∼58 million people world-wide
Hepatology, Department of Internal Medicine, Graz, Austria;
5 and ∼70% progress to chronic infection. Chronic hepatitis develops
Medizinische Universität Innsbruck, Department of Medicine I,
after the virus restricts pro-inflammatory macrophage activation
Gastroenterology, Hepatology and Endocrinology, Innsbruck, Austria;
6 necessary to control infection, contributing to T cell disfunction and
Hannover Medical School, Department of Gastroenterology, Hepatology
viral persistence. Intrahepatic macrophages represent ∼20% of non-
and Endocrinology, Hannover, Germany; 7University Hospital
parenchymal cells and greatly impact the hepatic microenvironment,
Regensburg, Center for Liver Cell Research, Children’s University Hospital
host immune response to liver injury and the development of fibrosis.
(KUNO), Regensburg, Germany; 8University Hospital Bern, Department
We hypothesized that variations in the heterogeneity of macrophages
of Anesthesiology and Pain Therapy, Inselspital, Bern, Switzerland;
9 determine disease progression in HCV + patients.
Medical University of Vienna, Department of Surgery, Division of
Method: We used multispectral imaging to phenotype and quantify
General Surgery, Wien, Austria; 10Clinic Favoriten, HPB Center, Health
resident Kupffer cells (CD68 +), monocyte-derived macrophages
Network Vienna, Surgery, Vienna, Austria; 11Siegmund Freud Private
(Mac387 +), pro-fibrogenic macrophages (CD163 +), and co-expres-
University, HPB Surgery, Vienna, Austria; 12Christian-Albrechts-
sion of pro-inflammatory (CD14) and anti-inflammatory (CD16) in
University Kiel (CAU), Institute for Experimental Cancer Research, Kiel,
patients with minimal (fibrosis stage: 0/6; n = 5) or advanced
Germany; 13Aravive Biologics, Houston, United States
(fibrosis stage: 6/6; n = 6) fibrosis. Next, we compared differences in
Email: [email protected]
the spatial distribution of the identified phenotypes (i.e., enrichment
Background and aims: The expression of the receptor tyrosine or depletion) within the hepatic microenvironment. Multiplex
kinase Axl and the release of its cleavage product soluble Axl (sAxl) stained liver biopsies were scanned with a spectral imaging
are highly elevated in hepatocellular carcinoma (HCC), advanced microscope (Vectra 3, Akoya Biosciences) and multi-component TIFF
fibrosis, and cirrhosis. Recent studies suggest that the expression of images and cell_seq_data files were analyzed to determine the
Gas6, the high affinity ligand of Axl, is also enhanced during liver heterogeneity of these various cell phenotypes. Both phenotype
fibrogenesis and HCC. In this study, we evaluated the diagnostic matrices and t-distributed stochastic neighbour embedding plots (t-
accuracy of sAxl and Gas6 in a large cohort of patients with HCC, liver SNE) were used (Visiopharm®; MATLAB 2020a, MathWorks inc.).
fibrosis and end-stage liver disease. Phenotypes that were significantly enriched were selected for spatial
Method: Levels of sAxl and Gas6 were analyzed by enzyme-linked proximity analysis using G-function calculations.
immunosorbent assays (ELISAs) in serum samples of patients with Results: Phenotype matrix analysis revealed the enrichment of
HCC, cholangiocarcinoma, colorectal liver metastases, chronic liver unique pathogenic macrophage phenotypes (CD163 + CD16 +, CD68 +,
disease of all fibrosis stages, end-stage liver disease, and healthy CD68 + MAC387 +) in the HCV + patients with advanced fibrosis
controls from five centers in Europe. ELISAs were optimized to ( p <0.05). Increased CD68 +, CD68 + MAC387 + macrophage
exclusively analyze either free sAxl or bioactive Gas6 levels. populations, in certain individuals, correlated with poor clinical
Results: A total of 1111 patients (median age 57.8y, 67.3 % male) was outcome (increased prothrombin time and decreased platelet counts).
included in the study. sAxl, Gas6 as well as their albumin (alb) ratios Spatial analysis showed significant ( p < 0.05) enrichment of CD14 +,
showed high diagnostic accuracy for the detection of HCC in CD68 + CD14 + CD163 +, CD68 + MAC387 +, and MAC387 +
comparison to healthy controls (AUC 0.765–0.942). sAxl/alb was macrophage populations near CD68 + cells and depletion of CD163
confirmed as an accurate biomarker of advanced liver fibrosis and + CD16 + population to CD14 + cells. Enriched interactions between
cirrhosis, and was even outperformed by Gas6/alb, which showed MAC387 + and CD163 + MAC387 + positive macrophages were
good accuracy (AUC 0.818–0.897) comparable to ELF™ test for the exclusively observed in the HCV + patients with advanced fibrosis.
detection of liver cirrhosis. sAxl, Gas6 and their albumin ratios Conclusion: Multispectral imaging with spatial analysis enabled
detected hepatic decompensation (Gas/alb: AUC 0.878), and were detailed evaluation of intrahepatic macrophages and their relation-
predictors of transplant-free survival. ship with neighbouring cells phenotypes. Unique phenotypes and
Conclusion: Gas6/alb shows high accuracy for the detection of interactions were observed among HCV patients with advanced
significant to advanced fibrosis and liver cirrhosis, as well as fibrosis and in those that had disease progression. This approach
decompensated liver cirrhosis superior to sAxl/alb. identified novel potential targets for inhibiting fibrosis development
and development of future personalized medicine approaches.

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 POSTER PRESENTATIONS
FRI161 FRI162
Neutrophil-specific NLRP3 activation triggers liver inflammation Imaging of fibrosis in metabolic associated liver disease by a
and fibrosis radiolabeled affibody targeting PDGFRB
Benedikt Kaufmann1,2, Yanfang Peipei Zhu1, Olivia Wegrzyniak1, Johanna Rokka2, Bo Zhang1, Maria Rosestedt1,
Aleksandra Leszczynska1, Agustina Reca1, Laela M. Booshehri1, Bogdan Mitran1,3, Pierre Cheung1, Emmi Puuvuori1, Sofie Ingvast4,
Alexander Wree3, Helmut Friess2, Daniel Hartmann2, Frederik Ponten4, Frederik Frejd5, Olle Korsgren4, Jonas Eriksson1,6,
Hal M. Hoffman1, Ben Croker1, Ariel Feldstein1. 1Department of Olof Eriksson1,7. 1Uppsala University , Department of Medicinal
Pediatrics, University of California San Diego, La Jolla; 2Department of Chemistry, Uppsala, Sweden; 2Uppsala University , Department of Public
Surgery, TUM School of Medicine, Klinikum rechts der Isar, Technical, Health and Caring Sciences, Uppsala, Sweden; 3Antaros Medical AB,
University of Munich; 3Charité, Campus Virchow Klinikum and Charité, Mölndal, Sweden; 4Uppsala University , Department of Immunology,
Campus Mitte, Department of Hepatology and Gastroenterology, Genetics and Pathology, Uppsala, Sweden; 5Affibody AB, Solna, Sweden;
6
Universitätsmedizin Berlin Uppsala University Hospital, PET Center, Uppsala, Sweden, 7Antaros
Email: [email protected] Tracer AB, Mölndal, Sweden
Email: [email protected]
Background and aims: Neutrophils have a key role in the acute
inflammatory response during liver inflammation and fibrosis and Background and aims: The pathological formation of fibrosis, is an
are hypothesized to promote chronic inflammation and liver fibrosis important feature in liver in Metabolic Associated Fatty Liver Disease
if they are not efficiently cleared by macrophages. The NLRP3 (MAFLD) as well as in many different other diseases. Platelet-derived
inflammasome is crucial in liver inflammation and fibrogenesis. In growth factor receptor beta (PDGFRB) is a known biomarker of
this study the role of neutrophil-specific NLRP3 inflammasome over- activated hepatic stellate cells, and thus play a key role in fibrosis in
activation in liver pathobiology was investigated. MAFLD. Today, the treatment and monitoring of hepatic fibrosis is
Method: Neutrophil-specific mutant NLRP3 knock-in mice were hampered by the lack of suitable methods for detecting and
generated by crossing Nlrp3 knock-in mouse strains with the diagnosing the disease. Therefore, it is of crucial importance to
presence of an intronic floxed neomycin resistance cassette with develop non-invasive methods in order to detect, diagnose, stage and
mice expressing Cre recombinase under the control of Calcium- study fibrosis. Herein, we report the preparation, characterization,
binding protein A8. Liver tissue and bone marrow were analysed by and evaluation of fluorine-18-labelled Affibody molecule Z09591, in a
immunohistochemistry, flow cytometry, and real-time quantitative mouse model of non-alcoholic steatohepatitis (NASH).
polymerase chain reaction. Method: Affibody molecule Z09591 was labelled with fluorine-18 via
Results: Mutant mice with neutrophil-specific NLRP3 activation tetrazine/trans-cyclooctene click chemistry. 18F-TZ-Z09591 was eval-
showed shortened survival, poor growth, and severe liver inflamma- uated in a 6 weeks CCl4 treatment mouse model of liver fibrosis by a
tion. Furthermore, neutrophil-specific NLRP3 activation resulted in PET study, including ex vivo biodistribution and autoradiography.
systemic changes in hematopoiesis and an accumulation of inflam- Binding results were correlated to staining and PDGFRB immunohis-
matory neutrophils, the key cells in the initial phase of inflammation, tochemistry (IHC) on post-mortem biopsies.
in the liver. Infiltrative inflammatory neutrophils were identified by Results: Affibody molecule Z09591 was successfully radiolabelled
elevated CD162 (PSGL-1) and increased expression of CD16/32 with fluorine-18 with high purity and reproducible yield. PET studies
(FcγRIII/II) analyzed by flow cytometry as well as increased positive demonstrated that liver uptake of 18F-TZ-Z09591 was higher in mice
myeloperoxidase staining in the liver of mutant mice. Inflammation with induced hepatic fibrosis compare to healthy liver (Figure). The
of liver tissue in mutant mice resulted in a decrease of resident liver binding could also be blocked by pre-treatment with Z09591 in
macrophages evident by reduced CLEC4f and F4/80 expression in excess, indicating receptor specific binding. Ex vivo autoradiography
both IHC staining and qRT-PCR. In contrast, pro-inflammatory demonstrated high signal intensity in positive hepatic sinusoids
macrophage population was increased in mutant mice demonstrated affected by fibrosis, as confirmed by Sirius red staining and PDGFRB
by Ly6C staining and upregulation of inducible nitric oxide synthase 2 IHC.
(iNOS2). Sirius Red staining revealed liver fibrosis in mutant mice,
whereas WT mice showed a healthy liver. The expression of the pro-
fibrotic genes metalloproteinases 1 (TIMP1) and connective tissue
growth factor (CTGF) was upregulated in the liver tissue of mutant
mice.
Conclusion: Neutrophil-specific NLRP3 overactivation resulted in
severe liver inflammation with accumulation of inflammatory
neutrophils and pro-inflammatory macrophage polarization.
Furthermore, it induced liver fibrosis and a pro-fibrotic gene
expression pattern. This data provides novel insights into the
complex relationship between liver neutrophil-driven inflammation,
macrophage polarization and liver fibrosis.

Conclusion: We describe the radiolabelling and evaluation of the

PDGFRB binding affibody Z09591. 18F-TZ-Z09591 exhibited specific
binding to hepatic fibrotic lesions. 18F-TZ-Z09591 is a promising tool
for PET imaging of fibrosis in MAFLD. The use of such a tracer
clinically could represent a non-invasive diagnostic, prognostic as
well as predictive tool for MAFLD patients.

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POSTER PRESENTATIONS
FRI163 Conclusion: Our study shows that advanced liver fibrosis is a
Liver complications in greek patients with sickle cell disease: a significant cause of morbidity in patients with SCD and is primarily
multicenter retrospective analysis from eight thalassemia and associated acute vaso-occlusive phenomena and chronic intravascu-
sickle cell units across Greece lar hemolysis of the disease itself.
Konstantinos Manganas1, Sophia Delicou1, Aikaterini Xydaki1,
Alexandra Kourakli2, Loukia Evliati3, Euthimia Vlahaki4, FRI164
Evangelos Klironomos5, Michail Diamantidis6, Ioannis Lafiatis7, Hemodynamic, molecular, and histological characterization of a
Antonis Kattamis8, Ioannis-Georgios Koskinas1. 1Ippokrateio General toxic liver fibrosis regression model
Hospital of Athens, Athens, Greece; 2General University Hospital of Philipp Königshofer1,2,3,4,5, Ksenia Brusilovskaya1,2,3,4,5,
Patras, Rio, Greece; 3Evangelismos General Hospital, Athens, Greece; Benedikt Hofer1,2,3, Benedikt Simbrunner1,2,3,4,5,
4
Ippokrateio-General Hospital of Thessaloniki, Thessaloniki, Greece; Oleksandr Petrenko1,2,3,4,5, Hubert Scharnagl6, Tatjana Stojakovic6,
5
Venizeleio General Hospital, Heraklion, Greece; 6General University Michael Trauner1, Philipp Schwabl1,2,3,4,5, Stefan Günther Kauschke7,
Hospital of Larissa, Larissa, Greece; 7General Hospital of Mytilene, Larissa Pfisterer7, Thomas Reiberger1,2,3,4,5. 1Division of
Mytilene, Greece; 8Agia Sofia Children’s Hospital, Athens, Greece Gastroenterology and Hepatology, Department of Internal Medicine III,
Email: [email protected] Medical University of Vienna, Vienna, Austria; 2Vienna Experimental
Hepatic Hemodynamic lab (HEPEX), Medical University of Vienna,
Background and aims: Sickle cell disease (SCD) is one of the most Vienna, Austria; 3Christian Doppler laboratory for Portal Hypertension
common monogenic disorders worldwide and liver complications, and Liver fibrosis, Vienna, Austria; 4Ludwig Boltzmann Institute for Rare
acute and chronic, are common in this group of patients. Our study and Undiagnosed Diseases (LBI-RUD), Vienna, Austria; 5CeMM Research
aims to highlight the prevalence and predisposing factors of liver Center for Molecular Medicine of the Austrian Academy of Sciences,
fibrosis in SCD patients. Vienna, Austria; 6Clinical Institute of Medical and Chemical Laboratory
Method: Eight Thalassemia and Sickle Cell Units across Greece and Diagnostics, University Hospital Graz, Graz, Austria; 7Boehringer
219 patients enrolled in our study and history of liver related disease Ingelheim Pharma GmbH, Biberach, Germany
complications was recorded, as well as a full laboratory and imaging Email: [email protected]
analysis concerning their liver function. Patients were divided in two
groups, those with indications of advanced liver fibrosis (Fibroscan Background and aims: Portal hypertension (PH) results from ‘static’
>13.5 kPa or Fib-4 >3.25 or APRI >1.5) and those without indications liver fibrosis and ‘dynamic’ vascular components. Liver disease
of advanced liver fibrosis. regression depends on cessation of liver injury to allow liver fibrosis
Results: The prevalence of significant liver fibrosis in SCD patients in regression and functional regeneration. We aimed to establish a toxic
our study was 10.7%. The presence of liver fibrosis was significantly liver disease regression model to investigate the ‘regressive’ course of
correlated with advanced age, male gender, cholelithiasis and higher PH and fibrosis.
LDH, γ-GT, INR, direct and indirect bilirubin levels. Noteworthy, Method: Male C57BL/6JRj mice were exposed to CCl4 for eight (8 w)
patients with advanced liver fibrosis had suffered significantly more or twelve (12 w) weeks (2 μL/g in olive oil, 3x/week, per oral),
acute liver crises, acute liver sequestration crises and acute respectively, to induce moderate (8 wC) and severe liver fibrosis
intrahepatic cholestasis in the last five years, while these patients (12 wC)-followed by one (+R1) or two (+R2) weeks of regression
were also receiving transfusion therapy more often and for a longer period, respectively (Figure). Healthy control groups received olive oil
period of time and had higher Liver Iron Concentration (LIC) levels, only (OO). Portal pressure (PP) was measured at end of each timeline.
but without statistical significance. No correlation was observed with Blood parameters were assessed. Fibrosis was quantified by collagen
ultra-sound findings of right hearth failure or previous viral hepatitis. proportionate area (CPA) in %. Matrix- and inflammation-related
gene-expression was measured in bulk liver tissue.

Patients with no Patients with

significant significant
fibrosis fibrosis p < 0.05
Hb (g/dl) 9.50 (1.37) 9.03 (1.09) 0.045**
HbS (%) 60.2% (14.5%) 63.9% (10.5%) 0.252*
HbF (%) 11.57% (8.3%) 13.39% (8.1%) 0.334*
PLTs (x109/L) 337.7 (178.81) 183.0 (145.50) <0.001*
Ferritin (ng/ml) 772.02 (1432.02) 771.86 (1018.94) 0.668**
AST (U/L) 35.78 (15.15) 55.15 (30.42) 0.007**
ALT (U/L) 27.69 (16.18) 35.21 (30.36) 0.994**
γ-GT (U/L) 44.19 (52.89) 72.33 (115.93) 0.042**
LDH (U/L) 386.21 (124.33) 568.76 (224.02) 0.000**
Direct bilirubin (mg/dl) 0.67 (0.35) 1.25 (0.83) 0.002**
Indirect bilirubin (mg/dl) 1.57 (1.40) 2.77 (1.95) 0.003**
CRP (mg/l) 5.43 (8.92) 2.50 (2.76) 0.336**
INR 1.17 (0.41) 1.33 (0.57) 0.003**
Albumin (g/dl) 4.33 (0.52) 4.17 (0.61) 0.228*
MRI T2* (LIC-mg Fe/gr dry 4.96 (7.19) 6.16 (7.04) 0.865**
weight)
Age (years) 46.75 (13.48) 52.56 (12.12) 0.05*
Duration of transfusions 7.85 (13.22) 8.71 (13.34) 0.443**
(years)
Transfusions (PRBC/year) 6.06 (8.72) 7.95 (8.95) 0.124**
Acute liver crises (per 5 0 (0.00) 0.16 (0.50) 0.000**
years)
Acute intrahepatic 0 (0.00) 0.11 (0.45) 0.010**
cholestasis (per 5 years)
Liver sequestration crises 0.06 (0.278) 0.38 (0.88) 0.046**
(per 5 years)

S472 Journal of Hepatology 2022 vol. 77(S1) | S389–S664

 POSTER PRESENTATIONS
Results: Diseased animals developed PH with PP (8wC: 8.5 ± Conclusion: There is a significant proportion of patients with ALT 31–
1.3 mmHg vs OO: 4.9 ± 0.8 mmHg; 12 wC: 10.0 ± 1.2 mmHg vs OO: 55 U/L who have underlying liver disease or fibrosis. Lowering the
5.2 ± 0.2 mmHg; all p < 0.001) and liver fibrosis with CPA% (8 wC: 8.5 ULN of ALT has increased the detection rate of liver disease and
± 5.0 % vs OO: 1.6 ± 0.9 %; 12 wC: 16.9 ± 3.9 % vs OO: 0.8 ± 0.2 %; all p < fibrosis in these patients.
0.001). In both models, PP regressed after one (8wC + R1: −31 %, p <
0.001; 12wC + R1: −16 %, p = 0.01) and after two weeks (8 wC + R2: FRI166
−29 %, p < 0.001; 12wC + R2: −21 %, p = 0.002), respectively. Fibrosis Inhibition of 11beta-hydroxysteroid dehydrogenase 1 relieves
regressed in the 8-weeks (8 wC + R1: −1 %, p < 0.99; 8 wC + R2: −37 %, fibrosis through depolarizing of hepatic stellate cell in NASH
p = 0.24) and significantly in the 12-weeks (12 wC + R1: −16 %, p = Su-Yeon Lee1, Hyung Chul Rhu2, Sanghwa Kim1, Yeonhwa Song1,
0.002; 12 wC + R2: −21 %, p < 0.001) setting. AST and ALT levels Inhee Choi3, Namjeong Kim1, Jee Woong Lim2, Hyo Jin Kang2,
significantly decreased after 1 week of regression (8 wC/12 wC+R1: Jason Kim2, Haeng Ran Seo1. 1Institut Pasteur Korea, Advanced
−99 %) and after 2 weeks of regression, transaminases were similar to Biomedical Research Lab, Seongnam-si, Korea, Rep. of South; 2J2H
healthy controls ( p < 0.001). Expression of fibrogenesis-related genes Biotech Inc., R&D Center, Suwon-si, Korea, Rep. of South; 3Institut
was significantly reduced: Col1a1 (8 wC + R1/2: −85/‐91 %; 12 wC + Pasteur Korea, Medicinal Chemistry, Seongnam-si, Korea, Rep. of South
R1/2: −83/−74 %), Tgf-beta (8 wC + R1/2: −71/−80 %; 12 wC + R1/2: Email: [email protected]
−62/−27 %), and alpha-Sma (8 wC + R1/2: −86/−85 %; 12 wC + R1/2: Background and aims: 11-beta-hydroxysteroid dehydrogenase type
−70/−42 %). Matrix-metalloproteinase activity was promoted by
1 (11betaHSD1) is a key enzyme that catalyses the intracellular
decreased Timp1 (8 wC + R1/2: −94/−95 %; 12 wC + R1/2: −92/−85 %)
conversion of cortisone to physiologically active cortisol. Although
expression. Pro-inflammatory Tnf-alpha (8 wC + R1/2: −69/−74 %; 11betaHSD1 has been implicated in numerous metabolic syndromes,
12 wC + R1/2: −70/−69 %) expression was also decreased.
such as obesity and diabetes, the functional roles of 11betaHSD1
Conclusion: The characterization of this toxic model of liver disease during progression of nonalcoholic steatohepatitis (NASH) and
regression suggests that the two-week regression period following consequent fibrosis have not been fully elucidated.
12-weeks of CCl4 exposure includes a suitable therapeutic window to
Method: the effects of J2H-1702 on steatosis and fibrogenesis were
investigate treatments to promote regression of PH and liver fibrosis. investigated in both multicellular hepatic spheroids (MCHSs) in vitro
systems and in vivo mouse models.
FRI165
Results: We found that pharmacological and genetic inhibition of
The upper limit of normal of alanine aminotransferase (ALT) in
11betaHSD1 resulted in reprogramming of hepatic stellate cell (HSC)
diagnosing liver disease and fibrosis by the Intelligent Liver
activation via inhibition of p-SMAD3, alpha-SMA, Snail, and Col1A1 in
Function Test (iLFT) system
a fibrotic environment and in multicellular hepatic spheroids
Jeremy Lee1, John Dillon1, Iain Macpherson1. 1University of Dundee,
(MCHSs). We also determined that 11betaHSD1 contributes to the
School of Medicine, Dundee, United Kingdom
maintenance of NF-kappaB signalling through modulation of TNF,
Email: [email protected]
TLR7, ITGB3, and TWIST, as well as regulating PPAR-alpha signalling
Background and aims: There is an increasing prevalence of liver and extracellular matrix accumulation in activated HSCs during
disease in the UK, and mortality from liver disease continues to rise. advanced fibrogenesis in MCHSs. Of great interest, the 11betaHSD1
Liver function tests (LFTs) are often used to investigate for liver inhibitor J2H-1702 significantly attenuated hepatic lipid accumula-
disease, but there remains a significant number of patients with tion and ameliorated liver fibrosis in diet- and toxicity-induced NASH
undiagnosed liver disease who could benefit from early detection and mouse models.
intervention. The intelligent LFT (iLFT) system is designed to cascade
further tests in patients with abnormal LFTs, generating a probable
liver diagnosis. This increased the rate of diagnosis of liver disease by
43%. One parameter used by iLFT is serum alanine aminotransferase
(ALT) level, using an upper limit of normal (ULN) of 30 U/L, given
recent evidence suggesting a lower ULN of ALT to diagnose liver
diseases. This study aims to determine the frequency of liver disease
and fibrosis at ALT level 31–55 U/L, compared to ALT >55 U/L, and
provide evidence for using an ULN of ALT of 30 U/L in the iLFT system.
Method: A retrospective analysis was done on patients undergoing
iLFT in 2018–19, comparing ALT levels to iLFT and fibrosis outcomes.
Results: 672 iLFT diagnoses were made in the ALT 31–55 U/L group,
with 148 (22.0%) alcoholic liver disease (ALD) diagnoses, 74 (11.0%)
non-alcoholic fatty liver disease (NAFLD) diagnoses, 30 (4.5%)
combined NAFLD and ALD diagnoses, 15 (2.2%) hepatitis B or C
diagnoses, 74 (11.0%) metabolic or autoimmune liver diseases. 1041
diagnoses were made in the ALT >55 U/L group, which is significantly
higher ( p < 0.05) compared to the ALT 31–55/L group. There were 137
(20.4%) fibrosis diagnoses in the ALT 31–55 U/L group, compared to
311 (29.9%) in the ALT >55 U/L group.

Figure: Frequency of fibrosis according to aetiology between both ALT

groups.

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POSTER PRESENTATIONS
Conclusion: Together, our data indicate that J2H-1702 is a promising Conclusion: Our in vitro findings demonstrate an anti-fibrotic
new clinical candidate for the treatment of NASH. therapeutic potential of miR-9-5p and miR-122 in activated human
stellate cells and liver fibrosis.
FRI167
Anti-fibrotic effects of microRNA-9-5p and microRNA-122 FRI168
Dana Eidelshtein1, Eithan Galun1, Jonathan Axelrod1. 1Hadassah Higher daily Aramchol dose results in higher effect size in fibrosis
University Hospital-Ein Kerem, The Goldyne Savad Institute of Gene and improvement in the ARMOR study open label part
Cell Therapy, Jerusalem, Israel Vlad Ratziu1, Yusuf Yılmaz2, Don Lazas3, Scott Friedman4,
Email: [email protected] Liat Hayardeny5, Shaul Kadosh6, Tali Gorfine5, Arun Sanyal7.
1
Sorbonne Université, Institute for Cardiometabolism and Nutrition
Background and aims: Liver fibrosis is the final consequence of (ICAN) and Hôpital Pitié-, Salpêtrier̀ e, INSERM UMRS 1138 CRC, Paris,
many chronic liver injuries and is an increasingly crucial health France; 2Liver Research Unit, Institute of Gastroenterology, Marmara
problem. MicroRNA’s (miR’s) are short single-stranded RNAs that University, and Department of Gastroenterology, School of Medicine,
regulate post-transcriptional mRNA expression by binding to com- Marmara University, Istanbul, Turkey; 3ObjectiveGI, Inc., Nashville,
plementary mRNA sequences, resulting in translational repression United States; 4Icahn School of Medicine at Mount Sinai, New York,
and gene silencing. In this in vitro study, we sought to identify United States; 5Galmed Pharmaceuticals Ltd., Tel Aviv-Yafo, Israel;
potential miRNAs that could serve as potential therapeutic targets 6
Statexcellence Ltd., Israel; 7Virginia Commonwealth University,
through which to ameliorate liver fibrosis. We identified and Department of Gastroenterology, Richmond, United States
validated fibrosis-reducing miRNAs based on their ability to suppress Email: [email protected]
two key fibrogenic pathways: 1) NADPH Oxidase 4 (NOX4), which
maintains stellate cells activation by generation of reactive oxygen Background and aims: Aramchol is a partial inhibitor of hepatic
species (ROS)-induced oxidative stress and DNA damage; and 2) TGF- stearoyl-CoA desaturase (SCD1) with direct anti-fibrotic activity
beta, a central molecular signaling pathway in fibrosis. demonstrated in pre-clinical models. In a 52-week phase 2b study,
Method: Potential miR candidates were identified by bioinformatics improvement in fibrosis by ≥1 stage without NASH worsening was
screening for miR seed sequences in the NOX4 3′UTR. Candidate observed in 17.5%, 21.3% and 29.5%, in the placebo, Aramchol 400 and
miRNA’s were evaluated for anti-fibrotic activity by transfection of 600 mg, respectively. A 53% higher exposure is achieved when
synthetic mimic-miRs into LX-2 cells, an established activated human dividing 600 mg QD Aramchol to 300 mg BID. Since this higher
stellate cell (HSC) line, and assessed for reduction of smooth muscle exposure was expected to improve efficacy, Aramchol 300 mg BID
actin (alpha-SMA) protein levels by flow cytometry. Target-sequence was selected for a phase 3 study in patients with NASH and fibrosis.
specificity of candidate miRs was validated by co-transfection into An Open-Label Part is designed to explore the kinetics of histological
LX-2 or HEK293 cells of mimic-miRs with a PmiRGLO vector outcome measures and non-invasive tests as a function of treatment
(Promega) containing a cloned NOX4-3′UTR (PmiRGLO-Nox4) or duration
mutant control (PmiRGLO-mutNox4) sequence and analysis of Method: 150 patients with histologically confirmed NASH and
luciferase activity. fibrosis are being enrolled to receive Aramchol 300 mg BID in the
Results: Bioinformatics screening identified miR-9-5p and miR-96- Open-Label Part of the study. Patients are randomized 1:1:1 to
5p miRs as having the highest predicted binding potential to NOX4 3′ perform a post-baseline liver biopsy at weeks 24, 48 or 72. The
UTR seed sequences and highest potential for NOX4 expression primary efficacy endpoints are the kinetics of fibrosis improvement
inhibition. miR-9-5p was also predicted to target TGF-beta receptor without NASH worsening and NASH resolution without fibrosis
(TGFbR2) as was miR-122, an important regulator of hepatic worsening. Biopsies are read by 3 independent pathologists, followed
metabolism. Co-transfection experiments in HEK293 demonstrated by a consensus reading
that mimic-miR-9-5p, but neither miR-96-5p nor miR-122, effect- Results: Herein we report the results from the first 20, F1-3 patients
ively suppressed PmiRGLO-Nox4 directed luciferase expression, but that received Aramchol in whom the scheduled post-baseline biopsy
not that of PmiRGLO-mutNox4. miR-96-5p transfection similarly was performed. At baseline, mean age ± SD was 58.5 ± 8.7 years; 70%
suppressed both NOX4 and TGFbR2 mRNA levels in LX-2 cells. In were females; 75% White; mean BMI 33.5. ± 3.6 kg/m2; 90% had type
contrast, both miR9-5p and miR-122, but neither miR-96-5p nor a 2 diabetes; 13 patients had stage 3 fibrosis; 4 stage 2, and 3 stage 1;
scrambled control-miR, effectively suppressed alpha-SMA expression Mean NAS was 4.8 ± 1.3. Post-baseline biopsies were performed for 9
in transfected LX-2 cells. Preliminary evidence suggests that LX-2 patients at 24 weeks, 9 at 48 weeks and 2 at 72 weeks. Altogether 12/
cells may also inherently express and perhaps secret both miR-9-5p 20 patients (60%) showed fibrosis improvement by ≥1 stage (5/9 after
and miR-122. 24 weeks, 6/9 after 48 weeks and 1/2 after 72 weeks). 19/20 patients
were either stable or reduced fibrosis measured by liver biopsy. In 5
patients, fibrosis was reduced by 2 points. In 9/20 (45%) patients there
was fibrosis improvement without NASH worsening. Statistically
significant reductions in ALT, AST and biomarkers associated with
liver fibrosis Fib-4 and ProC-3 were also observed corroborating the
histological effects. Reductions of a similar magnitude are seen in a
cohort of the first 20 patients for which paired biopsy have been
analyzed, a cohort of 50 patients for which biomarker data was
analyzed (ARCON Cohort) and a cohort of 139 of which ALT, AST and
FIB-4 were analyzed. Aramchol showed excellent safety and
tolerability. Updated data from the open label study will be
presented.
Conclusion: 60% of the 20 patients treated with Aramchol 300 mg
BID showed fibrosis improvement. Data is corroborated by congruent
changes in fibrosis biomarkers and by a biochemical response in
aminotransferases. The data presented here, albeit preliminary, is
aligned with the hypothesis that higher Aramchol exposure results in
Figure: miR-9-5p and miR-122 suppress alpha-SMA in HSCs in vitro. an improved efficacy profile and a direct anti-fibrotic effect may be
Transfection of LX-2 cells with miRNAs, miR-9-5 and miR-122 decreases manifested as early as 24 weeks.
alpha-SMA protein expression. *p < 0.05 by two-way Student’s t test.

S474 Journal of Hepatology 2022 vol. 77(S1) | S389–S664

 POSTER PRESENTATIONS
FRI169 display profibrogenic properties (Nat Commun 2018). Here, combin-
Development of a high precision liver biopsy method to improve ing studies in human precision-cut liver slices (PCLS) and experi-
the accuracy of fibrosis staging and collagen profiling mental models, we investigated whether and how targeting MAIT cell
Morten Christensen1, Ida Villesen1, Mette Juul Nielsen1, activation may impact fibrosis regression.
Morten Karsdal1, Diana Leeming1. 1Nordic Bioscience, Fibrosis Method: Liver PCLS were generated from patients with end-stage
Research, Herlev, Denmark fibrosis and cultured ex vivo with or without the MAIT cell antagonist
Email: [email protected] Acetyl-6-formylpterin (Ac-6-FP) for 48 hrs. Fibrogenic and inflam-
matory gene expression was evaluated by RT-qPCR and α-SMA by
Background and aims: Liver biopsy is the gold standard for diagnosis
immunostaining. Liver fibrosis was induced in mice by repeated
and staging of hepatic fibrosis, however it is associated with carbon tetrachloride (CCl4) injections for 4 weeks. For fibrosis
limitations such as the pathologist’s inter-variability, small sample
regression, CCl4 injections were discontinued and mice were daily
size, and patient discomfort. Currently, liver biopsy is required as a
administered with Ac-6-FP for up to 4 days. Comparison of genes
primary regulatory outcome in clinical trials on non-alcoholic differentially regulated by Ac-6-FP in Ly6Chigh profibrogenic macro-
steatohepatitis (NASH), which has increased the need for regulatory
phages and Ly6Clow restorative macrophages was performed by RNA
approved biomarkers as clinical endpoints. Additionally, hepatic sequencing.
fibrosis is characterized by the excessive accumulation of extracellu-
Results: Human PCLS from patients with end-stage fibrosis exposed
lar matrix (ECM) proteins such as collagens. Quantifying the ECM
to Ac-6-FP showed significant reduction in the expression of
might improve the precision of fibrosis staging in the liver biopsy. The fibrogenic genes such as TGFB, ACTA2, COL1A1 and COL1A2.
aim of this proof-of-concept study was to develop a high precision
Concordantly, the number of α-SMA+ cells was reduced in PCLS
biopsy method to effectively quantify the fibrosis in the liver of bile exposed to Ac-6-FP. Moreover, inhibiting MAIT cells decreased CCL2
duct ligated (BDL) rats using serological collagen degradation
and its receptor CCR2 expressions. Mice chronically exposed to CCl4
biomarkers.
and daily injected with Ac-6-FP showed accelerated fibrosis regres-
Method: Sprague Dawley rats underwent BDL surgery and were
sion associated with a decrease in CCR2+ Ly6Chigh and an increase in
terminated after 2 weeks. Post termination, 160 μg of snap frozen
Ly6Clow macrophages. RNAseq analyzes performed on Ly6Chigh and
liver tissue was cleaved with matrix metalloproteinase (MMP) -2 and
Ly6Clow macrophages in Ac-6-FP- and vehicle-exposed mice showed
-9 for 3, 24 and 72 hours, and protease activity halted by addition of
reprogramming of macrophage signature by Ac-6-FP. Apoptosis was
1 μM EDTA. MMP-2 and -9 degradation fragments of type III, IV, and
the most significant pathway deregulated by Ac-6FP, with upregula-
VI collagen were measured in the tissue extract by neo-epitope
tion of apoptotic genes in Ly6Chigh macrophages while induction of
specific competitive ELISAs (C3M and C6M, respectively) based on
survival genes was mainly observed in Ly6Clow. Genes of the
monoclonal antibodies. The activity of MMP-2 and MMP-9 was
autophagy pathway, an anti-inflammatory and antifibrogenic mech-
confirmed by their ability to cleave carboxymethylated transferrin
anism in the liver, were also induced in both populations by Ac-6-FP,
and visualized by Coomassie blue staining.
together with an increase in the number of LC3II+cells.
Results: Conditioned medium C3M increased significantly with
Conclusion: Inhibiting MAIT cell activation may offer new perspec-
increasing incubation time with MMP-2, thus a 78-fold increase
tives for antifibrogenic therapy, by promoting fibrosis resolution via
with3 hour incubation that increased to, 128-fold at 72 hours of
reprogramming of macrophage profile.
incubation. In comparison, MMP-9 showed an increase of 43-fold at 3
hours to, 150-fold at 72 hours. This was significant when compared to FRI171
tissue extract with no MMP added ( p < 0.0001). A significant increase The LiverPRO score, a multivariable model for prediction of
was also seen in C6M levels at incubation times of 24 hours (MMP2: significant fibrosis in primary care: derivation, validation and
66-fold and MMP9: 103-fold) and 72 hours (MMP2: 14-fold and comparison with FIB-4 and ELF-test in 5, 000 study participants
MMP9: 46-fold) ( p < 0.0001). MMP-2 and MMP-9 proved successful Katrine Prier Lindvig1,2, Maria Kjærgaard1,2,
in cleaving carboxymethylated transferrin. Johanne Kragh Hansen1,2, Katrine Thorhauge1,2,
Conclusion: A proof-of-concept high precision ex vivo model was Camilla Dalby Hansen1,2, Stine Johansen1,2, Mads Israelsen1,2,
established in BDL treated rodents showing MMP-2 and MMP-9 Peter Andersen1,2, Nikolaj Torp1,2, Taus Holtug3, Sönke Detlefsen4,
degraded collagen type III and VI was released from the liver tissue to Morten Beck Trelle5, Steen Antonsen6, Aleksander Krag1,2,
the conditioned medium as assessed by C3M and C6M. The high Maja Thiele1,2. 1Odense University Hospital, Department of
precision biopsy holds potential to improve the current liver biopsy Gastroenterology and Hepatology, Odense C, Denmark; 2University of
evaluation by providing a quantifiable measurement of liver fibrosis. Southern Denmark, Institute of Clinical Research, Odense C, Denmark;
3
LT Health, Taastrup, Denmark; 4Odense University Hospital,
FRI170
Department of Pathology, Odense C, Denmark; 5Odense University
MAIT cell inhibition promotes liver fibrosis regression by
Hospital, Svendborg, Department of Clinical Biochemistry, Svendborg;
reprogramming macrophage phenotype 6
Odense University Hospital, Svendborg, Department of Clinical
Morgane Mabire1, Hegde Pushpa1, Hammoutene Adel1, Biochemistry, Svendborg, Denmark
JingHong Wan1, Manon Allaire1, Al Sayegh Rola1,
Email: [email protected]
Tristan Thibault-Sogorb1,2, Emmanuel Weiss1,2, Valérie Paradis1,3,
Pierre de la Grange4, Hélène Gilgenkrantz1, Sophie Lotersztajn1. Background and aims: Significant liver fibrosis is the precursor of
1 progressive liver disease and predicts the risk of liver-related
Université de Paris, Centre de Recherche sur l’Inflammation (CRI),
INSERM, U1149, PARIS 18, France; 2Département d’Anesthésie et complications. We aimed to generate a decision aid for general
Réanimation, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, practitioners, to evaluate which patients to refer to secondary care, by
92110, Clichy, France, Clichy, France; 3Département de Pathologie, developing a multivariable model for diagnosis of significant fibrosis
Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, 92110, Clichy, in a biopsy-controlled cohort.
France; 4GenoSplice Technology, Paris, France Method: We derivated the LiverPRO score in a derivation cohort of
Email: [email protected] high-risk patients with an alcohol overuse and biopsy-controlled
fibrosis stage (F0–F4). Univariable logistic regression followed by
Background and aims: Mucosal-Associated Invariant T (MAIT) cells decision tree analysis detected nine routine liver blood markers and
are non-conventional T cells restricted by the non-classical MHC-1b age as predictors of significant fibrosis (≥F2). From these, we built the
molecule MR1 that display altered functions during chronic liver
final model as a software combining multiple algorithms derived
diseases. We recently reported that hepatic MAIT cells are activated from fractional polynomial regression that predicts the risk of
during fibrosis in human liver samples and in mice models and

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S475

POSTER PRESENTATIONS
significant fibrosis in a score range of 0–100%. We validated the FRI172
LiverPRO score in a screening study of randomly invited Danish The protective effect of time-caloric restriction in liver fibrosis
citizens at risk of NAFLD or alcohol-related liver disease, using a liver induced by nitrosamines in rat model
stiffness measurement ≥8 kPa as outcome. Finally, we compared the Christian Molina-Aguilar1,2, Fernanda Arriaga-González11,2,
diagnostic accuracy of the LiverPRO score with the serum markers Felipe Castañeda1,3, Kevin Villa-Malagon4,5, Irving Simonin-Wilmer1,
ELF-test and FIB-4. Obed Ramírez Sánchez1, Emilio Calderón Garza6,
Results: The derivation cohort included 463 patients, 75% male, with Mayra López Azuara2, Osiel Ledesma Juárez7,
a median age of 57 years (IQR 14). The majority (197/463, 55%) had Martín del Castillo Velasco-Herrera8, David Adams8,
significant liver fibrosis (≥F2), and 94 (20%) had advanced liver Mauricio Díaz-Muñoz9, Carla Daniela Robles-Espinoza1.
fibrosis (≥F3). The LiverPRO score diagnosed significant fibrosis with 1
International Laboratory for Human Genome Research, The Cancer
good diagnostic accuracy (AUC 0.84; 95% CI 0.81–0.88), similar as the Genetics and Bioinformatics Laboratory, Querétaro, Mexico; 2Centro de
ELF-test (AUC 0.84; 0.80–0.88), and superior to the FIB-4 (AUC 0.77; Bioingeniería, ITESM, Departamento de Bioingeniería, Querétaro,
95% CI 0.73–0.83). The same was observed for advanced fibrosis Mexico; 3Universidad Anáhuac, Facultad de Ciencias de la Salud, Ciudad
(LiverPRO AUC 0.92; 0.88–0.95 versus ELF-test AUC 0.92; 0.89–0.95 de México; 4Facultad de Biología UMSNH, Morelia, Mexico;
versus FIB-4 AUC 0.84; 95% CI 0.79–0.89). 5
International Laboratory for Human Genome Research, UNAM, The
The validation cohort included 4.722 participants, 49% male, median Cancer Genetics and Bioinformatics Laboratory, Querétaro, Mexico;
age 57 years (IQR 11), and 299 (6%) had a TE ≥8 kPa, of those 50% had 6
Facultad de Medicina-UNAM, Ciudad de México, Mexico; 7Hospital
risk factors for ALD, 46% for NAFLD and 4% had no risk factors for fatty General de Cadereyta, Cadereyta, Mexico; 8Wellcome Sanger Institute,
liver disease. In this low prevalence cohort, the LiverPRO score Cambridgeshire, United Kingdom; 9Instituto de Neurobiología UNAM,
detected TE ≥8 kPa with moderate accuracy (AUC 0.75; 95% CI 0.72– Neurobiología Celular y Molecular, Querétaro, Mexico
0.77), comparable to the ELF test (AUC 0.74; 95% CI 0.71–0.78) and Email: [email protected]
superior to FIB-4 (AUC 0.64; 95% CI 0.59–0.68).
Background and aims: Liver fibrosis is the first stage in the
progression of cirrhosis and hepatocellular carcinoma (HCC).
Around 80% of people with HCC developed cirrhosis as a previous
stage, being chronic inflammation a key factor in these maladies’
progression. Fibrosis is the only reversible stage of the liver injury
progression; however, the cellular and molecular mechanisms of this
stage are not fully understood. A better understanding of fibrotic
would represents an unprecedented opportunity to avoid complica-
tions (cirrhosis and HCC) in patients. It would also help improve
patient survival and ease the significant burden on the national
health system by reducing drastically the number of HCC patients,
which would also lower healthcare costs in many countries. In recent
years, our group has explored the beneficial effects that calorie
restriction (T-CR) without malnutrition has in rats treated with
diethylnitrosamine (DEN), a hepatotoxic that allows us to recapitulate
fibrosis-cirrhosis-HCC sequence to characterized better the liver
damage and identify potential therapeutic targets. We showed in
2017 that T-CR, in the HCC stage, avoided liver chronic inflammation,
the cirrhosis where established in early-stage preserving the hepatic
Figure: Overall diagnostic performance for Significant liver fibrosis and functions, and finally although HCC tumors developed, these had a
Liver Stiffness Measurement >8 kPa of the LiverPRO score, FIB-4 and ELF- slower evolution, all compared with rats Ad Libitum (24 h of food
test in the derivation and validation cohort. access)
Method: Forty male Wistar rats (with an initial weight of 240 ± 20 g)
Conclusion: The LiverPRO score accurately predicts significant and
were randomly assigned into one of four experimental groups. AL:
advanced liver fibrosis in both a high prevalence and a low prevalence
Control rats without DEN and 24 h of food access. AL + DEN: Rats with
cohort. Combined with a very low cost of the routine liver blood
24 h of food access and DEN treatment weekly during 10 weeks to
markers and an easy interpretable score from 0 to 100%, the score
induce fibrosis. T-CR: Rats with only 2 h of food access per day and
may be a useful screening tool and decision aide for primary care
without DEN. T-CR+DEN: Rats treated weekly for 10 weeks with DEN
referral pathways.
and only 2 h of food access.
Results: A) T-CR and T-CR+DEN groups had a reduction of 30 and 37
percent in food intake in comparison with the AL, inducing less
corporal weight gain but with normal nutritional state. B)
Histopathology, through Ishak stage estimation and blood chemistry
assessments, revealed that DEN induces fibrosis and light tissue
damage (seen in both groups treated with DEN), but was less
aggressive when rats are under caloric restriction. C) Preliminary
results suggested a lower “basal chronic inflammatory state" was
induced by caloric restriction in both healthy (T-CR) and fibrotic (T-CR
+DEN) groups evidenced in total Leucocytes levels. To complement
these results, we are analyzing RNAseq data from all these groups and
the results will be presented at the congress.
Conclusion: Our results so far suggest that T-CR maintains its
beneficial effects at a physiological level despite the damage caused
by DEN in fibrosis, and that one of the mechanisms of this effect is
through a decrease in the basal inflammatory state of the liver.

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 POSTER PRESENTATIONS
FRI173 to assess the fibrosis levels. Animals (n = 20/group) were dosed daily
Macrophage MerTK promotes a profibrogenic cross-talk with with OCA (30 mg/kg), seladelpar (10 mg/kg), resmetirom (1 mg/kg)
hepatic stellate cells via soluble mediators or vehicle in 0.5% CMC, PO for an additional 3 weeks while continuing
Mirella Pastore1, Chiara Raggi1, Nadia Navari1, Benedetta Piombanti1, CCl4 administration. Liver histology assessments (H&E and PSR) and
Giovanni Di Maira1, Elisabetta Rovida1, Marie-Pierre Piccinni1, hydroxyproline content were analyzed as measures of liver fibrosis.
Letizia Lombardelli1, Federica Logiodice1, Krista Rombouts2, Results: Average hydroxyproline content at treatment start was
Salvatore Petta3, Fabio Marra1. 1University of Florence, Firenze, Italy; 253 mg/g liver. Additional 3 weeks of CCl4 treatment increased the
2
University College London, United Kingdom; 3Università degli Studi di average hydroxyproline to 290 mg/g. Neither FXR nor THR agonists
Palermo, Palermo, Italy decreased hydroxyproline content (277 and 291 mg/g, respectively)
Email: [email protected] while PPARd decreased hydroxyproline to 215 mg/g. In addition to
the reduction in total hydroxyproline, the PSR staining demonstrated
Background and aims: Activation of Kupffer cells and recruitment of
a reduction in bridging fibrosis with seladelpar compared to both the
monocytes are key events in fibrogenesis. These cells release soluble vehicle at 8 weeks and the starting levels at 5 weeks. No apparent
mediators which induce the activation of hepatic stellate cells (HSC),
changes in fibrosis staining were observed with the other treatments.
the main fibrogenic cell type within the liver. Mer tyrosine kinase
(MerTK) signaling regulates multiple processes in macrophages and
has been implicated in the pathogenesis of NASH-related fibrosis. In
this study, we explored if MerTK activation in macrophages
influences the profibrogenic phenotype of HSCs.
Method: M2c-like (MerTK+/CD206+/CD163+/CD209−) macrophages
were differentiated from peripheral blood monocytes using M-CSF
and IL-10. The role of MerTK was assessed by stimulation with the
ligand Gas-6 and by pharmacologic inhibition with UNC569.
Results: MerTK+ macrophages exhibited activation of STAT3, ERK1/2,
and p38 and increased expression of VEGF-A. Exposure of MerTK+
macrophages to Gas-6 increased activation of MerTK and down-
stream pathways. These events were reverted by pretreatment with
UNC569. MERTK and Gas-6 mRNA levels were gradually increased
during macrophage polarization towards a M2c-like phenotype and
were significantly greater in Kupffer cells than in peripheral blood
monocytes. Gas-6 was released both by M2c-like macrophages and
Kupffer cells. Activation of MerTK in macrophages induced a
secretome which caused a significant increase in migration, prolif-
Conclusion: The CCl4 mouse model may be used to test for molecular
eration, viability and expression of profibrogenic factors in HSCs.
targets that will reduce established fibrosis. The combination of total
Conditioned medium of Gas-6-stimulated MerTK+ macrophages also
biochemical and histologic measurements are important to assess
induced a significant increase in phosphorylation of STAT3 and p38 in
the topographic changes. Reduction of the PSR positive fibrotic cords
HSCs, and upregulation of IL8 expression. These effects were
between the veins is generally considered beneficial and readily
specifically related to MerTK activity in macrophages, as indicated
observable in this model. We believe that this 8-week model can be
by pharmacologic inhibition.
used to dissect some of the molecular mechanisms for fibrogenesis,
Conclusion: MerTK activation in M2c-like macrophages modifies the
fibrolysis after cessation of CCl4, and fibrolysis in the presence of CCl4.
secretome to promote HSC profibrogenic features, indicating that this
Is treatment-related fibrolysis in the presence of CCl4 just a reduction
receptor may be implicated in the pathogenesis of hepatic fibrosis.
in the CCl4 mediated fibrogenesis or are there separate processes?
FRI174 This model can be used to attempt to answer these questions and
Comparative fibrosis-reducing activities of farnesoid X receptor build on the findings that PPARd agonists reduce established fibrosis
(FXR), peroxisome-proliferator activated receptor delta (PPAR) in the dietary NASH mouse, the foz/foz mouse, and the NIF mouse
and thyroid hormone receptor (THR) agonists in the carbon models.
tetrachloride mouse model
FRI175
Edward Cable1, Jeffrey Stebbins1, Yun-Jung Choi1, Jiangao Song1,
A novel role for serine protease Kallikrein 8 in liver fibrosis
Prasad Manchem2, Sanjay Pandy2, Charles McWherter1. 1CymaBay
through cleaving complement C3 and hepatic macrophage
Therapeutics Inc., Newark, United States; 2Triangulum Biopharma,
polarization
Carlsbad, United States
Cichun Wu1, Yao Liu1, Ying Li1, Wei Zhang1, Lei Fu1, Xin Ni2,
Email: [email protected]
Shifang Peng1. 1Xiangya Hospital Central South University, Department
Background and aims: Fibrogenesis is a key first step toward of Infectious Diseases, Changsha, China; 2Xiangya Hospital Central South
cirrhosis in the liver, independent of etiology. A limited number of University, International Collaborative Research Center for Medical
nuclear receptor agonists that have been tested in diseases with liver Metabolomics, Xiangya Hospital Central South University, Changsha,
fibrosis. The AIM of the current study is to test three of these agonists China
in established fibrosis in the mouse CCl4 model. These three selected Email: [email protected]
agonists are: the FXR agonist, obeticholic acid; the PPARd agonist,
Background and aims: Kallikrein 8 (KLK8), an emerging serine
seladelpar, and the THRb agonist, resmetirom. This model’s mech-
protease in the family of Kallikrein-related peptidases (KLKs), has
anism of liver injury is via the trichloromethyl radical, which is likely
been implicated in myocardial and renal fibrosis. To date, it remains
harsher than any human disease. The rationale for selecting this
unknown whether and how KLK8 is involved in liver fibrosis. In this
model is that fibrosis can be established prior to initiation of
study, we aimed to determine the role of KLK8 in liver fibrosis and the
treatment and the ability of these receptor agonists can be stringently
underlying molecular mechanisms.
tested for reduction of established fibrosis.
Method: KLK8 expression and localization were examined in liver
Method: Male C57B/6 mice were treated with 1 mL of CCl4 per g BW
tissues from fibrotic human subjects and rodent models. In vivo and in
via IP injection twice per week for 8 weeks. Concurrent with
vitro silencing or overexpression of KLK8 was used for functional
treatment initiation at week 5, a set of animals (n = 10) was sacrificed

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POSTER PRESENTATIONS
studies. The natural substrates of KLK8 were screened and character- KLK8, and eventually help unleash its therapeutic potential in the
ized in the liver. Mechanistic studies were performed to identify the development of novel treatments.
involving KLK8-dependent molecular pathways.
Results: Hepatocyte KLK8was significantly increased in liver fibrotic FRI176
patients and rodents, and the greater levels were correlated with the The modulation of NADPH oxidases by tyrosol-derived phenolic
higher degree of liver fibrosis. Notably, liver fibrosis occurred compounds prevents hepatic fibrogenesis
spontaneously in transgenic-mediated overexpression of KLK8 in Daniela Gabbia1, Sara Carpi2,3, Samantha Sarcognato4, Ilaria Zanotto1,
rats, suggesting apro-fibrotic effect. With hepatocyte-specific silen- Beatrice Polini2, Katia Sayaf5, Paola Nieri2, Francesco Paolo Russo5,
cing of KLK8 in rodent models, we found that liver fibrosis was Maria Guido4, Sara De Martin1. 1University of Padua, Department of
significantly attenuated compared with controls. Using immunopre- Pharmaceutical and Pharmacological Sciences, Padova, Italy; 2University
cipitation in combination with mass spectrometry, we identified of Pisa, Department of Pharmacy, Pisa, Italy; 3CNR PISA, NEST, Pisa, Italy;
4
complement C3 as the natural substrate of KLK8. Furthermore, in vitro University of Padua, Department of Medicine, Padova, Italy; 5University
and in vivo mechanistic studies reveled that KLK8 promoted liver of Padua, Department of Surgery, Oncology and Gastroenterology,
fibrosis through cleaving complement C3 to its active fragment C3a, Padova, Italy
which subsequently induced the macrophage polarization toward Email: [email protected]
M2 phenotype and secretion of transforming growth factor (TGF)-β1, Background and aims: Hepatic NADPH oxidases (NOXs) are devoted
leading to an indirect activation of hepatic stellate cells.
to the production of reactive oxygen species (ROS), thus regulating
inflammatory and fibrotic processes. Exaggerated NOX expression
and activation, particularly of NOX1 and NOX4, have been related to
the activation of hepatic stellate cells (HSCs) and the trigger of
fibrogenesis. Therefore, compounds modulating the expression and
activity of NOXs may represent promising agents for the manage-
ment of hepatic fibrosis. In this study we investigated the antifibrotic
and antioxidant action of the two phenolic compounds tyrosol and
hydroxytyrosol, known for their cardioprotective activity, with the
aim of unravelling their effect in vitro and in vivo on NOX-related
fibrogenetic pathways.
Method: We evaluated tyrosol and hydroxytyrosol activity by means
of LX2 and HepG2 cells, used as in vitro models of HSCs and
hepatocytes, respectively. A mouse model of liver fibrosis was
induced by a 4-week IP CCl4 administration to 6 Balb/C mice; 6
untreated mice were used as controls. Tyrosol and hydroxytyrosol
were administered daily by oral gavage. Levels of hepatic NOX1/4,
alphaSMA, COL1A1, IL-6, IL-10 were assessed by qPCR and Western
blot. Hepatic miR-181-5p, miR-221, miR-29b-3p and miR-101 were
measured by qPCR.
Results: Tyrosol significantly decreased the production of ROS by
HepG2 cells, and the mRNA levels of NOX1/4, alphaSMA and COL1A1
in TGFbeta1-activated LX2 cells, displaying an antifibrotic and
antioxidant activity comparable to the prototypical NOX1/4 inhibitor
Figure S1. Expression levels of human hepatic KLK8 in liver fibrosis and
control. (A) qRT-PCR analysis of themRNA expression levels of KLK1–
GKT136901. An increase of hepatic ROS ( p < 0.0001), alphaSMA,
KLK15 in the liver fibrosis group (n = 8) and the healthy control group (n = COL1A1, IL-6 and IL-10 mRNA levels ( p < 0.05) were observed in
6); (B) Western blot analysis of KLK8 protein levels in the liver fibrosis fibrotic mice, as well as a slight increase in NOX1/4 expression.
group (n = 10) and healthy control group (n = 10); (C) Serum KLK8 in Tyrosol and hydroxytyrosol were able to counteract these effects, by
patients with liver fibrosis (n = 108) and healthy control individuals (n = significantly downregulating alphaSMA, COL1A1, NOX1/4, IL-6 and
31); Data are expressed as means ± SEM; *P < 0.05; **P < 0.01; ***p < 0.001; IL-10 with respect to fibrotic mice. The profibrotic miRNAs miR-181-
****P < 0.0001 vs control. 5p and miR-221 were downregulated by tyrosol, whereas the
expression of antifibrotic miRNAs miR-29b-3p and miR-101 was
restored to physiological level by both tyrosol and hydroxytyrosol.
Liver histology confirmed a reduction of fibrosis in treated mice.
Conclusion: The phenolic compounds tyrosol and hydroxytyrosol
ameliorate hepatic fibrosis by reducing hepatic oxidative stress and
inflammation and modulating the hepatic expression of miRNAs
involved in fibrogenesis. Tyrosol-derived molecules should be
evaluated as promising antifibrotic candidates.

Proposed mechanisms. During liver injury, KLK8 secreted by hepatocytes

releases the active fragment C3a by shearing complement C3, which in
turn activates macrophages to secrete TGFβ1 and promotes the develop-
ment of liver fibrosis through the TGFβ1/smad2/3 signaling pathway

Conclusion: This study has delineated a novel role for KLK8in liver
fibrosis. As such, the new findings may advance our understanding of

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 POSTER PRESENTATIONS
FRI177 FRI178
Exploring gender-related differences in liver fibrosis and Multicenter external validation of FIB-6: a novel, machine-
regeneration through a new experimental carbon tetrachloride learning, simple bedside score to rule out severe liver fibrosis and
protocol in mice cirrhosis in patients with MAFLD
Katia Sayaf1, Ilaria Zanotto2, Daniela Gabbia2, Dafne Alberti3, Gamal Shiha1, Reham Soliman1, Nabiel Mikhail2, Khalid Alswat3,
Giulia Pasqual3, Sara De Martin2, Francesco Paolo Russo1. 1University Ayman Abdo3, Faisal Sanai4, Necati Ormeci5, George Dalekos6,
of Padova, Department of Surgery, Oncology and Gastroenterology, Amir Anushiravani7, Mai Mabrouk8, Samir Marzouk9. 1Egyptian Liver
Padova, Italy; 2University of Padova, Department of Pharmaceutical and Research Institute and Hospital (ELRIAH), Gastroenterology and
Pharmacological Sciences, Padova, Italy; 3University of Padova, Hepatology, Egypt; 2Egyptian Liver Research Institute and Hospital
Department of Surgery, Oncology and Gastroenterology, Padova, Italy (ELRIAH), Biostatistics and Cancer Epidemiology, Egypt; 3College of
Email: [email protected] Medicine, King Saud University, Medicine, Saudi Arabia; 4King Abdulaziz
Medical City, Gastroenterology, Saudi Arabia; 5Ankara University School
Background and aims: The incidence of chronic liver diseases (CLDs)
of Medicine, Gastroenterology, Turkey; 6National Expertise Center of
is two-fold higher in men than women and they display clinically
Greece in Autoimmune Liver Diseases, Medicine and Research
relevant differences. Thus, understanding the mechanistic gaps
Laboratory of Internal Medicine, Greece; 7Tehran University of Medical
between females and males by pre-clinical studies is fundamental
Sciences, Digestive Disease, Iran; 8Misr University for Science and
to increase the awareness on gender influence in the pathophysio-
Technology (MUST), Biomedical Engineering, Egypt; 9Arab Academy for
logical and regenerative mechanisms underlying liver fibrosis.
Science and Technology (AASTMT), Basic and Applied Science
Method: A new experimental protocol based on increasing doses of
Department, Egypt
carbon tetrachloride (CCl4) has been developed and performed in
Email: [email protected]
female and male Balb/C mice, by intraperitoneal injections for 12
weeks, followed by a washout period of 8 weeks. Mice were sacrificed Background and aims: Non-invasive tests (NITs) are urgently
at different timepoints (6, 12 and 20 weeks). Flow cytometry required to evaluate hepatic fibrosis in MAFLD. We previously
experiments were performed on fresh liver tissues to evaluate the developed and validated a non-invasive diagnostic index based on
amount of recruited monocytes-derived macrophages (MoMFs). routine laboratory parameters for predicting the stage of hepatic
Liver histology was assessed by Masson’s trichrome staining, and fibrosis in patients with chronic hepatitis C (HCV) called FIB-6
liver function was evaluated by the hydroxyproline assay. The gene through machine learning with random forests algorithm using
and protein expression of collagen, growth factors, and pro retrospective data of 7238 biopsy proven chronic hepatitis C (CHC)
inflammatory elements were evaluated by qPCR and immunohisto- patients. Our aim is to validate this novel score in patients with
chemistry, respectively. MAFLD.
Results: Both female and males developed a progressive liver fibrosis Method: Performance of the new score was externally validated in
during CCl4 treatment and showed liver regeneration during the cohorts from one site in Egypt (n = 674) and in 5 different countries
washout period. After 6 weeks of treatment, male mice showed more (n = 1798) in Iran, KSA, Greece, Turkey and Oman). Biopsy samples
fibrotic areas ( p < 0.05) and more activated stellate cells (HSCs) than were scored by experienced pathologists who used the METAVIR
female mice ( p < 0.05). Furthermore, a higher inflammatory status scoring system. Results were also compared with three established
within male liver was confirmed during the acute damage by the tools (FIB-4, APRI, and AAR).
intensive recruitment of pro-inflammatory Ly6Chigh F4/80med to high Results: In this study, 2472 patients met the criteria, and their liver
CD11bhigh MoMFS, together with higher levels of gene expression of biopsy results were included for analysis. Using the optimal cutoffs in
pro-inflammatory growth factors than females. On the other hand, the data of FIB-6 indicated a reliable performance in diagnosing
females developed a worse hepatic condition after 12 weeks of CCL4 cirrhosis, severe fibrosis, and significant fibrosis. Results indicated
treatment, showing a higher hydroxyproline content, more activated good sensitivity and NPV. Sensitivity = 70.5%, specificity = 62.9%. PPV
HSCs than males, and elevate amounts of Ly6Chigh F4/80med to high = 15.0% and NPV = 95.8% for diagnosis of cirrhosis. For diagnosis of
CD11bhigh MoMFS. During the washout period, female mice showed severe fibrosis (F3 and F4), the results were 86.5%, 24.0%, 15.1% and
less fibrotic areas than males ( p < 0.05) and the presence of small 91.9% respectively, while for diagnosis of significant fibrosis (F2, F3
amounts of MoMFs, while some activated HSCs but no pro- and F4), the results were 87.0%, 16.4%, 24.8% and 80.0%). Comparing of
inflammatory MoMFs were detected in males. the results of FIB-6 rule-out cutoffs with those of FIB-4, APRI, and AAR
Conclusion: This new model of fibrosis obtained with increasing showed that in ruling out severe fibrosis and cirrhosis, FIB-6 gave the
doses of CCl4 led to the development of liver damage without highest sensitivity and NPV (97.0% and 94.7%), as compared to FIB-4
adaptive responses of the liver to the injury. We observed gender- (71.6% and 94.7%), APRI (36.4% and 90.7%), and AAR (61.2% and
related differences in liver damage and regeneration, due to the fact 90.9%).
that gender influences the recruitment of pro-inflammatory MoMFs
and the activation of hepatic stellate cells.

Table: (abstract: FRI178): Diagnostic performance of FIB-6 optimal cutoffs in all cohorts compared to the liver biopsy results
Cutoff Sensitivity Specificity PPV NPV
Cirrhosis (F4 vs. F0123) 2.3159 70.5 (64.0–76.2) 62.9 (60.9–64.9) 15.0 (12.9–17.4) 95.8 (94.7–96.7)
Severe fibrosis (F34 vs. F012) 1.8992 86.5 (82.5–89.8) 24.0 (22.3–25.9) 15.1 (13.6–16.8) 91.9 (89.4–93.9)
Significant fibrosis (F234 vs. F01) 1.7720 87.0 (84.1–89.5) 16.4 (14.8–18.1) 24.8 (23.0–26.7) 80.0 (75.7–83.7)

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POSTER PRESENTATIONS
of immune cell interaction with normal or fibrotic ECM, and more in
Table: Diagnostic performance of FIB-6 rule-out cutoffs for severe general, with bioengineered constructs, and showed that mechan-
fibrosis (F3) or cirrhosis (F4) in all cohorts compared with that of FIB- isms of chronic inflammation observed in fibrosis can be replicated in
4, APRI, and AAR vitro.
Cutoff Sensitivity NPV FRI180
FIB-6 1.5023 97.0 (94.6–98.4) 94.7 (90.4–97.1) Clinical and genetic factors associated with regression of fibrosis
FIB-4 1.45 71.6 (66.6–76.2) 94.7 (93.6–95.7) in ACLD after etiological therapy
APRI 0.70 36.4 (31.5–41.7) 90.7 (89.5–91.8) Yuly Mendoza1,2, Mojgan Masoodi3, Sofia Tsouka3, Jaime Bosch2,
AAR 1.00 61.2 (55.9–66.3) 90.9 (89.3–92.3) Annalisa Berzigotti1,2. 1Department of Visceral Surgery and Medicine,
Inselspital, Bern University Hospital, University of Bern, Switzerland;
2
Department for BioMedical Research, Visceral Surgery and Medicine,
Conclusion: FIB-6 score is an accurate, simple, noninvasive test for
University of Bern, Switzerland; 3Institute of Clinical Chemistry, Bern
ruling out advanced fibrosis and liver cirrhosis in patients with
University Hospital, Bern, Switzerland
MAFLD better than APRI, FIB‐4 and AAR.
Email: [email protected]
FRI179 Background and aims: Liver fibrosis is the main determinant of
A bioengineered approach to re-create and study the extracellular clinical outcomes in advanced chronic liver disease (ACLD) of any
matrix-immune cell crosstalk in normal and fibrotic liver etiology. The introduction of effective etiological therapies has shown
Sara Campinoti1, Claire McQuitty1,2, Lorenzo Caciolli1, that liver fibrosis and even cirrhosis is reversible after eliminating the
Bruna Almeida1, Lai Wei1,2, Luca Zanieri3, Antonio Riva1,2, cause of ACLD. However, not all patients experience fibrosis
Alessandro F. Pellegata4, Paola Bonfanti3,5, Sara Mantero4, regression, evidencing that other factors modulate this process. In
Shilpa Chokshi1,2, Luca Urbani1,2. 1The Roger Williams Institute of order to better understand the genetic and molecular mechanisms
Hepatology, London, United Kingdom; 2King’s College London, Faculty of controlling fibrosis regression we analysed the genetic and tran-
Life Sciences & Medicine, United Kingdom; 3The Francis Crick Institute, scriptomic pathways in ACLD with or without regression of fibrosis
Epithelial Stem Cell Biology & Regenerative Medicine Lab, United using high-throughput technologies.
Kingdom; 4Politecnico Di Milano, Department of Chemistry, Materials Method: We conducted a case-control pilot study of 60 patients with
and Chemical Engineering “Giulio Natta”, Italy; 5University College of ACLD of different etiology, 30 with histological and/or clinical
London, Division of Infection and Immunity, Royal Free Hospital, United evidence of regression (Regressors, Re) and 30 without (Non-
Kingdom regressors, NRe), after a minimum of 24 months of etiological
Email: [email protected] therapy. In all patients we performed genotyping (TaqMan assay) of
gene variants associated with liver fibrosis (PNPLA3, TM6SF2,
Background and aims: Liver fibrosis is caused by progressive
SERPINA1, GCKR, TMC4, HSD17B13). Transcriptomic analysis
accumulation of extracellular matrix (ECM) coupled with chronic
(RNAseq) was done in 30 frozen paired liver biopsies (before and
inflammation. Bioengineering allows for the development of disease
after therapy) of 15 patients. Differentially Expressed Genes (DEGs)
models to study complex diseases, such as liver fibrosis, where both
analysis were determined using DESeq2 and selected for FDR <0.05.
cellular and extracellular microenvironment components contribute
The enrichment of biological pathways was determined with KEGG.
to the pathology. Bioengineered liver models have been developed by
Results: Lack of regression was associated with higher frequency of
combining decellularised liver scaffolds with liver cells. However, the
GCKR-rs1260326 CT-Allele (NRe 63.3% vs Re 36.7%; OR: 0.240, p =
lack of an immune compartment is an important drawback given the
0.020), obesity (63.7% vs. 36.7%, p = 0.041) and higher liver stiffness
role of inflammation in fibrosis. This study aims at establishing a
(33.3 vs. 21.8 kPa, p = 0.032). These three factors remained inde-
bioengineered liver model to study the immune cell-ECM crosstalk in
pendently associated with lower likelihood of ACLD regression on
fibrosis.
multivariate analysis (Figure). RNAseq data comparing Re vs. NRe in
Method: We developed two custom-made bioreactors for whole rat
the post-therapy samples disclosed 109 significantly DEGs out of 17,
livers or human tissue segment culture (WL and HuTS bioreactor
243 genes. Downregulated DEGs in Re showed significant enrichment
respectively). Decellularised normal and fibrotic rat and human livers
for the Hippo signaling pathway ( p < 0.05). Other pathways identified
were obtained following established protocols (detergent-enzymatic
included the PI3K-Akt signaling pathways, ECM-receptor interaction,
treatment). Human peripheral blood mononuclear cells (PBMCs)
focal adhesion and relaxin signaling pathways, already known to be
from healthy donors, were perfused in WL or HuTS bioreactor in
involved in liver fibrosis.
absence or presence of decellularised normal or fibrotic liver
scaffolds. Viability, phenotype, and cytokine production in the
medium were assessed (via FACS and Luminex) in comparison to
static culture conditions. Gene expression and cell phenotype of
PBMCs present in the scaffolds were examined via qPCR and
immunofluorescence.
Results: The bioreactors allowed for perfusion of PBMCs through
decellularised rat and human liver scaffolds. Circulated PBMCs
maintained cell viability and cell population frequency comparable
to static culture conditions. When PBMCs were perfused through
decellularised liver scaffolds, a portion of cells infiltrated the matrix,
with different cell types and frequency between normal and fibrotic
liver scaffolds. In fibrotic scaffolds, the number of circulating T cells
decreased, while more liver infiltrating monocytes were found in
respect to healthy condition. Cytokine analysis revealed that the ECM
triggers the release of innate and adaptive immune system cytokines
and those related to pro-regenerative immune response. Conclusion: Presence of obesity, high LSM and GCKR-rs1260326 CT-
Conclusion: Here we show the validation of two bioreactor-based Allele decrease the likelihood of fibrosis regression of ACLD. The liver
systems which allow to perfuse immune cells through decellularised transcriptome analysis suggests that the Hippo signaling pathway, a
liver matrix. This perfusion system proved to be suitable for the study pathway driving hepatic stellate cell activation, is involved in fibrosis

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 POSTER PRESENTATIONS
regression and may represent a novel potential therapeutic target to FRI182
reverse liver fibrosis in ACLD. Characterisation of the novel Galectin-3 inhibitor GB1107 on CCl4-
induced liver fibrosis in mice
FRI181 Alison MacKinnon1, Ross Mills2, Fredrick Zetterberg3, Rob Slack3.
Addressing the heterogeneity of fibrosis in liver biopsy specimens 1
Galecto Inc, Edinburgh, United Kingdom; 2University of Edinburgh,
with qFibrosis – a new paradigm for an old problem Centre for Inflammation Research, Edinburgh, United Kingdom; 3Galecto
David E. Kleiner1, Pik Eu Jason Chang2, Dean Tai3, Elaine Chng3, Inc, Copenhagen, Denmark
Yayun Ren3, Feng Liu4, Huiying Rao4, Lai Wei5, Arun Sanyal6. Email: [email protected]
1
Laboratory of Pathology, Center for Cancer Research, NCI, MD, USA;
2
Department of Gastroenterology and Hepatology, Singapore General Background and aims: Galectin-3 (Gal-3) is a pro-fibrotic β-
Hospital, Singapore; 3HistoIndex Pte. Ltd., Singapore; 4Peking University galactoside binding lectin highly expressed in fibrotic liver (1) and
People’s Hospital, Peking University Hepatology Institute, Beijing Key implicated in hepatic fibrosis (2). GB1107 is a novel orally active anti-
Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, Gal-3 small molecule inhibitor that has high affinity and selectivity
China; 5Hepatopancreatobiliary Center, Beijing Tsinghua Changgung for galectin-3 as well as high oral bioavailability in mice (3).
Hospital, Tsinghua University, Beijing, 102218, China; 6Virginia Method: Liver fibrosis was induced by administration of CCl4 (1:3
Commonwealth University, Richmond, Virginia, USA CCl4:olive oil) at 1 microlitre per g or olive oil control twice weekly by
Email: [email protected] intraperitoneal injection in male C57Bl/6 mice for 8 weeks. GB1107 or
vehicle control was administered once daily orally (10 mg/kg) for the
Background and aims: A 1-stage fibrosis improvement is key for last 4 weeks of CCl4 treatment. Livers were removed and fibrosis
therapeutic benefit assessment in NASH trials. But in trials with a 48- assessed by Sirius red staining of liver sections and gene sequencing.
week duration, most patients do not change their fibrosis stage Total RNA was extracted and libraries were prepared using the
according to the CRN system. This is due to either insufficient change NEBNEXT Ultra II Directional RNA Library Prep kit and the Poly-A
in collagen amount or fibrosis distribution. qFibrosis can analyse mRNA magnetic isolation module. Paired-end sequencing with a read
these differential changes which has been shown to provide insights length of 100 bp was performed using a single P3 flowcell on the
on drug effects. The generalisability in this approach beyond NASH NextSeq 2000 platform. The raw reads were aligned to the mouse
has not been established. In this exploratory analysis, a cumulative reference genome assembly GRCm39 using STAR. Pathway enrich-
qFibrosis score was used to identify fibrosis changes in different ment analysis was performed to determine enrichment of differen-
regions of the liver sections in treated hepatitis C (HCV) subjects who tially expressed genes (DEGs)within Reactome pathways and Gene
have achieved sustained virological response. Ontology (GO) terms.
Method: Paired biopsies from 35 patients assessed to have “no- Results: GB1107 significantly reduced CCl4-induced liver fibrosis
change” in fibrosis. Using qFibrosis, collagen proportionate area (CPA) (Sirius red, CCl4-vehicle 2.70 + 0.24%; CCl4-GB1107 1.99 + 0.10% ( p =
of 5 pre-defined fibrosis regions [portal, peri-portal (PP), peri-central 0.009)). Using a false discovery rate-adjusted statistical threshold
(PC), peri-sinusoidal (PS) and bridging] were quantified using second (FDR-adjusted p < 0.05) and a 2-fold change in expression cutoff, 1,
harmonic generation/two photon excitation fluorescence technology. 659 DEGs were identified with CCl4 treatment compared to control.
CPA values for each region were normalized to a 0–1 range with Comparing GB1107 treatment with CCl4 vehicle mice 1147 DEGs were
qFibrosis total weighted score (qF-TWS) calculated as a sum of all 5 identified. Pathways strongly enriched in up-regulated genes in the
CPA values. CCl4 group included those related to the extracellular matrix, and
Results: The baseline staging of the HCV patients were F0 (n = 1); F1 collagen biosynthesis and assembly, cell cycle and the immune
(n = 2); F2 (n = 2); F3 (n = 7); F4 (n = 9); F5 (n = 2); F6 (n = 12). This system whilst pathways related to fatty acid or lipid metabolism were
cohort was reclassified by qF-TWS as those with progression (n = 9), enriched in the down regulated genes. Principal component analysis
no change (n = 7) and regression (n = 19). Changes in different regions revealed that GB1107 overlapped significantly with the control group
of the tissue sections and their relationship to overall CPA response of and effectively reversed the CCl4 induced gene changes.
3 individuals from these representative groups is shown. We Conclusion: GB1107 inhibited CCl4-induced liver fibrosis and
observed differential changes in different regions of the liver, with reversed CCl4-induced gene changes. Small molecular weight and
specific changes in the perisinusoidal region even though the orally active inhibitors of galectin-3 show promise as potential new
conventional fibrosis stage did not change. oral anti-fibrotic agents for the treatment of liver fibrosis. A first-in-
human study with GB1211, an analogue of GB1107, has shown it to be
both safe and well tolerated in man, demonstrating a PK profile that
supports twice daily dosing (NCT03809052). GB1211 has now
progressed to a phase II study in patients with liver cirrhosis
(NCT05009680).
References
Gudowska M. et al. (2015). Ann. Clin. Lab. Sci., 45, 669–673
Figure: qF-TWS of 3 patients who have no change in fibrosis before and Henderson N. C. et al. (2006) Proc Natl Acad Sci U S A 103, 5060–5065
post-treatment. E.g., patient A showed increase in fibrosis (normalized) in Zetterberg et al. (2018) ChemMedChem 13, 133–137.
5 regions: 0.11 to 0.22 for portal, 0.17 to 0.30 for PP, 0.18 to 0.21 for PC,
0.21 to 0.33 for bridging, 0.48 to 0.36 for PS. FRI183
Quantitative digital pathology of 3D human NASH models
Conclusion: qF-TWS can differentiate subjects with fibrosis progres- establish continuous scores to evaluate the antifibrotic effects of
sion and regression post-treatment who were determined as no- Selonsertib, Firsocostat and Resmetiron
change by pathologists’ assessment. The ability of qFibrosis to assess Louis Petitjean2, Simon Ströbel3, Li Chen2, Eva Thoma3,
fibrosis heterogeneity on a continuous scale provides the potential of Radina Kostadinova3. 1PharmaNest, Inc, Princeton, United States;
detecting subtle fibrosis changes that cannot be captured by current 2
PharmaNest Inc, Princeton, United States; 3InSphero AG, Schlieren,
system. A separate study is planned to establish correlation to clinical Switzerland
outcomes. Email: [email protected]
Background and aims: Human in-vitro 3D NASH tissue model have
the potential to accelerate the discovery of new anti-fibrotic

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POSTER PRESENTATIONS
compounds. We have previously reported the performance of novel collagen content, collagen fiber morphometry and fibrosis architec-
Digital Pathology Quantitative AI to generate automatic, continuous ture. The aim of this study as to identify histological traits common to
and direct fibrosis endpoints to quantify fibrosis severity and a variety of liver disease aetiologies and use these to develop a new
compound treatment response. Here, we expand this validation quantitative etiology-independent fibrosis severity score.
effort to increasing concentartions of Selonsertib, Firsocostat and Method: Patients who had undergone liver biopsy for the assessment
resmetiron (MGL-3196) and their combinations. of diffuse liver disease were included. Liver biopsy histology slides
Method: Human in vitro 3D InSightTM liver microtissues containing stained with Sirius Red were digitally scanned and categorised as
primary hepatocytes, Kupffer cells, endothelial cells and hepatic mild (F0–2; n = 28), moderate (F3–4; n = 17) or severe (F5–6; n = 35)
stellate cells in 96-well plates were used to model NASH progression fibrosis using the Ishak staging system. Disease etiology was
using a defined cocktail of free fatty acids, LPS and high levels of classified as alcohol related liver disease (ARLD; n = 25), non-
sugars. For compound efficacy testing, the 3D NASH tissues were alcoholic fatty liver disease (NAFLD; n = 17), viral (chronic hepatitis
simultaneously treated with selonsertib (2 mM and 10 mM), firsoco- B or C; n = 20), or autoimmune (PBC, PSC or autoimmune hepatitis;
stat (0.5 mM and 10 mM), MGL-3196 (0.005 mM and 0.05 mM) AIH; n = 18). FibroNest™ was used to describe the fibrosis phenotype
andcombination of selonsertib (10 mM) with firsocostat (0.5 mM) for of each etiological group according to quantitative fibrosis traits
a total of 9 groups (n = 18 to 21 in each group). Liver microtissues parameters (qFTs; n = 220) from three phenotypic layers: collagen
slices were stained with Sirus Red and digitaly imaged at 40X. content, fibers morphometry and fibrosis architecture. For each
FibroNestTM, a cloud-based quantitative image analysis and quanti- etiological group, qFTs that showed significant variation (>20%; p <
tative AI platform, was used to quantify the fibrosis phenotype along 0.05) between the mild and severe groups of fibrosis were combined
32 traits for collagen content, morphometry, and architecture. Each to produce an etiology-specific score for fibrosis severity. We also
trait is described by up to seven quantitative fibrosis traits (qFTs, 315 combined qFTs common to all four aetiological groups (n = 77) to
in total). Principal qFTs are automatically detected and combined into produce etiology-independent score for fibrosis severity, morphom-
a normalized Phenotypic Composite Fibrosis Score (Ph-FCS). Each qFT etry, and architecture.
is described individulally for relative severity (green to red) in Results: Our etiology-independent fibrosis phenotypic score (2nd
Phenotypic Heatcharts. row of Figure 1) correlates with fibrosis stage and distinguishes mild
Results: The Ph-FCS offers a significant detection threshold and from severe fibrosis with acceptable performance. The etiology-
dynamic range to evaluate the antifibrotic response the seven specific phenotypic score (1st row of Figure 1) has a superior
treatment arms (box plot chart and p-value table below). performance for mild fibrosis. For each etiology [NAFLD, Viral,
Firsocostat (10 mM) and MGL-3196 (0.05 mM) antifibrotic effects AutoImmune, AR-SH], group mean values are comparable for the
are significant and comparable. The combination of selonsertib Mild [2.63;2.67;2.64;3.03], Moderate [3.03;3.04;3.04;2.90] and
(10 mM) with the low dose of firsocostat (0.5 mM) does not Severe [4.17;4.26;4.33;4.47] stages. The morphometric and architec-
demonstrate any synergestic effect. The dose response effects are tural scores (and their related qFTs) can be used to further enrich the
poorly detected except for the MGL-3196 arms ( p = 0.075) which understanding of fibrosis phenotypes.
demonstrate that the result is driven by the compounds, not the Ph-
CFS score and method. Each principal qFT is described individually
for relative severity (green to red) in phenotypic heatcharts which
can be used to quantified differences in the fibrosis phenotype in each
group, and quantify specific effects of each drug (and dose) on the
collagen distribution, collagen fibers morphometry and fibrosis
architecture.

Conclusion: The combination of FibroNestTM imaging analysis for

automated quantification of histological fibrosis severity phenotype
within vitro 3D InSightTM human NASHmodel provide powerful
platform for anti-fibrotic drug-candidates response evaluation.

FRI184
Etiology-independent fibrosis severity scoring by quantitative
digital pathology image analysis
Adam Watson1, Louis Petitjean2, Mathieu Petitjean2, Conclusion: Our data shows that quantitative digital pathology
Michael Pavlides1. 1University of Oxford, Oxford, United Kingdom; image analysis can phenotype fibrosis and quantify severity in
2
PharmaNest, Inc, Princeton, United States multiple liver disease aetiologies. We used this technology to develop
Email: [email protected] an etiology-independent score to assess the severity of fibrosis from
liver biopsies.
Background and aims: While fibrosis is the common end point of
many chronic liver disease, little is known about the possible subtle
histological differences between etiologies and the related perform-
ance of existing fibrosis staging system. Here, we used quantitative
Digital Pathology image analysis and quantitative AI to quantify the
phenotype of liver fibrosis using histological traits to describe to

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 POSTER PRESENTATIONS
FRI185 homogenous area and an IQR/M <30%. A cut-off of ≥9.5 kPa by TE was
Liver stiffness and autoimmune profile in a cohort of patients used to define advanced fibrosis (F ≥ 3).
with systemic sclerosis Results: Valid liver stiffness measurements (LSM) were obtained in
Davide Di Benedetto1,2, Maria Lorena1,2, Francesca Baorda1,2, 97.5% of patients using both elastography methods. Therefore, 196
Giulia Francesca Manfredi1,2, Antonio Acquaviva1,2, subjects were included in the final analysis (27.8% with TE ≥9.5 kPa).
Carla De Benedittis1,2, Cristina Rigamonti1,2, Mattia Bellan1,2, A moderate positive correlation was found between the LS values
Mario Pirisi1,2. 1AOU Maggiore della Carità, Division of Internal obtained by the 2 methods: r = 0.68, p < 0.0001 (Spearman correl-
Medicine, Novara, Italy; 2Università del Piemonte Orientale, Department ation). LS values obtained by p-SWE were significantly lower than
of Translational Medicine, Novara, Italy those obtained by TE: 8.3 kPa vs. 10.12 kPa ( p < 0.0001). The best p-
Email: [email protected] SWE cut-off value for advanced fibrosis (F ≥ 3) was 7.4 kPa (AUC-
0.95; Se-81.5%; Sp-98%; PPV-95.7%; NPV-93.3%) (fig 1).
Background and aims: Systemic sclerosis (SSc) is characterized by
skin fibrosis and involvement of esophagus, lungs, heart and kidneys.
Liver involvement in SSc is considered rare, but reports addressing
this issue are scarce. Here, we evaluated the prevalence of liver
fibrosis and hepatic autoimmunity in a cohort of SSc patients.
Method: A retrospective observational study was performed on 97
patients diagnosed with SSc or mixed connective tissue disease with
sclerodermic manifestations who underwent transient elastography
evaluating liver stiffness (LS) and controlled attenuation parameter
(CAP) due to clinical indication; a biochemistry assessment and major
antibodies associated to liver autoimmunity were recorded whether
performed together to clinical and demographic data.
Results: Among the 97 patients included, 16 (16.5%) had LS ≥7.5 kPa,
5 of whom had LS ≥12.5 kPa. Predictors of LS ≥7.5 were alcohol
consumption, waist circumference, elevated alkaline phosphatase
(ALP) levels, anti-La and anti-mitochondrial antibody (AMA) posi-
tivity. CAP values compatible with steatosis (≥280 dB/m) were
observed in 6 (6.2%) patients. Waist circumference, body mass
index and diabetes mellitus were significant predictors of steatosis.
Out of 97 patients, 19 (19.5%) were positive for AMA, 4 (4.2%) for anti-
Sp100, 1 (1%) for anti-gp210 and 7 (7.3%) were diagnosed with
primary biliary cholangitis.
Conclusion: Among SSc patients, the prevalence of biomarkers of
hepatic fibrosis and AMA is relatively high, suggesting the oppor-
tunity of performing a transient elastography and a screening for
hepatic autoimmunity at diagnosis and/or along the course of the
disease. Figure 1: Performance of p-SWE for predicting advanced fibrosis (F ≥ 3).

FRI186 Conclusion: Using the new US system, the best p-SWE cut-off value
Performance of a p-SWE method implemented on a new for predicting advanced fibrosis was 7.4 kPa.
ultrasound system for predicting advanced liver fibrosis
FRI187
Alexandru Popa1, Roxana Sirli1, Alina Popescu1, Andreea Borlea2,
Inhibition of tumour progression locus 2 (TPL2) halts the
Felix Bende1, Victor Baldea1, Raluca Lupusoru1, Camelia Foncea1,
progression of liver fibrosis in a stringent long term choline
Radu Cotrau1, Pascu Ariana1, Ioan Sporea1. 1Victor Babeş University of
deficient high-fat diet (CdHFD) rat model
Medicine and Pharmacy, Department of Internal Medicine II, Division of
Milessa Silva Afonso1, Rowena Suriben1, Natalie Sroda1,
Gastroenterology and Hepatology, Center for Advanced Research in
Sowjanya Dokku1, David Hollenback1, Mehdi Belkhodja1,
Gastroenterology and Hepatology, Timișoara, Romania; 2Victor Babeş
Wesley Minto1, Sangeetha Mahadevan1, Grant Budas1, Yeonju Lee1,
University of Medicine and Pharmacy, Department of Internal Medicine
Kelli Boyd1, Eda Canales1, Bernard Murray1, Matthew Warr1,
II, Division of Endocrinology, Timișoara, Romania
James Taylor1, James Trevaskis1, Ruchi Gupta1. 1Gilead Sciences, Inc,
Email: [email protected]
Foster City, United States
Background and aims: Ultrasound based elastography techniques Email: [email protected]
became in the last years reliable tools to predict the severity of liver
Background and aims: Chronic inflammatory stimuli exacerbate
fibrosis in chronic hepatopathies. Usually, these techniques are
liver damage and contribute to the development of fibrosis and
integrated in high-end US machines but recently they became
NASH. Inhibition of TPL2, a serine-threonine kinase downstream of
available in medium-range ones.
pattern recognition receptors, could halt or reverse NASH and liver
To evaluate the performance ofpoint Shear-Wave Elastography from
fibrosis. Previously reduced hepatic inflammation and fibrosis was
Siemens, implemented on the new ACUSON Juniper Ultrasound
observed with a TPL2 inhibitor (TPL2i) in the rat CDHFD model. Here
System, for the non-invasive assessment of liver fibrosis, and to
we explored the effect of TPL2i in an extended disease model.
identify liver stiffness (LS) cut-off value for predicting advanced
Method: Male Wistar rats on CDHFD for 8 weeks were treated with
fibrosis, using Transient Elastography (TE) as the reference method.
TPL2i (100 mg/kg, BID), ACC inhibitor (ACCi, 10 mg/kg, QD), cenicri-
Method: We included 201 consecutive subjects (60% men, mean BMI
viroc (CVC, 100 mg/kg BID) or combinations of ACCi (10 mg/kg QD) +
= 28.7 ± 4.9 kg/m2, mean age 59 ± 18.4 years) with or without chronic
TPL2i (100 mg/kg BID) or ACCi (10 mg/kg QD) + FXR agonist cilofexor
hepatopathies in whom LS was evaluated in the same session by
(CILO; 30 mg/kg BID) for 10 weeks (n = 10–15/group). Liver fibrosis
means of 2 elastography techniques: TE and p-SWE from Siemens.
was assessed by picrosirius red (PSR) and αSMA staining. Hepatic
Reliable LS measurements were defined for TE as the median value of
immune cell and cytokine content were assessed by immunohis-
10 measurements with an interquartile range/median (IQR/M) <30%,
tochemistry and ELISA, respectively. CCR2+ and Foxp3+/CD3+ (TReg)
and for p-SWE as the median value of 10 measurements acquired in a

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POSTER PRESENTATIONS
cells were measured by immunofluorescence and quantified using compounds. Gene expression of the fibrotic markers alpha-1 type I
Visiopharm. collagen (COL1a1), heat shock protein 47, alpha-smooth muscle actin,
Results: TPL2i reduced PSR by 48% and αSMA by 50% vs. vehicle (both connective tissue growth factor, plasminogen activator inhibitor-1,
p < 0.001). The combination TPL2i + ACCi reduced PSR by 63% and and inflammatory markers interleukin-1 beta, interleukin-6, tumor
αSMA by 72% vs. vehicle. No improvement in these endpoints was necrosis factor alpha were determined by qPCR. Pro-collagen 1a1
observed with either ACCi or CVC. TPL2i reduced the expression of (Pcol1a1) excreted by PCLS into the culture medium was determined
fibrogenic genes and hepatic content of macrophages and T-cells by an ELISA assay.
compared to vehicle (p < 0.001), but no further reductions were Results: NRG concentration-dependently inhibited COL1a1 gene
observed with the TPL2i + ACCi combination. A reduced number of expression in mouse and human PCLS. The highest non-toxic
CCR2+ cells and increased proportion of TRegs were observed in liver concentration of NRG (300 μM in mPCLS, 200 μM in hhPCLS and
from TPL2i-treated rats vs. vehicle. As expected, CVC reduced chPCLS) supressed fibrosis and inflammation related genes and
macrophage number (by 22%, p < 0.01) but did not alter T-cells. reduced the Pcol1a1 in the culture medium by 54 ± 21 % (mPCLS), 34
TPL2i reduced TNF-α by 64%, KC/GRO by 47% and IL-1β by 46% (vs ± 23 % (hhPCLS), and 75 ± 23 % (chPCLS). The highest non-toxic
vehicle, all p < 0.01). Further reductions in TNFα and KC/GRO were concentration of AA (30 μM) decreased only in hhPCLS COL1a1 and
observed with ACCi + TPL2i combination. CVC reduced TNF-α by 48%, Pcol1a1 by 34 ± 17 %, and downregulated fibrosis-related gene
KC/GRO by 32%, and IL-1β by 34% (vs. vehicle, all p < 0.05). As a expression. 25 μM of ICA, the highest non-toxic concentration, only
clinically relevant benchmark, the ACCi + CILO combination reduced supressed in mPCLS col1a1 gene expression, while decreasing
PSR and αSMA (by 30% and 52% vs. vehicle, both p < 0.001), as well as inflammation related genes in all PCLS types.
macrophages and T-cells (by 28% and 32% vs. vehicle, both p < 0.001). Conclusion: NRG showed the most promising antifibrotic potency in
Conclusion: TPL2i improved fibrotic and inflammatory endpoints in both mouse and human PCLS, with more profound effects in chPCLS
this extended rat CDHFD model, with greater or equivalent efficacy than in the early on-set of fibrogenesis in hhPCLS. Antifibrotic effects
compared to the clinically validated combination of ACCi + CILO. of AA were only shown in hhPCLS. ICA only exerted antifibrotic effects
These results provide rationale for inhibition of TPL2 for the on fibrosis related genes in mPCLS.
treatment of NASH and suggest potential for its use in novel
combination therapies. FRI189
Diagnostic efficacy of Mac-2 binding protein glycosylation isomer
FRI188 for predicting liver fibrosis in patients with metabolic associated
Evaluation of the antifibrotic effects of naringenin, asiatic acid fatty liver disease
and icariin by using precision-cut liver slices of mouse and human Se Young Jang1, Dae Won Jun2, Hoon Gil Jo3, Ki Tae Yoon4,
Ke Luo1, Yana Geng1, Vincent de Meijer2, Dorenda Oosterhuis1, Young Youn Cho5. 1School of Medicine, Kyungpook National University,
Peter Olinga1. 1University of Groningen, Department of Pharmaceutical Kyungpook National University Hospital, Internal Medicine, Korea, Rep.
Technology and Biopharmacy, Groningen, Netherlands; 2University of of South; 2Hanyang University College of Medicine, Internal Medicine,
Groningen, University Medical Center Groningen, Department of Korea, Rep. of South; 3Wonkwang University Hospital, Wonkwang
Surgery, Groningen, Netherlands University School of Medicine, Internal Medicine, Korea, Rep. of South;
4
Email: [email protected] Pusan National University Yangsan Hospital, Internal Medicine, Korea,
Rep. of South; 5Chung-Ang University Hospital, Internal Medicine, Korea,
Background and aims: Fibrosis is an exaggerated wound healing
Rep. of South
response defined by excessive accumulation of extracellular matrix,
Email: [email protected]
which may lead to organ dysfunction or even organ failure. Therapies
for liver fibrosis are lacking. Naringenin (NRG), asiatic acid (AA) and Background and aims: The definition of metabolic associated fatty
icariin (ICA) are three compounds that were reported to exert liver disease (MAFLD) has newly been proposed. We aimed to
antifibrotic effects in both in vitro and in vivo animal models of liver investigate the efficacy of Mac-2 binding protein glycosylation isomer
fibrosis. However, no human data is available. Our objective was to (M2BPGi), non-invasive fibrosis marker, for discriminating significant
investigate the potential antifibrotic effects of these three com- and advanced fibrosis, and cirrhosis, respectively according to MAFLD
pounds by using the ex vivo mouse and human precision-cut liver and NAFLD definitions.
slices (PCLS) model. Method: Serum M2BPGi levels were collected and analyzed from 950
Method: PCLS prepared from mouse liver tissue (mPCLS), healthy fatty liver patients in a tertiary hospital. Liver fibrosis was graded by
human liver tissue (hhPCLS) and cirrhotic human liver tissue transient elastography. Diagnostic efficacy of serum M2BPGi and
(chPCLS) were cultured for 48 h with or without different concentra- other serum based liver fibrosis markers [fibrosis index based on four
tions of the three compounds. The viability was assessed by factors (FIB-4) and NAFLD fibrosis score (NFS)] was evaluated using
evaluating the ATP content of PCLS to study the toxicity of the three correlation analysis and area under the ROC curve (AUC).

Table 1:(abstract: FRI189): Diagnostic efficacy of serum M2BPGi and other serum markers in predicting the liver fibrosis stage in patients with MAFLD.
Sensitivity Specificity PPV NPV
AUC (95% CI) Cut-off value (%) (%) (%) (%) P
M2BPGi
F >1 0.706 (0.657–0.755) 1.15 48.6 81.2 35.9 88.0 <0.001
F >2 0.719 (0.662–0.776) 1.19 50.5 80.4 24.6 92.8 <0.001
F >3 0.843 (0.774–0.912) 1.31 73.7 85.6 20.1 98.5 <0.001
FIB-4
F >1 0.703 (0.650–0.756) 1.61 68.8 66.2 30.6 90.7 <0.001
F >2 0.709 (0.643–0.774) 1.63 70.3 65.9 20.7 94.6 <0.001
F >3 0.796 (0.713–0.878) 2.40 65.8 82.8 15.8 98.0 <0.001
NFS
F >1 0.660 (0.608–0.713) −0.72 62.5 65.8 28.3 89.0 <0.001
F >2 0.682 (0.616–0.748) −0.72 68.1 64.4 19.5 94.1 <0.001
F >3 0.787 (0.711–0.863) −0.70 84.2 63.5 10.2 98.8 <0.001

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 POSTER PRESENTATIONS
Results: There were 810 patients and 687 patients by the MAFLD and may be able to predict fibrosis progression in patients with NASH. The
NAFLD definition, respectively. Serum M2BPGi level and other liver ability to identify at-risk patients by the presence of pathogenic
fibrosis markers showed a positive correlation with fibrosis grade. intrahepatic macrophages may also lead to future precision medicine
The AUC values of M2BPGi were 0.698, 0.698, and 0.828 for predicting approaches.
fibrosis (F) >1, F >2, and F >3, respectively in NAFLD group. The AUC
values of M2BPGi were 0.706, 0.719, and 0.843 for predicting F >1, F FRI191
>2, and F >3, respectively in MAFLD group. The AUC values of M2BPGi Diabetes, but not prediabetes, is associated with significant liver
for predicting severity of fibrosis were greater than those of serum fibrosis
based liver fibrosis markers (Table 1). Byung Ik Kim1, Yong Kyun Cho1, Won Sohn1. 1Kangbuk Samsung
Hospital
Conclusion: M2BPGi showed better diagnostic efficacy for diagnos-
Email: [email protected]
ing the severity of liver fibrosis in MAFLD patients.
Background and aims: This study aimed to assess the risk of liver
FRI190 fibrosis between no glucose intolerance, prediabetes and diabetes in
Multispectral imaging analysis of liver biopsies from patients the general population.
with non-alcoholic steatohepatitis reveals enrichment of Method: A cross-sectional study was conducted based on a cohort
pathogenic macrophage phenotypes associated with disease from a health examination program which included a magnetic
progression resonance elastography (MRE). The participants were classified into
Joseph Gosnell1, Omar Saldarriaga1, Santhoshi Krishnan2, three subgroups according to glucose tolerance: no glucose intoler-
Morgan Oneka2, Arvind Rao3, Daniel Millian1, Timothy Wanninger1, ance, prediabetes and diabetes mellitus. Liver fibrosis was evaluated
Jingjing Jiao4, Laura Beretta4, Heather Stevenson1. 1UTMB Health- by liver stiffness measurement (LSM) value using 2-dimensional real-
University of Texas Medical Branch at Galveston, Pathology, Galveston, time MRE. The risk of liver fibrosis was compared after adjusting for
United States; 2Rice University, Houston, United States; 3University of confounding factors including the presence of liver disease (non-
Michigan, Ann Arbor, United States; 4The University of Texas MD alcoholic fatty liver disease, significant alcohol consumption and viral
Anderson Cancer Center, Houston, United States hepatitis).
Email: [email protected] Results: A total of 2, 090 subjects was included: no glucose
intolerance (n = 889); prediabetes (n = 985); and diabetes (n = 216).
Background and aims: Non-alcoholic steatohepatitis (NASH) affects
The mean age was 50.6 years. The mean values of LSM in no glucose
3–6% of the US population and risk factors include obesity,
intolerance, prediabetes, and diabetes were 2.37 ± 0.43 kPa, 2.41 ±
dyslipidemia, metabolic disease, and type 2 diabetes. While many
0.34 kPa, and 2.65 ± 0.70 kPa, respectively ( p < 0.001). The proportion
patients diagnosed with NASH will not progress to cirrhosis,
of significant fibrosis (LSM ≥2.97 kPa) in no glucose intolerance,
identifying which patients will develop advanced fibrosis is a
prediabetes, and diabetes was 3.1%, 4.4%, and 16.7%, respectively ( p <
challenge. Intrahepatic macrophages are critical gate keepers in the
0.001). Compared with no glucose intolerance, the risk of significant
hepatic microenvironment that assist in maintaining immune
fibrosis was higher in diabetes (adjusted odds ratio [aOR] 3.37, 95%
tolerance. Upon activation, they can promote a pro-fibrotic hepatic
confidence interval [CI] = 1.78–6.40, p < 0.001). However, there was
microenvironment. We hypothesized that patient variation in
no difference between prediabetes and no glucose intolerance (aOR
intrahepatic macrophage phenotypes could predict disease progres-
0.94, 95% CI = 0.54–1.64, p = 0.940). A subgroup analysis also showed
sion in patients with NASH.
that prediabetes is not associated with significant fibrosis unlike
Method: We used multiplex staining followed by multispectral
diabetes in subjects with or without liver disease.
imaging to phenotype and quantify resident liver macrophages
Conclusion: Diabetes but not prediabetes is a risk factor for
(CD68+), monocyte-derived macrophages (Mac387+), pro-fibrogenic
significant liver fibrosis regardless of the pressence of liver disease.
macrophages (CD163+), and their co-expression of pro-inflammatory
(CD14) and anti-inflammatory (CD16) markers in the context of FRI192
hepatic architecture. We compared differences in spatial distribution Lysophosphatidylserine may stimmulate liver fibrosis
(i.e., in enrichment and/or depletion) of macrophage populations in
Takako Nishikawa1, Makoto Kurano2, Hitoshi Ikeda2,
patients with NASH and either minimal (n = 6; fibrosis stage: 0–1/4)
Nobutake Yamamichi1, Yutaka Yatomi2, Kazuhiko Koike3,
or advanced (n = 5, fibrosis stage: 4/4) fibrosis. First, multiplexed
Mitsuhiro Fujishiro3. 1The University of Tokyo Hospital, Center for
stained liver biopsies were scanned with a multispectral microscope
Epidemiology and Preventive Medicine, Tokyo, Japan; 2The University of
(Vectra 3, Akoya Biosciences). We then determined the heterogeneity
Tokyo, Clinical Laboratory Medicine, Tokyo, Japan; 3Graduate School of
of these various macrophage populations in the study groups using
Medicine, the University of Tokyo, Japan, Department of
phenotype matrices and t-distributed stochastic neighbor embed-
Gastroenterology, Tokyo, Japan
ding plots (t-SNE) (Visiopharm®; MATLAB 2020a). Phenotypes that
Email: [email protected]
were significantly increased in the patients with advanced fibrosis
were selected for spatial proximity analysis using G-function Background and aims: Lysophospholipids (LPLs), such as lysopho-
equations. sphatidic acid and sphingosine 1-phosphate are had an interest as
Results: Phenotype matrix analysis revealed the enrichment of second-generation lipid mediators. Lysophosphatidylserine (LysoPS),
unique pathogenic macrophage phenotypes (MAC387+, MAC387 + a phosphatidylserine-derived LPL, has recently been identified as a
CD163+, MAC387 + CD163 + CD68+, MAC387 + CD163 + CD16 + CD14 specific receptor, such as GPR34 and GPR174, P2Y10, and has begun to
+, MAC387 + CD163 + CD16 + CD14 + CD68+) in NASH patients with attract attention as a novel lipid mediator. In this study, we report the
advanced fibrosis when compared to those with minimal fibrosis. effect of LysoPS on liver fibrosis and their physiological roles in vitro.
Pathogenic macrophage populations (MAC387+, CD163 + MAC387+, Method: (1) The hepatic myofibroblast-like stellate cell line, CFSC-8B
CD163+, CD68 + CD163+) correlated with poor clinical outcome (CFSC), derived from a CCl4-induced cirrhotic rat liver was utilized.
(increased prothrombin time and decreased platelet counts) in two The cells were incubated with the medium added various concentra-
of the patients with minimal fibrosis. In patients with advanced tions of 18: 0 and 18: 1 LysoPS. Expressions of alfa-smooth muscle
fibrosis, spatial analysis also showed significant ( p < 0.05) infiltration actin (α-SMA) determined by western blotting. (2) Liver fibrosis was
of MAC387+ macrophages near CD68+ Kupffer cells. induced by intraperitoneal injection of carbon tetrachloride (CCl4)
two times a week for 8 weeks in mice. (3) The tissue of liver with
Conclusion: Multispectral imaging combined with spatial analysis
hepatocellular carcinoma in patient with hepatitis B virus and the
allows characterization of distinct macrophage subpopulations that
plasma in patients with liver dysfunction was utilized. Expressions of

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S485

POSTER PRESENTATIONS
GPR34 and GPR174, P2Y10 receptor and LysoPS levels in the plasma
were examinated.
Results: (1) When the cells were incubated with LysoPS for 24 hours,
expressions of alfa-smooth muscle α-SMA were up-regulated by
10 μM of 18: 0 and 18: 1 LysoPS treatment. Expressions of α-SMA were
inhibited by inhibitors of Smad3, p38 mitogen-activated Protein
kinase and Rho-associated kinase. (2) Expressions of GPR34 and
GPR174, P2Y10 receptor were up-regulated along Glisson’s capsule in
CCl4 treated mice. 16:1 and 20:4 LysoPS levels in the plasma were
increased in CCl4 treated mice. (3) Expressions of GPR34 and GPR174,
P2Y10 receptor, derived from a hepatic myofibroblast-like stellate
cell, were up-regulated along fibrous capsule of hepatocellular
Conclusion: In summary, immunohistochemistry-based quantitative
carcinoma in patient with hepatitis B virus. 16:0 and 18:2 LysoPS
pathology endpoints may identify drug effects that are not captured
levels and phosphatidylserine (PS) levels, as precursor of 16:0 LysoPS,
by categorical CRN endpoints.
in the plasma were increased in patients with liver fibrosis.
Conclusion: In this study, it was suggested that LysoPS is involved in FRI194
liver fibrosis in vitro. In vivo study, upregulation of LysoPS receptor Second harmonic generation microscopy can quantify and
was observed in hepatic myofibroblast-like stellate cells, suggesting subclassify early stages of NASH fibrosis progression: data from a
that LysoPS may also be involved in liver fibrosis. Furthermore, an screen-failure cohort of a NASH phase 2 study
increase in LysoPS of some fatty acid molecular species was observed
Dominique Brees1, Dean Tai2, Clifford Brass3, Nikolai Naoumov4,
in mouse plasma, suggesting the possibility of laboratory medical
Elaine Chng2, Yayun Ren2, Andreas Sailer1, Douglas Applegate3,
application of LysoPS as a marker of liver fibrosis.
Jossy George Kochuparampil1, Juergen Loeffler1, Li Chen3,
FRI193 Miljen Martic1, Zachary Goodman5, Marcos Pedrosa1,
Quantitative assessment of liver fibrosis in NASH patients Quentin Anstee6. 1Novartis Pharma AG, Basel, Switzerland; 2Histoindex
Pte. Ltd., Singapore; 3Novartis Pharmaceuticals Corporation, East
Luong Ruiz1, Tian Lan1, Wenhui Liu1, Amir Ashique1, Harry Chen1,
Hanover, NJ, United States; 4London, United Kingdom; 5Inova Health
Jiping Zha2, Alex DePaoli1, Igor Mikaelian1, Cynthia Guy3,
System, Director of Hepatic Pathology Consultation and Research, Falls
Eugenia Henry1, William Chang1, Corinne Foo-Atkins1, Hsiao Lieu1.
1 Church, VA, United States, 6Newcastle University, Translational & Clinical
NGM Biopharmaceuticals Inc., Translational Sciences, South
Research Institute, Faculty of Medical Sciences, Newcastle upon Tyne,
San Francisco, United States; 2Adagene Inc, San Diego, United States;
3 United Kingdom
Duke University Medical Center Greenspace, Department of Pathology,
Email: [email protected]
Durham, United States
Email: [email protected] Background and aims: The semiquantitative liver biopsy grading
and staging systems proposed by the non-alcoholic steatohepatitis
Background and aims: The success of clinical trials for the treatment
(NASH) clinical research network (CRN) are widely used in clinical
of nonalcoholic steatohepatitis (NASH) is dependent on the efficacy
trials due to regulatory authority recommendations. Other, more
evaluation of the liver fibrosis endpoint. Fibrosis is currently assessed
sensitive methods are available and have potential to provide more
visually using the NASH Clinical Research Network (CRN) staging
detailed and informative analyses of liver histology to inform our
scheme. However the NASH CRN scheme evaluates patterns of
understanding of natural history and therapeutic response. Herein we
fibrosis that are not related by a linear relationship to the quantified
describe the use of second harmonic generation/two-photon excita-
abundance of pathologic collagen deposition. Samples from a Phase 2
tion fluorescence (SHG/TPEF) microscopy with computer-assisted
clinical trial with aldafermin (NGM282), an engineered fibroblast
analyses to provide a standardised and reproducible approach for
growth factor 19 analogue, were used to develop a novel image
precise quantitative assessment of NASH fibrosis.
analysis readout for liver fibrosis.
Method: Liver biopsies from 138 patients with non-alcoholic fatty
Method: Liver biopsies were from a 24 week clinical trial with
liver disease (NAFLD) who failed screening for a NASH phase 2 clinical
aldafermin (NGM282): NCT02443116 ( placebo (PBO), n = 22; 1 mg,
trial (TANDEM, NCT03517540) were assessed for liver fibrosis using
n = 49). Biopsies and blood for non-invasive biomarkers were
SHG/TPEF microscopy measured on a continuous scale (qFibrosis).
collected at baseline and at the end of treatment. A 6-plex
The qFibrosis scores were converted into categorical scores (qF0–qF4)
immunohistochemistry panel that included Collagen 1A1 (COL1A1)
using cut-offs previously reported. qFibrosis was measured in the
was developed. The image analysis method for COL1A1% area utilized
liver sinusoids from the portal triad to correspond to zones 1, 2, and 3
morphological operations to eliminate normal collagen, adaptive
of the Rappaport acinus, where zones 1 and 3 are defined as 100 μm
thresholding to alleviate uneven signal intensities, and morpho-
away from the end of collagen connected to vessel structures.
logical erosion to remove edge effects. Parameters for the methods
Independently, all biopsies were assigned a NASH CRN fibrosis stage
were tuned on a subset of images and then applied to the whole
(F0–F4) by an expert central pathologist.
dataset.
Results: qFibrosis scores (continuous [r = 0.59]; categorical [r = 0.58])
Results: Fibrosis CRN reads correlated robustly with COL1A1% area
correlated moderately with NASH CRN scores ( p < 0.001). The main
(Kendall’s t = 0.644, p-value <0.001). In addition, image analysis
difference in scores between NASH CRN and SHG/TPEF was in F1/qF1
identified patients with decreases in COL1A1% area despite no
and F2/qF2 patients (F1 [n = 61]; F2 [n = 7] vs qF1 [n = 25]; qF2 [n =
changes in the CRN score. As a consequence, the COL1A1% area
42]). Additionally, SHG/TPEF microscopy classified more patients
identified a statistically significant proportion of responders in the
with stage 3 compared to NASH CRN (F3 [n = 12]; qF3 [n = 29]). The
treatment arm ( p = 0.037), which represented a 24% decrease in
NASH CRN scoring identified differences in the localization of fibrosis
COL1A1% area compared to the PBO group, and which was not
in portal, periportal and zone 1 fibrosis, but not in zone 1 alone,
reflected by the CRN score ( p = 0.12). The COL1A1% area and the CRN
between F1 and F2 stages. In contrast, SHG/TPEF microscopy
score correlated similarly to the non-invasive end points of serum N-
identified significant differences in portal, periportal and zone 1
terminal type III collagen propeptide and Enhanced Liver Fibrosis
fibrosis between qF1 and qF2 stages, as well as in zone 1 alone
(ELF) score (Kendall’s t ∼ 0.3 with p < 0.001). Finally, the coefficient of
(Table 1). Furthermore, there were no significant differences in mean
variation for COL1A1 in consecutive liver sections was 7%.
qFibrosis scores in other acinar zones.

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 POSTER PRESENTATIONS
variceal bleeding (4), ascites (5), Encephalopathy (5),
Hepatocarcinoma (4) without significant difference between
groups. ALT levels significantly decreased in groups 1 (44.6 ± 3.9
versus 30.7 ± 4.6, p = 0.003), and 2, (46.8 ± 4.0 versus 37.1 ± 4.6, p =
0.007). Albumin (4.1 ± 0.07 versus 4.4 ± 0.05, p = 0.000), platelets (117
± 7.9 versus 141 ± 9.2, p = 0.000) and quality of life (80.7 ± 2.2 versus
87.8 ± 2.5, p = 0.006) increased in group 1. Adverse events were mild
and affected mainly the GI tract (41, 21 and 45), and skin (14, 9, and
21) and 14 SAEs (5, 6, and 3), in groups 1, 2, and 3, respectively.

Conclusion: SHG/TPEF microscopy with computer-assisted image

analyses is a sensitive and reproducible methodology that may allow Conclusion: PR-PFD at doses of 1200, and 1800mg/day significantly
categorisation of subtle changes in liver fibrosis that might otherwise decreased indirect markers of liver fibrosis at 24mos, and improved
not be identified using the NASH CRN staging system. Further albumin, platelets and quality of life in patients with compensated
research is needed to determine the significance of such changes and cirrhosis. No liver toxicity was detected.
parameters to be used when evaluating therapeutic efficacy. SHG/
FRI196
TPEF microscopy may be a useful tool, in combination with the NASH
Endothelin receptor A antagonist functionalized magnetic
CRN scoring system, in assessing liver fibrosis.
nanoparticles as a promising approach for the treatment of liver
FRI195 fibrosis
Efficacy and safety of prolonged released pirfenidone in patients Marit ten Hove1, Andreas Smyris1, Carsten Höltke2, Ruchi Bansal1.
1
with compensated cirrhosis. A placebo controlled multicenter University of Twente, Translational Liver Research, Enschede,
study in Mexico Netherlands; 2University of Münster, Department of Clinical Radiology,
Linda Muñoz1, Aldo Torre2, Laura Esthela Cisneros Garza3, Münster, Germany
Iaarah Montalvo4, René Malé Velazquez5, Scherezada Mejia6, Email: [email protected]
Juan Ramón Aguilar7, Javier Lizardi8, Maru Icaza4, Frida Gasca8, Background and aims: Hepatic injuries, caused by various etiologies
Larissa Hernandez8, Paula Cordero-Pérez1, Luis Chi-Cervera4, such as excessive alcohol intake, fatty liver disease, viral hepatitis, or
Lilian Torres Made5, Graciela Tapia9, Poo Jorge8. 1University Hospital metabolic disorders, can lead to development of hepatic fibrosis.
“Dr. Jose E. Gonzalez” UANL, Liver Unit, Monterrey, Mexico; 2INCMN SZ, Hepatic stellate cells (HSCs) activated upon hepatic injury, that
Gastroenterology, Ciudad de México, Mexico; 3Investigaciones Médicas proliferate and secrete an excess of extracellular matrix (ECM),
Cisneros; 4Star Médica, Mérida, Mexico; 5Instituto de Salud Digestiva y remain an attractive target for the treatment of hepatic fibrosis.
Hepática S.A. de C.V., Guadalajara, Mexico; 6Hospital Juárez de México, During liver injury, endothelin-1 (ET-1) levels are upregulated and
Ciudad de México, Mexico; 7Clinica de Hepatologia, Mexico, Mexico; activate HSCs by interacting with endothelin A (ETA) receptor, which
8
Clínica REMEDHE, Ciudad de México, Mexico; 9Universidad Nacional is upregulated on activated HSCs upon hepatic injury. Several studies
Autónoma de México, Ciudad de México, Mexico also indicate that HSCs regulate the sinusoidal blood flow and portal
Email: [email protected] hypertension via ET-1, and hence antagonism of the endothelin
Background and aims: Advanced liver fibrosis (ALF) is a common pathway using endothelin receptor antagonist (ERA) may offer
finding in many chronic liver diseases and considering its predictive promising results. However, antagonism of ET pathway using small-
value for adverse outcomes new therapies are mandatory. Therefore, molecule ERAs can result in adverse systemic effects since high or
we aimed to evaluate efficacy and safety of prolonged release frequent dosing will be required to achieve desired therapeutic
pirfenidone tablets (PR-PFD) in a placebo controlled multicenter effects.
study. In this study, we conjugated ERA to superparamagnetic iron oxide
Method: 171 patients with ALF were blindely allocated to 3 groups to nanoparticles (SPIONs) to improve pharmacokinetics of endothelin
receive oral PR-PFD 1200 mg (G1) or 1800 mg per day (G2), or receptor antagonist (ERA) and to increase hepatic uptake thereby
placebo (G3) for 24 mos. Response criteria was defined as 30% reducing the high/frequent dosing, reducing the systemic side effects
variation in liver stiffness compared to baseline values estimated by while increasing the therapeutic efficacy. SPIONS are also biocom-
hepatic elastography and considering a reliability criteria as IQR/ patible and have magnetic properties, therefore can be detected using
median less than 30%. Fibrotest was also performed with 10% magnetic resonance imaging (MRI), making them suitable for
variation as predictive of response. Patients were classified as theranostic applications.
regressive fibrotic profile (RFP), stable fibrosis profile (SFP) or Method: First, we analyzed the association of ET-1 and ETA with HSCs
progressive fibrotic profile (PFP). Previous decompensation was an activation in vitro, and with liver fibrosis using human and murine
exclusion criteria. All participants had ultrasound, and esophageal liver tissues. Thereafter, we studied the therapeutic effects of ERA on
varices evaluation at baseline, and at 12, and 24 mos. activated HSCs in vitro. We then conjugated ERA on the surface of
Results: 150 patients were eligible for efficacy and 171 for safety dextran-PEG coated SPIONs using EDC-NHS conjugation chemistry
analysis. At baseline, demographic, etiology, cirrhosis stage, Child- (see the figure). Next, we examined the therapeutic effects of ERA-
Pugh class or MELD score, Quality of Life or Fatigue scales, as Liver SPIONs versus free ERA on activated HSCs in vitro and in carbon
stifness (kPa) and Fibrotest (units) scores (Mean ± 1SE) were similar tetrachloride (CCl4)-induced liver fibrosis mouse model in vivo.
(ANOVA or Pearson’s/Wald’s, Chi squared tests) but significantly
different at 24 mos (table). According to fibrotic profile in liver
sitiffness, 58.3 %, 47.4% and 35.1% were RFP; and, 8.3%, 13.3% and
24.3% were PFP, respectively. 19 patients had decompensation due to

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POSTER PRESENTATIONS
FRI198
Investigating the function of Endothelial-To-Mesenchymal
transition during liver fibrogenesis using a Liver-On-A-Chip
platform
James Whiteford1,2, Samantha Arokiasamy2, Clare Thompson1,
Results: We confirmed the overexpression of ET-1 and ETA in William Alazawi1, Neil Dufton2. 1Queen Mary University of London,
activated HSCs, and human and murine liver fibrosis. ERA dose- United Kingdom; 2Queen Mary University of London, Centre of
dependently inhibited TGFβ-induced HSCs activation, collagen-I Microvascular Research, London, United Kingdom
expression and contractility in vitro. ERA-SPIONs were synthesized Email: [email protected]
and attenuated TGFβ-induced HSCs activation, ECM production,
Background and aims: The plasticity of blood vessels, and
contractility via antagonizing the endothelin pathway. In CCl4- particularly the cells that line them, endothelial cells (EC), are
induced liver fibrosis mouse model, ERA-SPIONs treatment, com-
fundamental for our body’s rapid response to tissue injury. During
pared to ERA treatment, significantly reduced liver weight, ALT levels chronic disease, such as Non-Alcoholic Steatohepatitis (NASH), the
and inhibited collagen-I deposition indicating attenuation of liver
specialised liver sinusoidal EC (LSEC) are replaced by the emergence
fibrosis.
of new disease-associated EC populations. Our research has identified
Conclusion: In this study, we demonstrate that the delivery of ERA Endothelial-to-mesenchymal transition (EndMT), whereby LSEC loss
using SPIONs is a promising therapeutic approach for the treatment
their liver-specific identity and acquire mesenchymal cell traits, as a
of liver fibrosis that increases the therapeutic efficacy of ERA in vitro key aspect of liver fibrogenesis. The transcriptomic signature of
and in vivo.
EndMT is now well established but the functional contribution of
EndMT to the pathology of liver disease remains largely uninvesti-
FRI197
gated due to the challenges of performing high-resolution single cell
3D human NASH model as a screening-based discovery approach
for selecting and prioritizing drug candidates imaging in viable liver tissue. This project aims to understand the
cellular characteristics of EndMT by combining novel EndMT
Radina Kostadinova1, Simon Ströbel1, Jana Rupp1, Katia Fiaschetti1,
reporters with Liver-On-A-Chip (LOAC) platforms to model vascular
Agnieszka Pajak1, Katarzyna Sanchez1, Mathieu Petitjean2, Li Chen2,
changes in response to a NASH microenvironment.
Manuela Bieri1, Armin Wolf1, Sue Grepper1, Francisco Verdeguer1.
1 Method: Identification, creation, and application of EndMT-specific
InSphero, Schlieren, Switzerland; 2PharmaNest, Princeton, United
fluorescent reporter constructs (EndMT-Reps). Transduction of EC
States
using lentiviral packaged CNN1-eGFP construct as an inducible
Email: [email protected]
EndMT-Rep (CNN1-Rep) to 2D, 3D and 4D imaging techniques for
Background and aims: Non-alcoholic fatty liver disease (NAFLD) is a fixed and live cell imaging. Combined application of live and fixed
chronic liver disease, which includes hepatic steatosis that often imaging technologies to measure EndMT using CNN1-Rep on LOAC
progresses into steatohepatitis (NASH), characterized additionally by platform under physiological conditions. Demonstration of the high-
inflammation and fibrosis. We have modeled NASH using 3D human resolution single-cell EndMT tracking by live cell time-lapse
liver microtissues as a high-throughput tool for drug discovery. We microscopy and with post-acquisition processing (Volocity software)
present here a novel 3D human NASH model, which incorporates to perform a comparative study of CNN1-Rep and healthy LSEC
primary hepatocytes, Kupffer cells, liver endothelial cells, and hepatic within pro-fibrotic (TNFα + TGFβ2) and NASH-like (oleic and palmitic
stellate cells for high-throughput-compatible drug efficacy testing. acid) LOAC microenvironment.
Method: We generated liver microtissues by culturing human Results: We found CNN1-Rep was the most robust EndMT-reporter
primary hepatocytes, Kupffer cells, liver endothelial cells, and and was significantly induced in EC treatment with TNFα and TGFβ2
hepatic stellate cells in InSphero plates. Upon exposure to defined (1 ng/ml and 10 ng/ml respectively) for 48 h. Co-localisation of
lipotoxic and inflammatory stimuli, including free fatty acids and LPS CNN1-Rep with mesenchymal marker SMA confirmed specificity of
in media containing high levels of sugar and insulin, this 3D NASH the reporter for cell undergoing EndMT. By applying CNN1-Rep
model displayed pathophysiological hallmarks within 10 days of within LOAC we were able to track EndMT cells for the first time for up
treatment. The accumulation of intracellular triglycerides (biolumin- to 24 hours. We show that EndMT cells are significantly more motile
escent assay), secretion of pro-inflammatory cytokines/chemokines in pro-fibrotic and NASH-like than healthy EC within the same LOAC.
(Luminex), and pro-collagens type I and III (HTRF/ELISA) were
measured. Quantification of fibrosis based on Sirius Red-stained
tissue slices was performed using the PharmaNest imaging platform.
Results: We observed increases in intracellular triglyceride content
and the secretion of proinflammatory (e. g. IL-6, IL-1b, TNF-a) and
profibrotic (e.g. IL-10, GRO-a, IP-10, MCP-1) cytokines/chemokines in
the NASH-treated tissues as compared to the untreated controls.
Further, we detected increased fibril collagen deposition, and
increased secretion of procollagen type I/III peptides under NASH
conditions. Whole transcriptome analysis of NASH-treated tissues
versus control revealed activation of pathways and differential
regulation of genes associated with lipid metabolism, inflammation,
and fibrosis induction. Treatment with the anti-TGF-β antibody and
ALK5i (TGF-βRI inhibitor) concentration dependently decreased Conclusion: The combination of EndMT reporter, CNN1-Rep, with
secretion of pro-collagen type I/III. Decreased deposition of fibril LOAC technology can provide us with unrivalled opportunities to
collagens based on quantification of fibrosis of Sirius Red-stained understand the dynamic EndMT behaviour in homeostatic and
tissues was observed in the presence of anti-TGF-β antibody and disease liver microenvironments. Our data support the hypothesis
ALK5i. The efficacy results of drug clinical candidates Selonsertib and that EndMT cells are migratory and have the potential to be an
Firsocostat were in line with clinical observations. invasive cell type contributing to fibrotic cellular niche and driving
Conclusion: In summary, this high-throughput and compatible 3D fibrogenesis in the liver.
human NASH model represents a promising approach for NASH drug
candidate efficacy selection early within the drug discovery process.

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 POSTER PRESENTATIONS
FRI199
Discovery of AMS-III-1086, a novel LPA1 antagonist for the
treatment of liver fibrosis and liver cirrhosis
Nakcheol Jeong1, Peppi Prasit1, Jung-Hee Kim1, Misun Lee1,
Bo-Yeong Pak2, Sojin Ahn1, Gil Won Lee1, Seohyun Min1,
Sanghyeok Lee1, Yeup Yoon3,4,5, Wonseok Kang3,6, Hyeree Kim3,7. 1AM
Sciences, Seoul, Korea, Rep. of South, 2AM Sciences, Seoul, Korea, Rep. of
South; 3Samsung Advanced Institute for Health Sciences and Technology,
Sungkyunkwan University, Department of Health Sciences and
Technology, Korea, Rep. of South; 4Institute for Future Medicine, Samsung
Medical Center, Korea, Rep. of South; 5Sungkyunkwan University,
Department of Biopharmaceutical Convergence, Korea, Rep. of South;
6
Samsung Medical Center, Sungkyunkwan University School of
Medicine, Division of Gastroenterology, Department of Medicine, Korea,
Rep. of South; 7Institute for Future Medicine, Samsung Medical Center, Conclusion: AMS-III-1086 is a newly identified LPA1 antagonist
Korea, Rep. of South which shows a good therapeutic index with increased efficacy and
Email: [email protected] improved hepatobiliary toxicity and a favorable preclinical profile.
Background and aims: Activation of the lysophosphatidic acid 1
FRI200
(LPA1) receptor has been implicated in a various tissue fibrosis. LPA1
Integrated spatial-temporal mathematical liver lobule model for
receptor antagonists have shown efficacy in a wide range of animal
simulation of fibrotic wall formation
fibrosis models. Recently a human proof of concept in idiopathic
pulmonary fibrosis (IPF) was obtained with the first generation of Seddik Hammad1, Jieling Zhao2,3, Mathieu de Langlard2, Yueni Li1,
LPA1 antagonist in a 6-month Phase 2 clinical trial. But the compound Jan G. Hengstler3, Dirk Drasdo2,3, Steven Dooley1. 1Heidelberg
was withdrawn from clinical development because of hepatobiliary University, Molecular Hepatology Section, University Medical Center
toxicity, which was unrelated to LPAR1R antagonism but to the Mannheim, Medical Faculty Mannheim, Mannheim, Germany; 2Institute
inhibition of bile salt export pumps (BSEP). AMS-III-1086 is a novel National de Recherche en Informatique et en Automatique, (INRIA),
LPA1 antagonist designed to have a reduced risk of hepatobiliary Salacy, France; 3Leibniz Research Centre for Working Environment and
liability by minimizing bile acids transport inhibition while its Human Factors at the Technical University Dortmund, Dortmund,
efficacy both in vitro and in vivo was improved thus providing a larger Germany
therapeutic index. Email: [email protected]
Method: The potency and selectivity of AMS-III-1086 for LPA1 Background and aims: Upon different liver injuries, distinct patterns
receptors were determined in vitro by calcium flux and cell of fibrosis arise i.e. extracellular matrix (ECM) septa (fibrotic walls)
chemotaxis assays using B103 cells stably expressing LPA receptors connecting pericentral areas due to toxic drugs, or periportal
and A2058 cells. LX2 cells were used for evaluating anti-fibrotic compartments in cholestasis. Organ fibrosis is a highly coordinated
activities. Pharmacokinetic (PK) properties were assessed in rodent and complex multi-cellular process that is difficult to capture with
and non-human primates. N-nitrosodiethylamine (DEN)-induced rat experimental models.
fibrosis model was used for in vivo efficacy studies. BSEP inhibition Method: We stepwise developed a computational two liver-lobule
was determined by BIOIVT. In vivo liver toxicity was evaluated in the model that is continuously refined by iteration between modelers
cynomolgus monkeys. Human hepatotoxicity was ascertained by in and experimentalists. The model permits to assess the role of
vitro model using Hurel micro liver. biomechanics in the formation of the fibrotic scar. It for the first
Results: AMS-III-1086 inhibited LPA-stimulated intracellular calcium time integrates the orchestration of hepatocytes and non-parenchy-
release (IC50 = 5.3 nM) from B103 cells stably expressing human LPA1 mal cells (NPC) during fibrosis development, including their
and LPA-induced chemotaxis (A2058 cells; IC50 = 5.7 nM). AMS-III- interaction with the ECM network mechanics.
1086 showed selective antagonism on LPA1 over the other LPA Results: Model predictions are quantitatively confirmed with
receptors. Treatment with LPA in LX2 cells induced the expressions of experimental data. Pattern-characterizing model parameters, e.g.
the LPA1 gene as well as fibrotic genes, but these were significantly the density of hepatic stellate cells (HSC) and macrophages (Mph)
reduced by AMS-III-1086. Functionally, AMS-III-1086 inhibited LPA- were determined through analysis of experimental 2D and 3D
induced chemotaxis of LX2 cells. PK results showed good systemic images. A model of the ECM network, NPC and their intercellular
exposure and high oral bioavailability in multiple species. BSEP communication were integrated as new elements into the existing
inhibition was markedly improved, IC50 (20 uM) compared to the computational model of the basic liver micro-architecture that
first-generation clinical candidates (IC50 = 5 uM). In a DEN-induced already included hepatocytes, sinusoids, central and portal veins.
rat model of fibrosis and hepatocarcinogenesis, the therapeutic The newly advanced model was applied to test possible mechanisms
treatment of AMS-III-1086 (oral administration at 10 mg/kg once how the fibrotic scar may form during fibrosis in space and time.
daily) resulted in the attenuation of fibrogenesis as well as the Conclusion: Using this strategy, we propose a scenario that distin-
prevention of cirrhosis after 4 weeks of treatment. There were no guishes regeneration after a single acute toxic injury without scarring
significant changes in the levels of AST and ALT in the cynomolgus versus repeated toxic exposure leading to formation of (etiology
monkeys. Moreover, a cytotoxicity study using Hurel micro liver dependent) characteristic fibrotic scar patterns, as following: (i) The
predicted that AMS-III-1086 had reduced risk of drug-induced liver spatial pattern of CYP2E1 (key metabolizing enzyme) expressing
injury which was corroborated in vivo in cynomolgus monkey. hepatocytes determines the location of ECM deposition (collagen).
The tissue response is thereby mediated by the spatial-temporal
pattern of certain signaling molecules provided the CYP2E1-positive
damaged hepatocytes (DAMPs), leading to activation and attraction of
HSC and Mph. (ii) Surviving (CYP2E1-negative) hepatocytes sur-
rounding the CYP2E1 positive (and now damaged) region proliferate
and compress the deposited collagen network into the scar like shape.
The model may in the future permit us to propose targeted
manipulations to reduce scar formation and the transition to cirrhosis.

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S489

POSTER PRESENTATIONS
FRI201 Conclusion: Our results suggest that the absence of telomerase
Telomerase-null mice display defective immune activation causes a limited immune response following S. mansoni infection in
following the induction of liver fibrosis with S. mansoni mice, which mitigates the fibrotic process and cell activation. These
Willian Gomes1, Vinícius Carvalho1, Bárbara Santana1, findings also reveal that functional telomerase is critical for adequate
Leandra Naira Zambelli Ramalho2, Rodrigo Calado1. 1Ribeirão Preto immune response and, in patients harboring mutations in telomere-
Medical School, University of São Paulo, Department of Medical Imaging, biology genes, fibrogenesis must be modulated by other inflamma-
Hematology, and Clinical Oncology, Ribeirão Preto, Brazil; 2Ribeirão tion signaling pathways, which deserves further investigation.
Preto Medical School, University of São Paulo, Department of Pathology
and Forensic Medicine, Ribeirão Preto, Brazil FRI202
Email: [email protected] Multiplexed digital spatial protein profiling reveals potential non-
invasive biomarkers to predict advanced fibrosis
Background and aims: Telomeres are structures at the end of linear Chang Min Kim1, Pil Soo Sung2, Jung Hoon Cha2, Jin Young Park1,
chromosomes constituted by repetitive 5′-TTAGGG-3′ sequences Yun Suk Yu1, Hee Jung Wang3, Eun Sun Jung2, Si Hyun Bae2.
associated to protecting proteins. Human patients with germline 1
Cbsbioscience, Research & Business Development, Korea, Rep. of South;
pathogenic variants in telomere-biology genes present critically 2
Catholic University, Korea, Rep. of South; 3Inje University, Korea, Rep. of
short telomeres and usually develop bone marrow failure, but a South
considerable percentage also manifest pulmonary fibrosis and liver Email: [email protected]
cirrhosis, although the mechanisms for disease development are still
unclear. Here, we aim to investigate whether immune-mediated Background and aims: Innate and adaptive immune responses are
responses are skewed in telomerase- “knockout” (KO) mice chal- critically associated with the progression of fibrosis in chronic liver
lenged with Schistosoma mansoni-induced liver fibrosis. diseases. Among the immune cells, intrahepatic mononuclear
Method: Liver fibrosis was induced by inoculation of approximately phagocytes are critical for the initiation and progression of liver
100 cercariae to Terc−/− (n = 16), Tert−/− (n = 10) and wild-type (WT; fibrosis. In this study, using multiplexed digital spatial profiling, we
n = 8) C57BL/6 mice, which were euthanized after 12 weeks, along aimed to develop protein signature which can be used to predict
with a non-infected group (Terc−/n = 7−, Tert−/− n = 16 and WT n = 11). advanced fibrosis in a non-invasive approach.
Telomere length (TL) in leukocytes and liver fragments was Method: Snap-frozen liver tissues with various chronic liver diseases
determined by qPCR. Liver tissue samples were stained with at different fibrosis stages were subjected to spatially-defined
haematoxylin-eosin (HE) and Picro-Sirius Red. protein-based multiplexed profiling. CD3, CD68, and α-SMA
Immunohistochemical (IHC) staining to F4/80, iNOS and CD206 was markers were used to identify specific cell types. Single-cell RNA-
performed using diaminobenzidine. Bone-marrow derived macro- Seq analysis was performed using GEO datasets from normal livers
phages (BMDM) were isolated from a second group of animals (n = and cirrhotic livers. Public miRNA databse were used to find miRNA
12; 4/each genotype), cultured for 7 days in RPMI and stimulated with targeting protein signature.
lipopolysaccharide (LPS) or interleukin-4 (IL-4) for 24 hours. The Results: Eighty-eight portal ROIs were selected for the spatial
polarization to M1 or M2-like phenotypes was determined by nitrite profiling, with 24 ROIs classified into “inflammatory” (high T cell
levels and gene expression (IL-6, MMP9, TNF-alpha, CD206 and ARG1). number) and 64 ROIs classified into “non-inflammatory” (low T cell
Results: TL was significantly shorter in both KO groups ( p < 0.01). number). In “non-inflammatory” ROIs, which were used for the
Infected animals presented hepatosplenomegaly and multiple further analyses, there were liver tissues with various fibrosis grade
inflammatory foci in the liver and tissue darkening. Histopathology as F0–2 (n = 31), F3–4 (n = 33). In CD68+ areas, protein markers for
showed the presence of granulomas surrounding S. mansoni eggs activation of mononuclear phagocytes were detected significantly
trapped within the tissue. Terc−/− and Tert−/− mice developed less stronger in early stage fibrosis (F0, F1, and F2) than advanced fibrosis
fibrotic areas when compared to the WTs ( p < 0.05). IHC staining (F3 and F4). Conversely, CD68 and HLA-DR, which are known to be
revealed less macrophage infiltration within the tissue in KO animals. upregulated in SAMacs rather than KCs, were detected stronger in
BMDM assay showed that the telomerase KOs impair the classical advanced fibrosis. Using the results from CD68+ area, a highly
activation of macrophages, as indicated by nitrite concentrations and sensitive and specific, unique immune-related protein signature was
the differential expression of TNF-alpha, IL-6, and MMP9. developed to predict the advanced fibrosis. Combined analysis of
single cell RNA-Seq data from GEO datasets (GSE136103) and
spatially-defined protein-based multiplexed profiling revealed that
most proteins upregulated in F0, F1 and F2 livers in portal CD68+ cells
were specifically marked in TM (1), TM (3) and SAMacs (1) clusters,
whereas proteins upregulated in F3 and F4 livers were marked in
SAMacs (1), SAMacs (2), KC (1), and TM (3), highlighting the different
phenotypes of portal CD68+ cells according to the fibrosis stages. We
found the miRNAs targeting the protein signature in a public miRNA
database, as the the candidate biomarkers for a non-invasive
approach.
Conclusion: By establishing a GeoMx DSP method, we identified an
accurate protein signature to predict advanced fibrosis. The spatially-
defined protein-based multiplexed profiling demonstrated a critical
difference in the phenotypes of mononuclear phagocytes between
livers of early stage fibrosis and those of advanced fibrosis. Our results
suggest that portal mononuclear phagocytes are critical in inflam-
mation and fibrosis progression, and that miRNAs targeting the
protein signature of those cells may be ideal non-invasive biomarker
candidates.

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 POSTER PRESENTATIONS
FRI203 FRI204
Sex and diagnosis-specific differences in liver elastography and Progression of liver disease among patients with a new diagnosis
attenuation of protease inhibitor ZZ alpha-1 antitrypsin deficiency
Zhi Tan1, Marcelle Scagliotta1, Crystal Connelly1, Wendy Lam1, Harmeet Malhi1, Tiffany Wu1, May Hagiwara2, Gregory Donadio3,
Oyekoya Ayonrinde1. 1Fiona Stanley Hospital, Gastroenterology and Esteban Gnass3, Will Treem2, Kaili Ren2, Ed G. Marins2, Chitra Karki2.
1
Hepatology, Murdoch, Australia Mayo Clinic, Rochester, United States; 2Takeda Pharmaceutical
Email: [email protected] Company Limited, Cambridge, United States; 3Inference, Cambridge,
United States
Background and aims: Liver stiffness measurement (LSM) using
Email: [email protected]
Transient Elastography (TE), combined with liver attenuation
measurement using controlled attenuation parameter (CAP), allows Background and aims: Few studies have characterized disease
rapid, non-invasive assessment of liver fibrosis and steatosis. We progression in patients ( pts) with alpha-1 antitrypsin deficiency-
examined the usefulness of TE and CAP for assessment of liver associated liver disease protease inhibitor ZZ (AATD-LD PiZZ)
disorders in an adult hepatology outpatient population. genotype, who may progress variably with time and may remain
Method: In this cross-sectional study, we investigated the duration asymptomatic despite advanced liver fibrosis. We examined the
and findings of TE and CAP in adult outpatients with known or relationship between progression of disease and LD-related clinical
suspected chronic liver disease, between 2012 and 2021. LSM and events (LD events) over time in this population.
CAP were measured using a FibroScan® model 502 Touch. Each Method: Data were extracted from the nFerence database (a
procedure was performed by a hepatology nurse with experience of proprietary electronic medical record database from the Mayo
over 500 examinations. Patient age, sex, assessment indication, Clinic Healthcare System) between January 2004 and September
duration, LSM, CAP, and accuracy of the examination was recorded. 2021. Pts with AATD were defined by the presence of structured
Results: There were 5645 examinations performed on patients with diagnosis (dx) codes for AATD, or an alpha-1 antitrypsin serum level
various liver disorders, mean age 55.9 (standard deviation 12.9) of <100 mg/dL. LD was defined based on structured dx codes and
years, and 60.7% male. Of these, a medium (M) probe was used for surrogate measures. PiZZ genotype was defined by genotype results
4212 (74.6%), extra-large (XL) probe for 1422 (25.2%), and small (S or unstructured data through natural language processing. Index date
probe without CAP) in 11 (0.2%). The most common indications were was defined as the first date of dx of LD. Fibrosis stage (F0–F4) was
chronic hepatitis C (CHC, 46%), chronic hepatitis B (CHB, 22%), non- assessed at baseline (index date ± 90 days) and during follow-up
alcoholic fatty liver disease (NAFLD, 15%), and alcohol-related liver using a hierarchical approach: liver biopsy (METAVIR staging),
disease (ALD, 6%). Median LSM in the cohort was 6.8 (IQR 4.9–11.8) magnetic resonance elastography, Fibroscan, APRI and FIB-4. Pts
kPa and CAP 252 (IQR 204–307.5) dB/m. Both LSM and CAP were with <90 days of follow-up were excluded. LD events were defined as
higher in males, compared with females; (LSM 7.1 [5.3–12.2] kPa vs. development of ascites, spontaneous bacterial peritonitis, variceal
6.1 [4.6–10.7] kPa, p < 0.001) and (CAP 255 [208–309] dB/m vs. 241 bleeding, hepatic encephalopathy, hepatocellular carcinoma and
[196–298], p < 0.001) respectively. Also, median LSM was highest need for liver transplantation. Outcomes were analyzed using
with ALD (14.5 [7.5–35.3]), compared with CHC (7.6 [5.4–12.5]), descriptive statistics and Kaplan-Meier analysis for time-to-event.
NAFLD (7.6 [5.3–13.3]) and CHB (5.4 [4.3–7.1]). Median CAP was Results: Of 685 000 pts, 6315 had a dx of AATD; of these 501 had the
highest with NAFLD (315 [261–361] dB/m), compared with ALD (263 AATD PiZZ genotype, and 316 qualified for the study. Among pts with
[211–329] dB/m), CHC (245 [203–293] dB/m) and CHB (233 [189– AATD-LD PiZZ, the mean age was 50.5 years (y), 58.4% were male,
283] dB/m). There were sex-differences in CAP, LSM and duration of 100% were White, and 37.7% were diagnosed with chronic obstructive
the examination, across different liver disorders (Table 1). pulmonary disease, chronic bronchitis, bronchiectasis, or emphy-
sema. At baseline, 197 pts had fibrosis stage: F0/F1, 53; F2, 24; F3, 33;
and F4 with compensated cirrhosis (F4cc), 87 (119 pts were not
categorized owing to a lack of available data). Of 316 patients with 7.4
y of median follow-up, 17.4% underwent a liver transplant: 2%, 4%, 12%
and 44% among pts with baseline stage F0/F1, F2, F3 and F4cc,
respectively. Disease progression (≥1 fibrosis stage) occurred in 31 pts
at ≤2 y (F0/F1, 22%; F2, 5%; F3, 36%) and in 53 pts at ≤5 y (F0/F1, 49%;
F2, 38%; F3, 55%) (Figure A). At any time during follow-up (median 7.4
years), LD events occurred in 50.1% of pts, with a higher number of
events recorded for pts with baseline stage F4cc (98.2%) compared
with F3 (68.3%) and F2 (61.0%) (Figure B).

Conclusion: Across various liver disorders, CAP was significantly

higher in males overall, suggesting more severe hepatic steatosis. LSM
was higher in males with CHC and CHB, compared with females.
Severity thresholds for CAP and LSM should consider these
differences.

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POSTER PRESENTATIONS
Method: Fibrosis was induced in BALB/c mice (n = 12) by i.p. injection
of CCl4 diluted 1:8 v/v in corn oil twice a week for 8 weeks. Acellular
matrices or MEECs were surgically implanted between the median
and the right lobe in fibrotic mice. After one week, relative fibrosis
area was analyzed by Sirius Red staining. Liver function was evaluated
in serum samples. The expression of pro-inflammatory genes (nitric
oxide synthase 2 (NOS2), ciclooxigenase-2 (COX-2), interleukin 1
beta (IL1-B)), anti-inflammatory genes (arginase 1 (ARG1), mannose
receptor C-type 1 (MRC1), resistin (RETN1A)), hepatic stellate cell
(HSC) activation factors (oncostatin M (OSM), platelet derived growth
factor-BB (PDGFBB), transforming growth factor-beta (TGF-B)) and
genes related to the extracellular matrix turnover (collagen-I (COL-I),
alpha smooth muscle actin (ALPHA-SMA), tissue inhibitor of
metalloproteinases-1 (TIMP1)) was quantified by Real-time PCR.
Results: Implantation of MEECs for seven days promoted a 21%
reduction in the hepatic fibrosis area compared with fibrotic livers
implanted with acellular matrices. These anti-fibrotic effects trans-
lated into a significant improvement of liver function reflected by the
reduction of serum transaminases (ALT, 153.3 ± 15.8 vs 100.6 ± 14.5 U/
L, p < 0.05; AST, 477 ± 50.4 vs 288 ± 54 U/L, p < 0.05). Perihepatic
implantation of MEECs significantly reduced the hepatic expression
of pro-inflammatory genes (COX-2, 1.0 ± 0.1 vs 0.6 ± 0.1 fold change
(fc), p < 0.05; NOS2, 1.1 ± 0.3 vs 0.5 ± 0.1 fc, p < 0.01; IL1-B, 1.1 ± 0.1 vs
0.5 ± 0.1 fc, p < 0.01) and increased the hepatic expression of anti-
inflammatory genes (ARG1, 1.0 ± 0.1 vs 1.6 ± 0.1 fc, p < 0.05; MRC1, 1.0
± 0.1 vs 1.4 ± 0.1 fc, p < 0.05; RETN1A, 1.1 ± 0.1 vs 14.8 ± 4.8 fc, p < 0.01)
on fibrotic mice. Our results also revealed that MEECs promoted a
significant decrease in well-known stimulators of HSC (OSM, 1.0 ± 0.2
vs 0.35 ± 0.06 fc, p < 0.05; PDGF-BB, 1.0 ± 0.1 vs 0.57 ± 0.08 fc, p < 0.01,
TGF-beta 1.0 ± 0.1 vs 0.69 ± 0.05 fc, p < 0.05). This reduction was
associated with a fall in the hepatic expression of genes related to HSC
activation (COL-I, 1.0 ± 0.1 vs 0.49 ± 0.06 fc, p < 0.01; ALPHA-SMA, 1.1
± 0.2 vs 0.63 ± 0.08 fc, p < 0.05, TIMP-1 1.0 ± 0.2 vs 0.56 ± 0.07 fc, p <
0.05).
Conclusion: Perihepatic implants of MEECs display anti-inflamma-
tory and anti-fibrotic activity in liver fibrosis. This study highlights
Figure: KM estimates of fibrosis progression (A) and LD events (B) by the potential therapeutic utility of MEECs for chronic liver disease.
baseline fibrosis stage in pts with AATD-LD PiZZ.
FRI206
Conclusion: Almost 1/3 of F3 pts at baseline progressed to F4 and had LncRNA XR_592974.2 and circRNA _2599 regulated hypoxic stress
LD events in ≤2 y, and >2/3 of F4cc pts had LD events in ≤1 y. These response in hepatic stellate cells by targeting the miRNA-145/JMY/
clinically relevant findings need validation in independent cohorts. P53 pathway
FRI205 Dan Zhou1, Jing Gao2,3, Xiao-jun Wang4, Yujin Li5, Hong Chen6,
Perihepatic implantation of matrix-embedded endothelial cells Liting Zhang1. 1The First Hospital of Lanzhou University; 2Department of
reduce inflammation and collagen deposition in fibrotic mice Medicine, Karolinska Institute, Stockholm, Sweden; 3University of
Helsinki, Heart and Lung Centre, Helsinki, Finland; 4Gansu Provincial
Mireia Medrano-Bosch1, Alazne Moreno-Lanceta1,2,
Hospital; 5Capital Medical University, China; 6Xi’an International
Laura Macias-Muñoz2,3, Elazer Edelman4,5, Wladimiro Jiménez1,2,3,
Medical Center, China
Pedro Melgar-Lesmes1,2,4. 1Department of Biomedicine, School of
Email: [email protected]
Medicine, University of Barcelona, Barcelona, Spain; 2Institut
d’Investigacions Biomed ̀ iques August Pi-Sunyer (IDIBAPS), Centro de Background and aims: Non-coding RNAs contribute to the activation
Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas of hepatic stellate cells (HSCs) and the progression of liver fibrosis.
(CIBERehd), Barcelona, Spain; 3Biochemistry and Molecular Genetics Hypoxia serves as a pivotal microenvironmental factor that facilitates
Service, Hospital Clinic Universitari, Barcelona, Spain; 4Institute for the activation of HSCs. Our previous study demonstrated differen-
Medical Engineering and Science, Massachusetts Institute of Technology, tially expressed mRNAs and miRNAs in hypoxia-induced HSCs. Here,
Cambridge, MA, United States; 5Cardiovascular Division, Brigham and we investigated the interactions among lncRNAs/circRNAs, miRNAs,
Women’s Hospital, Harvard Medical School, Boston, Massachusetts, and mRNAs in HSCs under hypoxic stress.
United States Method: Hypoxia-induced HSCs model were treated with 400 μmol/
Email: [email protected] L CoCl2 in HSC-T6 cells. The differentially expressed mRNAs, miRNA,
circRNAs, and lncRNAs in hypoxia-induced HSCs were identified
Background and aims: Matrix-embedded endothelial cells (MEECs)
using whole-genome sequencing. Next, we constructed the ceRNA
are endothelial cells grown in a 3D collagen-based scaffold that
network based on the interactions among lncRNAs/circRNAs,
shields their immunogenicity in vitro and in vivo. This phenotype
miRNAs, and mRNAs in hypoxia-induced HSCs. The functional
conversion minimizes stress and maximizes the secretion of anti-
analyses were performed by the gene ontology analysis and the
inflammatory and anti-fibrogenic factors. Here, we aimed to test
Kyoto Encyclopedia of Genes and Genomes pathway analysis. Finally,
whether the perihepatic implantation of MEECs may interfere with
we performed the pathway analysis based on the public database and
the inflammatory and fibroproliferative processes occurring in
literature.
fibrotic mice.

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 POSTER PRESENTATIONS
Results: A total of 1423 mRNAs, 54 miRNAs, 288 lncRNAs, and 60 research ICF have been included in this analysis. Liver biopsies were
circRNAs were differentially expressed in hypoxia-induced HSCs evaluated by a central reader using NASH-CRN scoring system and
compared to the controls. Combined with our previous identified analyzed by HI-QDP algorithm. ALT, AST, ELF, GGT, FIB-4 and Pro-C3
miRNA-mRNA regulation network in HSCs under hypoxic stress, the were analyzed by central laboratory, Fibroscan liver stiffness
results presented that up regulation lncXR_592974.2 and up measurement (LSM) was assessed by a clinical site, while MRE LSM
regulation circRNA_2599 regulated in down regulation miRNAs was assessed by a central imaging reader.
(miRNA-145-3p and novel 500 mature) -up regulation mRNA Results: Statistical analysis on the entire cohort (n = 269) revealed
(Junction Mediating and Regulatory Protein (JMY, P53 Cofactor)) that MRE had the strongest correlation with both fibrosis assess-
network, respectively. These ncRNAs/circRNAs-miRNAs- mRNAs ments (NASH CRN and HI-QDP qFibrosis), followed by a MRI-
were involved in P53 signaling pathway (Figure 1). aspartate aminotransferase (MAST) score (Figure). As MRI and MRE
imaging were performed in a random subset of subjects, the MRE
based dataset is smaller than for Fibroscan and soluble biomarkers.
Interestingly, when correlating with qFibrosis, third and fourth
ranked biomarkers were Pro-C3 and ELF, compared to FIB-4 and ELF
when correlating with CR fibrosis assessment. In both cases,
Fibroscan LSM and FibroScan-AST (FAST) score ranked fifth and sixth.

Figure: Illustration of interactions among lncRNAs/circRNAs, miRNAs, and

mRNAs in hypoxia-induced hepatic stellate cells in rat.

Conclusion: Our results showed the lncRNAs XR_592974.2/

circRNA_2599-miR-145-3p/novel 500 mature -Jmy-p53 regulatory
axis that might participate in activated HSCs and might carry
potential therapeutic targets for restraining hypoxic stress.

FRI207
Magnetic resonance elastography (MRE) demonstrate the
strongest correlation with digital pathology and NASH CRN
fibrosis assessments, compared to transient elastography and
other assessed non-invasive tests (NITs)
Miljen Martic1, Dean Tai2, Nikolai Naoumov3, Elaine Chng2,
Clifford Brass4, Juergen Loeffler5, Jossy George Kochuparampil5,
Jia Ling Chong2, Shenglin Ma6, Andreas Sailer5, Dominique Brees5,
Zachary Goodman7, Marcos Pedrosa5, Quentin Anstee8,9. 1Novartis
Pharma AG, Translational Medicine, Biomarker Development, Basel,
Switzerland; 2HistoIndex Pte. Ltd., Singapore, Singapore; 3London, Conclusion: MRE LSM and MAST score had the strongest correlation
United Kingdom; 4Novartis Pharmaceuticals Corporation, East Hanover, with liver fibrosis staging (both NASH CRN and by HI-QDP qFibrosis).
NJ, United States; 5Novartis Pharma AG, Basel, Switzerland; 6Novartis Additional evaluation of other individual biomarkers, as well as
Institutes for BioMedical Research, Translational Medicine, Biomarker combination of imaging and soluble biomarkers is still ongoing and
Development, Cambridge, MA, United States; 7Inova Health System, will also include separate correlations for randomized and screen
Director of Hepatic Pathology Consultation and Research, Falls Church, failed subjects.
VA, United States; 8Translational and Clinical Research Institute, Faculty
of Medical Sciences, Newcastle University, Newcastle upon Tyne, United FRI208
Kingdom; 9Newcastle NIHR Biomedical Research Centre, Newcastle Autoantibodies to apolipoprotein A-1 in chronic hepatitis C
Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United infection: a role in hepatic fibrosis and cirrhosis?
Kingdom Simon Bridge1, Sabrina Pagano2, David Sheridan3, John Lodge1,
Email: [email protected] Matthew Cramp4, Simon Taylor-Robinson5, Dermot Neely6,
Nicolas Vuilleumier2, Margaret Bassendine7. 1Faculty of Health and
Background and aims: Correlation of a non-invasive test (NIT) with
Life Sciences, Newcastle upon Tyne, United Kingdom; 2Geneva University
histology-based readouts is one of the key aspects of NIT inclusion in
Hospitals, Geneva, Switzerland; 3Institute of Translational & Stratified
clinical trials and their adoption and impact on patient care. This sub-
Medicine, Hepatology, Plymouth, United Kingdom; 4Hepatology,
study aimed to explore correlation of different NITs with liver
Plymouth, United Kingdom; 5Department of Surgery and Cancer,
histology endpoints assessed by standard histology (NASH-CRN) and
London, United Kingdom; 6Clinical Biochemistry, Newcastle upon Tyne,
quantitative digital pathology (HistoIndex, HI-QDP).
United Kingdom; 7Liver Medicine & Hepatology Research Group, United
Method: As part of the TANDEM NASH Phase 2 trial [NCT 03517540],
Kingdom
the cross-sectional pre-treatment data has been collected from 269
Email: [email protected]
patients with NAFLD (138 screen-failed and 131 randomized
subjects). Key trial inclusion criteria were based on liver biopsy Background and aims: Approximately 40–70% of chronic HCV (CHC)
(NASH with F2 or F3 fibrosis). Only subjects who signed additional patients develop an autoimmune extrahepatic disorder. IgG auto-
antibodies against apolipoprotein A-1 (AAA1) are a robust biomarker

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POSTER PRESENTATIONS
of cardiovascular disease and predict all-cause mortality [1]. We Conclusion: AAA1 are found in a subgroup of CHC patients and are
previously reported the presence of AAA1 in 14/27 CHC patients [2]. found with higher incidence and magnitude in patients with
Here, we evaluated AAA1 in a larger cohort of CHC patients to explore advanced liver fibrosis. AAA1 are robust biomarkers for predicting
associations between AAA1, lipoproteins and severity of liver disease. cirrhosis. Human hepatic stellate cells in the presence of AAA1
Method: Serum samples were obtained from 126 treatment naïve showed a fibrotic phenotype. Further studies are warranted to define
CHC subjects (61 genotype (GT) 1 and 65 GT3) and assayed for AAA1 the role of AAA1 in the development of fibrosis and cirrhosis.
and lipoprotein profiles. Subjects were classified as cirrhotic by liver
References
imaging and/or histological assessment. Area under receiver operat-
ing characteristic curves (AUROC) were calculated for AAA1 and HDL- [1] Antiochos P, Marques-Vidal P, Virzi J, Pagano S, Satta N, Hartley O,
et al. Anti-Apolipoprotein A-1 IgG Predict All-Cause Mortality and
related parameters and used for predicting patients with cirrhosis. Are Associated with Fc Receptor-Like 3 Polymorphisms. Front
Fibronectin (FN) and messenger RNA (mRNA) were measured in Immunol 2017;8:437.
human hepatic stellate cells (LX2) in the presence or absence of AAA1. [2] Bridge SH, Pagano S, Jones M, Foster GR, Neely D, Vuilleumier N, et al.
Results: Fifty-nine (47%) CHC patients were AAA1 positive. Twenty- Autoantibody to apolipoprotein A-1 in hepatitis C virus infection: a
one (70%) of 30 cirrhotic patients were AAA1 positive and the median role in atherosclerosis? Hepatol Int 2018;12:17–25.
magnitude of AAA1 was also significantly higher than non-cirrhotic
FRI209
patients (48% vs. 31%; p < 0.001). The AUROC for AAA1, ApoA-1 and
Selectivity matters: novel ROCK2 inhibitor down-regulates
HDL-C for predicting cirrhosis was 0.72 ( p < 0.001), 0.65 ( p = 0.01)
established liver fibrosis via concurrent targeting of
and 0.64 ( p = 0.02) (Figure A, B & C respectively). After 48 hours in the
inflammatory, fibrotic and metabolic pathways
presence of AAA1, LX2 cells showed significantly increased levels of
FN compared to LX2 cells alone ( p = 0.02) and the LX2/IgG control ( p Alexandra Zanin-Zhorov1, Wei Chen1, Melanie Nyuydzefe1,
= 0.0016). This was further confirmed by quantitating FN mRNA, LX2 Julien Moretti1, Iris Zhorov1, Rashmi Munshi2, Malavika Ghosh2,
cells and AAA1 showed an 80% increase in FN mRNA compared to LX2 Kelli MacDonald3, Bruce Blazar4, Sam Waksal1. 1Graviton Biosciences,
cells alone ( p = 0.035) and the LX2/IgG control ( p = 0.028). B.V., Translational Medicine, Amsterdam, Netherlands; 2Aragen
Biosciences, Morgan Hill, United States; 3QIMR Berghofer Medical
Research Institute, Brisbane, Australia; 4University of MN, Masonic
Cancer Center, Division of Blood & Marrow Transplant & Cellular
Therapies, Minneapolis, United States
Email: [email protected]
Background and aims: The pathogenesis of hepatic fibrosis is caused
and driven by dysregulated metabolism precipitated by chronic
inflammation. Rho-associated coiled-coil-containing protein kinases
(ROCKs) have been implicated in these processes, however the
ability of selective ROCK2 inhibition to target simultaneously pro-
fibrotic, pro-inflammatory and metabolic pathways was not demon-
strated yet.
Method: We used the thioacetamide (TAA)-induced liver fibrosis
model in combination with or without high fat diet to examine the
efficacy of administration of the highly selective ROCK2 inhibitor
GV101 to treat liver fibrosis, and its impact on inflammatory, fibrotic,
and metabolic pathways in tissues.
Results: We found that therapeutic administration of GV101, a novel
ROCK2 inhibitor with more than 1000-fold selectivity over ROCK1,
attenuated established liver fibrosis induced by TAA alone or in
combination with high fat diet in mice. GV101 treatment significantly
reduced hydroxyproline levels in liver and serum AST/ALT ratio,
which was associated with downregulation of pCofilin ( pro-fibrotic),
pSTAT3 ( pro-inflammatory), while the levels of pSTAT5 (anti-
inflammatory) and pAMPK (anti-metabolic) were increased in
tissues of treated mice. In vitro experiments have shown that
pharmacological selective ROCK2 inhibition, but not pan-ROCK
inhibition down-regulates STAT3-dependent pro-inflammatory cyto-
kine secretion in T cells as well as adipogenesis of both 3T3L1 mouse
cells and primary human preadipocytes via AMPK-dependent
mechanism.

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 POSTER PRESENTATIONS
0.3 mg group, −13.8% (SD 7.3%) ( p = 0.030 vs PBO) in the 1 mg group,
and −30.2% (SD 7.1%) ( p < 0.001 vs PBO) in the 3 mg group. The LS
mean differences in the percent change from baseline in Pro-C8, a
marker of basement membrane collagen, were +21.4% (SD 14.3%) ( p =
0.07) in the 0.3 mg group, +49.2% (SD 14.7%) ( p < 0.001) in the 1 mg
group, and +37.6% (SD 14.4%) ( p = 0.005) in the 3 mg group. In
contrast, aldafermin did not reach statistical significance on the dose-
dependent improvement in fibrosis on liver biopsy (19%, 31%, 15% and
30% of the patients in the placebo, 0.3 mg, 1 mg and 3 mg groups,
respectively, achieved fibrosis improvement of ≥1-stage without
NASH worsening).

Conclusion: All together, these data further characterize the ROCK2-

specific molecular mechanism of action and highlight the therapeutic
potential of highly selective ROCK2 inhibitors in liver fibrosis

FRI210
Aldafermin rebalances collagen turnover in patients with NASH Conclusion: Our results revealed novel insights into aldafermin
and liver fibrosis in the ALPINE 2/3 study biology in reducing the fibrogenesis of type 3 collagen in the
Manal F. Abdelmalek1, Lei Ling2, Guy Neff3, Naim Alkhouri4, interstitial matrix, while strengthening type 8 collagen in the
Charles Chen2, Alex DePaoli2, Hsiao Lieu2, Diana Leeming5, basement membrane. Given the invasive and heterogeneous nature
Morten Karsdal5, Stephen Harrison6. 1Duke University, Durham, United of liver biopsy, these novel, non-invasive fibrosis markers may have
States; 2NGM Biopharmaceuticals, South San Francisco, United States; the potential to obviate the limitations of liver biopsy by providing
3
Covenant Research, Sarasota, United States; 4Arizona Liver Health, important information regarding the state of the liver and extracel-
Tucson, United States; 5Nordic Bioscience, Herlev, Denmark; 6Pinnacle lular matrix turnover.
Clinical Research, San Antonio, United States
Email: [email protected]
Background and aims: The most common method of evaluating liver
fibrosis in clinical studies is by microscopic analysis of biopsies
Non-invasive assessment of liver disease except
stained with Masson’s trichrome or sirius red—an approach that may NAFLD
be too simplistic and not able to specifically differentiate among the
many different collagen molecules. Recent research has demon-
strated that not all collagens are created equal, and that an array of FRI214
collagen-derived molecules has emerged with novel functions. Use of the enhanced liver fibrosis test to risk stratify patients in
Whereas the interstitial matrix collagens are increased with more the intelligent liver function test pathway: ruling out cirrhosis
severe disease, the basement membrane collagens are important for and advanced fibrosis
regeneration of hepatic tissue (Villesen et al., AASLD 2021). Madeline Pearson1, Iain Macpherson2, Jennifer Nobes3,
Aldafermin, an engineered analog of the human hormone FGF19, Elizabeth Furrie3, Michael Miller2, Ellie Dow3, John Dillon2.
1
inhibits bile acid synthesis and has improved liver histology in University of Dundee, School of Medicine, Dundee, United Kingdom;
2
previous phase 2 trials. Here we perform a non-invasive, more University of Dundee, Gut Group, Dundee, United Kingdom; 3Ninewells
granular analysis of both the steady-state and dynamics of collagen Hospital, Department of Blood Sciences, Dundee, United Kingdom
turnover in the multicenter, randomized, double-blind, placebo- Email: [email protected]
controlled, phase 2b ALPINE 2/3 study in patients with NASH.
Background and aims: The intelligent liver function testing (iLFT)
Method: 171 patients were randomized 1:1:1:1 to receive placebo
pathway is an innovative automated system designed to increase
(PBO, n = 43), aldafermin 0.3 mg (n = 43), 1 mg (n = 42), or 3 mg (n =
detection of liver disease in primary care. Its successful roll-out
43) SC QD for 24 weeks at 30 US study sites. Key inclusion criteria
within NHS Tayside significantly increased liver disease diagnosis,
included biopsy-proven NASH with NAS≥4, stage 2 or 3 fibrosis and
highlighting the need for a second ‘rule-out’ test to further risk
absolute liver fat content ≥8%. Serum concentrations of Pro-C3, Pro-
stratify patients and reduce unnecessary burden on secondary care.
C4, Pro-C6 and Pro-C8 were measured by ELISA methods.
The enhanced liver fibrosis (ELF) test comprises a panel of three direct
Results: Demographic and baseline characteristics were similar
serum biomarkers of fibrosis. In July 2020 the ELF score was
across the trial groups. At week 24, the LS mean differences in the
incorporated into the iLFT pathway in NHS Tayside; it is automatically
percent change from baseline in Pro-C3, a marker of interstitial
calculated for all samples with indeterminate or elevated fibrosis
matrix collagen, were −11.7% (SD 7.0%) ( p = 0.049 vs PBO) in the
scores after an abnormal LFT, and influences recommendations for

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POSTER PRESENTATIONS
patient management. The aim was to investigate if the ELF score could liver fibrosis. We sought to evaluate whether liver computed
be used safely and effectively as a rule out test for cirrhosis and tomography (CT) imaging could discriminate Metavir fibrosis (F)
advanced fibrosis within the iLFT pathway. stages.
Method: Outcomes for all patients who received an ELF test via the Method: 111 patients with Metavir F stage by liver biopsy, CT, liver
iLFT pathway between July 2020 and April 2021 were collected and stiffness measurement (LSM), blood test (FM) or their combination
analysed to compare ELF scores with the incidence of cirrhosis and (EFM) were retrospectively included. CT was prospectively evaluated
advanced fibrosis diagnoses. A further analysis of all patients who by a) an expert radiologist according to the 7 usual signs of cirrhosis +
had undergone ELF testing since its introduction in NHS Tayside, CT-F stage, equivalent to Metavir; b) semi-automated quantitative
regardless of involvement with iLFT, was undertaken to compare ELF morphometry (43 signs); c) 70 hepato-gastroenterologists according
score with Transient Elastography (TE) reading. to CT F-stage in 10 patients (2 per Metavir F stage) for whom 4
Results: 634 patients were included in the study; 62.3% of the independent diagnostic methods agreed for fibrosis stages (method
patients were male, with a mean age of 62.5 years and mean BMI of without gold standard). We developed multivariate scores predictive
31. 419 (66%) had a ‘high’ ELF score (≥9.8) and 219 had a ‘low’ ELF of Metavir F stages using CT signs assessed by the expert radiologist
score. Median ELF score was 10.2 (IQR 9.5–11.1). 139 patients received (expert score) or by morphometry (morpho score) and by all non-
TE, with a median ELF score of 10.7 (IQR 9.9–11.4) invasive methods (mixed score including EFM, expert and morpho
57 patients received a clinical diagnosis of cirrhosis; 56 (98%) had a scores).
high ELF score ( p < 0.0001). The negative predictive value (NPV) of Results: 1) Characteristics in all 111 patients were, age: 54.2 ± 12.8
ELF as a marker for cirrhosis is 99.5%, with a sensitivity of 98.2%. ELF years, male: 60.4%, BMI: 31.2 ± 6.6 kg/m², NAFLD: 75.7%, Metavir: F0:
score was an excellent predictor of advanced fibrosis (F3/4) on TE 15.3%, F1: 34.2%, F2: 18.0%, F3: 14.4%, F4: 18.0%. Spearman correlation
(AUROC 0.80, p < 0.001): the current cut-off value (9.8) had a coefficients (Rs) with Metavir F stages were, expert score: 0.605, FM:
sensitivity of 100% and specificity of 25%. 0.648, CT-F stage: 0.661, morpho score: 0.682, LSM: 0.737, EFM:
0.750, mixed score: 0.783. Obuchowski indexes for Metavir F stage
discrimination were, expert score: 0.830, FM or CT-F stage: 0.838,
morpho score: 0.855, LSM: 0.881, EFM: 0.889, mixed score: 0.909.
Concerning discrimination between adjacent Metavir F stages, a
significant difference was observed for the following tests, F0 vs F1:
FM, LSM, EFM, expert score; F1 vs F2: all tests; F2 vs F3: LSM, EFM; F3
vs F4: CT-F stage, FM, EFM, expert and mixed scores. 2) In the 10
patients evaluated with multiple F references: the Metavir F stages
were well-discriminated by CT-F stage with Rs: 0.914, Obuchowski
index: 0.950 and significant differences ( p < 0.001) between all
adjacent Metavir F stages (Figure).

Conclusion: The high sensitivity and NPV of the ELF test for cirrhosis
and advanced fibrosis confirms the safe implementation of ELF as an
additional fibrosis ‘rule-out’ within the iLFT pathway. It allows for a
streamlined, triaged referral system, ensuring that patients requiring
secondary care involvement are picked up, whilst reducing unneces-
sary referrals amongst lower risk patients who can be safely managed
in primary care. Conclusion: A CT expert score discriminates Metavir F0 to F2 stages.
The best single test to discriminate all Metavir F stages from each
FRI215 other is a combination of a blood test and elastometry. However,
Comparison of CT, blood test, elastometry and their combination combined methods (blood test, LSM and CT) offer better discrimin-
for non-invasive staging of liver fibrosis ation. Using multiple concordant F references, a simple CT semiology
Paul Cales1, Anita Paisant1, Clémence M. Canivet1, Jerome Lebigot1, discriminates between all Metavir F stages very well.
Lannes Adrien1, Carole Vitellius1, Julien Chaigneau1, Frédéric Oberti1,
Isabelle Fouchard1, Sophie Michalak1, Jerome Boursier1,
Christophe Aubé1. 1Angers University, HIFIH Laboratory, Angers, France
Email: [email protected]
Background and aims: The EASL 2021 guidelines on non-invasive
diagnosis state that imaging does not discriminate initial stages of

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 POSTER PRESENTATIONS
FRI216 Conclusion: A blood test reliability score estimates remarkably its
Reliability criteria of non-invasive tests for liver fibrosis own diagnostic and prognostic accuracies and discriminates diag-
Paul Cales1, Clémence M. Canivet2, Lannes Adrien3, Hunault Gilles2, nostic performances of other NITs. The combination of blood test and
Frédéric Oberti3, Valérie Moal3, Isabelle Fouchard3, Sophie Michalak2, elastometry reliability criteria dramatically reduces unreliable NIT
Jerome Boursier2. 1Angers University, Hepatology, Angers, France; prevalence (≤1%), improves accuracy and better individualizes
2
Angers University, HIFIH Laboratory, Angers, France; 3Angers University patients with under-accuracy.
Hospital, Hepatology, Angers, France
Email: [email protected] FRI217
Metabolomic profiling of capillary dry blood samples for the
Background and aims: The need for reliability studies on non- differential diagnoses of hepatocellular carcinoma and liver
invasive tests (NITs) was underlined in the 2021 EASL guidelines. diseases
Recently, we developed intrinsic blood test reliability criteria. We Philipp Brunnbauer1, Jennifer Kirwan2,3, Can Kamali1,
sought to validate these criteria and apply them to other NITs. Christian Benzing1, Katrin Splith1, Karl Hillebrandt1,
Method: 6858 patients with chronic liver disease (etiologies: virus, Johann Pratschke1, Moritz Schmelzle1, Felix Krenzien1. 1Charité-
NAFLD, alcohol) were recruited in one (cross-sectional) derivation Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin
and two (cross-sectional and longitudinal) validation sets. The main and Humboldt Universität zu Berlin, Department of Surgery,
fibrosis measurements were: blood test (FibroMeter FM2G), liver Experimental Surgery, Berlin, Germany; 2Berlin Institute of Health, Core
stiffness measurement (LSM), Metavir F (liver biopsy) and survival. Unit Metabolomics, Berlin, Germany; 3Max Delbrück Center for
We developed a reliability score (RS) for FM2G with Metavir F as Molecular Medicine, Metabolomics, Berlin, Germany
reference. It included FM2G markers + etiology and comprised 3 Email: [email protected]
classes: low, fair and high reliability.
Results: 1/In the derivation set, RS estimated FM2G accuracy for Background and aims: Hepatocellular carcinoma (HCC) remains the
fibrosis staging well (agreement coef: 0.96). Thus, cirrhosis AUROCs second most common tumour-associated cause of death globally, in
were, low RS: 0.686, fair RS: 0.824, high RS: 0.924, all: 0.883 ( p < part, due to a lack of viable screening options, non-specific clinical
0.001 vs each class); accuracy is detailed in the figure. presentation and late diagnosis. In fact, alpha-fetoprotein (AFP), the
2/In the cross-sectional validation set, these significant differences biomarker of choice, is of low diagnostic utility (sensitivity of 41–65%,
were confirmed. Moreover, FM2G RS was well-correlated with the specificity of 80–94%), which further deteriorates in the presence of
LSM AUROC (Rp: 0.83). Thus, the FM2G RS discriminated the cirrhosis cirrhosis or hepatitis. Herein, we present promising preliminary
AUROC of LSM better than did reliability criteria based on LSM and results of an untargeted metabolomics biomarker-discovery study,
the IQR/LSM ratio. Also, the FM2G RS discriminated well the cirrhosis based on dry blood sampling, demonstrating robust classification
AUROCs of other blood tests (APRI, Fib4, Fibrotest, Hepascore, ELF); accuracy, discriminating HCC (including HCC in cirrhosis) from severe
e.g. for Fibrotest, low RS: 0.569, fair RS: 0.680, high RS: 0.894 ( p < fibrosis or cirrhosis.
0.001 vs low). The FM2G and LSM reliability classes were comple- Method: Capillary blood samples (10 uL) were collected from the
mentary. Thus, we developed a sequential algorithm using first FM2G earlobe of patients using a volumetric absorptive microsampling
in high RS and otherwise LSM combined with FM2G. The algorithm (VAMS) device. Metabolomic analysis was performed using liquid
accuracy was, according to its reliability classes, low (0.6% of chromatography (LC) coupled to an electrospray ionisation mass
patients): 22.2%, high: 86.0%, p < 0.001 (Figure). Its overall accuracy spectrometry (ESI-MS). Raw LC/ESI-MS data were processed using a
was 85.6% vs FM2G: 78.3% or LSM: 81.1% ( p < 0.001). standard metabolomics workflow and peaks were annotated using an
3/In the longitudinal validation set, FM2G RS discriminated survival internal database of m/z and retention time with a 30 ppm mass
accuracy. Thus, logrank tests for Kaplan-Meier survival estimates of accuracy. Data were further corrected for technical variation and
fibrosis stages were, low RS: p = 2.10−7, fair RS, p = 1.10−18, high RS: background effects, followed by batch correction and data filtering in
3.10−92. RS was thus validated independently of Metavir F. MATLAB (R2021a). Random forest classification was conducted in
MetaboAnalyst 5.0.
Results: Having analysed dried blood samples from individuals with
liver disease and healthy controls, we obtained 297 metabolites from
483 samples (162 patients), deemed suitable for statistical analysis.
Although some patients presented with both, for the purpose of
classification, we separated preoperative samples into two mutually
exclusive groups: HCC (including HCC in cirrhosis, n = 36) and severe
fibrosis/cirrhosis (F3F4, n = 25). From 43 significantly altered meta-
bolites (fold-change ratio = 2.0, evaluated via t-test with p < 0.05), we
selected a panel of three metabolites (IDs available on request),
achieving an AUROC of 0.892 (95% CI: 0.777–0.985, Figure A), and
promising predicted class probabilities and confusion matrix
(Figure B).

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POSTER PRESENTATIONS
FRI218
Stable rates of cirrhosis diagnosed by Fibroscan despite changing
trends in liver disease epidemiology: a single centre retrospective
cohort study
Joan Ericka Flores1,2, Anne Craigie1, Lucy McDonald1, Amy Edwards1,
Tim Papaluca1,2, Michael MacIsaac1, John Gough1, Kate New1,
Susanne Glasgow1, Bradley Whitton1, Paul Desmond1,2,
Marno Ryan1,2, Thai Hong1, Zina Valaydon2, Jacinta Holmes1,2,
Barbara Demediuk1, Catherine Croagh1, David Iser1,
Kumar Visvanathan1,2, Swee Lin Chen Yi Mei1,
Alexander Thompson1,2, Jessica Howell1,2. 1St. Vincent’s Hospital
Melbourne, Fitzroy, Australia; 2University of Melbourne, Parkville,
Australia
Email: [email protected]
Background and aims: Data for cirrhosis prevalence in Australia are
urgently needed to plan health resourcing for hepatocellular
carcinoma (HCC) surveillance and liver disease prevention programs.
The aim of this study was to describe the prevalence of cirrhosis
diagnosed by Fibroscan within an urban tertiary health network and
linkage to specialist care.
Method: This retrospective cohort study was conducted at St
Vincent’s Hospital Melbourne, Australia. Raw Fibroscan data files
were extracted from three machines (one static, two portable) used in
hospital and community sites, and Fibroscan database. Cirrhosis was
defined by aetiology specific cut offs and ≥12.5 kPa where aetiology
was not available. Individuals with cirrhosis range Fibroscans were
cross referenced with hospital record data to describe the proportion
of patients referred for follow up. Median time intervals were
reported in months (IQR). Proportions of Fibroscans in cirrhotic range
and aetiologies compared with Chi square test.
Results: 10, 622 Fibroscans were performed in 8727 individuals from
9 April 2010 to 27 April 2021. Fibroscan data from 2012 was not
available. Peak number of Fibroscans in 2016, coincided with
availability of hepatitis C DAAs. Recorded liver disease aetiologies:
38% chronic hepatitis C (3358/8798), 25% hepatitis B (2231/8798),
15% fatty liver disease (1297/8798) and 10% alcohol (837/8798).
15% (1595/10622) of Fibroscan records were in cirrhosis range.
Proportion of Fibroscans with cirrhosis range were similar over time,
ranging between 15 and 19% without significant variation ( p = 0.68)
(Figure 1a). Proportion of fibroscans with cirrhosis due to most
common aetiologies showed significant downtrend with chronic
hepatitis C and chronic hepatitis B ( p = 0.018 and p = 0.012,
respectively). An uptrend with MAFLD ( p = 0.35) and alcohol was
observed, but only statistically significant for alcohol ( p = 0.009).

Conclusion: Dry blood sampling can identify promising biomarker

candidates that could improve HCC time-to- and stage-at-diagnosis.
While our findings will be confirmed in a prospective study, focusing
on age and risk factor stratification, we aim to translate our findings
into an easy-to-use, low-cost population screening tool for HCC.
MS&FK share senior authorship. 1045 patients with cirrhotic Fibroscan range had hospital records:
56% (584/1045) were known to the liver clinic at the time of
Fibroscan, 20% (205/1045) were referred following Fibroscan and 24%
(252/1045) had no referral. 3% (32/1045) required multiple referrals
until patient attendance was recorded and 1% (13/1045) patients
never attended liver clinic. Median time from Fibroscan to liver clinic
referral was 13 months (IQR 3–34).
Conclusion: The proportion of patients with cirrhosis diagnosed by
Fibroscan has remained stable over time, with changing trends of
chronic liver disease aetiology from viral hepatitis to fatty liver
disease and alcohol related liver disease. Despite this, linkage to care

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 POSTER PRESENTATIONS
of people with cirrhosis remains suboptimal. These data are limited FRI220
by focusing on one hospital’s liver clinic and no data of follow-up at Diagnostic accuracy of non-invasive imaging modalities for the
other health services, but suggest greater resourcing streamline diagnosis of liver cirrhosis compared to histological assessment in
linkage of people diagnosed with cirrhosis by Fibroscan into a clinical setting
specialist care is warranted. Liv Hetland1, Mira Thing1, Thit Kronborg1, Beth Hærsted Olsen2,
Nina Kimer1, Lise Lotte Gluud1,3. 1Hvidovre Hospital, Gastro Unit,
FRI219 Hvidovre, Denmark; 2Hvidovre Hospital, Department of Radiology,
Comparative assessment of noninvasive methods (NIMs)- Hvidovre, Denmark; 3Copenhagen University, Department of Clinical
LIVERFASt, liver stiffness measurement (LSM) with transient Medicine, København, Denmark
elastography (TE, Fibroscan) ELF and FiB-4-in a prospective cohort Email: [email protected]
with chronic liver diseases (CLD) from a tertiary liver center
Kawin Tangvoraphonkchai1, Tanita Suttichaimongkol2, Background and aims: Diagnostic imaging including abdominal
Prakasit Sangaimwibool3, Wattana Sukeepaisarnjaroen4, ultrasound (US) and computed tomography (CT) are important tools
Churaieat Kularbkaew. 1Khon Kaen University, Faculty of Medicine, in the initial evaluation of patients with liver disease. We evaluated
Division of Gastroenterology, Department of Medicine, Thailand; 2Khon the accuracy of US and CT in diagnosing liver cirrhosis using a
Kaen University, Division of Gastroenterology, Department of Medicine, prospective design with histological assessment as the gold standard.
Thailand; 3Khon Kaen University, Department of Pathology, Thailand; Method: This study included 369 patients from three prospective
4
Khon Kaen University, Department of Pathology, Faculty of Medicine, cohort studies between January 2017 and November 2021 who
Thailand underwent diagnostic imaging (US or CT) and a liver biopsy based on
Email: [email protected] clinical indication. Two cohorts (ProDoc, n = 34; StatLiver, n = 78)
included patients with suspected cirrhosis and one cohort (FLINC, n
Background and aims: CLD-related mortality in Thailand is = 257) included patients with non-alcoholic fatty liver disease
increasing due to high prevalence of obesity and not eradicated (NAFLD). US and CT scans were performed by experienced radiolo-
chronic viral hepatitis B (CHB) and C (CHC). LIVERFASt (LF, gists and the results were re-evaluated by a second radiologist in case
Fibronostics, US) is a new point-of-care proprietary technology to of inconclusive findings.
assess quantitatively liver fibrosis (LF-Fib) and steatosis (LF-Ste). Results: The cohorts include 369 patients who underwent a liver
(Hepatology Suppl. 2020) In NAFLD pts, LF-Fib predicted liver-related biopsy and an US (n = 279) and/or CT scan (n = 129). In addition, 291
events and overall mortality (Hepatology Suppl.2021). patients underwent a Fibroscan. In total 143 patients had histologi-
To assess: 1/LF-Fib performance for advanced (AF) and bridging cally confirmed cirrhosis (38.7%). Of patients who underwent US, 78
fibrosis (BF) vs LSM, FIB-4 and ELF in a prospective tertiary cohort were correctly diagnosed as having cirrhosis and 159 as correctly
with CLD and LB. 2/LF-Ste performance for mild (≥S1), moderate being non-cirrhotic; the sensitivity was 0.72, specificity 0.89, positive
(≥S2) and marked steatosis (S3) vs. imaging methods (CAP) in NAFLD predictive value (PPV) 0.88 and negative predictive value (NPV) 0.84.
pts, including a CHC/CHB control group without steatosis (S0). Of patients who underwent CT scan, 61 were correctly diagnosed as
Method: Pts with simultaneous LB, blood biomarkers (LF, FIB4 and having cirrhosis and 46 as correctly being non-cirrhotic, giving a
ELF) and LSM using TE were prospectively included. LB staging was as sensitivity of 0.75, specificity of 0.96, PPV 0.97 and NPV 0.70. The PPV
per METAVIR for CHB/CHC and NASH-CRN for NAFLD. Statistics were and NPV for Fibroscan was 0.71 and 0.91.
descriptive and using binary area under ROC [BinAUROC (95%CI)]. Conclusion: This study demonstrates that both US and CT provide
Results: 192 pts were included with concomitant LF, FIB4 and LSM. N important diagnostic information for ruling in cirrhosis. However,
= 157 patients had ELF determined along with LF and other SOC. Main this study includes a relatively high proportion of patients with
characteristics were: 52.7% males, median (range) age 50 (20–69) yrs, cirrhosis and the findings should therefore be re-evaluated in low risk
26.4% NAFLD, 23.9% CHB, 49.8% CHC, BMI 34.9 Kg/m2, HbA1c 5.5, LSM groups.
7.5 kPa, LF-Fib 0.29, LF-Act 0.29, LF-Ste 0.35, 49.5% severe NAI, 50.2%
AF and 9.5% cirrhosis (F4). FRI221
Overall Bin-AUROC (95%CI) for AF were: LSM 0.70 (0.62–0.77), FIB4 Use of Fibrosis-4 (FIB-4) in liver fibrosis screening: which
0.71 (0.63–0.77) and LF-Fib 0.81 (0.67–0.85) [p = ns vs LSM and p < thresholds to choose?
0.05 vs FIB4]. Denis Ouzan1, Jeremie Corneille2, Guillaume Penaranda3,
In N = 157 patients with concomitant ELF determination, overall Bin- Jean Marie Dubertrand4. 1Arnault Institute Tzanck, Saint-Laurent-du-
AUROC (95%CI) for AF were: LSM 0.79 (0.71–0.85), FIB4 0.69 (0.61– Var, France; 2BIOGROUP BIOESTEREL-Laboratoire Mougins-L’espérance,
0.77), ELF 0.63 (0.0.53–0.71) and LF-Fib 0.77 (0.61–0.77; p = ns vs LSM Mougins, France; 3BIOGROUP ALPHABIO-Laboratoire Européen,
and p < 0.01 vs FIB4 and ELF, respectively); for BF were: LSM 0.82 Marseille, France; 4BIOGROUP BIOESTEREL-Laboratoire Mandelieu-
(0.71–0.88), FIB4 0.75 (0.63–0.83), ELF 0.64 (0.49–0.77) and LF-Fib Passero, Mandelieu-la-Napoule, France
0.77 (0.65–0.85; p = ns vs all). Email: [email protected]
For ≥S1, ≥S2 and S3 steatosis-when taking into account 17 controls
without steatosis (S0)- LF-Ste and CAP performances were: 0.75 Background and aims: Rationale: Screening for liver fibrosis in the
(0.59–0.85)/0.75 (0.61–0.85)/0.70 (0.47–0.83) vs 0.81 (0.67–0.89)/ general population is a major public health issue. We have shown in a
0.81 (0.68–0.89)/0.74 (0.55–0.86), respectively, all p = ns. previous study (EASL 2020, Abs FRI225) that FIB-4, a simple score
Conclusion: LIVERFASt is a blood biomarker for fibrosis/steatosis combining age, ALT/AST activity and platelet count, can detect liver
staging with similar performances to TE/CAP in a tertiary cohort with fibrosis in general practice and identify a possible cause of chronic
CLD. In NAFLD pts, LF can be an alternative to imaging methods (e.g. liver disease. But the optimal FIB-4 threshold that detects hepatic
CAP and LSM) for stratifying the severity of the disease. fibrosis remains to be defined. The FIB-4 thresholds recently
proposed by a single study (1) are age-dependent: low risk if <1.30
(<65 years) and <2 (>65 years), intermediate risk between 1.3 and
2.67 (<65 years) and between 2 and 2.67 (>65 years), and high risk if
>2.67. The aim of our work is to explore the simpler, age-independent
FIB-4 threshold of 2 by performing a second-line ELF (Enhanced Liver
Fibrosis) score after automatic calculation of FIB-4.
Method: The FIB-4 score has been automatically generated since
October 1, 2020 by all city analysis laboratories in the Alpes-
Maritimes French aera as soon as ALT/ASAT and platelets are

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POSTER PRESENTATIONS
prescribed. The FIB-4 results, calculated by 80 laboratories, were Results: Using available tissue methylation data on HCC (n = 670) and
analyzed. The FIB-4 thresholds used are a function of age as defined control (n = 135) samples from three different studies (GSE56588,
above. The ELF score was performed in the second line in a group of GSE54503 and TCGA-LIHC) as well as from blood leukocyte samples
183 patients at intermediate or high risk of fibrosis. of healthy individuals (754 samples, GSE40279) and deep learning
Results: During the first 3 months of the implementation of the approaches we defined a blood-based HCC Methyl Diagnostic panel
automatic calculation of the FIB-4, 131, 861 subjects were screened, (HepaMet Panel) consisting on 27 CpG marks located within CpG
half of them were older than 65 years, 56% were women and 44% were islands and 2 located within lncRNA promoter regions. HepaMet
men. The distribution of fibrosis risk observed by the FIB-4 according to Panel revealed a robust performance (accuracy of 97.3%) for control
age was as follows: low risk for 107, 148 subjects (81.3%), intermediate and HCC patient classification. In silico validation of HepaMet Panel in
risk for 16, 297 subjects (12.4%), and high fibrosis risk for 8, 416 three independent HCC cohorts (GSE60753, GSE89852 and
subjects (6.4%). An ELF score >9.8 indicative of advanced fibrosis was GSE157341) showed a sensitivity range of 97%-100%. We first set up
observed in 14/54 subjects (26%) of those with a FIB-4 score between conditions to analyze 16 of these 29 marks. Validation of this sub-
1.3 and 2 and in 102/129 (79%) of those with a FIB-4 >2 (p < 0.001). panel using cfDNA from 7 early stage HCCs, 22 advanced HCCs as well
Conclusion: The automatic calculation of the FIB-4 showed in a large as 11 healthy controls succeeded to classify 76% of HCC patients (71%
cohort, a risk of hepatic fibrosis in almost 19% of the subjects: early and 77% advanced).
intermediate risk 12.4% and high risk of fibrosis 6.4%. The ELF test Conclusion: We have identified a blood-based HCC Methyl
performed in the second line significantly more often confirmed the Diagnostic panel that effectively classify control and HCC patients.
existence of advanced fibrosis in subjects with a FIB-4 >2 as compared Ongoing analyses will determine HepaMet Panel utility in the early
to those with a FIB-4 between 1.3 and 2 (79 versus 26%). The diagnosis of HCC and HCC recurrence-progression monitoring.
threshold of 2 could significantly reduce the number of subjects in
the intermediate zone of fibrosis, which is debated. FRI223
A derivation and validation study of paired liver and plasma
Reference proteomics in 659 individuals reveals circulating biomarkers for
McPherson S, et al. Age as a Confounding Factor for the Diagnosis of alcohol-related liver disease
Advanced NAFLD Fibrosis. Am J Gastroenterol 2017; 112:740–51.
Lili Niu1, Maja Thiele2,3, Philipp Geyer1, Ditlev Nytoft Rasmussen2,
Henry Emanuel Webel1, Alberto Delgado1, Rajat Gupta1,
FRI222
Florian Meier1, Maximilian Strauss1, Maria Kjærgaard2,3,
Plasma cell-free DNA methylation as biomarker for
Katrine Prier Lindvig2,3, Mads Israelsen2,3, Simon Rasmussen1,
hepatocellular carcinoma
Torben Hansen4, Matthias Mann1, Aleksander Krag2,3. 1University of
María Gárate-Rascón1, Miriam Recalde1, Idoia Bilbao2, Fabrice Daian3, Copenhagen, Center for Protein Research, Copenhagen, Denmark;
María Elizalde1, María Azkona1, José María Herranz1,4, Carla Rojo1, 2
Center for Liver Research, Odense University Hospital, Department of
Mercedes Iñarrairaegui2,4,5, Itziar Abete6, María A. Zulet6, Gastroenterology and Hepatology, Odense, Denmark; 3University of
Bruno Sangro2,4,5, Maite G. Fernandez-Barrena1,4,5, Loreto Boix7,
Southern Denmark, Faculty of Health Sciences, Department for Clinical
María Reig7, Andrea Casadei Gardini8, Matías A. Avila1,4,5, Research, Odense C, Denmark; 4University of Copenhagen, Center for
Manuel F. Landecho2, Carmen Berasain1,4,5, Maria Arechederra1,5. Basic Metabolic Research, Denmark
1
Center of Applied Medical Research (CIMA), Program of Hepatology,
Email: [email protected]
Pamplona, Spain; 2Navarra University Clinic, Hepatology Unit,
Pamplona, Spain; 3Developmental Biology Intitute of Marseille (IBDM), Background and aims: Alcohol-related liver disease (ALD) is the
Marseille, France; 4National Institute for the Study of Liver and most common cause of liver-related mortality, but diagnosis is often
Gastrointestinal Diseases (CIBERehd, Carlos III Health Institute), Madrid, delayed due to lack of accurate, circulating biomarkers. We aimed to
Spain; 5Navarra Institute for Health Research (IdiSNA), Pamplona, Spain; develop and validate diagnostic and prognostic protein marker
6 panels of fibrosis, hepatocyte injury with inflammation, and steatosis,
Food Sciences and Physiology and Center for Nutrition Research,
Department of Nutrition, Pamplona, Spain; 7Barcelona Clinic Liver using paired liver and plasma proteomics.
Cancer (BCLC). Hospital Clínic de Barcelona. IDIBAPS, Liver Unit, Method: We included 459 patients with early ALD in a prospective
Barcelona, Spain; 8IRCCS-San Raffaele Scientific Institute, Unit of derivation cohort, used mass spectrometry to measure plasma and
Oncology, Milan, Italy liver proteome, and integrated them to determine the tissue origin of
Email: [email protected] circulating proteins. We used machine learning with feature selection
to derive three proteomic panels of significant fibrosis (≥F2), mild
Background and aims: Hepatocellular carcinoma (HCC) is a global activity (sum of ballooning and lobular inflammation ≥2) and any
health concern with increasing impact on our societies. Nowadays, steatosis (≥S1), and validated their ability to rule out or rule in disease
there are limited diagnostic methods and most patients are in 137 healthy, age- and gender-matched controls, and 63 liver-
diagnosed at advanced stage when current treatments have little biopsied ALD patients from an independent screening cohort. Finally,
effectiveness. Moreover, although patients in early and intermediate we evaluated the proteomic biomarkers’ ability to predict liver-
stages might benefit from potentially curative treatments, there is a related events and all-cause mortality, and compared their diagnostic
high rate of recurrence. It is therefore essential to identify new non- performance with 15 best-in-class existing tests.
invasive reliable biomarkers for the detection of HCC at an early stage Results: The derivation cohort consisted of 76% males, age 57 ± 13
and the prediction of recurrence-progression to improve patient years, 44% significant fibrosis (≥F2), 46% mild activity, 44% steatosis
survival. In this regard, recent advances have demonstrated that (≥S1). 717 unique proteins were dysregulated during disease
circulating tumor DNA (ctDNA) methylation has a great potential to progression, accounting for 13% of the measured liver proteome,
serve as a blood-based biomarker for early diagnosis and precision but only half of liver proteome changes were transmitted to the
treatment. In this project, we aim to identify and validate new ctDNA circulation. Integrative analysis revealed 46 co-dysregulated proteins,
methylation markers for early HCC detection and HCC recurrence- representing mostly the downregulation of metabolic functions and
progression monitoring. upregulation of fibrosis signaling and immune response (figure).
Method: For in silico analyses we used available tissue methylation Feature selection found that 22 unique plasma proteins could be used
data on control and HCC patients, focusing on CpG islands and in different combinations to derive three proteomic biomarker
lncRNA promoter regions. We set up the protocol to isolate cfDNA panels. The panels performed better than all comparators (including
from 1 ml of plasma, to treat cfDNA with bisulfite and to perform elastography, ELF, FIB-4, cytokeratin-18) for detecting significant
targeted sequencing. Plasma from control and HCC patients were fibrosis (AUC 0.92) and mild activity (AUC 0.87). The ≥F2 proteomic
used for validations.

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 POSTER PRESENTATIONS
panel ruled out significant fibrosis in 99% of the healthy controls and FRI224
had the highest prognostic accuracy for liver-related events and all- Development and validation of a hepatic vascular geometrical
cause mortality (Harrell’s C 0.90 and 0.79). We successfully model for noninvasive diagnosis of clinically significant portal
reproduced the excellent proteomics performance in the independ- hypertension in cirrhosis (CHESS1802)
ent validation cohort (AUC 0.87 for significant fibrosis, and AUC 0.81 Chengyan Wang1, Yifei Huang2, Changchun Liu3, Fuquan Liu4,
for mild activity). Xumei Hu5, Xutong Kuang5, Weimin An3, Chuan Liu2, Yanna Liu2,
Xiaolong Qi2. 1Fudan University, Human Phenome Institute, Shanghai,
China; 2The First Hospital of Lanzhou University, CHESS Center, Institute
of Portal Hypertension, Lanzhou, China; 3Fifth Medical Center of Chinese
People’s Liberation Army General Hospital, Department of Radiology,
Beijing, China; 4Beijing Shijitan Hospital, Department of Interventional
Therapy, Beijing, China; 5Fudan University, Human Phenome Institute,
Shanghai, China
Email: [email protected]
Background and Aims: Noninvasive and accurate methods are
needed to identify patients with clinically significant portal hyper-
tension (CSPH). This study aims to explore the variations of hepatic
vascular geometries in patients with CSPH and investigate the
capability of using CT/MRI angiographic imaging-based vascular
geometrical model (VGM) to identify CSPH in patients with cirrhosis.
Method: The portal vein (PV), hepatic vein (HV), hepatic artery (HA)
and inferior vena cava (IVC) were segmented using a pre-trained
attention-based convolutional neural network (CNN). A total of 64
vascular geometrical parameters were automatically extracted from
those segmented vessels and then fed into the VGM to identify CSPH
patients. A total of 853 consecutive liver cirrhosis patients from two
centers who underwent contrast enhanced MRI/CT scans within 14
days of transjugular catheterization for hepatic venous pressure
gradient (HVPG) measurement were included in this study. The
model was trained and validated in a CT cohort (#1) containing 256
patients with cirrhosis and 267 age-matched participants without a
history of chronic liver diseases, and tested on another centers
including a CT cohort (#2) with 106 patients and an MRI cohort (#3)
with 224 patients. CSPH was defined as HVPG ≥10 mmHg.
Results: In PV, significant increase of vessel diameter (from 1.50 ±
0.91 to 2.20 ± 0.69 cm) and branch vessel diameter (from 0.41 ± 0.15
vs 0.73 ± 0.56 cm) were observed in CSPH patients. In contrast,
significant decrease of PV volume (from 31.01 ± 12.93 to 23.89 ±
9.68 cm3) and tortuosity (from 0.17 ± 0.05 to 0.13 ± 0.04°) were
observed in CSPH patients. In HV, significant decrease of vessel
volume (from 66.52 ± 16.91 to 33.31 ± 28.05 cm3) and length (from
812.42 ± 284.55 to 349.21 ± 185.87 mm) were observed in CSPH
patients. In HA, significant increase of vessel length (from 77.26 ±
64.31 to 143.38 ± 57.2 mm) were observed, which indicates signifi-
cant disruption of hepatic vascular system in CSPH patients. The AUC,
accuracy, sensitivity and specificity were 0.90 ± 0.02 (95% CI, 0.88–
0.93), 0.84 ± 0.01 (95% CI, 0.84–0.85), 0.87 ± 0.05 (95% CI, 0.80–0.92)
and 0.83 ± 0.04 (95% CI, 0.80–0.89) for Cohort #1; 0.84 ± 0.12 (95% CI,
0.67–1), 0.88 ± 0.10 (95% CI, 0.75–1), 0.88 ± 0.10 (95% CI, 0.73–1) and
0.88 ± 0.09 (95% CI, 0.76–1) for Cohort #2; and 0.87 ± 0.11 (95% CI,
0.74–1), 0.91 ± 0.08 (95% CI, 0.8–1), 0.90 ± 0.09 (95% CI, 0.77–1) and
0.92 ± 0.08 (95% CI, 0.82–1) for Cohort #3.

Conclusion: Plasma proteomics has a great potential for the

diagnosis and prognosis of overall liver health in people with a
history of harmful drinking.

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POSTER PRESENTATIONS
ruled-in at <6.2 kPa (Sens.: 90.2%) and >10.2 kPa (Spec.: 90.3%),
respectively (AUROC: 0.882, p < 0.001).

Figure 1: Workflow of the CT/MRI angiographic imaging-based vascular

geometrical model.

Conclusion: This study developed and validated a contrast-enhanced

CT/MRI-based VGM with good diagnostic consistency to the HVPG
measurement. It provided a noninvasive and effective method for
diagnosis of CSPH in patients with cirrhosis, which shows good
potential for clinical applications.
Figure 1: Scatterplot of VCTE-LSM vs. ElastQ-LSM (log10-transformed
FRI225 axis) with Pearson correlation separately shown for VCTE-LSM 0–30 kPa
The diagnostic accuracy of ElastQ 2-D shear wave elastography for (red) and >30 kPa (turquoise). Abbreviations: ElastQ-2-D shear wave elas-
liver fibrosis risk assessment in a mixed etiology, multinational tography technique; kPa-kilopascal, LSM-liver stiffness measurement,
VCTE-Vibration Controlled Transient Elastography.
cohort
David J. M. Bauer1,2, Annalisa De Silvestri3, Laura Maiocchi3, Conclusion: This prospective, multicentric study shows a moderate
Ruxandra Mare4, Ioan Sporea4, Theresa Müllner-Bucsics1,2, correlation of ElastQ -LSM to VCTE-LSM, with better correlations at
Giovanna Ferraioli3, Thomas Reiberger1,2. 1Medical University of VCTE-LSM≤30 kPa. ElastQ -LSM rules out significant fibrosis at
Vienna, Division of Gastroenterology and Hepatology, Department of <5.3 kPa and rules in advanced fibrosis/cirrhosis at >10.2 kPa.
Medicine III, Wien, Austria; 2Medical University of Vienna, Vienna
Reference
Hepatic Hemodynamic Lab, Division of Gastroenterology and
Hepatology, Department of Medicine III, Wien, Austria; 3University of 1. EASL Clinical Practice Guidelines on non-invasive tests for evaluation
of liver disease severity and prognosis-2021 update. J Hepatol.
Pavia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 4Victor
2021;75:659–689.
Babeş University of Medicine and Pharmacy, Department of Internal
Medicine II, Division of Gastroenterology and Hepatology, Center for FRI226
Advanced Research in Gastroenterology and Hepatology, Timișoara, Machine learning models for prediction of severe portal
Romania hypertension in patients with compensated cirrhosis
Email: [email protected] Oleksandr Petrenko1,2,3,4, Jirí̌ Reiniš1, Benedikt Simbrunner1,2,3,4,
Background and aims: The 2-D shear wave elastography technique Benedikt Hofer1,2,3,4, Pierre-Emmanuel Rautou5, Lucile Moga5,
ElastQ (Philips) shows promise for evaluating liver fibrosis risk Jonel Trebicka6,7, Wenyi Gu6,7, Philip Georg Ferstl6,7, Lise Lotte Gluud8,
assessment. Flemming Bendtsen8, Søren Møller9, Agustin Albillos10, Luis Téllez10,
Method: We prospectively recruited 875 patients for simultaneous Sven Francque11,12, Wilhelmus Kwanten11,12,
liver stiffness measurements (LSM) by ElastQ and Vibration Juan Carlos Garcia Pagan13, Valeria Perez13,
Controlled Transient Elastography (VCTE) in 3 European centers. Virginia Hernandez-Gea13, Filippo Schepis14, Marco Scoppettuolo14,
IQR/median ≤30% was used as a reliability criterion. The correlation Dario Saltini14, Càndid Villanueva15, Anna Brujats15,
of ElastQ-LSM to VCTE-LSM was assessed by Pearson correlation. The Mattias Mandorfer3,4, Thomas Reiberger1,2,3,4. 1CeMM Research Center
fibrosis stage was classified by VCTE: no significant fibrosis VCTE for Molecular Medicine of the Austrian Academy of Sciences, Vienna,
<6 kPa, grey area/significant fibrosis VCTE 6–12 kPa, severe fibrosis/ Austria; 2Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases
cirrhosis VCTE >12 kPa (EASL CPG 2021). This classification served as (LBI-RUD), Vienna, Austria; 3Vienna Hepatic Hemodynamic Lab
a basis for the ROC analysis and definition of 90%-specific rule-in, and (HEPEX), Division of Gastroenterology and Hepatology, Department of
90%-sensitive rule-out cutoffs for ElastQ. Internal Medicine III, Medical University of Vienna, Vienna, Austria;
4
Results: Among 875 participants, ElastQ failed in 26 (2.97%) and Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis,
VCTE in 7 (0.8%) and was unreliable (IQR/median >30%) in 24 (2.74%) Medical University of Vienna, Vienna, Austria; 5Service d’Hépatologie,
and 6 (0.69%) participants, respectively. The final population DMU Digest, Hôpital Beaujon, AP-HP, Clichy, France; 6Department of
consisted of n = 813 patients: 53.9% men (n = 438), median age: 57.0 Internal Medicine I, Goethe University Clinic, Frankfurt, Germany;
7
[IQR:19] years, median BMI: 25.3 [5.8] kg/m2. The leading etiologies European Foundation for the Study of Chronic Liver Failure, EFCLIF,
were HCV (50.1%), NAFLD (16.1%), HBV (12.1%), and ALD (10.1%). Barcelona, Spain; 8Gastro Unit, Medical Section, Hvidovre Hospital and
Fibrosis stages were no significant fibrosis in n = 286 (35.2%), Department of Clinical Medicine, University of Copenhagen,
significant fibrosis in n = 290 (35.7%), and severe fibrosis/cirrhosis Copenhagen, Denmark; 9Department of Clinical Physiology and Nuclear
in n = 237 (29.2%). The Pearson correlation of VCTE and ElastQ was R Medicine, Center for Functional and Diagnostic Imaging and Research,
= 0.64 overall, but higher in VCTE-LSM≤30 kPa (R = 0.70, Fig. 1). Faculty of Health Sciences Hvidovre Hospital, University of Copenhagen,
ElastQ -LSM ruled-out and ruled-in significant fibrosis risk at <5.3 kPa Hvidovre, Denmark; 10Department of Gastroenterology, Hospital
(Sens.: 91.0%) and at ≥6.8 kPa (Spec.: 91.3%), respectively (AUROC: Universitario Ramón y Cajal, IRYCIS, CIBEREHD, Universidad de Alcalá,
0.859, p < 0.001). Severe fibrosis/cirrhosis risk was ruled-out and Madrid, Spain; 11Department of Gastroenterology and Hepatology,
University Hospital Antwerp, Antwerp, Belgium; 12Laboratory of

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 POSTER PRESENTATIONS
Experimental Medicine and Pediatrics (LEMP), Faculty of Medicine and However, the external applicability of the 3-parameter logistic
Health Sciences, University of Antwerp, Antwerp, Belgium; 13Barcelona regression model to predict HVPG ≥16 mmHg is limited-likely due
Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de to differences in laboratory assays and patient characteristics.
Investigacions Biomed̀ iques August Pi i Sunyer (IDIBAPS), University of Training and applying of the models in the subsets of the same
Barcelona, Barcelona, CIBEREHD (Centro de Investigación Biomédica en cohort resulted in more sustained AUC. Invasive HVPG measurements
Red Enfermedades Hepáticas y Digestivas), Health Care Provider of the are hence still needed to reliably identify cACLD with HVPG
European Reference Network on Rare Liver Disorders; 14Unit of ≥16 mmHg.
Gastroenterology, Hepatic Hemodynamic Laboratory, Università degli
Studi di Modena e Reggio Emilia (UNIMORE), Modena, Italy; 15Hospital FRI227
de la Santa Creu i Sant Pau. Biomedical Research Institute Sant Pau (IIB Reproducibility and applicability of spleen stiffness measurement
Sant Pau), Universitat Autònoma de Barcelona, Barcelona, Spain by vibration controlled transient elastograghy in patients with
Email: [email protected] and without chronic liver disease
Cristina Rigamonti1,2, Micol Cittone1,2, Giulia Francesca Manfredi1,2,
Background and aims: Hepatic venous pressure gradient (HVPG) is Andrea Sorge3, Riccardo Moia1,4, Maria Francesca Donato5,
the gold standard for evaluation of the severity of portal hypertension
Gianluca Gaidano1,4, Mirella Fraquelli3. 1Università del Piemonte
(PH). In this multicenter study, we investigated the diagnostic value
Orientale, Department of Translational Medicine, Novara, Italy; 2AOU
of different machine learning models trained on standard laboratory Maggiore della Carità, Division of Internal Medicine, Novara, Italy;
parameters to predict severe PH in compensated advanced chronic 3
Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico,
liver disease (cACLD) patients. Gastroenterology and Endoscopy Unit, Milan, Italy; 4AOU Maggiore della
Method: The training cohort included cACLD patients recruited from Carità, Division of Hematology, Italy; 5Fondazione IRCCS Ca’ Granda-
the prospective VICIS study (NCT03267615). Regression and classi-
Ospedale Maggiore Policlinico, Gastroenterology and Hepatology Unit,
fication-based prediction models were applied to identify patients Italy
with severe PH (i.e., HVPG ≥16 mmHg) based on 52 widely available
Email: [email protected]
laboratory parameters. After feature selection, the models were
applied to an external multicenter validation cohort using a cross- Background and aims: Spleen stiffness measurement (SSM) by
validation approach with the AUC reported as the median value vibration controlled transient elastography (VCTE) has emerged as a
across 75 cross-validations. promising non-invasive tool with good diagnostic accuracy for
Results: The VICIS cohort included 139 cACLD patients (35.2% with predicting the degree of portal hypertension in patients with
HVPG ≥16 mmHg), main etiologies were viral hepatitis (32.4%), advanced chronic liver disease (CLD). This study investigated intra-
alcohol-related liver disease (ALD; 21.6%), and non-alcoholic fatty observer and inter-observer agreement and factors influencing SSM
liver disease (NAFLD; 16.5%). The external validation cohort included reproducibility.
834 cACLD patients (36.7% with HVPG ≥16 mmHg), with the most Method: In this prospective multicentre study 297 patients with CLD
prevalent etiologies being viral hepatitis (38.6%), NAFLD (24.2%), and of different aetiology (187 in Novara and 110 in Milan; 32% cirrhotics)
ALD (20.6%). and 123 controls (63 patients with Philadelphia negative (Ph-)
Recursive feature elimination identified three and five parameters as myeloproliferative neoplasms in Novara and 60 heathy volunteers in
most suitable for the models. Milan) consecutively underwent VCTE examination for SSM and liver
In the VICIS cohort, internal training-validation with the 5-parameter stiffness measurement (LSM). SSM was blindly performed twice by
( platelets, bilirubin, cholinesterase, GGT, aPTT) logistic regression two different operators. Intra-observer and inter-observer agreement
model outperformed the other models with AUC of 0.898 for was calculated using the intraclass correlation coefficient (ICC) in
prediction of HVPG ≥16 mmHg (Figure-A). relationship with different patient-related covariates.
Results: A total of 922 VCTE examinations for SSM were performed in
Novara and 680 in Milan, respectively, with an overall failure rate of
3.2% and 3.6%.
In CLD patients from Novara (33% cirrhotic, 26% with splenomegaly)
median SSM was 24.9 kPa (IQR 20.6–36.1) and LSM was 6.8 kPa (IQR
4.9–11.3). In CLD patients from Milan (31% cirrhotics, 40% with
splenomegaly) median SSM was 29.2 (IQR 16.7–34.5) and median
LSM 8.3 kPa (IQR 7.1–10.8).
Median SS value was 26.6 kPa (IQR 24.3 to 36.1) in the overall CLD
group, 26.3 kPa (IQR 22.3–33.6) in MPN patients and 16.1 kPa (IQR
14.6–18.7) in healthy volunteers.
In whole CLD group, SSM was significantly correlated with LSM (r =
0.67), spleen longitudinal diameter (r = 0.58), presence of cirrhosis (r
= 0.54), and BMI (r = 0.24) ( p < 0.0001 for all comparisons).
In CLD patients the overall inter-observer agreement ICC was 0.90
(0.88–0.92) and factors associated with a reduced agreement were:
absence of splenomegaly (ICC0.87 vs 0.91), BMI >25 kg/m2 (ICC 0.91
The best 3-parameter model included platelets, bilirubin, and aPTT.
vs 0.88) and absence of cirrhosis (ICC 0.84 vs 0.90). Intra-observer
After being applied to the external validation cohort, and following
agreement ICC for rater 1 and rater 2 respectively were 0.93 (95% CI
the training-validation split, logistic regression resulted in the
0.91–0.95) and 0.96 (95% CI 0.95–0.97) in Novara and 0.91 and 0.94
highest AUC of 0.751 (Figure-B). The other 3-parameter models
(95% CI 0.91–0.96) (95% CI 0.87–0.93) in Milan.
yielded median AUC of 0.681 (XGBoost), 0.726 (Random Forest),
Conclusion: SSM is a highly reproducible and feasible technique for
0.748 (Support Vector Machine), and 0.750 (Multilayer Perceptron).
assessing SSM in patients with CLD.
When trained on the VICIS cohort first and then applied to the
external cohorts, the 3-parameter model with logistic regression
resulted in AUC spread from 0.472 to 0.872 in the different centers’
cohorts.
Conclusion: The VICIS-trained 5-parameter and 3-parameter model
performed well to identify HVPG ≥16 mmHg in ‘local’ cACLD patients.

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POSTER PRESENTATIONS
FRI228 Conclusion: By using the continuous method, the intra examination
Validation of the continuous controlled attenuation parameter measurement variability of the CAP is decreased with a factor 2,
(CAPc) using the MRI-PDFF as reference keeping the global performance of the CAP algorithm. Furthermore,
Nathalie Ganne-Carrié1, Olivier Chazouillères2, Jerome Boursier3, the results of CAP and CAPc examinations are strongly correlated and
Christophe Aubé4, Yves Menu5, Olivier Seror6, Yves Gandon7, in agreement. Performances of CAP and CAPc are good for S >0 and
Edouard Bardou-Jacquet8. 1Avicenne Hospital (AP-HP), Department of S >1.
Hepatology, Bobigny, France; 2Hospital Saint-Antoine Ap-Hp,
Department of Hepato-gastroenterology, Paris, France; 3Angers FRI229
University Hospital Center, Department of Hepato-Gastroenterology and A novel non-invasive index for the prediction of liver fibrosis in
Digestive Oncology, Angers, France; 4Angers University Hospital Center, chronic hepatitis B patients with concurrent nonalcoholic fatty
Department of Radiology, Angers, France; 5Hospital Saint-Antoine Ap- liver disease
Hp, Department of Radiology, Paris, France; 6Jean-Verdier Hospital Ap- Jian Wang1, Jiacheng Liu2, Yiguang Li3, Li Zhu4, Minxin Mao2,
Hp, Department of Radiology, Bondy, France; 7CHU Rennes-Pontchaillou Weimao Ding5, Yuanwang Qiu3, Chuanwu Zhu4, Jie Li1, Rui Huang1,
Hospital, Department of Radiology and Medical Imaging, Rennes, Chao Wu1. 1Nanjing Drum Tower Hospital, The Affiliated Hospital of
France; 8CHU Rennes-Pontchaillou Hospital, Department of Liver Nanjing University Medical School, Department of Infectious Diseases,
Diseases, Rennes, France Nanjing, China; 2Nanjing Drum Tower Hospital Clinical College of
Email: [email protected] Traditional Chinese and Western Medicine, Nanjing University of
Chinese Medicine, Department of Infectious Diseases, Nanjing, China;
Background and aims: Controlled Attenuation Parameter (CAP) was 3
The Fifth People’s Hospital of Wuxi, Department of Infectious Diseases,
first introduced on the FibroScan (FS) device (Echosens, France) in Wuxi, China; 4The Affiliated Infectious Diseases Hospital of Soochow
2010 and has been shown to be well correlated with liver steatosis in University, Department of Infectious Diseases, Suzhou, China; 5Huai’an
patients with various chronic liver diseases [PMID:28039099]. A new No. 4 People’s Hospital, Department of Hepatology, Huai’an, China
acquisition method for CAP (continuous CAP, CAPc) has recently been Email: [email protected]
introduced in order to decrease the intra examination measurement
variability (IEMV) [ILC2020;poster FRI073]. The aim of this interim Background and aims: Few accurate non-invasive indexes are
analysis of an ongoing study is to compare the diagnostic perfor- available to evaluate liver fibrosis in chronic hepatitis B (CHB)
mances and the IEMV between CAP and CAPc. patients with nonalcoholic fatty liver disease (NAFLD). We aimed to
Method: Consecutive patients, all etiologies combined, underwent establish a predictive index for advanced fibrosis in CHB patients with
FS, Magnetic Resonance Imaging (MRI) within 21 days and CAPs NAFLD.
obtained by both methods (standard and continuous). A central Method: A total of 267 treatment-naïve CHB patients with NAFLD
reading of the MRI images was performed to assess the Proton underwent liver biopsy were enrolled from four hospitals and
Density Fat Fraction (PDFF) which was used as the reference to assess randomly divided into a derivation set (n = 134) and a validation set
the steatosis grades (S >0: PDFF ≥5% and ≤10%; S >1: PDFF ≥10%). The (n = 133). Receiver operating characteristic (ROC) curve was used to
CAPs standard deviations (SD) were compared using the unilateral compare predicting accuracy of different indexes.
Wilcoxon signed-rank test. The agreement between CAP and CAPc Results: In the derivation set, alanine aminotransferase, aspartate
was assessed with the average bias, the Pearson’s coefficient of aminotransferase (AST), prothrombin time, presence of hypertension,
correlation (CC) and the absolute agreement intraclass coefficient and type 2 diabetes were significantly associated with advanced
(AA-ICC). The CAPs performances versus the PDFF were estimated fibrosis (≥S3). Based on these parameters, a novel index namely
with operating characteristics curves (ROC), and their areas under the AAPHD for predicting advanced fibrosis was developed. The areas
curves (AUC). AUCs were compared with Delong’s bilateral test. under the ROC curves (AUROCs) of AAPHD index in predicting
Results: 157 patients were included (41% female, mean BMI = 28.4 ± advanced fibrosis was 0.88 (95%CI:0.82–0.94). The optimal cut-off
5.5 kg/m2, mean age = 55.0 ± 13.4 years, Prevalence of S >0 and S >1 value of AAPHD was −2.870, with a sensitivity of 72.73% and a
were 61% and 22%, respectively). The median CAPc SD (13.1 dB/m²) specificity of 90.10%. The predicting accuracy of AAPHD for advanced
was significantly lower to median CAP SD (28.4 dB/m²) ( p < 0.0001). fibrosis was significantly superior to AST-to-platelet ratio index
The median reduction in IEMV was 50% (Fig). The average bias (APRI) (AUROC = 0.70), fibrosis-4 score (FIB-4) (AUROC = 0.69), and
between the CAP and CAPc was 7.9 dB/m. The CC and AA-ICC were NAFLD fibrosis score (NFS) (AUROC = 0.68). In the validation set, the
0.90 and 0.89, respectively, highlighting a strong correlation and AUROCs of AAPHD (AUROC = 0.88) remains significantly higher than
agreement. AUCs for S >0 were 0.86 (0.79–0.92) and 0.85 (0.78–0.91) that of FIB-4 and NFS, while it was comparable with APRI for
for CAP and CAPc, respectively. AUCs for S >1 were 0.85 (0.78–0.92) predicting advanced fibrosis.
and 0.86 (0.79–0.93), for CAP and CAPc, respectively. AUCs of CAP and
CAPc methods were not significantly different.

Figure: Receiver operating characteristic (ROC) curves of non-invasive

tests for predicting advanced liver fibrosis in derivation set (A) and valid-
ation set (B).

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 POSTER PRESENTATIONS
Conclusion: AAPHD is a promising non-invasive index for predicting FRI231
advanced fibrosis with high accuracy in CHB patients with NAFLD. Shear wave elastography is a useful and accurate tool to triage
The application of AAPHD may reduce the necessary for liver biopsy patients with acute liver failure syndromes
in CHB patients with NAFLD. Francesca Maria Trovato1, Florent Artru1, Salma Mujib1, Ellen Jerome1,
Anna Cavazza2, William Bernal2, Brian J. Hogan2, Rosa Miquel2,
FRI230 Mark J. W. McPhail1. 1Institute of Liver Studies, Department of
Comparison between two 2D-SWE techniques using transient Inflammation Biology, London, United Kingdom; 2Institute of Liver
elastography as a reference method for liver stiffness assessment Studies, London, United Kingdom
Alina Popescu1,2, Camelia Foncea1,2, Raluca Lupusoru1,2,3, Email: [email protected]
Roxana Sirli1,2, Felix Bende1,2, Alexandru Popa1,2, Victor Baldea1,2,
Radu Cotrau1,2, Pascu Ariana1,2, Ioan Sporea1,2. 1Department of Background and aims: Shear wave elastography has been largely
Gastroenterology and Hepatology, Department of Internal Medicine II, used in chronic liver disease to assess liver stiffness non-invasively
Center for Advanced Research in Gastroenterology and Hepatology and estimate the grade of fibrosis. In acute settings, studies were
“Victor Babes” University of Medicine and Pharmacy Timisoara, inconclusive since the high stiffness is not related to fibrosis but to a
Romania; 2Center for Advanced Hepatology Research of the Academy of combination of other factors not completely identified, including,
Medical Sciences, Timișoara; 3Center for Modeling Biological Systems inflammation, necrosis and micro-thrombosis. We re-evaluated the
and Data Analysis, Department of Functional Sciences, “Victor Babes” usefulness of a non-invasive anatomically directed ultrasound
University of Medicine and Pharmacy Timisoara, Romania approach to patients with acute liver failure syndromes admitted to
Email: [email protected] intensive care.
Method: 18 patients with index presentation of acute liver failure
Background and aims: Ultrasound-based liver elastography techni- (ALF) requiring admission to liver intensive care, 3 known cirrhotics
ques are non-invasive methods used for the assessment of liver in acute on chronic liver failure (ACLF), 8 healthy controls were
stiffness (LS). In addition to Transient Elastography (TE), new included in the study. After collateral history, imaging and in some
methods were developed. To compare the performance of 2D-SWE case liver biopsy, acute patients were subsequently re-characterized
technique implemented on two different ultrasound probes from as 10 ALF and 8 ACLF. Shear wave velocity, hepatic vascular flows, size
different vendors for the assessment of liver stiffness measurements of liver and spleen were measured using the Philips Affinity 70, and
(LSM) using transient elastography (TE) as reference method. biopsy or explant histological findings were used as comparison.
Method: A prospective study was conducted in which LSM were Platelet endothelial cell adhesion molecule-1 (sPECAM-1) and von
performed in 201 consecutive patients with or without chronic liver Willebrand factor were measured in plasma by enzyme-linked
disease, evaluated in the same session by 2D-SWE and TE immunosorbent assay (ELISA) (n: 8HC, 20 ALF, 12 ACLF).
implemented on the following systems: Siemens ACUSON Sequoia Results: Liver stiffness measurement of the right lobe (RLSM)
(5C-1 convex transducer and Deep Abdominal Transducer-DAX), accurately identified healthy controls (5.9 ± 2 kPa), acute liver
Aixplorer Mach 30 (C2-1X convex transducer) and FibroScan failure (24.87 ± 9.3) and acute on chronic liver failure (92 ± 61.8 kPa)
Compact M 530 (M and XL probes). Reliable measurements were patients. In this population with hyperdynamic circulation, the
defined as the median value of 10 measurements and an IQR/M < 0.3. estimation of the left lobe stiffness was less accurate due to heart
For significant fibrosis a cut-off value for TE of 7 kPa was used, for beat artifacts. Spleen size, but not spleen stiffness, accurately
advanced fibrosis 9.5 kPa and for liver cirrhosis 12 kPa. discriminate between ALF and ACLF. In ACLF, RLSM correlates with
Results: From 201 patients, 198 patients had reliable measurements both age and severity of liver disease express by Child-Pugh score and
in all techniques and were included in the final analysis, mean age the highest values are found in alcoholic hepatitis and Wilson’s
54.8 ± 13.3 years, mean BMI 28.8 ± 5.0, 58% (116/198) men. 58.5% disease. sPECAM—1 correlates with bilirubin (Spearman r = 0.777, p <
were without or with mild fibrosis, 14.1% had significant fibrosis, 6.2% 0.001) and MELD (r = 0.05335, p = 0.029) in both acute liver failure
had advanced fibrosis and 21.2% had liver cirrhosis. For significant syndromes but no correlation was found with liver stiffness.
fibrosis the performance was slightly better for 2D-SWE.SSI (AUROC Conversely, vWF is highly directly correlated with RLSM, MELD and
= 0.89, p < 0.0001, >7.3 kPa, Se = 85.1%, Sp = 87.9%) followed by 2D- SOFA scores ( p < 0.001). 3 ALF explants and 4 explants/biopsies
SWE.5C1 (AUROC = 0.79, p < 0.0001, >6.9 kPa, Se = 33.7%, Sp = 96.7%) confirming the presence of cirrhosis in ACLF patients and higher
and 2D-SWE.DAX (AUROC = 0.78, p < 0.0001, >6.3 kPa, Se = 36.4%, Sp degree of cholestasis in all compartments (cytoplasmic, canalicular
= 96.7%), p = 0.01. For advanced fibrosis the best performance was and ductular), had respectively a mean RLSM of 26 ± 17.6 kPa and 109
slightly better by 2D-SWE.SSI (AUROC = 0.92, p < 0.0001, >8.8 kPa, Se ± 60 kPa.
= 92.5%, Sp = 91.9%), and by 2D-SWE.DAX (AUROC = 0.86, p < 0.0001,
>7.6 kPa, Se = 38.8%, Sp = 99.3%), followed by 2D-SWE.5C1 (AUROC =
0.84, p < 0.0001, >8.6 kPa, Se = 38.8%, Sp = 96.5%), p = 0.02. For liver
cirrhosis the performances were similar: 2D-SWE.SSI (AUROC = 0.91,
p < 0.0001, >10.3 kPa, Se = 92.8%, Sp = 90.3%), followed by 2D-SWE.
DAX (AUROC = 0.90, p < 0.0001, >10 kPa, Se = 23.8%, Sp = 98.7%) and
2D-SWE.5C1 (AUROC = 0.84, p < 0.0001, >9.9 kPa, Se = 33.3%, Sp =
96.7%), p = 0.10. The cut off values for predicting different stages of
fibrosis ranged from 6.3–7.3 kPa for F2, 7.6–8.8 kPa for F3 and 9.9–
10.3 for F4.
Conclusion: The performance of the evaluated 2D SWE techniques
for liver fibrosis assessment was similar.

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POSTER PRESENTATIONS
histological data within 6 months were collected. TE and CAP were
performed by 2 experienced operators using the classical technique
of 10 measurements at the midaxillary line. Measurements of SWE
and SCAP were performed in triplicate at the mid (MAL), posterior
(PAL) and anterior axillary lines (AAL) (total of 9 values). The
technique the simplest to perform and most reliable has been
analyzed. Performances of SWE and SCAP for the diagnosis of
advanced fibrosis and significant steatosis have been defined using TE
(≥9.5 kPa) and CAP (≥275 dB/m) as reference. Factors associated with
discordance have been evaluated.
Results: FS and SS data from 203 patients were analyzed (12 patients
excluded due to FS and/or SS failure). Baseline characteristics: mean
age 56 ± 14 years; male 58%; MAFLD 59%, viral hepatitis 24%; mean
BMI 28.3 ± 5.9 kg/m2. Median TE and CAP were 6.5 kPa (2.5–66.9) and
272 dB/m (141–400). Table 1 shows the performances of SCAP
according to different technique methods. The median of 3 SWE
values and 3 SCAP values (1st measurement at MAL, PAL and AAL) had
an AUROC of 0.96 [CI95%: 0.93–0.98] and 0.91 [CI95%: 0.86–0.95] for
the diagnosis of advanced fibrosis and significant steatosis, and
considered as the best technique. The accuracy of cut-off values for
SWE (≥8.5 kPa) and SCAP (≥0.44) were analyzed in 54 patients with
liver biopsy. There was only 1 false-negative for fibrosis (PPV = 50%,
NPV = 97%) and 2 false-negatives for steatosis (PPV = 69%, NPV = 87%).
The factors associated with discordance were skin-to-liver distance
(SLD) ≥2.4 cm ( p < 0.001), depth ≥5.5 cm ( p < 0.001), stability index
<70% ( p = 0.009) and viscosity ≥2.4 ( p = 0.026). In logistic regression,
the only factor associated with discordance was SLD ( p = 0.012).

Conclusion: In patients with acute liver failure syndromes, shear

wave elastography can help in the early clinical assessment at
admission in intensive care. Plasma vWF is highly correlated RLSM
and it can be speculated that the presence of platelets aggregates can Conclusion: A quick and reliable non-invasive diagnosis of advanced
be responsible of the increased values. Moreover histological analysis fibrosis and significant steatosis can be obtained with the median of 3
showed high degree of intrahepatic cholestasis in ACLF. Further measurements (1 mid, 1 posterior and 1 anterior axillary line) using
studies are needed to definitely explain the high level of stiffness SS. The only non-reliable criterion is skin-to-liver distance ≥2.4 cm.
reported in these patients.

FRI232
A novel simple and reliable 2D-shear wave elastography (SWE) and
ultrasound-guided coefficient attenuation parameter (SCAP)
technique for patients with chronic liver disease
Christiane Stern1, An Ngo2, Cristiane Villela-Nogueira3,
Dominique Thabut1, Vlad Ratziu1. 1Hôpital Pitié-Salpêtrier̀ e, Service
d’Hépato-gastroentérologie, Paris, France; 2Hôpital Pitié-Salpêtrier̀ e ,
Service d’Hépato-gastroentérologie, Paris, France; 3Federal University of
Rio de Janeiro, Serviço de Hepatologia, Rio de Janeiro, RJ, Brazil
Email: [email protected]
Background and aims: Different non-invasive methods are now
widely used for first line assessment of liver fibrosis and steatosis in
patients with chronic liver disease. The detection of advanced fibrosis
using 2D-shear wave elastography (SWE) and significant steatosis
using ultraSound-guided CAP (SCAP) measured by Aixplorer MACH
30 (SS) is simple, safe and overcomes several limitations of transient
elastography (TE) and CAP measured by FibroScan (FS). Nevertheless,
reliability criteria have not been well described for SS. The aims of this
study were to define the optimal technical procedure, the perform-
ance for the detection of fibrosis and steatosis and the reliability
criteria using SS.
Method: 215 consecutive patients with chronic liver disease that
underwent non-invasive tests were included. Clinical, biological and

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 POSTER PRESENTATIONS
after EOT (T2). Patients were followed up every 6 months according to
international clinical practice guidelines. Any LRE was registered
during follow-up. Uni- and multi-variate Cox regression analysis was
performed to determine parameters associated with the develop-
ment of LREs.
Results: At baseline, mean LS was 18.1 ± 6.6 kPa. Levels of LS
decreased to a mean of 13.6 ± 6.1 kPa and 12.5 ± 6.1 kPa at T1 ( p <
0.0001) and T2 ( p < 0.0001), respectively. The median follow-up was
3.25 years (range 0.2–4.7). HCC was the most frequent LRE (30
patients, 13.1%). 13 patients (5.7%) developed ascites, 11 (4.8%) portal
vein thrombosis (PVT), 8 (3.5%) hepatic encephalopathy (HE), 8 (3.5%)
infections and 5 (2.2%) variceal bleeding. 9 patients died (3.9%) and 5
were transplanted (2.2%).
Abstract withdrawn Male gender, bilirubin, international normalized ratio (INR), Model
for End-stage Liver Disease (MELD) score, prior history of harmful
alcohol intake, LS, portal velocity and a change in LS less than 20% at
T2 (1-y Delta-LSM) were associated with HCC occurrence by
univariate analysis. By Cox regression multivariate analysis, only
MELD score (HR 1.16; CI 95% 1.01–1.33; p = 0.026) and 1-year Delta
LSM <20% (HR 2.98; CI 95% 1.01–8.1; p = 0.03) were independently
associated with HCC risk. Interestingly, 1-year Delta LSM <20% was
independently associated with the development of ascites with
significant hazard ratio (HR 5.08; CI 95% 1.03–25.14; p = 0.04).
Since the variables maintained their predictive value over time, we
combined their HR in a simple model to estimate the probability of
HCC occurrence at 24, 36, 48 and 60 months after EOT.

FRI234
Dynamics of liver stiffness predicts hepatocellular carcinoma and
ascites occurrence in patients with hepatitis C virus related
cirrhosis treated with direct-acting antiviral agents
Alberto Nicoletti1, Maria Elena Ainora1, Marco Cintoni2,
Matteo Garcovich1, Martina De Siena1, Barbara Funaro1,
Francesca Ponziani1, Antonio Grieco3, Laura Riccardi1,
Maurizio Pompili1, Antonio Gasbarrini1, Maria Assunta Zocco1.
1
Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università
Cattolica del Sacro Cuore-Rome, Internal Medicine and
Gastroenterology, Rome, Italy; 2Fondazione Policlinico Universitario “A.
Figure: Predictive model for HCC occurrence.
Gemelli” IRCCS, Università Cattolica del Sacro Cuore-Rome, Clinical
Nutrition, Rome, Italy; 3Fondazione Policlinico Universitario “A. Gemelli” Conclusion: Alone and in association with clinical and biochemical
IRCCS, Università Cattolica del Sacro Cuore-Rome, Internal Medicine and variables, dynamic changes of 2D-SWE-measured LS after DAA
Liver Transplant, Rome, Italy therapy for HCV may be a useful tool to predict HCC and ascites
Email: [email protected] occurrence in cirrhotic patients.
Background and aims: The achievement of a sustained virologic
FRI235
response (SVR) with direct acting antivirals (DAAs) has been shown
The concordance within one blood test improves reliability
to prevent liver-related events (LREs) in patients with chronic
evaluation of liver fibrosis
hepatitis C virus (HCV)-related cirrhosis. Bidimensional shear wave
Paul Cales1, Clémence M. Canivet1, Lannes Adrien1, Frédéric Oberti1,
elastography (2D-SWE) is an effective and easy to perform technique
Isabelle Fouchard1, Jerome Boursier1. 1Angers University Hospital,
for the early assessment of liver fibrosis during DAA treatment.
Hepatology, Angers, France
The main aim of the study was to evaluate changes in liver stiffness
Email: [email protected]
(LS) using 2D-SWE in patients with HCV-related cirrhosis undergoing
DAA therapy. Secondary endpoint was to identify any correlation Background and aims: The improved reliability of non-invasive tests
between LS, ultrasound and clinical parameters that predict the of liver fibrosis is defined by agreement between a patented blood
occurrence of LREs. test and liver stiffness measurement (LSM) by transient elastography
Method: We enrolled 229 consecutive patients who received DAAs (TE) in 2021 EASL guidelines. The inconvenience is to require two
based regimens for HCV-related cirrhosis between December 2014 different tests adding cost and reducing availability. Our aim was to
and September 2016. Standard ultrasound, 2D-SWE measured LS, apply this agreement rule to a single blood test targeted either for
and clinical and laboratory data were assessed before treatment significant fibrosis (FibroMeterV2G: FM2G) or cirrhosis
(baseline), 24 weeks after end of treatment (EOT) (T1) and 48 weeks (CirrhoMeterV2G: CM2G) using the same markers.

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S507

POSTER PRESENTATIONS
Method: Patients with chronic liver disease of multiple untreated Results: Plasma protease activity was assessed in 43 HCC cases (65%
etiologies, with liver biopsy using Metavir F within 6 months of blood male, mean age 58 years, 49% HBV/7% HCV/44% unknown etiology)
test, were included in a derivation (n = 2159) and a validation (n = and 26 cirrhosis controls (30% male, mean age 57 years, 100% NASH
1476 with LSM by TE) sets. Agreement grade was calculated as the etiology). Nearly three-fourths (72%) of the cases had early-stage
absolute difference (AD) between fibrosis (FM) classifications of FM2G tumors (TNM stage I or II). The most significant biosensors in the
and CM2G. The main outcome was severe fibrosis (Metavir F ≥ 3). classification of HCC vs cirrhosis were substrates of MMPs, DPP4,
Outcome measures were AUROC and accuracy (correct diagnosis). ANPEP, ARTS-1, KLK14 and Cathepsins (L, S, K, B) and ADAM17. The
Results: In the derivation set, FM2G accuracy (and prevalences) were panel of protease biosensors had high accuracy for differentiating
according to agreement grade: high (FM AD ≤ 0.5): 83.1% (78.6%), fair patients with HCC vs those with cirrhosis (AUC = 0.93 [CI 0.86–0.98])
(FM AD = 1): 70.2% (16.3%), poor (FM AD >1): 50.0% (5.1%), p < 0.001. (Figure). Using the Youden’s cut-off, sensitivity and specificity of the
CM2G accuracy was, respectively 83.1%, 67.6%, 50.9% ( p < 0.001). protease biosensor panel for HCC detection were 0.84 and 0.85,
Then, agreement was classified as concordant or not for Metavir F ≥ 3. respectively.
FM2G accuracy (and prevalences) were, concordant: 83.9% (85.9%),
discordant: 51.3% (14.1%), p < 0.001. FM2G AUROCs were, respect-
ively: 0.866 and 0.519, p < 0.001. The overall accuracy of FM2G (79.3%)
and CM2G (79.0%) were not different ( p = 0.688) but they were
complementary (kappa: 0.573). So, a CM/FM algorithm was con-
structed. Its accuracy was significantly increased to 82.2% ( p < 0.001)
vs FM2G or CM2G and different between concordant (85.1%) and
discordant (64.1%, p < 0.001) blood tests. In the validation set,
previous results were confirmed, e.g. CM/FM accuracy was, concord-
ant blood tests: 79.9%, discordant: 60.5% ( p < 0.001). The concord-
ance prevalence was higher for FM2G vs CM2G (84.9%) than vs LSM
(70.9%, p < 0.001). Accuracy was globally, LSM: 78.8% vs CM/FM:
77.0%, ( p = 0.173) or FM2G: 75.5% ( p = 0.011) but in the 70.9% of
concordant FM2G/LSM it was, respectively: 88.0% vs 87.4% ( p = 0.210)
or 88.0% ( p = 1). The accuracy in concordant tests was however higher
in FM2G agreement vs LSM than vs CM2G, e.g. CM/FM: 88.0% vs 79.9%
( p < 0.001).
Conclusion: The concordance within a blood test significantly
increased the concordance prevalence. The limit was a reduced
accuracy; the advantages were a reduced cost and liver biopsy
recourse by half, and a simpler use (single time and greater ubiquity).

FRI236
Novel and accurate measurement of differential protease activity
in diagnosed HCC patients compared to non-HCC cirrhotic
patients
Amit Singal1, Tram Tran2, Ben Holmes2, Chris Gulka2, Conclusion: Novel non-invasive biosensors measuring protease
Anatoly Myaskovsky2, Andrea Shepard2, Mackenzie Rowe2, activity accurately differentiate HCC from cirrhosis and, if validated
Sophie Cazanave2, Faycal Touti2, Jina Lee2, Alejandro Balbin2, in larger biomarker studies, may serve as an alternative surveillance
Wendy Winckler2. 1UT Southwestern Medical Center, Department of tool to improve early HCC detection.
Internal Medicine, Dallas, United States; 2Glympse Bio, Cambridge,
United States FRI237
Email: [email protected] FIB-4 predicts severe hematological toxicity and 6-month
mortality in older patients with cancer: ELCAPA-LIVER.
Background and aims: The incidence of hepatocellular carcinoma
(HCC) is rising worldwide and projected to continue increasing Victoire De Salins1, Antoine Morel2, Claudia Martinez-Tapia2,
through 2030. HCC surveillance using ultrasound with or without Pierre-Emmanuel Rautou3, Florence Canoui-Poitrine2,
AFP has suboptimal sensitivity, missing over one-third of HCC at an Elena Paillaud4, Johanne Poisson5. 1AP-HP, Service de Gériatrie, Hôpital
early stage. We previously showed a panel of biosensors that Européen George Pompidou, Paris, France; 2University Paris Est Creteil,
interrogate biological pathways implicated in HCC pathogenesis INSERM, IMRB, F-94010 Créteil, France, Clinical Epidemiology and
(tumor invasion of extracellular matrix, matrix remodeling, inflam- Ageing Unit, Institute Mondor de Recherche Biomédicale, Paris-Est
mation, and fibrinolysis) was highly effective at differentiating University, F-94000 Créteil, France; 3Université Paris-Cité, AP-HP,
patients with HCC from healthy controls, with AUCs >0.94. The aim Hôpital Beaujon, Service d’Hépatologie, DMU DIGEST, Centre de
of this study was to assess accuracy of protease biosensor biomarker Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER,
panel to distinguish patients with HCC from those with cirrhosis Centre de recherche sur l’inflammation, Inserm, UMR 1149, Paris, France;
4
without HCC. Université Paris-Cité, AP-HP, Service de Gériatrie, Hôpital Européen
Method: Retrospective plasma samples were obtained from patients George Pompidou, Paris, France, Clinical Epidemiology and Ageing Unit,
diagnosed with HCC (cases) and those with cirrhosis without HCC Institute Mondor de Recherche Biomédicale, Paris-Est University, F-
(controls). Protease biosensor cleavage was assayed from plasma by 94000 Créteil, France; 5Université Paris-Cité, AP-HP, Service de Gériatrie,
fluorimetry. The relative signal was used for classification by Hôpital Européen George Pompidou. Centre de recherche sur
regularized logistic regression using 100 cross-validation (80% train, l’inflammation, Inserm, UMR 1149, Paris, France, France
20% validation splits). The maximum point from the Youden’s J index Email: [email protected]
in the training set was used to the define the optimal cut-off, which Background and aims: The current increased life expectancy is
was used to calculate sensitivity and specificity for HCC detection in associated with an increasing incidence of cancer in older patients.
the validation sets. Geriatric assessment has improved the management of this hetero-
geneous population with thorough evaluation of physiologic systems

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 POSTER PRESENTATIONS
i.e heart, lung, renal functions for cancer treatment choice, but no
study reported a comprehensive analysis of liver parameters and its
impact on mortality and toxicity. Yet, aging is thought to be associated
Nurses and Allied Health Professionals
with a liver functional decline and is an important risk factor for
developing chronic liver disease. FIB-4 has been shown to predict
FRI238
mortality in non-oncological young and older patients without
The main thing is to be alive-exploring patients’ experiences with
known chronic liver disease. Aims of this study were to evaluate
weight gain after liver transplantation: a qualitative study
predictive value of FIB-4 for 6-months survival and treatment
toxicities in patients age 70 yo or older with cancer. Sonja Beckmann1,2, Patrizia Kuenzler1,3, Kajetan Kabut4,
Method: Patients aged 70 or older with histologically documented Oliver Mauthner1,5. 1University of Basel, Institute of Nursing Science,
solid or hematological cancers and referred for geriatric assessment Basel, Switzerland; 2University Hospital Zurich, Center Clinicak Nursing
were included from the multicentric, French prospective open-cohort Science, Zurich; 3Cantonal Hospital St.Gallen, Department of
Elderly Cancer Patients (ELCAPA) from March 2015 to September Gastroenterology/Hepatology and Department of Nursing, St.Gallen;
4
2019. In the present study (ELCAPA-LIVER), patients, at any stage, BDH-Klinik Elzach, Zentrum für NeuroRehabilitation, Beatmungs-, und
treated by chemotherapy, immunotherapy or targeted therapy in 6 Intensivmedizin, Germany; 5University Department of Geriatric
different centers and for whom platelet count and serum AST and ALT Medicine Felix Platter, Basel, Switzerland
measurements were available at baseline, were selected. Patients Email: [email protected]
with known chronic liver diseases were excluded. Geriatric assess- Background and aims: Weight gain after liver transplantation (LTx)
ment was performed at baseline. FIB-4 cut-off values used to rule out is common, contributing to the development of new-onset obesity at
or to rule in advanced fibrosis in elderly patients with liver diseases 2- and 3-years post-LTx in 22% and 38% of patients. These significant
were used to classify patients into three prognostic groups (cut-offs weight gains prompt the question of how patients cope with this
were decided based on previous papers in older patients). Treatment increase of weight. Unfortunately, few studies examined the patients’
toxicities (grade 0/I/II vs grade III/IV) and mortality were assessed at 6 perspective. This study aimed to explore how patients’ experienced
months of follow-up. their weight gain after LTx.
Results: 989 patients were included: median age: 81 years (IQR: 77– Method: Individual interviews followed a guideline with open-
84); female, 58.8%; main cancer sites: digestive 29%, gynecological ended questions. Transcripts were analyzed according to the six
28%, urinary tract 14% and lung 12%; metastasic diseases 51%. At 6 phases of the reflexive thematic analysis approach by Braun and
months, 763 patients were dead (77%) and 355 patients (59%) Clarke.
experienced grade III/IV anticancer toxicities, including 123 patients Results: The 12 participants gained 11.5 kg weight (median) over a
(22.4%) with hematological toxicities. median of 23 months after LTx. The constitutive theme “The main
A FIB-4 index >2.67 before treatment was independently associated thing is to be alive” was a recurrent insight, captured in different
with hematological toxicities grade III/IV (adjusted OR = 1.92 (95% CI: facets in all three consecutive themes: “The arduous path back to
1.15–3.22), p = 0.02). living” was the emotional facet, expressing the ups and downs during
In addition, a FIB-4 index >2.67 was predictive for 6-month mortality the suffering from a life-threatening illness to finally being grateful
independently of cancer site, metastasis, chronic heart failure, and C- for the new life. “A pleasurable new phase of life” was the
Reactive Protein (aHR = 1.55 (1.10–2.20), p = 0.028). legitimation, reflecting the appreciation of gaining weight and
returning to a healthy appearance after having overcome the
illness. “I am allowed to look like this now” was the consoling facet
after a time of physical and emotional burden due to the increased
weight and frustration of being unsuccessful in losing weight. Finally,
the awareness of being a LTx survivor outplayed the burden of the
excess weight.

Conclusion: A FIB-4 index >2.67 was an independent predictor for 6-

month mortality and severe hematologic toxicity in older patients
treated for cancer. This shows the importance of evaluating liver
status to improve decision making in older patients with cancer.

Figure 1. Overview over the four themes and the seven subthemes.

Conclusion: Understanding the patients’ dynamic lived experiences,

beliefs and motivations on post-LTx weight gain is crucial in
providing tailored care. Interventions should be offered early
because the comforting insight “I am allowed to look like this now”
may hinder the patient’s motivation to further engage in weight loss
interventions. Our suggestions on time and content of education and
self-management support, based on the transtheoretical model, may
guide professionals’ clinical practice.

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POSTER PRESENTATIONS
FRI239 FRI240
Development of a nurse led hepatology ambulatory review service Development of a nurse led daycase abdominal paracentesis
Victoria Wharton1, Bryony Butler1. 1John Radcliffe Hospital, service
Hepatology, Oxford, United Kingdom Victoria Wharton1, Bryony Butler1. 1John Radcliffe Hospital,
Email: [email protected] Hepatology, Oxford, United Kingdom
Email: [email protected]
Background and aims: The Liver Unit in Oxford was significantly
impacted by COVID-19-highlighting a need for a nurse-led Background and aims: Patients living with advanced liver disease
Hepatology ambulatory review service to help minimise inpatient often require symptomatic management of ascites with abdominal
admissions and assess patients with newly diagnosed decompen- paracentesis. At Oxford University Hospitals Trust, there was
sated liver disease. The Hepatology DCU were providing a nurse led previously no routine care pathway to manage the accumulation of
abdominal paracentesis clinic and between appointments the team ascites. Instead, patients would frequently present to the emergency
were able to accommodate clinical reviews. The aims for this service department (ED) or to their GP in discomfort and then require
were to reduce Emergency Department (ED) and hospital admis- emergency admission to the hepatology ward for paracentesis. This
sions, facilitate safe and early discharges, expedite care for long term resulted in delayed care and often a lengthy hospital admission. A
management plans and to allow a single point of access for patients need was identified to provide a nurse-led, daycase paracentesis
and their families. service for these patients. The aim of this service was to improve
Method: Since its creation, the two founding Clinical Nurse patient experience, reduce ED attendances and inpatient admissions,
Specialists (CNS) have collated key metrics pertaining to the patients standardise care across the trust and build effective relationships
treated by the service. These metrics included the route of referral, with patients and their families.
hospital details, date of referral, the reason for referral and whether Method: The Hepatology Day Case Paracentesis service commenced
they needed a hospital admission. Using this dataset, the effective- in October 2018. Initially, clinics occurred once a week, a maximum of
ness of the service has been critically assessed. four patients were reviewed and paracentesis was performed by a
Results: Between April 2020–September 2021 the Hepatology DCU ward-based doctor. However, due to inpatient ward pressures,
reviewed a total of 407 patients. 210 patients were seen from April patients would often experience lengthy delays, when waiting for
2021-September 2021; a monthly average increase of 118%, when the doctor to insert their drains. This led to the development of a fully
compared to the previous year. Not included in these figures, were nurse delivered service. To facilitate its creation, a training pro-
patients reviewed by the hepatology medical team in ED and gramme was developed for the Clinical Nurse Specialists, in addition
medical/surgical ambulatory units. Of the 210 patients reviewed in to postgraduate study. A 5-year dataset on patients presenting to ED
DCU since April 2021, 76 patients were hepatology ward discharges with ascites ( provided by clinical coders) was used to critically assess
reviewed by either CNS, hepatology specialist registrar or a consultant the effectiveness of the nurse-led daycase paracentesis service.
within 7–10 days of discharge. Furthermore, since starting the service Results: Since the introduction of a fully nurse-led daycase
just 3.9% of patients required admission from daycase. 224 (55%) of paracentesis service in January 2020, we have performed 399
the patients seen in the ambulatory review service since April 2020 ultrasound guided paracentesis in 61 patients up to and including
were for ascites/oedema review ± diuretic management. The ambu- October 2021. Between April 2016–March 2021 a total of 124 patients
latory reviews are in addition to the patients’ routine follow up presented to ED with ascites; 104 of which required an inpatient
appointments-aiding close management of their liver disease and admission and 65 had a paracentesis. Furthermore, the number of
expedition of the relevant investigations required for their long-term patients needing admission specifically for a paracentesis fell from 20
management, resulting in early interventions. Following completion in 2016–2017 to 7 in 2020–2021. Whilst the number of patients
of an Independent and Supplementary Prescribing module by the attending ED and requiring admission does not appear to have
CNS, the ambulatory review service became nurse-led in September reduced, the number of patients admitted for paracentesis has
2020. reduced significantly.

Conclusion: Although the service is in its infancy, the number of Conclusion: The number of patients requiring admission to hospital
patients reviewed has doubled since starting the hepatology for a paracentesis has reduced by 65% since founding a nurse-led
ambulatory review service in April 2020. This has freed up outpatient daycase paracentesis service. The nurse-led abdominal paracentesis
clinic capacity and prevented delays to assessments. The Hepatology clinic has reduced the number of patients attending ED for ascites
DCU currently provides a five-day service to help reduce ED management alone and has provided patients with a single point of
attendances and reduce inpatient admissions; it is staffed by two contact for managing their ascites requiring paracentesis.
full time band 7 CNS.

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 POSTER PRESENTATIONS
FRI241 FRI242
Implementing a cirrhosis order set: a qualitative analysis of Quality of life in patients with advanced cirrhosis. Relationship
provider-identified barriers and facilitators with the development of complications
Ashley Hyde1, Emily Johnson1, Michelle Carbonneau2, Ana Belén Rubio1,2,3,4, Adria Juanola1,2, Martina Perez1,2,
Dawn Schroeder2, Thea Luig1, Denise Campbell-Scherer1, Marta Carol1,2,3,4, Carlota Riba1,4,5, Sara Martinez1,3,4,
Puneeta Tandon1. 1University of Alberta Faculty of Medicine and Marta Cervera1,2,3,4, Emma Avitabile1,2, Ann Ma1,2,
Dentistry, Edmonton, Canada; 2Alberta Health Services, Edmonton, Laura Napoleone1,2, Octavi Bassegoda1,2, Jordi Gratacós-Gines1,2,
Canada Elisa Pose1,2,3, Isabel Graupera1,2,3, Anna Soria1,2, Pere Ginès1,2,3,4,
Email: [email protected] Núria Fabrellas1,2,3,4. 1Hospital Clinic, Liver Unit, Barcelona, Spain;
2
University of Barcelona, Faculty of Medicine and Health Sciences,
Background and aims: Resulting from vascular and hepatocellular
Barcelona, Spain; 3Instituto de Investigaciones Biomédicas August Pi i
injury, cirrhosis is a chronic condition that results in profound
Sunyer (IDIBAPS), Barcelona, Spain; 4Centro de Investigación Biomédica
impairments in quality of life, and high rates of morbidity and
en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Madrid,
mortality. Hospitalizations and readmissions become more com-
Spain; 5Fundació Clínic per la Recerca Biomed ̀ ica (FCRB), Barcelona,
monplace as cirrhosis advances, with a 90-day readmission rate of
Spain
53% noted in a large North American cohort of over 1000 patients.
Email: [email protected]
Cirrhosis Care AB (CCAB) is a pragmatic trial which aims to address
current gaps in cirrhosis care in Alberta through the implementation Background and aims: Liver cirrhosis causes an alteration in the
of a standardized order set across multiple acute care sites. Prior to Quality of Life (QoL) of patients that is more intense in patients in the
implementation of such a large-scale quality improvement initiative, decompensated phase. The alteration of QoL affects both the physical
it is essential to understand the implementation contexts, including and mental dimensions of the patients. It is not known whether the
perceptions of the proposed intervention, and potential barriers and alteration of QoL correlates with a higher risk of developing
facilitators to implementation. complications of the disease.
Method: We used a qualitative descriptive approach to (i) understand To investigate whether the intensity of QoL alteration is associated
participant’s past experiences with implementation of standardized with a higher risk of developing complications of cirrhosis.
order sets, (ii) to identify potential barriers and facilitators to Method: This study was conducted in the cohort of patients of the
implementation of the cirrhosis order set, and (iii) to develop MACHT study (J Hepatol 2018; PMID: 30138685), a study investigating
tailored implementation strategies for each study site. We used the the effect of midodrine and albumin in patients with decompensated
Consolidated Framework for Implementation Research (CFIR) and the cirrhosis on the liver transplant waiting list. QoL was assessed using
Normalisation Process Theory (NPT) to guide development of our the Short Form Health Survey (SF-36) and the Chronic Liver Disease
interview guide and coding framework. We conducted focus groups Questionnaire (CLDQ). The relationship between different QoL
using a semi-structured interview guide. Focus groups were recorded parameters and the development of complications during follow-
and transcribed verbatim. A deductive content analysis approach up was investigated.
using the core constructs of CFIR and NPT was used. Results: Under baseline conditions the two groups of patients,
Results: We conducted a total of 8 focus groups, that were attended placebo and treatment, were similar with respect to QoL parameters,
by 54 healthcare providers. Of the attendees, 20% were prescribers and were therefore considered as a single cohort. Of the 159 patients
(MDs & NPs), with the remainder comprised of nurses, social included, 53 (33%) developed complications during follow-up
workers, pharmacists, and physiotherapists. Barriers to implemen- (median 80 days). Patients who developed complications had more
tation of the cirrhosis order set included the significant investment of marked alterations in CLDQ and most parameters of the physical and
time and resources required, the “change fatigue” of providers, and mental domains of SF-36 as compared to patients who did not
poor communication across provider groups. Facilitators included a develop complications measured under baseline conditions. The
recognized advantage of the efficiencies offered by the cirrhosis order more intense alteration of CLDQ and SF-36 was also associated with a
set, the strength of the evidence on which the order set was based, higher risk of developing hepatic encephalopathy during follow-up.
leadership support of the initiative, and recognition of the need to In a multivariate analysis, both the mental and physical components
improve care for patients with cirrhosis. of the SF-36 were independent predictive factors of development of
Conclusion: The findings of this study suggest that healthcare hepatic encephalopathy.
provider’s perceptions of the cirrhosis order set were greatly Conclusion: In patients with cirrhosis, the QoL parameters are not
influenced by their past experiences with the implementation of only useful to assess the degree of the patient’s impairment, but also
other quality improvement initiatives. Crucial to the success of the indicate a higher risk of developing complications, especially hepatic
cirrhosis order set will be the use of tailored implementation encephalopathy. These parameters provide useful clinical informa-
strategies to promote uptake including: (i) the identification of site tion for clinical practice and should be taken into account in clinical
champions, (ii) use of implementation meetings to share learnings studies evaluating the efficacy of new treatments for the disease.
across study sites, and (iii) leveraging the facilitators including
highlighting efficiencies in work processes that can be made possible
by the cirrhosis order set.

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POSTER PRESENTATIONS
FRI243 Conclusion: Despite the restrictions on face-to-face visits during the
Effects of the COVID-19 pandemic on the activity of an advanced first months of the COVID-19 pandemic, visits in the advanced
practice nurse clinic on liver cirrhosis practice nurse clinic have continued to increase, and it has been
Martina Perez1,2,3, Ann Ma1,3,4, Marta Cervera1,2,3,4, Marta Carol1,2,3,4, possible to respond to patients’ care needs. The specialized nurse
Ana Belén Rubio1,3,4, Sara Martinez1,3,4, Carlota Riba1,3,4, plays a key role in the management of patients with cirrhosis and has
Laura Napoleone1,3,4, Jordi Gratacós-Gines1,3,4, Anna Soria1,3, been fundamental in responding to their needs particularly in the
Emma Avitabile1,3,4, Octavi Bassegoda1,3,4, Adria Juanola1,3,4, context of the COVID-19 pandemic.
Elisa Pose1,3,4, Isabel Graupera1,3,4, Pere Ginès1,2,3,4,
Núria Fabrellas1,2,3,4. 1Hospital Clínic de Barcelona, Liver Unit, FRI244
Barcelona, Spain; 2Facultat de Medicina-Universitat de Barcelona, STIGMATIZATION IS COMMON IN PATIENTS WITH METABOLIC
Barcelona, Spain; 3Centro de Investigación Biomédica en Red de ASSOCIATED FATTY LIVER DISEASE AND CORRELATES WITH
Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain; QUALITY OF LIFE
4
Institut d’Investigacions Biomed̀ iques August Pi i Sunyer (IDIBAPS), Marta Carol1,2,3,4, Martina Perez1,3,4, Elsa Solà1,2,3,4,
Barcelona, Spain Marta Cervera1,2,3,4, Sara Martinez1,2,3, Adria Juanola1,2,3,
Email: [email protected] Carlota Riba1,2,3, Ann Ma1,2,3, Emma Avitabile1,2,3,
Laura Napoleone1,2,3, Elisa Pose1,2,3, Isabel Graupera1,2,3,
Background and aims: Liver cirrhosis is associated with significant Maria Honrubia4, Marko Korenjak5, Ferran Torres6,7, Pere Ginès1,2,3,4,
morbidity and mortality and is, in addition, responsible for a high Núria Fabrellas1,2,3,4. 1Hospital Clínic de Barcelona, Liver Unit,
number of hospitalizations, which represent a high burden for health Barcelona, Spain; 2Institut d’Investigacions Biomed ̀ iques August Pi i
systems. As the disease progresses, serious complications can occur, Sunyer (IDIBAPS), Barcelona, Spain; 3CIBEReHD-Centro de Investigación
such as ascites, gastrointestinal bleeding, encephalopathy and Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid,
jaundice, marking the transition to the decompensated phase. Due Spain; 4Universitat de Barcelona, School of Medicine and Health
to the high progression rate of the disease, these complications tend Sciences, Barcelona, Spain; 5ELPA European Liver Patient Organization,
to recur over time. The role of the nurse is increasingly recognized as Bruxelles, Belgium; 6Institut d’Investigacions Biomed ̀ iques August Pi i
instrumental in the management of patients with chronic liver Sunyer (IDIBAPS), Medical Statistics Core Facility, Barcelona, Spain;
disease, with positive impacts noted on patient education, patient 7
Universitat de Barcelona, Biostatistics Unit, Faculty of Medicine,
independence and early detection of complications. Nevertheless, Barcelona, Spain
patient care was severely impacted in the year 2020 by the COVID-19 Email: [email protected]
pandemic, profoundly changing the internal organisation of hospitals
and the type of care we have been able to offer to patients. Therefore, Background and aims: Stigmatization is a well-document problem
the aim of this study was to evaluate the evolution of the activity of of some diseases. Perceived stigma is common in alcohol-related liver
the advanced practice nurse clinic in liver cirrhosis, taking into disease and hepatitis C, but little information exists on stigma in
account its recent implementation and the COVID-19 pandemic. patients with metabolic associated fatty liver disease (MAFLD). Aim
Method: We performed a retrospective observational descriptive of the study was to investigate frequency and characteristics of
study, analyzing the activity of the liver cirrhosis outpatient nurse perceived stigma among patients with MAFLD.
clinic of the Hepatology Department of the Hospital Clinic in Method: One-hundred and ninety-seven patients seen at the liver
Barcelona. We included all patients visited by the specialized clinic were included: a study group of 144 patients with MAFLD, 50
hepatology nurse over a period of 2.5 years, from 01/03/2019 to 31/ with cirrhosis, and a control group of 53 patients with alcohol-related
08/2021. The data were analyzed considering five periods, each cirrhosis. Demographic, clinical, and laboratory data were collected.
lasting 6 months. The first corresponds to the beginning of the Quality-of-life was assessed by chronic liver disease questionnaire
implementation of the advanced practice nurse consultation, the (CLDQ). Perceived stigma was assessed using a specific questionnaire
third coincides with the beginning of the pandemic, the fourth and for patients with liver diseases categorized in 4 domains: stereotypes,
the fifth correspond to the consecutive months until August 2021. discrimination, shame, and social isolation.
Results: A total of 2398 visits were completed, 1772 (73.8%) by Results: Perceived stigma was common in patients with MAFLD (99
telephone and 626 (26.1%) in person. During the third period (01/03/ patients, 69%) and affected all 4 domains assessed. The frequency was
2020–31/08/2020), face-to-face visits decreased by 30% compared to slightly higher, yet not significant, in patients with MAFLD cirrhosis
previous periods, while telephone visits increased by 50%. There was vs those without (72% vs 67%, respectively; p = 0.576). In patients
an 8-fold increase in the total number of visits in the last period without cirrhosis perceived stigma was unrelated to stage of disease,
compared to the first. This increase is due to an increase in telephone since frequency was similar in patients with no or mild fibrosis
visits, a trend that was probably precipitated by the the COVID-19 compared to those with moderate/severe fibrosis (66% vs 68%,
pandemic, but that has persisted since. respectively). Among patients with cirrhosis, stigmatization was
more common in alcohol-related vs MAFLD-cirrhosis, yet differences
were only significant in two domains. In patients with MAFLD,
perceived stigma correlated with poor quality-of-life, but not with
demographic or clinical variables.

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 POSTER PRESENTATIONS
Conclusion: E-health-based interventions had a large effect on
weight loss in patients with NAFLD. E-health-based interventions can
assist in lifestyle change and weight loss in patients with NAFLD. In
this way, liver-related complications can be reduced. Nurses can use
affordable, practical and accessible e-health-based interventions to
assist with weight loss in patients with NAFLD.
Keywords: e-health-based interventions, liver disease, NAFLD,
nursing care, weight loss.

Rare liver diseases (including paediatric and

genetic)

FRI246
Role of mutant alpha-1-antitrypsin in determining liver cell fate
Conclusion: Perceived stigmatization is common among patients during embryonic development and in HCC origin
with MAFLD, is associated with impaired quality-of-life, and may be Francesco Annunziata1. 1TIGEM, Translational UNIT, Pozzuoli, Italy
responsible for stereotypes, discrimination, shame, and social Email: [email protected]
isolation, which may affect human and social rights of affected Background and aims: Alpha1-antitrypsin deficiency (AATD) is the
patients. most common genetic cause of liver disease in children. The toxic
gain-of-function mutation of alpha-1-antitrypsin (ATZ) leads to its
FRI245
accumulation and retention in the endoplasmic reticulum (ER) of the
Effect of e-health-based interventions on weight loss in patients
hepatocytes resulting in liver injury and, later in life, in increased risk
with NAFLD: a systematic review and meta-analysis of randomized
of hepatocellular carcinoma (HCC). Preliminary data suggest that ATZ
controlled trials
starts to be expressed and accumulated as globules early during
Ferya Celik1, Merve Yuksel1, Hicran Bektaş1. 1Akdeniz University, embryogenesis. However, it is not known whether ATZ may influence
Internal Medicine Nursing, Antalya, Turkey liver cell fate commitment and functionality during development. In
Email: [email protected] addition, it has been speculated that globule-devoid (GD) hepato-
Background and aims: The only effective treatment is 7%–10% cytes may have a proliferative advantage over globule-containing
weight loss of non-alcoholic fatty liver disease (NAFLD). Lifestyle (GC) hepatocytes and be responsible for HCC development and
changes consisting of diet and physical activity are the cornerstone of progression. However, it is not clear yet which cell has to be
weight loss. To synthesize the effect of e-health-based interventions considered the cell of origin of HCC in AATD patients. Therefore, our
on weight loss in patients with NAFLD. aims are: i) study the effects of ATZ expression and accumulation in
Design: A systematic review and meta-analysis of randomized liver cells during development and differentiation to evaluate
controlled trials following Cochrane methods. alterations in cellular identity that can be harmful during disease
Data resources: Systematic searches were conducted in Ovid, Science progression; ii) lineage trace liver cholangiocytes/progenitors (C/P)
Direct, Web of Science, CINAHL Complete, PubMed, Cochrane Library, cells and mature hepatocytes to identify the cell of origin of HCC in
Scopus for studies published in English without year limitations up to AATD patients.
January 2022. Method: To characterize the effects of ATZ expression on pathways
Method: The risk of bias in eligible studies was evaluated by two demonstrated to be crucial for cell fate commitment, we performed
researchers using the Cochrane Collaboration tool. Disagreements RNA sequencing analysis at several stages over embryonic develop-
were resolved with the third researcher. The meta-analysis data were ment on liver from the AATD mouse model (PiZ) and wild type (WT)
analyzed using the Comprehensive Meta-Analysis 3 program. mice. Histological analyses have been performed to confirm altera-
PRISMA-2020 was used to report the findings. tions in cell fate commitment.
Results: Four studies with 253 participants met the inclusion criteria. To investigate the cell of origin of the HCC in AATD, we are performing
Lifestyle intervention enabled by e-health-based interventions was lineage tracing experiments by using C/P- and hepatocyte- specific
dietary and/or physical intervention in all studies. E-health-based Cre-recombinase and reporter mouse lines. In addition, to support
interventions were applied by text messages, telephone/video calls, our in vivo experiments, we are investigating the capacity of both C/P
mobile applications. The overall effect of e-health-based interven- cells and hepatocytes to generate liver organoids.
tions on weight loss was statistically significant. E-health-based Results: We observed that pathways involved in cell differentiation/
interventions had a large effect on weight loss in patients with NAFLD proliferation (e.g., Wnt and Hippo pathways) were altered in PiZ
( p = 0.03, Hedge’s g = −0.91, 95% confidence interval [CI]−1.75 to − compared to WT livers. In addition, immunostainings for C/P- and
0.07) (Figure 1). hepatocyte- specific markers showed hybrid identity of liver cells in
PiZ at P0. These results suggest that at very early stages during
development ATZ accumulation impairs cell differentiation resulting
in immature hepatocytes that are not able to play their crucial role in
cell metabolism and homeostasis. Interestingly, we observed that PiZ
derived hepatocytes from adult mice are not able to form cysts/
organoids as the WT, while C/P form organoids faster than the WT.
These results may suggest that C/P cells and not hepatocytes are
involved in liver regeneration and are the cell of origin of HCC in PiZ
Figure 1: The results of the meta-analysis of the effect of e-health-based mice.
interventions on weight loss. Conclusion: In summary, our study evaluated the effects of ATZ
expression and accumulation in liver cells during embryogenesis and

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POSTER PRESENTATIONS
contribute to identify the cells responsible for HCC development in FRI248
AATD. In vitro rescue of nonsense variations by drug-induced
readthrough of premature termination codons in progressive
FRI247 familial intrahepatic cholestasis type 2
A pilot study of biliary atresia newborn screening using dried Martine Lapalus1, Elodie Mareux1, Rachida Amzal1, Marion Almes1,2,
blood spot matrix metalloproteinase-7 Alice Thebaut1,2, Mounia Lakli1, Thomas Falguières1, Sylvie Rebuffat3,
Chee Seng Lee1,2, Yen-Hsuan Ni2, Huey-Ling Chen2, Jia-Feng Wu2, Laure Bidou4,5, Olivier Namy4, Emmanuel Jacquemin1,2,
Hong-Yuan Hsu2, Yin-Hsiu Chien3, Ni-Chung Lee3, Emmanuel Gonzalès1,2. 1Inserm, Physiopathogénes̀ e et traitement des
Paul Wuh-Liang Hwu3, Yu-Ju Chen4, Yu-Lin Wang5, Mei-Hwei Chang2 maladies du foie, UMR_S 1193, Université Paris Saclay, Hepatinov, Orsay,
. 1National Taiwan University Hospital Hsin-Chu Branch, Department of France; 2Paediatric Hepatology and Paediatric Liver Transplant
Pediatric, Hsinchu County, Taiwan; 2National Taiwan University College Department, National Reference Center for Rare Paediatric Liver
of Medicine and Children’s Hospital, Department of Pediatric, Taipei, Diseases, FILFOIE, ERN RARE LIVER, Assistance Publique-Hôpitaux de
Taiwan; 3National Taiwan University Hospital, Department of Medical Paris, Faculté de Médecine Paris-Saclay, CHU Bicêtre, Le Kremlin-Bicêtre,
Genetics, Taipei, Taiwan; 4Institute of Chemistry, Academia Sinica, Taipei, France; 3Muséum national d’Histoire naturelle, Centre national de la
Taiwan; 5Institute of NanoEngineering and MicroSystems, National Tsing Recherche scientifique, Laboratory Molecules of Communication and
Hua University, Hinschu, Taiwan Adaptation of Microorganisms (MCAM), UMR 7245 CNRS-MNHN, CP 54,
Email: [email protected] Paris, France; 4Institute for Integrative Biology of the Cell (I2BC), CEA,
Background and aims: Timely diagnosis is a critical challenge and CNRS, Université Paris-Saclay, Gif sur Yvette, France; 5Sorbonne
crucial to improved survival of biliary atresia (BA) patients. We aim to Universités, Université Pierre et Marie Curie, UPMC, Paris, France
evaluate accuracy of Matrix Metalloproteinase-7 (MMP-7) protein as Email: [email protected]
a marker for screening BA at 3 days old. Background and aims: Progressive familial intrahepatic cholestasis
Method: Using dried blood spot screening for neonatal cholestasis type 2 (PFIC2) is a severe hepatocellular cholestasis due to biallelic
patients (DBS-SCReNC), this study had enrolled pediatric patients variations in ABCB11 gene encoding the canalicular bile salt export
with definite diagnosis of BA and compared with non-BA children. pump (BSEP/ABCB11). Nonsense variations are responsible for the
Children were recruited from September 12, 2018, to May 14, 2021 most severe phenotypes. We previously reported that gentamicin
and followed-up until at least 6-month-old. The study was conducted could partially rescue PFIC2-causing Abcb11 nonsense variations by
in a tertiary hospital, National Taiwan University Children Hospital inducing a pharmacological readthrough (RT). However, due to
hepatology clinic, general pediatric clinic and well-child clinic. Stored toxicity issues, there is a medical need to identify alternative
newborn screen dried blood spot (DBS) at 3 day old of children therapies. The aim was to assess the ability of H7 (a mushroom
enrolled in DBS-SCReNC study were retrieved from newborn screen- extract), 2, 6 diaminopurine (DAP) and CDX5-1 (an aminoglycoside-
ing (NBS) centers in Taiwan. There were 25 BA children and 107 non- induced readthrough potentiator) to induce RT of eight ABCB11
BA children. MMP-7 on DBS was quantified in 2021 using a sensitive nonsense variations ( p.Y354X, p.R415X, p.R470X, p.I528X, p.R1057X,
sandwich enzyme-linked immunosorbent assay. p.R1090X, p.Q1215X and p.E1302X) identified in PFIC2 patients.
Results: The age of the 25 children with BA (15 male, 10 female) was Method: The RT levels of the premature termination codon (PTC) in
3.3 ± 1.3 years, and age of 107 non-BA children (56 male, 51 female) their nucleotide environment were first quantified before and after
was 2.2 ± 1.2 years old. Of the non-BA children, 3 children were treatment with aminoglycosides (G418, gentamicin), CDX5-1 com-
diagnosed with choledochal cyst, 2 with liver hemangioma, 9 with bined to gentamicin, H7 and DAP using a dual reporter assay
cholestasis diseases and 93 children visited NTUH due to non- (luciferase/galactosidase) in NIH3T3 cells. Mutagenesis was used to
hepatobiliary diseases or for well-child visits. The time of BA patients reproduce nonsense variations in a plasmid encoding a rat Bsep-
received Kasai operation was at 43 ± 20 days old. The DBS MMP-7 green fluorescent protein. The ability of the drugs to induce RT and to
level of BA children was significantly higher than that of non-BA lead to the expression of a full-length protein was studied using
children (19.2 ± 10.4 vs 5.6 ± 2.7 ng/ml, p < 0.0001). The DBS MMP-7 immunodetection assays after transfection in human embryonic
level showed good diagnostic accuracy with AUC of 93.7% (95% CI, kidney (HEK293) and Can 10 cells. The function of the drug-induced
87.7%–99.7%). MMP-7 cut-off at 7.8 ng/ml has sensitivity of 92.0% full-length protein was studied by measuring the 3H taurocholate
(95% CI, 74.0%–99.0%), specificity of 92.5% (95% CI, 85.8%–96.7%), transport in Madin-Darby canine kidney (MDCK) clones co-expres-
positive predictive value of 71.9% (95% CI, 56.3%–87.5%), negative sing Abcb11 and the rat sodium taurocholate co-transporting
predictive value of 98.0% (95% CI, 95.3%–100.0%) ( p < 0.001). polypeptide (Ntcp/Slc10A1).
Results: In NIH3T3 cells, H7 and DAP induced a significant RT of p.
R415X, p.R470X, p.R1057X, p.R1090X (UGA nonsense variations)
while only H7 increased the RT levels of UAA nonsense variations ( p.
Y354X et E1302X). CDX5-1 increased the gentamicin-induced RT
levels of p.R415X, p.R470X, p.R1057X and p.R1090X (UGA PTCs). H7
and DAP-induced RT levels were significantly higher than gentami-
cin-induced RT level. Compared to gentamicin alone, CDX5-1
combined to gentamicin, H7 and DAP treatments resulted in an
increase of the full-length Abcb11R1090X protein expression in
HEK293 and Can 10 cells, including at the canalicular membrane of
Can 10 cells. Moreover, an additive effect was observed when H7 or
DAP were combined to gentamicin. In MDCK cells, these tested drugs
increased the bile acid transport of the full-length Abcb11R1090X
Figure 1. (A) The newborn screening dried blood spot MMP-7 levels protein.
within 3-day-old in biliary atresia (BA) and non-biliary atresia (non-BA) Conclusion: Our data provide an in vitro proof of concept that CDX5-1
children, (B) Diagnosis of BA using DBS MMP-7 at the cut-off of 7.8 ng/ml. (combined to gentamicin), H7 and DAP induce a pharmacological RT
(****: p < 0.0001). leading to a full-length protein expression and increase bile acid
Conclusion: In this study, DBS MMP-7 is able to distinguish BA from transport of Abcb11R1090X. These findings provide new insights for
the treatment of patients with PFIC2 due to selected nonsense
other conditions. This test allows us to screen BA children as early as 3
variations.
days old.

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 POSTER PRESENTATIONS
FRI249 FRI250
Search for biomarkers and prognostic indicators of liver Alpha-1 antitrypsin (AAT) augmentation therapy and liver
degeneration in glycogen storage disease type Ia phenotype in individuals with homozygous Pi*Z AAT mutation
Roberta Resaz1,2, Davide Cangelosi3, Daniela Segalerba1, (Pi*ZZ genotype)
Martina Morini1, Maria Carla Bosco1, Sabrina Paci4, Annalisa Sechi5, Malin Fromme1, Karim Hamesch1, Carolin Victoria Schneider1,
Daniela Melis6, Maja Di Rocco7, David Weinstein8, Alessandra Eva1. Mattias Mandorfer2, Katrine Thorhauge3, Vítor Pereira4,
1
IRCCS Istituto Giannina Gaslini, Laboratory of Molecular Biology, Genoa, Monica Pons5, Matthias Reichert6, Samira Amzou1, Robert Bals7,
Italy; 2Università degli Studi di Pavia, Department of Molecular Andreas Rembert Koczulla8, Marc Miravitlles9,
Medicine; 3IRCCS Istituto Giannina Gaslini, Bioinformatic Unit, Genova, Sabina Janciauskiene10, Joan Genesca5, Federica Benini11,
Italy; 4Ospedale San Paolo, Clinical Department of Pediatrics, Milan, Joanna Chorostowska-Wynimko12, Bill Griffiths13, Elmar Aigner14,
Italy; 5Presidio Ospedaliero Universitario di Udine, Regional Alexander Teumer15, Michael Trauner2, Aleksander Krag3,
Coordinating Center for Rare Diseases; 6Università degli Studi di Salerno, Christian Trautwein1, Pavel Strnad1. 1University Hospital RWTH
Department of Medicine, Surgery and Dentistry “Scuola Medica Aachen, Medical Clinic III, Gastroenterology, Metabolic diseases and
Salernitana”, Section of Pediatrics; 7IRCCS Istituto Giannina Gaslini, Intensive Care, Aachen, Germany; 2Medical University of Vienna,
Department of Pediatrics; 8University of Connecticut School of Medicine, Division of Gastroenterology and Hepatology, Vienna, Austria; 3Odense
Department of Pediatrics, Farmington, United States University Hospital, Department of Gastroenterology and Hepatology,
Email: [email protected] Odense, Denmark; 4Centro Hospitalar do Funchal, Department of
Gastroenterology, Funchal, Portugal; 5Vall d´Hebron University Hospital,
Background and aims: Glycogen storage disease type Ia (GSDIa) is an
Vall d`Hebron Research Institute (VHIR), Liver Unit, Barcelona, Spain;
inherited metabolic disorder caused by mutations in the enzyme 6
Saarland University Medical Center, Department of Internal Medicine II,
glucose-6-phosphatase-alpha (G6Pase-alpha). Affected individuals
Homburg, Germany; 7Saarland University Medical Center, Department
develop renal and liver complications, including the development of
of Medicine V, Homburg, Germany; 8Marburg University Hospital, Clinic
hepatocellular adenoma/carcinoma and kidney failure. The purpose
for Pneumology, Marburg, Germany; 9Vall d’Hebron Hospital Barcelona,
of this study was to identify potential biomarkers of the evolution of
Clinic for Pneumology, Barcelona, Spain; 10German Center for Lung
the disease in GSDIa patients. To this end, we analyzed the expression
Research (DZL), Medical University Hannover, Clinic for Pneumology,
of exosomal microRNAs (Exo-miRs) in the plasma exosomes of 45
Hannover, Germany; 11Spedali Civili and University, Gastroenterology
patients aged 6 to 63 years. We found that the altered expression of
Unit, Department of Medicine, Brescia, Italy; 12National Institute of
several Exo-miRs correlates with the pathologic state of the patients
Tuberculosis and Lung Diseases, Department of Genetics and Clinical
and might help to monitor the progression of the disease and the
Immunology, Warsaw, Poland; 13Cambridge University Hospitals NHS
development of late GSDIa-associated complications. In addition, the
Foundation Trust, Department of Hepatology, Cambridge, United
Exo-miRs expression profile obtained from the patients was
Kingdom; 14Paracelsus Medical University, First Department of Medicine,
correlated with the liver-specific Exo-miRs profile obtained from a
Salzburg, Austria; 15University Medicine Greifswald, Institute for
mouse model for GSDIa we have generated (LS-G6pc −/−), to derive a
Community Medicine, Greifswald, Germany
common signature that could be specific and prognostic of liver
Email: [email protected]
degeneration and connected with biological pathways associated
with tumor development and progression. Background and aims: The homozygous Pi*Z mutation (Pi*ZZ
Method: We analyzed the expression of exosomal microRNAs (Exo- genotype) in the SERPINA1 gene results in severe alpha-1 antitrypsin
miRs) in the plasma exosomes of 45 patients aged 6 to 63 years. deficiency (AATD) predisposing to lung and liver disease. While liver
Plasma from age-matched normal individuals were used as controls. transplantation is currently the only treatment option for the liver,
microRNAs were purified with exoRNeasy Serum/Plasma Midi kit intravenous augmentation with purified human AAT is available for
(Qiagen) from plasma exosomes. TaqMan Array Human microRNA A the lung. Since AAT administration displays hepatoprotective prop-
cards (Thermo Fisher Scientific), enabling the quantification of 381 erties in mouse models of AATD and alcohol-related liver disease, we
microRNAs each, were used to analyze exosomes-derived microRNA evaluated its effect on the liver phenotype in Pi*ZZ individuals.
(ExomiR) expression. Method: 259 non-augmented Pi*ZZ participants and 315 Pi*ZZ
Results: We found several deregulated Exo-miRs that correlate with subjects on augmentation therapy were systemically recruited in 11
the pathologic state of the liver patients. We identified microRNAs European countries and subjected to standardized clinical and
associated with liver disease and metabolic alterations of glucose and laboratory evaluation as well as vibration-controlled transient
lipid pathways. We also found deregulation of microRNAs relevant in elastography. Participants with hepatic comorbidities and significant
liver tumor development and, finally, several microRNAs whose alcohol consumption were excluded. Analyses were adjusted for age,
altered expression has been associated with diabetic and chronic sex, body mass index, diabetes mellitus, mean alcohol consumption,
kidney diseases. and recruitment center. In addition, liver biopsies of 35 non-
Interestingly, we found that deregulated Exo-miR profiles correlate augmented and 15 augmented Pi*ZZ subjects were evaluated.
with the altered proteome profile and the altered Exo-miR profile Results: As expected, Pi*ZZ individuals on augmentation therapy
identified in LS-G6pc −/−. presented with lower FEV1 values and increased COPD assessment
Conclusion: The altered expression of several Exo-miRs correlated test (CAT) scores. Despite higher age, augmented Pi*ZZ participants
with various pathologic liver states associated with the progression of displayed lower liver stiffness measurements (LSM), had less
the disease. Thus, our results provide evidence that the Exo-miRs frequently significant liver fibrosis (LSM ≥7.1 kPa), and significantly
profiles identified may relate to the specific affected organ gene lower AST and GGT levels, as compared to Pi*ZZ individuals without
expression and that the long-term consequences of GSDIa can be augmentation.
monitored through Exo-miRs assessment. In conclusion, our results Histological evaluation of liver biopsies revealed a lower fibrosis stage
may evolve into protocols to counteract both the progression of liver (Kleiner 2.0 vs. 4.0, p = 0.006) and lower presence of inflammation in
degeneration leading to HCA and HCC onset as well as kidney disease augmented vs. non-augmented Pi*ZZ subjects (14.3 vs. 45.7 %, p =
and failure using circulating microRNAs as biomarkers. 0.043).

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S515

POSTER PRESENTATIONS
symptoms, 83.3% of those in the sporadic (Figure 1C) and 90.6% in
Non- p value
augmented Augmented (multivariable) the recurrent group (Figure 1D) reported muscle weakness as a top 3
n = 259 n = 315 * symptom having a moderate to severe impact.

Age (years) 50 ± 15 58 ± 10 <0.0001*

Women (%) 48.3 43.8 0.29*
BMI (kg/m2) 24.4 ± 3.9 24.8 ± 4.5 0.96*
FEV1 (%) 78 ± 26 47 ± 18 <0.0001*
CAT (points) 12 ± 8 19 ± 7 <0.0001*
LSM (kPa) 6.5 ± 5.5 6.1 ± 3.9 0.042
LSM ≥7.1 kPa (%) 22.0 19.4 0.020
ALT (% ULN) 76 ± 45 77 ± 42 0.89
AST (% ULN) 74 ± 28 69 ± 26 <0.0001
GGT (% ULN) 92 ± 110 86 ± 74 0.021

Abbreviations: BMI, body mass index; FEV1, forced expiratory volume in 1

second; CAT, COPD assessment test; LSM, liver stiffness measurement; ALT,
alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-
glutamyltransferase; ULN, upper limit of normal. *Univariate.
Conclusion: AAT augmentation therapy seems to have a beneficial
association to the liver phenotype of Pi*ZZ individuals. Prospective
studies are needed to confirm this observation.

FRI251
Impact of acute hepatic porphyria attack frequency on patient-
Conclusion: While disease burden appeared greater for AHP patients
reported outcomes: results from the porphyria worldwide patient
experiencing recurrent attacks, both sporadic and recurrent group
experience research (POWER) study
patients experienced a substantial impact on physical, mental, and
Amy Dickey1, Kristen Wheeden2, Sue Burrell3, Rocco Falchetto4,
emotional quality of life.
Jasmin Barman-Aksözen4,5, Alison Bulkley6, Stephen Meninger7,
Stephen Lombardelli8, Danielle Nance9. 1Massachusetts General FRI252
Hospital, Boston, United States; 2American Porphyria Foundation, Large-scale, multi-centric prospective validation of the polycystic
Bethesda, United States; 3Global Porphyria Advocacy Coalition, Durham liver disease complaint-specific assessment (POLCA)
City, United Kingdom; 4Swiss Society for Porphyria, Zurich, Switzerland; Antoon Billiet1, Frederik Temmerman1, Walter Coudyzer2,
5
Stadtspital Waid and Triemli, Institute of Laboratory Medicine, Zurich, Natalie Van den Ende1, Isabelle Colle3, Sven Francque4,
Switzerland; 6Kantar Health, New York, United States; 7Alnylam Ho Thien Anh5, Stéphane De Maeght6, Filip Janssens7, Hans Orlent8,
Pharmaceuticals, Cambridge, United States; 8Alnylam Pharmaceuticals, Dirk Sprengers9, Jean Delwaide10, Sofie Decock11,
Maidenhead, United Kingdom; 9Banner Health, Gilbert, United States Jochen Decaestecker12, Schalk van der Merwe1, Jef Verbeek1,
Email: [email protected] Frederik Nevens1. 1University Hospitals KU Leuven, Gastroenterology
Background and aims: Acute hepatic porphyria (AHP), a group of and Hepatology, Leuven, Belgium; 2University Hospitals KU Leuven,
rare genetic diseases of haem biosynthesis, is characterised by Radiology, Leuven, Belgium; 3Algemeen Stedelijk Ziekenhuis Aalst,
neurovisceral pain attacks. This study evaluated the impact of AHP on Gastroenterology and Hepatology, Aalst, Belgium; 4Antwerp University
patient-reported outcomes (PROs) and disease burden in AHP Hospital, Gastroenterology and Hepatology, Antwerpen, Belgium;
5
patients who experience sporadic or recurrent attacks. Université Catholique de Louvain, Nefrology, Brussels, Belgium; 6Grand
Method: Adult patients having >1 AHP attack within the past 2 years Hôpital de Charleroi, Gastroenterology and Hepatology, Charleroi,
or receiving intravenous hemin and/or glucose for attack prevention Belgium; 7Jessa Ziekenhuis, Gastroenterology and Hepatology, Hasselt,
were recruited from the United States, Italy, Spain, Australia, Mexico, Belgium; 8AZ Sint Jan Brugge, Gastroenterology and Hepatology, Brugge,
and Brazil and administered an online survey from January 19 to April Belgium; 9GZA Antwerp, Gastroenterology and Hepatology, Antwerpen,
26, 2021. Patients taking givosiran were excluded. Descriptive and Belgium; 10C.H.U. de Lieg̀ e, Gastroenterology and Hepatology, Lieg
̀ e,
bivariate analyses were performed to evaluate differences between Belgium; 11AZ Sint Lucas Brugge, Gastroenterology and Hepatology,
patients with sporadic attacks (annualised attack rate [AAR], <6 Brugge, Belgium; 12AZ Delta, Gastroenterology and Hepatology,
within past 2 years) and recurrent attacks (AAR, ≥6). Attacks included Roeselare, Belgium
those leading to a hospitalisation, an emergency room visit, an Email: [email protected]
outpatient doctor visit, or self-management. PROs were assessed Background and aims: Polycystic liver disease (PCLD) can lead to
with the Generalized Anxiety Disorder-7 (GAD-7) scale (0–21) and extensive hepatomegaly, often associated with severe complaints.
the Patient Health Questionnaire (PHQ-8) scale (0–24). Burden of Indication for somatostatin-analogues (SA) or liver transplantation
chronic symptoms was also reported. (LT) is in part based on subjective, patient-reported symptoms. In
Results: Of the 92 AHP patients who completed the survey, 55 (60%; 2014 the PCLD-complaint-specific assessment (POLCA) score was
mean age, 40.3 years) reported sporadic attacks and 37 (40%; mean developed as a self-report instrument to objectively capture the
age, 42.3 years) reported recurrent attacks. Most patients were female presence and severity of disease-specific complaints (Temmerman F, J
(sporadic, 92.7%; recurrent, 86.5%), and the most frequent diagnosis Hepatol 2014).
was acute intermittent porphyria (sporadic, 83.6%; recurrent, 59.4%). The aim of this study was to validate the POLCA score and investigate
A majority of patients in the sporadic (52.7%) and recurrent (67.6%) the correlation with liver volume and need for volume-reduction
attack groups reported a PHQ-8 score ≥10, indicating moderate to therapy.
severe depression; 43.6% and 56.8% of patients in the sporadic and Method: A five year prospective multi-centric study in 21 hospitals in
recurrent groups, respectively, reported a GAD-7 score ≥10, indicat- Belgium gathered a cohort of 266 PCLD patients. Sequential
ing moderate to severe anxiety (Figure 1A). Pain was reported as one data including POLCA score, liver volumetry and the need for
of the top 3 most burdensome chronic symptoms in the sporadic volume-reduction therapy were recorded. Participants were
(50.9%) and recurrent (59.5%) groups (Figure 1B). Of patients asked to complete the POLCA questionnaire, as available online
reporting their daily activities being limited by severe chronic

S516 Journal of Hepatology 2022 vol. 77(S1) | S389–S664

 POSTER PRESENTATIONS
(https://www.uzleuven.be/polca). Liver volume was measured using Inventory (PedsQL) and family impact (FI) questionnaires, which
CT-volumetry and adapted as height-adjusted total liver volume output total impact scores ranging from 0 to 100; higher scores
(htLV). Combined liver-kidney transplant patients (n = 9) were indicate greater QoL. Treatment R was defined as sBA reductions of
excluded. ≥70% or levels ≤70 μmol/L and/or ≥1-point drop from baseline in
Results: For 198 patients, serial POLCA scores were available. The caregiver-reported pruritus score (on 0–4 scale) at last available
study group consisted of young (54.8y ± 11.3), mostly female (83%) assessment.
patients with predominant ADPKD (63%). Median time of follow-up Results: In the pooled population, 49/84 (58%) met R criteria, and 35/
was 48 months. Liver volumetry was available for 96 patients, 84 (42%) were NRs. In Rs, mean age was 4.8 years and 57% were
showing a median htLV of 1967 ml. female; in NRs, mean age was 5.5 years and 37% were female. Among
There was a significant correlation (Spearman’s rank) between POLCA patients with available QoL data (PedsQL: R: n = 31, NR: n = 22; FI: R:
severity of perceived illness (SPI) score and htLV (r = 0.48; 0.30–0.63). n = 46, NR: n = 33), mean (SE) PedsQL and FI total scores at baseline
Patients who underwent LT had significantly higher scores on all indicated that both Rs (PedsQL: 56.6 [2.3]; FI: 49.9 [2.8]) and NRs
POLCA subscales and htLV, compared to those not considered to be LT (PedsQL: 55.0 [3.5]; FI: 48.9 [3.4]) had impaired QoL at least some of
candidates (table 1). SPI score ≥16.5 predicted the need of LT with a the time, on average. At week 72 in patients with available data, the
sensitivity of 81.3% and a specificity of 88.9%. mean (SE) change from baseline (CFB) in PedsQL total score was 11.0
(4.6) in Rs and 2.3 (8.6) in NRs; the mean (SE) CFB in PedsQL FI total
Table: Comparison of POLCA subscales and htLV score was 22.5 (7.0) in Rs and −1.7 (4.6) in NRs (Figure).
POLCA No LT (n = 171) LT (n = 18) p value
Severity of 10.0 (6.0; 15.0) 23.5 (18; 26) <0, 0001
perceived illness
POLCA No LT (n = 122) LT (n = 17)
GERD complaints 2.0 (0.0; 5.0) 7.0 (4.5; 12.5) <0, 0001
Impact on food 2.0 (0.0; 5.0) 6.0 (4.5; 9.0) 0, 0004
intake
Perception of 6.0 (3.0; 8.0) 10.0 (7.5; 12.0) <0, 0001
enlarged LV
No LT (n = 71) LT (n = 16)
htLV (ml) 1707 (1173; 2690) 3607 (2901; 4337) <0, 0001

Longitudinal data showed a significant correlation between the Conclusion: Odevixibat Rs and, particularly, their families, experi-
change in SPI score and the change in htLV (r = 0.45; 0.26–0.61) and a enced QoL improvements that were sustained over time; QoL for NRs
significant reduction in htLV (−80 ml) by SA resulted in a decrease in and their families was largely unchanged with up to 72 weeks of
SPI score (−6.0 vs +4.5). treatment. Further analysis of specific domains within PedsQL and FI
Conclusion: This prospective study confirms the use of the POLCA that were most highly impacted in Rs is ongoing.
score as a self-report instrument to assess the severity of PCLD-
related symptoms. It is a clear reflection of both evolving symptom FRI254
severity as well as objective changes in liver volume. Our findings Total, primary, and secondary serum bile acid changes and
highlight the potential of the POLCA score as a tool for longitudinal pruritus improvement during odevixibat treatment in patients
follow-up of PCLD patients and as a guide for clinicians when with progressive familial intrahepatic cholestasis
evaluating the need for medical or surgical intervention. Henkjan J. Verkade1, Folkert Kuipers1, Quanhong Ni2,
Velichka Valcheva2. 1Department of Paediatrics, University of
FRI253 Groningen, Beatrix Children’s Hospital/University Medical Centre
Improvements in quality of life in odevixibat responders and Groningen, Groningen, Netherlands; 2Albireo Pharma, Inc., Boston, MA,
nonresponders: an analysis of pooled data from the PEDFIC 1 and United States
PEDFIC 2 studies Email: [email protected]
Cara L. Mack1, Chad Gwaltney2, Quanhong Ni3, Qifeng Yu3,
Background and aims: Children with progressive familial intrahe-
Velichka Valcheva3, Lise Kjems3, Patrick Horn3. 1Children’s Hospital
patic cholestasis who received odevixibat in the 24-week PEDFIC 1
Colorado, University of Colorado School of Medicine, Aurora, CO, United
study had significant reductions vs placebo-treated patients in total
States; 2Gwaltney Consulting, Westerly, RI, United States; 3Albireo
serum bile acids (sBAs) and pruritus. Here, we evaluated changes in
Pharma, Boston, MA, United States
sBAs and pruritus in patients from PEDFIC 1 categorised by sBA
Email: [email protected]
response (R) level and by factoring in ursodeoxycholic acid (UDCA)
Background and aims: Patients with progressive familial intrahe- use.
patic cholestasis (PFIC) may have debilitating pruritus that can impact Method: Patients eligible for PEDFIC 1 had elevated sBAs and
their and their families’ quality of life (QoL). The phase 3 PEDFIC 1 and significant pruritus at screening. Concomitant UDCA was allowed
PEDFIC 2 studies evaluated the efficacy and safety of odevixibat, an provided the patient’s dose was stable. Three categories of patients
ileal bile acid transporter inhibitor, in patients with PFIC. In these among those randomised to odevixibat (n = 42) were analysed here:
studies, odevixibat improved serum bile acids (sBAs), pruritus, and sBA Rs (ie, sBAs reduced ≥70% from baseline [BL] or levels ≤70 μmol/
sleep; QoL was also evaluated as an exploratory endpoint. Here, using L), sBA partial Rs (PRs [ie, did not meet sBA R criteria but had sBAs
pooled data from these studies, we describe patient- and family- reduced ≥30%), and sBA nonresponders (NRs [ie, did not meet either
focused QoL changes in odevixibat responders (Rs) and nonrespon- sBA R or PR criteria). Parameters evaluated included sBA composition
ders (NRs). (ie, total, primary, and secondary BAs, with UDCA concentration
Method: In PEDFIC 1, children with PFIC received placebo or included as secondary BA) as measured by liquid chromatography–
odevixibat (40 or 120 μg/kg/day) for 24 weeks. PEDFIC 2 is an tandem mass spectrometry and pruritus as rated by caregivers
ongoing 72—week extension study that enrolled patients from (range: 0–4; higher scores indicate worse symptoms, with pruritus R
PEDFIC 1 or new patients; all patients in PEDFIC 2 receive odevixibat defined as a ≥1-point reduction from BL); pruritus outcomes were
120 μg/kg/day. Data from these studies were pooled from patients’ also compared by whether patients had concomitant UDCA use and/
first dose of odevixibat to a cut-off date of 4 December 2020. To assess or sBA R.
QoL, caregivers of patients ≥2 years old completed the Pediatric QoL

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S517

POSTER PRESENTATIONS
Results: Mean BL total sBAs were higher with vs without UDCA FRI255
treatment in all 3 sBA R categories (Figure, A), which could be Changes in hepatic parameters, growth, sleep, and biochemical
primarily accounted for by UDCA concentrations (66, 116, and markers with odevixibat treatment across patients with various
42 μmol/L, in sBA Rs, PRs, and NRs, respectively). During odevixibat types of progressive familial intrahepatic cholestasis
treatment, sBA Rs (n = 17) had the largest decreases in total and Lorenzo D’Antiga1, Girish Gupte2, Richard J. Thompson3,
primary sBAs, whereas sBA PRs (n = 7) had intermediate decreases, Ekkehard Sturm4, Pier Luigi Calvo5, Mohammad Ali Shagrani6,7,
and sBA NRs (n = 18) had minimal changes. Among all odevixibat- Janis M. Stoll8, Reha Artan9, Buket Dalgıç10, Hasan Ozen11,
treated patients, sBA Rs experienced greater mean reductions in Kathleen M. Loomes12, Jennifer M. Vittorio13, Saul J. Karpen14,
monthly pruritus scores vs sBA PRs and sBA NRs (Figure, B). sBA PRs Angelo Di Giorgio15, Quanhong Ni16, Lise Kjems16, Patrick Horn16.
1
who used UDCA had smaller reductions in monthly pruritus score vs Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy; 2Liver Unit
those who did not (Figure, B). Among pruritus Rs with UDCA use, the and Small Bowel Transplantation, Birmingham Women’s and Children’s
rate of sBA R, PR, and NR was 69%, 0%, and 31%, respectively; among NHS Foundation Trust, Birmingham, United Kingdom; 3Institute of Liver
pruritus Rs without UDCA use, these rates were 50%, 25%, and 25%. Studies, King’s College London, London, United Kingdom; 4Paediatric
Gastroenterology and Hepatology, University Children’s Hospital
Tübingen, Tübingen, Germany; 5Paediatric Gastroenterology Unit,
Regina Margherita Children’s Hospital, Azienda Ospedaliera Città della
Salute e della Scienza di Torino, Turin, Italy; 6King Faisal Specialist
Hospital and Research Centre-Organ Transplant Centre, Riyadh, Saudi
Arabia; 7College Of Medicine-Alfaisal University, Riyadh, Saudi Arabia;
8
Department of Paediatrics, Washington University School of Medicine,
St. Louis, Missouri, United States; 9Akdeniz University, Antalya, Turkey;
10
Department of Paediatric Gastroenterology, Gazi University Faculty of
Medicine, Ankara, Turkey; 11Hacettepe University Faculty of Medicine,
Ankara, Turkey; 12Children’s Hospital of Philadelphia, Philadelphia, PA,
United States; 13Department of Surgery, Centre for Liver Disease and
Transplantation, Columbia University Medical Centre, New York, NY,
United States; 14Emory University School of Medicine, Children’s
Healthcare of Atlanta, Atlanta, GA, United States; 15Paediatric
Hepatology Gastroenterology and Transplantation, ASST Papa Giovanni
XXIII, Bergamo, Italy; 16Albireo Pharma, Inc., Boston, MA, United States
Email: [email protected]
Background and aims: PEDFIC 1 and PEDFIC 2 evaluated the safety
and efficacy of odevixibat, an ileal bile acid transporter inhibitor, in
patients with progressive familial intrahepatic cholestasis (PFIC).
Using pooled data from these studies, we analysed secondary and
exploratory endpoints in patients with PFIC type 1 (PFIC1), 2 (PFIC2),
3 (PFIC3), and 6 (PFIC6).
Method: PEDFIC 1 was a 24-week, randomised, placebo-controlled
study in children with PFIC1 and PFIC2. PEDFIC 2 is an ongoing 72-
week extension study in patients with any PFIC type. This pooled
analysis spans from patients’ first dose of odevixibat to a cut-off of 4
December 2020. Assessments included changes from baseline (BL) in
alanine aminotransferase (ALT), total bilirubin, growth, caregiver-
reported sleep parameters, autotaxin, and 7α-hydroxy-4-cholesten-
3-one (C4); data are presented to wk72 of odevixibat treatment for
patients with PFIC1 and PFIC2 and to wk36 or wk48 for patients with
PFIC3 and PFIC6 (who have less time on treatment vs patients with
PFIC1 or PFIC2, who could have participated in PEDFIC 1).
Results: Of 84 patients in the pooled population (mean age, 5.0
years), 26% had PFIC1 (n = 22), 67% PFIC2 (n = 56), 6% PFIC3 (n = 5),
and 1% PFIC6 (n = 1). With odevixibat, mean changes in ALT levels to
wk72 in patients with PFIC1 (n = 6) and PFIC2 (n = 15) who reached
this timepoint as of the data cut-off were −14 U/L and −85 U/L,
respectively; mean changes in ALT levels to wk36 in patients with
PFIC3 (n = 4) and PFIC6 (n = 1) were 67 U/L and 89 U/L. Patients with
PFIC1 and PFIC2 with available data at wk72 had mean changes in
total bilirubin of −6 μmol/L and −5 μmol/L, respectively; for patients
Conclusion: UDCA treatment resulted in higher sBAs at BL, but this with PFIC3 and PFIC6, mean changes to wk36 were 18 μmol/L and
did not seem to affect sBA R to odevixibat. A sBA PR was not −83 μmol/L. Mean height and weight Z scores increased with
associated with a mean decrease in pruritus with concomitant UDCA odevixibat treatment across the various types of PFIC. Sleep
use. All sBA R groups included patients for whom pruritus R did not parameters, C4, and autotaxin improved over time in almost all
correlate with sBA R. PFIC types (Figure). Across PFIC types, most treatment-emergent
adverse events with odevixibat were mild or moderate in severity.

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 POSTER PRESENTATIONS
UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, United States;
18
Children’s Hospital of Colorado, University of Colorado School of
Medicine, Aurora, CO, United States; 19Department of Paediatric
Gastroenterology Hepatology and Transplantation, ASST Papa Giovanni
XXIII, Bergamo, Italy; 20Albireo Pharma, Inc., Boston, MA, United States
Email: [email protected]
Background and aims: Patients with progressive familial intrahe-
patic cholestasis (PFIC), a group of rare paediatric cholestatic liver
diseases, have debilitating symptoms including severe pruritus that
can impact sleep and quality of life (QoL). In the phase 3 PEDFIC 1 and
PEDFIC 2 studies, the ileal bile acid transporter inhibitor odevixibat
reduced serum bile acids (sBAs) and improved pruritus and sleep in
children with PFIC. Using pooled data from these studies, we
examined secondary and exploratory efficacy endpoints and safety
outcomes in patients who met criteria for a pruritus response with
odevixibat treatment.
Method: PEDFIC 1 was a 24-week, randomised, placebo-controlled
study in children with PFIC1 or PFIC2. PEDFIC 2 is an ongoing 72-
week extension study in patients of with any PFIC type. Pruritus was
rated using the Albireo observer-reported outcome instrument
(range: 0–4). This pooled analysis spans from patients’ first dose of
odevixibat to a cut-off of 4 December 2020. We analysed sBAs, QoL
(Pediatric QoL Inventory [PedsQL] and PedsQL family impact [FI]
Conclusion: In patients with PFIC treated with odevixibat assessed to
questionnaire; higher scores indicate improved QoL), alanine
date, growth improved, autotaxin levels decreased, and C4 levels
aminotransferase (ALT), total bilirubin, sleep parameters, and
increased over time; changes in hepatic and sleep parameters in
treatment-emergent adverse events (TEAEs) in patients with a
some PFIC types were more variable (eg, PFIC3, PFIC6), but these
pruritus response (ie, ≥1-point drop in pruritus score from baseline)
conclusions may be limited by the small size of these subgroups,
following odevixibat treatment.
particularly at later timepoints. Odevixibat was generally well
Results: Of 82 patients in the pooled population (of whom, 49% were
tolerated.
female), 44 (54%) were pruritus responders. Of these 44 pruritus
FRI256 responders (mean age, 4.6 years), 24 (55%) were female; 23%, 68%,
Analysis of quality of life, hepatic biochemical markers, and sleep and 7% had PFIC 1, 2, and 3, respectively. Mean sBA levels were 247
in patients with progressive familial intrahepatic cholestasis who μmol/L at baseline (n = 44) and decreased over time by 77% at weeks
had a pruritus response with odevixibat treatment 70 − 72 in pruritus responders who reached this timepoint (n = 18).
Girish Gupte1, Richard J. Thompson2, Lorenzo D’Antiga3, Mean PedsQL and FI total scores were 56 (n = 30) and 50 (n = 42) at
Tassos Grammatikopoulos2,4, Emmanuel Gonzalès2, baseline and increased by 11 (n = 8) and 24 (n = 14) at week 72,
Florence Lacaille3, Alain Lachaux4, Bertrand Roquelaure5, respectively, in pruritus responders. Mean ALT and total bilirubin
Ulrich Baumann6, Elke Lainka7, Ekkehard Sturm8, Eyal Shteyer9, levels decreased over time from 109 U/L and 40 μmol/L at baseline to
Piotr Czubkowski10, Reha Artan11, Buket Dalgic12, Hasan Ozen13, 40 U/L and 18 μmol/L (n = 15) (Figure 1A, B), and sleep parameters
Kathleen M. Loomes14, Jennifer M. Vittorio15, Saul J. Karpen16, improved over time in these patients (Figure 1C, D). There were no
Patrick McKiernan17, Cara L. Mack18, Angelo Di Giorgio19, Qifeng Yu20, drug-related serious TEAEs.
Lise Kjems20, Patrick Horn20. 1Liver Unit and Small Bowel
Transplantation, Birmingham Women’s and Children’s NHS Foundation
Trust, Birmingham, United Kingdom; 2Institute of Liver Studies, King’s
College London, London, United Kingdom; 3Azienda Ospedaliera Papa
Giovanni XXIII, Bergamo, Italy; 4Paediatric Liver, GI and Nutrition Centre
and MowatLabs, King’s College Hospital NHS Trust, London, United
Kingdom; 5Hospital for Sick Children and the University of Toronto,
Toronto, ON, Canada; 6Paediatric Gastroenterology and Hepatology,
Hannover Medical School, Hannover, Germany; 7Children’s Hospital,
Department of Paediatric Gastroenterology, Hepatology, and Transplant
Medicine, University Duisburg-Essen, Essen, Germany; 8Paediatric
Gastroenterology and Hepatology, University Children’s Hospital
Tübingen, Tübingen, Germany; 9Faculty of Medicine, Hebrew University
of Jerusalem, Juliet Keidan Department of Paediatric Gastroenterology,
Shaare Zedek Medical Centre, Jerusalem, Israel; 10Department of
Gastroenterology, Hepatology, Nutritional Disorders and Paediatrics, The
Children’s Memorial Health Institute, Warsaw, Poland; 11Akdeniz
University, Antalya, Turkey; 12Department of Paediatric
Gastroenterology, Gazi University Faculty of Medicine, Ankara, Turkey; Conclusion: Overall, patients with PFIC with a pruritus response
13
Hacettepe University Faculty of Medicine, Ankara, Turkey; 14Children’s following treatment with odevixibat experienced improvements in
Hospital of Philadelphia, Philadelphia, PA, United States; 15Department sBAs, QoL, hepatic biochemical markers, and sleep parameters that
of Surgery, Center for Liver Disease and Transplantation, Columbia were sustained over time. Odevixibat was generally well tolerated.
University Medical Center, New York, NY, United States; 16Emory
University School of Medicine, Children’s Healthcare of Atlanta, Atlanta,
GA, United States; 17Division of Gastroenterology/Hepatology/Nutrition,

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POSTER PRESENTATIONS
FRI257 FRI258
Longitudinal follow-up data on adults with classic, severe alpha-1 Gender dependent neurological and hepatic improvement in
antitrypsin deficiency (Pi*ZZ genotype) Wilson disease patients treated with Trientine dihydrochloride:
Malin Fromme1, Samira Amzou1, Barbara Burbaum1, Philipp Striedl2, post hoc results from a prospective study
Mattias Mandorfer3, Elmar Aigner2, Christian Trautwein1, Karl Heinz Weiss1, Isabelle Mohr2, Carlot Kruse3, Aurelia Poujois4.
Pavel Strnad1. 1University Hospital RWTH Aachen, Medical Clinic III, 1
Salem Medical Centre, Department of Internal Medicine, Heidelberg,
Gastroenterology, Metabolic Diseases and Intensive Care, Aachen, Germany; 2Heidelberg University Hospital, Internal Medicine IV,
Germany; 2Paracelsus Medical University, First Department of Medicine, Department of Gastroenterology, Heidelberg, Germany; 3Univar
Salzburg, Austria; 3Medical University of Vienna, Division of Solutions B.V., Rotterdam, Netherlands; 4Rothschild Foundation Hospital,
Gastroenterology and Hepatology, Vienna, Austria Rare Disease Reference Centre “Wilson’s Disease and Other Copper-
Email: [email protected] Related Rare Diseases,” Neurology Department, Paris, France
Email: [email protected]
Background and aims: Homozygous Pi*Z mutation in the SERPINA1
gene (Pi*ZZ genotype) confers a strong predisposition to lung and Background and aims: Wilson disease (WD) is a rare autosomal
liver disease. Since the pace of liver disease progression and suitable recessively inherited disorder of the copper metabolism for which
prognostic factors remain unknown, we evaluated risk factors (i.e., liver and neurological manifestations are most common. Trientine
demographics and lifestyle) and the predictive utility of non-invasive dihydrochloride (TETA-2HCl; trientine) is a well-established second
tests in the European Pi*ZZ liver cohort. line treatment for WD patients intolerant to D-penicillamine. Data on
Method: 480 Pi*ZZ individuals without concomitant liver diseases or gender differences in WD progression for patients under trientine
pathological alcohol consumption, decompensated liver disease, or treatment are limited. The data presented are derived from a post hoc
hepatocellular carcinoma were evaluated by a standardized baseline analysis of a single centre prospective study (NCT: 02426905).
clinical, laboratory, and elastographic assessment. 340 of them had a Method: This study was a single centre, prospective study in adult
detailed follow-up interview at least 12 months after their baseline WD patients on maintenance treatment with TETA-2HCl 300 mg
examination. (equivalent to 200 mg of trientine base) with a follow up of 12
Results: During a median follow-up of 3.85 years, 23 Pi*ZZ months. All patients were previously treated with D-penicillamine.
individuals deceased. The main causes of fatality were lung and The neurological disease burden was measured by means of an
liver disease, each accounting for 8 deaths. 10/4 individuals received a investigator rated Unified Wilson’s Disease Rating Scale (UWDRS)
lung/liver transplant, 3 additional Pi*ZZ individuals developed and corresponding changes from baseline to 6 months and 12
hepatic decompensation. Compared to the remaining Pi*ZZ partici- months. To investigate corresponding liver disease, the parameters
pants, 15 individuals who developed a hepatic endpoint (liver analysed included alanine transferase (ALT) and aspartate transferase
transplant/death, or decompensated cirrhosis) presented with (AST) response.
significantly higher body mass index (29.3 vs. 24.5 kg/m2, p = Results: Of the 52 patients enrolled in the study, 51 (98.1%) patients
0.003), liver stiffness measurement (LSM, 14.0 vs. 5.2 kPa, p = 6.3 × were included in the full analysis set. The mean (SD) duration of
10−9), AST-to-platelet ratio index (APRI, 0.97 vs. 0.31 units, p = 9.4 × trientine treatment was 13.1 (1.62) months (range: 3 to 15 months)
10−7), fibrosis-4 index (FIB-4, 3.6 vs. 1.3, p = 6.0 × 10−6) and liver with a mean (SD) dose of 1377.6 (368.78) mg per day (range: 150 to
enzymes in their baseline examination. Multivariate Cox regression 2100 mg per day). The mean (SD) values for UWDRS-assessment
analysis revealed LSM ≥ 25 kPa (aHR 30.9, 95% CI 8.0–119.2, p = 6.1 × were 11.3 (24.31) at baseline, 9.7 (23.85) at month 6 and 8.8 (22.86) at
10−7) and APRI≥1.0 units (aHR 39.6, 95% CI 10.1–154.7, p = 1.2 × 10−7) month 12. The decrease of UWDRS values over time was shown to be
as strong predictors of liver-related mortality. significant ( p < 0.01) in a longitudinal regression model with log
(UWDRS + 1) as the regressor. Analyses based on gender showed a
mean UWDRS of 10.6 (n = 34) at baseline, 8.6 (n = 34) at 6 months and
Pi*ZZ without Pi*ZZ with hepatic 8.0 (n = 34) for females and 12.6 (n = 17) at baseline, 11.9 (n = 16) at 6
hepatic endpoint endpoint P value months and 10.4 (n = 17) for males. The gender differences in the
n = 325 n = 15 (univariable) UWDRS decrease were significant ( p = 0.02) in the longitudinal
Age (years) 57.5 [51.3–65.1] 57.9 [50.8–63.5] 0.828 model extended by gender as a covariate. AST and ALT results were
Women (%) 47.1 20.0 0.040 stable over time. There appears to be no gender difference in AST and
BMI (kg/m2) 24.5 [22.0–27.2] 29.3 [24.6–31.6] 0.003 ALT outcomes.
Mean alcohol 2.5 [0.0–8.2] 0.0 [0.0–8.2] 0.276 Conclusion: Post hoc analysis indicates that gender might have an
consumption (g/d) influence on neurologic symptom regression and disease course in
LSM <15 kPa + 88.9 33.3 8.4 × 10−10 WD patients on trientine maintenance therapy. The trend of
PLT ≥ 150 (%) continuous improvement in neurological symptoms is mainly seen
LSM ≥ 15 kPa (%)1 2.8 46.7 4.2 × 10−15
in female WD patients-even after long-term therapy. These findings
LSM ≥ 25 kPa (%)2 1.2 33.3 3.7 × 10−14
APRI ≥ 1.0 units 2.2 46.7 6.4 × 10−17 warrant further prospective evaluation and have implications for
(%)3 future study designs.
FIB-4 ≥ 1.3 (%)4 50.6 93.3 0.001
ALT ≥ ULN (%)5 21.5 73.3 4.0 × 10−6
AST ≥ ULN (%)6 13.2 66.7 2.4 × 10−8
PLT <150/nL (%)7 9.5 60.0 3.1 × 10−9

Abbreviations: BMI, body mass index; LSM, liver stiffness measurement; APRI,
AST-to-platelet ratio index; ALT, alanine aminotransferase; AST, aspartate
aminotransferase; PLT, platelet count; ULN, upper limit of normal. Adjusted
1 2 3
Hazard ratios with 95%CI: 26.2 (7.4–93.2), 30.9 (8.0–119.2), 39.6 (10.1–
4 5 6 7
154.7), 14.7 (1.6–135.9), 9.0 (2.4–33.5), 19.3 (5.2–71.8), 17.0 (4.6–62.0).

Conclusion: LSM and APRI accurately stratify Pi*ZZ individuals

according to their risk of liver-related events. Thus, these non-
invasive tests may facilitate risk stratification in clinical practice as
well as patient selection for clinical trials.

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 POSTER PRESENTATIONS
FRI259 ursodeoxycholic acid (UDCA), 56% were using rifampicin, and 89%
Efficacy and safety of odevixibat over 72 weeks of treatment in were using UDCA and/or rifampicin. Mean (SE) sBA levels at baseline
patients with progressive familial intrahepatic cholestasis were 291 (26) μmol/L, which decreased by −185 (28) at weeks 70–72
Richard J. Thompson1, Emmanuel Gonzalès2, Reha Artan3, of odevixibat treatment (Figure). Mean (SE) pruritus score at baseline
Winita Hardikar4, Florence Lacaille5, Alain Lachaux6, was 2.9 (0.1), which decreased by −1.56 (0.2) at weeks 61–72 (Figure).
Bertrand Roquelaure7, Ulrich Baumann8, Ekkehard Sturm9, At week 72 of odevixibat treatment, decreases in alanine amino-
Eyal Shteyer10, Pier Luigi Calvo11, Henkjan J. Verkade12, transferase (−64.9 U/L), aspartate aminotransferase (−18.8 U/L), and
Mohammad Ali Shagrani13,14, Janis M. Stoll15, Piotr Czubkowski16, total bilirubin (−5.4 μmol/L) were also observed; mean (SE) height
Buket Dalgıç17, Girish Gupte18, Tassos Grammatikopoulos19, and weight Z scores increased by 0.8 (0.1) and 0.5 (0.2), respectively.
Patrick McKiernan20, Qifeng Yu21, Lise Kjems21, Patrick Horn21. In this group of patients with ≥72 weeks of odevixibat treatment, 26
1 (96%) patients experienced any treatment-emergent adverse event
Institute of Liver Studies, King’s College London, London, United
Kingdom; 2Hépatologie et Transplantation Hépatique Pédiatriques, (TEAE) and 52% experienced drug-related TEAEs. There were no
Centre de Référence de l’Atrésie des Voies Biliaires et des Cholestases TEAEs leading to discontinuation.
Génétiques, FSMR FILFOIE, ERN RARE LIVER, Hôpital Bicêtre, AP-HP,
Université Paris-Saclay, Hépatinov, Inserm U 1193, Paris, France;
3
Akdeniz University, Antalya, Turkey; 4Royal Children’s Hospital,
Melbourne, Australia; 5Paediatric Gastroenterology-Hepatology-
Nutrition Unit, Hôpital Universitaire Necker-Enfants Malades, Paris,
France; 6Hospices Civils de Lyon, Hôpital Femme-Mer̀ e-Enfant, Service
D’hépatogastroentérologie et Nutrition Pédiatrique, Lyon, France; 7CHU,
Hospital de la Timone, Marseille, France; 8Paediatric Gastroenterology
and Hepatology, Hannover Medical School, Hannover, Germany;
9
Paediatric Gastroenterology and Hepatology, University Children’s
Hospital Tübingen, Tübingen, Germany; 10Faculty of Medicine, Hebrew
University of Jerusalem, Juliet Keidan Department of Paediatric
Gastroenterology, Shaare Zedek Medical Centre, Jerusalem, Israel;
11
Paediatric Gastroenterology Unit, Regina Margherita Children’s
Hospital, Azienda Ospedaliera Città della Salute e della Scienza di Torino,
Turin, Italy; 12Department of Paediatrics, University of Groningen,
Beatrix Children’s Hospital/University Medical Centre Groningen,
Groningen, Netherlands; 13King Faisal Specialist Hospital and Research
Centre-Organ Transplant Centre, Riyadh, Saudi Arabia; 14College Of
Medicine-Alfaisal University, Riyadh, Saudi Arabia; 15Department of
Paediatrics, Washington University School of Medicine, St. Louis,
Missouri, United States; 16Department of Gastroenterology, Hepatology,
Nutritional Disorders and Paediatrics, The Children’s Memorial Health Conclusion: Odevixibat was well tolerated and demonstrated
Institute, Warsaw, Poland; 17Department of Paediatric Gastroenterology, durable clinical treatment benefits for up to 72 weeks in improving
Gazi University Faculty of Medicine, Ankara, Turkey; 18Istanbul sBA levels, pruritus scores, hepatic parameters, and growth in
University, Istanbul Faculty of Medicine, Istanbul, Turkey; 19Liver Unit patients with PFIC who were treated for at least 72 weeks.
and Small Bowel Transplantation, Birmingham Women’s and Children’s
NHS Foundation Trust, Birmingham, United Kingdom; 20Division of FRI260
Gastroenterology/Hepatology/Nutrition, UPMC Children’s Hospital of In vitro rescue of the bile acid transport function of some ABCB11
Pittsburgh, Pittsburgh, PA, United States; 21Albireo Pharma, Inc., Boston, variants by CFTR potentiators: a targeted pharmacotherapy in
MA, United States progressive familial intrahepatic cholestasis type 2
Email: [email protected] Elodie Mareux1, Martine Lapalus1, Marion Almes1,2, Pauline Adnot1,
Mounia Lakli1, Amel Ben Saad1, Jean-Luc Decout3, Thomas Falguières1,
Background and aims: Progressive familial intrahepatic cholestasis
Isabelle Callebaut4, Emmanuel Gonzalès1,2, Emmanuel Jacquemin1,2.
(PFIC) is a group of paediatric cholestatic liver diseases characterised 1
Inserm, UMR_S1193 Physiopathogénes̀ e et traitement des maladies du
by disruption of bile production and transport, pruritus, and
foie, Université Paris-Saclay, Hepatinov, Orsay, France; 2Assistance
progressive liver disease. Here, using pooled data from two phase 3
Publique-Hôpitaux de Paris, Faculté de médecine Paris-Saclay, CHU
studies in patients with PFIC (PEDFIC 1 and PEDFIC 2), we describe
Bicêtre, Paediatric Hepatology and Paediatric Liver Transplant
key long-term outcomes with odevixibat, an ileal bile acid trans-
Department, National Reference Center for Rare Paediatric Liver
porter inhibitor, in the subgroup of patients treated with odevixibat
Diseases, FILFOIE, ERN RARE LIVER, Le Kremlin-Bicêtre, France; 3CNRS,
for ≥72 weeks.
Département de pharmacochimie moléculaire, Université de Grenoble
Method: PEDFIC 1 was a 24-week, placebo-controlled, double-blind
Alpes, Grenoble, France; 4CNRS, UMR 7590, Institut de Minéralogie, de
study of odevixibat in children with PFIC1 or PFIC2. PEDFIC 2 is an
Physique des Matériaux et de Cosmochimie, Sorbonne Université,
ongoing, 72-week extension study in patients of any age with any
Muséum National d’Histoire Naturelle, Paris, France
type of PFIC. This pooled analysis spans from patients’ first dose of
Email: [email protected]
odevixibat in PEDFIC 1 or PEDFIC 2 to a cut-off of December 4, 2020.
The following outcomes are described over time in the subgroup of Background and aims: ABCB11 is expressed at the canalicular
patients who had ≥72 weeks of exposure to odevixibat: serum bile membrane of hepatocytes and is responsible for biliary bile acid
acids (sBAs), caregiver-reported pruritus score (range, 0–4; higher secretion. Variations in the ABCB11 gene cause a spectrum of rare liver
scores indicate worse symptoms), laboratory parameters, growth, diseases. The most severe form is progressive familial intrahepatic
and safety. cholestasis type 2 (PFIC2). Current medical treatments of these
Results: Of 84 patients in the pooled population, 27 were treated with conditions have limited efficacy. Hence, the identification of
odevixibat for ≥72 weeks (median [range], 92 [76–128] weeks). Of alternative therapies is a major challenge.
these 27 patients (mean age, 3 years), 52% were male, 70% had PFIC2, Method: Three ABCB11 disease-causing variations identified in PFIC2
and 30% had PFIC1. At baseline, 82% of these 27 patients were using patients (A257 V, T463I and G562D) were studied by 3D structure

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POSTER PRESENTATIONS
modelling. The variations were reproduced in a plasmid encoding a 16 independent serum samples were collected, and detected by ELISA
rat Bsep—green fluorescent protein. After transfection, the expression method to validate the disease-associated DEPs and the diagnostic
and the localisation of the variants were studied in HepG2 and Can 10 classifier.
cells. Tritiated taurocholate ([3H]TC) transport activity and the effect Results: Of all the identified DEPs of liver-type WD and brain-type
of Ivacaftor (VX-770, Kalydeco®), a clinically approved cystic fibrosis WD, there were 62 common DEPs between the two types including
(CF) treatment, GLPG1837 in phase 2 CF clinical trials as well as 18 were up-regulated and 44 were down regulated. GO enrichment
SBC040 and SBC219, known as potentiators of CFTR were studied in analysis revealed that the common DEPs were mainly involved in
Madin-Darby canine kidney (MDCK) clones co-expressing Abcb11 inflammation, coagulation cascade, protein transport and activation.
and the rat sodium taurocholate co-transporting polypeptide (Ntcp/ And the coexpression PPI network showed that several DEPs
Slc10A1). interacted with many DEPs implicated in WD, such as Heparin
Results: As predicted by 3D structure modelling, the three variants cofactor 2 (SERPIND1), Transthyretin (TTR) and Coagulation factor IX
were correctly expressed at the canalicular membrane of HepG2 and (F9). Hereby, we constructed a classifier consisting of two down-
Can 10 cells but had a defective function when studied in MDCK cells regulated proteins (F9 and C4b-binding protein beta chain (C4BPB)
with a [3H]TC transport activity ranging from 28 to 70 % of the one with 100% accuracy. ELISA test validated the differential down-
observed in MDCK cells expressing the wild type (wt) Abcb11 regulations of F9 and C4BPB in 16 independent WD samples when
(Figure). Ivacaftor, GLPG1837, SBC040 and SBC219 increased the [3H] comapared with 26 healthy controls. In the independent samples, the
TC transport activity of A257 V, T463I and G562D by 1.3 to 1.9-fold, area under the ROC curve (AUC) of the diagnostic classifier was 0.986,
allowing the [3H]TC transport activity of the A257 V variant to reach and its sensitivity and specificity was 93.8% and 96.2%, respectively.
the one of the wt Abcb11. Furthermore, an additive effect was
observed for the T463I variant when ivacaftor was combined with
SBC040 or SBC219.

Conclusion: Potentiator drugs could increase the pharmacopoeia

available for patients with ABCB11 deficiency due to missense
variations affecting the transport function and may delay or even
suppress the need for liver transplantation in these patients.

FRI261
Plasma-based proteomics profiling of patients with Wilson’s
disease
Rui Hua1, Jie Su1, HaiTao Qi2, Yonggeng Jiao3, Lishuang Qi2, Junqi Niu1. Conclusion: Our study demonstrates for the first time that mass
1
The First Affiliated Hospital of Jilin University, Hepatology, Changchun, spectrometry proteomic combined with bioinformatics analysis of
China; 2Harbin Medical University, College of Bioinformatics Science and serum samples is a potential approach to identify candidate markers
Technology, Harbin, China; 3Jilin Province FAW General Hospital, associated with WD. Further studies are warranted to evaluate the
Anesthesiology, Changchun, China clinical utility of these biomarkers in patients with WD.
Email: [email protected]
Background and aims: Wilson’s disease (WD) is an inherited
disorder resulting from abnormal copper metabolism. Current
diagnostic criteria is inadequacy since biochemical indexes related
to copper are unreliable and genetic testing is expensive. The study
aimed to reveal WD-related proteomic alterations, from which
protein based molecular diagnostic model was developed.
Method: We performed a LTQ-Orbitrap (LC-ESI-MS/MS) comparative
quantitative proteomics analysis to reveal the differentially expressed
proteins (DEPs) between 20 WD subjects (10 liver type and 10 brain
type) and 10 healthy controls. Then, functional enrichment analysis
of Gene Ontologyand (GO) and coexpression protein-protein inter-
action (PPI) network based on STRING database were performed to
reveal the dysregulated biological functions. Next, eXtreme Gradient
Boosting (XGboost) was used to construct an optimal classifier to
distinguish liver- and brain-type WDs from healthy controls. Finally,

S522 Journal of Hepatology 2022 vol. 77(S1) | S389–S664

 POSTER PRESENTATIONS
FRI262 FRI263
Management of hepatic sarcoidosis-multicentric approach Plasma proteomics identifies hepatic steatosis and sex differences
Janina Sollors1, Andreas Teufel2, Christoph Antoni1, Matthias Ebert2, in 2, 147 children and adolescents
Svetlana Hetjens3, Yuquan Qian1, Bernhard Schlevogt4, Lili Niu1,2, Sara Stinson3, Louise Holm3,4, Morten Lund4,5,
Marcus-Alexander Woerns5, Peter Galle5, Cleo-Aron Weis6, Cilius Fonvig3,4, Helene Bæk Juel3, Simon Rasmussen1,
Raoul Bergner7. 1University Medical Center Mannheim, Department of Jens-Christian Holm3,4,5, Torben Hansen3, Matthias Mann1,2.
Internal Medicine II, Mannheim, Germany; 2University Medical Center 1
University of Copenhagen, Novo Nordisk Foundation Center for Protein
Mannheim, Medical Faculty Mannheim, Heidelberg University, Research, Copenhagen, Denmark; 2Max Planck Institute of Biochemistry,
Department of Internal Medicine II, Mannheim, Germany; 3Medical Department of Proteomics and Signal Transduction, Martinsried,
Faculty University Heidelberg, University Hospital Mannheim, Internal Germany; 3University of Copenhagen, Novo Nordisk Foundation Center
Medicine II, Germany; 4University Medical Center Muenster, for Basic Metabolic Research, Copenhagen, Denmark; 4Copenhagen
Department of Medicine B, Muenster, Germany; 5University Medical University Hospital Holbæk, The Children’s Obesity Clinic, Department of
Center Mainz, Department of Internal Medicine I, Mainz, Germany; Pediatrics, Holbæk, Denmark; 5University of Copenhagen, The Faculty of
6
University Medical Center Mannheim, Medical Faculty Mannheim, Health and Medical Sciences, Copenhagen, Denmark
Heidelberg University, Department of Pathology, Mannheim, Germany; Email: [email protected]
7
Ludwigshafen Medical Center, Division of Rheumatology, Department
Background and aims: Childhood obesity constitutes a serious
of Medicine A, Ludwigshafen, Germany
health challenge predisposing children and adolescents to cardio-
Email: [email protected]
metabolic- and liver diseases. In particular, the prevalence of
Background and aims: Sarcoidosis is systemic granulomatous pediatric non-alcoholic fatty liver disease (NAFLD) is estimated to
disorder of unknown cause, characterized by activation of T- be 36% in the context of obesity. Percutaneous liver biopsies are
lymphocytes and macrophages involving multiple organs. Main considered the gold standard for diagnosing NAFLD, but due to its
manifestations are bihilar lymphadenopathy, pulmonary densifica- invasive nature, its clinical application is limited in children. This
tion but also skin, joint and eye involvement. However, liver study aims to use mass spectrometry-based proteomics to identify
involvement may occur in up to 60% of all patients. As many patients non-invasive biomarkers for early detection of hepatic steatosis in
experience only minor symptoms, a high number of undiagnosed children and adolescents, taking into account sex-specific changes in
cases must be assumed. plasma proteins during puberty.
In order to successfully identify patients with hepatic sarcoidosis, a Method: We included 2, 147 children and adolescents, aged 5
throughout characterization of these patients and their course of through 20, from an obesity clinic cohort and a population-based
disease is necessary. However, the currently available evidence was cohort in Denmark, in a cross-sectional study design. We acquired
mostly collected several decades ago. plasma proteomics data using the Evosep One liquid chromatography
Method: We collected 40 patients from four German centers to system coupled online to an Orbitrap Exploris 480 mass spectrom-
evaluate current treatment standards and course of disease. All of our eter. We performed adjusted correlation analysis to identify
patients underwent liver biopsy with histologically proven granu- age-associated proteins. We then used unsupervised hierarchical
lomatous hepatitis. clustering to identify clusters of protein trajectories changing with
Results: Detailed characterization of these patients showed an overall age. Liver fat percentage, as quantified by proton magnetic resonance
benign course of disease. Treatment of these patients was very spectroscopy, was available for 764 children (80% of whom were from
diverse with glucocorticoids for 1 year in 55% (22/40), 5–10 years in the obesity clinic). Among these, 13.5% exhibited hepatic steatosis,
18% (7/40), and permanently in 18% (7/40). defined as a liver fat percentage above 5%. We performed student’s t-
Other treatments included Disease-Modifying Anti-Rheumatic Drugs test (two-sided) to identify differentially abundant proteins between
(DMARDs) of the conventional e.g. non-biological type (metotrexate children and adolescents with and without hepatic steatosis. Receiver
(MTX), azathioprine (AZA), hydroxychloroquine (HCQ), sulfasalazine operator characteristics area under the curve (ROC-AUC) was used to
(SSZ), leflunomid (LEF)) in 53 %, of these, AZA 81%, MTX 46%, HCQ identify potential biomarkers. We used the liver damage marker,
10%, furthermore mycofenolatmofetil (MMF) in 10% and cyclophos- alanine aminotransferase (ALT) ( plasma concentrations) as a
phamide in 10% and biologicals in 8% of all patients in whom detailed benchmark.
documentation was available. Results: On average, 394 proteins were quantified per sample.
Among these, 70 proteins significantly correlated with age.
Hierarchical clustering identified puberty-related clusters of protein
trajectories, which exhibited sex-dependent differences, such as sex
hormone-binding globulin. Student’s t-test identified 84 significantly
differentially abundant proteins, including 44 upregulated and 40
downregulated in the group with hepatic steatosis. The top 20 best-
performing proteins which predicted hepatic steatosis, exhibited
ROC-AUCs between 0.63 and 0.81. Combining the top two and top
eight proteins resulted in an ROC-AUC of 0.82 and 0.87, respectively,
which was superior to ALT.

Conclusion: Despite these very diverse treatments, patients gener-

ally showed only slow progression of the disease. Only one patient
died due to spontaneous bacterial peritonitis. None of our patients
received liver transplantation. Based on our experience, we proposed
a diagnostic work up and surveillance strategy as a basis for future,
prospective register studies.

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POSTER PRESENTATIONS
Conclusion: Infertility is common in patients with BCS. Pregnancy is
well tolerated in those with compensated liver disease. Normal
vaginal delivery is a safe method of childbirth in these patients. No
fetal malformations or major bleeding episodes were noted despite
the use of oral anticoagulants.

FRI265
New cases of Budd-Chiari syndrome and splanchnic vein
thrombosis after COVID-19 vaccination-a vascular liver disease
group (VALDIG) initiative
Raoel Maan1, Aurélie Plessier2, Louise China3, David Patch4,
Anna Baiges5, Juan Carlos Garcia Pagan5, Virginia Hernandez-Gea5,
Marie-Noëlle Hilleret6, E.T.T.L. Tjwa7, Ilias Kounis8,
Christophe Bureau9, Baptiste Giguet10, Alexandra Heurgue-Berlot11,
Isabelle Ollivier-Hourmand12, Xavier Causse13,
Filipe Gaio Castro Nery14, Mandy Lauw15, Sarwa Darwish Murad1.
1
Erasmus University Medical Centre, Department of Gastroenterology
Conclusion: Temporal plasma proteome trajectories reflect sex and Hepatology, Rotterdam, Netherlands; 2Beaujon Hospital,
differences during puberty. A panel of eight proteins shows Department of Hepatology, Paris, France; 3University College London,
promising potential as a non-invasive diagnostic marker for hepatic Institute of Liver and Digestive Health, London, United Kingdom; 4Royal
steatosis in children and adolescents. This would need to be Free London NHS Foundation Trust, Hepatology and Liver
externally validated. Transplantation, London, United Kingdom; 5Hospital Clínic, Institut de
Investigacions Biomed ̀ iques August Pi i Sunyer (IDIBAPS), University of
FRI264 Barcelona, Barcelona, Barcelona Hepatic Hemodynamic Laboratory,
Pregnancy outcomes in women with Budd Chiari syndrome: a Liver Unit, Barcelona, Spain; 6CHU Grenoble Alpes, 38043 Grenoble
single center experience Cedex, Service d’Hépato-Gastroentérologie, Grenoble, France; 7Radboud
Sagnik Biswas1, Sabreena Sheikh1, Manas Vaishnav1, University Medical Center, Department of Gastroenterology and
Anshuman Elhence1, Naba Farooqui2, Abhinav Anand1, Hepatology, Nijmegen, Netherlands; 8AP-HP Hôpital Paul-Brousse,
Shivanand Gamanagatti3, Shalimar1. 1All India Institute of Medical Inserm, Université Paris-Saclay, UMR-S 1193;, Université Paris-Saclay,
Sciences, New Delhi, Gastroenterology and Human Nutrition, New Delhi, Inserm, FHU Hepatinov, 94800, Centre Hépato-Biliaire;,
India; 2Mayo Clinic, Rochester, Rochester, United States; 3All India Physiopathogénes̀ e et traitement des maladies du Foie, Villejuif, France;
9
Institute of Medical Sciences, New Delhi, Radiodiagnosis, New Delhi, University Hospital of Toulouse and Toulouse III Paul Sabatier
India University, Toulouse, France; 10CHU Rennes, Univ Rennes, F-35000, Liver
Email: [email protected] Disease Department, Rennes, France; 11CHU Reims, Department of
Hepato-Gastroenterology, Reims, France; 12University Hospital, Côte de
Background and aims: Budd Chiari Syndrome (BCS) is associated
Nacre, Department of Hepatology and Gastroenterology, Caen, France;
with primary infertility and adverse pregnancy outcomes in affected 13
Department of Hepatology and Gastroenterology, Orleans, France,
females. Scant literature is available on the effect of an endovascular
Orleans, France; 14Centro Hospitalar Universitário do Porto, EpiUnit,
intervention on fertility and the outcome of future pregnancies in
Instituto de Saúde Pública da Universidade do Porto, Porto, Portugal;
these patients. 15
Erasmus University Medical Centre Rotterdam, Department of
Method: In this retrospective analysis, 121 female patients with BCS
Hematology, Rotterdam, Netherlands
attending our liver clinic from 2017 to 2020 were included. Patients
Email: [email protected]
were categorized into three groups- no prior conception (group 1),
any conception before disease onset but before completion of the Background and aims: Since the world-wide COVID19 vaccination
family (group 2), and disease onset post completion of the family efforts, several studies have reported on a rare side effect of ChAdOx1
(group 3). Pregnancy outcomes (live birth, stillbirth, or abortions), nCoV-19 (AstraZeneca) with vaccine-induced immune thrombocyto-
mode of delivery, teratogenicity in the fetus, bleeding risk in the penia and thrombosis (VITT). We aimed to collect consecutive new
mother, decompensation of liver disease, or occlusion of the stent cases of splanchnic vein thrombosis (SVT) or Budd-Chiari Syndrome
during pregnancy were assessed. (BCS) following SARSCOV2 vaccination within the Vascular Liver
Results: BCS was diagnosed before any conception in 58 women Disease Group (VALDIG) network.
(Group 1; median age: 22 years), during or after pregnancy but before Method: This prospective international cohort study started on
completion of family in 39 (Group 2; median age: 27 years) and after 01.05.2021 to include all incident cases of definite VITT (5/5 criteria:
completion of family in 24 women (Group 3; median age: 34 years). onset of symptoms 4–42 days post COVID vaccination, new
Median CTP and MELD scores of the whole cohort were 7, and 12 thrombosis, platelets <150 × 109, positive anti-PF4/HIT ELISA and D-
respectively. The primary infertility rate was 19.8% (24/121). In Group dimer >4000 FEU) or otherwise vaccine-related (<5/5 criteria) SVT or
1: 15 women with primary infertility underwent endovascular BCS. Diagnosis was radiologically confirmed, and onset of symptoms
intervention with 5/15 (33%) women conceiving subsequently, was within 6 weeks after 1st or 2nd SARSCOV2 vaccination. Patients
resulting in 4 live births and 7 abortions. In Group 2: 5 women had with malignancy or cirrhosis were excluded. Statistics were descrip-
developed BCS during pregnancy, and 11 in the postpartum period; tive with frequency (%) and median (range) values. We are presenting
11/39 patients had a history of one or more abortions. Overall, 8/34 our data until 01.11.2021.
(23.5%) patients who underwent endovascular intervention could Results: In total, 22 patients were included from 13 centers with
conceive, resulting in 4/8 (50%) live births. However, no patient median age 47 (21–66) and 46 % females. Median time from
developing BCS during pregnancy was able to conceive subsequently vaccination (AstraZeneca N = 11, Pfizer N = 9, Moderna N = 1,
despite endovascular intervention. Group 3: No patient had any Johnson N = 1) to symptoms was 10 (2–32) and to diagnosis was 16
major complications during past pregnancies. Only one patient days (3–56). Patients presented with abdominal pain (86%), ascites
developed a TIPSS block in the postpartum period. The mode of (41%), fever (32%), elevated AST (35 U/L; 22–20100), ALT (45 U/L; 17–
delivery was vaginal in 88% of cases. No congenital anomaly/major 6928), INR (1.18; 0.88–5.1), D-dimer (6, 570 FEU; 530–63, 000), white
bleeding episodes/decompensation/maternal mortality occurred. blood cell count (10, 7 × 109/L; 4, 2–26) and decreased platelets

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 POSTER PRESENTATIONS
(160 × 109/L; 51–537). Four patients (18%) fulfilled criteria for VIIT. hernias (25.8%, n = 125) while multiple hernias were present in 6.2%
Location of thrombosis was portal vein in 18 (82%), hepatic vein (s) in (n = 30). Using multivariate analysis, male sex (OR 2.727 p < 0.001),
8 (36%), superior mesenteric vein in 15 (68%) and splenic vein in 9 abdominal surgery (OR 2.575, p < 0.001) and disease severity
(41%). Combined SVT-BCS was present in 18%, and concomitant according to the Gigot classification (Type 3 OR 2.853, p < 0.001)
cerebral/pulmonary/deep vein thrombosis was observed in 23%. An were identified as risk factors. Total liver volume was an independent
underlying prothrombotic cause was found in only 5 patients (23%; PLD specific risk factor in the subgroup of patients with known total
myeloproliferative neoplasm, antiphospholipid syndrome, protein S liver volume (OR 1.203, p = 0.001). Patients with multiple hernias
and antithrombin deficiency, Factor V Leiden). Eight patients (36%) were older (62.1 vs 55.1, p = 0.001) and more frequently male (22.0 vs
were admitted to the intensive care unit. Eight patients had intestinal 50.0%, p = 0.001).
ischemia (36%) of whom 5 underwent bowel resection. Patients were
treated with LMWH (64%), DOAC (18%) or VKA (59%). Six patients (3/6
with VIIT) received IVIG and six underwent recanalization proce-
dures. One patient died (no VIIT).
Conclusion: Within 6 months, 22 new cases of BCS or SVT following
SARSCOV2 vaccination were identified in 4 countries. Not all were
AstraZeneca related. Although definite VIIT was relatively rare, most
patients did not have another cause-in contrast to typical SVT or BCS.
Also, these patients presented with extensive multiple site throm-
bosis and high rates of bowel ischemia and ICU admission.
Concomitant extra-abdominal thrombosis, rare in typical BCS or
SVT, was not uncommon. Further results are awaited from this IQR = interquartile range. * N represents the number of hernias in which
expanding cohort. the diameter could be measured in two different directions (laterolateral
and craniocaudal). ** Complex hernia according to Slater criteria; 13 cases
FRI266 were unknown because hernia repair was performed before the imaging.
Abdominal wall hernia is a frequent complication of polycystic
Conclusion: Abdominal wall hernias occur frequently in polycystic
liver disease and associated with hepatomegaly
liver disease with a predominance of umbilical hernias.
Thijs Barten1, Roos-Anne Bökkerink1, Wulphert Venderink2,
Hepatomegaly is a clear disease-specific risk factor.
Tom Gevers1,3, Richard ten Broek4, J.P.H. Drenth1. 1Radboudumc,
Department of Gastroenterology and Hepatology, Nijmegen, FRI267
Netherlands; 2Radboudumc, Department of Radiology, Nijmegen, MR-derived metrics have utility in identifying paediatric patients
Netherlands; 3Maastricht UMC, Department of Gastroenterology and with stable autoimmune hepatitis
Hepatology, Maastricht, Netherlands; 4Radboudumc, Department of Piotr Pawliszak1, Elizabeth Shumbayawonda2, Ję drzej Sarnecki1,
Surgery, Nijmegen, Netherlands Paulina Opyrchał1, Kamil Janowski3, Piotr Socha3,
Email: [email protected] Małgorzata Wozn ́ iak3, Elżbieta Jurkiewicz1. 1Children’s Memorial
Background and aims: Polycystic liver disease is related to Health Institute, Radiology, Warsaw, Poland; 2Oxford, Oxford, United
hepatomegaly which causes an increased mechanical pressure on Kingdom; 3Children’s Memorial Health Institute, Gastroenterology,
the abdominal wall. This may lead to abdominal wall herniation. We Warsaw, Poland
set out to establish the prevalence of abdominal wall hernia in Email: [email protected]
polycystic liver disease and explore risk factors. Background and aims: Paediatrics with autoimmune hepatitis (AIH)
Method: In this cross-sectional cohort study we assessed the are monitored using liver biochemistry and histology, however, liver
presence of abdominal wall hernias from polycystic liver disease biopsy is invasive, expensive and carries the risk of pain and bleeding.
patients with at least 1 abdominal computed tomography or Non-invasive imaging techniques (NITs) such as elastography and
magnetic resonance imaging scan. Abdominal wall hernia presence multiparametric MRI are showing increasing utility in supporting
on imaging was independently evaluated by two researchers. Data on patient management and disease stratification, but have never been
potential risk factors were extracted from clinical files. compared head-to head in children. The aim of this study was to
Results: We included 484 patients of which 40.1% (n = 194) had an investigate the utility of imaging markers to stratify those with stable
abdominal wall hernia. We found a clear predominance of umbilical from those with active disease and thus identify those who may not

Figure: (abstract: FRI267): Diagnostic accuracy of individual imaging markers to identify AIH patients with stable disease.

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POSTER PRESENTATIONS
require a biopsy or in whom a it may be delayed leading to 1000 ng/ml (0.08–15.75 μM) for CP-Cu, direct NCC, LBC, and 5.00–
improvement in cost-effectiveness of AIH patient management. 800 μg/ml (0.03–5.97 μM) for CP-protein. The mean [95% confidence
Method: N = 36 with biopsy-confirmed AIH (14 ± 3 years) and N = 16 interval] for the CP-Cu:CP ratio was 4.68 [4.35, 5.00] in healthy
healthy controls [HC; 14 ± 2 years) underwent non-invasive imaging volunteers and 4.09 [3.36, 4.82] in patients with WD, both being
to obtain liver stiffness (LS; magnetic resonance elastography), spleen below the assumed ratio of 6.
stiffness (SS) and corrected T1 (cT1). All AIH patients also underwent
a liver biopsy. Kruskal-Wallis test was used to compare imaging
markers between HC and AIH patients, as well as those with active vs
stable disease. Correlations between NITs and histological scores
were performed using Spearman’s rank tests. Stable disease was
defined as having both lobular and portal inflammation ≤1 and Ishak
fibrosis ≤2. Discrimination between active and stable disease using
NITs was investigated using area under the receiver operator
characteristic curve (AUC).
Results: Compared to HC, AIH patients had higher cT1 (827 ms vs
756 ms; p < 0.001) and LS (3 kPa vs 2.6 kPa; p = 0.031) but not SS
(4.9 kPA vs 5.6 kPA, p = 0.068). N = 18 had stable disease and lower
mean cT1 ( p = 0.011), LS (p = 0.017) and SS ( p = 0.048) compared to
those with active disease. cT1 correlated with fibrosis (r = 0.37; p =
0.049), lobular (r = 0.42, p = 0.025) and portal inflammation (r = 0.5, p
= 0.005), LS (r = 0.42, p = 0.007) and SS (r = 0.43, p = 0.028). LS Figure: Method scheme. (a) overview of assay procedure (TTM, the active
correlated with fibrosis (r = 0.47, p = 0.005), SS (r = 0.5, p = 0.004) moiety of ALXN1840 which can bind to Cu and Albumin); (b)
and portal inflammation (r = 0.37, p = 0.029). For predicting disease Immunocapture steps to obtain direct NCC, CP-protein, and CP-Cu frac-
activity, cT1 had AUC:0.77 (0.6–0.94), SS had AUC:0.75 (0.54–0.96) tions; (c) Chelation and filtration steps to isolate LBC.
and LS had AUC:0.74 (0.57–0.9).
Conclusion: Conventional calculated NCC is inaccurate and cannot be
Conclusion: Those with active AIH have higher fibroinflammation,
used for therapeutic guidance for WD. A novel method was
liver and spleen stiffness compared to those with stable AIH. NITs
developed that utilizes an immunocapture step and subsequent
have utility in identifying paediatric patients with stable disease who
quantification of various fractions, including CP-Cu, direct NCC, LBC,
may not benefit from invasive liver biopsy. Further work exploring
and CP-protein. Validation data met defined acceptance criteria in
the utility of these NITs in the AIH clinical pathway is warranted.
terms of precision, accuracy, selectivity and stability. The assay is
FRI268 precise and reproducible and is valuable for accurate quantification of
Development and validation of a novel ICP-MS method to quantify CP-Cu:CP-protein ratio, direct NCC and LBC, which may benefit WD
different copper species in human plasma from patients with therapy development.
Wilson disease
FRI269
Tao Liang1, Haiting Zhang2, Linwen Zhang1, Scott Moseley1, Ping Guo2,
Quantitative magnetic resonance cholangiopancreatography
Meng Chen1, Tracey Hall1, Ming Li1, Eugene Swenson1, Wei-Jian Pan1,
identifies features of ductal disease change in primary sclerosing
Brian Meltzer1, Ryan Pelto1, Mark Ma1. 1Alexion, AstraZeneca Rare
cholangitis: a prospective observational cohort study
Disease, Boston, United States; 2Frontage Laboratories Inc., Exton, United
Palak Trivedi1,2,3,4, Katherine Arndtz1,2,3, Nadir Abbas1,2,3,
States
Alison Telford5, Liam Young5, Rajarshi Banerjee5, Peter Eddowes1,2,6,7,
Email: [email protected]
Kartik Jhaveri8, Gideon Hirschfield1,2,3,9,10. 1National Institute of
Background and aims: Wilson disease (WD) is a rare autosomal Health Research (NIHR) Birmingham Biomedical Research Centre (BRC),
recessive genetic disorder. Functional mutation of ATP7B causes Centre for Liver and Gastrointestinal Research, University of Birmingham,
inadequate loading of copper (Cu) into ceruloplasmin (CP) and Birmingham, United Kingdom; 2Institute of Immunology and
defective Cu excretion into bile, resulting in Cu accumulation in liver Immunotherapy, University of Birmingham, Birmingham, United
and other organs. Currently, WD treatment monitoring lacks reliable Kingdom; 3Institute of Applied Health Research, University of
and fully validated bioanalytical methods. The calculated non-CP Cu Birmingham, Birmingham, United Kingdom; 4Liver Unit, University
(NCC) method assumes a CP-Cu:Cp ratio of 6:1 and can yield negative Hospitals Birmingham, Birmingham, United Kingdom; 5Perspectum Ltd,
NCC values, which are biologically implausible. A direct assay is Oxford, United Kingdom; 6NIHR Nottingham BRC, University of
needed to monitor NCC, especially for patients treated with an Nottingham, Nottingham, United Kingdom; 7Nottingham University
investigational Cu-binding agent, ALXN1840 (bis-choline tetrathio- Hospitals NHS Trust, Nottingham, United Kingdom; 8Joint Department of
molybdate), which mobilizes tissue Cu, contributing to a non- Medical Imaging, University Health Network, University of Toronto,
bioavailable pool of circulating Cu. Toronto, Canada; 9Toronto Centre for Liver Disease, University Health
Method: A novel method utilizing immunocapture of CP, followed by Network, Toronto, Canada; 10Department of Medicine, University of
chelation and filtration to isolate different Cu fractions subject to ICP- Toronto, Toronto, Canada
MS analysis (Figure) was developed to fractionate and directly Email: [email protected]
quantify multiple Cu species from human plasma. It permits
Background and aims: Primary sclerosing cholangitis (PSC) is a
measurement of CP-protein via LC-MS method and Cu species
chronic, progressive liver disease, characterised by multi-focal
including CP bound Cu (CP-Cu), direct NCC, and labile bound Cu
stricturing throughout the biliary tree. Biomarkers of parenchymal
(LBC) via one workflow. Methods were validated for precision,
fibrosis are widely used for risk stratification. However there is a need
accuracy, selectivity and stability following the FDA guidance for
to better characterise the extent of ductal disease involvement, its
Bioanalytical Method Validation. A monoclonal anti-CP antibody was
evolution over time, and the utility of quantitative biliary metrics for
screened and selected for long-term assay use. Samples from healthy
monitoring disease progression longitudinally. This study aimed to
volunteers and from patients with WD were assessed for the Cu
evaluate the utility of quantitative MRCP (MRCP+) in characterising
concentration in the CP fraction and the CP-Cu:Cp ratio.
Results: Full validations were successfully performed for each Cu
fraction as well as CP-protein and showed a linear range from 5 to

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 POSTER PRESENTATIONS
the extent of ductal disease involvement and monitor changes over 1 the condition. Treatment by therapeutic phlebotomy reduces
year in patients with stable biochemical and liver fibrosis readings. morbidity and mortality.
Method: Patients ( pts) with PSC were prospectively recruited for Method: This study aimed to identify factors associated with
standardized heavily T2-weighted MRCP imaging on a Siemens Verio mortality in HH patients attending a Hemochromatosis service.
3 T system at baseline and 1-year thereafter. Scans were processed Results: 1043 patients with HH were identified; 65% were male and
with MRCP+ to enhance and quantify tubular structures using multi- 35% were female. Fatigue was the most common presenting
scale Hessian analysis, gradient vector flow analysis, an intelligent complaint (37%), with family history (22%), incidental finding of
path search algorithm and novel duct modelling algorithms. The 92 raised iron studies (16%) and screening programs (13%) being other
metrics generated by MRCP+ were reduced to 24 metrics expected to common causes of referral to the service. Homozygosity for C282Y
have clinical significance by an expert hepatopancreatobiliary was the most common HFE genetic mutation in this cohort (68%)
radiologist. Changes in selected metrics over time were analyzed with compound HFE heterozygosity accounting for 26%.
using linear mixed-effects models assuming patients as random Median Ferritin at diagnosis was 332 ug/L (range 22–4655 ug/L).
effects. Mean Transferrin saturation at diagnosis: 68% (SD ± 17).
Results: Non-cirrhotic pts with PSC were enrolled (n = 27; median At the time of assessment, 0.03% (30/1043) of patients had died, with
age 45 yr, 70 % male) with a baseline PSC Mayo Risk Score −0.93 (IQR a median follow up time of 10 years (range 0.06–26). Of those that
−1.2–0.3), ALP 142 iU/L (IQR 84–281), ALT 51 iU/L (IQR 26–91), and died, 70% were male, 43% were homozygous for C282Y, and 36% were
transient elastography score of 7.7 kPa (IQR 6.2–11.5). Intra- and compound heterozygotes. Median ferritin at diagnosis was 265 ug/L
extra-ductal involvement was seen in 92% and 36% pts with median (dead) vs 264 ug/L (alive). Median age at diagnosis was significantly
modified Amsterdam cholangiographic score (MAS) of 2 (IQR 2–2) higher in those that died, 63.9 yrs vs 49.1 yrs for those alive at follow
and 0 (IQR 0–2), respectively. Over a median 371-day follow-up (IQR up ( p < 0.0001). No significant difference was observed between
365–442), 67% pts manifested features of ductal disease change, groups based on gender, HFE genotype, or serum ferritin at diagnosis.
evidenced by an increase in the total number of strictures (n = 15, p = Conclusion: In a large sample of patients with patients with
0.036, the total length of strictures (n = 17, p = 0.030), the total Haemochromatosis, age at diagnosis appears to be associated with
stricture burden (n = 17; p = 0.012), or a combination of metrics, death. Further investigation is warranted to detail the causes of death,
which showed a significant dependence on time (Figure 1). Serum and to determine whether HH screening in an at-risk population
ALP ( p = 0.51), ALT ( p = 0.40), bilirubin ( p = 0.39), liver stiffness values would reduce morbidity and mortality.
(transient elastography, p = 0.07) and biliary strictures assessed using
MAS ( p = 0.80) did not change significantly over time. FRI271
Development of Hepatoblastoma organoids as a patient-derived
ex-vivo system
Laura Zanatto1, Paula Cantallops Vilà1, Silvia Ariño Mons1,
Beatriz Aguilar-Bravo1, Juan Carrillo2, Laura Royo2, Joan Pallares1,
Montserrat Domingo-Sàbat2, Alvaro del Rio2, Juanjo Lozano3,
Francisco Hernandez Oliveros4, Laura Guerra5,
Barbara Torres Guerola6, Constantino Sábado7, Gabriela Guillén8,
Marta Garrido9, José Antonio Salinas10, Moira Garraus11,
María Esther Llinares12, Silvia Affo1, Carolina Armengol2,
Pau Sancho-Bru1. 1Insititut d’Investigacions Biomed ̀ iques Augustí Pi I
Sunyer (IDIBAPS), Liver Cell Plasticity and Tissue Repair, Barcelona,
Spain; 2Health Sciences Research Institute Germans Trias i Pujol (IGTP),
Childhood Liver Oncology Group (c-LOG), Badalona, Spain; 3Centro de
Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas,
Barcelona, Spain; 4University Hospital La Paz, Pediatric Surgery
Department, Madrid, Spain; 5University Hospital La Paz, Pathology
Department, Madrid, Spain; 6University Hospital La Fe, Medical
Oncology Department, Pediatric Oncology Department, Valencia, Spain;
7
Hospital Vall d’Hebron, Pediatric Oncology Department, Barcelona,
Spain; 8Hospital Vall d’Hebron, Pediatric Surgery Department,
Barcelona, Spain; 9Hospital Vall d’Hebron, Pathology Department,
Barcelona, Spain; 10Hospital Universitari Son Espases, Division of
Conclusion: When quantitative imaging is reviewed one year apart,
Hematology-Oncology, Department of Pediatrics, Palma de Mallorca,
ductal disease change is apparent in the majority of pts with PSC, in
Spain; 11Hospital Sant Joan de Déu, Pediatric Cancer Center Barcelona,
the absence of significant variation in liver biochemistry or fibrosis
Barcelona, Spain; 12Instituto Murciano de Investigación Biosanitaria
values. Larger scale validation, alongside robust clinical outcome
(IMIB), Pediatric OncoHematology Service, Clinic University Hospital
data, is essential to develop quantitative MRCP+ as a radiological
Virgen de la Arrixaca, Murcia, Spain
toolkit for future PSC clinical trials.
Email: [email protected]
FRI270 Background and aims: Hepatoblastoma (HB), the main pediatric
Age at diagnosis is associated with mortality in patients with liver tumor, is a rare disease with few therapeutic options and
hereditary hemochromatosis increasing incidence. With chemotherapy being the only effective
Clare Foley1, Sophie Diong2, Fiona Colclough2, John Ryan2. 1Beaumont treatment, survivors are doomed to suffer serious side effects and
Hospital, Hepatology, Gastroenterology, Dublin, Ireland; 2Beaumont new therapeutic options are urgently needed. The lack of suitable
Hospital, Dublin, Ireland models has strongly compromised the investigation of this pediatric
Email: [email protected] tumor. Here we hypothesize that patient-derived organoids may
Background and aims: Hereditary Haemochromatosis (HH) a represent a novel tool to explore the mechanisms involved in HB
disorder of iron metabolism, is the most common autosomal development and to design new therapeutic options.
recessive disorder in Caucasians, with Ireland having the highest Method: Parental tumor (T) and non-tumor (NT) tissues collected
prevalence in the world. Despite this, no formal screening exists for from different Spanish hospitals were used to generate a collection of

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POSTER PRESENTATIONS
patient-derived organoids. Organoids and primary tissues were 57), without any clinical signs of portal hypertension, in only one
characterized through: (i) RT-qPCR to analyze the mutation status; patient FIB-4 score was compatible with advanced liver disease.
(ii) immunofluorescence analysis to evaluate the expression of HB When comparing patients with PSVD to patients with any other liver
biomarkers; (iii) transcriptmic studies by performing total- and etiology, we found no difference in gender, age, BMI, smoking habit,
small- RNA sequencing. FIB-4, GGT, albumin and bilirubin values.
Results: Fourteen stable organoid lines have been successfully Conclusion: Liver histology in patients with isolated elevated GGT
generated from T and NT tissues using a specific isolation protocol levels is useful as it allows to diagnose chronic liver conditions
and have been grown in expansion media enriched in growth factors. associated with a significant impact on survival. The high rate of
T- and NT-organoids present differences in morphology and doubling patients with histological findings compatible with PSVD in the
time, with T organoids growing slower and in darker small structures absence of signs of portal hypertension, requires careful assessment
compared to the NT organoids. Moreover, the T-organoids present the on how to manage these patients in the long term.
same mutations of the primary tissues. Additionally, T- and NT-
organoids show different gene and protein expression of markers FRI273
associated with hepatocyte- (HNF4) and progenitor-phenotype Plasma metabolomics and machine learning characterizes
(KRT19, EpCAM), as well as HB-related genes, such as DLK1; and metabolite signature capable of segregating patients with poor
cytoplasmic localization of both GS and β-catenin. Interestingly, outcome in pediatric cirrhosis
principal component analysis of total RNA and small RNA transcrip- Babu Mathew1, Gaurav Tripathi1, Vipul Gautam2, Akhilesh Saini1,
tome revealed that HB organoids maintain general features of the Manisha Yadav1, Nupur Sharma1, Vasundhra Bindal1,
tumor of origin. Finally, functional analysis has revealed conserved Bikrant Bihari Lal2, Vikrant Sood2, Rajeev Khanna2, Jaswinder Maras1,
pathways between T- and NT-primary tissues and T- and NT- Seema Alam2. 1Institute of Liver and Biliary Sciences, Molecular and
organoids, among them epigenetic regulation, proliferation, Wnt Cellular Medicine, New Delhi, India; 2Institute of Liver and Biliary
activaction and altered metabolism, indicating the maintenance of Science, Pediatric Hepatology, New Delhi, India
tumor features by organoids. Email: [email protected]
Conclusion: In conclusion, we have developed a new patient-derived
Background and aims: Pediatric cirrhosis is a life-threatening illness
ex vivo 3D system mimicking HB features, including specific gene and
with high mortality up to 40%. Primary causes of cirrhosis in children
protein expression. Specifically, these data suggest that HB-derived
are biliary atresia, genetic-metabolic diseases, autoimmune hepatitis,
organoids are a reliable model to investigate this poorly understood
Wilson’s disease and others. Development of cirrhosis in children’s
pediatric tumor towards the development of personalized
predisposes them to early development of sepsis and/or poor
treatments.
outcome. Early diagnosis of cirrhosis, sepsis and/or poor outcome
FRI272 in such patients may increase survival rate; therefore, development of
High rates of histological findings compatible with porto- new diagnostic methods is crucial. We investigated whether
sinusoidal vascular disease in patients with constantly elevated metabolomics and machine learning (ML) approaches could segre-
gamma-glutamyl transferase levels undergoing a liver biopsy gate patients with poor outcome (sepsis/mortality) in pediatric
cirrhosis at baseline.
Nicola Pugliese1, Luca Di Tommaso1, Roberto Ceriani1,
Method: Plasma metabolomics was studied using ultra-high-
Ludovico Alfarone1, Elisabetta Mastrorocco1, Maria Terrin1,
performance liquid chromatography and high-resolution mass-
Virginia Solitano1, Francesca Colapietro1, Chiara Masetti1, Ana Lleo1,
spectrometry to identify patients with poor outcome (sepsis/
Luigi Terracciano1, Alessio Aghemo1. 1Humanitas Research Hospital,
mortality) in pediatric cirrhosis at baseline. Altogether, 154 pediatric
Cascina Perseghetto, Italy
patients were analysed of them, 54 in derivative [40 Cirrhotics (C) and
Email: [email protected]
14 Non-cirrhotics (NC) ] and 100 in validation cohort [75 C, 25 NC].
Background and aims: Isolated elevations in gamma-glutamyl Differentially expressed metabolites (DEM) with highest AUC and
transferase (GGT) levels are commonly found in patients referred to lowest mean decrease in accuracy were identified in cirrhotics, sepsis
liver specialists, however their clinical impact is unknown. Data on and were correlated with the severity (PELD score) and outcome
the histological findings in these patients are scarce. (mortality) in pediatric patients.
Method: All consecutive patients who underwent a liver biopsy Results: Of the 762 annotated features (metabolomic/biochemical/
between March 1st, 2015 and December 1st, 2020, in our Liver Unit spectral databases), at baseline 120 plasma metabolites (Up-109,
for isolated and persistent (at least 2-fold ULN for three tests within Downregulated-11) discriminated Cirrhotics from Non-Cirrhotics in
12 months) elevation of GGT value were retrospectively analyzed for pediatric patients (FC > 1.5, p < 0.05). Cirrhotics documented signifi-
clinical and histological features. Excluded were patients with cant increase in Tryptophan metabolism, steroid hormone biosyn-
concomitant ALT or AST elevation, intake of Hepato-toxic drugs or thesis, purine metabolism and others ( p < 0.05). Most importantly
over the counter medications, alcohol intake >20 g/day and metabolic high L-Formylkynurenine (546 Folds), 3-Hydroxy-1H-quinolin-4-one
associated fatty liver disease (MAFLD). Data about age, gender, body (20 Folds), Cortisone (18 Fold), 12-Hydroxydodecanoic acid (12
mass index (BMI), comorbidities (including findings compatible with Folds), L-Isoleucine (11 Folds), Hypoglycine-A (5 folds),
portal hypertension), smoking habit and disease severity (APRI and Aminopropylcadaverine (5 Folds), 2, 3, 4, 5-Tetrahydrodipicolinate
FIB-4), were collected. All liver biopsies were blindly reviewed by 2 (3 Folds) and others segregated Cirrhosis from Non-Cirrhosis ( p <
experts in liver pathology. 0.05). Additionally, plasma L-Formylkynurenine, 3-Hydroxy-1H-
Results: During the study period a total of 640 patients performed a quinolin-4-one, 12-Hydroxydodecanoic acid, L-Isoleucine and
liver biopsy. 29 patients (4.5%) met the inclusion criteria and were Cortisone segregated sepsis and non-survivors (FC > 2, p < 0.05,
enrolled. Most of the patients were males (19/29, 65.5%) and their AUC > 0.8). In validation cohort, baseline plasma L-
mean age was 49.7 ± 11.4 years (28–73). The mean BMI was 24.5 ± Formylkynurenine; hazard-ratio (HR) of 3.5 (1.2–5.6), and
2.97 (18.8–30) and only two patients presented FIB-4 suggestive of Cortisone; HR:3 (1.5–5.2) showed high reliability [AUC > 0.95 (0.91–
advanced liver disease. The histological findings were compatible 0.97)] for predicting non-survivors and correlated with PELD score
with porto-sinusoidal vascular liver disease (PSVD) in 13/29 (45%) (r2 > 0.5, p < 0.05). L-Formylkynurenine (9.5 FC), and Cortisone (9 FC)
patients, hepatic sarcoidosis in 3/29, non-alcoholic steatohepatitis cut-off reliably segregated non-survivors (log-rank p < 0.01) and
(NASH) in 3 and congenital hepatic fibrosis (CHF) in 3. Histology did showed <96% accuracy, <95% sensitivity and <95% specificity using
not allow a definite diagnosis in 6/29 (21%) patients. Patients with Random Forest-based Machine-Learning model.
PSVD were male in 10/12 (%), with a mean age of 47 ± 10.9 years (28–

S528 Journal of Hepatology 2022 vol. 77(S1) | S389–S664

 POSTER PRESENTATIONS
Using PBC Foundation’s App, we collected insights from Primary
Biliary Cholangitis patients with pruritus, focussing on what may
affect patient’s daily experience of itch.
Method: An ongoing itch survey, live for over 6 months, was cross
referenced with a previous survey exploring demographics and
treatments. Due to cross-referencing, the number of respondents
varies between questions. The main survey has 455 respondents. We
defined mild, moderate and severe itch as at least 1, 4 and 7
respectively, on a numerical scale of 0 (no itch) to 10 (worse itch).
Results: Overall, similar to other studies 73% respondents suffer from
itch. Over half of those itch daily and 3 in 4 patients have moderate to
severe itch on their worst day.
In those aged <50 itch occurred more likely than in those >50 yr (77%
vs 64%) and was more likely to be present daily (53% vs 44%). Itch
occurred in the highest frequency in those within the first 5 yr of
Conclusion: Plasma metabolite L-Formylkynurenine (>9.5 FC), and diagnosis (76%) with the lowest occurring in those >20 yr (45%).
Cortisone (>9 FC) can reliably predict cirrhosis, sepsis and poor Looking at disease modifying treatments: itch, daily itch, normal day
outcome in pediatric patients. severity and worst day severity for those on obeticholic acid were no
worse than other therapies.
FRI274
Information was only available for those taking cholestyramine,
Experience of cholestatic pruritus emphasized by patients with
antihistamines or emollients and shows that itch is not present daily
PBC: results from the PBC Foundation app survey
while on these therapies suggesting potential benefit. However itch
Chris Mitchell1, James Neuberger2, Terri Kim3, Andrew Yeoman4, on the worst day was almost exclusively severe and only partially
Robert Mitchell-Thain1. 1PBC Foundation, Edinburgh, United Kingdom; ameliorated by therapy.
2
Birmingham Community Healthcare NHS Foundation Trust, United Conclusion: This study has a number of limitations, e.g. cross
Kingdom; 3Escient Pharmaceuticals, San Diego, United States; 4Royal referencing different surveys taken at different times, and the risk of
Gwent Hospital: Opthalmology, United Kingdom only itch-affected patients engaging. These surveys show that whilst
Email: [email protected] some of the treatments may decrease the incidence of pruritus on a
Background and aims: Pruritus is a common symptom of cholestatic daily basis, severity of pruritus on a normal day is only slightly
liver disease and treatment has limited efficacy. Patients with improved compared to the severity on the worst day. Pruritus can
pruritus often suffer from intense itch, associated stress, and a affect anyone within the PBC patient population and does so often
negative effect on overall quality of life, including mental health and with profound effect.
issues.

Table: (abstract: FRI274).

Survey results

Moderate to
severe itch on Modest to
PBC management Respondents normal day severe itch on
medication N who itch (%) Itch daily (%) (%) worse day (%)
Ursodiol 307 69 50 60 85
Obeticholic acid 118 67 52 64 86
Bezafibrate 153 70 49 54 75
Fenofibrate 16 44 30 0 100
Itch remedy
Cholestyramine 312 87 52 90 99
Antihistamines 390 90 50 76 92
Topical emollients 411 91 49 66 88
Prednisone 42 71 59 62 75
Age in years
21–30 1 100 100 100 100
31–40 8 75 67 67 100
41–50 21 76 47 61 83
51–60 44 63 55 71 88
61–70 35 63 31 44 74
>70 9 78 43 71 100
Years diagnosed
<1 22 68 44 63 78
1–2 17 59 36 37 67
3–5 19 100 37 53 83
6–10 21 67 57 67 86
11–15 14 71 70 70 100
16–20 14 57 55 50 78
21–25 10 40 30 40 40
>25 1 100 0 100 100
Sex
Female 315 72 52 60 80
Male 11 55 45 33 55

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S529

POSTER PRESENTATIONS
FRI275 infectious. Clinical metagenomics (CMg) is a new technique based on
Cancer risk in acute hepatic porphyria: a nationwide matched sequencing of nucleid acids allowing the identification of micro-
cohort study in 1, 245 individuals organisms in an exhaustive manner. Our aim was to evaluate the
Mattias Lissing1,2, Daphne Vassiliou3,4,5, Ylva Floderus4,6, performance of CMg for the diagnosis of non-elucidated liver
Jacinth Yan7, Hannes Hagström1,2, Eliane Sardh3,4,5, Staffan Wahlin1,2. diseases.
1
Karolinska University Hospital, Dept of Upper GI Diseases, Sweden; Method: All patients seen between 2019 and 2021 in a single tertiary
2
Karolinska Institutet, Dept of Medicine, Huddinge, Sweden; 3Karolinska centre for a non-elucidated liver disease were included. Inclusion
University Hospital, Dept of Endocrinology, Sweden; 4Karolinska criteria were elevated biochemical liver tests with no definite
University Hospital, Centre for Inherited Metabolic Diseases (CMMS), diagnosis after a comprehensive work-up including a liver biopsy.
Porphyria Centre Sweden, Sweden; 5Karolinska Institutet, Dept of Patients with known CLD could be included if their features were not
Molecular Medicine and Surgery, Sweden; 6Karolinska Institutet, Dept of consistent with the etiology. The cut-off of 6 months discriminated
Medical Biochemistry and Biophysics, Sweden; 7Karolinska Institutet, acute and chronic profiles. Shotgun metagenomics was performed on
Division of Biostatistics, Institute of Environmental Medicine, Sweden each liver biopsy specimen with the aim to detect unexpected
Email: [email protected] microorganisms.
Results: 48 patients (median age: 49, male: 58%) were included.
Background and aims: The acute hepatic porphyrias (AHP) are Their clinical presentations consisted of acute cytolysis with or
associated with a high risk of hepatocellular carcinoma (HCC). without jaundice (n = 9, 19 %, median ALT: 284 IU/l), acute cholestatis
Patients with AHP-associated liver cancer typically do not have a or mixed pattern (n = 19, 40 %, median ALP: 225 IU/L), chronic
well-defined underlying liver diseases or cirrhosis. Although the cytolysis (n = 8 , 16.7 %, median ALT 166 IU/L) and chronic cholestasis
carcinogenic mechanisms are unknown, a strong association (n = 12, 25%, median ALP: 146 IU/L). 20 patients (42%) had immuno-
between HCC and biochemical AHP-activity with elevated porphyrin suppression due to solid organ transplantation (n = 9, 19%), HIV
precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG) infection (n = 6, 13%) and hematopoietic cancer (n = 5, 10%). Results of
has been established. The cancerogenic potential of ALA and findings CMg were negative in 36 (75%), false positive due to contamination in
of increased cancer risks in small cohort studies have led to an 3 (6%), and positive in 9 (19%) patients. In 7 patients, CMg results
assumption that AHP is a risk factor for cancer in general. Risk allowed an etiologic diagnosis that changed the clinical management.
estimates are however uncertain, and little is known about how Pathogens identified were adenovirus in one patient presenting with
biochemical activity affects the risk. Our aim was to assess the risks of acute hepatitis, HCV in one seronegative liver-transplant recipient
non-hepatic cancers in correlation to biochemical activity in the with recently acquired infection, HBV in one patient with unex-
largest AHP cohort assembled to date. plained cytolysis and low HBV DNA, HDV in 2 seronegative HBsAg (+)
Method: All patients in the Swedish porphyria registry with verified patients, Mycobacterium spp in an HIV-infected patient with
AHP were included and matched 1:10 to reference individuals from unexplained granulomatosis, and Shingobium spp in a cirrhotic
the general population by age, sex and municipality. Data on incident patient presenting with uncommon ACLF. Additionally, 2 patients had
cancers were collected from the national cancer and cause-of-death positive results that were considered as putative cofactors. Pathogens
registries. Overall cancer incidence and incidence of a predetermined were EBV in one HIV-infected patient with tuberculosis, and TTV in
set of specific cancers were compared by incidence rate ratio. Data on one patient on immunotherapy for hematopoietic cancer. Taking the
biochemical disease activity based on maximal urinary PBG were whole population, a definite diagnosis was eventually made after a
used to assess the correlation between biochemical AHP activity and comprehensive work-up combined to follow-up in 35 patients
cancer risk. including 7 infectious diseases diagnosed by CMg (20%), and 13
Results: We identified 1, 245 patients with AHP between 1987 and patients remained with no definite diagnosis.
2015 with a median follow-up of 19 years. Health registries identified Conclusion: CMg performed on liver tissue is technically feasible and
150 AHP-subjects (12.2%) with non-hepatic cancer, similar to 1607 may bring etiologic diagnostic in patients with non-elucidated acute
(13.3%) in the matched reference population (n = 12, 367). or chronic liver disease.
Preliminary results indicate that AHP patients have a higher risk of
kidney cancer 0.8% (n = 10) vs. 0.2% (n = 27) in the matched reference FRI277
population (p < 0.001), confirming findings in previous smaller Accumulation of molybdenum in major organs following chronic
cohorts. The risks of other common forms of cancer are however oral administration of bis-choline tetrathiomolybdate in Sprague
not significantly different in patients with AHP compared to the Dawley rats
reference population. More detailed risk estimates regarding each Kharmen Billimoria1, Timothy Morley2, Maria Estela del Castillo3,
cancer type, combined with subgroup analysis based on biochemical Stanislav Stekopytov3, Heidi Goenaga-Infante1, John Foster4. 1LGC,
AHP-activity will be presented at the conference. National Measurement Laboratory, Teddington, United Kingdom;
Conclusion: In addition to the increased risk of hepatocellular 2
Advotox, Harrogate, United Kingdom; 3LGC, National Screening
carcinoma, patients with AHP have an increased risk of kidney cancer. Laboratory, Teddington, United Kingdom; 4ToxPath Sciences Ltd,
Preliminary results have not identified increased risks for other non- Congleton
hepatic cancers. Email: [email protected]
FRI276 Background and aims: Molybdenum (Mo) is an essential dietary
Innovative approach using clinical metagenomics for the element, functioning as a cofactor to activate essential enzymes
diagnosis of non-elucidated liver disease including sulphite, aldehyde and xanthine oxidases. Bis-choline
Anna Sessa1,2, Christophe Rodriguez3, Julien Calderaro1, Slim Fourati1, tetrathiomolybdate (BC-TTM) is under development as a therapeutic
Giuliana Amaddeo3, Jean-Michel Pawlotsky1, Vincent Leroy3. 1APHP, copper chelating agent for Wilson Disease with doses administered
Hopital Henri Mondor, Hepatology, Créteil, France; 2Henri Mondor ranging from 15 to 60 mg/day (equivalent to 0.2 to 0.9 mg/kg/day in a
Hospital, Hepatology, Créteil, France; 3APHP, Hopital Henri Mondor, 70 kg man). In a rat preclinical model (average bodyweight of 250 g),
Hepatology, Créteil, France this would equate to a range of 0.8 to 3.6 mg/kg. The aim of this study
Email: [email protected] was to determine if chronic administration of BC-TTM is associated
with accumulation of molybdenum in major organs of a non-WD
Background and aims: Diagnostic of acute and chronic liver diseases animal model and if tissue deposits of this metal are associated with
(CLD) may be challenging when main etiologies are absent. Liver
haematological and biochemical abnormalities.
histology usually provides hints but often fails to accurately identify
the etiologic factor that can be toxic, genetic, auto-immune or

S530 Journal of Hepatology 2022 vol. 77(S1) | S389–S664

 POSTER PRESENTATIONS
Method: Sprague Dawley (SD) rats were randomised to 3 groups of 12 measurement (LSM), and provides a measure of hepatic steatosis, the
[control, 15 mg/kg (low), 60 mg/kg (high)] and the BC-TTM was dosed Controlled Attenuation Parameter (CAP).
by single oral gavage each day at volume of 5 ml/kg for 3 months. This Our aim is to assess the prevalence of liver fibrosis and steatosis in
drug exposure was equivalent to 3.75 to 15 mg/day in humans for AATD patients, using transient elastography.
nine years. Blood samples for clinical monitoring were taken at Method: Clinical data along with TE measurement was obtained on
baseline, monthly and prior to euthanasia. Laser ablation inductively adult patients attending a dedicated AATD at our centre over a 4-
coupled plasma time-of-flight mass spectrometry (LA-ICP-ToF-MS) is month period (July–October 2021). LSM cutoffs used were >7.1 kPa
an imaging technique used to confirm and spatially resolve the for fibrosis, and >10 kPa for advanced fibrosis/cirrhosis
elemental distribution within a tissue. Tissue samples from major Results: 80 patients were recruited; TE failed on 4 patients; 48 (60%)
organs were prepared for conventional histopathology and LA-ICP- were female.
ToF-MS, to produce maps of Mo accumulation, quantified using a 39/80 (48%) were homozygous PiZZ, 24/80 PiMZ (30%), 12 PiSZ and 4
novel calibration strategy. were PiSS.
Results: Animals tolerated medication and no adverse clinical 29/76 (38%) had LSM >7.1 KPa; of these 12 (16%) had LSM>10 KPa. Of
observations were made during the study. Dose dependent changes the patients with advanced fibrosis, 8 were PiZZ, 2 were PiMZ and 1
included increasing pigmentation of phagocytic and epithelial cells each of PiSZ and PiMS. 16/39 (41%) PiZZ had evidence of fibrosis; 9
within each organ using conventional histopathological techniques PiMZ (37.5%) had evidence of fibrosis, but only 2 had advanced
were observed. However, data from LA-ICP-ToF-MS (Figure shown is fibrosis.
from liver and brain) shows scaled spatial distribution of molyb- For PiZZ homozygotes, the median LSM was 6.3 kPa, and 6.25 kPa for
denum deposits by concentration, increasing from blue to red. This heterozygotes (PiMZ/PiSZ); there was no significant difference in LSM
accumulation was not associated with either biochemical or between heterozygotes and homozygotes (Mann-Whitney U test, p =
haematological abnormalities. 0.84).
The median CAP for homozygotes PiZZ was 252 dB/m, and for
heterozygotes (PiMZ/PiSZ) was 282.5 dB/m; there was no statistical
significance between the 2 groups (Mann-Whitney U test p = 0.128)
6/12 (50%) individuals with advanced fibrosis were obese (BMI
>30 kg/m2). In total 17 out of 29 (59%) patients with evidence of
fibrosis were either overweight or obese. Of the 29 individuals found
to have liver fibrosis by TE, only 6 were known to have chronic liver
disease, the rest (79%) were all new diagnoses.
Among the patients with PFTs available, fibrosis was evident on TE in
3/14 (21.4%) patients with GOLD stage IV COPD, 4/14 (28.5%) with
GOLD stage II/III COPD, and 10/34 (29.4%) with GOLD stage 0.

Conclusion: LA-ICP-ToF-MS demonstrated dose dependent Mo

accumulation in major organs and our findings show the limitations
of conventional histopathology to characterise these deposits. SD rats
exposed to BC-TTM for 3 months did not exhibit blood or biochemical
abnormalities; this may provide false reassurance of molybdenum
accumulation following chronic exposure.

FRI279
Liver fibrosis and fat by transient elastography in patients with
Alpha-1 antitrypsin deficiency
Hassaan Yousuf1,2, Tobias Maharaj1,2, Daniel Fraughen2,3,
Noel G. McElvaney2,3, John Ryan1,2. 1Beaumont Hospital, Hepatology,
Dublin, Ireland; 2Royal College of Surgeons in Ireland, Ireland;
3
Beaumont Hospital, Respiratory Medicine, Dublin, Ireland
Email: [email protected]
Background and aims: Alpha-1 Antitrypsin Deficiency (AATD) is a Conclusion: In this study, a high rate of undiagnosed advanced liver
common, inherited disorder which can lead to significant morbidity fibrosis in AATD individuals was evident on routine screening using
and mortality. The most severe form is seen in individuals with the transient elastography. No association between lung and liver disease
homozygous PiZZ variant, with almost no circulating levels of AAT, severity was noted, nor were there significant differences in liver
while heterozygous (PiMZ; PiSZ) variants are associated with milder stiffness or steatosis between AATD genotypes. Of note, a high
disease. While AATD effects on the lung have been extensively prevalence of overweight/obesity was seen in those with liver
studied, its effects on the liver are poorly understood. Transient fibrosis.
Elastography is widely used to stage liver disease by liver stiffness

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S531

POSTER PRESENTATIONS
This study highlights the importance of screening AATD patients for
liver fibrosis, and the potential clinical utility of transient elasto-
graphy for these patients.

FRI280
Novel imaging feature in patients with porto-sinusoidal vascular
disorder (PSVD)-radiological evaluation guiding diagnosis
Georg Semmler1,2, Katharina Lampichler3, Katharina Wöran4,
Benedikt Simbrunner1,2, Mathias Jachs1,2, Lukas Hartl1,2,
David J. M. Bauer1,2, Lorenz Balcar1,2, Matthias Pinter1,2,
Michael Trauner1, Mattias Mandorfer1,2, Dietmar Tamandl3,
Judith Stift4, Ahmed Ba-Ssalamah3, Thomas Reiberger1,2,
Martina Scharitzer3, Bernhard Scheiner1,2. 1Medical University of
Vienna, Division of Gastroenterology and Hepatology, Department of
Internal Medicine III, Vienna, Austria; 2Medical University of Vienna,
Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and
Hepatology, Department of Internal Medicine III, Vienna, Austria;
3
Medical University of Vienna, Department of Biomedical Imaging and
Image-Guided Therapy, Vienna, Austria; 4Medical University of Vienna,
Clinical Institute of Pathology, Vienna, Austria
Email: [email protected]
Figure: Periportal hyperintensity on the HBP in patients with PSVD.
Background and aims: Porto-sinusoidal vascular disorder (PSVD) is
a recently defined vascular liver disease often complicated by pre- Conclusion: Diagnosis of PSVD must be considered in younger
sinusoidal portal hypertension (PH). Diagnosis is challenging and patients presenting with clinical features of PH, portal tract
requires liver biopsy, and thus, PSVD is often misdiagnosed as abnormalities, splanchnic vein thrombosis, and FNH-like lesions on
cirrhosis. We investigated radiological features that are distinct CT/MRI. ‘Periportal hyperintensity’ on HBP-MRI was identified as a
between PSVD and cirrhosis. very specific radiological feature of PSVD patients.
Method: Demographic, clinical and laboratory parameters of patients
FRI281
with histologically-confirmed PSVD vs. cirrhosis vs. non-cirrhotic
Liver involvement in systemic light chain amyloidosis: is the heart
liver disease and available CT/MRI scans were retrospectively
guilty?
evaluated. The following imaging features were analyzed:
Portosystemic collaterals, ascites, splanchnic vein thrombosis, Margaux Charles1, Amira Zaroui2, Sebastien Mulé2,
spleen size, portal tract abnormalities, perfusion disorders, FNH- Francoise Roudot Thoraval3, Christophe Duvoux1, Damy Thibaud2,
like lesions, changes in liver morphology and liver surface nodularity. Edouard Reizine3, Vincent Leroy4. 1Hôpital Henri Mondor, Hepatology,
Results: 54 PSVD, 156 cirrhosis, and 41 non-cirrhotic patients were Créteil, France; 2Hôpital Henri Mondor, Cardiology, Créteil, France;
3
included. PSVD patients were younger (45.6 ± 16.3 vs. 56.4 ± 12.8, p < Hôpital Henri Mondor, Radiology, Créteil, France; 4Hôpital Henri
0.001) and had lower HVPG (8 [IQR: 5–12]mmHg vs. 15 [IQR: 10–21] Mondor, Hepatology, Créteil, France
mmHg, p < 0.001), liver stiffness (8.4 [IQR: 6.8–12.2]kPa vs. 29.2 [IQR: Email: [email protected]
16.0–65.1]kPa, p < 0.001), and MELD (9 ± 3 vs. 13 ± 6points, p < 0.001). Background and aims: Systemic light-chain (AL) amyloidosis is a
Specific clinical signs of PH according to PSVD-definition were systemic disease caused by the deposition in organs of unstable
similarly common in both groups. Intrahepatic portal tract abnor- monoclonal light chains secreted by clonal plasma cells. Prognosis is
malities (52% vs. 15%; p < 0.001), splanchnic vein thrombosis (24% vs. mainly related to the degree of cardiac involvement. Elevated liver
12%; p = 0.025) and FNH-like lesions (33% vs. 1%; p < 0.001) were enzymes and/or hepatomegaly are frequently observed and may be
significantly more common in PSVD patients. Hypertrophy of related to deposition of amyloid fibrils in the liver, congestive
segment I (43% vs. 69%; p < 0.001), atrophy of segment IV (24% vs. hepatopathy or confounding factors such as DILI. Diagnostic approach
46%; p = 0.004) and nodular liver surface (19% vs. 87%; p < 0.001) were for hepatologists can be extremely challenging, with certain
more common in patients with cirrhosis. In patients with adequate reluctance to perform liver biopsies. The aim of our study was to
gadoxetic acid-enhanced MRI (PSVD: n = 25, cirrhosis: n = 95, non- describe in a large cohort of patients with cardiac AL amyloidosis the
cirrhotic controls: n = 41), we identified the imaging feature of characteristics of liver abnormalities, their relationships with cardiac
‘periportal hyperintensity’ in the hepatobiliary phase (HBP) as very status and their potential prognostic value.
specific for patients with PSVD: 52% in patients with PSVD vs. 1% in Method: All patients seen from 2008 and 2021 in a single national
cirrhosis vs. 0% in non-cirrhotic controls; p < 0.001). reference centre for new diagnosis of histologically proven AL
amyloidosis with cardiac involvement and available longitudinal
liver features were included. Clinical, biological and echocardio-
graphic data were collected. Liver imaging mainly consisted of MRI, or
when not available CT-scan. All images were read by a single expert
radiologist with specific attention to liver morphometry and signs of
congestion.
Results: 200 patients (median age: 66 years, male: 61%) were
included. The majority of them had severe heart failure (stage III of
Mayo Clinic). Chemotherapy was given in 90% of patients. At baseline,
98 (49%) patients had elevated liver enzymes greater than 1.5 fold the
upper limit of normal. Liver abnormalities were associated to higher
Pro-BNP and Troponin serum levels. Enzyme patterns were choles-
tatis, cytolysis and mixed in 81%, 4% and 15%, respectively. Liver
abnormalities were significantly associated with higher concentra-
tions of troponin and Pro-BNP. Liver imaging showed hepatomegaly

S532 Journal of Hepatology 2022 vol. 77(S1) | S389–S664

 POSTER PRESENTATIONS
in 31% of cases, sinusoidal dilation in 43% and hepatic vein dilation in Method: After biochemical diagnosis, CTX patients were monitored
26%. Compared to patients with normal liver tests, the cholestatic in 6-month intervals with abdominal ultrasound, cMR imaging,
pattern group had more often hepatic vein dilation (40% vs 12%, p < ophthalmologic examinations and determination of cholestanol
0.006) and sinusoidal dilation (57% vs 30%, p < 0.04), these features blood levels. Therapy with CDCA (10–15 mg/kg body wt.) was
being significantly associated with lower cardiac flow and echocar- initiated along with lipid-lowering combination therapy and in one
diographic features of right ventricular dysfunction. There was no female patient, after positive pregnancy testing in 2019, CDCA was
association between liver abnormalities and left ventricular ejection continued and monitoring intervals were shortened.
fraction. A liver biopsy was performed in 11 patients and showed Results: Three siblings, their mother and aunt from a consanginous
amyloid deposits in 9 and features of congestion in 5 patients. During family were diagnosed with CTX at ages of 38, 27, 18, 14, and 9
the follow-up, a significant increase of liver tests was observed after 3 respectively. The aunt was diagnosed in 1997, the mother in 2003 and
months. A cytolysis pattern was associated with a peak of Pro-BNP the siblings in 2005. Mean follow-up in this cohort was 18 ± 2 years.
and short-term mortality. At baseline, tendinous xanthomas were present in 4/5, diarrhea and
Conclusion: Liver involvement is frequent in patients with cardiac AL ataxia in 1/5, hypercholesterolemia and hypertriglyceridemia in all
amyloidosis and seems mainly related to right cardiac dysfunction. patients. 3/5 patients suffered from cataracts and required surgical
The potential role of hepatic amyloid deposits is under investigation therapy. Slight cognitive impairment occurred in 4/5 patients. Ataxia
by scintigraphy and final results will be presented. and diarrhea subsided. Total cholesterol (TC), LDL-C and HDL-C at
baseline were 217 ± 16 mg/dl, 108 ± 15 mg/dl and 77 ± 5 mg/dl and
FRI282 were reduced to 195 ± 7 mg/dl, 115 ± 12 mg/dl and 53 mg/dl ± 6 mg/
The role of the mechanistic target of rapamycin (mTOR) in Alpha- dl at last visit. Pretherapeutic cholestanol levels and 7alpha—
1 Antitrypsin Deficiency hydroxycholesterol were 3.1 ± 0.2 mg/dl (ref. range 0.21 to 0.67 mg/
Lisa Bewersdorf1, Pavel Strnad1, Annika Gross1, Yizhao Luo1, dl) and 3857 ± 802 ng/ml (ref. range <0, 5 ng/ml) decreased to 0.3 ±
Thorsten Cramer2. 1University Hospital RWTH Aachen, Medical Clinic 0.02 mg/dl and 76 ± 10 ng/dl. In a pregnant patient, blood cholestenol
III, Aachen, Germany; 2University Hospital RWTH Aachen, Clinic for and cholesterol levels were stable, and after an uncomplicated
General, Visceral and Transplant Surgery, Aachen, Germany pregnancy, she gave birth to a healthy baby boy in term on 08/2020,
Email: [email protected] who was age appropriate and reached normal developmental
milestones up to now.
Background and aims: Alpha1-antitrypsin (AAT) mutations lead to
Conclusion: Oral CDCA therapy can help stabilize/reverts the control
the retention of the otherwise secreted hepatocellular protein in the
clinical symptoms of CTX and can successfully be continued during
endoplasmic reticulum (ER) thereby giving rise to AAT deficiency
pregnancy. CTX is underdiagnosed and should be suspected in any
(AATD). Liver disease arising due to the proteotoxic stress is the
adult dyslipidemic patients with heterogeneous neurologic manifes-
second leading cause of mortality in AATD. mTOR signalling acts as
tations and cataracts.
the central proteostatic regulator. Our aim was to study the
importance of mTOR signalling in AATD. FRI284
Method: Animals overexpressing the characteristic AAT mutation A rare genetic variant in the manganese transporter SLC30A10 and
(PiZ mice) were cross-bred with rodents harboring a hepatocyte elevated liver enzymes in the general population
specific-ablation of the interaction partners RAPTOR/RICTOR corre-
Anne-Sofie Seidelin1, Børge Nordestgaard2, Anne Tybjaerg Hansen1,
sponding to mTOR complexes 1/2 (mTORC1/2) or with mice lacking
Hanieh Yaghootkar3, Stefan Stender1. 1Rigshospitalet, Clinical
hepatocellular mTOR.
Biochemistry, København, Denmark; 2Herlev Hospital, Clinical
Results: At two month of age, PiZ-mTORΔhep and PiZ-RAPTORΔhep but
Biochemistry, Herlev, Denmark; 3University of Exeter, United Kingdom
not PiZ-RICTORΔhep mice showed elevated liver enzyme levels, signs
Email: [email protected]
of increased liver injury and apoptosis despite diminished AAT
accumulation. While PiZ-RAPTORΔhep animals displayed increased Background and aim: A rare genetic variant in the manganese
levels of the pro-apoptotic protein CHOP, CHOP ablation did not transporter SLC30A10 (rs188273166, p.Thr95Ile) was associated with
rescue the phenotype. As a potential underlying mechanism, we increased plasma alanine transaminase (ALT) in a recent genome-
observed reduced levels of several chaperones, i.e., Hsp90 or Grp94. wide association study in the UK Biobank (UKB). The aims of the
Conclusion: mTORC1 but not mTORC2 plays an important role in PiZ present study were to validate the association of rs188273166 with
induced liver injury. ALT in an independent cohort, and to begin to test the clinical, hepatic
and biochemical phenotypes associated with the variant.
FRI283 Method: We included n = 334, 886 white participants from UKB,
Cerebrotendinous xanthomatosis: long-term course in 5 patients including 14, 462 with hepatic magnetic resonance imaging (MRI),
and first description of a successful pregnancy management and n = 113, 612 individuals from two Danish general population
during therapy with chenodesoxycholic acid (CDCA) cohorts, the Copenhagen City Heart Study and the Copenhagen
Jan Köhler1, David Schoeler1, Petra May1, Linus Mrozek1, General Population Study combined.
Renate Kimmerle2, Tom Lüdde1, Stephan vom Dahl1. 1University Results: Genotyping SLC30A10 p.Thr95Ile identified 816 heterozy-
Hospital Duesseldorf, Heinrich-Heine-University, Department of gotes in the UKB and 111 heterozygotes in the Copenhagen cohort.
Gastroenterology, Hepatology and Infectious Diseases, Duesseldorf, Compared to non-carriers, heterozygotes had 4 U/L and 5 U/L higher
Germany; 2Endokrinologische Schwerpunktpraxis, Düsseldorf, Germany levels of plasma ALT in the UKB and Copenhagen cohort, respectively,
Email: [email protected] and 3 U/L higher plasma aspartate transaminase and gamma
glutamyl-transferase in the UKB. Heterozygotes also had higher
Background and aims: Cerebrotendinous xanthomatosis (OMIM
corrected T1 on liver MRI, a marker of hepatic inflammation (p = 4 ×
#231700) is a rare autosomal-recessive bile acid synthesis defect due
10−7), but no change in MRI-quantified steatosis ( p = 0.57). SLC30A10
to defective mitochondrial sterol 27-hydroxylase CYP27A1, leading to
tendon xanthomas, bilateral cataracts, diarrhea and progressive p.Thr95Ile heterozygotes had an eight-fold increased risk of biliary
tract cancer in UKB ( p = 5 × 10−7), but this association was not
neurologic manifestations. Patients are usually diagnosed during
replicated in the Copenhagen cohort.
adulthood. Oral therapy with CDCA, a bile acid, reverses the
potentially debilitating symptoms and prolongs life span. To our
knowledge, this is the first description of a successful pregnancy with
CTX.

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POSTER PRESENTATIONS
significant decrease of GRP78 and increase of FVII towards wildtype
levels, demonstrating BMN 349 helped reduce cellular stress and
restore normal biosynthetic function of the liver in PiZ mice in
addition to reducing liver polymer burden.
Conclusion: Taken together, these data indicate that BMN 349 is
effective in reducing Z-AAT polymer burden, reversing liver damage,
and restoring liver function in the PiZ mouse model.

FRI286
A ‘melting pot’ of genetic variability in Wilson’s disease-real
Conclusion: SLC30A10 p.Thr95Ile was associated with elevated liver world study from London, UK
enzymes in two large general population cohorts, and with MRI- James Liu Yin1, Aftab Ala1. 1King’s College Hospital, Institute of Liver
quantified hepatic inflammation. We hypothesize that Thr95Ile Studies, London, United Kingdom
heterozygosity associates with a mild form of hepatic manganese Email: [email protected]
accumulation leading to liver damage.
Background and aims: Wilson’s disease (WD) has been shown to
FRI285 have more than 600 different variants causing abnormal function of
A small molecule chaperone for alpha-1 antitrypsin deficiency- the ATP7B peptide. There is wide global diversity in these variants
associated liver disease reduces liver polymer burden in the PiZ with different variants appearing to be more prominent in certain
mouse model geographical areas and populations than others. London, UK is one of
Britta Handyside1, Lening Zhang1, Katina Ngo1, Ryan Murphy1, the largest, ethnically diverse cities in Western Europe with a growing
Joseph Chen1, Nicole Galicia1, Olivia Gorostiza1, Glenn Pacheco1, population of over 9 million. It receives over 100, 000 international
Lin Xie1, Donald Mackenzie1, Heidi Jones1, Brian Heglar1, Bing Wang1, migrants a year, with the largest proportions from the European
Shripad Bhagwat1, David Lomas2, James Irving2, Riccardo Ronzoni2, Union and Indian Subcontinent. We aimed to review the genetic
Sherry Bullens1, Sylvia Fong1, Stuart Bunting1. 1BioMarin results at Kings College Hospital, London from patients with
Pharmaceutical Inc., Novato, United States; 2University College London, abnormal WD genetics and compare this to known global
London, United Kingdom distribution.
Email: [email protected] Method: We retrospectively collected data on all WD genetic testing
done at KCH since becoming one of the national testing centres
Background and aims: Alpha-1 antitrypsin deficiency (AATD) is (2015-present). We further extracted information on specific cDNA,
caused by mutations in the SERPINA1 gene encoding alpha-1 protein change and zygosity status. We subsequently used WilsonGen,
antitrypsin (AAT). AAT is primarily produced by hepatocytes and is (Comprehensive genomic variant resource) which has compiled the
secreted into the blood stream where it functions as a neutrophil largest database of variants, (2267 entries currently) to compare
elastase inhibitor. whether our variants were unique or previously documented.
The most clinically severe form of AATD is caused by the Z mutation Results: We identified 207 WD patients, 30 homozygous, 91
(Glu342Lys) resulting in expression of the mutant protein Z-AAT. compound heterozygotes and 86 heterozygotes (Mean 28.9 years,
Pathogenic Z-AAT protein can misfold, polymerize and accumulate in range 4–70). Within this, there were 113 different variants identified.
the endoplasmic reticulum (ER) of hepatocytes leading to progressive The most common was His1069Gln (11%), followed by Cys271Ter
liver fibrosis and low levels of circulating AAT. There is currently no (3.6%), Met769Val (3.6%) and Ser1365fs (3.2%). On comparison with
effective treatment for AATD-associated liver disease. Here we tested the WilsonGen database we found that 44 variants were not listed on
BMN 349, a molecular chaperone, for its ability to prevent Z-AAT their records (38.9%). We had ethnicity data accessible for 137
polymerization in hepatocytes while increasing circulating Z-AAT in patients, 49% were documented as unspecified and the remaining
the PiZ mouse, a model for AATD-associated liver disease. were; Caucasian (35%), Indian Subcontinent (7%), Middle Eastern
Method: Young (5 week) and adult (12 week) female heterozygous (4%), Black/Caribbean (3%), Chinese (1%) and other (<1%).
PiZ mice expressing human Z-AAT were treated twice daily for 30 Conclusion: Our results demonstrate significant genetic variation in
days with 50 or 100 mg/kg of BMN 349 via oral gavage (10–13 mice London with the most common mutation only accounting for 11% of
per group). Plasma and liver Z-AAT levels were analyzed by ELISA. Z- the overall total. As genetic testing becomes a more utilized tool in
AAT polymer globules in hepatocytes were evaluated using Periodic furthering diagnostic pathways we need to understand that this
Acid-Schiff with Diastase (PAS-D) stains. Liver and plasma pharma- variation may have significance. A recently suggested ATP7B-
codynamic biomarkers were assessed using mass spectrometry- mutation specific diagnostic test would be less effective in a
based proteomics. population like London and other Metropolitan cities. This needs to
Results: Treatment with BMN 349 increased levels of circulating Z- be taken into account in further studies to ensure that genetic
AAT and reduced liver polymer levels in both age groups. In adult variation will not delay or prevent diagnosis of new cases.
mice a dose-response was observed with a liver polymer reduction of The importance of ATP7B genetic variation is yet to be fully
33% with 50 mg/kg ( p = 0.00098) and 49% with 100 mg/kg ( p < understood and characterised with respect to the pathogenesis of
0.0001) of BMN 349 compared to vehicle as determined by ELISA. WD. Within our cohort, the presence of novel variants was 39% which
Histological analysis using the PAS-D stain confirmed a significant is a significant portion and higher than previously reported UK data
reduction in liver Z-AAT polymer globules by 25% ( p = 0.0008) and by (27% Coffey et al). Considering the wide spread of variation including
34% ( p = 0.0232) with 50 or 100 mg/kg of BMN 349, respectively. In novel variants, specific mutations have not been shown to confer
young mice, a greater than 80% reduction in liver polymers was benefit thus far and therefore further understanding of its signifi-
detected by ELISA ( p < 0.0001) and a >85% reduction of Z-AAT cance is needed.
polymer globules ( p < 0.0001) was observed with either dose of BMN
349 compared to vehicle. Together, the data from both age groups
showed that a greater effect on liver polymer burden was achieved
when treatment was initiated early. Proteomics analysis revealed an
increase in ER stress markers including GRP78 in PiZ mouse liver and
plasma and reduced levels of circulating liver-derived clotting factor
VII in PiZ mouse plasma compared to wildtype mice, suggesting
impaired liver function. Treatment with BMN 349 resulted in a

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 POSTER PRESENTATIONS
FRI287 should be evaluated as disease-modifying treatments in Pi*Z allele
The alpha-1 antitrypsin Pi*Z allele is an independent risk factor carriers with ACLD.
for liver transplantation/death in patients with advanced chronic
liver disease FRI288
Lorenz Balcar1,2, Bernhard Scheiner1,2, Markus Urheu1, Fontan associated liver disease: a cohort review into the
Patrick Weinberger1, Rafael Paternostro1,2, Benedikt Simbrunner1,2, prevalence of portal hypertension
Lukas Hartl1,2, Mathias Jachs1,2, David Jm Bauer1,2, Georg Semmler1,2, Hannah Donnelly1, James Orr2. 1Bristol Royal Infirmary, Bristol, United
Claudia Willheim1, Matthias Pinter1, Peter Ferenci1, Michael Trauner1, Kingdom; 2Bristol Royal Infirmary, United Kingdom
Thomas Reiberger1,2, Albert Stättermayer1,2, Mattias Mandorfer1,2. Email: [email protected]
1
Medical University of Vienna, Division of Gastroenterology and Background and aims: The Fontan procedure is a palliative operation
Hepatology, Department of Internal Medicine III, Vienna, Austria; for patients with functional univentricular congenital heart disease. It
2
Medical University of Vienna, Vienna Hepatic Hemodynamic Lab, directs the systemic venous return directly into the pulmonary
Vienna, Austria circulation without ventricular propulsion preventing mixing of
Email: [email protected] blood. Up to 70 000 Fontan patients are alive worldwide today, and
Background and aims: Alpha-1 antitrypsin (AAT) deficiency causes/ this is expected to double in the next 20 years. Fontan-associated liver
predisposes for advanced chronic liver disease (ACLD). However, the disease (FALD) is emerging as a common complication and consensus
role of the SERPINA1 Pi*Z allele in patients who have already recommends evaluation for FALD but specific guidelines on screening
progressed to ACLD is unclear. Thus, we aimed to evaluate the are not established. The Bristol Liver Unit and Heart Institute are
impact of the Pi*Z allele on the requirement of liver transplantation/ collaborating to review their cohort of patients, particularly looking
liver-related death in ACLD, while adjusting for the severity of liver into the prevalence of portal hypertension.
disease at inclusion. Method: A database of Fontan patients was gathered, and demo-
Method: 1118 ACLD patients who underwent HVPG-measurement graphics, bloods, imaging, and endoscopy results were collected from
and genotyping for the Pi*Z/Pi*S allele at the Vienna Hepatic the electronic patient record.
Hemodynamic Lab were included in this retrospective analysis. Results: From the 101 Fontan patients on the database 11 had had
Requirement of liver transplantation/liver-related death was the gastroscopies. 10 patients had gastroscopies to look for signs of portal
outcome of interest, while non-liver-related death and removal of the hypertension, and one due to a hereditary condition. One patient had
primary etiological factor were considered as competing risks. presented with bleeding, with coffee-ground vomiting, all others
Results: Viral hepatitis was the most common etiology (44%), were elective. 6/11 had signs of portal hypertension, details in table 1.
followed by alcoholic (31%) and non-alcoholic fatty liver disease 5/6 (83%) of those with endoscopic evidence of portal hypertension
(11%). Forty-two (4%) and forty-six (4%) patients harboured the Pi*Z had either splenomegaly (>13 cm), Fibroscan >20 kpa or thrombo-
and Pi*S variants, respectively. cytopenia ( platelet count <150). These are all established markers of
Pi*Z carriers had more severe portal hypertension (HVPG: 19 ± 6 vs. possible portal hypertension. The patient that did not have any of
15 ± 7 mmHg; p < 0.001) and hepatic dysfunction (Child-Turcotte- these had varices shown on a USS and this was confirmed on
Pugh: 7.1 ± 1.9 vs. 6.5 ± 1.9 points; p = 0.050) at inclusion, as compared endoscopy. In the cohort 37% (38/101) met one or more of these
to non-carriers. Contrarily, the Pi*S allele was unrelated to liver criteria.
disease severity.
Table 1: Findings of portal hypertension on endoscopy
In competing risk regression analysis, harbouring the Pi*Z allele was
significantly associated with an increased probability of liver Portal hypertensive gastropathy 5/6
transplantation/liver-related death (Figure), even after adjusting for (With GOV 4/6)
liver disease severity at inclusion. The detrimental impact of the Oesophageal varices 4/6
Grade 1
common Pi*MZ genotype (vs. Pi*MM) was confirmed in a fully
Gastric varix 1/6
adjusted subgroup analysis. In contrast, Pi*S carriers had no increased
risk for events. Conclusion: Non-invasive markers of portal hypertension seem to
predict the presence of portal hypertension detected on endoscopy.
Our Fontan patients have a high prevalence of these non-invasive
markers and this is with missing data. We plan to explore the
prevalence further by establishing a joint clinic with Cardiology to
assess the patients and perform gastroscopies if non-invasive
markers indicate possible portal hypertension. We will also be
looking at the relevance of portal hypertension in this patient group,
considering the bleeding risk and impact on transplantation
assessment.

FRI289
Senolytic therapies have a place in pediatric biliary cirrhosis
Giulia Jannone1, Eliano Bonaccorsi2, Catherine de Magnée3,
Roberto Tambucci3, Jonathan Evraerts1, Joachim Ravau1,
Mustapha Najimi1, Etienne Sokal1. 1Université catholique de Louvain,
IREC Institute, Laboratory of Pediatric Hepatology and Cell Therapy,
Brussels, Belgium; 2Université catholique de Louvain, IREC Institute,
Laboratory of Experimental Surgery and Transplantation, Brussels,
Belgium; 3Cliniques Universitaires Saint-Luc, Pediatric Surgery and
Transplantation Unit, Brussels, Belgium
Email: [email protected]
Conclusion: Genotyping for the Pi*Z allele identifies ACLD patients at
increased risk for adverse liver-related outcomes, thereby improving Background and aims: Premature senescence has been extensively
prognostication. Therapies targeting accumulated abnormal AAT characterized in adult chronic hepatobiliary diseases and can worsen
liver function and fibrosis evolution. Since new therapeutic options

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POSTER PRESENTATIONS
are needed in pediatric biliary cirrhosis to delay liver transplantation, were stained by PAS-D and immunostained with an anti-A1AT
our aim was to investigate the presence of premature senescence in polyclonal rabbit antibody (Cell Marque, Inc., Rocklin, CA, USA).
biliary atresia (BA) and to test the senolytic properties of Medicinal Results: The frequency of SERPINA1 MZ heterozygotes was signifi-
Signaling Cells in a preclinical model of biliary cirrhosis. cantly higher in the group with liver cirrhosis in comparison with the
Method: Senescence was investigated through senescence-asso- control group, 56/1079 (5.2%) vs. 89/3329 (2.7%), p < 0.0001, MZ
ciated β-galactosidase activity assay (SA-beta-gal) as well as p16 and heterozygotes thus have an increased risk of liver cirrhosis (OR 2.0, CI
p21 gene/protein expression in BA livers at the time of hepatopor- 95% 1.4–2.8).
toenterostomy (n = 5) or liver transplantation (n = 30) as compared to Re-evaluation of 1009 histopathological reports of the explanted liver
control livers (n = 10). Co-localized expression of senescence specimens revealed that PAS-D positive aggregates were detected in
(gammaH2AX or p21) with CK19, HNF4alpha, alphaSMA and Ki67 52/56 (93%) MZ heterozygotes and 18/953 (1.9%) MM homozygotes
was also assessed. Bile duct ligation (BDL) was performed on 2- ( p < 0.0001). Forty-six out of 56 available specimens of MZ hetero-
months old rats and senescence was characterized in the model zygotes were assessed by immunohistochemistry; A1AT aggregates
through above-mentioned techniques. Human allogeneic liver- were confirmed in all cases.
derived progenitor cells (HALPC) were injected in BDL rats 48 hours PNPLA3 rs738409 genotype frequencies were 21 CC (37.5%), 24 CG
after the surgery at high (12.5 × 106 cells/kg, n = 6) versus low dose (42.9%), and 11 GG (19.6 %) in 56 SERPINA1 MZ heterozygotes with
(1.25 × 106 cells/kg, n = 6) and compared to the vehicle (n = 6). cirrhosis and 59 CC (66.3%), 26 CG (29.2%) and 4 GG (4.5%) in 59 MZ
Results: Senescence was similarly increased in both BA stages as heterozygotes in the control group. The frequency of the unfavour-
compared to control livers (SA-beta-gal: 5.9 ± 1.4 and 5.4 ± 1 vs 0.6 ± able PNPLA3 G allele was significantly higher in SERPINA1 MZ carriers
0.1 %stained area/total, p < 0.01) and was also confirmed in BDL livers with cirrhosis than in healthy heterozygotes, and the carriage of the
one and two weeks after the surgery (SA-beta-gal: 1.6 ± 0.6 and 6.6 ± PNPLA3 G allele increased the risk of liver cirrhosis ( p = 0.001; OR =
2.4 vs 0.2 ± 0.1 %stained area/total, p < 0.05). The pattern of 3.278, CI 95% 1.633–6.581). Contrarily, the frequencies of the TM6SF2
senescence in BA and BDL was similar as senescence first appeared and GCKR genotypes in SERPINA1 MZ heterozygotes did not differ
in cholangiocytes of the ductular reaction and subsequently devel- significantly between the patients with cirrhosis and controls.
oped in hepatocytes. HALPC transplantation at both doses decreased Conclusion: Our results suggest that the risk genotypes of PNPLA3
senescence in BDL rats ( p21 gene expression: 0.4 ± 0.04 and 0.5 ± 0.1 accelerate the progression of fibrosis in SERPINA1 MZ heterozygotes
vs 1 ± 0.2 fold change; p < 0.05). with chronic liver disease.
Conclusion: Premature senescence occurs in BA livers and HALPC
display senolytic properties in a preclinical model of biliary cirrhosis. FRI291
Patient experience of their Primary Biliary Cholangitis (PBC)
FRI290 management compared to clinical practice guidelines
PNPLA3 rs738409 G allele increases the risk of liver cirrhosis in Chris Mitchell1, Angela Eddy2, James Neuberger3. 1PBC Foundation,
SERPINA1 MZ heterogygotes Edinburgh, United Kingdom; 2PBC Foundation, Edinburgh, United
Sona Frankova1, Zuzana Rabekova2, Magdalena Neroldova3, Kingdom; 3NHS, Birmingham Queen Elizabeth Medical Centre,
Ondrej Fabian4, Martin Kveton4, Jaroslav A. Hubacek5, Julius Spicak1, Birmingham, United Kingdom
Vera Adamkova6, Milan Jirsa3, Jan Sperl1. 1Institute for Clinical and Email: [email protected]
Experimental Medicine, Department of Hepatogastroenterology, Praha,
Background and aims: Primary Biliary Cholangitis (PBC) is a chronic,
Czech Republic; 2Institute for Clinical and Experimental Medicine,
cholestatic, autoimmune liver disease, which can have a profound
Department of Hepatogastroenterology, Prague, Czech Republic;
3 impact on patients’ quality of life and a significant demand for
Institute for Clinical and Experimental Medicine, Laboratory of
healthcare services. PBC management guidelines were published in
Experimental Hepatology, Praha, Czech Republic; 4Institute for Clinical
2017 by European Association for the Study of the Liver (EASL), which
and Experimental Medicine, Department of Clinical and Transplant
include recommendations for daily dosage (13–15 mg/kg) of licensed
Pathology, Praha; 5Institute for Clinical and Experimental Medicine,
first-line therapy (ursodeoxycholic acid (UDCA)) and referrals for
Atherosclerosis Research Laboratory, Praha; 6Institute for Clinical and
alternative treatment if UDCA response is inadequate, of which
Experimental Medicine, Preventive Cardiology Centre, Praha, Czech
obeticholic acid (OCA) is the only licensed treatment alongside other
Republic
re-purposed agents.
Email: [email protected]
This study explored the efficacy of patient-clinician collaborations to
Background and aims: Homozygous carriage of mutated Z allele in manage PBC in accordance with EASL guidelines from a patient
rs28929474 locus of SERPINA1 encoding alpha-1-antitrypsin (A1AT) perspective.
leads to lung emphysema and liver cirrhosis. Recent data show that Method: A closed question questionnaire was designed focussing on
the SERPINA1 MZ genotype increases the risk of liver cirrhosis in the application of treatments and the inclusion of patients in the
patients with various liver diseases. The mechanism behind this management of their PBC. The questionnaire was piloted with PBC
finding has not been elucidated so far. Our study aimed to Foundation service users during a focus group testing its reliability
demonstrate the synergy between the SERPINA1 Z allele and and face validity. A convenience sample was used and participants
unfavourable alleles in other liver disease-modifying genes. recruited via the PBC Foundation’s app during March 2022. Intercept
Method: The study group consisted of 1079 liver transplant Pharmaceuticals provided financial support and input into the
candidates with liver cirrhosis of various aetiology (642 males, 437 questionnaire, however the PBC Foundation has retained editorial
females, average age of 54 years). The aetiology of cirrhosis was as discretion over survey outputs.
follows: 352 alcoholic, 309 cholestatic, 217 viral, 142 NASH, 59 Results: 172 patients completed the survey.
metabolic. Patients with A1AT deficiency were excluded. The control 154 respondents (90%) take UDCA and 132 respondents (77%)
group consisted of 3329 healthy individuals from the MONICA study received a timely UDCA prescription (0–3 months after diagnosis).
(WHO Multinational Monitoring of Trends and Determinants in 91% of UDCA patients believe they are taking the recommended
Cardiovascular Disease Project). dosage however only 54% of UDCA patients report taking dosage
Genomic DNA was isolated from peripheral blood by Qiagen QIAamp within guidelines.
kit (Qiagen, Hilden, Germany). SERPINA1 rs28929474, PNPLA3 Of those patients who are unresponsive or intolerant to UDCA, 68%
rs738409, TM6SF9 rs rs58542926 and GCKR rs1260326 loci were were offered alternative treatment and 57% were included in
genotyped by TaqMan RT-PCR SNP assays (Thermo Fisher Scientific, discussions about the most suitable option.
Waltham, MA). Aggregates of A1AT in hepatocytes in liver explants

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 POSTER PRESENTATIONS
22% of all patients take 2nd line treatment (5% OCA and 17% in survival probability was observed when patients were stratified
unlicensed). 8% of all patients take no treatment for PBC according to CP genotype. Cox regression analysis including age and
management. NaMELD showed that CP serum concentration but not p.Thr551Ile
54% of patients had no access to face-to-face clinical appointments genotype was an independent predictor of transplant-free survival.
and 39% had appointments delayed or cancelled during the COVID
pandemic. Patient comfort in raising PBC related queries ranges from
86% in face-to-face meetings, 46% on the telephone and 31% on
screen-calls.
Latest blood test results were discussed with 73% of patients. 50% of
patients believe they understand their test results and 40% say their
test results help them manage their PBC.
Conclusion: Unmet PBC patient needs are evident in numerous
stages of the life-long clinical journey. Data indicates substantial
disparity between published PBC treatment guidelines and actual
care delivered to patients, particularly relating to optimal application
of PBC management therapies and patient inclusion in important
discussions (test results and further treatment referrals). Unmet
needs have been exacerbated during the COVID pandemic when
timely appointments in patients’ preferred formats were adversely
affected.

FRI292
Evaluation of the clinical impact of the Ceruloplasmin variant p.
Thr551Ile in liver cirrhosis
Marlene Panzer1,2, Benedikt Schaefer1, André Viveiros1, Herbert Tilg1,
Heinz Zoller1,3. 1Medical University of Innsbruck, Department of
Medicine I, Innsbruck, Austria; 2VASCage Reserch Center of Vasuclar
Ageing and Stroke, Innsbruck, Austria; 3Christian Doppler Laboratory on
Iron and Phosphate Biology, Innsbruck, Austria Conclusion: Reduced serum ceruloplasmin is common in patients
Email: [email protected] with liver cirrhosis and is independently associated with reduced
transplant-free survival in unselected patients with cirrhosis. The CP
Background and aims: Ceruloplasmin is a multicopper oxidase and variant p.Thr551Ile shows no association with serum iron parameters
is involved in cellular iron efflux. Aceruloplasminemia (ACP) is a or transplant-free survival.
recessive disease, caused by pathogenic variants in the gene encoding
ceruloplasmin (CP). The disease is characterized by iron accumulation FRI293
in liver, pancreas and brain. Patients typically present in their 5th Circulating miR-21 parallels the incidence of IBD in PSC patients
decade of life with the triad of retinal degeneration, diabetes mellitus André A. Santos1, Joana Torres2, Susana Saraiva2,
and neurodegeneration. Early biochemical signs of ACP include Catarina Ferreira Gouveia2, Catarina Bravo2, Marília Cravo2,
hyperferritinemia and low transferrin saturation. Recent reports Cecília M. P. Rodrigues1. 1Research Institute for Medicines (iMed.
suggest that heterozygous variants in CP can also cause hyperferri- ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal;
tinemia and hepatic siderosis in patients with non-alcoholic fatty 2
Hospital Beatriz Angelo, Loures, Portugal
liver. The aim of the present study was to investigate the allele Email: [email protected]
frequency and the clinical impact of the common ceruloplasmin
variant p.Thr551Ile in an unselected cohort of patients with liver Background and aims: Primary sclerosing cholangitis (PSC) is a
cirrhosis. chronic and progressive cholestatic liver disease. The major risk factor
Method: A cohort of patients referred to the Hepatology Laboratory at for developing PSC is having a concomitant diagnosis of inflamma-
the Medical University of Innsbruck for PNPLA3 genotyping was tory bowel disease (IBD). Around 71% of PSC patients have IBD.
retrospectively assessed. Patients diagnosed with liver cirrhosis and Conversely, PSC is present in only 3–8% of patients with established
available serum CP concentrations were included in this study (n = IBD. Although both diseases run distinct courses, patients with PSC-
568). Demographic, biochemical and clinical parameters were IBD present a characteristic phenotype, contributing to a high risk of
collected by review of patient records. Genotyping for the CP colitis-associated neoplasia. Recently, small non-coding RNAs such as
variant p.Thr551Ile (rs61733458) was performed by allelic discrim- microRNAs (miRNAs) have been correlated with disease onset and
ination PCR. progression. miR-21, one of the most studied oncogenic miRNAs, is
Results: Genotyping results revealed 2 homozygous and 27 heter- known to be overexpressed in IBD. Here we aim to further explore
eozygous patients for p.Thr551Ile. This corresponds to an allele miR-21 in patients in a systematic manner and determine its
frequency of 2.73% (31 of 1136) in the liver cirrhosis cohort which is contribution to the typical PSC-IBD phenotype.
not different from the general population as reported in gnomAD Method: In this case-control study we included 12 patients in the PSC
(7795 of 282414; 2.76%). Biochemical surrogates of liver disease —IBD group, 30 patients in the IBD-alone group, and 19 patients in the
severity and serum iron parameters did not show significant control group. Serum samples were collected for fasting serum miR-
differences when patients were stratified according to CP genotype. 21 expression. Stool samples were used for calprotectin analysis and
Reduced CP concentrations (≤20 mg/dL) were detected in 17.2% of miR-21 expression. Gut microbiome was investigated using next
patients carrying the variant p.Thr551Ile and in 11.7% in the normal generation sequencing analysis. During colonoscopy, two biopsies in
group, which is not significantly different. Median CP concentrations the right and left colon were performed and expression analysis of
were also numerically lower in patients heterozygous or homozygous miR-21 and inflammation, tight junction and oncogene analysed. In
for p.Thr551Ile, but this difference did not reach statistical signifi- statistical data analysis, outliers were removed (ROUT Q = 1%) and
cance (27.7 mg/dl vs 27.8 mg/dl; p = 0.368). Median time of trans- Kruskal-Wallis test or ANOVA Tukey’s multiple comparisons test were
plant-free survival was significantly reduced in the group with performed on non-parametric or parametric data, respectively.
decreased CP concentration ( p = 0.004), but no significant difference

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POSTER PRESENTATIONS
Results: Serum and fecal miR-21 expression were significantly FRI295
increased in PSC-IBD patients compared to IBD alone. miR-21 Are patients with Fontan-associated liver disease (FALD)
expression in the right colon was similar in both PSC-IBD and IBD appropriately screened for oesophageal varices? Queensland
alone but increased when compared to controls. The inflammatory quaternary adult congenital heart disease referral centre
marker IL-8 was more elevated in both left and right colon of PSC-IBD experience
patients than in IBD alone. Moreover, macrophage recruitment Anthony Bergin1, Yuming Ding1, Michael Christmas1, Wei Lian Tan1,
markers TWIST1, COX2, and CCL2 were also significantly increased Lei Lin1, Myat Khaing1, Alexandra Schlimmer1, Ann Vandeleur1,
in both left and right colon tissue of PSC-IBD patients compared to Hayley Thompson1, Ryan Maxwell1, Vishva Wijesekera1,
IBD alone or in control groups. Finally, the genus Intestinibacter, often Tony Rahman1. 1The Prince Charles Hospital, Gastroenterology,
associated with IBD, was elevated in PSC-IBD patients compared to Chermside, Australia
IBD alone. Email: [email protected]
Conclusion: Our data show that miR-21 in circulation, but not in
colon tissue, together with macrophage recruitment and distinct Background and aims: The Fontan procedure is palliative manage-
ment of univentricular congenital heart disease. An extracardiac
microbiota profiles parallel the incidence of IBD in PSC patients. Given
the proinflammatory and oncogenic activities of miR-21, its role in complication of haemodynamic changes from Fontan circulation is
Fontan-associated liver disease (FALD). Variceal bleeding is the most
PSC-IBD disease pathogenesis and phenotype merits further evalu-
severe and life-threatening complication of chronic liver disease and
ation. Supported by FCT CEECIND/04663/2017, GEDII Project Award
2019, and EASL Daniel Alagille Award 2019. portal hypertension (1). Studies suggest that 15 years post-
Fontan procedure greater than 27% of patients had oesophageal
FRI294 varices on oesophago-gastroduodenoscopy (OGD) (2). An ageing
Hepatocellular carcinoma in fontan associated liver disease: Fontan population is a new clinical phenotype due to advances in
uncharted territory-are we doing enough? healthcare. It is thus imperative that cirrhotic Fontan patients are
Michael Christmas1, Anthony Bergin1, Wei Lian Tan1, Myat Khaing1, screened for oesophageal varices, however, no formal guidelines
Lei Lin1, Yuming Ding1, Tony Rahman1, Ryan Maxwell2, currently exist.
Vishva Wijesekera2. 1The Prince Charles Hospital, Gastroenterology, Method: Retrospective analysis of Fontan patients and clinical,
Chermside, Australia; 2The Prince Charles Hospital, Cardiology, biochemical, radiological and endoscopic databases correlation was
Chermside, Australia undertaken at the Hepatology clinic serving the quaternary regional
Email: [email protected] referral centre for adult congenital heart diseases in Queensland (The
Prince Charles Hospital, TPCH). Cirrhosis was identified in patients
Background and aims: Fontan associated liver disease (FALD) is a who had features identified on their liver ultrasound. The current
well-recognised consequence of the congestion and hypoxia created conventional HCC screening requirements were then applied to
from the Fontan palliative procedure. Improved clinical management identified patients. For each OGD, procedure indication, endoscopic
has led to significantly improved life expectancy and thus the findings and therapeutic interventions were noted.
paradigm of increased risk of developing FALD and HCC. There are no Results: Seventy-two post-Fontan patients were identified from our
FALD specific surveillance guidelines for HCC. AASLD and EASL database. Of which 49% (n = 35) were female with a mean age of 30.3
suggest biannual monitoring of serum alpha fetoprotein and years. Only 44% (n = 32) had an OGD, the indications included variceal
ultrasound imaging as the gold standard for HCC screening in the surveillance, iron deficiency and dyspepsia. Among the cirrhotic FALD
cirrhotic population. This clinical audit seeks identify and audit patients (n = 32), only 43.7% (n = 14) had an OGD. Of this subgroup
compliance to the gold standard being offered in our Hepatology 22.8% (n = 7) had grade I oesophageal varices, none of which required
clinics. treatment. None were taking primary prophylaxis.
Method: Retrospective analysis of Fontan patients and clinical, Conclusion: FALD patients with cirrhosis should at least have one
biochemical, radiological and endoscopic databases correlation was screening OGD. While 25% of our screened cirrhotic patients had
undertaken at the Hepatology clinic serving the quaternary regional varices, concerningly only 43.7% had underwent an OGD. Future
referral centre for adult congenital heart diseases in Queensland (The multi-centre collaborative research is needed to facilitate the devel-
Prince Charles Hospital, TPCH). Cirrhosis was identified in patients opment of guidelines on variceal surveillance for this growing cohort
who had features identified on their liver ultrasound. The current of FALD patients. The majority of cirrhotic patients in this cohort are
conventional HCC screening requirements were then applied to linked in with a liver clinic. The young age of this cohort should not
identified patients. disguise or detract from the risk of cirrhosis and life threatening
Results: In the data set of 72 Fontan patients, 49% (35) were female variceal bleeding. This study has identified an opportunity for
and an average age of 30.3 years. Features of cirrhosis were identified education to improve the awareness and importance of variceal
in 44% (32). Of these 32, 90% (29) patients were linked in with an screening and this unique evolving population, for staff, patients and
outpatient liver clinic. Only 66% (19) liver clinic patients had standard carers.
HCC surveillance. In our data set one patient has had treatment for
HCC. Four patients had died due to causes unrelated to HCC. FRI296
Conclusion: The majority of cirrhotic patients in this cohort are Primary liver malignancies in patients with Wilson’s disease
linked in with a liver clinic. Sub-optimal HCC screening is taking place Rodolphe Sobesky1,2, Olivier Guillaud2,3, Aurelia Poujois2,4,
in this very vulnerable cohort with one third of patients not receiving Audrey Coilly1,2, Eric Vibert1,2, René Adam1,2, Daniel Cherqui1,2,
minimum surveillance potentially leading to missed detection of Cyrille Feray1,2, Didier Samuel1,2, Jean-Charles Duclos-Vallée1,2. 1CHB-
curable HCC. The young age of this cohort should not disguise or Centre Hépato-Biliaire, Villejuif, France; 2Centre référent Maladie de
detract from the risk of cirrhosis and HCC. This has identified an Wilson, France; 3CHU Lyon, Gastro-entérologie, Hépatologie, Lyon,
opportunity for education to improve the awareness and importance France; 4Hôpital Fondation Rothschild, Neurologie, Paris, France
of HCC and screening in this unique population, for staff, patients and Email: [email protected]
carers. International guidelines would be very valuable in this new
cohort of cirrhotic patients. Background and aims: Wilson’s disease (WD) can induce chronic
liver disease, cirrhosis and its complications. Primary liver cancer in
WD patients is currently believed to be rare. Reports of primary
hepatobiliary malignancies in these cases are sparse. Our aim was to
assess the frequency and characteristics of primary liver cancer in WD
patients on long-term follow-up.

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 POSTER PRESENTATIONS
Method: We retrospectively analysis a monocentric cohort of WD Results: Twenty-five of 76 (33%) screened patients had NCC-Sp
patients with liver damage from a referral center for rare diseases. <50 mcg/L at first sampling, majority (20/25) between 25 and
Patients of the cohort were regularly assessed with a maximal 50 mcg/L. The mean (SD) age was 40.4 (14.3) years; 13 were female.
interval of 6 months. Patients with a history of cirrhosis had a Serum NCC-Sp, UCE, ALT and dose of DPA in mg/kg are shown in the
biannual ultrasound examination. Occurrence, treatment and Table. For comparison, graphs of NCC-Sp and NCC-Ex versus UCE at
outcome of primary liver tumors were analyzed. screening are shown in the figure. Though a wide range of UCE was
Results: We analyzed 149 WD patients of the cohort, with a mean observed, UCE and NCC had a positive correlation. Two subjects with
follow up of 15 years. The mean age at diagnosis of WD was 20.1 ALT >ULN of 54 (73 and 61) U/L, had corresponding NCC-Sp of 41 and
years. Sixteen patients were diagnosed with a primary liver tumor 44.8 mcg/L respectively. UCE ranged widely, however mean UCE was
during follow up. The mean age at onset of a liver tumor was 52.5 within 200–500. Dose of DPA was 13.2 ± 3.5 mg/kg (7.4–19), within
years, with a mean interval between diagnosis of WD and occurrence the recommended guidance of 10–15. Sixteen (64%) with NCC -Sp
of tumor of 19.2 years. We diagnosed a hepatocellular carcinoma <50, including 3/4 who underwent re-screening, were randomized.
(HCC) for 10 patients and a cholangiocarcinoma (CCK) for 6 patients.
Histological proof could be obtained for 7/10 patients with HCC and
for all patients (6/6) with CCK. For the 3 other patient, diagnosis of
HCC was based on the morphological aspect (hyper vascular tumor
with washout) and elevated AFP markers. All patients who developed
a liver tumor had evidence of cirrhosis at the diagnosis of WD. At the
diagnostic of tumor, there was no cirrhosis on the pathological
examination of the non-tumoral liver for 6 patients (2/10 patients
with histological proof of HCC and 4/6 patients with CCK). For all
patients with primary liver tumor, a treatment could be proposed.
Resection was possible for 8 patients and liver transplantation for 5
patients. During follow up, six patients died from complications of
tumor extension (3 from HCC and 3 from CCK).
Conclusion: WD patients with history of cirrhosis are at risk of
Figure: UCE- NCC scatter plots (A-NCC Sp and B-NCC Ex).
developing primary liver tumor and require morphological screening,
even if there is a regression of fibrosis. The proportion of CCK (37.5%) Table: Patients with Serum NCC-Sp <50 mcg/L at trial screening
among these tumors suggests an interest of the biopsy for diagnosis
Mean Max Min SD
of liver cancer in WD patients.
NCC-Sp (mcg/L) 32.4 46.9 17.0 8.9
FRI297 NCC-Ex 36.5 48.8 13.1 8.5
Defining the boundaries for “stability” in Wilson disease patients UCE (mcg/24 hr) 475 798 47 221
on maintenance chelation therapy: lessons from the CHELATE ALT (U/L) 26 73 6 16.3
trial DPA dose (mg/kg) 13.2 19.0 7.4 3.5
C. Omar Kamlin1, Michael Schilsky2, Peter Ott3, Karl Heinz Weiss4,
Massimo Giovanni Zuin5, Aurelia Poujois6, Aftab Ala7,
Conclusion: Re-screening of patients in clinical trials of rare disease
Koenraad D’Hollander8. 1Orphalan SA France, Medical Affairs, London,
facilitates recruitment. Single and multiple biochemical parameter
United Kingdom; 2Yale University, Division of Internal Medicine and
analyses are helpful in defining the boundaries for “stability” of WD
Liver Unit, United States; 3Aarhus University Hospital, Aarhus, Denmark;
4 patients and lower values of NCC are common with the optimal lower
Salem Medical Center, Heidelberg, Germany; 5University of Milan,
limit requiring further study. Dosing in patients with very low NCC
Milan, Italy; 6Fondation Hopital Rothschild, Department of Neurology,
(<25 mcg/L) should be re-evaluated to avoid overtreatment. NCC may
Paris; 7Kings College University Hospital, London, United Kingdom;
8 be a useful parameter for response guided dosing of therapy for
International Drug Development Institute (IDDI), Belgium
chelation in WD.
Email: [email protected]
Background and aims: “Clinical stability” of patients with Wilson FRI298
disease (WD) is a treatment goal for long-term maintenance therapy Precision-cut liver slices as an ex vivo model to assess impaired
and a desired entry point for interventional therapeutic trials in this hepatic glucose production
patient population. Stability evaluation relies on laboratory para- Kishore Alagere Krishnamurthy1, Ligia Akemi Kiyuna1,
meters and clinical assessment. Published guidance and practice Miriam Langelaar1, Albert Gerding1, Trijnie Bos1,
guidelines are not aligned, leading to variations in assessments and Dorenda Oosterhuis2, Peter Olinga2, Karen Van Eunen1,
therapeutic targets. We performed a descriptive secondary analysis of Barbara Bakker1, Maaike Oosterveer1. 1University Medical Center
“clinically stable” patients enrolled into the Chelate trial to define the Groningen, Groningen, Netherlands; 2University of Groningen,
boundaries of biochemical stability (clinicaltrials.gov; Groningen, Netherlands
NCT03539952). Email: [email protected]
Method: Clinically stable patients on D-penicillamine (DPA) >1 y
were randomised to DPA or trientine tetrahydrochloride if 24-h Background and aims: Disturbed glucose metabolism is a common
feature of metabolic diseases. For example, fasting hypoglycemia is a
urinary copper excretion [UCE] was 200–500 mcg/L (amended 100–
900), alanine aminotransferase[ALT] <2× ULN IU/L, serum non- severe symptom of various inborn errors of metabolism, among
caeruloplasmin bound copper[NCC] 50–150 mcg/L, (amended 25– which glycogen storage disease type 1 (GSD I). Due to the liver’s
central role in endogenous glucose production, the availability of a
50) determined initially by EDTA method (NCC-Ex). NCC by
speciation coupled with ICP-mass spectroscopy (NCC-Sp) was liver-specific ex vivo model will enable unravelling the mechanisms
performed retrospectively. Amendments to these ranges and oppor- underlying perturbed glucose homeostasis. Given the limitations of
tunities for biochemical screen failures to re-enter trial were made to in vitro hepatocyte cultures (e.g. reduced Glucose-6-phosphatase
improve trial feasibility. We reviewed day 1 data for all screened activity, proliferative nature), this study aims to optimize and
characterize precision-cut liver slices (PCLS), both from the human
patients.
and murine liver, as a model to study hepatic glucose production ex
vivo.

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POSTER PRESENTATIONS
Method: PCLS were prepared from fed and 12h-fasted male C57BL/6 FRI299
mice and incubated in Williams E glucose-free medium supplemen- Interim 52-week analysis of immunogenicity to the vector capsid
ted with gluconeogenic precursors: (1) 10 mM glycerol, (2) 20 mM and transgene-expressed human FVIII in GENEr8-1, a phase 3
lactate plus 2 mM pyruvate, or (3) 10 mM dihydroxyacetone (DHA). clinical study of valoctocogene roxaparvovec, an AAV5-mediated
Net cumulative glucose production was assessed at different time gene therapy for hemophilia A
intervals (2 h–24 h). The amino acids in the medium and slice Brian Long1, Sylvia Fong1, Britta Handyside1, Tara Robinson1,
glycogen content were quantified at different time points to assess Jonathan Day1, Hua Yu1, Kelly Lau1, Kathryn Patton1, Greg de Hart1,
the source of glucose. Additionally, the efficacy of glucose production Josh Henshaw1, Suresh Agarwal1, Christian Vettermann1,
in response to fatty acid supplementation (500 μM palmitate), Soumi Gupta1. 1BioMarin Pharmaceutical Inc. San Rafael, CA. USA 94901
hormonal (0.1–1 μM glucagon or insulin), and pharmacological Email: [email protected]
(10–20 μM forskolin or 50–100 μM dibutyryl-cAMP) stimulation
Background and aims: Valoctocogene roxaparvovec is an AAV5-
were evaluated. Finally, to study GSD type 1 ex vivo, we used either
PCLS derived from GSD Ia/Ib mouse models (L-G6PC−/− and mediated gene therapy under investigation for the treatment of
hemophilia A and encodes a codon-optimized B-domain deleted
L-SLC37A4−/−) or subjected wildtype PCLS to pharmacological
inhibition of G6P exchanger SLC37A4 (S4048). human FVIII protein (hFVIII-SQ) under control of a liver-selective
promoter. This report describes clinical immunogenicity monitoring
Results: PCLS derived from fed and fasted mice produced glucose,
data from up to 1 year of follow-up from GENEr8-1, an ongoing, fully
both in the presence and absence of gluconeogenic precursors. The
glycogen content in the PCLS was substantially and equally reduced enrolled, Phase 3, single-arm, open-label study in 134 male
participants with severe hemophilia A.
in all conditions after 5 h in culture. No substantial changes were
observed in the amino acid concentrations in any condition. Both Method: Participants were required to test negative for anti-AAV5
total antibody (AAV5 TAb) utilizing a bridging electrochemilumines-
forskolin and dibutyryl-cAMP increased net cumulative glucose
cent (ECLA) screening assay being developed as a companion
production, while palmitate, glucagon or insulin did not alter
glucose production. Lastly, PLCS from both pharmacological and diagnostic by ARUP Laboratories (Salt Lake City, USA). Additionally,
all participants were required to be on FVIII prophylaxis and have had
genetic models of GSD type 1 showed markedly reduced glucose
production and elevated lactate production, in line with the clinical at least 150 exposure days to FVIII replacement products without
disease phenotype. previous clinically detectable FVIII inhibitor development. Following
dose administration, plasma was analyzed for AAV5 TAb, and a cell-
based AAV5 transduction inhibition (TI) assay was used to further
characterize the capsid-neutralizing potential of the anti-AAV5
antibodies. Development of FVIII inhibitors was monitored using
the Nijmegen-modified Bethesda assay, and FVIII-specific TAb were
assessed by bridging ECLA. Additionally, peripheral blood mono-
nuclear cells were collected for analysis in a validated IFN-γ ELISpot
assay for detection of capsid-specific and hFVIII-SQ-specific cellular
immune responses.
Results: All participants developed a humoral antibody response to
valoctocogene roxaparvovec following dose administration.
Transient, low level AAV5 capsid-specific cellular immune responses
were detected in the majority of subjects where incidence peaked at
Week 2 following dose administration and often declined or reverted
to negative over the first 52 weeks. Similarly, sporadic positive FVIII
cellular immune responses were detected in a limited number of
Conclusion: PCLS can be used to study glucose production ex vivo up subjects. No subjects developed FVIII inhibitors following adminis-
to 24 h in culture and DHA seems to result in the higher net glucose tration of BMN 270.
production. In ongoing follow-up experiments, 13C-labelled DHA Conclusion: Immune responses to valoctocogene roxaparvovec were
and/or glycerol are used to test their role as a gluconeogenic predominantly directed toward the AAV5 capsid, characterized by the
precursor or a gluconeogenic regulator. Finally, PCLS offer the production of anti-AAV5 binding and neutralizing antibodies as well
possibility to use patient liver biopsy, murine genetic models and as transient AAV5 capsid-specific cellular immune responses. Capsid-
pharmacological intervention. Hence, they are an excellent and specific cellular immune responses showed a moderately positive
promising ex vivo platform to study endogenous glucose production correlation with plasma levels of the liver enzyme ALT suggesting
in GSD type 1 and other inborn errors of metabolism. these responses may be a contributing factor to transient elevations
in ALT in some participants. There was no clinical evidence of
inhibitor formation in subjects dosed with valoctocogene
roxaparvovec.

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 POSTER PRESENTATIONS
Friday 24 June factors (disease status, sex, genotype, age) and viral factors (load,
mutation) on transcriptional responses.
Results: We observe key modules of transcription which can be
impacted differentially by host and viral factors. Underlying cirrhotic
state had the most substantial impact, even in a stable, compensated
population. Notably, sex had a major impact on antiviral responses in
Viral hepatitis C: Clinical aspects except therapy concert with IL28B (interferon lambda) genotype, with stronger
interferon and humoral responses in females. Males tended towards a
dominant cellular immune response. In both sexes there was a strong
FRI301 influence of the underlying host disease status and of specific viral
Sex effect on key intrahepatic gene networks in hepatitis C virus mutations, and sex-specific eQTLs were also observed.
infection Conclusion: These features help define the major influences on
Emanuele Marchi1, Paul Klenerman1, Narayan Ramamurthy1, tissue responses in HCV infection, impacting on the response to
Azim Ansari1, Eleanor Barnes1, Caroline Harrer1. 1University of Oxford, treatment and with broader implications for responses in other sex-
NDM-Nuffield Department of Medicine, Oxford, United Kingdom biased infections.
Email: [email protected]
FRI302
Background and aims: Spontaneous HCV clearance and successful
Active case management to connect hepatitis C notifications to
antiviral therapy rates are largely in favour of women and/or in
care and treatment in Australia (CONNECT study), a randomised
subjects with a specific IFNL4 genotype. The unfavourable IFNL4
controlled trial
genotype leads to an exaggerated interferon response eventually
detrimental for the patient. However, women tend to have a more Tafireyi Marukutira1,2, Karen Moore3, Margaret Hellard1,
robust and prompt interferon activity. Beyond this, the causes of sex Jacqui Richmond1, Kate Turner3, Alisa Pedrana1, Shannon M. Melody3,
differences in infections are insufficiently understood. The transcrip- Louise Owen3, Wijnand Van Den Boom1, Nick Scott1,
tional response in the liver during hepatitis C virus (HCV) infection is Alexander Thompson4, David Iser4, Tim Spelman1, Mark Veitch3,
critical for determining clinical outcomes. This issue remains Mark Stoove1, Joseph Doyle1. 1Burnet Institute, Melbourne, Australia;
2
relatively unexplored as tissue access to address this at scale is Monash University, Melbourne, Australia; 3Tasmanian Department of
usually limited. We aimed to profile the transcriptomics of HCV Health, South Launceston, Australia; 4St. Vincent’s Hospital Melbourne,
infected livers to describe the expression networks involved and Fitzroy, Australia
assess the effect on them of major predictors of clinical outcome such Email: [email protected]
as IFNL4 host genotype and sex. Background and aims: Despite the simplicity, tolerability and
Method: We took advantage of a large clinical study of hepatitis C subsidised access of directly acting antivirals (DAAs), hepatitis C
therapy accompanied by baseline liver biopsy to examine the drivers (HCV) treatment uptake in Australia is declining. Initiatives are
of transcription in tissue samples in 195 patients also genotyped needed to actively engage people living with HCV to link them to care
genome-wide for host and viral SNPs. We addressed the role of host and treatment. In this study, we measured the impact of using

Figure: (abstract: FRI301)

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S541

POSTER PRESENTATIONS
hepatitis C notifications systems to engage diagnosing general FRI303
practitioners (GPs) and improve patient access to treatment. Find out HCV patients: systematic study of 2013–2020 HCV files of
Method: The CONNECT study was a randomised controlled trial that a MDT viral hepatitis expert unit on the future of patients has
compared enhanced case management delivered to clinicians made it possible to find out the lost ones and put them into
notifying new/repeat HCV diagnoses to standard of care in treatment
Tasmania, Australia over 12 months in 2020–2021. GPs were André-Jean Remy1, Sonia Djazouli1, Hakim Bouchkira1,
randomised based on their first HCV notification during the study Jeremy Hervet1, Berengere Roy1. 1Perpignan Hospital, Mobile Hepatitis
period. The intervention involved a health department nurse Team, Perpignan, France
specialist contacting notifying GPs directly and providing stepwise Email: [email protected]
support by telephone, and direct patient contact if required. The
Background and aims: Access to direct antiviral agents (DAA) has
primary outcome was the proportion of individuals with HCV who
been progressively needed since 2013. But what happened to the
initiated DAAs within 12 weeks of HCV antibody notification.
Secondary outcomes compared proportion completing pre-treat- patients, treated or not, seen since that date? Several studies have
been conducted to find patients seen in consultation or hospitaliza-
ment HCV RNA testing and blood work-up.
Results: A total of 171 GPs were enrolled and randomised to the tion but without assessing the fate of the entire active queue. Our
objectives were to evaluate follow-up of patients spent in multidis-
intervention (n = 85) or the standard of care (n = 86) arms. Over the
ciplinary team meeting (MDT) within our hospital viral hepatitis
observation period, GPs in the intervention notified 111 HCV antibody
positive cases compared to 115 in standard of care. A higher expert unit, even when it was no longer mandatory for an DAA,
treatment decision in the absence of current healing, to offer them
proportion of HCV notifications in the intervention compared to
standard of care completed HCV RNA testing (96% vs. 86%; p = 0.03) DAA treatment.
Method: All MDT sheets from September 2013 to December 2020
and 33% compared to 30% were HCV RNA+ve ( p = 0.19) respectively.
have been reviewed. We contacted GP, patient or private hepatologist
Pre-treatment workup among those eligible for treatment (RNA+ve)
was similar between intervention and standard of care arms (62% vs. by email or telephone for an estimated 5 hours of work per week.
Follow-up data were collected via our hospital’s computerized file. In
65%; p = 0.82). The proportion of all HCV notifications that initiated
treatment was similar between intervention and standard of care the absence of direct contact; national death database was consulted.
arms (20% vs. 14%; p = 0.24). The proportion of treatment eligible Results: As of 31th August 2021, 1158 MDT files were initially studied
corresponding to 1032 different patients; there were 683 men and
cases initiating treatment within 12 weeks of notification was also
similar between study arms (38% vs 32%; p = 0.63) (Figure 1). Most 349 women of average age 37 years and 41% of F3F4 fibrosis; 97
patients were known to have died (69% of non-hepatic cause), 413
cases who did not initiate were lost to follow up or were referred to a
cured without liver complications; 153 followed for their cirrhosis
specialist.
and 41 for hepatocellular carcinoma; 328 were lost of sight of 68
previously followed by our team and 146 by liberal hepatologists. As
of 31th October 2021, the contact information for 54patients was
missing or incorrect; no information had yet been obtained for 126
patients followed in liberal; 37 additional patients were found within
one month of which 8 were already cured and 15 died; 14 were
eligible for immediate treatment due to an available positive viral
load; 11 patients accepted an appointment for a referral of which 9
had already started the treatment and 2 patients refused the care;
there were 90 patients followed by our team to contact or relaunch,
which should be achieved within 3 months.
Conclusion: Maintaining MDT transition of all patients with chronic
hepatitis C allows for an efficient database and to find untreated and/
or untreated patients and offer them treatment. Number of refusals to
care remains low, less than 10%. Our study, initially planned as a
cohort retrospective analysis, found patients with chronic hepatitis C
with RNA positive and untreated and immediately treated. This work
Figure: HCV Testing and Treatment Cascade. shows that there are still patients who know they are infected with
Conclusion: This is the first prospectively randomised study that HCV but have not yet been treated. The research and treatment of
explored the utilisation of HCV surveillance data to enhance linkage these patients is essential to the elimination of hepatitis C.
to HCV treatment. While there was no difference in treatment
FRI304
initiation, the intervention encouraged more GPs to complete RNA
Effectiveness of a central monitoring system for the continuum of
testing as the initial stage of assessing DAA eligibility. Health
care of hepatitis C in Brazil during COVID-19 pandemic
Department follow up could potentially augment HCV antibody
Paulo Bittencourt1, Liana Codes1, Maria Lucia Ferraz1. 1Brazilian Liver
testing to ensure DAA eligibility is assessed early.
Institute
Email: [email protected]
Background and aims: Several healthcare facilities dedicated to
hepatitis C testing and linkage and retention to care were closed in
Brazil due to the COVID-19 pandemic, leading to a 40%-50% reduction
in the distribution of HCV rapid tests as well as new treatments for
HCV in 2020. To mitigate the adverse impact of the pandemic on the
hepatitis C elimination plan, the Brazilian Liver Institute (Ibrafig)
sponsored a remote patient support program (PSP) to monitor all
aspects of the HCV care continuum (HCV CC) in the public health
system. The aims of the present study were to assess the results of this
strategy in different steps of the HCV CC in Brazil.

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 POSTER PRESENTATIONS
Method: After mapping of the active healthcare facilities offering Conclusion: Our preliminary data showed that identification and
HCV rapid tests to the general population as well as diagnosis and retrieval for treatment of HCV patients lost to FU is an effective
treatment for HCV, Ibrafig launched a remote PSP to follow-up microelimination strategy despite the low callback success rate.
subjects in all steps of HCV CC from testing of hepatitis C until HCV
cure. The remote PSP wascomprised by trained healthcare personnel FRI306
and contacts were made through phone calls, SMS, email or Reorganizing and simplifying HCV diagnosis and treatment in
whatsapp according to users preferences. Awareness campaigns special populations during COVID pandemic and beyond
concerning hepatitis C elimination were coupled with nationwide Paolo Scivetti1, Elisa Perfetti1, Lorenzo Somaini2, Sarah Vecchio2,
advertising of the remore CMS on social media, TV and radio. Antonio Panero1, Paola Zaldera3. 1ASLBI Ospedale degli Infermi, SOC
Results: From August 2020 to July 2021, 11.049 interactions were Internal Medicine-Hepatology Centre, Ponderano, Italy; 2Aslbi, Addiction
recorded between usersand CMS, most of them by Whatsapp (91%). Treatment Centre, Biella, Italy; 3Aslbi, Casa Circondariale-Health Section,
Most of them became aware of the PSP by radio and/or TV (41%) and Biella, Italy
social media (31%). After informed consent, 601 subjects were Email: [email protected]
registered in the PSP including 74 patients already diagnosed with Background and aims: Hepatitis C infection has a high prevalence
HCV who were lost in the public healthcare system due to the COVID-
among prisoners and in people who use drugs (PWUDs) and his
19 pandemic. Overall, 501 subjects were referred for HCV testing. identification and treatment are a pivotal factor to achieve HCV
Fifteen (9%) out of the 115 subjects who reported their test results
elimination by 2030. However, PWUDs and prisoners often face
were positive for HCV. Up to now, 53 (60%) out of 89 HCV positive
multiple barriers during the treatment cascade. In our Local Health
patients have scheduled their 1rst consultation, 12 (13%) are enrolled Unit of Biella we have already developed a shared model of care
in care and 14 (16%) are under antiviral treatment. Seven (8%) who
between Addiction Treatment Centre (SerD), prison and hospital
achieved end of treatment response are waiting HCV sustained hepatology centre, to gather clinical evaluations within a single visit
virological response. in order to ameliorate the HCV treatment rate. Subsequently, the
Conclusion: Our preliminary data showed that a remote PSP was an
treatment journey has been complicated by Covid pandemic. The aim
effective strategy to monitor the HCV CC. It was capable to refer at risk of this study is to describe the new model of care we have developed
subjects for HCV testing and to provide linkage and retention to care
to overcome old and new barriers to HCV treatment in these special
of those HCV positive subjects in the Brazilian public health system
populations.
during the COVID-19 pandemic. Method: Since march 2020 a new model of care has been developed
FRI305 and centered on three crucial elements: a collaboration between
SerD, prison and hospital hepatology centre; the introduction by AIFA
Retrieval of HCV patients lost to follow-up as a strategy as a
strategy for hepatitis C microelimination: results of a brazilian (Italian Agency of Drugs) of the “criterion 12” that allows treatment
after ruling out liver fibrosis by APRI and FIB-4 without elastography;
multicentric study
the evidence that these scores allow us to exclude severe fibrosis, the
Paulo Bittencourt1, Maria Lucia Ferraz1,
risk of a hepatocarcinoma and the need of an ultrasound test. Patients
Gustavo Henrique Santos Pereira2, Liana Codes1, Antonio Andrade2,
attending SerD performed HCV viral load by mean of on-site
Carlos Brandão-Mello2. 1Brazilian Liver Institute; 2Brazilian Society of
fingerstick assay and inmates by mean of salivary test for antiHCV.
Hepatology
HCVrna positive patient’s data were recorded into a database shared
Email: [email protected]
between the three services. After ruling out severe fibrosis by APRI
Background and aims: Several HCV positive patients in Brazil were and FIB-4, hepatologist prescribed the DAAs (direct-acting antiviral
lost to follow-up in the last two decades before achievement of agent) with virtual “computer-generated” evaluation of the patients.
sustained virological response (SVR) due to either non-response to DAAs were delivered by the SerD’s or prison’s health professionals.
interferon-based therapy or lack of treatment due to comorbidity or The patients were directly visited by the hepatologist only in the case
mild fibrosis. The purpose of the present study was to identify and of severe fibrosis at the scores.
retrieve those lost patients to offer treatment with the current highly Results: HCVrna was detected in out of 33/250 SerD patients’ and in
effective direct acting antivirals (DAAs). out of 4/44 inmates, respectively. Linkage to care was possible for a
Method: All medical charts from three major reference centers for total of 34 patients (30 SerD and 4 Prison). The patients were mostly
treatment of hepatitis C were retrospectively reviewed by trained male, and heroin addicted. Sixteen of them had only a virtual
healthcare personel to identify all HCV positive subjects, their evaluation, conversely 18 patients underwent to direct examination.
treatment status and, in those HCV RNA positive patients, the main Overall, 34 patients completed the treatment, and all of them
reasons for non-achievement of SVR or lack of treatement. After achieved Sustained Virologic Response.
review of a local senior hepatologist, all patients who were not Conclusion: Our new model of care highlights the feasibility of the
treated or cured were contacted in order to offer therapy with DAAs. on-site HCV testing and the efficacy of this simplified virtual
Results: 7.498 medical charts were reviewed, 5549 (74%) from HCV “computer-generated” procedure for the treatment of HCV in
positive patients (50, 1% males, mean age 51±12years). Advanced special populations. This new model of care has allowed us to
fibrosis or cirrhosis and hepatocellular carcinoma were observed in continue the diagnosis, the linkage to care and the treatment of
1929 and 95 subjects, respectively. Only 3272 (59%) were submitted patients even during COVID-19 pandemic and hopefully beyond.
to treatment. SVR, non-response to IFN-based and IFN-free regimens
was observed in 2348 (72%), 658 (20%) and 266 (8%) subjects,
respectively. Lack of treatment due to loss of FU (29%) or other reasons
(12%) such as comorbidity, mild fibrosis or treatment refusal were
reported in the remaining patients. Until October 2021, 2745 patients
were considered eligible to be retrieved by local investigators and
1593 phone calls were made with a callback success rate of 15%. 43
(2%)patients were retrieved for treatment. Most of the remaining
patients have been treated elsewhere (n = 61) or have died or
underwent liver transplantation (n = 69).

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POSTER PRESENTATIONS
FRI307 FRI308
The health economic outcomes of trial ACTG5360/MINMON Hepatitis C treatment during the COVID-19 pandemic has similar
Benjamin Linas1,2, Michelle Weitz1, Tannishtha Pramanick3, efficacy with less resource utilization: analysis from the British
Mark Sulkowski4, Irena Brates5, Laura Smeaton6, Sandra Cardoso7, Columbia HCV network
Sunil Suhas Solomon4. 1Boston Medical Center, Section of Infectious Shirley Jiang1, Jeanette Feizi1, Julia MacIsaac1, Edward Tam2,
Diseases, Boston, United States; 2Boston University School of Medicine, Hin HIn Ko1, Alnoor Ramji1. 1The University of British Columbia,
Medicine, Infectious Diseases, Boston, United States; 3Boston Medical Vancouver, Canada; 2Pacific Gastroenterology Associates, Vancouver,
Center, Section of Infectious Diseases, Boston, United States; 4Johns Canada
Hopkins University School of Medicine, Division of Infectious Diseases, Email: [email protected]
Baltimore, United States; 5Harvard T.H. Chan School of Public Health,
Background and aims: During the COVID-19 pandemic, a 49%
Center for Biostatistics in AIDS Research (CBAR), Boston, United States;
6 decrease in dispensation of direct-acting anti-virals (DAAs) for
Harvard T.H. Chan School of Public Health, Center for AIDS Research
hepatitis C (HCV) infection has been observed in Canada. We
(CFAR), Boston, United States; 7Instituto Nacional de Infectologia
sought to characterize HCV patients, treatments, and outcomes
Evandro Chagas, Rio de Janeiro, Brazil
during the pandemic.
Email: [email protected]
Method: Single-centre retrospective chart review at a site of the
Background and aims: The ACTG MINMON trial demonstrated that British Columbia HCV Network. Patients initiated on DAAs from
HCV treatment with no planned in-person monitoring is safe and 17/12/2018–16/3/2020 were included as the pre-pandemic group
efficacious. We report resource utilization and cost in the MINMON ( pre-PG), and compared to those treated from 17/3/2020–16/6/2021,
trial. who were included as the comparison pandemic group (PG).
Method: ACTG A5360 (MINMON) was a 5 country, single arm study Results: Over a 15-month period, 139 HCV patients were initiated on
providing 12 weeks of sofosbuvir/velpatasvir to people with HCV treatment as part of the PG compared to 179 patients in the pre-PG,
infection with no planned visits prior to SVR evaluation (Week 24). representing a 22% decline. Pandemic patients were significantly
Trial records included planned/unplanned lab tests and visits. younger (mean age 56.1 vs 59.5 years, p = 0.01) and a greater
Participants completed a 4-week recall questionnaire at weeks 0, proportion were on opioid agonist therapy (27% vs 12%, p < 0.01).
24, and 48 reporting hospital nights, emergency department visits, Patients had similar HCV genotypes and FIB-4 score. Significantly
and ambulatory visits. To cost MINMON, we tabulated consumption fewer PG patients had transient elastography (TE) within 6 months of
and multiplied units of consumption by country-specific cost. We initiating DAAs (52% vs 91%, p < 0.01). Of patients with TE scores,
report cost of MINMON per SVR attained (2020 US$) from the cirrhosis was found in 12 (8.6%) PG patients compared to 29 (16.2%)
program perspective (includes costs of medications and monitoring pre-PG. Patients treated during the pandemic also had fewer total
from study entry to Week 24), and the health sector perspective appointments (median 2 per patient vs 4 per patient pre-PG, p <
( program perspective plus healthcare utilization outside the study 0.01), with fewer office appointments (median 1 per patient vs 2 per
prior to cure, plus the additional (or reduced) healthcare utilization patient pre-PG, p < 0.01) but a similar number of telehealth
observed after HCV treatment). appointments (median 2 per patient for each group). Treatment
Sensitivity analyses explored potential cost savings of MINMON patterns were similar with predominant use of glecaprevir/pibren-
compared to the standard of care (SoC). We consulted in-country tasvir and sofosbuvir/velpatasvir. Treatment completion rate was
experts to develop country-specific SoC treatment protocols and higher for the PG vs pre-PG (96% vs 86%, p < 0.01). Fewer patients
employed standard micro costing to estimate cost. We present cost/ obtained lab work for sustained virologic response (SVR) in the PG
SVR in MINMON along with that of the simulated SoC, ranging the compared to pre-PG (74% vs 86%, p < 0.01). SVR rate was similar in
expected SVR with the SoC. both groups at 96% in the PG compared to 99% pre-PG ( p = NS).
Results: MINMON cost/SVR (healthcare sector perspective) varied by
country from $5, 256/SVR in Brazil, to $149, 257/SVR in the U.S.
(Graph). The program perspective ranged from $1, 637/SVR in Uganda
to $27, 641/SVR in the U.S. The cost of pharmaceuticals was the largest
component of treatment cost, ranging between 76%–96% of cost from
the program perspective.
MINMON had a lower cost/SVR ( program perspective) than the SoC
across broad assumptions about cure rates. Outside of the U.S., the
cost/SVR of MINMON was lower than that of the SoC even when the
SoC achieved higher cure than MINMON. In the U.S., the MINMON
cost/SVR was lower than the SoC unless the SoC would be expected to
achieve at least a 4-percentage point higher cure rate.
Figure: Patients started on HCV treatment and corresponding SVR rate

Conclusion: Patients with HCV infection treated during the COVID-19

pandemic utilized significantly less resources, had a higher rate of
treatment completion, and similar rate of SVR. Treatment simplifi-
cation through the use of telemedicine, minimizing investigations,
and leveraging fewer healthcare resources can maintain high
treatment completion and SVR rates.

Conclusion: MINMON is likely a cost saving strategy compared to the

SoC for HCV treatment.

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 POSTER PRESENTATIONS
FRI309 recall (172; 9.6%) and death (289; 16.1%). Successful DAA therapy at
ELIMINATE-interim results of an Austrian HCV macro-elimination other centers had already been conducted in 366 patients (20.4%).
project
Caroline Schwarz1,2,3, David Jm Bauer1,2, Livia Dorn4, Mathias Jachs1,2,
Lukas Hartl1,2, Heidemarie Holzmann5, Nikolaus Pfisterer1,2,6,
Barbara Hennlich6, Florian Mayer7, Ralf Schmidt7,
Astrid Voll-Glaninger8, Wolfgang Hübl9, Martin Willheim10,
Karin Köhrer11, Sonja Jansen-Skoupy12, Sabine Tomez13,
Walter Krugluger13,14, Christian Madl6,15, Michael Schwarz1,2,3,
Leonard Brinkmann1,2,3, Lukas Burghart1,2,3, Gerhard Weidinger16,
Florian Riedl4, Hermann Laferl17, Christoph Wenisch17,
Abdelrahman Aburaia18, Christian Sebesta18,19, Daniela Schmid20,
Thomas Reiberger1,2, Andreas Maieron4, Michael Gschwantler3,15.
1
Medical University of Vienna, Department for Internal Medicine III,
Division of Gastroenterology and Hepatology, Vienna, Austria; 2Medical
University of Vienna, Vienna HIV & Liver Study Group, Vienna, Austria;
3
Klinik Ottakring, Department for Internal Medicine IV, Vienna, Austria;
4
University Clinic St. Pölten, Department for Internal Medicine II,
St. Pölten, Austria; 5Medical University of Vienna, Center for Virology,
Vienna, Austria; 6Klinik Landstraße, Department for Internal Medicine
IV, Vienna, Austria; 7Medical University of Vienna, Clinical Institute for
Laboratory Medicine, Vienna, Austria; 8Klinik Landstraße, Central
Laboratory and Blood Bank, Vienna, Austria; 9Klinik Ottakring, Central
Laboratory, Vienna, Austria; 10University Clinic St. Pölten, Clinical
Institute for Laboratory Medicine, St. Pölten, Austria; 11Landesklinikum
Wiener Neustadt, Institute for Medical-Chemical and
Molecularbiological Laboratory Diagnostics with Blood Depot, Wiener Figure 1: Cascade of care for the ELIMINATE project.
Neustadt, Austria; 12Klinik Favoriten, Institute for Laboratory
Conclusion: This lab record-based ELIMINATION project identified a
Diagnostics, Vienna, Austria; 13Klinik Donaustadt, Institute for
considerable number of 6223 HCV patients with potential persisting
Laboratory Medicine with Blood Depot, Vienna, Austria; 14Klinik
viremia. Invalid contact data (36.9%) and pre-treatment death (16.1%)
Floridsdorf, Institute for Laboratory Medicine and Blood Depot, Vienna,
represent major problems/barriers. Importantly, at this interim stage
Austria; 15Sigmund Freud University, Vienna, Austria; 16Landesklinikum
305 (17.0%) patients were successfully linked to care and 64 (3.6%)
Wiener Neustadt, Department for Internal Medicine, Gastroenterology
patients started DAA therapy.
and Hepatology, Wiener Neustadt, Austria; 17Klinik Favoriten,
Department for Internal Medicine IV, Vienna, Austria; 18Klinik FRI310
Floridsdorf, Department for Internal Medicine and Gastroenterology, The korean hepatitis C virus care cascade in a tertiary institution:
Vienna, Austria; 19Klinik Donaustadt, Department for Internal Medicine current status and changes in testing, link to care, and treatment
II, Vienna, Austria; 20Austrian Agency for Health and Food Safety (AGES), Jonggi Choi1, Jina Park1, Danbi Lee1, Ju Hyun Shim1, Kang Mo Kim1,
Vienna, Austria Young-Suk Lim1, Han Chu Lee1. 1Asan Medical Center, University of
Email: [email protected] Ulsan College of Medicine, Department of Gastroenterology, Seoul, Korea,
Background and aims: The WHO has declared the elimination of Rep. of South
HCV until 2030 a global public health goal. We present the Email: [email protected]
preliminary results of an Austrian macro-elimination approach Background and aims: The care cascade for hepatitis C virus (HCV)
aiming to provide linkage to care and treatment initiation for infection is impeded by multiple barriers, including suboptimal HCV
persons who are recalled based on a “last-positive” HCV-RNA PCR Ab testing, link to care, and diagnosis. We explored the changes in the
result. Importantly, many of these lost-to-follow-up patients do not care cascade of HCV for the past 20 years and its current status in a
belong to known HCV risk groups and are, thus, often not recognized large cohort from a tertiary referral center.
by targeted HCV screening/elimination projects. Method: We analyzed 1, 144, 468 patients who had HCV Ab testing
Method: First, we identified patients with a “last-positive” HCV-RNA between January 2001 and June 2020. Metrics related to the care
PCR result between 2010 and 2020 in laboratories of Eastern Austria cascade of HCV infection and the long-term prognosis of patients
(Burgenland, Lower Austria, Vienna) and (i) described their demo- were explored.
graphic characteristics. Subsequently, (ii) a systematic recall of these Results: The seroprevalence of HCV Ab was 1.8%, with a recent
patients to the respective HCV treatment centers was performed, and decreasing trend. In all, 69.9% of HCV Ab-positive patients performed
(iii) HCV-DAA was initiated and SVR was monitored. Here we report HCV RNA testing, with a 65.7% positivity. Patients who did not have
the interim results of this ELIMINATE project including data/results HCV RNA testing were older and more likely to have a non-
from eight centers. hepatocellular carcinoma (HCC) malignancy, normal ALT level, and
Results: Overall, 22692 patients underwent HCV-RNA PCR testing, good liver function. Linkage times for HCV RNA testing from the HCV
11216 (49.4%) ever showed a positive HCV-RNA result, and in 6223 Ab positivity and for antiviral treatment from HCV diagnosis
(27.4%) patients the last available HCV-RNA result was positive decreased, notably after 2015, when highly efficacious oral antiviral
(suggesting persisting HCV-viremia). treatment was introduced to Korea. The average treatment uptake
For this interim report, 1795/6223 HCV-RNA PCR (+) patients were rate was 35.4%, which increased to 38.9% after 2015. Of the 5, 302
evaluated: 305 (17.0%) were linked to HCV-care. 82 (4.6%) underwent patients analyzed regarding long-term prognosis, the annual inci-
liver disease evaluation and in 64 (3.6%) DAA treatment was initiated. dences of HCC were 1.02 and 2.14 per 100 person-years in patients
In 10 (0.6%) sustained virologic response was documented. with and without a sustained virological response, respectively.
Main reasons for the suboptimal cascade of care included invalid
contact data (663; 36.9%) or patients’ unavailability at the time of

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POSTER PRESENTATIONS
prior to DAA availability ranged between $5.3–5.8B then peaked at
$9.0B in FY2015 due to massive increases in pharmacy-related costs
(Figure 1B) then declined to pre-DAA levels by FY2020. Modest
increases of outpatient and inpatient costs were observed from
FY2010 to FY2018 at which point a significant decline occurred.
However, the cost per-patient under care never declined to pre-DAA
levels and only a modest decline in outpatient and inpatient
expenditures was observed FY2019–2020 (Figure 1C).

Conclusion: These data suggest that reductions in overall healthcare

costs for a hepatitis C-infected population cannot be observed within
the first several years after implementation of universal treatment.
Reductions in total cost to pre-DAA levels appear more related to
Conclusion: The care cascade of HCV infection has been suboptimal patient attrition than to reduction of average patient treatment costs.
for the past 20 years, despite the recent changes. More effort should
be made to increase HCV RNA testing and treatment uptake. FRI312
Awareness of chronic hepatitis B and C among men who have sex
FRI311 with men (MSM): epidemiological survey and on-site screening
Macroeconomic assessment of overall and per-patient healthcare Marie Coessens1,2,3, Tom Holvoet4, Jeoffrey Schouten4,5,
costs of Hepatitis C-infected patients in an integrated health Wim Verlinden2,5. 1VITAZ, Gastroenterology and Hepatology,
system in the era of direct-acting antiviral therapy Sint-Niklaas, Belgium; 2University of Antwerp, Department of Medicine
David Kaplan1,2, Claire Durkin1, Marina Serper1. 1University of and Health Sciences, Antwerp, Belgium; 3Laboratory of Experimental
Pennsylvania, Medicine/Gastroenterology and Hepatology, Philadelphia, Medicine and Pediatrics (LEMP), University of Antwerp, Antwerpen,
United States; 2Corporal Michael J. Crescenz VA Medical Center, Belgium; 4UZ Gent, Gastroenterology and Hepatology, Gent, Belgium;
Medicine/Gastroenterology and Hepatology, Philadelphia, United States 5
AZ Nikolaas, Gastroenterology and Hepatology, Sint-Niklaas, Belgium
Email: [email protected] Email: [email protected]
Background and aims: Treatment of acute and chronic hepatitis C Background and aims: In order to eradicate Hepatitis B (HBV) and
infection on a national or system-wide scale requires significant Hepatitis C (HCV) by 2030, the WHO focuses on screening in targeted
investment to acquire, dispense and monitor antiviral therapy with high-risk populations, including men who have sex with men (MSM).
the intent to reduce downstream costs related to reduced liver- The objectives of this study are to assess awareness and knowledge
related complications. The US Veterans Administration (VA) initiated (1) and prevalence (2) of HBV and HCV infections in the MSM
universal access to HCV direct acting antiviral (DAA) therapy in 2015. population in Flanders and Brussels.
The Aim of this study was to quantify the total healthcare costs Method: An online questionnaire in Dutch of 5 to 10 minutes was
expended on prior and current hepatitis C-infected individuals used, as well as face-to-face questionnaire using a tablet at the
before, during after the universal introduction of DAA therapy. Belgian and Antwerp Pride (1). In 2018–2020 we joined Sensoa
Method: All patients in the VA healthcare system with a positive HCV (a Flemish expertise center for sexual health) during outreach
RNA by a qualitative or quantitative PCR tests at any time between projects and tested visitors voluntarily at 14 gay bars, parties and
1999 and 2020 were identified. Exposure to antiviral therapy was saunas in Flanders by means of an oral quick test for HCV (e.g. OraSure
identified by prescription fills for interferons and DAA medications. Intercept 2). In addition, HCV test results collected by Ex Aequo (an
Treatment completion was assigned as 28 days after the final release MSM organization in Brussels that provides sexually transmitted
for a specific regimen and the first date for possible assessment of diseases (STD) screening at offices and during on-site actions) in 2019
SVR12 assigned to 84 days after treatment completion. Each course of were analyzed (2).
therapy was characterized based on post-SVR12 date PCR results as Results: 300 MSM participated in the online Dutch questionnaire
cured, relapsed or untested if no PCR test was available. Health with a median age of 36 years old. HIV status was known to be
Economics Research Center (HERC) average cost estimates and Fee- positive in 7.7%. Knowledge of HBV and HCV infections was poor. Of
Basis costs were utilized for outpatient and inpatient care within the all participants, 40.5% and 47, 6% thought HBV and HCV patients
VA and external costs, respectively. Cost of outpatient pharmacy were would always have symptoms; 52.9% thought there was an HCV
obtained from Managerial Cost Accounting data. For this analysis, vaccine; 37.1% thought there was no medication against HCV and of
total, outpatient, inpatient and pharmacy were aggregated by fiscal those who knew there was medication, 75% thought that treatment
year (years 2010–2020) and presented as aggregate or per-patient was long and hard. Only 15% and 1%, respectively, knew which sexual
costs. All costs were inflation-adjusted to year 2021 dollars using the practices were with or without risk for HBV and HCV infection.
consumer price index and post-treatment costs were discounted by The knowledge of HBV was significantly correlated to the knowledge
3% per year. of HCV ( p < 0.0001, rs 0.324) and the degree of education ( p < 0.001,
Results: During fiscal year 2010, 214, 531 unique infected individuals rs 0.209). The knowledge of HCV was significantly correlated to the
were under care. By 2020, only 68, 086 HCV-infected patients did not number of sexual partners in the last six months (p = 0.024, rs 0.131),
have documentation of SVR12 (Figure 1A). Total cost expenditures the number of risky sexual practices ( p < 0.0001, rs 0.205).

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 POSTER PRESENTATIONS
In Sensoa’s HCV prevalence study, only 1 of 260 test results was
positive (0.38%) and this was an HIV co-infected patient. The Ex
Aequo’s HCV prevalence study yielded no positive test results. The
HIV prevalences were 1, 15% (Sensoa) and 1, 3% (Ex Aequo) and the
syphilis prevalence was 2, 5% (Ex Aequo).
Conclusion: There is a big knowledge gap of HBV and HCV infections
in the MSM community in Flanders. More awareness campaigns that
focus on transmission, disease process, treatment and vaccination
need to be created that also target people with a low educational
level.
The prevalence of hepatitis C infection and other STD’s was low in the
MSM population studied of 500 participants. Presumably a young
MSM population that voluntarily has themself tested represents a
rather low risk profile for HCV infection. HCV prevalence may be
higher in an older population and/or in an illegal environment where Figure: Co-morbidity: DM, cardiac, renal, NASH; *p-value based on Chi-
more risk factors for HCV infection co-exist and that is more difficult square
to reach. However, given the high workload and low case finding, an Conclusion: Male gender, history of psychiatric disorder, IDU, or and
on-site screening approach cannot be recommended. heavy alcohol use are predictive of LFU both pre- and post-HCV
therapy. Successful HCV elimination strategies will need to incorp-
FRI313
orate interventions to improve durable engagement of these
Predictive factors for lost to follow-up pre and post-hepatitis C
populations.
treatment: Data from the British Columbia hepatitis C virus
network FRI314
Alnoor Ramji1, Edward Tam2, Julia MacIsaac3, Jean-Philippe Wallach3, HCV screening in a tertiary french hospital: just do it !
Jeanette Feizi2, Hin Hin Ko1. 1University of British Columbia, Si Nafa Si Ahmed1, Souad Benali1, Magalie Madau1, Rania Kibeche1,
Gastroenterology, Vancouver, Canada; 2Pacific Gastroenterology Romain Albenois2, Michaël Ghez3, Ines Belasri1,
Associates, Vancouver, Canada; 3University of British Columbia, Christine Hernandez1, Paola Ramirez1, Julien Negre1,
Vancouver, Canada Laurence Lecomte1, Floriane Sellier1, Olivia Pietri1, Paul Castellani1,
Email: [email protected] Xavier Adhoute1, Marc Bourliere1. 1Hopital Saint Joseph, Hepatology
Background and aims: In British Columbia (BC) 60% of identified Unit, Marseille, France; 2Hopital Saint Joseph, Laboratory Unit, Marseille,
HCV RNA (+) individuals remain untreated. A major challenge is the France; 3Hopital Saint Joseph, DIM, Marseille, France
durable linkage to care of persons who are HCV RNA (+), many are lost Email: [email protected]
to follow-up (LFU) prior to therapy ( pre-LFU), or post therapy ( post- Background and aims: Universal screening appears to be the most
LFU). Understanding patient profiles will inform resources for HCV cost-effective strategy to reach the HCV elimination planned by WHO
elimination. Our aim was to determine predictive factors of HCV for 2030. All HCV patients have currently access to treatment. In
patients who are LFU pre- and post-treatment. France HCV screening is based on identification of Risk Factor. The
Method: Retrospective review of HCV RNA (+) persons in the BC HCV aim of the present study was to test universal screening strategy in all
Network to determine the predictive factors of pre-LFU and post-LFU hospitalized patients.
compared to treated persons with SVR12. Chi-square and multi- Method: From November 2019 to November 2021, we conduct a
variable regression analysis were performed. prospective, longitudinal monocentric study screening all consent
Results: A total of 4057 patients were included, 2823 (70%) patients for HCV regardless identification of Risk Factor. All HCV Ab
completed HCV therapy, 111 (2.5%) awaiting therapy, and 1123 positive was followed by HCV RNA screening. All replicating patients
(27.5%) were pre-LFU. See table. Pre-LFU patients were more likely to were proposed to be treated according to the other pathologies for
be male (70%), have psychiatric disorder (30%), history of injection which the patients were hospitalized. The study was authorized by
drug-use (IDU) (37%), and heavy alcohol use (38%) compared to CPP Toulouse.
treated patients (64%, 18%, 26%, and 27% respectively, p < 0.001). Because of occurrence COVID 19 pandemics, conducting this study we
Fewer persons with advanced fibrosis (FIB4 > 3.25 or LSM > 12.5 kPa) identify several limitations leading to the prolongation of inclusion
were in the pre-LFU group (22%) compared to treated group (30%), time and to develop adaptive measures such as oral consent.
p < 0.001. Results: As of September 30, 2021 results are shown in this figure:
2823 patients completed HCV therapy, 2410 (85.5%) had SVR
bloodwork, and 413 (14.5%) did not ( post-LFU). Male gender (69%),
history of psychiatric disorder (24%), IDU (36%), and heavy alcohol use
(35%) were more likely to be post-LFU compared to treated patients
(63%, 16%, 26%, 27% respectively, p < 0.001). Persons age > 60 years
(57%), with a co-morbidity (12%), or advanced fibrosis (20%) were
more likely to have SVR12 results documented than the post-LFU
group (65%, 17%, and 29% respectively), p < 0.001. Multivariable
regression for pre and post LFU compared to treated or followed
persons, determined that male gender (OR:2.12 and 2.70), psychiatry HCV Ab + patients seemed older; however this difference is not
disease (OR:3.45 and 3.33), IDU (OR:4.25 and 3.05), or heavy alcohol statistically different. Large part of patients (2/3) were unware of the
use (OR:3.65 and 2.90) were associated with pre and post-LFU. HCV status.
49 (39.5%) patients come from surgical departments, 38 (30.5%) from
the medical department and 37 (30%) are followed in gastroenter-
ology office.
All HCV RNA+ patients have been evaluated for treatment. 8 are
eradicated, 2 DAA therapy are still on going, 1patient refuse treatment
(89 years old), 5 patients suffer from HCC and treatment was delayed,
2 patients died during palliative management

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POSTER PRESENTATIONS
Conclusion: HCV Ab prevalence recorded is significantly higher than FRI316
that observed in the general population in France. However only Maximizing the potential of Cepheid, GeneXpert PCR rapid testing
15.8% of hospitalized patients have been included. Motivation of all for hepatitis C through use of finger prick blood samples collected
health care workers is essential. Final results of the study will be into EDTA capillary tubes
present at the meeting Anam Choudhry1, Louise Davies2, Nicki Palmer2, Jade Davies3,
Bazga Ali4, Rhys Oakley5, James Plant6, Louise Evans6, Chinlye Chng6,
FRI315 Helen Thompson-Jones6, Lorraine Wall7, Sarah Nicholas7,
Hepatitis C screening rates by age cohort 1945–1965 in a large Brendan Healy4,8. 1Cardiff University School of Medicine, Cardiff, United
community health system before, during and after the COVID Kingdom; 2Public Health Wales Cardiff, Cardiff, United Kingdom; 3Public
pandemic Health Wales Swansea, Swansea, United Kingdom; 4University Hospital
David Bernstein1, Nitzan Roth1, Ben Da1, Sanjaya Satapathy1, Wales, Cardiff, United Kingdom; 5Cardiff and Vale Pharmacy, United
Henry Bodenheimer1, Christian Kuntzen1, Tai PIng Lee1. 1Donald and Kingdom; 6Swansea Bay UHB BBV Team, Swansea, United Kingdom;
Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, 7
Cardiff and Vale UHB BBV Team, Cardiff, United Kingdom; 8Public
United States Health Wales, United Kingdom
Email: [email protected] Email: [email protected]
Background and aims: In the outpatient primary care setting, Background and aims: The Cepheid, GeneXpert provides hepatitis C
New York State mandates the offering of hepatitis C (HCV) testing for virus (HCV) PCR results <90 minutes. A major limitation is the need to
persons born between 1945 and 1965. Despite this mandate, <50% of load finger prick samples <15 minutes, as patients must be co-located
HCV screening candidates are offered screening and among those with the machine. Venous blood collected into EDTA tubes can be
found to be HCV Ab positive, not all patients undergo HCVRNA testing stored for up to 72 hours at 2–8°C prior to processing. In this project
and even fewer are referred for treatment. finger-prick blood collected into EDTA capillary tubes and processed
Method: We implemented a system where nurse educators person- >15 minutes after collection was compared with venepuncture (gold
ally visited 60 outpatient primary care offices to educate regarding standard) and dried-blood spot testing (DBST) to facilitate testing
HCV screening. Visits occurred for the first 2 years of the project and remote from the machine (e.g. prison clinics on different wings
then were stopped due to the COVID pandemic. We evaluated our remote from a centrally located machine) but still delivering rapid
results by birth year, dividing patients into 4 groups, those born turn-around times with testing in close proximity to the point of
between 1945 and 1950, between 1951 and 1955, between 1956 and need.
1960 and between 1961 and 1965. Method: Capillary tubes (MiniCollect® Tube 0.25/0.5 ml K3E
Results: From April 1, 2018–August 31, 2021, 50, 047 previously K3EDTA-450530) were spiked with venepuncture blood from 25
unscreened patients born between 1945 and 1965 were screened adult patients undergoing HCV testing, processed on the Cepheid and
with an HCV AB with reflex testing to HCVRNA in all positive HCV ABs. the results compared. HCV positive patients in the community
10819 were born between 1945 and 1950, 11573 were born between undergoing testing (venepuncture or DBST) were then approached to
1951 and 1955, 13586 were born between 1956 and 1960 and 14069 provide an additional EDTA capillary tube finger-prick sample.
were born between 1961 and 1965. Screening decreased during the Samples were left for >15minutes <72 hours prior to processing
peak pandemic months of March-June 2020 but levels returned to and results compared. As the lower limit of quantification on the
baseline screening numbers by July 2020 and continued at a steady Cepheid is 40 IU/ml, results below this level were analysed separately.
state for the duration of the study. Results: Results from the first 36/50 patients are reported here. The
Subjects born 1945–1950, 234/10819 (2.2%) were HCV AB positive time between sample collection and testing ranged from 44 minutes
with 67/10819 HCVRNA positive (0.6%). Subjects born 1951–1955, to 94 hours 34 minutes. Samples with longest delays tested positive
326/11573 (2.8%) were HCV AB positive with 76/11573 HCVRNA (no suggestion of the results being affected). Two venepuncture
positive (0.7%). Subjects born 1951–1955, 303/13586 (2.2%) were HCV results were detected, viral load <12 IU/ml. Corresponding Cepheid
AB positive with 58/13586 (0.4%) HCVRNA positive. Subjects born results were negative as expected (results are not included below).
1961–1965, 230/14069 (1.6%) were HCV AB positive with 44/14069 One sample registered as “error” (Cepheid) and was not detected by
(0.3%) HCVRNA positive. DBST. In one sample the Cepheid result was not detected and
All patients were referred to a hepatitis C treating practitioner. 101 the DBST result detected in the “unreliable zone” −10 IU/ml. The LLD
patients completed therapy and 93 remain on treatment. There were of DBST is 1000 IU/ml and this likely is a false positive DBST result. Of
no differences by age groups in those accepting DAA treatment, in the remaining HCV positive samples (n = 32, log viral loads 0.19–
declining DAA therapy or in the numbers of patients who died during 2.05 IU/ml). The Cepheid successfully detected HCV in 30 (93.75%)
the study. (Figure 1). In the remaining two samples the Cepheid result was
Conclusion: This large community-based HCV screening program “invalid.” This could be due to internal quality standards, probe check
confirmed the NHANES study that approximately 2–2.5% of people failures, system computer failures or PCR process inhibition.
born between the years 1945–1965 are HCV AB positive. There were
no significant differences by age cohort in this group although there
was a trend for patients born between 1956 and 1965 to spontan-
eously clear the HCV virus without treatment. The COVID pandemic
temporarily led to decreased HCV screening but once the pandemic
began to ease, screening rates rapidly returned to pre-COVID levels as
did DAA treatment rates. The positive effects of in-person nurse
educators on primary care providers and their staffs persisted even
after these visits were stopped due to COVID.

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 POSTER PRESENTATIONS
Salerno, Italy; 18University of British Columbia, Vancouver, BC, Canada;
19
UC Gastroenterologia, Dipartimento di SpecialitàMediche, Azienda
Ospedaliera Universitaria di Modena, Modena, Italy
Email: [email protected]
Background and aims: Identifying factors that may influence
healthcare resource utilization (HCRU) among patients with hepatitis
C virus (HCV) infection is important to support the development of
initiatives that reduce healthcare resource burden and allow for more
patients to be treated. This study describes HCRU among treatment-
naïve, compensated cirrhotic patients treated with 8-weeks’ gleca-
previr/pibrentasvir (G/P), according to their history of drug use (DU)
and socioeconomic status.
Method: Here we present an interim subanalysis of the ongoing,
noninterventional, multicenter CREST study which includes chart
review data from France, Canada, Italy, and Spain. Demographic and
baseline characteristics were reported overall and for patients with
history of DU. HCRU was described by history of DU and occupational
status. In the group of patients with DU, HCRU was described
according to active vs former drug use, and route of drug
administration.
Results: This analysis included 206 patients who received ≥1 dose of
G/P; 139 (67.5%) were male, the median (range) age was 57 (31–88)
years (assessed in 203 patients), 185 (89.8%) had stable housing, and
52 (25.2%) were employed full-time. Among 75 (36.4%) patients with
history of DU, 52 (69.3%) were intravenous drug users (IVDUs), and 23
Conclusion: The Cepheid successfully detected 93.75% of the HCV (30.7%) were active drug users. Other characteristics included: aged
positive samples detected by venepuncture or DBST. The two samples >50 years (n = 51; 68.0%), stable housing (n = 63; 84.0%), and
that were not positive returned invalid results which would have employed full-time (n = 16; 21.3%). Full-time employed patients,
prompted retesting. The one discordant result with a very low level compared with those not in full-time employment, had fewer visits
DBST result is likely due to a false positive result on DBST. As such, to general physicians (0.9 vs 2.0), but more visits to hepatologists (2.0
none of the results from finger prick samples collected into EDTA vs 1.4) and gastroenterologists (0.2 vs 0.1), and a greater number of
capillary tubes and processed on the Cepheid returned false negative noninvasive procedures (1.9 vs 0.9). Patients with history of DU,
results. This method of sampling is now going to be adopted in Wales especially IVDUs, had more general physician and nurse visits and
with ongoing monitoring of results over the next 12 months. fewer hepatologist and gastroenterologist visits than those with no
history of DU. Additionally, active drug users had higher on-treatment
FRI317
laboratory test (3.7 vs 2.1) and noninvasive diagnostic procedures (1.7
Healthcare resource utilization in treatment-naïve patients with
vs 1.3) compared with former drug users. HCRU in IVDUs was mostly
compensated cirrhosis receiving 8-weeks’ glecaprevir/
similar to those administering drugs through other routes (Figure).
pibrentasvir stratified by drug use and socioeconomic status: a
retrospective chart review
Juan Isidro Uriz Otano1,2, Armand Abergel3, Alessio Aghemo4,5,
Adriana Ahumada6, Massimo Andreoni7, Tarik Asselah8,
Abhi Bhagat9, Isabel Butrymowicz9, Brian Conway10,
Antonio Gasbarrini11, Francisco Jorquera12, Pietro Lampertico13,14,
Maria Luisa Manzano Alonso15, Lindsy Myles16, Marcello Persico17,
Alnoor Ramji18, Dimitri Semizarov9, Yanna Song9, Erica Villa19,
Qingqing Xu9. 1Navarra Institute for Health Research (IdiSNA),
Pamplona, Spain; 2Department of Gastroenterology, Liver Unit, Complejo
Hospitalario de Navarra, Pamplona, Spain; 3CHU Estaing, UMR 6602
CNRS Université d’Auvergne, Clermont Ferrand, France; 4Department of
Biomedical Sciences, Humanitas University, Rozzano, Italy; 5Department
of Gastroenterology, Humanitas Research Hospital IRCCS, Rozzano, Italy; Figure: Healthcare resource utilization stratified by patients’ occupational
6 status, history of drug use, and current use of drugs. *Patients with history
Hospital General Universitario Gregorio Marañón, Liver Unit, Madrid,
Spain, 7University of Tor Vergata, Rome, Italy; 8Service d’Hépatologie, of illicit drug use included both active and former drug users administer-
ing drugs either IV, nasally, through inhalation, or sublingually. FT, full
Hôpital Beaujon, INSERM UMR 1149, Université de Paris, Clichy, France;
9 time; IV, intravenous; PT, part time; SD, standard deviation.
AbbVie Inc., North Chicago, United States; 10Vancouver Infectious
Diseases Center and Simon Fraser University, Vancouver, Canada; Conclusion: In this real-world cohort, HCRU was observed to vary by
11
Internal Medicine and Gastroenterology, Fondazione Policlinico occupational status and history of DU among patients with HCV
Universitario A. Gemelli IRCCS, Rome, Italy; 12Digestive System Service, receiving G/P, with active drug users having the highest number of
Complejo Asistencial Universitario de León, IBIOMED and CIBERehd, physician and nurse practitioner visits. Additional results will be
León, Spain; 13Foundation IRCCS Ca’ Granda, Ospedale Maggiore presented at the congress.
Policlinico, Policlinico-Division of Gastroenterology and Hepatology-CRC
‘AM and A Migliavacca’ Centre for Liver Disease, Milan, Italy;
14
University of Milan, Milan, Italy; 15Liver Unit, Hospital Universitario 12
De Octubre, Madrid, Spain; 16Barrie GI Associates, Barrie, Ontario,
Canada; 17Dipartimento di Medicina Clinica Medica, Epatologica e
Lungodegenza, AOU OO. RR. San Giovanni di Dio Ruggi e D’Aragona,

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POSTER PRESENTATIONS
1
FRI318 MacIsaac MB, et al. ILC 2021.
Progress towards hepatitis C elimination: the feasibility and
success of a nurse and harm reduction practitioner led model of FRI319
care utilising rapid point of care HCV RNA testing at a medically Screening for hepatitis C in Denmark-the effect of a mobile
supervised injecting room in Melbourne, Australia outreach intervention
Michael MacIsaac1,2, Bradley Whitton1, Jenine Anderson3, Sandra Droese1,2,3, Lone Wulff Madsen1,2, Gustav Bang Harvald1,
Matthew Penn3, Anthony Weeks3, Shelley Cogger3, Kasey Elmore3, Søren Grinderslev1, Karen Kofoed1, Lene Kræmer1, Anne Øvrehus1,2,
David Pemberton3, Tim Papaluca1,2, Margaret Hellard4,5,6, Peer Christensen1,2,3. 1Odense University Hospital, Department of
Mark Stoove4,6, David Wilson4, Alisa Pedrana4,6, Joseph Doyle4,5, Infectious Diseases, Odense, Denmark; 2University of Southern
Nico Clark3,7, Jacinta Holmes1,2, Alexander Thompson1,2. 1St Vincent’s Denmark, Clinical Institute, Odense, Denmark; 3Odense University
Hospital Melbourne, Gastroenterology, Fitzroy, Australia; 2University of Hospital, Open Patient Data Explorative Network, Odense, Denmark
Melbourne, Faculty of Medicine, Parkville, Australia; 3North Richmond Email: [email protected]
Community Health, Medically Supervised Injecting Room, Richmond,
Background and aims: The prevalence of hepatitis C (HCV) in
Australia; 4Burnet Institute, Disease Elimination Program, Melbourne,
Denmark is low (0.21% of the adult population), 24% of HCV infected
Australia; 5Alfred Hospital, Infectious Diseases, Melbourne, Australia;
6 are undiagnosed (corresponding to 700 HCV patients in the Region of
Monash University, School of Public Health and Preventive Medicine,
Southern Denmark (RSD)) and among diagnosed less than half have
Melbourne, Australia; 7The Royal Melbourne Hospital, Addiction
been cured. As part of the “C-Free-South” program we launched an
Medicine, Parkville, Australia
outreach test and treat center on wheels in the Region of Southern
Email: [email protected]
Denmark in June 2020, targeting people with drug or alcohol use and/
Background and aims: To achieve HCV elimination targets, efforts or psychiatric illnesses as well as festivals and open markets. The aim
must focus on models of care engaging people who inject drugs of this study is to describe the results of the intervention after the first
(PWID). The XpertÒ HCV viral load fingerstick point of care (POC) test 17 months.
provides an HCV RNA level within 1 hour, allowing rapid diagnosis Method: Low threshold non governmental organizations were
and treatment. We previously reported a successful nine-week pilot approached by a mobile unit with medical personnel from the
study incorporating HCV RNA POC testing at a medically supervised infectious disease department at Odense University Hospital. We
injecting room (MSIR) in Melbourne, Australia.1 We now present the used an HCV point of care rapid test for antiHCV, dried blood spot test
12-month outcomes of this program. for HCVRNA and a FibroScan™ Devise for diagnosis of liver fibrosis.
Method: Prospective cohort study recruiting PWID attending a high- Infected patients were offered treatment either by referral to the
volume MSIR in Melbourne, Australia between 9/11/20 to 9/11/21. nearest clinic or in the mobile unit, as deemed feasible.
Clients were offered HCV screening using the XpertÒ HCV RNA POC Results: 584 persons were tested in 37 different locations of whom
test. Venepuncture for HBV/HIV screening and fibrosis assessment 148 were in shelters or other residential institutions. Overall 7% (43)
(APRI/FibroScan) were also offered to clients, regardless of HCV RNA had a positive antiHCV by POC test and 2% (12) had current infection
status. HCV RNA results were returned same day if clients were still of whom at least 5 (42%) were reinfected after HCV cure. Men
present, or via phone or at next MSIR visit if they had already constituted 55% of all tested, and 70% of all antiHCV positives ( p <
departed. POC testing/treatment was led by a full-time hepatology 0.05). Median age at test was 50 years (IQR 40–60) with no relation to
fellow during the initial nine-week pilot program, and a nurse or HCV status. Overall 95% of the 43 antiHCV positives had been tested
harm reduction practitioner (HRP) for the remainder of the study before, 81% recalled being antiHCV positive at last test, 5% recalled
period. DAA treatment was prescribed immediately upon return of a being negative, (suggesting resent infection) and a total of 71%
positive HCV test if the hepatology fellow was on-site, or by a reported to have been cured for HCV (universal treatment for HCV
GP/hepatologist after remote consultation for nurse/HRP assess- became available Denmark in 2018). The prevalence of antiHCV was
ments. Clients were invited to be followed 4-weekly during 16% (26/162) in facilities open to all (who accepted drug users) and 0%
treatment and at SVR12. Primary endpoints were number of clients (0/187) in facilities restricted to psychiatric patients or alcohol users.
screened for HCV and number commencing DAAs. Testing rates were Correspondingly, 91% of the 43 antiHCV positives had injected drugs
compared to a historical control period (9/11/18–9/11/19) of standard compared to 8% of antiHCV negatives. We found no infections (0/71)
of care HCV venepuncture testing at the MSIR. when testing the general population (i.e. at markeds).
Results: 573 PWID consented to HCV RNA POC testing. By Conclusion: Our study suggests that most hepatitis C infected in
comparison, 180 clients underwent HCV testing during the control Denmark have been identified and cured, and we found a very low
period, representing a 218% increase with POC testing. Median age proportion of undiagnosed (5%) compared to the previous national
was 42 yrs (IQR 37–49) and 75% male. 161 (28%) were HCV RNA+. An estimate of 24%. However our study is a selected sample of the
APRI score was calculated for 337 clients and 154 (16/32, 50% with population at risk for HCV and may not be representative for our
APRI ≥1) had a FibroScan performed. Cirrhosis was uncommon (6% region or Denmark. The low absolute number of current infection (2%
HCV RNA+, 5% overall), as was HBV (n = 3, 2%) and HIV co-infection of tested) suggest that our outreach campaign in its current form is
(n = 0). 90% (n = 145/161) of HCV RNA+ clients were prescribed DAA unlikely to diagnose and treat the remaining patients with HCV in our
therapy. Median time to treatment start was 8 days (IQR, 2–22); 13 region. An improved case finding strategy is needed to reach the
clients (9%) initiated treatment same day as diagnosis. There was no WHO target of 90% diagnosed and 80% cured by 2030. This could be
difference in the number of clients linked to treatment with monetary incentives to be tested, and increased use of peer based
hepatology fellow led on-site prescribing compared to remote testing (“snowballing”). A full update of treatment results and new
prescribing following nurse or HRP assessment (94% vs 88%, p = screening methods will be presented at the meeting.
0.204). Among those with complete follow up data (n = 43), SVR was
74%. Causes of non-SVR were re-infection (n = 3), relapse (n = 4), and
non-response from medication non-adherence (n = 4).
Conclusion: Rapid HCV POC testing in a MSIR rapidly upscales testing
and was associated with high rates of treatment initiation. Nurse or
HRP led POC testing/treatment with remote prescribing is highly
feasible, with similar rates of treatment initiation achieved.

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 POSTER PRESENTATIONS
FRI320 FRI321
Screening for HCV infection combined with SARS-CoV-2 Treating children with HCV close to home through a virtual
vaccination in the Campania region national multidisciplinary network
Pietro Torre1, Mario Masarone1, Roberta Sciorio1, Monica Annunziata1, Deirdre Kelly1,2, Carla Lloyd1, Maxine Brown1, Kinza Ahmed1,
Roberta Coppola1, Laura Staiano2, Carmine Coppola2, Ivana Carey3, Sarah Tizzard3, Joanne Crook3, Penny North-Lewis4,
Marcello Persico1. 1University of Salerno, Internal Medicine and Palaniswamy Karthikeyan4, Sanjay Bansal3, Graham Foster5.
1
Hepatology Unit, Department of Medicine, Surgery and Dentistry, Birmingham Children’s Hospital, United Kingdom; 2University of
“Scuola Medica Salernitana”; 2OORR Area Stabiese, Plesso Nuovo Birmingham, United Kingdom; 3King’s College Hospital, United
Gragnano, Naples, Italy, Department of Internal Medicine-Unit of Kingdom; 4Leeds General Infirmary, United Kingdom; 5Barts and The
Hepatology and Interventional Ultrasonography London School of Medicine and Dentistry, United Kingdom
Email: [email protected] Email: [email protected]
Background and aims: The health emergency caused by the SARS- Background and aims: Hepatitis C virus (HCV) infection is a major
CoV-2 pandemic has negatively impacted the management of HCV global health problem in adults & children. The recent efficacy of
infection, potentially jeopardizing the achievement of the goal of Direct Acting Anti-viral therapy (DAA) has cure rates of 99% in adults
eliminate hepatitis C by 2030. To take advantage of the current and adolescents. These drugs were licensed for children 3–12 yrs
sanitary situation, associated screening for HCV and SARS-CoV-2 during the recent coronavirus pandemic. To ensure equitable access,
infection have been carried out. We decided to propose HCV safe & convenient supply during lockdown, we established a virtual
screening also to people who undergone SARS-CoV-2 vaccination. national treatment pathway for children with HCV in England &
Method: Screening for hepatitis C was carried out by finger-prick test evaluated its feasibility, efficacy & treatment outcomes.
to search for HCV antibodies. It took place in the minutes following Method: A paediatric Multidisciplinary Team Operational Delivery
the SARS-CoV-2 vaccination, in two different vaccination centers of Network ( pMDT ODN), supported by NHS England (NHSE), was
the Campania region, and in two different time frames. In the period established with relevant paediatric specialists to provide a single
1 May–20 July 2021, screening for hepatitis C was offered to the point of contact for referrals & information. Referral & treatment
general population who got the vaccine at the Fisciano ( province of protocols were agreed for HCV therapy approved by MHRA & EMA. On
Salerno) vaccination center. In the period 20 September–11 October referral the pMDT ODN agreed the most appropriate DAA therapy
2021, screening for hepatitis C was offered to the general population based on clinical presentation & patient preferences, including ability
who underwent vaccination at the San Leonardo Hospital to swallow tablets. Treatment was prescribed in association with the
(Castellammare di Stabia, metropolitan city of Naples). In both sites, local paediatrician & pharmacist, without the need for children &
Pfizer-BioNTech, Moderna, or Oxford-AstraZeneca vaccines were families to travel to national centres. All children were eligible for
used. NHS funded therapy; referral centres were approved by the pMDT
Results: Out of 5095 people who underwent vaccination at the ODN to dispense medication; funding was reimbursed via a national
Fisciano vaccination center, 1952 (38, 3%, average age 41, 6 years) NHSE agreement. Demographic & clinical data, treatment outcomes &
performed screening for hepatitis C. 5 of these (0, 25%, average age 54, SVR 12 were collected. Feedback on feasibility & satisfaction on the
2 years) resulted HCV-Ab positive; all 5 were aware of their condition; pathway was sought from referrers.
4 had previous treatment; 1 (0, 05%) was found to have active HCV Results: In the first 6 months, 34 children were referred; 30- England;
infection. Out of 2202 people vaccinated at the San Leonardo 4-Wales; median (range) age 10 (3.9–14.5) yrs; 15M; 19F: Most were
Hospital, 1207 (54, 8%, average age 43, 1 years) underwent screening genotype type 1 (17) & 3 (12); 2 (1); 4 (4). Co-morbidities included:
for hepatitis C. Among these, 9 (0, 7%, average age 54, 3) resulted obesity (2); cardiac anomaly (1); Cystic Fibrosis (1); Juvenile Arthritis
positive. 5/9 tested negative on the confirmatory test; 2/9 were aware (1). No child had cirrhosis. DAA therapy prescribed: Harvoni (21);
of their condition and had previous treatment; 1 subject (0, 08%) was Epclusa (11); Maviret (2). 27/34 could swallow tablets; 3/7 received
found to have active HCV infection; 1 subject is awaiting the results at training to swallow tablets; 4/7 are awaiting release of granules.11/27
time of writing. have completed treatment and cleared virus; of these 7/11 to date
In both sites a consistent percentage of people refused the HCV-Ab achieved SVR 12. 30 children requiring DAA granule formulation are
test. Moreover, the prevalence of HCV-Ab positivity and HCV active awaiting referral and treatment.
infection was found to be lower than the national data. Frequent Referrers found the virtual process easy to access, valuing opportun-
reasons for refusing the test were lack of knowledge of the disease, ity to discuss their patient’s therapy with the MDT & many found it
fear of a positive result, and distrust in the test’s effectiveness. educational. There were difficulties in providing the medication
Someone refused the test because vaccination was considered a through the local pharmacy. However there are manufacturing delays
particularly stressful event. The low prevalence of HCV infection in providing granule formulations because suppliers focused on
found in these projects could be at least partly attributable to the treatments for COVID, leading to delays in referring and treating
under-participation of the elderly, as at the time the screenings were children unable to swallow tablets.
carried out most of them had probably already received the expected Conclusion: The National HCV pMDT ODN delivers high quality
doses of SARS-CoV-2 vaccine. treatment & equity of access for children & young people, 3–18 yrs
Conclusion: In conclusion, we believe that SARS-CoV-2 vaccination with HCV in England, ensuring they receive care close to home with
could be an opportunity to screen for HCV infection, but to maximize 100% cure rates.
the benefits of this screening, the characteristics of the subjects to be
tested should be reconsidered, by focusing particularly on the elderly
population.

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POSTER PRESENTATIONS
FRI322 Conclusion: In this analysis of 628 individuals treated with DAA, 10%
Association of sustained virologic response with measures of did not complete treatment, and more than a third had medication
direct-acting antiviral adherence in patients with Hepatitis C: data gaps, which were inversely associated with SVR. Despite this, patients
from the ASCEND and ANCHOR investigations with imperfect adherence still achieved rates of SVR greater than 75%.
Sarah Kattakuzhy1, Vivian Wang2, Catherine Gannon2, These data suggest that while nonadherence to DAA is common,
Sarah Mollenkopf3, Charisse Ahmed2, Sanjay Chainani3, Junfeng Sun2, patients should be continued on treatment regardless of imperfect
Henry Masur2, Shyamasundaran Kottilil1, Elana Rosenthal1. 1Institute adherence. Finally, these data support removal of polices which can
of Human Virology, University of Maryland School of Medicine, delay medication receipt, such as mandatory on-treatment phone
Baltimore, United States; 2National Institutes of Health, Bethesda, United calls, visits, or lab checks.
States; 3University of Maryland School of Medicine, Baltimore, United
States FRI323
Email: [email protected] ATA haplotype of the interleukin-10 gene and low phase angle are
associated with liver cirrhosis in chronic hepatitis C
Background and aims: While HCV treatment with direct-acting Nataly Lopes Viana1,2, Diego Alves Vieira2,3, Thais Pontelo de Vries1,2,
antivirals is highly efficacious in clinical trials, medication receipt and Marta Paula Pereira Coelho1,2, Pedro Alves de Castro2,3,
adherence is challenged by both policy and patient-specific barriers Tatiana Bering Bering4, Maria Isabel Toulson Davidson Correia5,
in real-world settings. Previous research suggests that sustained Gifone Aguiar Rocha6, Luciana Diniz Silva1,2,7. 1UFMG Faculty of
virologic response can be achieved with imperfect adherence1, but Medicine, Sciences Applied to Adult Health Care Post-Graduate
current data is unclear on how the amount and timing of Programme, Belo Horizonte, Brazil; 2UFMG Faculty of Medicine,
nonadherence impacts sustained virologic response (SVR). Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia,
Method: Data was pooled from two real-world investigations of HCV Faculdade de Medicina, Brazil; 3UFMG Faculty of Medicine, Medical
treatment using direct-acting antivirals from 2015 to 2020, ASCEND2 Undergraduate Student, Brazil; 4UFMT-Universidade Federal de Mato
and ANCHOR3. The analysis was limited to individuals with an Grosso, Department of Food and Nutrition, Brazil; 5UFMG Faculty of
anticipated duration of 12 weeks, who were dispensed at least one Medicine, Department of Surgery, Brazil; 6UFMG Faculty of Medicine,
month of medication, on whom SVR was assessed. Measures of Laboratory of Research in Bacteriology, Brazil; 7UFMG Faculty of
adherence were assessed in three ways: (1) medication receipt (MR), Medicine, Department of Internal Medicine, Brazil
defined as the actual number of 28-pill bottles dispensed; Email: [email protected]
(2) medication gap (MG), defined as the difference in days between
expected medication receipt and actual medication receipt; and Background and aims: Chronic infection caused by Hepatitis C virus
(3) on treatment detectable viral load (DVL), defined as viral load (HCV) is a major public health problem. It is estimated that, globally,
>1000 IU/ml at week 4 or >100 IU/ml at week 12. about 71 million people are infected. Approximately 55.0% to 85.0% of
Results: Of 628 individuals, 472 were treated with LDV/SOF (75%), 93 the infected individuals will develop chronic hepatitis C. Of those
with SOF/VEL (15%), and 63 with ELB/GZV (10%). Overall the cohort chronically infected by HCV, the risk of liver cirrhosis varies from
was median age 59, majority (69%) male, with 94% Black race, 28% 15.0% a 30.0% in 20 years. In this context, the progression of hepatic
with current heroin use, 16% with current cocaine use, and 27% fibrosis may be influenced by host, viral and environmental factors.
unstably housed. Among the host factors, the role played by the imbalance between
Fifteen patients (2.3%) received 1 bottle, 43 (6.8%) received 2 bottles, pro- and anti-inflammatory cytokines and the development/pro-
and 570 (90.8%) received 3 bottles, and MR was significantly gression of liver cirrhosis is highlighted. Interleukin-10 (IL-10) is
associated with SVR ( p < 0.00001), but was not associated with considered a key cytokine in the control of the secretion of pro-
gender, race, or substance use. Of the 570 who received all 3 bottles, inflammatory mediators. IL-10, single nucleotide polymorphisms
211 (37%) had a MG of at least 1 day (range 1–197, median 7). MG of 14 (SNPs) in the positions −1082A/G (rs1800896), −819C/T (rs1800871)
days or more was inversely associated with SVR ( p = 0.037), however and −592C/A (rs1800872) in the promoter region of the gene
MG of 7 days or more was not associated with SVR. Of the 211 with encoding are associated with changing the transcription rates of
MG, 89 individuals had a gap between months 1 and 2, 79 between this gene. Haplotypes GCC, ACC and ATA determine the production of
months 2 and 3, and 43 between both. There was no association with high, intermediate and low levels of IL-10, respectively. Based on
timing of MG and SVR. Of 567 patients who received 3 bottles and these findings, the objective of this present study was to evaluate
who had on treatment VL assessment, 22 (3.9%) had DVL, which was whether SNPs in the promoter region of the IL-10 coding gene are
inversely associated with SVR ( p < 0.0001). Current cocaine ( p = 0.05) associated with liver cirrhosis in patients chronically infected with
and opioid use ( p < 0.0001) were significantly associated with DVL, HCV.
but race, gender, and housing status were not. Method: We prospectively evaluated 155 patients [mean age, 51.3 ±
11.5 years; 94 (60.6%) men, 60 (38.7%) with cirrhosis]. Diagnosis of
cirrhosis was performed based on clinical, laboratory, radiological
and histological parameters. SNPs were genotyped by RT-PCR. Phase
angle was obtained by electrical bioimpedance analysis. The data
were analyzed by SPSS 21.0. The associations were analyzed by
logistic regression models. Variables with p ≤ 0.25 in the univariate
analysis were selected for the multivariate model.
Results: Polymorphisms were in balance of Hardy-Weinberg. The ATA
haplotype was observed in 43 (72.0%) and in 52 (55.0%) of the
patients with and without liver cirrhosis, respectively ( p = 0.04). In
multivariate analysis, ATA haplotype (OR = 2.39; 95.0%CI = 1.10–5.19;
p = 0.03), phase angle (OR = 0.58; 95.0%CI = 0.38–0.89; p = 0.01) and
arterial hypertension (OR = 3.55; 95.0%.0CI = 1.72–7.33, p = 0.001)
were independently associated with liver cirrhosis.

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 POSTER PRESENTATIONS
Conclusion: The ATA haplotype, which is related to lower IL-10 Method: The ECHO+ telehealth program in Alberta aims to increase
production, associated with liver cirrhosis in patients chronically access to HCV treatment through a hub-and-spoke model led by a
infected with HCV. Also, phase angle, a nutritional marker that hepatologist (hub) working with Indigenous communities (spokes)
reflects the integrity of cell membranes, was inversely associated designing a model of care tailored to local needs. We incorporated
with cirrhosis in patients with chronic hepatitis C. Indigenous ways of knowingl (see figure), including building a
predominantly Indigenous team, and embedding the 5 R’s of
FRI324 Indigenous Research Methodology (Respect, Relationship,
Use of Glecaprevir/Pibrentasvir (G/P) for the treatment of HCV Relevance, Reciprocity, and Responsibility). ECHO+ builds relation-
infection among fentanyl users: an interim analysis of the GRAND ships with Indigenous community healthcare teams while using a
PLAN study novel co-design approach to remove barriers while increasing
Brian Conway1,2, David Truong1, Leo Yamamoto1, Rossitta Yung1, awareness, screening for HCV, and providing telehealth access to
Shawn Sharma1. 1Vancouver Infectious Diseases Centre, Vancouver, specialist care.
Canada; 2Simon Fraser University, Burnaby, Canada Results: Collaborative methods included developing information
Email: [email protected] resources translated into local languages; building infrastructure and
supporting community-directed implementation to include other
Background and aims: To achieve the World Health Organization
health topics. Due to the COVID-19 pandemic, virtual awareness
mandate of eliminating Hepatitis C Virus (HCV) infection as a public
presentations (HCV awareness topics, community interaction and
health concern by the end of the decade, we must design and
knowledge sharing, opportunity to follow up with mailed resources
implement plans of intervention for all affected populations,
packages, and sharing lived experience stories from Indigenous youth
including the most vulnerable and difficult to reach. We describe a
and Elders) have been shared with every Indigenous community in
community-based program targeting HCV-infected inner-city resi-
Alberta. Practitioners were interviewed to identify barriers to care.
dents with active fentanyl use.
Biweekly Zoom meetings with community healthcare teams have
Method: Through weekly events held at single room occupancy
expanded during the pandemic to include pandemic topics, and
dwellings in the inner city of Vancouver, Canada, we identified
other liver diseases. Collaboration between ECHO+ and Indigenous
subjects with HCV infection and a history of ongoing fentanyl use. We
community leadership and healthcare teams has improved HCV
engaged them in a multidisciplinary program of care to meet medical,
screening, de-stigmatization, increased treatment access, and sup-
psychological, social and addiction-related needs and provided HCV
ported local community healthcare providers to effectively access
treatment with Glecaprevir/Pibrentasvir (G/P) within this context.
DAA therapy. Thus, currently 92% of the 53 Indigenous communities
HCV medications were administered in a way to maximize the
in Alberta have engaged with ECHO+, compared to 23% before this
likelihood of adherence and follow-up to the sustained virologic
approach. This reflects success of the 5R method.
response (SVR) 12 time point. This included daily dispensing with
opiate agonist therapy or weekly delivery of medications to the place
of residence. If a subject was unavailable for weekly check-ins,
interventions were immediately implemented to re-integrate into
care. This analysis presents the rate of documented cure (achieve-
ment of SVR12) in the target population.
Results: We identified 118 eligible HCV-infected fentanyl users who
were enrolled in the program. Key demographic characteristics
include: 91 (77%) male, median age 47 (26–75) years, 102 (86%) on
opiate agonist therapy, F0/1 (86, 73%), ≥F2 (32, 77%), known fentanyl
use (74, 63%), other drug use (92, 78%). Of 107 who initiated
treatment, 88 completed treatment to date and 82 achieved cure at
the SVR12 and/or SVR24 time point. Those lost to follow-up included
2 overdose-related deaths prior to SVR12 time point and 4
disengaged from care. There were no cases of documented virologic
failure.
Conclusion: To treat HCV infection among the most vulnerable inner-
city populations, specific programs for integration and maintenance
in care must be designed and evaluated. We have shown that this can
be accomplished even among active fentanyl users who are
precariously housed. This may provide the basis for successful
interventions among similar populations in different settings.

FRI325
Indigenous methodologies in practice through community Conclusion: A culturally-sensitive framework combines Indigenous
engagement and telehealth outreach increase hepatitis C access to with western approaches to improve access to HCV awareness and
care in Alberta, Canada care in remote Indigenous communities. This approach has increased
Kate Dunn1, Samuel Lee2. 1Indigenous Wellness Core, Calgary, Canada; community communication and involvement, facilitated engage-
2
University of Calgary Cumming School of Medicine, Medicine, Calgary, ment with every Indigenous community, and provided practical
Canada support throughout the pandemic.
Email: [email protected]
Background and aims: Hepatitis C virus (HCV) is a major public
health burden in Canada, with prevalence in Indigenous (First Nation,
Metis and Inuit) communities 4–6 times higher than non-Indigenous
population. Conventional care models have created barriers to
curative DAA therapy in remote Indigenous communities.
Innovative approaches are required to improve access to HCV
services.

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POSTER PRESENTATIONS
FRI326 Conclusion: In the studied population MAFLD is a risk factor for
Implication of metabolic associated fatty liver disease and sex developing fibrosis in men. Men without MAFLD had lower risk of
differences in the risk of developing liver fibrosis in patients with developing fibrosis than women without MAFLD. Although the
Hepatitis C literature mentions a lower risk in women of developing fibrosis in
Martín Uriel Vázquez Medina1, Eira Cerda Reyes2, hepatitis C, our results could be explained by the age range of our
Cruz Vargas-De-León1, Patty Marlen Ramírez Portillo3, patients in which most of the women were postmenopausal.
Alejandro Gutierrez Atemis2, Juan Armendariz-Borunda2. 1ESM-
Escuela Superior de Medicina-IPN, Laboratorio de modelación FRI327
biomatemática y bioestadística para la salud, Ciudad de México, Mexico; Micro-eliminating hepatitis C in a network of 47 English Prisons
2
Hospital Central Militar Mexico, Ciudad de México, Mexico; through an industry, prison healthcare and patient organisation
3
Benemérita Universidad Autónoma de Puebla, Heroica Puebla de partnership
Zaragoza, Mexico Andrew Jones1, Nichola Royal2, Arran Ludlow-Rhodes2,
Email: [email protected] Rob Cheetham2, Emily Mongale2, Julie Henderson2, Katie Abraham2,
Hayley Cubbage2, Samantha Allen2, Lee Christensen3,
Background and aims: Hepatitis C (HCV) is a global health problem Kate Dorrington1, Andrew Milner1, Louise Missen1, Phil Troke1. 1Gilead
since it affects about 3% of the world’s population. The major Sciences Ltd, Medical Affairs, London, United Kingdom; 2Practice Plus
complications during the disease are related to the progression of Group Health and Rehabilitation, Reading, United Kingdom; 3Hepatitis C
liver fibrosis. Therefore, it is of great importance to study the Trust, United Kingdom
sociodemographic factors that increase or decrease the risk of Email: [email protected]
developing fibrosis. The aim of this work was to evaluate the
involvement of Metabolic associated fatty liver disease (MAFLD) and Background and aims: National Health Service England (NHSE)
sex of patients in the risk of developing liver fibrosis during hepatitis plans to eliminate Hepatitis C (HCV) in England by 2025, five years
C infection. earlier than World Health Organisation goals. With a reported HCV
Method: Cross-section study of Hepatitis C (HCV) newly diagnosed prevalence of ∼6% in male prisons, and ∼12% in female prisons, secure
patients, information of age, sex, BMI, comorbidities, and laboratory environments are an essential component of this elimination plan. In
results were obtained in the first medical consultation with a certified 2020, NHSE defined HCV micro-elimination as ³95% of prison
hepatologist, HCV was diagnosed by qualitative RT-PCR test COBAS residents tested within the previous 12 months, ³90% of RNA positive
AMPLICOR and MAFLD was diagnosed according to the international patients treated or initiated on treatment and presence of a robust
expert consensus statement Eslam (2020). Liver fibrosis was system to review ongoing testing and treatment performance to
quantified using The Fibrosis-4 (FIB-4) Index. Four groups were ensure these targets are maintained.
formed: 1.- Men+NonMAFLD, 2.- Men+MAFLD, 3.- Women Method: To support NHSE in their HCV Elimination Program, a
+NonMAFLD and 4. Women+MAFLD. Level of FIB-4 was obtained of partnership between Gilead Sciences, Practice Plus Group (PPG) and
each group and global statistical significancy (SSi) of the distribution the Hepatitis C Trust (HCT) was formed in 2019. PPG is the provider of
of FIB-4 among groups was evaluated with the Kruskal Wallis test. healthcare to 47 English prisons with approximately 30, 000
Post Hoc analysis was performed using the Kruskal Wallis test, alpha residents. PPG Regional BBV Lead Nurses, and Gilead Medical
was adjusted with the Bonferroni method to obtain the SSi of the FIB- Scientists worked with prison and HCV stakeholders to optimise
4 distribution within the groups. test and treat pathways for new prison admissions. Whole prison
Results: A total of 84 patients (26.2% Male) were studied. The median HCV Intensive Test and Treat events (HITTs) were also run in targeted
age of the patients were 62 years (IQR 53–71), Distribution in the age prisons to ensure testing of residents who were incarcerated before
and FIB-4 between men and women was not SSi. The prevalence of these optimisations were implemented.
MAFLD was 73.75%. The difference of MAFLD between sexes was not Results: Following pathway optimisation across the PPG network of
SSi. The global difference among FIB-4 levels between the four groups 47 prisons, the HCV screening within 7 days of prison entry increased
was very close to SSi ( p = 0.07). The Post Hoc analysis (Figure 1) found from 41% in May 2019 to 84% in October 2021. This increase was
differences in the levels of FIB-4 between the groups Men achieved despite there being significant restrictions to reduce the
+NonMAFLD with Men+MAFLD (2.25 (IQR 1.68–2.67) vs 4.98 (IQR transmission of COVID-19 being in place across all English prisons.
2.99–8.35), p = 0.01) and Men+NonMAFLD with Women+NonMAFLD HITTs have been performed in 15 PPG prisons to-date. 1, 909 new
(2.25 (IQR 1.68–2.67) vs 5.56 (IQR 2.98–6.89), p = 0.01). No SSi RNA+ diagnoses were made during this time with 1, 848 patients
differences in FIB-4 levels were found between women with and started on direct-acting antiviral treatments. By November 2021, 16
without MAFLD. out of the 47 prisons have been given micro-elimination status by
NHSE with 4 more having submitted data demonstrating achieve-
ment of this target and awaiting decision. A further 4 more prisons
are on track to achieve micro-elimination by April 2022.
Conclusion: This partnership has demonstrated that, even during a
global pandemic, it is possible to achieve the micro-elimination of
HCV in a defined setting. Maintenance of micro-elimination status is
essential if we are to achieve the WHO HCV targets, requiring robust
pathways that are regularly adapted to the changing environment,
and systems for tracking performance, both of which have been put in
place by this partnership.

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 POSTER PRESENTATIONS
FRI328 Conclusion: We observed a high incidence of AHC in Vienna in the
The ‘Viennese epidemic’ of acute HCV in the era of direct-acting DAA-era -primarily among HIV-positive MSM, but increasingly also in
antivirals HIV-negative MSM. Sufficient screening and prevention strategies
David Chromy1,2,3, David Jm Bauer1,2, Benedikt Simbrunner1,2, combined with fast treatment initiation are needed to confine further
Mathias Jachs1,2, Lukas Hartl1,2, Philipp Schwabl1,2, spread of HCV.
Caroline Schwarz1,2,4, Armin Rieger2,3,
Katharina Grabmeier-Pfistershammer2,5, Mattias Mandorfer1,2, FRI329
Michael Trauner1, Peter Ferenci1, Michael Gschwantler2,4, Approaches for a hepatitis C-free city: preliminary results
Thomas Reiberger1,2. 1Medical University of Vienna, Division of Maria Angelica Luque Gonzalez1, Yolanda Sánchez1,2,
Gastroenterology and Hepatology, Department of Internal Medicine III, Carmen Lara Romero1,2, Ana Lucena1,2, Javier Ampuero1,2,3,4,
Vienna, Austria; 2Vienna HIV & Liver Study Group; 3Medical University of Francisco Atienza5, Valentin Marquez6, Briones Eduardo5,
Vienna, Department of Dermatology, Vienna, Austria; Rosa Maria Ufano Lopez5, Fernando Martinez7,
4
Wilhelminenspital, Wiener Gesundheitsverbund (WiGeV) der Stadt María Carmen Lozano Domínguez8, Tinidad Desongles Corrales9,
Wien, Department of Internal Medicine IV, Vienna, Austria; 5Medical Lola Martinez7, Rocio Valero10, Manuel Torralbo11, Diego García12,
University of Vienna, Institute of Immunology, Center for Maria Jose Melero13, Lutgarda Conde Crespillo5,
Pathophysiology, Infectiology and Immunology, Vienna, Austria Minerva Blazquez Barba5, Miguel Angel Calleja14,
Email: [email protected] Francisco Javier Garcia-Samaniego Rey15,16,
Felipe Fernández-Cuenca17, Isabel Carmona18, Susana Padrones5,
Background and aims: An epidemic of acute hepatitis C virus (HCV)
Antonio Sanchez7, Manuel Romero Gomez1,2,3,4. 1University Hospital
infections (AHC)-observed predominantly among men who have sex
Virgen del Rocio, Unit of Digestive Diseases, Sevilla, Spain; 2CIBEREHD;
with men (MSM)-may now decline due to wide availability of direct- 3
University of Sevilla; 4Ibis-, Biomedicine Institute of Sevilla, Sevilla,
acting antivirals (DAAs). This study aimed to investigate changes in
Spain; 5Primary Health Care Distrito Sevilla; 6Médicos del Mundo-
the epidemiology of AHC in a Viennese referral center over a 13-year
Sevilla, Sevilla, Spain; 7City Council of Sevilla, Sevilla, Spain; 8University
period.
Hospital Virgen del Rocio, Microbiology Unit, Sevilla, Spain; 9University
Method: Patients presenting with AHC between 01/2007–12/2020 at
Hospital Virgen del Rocio, Pharmacy Unit, Sevilla, Spain; 10Fundación
the Vienna General Hospital were retrospectively enrolled and
Atenea Grupo Gid, Sevilla, Spain; 11Fundación Triángulo Andalucía,
followed after virologic clearance/eradication. AHC was defined by
Sevilla, Spain; 12Adhara, Sevilla, Spain; 13DG Salud Publica; 14hospital
the European AIDS treatment network (NEAT) criteria. The introduc-
universitario virgen macarena, Pharmacy Unit, Sevilla, Spain; 15La Paz
tion of unrestricted DAA-access after 09/17 defined the ‘DAA-era’, as
University Hospital, Madrid, Spain; 16Coordinador AEHVE; 17University
compared to the ‘pre-DAA-era’ prior to 09/17.
Hospital Virgen Macarena, Microbiology Unit, Sevilla, Spain;
Results: We identified 134 AHC cases in 119 patients with a mean age 18
University Hospital Virgen Macarena, Digestive Diseases, Sevilla, Spain
of 39 ± 9 years at inclusion. The majority of patients were male (92%),
Email: [email protected]
HIV-positive (88%), and MSM (85%). In the DAA-era, a history of prior
chronic HCV infection at inclusion was found in 24% (11/46) Background and aims: We aimed to develop a Hepatitis C
compared to 7% (5/73) in the pre-DAA-era ( p = 0.012). The annual elimination program to make Seville a Hepatitis C free city. The
rate of AHC cases increased in the DAA-era (17.11 per-year) compared main concern was the capability to reach marginal and vulnerable
to the pre-DAA-era (7.76 per-year). The DAA-era included an populations. To overcome this drawback, a collaboration between
AHC-genotype-2 cluster and more HIV-negative AHC cases (0% different organizations is needed.
(0/73) vs. 30% (14/46), p < 0.001). Patients were followed after Method: Three groups were addressed: a) patients from primary care
spontaneous clearance or sustained virologic treatment response health centers database were classified according to anti-HCV status
(SVR) for a total of 251.88 patient-years (median 1.39 years and viral load (HCVRNA); b) patients attended at addiction treatment
per patient). In the DAA-era, we recorded 15 AHC-reinfections- centers; and c) homeless attended by non-profit organizations like
corresponding to an incidence rate of 5.96 (95%CI: 3.57–9.66) re- Médicos del Mundo and Fundación Atenea, and social services from
infections per 100-patient-years. City Council in Seville.
Anti-VHC was offered by Oralquick® test in saliva or blood test and, if
positive, by dry blood spot (DBS) tests or serum samples to detect
HCVRNA. Positive patients got an appointment in clinical hepatology
or if not possible, a phone visit can be arranged to allow patient
evaluation and remote drug dispensation.
Results: Anti-HCV and HCVRNA tested positive in n = 92/243 (38%)
and 17 (6.9%) [10 treated with AAD] from addiction centers and n = 8/
56 (14%) and 5 (8.9%) [all 5 treated with AAD] in homeless population.
In primary care centers n = 849/870 tested anti-HCV positive and 249
HCVRNA positive. We have identified 271 patients with a positive
HCV viral load which may benefit from this Hepatitis C-free city
program.

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POSTER PRESENTATIONS
Conclusion: Collaborations between health, social and non-profit
organizations is key for Hepatitis C elimination. In this sense,
enabling HCV detection assays to be performed outside the hospital
enhances the chances of identifying positive patients. Moreover, the
short-cut for setting up the appointment allows faster access to
treatment ( presential or remote antiviral dispensation) at hepatology
unit. At the same time, the possibility of doing phone visits and
remote antiviral dispensation in patients refusing to be attended at
the hospital increases treatment success rate. Coordinating these
actions together can lead to a Hepatitis C-free city.
Acknowledgement: AEEH and Gilead Science for research grant and
SAPD and Abbvie for providing Oralquick® and DBS®.

FRI330
Success of a peer-led community based model of hepatitis C
treatment support for marginalised populations
Binta Sultan1,2, John Gibbons1, Indrajit Ghosh3, Julian Surey1,2,
Mark Leonard4. 1University College London Hospital, Find&Treat, United
Kingdom; 2University College London; 3Mortimer Market Centre, United Conclusion: A peer-led community-based HCV treatment model is
Kingdom; 4Groundswell, United Kingdom effective at supporting people with social complexity to complete
Email: [email protected] treatment. The components of the peer-led intervention addressed
multiple domains in the candidacy framework for engagement of
Background and aims: Community-based models of HCV care have
vulnerable populations. This model of care is essential to achieving
been developed and shown to be an effective way of supporting
HCV elimination targets and improved health outcomes, especially
marginalised people. Many outreach models of HCV care were scaled
for vulnerable populations.
down during the pandemic. The Find&Treat team established a peer-
led HCV outreach treatment service for vulnerable people in North FRI331
London during the pandemic, to ensure continued access to care for Impact of hepatitis C virus point-of-care (PoC) viral load assay
these patients. We present a description and evaluation of this model compared to laboratory-based assays on uptake of testing and
of care, which was a multi-component intervention delivered by a treatment, and turnaround times: a systematic review and meta-
highly trained peer. analysis
Method: The model of care was peer-led with clinician support as Philippa Easterbrook1, Adam Trickey2, Emmanuel Fajardo3,
needed and began in June 2020. Patients with confirmed current HCV Daniel Alemu3, Adelina Artenie2. 1World Health Organization, Global
infection were referred by drug services, Find&Treat service outreach Hepatitis Programme, Geneva, Switzerland; 2University of Bristol, Bristol,
HCV testing team and local clinics. All patients had a degree of social United Kingdom; 3World Health Organization, Geneva, Switzerland
complexity, which included drug use and or experience of home- Email: [email protected]
lessness. The peer and clinician reviewed all patients who were
referred. The whole HCV assessment and treatment cascade was Background and aims: The requirement for a confirmatory hepatitis
managed in the community. C virus (HCV) viral load (VL) test for diagnosis of chronic HCV
Interventions; Confirmatory bloods and liver fibroscan assessment infection leads to significant loss to follow-up in the care cascade.
was undertaken by the peer and a treatment referral was made to the Point of care (PoC) HCV VL assays are now being used as an alternate
local treatment approval centre. The peer took HCV medication to the to laboratory-based HCV RNA NAT assays. We undertook a systematic
patient at their place of residence, provided in monthly or weekly review and meta-analysis to evaluate the impact of using PoC HCV VL
dosset boxes. The peer engaged the patient with appropriate compared to laboratory-based standard-of-care approaches on
treatment support which included daily text reminders, telephone uptake of HCV RNA testing and treatment, and turnaround times
calls, home visits, video supported care, blood tests for monitoring (TAT) from HCV antibody (HCVAb) testing to treatment initiation.
side effects and treatment response with capillary bloods, and Method: We searched PubMed, Embase, and Web of Science on
support for hospital appointments. The clinician reviewed patients 23/09/2020 for studies in English that used HCV PoC RNA assays and
who had co-morbidities e.g. cirrhosis or other acute health needs and had data on key outcomes. We also searched relevant conference
made referrals to secondary care as necessary. The peer supported abstracts from 2016 to 2020 not picked up by the main search. We
people with engagement with drug and alcohol services and GP categorised study arms according to whether the PoC HCV VL assay
engagement. Routine clinical data was collected in electronic medical was based on-site at the clinic (Model 1), in a mobile unit (Model 2),
records. Data was captured about all interventions and healthcare or in a laboratory (Model 3) versus a HCV lab-based high-throughput
interactions. This model of care is being evaluated using the viral load assay (Model 4). For each model, studies were further
integrated HCV candidacy framework developed by Hoj and stratified by whether testing and treatment were delivered at the
colleagues (2019). same or different sites, and on the same day. For TATs we calculated
Results: As of October 2021, 72 patients were referred to the service, the weighted median of medians. We analysed RNA testing and
all with confirmed HCV infection. 2/72 had HIV co-infection, 2/72 had treatment uptake using random effects meta-analysis. Risk of bias
HBV co-infection, 57 were male, 42/72 had unstable housing, 72/72 was assessed using a tool adapted from Hoy et al and the ROBINS-I
had problematic drug or alcohol use. 72/72 had treatment approved, tool.
68/72 have started treatment, 66/72 currently in or completed Results: We included 45 studies with 64 within-study arms: 28
treatment, 48/72 completed treatment, 25/72 have SVR 12, 1/72 failed studies among people who inject drugs (PWID)/homeless, 4 among
treatment. prisoners, 9 among general populations, and 4 among persons with
HIV. All were observational studies. The pooled median TAT between
HCVAb test and treatment was shorter with PoC RNA assays on site
(18.5 days [95% CI: 14–53]) than with use of either lab-based PoC RNA
assays (64 [64–64]), or lab-based high-throughput RNA assays (67
[50–67]). Treatment uptake was higher with onsite PoC RNA assays

S556 Journal of Hepatology 2022 vol. 77(S1) | S389–S664

 POSTER PRESENTATIONS
77% (95% CI: 72%-83%), and PoC assays in a mobile unit 81% (60%– FRI333
97%) compared to lab-based high-throughput assays 53% (31%–75%), Hepatitis-C virus viral load reflex testing following an innitial
p value = 0.03 (models 1/2 vs 4). The effects were greatest among positive HCV antibody test: a global systematic review and meta-
PWID. 4 studies had direct within-study comparisons between a PoC analysis
assay arm and a lab-based assay arm. The pooled relative risk for Yusha Tao1, Weiming Tang1, Mengyuan Cheng1, Jennifer Bissram2,
testing uptake was 1.11 (95% CI: 0.89–1.38) and 1.32 (1.06–1.64) for Emmanuel Fajardo3, Lindsey Hiebert4, John Ward4, Roger Chou5,
treatment uptake. Risk of bias was high for 36% of studies and Philippa Easterbrook3, Jo Tucker1. 1UNC Project-China; 2UNC Chapel
moderate for 40%. Hill; 3WHO; 4Task force/USCDC; 5Oregon Health & Science University
Conclusion: Access to PoC HCV VL was associated with reduced time Email: [email protected]
to treatment initiation and increased treatment uptake, especially
Background and aims: A significant proportion of persons who are
among PWID. It is now recommended by WHO guidelines as an
HCV antibody positive do not in HCV viral load testing following a
additional strategy to promote access to VL testing, especially in
marginalised populations with high rates of loss to follow-up. positive antibody test slow linkage to essential HCV services. HCV
programmes have introduced reflex viral load testing (either lab-
FRI332 based reflex testing or clinic based reflex sample collection) as a
Diagnostic accuracy of point-of-care HCV viral load assays for HCV strategy to reduce the steps in the HCV diagnostic pathway and
diagnosis: a systermatic review and meta-analysis improve linkage to care. A systematic review evaluated the
Weiming Tang1, Yusha Tao1, Emmanuel Fajardo2, Elena Ivanova2, effectiveness of reflex viral load testing in increasing uptake of HCV
Roger Chou3, Jo Tucker1, Philippa Easterbrook2. 1UNC Project-China; viral load testing and treatment, and in reducing turn-around time
2
WHO; 3Oregon Health & Science University from HCV Ab screening to viral load testing, linkage to care, and
Email: [email protected] treatment, compared to a standard multi-step viral load testing
strategy.
Background and aims: Despite the widespread availability of short- Method: We searched three databases (Medline, EMBASE, and
course curative HCV treatment, a significant proportion of HCV Google Scholar) for studies in English to used either reflex lab-
patients remain undiagnosed and untreated. The requirement for a based viral load testing or clinic-based reflex sample collection and
confirmatory HCV viral load (HCV VL) test can result in substantial had data on the key outcomes. Laboratory-based HCV reflex testing
care cascade attrition. New point-of-care HCV RNA assays may refers to a testing algorithm in which patients have only a single
enhance access to testing by decentralizing HCV RNA testing outside clinical encounter and only one blood draw or specimen taken and
of laboratory settings. We undertook a systematic review and meta- sent to the lab. If the sample for anti-HCV testing in the lab is positive,
analysis to compare the diagnostic performance of PoC HCV viral load then the same existing or duplicate sample is used for a “reflex” lab-
assays to laboratory-based nucleic acid testing. based HCV viral load test. No further visit or sample collection is
Method: We searched three databases, used Cochrane methods, and required. Clinic-based reflex testing refers to a testing algorithm
registered the protocol Studies were eligible if they utilized a where there is only a single clinical encounter/visit for an initial rapid
laboratory reference standard to evaluate POC HCV RNA assays and diagnostic HCV antibody test, but with two blood draws. A fingerstick
if they reported or had raw data that could be extracted to calculate sample is taken and tested using a rapid diagnostic HCV antibody test,
sensitivity, specificity, the limit of detection, and bias. Data were which if positive is then immediately followed by a “reflex” blood
extracted by geographic region, collection year, risk group, and draw (either venous blood sample or fingerstick) for HCV viral load
specimen type. Random effects bivariate models were used to confirmation of current infection. Data were extracted by geographic
summarize estimates and describe the variability in test performance region, collection year, and risk group. Summary estimates (95%
across studies. We used the GRADE approach to assess the certainty of confidence intervals [CI]) were calculated using random-effects
the evidence. meta-analyses.
Results: A total of 25 studies including data from 8, 791 people were Results: 51 studies met the inclusion criteria reporting laboratory-
summarized. XX studies in high-income countries and XX in low and based reflex testing (n = 32) and clinic-based reflex sample collection
middle-income countries. Assays included the Xpert HCV Viral Load (n = 19). Forty-two were in high-income and nine were in low or
assay (Cepheid, USA) Xpert HCV VL Fingerprick (Cepheid, USA) middle-income countries. All studies were cross-sectional or cohort
Genedrive HCV ID Kit, Truenat HCV assay, and SAMBA II. Across all studies. Compared to laboratory non-reflex testing, laboratory reflex
assays, the pooled sensitivity and specificity were 99% (95% CI: 98– testing increased the likelihood of viral load testing among patients
99%) and 99% (95% CI: 99–100%), respectively, compared to a lab- screened as HCV antibody positive (RR: 1.35 (1.16–1.58)), and may
based reference standard. High sensitivity and specificity were also improve linkage to care among patients diagnosed with HCV
observed across different study settings (including LMICs and HICs) infection with RNA testing (RR: 1.47 (0.81–2.67)).
and populations, using different assays. The evidence was moderate- Conclusion: HCV viral load reflex testing increased uptake and
high certainty. Specificity showed no difference among different reduced time to HCV viral load testing and may enhance linkage to
specimen types. care. In addition, laboratory and clinic reflex testing were feasible in a
Conclusion: POC HCV viral load assays have excellent sensitivity and diverse range of LMIC settings. WHO now recommends the adoption
specificity compared to gold standard laboratory-based nucleic acid of reflex viral load testing as an additional strategy to promote linkage
testing methods across diverse settings and populations. WHO now to care.
recommends the use of POC HCV viral load assays as an additional Disclosure: No significant relationships.
strategy to promote access to treatment. The adoption of POC viral
load assays will be facilitated through increasing availability of
integrated molecular multiplex technologies that utilize the same
technology for several assays and/or across diseases.
Disclosure: No significant relationships.

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POSTER PRESENTATIONS
FRI334 FRI335
Finding cases of hepatitis C for treatment using automated A cluster randomized controlled study of secondary distribution
screening in the emergency department is effective, but what is of HCV self-test to support micro-elimination in Karachi,
the cost? Pakistan.
David Prince1,2, Julia Di Girolamo1,3, Joseph Pipicella1,3, Aliya Hasnain1, Sonjelle Shilton2, Wasiuddin Shah1, Jessica Markby2,
Melissa Fraser1, Tahrima Kayes1, Frank Alvaro4,5, Michael Maley2,4,5, Niklas Luhmann3, Muhammad Jamil3, Elena Ivanova2,
Hong Foo4,5,6, Paul Middleton2,3,7,8, Miriam Levy1,2,3. 1Liverpool Saeed Sadiq Hamid4. 1Aga Khan University, Karachi, Pakistan; 2FIND,
Hospital, Gastroenterology and Liver, Liverpool, Australia; 2UNSW Geneva, Switzerland; 3WHO, Switzerland; 4Aga Khan University,
Sydney, Medicine, Sydney, Australia; 3Ingham Institute, Liverpool, Medicine, Karachi, Pakistan
Australia; 4Liverpool Hospital, Pathology, Liverpool, Australia; 5NSW Email: [email protected]
Health Pathology, Liverpool, Australia; 6Western Sydney University,
Background and aims: Pakistan has a nationwide HCV prevalence of
Medicine, Parramatta, Australia; 7Liverpool Hospital, Emergency
6% with majority of cases undiagnosed due to lack of comprehensive
Department, Liverpool, Australia; 8The University of Sydney, Medicine,
screening programmes. Self-testing has shown to acceptable and
Camperdown, Australia
increases testing uptake for HIV due to its convenience and privacy
Email: [email protected]
advantages. This study aims to evaluate the acceptability and effect of
Background and aims: Case detection remains a major challenge for a program enabling home delivery of HCV self-testing using the oral-
hepatitis C virus (HCV) elimination. We have previously published based OraQuick® HCV rapid antibody test. HCV self-testing study is
results from a pilot of an emergency department (ED) semi- nested within a community-based micro elimination project in an
automated screening program, SEARCH; Screening Emergency HCV endemic district of Karachi, Pakistan.
Admissions at Risk of Chronic HCV. In this pilot, 5000 consecutive Method: This ongoing cluster randomized control study targets
patients were screened including 4778 overseas born (targeted) from persons missed during house-to-house screening done as part of a
14, 093 ED presentations. HCVAb was positive in 181 patients (3.6%); micro-elimination study in two Union Councils in district Malir of
51 (1.0%) were HCV RNA positive. This cost analysis aimed to Karachi. During house visits, individuals not found at home are
accurately describe the overall costs of this pilot service. It also eligible for participation. Target sample size is 1000 participants each
aimed to report on costs per patient tested, per HCV Ab positive in intervention and control group. In the intervention group, an HCV
patient detected and per RNA positive patient treated. We modelled self-test is left with instructions for use explained to a senior
the effect of proposed service refinements (SEARCH 2.0). household member. In the control group, a pamphlet is left with
Method: All direct costs of HCV testing until direct acting anti-viral directions to visit the nearest clinic for HCV screening. Both groups
(DAA) therapy initiation were calculated. Cost was assessed in 2018 are followed up within 4 weeks to inquire if testing was completed
Australian Dollars. A cost analysis of the initial program and and a brief acceptability survey is conducted with the tester. Results
refinements are presented. Sensitivity analysis to understand report are incentivized and individuals with positive tests are linked
impact of variation in staff time, laboratory test cost, changes in for further management.
HCV antibody (Ab) prevalence, RNA positivity percentage and rate of Results: 1637 participants were recruited between 29th Nov 2021 and
linkage to care was conducted. Impact of refinements (SEARCH 2) to 22nd March 2022, with 993 in the intervention group and 644 in the
cost is presented. control group, from rural and peri-urban clusters of the district.
Results: The total SEARCH pilot, testing 5000 patients was estimated Median (IQR) age across both groups is 30 (24–42) years with 82%
to cost $110, 549.52 (range $92, 109.79−$129, 581.24) comprising of (1337/1637) male participants. Half (51%) of the participants who
$68, 278.67 for HCV Ab testing, $21, 568.99 for follow up and linkage completed self-testing had received no formal education. The
to care of positive patients and $20, 701.86 to prepare HCV RNA proportion of participants who reported completing the HCV
positive patients for treatment. Refinements resulted in a 32% cost antibody test was 79% (782/993) in the intervention group compared
reduction overall and reduced the cost of HCV antibody screening to 18% (117/644) in the control group ( p < 0.05). Nearly all (95%)
from $13.66 to $8.46 per test and the total cost per positive HCV Ab, participants who reported completing the test demonstrated
positive HCV RNA and treated patient to $611.77, $2, 168.64 and willingness to perform HCV self-test in the future.
$3, 566.11 respectively. Our sensitivity analysis indicates costs are
modest so long as HCV Ab prevalence was 1% or greater.

Figure: Costs of HCV screening in SEARCH 1 compared to costs modelled

with SEARCH 2 program refinements

Conclusion: ED screening is an affordable strategy for HCV case

detection and elimination.

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 POSTER PRESENTATIONS
Conclusion: Preliminary results of this study demonstrate that HCV FRI337
self-testing increases HCV screening rates in a peri-urban/rural From extensive to intensive screening, co-operations model of
setting consistent of a mostly illiterate population in a low-middle hepatitis C elimination in out-patients and people who inject
income country like Pakistan. drug population in southwest of China
Qing Lin1, Youzhi He2, Long Chen3, Jingchun He4, Xiaojian Yuan5,
FRI336 Zhenglin Wang1, Guohui Wu6. 1The People’s Hospital of Jiulongpo
HCV-viral load fingerstick assay to simplify screening and linkage District, Chongqing, China; 2Methadone Maintenance Therapy Clinic of
to care of people who use drugs attending Italian addiction Jiulongpo District, Chongqing, China; 3Chongqing Public Health Medical
treatment centres Center, Chongqing, China; 4Jiulongpo District Center for Disease Control
Sarah Vecchio1, Lorenzo Somaini2, Luigi Bartoletti3, Daniela Mussi3, and Prevention, Chongqing, China; 5Xiejiawan Street Community Health
Roberta Gaudenzi4, Eugenia Vernole5, Claudio Leonardi6. 1ASL Biella, Service Center, Jiulongpo District, Chongqing, China; 6Chongqing Center
Addiction Treatment Center, Biella, Italy; 2ASL Biella, Addiction for Disease Control and Prevention, Chongqing, China
Treatment Center, Biella, Italy; 3ASL Alessandria, Addiction Treatment Email: [email protected]
Center, Alessandria, Italy; 4ASL Umbria 1, Addiction Treatment Center,
Perugia, Italy; 5ASL Bari, Addiction Treatment Center, Bari, Italy; 6ASL Background and aims: The Southwest China has a relatively higher
Roma 2, Addiction Treatment Center, Roma, Italy HCV prevalence rate among the whole country for large proportion of
Email: [email protected] people who inject drugs (PWID) reside here. We established a co-
operation model combined with intensive and extensive HCV
Background and aims: People who use drugs (PWUDs) are the major screening, and this study aimed to determine its efficacy on the
drivers of HCV transmission in the world, representing the target HCV elimination in PWIDs and general out-patients (GOP).
population for HCV screening and treatment. In Italy, the estimate Method: The co-operation network consists of local Centers for
prevalence of HCV infection in drug users exceeds the 80%, with Disease Control and Prevention (CDC) and the medical association
205.000 PWUDs not yet treated. Simplified strategies are required for including 39 community health centers, 15 district hospitals and 1
the screening and diagnosis of hepatitis C infection among PWUDs, methadone clinic. The CDC was responsible for educational training,
and HCV-RNA viral load fingerstick assay can help in overcoming funding and patient-network management. The medical association
existing challenges and barriers to HCV diagnosis and care. The aims was responsible for HCV antibody screening and linkage to care with
of this prospective study were to evaluate the feasibility and the the cascade referral system. Patients with positive HCV antibody were
acceptability of HCV-RNA viral load fingerstick assay use to improve referred to the designated hospital for HCV RNA testing, in which
HCV screening and treatment among Italian PWUDs attending positive patients will receive anti-HCV treatment of sofosbuvir/
different Italian Addiction Treatment Centres (Ser.D) in an outpatient velpatasvir (SOF/VEL) for 12 weeks with or without RBV. The call-
setting. back system in methadone clinic requested the HCV RNA-positive
Method: Between October 2020 and December 2021, the HCV PWID patients to return for further therapy. The patient-education
screening was offered to 1258 consecutive PWUDs from 5 Addiction and management were carried out in the district hospitals monthly.
Treatment Centres of 4 Regions of Northern, Central and Southern Reimbursement and free RNA testing were provided to enhance
Italy. HCV analysis was carried out by means of a fingerstick capillary treatment affordability. The effect and safety of SOF/VEL were
whole blood RNA test. Results were given in 60 minutes. evaluated.
Results: 1221/1258 (97%) consecutive PWUDs were enrolled. Patients Results: From March 2021 to March 2022, 102873 residents and 1, 199
were mostly male (973/1221, 80%), with a mean age of 42.9 years ± PWIDs were screened. The seropositive rate of anti-HCV and HCV
10.7 and a mean addiction treatment duration of 10.1 years ± 8.5. The RNA were 0.58% (595/101674), 22.01% (131/595) in GOPs and 87.49%
main HCV risk factors identified were heroin addiction (935/1221, (1049/1199, 68.95% (171/248)) in PWIDs, respectively. 85.49% (112/
76%), a history of injecting drug use (700/1221, 57%) and tattooing 131) GOPs patients and 41.52% (71/171) PWIDs initiated anti-HCV
(794/1221, 65%). HCV RNA was identified in 240/1221 patients (20%) treatment, while only 8% before the model establishment. The
participants. The most common HCV genotypes, among available genotype distribution is as follows: GT3a 22.13% (29/131), GT3b
data, were 3 (40/240, 17%) and 1a (38/240, 16%). Among patients with 20.61% (27/131), GT1b 18.32% (24/131) in GOPs, while GT3a 47.37%
detectable HCV RNA, 89% (214/240) were referred to specialists for (81/171), GT3b 42.69% (73/171) and GT1b 9.94% (17/171) in PWIDs.
HCV treatment and, at the time of writing, 53% (127/240) completed The percentage of liver fibrosis, cirrhosis and hepatocellular
the treatment. All the treated patients achieved SVR (Sustained carcinoma was 9.1% (12/131), 9.1% (12/131) and 0.7% (1/131) in
Virologic Response). GOPs, while 26.31% (45/171), 13.45% (23/171) and 1.75% (3/171) in
Conclusion: This is one of the largest HCV-RNA screening projects, PWIDs. The co-infection rate of HBV or HIV was 3.8% (5/131) or 1.5%
highlighting the feasibility and the acceptability of onsite testing (2/131) in GOPs and 7.6% (13/171) or 14.03% (24/171) in PWIDs. Both
performed with HCV-RNA viral load fingerstick assay in PWUDs groups achieved high SVR12 as 99.10% (111/112) in GOPs and 97.18%
attending Ser.Ds. At present, HCV screening and linkage to care (69/71) in PWIDs. None of patients discontinued anti-HCV treatment
remain worldwide far from comprehensive. The described easy to use due to adverse events.
approach favours PWUDs engagement and increases HCV treatment
and elimination, as evidenced by the high rate of completed
treatments.

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POSTER PRESENTATIONS
Conclusion: The co-operation model was effective in HCV elimin- can be initiated using rapid test-and-treat models reducing loss to
ation in both groups. The HCV prevalence of PWIDs was significantly follow up and need for HCV RNA testing in resource limited settings.
higher than GOPs in the district scale. Although PWIDs had lower
treatment adherence, the treatment rate in PWIDs were improved FRI339
significantly by intensive follow-up. Both groups achieved high SVR Liver-related mortality among people with hepatitis B and C: a
with good safety profile by SOF/VEL treatment. The co-operations validation study using linked healthcare administrative datasets
model with intensive and extensive screening was an optimal option Syed Hassan Bin Usman Shah1, Maryam Alavi2, Behzad Hajarizadeh2,
for GOP and PWID to eliminate HCV. Gail Matthews2, Marianne Martinello2, Mark Danta3, Janaki Amin4,
Matthew Law5, Jacob George6, Hamish Innes7, Gregory Dore2. 1The
FRI338 Kirby Institute, Viral Hepatitis Clinical Research Program, Kensington,
Using time to positivity of hepatitis rapid detection test results to Australia; 2The Kirby Institute, Viral Hepatitis Clinical Research Program,
determine active viremia UNSW, Kensington, Australia; 3St Vincent’s Hospital Sydney,
Saeed Sadiq Hamid1, Sultan Salahuddin2, Wasiuddin Shah2, Darlinghurst, Australia; 4Macquarie University, Macquarie Park,
Aliya Hasnain2, Muraduddin Gulab2, Taj Muhammad2, Sabiha Khan2. Australia; 5The Kirby Institute, Kensington, Australia; 6Westmead
1
Aga Khan University, Karachi, Pakistan; 2Aga Khan University, Hospital, Westmead, Australia; 7Glasgow Caledonian University, United
Medicine, Karachi, Pakistan Kingdom
Email: [email protected] Email: [email protected]
Background and aims: The recommended time taken to run the Background and aims: Routinely collected and linked healthcare
Rapid Diagnostic tests (RDTs) for HCV screening is 20 mins, which is administrative datasets could be used to monitor mortality among
followed by reflex PCR testing for confirmation of chronic HCV people with hepatitis B and C virus (HBV and HCV). This study aimed
infection. Confirmatory viral load testing is a barrier in the HCV to validate a definition for liver-related mortality among people with
cascade of care as it is a cost and time-intensive step. This study an HBV or HCV notification, including any death (i.e. all-cause)
hypothesises the correlation between shorter read time and active following hospitalization for end-stage liver disease (ESLD), which
viremia in HCV infected patients, which can reduce the need for included a first-time hospital admission due to decompensated
reflex RNA tests and help implement rapid-test-and-treat models for cirrhosis (DC) or hepatocellular carcinoma (HCC).
HCV. Method: In New South Wales, Australia, HBV and HCV notifications
Method: The findings from this study were obtained from a (1993–2017) were linked to hospital admissions (2001–2018), all-
community-based micro-elimination study which targets a high cause mortality (1993–2018), and cause-specific mortality (1993–
burden HCV endemic area in Karachi, Pakistan. Door-to-door visits 2016) databases. Hospitalization-defined ESLD-related mortality was
were performed to conduct rapid screening of individuals with validated in comparison with two death certificate-based definitions
unknown HCV status, using the finger-stick Abbott SD Bioline HCV of liver deaths coded among primary and secondary cause-specific
diagnostic kits. The time taken for the RDT to display a positive result mortality data, including ESLD-related (deaths due to DC and HCC)
was measured using a stopwatch to record the duration from the and all-liver deaths (ESLD-related and other liver-related causes).
point the blood sample was placed in the test kit till the point the test Results: Of 63, 292 and 107, 430 individuals with an HBV and HCV
line appeared. Blood samples of individuals with a positive screening notification, there were 4, 478 (2.6%) post-ESLD hospitalization
test were collected for Hepatitis C core antigen testing, on Abbott deaths, 5, 572 (3.3%) death certificate liver disease deaths, and
Architect i1000SR, to determine viremia. 2, 910 (1.7%) death certificate ESLD deaths. Between 2001 and 2016,
Results: A total of 1327 participants, median age (IQR) 47 years (39– 63% (562/891) of HBV post-ESLD hospitalization deaths had death
56), with 70% females, who screened positive on HCV RDT and had certificate ESLD deaths recorded, including 58% (390/676) of DC and
HCV core antigen testing done, were included. Overall, 730/1327 85% (431/510) of HCC deaths. Further, 83% (741/891) of HBV post-
(55%) patients were viremic and in all cases, the HCV RDT test was ESLD hospitalization deaths had death certificate liver disease deaths,
positive within 5 minutes. 50% (366/730) of all viremic cases had a including 81% (546/676) of DC and 95% (482/510) of HCC deaths.
positive screening result within 20–30 seconds. No. of cases with Similarly, 58% (2, 082/3, 587) of HCV post-ESLD hospitalization
active viremia decreased as the time taken for a positive result to deaths had death certificate ESLD deaths recorded, including, 56% (1,
appear on rapid screening increased (r = −0.63). Less than 1% of cases 817/3, 236) of DC and 82% (1, 007/1, 224) of HCC deaths. Further, 87%
with active viremia were found amongst those who had a positive (3, 135/3, 587) of HCV post-ESLD hospitalization deaths had death
screening result from 120 seconds to 300 seconds. certificate liver disease deaths, including 87% (2, 812/3, 236) of DC
and 96% (1, 171/1, 224) of HCC deaths.
Conclusion: Our findings support the use of healthcare administra-
tive datasets as an efficient method and a reliable information source
to represent liver-related mortality rates accurately; however,
concordance between post-hospitalization and death certificate-
based cause of death is clearly higher for HCC than DC.

FRI340
Identifying risk factors associated with hepatitis C virus infection
in participants in the national health and nutrition examination
survey using Super Learner
Laura Telep1,2, Rachael Phillips3, Anand Chokkalingam1,2. 1Gilead
Sciences, Inc., Foster City, United States; 2University of California,
Berkeley, Epidemiology, Berkeley, United States; 3University of California,
Berkeley, Biostatistics, Berkeley, United States
Email: [email protected]
Conclusion: The time to read SD Bioline HCV RDT can be reduced to 5
mins to identify patients with HCV infection. In patients displaying a Background and aims: Under-diagnosis is a key impediment to
positive result between 20 and 30 seconds HCV treatment using DAAs eliminating hepatitis C virus (HCV) infection in the United States (US).

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 POSTER PRESENTATIONS
Machine learning methods offer an opportunity to support expanded
HCV screening in a resource-optimized way by identifying the
characteristics that are most influential in predicting HCV.
Viral Hepatitis C: Post SVR and long term
Method: The ensemble machine-learning method Super Learner (SL) follow up
was used with National Health and Nutrition Examination Survey
(NHANES) data collected from 2013 to 2018 to build an HCV infection
risk prediction algorithm. Because only 1% of survey participants FRI343
tested positive for HCV RNA, case-control sampling was used to Hepatocellular carcinoma incidence after hepatitis C cure among
address class imbalance, with five HCV-uninfected individuals patients with advanced fibrosis or cirrhosis: a meta-analysis
randomly selected for each HCV-infected individual (n = 1, 008). Ian Lockart1,2, Malcolm Guan Hin Yeo2, Behzad Hajarizadeh3,
The SL was fit to the case-control data, its performance was evaluated Gregory Dore1,3, Mark Danta1,2. 1St Vincent’s Hospital, Sydney,
with the area under the precision-recall curve (AUC-PR), and then it Australia; 2St Vincent’s Clinical School, UNSW Sydney, Australia; 3The
was used to predict HCV infection in the full NHANES dataset (n = 15, Kirby Institute, UNSW Sydney, Australia
237). We also identified the features that had the greatest impact on Email: [email protected]
AUC-PR, and thus were most predictive of HCV infection.
Background and aims: Hepatitis C virus (HCV) cure reduces but does
Results: The SL’s AUC-PR on the full NHANES dataset was 52%, a 47-
not eliminate the risk of hepatocellular carcinoma (HCC). HCC
fold improvement over baseline. At the probability threshold that
surveillance is recommended in populations where the incidence
optimized the F1 score, the SL achieved 55.4% precision and 61.3%
exceeds 1.5% per year. In cirrhosis, HCC surveillance should continue
recall; that is, if the goal was to identify at least 60% of those infected
after HCV cure, although it is uncertain if this should be indefinite. For
with HCV, then for every 100 individuals classified as HCV-infected,
patients with advanced fibrosis (F3), guidelines are inconsistent in
more than 50% would be true positives. Features that were most
their recommendations. This systematic review evaluated the
predictive of HCV infection included alanine aminotransferase (ALT),
incidence of HCC after HCV cure among patients with F3 fibrosis or
aspartate aminotransferase (AST), injection drug use, age, albumin,
cirrhosis.
globulin, and HBV infection status. Additional influential predictors
Method: We searched bibliographic databases and conference
included smoking-related features, risk factors for heart disease or
abstracts for studies assessing the incidence of HCC after HCV cure
stroke (triglycerides, total cholesterol, recommendations by a doctor
among patients with F3 fibrosis or cirrhosis. Meta-analyses were used
to take low dose aspirin), and features related to oral health.
to cumulate HCC rates and meta-regression was used to explore
heterogeneity across studies.
Results: Forty-four studies were included (36, 183 patients; 109, 385
person-years of follow up). The incidence of HCC was 2.2 per 100
person-years (95% CI 1.9–2.4) among patients with cirrhosis, and 0.5
per 100 person-years (95% CI 0.3–0.7) among patients with F3
fibrosis. In meta-regression analysis among patients with cirrhosis,
older age (adjusted rate ratio [aRR] per 10-year increase in mean/
median age: 1.34; 95% CI 1.04–1.74) and prior decompensation (aRR
per 10% increase in the proportion of patients with prior decompen-
sation: 1.05; 95% CI 1.00–1.11) were associated with an increased
incidence of HCC. Longer follow-up after HCV cure was associated
with a decreased incidence of HCC (aRR per year increase in mean/
median follow-up: 0.87; 95% CI 0.80–0.96).

Conclusion: As outreach continues to identify the undiagnosed HCV-

infected population in the US, knowledge of the characteristics most
predictive of HCV infection should be utilized to guide screening and
prevention efforts. Next steps include identifying HCV infection
predictors from widely available data such as features collected in a
single routine medical care visit and exploring variation in highly
predictive features by age category. Algorithms such as the one
demonstrated here can be useful tools to support these activities.

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POSTER PRESENTATIONS
Conclusion: Among patients with cirrhosis, the incidence of HCC
decreases over time after HCV cure and is lowest in patients with
younger age and compensated cirrhosis. The substantially lower
incidence in F3 fibrosis is below the recommended threshold for cost-
effective screening.

FRI344
Glycomics-based serum marker as reliable tool for assessment of
viral response after treatment with direct-acting antiviral drugs
in hepatitis C virus infection
Nicky Somers1, Elisabeth Vandekerckhove1, Anja Geerts1,
Helena Degroote1, Sander Lefere1,2, Lindsey Devisscher2,
Leander Meuris3,4, Nico Callewaert3,4, Hans Van Vlierberghe1,
Xavier Verhelst1. 1Ghent University, Ghent University Hospital,
Hepatology Research Unit, Department Internal Medicine and
Paediatrics, Liver Research Center Ghent, Ghent University, Ghent
University Hospital, Ghent, Belgium, Belgium; 2Ghent University, Gut-
Liver Immunopharmacology Unit, Department of Basic and Applied
Medical Sciences;, Liver Research Center Ghent, Ghent University, Ghent,
Belgium, Belgium; 3Vlaams Instituut voor Biotechnologie, Center for
Medical Biotechnology, VIB, Ghent, Belgium, Belgium; 4Ghent University,
Department of Biochemistry and Microbiology, Ghent University, Ghent,
Belgium
Email: [email protected]
Background and aims: Patients with chronic hepatitis C virus (HCV)
infection have a genuine risk of developing liver fibrosis and cirrhosis, Conclusion: In this study, we illustrated that changes in serum
potentially resulting in hepatocellular carcinoma (HCC), a risk that protein glycosylation that are observed with increasing levels of
remains even after sustained viral response (SVR). It is of utmost fibrosis decline after the decrease of viral load during treatment with
importance to closely monitor these patients during and after DAAs of HCV-infected patients (all genotypes). The decrease started
antiviral treatment, which today consists of direct-acting antiviral early after initiation of treatment and remained stable during post-
drugs (DAAs). Glycomics-based biomarkers are an attractive tool to treatment observation. The rapid decrease of glycomics-based
answer this medical need, as alterations in the abundance of N- fibrosis biomarkers probably reflects the amelioration of liver
glycans reflect an altered state of the liver. Progression of liver fibrosis inflammation as underlying process rather than the improvement
has been linked to changes in serum glycosylation patterns before. of liver fibrosis itself, which cannot occur in such a short timeframe.
Accordingly, our previously developed GlycoFibroTest measures the In conclusion, this study suggests that GlycoFibroTest shows an
ratio of NGA2FB to NA3. The aim of this study was to assess the excellent correlation with viral response in HCV patients.
GlycoFibroTest for the evaluation of fibrosis regression during and
after treatment of HCV with DAAs. FRI345
Method: N-glycosylation patterns were analyzed in sera from 36 Post-treatment elevated gamma-glutamyl transferase is the best
HCV-infected patients, collected between January 2015 and June predictor for future outcomes in HCV patients achieving
2016. Patients showed liver biopsy-proven advanced fibrosis (F3, n = sustained virological response-data from the german hepatitis C-
12) or established cirrhosis (F4, n = 24) before therapy initiation, registry (DHC-R)
which consisted of a twelve-week oral administration of DAAs. The Stefan Mauss1, Hartwig Klinker2, Klaus Boeker3, Uta Merle4,
GlycoFibroTest was measured on serum samples at three timepoints: Ralph Link5, Peter Buggisch6, Dietrich Hüppe7, Markus Cornberg8,
at the start (week 0), the end (week 12) and during follow up (week Christoph Sarrazin9,10, Heiner Wedemeyer8,11, Thomas Berg12,
24), by the use of an optimized glycomic technology on a DNA Frank Tacke13, German Hepatitis C-Registry11. 1Center for HIV and
sequencer (DSA-FACE, Applied Biosystems). Hepatogastroenterology, Düsseldorf, Germany; 2University Hospital
Results: All patients achieved SVR after treatment and none of them Würzburg, Würzburg, Germany; 3Center of Hepatology, Hannover,
developed HCC. Figure 1 demonstrates the significant decrease of the Germany; 4Heidelberg University Hospital, Heidelberg, Germany; 5MVZ-
GlycoFibroTest ( p < 0.0001) in all patients (F3 + F4)[12]. More Offenburg GmbH/St. Josefs-Klinik, Offenburg, Germany; 6ifi-Institute for
specifically, this decrease was seen from week 0 to weeks 12 and Interdisciplinary Medicine, Hamburg, Germany; 7Gastroenterologische
24, but no significant decline could be retained between weeks 12 Gemeinschaftspraxis Herne, Herne, Germany; 8Hannover Medical
and 24. Statistical analysis was performed using IBM SPSS Statistics School, Hannover, Germany; 9St. Josefs-Hospital, Wiesbaden, Germany;
10
version 28.0. Since measurements were repeated on the same subject Goethe University Hospital, Frankfurt, Germany; 11Leberstiftungs-
and values were not normally distributed, the non-parametric GmbH Deutschland, Hannover, Germany; 12University Hospital Leipzig,
Friedman’s test was used. Statistical significance was set at the Leipzig, Germany; 13Charité-Universitätsmedizin Berlin, Department of
alpha level of 0.05. Hepatology & Gastroenterology, Campus Virchow-Klinikum and Campus
Charité Mitte, Berlin, Germany
Email: [email protected]
Background and aims: While direct acting antivirals (DAA) can cure
chronic hepatitis C virus (HCV) infection in almost all patients, some
patients remain at risk of liver disease despite HCV cure. We aimed at
identifying predictors for liver-related morbidity and death after viral
cure.
Method: The DHC-R (German Hepatitis C-Registry) is a national
multicenter real-world registry. Patients are followed for up to 7 years
after DAA therapy. Normal alanine transaminase (ALT; at 37°C) was

S562 Journal of Hepatology 2022 vol. 77(S1) | S389–S664

 POSTER PRESENTATIONS
defined as (i) ≤35 U/l for females and ≤50 U/l for males and or University Graduate School of Medicine, Department of
(ii) according to AASLD as ≤19 U/l for females and ≤30 U/l for males. Gastroenterology and Hepatology; 2Saitama Medical University,
Normal gamma-glutamyl transferase (GGT) (at 37°C) was defined as Department of Gastroenterology and Hepatology; 3University of
≤40 U/l (female) and ≤60 U/l (male). The present analysis is based on Yamanashi, First Department of Internal Medicine, Faculty of Medicine;
4
6982 patients with available data as of January 1st, 2021. Graduate School of Medicine, Osaka City University, Department of
Results: 97.4% of patients achieved sustained virological response Hepatology; 5Musashino Red Cross Hospital, Department of
(SVR). In patients achieving SVR, elevated ALT at SVR24 was Gastroenterology and Hepatology; 6Kagoshima University Graduate
documented in 657/6982 (9.4%), elevated ALT (AASLD) in 2609/ School of Medicine and Dental Sciences, Digestive and Lifestyle Diseases,
6982 (37.4%) and elevated GGT in 1777/6982 (25.5%). At SVR24, Department of Human and Environmental Sciences; 7Nara Medical
elevated ALT was associated with categorized higher body mass index University, Department of Gastroenterology; 8Graduate School of
(BMI; p < 0.05), liver cirrhosis (OR 2.29, p < 0.0001), alcohol con- Biomedical and Health Sciences, Hiroshima University, Department of
sumption (>30/40 g/day) (OR 2.93, p < 0.001), elevated ALT at baseline Gastroenterology and Metabolism; 9Iwate Medical University, Division
(OR 4.46, p < 0.0001) and no SVR (OR 43.49, p < 0.0001). The same of Hepatology, Department of Internal Medicine; 10Ehime University
variables were identified using AASLD criteria plus female sex (OR Graduate School of Medicine, Department of Gastroenterology and
2.39, p < 0.001). Increased GGT at SVR24 was associated with male sex Metabology; 11National Hospital Organization Nagasaki Medical Center,
(OR 2.12, p < 0.001), higher BMI (OR1.04, p < 0.05), age >50 years (OR Clinical Research Center; 12Nagasaki University of Graduate School of
1.60, p < 0.01), liver cirrhosis (OR 3.97, p < 0.0001), alcohol consump- Biomedical Sciences, Department of Gastroenterology and Hepatology;
13
tion (OR 2, 99, p < 0.001), diabetes mellitus (OR 1.63, p < 0.001), non- Graduate School of Medicine, Chiba University, Department of
SVR (OR 8.00, p < 0.0001) and elevated GGT at baseline (OR 17.12, p < Gastroenterology; 14Faculty of Medicine, Yamagata University,
0.001). More importantly, we identified elevated GGT at SVR24 as the Department of Gastroenterology; 15Graduate School of Medical Science,
best predictor of overall survival, hepatic decompensation or HCC Kyoto Prefectural University of Medicine, Department of Molecular
development over elevated ALT or ALT (AASLD; Figure). Combining Gastroenterology and Hepatology; 16Graduate School of Medicine, The
ALT and GGT did not improve sensitivity substantially. University of Tokyo, Department of Gastroenterology; 17Graduate School
of Medicine, Hokkaido University, Department of Gastroenterology and
Hepatology; 18Yamaguchi University Graduate School of Medicine,
Department of Gastroenterology and Hepatology; 19Nagoya City
University Graduate School of Medical Sciences, Department of
Gastroenterology and Metabolism; 20Kanazawa University Hospital,
Department of General Medicine; 21Toranomon Hospital, Department of
Hepatology; 22National Center for Global Health and Medicine, The
Research Center for Hepatitis and Immunology; 23Faculty of Medical
Sciences, University of Fukui, Second Department of Internal Medicine;
24
Tokyo Medical and Dental University, Department of Gastroenterology
and Hepatology, Department of Liver Disease Control; 25Graduate School
of Medicine and Dental Sciences, Niigata University, Division of
Gastroenterology and Hepatology; 26Gifu University Graduate School of
Medicine, Department of Gastroenterology/Internal Medicine; 27Osaka
University Hospital, Department of Medical Innovation
Email: [email protected]
Background and aims: Direct-acting antiviral (DAA) therapy can
improve liver function in the short term even in patients with
hepatitis C virus (HCV)-related decompensated cirrhosis. However,
the impact of DAA therapy on long-term outcome among patients
with decompensated cirrhosis is unclear.
Method: This study enrolled 396 patients with HCV-related
compensated or decompensated cirrhosis who started DAA therapy
between February 2019 and December 2020 at 33 Japanese hospitals.
Patients were excluded when sustained virologic response (SVR)
Conclusion: We here define risk factors for developing clinical could not be determined or died before SVR confirmation. SVR was
complications after cure form HCV infection. In this context, elevated defined as undetectable serum HCV-RNA for at least 12 weeks after
GGT may highlight the relevance of non-alcoholic fatty liver disease the end of treatment (EOT). Our endpoints are the incidence of
(NAFLD), diabetes mellitus, and alcohol consumption. decompensated cirrhosis events with hospitalization and overall
survival. Decompensated cirrhosis events were defined as aggrava-
FRI346 tion of ascites or encephalopathy, rupture of varix, and the onset of
The impact of liver function improvement after direct-acting spontaneous bacterial peritonitis, sepsis or acute kidney injury. We
antiviral therapy on the outcome in hepatitis C virus patients with evaluated the impact of delta MELD score between at baseline and at
decompensated cirrhosis 12 weeks after the EOT on these endpoints. Delta MELD score was
Yuki Tahata1, Hayato Hikita1, Satoshi Mochida2, Nobuyuki Enomoto3, classified into three groups: the MELD score decreased 2 points or
Norifumi Kawada4, Masayuki Kurosaki5, Akio Ido6, Hitoshi Yoshiji7, more (MELD improved), the MELD score increased 2 points or more
Daiki Miki8, Yasuhiro Takikawa9, Ryotaro Sakamori1, Yoichi Hiasa10, (MELD deterioration) and others (MELD stable).
Hiroshi Yatsuhashi11, Kazuhiko Nakao12, Naoya Kato13, Results: The median age was 70 years. The SVR rates of patients with
Yoshiyuki Ueno14, Yoshito Itoh15, Ryosuke Tateishi16, Goki Suda17, CP class A, B and C were 100% (224/224), 96% (142/148) and 96% (22/
Taro Takami18, Kentaro Matsuura19, Taro Yamashita20, Norio Akuta21, 23), respectively. Among 396 patients, delta MELD score were
Tatsuya Kanto22, Yasunari Nakamoto23, Yasuhiro Asahina24, evaluated in 347 patients. The number of patients with MELD
Shuji Terai25, Masahito Shimizu26, Ryoko Yamada1, Takahiro Kodama1, improved, MELD stable and MELD deterioration were 41, 275 and 31,
Tomohide Tatsumi1, Tomomi Yamada27, Tetsuo Takehara1. 1Osaka respectively. During the median observation period of 20 months, 34
patients experienced decompensated cirrhosis events (the most

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POSTER PRESENTATIONS
frequent event was ascites), 10 patients died, and two patients patients who achieved the SVR and 93% for those who didn’t ( p =
underwent liver transplantation. In patients with CP class A, five 0.002). Of 1555 patients who achieved the SVR (median age 65 years,
patients experienced decompensated cirrhosis events and two 55% males, 85% Child A and 15% Child B), 34 (2.2%) experienced de-
patients died. MELD changes at 12 weeks after the EOT were not novo PVT (median follow-up 36 months after EOT; IQR 24–44.7). Of
associated with the incidence of decompensated cirrhosis events and them, 18 reported HCC development previous or after achieving the
overall survival. In patients with CP class B or C, the cumulative SVR; in 6 of whom (17.6%) PVT was of neoplastic nature. The PVT
incidence rate of decompensated cirrhosis event at 2 years with occurrence in patients who achieved the SVR, not related to HCC
MELD improved, MELD stable, MELD deterioration were 7%, 22% and development, was 1.8% (28 patients); the median time to de-novo PVT
58%, respectively. Overall survival rates of patients at 2 years with occurrence was 33.8 months (IQR 17–45 months) after EOT. At
MELD improved, MELD stable and MELD deterioration were 100%, pretreatment evaluation, patients who experienced de-novo non-
97% and 69%, respectively. Patients with MELD deterioration had a neoplastic PVT were more likely Child B (39.3% vs. 14.2%, p < 0.001)
higher incidence of decompensated cirrhosis events and poorer and by Cox regression analysis, pre-treatment variables independ-
overall survival than the other two groups. ently associated with de- novo PVT development were: platelet count
Conclusion: In patients with decompensated cirrhosis who were ≤120.000/μL (HR: 3.56, CI 95%: 1.03–12.33), albumin level <3.5 g/dL
treated with DAA, MELD score deterioration at 12 weeks after the EOT (HR: 2.66, CI 95%: 1.15–6.15) and bilirubin level >1.1 mg/dL (HR: 2.70,
indicated an unfavorable outcome. CI 95%:1.10–6.65). Patients with de-novo, non-neoplastic PVT had
higher risks of hepatic decompensation (39.3% vs. 4.9%; p < 0.001)
FRI347 and liver-related death (13% vs. 2%, p < 0.001) regardless the SVR
De-novo occurrence of portal vein thrombosis in patients with achievement following the DAA treatment.
HCV-related cirrhosis after sustained virological response: Conclusion: The risk of de-novo non-neoplastic PVT in patients with
medium to long term observations from the ongoing PITER cirrhosis who achieved the SVR is low and mainly related to the
cohort severity of liver disease. Development of de-novo, non-neoplastic PVT
Loreta Kondili1, Maria Giovanna Quaranta1, Luigina Ferrigno1, following the SVR may identify patients with higher risks of hepatic
Carmine Coppola2, Monica Monti3, Roberto Filomia4, decompensation and mortality despite viral eradication by DAA
Giuseppina Brancaccio5, Maurizia Brunetto6, Elisa Biliotti7, treatment.
Donatella Ieluzzi8, Andrea Iannone9, Salvatore Madonia10,
Xhimi Tata1, Luisa Cavalletto11, Valentina Cossiga12, FRI348
Simona Amodeo13, Vincenza Calvaruso14, Elena Rosselli Del Turco15, Suboptimal follow-up, high re-infection, and drug-related death,
Maria Grazia Rumi16, Maurizio Pompili17, Alessia Ciancio18, among HCV-treated people who inject drugs in Tayside, Scotland
Lucia Brescini19, Francesco Paolo Russo20. 1Istituto Superiore di Sanità, Christopher Byrne1,2, Lewis Beer2, Sarah Inglis2, Emma Robinson1,
Center for Global Health, Roma, Italy; 2Gragnano Hospital, Gragnano Andrew Radley3, Sharon Hutchinson4,5, David Goldberg4,5,
(NA), Italy; 3University of Florence, Interdepartmental Centre MASVE, Matthew Hickman6, John Dillon1,7. 1University of Dundee, Molecular
Firenze, Italy; 4University Hospital of Messina, Messina, Italy; and Clinical Medicine, Dundee, United Kingdom; 2University of Dundee,
5
University of Padua, Department of Molecular Medicine, Infectious Tayside Clinical Trials Unit, Dundee, United Kingdom; 3NHS Tayside,
Diseases, Padova, Italy; 6University of Pisa, Pisa, Italy; 7Umberto I Public Health, Dundee, United Kingdom; 4Glasgow Caledonian
Hospital-“Sapienza” University, Rome; 8University Hospital of Verona, University, School of Health and Life Sciences, Glasgow, United Kingdom;
Verona, Italy; 9University of Bari, Bari, Italy; 10Azienda Ospedaliera 5
Health Protection Scotland, Glasgow, United Kingdom; 6University of
“Ospedali Riuniti Villa Sofia-Cervello”, Palermo, Italy; 11University Bristol, Population Health Sciences, Bristol, United Kingdom; 7NHS
Hospital of Padua, Padua, Italy; 12University of Naples Federico II, Napoli, Tayside, Gastroenterology, Dundee, United Kingdom
Italy; 13University of Palermo, Gastroenterology and Hepatology Unit Email: [email protected]
(DiBiMIS), Palermo, Italy; 14University of Palermo, GI & Liver Unit,
Background and aims: In 2017, Tayside, in East Scotland, rapidly
Department of Health Promotion Sciences Maternal and Infantile Care,
scaled-up Hepatitis C Virus (HCV) treatment among People Who
Internal Medicine and Medical Specialties (PROMISE), Palermo, Italy;
15 Inject Drugs (PWID) using new care pathways. This study aimed to
Alma Mater Studiorum-Università di Bologna, Bologna, Italy; 16San
quantify HCV re-infection and routes of re-treatment; mortality; and
Giuseppe Hospital, Milano, Italy; 17Fondazione Policlinico Universitario
efficacy of re-infection follow up.
Agostino Gemelli IRCCS, Roma, Italy; 18Città della Salute e della Scienza
Method: Annual follow-up RNA testing is offered. Re-infection
of Turin, University Hospital, Turin, Italy; 19Marche Polytechnic
follow-up was measured by calculating the proportion of cases
University, Ancona, Italy; 20University of Padua, Gastroenterology Unit,
with follow-up tests received in line with local policy. We estimated
Department of Surgery, Oncology and Gastroenterology, Padova, Italy
re-infection incidence, overall and by pathway, per 100 person-years
Email: [email protected]
(PY), assuming a Poisson distribution. Mortality was similarly
Background and aims: Achievement of sustained virological calculated; time-at-risk was from primary HCV treatment to censor
response (SVR) by direct-acting antiviral therapy (DAAs) ameliorates date or death.
portal hypertension, improves hepatic function, and may reverse Results: There were 713 treatments and 577 SVRs. 236 cases among
hyper-coagulability driven by cirrhosis. However, an unexpected 231 people were followed-up for re-infection. Of cured cases, 39% had
finding of de-novo portal vein thrombosis (PVT) immediately after ≥1 follow-up test. 87 (15%) cases had repeat testing in the first 12
DAAs has been reported. Here, we analyzed the long-term impact of months, in line with policy. Within 2 years, 110 (19%) had a follow-up
SVR on the development of PVT in patients with cirrhosis. test. Of those, 20 (18%) were continued follow-up. Within 3 or 4 years,
Method: Consecutive patients with liver cirrhosis, enrolled in the 19 were tested.
multicenter Italian PITER cohort and treated with DAAs were Re-infection occurred 39 times over 256.57 PY, yielding a rate of 15.20
prospectively evaluated. Patients with history of PVT prior to start per 100 PY (95% CI 10.81–20.78). For recent injectors, there were 26
of DAAs, and those with no follow-up data after end of treatment re-infections over 175.43 PY, yielding a rate of 14.82 per 100 PY
(EOT) were excluded. Stepwise Cox regression analysis was used to (95% CI 9.68–21.72). Re-infection incidence was highest among
evaluate factors independently associated with de-novo PVT. Kaplan needle exchanges (table 1), as was subsequent re-treatment.
Meier analysis and log rank test evaluated the PVT rates by DAA
treatment response.
Results: Of 1632 patients evaluated, 40 (2.5%) developed de-novo PVT
after DAA treatment. The two year PVT free survival was 99% for

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 POSTER PRESENTATIONS
Table 1: Clinical pathways of re-infected PWID, Tayside 2017–20.
Incidence per 100
Clinical pathway n (%) PY PY*
Pathway prior to re-
infection (n = 39)
Community pharmacy 12 (30.8) 92.25 13.01 (6.72–22.73)
Needle exchange 19 (48.7) 64.08 29.65 (17.85–46.30)
Other‡ 8 (20.5) 77.31 10.35 (4.47–20.39)
Pathway post re-infection
(n = 25)
Drug treatment centre 4 (16.0)
Needle exchange 15 (60.0)
Nurse-led community 4 (16.0)
clinic
Prison 2 (8.0)

Abbreviations: HCV, hepatitis c virus; PWID, people who inject drugs; PY,
person-years.
*95% CI in brackets.
Fifty-four patients died over 1, 553.04 PY, all-cause mortality was 3.48
per 100 PY (95% CI 2.61–4.54); 29 were drug related, drug-related
mortality was 1.87 per 100 PY (95% CI 1.25–2.68). Conclusion: A high rate of HCV reinfection was observed within a
four-prison network. Post-treatment surveillance and retreatment
Conclusion: Re-infection and drug-related mortality were high in are essential to limit the impact of reinfection. Enhanced access to
this cohort of HCV-treated PWID, and follow-up was suboptimal. harm reduction services, including needle and syringe programs,
Harm reduction services in Tayside need strengthening alongside should be considered within prisons.
comprehensive follow-up RNA testing.
FRI350
FRI349 Five-years follow-up of cured HCV patients with or without
Hepatitis C virus reinfection following direct acting antiviral cirrhosis under real-world interferon-free therapy
treatment in the prison setting: the SToP-C study Robert Flisiak1, Dorota Zarę bska-Michaluk2, Ewa Janczewska3,
Joanne Carson1, Gregory Dore1, Andrew Lloyd1, Jason Grebely1, Magdalena Rogalska1, Ewa Karpiń ska4, Tomasz Mikuła5,
Marianne Byrne1, Evan B Cunningham1, Janaki Amin2, Beata Bolewska6, Jolanta Białkowska7,
Peter Vickerman3, Natasha Martin4, Carla Treloar5, Gail Matthews1, Katarzyna Flejscher-Stępniewska8, Krzysztof Tomasiewicz9,
Behzad Hajarizadeh1. 1The Kirby Institute, UNSW Sydney, Sydney, Kornelia Karwowska10, Monika Pazgan-Simon11, Piekarska Anna12,
Australia; 2Macquarie University, Sydney, Australia, Faculty of Medicine Hanna Berak13, Tronina Olga14, Aleksander Garlicki15,
and Health Sciences, Sydney, Australia; 3University of Bristol, Population Jerzy Jaroszewicz16. 1Medical University of Białystok, Department of
Health Sciences, Bristol, United Kingdom; 4University of California San Infectious Diseases and Hepatology, Poland; 2Jan Kochanowski
Diego, Division of Infectious Diseases & Global Public Health, San Diego, University, Department of Infectious Diseases; 3Medical University of
United States; 5Centre for Social Research in Health, UNSW Sydney, Silesia, Bytom, Department of Basic Medical Sciences, Faculty of Health
Sydney, Australia Sciences in Bytom; 4Pomeranian Medical University, Department of
Email: [email protected] Infectious Diseases, Hepatology and Liver Transplantation, Szczecin;
5
Background and aims: Ongoing injecting drug use risk behaviours Medical University of Warsaw, Department of Infectious and Tropical
following successful treatment for hepatitis C virus (HCV) may lead to Disease and Hepatology, Warsaw; 6Poznan University of Medical
reinfection, reversing benefits of cure, particularly if harm reduction Sciences, Poznan, Department of Infectious Diseases; 7Medical
measures are not optimal. This study assessed HCV reinfection risk University of Lodz, Department of Infectious and Liver Diseases;
8
following direct-acting antiviral therapy in Australian prisons, where Wroclaw Medical University, Department of Infectious Diseases, Liver
opioid agonist therapy is available, but not needle-syringe programs. Diseases and Immune Deficiencies; 9Medical University of Lublin,
Method: The Surveillance and Treatment of Prisoners with hepatitis Department of Infectious Diseases and Hepatology; 10Collegium
C (SToP-C) study enrolled people incarcerated in four prisons in Medicum, Nicolaus Copernicus University, Department of Infectious
Australia between 2014 and 2019. Participants successfully treated Diseases and Hepatology, Bydgoszcz; 11Wroclaw Medical University,
for HCV were followed every 3–6 months to assess for reinfection Department of Infectious Diseases and Hepatology; 12Medical University
(identified by HCV sequencing). The incidence of HCV reinfection and of Lodz, Department of Infectious Diseases and Hepatology; 13Hospital of
associated factors were evaluated. Infectious Diseases in Warsaw, Daily Unit; 14Medical University of
Results: Among 388 participants receiving treatment, 161 had Warsaw, Department of Transplantation Medicine, Nephrology and
available post-treatment follow up (92% male; median age 33 Internal Medicine; 15Jagiellonian University Medical College,
years; 67% injecting drug use in prison; median follow-up 9 Department of Infectious and Tropical Diseases; 16Medical University of
months). During 145 person-years ( py) of follow up, 18 cases of Silesia, Department of Infectious Diseases and Hepatology, Katowice
reinfection were identified. Reinfection incidence was 12.5 per 100 py Email: [email protected]
(95%CI: 7.9–19.8) overall and 11.6 per 100 py (95%CI 6.6–20.4) among Background and aims: Treatment of hepatitis C virus (HCV)
those continuously incarcerated. Incidence was highest among those infections with direct-acting antivirals (DAA) has demonstrated
injecting in the past month and sharing needles/syringes (28.7 per high efficacy even in patients with liver cirrhosis. The three-year
100 py; 95%CI 16.3–50.6). In adjusted analysis, injecting drug use stability of a sustained virological response (SVR) and an improve-
with sharing needles/syringes was associated with increased ment in liver function with a persistent risk of hepatocellular
reinfection risk (adjusted hazard ratio 14.62; 95%CI 1.84–116.28; carcinoma (HCC) has so far been confirmed in the literature. The
p = 0.011). purpose of the current study is to evaluate the virologic response,
changes in liver function, stiffness and risk of HCC five years following
the treatment.

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POSTER PRESENTATIONS
Method: A total of 192 patients originally infected with HCV advancement and schistosomiasis. Treatment and SVR achievement
genotype 1 or 4 were analyzed five years after treatment with did not ameliorate this response.
ombitasvir/paritaprevir/ritonavir with or without dasabuvir and
with or without ribavirin. Most of the patients were diagnosed FRI352
with cirrhosis before treatment (57%) and did not respond to Reverse Inflamaging: biological age is accelerated in chronic HCV
previous treatment attempts (69%). patients and decelerates after HCV cure
Results: We confirmed that HCV clearance after DAA treatment is Carlos Oltmanns1,2, Zhaoli Liu1, Jasmin Mischke1,2, Jan Tauwaldt1,2,
stable regardless of baseline advancement of the disease. We found Yonatan Mekonnen1, Heiner Wedemeyer2, Anke Kraft1,2,3,
that SVR is associated with a gradual but significant reduction in liver Cheng-Jian Xu1,2,4, Markus Cornberg1,2,3,4. 1TWINCORE a joint venture
stiffness over 5 years. Liver function improved during the first 2 years of Helmholtz Centre for Infection Research and Hannover Medical School
of follow-up and remained stable thereafter. The risk of death due to Hannover Germany, Hannover, Germany; 2Hannover Medical School,
HCC or any reason persists through 5 years after successful DAA Department of Gastroenterology, Hepatology and Endocrinology,
treatment. However, in non-cirrhotic patients, it appears to clear up 3 Hannover, Germany; 3German Center for Infection Research, Partner-Site
years after treatment. Hannover-Braunschweig, Hannover, Germany; 4Centre for
Conclusion: Despite the successful treatment of HCV infection 5 Individualised Infection Medicine (CiiM), Hannover, Germany
years after its completion, patients with cirrhosis are still at risk of Email: [email protected]
developing liver cancer. This justifies screening for HCV, allowing
Background and aims: Recently, HIV and HBV infections have been
therapy before the development of liver cirrhosis.
shown to cause significant biological age acceleration. Accelerated
FRI351 epigenetic or biological age may be a predictor of all-cause and cancer
Clearance of hepatitis C virus infection did not ameliorate the mortality. Thus, we analyzed if HCV is associated with biological age
response to hepatitis B vaccine acceleration and if this is reversible after HCV cure.
Method: We included well-characterized 54 patients (mean age 56
Ebada Said1, Tamer Al Eraki2, Dalia Abdelhasseb2, Shaimaa Ragab2,
years) with chronic hepatitis C at three time points (baseline, end of
Mona El Awady2. 1Benha University, Egypt; 2
treatment and follow-up 24–240 (mean 96 weeks) weeks after the
Email: [email protected]
end of treatment). Genome-wide DNA methylation data were
Background and aims: In Egypt, citizens older than 30 years did not generated using the illuminaEpic array on PBMC and were used to
get the compulsory vaccination against hepatitis B virus (HBV) calculate the epigenetic age acceleration (Horvath clock).
infection during infancy. Patients with chronic hepatitis C (CHC) are Results: Our results show that chronic HCV infection leads to a
advised to get vaccinated against HBV. The aim was to assess the significant acceleration of epigenetic age ( p = 3.577e-05). While
response to HBV vaccine in CHC patients treated with direct acting chronic HCV patients without evidence of cirrhosis have a lower
antivirals (DDAs) in comparison to treatment-naive patients and age acceleration, patients with cirrhosis have a higher biological age.
healthy subjects and to identify predictors of weak response. Treatment of HCV patients with DAA results in reversal of age
Method: This prospective study was carried out on 360 adult subjects acceleration, but this effect is only detectable at long-term follow-up
subdivided into 3 groups. Group I (GI) included 150 consecutive CHC ( p = 0.02). Epigenetic age acceleration does not correlate with
patients who initiated vaccination after getting sustained virologic estimated blood cell counts.
response (SVR) following treatment with DAAs. Group II comprised Interestingly, patients who developed HCC after SVR (n = 8) have the
110 consecutive CHC treatment- naive patients while the control highest age acceleration and show no evidence of complete reversion
group (GIII) comprised 100 healthy subjects. The mean age of the 3 after treatment.
groups was 50, 45 and 39 year, respectively. Demographic and
laboratory variables including HCV-viral load, FIB-4 score,
Schistosomal antibody (Ab) titre, and Fibroscan® values were
assessed. All the studied groups had received 3 intradeltoid, 20 μg,
doses of HBV-vaccine (Euvax B, LG Life Sciences, Korea) given at 0, 1 &
6 months. Hepatitis B surface antibody (HBsAb) titres were tested 6–8
weeks after the 3rd dose.
Results: Patients of groups I & II showed a mean FIB4 score of 1.4 & 1.8
while a mean fibroscan value of 8.2 & 9.8 KPa, respectively.
CHC patients either treated (GI) or treatment-naïve (GII) had highly
significant lower mean HBs Ab titre than controls ( p < 0.001). Twelve
patients (8%) in GI had negative response to the HBV-vaccine (HBsAb
titres of <10 mIU/ml) compared to 5 patients (4.5%) in GII and only
one subject (1%) in the control group. Those who got HBsAb titres of
>100 mIU/ml were 125/150 (83.3%), 89/110 (85.5%) and 98/100 (98%)
in group I, II and III respectively.
Regarding patients with SVR, univariate regression analysis showed
that HBsAb titre was negatively associated with higher age ( p <
0.001), FIB-4 score ( p < 0.001), fibrosis stage ( p = 0.001) and ALT
levels ( p = 0.03) while positively associated with platelet count ( p <
0.001). Higher fibroscan values (KPa) were the most significant
predictors of weak response to HBV vaccine. In treatment naïve CHC
patients, HBsAb titre was negatively associated with ALT ( p = 0.001),
AST ( p = 0.03), FIB-4 score ( p = 0.01) and schistosomal Ab titre ( p <
0.001) and positively associated with platelet count ( p = 0.001). Conclusion: Hepatitis C patients with cirrhosis show biological age
Vaccination response showed no association with gender, body mass acceleration that may be reversible after HCV cure. Lack of reversibility
index, viral load or other variables. appears to be associated with HCC risk. Our findings underline the
Conclusion: Patients with CHC demonstrate a significantly weak need for more individualized infectious disease medicine based on
response to HBV-vaccine, particularly those with older age, fibrosis biological rather than chronologic age in the future.

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 POSTER PRESENTATIONS
FRI353 FRI354
Overall mortality in patients with chronic hepatitis C: major Is routine Ribavirin mandatory for genotype 3 hepatitis C
effects of social vulnerability, tobacco smoking, and history of compensated cirrhosis patients receiving Sofosbuvir/Velpatasvir?
unhealthy alcohol use (ANRS CO22 HEPATHER cohort) A meta-analysis
Lauren Perieres1, Fabrice Carrat2, Marta Lotto1, Celine Dorival3, Jing Hong Loo1, Flora Xu1, Gerald Low1, Wei Xuan Tay1, Le Shaun Ang1,
Clémence Ramier1, Fabienne Marcellin1, Carole Cagnot4, Steve Yew-chong Tam2, Prem Harichander Thurairajah3,
Elizabeth Delarocque-Astagneau5, Patrizia Carrieri1, Stanislas Pol6, Rahul Kumar4, Yu Jun Wong5. 1Yong Loo Lin School of Medicine,
Helene Fontaine6, Camelia Protopopescu1. 1Aix Marseille Univ, National University of Singapore; 2Education Resource Centre, Medical
INSERM, IRD, SESSTIM, Sciences Économiques & Sociales de la Santé & Board, Singapore General Hospital; 3National University Hospital,
Traitement de l’Information Médicale, ISSPAM, Marseille, France; Division of Gastroenterology & Hepatology, Singapore, Singapore;
2 4
Institut National de la Santé et de la Recherche Médicale (INSERM), Changi General Hospital, Department of Gastroenterology &
Institut Pierre Louis d’Epidémiologie et de Santé Publique, Sorbonne Hepatology; 5Department of Gastroenterology & Hepatology, Changi
Université, Hôpital Saint-Antoine, Unité de Santé Publique, Assistance General Hospital, Singapore
Publique-Hôpitaux de Paris (AP-HP), Paris, France; 3Institut National de Email: [email protected]
la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis
Background and aims: Simplified treatment regimen is crucial for
d’Epidémiologie et de Santé Publique, Sorbonne Université, Paris, France;
4 rapid treatment upscale to achieve hepatitis C virus (HCV) elimin-
ANRS|Emerging Infectious Diseases, Paris, France; 5Université Paris-
ation. Addition of ribavirin (RBV) to Sofosbuvir/Velpatasvir (SOF/VEL)
Saclay, UVSQ, Inserm, CESP, Team Anti-infective Evasion and
has been showed improved sustained virological response at 12
Pharmacoepidemiology, Montigny, France; 6Université de Paris, AP-HP,
weeks (SVR12) in genotype 3 (GT3) decompensated cirrhosis
Hôpital Cochin, Département d’Hépatologie/Addictologie, Paris, France
patients. However, the benefits of RBV in GT3 compensated cirrhosis
Email: [email protected]
patients receiving SOF/VEL, remains unclear. We aim to systematic-
Background and aims: The advent of direct acting antivirals has ally review the efficacy and safety of SOF/VEL, with or without RBV in
paved the way for a hepatitis C-free world. However, patients with GT3 compensated cirrhosis patients.
hepatitis C virus (HCV) infection remain at high risk of morbidity and Method: With help of medical librarian, we systemically searched
mortality, even after cure. We identify socio-behavioural factors four electronic databases (PubMed/MEDLINE, EMBASE, Cochrane
associated with overall (i.e., all-cause) mortality in chronic HCV- Library and Web of Science) from inception up to June 2021 using
infected patients. both free text and MeSH terms. There was no restriction on language,
Method: We used data collected from August 2012 to June 2018 in the geography, publication dates and publication status. All GT3
French, multicentre, prospective cohort ANRS CO22 HEPATHER. The compensated cirrhosis patients treated with 12 weeks of SOF/VEL,
study sample comprised chronic HCV-infected patients who with or without RBV, were included, regardless of age, gender or prior
attended at least one annual follow-up visit. Analyses focused on treatment experience. The primary outcome was the SVR12. The
the first five years of follow-up. Socio-behavioural data were collected secondary outcome was treatment-related adverse events, as defined
at cohort enrolment (questionnaire administered by a physician). by symptomatic anaemia requiring transfusion or a drop in
Living in poverty was defined as a standard of living below 1015€ haemoglobin beyond 2 g/dL. The pooled relative risk (RR), 95%
(French poverty threshold in 2015), low educational level as level confidence interval (CI) and heterogeneity (I2) were estimated using
<high school diploma, unhealthy alcohol use as drinking >2 and >3 Review Manager Version 5.3.
alcohol units/day for women and men, respectively, and elevated Results: From 1, 752 citations, a total of 7 studies (2 RCTs, 5 cohort
coffee intake as drinking ≥3 cups of coffee/day. Factors associated studies) with 1, 088 subjects were identified. The SVR12 was similar
with overall mortality were identified using a Cox proportional in GT3 compensated cirrhosis patients, regardless of the use of RBV,
hazards model. Adjusted population attributable fractions (PAF) were for both the intention-to-treat (RR: 1.03, 95%CI: 0.99–1.07; I2 = 0%)
estimated for the modifiable factors of the multivariable analysis. and the per-protocol analysis (RR: 1.03, 95%CI: 0.99–1.07; I2 = 48%).
Results: Of the 10, 366 patients in the study sample, 697 died The overall pooled rate of treatment-related adverse events was 7.2%.
during follow-up. After multivariable adjustment (for sex, age, Addition of RBV was associated with 4-fold higher risk of treatment-
educational level, HCV genotype, HCV transmission category, and related adverse events in GT3 compensated cirrhosis patients
HCV cure), living in poverty (adjusted hazard ratio [aHR]: 1.34 [95% receiving SOF/VEL (RR: 4.20, 95%CI: 1.29–13.68; I2 = 0%). Subgroup
confidence interval, 1.13–1.60]), tobacco smoking (1.70 [1.35–2.14]), analysis showed that RBV was associated with a numerically higher
and a history of unhealthy alcohol use (1.48 [1.18–1.86]) were SVR12 (96% vs 87%, p = 0.12) in GT3 compensated cirrhosis patients
independently associated with increased overall mortality. By with baseline resistance-associated substitutions (RAS). However,
contrast, elevated coffee intake was associated with lower overall addition of RBV did not significantly increase the SVR12 among
mortality (0.63 [0.52–0.77]). The risk factors accounting for the treatment-experienced GT3 compensated cirrhosis patients.
greatest mortality burden were tobacco smoking, low educational Conclusion: Ribavirin did not significantly increase the SVR12 in GT3
level, living in poverty, and a history of unhealthy alcohol use (PAF: compensated cirrhosis patients receiving SOF/VEL. Our findings
16.6%, 14.9%, 9.8%, and 7.4%, respectively), whilst HCV cure and suggest limited role for RBV as routine add-on therapy to SOF/VEL
elevated coffee intake averted a high proportion of deaths (86.0% and in GT3 compensated cirrhosis patients.
13.4%, respectively).
Conclusion: In the era of HCV cure, tobacco cessation must be further FRI355
encouraged in patients with chronic HCV infection, as a modifiable High frequency of hepatitis C virus reinfection following antiviral
risk factor of mortality. Specific interventions should be developed to treatment in the North East of England
target socially vulnerable patients and those with a history of Sumar Askar1, Ryan Jelley1, Kate Mcque1, Caroline Allsop1,
unhealthy alcohol use, who are at higher risk of mortality. Francesca McCullough1, Carolyn Miller1, Yusri Taha1,
Steven Masson1,2, Stuart Mcpherson1,2. 1Newcastle Freeman Hospital,
Liver Unit, High Heaton, United Kingdom; 2Translational and Clinical
Research Institute, Newcastle University, Newcastle Upon Tyne, United
Kingdom
Email: [email protected]
Background and aims: Hepatitis C virus infection (HCV) is common,
and injecting drug use (IDU) is the major risk factor for acquisition in

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POSTER PRESENTATIONS
Europe. Health services are working towards achieving the WHO FRI356
target of HCV elimination by 2030. Reinfection following treatment is Incidence and risk factors of hepatitis C liver morbidity and
an important consideration for HCV elimination programmes mortality in the era of direct-acting antiviral therapies: a
because this has the potential to hamper elimination efforts. The population-based linkage study
aim of this work was to assess the rate of HCV reinfection in our Maryam Alavi1, Heather Valerio2, Matthew Law1, Ian Lockart3,4,
region, where IDU is the predominant risk factor (>90%). Mark Danta3,4, Jason Grebely1, Janaki Amin5, Behzad Hajarizadeh1,
Method: All patients who completed treatment with direct acting Jacob George6, Gregory Dore1. 1Kirby Institute, UNSW Sydney,
antiviral (DAA) treatment for HCV in Tyne and Wear, North East Australia; 2Kirby Institute, UNSW Sydney; 3St Vincent’s Clinical School,
England between Jan 2016 and May 2021 were included. Sustained UNSW Sydney, Australia; 4St Vincent’s Hospital, Sydney, NSW, Australia;
virological response (SVR12) was defined as negative HCV RNA 12 5
Department of Health Systems and Populations, Macquarie University,
weeks post treatment. Data was collected from our HCV database Australia; 6Storr Liver Centre, Westmead Millennium Institute, University
(HepCare), which automatically gathers laboratory data in real time of Sydney, Australia
from our hospital laboratory database. HCV reinfection was defined Email: [email protected]
as a positive HCV RNA after achieving SVR12 or where a genotype has
changed after completing DAA treatment when the SVR12 was not Background and aims: Monitoring trends in hepatitis C virus (HCV)
documented. liver morbidity and mortality is increasingly crucial as direct-acting
Results: 788 of the 840 patients (76% males; mean age 45.7 ± 11.4 antiviral (DAA) therapy expands and we move towards World Health
years; 47% G1; 39% G3; 12% Cirrhosis) completing treatment achieved Organization HCV elimination targets. In New South Wales, Australia,
SVR (94%). 459 patients (58%) had a follow-up HCV RNA tested post we aimed to evaluate trends in decompensated cirrhosis (DC),
SVR after a median 0.79 years (range 0.1–5.2 years). 56 reinfections hepatocellular carcinoma (HCC), and liver mortality in the pre-DAA
(7.1% of all SVRs and 12.2% of those SVRs who had follow up blood (2001–2014) and DAA eras (2015–2020). Further, we assessed factors
testing) were diagnosed. The median time to reinfection was 1.37 associated with each liver-related outcome in the DAA era.
years (range 0.1–5.2 years) and the rate of reinfection was 0.1 per Method: HCV notifications (1995-mid 2020) were linked to hospital
person years. 45 of the 56 (80%) reinfections developed chronic admissions (2001–2020) and mortality (1995–2020). DC, HCC, and
infection, 17 of which were retreated and achieved SVR, while 28 liver death numbers and age-standardised incidence rates [ per 100
remain viraemic. 5 patients developed a second reinfection. person-years (PY)] and corresponding 95% CIs were calculated
Individuals with reinfection were significantly younger than those assuming a Poisson distribution. We used Cox Proportional Hazards
maintaining SVR (38.9 ± 7.9 vs 46.2 ± 11.9 years, p < 0.001). Regression analyses to evaluate factors associated with each liver-
Reinfection was more common in those with primary G3 infection related outcome.
compared with other genotypes (9.8% vs 5.7% p = 0.049). Reinfections Results: Among 110, 022 people with an HCV notification, 5.2% and
were similar between males and females (4.4% females vs 7.4% males 2.1% had a DC and HCC diagnosis, respectively, and 4.2% died of liver-
p = 0.15). related causes. In the pre-DAA era, DC and HCC diagnoses, and liver-
related mortality consistently increased, while age-standardised
incidence rates were stable or increased: 0.39, 0.15 and 0.13 in 2001
to 0.40, 0.18, and 0.37 per 100 PY in 2014, respectively. Each liver-
related outcome declined in the DAA era; in 2020, age-standardised
incidence rates of DC, HCC, and liver-related mortality were 0.20 (95%
CI 0.17, 0, 23), 0.12 (95% CI 0.10, 013), and 0.19 (95% CI 0.17, 0.22) per
100 PY, respectively (Figure 1). In the DAA era, a history of alcohol-use
disorder was common among people with DC (64%) and HCC (48%).
In the DAA era, following older age, a history of alcohol-use disorder
was the strongest predictor of DC [adjusted hazard ratio (aHR) 6.70,
95% CI 6.08, 7.39] and HCC diagnoses (aHR 3.53, 95% CI 3.13, 3.99), and
liver-related mortality (aHR 5.59, 95% CI 5.08, 6.16).

Conclusion: HCV reinfection is common in our cohort and may slow

our HCV elimination efforts. In order to address our high reinfection
rates we need to improve harm reduction and increase treatment of
active IDUs. We aim to implement ‘HCV track and trace’ for recent
infections and reinfections to try to reduce onward HCV transmission.

Figure: Trends in diagnoses and age-standardised rates of decompensated

cirrhosis, HCC, and liver-related mortality among people with an HCV
notification in New South Wales, 1995-mid 2020, n = 110, 022.

Conclusion: DAA scale-up in New South Wales, Australia, has

reduced the HCV liver disease burden, most remarkably on DC
diagnosis and liver-related mortality. However, alcohol-use disorder
remains a significant cause of liver disease, both on its own and as a
risk factor in the progression of chronic HCV. A broader focus on liver
disease prevention is required, encompassing alcohol-use disorder

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 POSTER PRESENTATIONS
treatment, to facilitate enhanced declines in advanced liver disease 0.001). In linear regression analysis, reduction in AFP was found to
complications in the DAA era. positively correlate with reduction in Fibroscan scores (coefficient =
0.04, p = 0.91). We defined improvement in AFP levels as a pre-
FRI357 treatment value of >10 which reduced to ≤10 after treatment. 47
Direct acting antiviral agents improve survival in patients with patients (61.0%) had a normal AFP at baseline, 24 patients (31.2%)
hepatitis C virus related hepatocellular carcinoma improved and 6 (7.8%) remained high. The cumulative HCC risk was
Hyun Young Woo1, Won Lim2, Jeong Heo1, Young Joo Park1. 1Pusan 50% for patient whose AFP remained high, 12.5% in those whose AFP
National University Hospital, Internal Medicine, Busan, Korea, Rep. of improved, and 10.6% those whose AFP remained normal (chi-squared
South; 2Good Samsun Hospital, Internal Medicine, Busan, Korea, Rep. of test p = 0.068).
South Conclusion: The risk of HCC after successful HCV treatment in
Email: [email protected] cirrhotic patients remains high. Overall, AFP levels improve with DAA
treatment in patients with cirrhosis. Fibroscan scores improve with
Background and aims: Survival data in patients with hepatitis C
DAA treatment. Failure to see an improvement in AFP after treatment
virus (HCV) associated hepatocellular carcinoma (HCC) treated with
predicts the development of HCC. This should be considered in
direct acting antivirals (DAAs) are limited. Survival rates were
stratifying individual patient HCC risk during real-world follow-up
compared between patients with HCV-related HCC who were
surveillance protocols.
untreated for HCV and who treated with DAA.
Method: From 2010 to 2019, a total of 469 patients who were FRI359
monoinfected with HCV-related HCC was categorized into patients Patients with chronic HCV and decompensated cirrhosis are at
untreated for HCV and patients treated with DAA. Multivariable Cox risk for MELD purgatory
regression with HCV treatment status as a time-varying covariate was
Lisette Krassenburg1,2, Grishma Hirode1,3,
used to determine mortality risk. Hooman Farhang Zangneh1, Raoel Maan2, Alnoor Ramji4,
Results: There were 95 untreated group and 94 DAA group. Of DAA
Michael P. Manns5, Heiner Wedemeyer5, Markus Cornberg5,
group, 42 was active HCC state ( patients without viable HCC). Robert De Knegt2, Kosh Agarwal6, Zillah Cargill6, Gonzalo Crespo7,
Baseline characteristics between untreated group and DAA with Giuseppina Brancaccio8, Maria Cristina Morelli9, Ilaria Lenci10,
active HCC were balanced except genotype. Sustained virologic
Chiara Mazzarelli11, Paolo Angeli12, Patrizia Burra13,
response rate was 88.2% by per protocol analysis in DAA treated
Gabriella Verucchi14, Maria Francesca Donato15, Paola Carrai16,
patients. After time-varying adjustment for DAA treatment initiation
Silvia Martini17, Paolo Caraceni18, Francesco Paolo Russo19,
compared with untreated patients, patients with DAA had signifi-
Robert De Man2, Harry Janssen1, Bettina Hansen1,
cantly higher 5-year overall survival (76.7% vs. 22.4%, p < 0.001).
Adriaan Van der Meer2, Jordan Feld1. 1Toronto Centre for Liver Disease,
Multivariate Cox regression showed that survival was significantly
Toronto General Hospital, University Health Network, Toronto, Canada;
improved in patients with DAA treatment ( p < 0.001), patients who 2
Department of Gastroenterology and Hepatology, Erasmus MC
were treated with curative treatment (0.034) and with history of
University Medical Center Rotterdam, Rotterdam, Netherlands; 3Toronto
interferon exposure ( p = 0.045).
Viral Hepatitis Care Network (VIRCAN), Toronto, Canada; 4Department
Conclusion: In this study, patients in HCV related HCV who treated
of Medicine, Division of Gastroenterology, University of British Columbia,
DAA achieved 88.2% of SVR and showed significant improvement of
Vancouver, Canada; 5Department of Gastroenterology, Hepatology and
survival compared with patients untreated with DAA.
Endocrinology, Hannover Medical School, Hannover, Germany; 6Institute
of Liver Studies, King’s College Hospital, London, United Kingdom; 7Liver
FRI358
Transplant Unit, Liver Unit, University of Barcelona, Barcelona, Spain;
Lack of Alpha-fetoprotein reduction after successful Hepatitis C 8
Department of Infectious Diseases, Second University of Naples, Naples,
treatment in patients with cirrhosis predicts the development of
Italy; 9Department of Organ Failures and Transplantation, Universita
hepatocellular carcinoma during surveillance-a single unit real-
degli Studi di Bologna Azienda Ospedaliera di Bologna Policlinico
world experience
Sant’Orsola-Malpighi, Bologna, Italy; 10Hepatology Unit, Department of
Aoife Alvain1, Jack Lee1, Eileen Shannon1, Mary Kavanagh1, Internal Medicine, Tor Vergata University, Rome, Italy; 11Hepatology and
Mary Bohan-Keane1, Margaret Scarry1, John Lee1,2. 1University Gastroenterology Unit, ASST Ospedale Niguarda, Milan, Italy; 12Unit of
Hospital Galway, Hepatology unit, Galway, Ireland; 2National University
Internal Medicine and Hepatology (UIMH), University of Padua, Padua,
of Ireland, Galway, Galway, Ireland Italy; 13Multivisceral Transplant Unit, Department of Surgery, Oncology
Email: [email protected] and Gastroenterology, University Hospital Padua, University of Padua,
Background and aims: The value and limitation of alpha-fetoprotein Padua, Italy; 14Infectious Diseases Unit, Department of Medical and
(AFP) in hepatocellular carcinoma (HCC) screening is well estab- Surgical Sciences, University of Bologna, Bologna, Italy; 15Fondazione
lished. In patients with chronic hepatitis C virus (HCV) infection and IRCCS Ca, Granda Ospedale maggiore Policlinico and CRC “A.M. &
cirrhosis, AFP is often elevated in the absence of HCC. The aim of this A. Migliavacca Center for Liver Disease,” Division of Gastroenterology
study was to measure the impact of DAA treatment on AFP levels and and Hepatology, Milan, Italy; 16Hepatobiliary Surgery and Liver
correlate this with clinical outcomes. Correlation with changes in Transplantation, University of Pisa Medical School Hospital, Pisa, Italy;
17
transient elastography (Fibroscan) scores were also evaluated. Gastrohepatology Unit, Azienda Ospedaliero Universitaria Citta della
Method: Patients with established cirrhosis prior to successful direct Salute e della Scienza di Torino, Turin, Italy; 18Department of Medical
acting anti-viral (DAA) treatment were included. Patients with HCC and Surgical Sciences, University of Bologna, Bologna, Italy;
19
were excluded. Laboratory values including AFP, transaminases, Department of Surgery, Oncology and Gastroenterology,
platelet count and Fibroscan scores were measured at baseline and Gastroenterology/Multivisceral Transplant Section, University/Hospital
post-treatment. Patients were followed-up for the development of Padua, Padua, Italy
HCC. Factors associated with improvement in AFP were investigated. Email: [email protected]
Further analysis was carried out classifying patients based on a Background and aims: Treatment decisions are challenging in
clinically relevant threshold. patients with decompensated cirrhosis due to chronic hepatitis C
Results: 77 patients (male n = 47, 61.0%) and median follow-up of 5.7 (HCV). Some patients might benefit from delaying HCV treatment
years. 11 (14.3%) have developed HCC during follow-up. Overall, the until after liver transplantation, as a decrease in MELD-score without
mean AFP significantly improved with treatment (Mean 17.69 ± SD
clinical benefit may limit transplant eligibility, also known as MELD
31.44 vs 7.27 ± 16.80, p = 0.0015). The mean Fibroscan score signifi- purgatory. This study aims to predict the probability of a poor
cantly improved with treatment (22.96 ± 14.07 vs 13.73 ± 9.05, p <

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POSTER PRESENTATIONS
outcome among patients who were eligible for a liver transplant at Hospital Galway, Hepatology Unit, Galway, Ireland; 2National University
treatment initiation. of Ireland, Galway, Galway, Ireland
Method: Retrospective cohort study including HCV patients with a Email: [email protected]
history of/current decompensated cirrhosis treated with DAAs in
Background and aims: Direct-acting antiviral (DAA) treatments are
Europe and Canada. MELD purgatory was defined as presence of
established to be well tolerated and achieve Hepatitis C virus (HCV)
ascites or hepatic encephalopathy with sustained MELD-Na<15 after
eradication in the quasi-totality of patients. This prevents progression
treatment initiation. The cumulative probability and factors asso-
to liver cirrhosis, reduces the risk of hepatocellular carcinoma, and
ciated with a poor outcome (sustained MELD purgatory, HCC or
improves overall prognosis. The aim of this study was to investigate
death) after treatment initiation were analyzed using Kaplan-Meier
the long-term effects of HCV eradication by DAA on patient’s mood
plots and multivariable (MV) Cox regression. The risk of death/HCC vs
and quality of life.
transplantation post-treatment was compared in those who were
Method: HCV patients completed a baseline Beck’s Depression
transplant ineligible at baseline.
Inventory and Quality of Life Questionnaire (EQ5D) prior to DAA
Results: Among 877 patients: mean age 55 ± 9 years, 68% male, 86%
treatment and were prospectively evaluated. After anti-viral therapy,
Caucasian, median BMI 27 [24–30] kg/m2, 24% diabetes and 44%
the questionnaires were repeated with a minimum of 12 months
history of alcohol abuse. At baseline, median INR was 1.3 (1.2–1.5),
follow-up. A Beck’s score of <10 is considered to be within the normal
ALT was 54 (37–84) U/L, platelets were 77 (55–105) × 109/L, total
range of mood variation. An EQ5D of 5 represents optimal quality of
bilirubin was 1.9 (1.2–2.8) mg/dL and mean albumin was 32 ± 5.8 g/L.
life.
Mean MELD-Na was 15 ± 5.5. The majority had MELD-Na ≥15 (62%),
Results: A total of 54 patients with a mean age of 49.5 years were
and 51% were decompensated at baseline. A total of 665 (80%)
included (51.8% male). All patients had a sustained virological
achieved SVR12. During a median follow-up of 35 (8–90) weeks after
response to DAA treatment; the median follow-up was 4.1 years.
treatment initiation, 194 (22%) entered sustained MELD purgatory,
Prior to treatment, 9 (16.7%) had established cirrhosis, and 14 (25.9%)
114 (13.0%) developed HCC, and 106 died (12.1%). Cumulative
had at least one psychiatric co-morbidity. The mean Beck’s score pre-
probabilities of a poor outcome at 36, 72, and 108 weeks were 15%,
treatment (Mean 7.88 ± SD 7.88) and at long-term follow-up (7.31 ±
24%, and 32%, respectively (Figure). On MV Cox regression, older age
6.22) was not significantly different ( p = 0.29). Median Beck’s score
(aHR 1.02, p = 0.037), lower sodium (aHR 0.95, p = 0.014), and lower
pre-treatment (7) and at follow-up (6) were comparable, as were the
albumin (aHR 0.97, p = 0.032) at baseline were associated with higher
number of patients with a Beck’s score <10 pre-treatment (n = 37,
rates of a poor outcome. Of those who met the definition of MELD-
68.5%) and at follow-up (n = 37, 68.5%). In the sub-group analysis, no
purgatory before treatment initiation (n = 195), cumulative probabil-
significant difference was found with sub-groups defined by patient’s
ities of death/HCC were 5.1%, 8.1% and 9.0% at 36, 72, 108 weeks post-
background psychiatric history, pre-treatment cirrhosis status or HCV
treatment start, whereas rates of liver transplant were 4.2%, 9.0% and
mode of transmission ( pre-treatment and follow-up median scores
12.3% at the same time points.
were comparable and so were the number of patients with a Beck’s
score <10). There was no significant difference in the EQ5D pre-
treatment (6.88 ± 2.30) and at follow-up (6.74 ± 2.45) ( p = 0.39).
Median score pre-treatment (6) and at follow-up were comparable
(6), as were the number of patients with EQ5D = 5 pre-treatment (n =
16) and at follow-up (n = 18).
Conclusion: In this prospective study of patients successfully treated
for HCV with DAA treatment, the reported mood and quality of life at
long-term follow-up did not significantly change from their pre-
treatment baseline. It is expected that quality of life and mood would
deteriorate in un-treated patients as they develop complications of
chronic HCV and as such this study demonstrate the benefit of DAA
treatment on mood and quality of life.

FRI361
Assessing sustained virological response and reinfection from
dried blood spots within an on-site hepatitis C diagnosis and
treatment model of care in a harm reduction centre
Anna Not1, Verónica Saludes1,2, Anna Miralpeix3,4, Mont Gálvez3,4,
Conclusion: Patients with chronic HCV and decompensated cirrhosis Antoni E. Bordoy1, Sara González-Gómez1, Noemí González5,
are at risk for MELD purgatory, HCC or death, even when SVR is Juliana Reyes-Ureña6, Xavier Major7, Joan Colom7, Xavier Forns3,4,8,
achieved. Caution should be taken when treating these patients, Sabela Lens3,4,8, Elisa Martró1,2. 1Hospital Universitari Germans Trias i
especially transplant-eligible patients who may be better off with Pujol, Institut d’Investigació Germans Trias i Pujol (IGTP), Microbiology
liver transplantation prior to HCV treatment. Decompensated Department, Badalona, Spain; 2Consorcio de Investigación Biomédica en
patients who are not transplant-eligible at treatment start have a Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain;
similar probability of HCC/death as of receiving a transplant post- 3
Hospital Clínic, Liver Unit, Barcelona, Spain; 4IDIBAPS, Barcelona,
treatment, making treatment decisions particularly challenging and Spain; 5REDAN La Mina. Parc de Salut Mar. Sant Adrià del Besòs
highlighting the need for careful post-treatment follow-up. (Barcelona), Spain; 6Center for Epidemiological Studies on HIV/AIDS and
STIs of Catalonia (CEEISCAT), ASPCAT, Barcelona, Spain; 7Program for the
FRI360
Prevention, Control and Care of HIV, Sexually Transmitted Infections and
The long-term effect of Hepatitis C eradication by direct-acting
Viral Hepatitis, ASPCAT, Barcelona, Spain; 8Consorcio de Investigación
antivirals on patient’s mood and quality of life as determined by
Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD),
the Beck’s Depression Inventory and EQ5D Quality of Life
Madrid, Spain
questionnaires-a single unit study
Email: [email protected]
Aoife Alvain1, Sarah Lanigan1, Mary Bohan-Keane1, Margaret Scarry1,
Lynda Jordan1, Cynthia Garvey1, Priyanka Jose1, John Lee1,2. 1University Background and aims: Dried blood spot (DBS) samples are a reliable
tool to diagnose viremic HCV infection. However, there is scarce data
on the usefulness of DBS to assess cure and reinfection after antiviral

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 POSTER PRESENTATIONS
therapy. Here, we aimed to evaluate the use of DBS for the assessment study, we evaluated the immune correlates that are associated with
of sustained virological response (SVR) and reinfection 12 weeks after re-infection of HCV in PWID after achieving sustained virologic
on-site treatment with direct-acting antivirals at a harm reduction response (SVR).
service (HRS) in Catalonia. Method: ANCHOR is a study of 198 people with opioid use disorder,
Method: This evaluation was performed within the context of an ongoing opioid misuse and chronic HCV. All participants received
ongoing micro-elimination study targeting people who inject drugs DAAs, 157 achieved SVR, and 17 were reinfected. We studied 27
(PWID) in the largest HRS in Barcelona. At the time of SVR assessment patients who achieved SVR without reinfection (Non-RI) and 13
(FU12), HCV-RNA was detected from DBS with an in-house real-time patients who were reinfected (RI). Changes in the phenotypic profile
RT-PCR assay (lower limit of detection -LoD-, 541 IU/ml of blood) in of T cells were determined in the peripheral blood mononuclear cells
comparison with the reference method (viral load in fingerstick (PBMCs) by flow cytometry. HCV specific T cell functions were
capillary blood by GeneXpert®; LoD, 40 IU/ml). Additionally, DBS investigated by stimulating the PBMCs with a pool of 21 overlapping
samples (baseline vs. FU12) were used to assess reinfection vs. peptides from envelop, core and NS3-NS5 regions of HCV. Immune
treatment failure by an in-house method based on NS5B nested-PCR profiles were evaluated at baseline ( prior to HCV treatment) and after
amplification followed by Sanger sequencing and phylogenetic SVR ( prior to reinfection) and compared between the two groups.
analysis. When mixed or no signal was obtained, samples were Results: At baseline, RI group displayed higher expression
genotyped by a commercial real-time PCR genotyping assay (Abbott). of inhibitory receptors including programmed death-1 (PD-1) (CD4
Results: Among treated patients, 105 DBS samples corresponding to P = 0.002, CD8 P = 0.02) and 2B4 (CD4 P = ns, CD8 P = 0.01), and lower
FU12 were tested (55 negative and 50 positive). The DBS-based HCV- expression of activation markers CD38 (CD4 P = 0.02, CD8 P = ns) and
RNA assay showed 100% specificity (55/55). Nine cases were not HLA-DR (CD4 & CD8 T cells P = 0.02) on T cells than Non-RI group and
detected, with viral loads between 116 and 4660 IU/ml; sensitivity continuously maintained exhaustive phenotype even after achieving
ranged from 82.0% to 95.0% according to different viral load cut-offs SVR, suggesting persistent exhaustion of T cells in RI. At baseline, RI
(Table 1). FU12 RNA positive samples (n = 50) were genotyped by group constituted lower frequencies of naïve (14% vs. 29%) and
sequencing (n = 32) or by the commercial genotyping assay (n = 15) in terminally differentiated effector memory cells (3% vs. 10%) in CD4 T
comparison with baseline DBS samples. Results evidenced the cell population that did not change upon SVR, while a marked
presence of reinfection in 29 cases and of treatment failure in seven reduction in effector memory cells were observed (48% vs. 31%) at
cases with high viral loads. The rest of cases could not be classified by SVR. Moreover, CD8 T cell population exhibited decreased percentage
any of the two methods: three with low viral loads could not be of naïve (17% vs. 35%) and central memory cells (3% vs. 8%) in RI group
amplified, one was indeterminate, and in seven cases the same and similar profile was maintained upon SVR. However, the
genotype/subtype was detected at FU12 and baseline samples, with expression of the transcription factors Tbet and Eomes (CD4: 2%
phylogenetic classification not assessable from the commercial and 5%, CD8: 7% and 20%) was similar between both groups. Further, T
genotyping assay. cells from RI group persistently produced lower amounts of antiviral
cytokines such as IFN-γ and TNF-α at baseline and after achieving SVR
compared to the Non-RI (CD4 IFN-γ & TNF-α P = 0.04, P = 0.01) (CD8
IFN-γ & TNF-α P = 0.01, P = ns). In fact, polyfunctional T cell response
determined by IFN-γ and TNF-α co-producing cells was also impaired
in the RI compared to the Non-RI group (CD4 P = 0.03 and CD8 P =
0.04). However, cytotoxic potential of T cells evaluated by CD107a and
perforin expression were maintained between both groups.
Conclusion: Peripheral T cells from PWID who were reinfected with
HCV after achieving SVR displayed an exhaustive phenotype and had
depressed anti-HCV response after SVR, suggesting a role for
protection from re-infection by T cells in a non-cytolytic fashion.
Conclusion: This study shows the usefulness of DBS samples for
FRI363
assessing cure and differentiating reinfection from relapse after HCV
Lack of fibrosis remodelling in chronic hepatitis C post SVR, as
antiviral treatment in the real world, facilitating treatment decen-
demostrated by YKL-40, is predictive of hepatocellular carcinoma
tralization in PWID attending HRS. However, some patients presented
ocurrence
with low viral loads at FU12, limiting detection and genotyping.
Maria Guerra Veloz1, James Lok1, Chiara Mazzarelli2, Mary D Cannon1,
While the latter cases might reflect acute infections that may be
Ivana Carey1, Kosh Agarwal1. 1King’s College Hospital, Institute of Liver
spontaneously cleared, repeat testing over time would be required to
Studies, United Kingdom; 2ASST Grande Ospedale Metropolitano
identify all viremic cases.
Niguarda-Milano
FRI362 Email: [email protected]
Hepatitis C virus (HCV)-specific T cell confer resistance to HCV Background and aims: The introduction of new direct-acting
re-infection after sustained virologic response in a non-cytolytic antivirals agents (DAA) have revolutionized the natural history of
fashion among people who inject drugs: results from ANCHOR the chronic hepatitis C virus (HCV). However, the course of
study progressive liver damage, as well as the risk of developing HCC
Arshi Khanam1, Alip Ghosh2, Sarah Kattakuzhy1, after achieving sustained virological response (SVR), is still uncertain.
Shyamasundaran Kottilil1, Elana Rosenthal1. 1Institute of Human Our group´s preliminary data1 showed that YKL-40 (acting as a
Virology University of Maryland School of Medicine, Division of Clinical growth factor for fibroblasts and being involved in matrix remodel-
Care and Research, Baltimore, United States; 2Institute of Human ling) and Hyaluronic acid (HA, acting as promoter of hepatic
Virology, University of Maryland School of Medicine, Baltimore, United fibrogenesis) decreased in patients who achieved SVR. The aim of
States our study was to determine whether YKL-40 and/or HA could be a
Email: [email protected] predictor of HCC occurrence in patients with cirrhosis who achieved
Background and aims: People who inject drugs (PWID) remain a SVR.
major reservoir of chronic hepatitis C virus (HCV) infection. Ongoing Method: In this retrospective study, we included patients with
injecting drug use is associated with re-infection, however the role of hepatitis C related cirrhosis, who achieved SVR after DAA therapy, in
HCV specific immune response in PWID is not understood. In this whom YKL-40 and HA were measured prior to treatment and at 36

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POSTER PRESENTATIONS
weeks post SVR. Cirrhosis was defined based on FibroScan® >14.5 kPa rate of reinfection and factors associated with reinfection in a cohort
and/or a combination of endoscopy and imaging criteria. Only those of high-risk patients over a 4 year follow-up period.
treated with DAA therapy between January 2015 and December 2016 Method: ANCHOR is a 96 week, prospective cohort study of people
were included. Patients were followed-up with until November 2021 with OUD, opioid misuse within a year and chronic HCV. All
or until HCC occurred. participants received HCV treatment. Those who achieved SVR were
Results: Our study included 71 patients of whom 64.8% were males followed for reinfection for 18 months, and subsequently had the
with a mean age of 61 (±8) years. Of our total cohort, 62% had option to enroll in LOOP, a 2 year long-term follow-up study.
genotype 1, 55% were Child Pugh A (CPA), 24% were CPA with a Reinfection was defined as a genotype switch or detectable viral
previous decompensation, and 21% were CP B/C. load after SVR. Patients were administered surveys at each visit to
During a median follow up of 60 months (IQR 41–70), 25.4% (18) of assess for ongoing risk behaviors and medication for OUD (MOUD)
patients had developed HCC. Patients who developed HCC had more status. A logistic regression model with GEE was created using
advanced liver disease (CP B/C 53.3% vs 20.5% CPA vs 11.8% CPA covariates with p < 0.10 to model the probability of reinfection.
previous decompensation; p = 0.031), a lower baseline albumin (34.7 Results: 157 individuals achieved SVR and were followed for 273.2
vs 38.4; p = 0.004) and an elevated YKL-40 at 36 weeks after SVR person-years, median 86.2 weeks (range 12–210 weeks). Subjects
(4789 vs 3333; p = 0.036) compared to those who had not developed were predominantly male (69%), black (84%), middle-aged (median
HCC (table 1). Between start of treatment and 36 weeks post SVR, the 57 years), and 50.3% unstably housed. Seventeen individuals (10.8%)
mean decrease in YKL-40 was significantly greater in those who did were reinfected a median of 76.1 weeks (range 21–175 weeks) after
not develop HCC (from 5098 to 3333, p < 0.001; vs 4752 to 4789 p = HCV treatment, a rate of 6.2/100 person-years. Reinfection was
0.987). There was no difference in the dynamics of HA between the associated with past month IDU ( p = 0.006), and cocaine positive UDS
two groups. In the multivariate analysis, YKL-40 at 36 weeks post SVR ( p = 0.03), however was not associated with age, race, gender,
(HR 1; CI 95% 1–1) was an independent factor associated with HCC. education, or visit specific opioid positive UDS, housing stability,
Child Pugh status A (HR 0.36; IC 95% 0.142–0.937) was an MOUD engagement, or HIV risk score (all p > 0.05). Of the 17
independent factor associated with lower HCC. reinfected individuals, 12 (71%) initiated HCV re-treatment, with 10
achieving SVR and 2 deaths.
Conclusion: In this cohort of high-risk people with OUD, we found
high rates of HCV reinfection which were associated with past-month
IDU and cocaine positive UDS at the time of detection. Given the rate
and timing of reinfection, these data reinforce the importance of
long-term engagement, ongoing HCV testing, and low-barrier
treatment of HCV reinfection. Further, in the era of rising stimulant
use, these data highlight the importance of assessing for and reducing
harms associated with polysubstance use and injection drug use in
people with opioid use disorder.

FRI365
Noninvasive prediction of hepatocellular carcinoma development
after oral antiviral therapy in patients with chronic hepatitis C: a
multicenter study
Yu Rim Lee1, Jung Gil Park2, Min Kyu Kang2, Jung Eun Song3,
Byoung Kuk Jang4, Young Oh Kweon1, Won Young Tak1,
Se Young Jang1, Changhyeong Lee3, Byung Seok Kim3,
Jae-Seok Hwang4, Woo Jin Chung4, Soo Young Park1, Nae-Yun Heo5,
Jeong Heo6, Hyun Young Woo6, Yanghyon Baek7, Jun Sik Yoon8,
Joonho Jeong9, Jae Young Jang1. 1Kyungpook National University,
Conclusion: HCC occurrence was higher in patients with CP B/C and Kyungpook National University Hospital; 2Yeungnam University College
those who did not decrease YKL-40 after achieving SVR. YKL-40 could of Medicine; 3Daegu Catholic University School of Medicine; 4Keimyung
be a predictive factor of HCC occurrence however further studies with University School of Medicine; 5Inje University Haeundae Paik Hospital,
a larger sample are necessary to confirm these results. Inje University College of Medicine; 6Pusan National University; 7Dong-A
University Hospital; 8Busan Paik Hospital, Inje University College of
Mazzarelli C et al. Direct fibrosis markers kinetic in patients undergoing Medicine; 9University of Ulsan College of Medicine, Ulsan University
antiviral treatment with DAA for chronic hepatitis C. Journal of Hepatology
68 (1):S403. Hospital
Email: [email protected]
FRI364 Background and aims: Hepatocellular carcinoma (HCC) can still
HCV reinfection associated with IDU and cocaine use in a cohort of occur after achieving a sustained virologic response (SVR) to direct-
people with OUD: 4 Year follow-up data from the ANCHOR cohort acting antiviral (DAA) therapy in patients with hepatitis C. We aimed
Elana Rosenthal1, Junfeng Sun2, Britt Gayle1, Amelia Cover1, to identify non-invasive parameters that predict the HCC develop-
Ashley Davis1, Shivakumar Narayanan1, Catherine Gannon2, ment for patient with chronic hepatitis C after SVR.
Grace Garrett2, Vivian Wang2, Meghan Derenoncourt2, Henry Masur2, Method: A total of 3, 489 HCV patients who treated with DAAs and
Shyamasundaran Kottilil1, Sarah Kattakuzhy1. 1Division of Clinical Care had achieved SVR from nine hospitals in South Korea were included
and Research, Institute of Human Virology, University of Maryland in this study. Predictors of HCC occurrence and HCC risk scores were
School of Medicine, United States; 2National Institutes of Health/Critical assessed.
Care Medicine Department, Bethesda, United States Results: During a median follow-up of 2.3 years, HCC occurred in 158
Email: [email protected] patients (4.5%). LSM gradually decreased from baseline to SVR and 1
year after treatment ( p < 0.001). Platelet count, bilirubin, and
Background and aims: People with HCV and opioid use disorder albumin levels also improved from before treatment to 1 year after
(OUD) who achieve sustained virologic response (SVR) may remain at treatment (all P < 0.05). Multivariate analysis using the Cox regression
risk of reinfection. Identification and retreatment of reinfected test identified that age (HR 1.055, 95% CI 1.036–1.074, P < 0.001), sex
individuals is critical to HCV elimination. We sought to evaluate the

S572 Journal of Hepatology 2022 vol. 77(S1) | S389–S664

 POSTER PRESENTATIONS
(HR 1.942, 95% CI 1.326–2.844, P = 0.001), platelet count (HR 0.987, FRI367
95% CI 0.984–0.991, P < 0.001), and albumin (HR 0.525, 95% CI 0.353– Direct-acting antiviral treatment in Albanian patients with
0.780, P = 0.004) at 1 year follow-up were independently associated chronic hepatitis C and advanced liver fibrosis
with the risk of HCC. HCC risk scores including Modified PAGE-B Liri Cuko1, Eva Shagla1, Adriana Babameto1, Jovan Basho1,
scores (AUROC = 0.814) and aMAP risk score (AUROC = 0.826) at 1 Arlinda Hysenj1, Stela Taci1, Irgen Tafaj1, Eno Pengili1. 1Mother Teresa
year after SVR using age, gender, platelet counts, serum albumin Hospital, Department of Gastrohepatology, Tiranë, Albania
levels can discriminate the risk of HCC. Email: [email protected]
Conclusion: In patients with chronic hepatitis C who have achieved
Background and aims: Treatment of chronic hepatitis C with direct-
SVR with DAAs, the use of HCC risk scores including Modified PAGE-B
scores and aMAP risk score at 1 year after SVR accurately predicted acting antiviral (DAA) is very effective at clearing the infection in
more than 90% of people. In Albania treatment with DAA is limited to
the risk of HCC.
patients with liver stiffness F3-F4, and with other co-infections. The
FRI366 objective of this study was to evaluate the efficacy of DAA in Albanian
Sustained low prevalence of HCV viremia among people who patients with genotype 1–5, where most of patients are with
inject drugs following the treatment as prevention for hepatitis C advanced liver fibrosis.
(TraP HepC) nationwide elimination program in Iceland Method: This was a retrospective study realized at University
Magnús Gottfredsson1,2, Valgerdur Runarsdottir3, Hospital Center of Tirana during 2014–2019, including naïve and
Thorvardur J. Löve4,5, Ragnheidur H. Fridriksdottir6, experienced patients with genotype 1–5. All patients are evaluated
Thorarinn Tyrfingsson3, Ingunn Hansdottir3, Ottar M. Bergmann6, with elastography and most of them were F3-F4. The primary
Einar S. Björnsson2,6, Birgir Johannsson1, Bryndis Sigurdardottir1, endpoint was SVR-12. In patients without genotype we have used pan
Arthur Löve7, Guðrún Erna Baldvinsdóttir7, Marianna Thordardottir8, genotypic regimen. All patients are treated with genotypic and
Ubaldo Benitez Hernandez4, Maria Heimisdottir9, pangenotypic DAA and are assessed for adverse event during the
Sigurdur Olafsson2,6. 1Landspitali University Hospital, Infectious treatment.
Diseases, Reykjavik, Iceland; 2University of Iceland, Medicine, Reykjavik, Results: In this study are included 207 patients, main age 48.9 ± 13.1
Iceland; 3SAA National center for addiction medicine, Reykjavik, Iceland; years, 56% male and 44% female. 152 (73%) were genotype 1, 24
4
Landspitali University Hospital, Science, Reykjavik, Iceland; 5University (11.5%) genotype 2, 9 (4.3%) genotype 3, 14 (6.7%) genotype 4, 1 (0.4%)
of Iceland, Public Health, Reykjavik, Iceland; 6Landspitali University genotype 5, and 7 (3.8%) anassigned genotype. SVR percentage
Hospital, Gastroenterology and Hepatology, Reykjavik, Iceland; according to genotype is shown in table. SVR to all patients was 93.2%.
7
Landspitali University Hospital, Virology, Reykjavik, Iceland; 8State According to elastography 127 (66%) were F3-F4, 80 (44%) F1-F2. Two
Epidemiologist, Infectious Diseases, Reykjavik, Iceland; 9Icelandic Health patients with decompesated cirrhosis discontinued treatment due to
Insurance, Reykjavik, Iceland side effect.
Email: [email protected]
Background and aims: Injection drug use (IDU) and sharing of Genotype (n, %) SVR-12 (% n|n)
injection equipment and paraphernalia is the main mode of 1 (152, 73%) 95% (145 ̸ 152)
transmission of Hepatitis C Virus (HCV) in most Western societies. 2 (24, 11.5%) 95.8% (23 ̸ 24)
People who inject drugs (PWID) therefore need to be diagnosed, 3 (9, 4.3%) 88.8% (8 ̸ 9)
treated and cured in order to curb transmission and achieve the WHO 4 (14, 6.7%) 78.5% (11 ̸ 14)
goal of eliminating HCV infection as a public health threat by 2030. 5 (1, 0.4%) 100% (1 ̸ 1)
Starting in 2016, the Treatment as Prevention for Hepatitis C (TraP anassigned (4, 6.7%) 71.4% (5 ̸ 7)
HepC) program in Iceland has offered direct acting antiviral agents
(DAA) to all HCV-infected patients with permanent residence in the Conclusion: Treatment with DAA proved to be very effective in our
country without restrictions. It has from its inception focused on patient, most of them with advanced liver fibrosis, compensated or
PWID, with special emphasis on active IDU. Vogur addiction hospital decompesated liver cirrhosis. SVR in total patients was 93.2%. The
screens all patients who report IDU activity upon admission for HCV results about genotype 3, 5, are not significant due to the small
and therefore is as an ideal sentinel site to monitor the prevalence of number of patients. In our country need to treat all patients with
HCV viremia in this key population. chronic hepatitis C without limitations to reach the objective of WHO.
Method: We analysed the prevalence of HCV viremia by PCR among
PWID who were admitted to Vogur for addiction treatment, 6 years FRI368
before (2010–2015) and 5 years during the TraP HepC program Improved recurrence-free survival rates in patients with HCV-
(2016–2020). related hepatocellular carcinoma and sustained virological
Results: Prior to Trap HepC, 2010–2015 the prevalence of HCV response to direct-acting antivirals
viremia among admitted patients who gave history of ever injecting Cristina-Maria Muzica1, Anca Trifan1, Laura Huiban1, Oana Stoica1,
drugs was stable at 39.5–40.6%. Among those who were currently Irina Girleanu1, Stefan Chiriac1, Ana-Maria Singeap1,
injecting at the time of admission (injecting within 6 months) the Camelia Cojocariu1, Tudor Cuciureanu1, Sebastian Zenovia1,
prevalence was stable at 53.2–57.7% during the same period. The Robert Nastasa1, Carol Stanciu1. 1Grigore T. Popa University of Medicine
prevalence of HCV viremia in the former group dropped to 32.9%, and Pharmacy, Gastroenterology, Iasi, Romania
12.0% and 8.6% during 2016, 2017 and 2018, respectively ( p < 0.001) Email: [email protected]
and subsequently has remained stable at 12.9% and 13.3% in 2019 and
2020. Background and aims: Despite the high efficacy of direct-acting
Conclusion: In the absence of an effective vaccine, treatment with antivirals (DAAs) in chronic HCV infection, a more aggressive pattern
DAA remains the most efficient way to lower the prevalence of HCV. of hepatocellular carcinoma (HCC) in patients previously treated with
Efficacy among PWID is excellent and treatment has resulted in a DAAs, has been reported. Tumor aggression in HCV-related HCC after
sustained drop in HCV viremia in this population but continued DAAs has been linked to impaired outcome. On this basis, we aimed
monitoring of these patients is needed. Further studies and longer to assess the pattern of HCC and survival rates in patients previously
follow-up is needed to evaluate whether this drop eventually treated with DAAs therapy.
translates into a lower nationwide incidence of HCV in Iceland. Method: This is a case-control study investigating the features of HCC
and survival rates in patients with chronic HCV infection whom were
previously treated with DAAs versus naïve patients. Patients were

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POSTER PRESENTATIONS
matched for sex and age in a 1:3 fashion. HCC infiltrative pattern, Twenty-five patients died during the follow up period. There was a
portal vein thrombosis (PVT), metastases, Milan criteria, Barcelona significant difference in morality rates based on SVR status, with 4.1%
Clinic Liver Cancer (BCLC) staging, tumor-node-metastasis (TNM) mortality in those with SVR, compared to 35.7% with NSVR ( p < 0.5).
staging, Cancer of the Liver Italian Program (CLIP), as well as the Of 14 individuals with known cause of death, 5 patients died from
recurrence and overall survival rate at 18 months of follow-up, were HCV-related causes.
compared in the 2 groups. This research was carried out in the When comparing outcomes by original ASCEND treatment provider
Institute of Gastroenterology Iasi, Romania, between January 1st, 2017 type, there were no significant differences in rates of loss to follow-
and December 31, 2019. up, SVR, HCV re-screening, HCV reinfection or mortality ( p > 0.05)
Results: The study included 124 patients that were divided into two between nurse practitioners, primary care physicians, and specialist
groups according to DAAs status: 31 DAAs-treated HCC patients and physicians.
93 non-DAAs HCC patients. Overall, 65% were males, and the mean
age was 58.9 ± 6.8 years. The mean values of APRI and Fib-4 scores
were significantly higher in the DAAs-treated group than in naïve
patients ( p < 0, 001). The frequency of the infiltrative HCC pattern,
PVT, and metastasis was higher in the non-DAAs group ( p = 0, 002).
According to BCLC, CLIP, and TNM, HCC patients in the non-DAAs
group had more advanced stages and limited treatment options ( p <
0, 001). Furthermore, HCC recurrence rate was higher in naïve
patients than in those DAAs-treated (16, 2% versus 8, 6%, p = 0, 002).
The 18-months overall survival rate was 73.3% in the DAAs-treated
group and 43.7% in non-DAAs group ( p = 0, 008).
Conclusion: Our study indicates a better recurrence-free overall
survival rate in patients with HCV-related hepatocellular carcinoma
with SVR to DAAs compared with naïve patients, demonstrating the Conclusion: This five-year longitudinal follow-up of the ASCEND
beneficial impact on the outcome of these patients. cohort identifies an even higher rate of SVR of 93.5% in an urban
cohort, with limited reinfection. These data reinforce that task-
FRI369 shifting of HCV therapy to non-specialist providers results in both
Long-term outcomes associated with task-shifting of HCV high rates of HCV cure, as well as favourable long-term outcomes.
treatment by non-specialist providers: five year follow-up from These data emphasize that restrictions on the basis of treating
the ASCEND cohort provider type stand as unnecessary hurdles in the HCV care
Sarah Mollenkopf1, Elana Rosenthal2, Gebeyehu Teferi3, Rachel Silk2, continuum.
Nivya George2, Henry Masur4, Shyamasundaran Kottilil2,
Sarah Kattakuzhy2. 1University of Maryland School of Medicine, FRI370
Baltimore, United States; 2Institute of Human Virology, Division of Risk stratification of hepatocellular carcinoma in cirrhotic
Clinical Care and Research, Baltimore; 3Unity Health Care, Washington, patients after hepatitis C virus eradication: russian single-center
United States; 4NIH, Critical Care Medicine Department, Bethesda, experience
United States Ekaterina Nabatchikova1, Daria Zasorina1, Teona Rozina1,2,
Email: [email protected] Elena Nikulkina1, Elena Tanashchuk1, Dzhamal Abdurakhmanov1,
Sergey Moiseev1,2. 1I.M. Sechenov First Moscow State Medical
Background and aims: Since 2015, an increasing body of evidence
University (Sechenov University), Russian Federation; 2M.V. Lomonosov
has supported task-shifting of Hepatitis C (HCV) treatment with
Moscow State University, Russian Federation
direct-acting antivirals (DAA) to non-specialist providers, however,
Email: [email protected]
there are limited data on longitudinal outcomes associated with this
treatment paradigm. We sought to assess outcomes of patients in the Background and aims: The risk of hepatocellular carcinoma (HCC) in
5 years after initial DAA treatment by specialist and non-specialist cirrhotic patients after HCV eradication with direct-acting antivirals
providers, to evaluate the longitudinal evidence for task-shifting in (DAAs) is reduced, but not completely eliminated. The aim of our
the ASCEND cohort. study was to assess incidence, risk factors of HCC and develop a
Method: This analysis included 525 patients treated for HCV with scoring system to predict in patients with HCV-related cirrhosis
ledipasvir-sofosbuvir in the ASCEND investigation who had long term treated by DAAs.
follow up data available. Chart review and abstraction of variables of Method: The prospective single-center cohort study included
interest from date of sustained virologic response (SVR) to June 2020 patients with HCV-related cirrhosis treated by DAAs between July
was completed. Baseline demographic and clinical characteristics 2015 and May 2020. Exclusion criteria was previous and present HCC.
were compared using t-tests, while change in outcomes was assessed Patients who achieved sustained virological response underwent
using McNemar’s or chi-squared tests. All analysis was conducted in clinical, laboratory and imaging assessment every 3–6 months after
R, version 4.1.0. the end of therapy.
Results: Amongst 525 patients at ASCEND baseline, the mean age was Results: : A total of 232 cirrhotic patients were enrolled. The median
59.5 years, with majority male (69%), Black race (95%), and genotype age was 54 (47; 60) years, 49.3% were males, diabetes was present in
1a (71%), with 20% with HIV, 20% with cirrhosis and 18% IFN- 19.8%, obesity-in 20.2%, HCV genotype 3-in 25.4% and 29.7% were
treatment experienced. treatment-experienced. Child-Pugh class B/C were found in 29.3%.
In addition to 458 (87.2%) of patients with SVR at the end of the Baseline median MELD score was 11 (9; 13), liver stiffness (n = 133)-
original investigation, 16 patients who were lost to follow up were 23 (17.4; 30.6) kPa, platelet count ≤100 × 103/ml were in 54% of
found to have achieved SVR. Furthermore, of 32 patients with known patients, albumin ≤35 g/l–35.3%, bilirubin ≥34 μmol/l–19.4%, pro-
NSVR, 23 were re-treated, 17 of whom achieved SVR. Therefore, 491 thrombin time ≤60%–19.4%, aspartate aminotransferase-platelet
(93.5%) of ASCEND participants ultimately achieved HCV cure during ratio index >2–56%, fibrosis-4 score (FIB-4) ≥3.25–67.7%.
the five-year follow up period. Esophageal varices 2/3 were in 60.3%, ascites-25.4%. The median
Of the 458 patients who achieved SVR, 97% returned to clinic, of follow-up time after EOT was 36 (24; 48) months. De novo HCC
whom 70% were screened for HCV reinfection. Of 336 patients occurred in 19 (8.2%) patients. Median alpha-fetoprotein was 6.3 (2.8;
screened, only two (0.6%) were found to be reinfected. 31) IU/ml. Sixteen patients (89%) were within the Milano criteria. The

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 POSTER PRESENTATIONS

Figure: (abstract: FRI370)

median time from EOT to HCC diagnosis was 18 (12; 42) months. At aims to compare the predictability of HCC among CHC patients with
the multivariate analysis, baseline bilirubin level ≥34 μmol/l (HR SVR who meet ACLD criteria by different diagnostic measurements.
4.19; p = 0.002), baseline ascites (HR 6.6; p < 0.001), MELD ≥15 (HR Method: CHC achieved SVR by interferon-free direct acting anti-viral
3.82; p = 0.007) and FIB-4 >3.25 (HR 6.4; p = 0.015) at the SVR time agents (DAA), whose LSM by transient elastography (TE, Fibroscan)
were independent risk factors for HCC. We determined the weight of and FIB-4 index were both available before DAA therapy were
each factor equal to HR, and then converted it into an integer: enrolled. The ACLD was defined as LSM >10 kPa and/or FIB-4 >3.25
baseline bilirubin level ≥34 μmol/l-1 point, baseline ascites-2 points, and/or ultrasound signs of cirrhosis. Predictabilities for HCC and 3-
MELD ≥15 at the SVR time-1 point, FIB-4 >3.25 at the SVR time-2 year cumulative HCC incidences were compared among four groups
points. The resulting scale allows to set from 0 to 6 points. Patients of ACLD patients diagnosed by different non-invasive assessments
with HCC had a large sum of points compared to patients without (group A: FIB-4 > 3.25 but LSM ≦ 10; group B: FIB-4 ≦ 3.25 but LSM >
HCC (4 (3; 6) points vs. 1 (0; 2) points, p < 0.001). The AUROC of the 10; group C: FIB-4 > 3.25 + LSM > 10; group D: FIB-4 ≦ 3.25 and
model was 0.82 (0.71–0.93, p < 0.001). The sum of points equal to ≥3 LSM ≦ 10 but ultrasonography showed cirrhosis.).
has the maximum values of sensitivity (73%) and specificity (78%) and Results: Among 1600 enrolled patients, 922 (58%) patients met
can be used as a threshold value for determining the HCC risk (figure criteria of ACLD (group A, N = 128; group B, N = 369; group C, N = 406;
a). The cumulative risk of developing HCC in patients with ≥3 points group D, N = 19). The mean age was 62 years old, 41% was male and
is significantly higher (HR 12.03, log-rank p < 0.001) (figure b). 63% was genotype 1. The annual incidence and 3-year cumulative
Conclusion: We developed a predictive score using four risk factors, HCC incidences showed 0.3% and 0.8%, 2.2% and 4.6%, 3.8% and 9.1%
which can help to customize HCC surveillance strategies in cirrhotic and 3.9% and 10.5% in patients with group A, group B, group C and
patients after HCV eradication. group D (Log-rank p < 0.01), respectively (Figure). The negative
predictive values (NPVs) for HCC were all the above 95% among
FRI371 these four groups with different ACLD definitions, while the
Distinct hepatocellular carcinoma risks in treated chronic sensitivity was much higher in group C of 62.5% compared to group
hepatitis C patients with different definitions of advanced chronic A (1.4%), B (27.8%) and D (2.8%).
liver disease
Yen-Chun Liu1,2, Cheng Er Hsu1,2, Ya-Ting Cheng1,2, Chung-Wei Su1,2,
Chia-Hung Tai1,2, Yi-Cheng Chen1,2, Yi-Chung Hsieh1,2, Wei Teng1,2,
Rachel Wen-Juei Jeng1,2, Chun-yen Lin1,2, Rong-Nan Chien1,2,
Tai Dar-In1,2, I-Shyan Sheen1,2. 1Chang Gung Memorial Hospital, Linkou
Branch, Taiwan; 2College of Medicine, Chang Gung University, Taiwan
Email: [email protected]
Background and aims: To identify target population for hepatocel-
lular carcinoma (HCC) is an important issue in chronic hepatitis C
(CHC) patients after antiviral treatment. Advanced chronic liver
disease (ACLD) patients have been suggested by the guideline as the
target surveillance group for their remnant HCC risk after sustained
virological response (SVR). However, the definition of ACLD com-
posed of different diagnostic tools including liver stiffness measure-
ment (LSM), FIB-4 or both or by ultrasonography image. This study

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S575

POSTER PRESENTATIONS

Figure: (abstract: FRI371)

Conclusion: LSM >10 kPa ± FIB-4 >3.25 are more appropriate criteria FRI372
for ACLD than FIB-4 >3.25 alone which PPV is only 0.8% and its 3-year Hepatocellular carcinoma risks of liver fibrosis changes after viral
HCC cumulative incidence be approximate to that of the non-ACLD eradication in chronic hepatitis C patients
(0.4%). Those with echo appeared cirrhotic features but not fit the Yen-Chun Liu1,2, Cheng Er Hsu1,2, Ya-Ting Cheng1,2, Chung-Wei Su1,2,
criteria of ACLD due to LSM<10 kPA and FIB-4 < 3.25 were still at high Chia-Hung Tai1,2, Yi-Cheng Chen1,2, Wei Teng1,2,
risk of HCC and also shall be under HCC surveillance program. Rachel Wen-Juei Jeng1,2, Chun-yen Lin1,2, Rong-Nan Chien1,2,
Tai Dar-In1,2, I-Shyan Sheen1,2. 1Chang Gung Memorial Hospital, Linkou

Figure: (abstract: FRI372)

S576 Journal of Hepatology 2022 vol. 77(S1) | S389–S664

 POSTER PRESENTATIONS
Branch, Taiwan; 2College of Medicine, Chang Gung University, Taiwan baseline to 3y [−3.0 kPa (−7.6 to 1.2); −0.4 points (−0.9 to 0.2); −0, 5
Email: [email protected] points (−1.3 to −0.1)] and major changes were observed from baseline
to SVR12. Before the HCV treatment 30.0%, 35.1% and 26.5% subjects
Background and aims: Hepatocellular carcinoma surveillance is
were considered as having cirrhosis according to LSM, APRI or FIB4.
suggested for chronic hepatitis C (CHC) patients with advanced
More than half of them (58.8%, 87.2% and 70.7% respectively) did not
chronic liver disease (ACLD) by the guideline. It is reported liver
remain in that cathegory at the end of the study. Four HCC were
fibrosis in patients with advanced fibrosis or cirrhosis can be reversed
detected [3y risk: 0.8% (0.3–2.4)]. At least one episode of PHD was
after viral eradication by direct acting antivirals (DAA). The study
reported in 13 patients [3y risk: 2.6% (1.4–4.8)]. 23 patients died [3 y
aims to investigate the HCC risks among CHC sustained virological
overall mortality: 3.9% (2.4–6.4)] but only 3 of them due to liver-
response (SVR) patients with fibrosis regression, stationary or
related causes [3 y related mortality: 0.3% (0.0–1.8)]. 15 patients
progression after SVR, and predictors for ACLD regression.
developed the composite endpoint [3 y risk of any of the covered
Method: CHC achieved SVR by interferon-free DAA, whose LSM by
outcomes: 3.1% (1.8–5.4)]. Estimated liver fibrosis improvement from
transient elastography (TE, Fibroscan) and FIB-4 index were both
baseline to SVR12 was associated to lower risk of presenting any of
available before DAA therapy and after SVR were enrolled. The ACLD
these clinical outcomes, both in the global cohort and in the subgroup
was defined as LSM >10 kPa and/or FIB-4 >3.25 and/or ultrasound
of patients with cirrhosis or advanced fibrosis.
signs of cirrhosis. The 3-year cumulative HCC incidences were
compared among four groups of dynamic fibrotic changes (group
A: both pre-DAA and post-SVR timepoints: non-ACLD; group B: pre-
DAA non-ACLD progressed to post-SVR ACLD; group C: pre-DAA ACLD
regressed to post-SVR non-ACLD; group D: both pre-DAA and post-
SVR: ACLD). Logistic regression was applied to find predictors for
ACLD regression.
Results: There were 906 patients (group A: 378 (42%), group B: 18
(2%), group C: 153 (17%), group D: 357 (39%)) enrolling into the study
with mean age of 62 years old, 38% of male and 92% of genotype 1.
The 3-year cumulative HCC incidences showed 0.5%, 0%, 2.6% and
10.4% in patients with group A, group B, group C and group D (Log-
rank p < 0.01), respectively (Figure). Logistic model showed that
higher baseline ALT [adjusted OR (aOR): 1.006 (95% CI: 1.002–1.010),
p = 0.007] was a predictor for ACLD regression, while higher baseline
LSM [aOR:0.870 (0.825–0.917), p < 0.001] and FIB-4 [aOR:0.655 Figure: Patients distribution according to estimated liver fibrosis stage
(0.496–0.864), p = 0.003] were unfavorable factors for post-SVR Conclusion: There is a clinically relevant improvement in non-
ACLD regression. invasive liver fibrosis markers after 3 years of DAA-induced SVR in
Conclusion: Patients with persistent ACLD after SVR posed the PLWH with HCV infection. Estimated fibrosis regression from
highest HCC risks, followed by those with ACLD regression. Those baseline to SVR12 is associated with a reduction in liver-related
progressed from pre-therapy non-ACLD to post SVR ACLD occurred in complications.
2% of all population with minimal HCC risk as that in the persistent
non-ACLD group. FRI374
FOCUS Project: preliminary results toward hepatitis C Virus
FRI373 screening and elimination in Almería, Spain
Change in fibrosis and clinical progression three years after Anny Camelo Castillo1, Marta Casado1, Teresa Cabezas Fernandez1,
sustained virological response induced by direct antiviral agents Pedro Amado Villanueva1, Alba Carrodeguas2, Diogo Medina2,
in HIV/HCV subjects José Luis Vega Sáenz1, Manuel Rodriguez Maresca1. 1Torrecárdenas
Maria Carnevali Frias1, Lourdes Dominguez2, David Rial Crestelo1, University Hospital, Almería, Spain; 2GILEAD SCIENCES INC, Madrid,
Otilia Bisbal1, Rafael Rubio Garcia1, Federico Pulido Ortega1. 1Hospital Spain
12 de Octubre, Medicina Interna, Madrid, Spain; 2King’s College Hospital, Email: [email protected]
HIV/Sexual Health, London, United Kingdom
Email: [email protected] Background and aims: Hepatitis C virus (HCV) elimination is a global
challenge, and Spain may be one of the first countries to achieve the
Background and aims: Sustained virological response (SVR) World Health Organization’s goal of eliminating viral hepatitis by
achieved after treatment of HCV infection with direct-antiviral 2030. A 2017–2018 Ministry of Health serosurvey estimated 0.22%
agents (DAA) is associated with long-term clinical benefits. We active HCV infection among the general Spanish population, 29.4%
evaluate changes in the estimated fibrosis on SVR confirmation and 3 without prior infection records.
years after SVR, and if changes on SVR confirmation are related to a Increasing HCV screening is key, particularly among vulnerable
decrease in the risk of liver events in people living with HIV (PLWH). populations with high prevalence. Emergency departments (ED)
Method: A prospective observational cohort of PLWH with HCV often act as safety nets due to health equity issues for key populations
infection and SVR after DAA therapy (January 2015–August 2016) was affected by viral hepatitis, as they often lack optimal links with their
followed up until December 2020. Liver fibrosis was estimated by primary care providers.
non-invasive methods: liver stiffness (LS), APRI and FIB4. Measures Therefore, we aimed to evaluate HCV screening efficacy in the ED of
were done prior to treatment (baseline), 12 weeks post treatment Torrecárdenas University Hospital, in Almería, Andalusia, Spain.
(SVR12) and 3 years after SVR12 (3 y). Cut-off values for cirrhosis Method: We implemented opportunistic HCV screening in the ED,
were ≥14.6 kPa (LS), ≥1 point (APRI), ≥3.25 points (FIB4). Cirrhosis using existing infrastructure and staff, aided by electronic health
regression or non-progression from non-cirrhosis was considered as record system modifications to identify eligibility for the test and
fibrosis improvement. Clinical outcomes considered were liver- request serologies automatically. Patients were eligible for testing
related complications occurred after SVR: death, portal hypertension upon verbal consent if they were between 18 and 69, and had no
decompensation (PHD), hepatocarcinoma (HCC) and a composite known diagnosis or test performed in the previous year, and required
endpoint of these three. blood tests in the current visit to the ED.
Results: 393 people were followed-up for a median of 3.8 years (3.5–
4.0). There was a significant improvement in LS, APRI and FIB4 from

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POSTER PRESENTATIONS
We used the LIAISON®X- Diasorin assay for HCV antibodies (anti-
HCV) and the Roche Cobas® 6800 for viral RNA (HCV RNA) in the
same specimen (i.e., reflex or single-step testing). Appropriate follow-
up or discharge was given, regardless of test results. We contacted
positive patients to ensure and monitor linkage to specialist medical
care. FRI376
Results: We screened 1, 131 patients for HCV from August to October Usefulness of longitudinal assessment of AFP in DAA cured HCV
2021, finding 28 (2.47%) anti-HCV positive patients (with an average cirrhotic patients to predict the developmente of HCC
age of 55, 71% males), and 5 (0.44%) HCV RNA positive patients (80% Angelo Sangiovanni1, Eleonora Alimenti1,2, Riccardo Gattai3,
males), 80% of whom had no prior records or knowledge of their Roberto Filomia4, Elisabetta Parente5, Luca Valenti6,7, Luca Marzi8,
infection. Giulia Pieri9, Guglielmo Borgia10, Martina Gambato11,
Conclusion: Undocumented HCV infection among our ED population Natalia Terreni12, Ilaria Serio13, Luca Saverio Belli14, Filippo Oliveri3,
is higher than estimated in the general population, with twice the Sergio Maimone4, Maria Corinna Plaz Torres9, Roberta D’Ambrosio1,
active infection rate and nearly two times undiagnosed infection. Massimo Iavarone1, Laura Virginia Forzenigo15,
Thus, opportunistic HCV screening in EDs is feasible, non-disruptive, Francesco Paolo Russo11, Maria Grazia Rumi16, Michele Barone5,
and effective in increasing diagnosis. Anna Ludovica Fracanzani7,17, Giovanni Raimondo4,
Edoardo Giovanni Giannini18, Maurizia Brunetto3,19, Erica Villa8,
Annalisa De Silvestri20, Massimo Colombo21, Pietro Lampertico1,22.
1
Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Division of
Gastroenterology and Hepatology, Milan, Italy; 2University of Pavia,
Department of Medical Sciences, Pavia, Italy; 3University Hospital of
Pisa, Hepatology Unit and Laboratory of Molecular Genetics and
Pathology of Hepatitis Viruses, Pisa, Italy; 4University Hospital of
Messina, Division of Clinical and Molecular Hepatology, Messina, Italy;
5
University of Bari, Gastroenterology Unit, Department of Emergency
and Organ Transplantation (D.E.T.O.), Bari, Italy; 6Foundation IRCCS Ca’
Granda Ospedale Maggiore Policlinico, DivisionTrasfusion Medicine and
Hematology, Milan, Italy; 7University of Milan, Department of
Pathophysiology and Transplantation, Milan, Italy; 8Azienda
Ospedaliero-Universitaria Policlinico di Modena, Gastroenterology Unit,
Modena, Italy; 9University of Genoa, Gastroenterology Unit, Department
of Internal Medicine, Genoa, Italy; 10University of Naples ‘Federico II’,
Department of Clinical Medicine and Surgery, Section of Infectious
Diseases, Naples, Italy; 11Padua University Hospital, Multivisceral
Transplant Unit, Department of Surgery, Oncology, and
Gastroenterology, Padua, Italy; 12Valduce Hospital, Division of
Gastroenterology, Como, Italy; 13University of Bologna, Department of
Medical and Surgical Sciences, Bologna, Italy; 14Ospedale Niguarda, UOC
Epatologia e Gastroenterologia, Milan, Italy; 15Fondazione IRCCS Ca’
Granda Ospedale Maggiore Policlinico, Unit of Radiology, Milan, Italy;
16
Ospedale San Giuseppe, Università degli Studi di Milano, Division of
Hepatology, Milan, Italy; 17Foundation IRCCS Ca’ Granda Ospedale
Maggiore Policlinico, Internal Medicine and Metabolic Diseases, Milan,
Italy; 18University of Genoa, Gastroenterology Unit, Department of
Internal Medicine, Genoa, Italy; 19University of Pisa, Internal Medicine,
Department of Clinical and Experimental Medicine, Pisa, Italy;
20
Foundation IRCCS Policlinico San Matteo, Clinical Epidemiology and
Biometeric Unit, Pavia, Italy; 21San Raffaele Hospital, Liver Center, Milan,
Italy; 22University of Milan, CRC “A. M. and A. Migliavacca” Center for
Liver Disease, Department of Pathophysiology and Transplantation,
Milan, Italy
Email: [email protected]
Abstract withdrawn
Background and aims: The usefulness of serum alfafetoprotein (AFP)
assessment after sustained virologic response (SVR) in HCV cirrhotic
patients treated with direct antiviral agents (DAA) in surveillance
programs for the early diagnosis of hepatocellular carcinoma (HCC) is
debated. Aim of this study was to evaluate the time course of AFP and
its performance in predicting HCC development in this setting.
Secondary aim was to define the AFP value predicting HCC
development with at least 99% specificity.
Method: In a post-hoc analysis of consecutive cirrhotic patients
treated with DAA in a multicenter national study, we enrolled all
HCC-free patients with at least one AFP value available at or after SVR
and extended the follow-up until 30 September 2020. HCC
surveillance program was based on abdominal ultrasound (US)
every 6 months. AFP was tested during follow-up on clinical basis
depending on the policy of each centre. Joint modelling of

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 POSTER PRESENTATIONS
longitudinal data of log AFP and time-to-event endpoint (HCC) were
applied for analysis, combining the linear mixed effects model and
the Weibull model for survival.
Results: 870 SVR patients, median age 65 (IQR 55–73, 58% males),
92% Child-Pugh A were enrolled. During a median 34 (IQR 14–43)
months of post SVR follow-up, 71 patients developed HCC,
corresponding to a cumulative incidence at 1, 2 and 3 years of 3.3%
(95% CI 2.3–4.8), 5.4% (95% CI 4.0–7.4), 8.3% (95% CI 6.4–10.7),
respectively. The joint model considering log AFP values in a time
dependent way achieved the best performance to predict the risk of
developing HCC, HR 2.44 (95% CI 2.10–2.82, p < 0.001). The log-AFP
value progressively increased in patients who developed HCC as
compared to those who did not ( p < 0.001). A log AFP increase was
associated to increased risk of developing HCC with HR 21.9 (95% CI
4.6–103, p < 0.001). By Youden’s index an AFP value above 8 ng/ml
detected at any time defines the most accurate threshold to predict
HCC, corresponding to a 59.6% sensitivity and 96.5% specificity. A 99%
specificity was achieved for AFP value >21 ng/ml corresponding to a
sensitivity of 23.9%. By Kaplan-Meier curve in a time-dependent
association structure, HCC incidence was 10.8 per 100 patient-year
(95% CI 7.2–16.1) in patients with AFp >21 ng/ml as compared to 2.2 Figure: Patients distribution according to estimated liver fibrosis stage
(95% CI 1.7–3.0) in patients with AFP value ≤21 ng/ml ( p < 0.001).
Conclusion: In cured HCV cirrhotic patients the AFP value over time Conclusion: The outreach set up of the study enabled insights in to
is associated to HCC development and may help to refine the HCC the treatment and HCV status of PWID, which the authors feel is a
surveillance strategies. The increase of AFP levels above 21 ng/ml at closer representation of reality. HCV prevalence was comparable to
any time after SVR is associated with a specificity of 99% for the other study estimates in the literature. Treatment uptake was low,
prediction of HCC development, albeit with low sensitivity. despite the free DAA treatment offered, however within this subset
only 27% went on to be reinfected. What is worrying, however, is that
FRI377 47% of participants continued to be infected with HCV. This begs the
A 4 year multi-centre study of persons who inject drugs in question as to which barriers to care within a psychosocial framework
Luxembourg, looking at hepatitis C virus seroprevalence, need to be addressed to enable the World Health Organisation’s
treatment uptake and reinfection rates (WHO) target of eradicating HCV as a public health risk by 2030.
Madiha Sharaf1, Vic Arendt2, Thérése Staub3, Carole Devaux4,
Emily Montosa Nunes4. 1Centre Hospitalier Luxembourg, Emergency
Department, Luxembourg, Luxembourg; 2Centre Hospitalier
Luxembourg, National Service of Infectious Diseases, Luxembourg, Viral hepatitis C: Therapy and resistance
Luxembourg; 3Centre Hospitalier Luxembourg, National Service of
Infectious Diseases, Luxembourg, Luxembourg; 4Luxembourg Institute of
Health, Department of Infection and Immunity, Esch-sur-Alzette, FRI381
Luxembourg Benefits associated with HCV cure in people with mental
Email: [email protected] disorders
Background and aims: The global figure of persons who inject drugs Benjamin Rolland1, Elias Benabadji2, Olivier Lada2,
(PWID) stands at 15.6 million persons. 50% of PWID have been Pascaline Rabiega3, Fayssoil Fouad3, Nabil Hallouche4, Stanislas Pol5.
1
estimated to be exposed to the Hepatitis C virus (HCV), and 39% are Université de Lyon-Sud et Service d’Addictologie de Lyon (HCL/CH
said to suffer from chronic HCV, in comparison to 1% of the general Vinatier), Lyon, France; 2Gilead Sciences, Boulogne-Billancourt, France;
3
population. Chronic HCV can result in liver cirrhosis, hepatocellular IQVIA, France; 4GHU Paris Psychiatrie et Neurosciences, Paris;
5
carcinoma and premature death over 20 to 40 years. The “Hepatitis C Université de Paris et Hépatologie de Cochin (AP-HP), Paris, France
among Drug Users”-“HCV-UD” study is the largest multi-centre study Email: [email protected]
in Luxembourg looking at patterns of HCV prevalence amongst PWID, Background and aims: Retrospective and prospective studies have
including uptake of treatment and reinfection. reported hepatic and extra-hepatic benefits after direct-acting
Method: 480 participants were recruited at harm reduction sites antivirals (DAAs) treatment of hepatis C virus (HCV) chronic infection.
throughout the country from November 2015 to December 2019. However, the ability of virologic cure to improve the neuro-cognitive
Participants were offered HCV screening, direct acting anti-viral troubles is still questioned: HCV cure could improve neuro-cognitive
(DAA) treatment and follow-up with an infectious disease specialist, troubles as the neurotropism of HCV has been suggested (in glial cells
without cost. and astrocytes). Our main objective was to evaluate, in the
Results: 356 participants (74%) were exposed to HCV versus 124 subpopulation of patients with psychiatric disorders, the impact of
participants (26%) who had no evidence of exposure. 51% were cured DAAs (assimilated to HCV cure) on hospitalizations, both in general
of which 25% were cured through treatment, as evaluated with a medicine and in psychiatric ward.
sustained viral response at 12 weeks or more. Of these, 27% were Method: All adult patients identified in the French administrative
reinfected again with HCV. 75% were cured during the course of the health care databases (SNDS) with DAAs treatment initiation
study, attributed to previous unrecorded treatment or spontaneous between 2015 and 2018, and with at least one psychiatric disorder,
cure. 47% of participants continued to have ongoing infection, of were included. Individuals were assigned into one or several
which 7% had undergone treatment, and 93% had not taken any psychiatric disorder sub-groups based on algorithms: “addictive
treatment. There was missing data for 6 participants. The results are disorders,” “neurotic and mood disorders,” “psychotic disorders” and
summarised in the figure below. “other psychiatric disorders.” A longitudinal approach was then used
to compare the frequency and the duration of hospitalizations one

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 POSTER PRESENTATIONS
year before and one year after HCV treatment, both in general patients received a third treatment course as second rescue treatment
medicine (all-cause) and in psychiatric ward. after a further median delay of 193 (IQR: 160–378) days. One-
Results: Between 2015 and 2018, a total of 17, 203 HCV patients with hundred-eleven out of 124 (90%) non-cirrhotic and 62/79 (78%)
at least one psychiatric disorder initiated a treatment in France. 57.4% cirrhotic patients achieved SVR following the first rescue treatment.
of the subjects were hospitalized at least once the year before DAAs SVR was achieved by 108/112 (96%) patients after a triple DAA
initiation, while only 41.6% were during the year following treatment regimen. In total 69 (24%) patients were lost to follow-up or died
( p < 0.0001). Put differently, the number of patients with at least one waiting for rescue treatment. Baseline cirrhosis was associated with
hospitalization decreased by 28% after HCV cure (9, 874 versus 7, 153 poor long-term survival. Overall survival 3 years after initial
patients hospitalized respectively). treatment failure was 70% for patients compared with over 90% for
The mean number of hospitalizations per patient per year in general patients without baseline cirrhosis (Figure 1).
medicine department was 1.2 during the pre-DAAs year and
decreased to 0.8 the post-treatment year ( p < 0.0001). Similarly,
this number decreased from 1.4 to 1.2 in psychiatric ward.
Among the patients hospitalized at least once in general medicine
(n = 2, 515), both the year before and the year after treatment, the
duration of hospital stays decreased significantly from 20.5 days to
16.7 days after HCV treatment ( p < 0.0001). In psychiatric wards (n =
589) a decreasing trend was also observed from 73, 9 days to 68, 9
days but was not significant ( p = 0.2132).
Interestingly, similar results were also observed in all four sub-groups
and were statistically significant.

<0.0001
10000
<0.0001 At least one hospitalization
9000
+57%
8000
7000 +34% No hospitalization
Number of patients

6000
5000
<0.0001 Year before DAAs
4000
3000
-33%
+29%
<0.0001 Year after DAAs
Conclusion: Our study indicates that rescue therapy in most patients
2000 -24% +84% with primary DAA failure have an excellent outcome, in particular
1000 -21%
-28% when a triple DAA regimen was given. A significant number of
0
patients were lost to follow-up or died waiting for rescue therapy, and
the overall long-term prognosis for patients with baseline cirrhosis
was poor. This indicates that patients with primary DAA failure
should be offered rescue therapy, using a triple DAA regimen, without
delay.
Conclusion: DAAs treatment in patients with psychiatric disorders
results in a significant reduction in the frequency and the duration of FRI383
hospitalizations the year following treatment, and even for the Requests for drug-drug interaction data on direct-acting
patients with severe psychiatric conditions. These results point out antivirals and enzyme inducing anti-epileptic agents: an overview
both the individual benefit-a better global and psychiatric prognos- of the HEP Interaction checker database of the University of
tic-and the collective benefit-fewer resource utilization-of HCV cure Liverpool
in patients with psychiatric disorders. David Burger1, David Back2, Jasmine Martin2, Daryl Hodge2,
Minou Van Seyen3, Justin Chiong2, Alison Boyle2, Fiona Marra2.
FRI382 1
Radboud University Medical Center, Pharmacy, Nijmegen, Netherlands;
Dismal prognosis for cirrhotic HCV patients after initial DAA 2
University of Liverpool, Liverpool, United Kingdom; 3Jeroen Bosch
treatment failure, rescue therapy may be life-saving
Ziekenhuis, ‘s-Hertogenbosch, Netherlands
Johan Westin1, Rune Wejstål1, Christian Kampmann2,
Email: [email protected]
Magdalena Ydreborg1, Ola Weiland3. 1University of Gothenburg and
Sahlgrenska University Hospital, Department of Infectious diseases; Background and aims: Drug-drug interactions (DDIs) between
2
Skåne University Hospital, Department of Infectious Diseases, Lund, direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection
Sweden; 3Karolinska Insititute and Karolinska University Hospital, Dept and enzyme inducing anti-epileptic agents (eiAEs) are among the
of Medicine, Division of Infectious Diseases, Stockholm, Sweden most difficult to manage, and form a potential barrier towards
Email: [email protected] elimination of HCV. When patients are not able to switch the eiAE to a
non-eiAE, DAA treatment is often deferred. With new data published
Background and aims: Effective direct-acting antiviral (DAA)
recently on successful combined treatment of eiAEs and DAAs (Buti
treatment against hepatitis C virus (HCV) infection is universally
et al J Hepatol 2021; Natali et al J Pharm Practice 2021) we wondered
available. A small portion of HCV patients does not respond,
how often people are looking for eiAE-DAA interactions at the
irrespective of treatment regimen. The aim was to study the long-
University of Liverpool’s HEP Interaction Checker (www.hep-
term prognosis after initial DAA treatment failure in HCV infected
druginteractions.org) to gauge some information about how wide-
patients, in a real-life setting.
spread this problem may be.
Method: Data from all adult patients registered in the national
Method: We extracted DDI queries submitted to the HEP Interaction
Swedish HCV treatment register who did not achieve sustained
Checker between July 1, 2017 and September 30, 2021. We removed
virological response (SVR) after their initial DAA treatment course,
queries on DAAs that are no longer in use (e.g. boceprevir, telaprevir).
were retrieved from 2014 through 2018.
We only looked at eiAEs (including: carbamazepine, phenytoin,
Results: In total, 288 patients with primary DAA failure were
phenobarbital, primidone, oxcarbazepine and eslicarbazepine) as
included, of whom 236 underwent a second treatment course as
non-eiAEs (e.g. gabapentin, pregabalin) are less of interest from a DDI
rescue therapy after a median delay of 353 (IQR: 215–650) days. 15
perspective, and are more often used for other indications such as

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 POSTER PRESENTATIONS
neuropathic pain, mood stabilization, etc. Queries to the database are Gatroenterology and Digestive Oncology, Liege, Belgium; 24Liver Unit,
anonymous, the key information that is recorded is the country of Department of Internal Medicine, Vall d’Hebron University Hospital,
origin. Barcelona, Spain; 25Virgen Macarena University Hospital, Seville, Spain;
26
Results: During 51 months of follow-up, a total of 94, 695 queries Penitentiary Health Service Region Lombardy, San Paolo Hospital
from 98 countries were recorded by website users to check DDIs University of Milan, Italy; 27Infectious Diseases, William Osler Health
between eiAEs and DAAs. The most frequently requested DAAs were System, Brampton, Ontario, Canada; 28Hospital Universitario Fundación
glecaprevir/pibrentasvir (GP; 23.3%) and sofosbuvir/velpatasvir Alcorcón, Alcorcón, Spain; 29Vancouver Infectious Diseases Centre,
(22.3%). Among the eiAEs, carbamazepine was the most frequently Vancouver, Canada; 30Centre Hospitalier Universitaire Bordeaux, France;
31
requested eiAE (37.9%) followed by phenytoin (19.9%) and oxcarba- QuIHN Ltd, Better Access Medical Clinic, Brisbane, Australia; 32Infanta
zepine (18.7%). Until recently, all of these combinations were contra- Leonor Hospital, Madrid, Spain; 33Department of Medical, Surgical and
indicated (red flag). On an individual level, the most frequently Experimental Sciences, University of Sassari, Italy; 34Hospital Prof Dr
requested DDI between an eiAE and a DAA was carbamazepine & GP Fernando Fonseca, Amadora, Portugal; 35Medical Affairs, Gilead Sciences
(n = 7, 773 queries). International, San Francisco, United States; 36Clinical Data Science,
Conclusion: During our observation period, we received an average Epidemiology, Gilead Sciences Europe Ltd, London, United Kingdom;
37
number of 1, 857 requests per month for a potential DDI between an Medical Affairs, Gilead Sciences Europe Ltd, London, United Kingdom;
38
eiAE and a DAA, demonstrating a huge demand globally for advice on Department of Gastroenterology and Hepatology, CHU Pontevedra &
concomitant use of these drugs. Our recommendations have recently IIS Galicia Sur-HEPA-C cohort, Spain
been updated to reflect recent real-life data. Given the high number of Email: [email protected]
DDI requests involving an eiAE and DAAs, we believe physicians
Background and aims: The profile of HCV patients ( pts) being
should be informed that treatment options have now been improved,
started on direct-acting antivirals (DAAs) has shifted towards more
and HCV treatment should no longer be deferred when an eiAE is on
vulnerable populations. This large real-world analysis describes the
board.
diverse profile of these populations according to age and sex.
FRI384 Method: Adult HCV pts (aged 18+ years [y]) from 37 clinical cohorts
Changing HCV patient profiles: insights from a large across nine countries treated with SOF/VEL for 12 weeks without
multinational real-world sofosbuvir/velpatasvir (SOF/VEL) ribavirin were included. Those with a history of decompensation or
dataset prior NS5A-inhibitor exposure were excluded. This descriptive
analysis evaluated pt characteristics, time to treatment (TT [time
Alessandra Mangia1, Stefano Fagiuoli2, Vito Di Marco3,
from HCV RNA diagnosis to DAA initiation]), and sustained virological
Stephen Shafran4, Mandana Khalili5, Scott Milligan6,
response ≥12 weeks after end of treatment (SVR), stratified by age
George Papatheodoridis7, Denis Ouzan8, Silvia Rosati9,
and sex.
Alnoor Ramji10, Elisabetta Teti11, Montserrat Garcia-Retortillo12,
Results: Among 6356 pts, 2274 were aged <50 y, 2568 50−65 y, and
Francisco Andrés Pérez Hernández13, Alexander Wong14,
1514 > 65 y. Within these age strata, 73%, 65%, and 45%, respectively,
Chris Fraser15, Sergio Rodriguez-Tajes16, Elena Jimenèz Mutiloa17,
were male. Vulnerable populations were well represented, and ∼20%
Luis Enrique Morano Amado18, Joss O’Loan19, Francesca Campanale20,
of all pts had a history of IV drug use. Irrespective of age, male pts
Guilherme Macedo21, Michele Milella22, Christian Brixko23,
were more likely to have compensated cirrhosis and to be infected
Maria Buti24, María Guerra Veloz25, Roberto Ranieri26,
with HCV genotype (GT) 3 (Table). Within vulnerable populations,
Sergio Borgia27, Annalisa Bascia1,
higher likelihood of incarceration among male pts was restricted to
Conrado Manuel Fernandez Rodriguez28, Brian Conway29,
those aged ≤65 y. Significantly fewer mental health disorders were
Victor de Lédinghen30, Mary Fenech31, Pablo Ryan32, Ivana Maida33,
seen in male pts. However, use of antipsychotics appeared similar,
Alexandra Martins34, Stacey Scherbakovsky35, Ioanna Ntalla36,
irrespective of sex. Median TT was shorter in male pts across the age
Candido Hernández37, Kim Vanstraelen37, Juan Turnes38. 1IRCCS-
spectrum.
Ospedale Casa Sollievo Della Sofferenza, San Giovanni Rotondo, Italy;
2 In 5845 pts with a valid result, SVR was high across age ranges, with
Asst Papa Giovanni XXIII-Lombardia HCV Network, Italy;
3 no significant differences observed between male and female pts
Gastroenterology and Hepatology Unit, Department of Health
(<50 y: female 98.7%, male 99.2%; 50−65 y: female 98.7%, male 98.1%;
Promotion Sciences Maternal and Infantile Care, Internal Medicine and
>65 y: female 99.3%, male 98.3%). 475 pts did not achieve SVR for a
Medical Specialities, PROMISE, University of Palermo, Italy; 4University
non-virological reason; mostly loss to follow-up, with no differences
of Alberta, Edmonton, Canada; 5University of California San Francisco,
between males and females across age strata.
California-TARGET cohort, United States; 6Trio Health Analytics, La Jolla,
Conclusion: SOF/VEL shows high cure rates across different age and
CA, United States; 7Department of Gastroenterology, Medical School of
sex groups. Antipsychotic drug use appeared similar in males and
National and Kapodistrian University of Athens, Laiko General Hospital
females, despite significantly fewer mental health disorders in male
of Athens, Greece; 8Institut Arnault Tzanck, Saint-Laurent du Var-HELIOS
pts. TT varied from 1 day to >6 months and was shorter in males.
cohort, France; 9INMI Lazzaro Spallanzani IRCCS Rome, Italy;
10
University of British Columbia, Vancouver, Canada; 11Infectious
Diseases Clinic, Tor Vergata University, Rome, Italy; 12Liver Section,
Gastroenterology Department, Hospital del Mar Medical Research
Institute (IMIM), Parc de Salut Mar, Barcelona, Spain; 13Head of Digestive
Disease Department, Complejo Hospitalario Nuestra Señora de
Candelaria, Santa Cruz, Spain; 14Department of Medicine, University of
Saskatchewan, Regina, Saskatchewan, Canada; 15Cool Aid Community
Health Centre, Victoria, British Colombia, Canada; 16Liver Unit, Hospital
Clinic Barcelona, IDIBAPS, Ciberehd, Spain; 17Hospital Universitario
Insular de Gran Canaria, Spain; 18Unit of Infectious Diseases, Alvaro
Cunqueiro University Hospital, Vigo, Spain; 19Kombi Clinic and Medeco
Inala, Brisbane, Australia; 20Local health department BAT, ASL BAT and
Infectious Disease Consultant of Detention Center, Trani, Italy;
21
Department of Gastroenterology and Hepatology, Centro Hospitalar
São João, Porto, Faculty of Medicine, Porto, Portugal; 22Clinic of Infectious
Diseases, University of Bari, Italy; 23CHR Citadelle, Department of

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POSTER PRESENTATIONS
Table: (abstract: FRI384): Characteristics of HCV pts in the overall population, stratified by age and sex
<50 y 50−65 y >65 y
F (n = 608) M (n = 1666) p-value F (n = 905) M (n = 1663) p-value F (n = 833) M (n = 681) p-value
F4, % 7.2 13.4 <0.001 18.7 26.1 <0.001 24.2 29.5 <0.05
GT3, % 46.7 48.3 NS 32.5 37.9 <0.01 5.3 10.9 <0.001
Vulnerable*, % 30.4 47.6 <0.001 20.0 24.3 <0.01 17.3 13.1 <0.05
Homeless, % 6.5 12.0 <0.05 2.2 8.4 <0.05 0.0 4.5 <0.05
Imprisoned, % 18.9 45.6 <0.001 5.0 29.0 <0.001 0.7 2.2 NS
Mental health disorder, % 74.6 42.4 <0.001 92.8 62.6 <0.001 99.3 93.3 <0.05
Antipsychotic drug use, % 9.2 11.8 NS 5.1 5.5 NS 2.5 3.1 NS
Median TT, days (IQR) 63 (28−128) 51 (22−113) − 69 (31−133) 56 (24−115) − 68 (31−132) 55 (28−112) −

F, females; M males; NS, not significant; IQR, interquartile range.

*Proportions of patients belonging to vulnerable subpopulations are expressed as % of the total vulnerable population.

FRI385 medication for HIV pre-exposure prophylaxis. Two patients were

Sofosbuvir plus velpatisvir for 8 weeks in patients with acute lost to follow-up. In the per protocol analysis, all patients achieved
hepatitis C: multicenter, single arm, phase 2 study (The HepNet SVR12 (n = 18/18 [100%]). Median ALT levels were 249 U/L at baseline
acute HCV-V study) and 22 U/L 12 weeks after the end of treatment, with all but one
Benjamin Maasoumy1,2,3, Patrick Ingiliz4, Christoph Spinner5, patient (94%) achieving ALT normalization. Treatment was well
Christiane Cordes6, Hans-Jürgen Stellbrink7, tolerated; by 12 weeks post-treatment, there was one serious adverse
Julian Schulze zur Wiesch8,9, Stephan M Schneeweiß10, event unrelated to study drug and 6 possible or probable drug-related
Katja Deterding11, Tobias Müller12, Julia Kahlhöfer3, Petra Dörge3, adverse events with only mild symptoms.
Maria von Karpowitz13, Michael P. Manns1, Heiner Wedemeyer1,
Markus Cornberg3,14,15,16. 1Hannover Medical School, Deptment of
Gastroenterology, Hepatology and Endocrinology, Hannover, Germany;
2
German Center for Infection Research (DZIF), Partner Site Hannover-
Braunschweig, Hannover, Germany; 3German Center for Infection
Research (DZIF), HepNet Study-House, German Liver Foundation,
Hannover, Germany; 4Zentrum für Infektiologie Berlin-Prenzlauer Berg,
Berlin, Germany; 5Technical University of Munich-School of Medicine,
Hospital Rechts der Isar, Munich, Germany; 6Praxis Dr. Cordes, Berlin,
Germany; 7Infectiology Center Hamburg (ICH), Hamburg, Germany;
8
University Medical Center Hamburg-Eppendorf, Medical Department,
Hamburg, Germany; 9German Center for Infection Research (DZIF),
Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany;
10
Praxis Hohenstaufenring, Cologne, Germany; 11University Hospital
Essen, Department of Gastroenterology and Hepatology, Essen,
Figure: Response to 8 weeks sofosbuvir (SOF) plus velpatasvir (VEL) (A)
Germany; 12Charité Campus Virchow-Klinikum (CVK), Department of
Patients with serum HCV RNA levels below <10 IU/ml in the intention-to-
Gastroenterology and Hepatology, Berlin, Germany; 13Hannover Medical
treat (ITT) and per protocol (PP) analysis. percentage ± CI (B) Decline of ALT,
School, Institute for Biometry, Hannover, Germany; 14Hannover Medical median, Friedman test with post hoc analysis
School, Deptment of Gastroenterology, Hepatology and Endocrinology,
Hannover, Germany; 15German Center for Infection Research (DZIF), Conclusion: The 8-week treatment with SOF/VEL was well tolerated
Partner Site Hannover-Braunschweig, Hannover, Germany; 16Center for and highly effective in patients with acute HCV monoinfection. Early
Individualized Infection Medicine (CiiM), Hannover, Germany treatment of hepatitis C might effectively prevent the spread of HCV
Email: [email protected] in high-risk groups and should therefore be more targeted; ideally,
approval for hepatitis C therapy should be pursued independently of
Background and aims: Sofosbuvir plus velpatasvir (SOF/VEL) is
chronic hepatitis C.
highly effective for the treatment of hepatitis C virus (HCV) infection,
but it is only approved in chronic hepatitis C. The EASL recommenda- FRI386
tions suggest 8-weeks of SOF/VEL for the treatment of acute or Full-length genome characterization of inherently resistant
recently acquired HCV infection. However, to date there are only data african HCV genotype 1, subtype 1l in patients failing DAA-based
published for 6 and 12 weeks for recently acquired HCV infection. The therapy
objective of this study was to evaluate the safety and efficacy of 8 Slim Fourati1,2,3, Erwan Vo Quang2,4, Christophe Rodriguez1,2,3,
weeks of SOF/VEL treatment for acute HCV monoinfection. Alexandre Soulier1,2, Vanessa Demontant1,2, Stéphane Chevaliez1,2,3,
Method: In this investigator-initiated, prospective, multicentre, Vincent Leroy2,3,4, Jean-Michel Pawlotsky1,2,3. 1APHP-Henri Mondor
single-arm study, we recruited a total of 20 adults (≥18 years) with Hospital, Virology, France; 2INSERM U955, “Virus Hepatology, Cancer”
acute HCV monoinfection ( proven antibody or RNA seroconversion or Team, Créteil, France; 3Paris-Est Créteil University, Créteil, France;
ALT >10 ULN with known exposure within 4 month) from nine 4
APHP-Henri Mondor Hospital, Hepatology, Créteil, France
centers in Germany between March 2019 and June 2021. Patients Email: [email protected]
received SOF/VEL (400/100 mg) as a fixed-dose combination tablet
once daily for 8 weeks. The primary efficacy endpoint was the Background and aims: Among the so-called “unusual” HCV
proportion of patients with sustained virological response (undetect- genotypes, genotype 1, subtype 1l (GT-1l) is common in patients of
able HCV RNA 12 weeks after the end of treatment, SVR12). Other African origin. GT-1l has recently been suggested to be less
endpoints included biochemical response and safety of SOF/VEL. responsive to NS5A inhibitor-containing regimens than GT-1a or
Results: The median HCV RNA viral load at baseline was 5.0 log10 IU/ GT-1b. Here, we used shotgun metagenomics based on deep
ml; the distribution of HCV genotypes was as follows: GT1a/1b/2/3/4: sequencing to generate full-length HCV genome sequences and
n = 12/1/1/3/3. Thirteen (65%) of the 20 patients were taking characterize amino acid substitutions present at baseline and

S582 Journal of Hepatology 2022 vol. 77(S1) | S389–S664

 POSTER PRESENTATIONS
selected by DAA therapy in regions targeted or not targeted by DAAs administered during hospitalization; all patients undergo monthly
in GT-1l infected patients who failed to achieve SVR. clinical and laboratory assessment.
Method: Shotgun metagenomics were used to generate full-length Patients discharged from the facility are referred for follow-up to the
HCV GT-1l genome sequences. Briefly, library preparation was Hepatology Clinic. We keep close contact with family physicians,
performed using Total RNA and Nextera XT kit (Illumina). Deep rehab centers, medical care providers and families.
sequencing was performed by means of NextSeq500 (Illumina). Full- Results: From January 2020 to November 2021 we allocated a cohort
length HCV sequences were analyzed using our original in-house of 56 HCV patients at different stages of diagnosis and treatment
MetaMIC ® software (1% cutoff ). (Table).
Results: Among 771 patients with HCV infection treated with DAAs We were able to treat 22 patients. 7 have already achieved SVR, 5 have
who experienced a virological failure and were referred to our center completed treatment and are waiting for SVR, 5 are now being treated
between 2015 and 2019, 316 (41.0%) were infected with genotype 1, and 5 are under investigation. 13 patients had negative HCV PCR due
and 20 of them (6.3%) with GT-1l. All GT-1l-infected patients were of to spontaneous recovery. Two patients died during the follow-up
African origin. Deep sequencing of full-length HCV GT-1l genomes period not due to liver disease. 7 patients were treated for HCV before
was performed in 10 patients at baseline and at time of relapse. the psychiatric hospitalization, 12 were not treated. FIB 4 was
Treatment regimens were SOF/LDV ± RBV (n = 8), SOF/VEL (n = 1) and measured in 30 patients; 43% (13 patients) were with FIB-4 score
SOF/SIM (n = 1). greater than 1.45. Fibroscan/Fibrotest examination was performed in
At baseline, all of the 10 GT-1l patients had ≥3 dominant NS5A 26 patients, with evidence of advanced fibrosis in 19% (5 patients). 19
resistance-associated substitutions (RASs), including K24G/S (>99%), patients were treated by Sofosbuvir/Velpatasvir for 12 weeks and 3
L31M (>99%) and H58P (>99%). Additionally, baseline NS5A-Q30R patients were treated with Glecaprevir/Pibrentasvir for 8 weeks.
was present in 3 patients (>99% in 2 patients; 25% in 1 patient). There were no severe adverse events during treatment.
Sequential analysis of full-length HCV genome sequences showed
enrichment of NS5A-Q30R in one patient at failure (>99%) and the
selection of NS5A RASs in other patients: baseline K24S (8% and 40%,
respectively) replaced by K24G (>99%) in 2 patients; selection of Y93F
and Y93H RASs at failure in 2 other patients (20% and 40%
respectively).
No NS5B RASs were detected. NS3 R155 K was selected in one patient
failing SOF/SIM (30%). No amino acid changes of interest were
observed at treatment failure in genome regions other than those
targeted by the HCV DAAs administered.
Data on retreatment by triple-combination regimens are ongoing and
will be presented.
Conclusion: We report the largest cohort of GT-1l-infected African
patients failing DAAs thus far. The large number of NS5A RASs present
at baseline explains lower SVR rates with NS5A inhibitor-based
therapies in these patients. Our results emphasize the need for
identifying this subtype and other “unusual” subtypes (e.g. GT-4r) in
Africa where they are common, and the urgent need to guarantee
equal access to last-generation DAA therapies in Africa.

FRI387
Treating HCV in dual diagnosis acute psychiatric inpatients with Conclusion: We present our ongoing experience of treating HCV in a
substance use disorder population of drug dependent patients with SMI during their in-
Vera Dreizin1, Yael Delayahu2, David Hovel1, Gabriela Ilionsky3, hospital stay. This model has proved efficiency in facilitating their
Neil Mfaria4, Eran Israeli1. 1Wolfson Medical center, Institute of access to care and achieving SVR where no other approach proved
Gastroenterology, Holon, Israel; 2Yehuda Abarbanel Mental Health successful.
Center, Dual Diagnosis (D) Ward, Bat Yam, Israel; 3Yehuda Abarbanel
Mental Health Center, Dual Diagnosis (D) Ward, Bat Yam, Israel; 4Yehuda
Abarbanel Mental Health Center, Bat Yam, Israel
Email: [email protected]
Background and aims: People with severe mental illness (SMI) and
substance use disorder (SUD) are at increased risk for hepatitis C
(HCV). However, only 4.7% receive screening for HCV.
Psychiatric patients with dual diagnosis (DD) of SMI and SUD have
multiple risk factors for HCV: homelessness, immigration, imprison-
ment, coinfections such as HIV or hepatitis B.
However, few treatment approaches have been studied in this patient
group.
To describe an on-going project of accessing DD patients during their
stay at a psychiatric facility for diagnostic work-up, treatment and
follow-up.
Method: We initiated a collaboration between Hepatology clinic of a
general hospital and Dual Diagnosis acute Ward (DDW) of a
psychiatric hospital for treating HCV patients.
All patients admitted to the DDW are screened for HCV AB. Patients
positive for HCV are examined at the facility by the project’s expert
hepatologist and undergo a full diagnostic workup. Treatment is

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S583

POSTER PRESENTATIONS
FRI388 Of 117 (26.8%) patients with an adverse event (AE), 5 (1.1%) had a
Eight-weeks of glecaprevir/pibrentasvir is well tolerated and serious AE (SAE), with 1 (0.2%) discontinuing the study drug due to an
yields high sustained virological response in HCV-infected AE. None of the SAEs were drug related. The most common AEs (>5%)
treatment-naive patients with compensated cirrhosis: the CREST were fatigue (9.6%; 42/437) and headache (6.4%; 28/437). Of 421
study patients with laboratory data available, 9 (2.1%) and 10 (2.4%) had
Markus Cornberg1, Armand Abergel2, Alessio Aghemo3, alanine or aspartate aminotransferase, respectively, >5x upper limit
Adriana Ahumada4, Massimo Andreoni5, Tarik Asselah6, of normal.
Abhi Bhagat7, Isabel Butrymowicz7, Michal Carmiel8,9,
Gabriel Chodik10,11, Brian Conway12,13, Antonio Gasbarrini14,
Dietrich Hüppe15, Francisco Jorquera16, Pietro Lampertico17,18,
Maria Luisa Manzano Alonso19, Lindsy Myles20, Marcello Persico21,
Alnoor Ramji22, Christoph Sarrazin23, Dimitri Semizarov7,
Yanna Song7, Erica Villa24, Clara Weil10, Juan Isidro Uriz Otano25,26.
1
Hannover Medical School, Department of Gastroenterology, Hepatology
and Endocrinology, Hannover, Germany; 2UMR 6602 CNRS Université
d’Auvergne, CHU Estaing; 3Humanitas Research Hospital IRCCS,
Department of Biomedical Sciences, Humanitas University, and
Department of Gastroenterology, Rozzano, Italy; 4Hospital General
Universitario Gregorio Marañón, Liver Unit; 5University of Tor Vergata,
Rome; 6Hôpital Beaujon, INSERM UMR 1149, Service d’Hépatologie;
7
AbbVie Inc., North Chicago, United States; 8Galilee Medical Center, Liver
Unit; 9Bar-Ilan University, The Azrieli Faculty of Medicine; 10Maccabi
Healthcare Services, Maccabitech; 11Tel-Aviv University, Sackler Faculty
of Medicine; 12Vancouver Infectious Diseases Center; 13Simon Fraser
University; 14Fondazione Policlinico Universitario A. Gemelli IRCCS,
Internal Medicine and Gastroenterology; 15Gastroenterologische
Gemeinschaftspraxis Herne; 16Complejo Asistencial Universitario de
León, IBIOMED and CIBERehd, Digestive System Service, Spain;
17
Ospedale Maggiore Policlinico, Foundation IRCCS Ca’ Granda; 18CRC
‘AM and A Migliavacca’ Centre for Liver Disease, Division of Conclusion: In this real-world cohort, 8-week G/P therapy was well-
Gastroenterology and Hepatology; 19Hospital Universitario 12 De tolerated, with SVR12 rates similar to those in clinical trials. These
Octubre, Liver Unit, Spain; 20Barrie GI Associates; 21AOU OO. RR. San results support the use of G/P therapy in TN patients with CC,
Giovanni di Dio Ruggi e D’Aragona, Dipartimento di Medicina Clinica regardless of liver disease severity or GT, including GT3. Additional
Medica, Epatologica e Lungodegenza; 22University of British Columbia; efficacy data in special populations will be presented at the congress.
23
Goethe-University Hospital Frankfurt, Department of Internal Acknowledgements: The authors would like to express their
Medicine and Liver Center, St. Josefs-Hospital Wiesbaden and Viral gratitude to the patients who participated in this study and their
Hepatitis Research Group; 24Azienda Ospedaliera Universitaria di families, as well as the study investigators and coordinators of the
Modena, UC Gastroenterologia, Dipartimento di SpecialitàMediche; study. Glecaprevir was identified by AbbVie and Enanta. Medical
25
Navarra Institute for Health Research (IdiSNA); 26Complejo writing support was provided by Marta Rossi, PhD, of Fishawack
Hospitalario de Navarra, Department of Gastroenterology, Liver Unit Communications Ltd, and funded by AbbVie.
Email: [email protected]
Background and aims: The direct-acting antiviral glecaprevir/ FRI389
pibrentasvir (G/P) is approved for 8-week treatment of chronic HCV-RNA viral load fingerstick assay as a simplified strategy for
hepatitis C genotypes (GT) 1–6 in patients with or without screening and linkage to care of people who use drugs attending 3
compensated cirrhosis (CC). To support clinical trials findings, this french addiction centers
study assessed real-world effectiveness and safety in treatment-naïve Denis Ouzan1,2, Joris Herin3, Nicolas Camerlo4, Patrick Favot5,
(TN) patients with CC treated with 8-weeks’ G/P, with a focus on Bruno Blasi4, Maella Lebrun6, Henriette Thiercelin4, Nathalie Legros7,
challenging-to-treat patients with advanced liver disease ( platelets Teresa Namouni8, Perrine Roux9, Stéphane Chevaliez10. 1Arnault
<150, 000/μl, elasticity >20 kPa [FibroScan®, Echosens, Paris, France], Institute Tzanck, Saint-Laurent-du-Var, France; 2RHECCA, NICE, France;
3
or both), and special populations such as drug users, human Bus 31/32, Marseille, France; 4CAARUD LOU PASSAGIN, Nice, France;
5
immunodeficiency virus coinfection, and psychiatric disorders. CSAPA FONDATION DE NICE, France; 6Bus 31/32, France; 7CSAPA
Method: Here we present updated interim results from the CREST FONDATION DE NICE, Nice, France; 8CSAPA EMERGENCE, Nice, France;
9
study, an ongoing, noninterventional, multicenter study including INSERM, France; 10CNR HOPITAL MONDOR, France
data from Canada, Germany, Israel, Italy, France, and Spain. The Email: [email protected]
primary endpoint was sustained virologic response at posttreatment Background and aims: Rational: The number of people who inject
Week 12 (SVR12) based on the modified analysis set (MAS) which
drugs (PWID) that are screened and treated for hepatitis C remains
excluded patients who discontinued G/P for reasons other than
low. Many of them are lost to follow-up after serological testing. It is
nonvirologic failure or with missing SVR12. Safety and laboratory
currently estimated that 20% of patients are treated in Harm
abnormalities were assessed on the full analysis set.
reduction centers (CSAPAs) and in Needle exchange structures
Results: Of 437 patients who received ≥1 dose of G/P, 24.5% (107/437) (CAARUDs). The measurement of the viral load by rapid RT-PCR
had GT3, 46.0% (189/411) had platelets <150, 000/μl, 16.4% (61/373)
from capillary blood (Xpert® HCV Viral Load Fingerstick) allows to
had elasticity >20 kPa, and 9.8% (36/366) had platelets <150, 000/μl
obtain a result in <1 hour and thus to increase the percentage of HCV-
and elasticity >20 kPa. Of 375 patients in the MAS with data available,
seropositive patients who could benefit from treatment.
SVR12 was reached by 371 (98.9%). SVR12 was 97.7% (84/86) in
Aims: The aims of this prospective study were to evaluate the
patients with GT3, 99.4% (165/166) in those with platelets <150, 000/ feasibility and the acceptability of HCV-RNA viral load fingerstick
μl, 98.1% (53/54) in those with elasticity >20 kPA, and 100% (32/32) in
assay use to improve HCV screening and treatment among French
those with both elasticity >20 kPa and platelets <150, 000/μl (Figure).
PWIDs attending 3 Addiction Centers.

S584 Journal of Hepatology 2022 vol. 77(S1) | S389–S664

 POSTER PRESENTATIONS
Method: From March 1, 2021, all HCV seropositive PWIDs ( previously treatment-naïve patients (87.5% vs. 76.7%) were documented in HIV
known positive for serology or determined using a rapid diagnostic coinfected individuals. The overall sustained virologic response after
test (RDT) simultaneous targeting HCV, HBV, and HIV) followed up in exclusion of non-virologic failures was achieved in 98% with no
3 Addiction Centers CAARUD/CSAPA (2 in Nice, 1 in Marseille) were significant difference between HIV-positive and HIV-negative
offered a rapid RNA testing using a molecular point of care testing patients, 96.2% vs. 98.5%, respectively. While the genotype-specific
(POCT) (Xpert HCV Viral Load Fingerstick). If the RNA testing was regimens resulted in a similar cure rate regardless of the HIV status,
positive, treatment was proposed. the pangenotypic options were more efficacious in patients with HCV
Results: From March 1 to August 31, 2021, 119 PWID were included: monoinfection as compared to HIV coinfected (99.3% vs. 94.4%, p =
76.5% men with an average age of 45 years, 22 were without social 0.05). No significant differences in demographic, clinical, and
rights, 26 with precarious housing and 22 homeless, 41 declared laboratory parameters were found between 13 virologic nonrespon-
having injected: heroin, crack, other, 34 inhaled: cocaine, crack, other, ders and responders.
65 having multiple addictions of which cannabis 35 and drugs 11 and Conclusion: We demonstrated the high effectiveness and good safety
67 excessive alcohol consumption. 46 were receiving substitution profile of DAA regimens in GT4 infected patients with HIV coinfec-
treatment. HCV serology was documented in 117 of the 119 DU and tion. However, the current analysis demonstrated lower effectiveness
was positive in 43 (37%) of them. HBV surface antigen (HBsAg) was of pangenotypic regimens in HIV/HCV GT4 coinfected patients
positive in 4 and HIV in 3 DU PWID (all previously known). Among compared to genotype-specific regimens.
39/43 anti-HCV+ subjects agreed to perform a rapid RNA testing, HCV
RNA was positive in 20, i.e. a prevalence of 16%. Antiviral treatment FRI391
was initiated in 12. The rate of treatment success will be presented. Long-term follow-up of HCV resistance-associated substitutions
Conclusion: Despite the high rate of HCV infection among PWIDs, after DAA treatment failure
screening and linkage to care remain far from comprehensive. Our Julia Dietz1, Beat Müllhaupt2, Peter Buggisch3, Christiana Graf1,
HCV-RNA screening project, highlights the feasibility and the Kai-Henrik Peiffer1, Katrin Matschenz3, Jörn Schattenberg4,
acceptability of onsite testing performed with HCV-RNA viral load Stefan Mauss5, Christoph Antoni6, Elena Durmashkina7,
fingerstick assay in PWIDs. This easy to use approach increases the Claus Niederau8, Thomas Discher9, Janina Trauth9, Georg Dultz1,
frequency of HCV RNA testing and the prescription of treatment. Julian Schulze zur Wiesch10, Felix Piecha10, Hartwig Klinker11,
Tobias Müller12, Christoph Neumann-Haefelin13, Thomas Berg14,
FRI390 Christoph Berg15, Stefan Zeuzem1, Christoph Sarrazin1,7. 1Goethe
Pangenotypic and genotype-specific antivirals in the treatment of University Hospital, Department of Internal Medicine I, Frankfurt,
genotype 4 infected patients with HIV coinfection Germany; 2University Hospital Zürich, Zürich, Switzerland; 3Institute for
Dorota Zarębska-Michaluk1, Jerzy Jaroszewicz2, Interdisciplinary Medicine IFI, Hamburg, Germany; 4University Medical
Anna Parfieniuk-Kowerda3, Beata Lorenc4, Małgorzata Pawłowska5, Center Mainz, Mainz, Germany; 5Center for HIV and
Wlodzimierz Mazur6, Marek Sitko7, Ewa Janczewska8, Hanna Berak9, Hepatogastroenterology, Düsseldorf, Germany; 6University Hospital
Janocha-Litwin Justyna10, Jakub Klapaczynski11, Mannheim, Mannheim, Germany; 7St. Josefs-Hospital, Wiesbaden,
Krzysztof Tomasiewicz12, Piekarska Anna13, Beata Dobracka14, Germany; 8St. Josef-Hospital, Oberhausen, Germany; 9Justus Liebig
Rafal Krygier15, Jolanta Citko16, Tronina Olga17, University Gießen, Gießen, Germany; 10University Medical Center
Krystyna Dobrowolska18, Robert Flisiak3. 1Jan Kochanowski University, Hamburg-Eppendorf, Hamburg, Germany; 11University Hospital
Department of Infectious Diseases, Kielce, Poland; 2Medical University of Würzburg, Würzburg, Germany; 12Charité Universitätsmedizin Berlin,
Silesia, Department of Infectious Diseases and Hepatology, Katowice, Berlin, Germany; 13University Hospital Freiburg, Freiburg, Germany;
Poland; 3Medical University of Białystok, Department of Infectious 14
University Hospital Leipzig, Leipzig, Germany; 15University Hospital
Diseases and Hepatology, Białystok, Poland; 4Medical University of Tübingen, Tübingen, Germany
Gdańsk, Poland; 5Ludwik Rydygier Collegium Medicum in Bydgoszcz Email: [email protected]
Faculty of Medicine Nicolaus Copernicus University in Toruń, Bydgoszcz,
Background and aims: The approval of direct acting antivirals (DAA)
Poland; 6Medical University of Silesia, Katowice, Poland; 7Jagiellonian
for the treatment of chronic hepatitis C virus (HCV) infection resulted
University, Kraków, Poland; 8Medical University of Silesia, Bytom,
in high sustained virologic response (SVR) rates. Virologic failure is
Poland; 9Hospital for Infectious Diseases, Warszawa, Poland; 10Medical
associated with the selection of resistance-associated substitutions
University of Wrocław, Wrocław, Poland; 11Central Clinical Hospital of
(RASs). Long-term persisting RASs may have an impact on retreat-
the Ministry of Internal Affairs and Administration, Warszawa, Poland;
12 ment with first generation DAAs in resource-limited settings. This
Medical University of Lublin, Lublin, Poland; 13Medical University of
study evaluated the persistence of HCV RASs up to more than 24
Łódz,́ Łódz,́ Poland; 14MED-FIX, Wrocław, Poland; 15State University of
months after end of DAA treatment (EOT).
Applied Sciences, Konin, Poland; 16Regional Hospital Olsztyn, Olsztyn,
Method: We included samples form n = 715 patients with a HCV GT1
Poland; 17Medical University of Warsaw, Warszawa, Poland; 18Jan
and GT3 infection and virologic treatment failure which were
Kochanowski University, Collegium Medicum, Kielce, Poland
collected in the European Resistance Database. HCV NS3, NS5A and
Email: [email protected]
NS5B genes were sequenced population-based and RASs conferring a
Background and aims: The introduction of the direct-acting >2-fold increased DAA susceptibility were analyzed and clinical
antivirals (DAA) has improved substantially the therapy effectiveness parameters were evaluated retrospectively.
in patients with chronic hepatitis C and we aimed to compare the Results: A total of 253 patients with HCV genotype (GT)1a (35%), 250
efficacy of pangenotypic and genotype-specific DAA in the cohort of with GT1b (35%) and 212 with GT3 (30%) were included and the mean
genotype (GT) 4 patients with HCV monoinfection and HIV sampling time point after EOT was 7.6 months (0.0–63.0). The
coinfection. majority of patients with GT1 had failed to LDV/SOF (53%) or PrOD
Method: The analysis included patients selected from the EpiTer-2 (17%) and those with GT3 to DCV/SOF (46%) or VEL/SOF (35%). NS3
database, a large retrospective multicenter national real-world study RASs reached frequencies of 70–90% after EOT in GT1 and 50% in GT3
evaluating DAA treatment in 13, 554 consecutive individuals with after PI failure and disappeared rapidly in GT1b and GT3 after follow-
hepatitis C virus (HCV) infection. up month 3 (FU3), while in GT1a RASs were stable (≥60%), due to
Results: A total of 662 GT4-infected patients, of whom 168 (25.3%) Q80 K.
were coinfected with HIV, treated in 2015–2020 were enrolled in the Within NS5B, SOF-resistant RAS S282 T was only found in individual
analysis. Significantly higher rate of males (67.9% vs. 57.7%), a lower patients with GT3a. Non-nucleoside NS5B RASs were frequent (60%–
proportion of liver cirrhosis (10.2% vs. 18.1%), and higher of 90%) in GT1 and declined to 27% in GT1a while remaining stable in

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POSTER PRESENTATIONS
GT1b. NS5A RASs were very common (90%–95% after EOT) in all GT FRI393
and even after FU24, RASs were detectable in more than 70% of the Polypharmacy and prevalence of multi drug-drug interactions in
patients. RAS patterns in GT1b were dominated by L31M and Y93H hepatitis C patients treated with pangenotypic direct acting
and both variants showed a stable course over time (FU24: 95% antivirals: an analysis from three European countries
patients with RASs). Several different RASs were detected in GT1a, Frank Tacke1, Juan Turnes2, Andreas Hintz3, Stefano Fagiuoli4,
most common were M28 T, Q30H/R, L31M and Y93H. However, NS5A Antoni Sicras-Mainar5, Tim Umland3, Luca Degli Esposti6,
RASs slightly decreased in GT1a and GT3a which was mainly caused Ramón Morillo Verdugo7, Antonio Garcia Herola8,
by the decline of high-level resistant Y93H (FU24: GT1a, 71% and GT3, Mehtap Guendogdu9, Marinela Mendez10, Gema Alvarez Nieto11,
73% of patients with RASs). Kim Vanstraelen12, Candido Hernández12, Alessandra Mangia13.
Conclusion: After DAA failure, NS3 and NS5B RASs disappeared 1
Charité-Universitätsmedizin Berlin, Berlin, Germany; 2Complejo
quickly and NS5A RASs persisted beyond two years after EOT. While Hospitalario Universitario de Pontevedra, Gastroenterology and
NS5A RASs remained stable in HCV GT1b, patients with GT1a and GT3 Hepatology, Spain; 3Alexander Apotheke, Hamburg, Germany; 4ASST
showed a decrease in particular of Y93H two years after EOT. Papa Giovanni XXIII Hospital, Bergamo, Italy; 5Atrys health, HEOR,
Barcelona, Spain; 6Clicon S.r.l., Health Economics and Outcomes
FRI392 Research, Ravenna, Italy; 7Hospital Universitario de Valme, Hospital
Real-life effectiveness and safety of sofosbuvir/velpatasvir in Pharmacy, Sevilla, Spain; 8Hospital Marina Baixa, Villajoyosa, Spain;
difficult to treat hepatitis C patients 9
Gilead Sciences GmbH, Medical Affairs, München, Germany; 10Gilead
Hyun Young Woo1, Jeong Heo1, Young Joo Park1. 1Pusan National Sciences S.L., Medical Affairs, Madrid, Spain; 11Gilead Sciences S.r.l,
University Hospital, Internal Medicine, Busan, Korea, Rep. of South Medical Affairs, Milan, Italy; 12Gilead Sciences, Global Medical Affairs,
Email: [email protected] United Kingdom; 13Fondazione "Casa Sollievo della Sofferenza" IRCCS,
Background and aims: In spite of recent advance in the treatment of San Giovanni Rotondo, Italy
hepatitis C virus (HCV), there are still difficult to treatment Email: [email protected]
population such as prior direct antiviral agents (DAA) failure, Background and aims: Current EASL, AASLD and APASL guidelines
decompensated cirrhosis or presence of hepatocellular carcinoma recommend a thorough drug–drug interaction (DDI) evaluation
(HCC). Here we report our experience about these patients treated before starting pangenotypic direct-acting antiviral ( pDAA) therapy.
Sofosbuvir/Velpatasvir (SOF/VEL) in real world setting. Previous studies have analyzed DDIs in HCV patients receiving pDAAs
Method: All consecutive patients with HCV receiving SOF/VEL and comedications only by pairwise interactions. However, this does
between August 2017–May 2021 in South Korea were enrolled. not reflect the polypharmaceutical reality of many HCV patients. The
Sustained virological response (SVR) was defined as undetectable aim of this study was to evaluate the proportion of HCV patients with
HCV-RNA 12 (SVR12) weeks after the end-of-treatment. multiple comedications causing potential DDIs in three European
Results: A total of 37 patients were included: median age 65 (45–83) countries.
years, 59.5% males, median HCV-RNA 852, 500 (11, 100–10, 800, 000) Method: Comedication prescription data were collected from
IU/ml. HCV genotype was 1b in 67.6%, 2 in 29.7%, 1b &2b in 2.7%. 37.8% patients treated with pDAAs in Germany, Italy, and Spain. DDIs
have concomitant HCC (BCLC stage A/B/C; 4/8/2). 56.8% have were identified using the Liverpool Hep Interaction checker. A multi-
underlying cirrhosis and 7.5% was decompensated cirrhosis. 70.3% DDI profile was defined as the use of ≥2 comedications each predicted
have failed prior DAA treatment (Daclatasvir + asunaprevir n = 16, with a DDI with the administered pDAA. Potential DDI outcomes
sofosbuvir+ribavirin n = 3, sofosbuvir + ledipasvir n = 2, glencaprevir+ were summarized as an increase in comedication exposure (impact
pibrentasvir n = 3, boceprevir n = 1) Naïve patients received SOF/VEL on safety) or a decrease in DAA exposure (impact on efficacy).
for 12 weeks and the patients with prior DAA failure received SOF/VEL Results: A total of 10, 755 HCV patients (mean age: 53.6 years, 64.2%
for 24 weeks, ribavirin was added in 78.4% of treatment schedules. male) treated with either sofosbuvir/velpatasvir (n = 4583) or
Undetectable HCV-RNA was achieved by 97.2% of patients at week 4 glecaprevir/pibrentasvir (n = 6172) were included in this multi-
and end of treatment response was 97.2%. Overall, 36/37 (97.2%) national analysis: 4950 from Germany, 4185 from Italy, and 1620
patients by intention to treat analysis and 36/36 (100%) by per protocol from Spain. Over one-half, 58.9% (6333/10, 755) received any
analysis achieved SVR12, respectively; One patient was expired due to comedication during their pDAA therapy, and 20.2% (2177/10, 755)
HCC progression during SOF/VEL treatment. Most patient well were at risk of a DDI with their pDAA. In terms of multi-DDI risk, 566
tolerated treatment without adverse events. patients were taking ≥2 comedications, each with a potential DDI
Conclusion: SOF/VEL is an effective and safe retreatment for difficult with their pDAA. This represented 5.3% (566/10, 755) of the HCV
to treat HCV population in a real-life setting. patient population and 8.9% (566/6333) of patients receiving any
comedication. Evaluation of predicted DDI impact revealed that
approximately one-quarter (23.9%; 135/566) of patients taking ≥2
comedications had a risk of decreasing DAA plasma exposure, mainly
caused by gastrointestinal drugs, such as proton-pump inhibitors,
and analgesics, such as metamizole. This was observed mainly in
Germany and Spain. A further one-quarter of patients (26.5%; 150/
566) had a risk of increasing comedication, posing a potential safety
risk, mainly in cardiovascular drugs, such as statins, and nervous
system drugs, such as antipsychotics.
Conclusion: Across Germany, Italy, and Spain, 8.9% of HCV patients
taking medications concomitantly during their pDAA therapy are at
risk of multiple DDIs. Accurate prediction of the impact of multiple
DDIs on pDAA efficacy and safety is difficult; this should prompt a
thorough pDDI assessment before HCV therapy in comorbid patients.

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 POSTER PRESENTATIONS
FRI394 FRI395
Use of comedication in patients with hepatitis C and addiction or Five years of progress towards achieving hepatitis C elimination in
drug abuse treated with direc-acting antivirals: implication in the country of Georgia, April 2015-October 2021
drug-drug interactions Tengiz Tsertsvadze1,2, Amiran Gamkrelidze3, Nikoloz Chkhartishvili1,
Juan Turnes1, Antonio Garcia Herola2, Ramón Morillo Verdugo3, Akaki Abutidze1,2, Lali Sharvadze2,4, Vakhtang Kerashvili1,
Marinela Mendez Pertuz4, Cristina De Alvaro5, Candido Hernández6, Maia Butsashvili5, David Metreveli6, Lia Gvinjilia7,
Antoni Sicras-Mainar7. 1CHU, Pontevedra, Gastroenterology and Tinatin Kuchuloria7, Shaun Shadaker8, Tamar Gabunia9,
Hepatology Department, Pontevedra, Spain; 2Hospital Marina Baixa de Ekaterine Adamia10, Stefan Zeuzem11, Nezam Afdhal12,
Villajoyosa, Digestive Medicine Department, Alicante, Spain; 3Hospital Sanjeev Arora13, Karla Thornton13, Paige A Armstrong8. 1Infectious
de Valme, AGS Sur de Sevilla, Hospital Pharmacy, Sevilla, Spain; 4Gilead Diseases, AIDS and Clinical Immunology Research Center, T’bilisi,
Sciences S.L., Madrid, Spain, Medical Affairs, Madrid, Spain; 5Gilead Georgia; 2Ivane Javakhishvili Tbilisi State University, T’bilisi, Georgia;
3
Sciences S.L., Madrid, Spain, Medical Affairs, Madrid, Spain; National Center for Disease Control and Public Health, T’bilisi, Georgia;
6 4
Gilead Sciences Europe Ltd, Global Medical Affairs, United Kingdom; Clinic Hepa, T’bilisi, Georgia; 5Health Research Union, Tbilisi; 6Medical
7
Atrys Health, Health Economics and Outcomes Research, Barcelona, Center Mrcheveli; 7The Task Force for Global Health; 8Centers for Disease
Spain Control and Prevention, Division of Viral Hepatitis National Center for
Email: [email protected] HIV, Hepatitis, STD&TB Prevention, Atlanta, USA; 9Ministry of IDPs,
Labour, Health and Social Affairs of Georgia, Tbilisi, Georgia; 10Ministry
Background and aims: In previous studies we have analysed drug-
of IDPs from the Occupied Territories, Labour, Health, and Social Affairs
drug interactions (DDIs) in the general population. In this sub-
of Georgia; 11University of Frankfurt; 12Beth Israel Deaconess Medical
analysis we focus on patients with addiction to substance or drug
Center Liver Center; 13University of New Mexico
abuse. The objective is to describe the drug use, comedication and the
Email: [email protected]
associated risk of drug interactions.
Method: Retrospective observational study, obtained from the BIG- Background and aims: Georgia launched the world’s first national
PAC database (Atrys Health), on HCV patients ( pts) treated between hepatitis C elimination program in April 2015. Key strategies include
2017 and 2020. Possible DDIs with direct-acting antivirals (DAAs) nationwide screening, active case finding, linkage to care, decen-
(Sofosbuvir/Velpatasvir [SOF/VEL] and Glecaprevir/Pibrentasvir tralized care, and provision of treatment for all persons with hepatitis
[GLE/PIB]) were evaluated using the University of Liverpool C virus (HCV) infection, along with effective prevention interven-
Interactions for Hepatitis database. The risk of DDIs was analyzed, tions. The elimination program aims to achieve the following targets:
as well as their potential outcome: increase (↑) in comedication a) diagnose 90% of HCV-infected persons, b) treat 95% of those
concentration or ↑ DAA ( possible impact on safety) and decrease in diagnosed, and c) cure 95% of those treated. We report progress
DAA, ↓DAA ( possible impact on efficacy). towards elimination targets 5 years into the elimination program.
Results: 985 pts with history or current consumption of abuse and Method: The estimated number of persons living with HCV infection
recreational substances were included, 450 for SOF/VEL (mean age: was based on a 2015 population-based national seroprevalence
53 years; men 65%; F3/4 42%) and 535 with GLE/PIB (mean age: 50 survey, which showed that 5.4% of the adult general population had
years; men 65% F3/4 30%). The most consumed substances are chronic HCV infection (approximately 150, 000 persons). We
described in the table, highlighting the higher consumption of analyzed data in the national HCV screening and treatment databases
opioids in pts treated with SOF/VEL vs GLE/PIB (13% vs 9%, p < 0.05, during April 2015–October 2021.
respectively). Results: As of October 31, 2021, 146, 533 persons screened positive for
The mean number of medications prescribed was 3.9 for SOF/VEL and HCV antibodies, 145, 572 of whom were adults. Of the adults who
2.1 for GLE/PIB ( p < 0.001). The most prescribed drugs belonged to screened positive, 119, 280 (81.9%) underwent HCV viremia testing. A
the nervous system (40%); anti-infectives for systemic use, (13%); total of 94, 891 (79.6%) persons tested had active HCV infection, and
cardiovascular (12%) and alimentary system (12%). 76, 149 (80.2%) of them initiated treatment. Of 53, 806 patients who
GLE/PIB presented a higher percentage of potential DDIs than SOF/ were evaluated for sustained virologic response (SVR), 53, 230
VEL, with nervous system medication (8.5% vs 4.9%, p < 0.01) and (98.9%) tested negative for HCV by PCR. Based on the 90-95-95
cardiovascular (36.8% vs 13.7%, p < 0.001); and similar for alimentary program goal, Georgia has diagnosed 63.3% of the estimated 150, 000
system (45.4% vs 44.7%, ns) and anti-infectives (5.8% vs 6.9%, ns). The adults living with chronic HCV, treated 59.4% of the target 128, 250,
most prescribed nervous system drugs with potential DDIs were and cured 43.7% of the target 121, 837.
quetiapine and metamizole. High cure rates were achieved for all HCV genotypes: 98.9% in
genotype 1, 98.9% in genotype 2 and 98.3% in genotype 3, typically
the most challenging to treat. Treatment effectiveness was compar-
able among persons with advanced fibrosis (F3 and F4) with 98.2%
achieving SVR, and among patients with mild or no liver fibrosis
(≤F2), SVR = 99.1%.
Conclusion: Georgia has made substantial progress towards elimin-
ating hepatitis C. Over 60% of persons with chronic HCV infection
have been diagnosed, and most have initiated treatment with high
cure rates regardless of fibrosis status. Challenges remain in
identifying and linking to care persons living with HCV in Georgia.
The Nationwide integrated, decentralized model of HCV treatment,
Conclusion: In Spain, 9% of HCV patients with addictions to which has already been implemented in many locations, will be
substance or drug abuse taking ≥2 comedications are at risk of critical to improve linkage to care and close gaps in the HCV cascade
multi-DDIs. of care.

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POSTER PRESENTATIONS
FRI396 FRI397
Simplifying mathematical-based response guided therapy for Epidemiology of hepatitis B virus infection among hepatitis C
reducing duration of direct acting antivirals in chronic hepatitis C (HCV) infected patients treated within HCV elimination program
infected patients in Georgia
Ashish Goyal1, Alex Churkin2, Danny Barash3, Scott Cotler1, Senad Handanagic1, Maia Butsashvili2, Shaun Shadaker1,
Amir Shlomai4,5, Ohad Etzion6, Harel Dahari1. 1Program for Irina Tskhomelidze3,3,3, Paige A Armstrong1. 1Centers for Disease
Experimental & Theoretical Modeling, Division of Hepatology, Control and Prevention, Division of Viral Hepatitis, Atlanta, United
Department of Medicine, Stritch School of Medicine, Loyola University States; 2Health Research Union, Tbilisi, Georgia; 3The Task Force for
Chicago, Maywood, United States; 2Department of Software Global Health, Tbilisi, Georgia
Engineering, Sami Shamoon College of Engineering, Beer-Sheba, Israel; Email: [email protected]
3
Department of Computer Science, Ben-Gurion University, Beer-Sheba,
Background and aims: Patients with hepatitis C virus (HCV) and
Israel; 4Department of Medicine D and The Liver Institute, Rabin Medical
hepatitis B virus (HBV) co-infection are at an increased risk of
Center, Beilinson Hospital, Petah-Tikva; 5Sackler Faculty of Medicine, Tel
developing liver disease compared with mono-infected individuals.
Aviv University, Tel Aviv; 6Soroka University Medical Center, Beer-Sheba
The Georgia Hepatitis C Elimination Program was established in 2015
Email: [email protected]
and offers free treatment with direct-acting antivirals (DAA) to all
Background and aims: We recently reported the first proof-of- persons with HCV infection. The program includes HBV screening for
concept clinical trial assessing in real-time the utility of response- all HCV infected patients. We describe the epidemiology of HBV/HCV
guided therapy (RGT) with direct-acting antivirals (DAA) in chronic co-infection among patients treated within the HCV elimination
hepatitis C virus (HCV) infected patients, based on a mathematical program.
modeling approach (Etzion et al. Scientific Reports. 2020;10:17820). Method: Data for this analysis comes from the national electronic
The RGT modeling approach relies on measuring HCV at baseline and HCV elimination program treatment database. Persons aged ≥18
days 2, 7, 14 and 28 after initiation of DAA therapy. A simplified on- years with active HCV infection who initiated HCV treatment within
treatment HCV monitoring procedure is highly warranted. the program during May 2015–September 2021 were included.
Method: The mathematical model used in the proof-of-concept Patients were grouped as HCV mono-infected, HCV/HBV coinfected
study was re-fitted with the measured HCV kinetic data obtained (HBV surface antigen [HBsAg] positive), and HBV immune but not
from the 10 patients for whom the model was used to shorten the infected (HBV surface antibody or HBV core antibody positive, HBsAg
standard 12-week DAA therapy duration. The fitting procedure negative). We present descriptive analysis and adjusted prevalence
consisted of finding the best fits using corrected Akaike Information ratios (aPR) with 95% confidence intervals (CI) for HCV/HBV
Criteria. The predicted time to cure (TTC) was defined as the time it coinfection compared to HCV mono-infection for demographic,
takes during DAA therapy to reach less than 1 viral copy in the serum risk, clinical and treatment outcomes. aPRs were adjusted for age,
(i.e. 7 × 10−5 copies/ml). The first data point below detection or lower sex, HCV genotype, and history of injection drug use in a multi-
limit of quantification (LLOQ) was assigned a value (∈[0.2, 15] IU/ml) variable model.
as done in the proof-of-concept study. We next removed either day 2 Results: As of September 2021, 71, 931 adult persons were treated for
or day 7 from the 10 patients and repeated the same procedure HCV and screened for HBV within the HCV elimination program in
projecting TTC. Modeling calibration was done using MATLAB Georgia. The majority were 18–45 years old (48%; median age 46,
R2021a. interquartile range 39–55 years), male (78%), and did not report a
Results: We first verified that fitting the model to all the measured history of injection drug use (57%).
data points measured in the proof-of-concept study were in Overall, 70% (n = 50, 103) had HCV mono-infection, 28% (n = 2, 202)
agreement with the current modeling approach (Table 1). had HCV mono-infection and were immune to HBV, and 2% (n = 1,
Excluding day 2 did not affect maximum TTC projections (Table 1) 626) had HBV/HCV co-infection. HBV/HCV co-infection was more
and TTC were significantly correlated (r = 0.91, p = 0.0007) with the common among persons who were 18–45 compared to 46–60 years
predicted TTC based on all measured data points. Notably, while old (aPR: 1.7, 95% CI: 1.5–2.0), male (aPR: 1.3, 95% CI: 1.1–1.6),
excluding day 2 caused potential non-identifiability in estimating reported a history of injection drug use (aPR: 1.3, 95% CI: 1.1–1.5), had
HCV viral clearance from circulation, the estimation of TTC remained serum end of treatment (EOT) ALT >80 U/L compared to <40 U/L (aPR:
unaffected. In contrast, excluding day 7 would lead to overestimation 2.3, 95% CI: 1.6–3.4), and did not achieve sustained virologic response
of the maximum TTC projections (r = 0.29, p = 0.45) (Table 1). (aPR: 1.4, 95% CI:1.1–1.9).
Conclusion: HBV/HCV co-infection is associated with higher risk of
liver disease, elevated EOT ALT, and DAA treatment failure. To improve
outcomes for patients with HBV/HCV co-infection, it is essential to
evaluate them for HBV treatment. Promoting preventative measures,
such as HBV vaccination among patients with HCV infection, is also
important to reduce mortality from hepatitis.

Conclusion: The current analysis indicates that on-treatment day 2

viral load measurement is not necessary to predict TTC. Measuring
HCV at baseline and days 7 and 14 after initiation of DAA therapy
provides a simplified on-treatment monitoring procedure during
modeling-based RGT. Further validation in a large-scale clinical trial,
will support the routine implementation of our individualized
treatment approach in patients receiving DAA for HCV.

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 POSTER PRESENTATIONS
FRI398 lethal mutagenesis against HCV. Here we have investigated the
Direct-acting antivirals and the risk of hepatitis B reactivation in effectiveness of these strategies once the infection has been initiated,
hepatitis B and C coinfected patients: a systematic review and as a stringent tests of antiviral efficacy. Combinations of inhibitors
meta-analysis and combinations of lethal mutagens were compared. Since new
Joo Hyun Oh1, Sang Bong Ahn1, Jeong-Ju Yoo2, Dae Won Jun3, antiviral designs based on sequential inhibitor-mutagenic have
Hyunwoo Oh4, Huiyul Park5, Joo Hyun Sohn6, Hyo Young Lee4, proven effective for the extinction of RNA viruses, sequential versus
Bo-Kyeong Kang7, Mi Mi Kim7, Eileen Yoon3, Chul-min Lee7. 1Nowon combination therapies have been also examined for suppression of
Eulji Medical Center, Eulji University School of Medicine, Department of high fitness HCV infectivity once the infection was ongoing.
Medicine, Seoul, Korea, Rep. of South; 2Soonchunhyang University Method: Low and high fitness HCV populations were used to infect
Bucheon Hospital, Department of Medicine, Gyeonggi-do, Korea, Rep. of Huh-7.5 hepatoma cells in the absence and presence of mutagenic
South; 3Department of Internal Medicine, Hanyang University College of (ribavirin and favipiravir) and non-mutagenic (sofosbuvir and
Medicine, Seoul, Korea, Rep. of South; 4Uijeongbu Eulji Medical Center, daclatasvir) antiviral agents. Treatment efficacy was analyzed by
Department of Medicine, Gyeonggi-do, Korea, Rep. of South; 5Uijeongbu measuring virus progeny production when antivirals were adminis-
Eulji Medical Center, Department of Family Medicine, Gyeonggi-do, tered at different times after infection. In addition, sequential and
Korea, Rep. of South; 6Hanyang University College of Medicine, combination treatments were compared for the extinction these
Department of Medicine, Gyeonggi-do, Korea, Rep. of South; 7Hanyang viruses.
University College of Medicine, Department of Radiology, Seoul, Korea, Results: The results indicate that low and high fitness viruses were
Rep. of South not extinguished by combinations of mutagenic antivirals once the
Email: [email protected] infection is ongoing. Treatment efficacy was lower when time of
infection increased. Sequential and combination therapies produced
Background and aims: Hepatitis B virus (HBV) reactivation may a similar inhibition, without achieving viral extinction.
occur in chronic hepatitis C (CHC) coinfected patients using direct-
acting antivirals (DAAs). However, previous studies have reported
inconsistent findings on this issue. We investigated the association
between DAA and HBV reactivation by conducting a meta-analysis.
Method: Relevant studies were identified by searching Medline,
EMBASE, Cochrane Central Register of Controlled Trials, KoreaMed,
KMbase, and RISS to September 4th, 2020. The primary outcome was
HBV reactivation. Random effect method was used for pooling the
data.
Results: We identified 39 articles, comprising 119, 484 patients with
chronic (n = 1, 673) or resolved (n = 13, 497) HBV infection who
treated with DAA. When all studies were pooled, the rate of HBV
reactivation was 12% (95% confidence interval (CI) 0.06–0.19). When
stratified by baseline HBV DNA, undetectable HBV DNA (HBV DNA
<20 IU/ml) group showed significantly lower risk of reactivation
compared to detectable HBV DNA group (odds ratio (OR) 0.30, 95% CI
0.11–0.86). Although patients on prophylactic anti-HBV therapy
showed a lower reactivation rate, there was no significant difference
(OR 0.27, 95% CI 0.07–1.01). The rate of HBV reactivation was only 0.4%
in patients with resolved HBV infection.
Conclusion: The risk of HBV reactivation was not negligible in HCV
coinfected patients using DAAs, indicating watchful attention for HBV
reactivation is still needed.
Key Words: Direct -acting antivirals, hepatitis B virus, hepatitis C
virus, reactivation

FRI399
Inhibition of high fitness viruses by different antiviral strategies
when the infection has started
Carlos García-Crespo1, Lucía Vázquez-Sirvent1, Maria Eugenia Soria1,
Isabel Gallego1, Ana Isabel de Ávila1, Brenda Martínez-González1,2,
Esteban Domingo1,3, Celia Perales1,2,3. 1Centro de Biología Molecular
Severo Ochoa, Department of Interactions with the environment,
Madrid, Spain; 2Hospital Universitario Fundación Jiménez Díaz,
Department of Clinical Microbiology, Madrid, Spain; 3Centro de
Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas,
Spain
Email: [email protected]
Background and aims: Previous results from our laboratory have
documented that high fitness hepatitis C virus (HCV) can be a
determinant of multidrug resistance, including nucleotide analogues,
without the acquisition of specific resistance mutations. However, we
recently demonstrated using favipiravir (T-705) and ribavirin that
analogue concentrations that individually did not extinguish high
fitness HCV in ten serial infections, when used in combination led to Conclusion: The time at which antiviral agents were administered
extinction in a few passages. With these two nucleotide analogues, once the infection have been initiated influenced viral extinction
we have described for the first time a new synergy mechanism in independently of the mechanism of action of the antivirals (both

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POSTER PRESENTATIONS
non-mutagenic and mutagenic agents). Also, the data reinforce that FRI401
high viral fitness is a determinant of drug resistance independently of Optimal screening and linkage to care model to achieve hepatitis
the type of therapy used (sequential and combination therapies). No C elimination targets in Georgia
significant differences were observed between both therapies for the Tengiz Tsertsvadze1,2, Amiran Gamkrelidze3, Nikoloz Chkhartishvili1,
extinction of high fitness HCV. Akaki Abutidze1, Lali Sharvadze2,4, Vakhtang Kerashvili1,
Manana Todua2, Maia Butsashvili5, David Metreveli6, Lia Gvinjilia7,
FRI400 Tinatin Kuchuloria7, Shaun Shadaker8, Tamar Gabunia9,
Treatment of hepatitis C in primary healthcare in the country of Ekaterine Adamia9, Stefan Zeuzem10, Nezam Afdhal11,
Georgia Sanjeev Arora12, Karla Thornton12, Paige A Armstrong8. 1Infectious
Tengiz Tsertsvadze1,2, Amiran Gamkrelidze3, Nikoloz Chkhartishvili1, Diseases, AIDS and Clinical Immunology Research Center; 2Ivane
Akaki Abutidze1, Lali Sharvadze2,4, Maia Butsashvili5, Javakhishvili Tbilisi State University; 3National Center for Disease
David Metreveli6, Lia Gvinjilia7, Tinatin Kuchuloria7, Control and Public Health; 4Clinic Hepa; 5Health research union;
Shaun Shadaker8, Tamar Gabunia9, Ekaterine Adamia9, 6
Medical Center Mrcheveli; 7The Task Force for Global Health; 8Centers
Stefan Zeuzem10, Nezam Afdhal11, Sanjeev Arora12, Karla Thornton12, for Disease Control and Prevention, Division of Viral Hepatitis National
Paige A Armstrong8. 1Infectious Diseases, AIDS and Clinical Center for HIV, Hepatitis, STD&TB Prevention, Atlanta, USA; 9Ministry of
Immunology Research Center; 2Ivane Javakhishvili Tbilisi State IDPs, Labour, Health and Social Affairs of Georgia, Tbilisi, Georgia;
University; 3National Center for Disease Control and Public Health; 10
University of Frankfurt; 11Beth Israel Deaconess Medical Center Liver
4
Clinic Hepa; 5Health research union; 6Medical Center Mrcheveli; 7The Center; 12University of New Mexico
Task Force for Global Health; 8Centers for Disease Control and Email: [email protected]
Prevention, Division of Viral Hepatitis National Center for HIV, Hepatitis,
STD&TB Prevention, Atlanta, USA; 9Ministry of IDPs, Labour, Health and Background and aims: Access to care and treatment is essential to
Social Affairs of Georgia, Tbilisi, Georgia; 10University of Frankfurt; achieving hepatitis elimination, however, ensuring all patients can
11
Goethe University Hospital; 12University of New Mexico navigate the care pathway is challenging and involves multiple steps.
Email: [email protected] Despite marked success of Georgia’s National Hepatitis C Elimination
Program, with over 75, 000 persons initiating treatment April 2015–
Background and aims: With technical assistance from the U.S. CDC October 2021, since a peak in October 2016, patient enrollment in
and support from Gilead Sciences, Georgia launched the world’s first treatment has slowed. Developing an optimal model to ensure
national hepatitis C elimination program in April 2015. By October linkage-to-care at critical steps in the care cascade is paramount for
2021, more than 75 thousand persons initiated treatment, achieving the elimination program.
>98% cure rates. Patient enrollment in hepatitis C virus (HCV) Method: We evaluated the effectiveness of various linkage-to-care
treatment sharply increased in 2016, but has since slowed due to modalities to assess diagnostic yield and engagement in hepatitis C
challenges in HCV testing and linkage to care. To increase initiation of virus (HCV) treatment. HCV care cascades for the period of March
treatment, Georgia began service decentralization in 2018 by 2018–November 2020 were analysed and classified into 6 categories
integrating HCV screening and treatment in primary healthcare based on where the initial screening was performed: centralized and
centers (PHCs). decentralized hospital sector, primary healthcare, harm reduction,
Method: By July 31 2021, a total of 10 PHCs were providing HCV care specialized HCV provider sites and integrated HCV/HIV/TB screening
services throughout the country. The integrated model is based on locations. We defined linkage to care as: 1) completion of a viremia
“one stop shop” approach, where patients receive all HCV screening test after screening HCV antibody (anti-HCV) positive; and 2)
and care services in selected PHCs. Treatment naïve patients with no establishment of a follow-up appointment for treatment with a
or mild fibrosis (FIB-4 score <1.45) receive care at PHCs and hepatitis C specialist.
completed examinations according to a simplified diagnostic and Results: Analysis included 24, 460 anti-HCV positive persons.
treatment monitoring algorithm, and persons with FIB-4 score >1.45 Persons engaged through the HCV provider site model had the
were referred to specialized clinics. Patients received Sofosbuvir/ highest rates of both viremia testing and engagement in treatment
Ledipasvir or Sofosbuvir/Velpatasvir for 12 weeks. Sustained viro- (91.5% and 87.1%, respectively). These were significantly higher than
logical response (SVR) was defined as undetectable HCV RNA 12–24 all other models, including harm reduction (86.2% and 77.8%),
weeks after end of therapy. The Extension for Community Healthcare decentralized hospital sector (79.5% and 61.6%), integrated HCV/
Outcomes (ECHO) telemedicine model was used to train and support HIV/TB (75.1% and 79.9%), centralized hospital sector (74.5% and
primary healthcare providers. Regular teleECHO videoconferencing 45.6%), and primary healthcare (63.6% and 69.1%) models; all p <
was conducted to provide primary care providers with advice and 0.0001. The primary healthcare model had the lowest rate of viremia
clinical mentoring. testing (63.6%), while the centralized hospital sector had the lowest
Results: Among persons diagnosed with active HCV infection, 1, 454 engagement in treatment (45.6%).
were evaluated for FIB-4 score. A total of 954 patients initiated Conclusion: Our data suggest the HCV provider site screening model
treatment, and of them 883 (92.6%) completed treatment. Of 864 has been most successful in linking persons to care, for both viremia
patients eligible for SVR testing, 696 (80.6%) had been tested at the testing and initiation of treatment. Universal inpatient screening has
time of analysis, and 683 (98.1%) achieved SVR, yielding a >98% cure been effective at testing large numbers of people; among the hospital
rate. sector models, the decentralized approach to testing had higher rates
Conclusion: Our study reported the effectiveness of a simplified HCV of viremia testing and treatment. Decentralization of care is key to
treatment model in PHCs. Expanding this integrated decentralized providing access to all, but the primary healthcare model showed the
model of HCV treatment nationwide would provide an opportunity to lowest rate of viremia testing in our study.
improve linkage to care and close gaps in the HCV cascade of care.
FRI402
Establishing a protocol for management and DAA treatment of
HCV during pregnancy: adherence to a co-located care protocol
Tatyana Kushner1, Marcia Lange1, Rhoda Sperling1,
Douglas T Dieterich1. 1Icahn School of Medicine at Mount Sinai
Email: [email protected]
Background and aims: There are currently no recommendations for
directly acting antiviral (DAA) therapy during pregnancy. Emerging

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 POSTER PRESENTATIONS
data suggests that DAAs are safe and effective during pregnancy. We clinical trials enrolling other patient populations. There remains a
evaluated our center experience in implementing DAA treatment need to replicate these results in more vulnerable populations,
during pregnancy. including those using fentanyl and not currently engaged in health
Method: After establishment of a sub-specialty Women’s Liver Clinic care.
(WLC) co-located in the ambulatory obsetrics practice and imple- Method: Through dedicated outreach events, we identified HCV-
mentation of universal antepartum HCV screening, we offered DAA infected patients who resided in single room occupancy dwellings
treatment during pregnancy to women with active HCV. We who were not currently engaged in health care and who were eligible
evaluated adherence to each step in the HCV treatment cascade of to receive government-funded antiviral treatment for HCV infection.
care. We offered them the opportunity to enrol in a multidisciplinary
Results: Twenty-three pregnant women with active HCV infection program of care to address medical, psychological, social and
were referred to WLC for consideration for HCV treatment; they were addiction-related needs and provide S/V therapy in this context,
of median age 31 (IQR 24, 36); predominantly white (39%) non- with daily or weekly supervision of adherence, as appropriate. The
Hispanic (52%), and medicaid-insured (78%); 30% with injection drug endpoint of this preliminary analysis is the achievement of SVR12 in
use as a risk factor; 9% who acquired HCV through perinatal those who initiated therapy.
transmission; 26% with no known risk factors. Fifteen (65%) reported Results: We identified 172 eligible HCV-infected treatment-naïve
that HCV was initially diagnosed during pregnancy. Adherence to subjects who were subsequently enrolled in the program. HCV
cacade of care is shown in the Figure. Initial DAA ordered was diagnosis was documented 1–41 years before enrolment. Key
ledipasvir/sofosbuvir for 7 (42%), ledipasvir/velpatasvir for 7 (42%) demographic characteristics include: 126 (73%) male, median age
and gleceprevir/pibrentasvir for 2 (12%). Among those with DAA 47 (23–75) years, F0/1 (120, 70%), ≥F2 (52, 30%), opiate/cocaine/
approval, nine (45%) received their DAA during pregnancy and seven amphetamine use (126/66/112, 73%/38%/65%). Once enrolled in care,
(35%) initiated DAA treatment during pregnancy; eight (40%) 38 (22%) initiated addiction care with opiate agonist therapy. Of 142
initiated postpartum. Twelve (70%) had documented completion of who initiated treatment, 95 were available at the SVR12 time point to
DAA treatment; only 7 (35%) showed up to their SVR12 check; 6/7 date. Of these, 88 achieved a cure. The main reasons an endpoint was
(86%) had documented SVR12; one patient required re-treatment. In not measured included 3 overdose-related deaths prior to SVR 12
regards to pregnancy outcomes, 35% had intrahepatic cholestasis of time point and 4 disengaged from care. There were no cases of
pregnancy; two (9%) had preterm birth; one patient had pregnancy virologic failure or relapse.
loss prior to DAA treatment initiation. There was one documented Conclusion: Through dedicated initiatives, it is possible to identify
mother-to-child transmission in a patient treated with DAA vulnerable inner-city residents who were previously diagnosed with
postpartum. HCV infection and had never been offered treatment for it. These
initiatives, combined with dedicated programs to provide HCV
treatment in an optimized manner, must be considered to achieve
HCV elimination in this unique population.

FRI404
High efficacy and safety of pan-genotypic direct-acting antiviral
regimens in adolescents and children: a global systematic review
to inform new World Health Organization recommendations
Giuseppe Indolfi1, Sabrina Giometto2, Farihah Malik3, Roger Chou4,
Philippa Easterbrook5, Ersilia Lucenteforte2. 1Università di Firenze,
Dipartimento Neurofarba, Firenze, Italy; 2Università di Pisa; 3UCL;
4
Oregon Health & Science University; 5World Health Organization
Email: [email protected]

Conclusion: Pregnancy offers an important opportunity to link Background and aims: The global hepatitis C virus (HCV) response
women with HCV to treatment-the majority were diagnosed initially has to date largely focused on adults who bear the greatest burden of
during routine screening during pregnancy. Cholestasis of pregnancy morbidity and mortality. There had been less attention to addressing
was a prevalent complication. HCV treatment during pregnancy is case-finding and treatment of the estimated 3.26 million HCV
feasible and will likely offer benefits to maternal and child health, infected children and adolescents. The recent regulatory approval of
however significant challenges remain to ensure adherence through two pan-genotypic regimens down to 3 years provides opportunity to
the vulnerable postpartum period. Similar to the management of extend treatment opportunities down to all children above 3 years. To
other chronic conditions in the postpartum period, linkage to care inform new World Health Organization (WHO) guidelines, we
and case management programs designed specifically for post- undertook a systematic review and meta-analysis of treatment
partum women should be evaluated to improve DAA therapy outcomes in adolescents and children down to 3 years based on the
completion and documentation of SVR12. key pan-genotypic direct-acting antiviral (DAA) regimens.
Method: We searched two databases and key conference abstracts for
FRI403 studies from inception to August 2021 that evaluated three pan-
Sofosbuvir/Velpatasvir (S/V) for the treatment of HCV infection genotypic DAA regimens recommended by WHO for use in adults
among vulnerable inner-city residents: extending the results of (sofosbuvir/daclatasvir, SOF/DCV, sofosbuvir/velpatasvir, SOF/VEL,
clinical trial glecaprevir/pibrentasvir, GLC/PIB) in HCV infected adolescents (12–
Brian Conway1,2, David Truong1, Leo Yamamoto1, Rossitta Yung1, 18 years), older children (6–11 years) and young children (3–5 years).
Shawn Sharma1. 1Vancouver Infectious Diseases Centre, Vancouver, Randomised controlled trials (RCT), non-RCT, and prospective
Canada; 2Simon Fraser University, Burnaby, Canada observational studies were eligible for inclusion. Key outcomes
Email: [email protected] evaluated were attainment of sustained virological response (SVR12),
any adverse events, and discontinuation. Estimates were pooled
Background and aims: The SIMPLIFY study demonstrated that using random-effects models.
sofosbuvir/velpatasvir (S/V) can be used to treat Hepatitis C Virus Results: 3 RCTS, 28 non-RCTs and 18 observational studies reported
(HCV) infection among active drug users, achieving sustained treatment experience in 167 young children (3–5 years), 472 older
virologic response (SVR) 12 rates comparable to those achieved in children (6–11 years), and 2228 adolescents (12–18 years). Across all

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POSTER PRESENTATIONS
studies, there were 15 cirrhotic children, 304 treatment-experienced, and for late treatment was 0.02 (0.002–0.03). There were no cases of
and 157 with genotype 3 infection. SVR12 was high>95% for all three glomerulonephritis reported and only 5 cases of FCH. Of the FCH
regimens and across age groups. There was a clear trend towards a cases, 4/5 occurred in patients treated >28 after transplant. Early
higher rate of any adverse event with younger age groups (50% in treatment was associated with 30% lower incidence of detectable
adolescents, 53% in older children, and 72% in young children) but viremia.
serious adverse events and treatment discontinuations were uncom- Conclusion: Overall, early DAA initiation (within 28 days) and late
mon. There were 7 discontinuations of SOD/VEL in young children, initiation (after 28 days) achieved similar SVR rates, although the
because of palatability of the oral formulation. early strategy reported 30% lower incidence of viremia. Early DAA
Conclusion: SOF/DCV, SOF/VEL, and GLC/PIB regimens were highly initiation strategies reported a lower proportion of ACR than the
effective and well tolerated in adolescents and older children, and delayed strategy, but this estimate was not statistically significant. On
SOF/VEL and GLC/PIB in young children and are now recommended balance these results would support current guidelines recommend-
by WHO. There is currently no direct evidence for SOF/DCV in young ing early treatment initiation, however randomized clinical trials may
children, and studies are planned for 2022. SOF/DCV remains the be required to more clearly define short-term responses and long-
most affordable and available DAA regimen for adults globally, and term clinical outcomes for these strategies.
alignment of adult and paediatric procurement would simplify
supply chain management. FRI406
Effectiveness of pangenotypic retreatment of HCV infection after
FRI405 prior failure of pangenotypic therapies
Early vs. late treatment for hepatitis C virus discordant solid organ Robert Flisiak1, Justyna Janocha-Litwin2, Anna Parfieniuk-Kowerda1,
transplantation and direct acting antivirals: a meta-analysis Dorota Zarębska-Michaluk3, Marek Sitko4, Piekarska Anna5,
Madison Gunn1, George Agyapong2, Victor Eligah3, Enoch Chung4, Jolanta Białkowska5, Dorota Dybowska6, Witold Dobracki7,
Sara Young5, Lauren Hulshof6, Camilla Mills7,8, Alexandra Gorham9, Simon Krzysztof2, Aleksandra Murawska-Ochab8,
Jordan Feld10,11,12, Raymond Chung7,13. 1Schulich School of Medicine & Małgorzata Pawłowska6. 1Medical University of Białystok, Białystok,
Dentistry, London, Canada; 2Yale School of Medicine, Internal Medicine, Poland; 2Medical University Wrocław; 3Jan Kochanowski University
New Haven, United States; 3Howard University, Pharmaceutical Kielce; 4Jagiellonian University, Kraków; 5Medical University of Łódz;́
Sciences, Washington DC, United States; 4Boston University School of 6
Ludwik Rydygier Collegium Medicum in Bydgoszcz Faculty of Medicine
Medicine, Boston, United States; 4Boston University School of Medicine, Nicolaus Copernicus University in Toruń, Department of Infectious
Boston, United States; 6Northeastern University, Boston, United States; Diseases and Hepatology, Poland; 7MED-FIX Wrocław; 8Voivodship
7
Harvard Medical School, Boston, United States; 8Boston Children’s Hospital, Kielce, Kielce
Hospital, Pediatric Gastroenterology, Hepatology, & Nutrition, Boston, Email: [email protected]
United States; 9Johns Hopkins University, Baltimore, United States;
10 Background and aims: Pangenotypic therapies for HCV infections,
Toronto Center for Liver Disease, Toronto, Canada; 11University Health
although universal and highly effective, leave the risk of treatment
Network, Toronto, Canada; 12University of Toronto, Toronto, Canada;
13 failure. The aim of the analysis was to assess the effectiveness of
Massachusetts General Hospital, Division of Gastroenterology,
pangenotypic re-treatment in patients with failure of previous
Department of Medicine, Boston, United States
treatment also with pangenotypic drugs; to our knowledge, the
Email: [email protected]
results of such real world experience studies have not been published
Background and aims: The advent of curative direct-acting antiviral so far.
(DAA) therapy for hepatitis C virus (HCV) has broadened the donor Method: The analysis included patients selected from the EpiTer-2
pool for solid organ transplants, allowing the use of organs from HCV database, a large retrospective, multicentre, national real-world
+ donors that were previously discarded. Although many centers have study evaluating DAA treatment during 2015–2021 in 14, 450
embraced this practice, the optimal timing of DAA initiation remains consecutive subjects with hepatitis C virus (HCV) infection.
unclear. This study aims to summarize the virologic and clinical Results: A total of 3, 985 patients were treated with pangenotypic
outcomes of DAA therapy in HCV donor+/recipient- solid organ regimens, of which 37 (0.9%) received them as retreatment after
transplants. failure of prior pangenotypic therapy. This group was significantly
Method: Bibliographic databases were searched for studies pub- dominated by males (78%), cirrhotics (49%) and genotype 3 infection
lished in English between Jan 2013 and Sept 2020. Using random (67%) compared to the general population of patients treated with
effects models, meta-analysis was performed to pool estimates for pangenotypic regimens (54%, 21%, 29%, respectively). As shown in
sustained virologic response (SVR) and a composite adverse outcome figure 1 primary glecaprevir/pribrentasivir (GP) based therapy was
of acute cellular rejection (ACR) and HCV-related complications changed to velpatasvir/sofosbuvir (VS) based in 18, and VS to GP in 13
(fibrosing cholestatic hepatitis and glomerulonephritis). Risk of bias patients. In 6 patients, the same regimen was used, extending the
was assessed using a modified Ottawa-Newcastle score. duration of therapy or supplementing it with an additional drug
Results: We included 25 non-randomized trials and observational (ribavirin (R), sofosbuvir (S), voxilaprevir (V)). The response rate at
studies with 635 participants, including 32 observations by organ the end of treatment was 95%, while the overall SVR was 89%. There
type: 9 studies reported on heart transplantation (n = 185), 4 on lung was no significant difference in SVR between patients retreated with
(n = 93), 12 on kidney (n = 278) and 7 on liver (n = 79). 16 studies GP (93%) and VS based regimen (87%), which included also two
started DAAs <28 days after transplant (early) while 9 initiated DAAs patients on voxilaprevir/VS (VVS) regimen. All four non-responders
>28 days post-transplant (late). The overall pooled SVR for all organ were cirrhotic males infected with genotype 3 in age of 54–59 years.
types was 0.96 (CI 0.95–0.98). SVR for non-liver organs was 0.97 (CI
0.94–0.98) and 0.96 (CI 0.91–1.0) for liver. For studies that had
available data, the overall proportion of ACR was 0.10 (CI 0.06–0.15).
In subgroup analyses, the SVR for early treatment was 0.97 (CI 0.96–
0.99), while the SVR for late treatment was 0.95 (0.91–0.98). The
proportion of the composite adverse outcome was 0.06 (CI 0.02–0.09)
for early treatment and 0.18 (0.06–0.30) for late treatment.
Proportion of ACR was 0.06 (CI 0.02–0.09) for early treatment
compared to 0.17 (CI 0.01–0.28) for late treatment. Proportion of
HCV-related complications for early treatment was 0.02 (0.01–0.04)

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 POSTER PRESENTATIONS
fibrosis. SVR12 was 83.3% (10/12). One cirrhotic genotype 1d patient
failed 2 one-DAA-based regimens (telaprevir (TPV)/pegylated inter-
feron ( pegIFN)/Ribavirin (RBV); sofosbuvir (SOF)/pegIFN/RBV) was
successfully retreated with SOF/ledipasvir (LDV). One cirrhotic
genotype 1 k patient failed 4 DAA-based regimens (SOF/simeprevir
(SIM); SOF/LDV 24/48 weeks; SOF/LDV/RBV).
In a subgroup analysis of patients treated with a 2-last generation
DAA (SOF/velpatasvir (VEL), SOF/VEL/RBV, glecaprevir (GLE)/pibren-
tasvir (PIB)), 50 patients were identified. SVR12 was 90.0% (45/50).
Among the 106 treated patients, 6 were treated after liver
transplantation. One patient presented with fibrosing cholestatic
hepatitis. The SVR12 was 83.3% (5/6). A genotype 3b patient failed
SOF/VEL for 12 weeks and was successfully retreated with SOF/VEL/
voxilaprevir (VOX) for 12 weeks.

Figure: Change from primary to secondary pangenotypic regimens (letter

abbreviations in abstract, numbers represent weeks of treatment).

Conclusion: We have demonstrated a high, almost 90% effectivenes

of pangenotypic retreatment after failure of the primary pangenoty-
pic therapy. Only men with cirrhosis, infected with genotype 3, did
not eliminate HCV infection despite double pangenotypic treatment.
We hope to provide data from more patients at the ILC.

FRI407
Infrequent hepatitis C genotypes/subtypes in patients treated
with DAA-based regimens: successes and failures
Donald Murphy1, Isaac Ruiz2, Jean-Pierre Villeneuve2,
Catherine Vincent2, Julian Hercun2, Daphna Fenyves2,
Denis Marleau2, Helene Castel2, Julien Bissonnette2,
Genevieve Huard2, Claire Fournier2, Jeanne-Marie Giard2,
Daniel Corsilli3, Ziad Hassoun2, Philippe Willems2, Iris Soto2,
Marc Bilodeau2, Bernard Willems2. 1Institut national de santé publique
du Québec, Laboratoire de santé publique du Québec (LSPQ), Montréal,
Canada; 2Centre hospitalier de l’Université de Montréal (CHUM), Liver
Unit, Canada; 3Centre hospitalier de l’Université de Montréal (CHUM),
Intensive Care Unit, Canada
Email: [email protected]
Background and aims: Patients with infrequent Hepatitis C virus
(HCV) genotypes/subtypes are characterized by resistance-associated
substitution (RAS) profiles that have been associated with lower
sustained virological responses (SVR). Real-world data regarding
efficacy of direct-acting antiviral (DAA)-based regimens are needed in Conclusion: Our real-world data show that in patients with
order to optimize HCV therapy and to further support expert infrequent HCV genotypes/subtypes treated with 2 last-generation
recommendations. DAA the SVR rate is 90%. Although the data are limited, these results
The aim of this study was to evaluate the efficacy of DAA-based support the possibility of initially treating them with 2 last-
regimens in patients infected with infrequent HCV genotypes/ generation DAA. More data are needed to determine optimal
subtypes in a real-world cohort at the Centre hospitalier de treatment regimen by genotype/subtype and the benefits of a
l’Université de Montréal (CHUM). rational approach based on RAS determination.
Method: A retrospective analysis of every patient referred to the
CHUM was performed. Between 2014 and 2021, patients with an FRI408
infrequent HCV genotype/subtype according to EASL guidelines Preemptive treatment with glecaprevir and pibrentasvir prevents
definition were identified. HCV transmission from HCV viraemic donors to solid organ
Patients treated with at least 1 DAA-based regimen were included. transplant recipients (single centre experience)
Patients enrolled in clinical trials were excluded. Liver fibrosis was Sona Frankova1, Ondrej Viklicky2, Veronika Pitova1, Janka Slatinska2,
assessed by means of liver elastography or by histological evaluation Jan Sperl1. 1Institute for Clinical and Experimental Medicine,
of liver biopsy. SVR was defined as an undetectable HCV RNA 12 Department of hepatogastroenterology, Prague, Czech Republic;
2
weeks after the end of treatment (SVR12). The choice of the DAA Institute for Clinical and Experimental Medicine, Department of
combination was made at the physician’s discretion. nephrology, Prague, Czech Republic
Results: Among the 801 patients of the cohort, 106 (13.2%) had an Email: [email protected]
infrequent genotype/subtype. Among them, median age was 64 (17– Background and aims: Organs from hepatitis C viraemic (HCV)
96), 54 (50.9%) were male, 54 (50.9%) had F3–F4 fibrosis. donors were not used for transplantation in the past because the
The overall SVR12 rate following initial treatment with at least one transmission of HCV infection to uninfected recipients used to be
DAA-based regimen was 87.7% (93/106). Twelve patients received a universal. Treatment of HCV infection in organ transplant recipients
second-line DAA regimen. Before retreatment, 75.0% had F3-F4 was complex and poorly effective before the introduction of direct-

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POSTER PRESENTATIONS
acting antivirals (DAA) into clinical practice. Glecaprevir and drug use, active alcohol consumption, were on opioid substitution
pibrentasvir (GLE/PIB) represent a pangenotypic anti-HCV DAA therapy, advanced fibrosis (23.5 vs 10%) and had lower rates of
combination also approved for patients with severe renal impairment previous treatment in comparison with HCV RNA negatives
or on maintenance haemodialysis. The study aims to analyze the (Figure 1c). The overall treatment initiation was 70.4% (114/162)
efficacy and safety of GLE/PIB combination as preemptive therapy of and SVR 12 was 75.5% (83/110). In the multivariate analysis being
HCV infection when using grafts from HCV viraemic donors. screened in temporary housing (OR 2.755, 95%CI 1.356–5.600; p =
Method: The solid organ transplant recipients, to whom an organ 0.005) and having opioid substitution treatment (OR 2.288, 95%CI
from HCV viraemic donor was allocated, were given a single dose of 1.041–5.026; p = 0.039) were positively associated with treatment
GLE/PIB (300 mg/120 mg) 2–6 hours before transplant, followed by a initiation. HCV treatment adherence (OR 25.05, p < 0.001) was the
once-daily administration for 12 weeks after transplantation, as only factor associated with achieving SVR.
recommended for liver and kidney transplant recipients by the
manufacturer. HCV RNA levels were assessed weekly in the first four
weeks post-transplant, in the treatment weeks 8 and 12, and 12
weeks after the cessation of therapy. The endpoints were negative
HCV RNA levels at the end of treatment and 12 weeks post-treatment.
Results: Twelve organs (two liver and ten kidney grafts) from 5 HCV
viraemic cadaveric donors were allocated to 12 HCV uninfected
recipients. All the recipients presented with an uncomplicated post-
transplant course with the rapid development of graft function. None
of the recipients presented with an acute rejection episode or severe
graft dysfunction during the treatment and follow-up period. All the
recipients completed the planned 12 weeks of preemptive antiviral
treatment. None of them experienced an adverse event related to
antiviral therapy or drug-drug interactions. HCV RNA was undetect-
able at all checked timepoints in all recipients. HCV infection was
transmitted to none of the twelve recipients.
Conclusion: Preemptive treatment with GLE/PIB is safe and effective
and allows the use of organs from HCV viraemic donors, so far
considered marginal, to uninfected recipients. Organ procurement
from HCV viraemic donors became a routine at our centre.

FRI409
Hepatitis C care cascade challenges in the homeless population.
A case by case model of delivering care
Maria Guerra Veloz1, Khin Aye Wint Han1, Almuthana Mohamed1,
Kathryn Oakes1, David Robertson1, Mary D. Cannon1,
Ashley Barnabas1, Sital Shah1, Geoffrey Dusheiko1, Kosh Agarwal1.
1
Institute of Liver Studies. King’s College Hospital, London, United
Kingdom, London, United Kingdom
Email: [email protected]
Background and aims: Given the significant Hepatitis C Virus (HCV)
burden, despite curative treatments, efforts focusing on the scaling
up of testing and treatment in the homeless population are still
needed. The aim of this project was to implement education and
flexible onsite HCV incentivised testing, treatment and follow up for
the homeless population and evaluate their rates of engagement,
therapy initiation and cure in the South London area.
Method: This project was conducted by a multidisciplinary team
from Jan 2018 to Sept 2021. A mobile unit “van” for onsite HCV
education, flexible screening (InTec HCV Rapid Antibody Test, Figure: a) Flow chart project b) Characteristics divided by HCV antibody
Cepheid GeneXpert RNA test, DBS or classic venipuncture), treatment and RNA status
and follow up was placed on the street in well-known homeless
Conclusion: Promoting education and having flexible onsite-testing
population areas. Homeless was defined as living in temporary-
(hostel/hotel-based) or as being on the street or visiting daily soup and treatment for HCV in the homeless population improves their
kitchens across the area (street-based). Sociodemographic status, risk engagement with the healthcare system, leading to higher rates of
factors, comorbidities, concomitant medication, clinic data, the rates treatment initiation and SVR. However, street based homeless people
of treatment initiation and cure were recorded. Treatment adherence who are not linked with harm reduction services are less likely to
initiate HCV treatment, highlighting that there is an urgent need for a
was defined as taking ≥75% of doses as self-reported by clients.
Results: 940 clients were identified as homeless and 933 (99.3%) broad health inclusion system.
participated. Of them 56.2% who were screened were street-based,
243 (26%) tested positive for HCV antibody and of these, 162 (67%)
had detectable viremia. Clients with a positive HCV antibody had
significantly higher rates of previous injection drug use (71.2 vs 8.6%),
previous incarceration (12.3 vs 2.8%), previous HCV tests (28.8 vs
0.1%), as well as being active drug (36.2 vs 3.3%) and alcohol users
(43.6 vs 5.2%) than those who were negative. HCV RNA positive
clients had significantly more frequent psychiatric disorders, active

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 POSTER PRESENTATIONS
FRI410 Hospital, Division of Gastroenterology and Hepatology, Department of
Effectiveness and safety of 8-week glecaprevir/pibrentasvir in Internal Medicine, Taiwan; 36Taipei Medical University, School of
HCV treatment naïve patients with compensated cirrhosis: real- Medicine, College of Medicine, Taiwan; 37Yang Ming Hospital, Chiayi,
world experience from Taiwan HCV registry Taiwan; 38Penghu Hospital, Ministry of Health and Welfare, Taiwan;
39
Chao-Hung Hung1, Te-Sheng Chang2, Chung-Feng Huang3, National Taiwan University Hospital Hsin-Chu Branch, Taiwan; 40E-Da
Hsing-Tao Kuo4, Ching-Chu Lo5, Chien‐Wei Huang6, Hospital, Department of Internal Medicine, Taiwan; 41National Taiwan
Lee‐Won Chong7,8, Pin-Nan Cheng9, Ming-Lun Yeh10,11, University Hospital, School of Medicine, Internal Medicine, Taiwan;
42
Cheng-Yuan Peng12,13, Chien-Yu Cheng14, Jee-Fu Huang10,15, National Taiwan University Hospital, Hepatitis Research Center and
Ming-Jong Bair16,17, Chih‐Lang Lin18, Chi-Chieh Yang19, Department of Internal Medicine, Taiwan; 43National Yang-Ming Chiao
Sih-Ren Wang20, Tsai-Yuan Hsieh21, Tzong-Hsi Lee22, Pei‐Lun Lee4, Tung University, Institute of Clinical Medicine, Taiwan; 44Ditmanson
Wen‐Chih Wu23, Chih-Lin Lin24, Wei-Wen Su25, Shengshun Yang26, Medical Foundation Chiayi Christian Hospital, Division of
Chia-Chi Wang27,28, Jui-Ting Hu29, Lien-Juei Mou30, Gastroenterology and Hepatology, Department of Medicine, Taiwan;
45
Chun-Ting Chen31,32, Yi-Hsiang Huang33,34, Chun-Chao Chang35,36, Dalin Tzu Chi Hospital, Department of Internal Medicine, Taiwan;
46
Jia-Sheng Huang37, Guei-Ying Chen38, Jian-Neng Gao39, Tzuchi University, School of Medicine, Taiwan; 47Kaohsiung Medical
Chi-Ming Tai40,41, Chun-Jen Liu42, Mei‐Hsuan Lee43, Pei-Chien Tsai10, University Hospital, Kaohsiung Medical University, Hepatobiliary
Chia-Yen Dai10, Jia-Horng Kao42, Han-Chieh Lin33,34, Division, Department of Internal Medicine and Hepatitis Center
Wan-Long Chuang10, Chiyi Chen44, Kuo-Chih Tseng45,46, Email: [email protected]
Ming-Lung Yu47. 1ChiaYi Chang Gung Memorial Hospital and College of
Background and aims: The once-daily, oral, fixed-dose, direct-acting
Medicine, Chang Gung University, Division of Hepatogastroenterology,
antiviral combination of glecaprevir/pibrentasvir (G/P) is indicated
Department of Internal Medicine; 2ChiaYi Chang Gung Memorial for chronic hepatitis C (CHC) infection with HCV genotypes 1–6 in
Hospital, Division of Hepatogastroenterology, Department of Internal
patients with or without compensated cirrhosis (CC). Treatment
Medicine, Taiwan; 3Kaohsiung Medical University Hospital, Kaohsiung duration of 8 weeks is recommended in most cases. Recent
Medical University, Hepatobiliary Division, Department of Internal retrospective data from Taiwan revealed that G/P treatment resulted
Medicine and Hepatitis Center, Taiwan; 4Chi Mei Medical Center,
in high SVR12 rates according to label recommendations, comparable
Division of Gastroenterology and Hepatology, Department of Internal to those reported in the pivotal clinical trials. To further validate the
Medicine, Taiwan; 5St. Martin De Porres Hospital, Division of
data in the real-world setting, this study investigated effectiveness
Gastroenterology, Department of Internal Medicine, Taiwan; 6Kaohsiung and safety of 8-week G/P therapy in treatment-naïve (TN), CC
Armed Forces General Hospital, Division of Gastroenterology, Taiwan; patients, with an emphasis on those with advanced liver disease in
7
Shin Kong Wu Ho-Su Memorial Hospital, Division of Hepatology and TASL HCV Registry (TACR).
Gastroenterology, Department of Internal Medicine, Taiwan; 8Fu-Jen Method: The TACR is an ongoing nationwide registry program
Catholic University, School of Medicine, Taiwan; 9National Cheng Kung organized and supervised by Taiwan Association for the Study of
University Hospital, Division of Gastroenterology and Hepatology, the Liver (TASL), which aims to setup a database and biobank of
Department of Internal Medicine, Taiwan; 10Kaohsiung Medical patients with CHC in Taiwan. Data were analyzed as of 31 October
University Hospital, Hepatobiliary Division, Department of Internal 2021 for patients treated with G/P for TN, CC patients. In this
Medicine and Hepatitis Center, Taiwan; 11Kaohsiung Municipal Siaogang analysis, effectiveness reported as sustained virologic response at
Hospital, Department of Internal Medicine, Taiwan; 12China Medical post-treatment week 12 (SVR12) was assessed by modified intent-to-
University Hospital, Center for Digestive Medicine, Department of treat (mITT) populations that excluded patients who lost to
Internal Medicine, Taiwan; 13China Medical University, School of follow-up, underwent treatment and/or traced SVR12 data. Safety
Medicine, Taiwan; 14Taoyuan General Hospital, Division of Infectious profile was assessed in the ITT population.
Diseases, Department of Internal Medicine, Taiwan; 15Kaohsiung Results: Of 806 TN, CC patients treated with G/P, 301 patients
Municipal Ta‐Tung Hospital, Department of Internal Medicine, Taiwan; received 8-week regimen (ITT), and 275 of which had SVR12 data
16
Taitung Mackay Memorial Hospital, Division of Gastroenterology, available (mITT). Of the 301 ITT population, mean age was 63.0 years,
Department of Internal Medicine, Taiwan; 17Mackay Medical College, 53.8% were male, 27.2% were with chronic kidney disease and 2.3%
Taiwan; 18Chang Gung Memorial Hospital at Keelung, Liver Research were coinfected with human immunodeficiency virus. The overall
Unit, Department of Hepato‐Gastroenterology and Community Medicine SVR12 rate was 98.2% (270/275) in the mITT population. For selected
Research Center, Taiwan; 19Show Chwan Memorial Hospital, special patient groups including patients with HCV genotype 3 (GT3),
Department of Gastroenterology, Division of Internal Medicine, Taiwan; platelets counts <150, 000/μl, FibroScan >20 kPa, or both platelet
20
Yuan’s General Hospital, Division of Gastroenterology, Department of counts <150, 000/μl and FibroScan >20 kPa, the SVR12 rate was 100%
Internal Medicine, Taiwan; 21Tri‐Service General Hospital, Division of (6/6), 98.0% (144/147), 100.0% (12/12) and 100.0% (7/7), respectively.
Gastroenterology, Department of Internal Medicine, Taiwan; 22Far Overall, 24.9% (75/301) of the patients experienced adverse events
Eastern Memorial Hospital, Division of Gastroenterology and (AEs)in the ITT population. Seven patients (2.3%) experienced serious
Hepatology, Taiwan; 23Wen-Chih Wu Clinic, Taiwan; 24Renai Branch, adverse events and two (0.7%) resulted in permanent drug
Taipei City Hospital, Department of Gastroenterology, Taiwan; discontinuation. None of them were considered as treatment drug
25
Changhua Christian Hospital, Department of Gastroenterology and related. The most frequent AEs (>5%) were fatigue (9.0%) and pruritus
Hepatology, Taiwan; 26Taichung Veterans General Hospital, Division of (7.0%). Laboratory data including international ratio of prothrombin
Gastroenterology and Hepatology, Department of Internal Medicine, time, total bilirubin, alanine aminotransferase, aspartate aminotrans-
Taiwan; 27Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, ferase and albumin significantly improved after HCV eradication at
Taiwan; 28Tzu Chi University, School of Medicine, Taiwan; 29Cathay SVR12.
General Hospital, Liver Center, Taiwan; 30Tainan Municipal Hospital,
Division of Gastroenterology, Taiwan; 31Tri‐Service General Hospital,
National Defense Medical Center, Division of Gastroenterology,
Department of Internal Medicine, Taiwan; 32Tri‐Service General Hospital
Penghu Branch, Division of Gastroenterology, Department of Internal
Medicine, Taiwan; 33Taipei Veterans General Hospital, Division of
Gastroenterology and Hepatology, Department of Medicine, Taiwan;
34
National Yang-Ming Chiao Tung University, Institute of Clinical
Medicine, School of Medicine, Taiwan; 35Taipei Medical University

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POSTER PRESENTATIONS
Table 1: FAERs AEs and deaths with opioids and with concomitant
HCV DAAs.
Oxycodone/
Fentanyl Fentanyl Hydrocodone Oxycodone/ Overdose Overdose
AEs deaths AEs Hydrocodone AEs* deaths*
(N = 58, (N = 29, (N = 290, deaths (N = 98, (N = 52,
n 001) 850) 224) (N = 119, 013) 037) 318)

All DAAs 40 14 626 28 196 32

G/P 13 3 153 6 24 11
SOF/VEL 22 11 269 13 99 14
Figure: G/P-treated Patients with SVR12 data available as of Oct 2021 for LDV/SOF 3 0 100 5 50 5
analysis, n = 275 (mITT). SOF/VEL/VOX 0 0 14 0 8 0
EBR/GZR 2 0 90 4 15 2
Conclusion: In this real-world Taiwanese cohort, 8-week G/P therapy
*N represents the sum of fentanyl, oxycodone, and hydrocodone overdose AEs
was well-tolerated in TN, CC patients. SVR12 rates were similarly high
and deaths, whereas n’s for DAA overdose AEs and deaths are irrespective of
as in the clinical trials, including those with characteristics of concomitant opioids.
advanced liver disease.
Conclusion: With the limitations of FAERS data (under or duplicate
FRI411 reporting, inability to establish causation or incidence), these data
Reported safety of HCV direct-acting antivirals with opioids: 2017 show that among ∼58, 000 fentanyl, ∼189, 000 oxycodone, and ∼100,
to 2021 000 hydrocodone AEs reported to FAERS since 2017, a small
Anthony Martinez1, Tipu Khan2, Doug Dylla3, John Marcinak3, proportion (0.19%) have been reported in association with concomi-
Michelle Collins3, Brad Saget3, Brian Conway4. 1State University of tant DAA therapy, with no association between recorded events and a
New York, Buffalo, New York, United States; 2Ventura County Medical specific DAA regimen. This should reassure HCV treaters on a lack of
Center, Ventura, United States; 3AbbVie Inc, United States; 4Vancouver safety signal for concomitant opioid and DAA use.
Infectious Diseases Centre, Canada
Email: [email protected] FRI414
Impact of the presence of the infectious disease specialist in
Background and aims: As a result of disengagement in addiction addiction services (SerDs) as a point-of-care to meet WHO goal of
care during the COVID-19 pandemic, there has been a record increase HCV eradication
in mortality associated with opioid overdoses ( primarily fentanyl),
Chiara Fanelli1, Elija Princic1, Andrea De Vito1, Claudia Marcia1,
particularly in North America. In the USA there were over 100, 000
Giordano Madeddu1, Sergio Babudieri1, Ivana Rita Maida1. 1University
overdose deaths in 2021, while over 2000 were recorded in the
of Sassari, Department of Medical, Surgical and Experimental Sciences,
province of British Columbia. As we attempt to develop novel ways to
Sassari, Italy
increase HCV treatment following ≥30% declines during the
Email: [email protected]
pandemic, we evaluated publicly available adverse events (AEs)
reports for opioids and DAAs to assess whether safety concerns from Background and aims: The World Health Organization (WHO) aim
potential drug interactions are warranted, particularly amongst those for Hepatitis C virus (HCV) elimination by 2030 appears to be
using fentanyl. threatened by most patients remaining undiagnosed, despite the
Method: Data were downloaded from the US Food and Drug availability of effective and safe antivirals. The main reservoir of HCV
Administration (FDA) Adverse Event Reporting System (FAERS) Public is represented by people who inject drugs (PWIDs). This study aimed
Dashboard. AEs with the DAAs glecaprevir/pibrentasvir (G/P), sofosbu- to assess the crucial role of the infectologist at the Addiction Services
vir/velpatasvir (SOF/VEL), ledipasvir/sofosbuvir (LDV/SOF), sofosbuvir/ (SerDs) and its potential as a linkage to care of PWID HCV carriers.
velpatasvir/voxilaprevir (SOF/VEL/VOX), and elbasvir/grazoprevir (EBR/ Method: This retrospective study compares the number of new
GZR) listed as the suspect product were analyzed with an initial diagnosis and treatments among PWIDs before and after the
received date from July 28, 2017-December 31, 2021, as were opioid- introduction of an infectologist at SerDs Point of Care of Sassari,
associated AEs for all 2017–2021. Subsequently, AEs were counted Italy. Data were collected from February 2015 to August 2020. The
based on listed concomitant use of opioids (fentanyl, oxycodone, watershed day was the 1st of May 2019, when the infectologist was
hydrocodone), or overdose outcomes irrespective of concomitant integrated in the personnel of SerD. Logistic regression analysis was
opioid use. Data are descriptive without any statistical analyses. performed to assess the relationship between variables before and
Results: In the reporting period, 40 total AEs were recorded with after the introduction of the infectologist.
concomitant DAA and fentanyl use, 14 resulting in death (G/p = 3, Results: From February 2015 to August 2020, 901 users took
SOF/VEL = 11; Table 1); 626 total AEs were recorded with concomi- advantage of at least one dose of under opiate substitution treatment
tant DAA and oxycodone or hydrocodone use, 28 resulting in death. (OST) at the SerDs of Sassari, Italy. In total, 419 users (46.5%)
Separately, overdose events were reported 196 times, 32 resulting in underwent HCV-screening test, of which 333 (79.47%) tested positive
death. The number of overdoses declined each year from 2018 (N = and 191 taken in charge by the infectologist. Of 157 patients with
56) to 2021 (N = 29). Fentanyl AEs showed no trend year to year. detectable HCV-RNA, 138 (87.89%) started HCV treatment. Comparing
the group treated with Direct-acting Antiviral Agents (DAA) before
and after May 2019, a statistical significance was found in age ( p =
0.0018) and diagnose-to-treatment prescription time ( p < 0.001).
When comparing PWIDs taken in charge in the two periods,
statistical significance emerged for median age ( p < 0.001), alcohol
dependence ( p = 0.005), active PWID ( p = 0.01), cirrhosis ( p = 0.006)
and DAA prescription ( p = 0.014) (Table). The number of new
diagnoses and treatments from May 2019 until August 2020 was
higher than those between February 2015 and May 2019 (respect-
ively, 72 in 15 months versus 66 in 50 months).

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 POSTER PRESENTATIONS
Glecaprevir/Pibrentasvir. All were considered cured by achieving
virological response 12 weeks post-treatment.
Take-in- Take-in- Conclusion: Our encouraging data is a result from an optimized
charge before charge after
partnership between the healthcare team in prisons and our hospital,
Total May 2019 May 2019 p-
Variables (N = 191) (N = 81) (N = 110) value* allowing a fast diagnosis, an agile disease staging and adequate
treatment, minimizing future risk of transmission and taking us
Age, n (IQR) 48, 9 (40, 1– 50, 6 (43, 6– 45, 7 (38, 6– <0, closer to eliminating the infection by 2030.
53, 8) 55, 4) 52, 2) 001
Male sex, n (%) 177 (92, 7%) 78 (96, 3%) 99 (90%) 0, 099 FRI416
Alcohol abuse, n (%) 10 (5, 2%) 0 (0%) 10 (9, 1%) 0, 005 Real-world value and innovation of direct-acting antivirals for the
Active PWID, n (%) 26 (13, 6%) 5 (6, 2%) 21 (19, 1%) 0, 01
treatment of chronic hepatitis C at Kaiser Permanente Southern
Cirrhosis, n (%) 64 (33, 5%) 36 (44, 4%) 28 (25, 5%) 0, 006
Prescribed DAAs 138 (72, 3%) 66 (81, 5%) 72 (65, 5%) 0, 014 California
therapy, n (%) Lisa Nyberg1, Ankita Kaushik2, Nate Smith3, Fadoua El-Moustaid3,
Anders Nyberg1, Su-Jau Yang4, Kevin Chiang5, Alon Yehoshua2. 1Kaiser
*Determined by chi-square test or wilcoxon test. IQR: range interquartile. Permanente Hepatology Research, San Diego, United States; 2Gilead
Sciences, Inc., Foster City, United States; 3Maple Health Group, New York,
Conclusion: The improvement of the Meet-Test-Treat has been
United States; 4Kaiser Permanente Research and Evaluation, Pasadena,
related to the introduction of the infectologist at SerDs. This work
United States; 5Kaiser Permanente Pharmacy Analytical Services,
highlights the increase in patients’ compliance to treatment and take-
Downey, United States
in-charge by a doctor in hard-to-reach population. Furthermore, it
Email: [email protected]
provides a higher chance of early diagnosis of patients with a still
reversible degree of fibrosis and how to significantly reduce the Background and aims: Direct-acting antivirals (DAAs) have been a
management time. breakthrough therapeutic innovation in the treatment of chronic
hepatitis C virus (HCV) with high efficacy rates and excellent safety
FRI415 and tolerability profiles. The objective of this study was to assess the
Eliminating hepatitis C virus infection in prisons: 7 years of long-term health and economic benefits associated with direct-
experience acting antivirals (DAAs) vs. no treatment in the Kaiser Permanente
Frederico Duarte1, Luís Manuel Moura1, Clara Batista1, Southern California (KPSC) healthcare delivery system.
Ricardo Correia de Abreu1, Isabel Neves1. 1Unidade Local de Saúde de Method: A hybrid decision-tree and Markov model was used to
Matosinhos, Infectious Diseases, Matosinhos, Portugal evaluate the long-term health and cost outcomes associated with
Email: [email protected] treating HCV patients with DAAs (either sofosbuvir/velpatasvir [SOF/
VEL] or ledipasvir/sofosbuvir [LDV/SOF]) vs. no treatment in the KPSC
Background and aims: Hepatitis C virus (HCV) infection is a major
setting. A cohort of 7, 255 HCV patients, based on the total number of
global health problem. The micro-elimination approach implies
DAA-treated patients from 2014 to 2019, with an average age of 59
reaching specific populations, like people living in prisons. The
years was simulated over a lifetime (50 year) horizon. Demographic
introduction of direct-acting antiviral agents (DAAs) allowed a
data included baseline distributions of genotype, cirrhosis, prior
considerable change in public health.
treatment/naïve, and mix of DAAs. Treatment efficacy by subpopula-
Since 2015, the use of these drugs in HCV-infected inmates has
tion was determined from a secondary, real-world, database analysis
allowed their cure, resulting from an ongoing optimized care
of HCV patients in the KPSC setting. Utility values, transition
partnership between two prisons and our healthcare unit in
probabilities, and health state costs were sourced from published
Matosinhos, bringing us closer to public health targets in eliminating
literature, prioritizing data from the KPSC setting where possible.
the infection by 2030.
Treatment costs based on wholesale acquisition costs were sourced
Method: The authors describe the epidemiological, clinical, analyt-
from publicly available databases. The model considered only direct
ical and imaging data of inmates with confirmed HCV infection
medical costs, presented in 2021 USD.
undergoing treatment with DAAs since their availability in our
Results: Approximately 78% of patients were treated with LDV/SOF
healthcare unit.
and 22% with SOF/VEL in the DAA scenario. DAAs use led to a
Between 2015 and 2022 we identified 118 inmates with positive HCV
reduction of 3, 179 cases of compensated cirrhosis (−98%), 3, 318
antibody (65 men, 53 women), 16 have ongoing disease staging, 14
cases of decompensated cirrhosis (−96%), 646 cases of hepatocellular
with spontaneous cure and 9 were released before complete staging.
carcinoma (−80%), 447 cases of liver transplants (-86%), and 3, 078
Twenty four HIV coinfected patients, all under treatment, 100% with
events of liver-related mortality (−86%) as compared to no treatment.
viral suppression and 75% with CD4+ count greater than 500/uL. Four
In the DAAs scenario, life-years, and quality-adjusted life-years
patients were coinfected with HBV. Almost 55% of the patients were
(QALYs) improved by +25% (+3.21 LYs) and +36% (+3.53 QALYs) vs. the
diagnosed with psychiatric illness and were under treatment.
no-treatment scenario. DAAs use also resulted in a reduction of total
Results: The 79 inmates with confirmed HCV infection (51 men, 28
costs of −72% (−$144, 592 per person) vs. no treatment. Furthermore,
women) showed an average of 42 years [24–72 years], 11 years of
use of DAAs was found to lead to cost savings within 3 years.
known infection [1–30 years] and 85% had intravenous drug use in
Conclusion: Treating patients with DAAs resulted in a reduction in
the past. HCV genotypes distribution: 1–48%; 3–30%; 4–22%. Liver
HCV-related morbidity and mortality and significant improvement in
fibrosis stages ranged from 4 to 64 kPa (F0–F2 85%, F3–F4 15%).
QALYs. Furthermore, use of DAAs was dominant (less costly and more
All the 79 patients were initially treated with Sofosbuvir/Ledipasvir
effective) as compared to no treatment offering cost-savings within 3
and Daclatasvir with or without ribavirin (according to criteria
years post-treatment. These findings highlight the substantial value
defined in initial protocols) and more recently, Grazoprevir/Elbasvir
of DAA treatment offered to HCV patients.
and pangenotypic drugs, namely Sofosbuvir/Velpatasvir, and

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POSTER PRESENTATIONS

FRI418
Treatment options for hepatitis C in pregnancy: a systematic
review of the evidence and future research needs
Neil Gupta1, Lindsey Hiebert1, Carolyn Wester2, Paige A Armstrong1,2.
1
Task Force for Global Health, Coalition for Global Hepatitis Elimination,
United States; 2US Centers for Disease Control and Prevention, Division of
Viral Hepatitis, United States
Email: [email protected]
Background and aims: Treatment for hepatitis C virus (HCV)
infection during pregnancy has the potential to substantially increase
HCV treatment coverage and prevent mother-to-child transmission.
Although direct-acting antiviral (DAA) medications for the treatment
of HCV infection have demonstrated excellent safety and efficacy in
non-pregnant persons, HCV treatment is not recommended in
pregnancy due to a lack of safety data. We assessed the published
literature for information on treatment options for HCV infection in
pregnancy, including linkage to care and treatment during
pregnancy.
Method: We conducted a systematic literature review in PubMed for
articles published in English from January 1, 2013–July 1, 2021. We
searched using MESH and non-MESH equivalent search terms for
“Hepatitis C virus” AND “pregnancy” AND “treatment” OR “direct-
acting antivirals.” All articles were reviewed and thematically coded
by dual reviewers..
Results: Overall, 486 articles were identified, of which 219 were
included as relevant with full-text available. Of these, 118 contained
results of primary research and 101 were secondary research. Of the
118 primary research articles, most focused on outcomes of HCV
vertical transmission in infants (n = 28, 23.7%), HCV screening results
(n = 25, 21.2%), epidemiology of HCV (n = 19, 16.1%), and cost-
effectiveness or policies for HCV testing (n = 19, 16.1%). Fourteen
(11.9%) assessed linkage to care or follow-up for persons who tested
HCV positive. Five (4.2%) studies described results of DAA exposure in
pregnancy. This included one prospective trial that reported minor
(grade I/II) adverse events in 4 out of 9 participants, one retrospective
study that reported no adverse events among 100 participants, one
Abstract withdrawn case study with no reported adverse events, and 2 clinical trials that
reported DAA discontinuation due to pregnancy in 6 enrolled
participants (no clinical outcomes reported). Of the 101 studies
without primary research, 13 explicitly included the possibility of
HCV treatment during pregnancy.
Conclusion: Despite a substantial body of literature on HCV infection
in pregnancy, there are very few reports on maternal linkage to HCV
treatment and extremely limited data regarding the safety or
effectiveness of DAA treatment in pregnancy. To improve the
evidence base on HCV treatment in pregnancy, additional approaches
are needed to collect and report relevant data. In response, the
Coalition for Global Hepatitis Elimination, with support from the US
Centers for Disease Control and Prevention, developed the first
clinical case registry to record maternal and infant outcomes for
persons exposed to DAAs during pregnancy (“TiP-HepC” Registry).
The TiP-HepC registry, in complement to clinical studies and other
real-world experiences, will provide urgently needed data to inform
optimal treatment options for HCV in pregnancy.

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 POSTER PRESENTATIONS
FRI452
Dosing ileal bile acid transporter inhibitors in the fasted state
Immune-mediated and cholestatic: minimizes gastrointestinal adverse effects while maintaining
Experimental and pathophysiology pharmacodynamic effect
Cory Kostrub1, Rakesh Raman1, Douglas Mogul1, Pamela Vig1. 1Mirum
Pharmaceuticals Inc, Foster City, CA, United States
FRI451 Email: [email protected]
Over-responsiveness of the IL-6/STAT3 pathway in inflammatory
CD4+ T cells of patients with primary sclerosing cholangitis Background and aims: Ileal bile acid transporter inhibitors (IBATi)
Leona Dold1, Leonie Frank1, Philipp Lutz1, Tobias Weismüller1, interrupt enterohepatic circulation of bile acids (BAs) and increase
Dominik Kaczmarek1, Vittorio Branchi2, Marieta Toma2, fecal BA (fBA) excretion, thereby reducing serum BA (sBA). IBATi,
Christian Strassburg1, Ulrich Spengler1, Bettina Langhans1. 1University including maralixibat (MRX; approved for the treatment of chole-
Hospital Bonn, Department of Internal Medicine I, Bonn, Germany; static pruritus in patients with Alagille syndrome [ALGS] ≥1 year of
2
University Hospital Bonn, Institute of Pathology, Bonn, Germany age) and volixibat (VLX), decrease the toxic accumulation of BAs in
Email: [email protected] the liver and mitigate cholestasis. GI adverse events (AEs; diarrhea,
abdominal pain) are side effects of IBATi due to increased excretion of
Background and aims: Primary sclerosing cholangitis (PSC) is a fBA. The aim of this analysis was to assess the impact of timing of
chronic inflammatory disorder of the biliary ducts, which leads to IBATi dosing, relative to food, on GI AEs and pharmacodynamic (PD)
fibrosis and predisposes to cholangiocellular carcinoma. Although effects to inform the optimal dosing approach for IBATi.
the exact pathogenesis of PSC remains unclear, proinflammatory Method: AE data from 3 phase 1 clinical studies on MRX and VLX in
CD4+ immune cells seem to play a pivotal role. Current treatment healthy participants were compiled to assess relative tolerability with
options are limited but over-activation of STATs (Signal Transducers different timing of IBATi dosing vs mealtime. In Study 1, 75 mg of VLX
and Activators of Transcription protein) was observed in CD4+ was dosed fasted (overnight fast and no food for 4 hrs post-dose) vs
immune cells and linked to disease activity in various autoimmune right after breakfast; in Study 2, 10 mg of MRX was dosed fasted vs
diseases. Thus far, activation of STATs has been poorly studied in PSC. immediately before breakfast, and in Study 3, 30 mg of MRX was
Method: Using multicolor flow cytometry we analyzed activation of dosed fasted vs right after breakfast. The PD of IBATi is challenging to
STAT1 and STAT3 at baseline and after in vitro stimulation with directly measure in clinical trials, so the PD impact of IBATi dosing
recombinant IL-6 and IFN-gamma in immune cells from peripheral time relative to mealtime was investigated in healthy dogs by
blood (PBMC) and from biliary tissue specimens collected by measuring fBA excretion over 7 days of dosing, comparing IBATi
endoscopic retrograde cholangiopancreaticography (ERCP) from dosing 4 hr prior, 30 minutes prior, or 4 hours after the daily meal.
patients with PSC. In addition, we measured soluble factors in Results: Across the 3 phase 1 clinical studies there was a lower rate of
serum and bile via bead-based immunoassay and compared results to GI AEs when dosing IBATi in the fasted state (0%, 0%, and 50% of
healthy controls. participants reported a GI AE in Study 1, 2, and 3 respectively)
Results: Serum levels of IL-6 (mean ± SEM; 62.1 ± 28.1 pg/ml, p = compared to the fed state or at mealtime (75%, 33%, and 100% in Study
0.0279), IFN-gamma (26.7 ± 11.7 pg/ml, p = 0.0082) and IL-17A (9.1 ± 1, 2, 3 respectively). In healthy dogs, MRX significantly increased fBA
3.0 pg/ml, p = 0.0356), were higher in PSC patients than in healthy excretion ( p < 0.01 vs pretreatment baseline by paired t-test)
controls (IL-6: 10.5 ± 3.6 pg/ml; IFN-gamma: 6.1 ± 2.9 pg/ml; IL-17A: regardless of dosing time relative to the daily meal, with maximal
2.7 ± 1.1 pg/ml). Of note, in PSC patients, inflammatory cytokines increases in fBA excretion when dosing 30 minutes prior (231%
were conspicuously higher in bile than in serum. Unlike phospho- increase) or 4 hrs after (229% increase) the meal, indicating flexibility
STAT1, which was refractory to IFN-gamma and IL-6 stimulation, in the timing of IBATi dosing vs mealtime to maintain maximal PD
activation with recombinant IL-6 lead to higher frequencies of effect.
phospho-STAT3-positive cells in the IFN-gamma+ (80.2 ± 2.3%, p =
0.0055) and IL-17A+ CD4+ T cell subsets (79.0 ± 2.4%; p = 0.0197) in
patients with PSC than in healthy controls (66.1 ± 4.6% in IFN-gamma+
and 68.4 ± 4.1% in IL-17A+CD4+ T cells). Frequencies of phospho-
STAT3-positive cells in the IFN-gamma+ and IL-17A+ CD4+ T-cell
subsets were higher in bile duct tissue (from ERCP) when compared
to peripheral blood (Fig. 1). Finally, the pan-Jak inhibitor baricitinib
dose-dependently reduced IFN-gamma- and IL-17A-secretion of
mitogen-stimulated PBMCs from PSC patients in vitro.

Conclusion: These data demonstrate that GI tolerability is improved

when dosing an IBATi in the fasted state, versus dosing at mealtime or
immediately after food intake. Animal data show that PD effect is
maintained regardless of dosing time relative to mealtime, suggest-
Conclusion: Patients with PSC exhibit increased phospho-STAT3 ing that efficacy can be maintained while minimizing GI events.
induction in pro-inflammatory CD4+ T cells from blood and bile duct
tissue, suggesting enhanced responsiveness of the STAT3 pathway in
PSC. Although the cause of STAT3 over-responsiveness in PSC remains
to be elucidated, targeted STAT3 inhibition may offer a novel approach
to modify the course of PSC.

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POSTER PRESENTATIONS
FRI453 FRI454
Magnesium accumulation by CNNM4 GalNAc-siRNA mediated Association of bile acids composition and synthetic pathway with
silencing reduces cholestasis-associated liver fibrosis therapeutic effect of bezafibrate in chronic cholestatic liver
Marina Serrano-Macia1, Naroa Goikoetxea2, disease
Rubén Rodríguez Agudo2, Miren Bravo2, Sofia Lachiondo-Ortega2, Manami Iida1, Atsuko Higashide2, Shuichi Ohtomo1, Naoshi Horiba1,
Marcos Fernandez Fondevila3, Petar Petrov2,4, Irene González-Recio2, Atsushi Tanaka3. 1Chugai Pharmaceutical Co., Ltd., Japan; 2Chugai
Maria Mercado-Gómez2, Claudia Gil-Pitarch2, Marta Romero5, Research Institute for Medical Science, Inc., Japan; 3Teikyo University
Teresa Cardoso Delgado2, Luis Alfonso Martinez-Cruz2, School of Medicine, Medicine, Japan
Ruben Nogueiras3, Cesar Martin6, Piotr Milkiewicz7, Email: [email protected]
Malgorzata Milkiewicz8, Ute Schaeper9,10, Daniela Buccella11,
Background and aims: While ursodeoxycholic acid (UDCA) and
Jose Juan G. Marin4,5, Jorge Simón Espinosa1,4,
bezafibrate (BZF) are therapeutic options in primary biliary cholan-
María Luz Martínez-Chantar1,4. 1CIC bioGUNE-Centro de Investigación
gitis (PBC) and primary sclerosing cholangitis (PSC), there are
Cooperativa en Biociencias, Liver Disease Lab, Derio, Spain; 2CIC
treatment resistance cases that do not respond to the combination.
bioGUNE-Centro de Investigación Cooperativa en Biociencias, Liver
Here, we investigated the mechanism of UDCA + BZF treatment
Disease Lab, Derio, Spain; 3CiMUS-Centro Singular de Investigación en
resistance in terms of the bile acid composition and synthesis
Medicina Molecular y Enfermedades Crónicas, Molecular Metabolism
pathway in patients with PBC and PSC.
Lab, Santiago de Compostela, Spain; 4Carlos III National Health Institute,
Method: The subjects were PBC and PSC patients as well as control
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y
patients whose liver function test values were all within the normal
Digestivas (CIBERehd), Madrid, Spain; 5Instituto de Investigación
limits. Fasting plasma was collected and the plasma levels of various
Biomédica de Salamanca, Experimental Hepatology and Drug Targeting
bile acids, 7a-hydroxy cholesterol (7a-HC), 27-hydroxy cholesterol
(HEVEFARM), Salamanca, Spain; 6Campus De Bizkaia-Campus of Biscay,
(27-HC), and C4 were measured by liquid chromatography-tandem
Instituto Biofisika, Lejona, Spain; 7Medical University of Warsaw, Liver
mass spectrometry. In addition, various clinical test values tested on
and Internal Medicine Unit, Warszawa, Poland; 8Pomeranian Medical
the same day and therapeutic agents were collected. The relationship
University, Department of Medical Biology, Szczecin, Poland; 9Silence
between bile acid composition and synthetic pathway, UDCA and BZF
Therapeutics GmbH, Berlin, Germany; 10Silence Therapeutics GmbH,
treatment, and liver function tests was examined.
Berlin, Germany; 11New York University, Department of Chemistry,
Results: Patients with PBC (n = 30, all females, mean age 67 yrs,
New York, United States
UDCA/BZF administration: 26/8), PSC (n = 10, male/female = 7/3,
Email: [email protected]
mean age 44 yrs, UDCA/BZF administration: 10/5), and control
Background and aims: Primary biliary cholangitis (PBC) and primary patients (6 chronic hepatitis B, 23 chronic hepatitis C, 1 dyslipidemia,
sclerosing cholangitis (PSC) are progressive diseases that eventually M/F = 16/14, mean age 66 yrs, UDCA/BZF administration: 3/0) were
culminate in cirrhosis and related complications, as liver failure or enrolled in the study. The plasma level of UDCA-related bile acids
portal hypertension among others. However, cholestasis is com- were high in PBC/PSC, reflecting UDCA administration. Furthermore,
monly present in these patients. Hepatocytes are adversely affected GCA, TCA, and TCDCA were higher in PBC/PSC than those in the
by the accumulation of bile acids and trigger inflammatory and cell controls, and the concentrations of these three types of bile acids
death responses leading to development of fibrosis. Magnesium is were significantly correlated with the liver enzymes and bilirubin
known to play an important role in inflammatory and immune levels. In terms of the bile acid synthetic pathway, 27-HC was
responses. Since magnesium distribution can be modulated by positively correlated with liver enzyme levels, and 27-HC was high in
silencing Cyclin M4 (CNNM4), CNNM4 expression levels and the cases with elevated liver enzymes. In relation to BZF administration,
effectivity of a CNNM4-targeting therapy were evaluated in preclin- BZF-administered PBC/PSC cases (PBC 8, PSC 5) had significantly
ical models for cholestasis. lower values of 7a-HC and C4 and higher 27-HC than non-
Method: Hepatic CNNM4 expression was evaluated in PBC and PSC administered cases (PBC 22, PSC 5) (Figure).
biopsies and in samples from rodent models by immunohistochem-
istry. An in vitro cholestasis model was set up by incubating primary
hepatocytes with supraphysiological concentrations of glycodeoxi-
cholic acid (GCDCA). Animal models of cholestasis were generated by
bile-duct ligation (BDL) for 14 days and by the use of mice lacking
Mdr2 (Mdr2-/-) at 3, 5 and 8 months of age. The functional role of
CNNM4 in disease progression was characterized in in vitro and in
vivo models of cholestasis via GalNAc-siRNA mediated silencing
approach.
Results: CNNM4 upregulation was detected in liver samples of
patients with PBC and PSC. Furthermore, we found that CNNM4
expression was enhanced in mice that underwent BDL and in mice
lacking Mdr2. GalNAc-siRNA mediated silencing of CNNM4 protected Conclusion: GCA, TCA, and TCDCA were higher in treatment-resistant
primary mouse hepatocytes from GCDCA-induced cell death, PBC/PSC cases with elevated liver enzymes. In addition, 27-HC was
mitochondrial dysfunction, oxidative stress and endoplasmic reticu- elevated, suggesting that the alternative pathway was activated in
lum stress. In rodent models for cholestasis, GalNAc CNNM4 siRNA these treatment resistant cases. In the BZF-administered cases, 7a-HC
treatment protected the liver from fibrotic development and and C4 levels were low (Figure), indicating that Cyp7a1 was
inflammation. Silencing Cnnm4 in hepatocytes induced intracellular suppressed and the classical pathway was suppressed as previously
magnesium accumulation, which may protect these cells by affecting reported. On the other hand, 27-HC was not decreased and the
the bile acid homeostasis. alternative pathway was not suppressed, irrespective of liver enzyme
Conclusion: CNNM4 has been identified as a potential novel levels (Figure). Taken together, BZF treatment failed to inhibit the
therapeutic target for bile acid-induced liver damage. Herein, we alternative pathway of bile acids which were activated in cases with
show evidence that silencing CNNM4 by a GalNAc siRNA-approach elevated liver enzymes, possibly, in part, explaining the mechanism
could also be a novel effective approach for treatment of cholestasis- of treatment resistance.
associated liver fibrosis.

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 POSTER PRESENTATIONS
FRI455 phospholipid receptor 1 (S1PR1) is distributed in various organs, it is
Reduced hepatic expression of PPAR alpha in primary biliary the receptor of endogenous substance sphingosine-1-phospholipid
cirrhosis is modulated by miR-155 (S1P) and participates in a variety of physiological and pathological
Monika Adamowicz1, Agnieszka Kempinska-Podhorodecka1, process. But its role in cholestatic liver disease has not yet been
Joanna Abramczyk1, Jesus Maria Banales2, Piotr Milkiewicz3, elucidated clearly.
Małgorzata Milkiewicz1. 1Pomeranian Medical University, Department Method: To study the cholangiocyte-specific role of S1PR1, we
of Medical Biology, Szczecin, Poland; 2Biodonostia Health Research generated a novel knock-out mouse strains by breeding Krt19Cre
Institute, Department of Liver and Gastrointestinal Diseases, Donostia mice with S1pr1 floxed mice. S1PR1 cell specific deletion was
University Hospital, Ikerbasque, CIBERehd, San Sebastian, Spain; confirmed in primary isolated intrahepatic cholangiocytes by PCR,
3 WB, and IF, and in liver frozen section by IF. Fibrosis was established
Medical University of Warsaw, Liver and Internal Medicine Unit,
Warsaw, Poland by common bile duct ligand (BDL) (14 days) and CA (0.5%) chow diet
Email: [email protected] (4 months). Liver damage was determined by serum ALT, AST, ALP,
TBA, and H&E staining. Fibrosis was determined by hepatic hydro-
Background and aims: Peroxisome proliferator-activated receptor xyproline, Masson trichrome staining, Sirius staining, and IHC.
alpha (PPARa) regulates expression of multiple genes involving lipid Comprehensive serum and liver bile acids profiling were performed
metabolism, bile acids (BA) homeostasis, and shows protective effects using HPLC-MS/MS. RNA-seq was performed in whole liver and
against inflammation and apoptosis. Progressive diseases such as primary cholangiocytes after BDL.
primary biliary cirrhosis (PBC) and primary sclerosing cholangitis Results: First we observed that S1PR1 was more expressed on
(PSC) result in intrahepatic retention of toxic BA that may lead to liver cholangiocytes after 14 days BDL and 4 months CA chow diet.
dysfunction and failure. Small non-coding RNA molecules (miRNAs) Interestingly, S1PR1Krt19CreERT+/+ mice displayed a trend towards
regulate gene expression, and miR-155 was associated with silencing
attenuated liver injury and liver fibrosis compared to WT mice after
of PPARa. Since PPARa activation decreases inflammation and fibrosis
BDL and CA chow diet, demonstrated by significantly decrease in
we evaluated PPARa and miR-155 expressions in cholestatic livers. serum ALT, AST, ALP, TBA, hepatic hydroxyproline, Masson Trichrome,
We have also analyzed the regulatory effect of miR-155 on PPARa
H&E, and Sirius red staining as well as immunohistochemistry
expression in vitro. staining of α-SMA. BA profiling and PCA analysis indicated that
Method: Liver samples were taken from biopsies at early stages (F1- S1PR1Krt19CreERT+/+ mice alleviates the destruction of bile acid
F2) of PBC (n = 12) or from explanted livers in patients with cirrhotic
homeostasis induced by BDL and CA chow diet. RNA-seq analysis in
PBC (n = 11) and PSC (n = 17). The functional role of miR-155 was
BDL liver showed downregulation of ROS, ER stress, and CCR1
characterized in vitro in hepatocytes (HepG2) and primary cholan-
chemokine receptor binding signaling in S1PR1Krt19CreERT+/+ mice
giocytes (NHC) where overexpression of miR-155 was induced by
compared to WT mice. WB analysis showed that cholangiocytes-
mirVana miRNA Mimic. miR-155 expression levels were evaluated
specific deletion of S1PR1 attenuates CHOP induction, phosphoryl-
after treatment with lipopolysaccharide (LPS), glycodeoxycholic acid
ation of JNK, eif2α, and PERK induced by BDL. Q-PCR analysis showed
(GCDCA), lithocholic acid (LCA) or ursodeoxycholic acid (UDCA).
that cholangiocytes-specific deletion of S1PR1 attenuates the
Results: When compared to controls hepatic PPARa mRNA and
upregulation of Ccl4, Ccl6, and Ccl7 induced by BDL.
protein levels were reduced in cirrhotic PBC (both 50% reduction, P =
Conclusion: Our results illustrate that the cholangiocytes-specific
0.01), but not in PSC livers. In PBC livers this phenomenon was
deletion of S1PR1 can alleviate liver fibrosis and injury caused by
accompanied with induction of miR-155 (3.7-fold increase, P = 0.004
biliary obstruction or chronic cholestasis, which helps to develop
vs. control). Experimental overexpression of miR-155 in HepG2 led to
S1PR1 as a target for the treatment of liver fibrosis and cholestasis.
the inhibition of PPARa (50% reduction, P = 0.02). LPS stimulated miR-
155 expression in HepG2 (over 40-fold increase, p = 0.009), whereas FRI457
the treatment with GCDCA or LCA enhanced the expression of Pruriceptor activating compounds in the eneterohepatic cycle in
miR-155 in NHC (2-fold p < 0.05, or 2.4 fold p < 0.05, respectively). cholestatic itch
UDCA suppressed the basal expression of miR-155 in NHC (20% Frank Wolters1, Jacqueline Langedijk1, Dagmar Tolenaars1,
reduction, p = 0.02 vs. control) as well as the LPS-induced miR-155 in Michel van Weeghel2, Rudi de Waart1, Stan van de Graaf1,
HepG2 ( p = 0.009 vs LPS). Coen Paulusma1,3, Wendy L. van der Woerd4, Henkjan J. Verkade5,
Conclusion: We showed that PPARa is substantially reduced in PBC Arthur Verhoeven1, Ulrich Beuers1, Ronald Oude Elferink1.
livers, and the observed concomitant overexpression of miR-155 1
Amsterdam UMC, Tytgat Institute, Amsterdam, Netherlands;
induced either by inflammation or bile acids may be accountable for 2
Amsterdam UMC, Core Facility Metabolomics, Amsterdam,
this suppression. Inhibition of miR-155 may be a potential novel Netherlands; 3Amsterdam UMC, locatie AMC, Tytgat Institute for Liver
therapeutic target in PBC. and Intestinal Research, Amsterdam, Netherlands; 4Utrecht UMC,
Department of Pediatric Gastroenterology, Utrecht, Netherlands; 5UMC
FRI456
Groningen, Department of Pediatrics, Groningen, Netherlands
cholangiocytes-specific deletion of sphingosine-1-phospholipid
Email: [email protected]
receptor 1 attenuate cholestasis induced liver injury and fibrosis
Yuan Zihang1, Jie Wang1, Yingying Miao1, Haoran Zhang1, Background and aims: Pruritus can be a major and debilitating
Xinliang Huang1, Luyong Zhang1,2, QW Yu1, Zhenzhou Jiang1,3,4. symptom in cholestasis. Treatment is difficult, as the pathophysiology
1 of this symptom remains elusive. This study aims to identify
China Pharmaceutical University, New drug screening center, Jiangsu
center for pharmacodynamics research and evaluation, Nanjing, China; circulating agonists for TRPA1 and other pruriceptors in the
2 enterohepatic circulation, in bile and blood, as a possible cause for
Guangdong Pharmaceutical University, Center for drug research and
development, Guangdong, China; 3China Pharmaceutical University, Key itching in cholestatic patients.
laboratory of drug quality control and pharmacovigilance, Nanjing, Method: Bile of 5 cholestatic patients with and without itch (various
China; 4China Pharmaceutical University, State key laboratory of natural cholestatic liver diseases), was fractionated and assessed for in vitro
medicines, Nanjing, China pruriceptor activation ([Ca2+]I and luciferase assays) in HEK293T
Email: [email protected] cells. Collected fractions were tested for activation of specific
receptors (TRPA1, TRPV1, TRPV3, TRPV4, MRGPRX1, MRGPRX4, FXR)
Background and aims: Cholestasis is a pathophysiological process and active fractions were subfractionated and again tested. The
caused by disorders involving bile secretion and excretion. Chronic content of positive fractions was identified by means of HPLC-MS/MS
cholestasis can cause bile acids (BAs) to accumulate in the liver, and, if possible, validated with commercially available standards.
induce liver injury, inflammation, and liver fibrosis. Sphingosine-1-

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S601

POSTER PRESENTATIONS
Pruritogenic activity of these compounds was assessed by intrader- A key challenge to characterising early pathology in PSC has been
mal injection in wild type and TRPA1-deficient mice. related to acquiring liver biopsies. However, fine needle aspiration
Results: Several fractions from bile activated the TRPA1 receptor (and (FNA) has emerged as a safe technique for obtaining liver infiltrating
several other receptors) in vitro. One of these fractions contained a immune cells. We sought to assess the experimental efficacy of FNA to
compound with m/z 311.22 which could be identified as a hydrophilic adequately sample liver immune cells, and to map the early
isomer of hydroperoxylinoleic acid (HpODE). We could also show that inflammatory landscape in the liver relative to matched peripheral
in bile HpODE is rapidly converted into a hydrophilic isomer. Upon blood using single-cell profiling technologies. We also sought to
biliary diversion of a BRIC type 1 patient we could show that the assess how inflammation in the liver compares to pathology in the
initial excretion of HpODE and its metabolites is very high with gut of PSC patients presenting with UC.
gradual decrease concomitant with the disappearance of itch. In Method: We obtained liver-infiltrating mononuclear immune cells
plasma of pruritic cholestatic patients HpODE concentrations were via FNA and peripheral blood mononuclear cells (PBMCs) from
significantly increased compared to cholestatic patients without itch patients with PSC and with non-alcoholic fatty liver disease/
and healthy controls. Wild type mice exhibited scratching behavior steatohepatitis. Cells were analysed by polychromatic flow cytometry
upon intradermal injection of HpODE, whereas TRPA1 deficient mice and by 10× Genomics single-cell RNA sequencing (scRNAseq). In
did not. addition, gut biopsies from PSC-UC patients were obtained and also
Conclusion: HpODE, a pruritogen in vitro and in vivo is present in analysed by scRNAseq.
elevated levels in cholestatic patients who experience itch. This Results: We obtained liver FNAs from 38 patients (21 PSC, 17 control
compound, and its metabolites is highly secreted into bile upon patients). The median pain score was 0 and no serious adverse effects
biliary diversion. Pruriceptor antagonists may be useful in the were reported. Flow cytometry analysis demonstrated a significant
treatment of cholestatic pruritus. enrichment of natural killer (NK) cells, CD8+ T cells, and CD69+ T cells
in the liver (all p < 0.05). High-resolution profiling of 38, 012 liver
FRI458 immune cells and 78, 751 PBMCs by scRNAseq in a patient subset
Characterising the early inflammatory landscape of primary specifically showed an enrichment of CXCR6+ NK cells, CD8+ central
sclerosing cholangitis memory T cells, and mucosal-associated invariant T cells in the liver,
Calli Dendrou1, Kate Lynch2,3, Fabiola Curion1,4, and a relatively lower abundance of CD4+ regulatory T cells (all p <
Charlotte Rich-Griffin1, Hing-Yuen Yeung1, Nicholas Provine2, 0.05). Among other immune cell types captured, dendritic cells were
Nicholas Ilott2, Helen Ferry2, Eve Fryer5, Holm Uhlig2, enriched in the liver whilst FOShi classical monocytes were reduced
Roger W.G. Chapman2, Satish Keshav2, Paul Klenerman2. 1Wellcome ( p < 0.05). Gene expression analyses also revealed PSC-specific
Centre for Human Genetics, University of Oxford, Oxford, United inflammatory pathways, such as an increase in cytokine responsive-
Kingdom; 2Translational Gastroenterology Unit, University of Oxford, ness, and analogous analyses were applied to the PSC gut samples.
Oxford, United Kingdom; 3Royal Adelaide Hospital, University of Conclusion: FNA sampling is a safe approach for obtaining insights
Adelaide, Adelaide, Australia; 4Institute of Computational Biology, into the early inflammatory landscape of the liver in PSC and other
Helmholtz Munich, Neuherberg, Germany; 5John Radcliffe Hospital, diseases, with the application of single-cell methods across tissues
Nuffield Division of Clinical and Laboratory Sciences, Oxford, United revealing tissue-specific and shared inflammatory pathways that may
Kingdom provide a basis for further experimental medicine analyses.
Email: [email protected]
FRI460
Background and aims: Primary sclerosing cholangitis (PSC) is a Copper accumulation in chronic cholestatic disease augments
chronic inflammatory biliary disease characterised by progressive liver damage by impairment of mitochondrial function
fibrosis that can lead to cirrhosis and liver failure. Over 70% of PSC
Dennis Koob1, Judith Nagel2,3, Sebastian Zimny1, Jingguo Li1,4,
patients also have gut co-morbidities, typically ulcerative colitis (UC),
Renate Artmann1, Ralf Wimmer1, Gerald Denk1, Martin Roderfeld5,
suggesting a link between liver pathology and gut microbial
Elke Roeb5, Hans Zischka2,3, Simon Hohenester1. 1University Hospital
dysbiosis. Therapeutic options for PSC are limited, with liver
LMU, Department of Medicine II, Munich, Germany; 2Technical
transplantation being most effective, although disease may recur.
University of Munich, Department of Toxicology and Environmental
Thus, there is a dire need to better understand and target the
Hygiene, Munich, Germany; 3Helmholtz Center Munich, Institute of
pathological mechanisms of PSC, particularly those acting early on.
Molecular Toxicology and Pharmacology, Munich, Germany; 4Affiliated

Figure: (abstract: FRI458)

S602 Journal of Hepatology 2022 vol. 77(S1) | S389–S664

 POSTER PRESENTATIONS
Hospital of Zunyi Medical University, Department of Gastroenterology, FRI461
Zunyi, China; 5Justus Liebig University, Gastroenterology, Center for The IgG4-related cholangitis autoantigen laminin 511-E8
Internal Medicine, Gießen, Germany stabilizes the biliary bicarbonate umbrella in human
Email: [email protected] cholangiocytes
Background and aims: Derangement of copper homeostasis, as seen David Trampert1, Remco Kersten1, Dagmar Tolenaars1,
Ronald Oude-Elferink1, Stan van de Graaf1, Ulrich Beuers1. 1Tytgat
in Wilson’s disease, causes liver damage. Copper accumulation also
occurs in chronic cholestatic liver disease. In primary sclerosing Institute for Liver and Intestinal Research, Amsterdam Gastroenterology
Endocrinology Metabolism (AGEM), Amsterdam University Medical
cholangitis, copper accumulation, i.e. Orcein staining as a component
Centers, Department of Gastroenterology and Hepatology, Amsterdam,
of the Nakanuma score, even predicts reduced transplant-free
survival. We hypothesize that copper accumulation might not only Netherlands
Email: [email protected]
be a consequence of cholestasis, but modulate the course of disease.
We aimed to investigate the role of copper accumulation in animal Background and aims: IgG4-related cholangitis (IRC) is the
models of cholestasis and identify potential molecular targets of hepatobiliary manifestation of IgG4-related disease (IgG4-RD), a
copper and bile salt co-toxicity. systemic, B-cell driven, fibroinflammatory disorder. To date four
Method: Hepatic copper content was determined in wild type and autoantigens with pathogenetic relevance have been described by
Mdr2−/− animals on both FVB and BALBc backgrounds. Liver damage our group and others in IgG4-RD, namely annexin A11, laminin
and liver fibrosis were quantified. Mdr2/FVB animals were fed a 511-E8, galectin 3 and prohibitin 1 (PMID 28765476, 30089633). We
copper-enriched diet (2 g/kg). The hepatocyte cell line HepG2 was recently demonstrated that patient anti-annexin A11 autoantibodies
stably transfected with Ntcp to allow for bile salt uptake and was destabilize the ‘biliary bicarbonate umbrella’ (PMID 34718050), a
stimulated with glycochenodeoxycholate (GCDC) and copper (5– protective mechanism against toxic hydrophobic bile acids (PMID
10 μM, each). Cell survival, apoptosis, proliferation, and metabolic 20721884). Another autoantigen, laminin 511-E8, is an extracellular
activity were assessed. In mitochondria from stimulated cells, oxygen matrix protein that functions as a ligand of the integrin A6B1
consumption and ATP production were quantified. (ITGA6B1) receptor (PMID 28879238). Laminin 511-E8 has been
Results: While hepatic copper content was not different from shown to upregulate critical components of the ‘biliary bicarbonate
wildtype in Mdr2/FVB animals, it was increased 1.5 ± 0.2-fold in umbrella’ (PMID 27103433) and ITGB1 signaling is important for bile
Mdr2/BALBc (wt/BALBc vs. Mdr2/BALBc, n = 5, p < 0.05). Overall, duct development (PMID 22761447). Therefore, we aimed to
hepatic copper content correlated with liver fibrosis as determined by investigate the role of laminin 511-E8 in human cholangiocytes.
liver hydroxyproline (r2 = 0.8, p < 0.05, n = 9). Copper feeding was well Method: Laminin 511-E8 expression was confirmed in RNA sequen-
tolerated in wt animals and was associated with a slight but cing datasets of human cholangiocyte organoids. Human H69 cells
insignificant increase in serum ALT only in Mdr2/FVB animals. were subjected to shRNA knockdown using lentiviral transduction.
However, it led to an increase in hepatic copper content (13.5 ± 1.2 Individual knockdown cell lines were generated targeting the mRNA
vs. 1898.3 ± 445.7 mg/kg, n = 6, p < 0.01) and liver fibrosis (Desment transcripts encoding laminin 511-E8 (LAMA5, LAMB1, LAMC1).
score, 0.4 ± 0.5 vs. 1.3 ± 0.5, p < 0.05) in Mdr2/FVB. In HepG2, doses Knockdown of LAMB1 and LAMC1 was verified on mRNA and
applied of both GCDC and copper were non-toxic in WST assays. protein level using qPCR and western blot. A parallel approach was
Combination of both stimuli, however, led to a marked impairment of taken subjecting H69 cells to recombinant laminin 511-E8 (0.25 ug/
metabolic activity to 65.9 ± 4.3% (n = 6, p < 0.05). While caspase-3/7 cm2). The function of laminin 511-E8 in human cholangiocytes was
assays excluded apoptosis, reduced proliferative activity was found assessed by three approaches: (i) intracellular pH ( pHi) measure-
upon dual treatment. In isolated mitochondria from stimulated ments microspectrofluorimetrically using BCECF-AM; (ii) rate of bile
HepG2 cells, ATP production was unaffected by each stimulus alone. acid influx radiochemically by measuring 22, 23-3H-glycocheno-
Combined treatment, however, led to a drop in ATP production from deoxycholic acid (3H-GCDC) permeation over time; (iii) GCDC-
100 ± 4.1% to 46.1 ± 9.7% (n = 3, p < 0.05) (Figure 1), accompanied by induced apoptosis determined dynamically by real-time imaging of
an increase in mitochondrial oxygen consumption. Caspase-3/7 Green signal and statically by conventional bulk
Caspase-3/7 assays.
Results: Screening of the laminin 511-E8 constituent knockdown cell
lines revealed that at least LAMB1 and LAMC1 could be of functional
importance in cholangiocytes. 3H-GCDC permeation was larger in
LAMB1 and LAMC1 knockdown H69 cells compared to Sham controls.
Treatment of human cholangiocytes with the recombinant 511-E8
fragment resulted in a decreased pHi and significantly reduced the
rate of 3H-GCDC permeation (Figure).

Conclusion: Hepatic copper deposition in experimental cholestasis is

associated with progression of liver fibrosis, mimicking the human
phenotype. On a cellular level, bile salt and copper synergistically
impair ATP production. Since the respiratory chain was unaffected
(increase rather than drop in oxygen consumption), the adenine
nucleotide translocator (ANT) is a likely molecular target. These
results encourage testing of copper chelating strategies in cholestatic
liver disease.
Conclusion: Collectively, our study indicates that the IgG4-RD
autoantigen laminin 511-E8 has a protective role in human

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POSTER PRESENTATIONS
cholangiocytes against toxic bile acids, similar as recently described dysregulated T cell phenotype in patients with PSC. Decoding how
for annexin A11. We speculate that autoantibodies against laminin genetic risk contributes to disease pathogenesis is the first step in
511-E8 may destabilize the biliary bicarbonate umbrella, thereby understanding how the environment interacts with the immune
contributing to the pathogenesis of IRC. system to fuel disease pathogenesis.

FRI462 FRI463
The risk-variant rs56258221 at the BACH2-locus associates with Single-cell profiling of liver B cells identifies distinct gene
skewed polarization of naive CD4+ T cells towards pro- expression and reactivities of expanded B cell clonotypes in
inflammatory phenotypes in primary sclerosing cholangitis primary sclerosing cholangitis
Jonas Bahn1, Lilly K. Kunzmann1, Jenny Krause1, Christian Casar1,2, Markus Jördens1,2,3, Tom Hemming Karlsen1,2,4,5,
Silja Steinmann1, Marcial Sebode1, Samuel Huber1,3, Espen Melum1,2,4,5,6, Johannes R. Hov1,2,4,5, Brian K. Chung1,2.
Ansgar W. Lohse1,3, Andre Franke4, Nicola Gagliani1,3,5,6, 1
University of Oslo, Norwegian PSC Research Center, Oslo University
Dorothee Schwinge1, Christoph Schramm1,3,7, Tobias Poch1. Hospital and Institute of Clinical Medicine, Oslo, Norway; 2Oslo
1
University Medical Center Hamburg-Eppendorf, I. Department of University Hospital, Research Institute of Internal Medicine, Oslo,
Medicine, Hamburg, Germany; 2University Medical Center Hamburg- Norway; 3University Hospital Düsseldorf, Clinic for Gastroenterology,
Eppendorf, Bioinformatics Core, Hamburg, Germany; 3University Hepatology and Infectious Diseases, Medical Faculty, Heinrich Heine
Medical Center Hamburg-Eppendorf, Hamburg Center for Translational University Düsseldorf, Düsseldorf, Germany; 4University of Oslo,
Immunology, Hamburg, Germany; 4Christian-Albrechts-University of Institute of Clinical Medicine, Oslo, Norway; 5Oslo University Hospital,
Kiel, Institue of Clinical Molecular Biology, Kiel, Germany; 5University Section for Gastroenterology, Department of Transplantation Medicine,
Medical Center Hamburg-Eppendorf, Department for General, Visceral Division of Surgery, Inflammatory Diseases and Transplantation, Oslo,
and Thoracic Surgery, Hamburg, Germany; 6Karolinska Institute, Norway; 6University of Oslo, Hybrid Technology Hub-Centre of
Immunology and Allergy Unit, Department of Medicine Solna, Excellence, Institute of Basic Medical Sciences, Faculty of Medicine, Oslo,
Stockholm, Sweden; 7University Medical Center Hamburg-Eppendorf, Norway
Martin Zeitz Center for Rare Diseases, Hamburg, Germany Email: [email protected]
Email: [email protected]
Background and aims: Primary biliary cholangitis (PBC) and primary
Background and aims: Primary sclerosing cholangitis (PSC) is an sclerosing cholangitis (PSC) are autoimmune hepatobiliary diseases
enigmatic disease of presumably multifactorial pathogenesis, includ- with a high prevalence of autoantibodies. In PBC, anti-mitochondrial
ing genetic predisposition and dysregulated immune responses as antibodies (AMA) serve as robust biomarkers whereas autoanti-
likely key contributors to the disease development. We have bodies against relevant antigens in PSC remain undefined. Using anti-
previously described an intrahepatic naive-like population of CD4+ mitochondrial reactivity as a proxy of disease-relevance, we assessed
T cells in patients with PSC, prone to polarize towards a pro- if expanded B cell clonotypes in PBC livers recognize AMA targets and
inflammatory TH17 phenotype. Genome-wide association studies whether analogous B cells in PSC harbour unique gene expression
(GWAS) have linked PSC to several polymorphisms in immune- and antigen specificities.
related genes. We here hypothesized that genetic predisposition Method: Liver B cells from PBC (n = 3) and PSC explants (n = 3) were
contributes to the observed T cell phenotype in patients with PSC. enriched by negative bead selection (Stemcell Technologies, Canada)
Method: Patients with PSC (n = 270) were genotyped for the disease- and assessed for B cell receptor (BCR) and total gene expression by
associated risk variants rs56258221 (BACH2), rs80060485 (FOXP1), single-cell RNA sequencing (scRNAseq). B cell clonality and differen-
rs4147359 (IL2RA) and rs7426056 (CD28). To determine T cell function tial gene expression (DEG) was analyzed by Cell Ranger and Loupe
and phenotype, comprehensive immunophenotyping, in vitro experi- Browser (10X Genomics, USA). Monoclonal antibodies (mAb)
ments on polarization and proliferation, microRNA-assays, western generated from BCR sequences of expanded B clonotypes
blots and single-cell RNA sequencing from peripheral blood naive (GenScript, USA) were pooled and screened against >20, 000
CD4+ T cells was performed. The data generated was correlated to the human proteins using HuProt v4 microarrays (Cambridge Protein
underlying genotype of the patients. Arrays, UK). A subselection of mAb microarray targets were verified
Results: Functional in vitro experiments with naive CD4+ T cells from by immunoblotting or enzyme-linked immunosorbent assays
patients with PSC and healthy donors (HD) showed an increased (ELISA).
capacity of PSC-derived cells to convert into pro-inflammatory T Results: Cumulative frequencies of the five most-expanded B
Helper 1 (TH1, 50.7% vs. 42.9%, p = 0.027) and T Helper 17 (TH17, 5, 5% clonotypes as a percentage of total liver clonotypes were similar
vs. 2, 2%, p = 0.042) subsets, which was accompanied by a lower amongst PBC and PSC explants (mean: 16.8% vs 15.4%, range: 9.1–
conversion rate into induced regulatory T cells (iTREG, 9.6% vs. 17.3%, 30.42% to 0.68–41.17%). In contrast, transcriptomes of expanded PBC
p = 0.022). The observed effects were significantly increased in clonotypes significantly differed from PSC clonotypes; plasma cell
carriers of the PSC-associated risk variant rs56258221 (BACH2), markers such as CD38, JSRP1 and MZB1 were significantly higher in
which was not seen for the other variants in immune-related genes PBC clonotypes while the naïve and memory B cell markers MS4A1,
assessed. Interestingly, single-cell RNA sequencing of the T cell CD79A, CD79B and HLA-DP, -DQ, -DR were significantly enriched in
compartment in homozygous SNP carriers vs. non-carriers identified PSC clonotypes (log2 fold-change >2.5, p < 0.05, Benjamini-Hochberg
a composition skewed towards activated phenotypes in rs56258221- corrected). mAbs generated from the BCR sequences of expanded PBC
carriers. Reduced expression of BACH2 itself was detected on protein clonotypes strongly recognized the AMA targets PDC-E2, PDHA1,
but not mRNA level in naive CD4+ T cells, which could be linked to a PDHA2, PDHX whereas PSC mAbs did not recognize AMA targets but
strongly increased expression of a microRNA located in close genomic strongly bound ACTN4, SFMBT2 and RBP ( p < 0.001). PBC mAbs (5 of
proximity to the SNP and imputed to inhibit translation of BACH2. 15) stained a pooled mixture of AMA antigens (PDC-E2, OGDC-E2,
Conclusion: We here present comprehensive data linking the risk BCOADC-E2) by immunoblotting and ACTN4 binding was assigned to
variant rs56258221 at the BACH2-locus to the recently described a single PSC mAb (1 of 14) by ELISA.

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 POSTER PRESENTATIONS
between the genetic variant in APOE and higher ALT was also noticed
in the entire cohort ( p = 0.054). No link was found between the
studied variant and results of liver biopsies, transient elastography or
CAP (all P > 0.05). The protective effect of the MARC1 polymorphism
on serum ALT ( p = 0.045) and AST ( p = 0.024) activities were more
pronounced in patients with APOE wild-type variant. The effect of the
PNPLA3 p.I148M polymorphism on liver phenotypes was not
modulated by the APOE genotype.
Conclusions: Patients with AIH who carry the APOE polymorphism
might manifest a more pronounced liver injury. Variant APOE
(rs429358) together with previously detected MARC1 p.A165T
Figure: scRNAseq of expanded B clonotypes in PBC and PSC liver explants. polymorphism might help to stratify patients with AIH concerning
UMAP shows cluster analysis of expanded clonotypes and heatmap indi-
their risk of progressive liver injury.
cates comparison of top 20 DEG amongst expanded PBC and PSC
clonotypes.
FRI465
Conclusion: Our results show that expanded B clonotypes in PBC Intrabiliary injection of MAIT antigens induces cholangitis in
livers resemble antibody-secreting plasma cells while expanded PSC mice
clonotypes mirror naïve and memory B cell states. These findings Kathrine Sivertsen Nordhus1,2,3, Freeman Zheng1,2,3,
may explain the lack of specific antibodies in PSC and underscore the Natalie Lie Berntsen1,2,3, Laura Valestrand1,2,3, Jonas Øgaard1,2,3,
utility of scRNAseq in generating mAbs for future antigen studies in Tom Hemming Karlsen1,2,3,4, Xiaojun Jiang1,2,3, Espen Melum1,2,3,4,5.
1
PSC. Norwegian PSC Research Center, Division of Surgery, Inflammatory
Diseases and Transplantation, Oslo University Hospital, Oslo, Norway;
FRI464 2
Research Institute of Internal Medicine, Division of Surgery,
The rs429358 apolipoprotein E (APOE) polymorphism is Inflammatory Diseases and Transplantation, Oslo University Hospital,
associated with increased liver injury in patients with Oslo, Norway; 3Institute of Clinical Medicine, University of Oslo, Olso,
autoimmune hepatitis Norway; 4Section of Gastroenterology, Division of Surgery, Inflammatory
Maciej K. Janik1, Wiktor Smyk2, Beata Kruk3, Diseases and Transplantation, Oslo University Hospital, Oslo, Norway;
5
Benedykt Szczepankiewicz4, Barbara Górnicka4, Susanne N Weber5, Hybrid Technology Hub-Centre of Excellence, Institute of Basic Medical
Piotr Milkiewicz1,6, Marcin Krawczyk3,5. 1Medical University of Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway
Warsaw, Liver and Internal Medicine Unit, Warsaw, Poland; 2Medical Email: [email protected]
University of Gdansk, Department of Gastroenterology and Hepatology,
Background and aims: Mucosal-associated invariant T (MAIT) cells
Gdansk, Poland; 3Medical University of Warsaw, Laboratory of Metabolic
are a subset of unconventional T-cells that recognize microbial-
Liver Diseases, Department of General, Transplant and Liver Surgery,
derived vitamin B metabolites presented by MR1. Previously we have
Laboratory of Metabolic Liver Diseases, Centre for Preclinical Research,
demonstrated that bile from patients with chronic biliary inflamma-
Warsaw, Poland; 4Medical University of Warsaw, Department of
tion contains MAIT antigens. Therefore we now aimed to determine if
Pathology, Warsaw, Poland; 5Saarland University Medical Center,
MAIT cells could drive inflammation in the bile ducts by challenging
Saarland University, Department of Medicine II, Homburg, Germany;
6 mice with an increased frequency of MAIT cells (Mr1+ B6-MAITCAST
Pomeranian Medical University, Translational Medicine Group
and iValpha19 Tg Calpha −/− mice) with intrabiliary injection of MAIT
Email: [email protected]
cell activating antigens in terms of fixed E.coli and 5-OP-RU.
Background and aims: The natural course of autoimmune hepatitis Method: E.coli, 5-OP-RU and PBS were injected into bile ducts of Mr1+
(AIH) varies between patients; therefore, the potential role of genetic B6-MAITCAST and iValpha19 Tg Calpha −/− mice. Weight and general
modifiers might be suspected. Recent analyses linked the variant well-being were monitored daily. The mice were sacrificed after 2, 7
rs429358 in apolipoprotein E (APOE) with steatosis and liver injury in or 14 days. Isolated lymphocytes from liver and spleen were stained
fatty liver disease (Jamialahmadi et al., Gastroenteorology 2021). Here, with monoclonal antibodies and an MR1 tetramer, then analyzed by
we analyse this APOE variant in patients with AIH. flow cytometry. Serum was analyzed for alanine transaminase (ALT).
Method: The study cohort consisted of 312 non-transplanted (70% Results: Intrabiliary fixed E.coli injection in iValpha19 Tg Calpha −/−
women, age 18–83 years) adults with AIH. Pure AIH and its mice caused a biliary immune response with increased histological
cholestatic variants, namely AIH-primary sclerosing cholangitis cholangitis score (E.coli: 1.29 vs. PBS: 0.24, p = 0.013) after 2 days, but
(PSC) and AIH-primary biliary cholangitis (PBC), were diagnosed with similar weight loss and ALT levels compared to vehicle control.
according to the EASL 2015 guidelines. The APOE rs429358 Importantly, a clear activation of hepatic MAIT cells were seen after
polymorphisms were genotyped using TaqMan assays. The liver injection of fixed E.coli (MFI CD69 E.coli vs. PBS: p = 0.0015) in
fibrosis was assessed by liver biopsy, liver stiffness and serum indices contrast to a minor increase in CD69 MFI for non-MAIT T-cells. In
(APRI, FIB-4), whereas liver steatosis was evaluated by controlled Mr1+ B6-MAITCAST mice, which has an increased frequency of MAIT
attenuation parameter (CAP). The effects of the APOE polymorphism cells independent of genetic manipulation, an increased cholangitis
were analysed in combination with the mitochondrial amidoxime- score ( p = 0.0485) was also observed after injection of fixed E. coli.
reducing component 1 (MARC1) p.A165T and adiponutrin (PNPLA3) p. In experiments with intrabiliary 5-OP-RU injection in iValpha19 Tg
I148M variants, which were previously shown to modulate liver Calpha −/− mice a clear increase in proportion of CD69+CD25+ MAIT
injury in AIH. cells was observed in the liver (5-OP-RU: 18% vs. PBS: 7%, p < 0.0001)
Results: Among recruited patients, the median duration of the that translated into an increased histological cholangitis score (5-OP-
disease was 4 (range 0–33) years. Liver cirrhosis was present in 130 RU: 1.78 vs. PBS: 0.47, p = 0.021). This suggests that direct activation of
(42%) patients, and 70% of the entire cohort received steroid-based MAIT cells leads to cholangitis. A systemic effect, most likely
therapy. Sixty (19%) patients were therapy naïve at inclusion. In total, mediated by the portal circulation, was also observed as the
26% of patients with AIH carry at least one copy of the APOE rs429358 proportion of CD69+CD25+ MAIT cells in the spleen was also increased
minor allele. The APOE polymorphism was associated with more (5-OP-RU: 6% vs. PBS: 3%, p = 0.0386).
pronounced liver fibrosis according to APRI score ( p = 0.035) and liver
injury as reflected by increased AST ( p = 0.049) and a trend for higher
ALT ( p = 0.055) activities in therapy-naïve patients with AIH. A trend

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POSTER PRESENTATIONS
fraction in the periportal area correlated with disease progression.
Inhibiting TGF-β2 expression with antisense oligonucleotides leads to
reduced pSmad3 positive cell numbers, suggesting that TGF-β2 is
triggering Smad3 signaling.

Figure: Intrabiliary 5-OP-RU injection in iValpha19 Tg Calpha −/− mice acti-

vates MAIT cells.

Conclusion: We observed a clear activation of hepatic MAIT cells in a

mouse model of bile duct inflammation that led to cholangitis. Biliary
antigens potentially derived from gut microbiota present in the bile
ducts could therefore be speculated to induce an immune response
where MAIT cells play a role.

FRI466 Conclusion: TGF-β2 expression is upregulated in cholangiocytes in

TGF beta 2 fuels inflammation and fibrosis in cholestatic liver patients and mouse models with cholestatic liver disease.
disease through macrophage and myofibroblast recruitment and Neighboring inflammatory and fibrogenic cells display pSmad3
activation staining and increase in numbers. Next, we search for stress factors
and upstream signals that induce TGF-β2 expression during chole-
Jan Albin1, Nadja Meindl-Beinker2, Matthias Ebert2, Andreas Teufel3,
static liver damage.
Steven Dooley1, Anne Dropmann1,3. 1Medical Faculty Mannheim,
Heidelberg University, Department of Medicine II, Molecular Hepatology, FRI467
Mannheim, Germany; 2Medical Faculty Mannheim, Heidelberg Liver-specific Tsg101 depletion causes apoptosis, cell death and
University, Department of Medicine II, Mannheim, Germany; 3Medical liver failure
Faculty Mannheim, Heidelberg University, Department of Medicine II,
Surui Wang1,2, Revathi Sekar1,2, Jaroslaw Cendrowski3,
Clinical Bioinformatics, Mannheim, Germany
Ahmed Ghallab4, Karsten Motzler1,2, Yun Kwon1,2, Susanne Seitz1,2,
Email: [email protected]
Michael Roden2,5,6, Adriano Maida1,2, Jan G. Hengstler4,
Background and aims: We have identified TGF-β2 as an important Stephan Herzig1,2, Marta Miaczynska3, Anja Zeigerer1,2. 1Institute for
mediator and potential therapeutic target in cholestatic liver disease, Diabetes and Cancer, Helmholtz Center Munich, Joint Heidelberg-IDC
in mouse and human. The aim of this study was (1) to correlate TGF- Translational Diabetes Program, Inner Medicine 1, Heidelberg University
β2 expression with disease activity, fibrotic stage and degree of Hospital, Neuherberg, Germany; 2German Center for Diabetes Research
ductular reaction (DR), and (2) to identify the cell populations in the (DZD), Neuherberg, Germany; 3International Institute of Molecular and
diseased liver that are source for and target of TGF-β2 and delineate Cell Biology, Warszawa, Poland; 4Leibniz Research Centre for Working
their role in the disease course. Environment and Human Factors, Dortmund, Germany; 5Heinrich Heine
Method: Liver tissues from Abcb4KO, CDE & DDC diet, bile duct University Düsseldorf, Division of Endocrinology and Diabetology,
ligated and CCl4 treated mice, as well as patient samples were stained Medical Faculty, Düsseldorf, Germany; 6Leibniz Center for Diabetes
for H&E and Sirius Red. Histologic evaluation of disease activity and Research at Heinrich Heine University, Institute for Clinical Diabetology,
stage of fibrosis were determined with the Ishak score and compared German Diabetes Center, Dusseldorf, Germany
to age-matched wild type mice and healthy controls respectively. Email: [email protected]
TGF-β2, pSmad3 and cell type markers were analysed by in-situ
Background and aims: The endosomal sorting complexes required
hybridisation and immunohistochemistry. TGF-β2 expression levels
for transport (ESCRT) play a key role in lysosomal degradation of
were evaluated with H-Score.
membrane signaling receptors. The machinery consists four protein
Results: TGF-β2 is produced by cholangiocytes during disease
complexes (ESCRT −0 to −III), that are successively recruited to
progression in ABCB4KO mice and primary sclerosing cholangitis
maturing endosomes, sorting ubiquitinated cargos into intraluminal
patients, especially in regions of DR. This is also seen in BDL and DDC
vesicles destined for degradation. Recently, activation of the ESCRT-I
models, both displaying phenotypes of cholestatic liver disease and
has been reported to protect mice against non-alcoholic steatohepa-
TGF-β2 expression levels that increase with severity of the injury. In
titis (NASH) by targeting TLR4 for degradation, suggesting its
contrast, CDE fed and CCl4 treated mice show low TGF-β2 expression,
potential role for treating non-alcoholic fatty liver disease (NAFLD)
even if DRs are present. In patients and mouse models of cholestatic
and NASH. Thus, the aim of this project is to identify the function of
liver disease mRNA expression levels of TGF-β2 highly correlate with
ESCRT-I in liver physiology by interfering with the major regulator of
disease activity-especially inflammation, stage of fibrosis and extent
ESCRT-I stability and function, the tumor susceptibility gene 101
of DRs. The data suggest that TGF-β2 is a biomarker of cholestatic liver
(Tsg101).
damage, but not of hepatocellular injury without cholestasis.
Method: Tsg101 was downregulated using lipid nanoparticle
In line with high TGF-β2 levels, Abcb4KO livers show an increased
induced hepatocyte-specific in vivo and adenovirus based primary
Smad3 phosphorylation in Kupffer cells (KC) and other macrophages,
hepatocytes in vitro knockdown. The in vivo experiments were
as well as in hepatic stellate cells (HSC) or portal fibroblasts in the
conducted in time course while serum and livers are collected for
portal field area. In contrast Smad3 phosphorylation levels of
functional analysis.
hepatocytes and cholangiocytes did not change. KC/HSC also show
Results: Consistent with previous data, we found Tsg101KD leads to
upregulated TGF receptor expression and presence of activation
ESCRT-I instability, supporting an essential role of Tsg101 on ESCRT-I
markers (e.g. αSMA in HSC). The numbers of activated non
function. Remarkably, loss of Tsg101 induces severe liver
parenchymal cells and the percentage of the pSmad3-positive

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 POSTER PRESENTATIONS
inflammation and organ damage leading to animal lethality 8 days and early plasmablasts relative to patients who presented a flare ( p =
after injection. This is associated with a vast elevation of aspartate 0.02 and p = 0.03, respectively). However, both B cell populations
aminotransferase (AST), alanine aminotransferase (ALT) and bile acid together with the transitional T1, T2 and T3 subsets increased in all
levels in the serum accompanied by a decrease in blood glucose patients regardless of the outcome of ISW, and positively correlated
concentrations, indicating severe liver pathologies. Also, the size of with serum transaminases and IgG levels after discontinuation of
the gallbladder is increased in Tsg101KD mice with disrupted bile treatment ( p < 0.01). Of note, the expansion of B cell precursors was
canaliculi structure, pointing towards impairment of bile acid accompanied by a decrease in the frequency of switched resting
homeostasis. Initiation of the inflammatory response is dependent memory cells ( p < 0.01). In contrast, no differences were observed in
on the endosomal accumulation of tumor necrosis factor receptor the T cell compartment before or after ISW.
(TNFR), which leads to the activation of canonical and non-canonical Conclusion: In AIH patients, ISW results in a state of immune
transcription factor nuclear factor kB (NF-kB) signaling and the activation orchestrated by B cells with no detectable changes in the T
upregulation of downstream cytokines. Moreover, we observe a time- cell compartment, regardless of the clinical outcome. This suggests
dependent decrease in mitochondrial function, characterized by that clinical remission does not entail the restoration of immune
mitochondrial uncoupling and enhanced proton leak, which man- tolerance to liver antigens and provides an explanation for late
ifests into activation of caspase-3 cleavage and induction of relapses observed after ISW.
apoptosis. The activation of inflammation upon Tsg101 KD is in line
with data from NASH patients, where TSG101 expression is decreased FRI469
and negatively correlated with interleukin 6 (IL6) and 1 beta (IL1b) Serum sterols indicate modified cholesterol homeostasis in
levels, highlighting a potential regulatory function of Tsg101 in liver cirrhotic patients with PBC and correlate with response to
inflammation. treatment with ursodeoxycholic acid
Conclusion: Altogether, liver-specific Tsg101KD causes a time Wiktor Smyk1, Beata Kruk2, Tadeja Rezen3, Miha Moskon4,
dependent activation of inflammation and apoptosis, accumulating Ewa Wunsch5, Dieter Lütjohann6, Frank Lammert7,
into hepatocyte death, organ failure and ultimately a lethal Piotr Milkiewicz5,8, Marcin Krawczyk2,9. 1Medical University of
phenotype. Our finding suggests a regulatory role of Tsg101 in Gdansk, Department of Gastroenterology and Hepatology, Gdańsk,
TNFR signaling and degradation, where Tsg101 protects against liver Poland; 2Medical University of Warsaw, Laboratory of Metabolic Liver
inflammation. Diseases, Department of General, Transplant and Liver Surgery, Centre
for Preclinical Research, Warsaw, Poland; 3University of Ljubljana, Centre
FRI468 for Functional Genomics and Bio-Chips, Institute for Biochemistry and
B cell reactivation in autoimmune hepatitis after Molecular Genetics, Faculty of Medicine, Ljubljana, Slovenia; 4University
immunosuppression withdrawal of Ljubljana, Faculty of Computer and Information Science, Ljubljana,
Elena Perpinan1, George Koutsoudakis2, Laura Patricia Llovet3, Slovenia; 5Pomeranian Medical University in Szczecin, Translational
Thais Leonel3, Mar Riveiro Barciela4, Montserrat García-Retortillo5, Medicine Group, Szczecin, Poland; 6University Hospital Bonn, Institute of
Mercé Roget6, Alberto Sanchez-Fueyo7, Maria Carlota Londoño3. Clinical Chemistry and Clinical Pharmacology, Bonn, Germany;
1
King’s College Hospital, London, United Kingdom; 2Hospital Clínic 7
Hannover Medical School (MHH), Health Sciences, Hannover, Germany;
Barcelona; 3Hospital Clínic Barcelona, Liver Unit, Barcelona, Spain; 8
Medical University of Warsaw, Liver and Internal Medicine Unit,
4
Hospital Vall d’Hebron, Liver Unit, Barcelona, Spain; 5Hospital del Mar, Department of General, Transplant and Liver Surgery, Warsaw, Poland;
Barcelona, Spain; 6Consorci Sanitari de Terrassa, Terrassa, Spain; 7King’s 9
Saarland University, Department of Medicine II, Saarland University
College Hospital, London, United Kingdom Medical Center, Homburg, Germany
Email: [email protected] Email: [email protected]
Background and aims: Long-term immunosuppression therapies Background and aims: Primary biliary cholangitis (PBC) is a chronic
increase the risk of treatment-related side effects and subsequent autoimmune cholestatic liver disease of unknown aetiology.
reduce quality of life in autoimmune hepatitis (AIH) patients. The Ursodeoxycholic acid (UDCA) is the first-line therapy in PBC
optimal strategy for immunosuppression withdrawal (ISW) is still however, some patients present insufficient biochemical response
controversial as relapse rates vary between 25 and 100% despite to UDCA, indicating worse disease course and survival. Cholesterol is
previous sustained complete biochemical response. Moreover, the involved in diverse biological activities and derives from de novo
pathogenesis of AIH is uncertain and no studies have explored the synthesis or intestinal absorption. Here, we aim to investigate and
effect of ISW on the immune response. Therefore, we aim to correlate serum sterol profiles and PBC phenotypes.
understand the B and T cell repertoire in AIH patients undergoing Method: Overall, we included 129 patients with PBC (age 32–93
ISW. years, 119 women). A total of 44 individuals presented with cirrhosis
Method: Thirty-seven patients with type 1 AIH, complete biochem- at diagnosis, and 13 were transplanted due to PBC before inclusion.
ical response on first-line treatment for at least 3 years and Biochemical response to UDCA was assessed according to Barcelona
histological activity index <3 were prospectively included. Detailed criteria. Follow-up data (range: 1–13 years) were available in 62 (48%)
characterization of peripheral B and T cell responses was performed patients. Serum sterol levels were measured by gas chromatography/
through high-dimensional spectral flow cytometry and unsupervised mass spectrometry (GC/MS) at inclusion. Machine learning (ML)
clustering before and after ISW (median time of 9 months). algorithms were used to determine a model that can predict UDCA
Results: Fifty-one percent of patients were female (n = 19) with a response.
median age of 60 years (22–80), and a median time on remission of 4 Results: Cirrhotic patients with PBC demonstrated significantly
years (3–11). Most of the patients were on monotherapy with higher sitosterol ( p = 0.0001), campesterol ( p = 0.0042) and choles-
azathioprine at the time of ISW (n = 27, 74%). After a median follow- tanol ( p < 0.0001) serum concentrations as compared to non-
up of 31 months (12–34), 21 (57%) patients remained in remission cirrhotic individuals. Patients with cirrhosis showed increased
and 16 (43%) patients required reinstitution of therapy (6 of them phytosterols:cholesterol but decreased lathosterol:cholesterol ratios
were still on low-dose immunosuppression when presented the (all p < 0.0001). Desmosterol:cholesterol ratio did not differ between
flare). Before ISW, patients who reached remission displayed elevated patients with or without cirrhosis. Individuals after transplantation
frequencies of immature transitional 2 marginal zone precursor cells displayed increased serum concentrations of 7α-hydroxycholesterol

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POSTER PRESENTATIONS
compared with non-transplanted patients, which might indicate
increased radical oxidation. The ML Support Vector Classifier model
including 24-hydroxycholesterol, 27-hydroxycholesterol, campes-
terol, cholesterol, desmosterol, lanosterol and stigmasterol, revealed
high accuracy, precision and sensitivity (all >80%) in predicting non-
response to UDCA treatment. In contrast, none of the used sterol
models was not able to accurately forecast the deterioration of LFTs
during follow-up.
Conclusion: PBC patients with cirrhosis are characterized by
decreased cholesterol synthesis and increased sterol absorption as
compared to individuals without cirrhosis. Serum levels of algor-
ithmically selected sterols correlate with biochemical non-response
to therapy with UDCA in PBC.

FRI470
Preserved MAIT cell proinflammatory function in children with
autoimmune liver disease Conclusion: Peripheral blood MAIT cell cytokine profile in children
Suzan Warner1, Deirdre Kelly2, David Wraith1, Ye Htun Oo3. with AIH Type 1 and PSC are similar to MAIT cells from healthy
1
University of Birmingham, Institute of Immunology and children. Furthermore, MAIT cells from children with AIH Type 1 and
Immunotherapy, Birmingham, United Kingdom; 2Birmingham PSC have greater RORγt expression and IL-17A activity at rest and post
Children’s Hospital, The Liver Unit, Birmingham, United Kingdom; stimulation, suggesting that MAIT cells with a Th17-like phenotype
3
University of Birmingham, Centre for Liver and Gastrointestinal may play a role in disease pathogenesis.
Research, Birmingham, United Kingdom
Email: [email protected]
Background and aims: Mucosal-associated invariant T (MAIT) cells
are significant players in autoimmune liver disease (AILD), a Cirrhosis and its complications: Portal
spectrum of conditions which often starts in childhood. Biological Hypertension
characterisation of MAIT cells and their functional activity in children
with AILD has seldom been investigated. We aim to 1) characterise
the deep immunophenotype of paediatric MAIT cells in AILD FRI485
compared to healthy controls and 2) assess their cytokine TIPS insertion leads to partial reversal of systemic inflammation
capabilities. in patients with decompensated liver cirrhosis
Method: We performed mass cytometry (CyTOF; Cytometry by time
Lena Stockhoff1, Anja Tiede1, Zhaoli Liu2, Hannah Schneider3,
of flight) analysis of peripheral blood mononuclear cells (PBMC) from
Valerie Ohlendorf3, Jan Hinrichs4, Jennifer Witt3, Denise Menti3,
paediatric patients with AILD (AIH Type 1, N = 4, median age 14 yrs
Heiner Wedemeyer3, Bernhard Meyer4, Markus Cornberg2,3,
(range 9–14), and PSC, N = 4, median age 14 yrs (range 12–14)) and
Cheng-Jian Xu2, Christine Falk5, Benjamin Maasoumy1,2. 1Hannover
from healthy children (HC) (N = 4, median age 8.5years (range 5–14).
Medical School, Gastroenterology, Hepatology and Endocrinology,
These PBMC samples were treated with a cell stimulation cocktail
Hannover, Germany; 2Centre for Individualised Infection Medicine
containing phorbol 12-myristate 13-acetate (PMA) and ionomycin
(CIIM), Hannover, Germany; 3Hannover Medical School,
and incubated for 4hours prior to downstream investigation by mass
Gastroenterology, Hepatology and Endocrinology, Hannover, Germany;
cytometry with a custom MAIT cell CyTOF panel designed by the 4
Hannover Medical School, Diagnostic and Interventional Radiology,
investigators. Results were compared to controls (unstimulated
Hannover, Germany; 5Hannover Medical School, Institute of Transplant
matched PBMCs from the same patients). Cytobank and GraphPad
Immunology, Hannover, Germany
Prism 9 were used for data analysis..
Email: [email protected]
Results: Compared to the cohort of healthy children, peripheral blood
MAIT cells from children with AILD had increased expression of Background and aims: Patients with decompensated liver cirrhosis
retinoic acid related orphan receptor gamma t (RORγt), a transcrip- are characterized by a state of systemic inflammation (SI), which is
tion factor of T helper 17 (Th17) cells, and the proinflammatory closely linked to several complications e.g. sarcopenia. Portal
cytokine interleukin 17A (IL-17A). This was observed at baseline ( p = hypertension is widely considered to play a central role in this
0.002) and post stimulation (( p = 0.001). process. Transjugular intrahepatic portosystemic shunt (TIPS) is an
Higher expression of RORγt was observed in AIH Type 1 patients effective treatment option for portal hypertension. The aim of this
compared to healthy children ( p = 0.005) Figure 1. There was also a study was to investigate the impact of TIPS insertion on SI in patients
significant difference between AIH Type 1 and PSC IL-17A activity with liver cirrhosis.
post stimulation ( p = 0.034). Post-stimulation IL-17A expression was Method: In this cross-sectional study a number of 177 consecutive
highest in the PSC cohort compared to their unstimulated counter- cirrhotic patients receiving a TIPS at Hannover Medical School were
parts ( p = 0.003). In addition, TNFα, IFNγ and GMCSF cytokine included. C-reactive protein (CRP) and white blood cells (WBC) were
production were preserved in the children with AILD (AIH Type 1 compared between baseline and 6/12, 24 and 36 months after TIPS
and PSC), with levels comparable to those in the healthy cohort. This insertion. In a subset of 59 patients we were able to perform more
finding was most pronounced in TNFα production ( p = 0.0042) which detailed analysis on the inflammation status measuring 48 different
differs from peripheral blood MAIT cells in adults with AILD where cytokines. The respective plasma samples were prospectively
there is decreased cytokine production. collected from the cubital vein at baseline as well as 1, 3 and 6
months after TIPS insertion. Blood samples from 5 healthy indivi-
duals served as control. Changes of cytokine levels were correlated
with the physical status as indicated by body mass index (BMI), hand
grip strength (HGS) and mid-arm muscle circumference (MAMC).
Results: Median age of the patients was 56 years and median MELD
was 12. Most frequent TIPS indication was refractory ascites (RA)

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 POSTER PRESENTATIONS
(76%). Median CRP and WBC were 9.2 mg/L and 5 × 103/μL, Conclusion: In the absence of variceal haemorrhage portal hyper-
respectively. CRP levels but not WBC significantly decreased after tension is under recognised. Comorbidities affecting patients in
TIPS ( p < 0.001). Of note, decrease in CRP levels was significantly group 3 reported at higher levels than in groups 1 and 2 include CKD,
associated with a better survival ( p = 0.012). As expected, cytokine IHD and heart failure. In patients with portal hypertension it’s
levels were significantly higher in the cirrhotic patients as compared important to address comorbidities in addition to the underlying
to healthy controls affecting 30 of 48 measured cytokines (FDR < liver disease.
0.05). Pattern of SI did not differ between patients with RA and
variceal bleeding except from IL-6, which was significantly higher in FRI487
patients with RA ( p < 0.001). One month after TIPS most cytokines Durability of immune response to SARS-CoV-2 vaccination in
were still measured at levels comparable to baseline and some, e.g. IL- patients with liver cirrhosis (LC) as compared to healthcare
2, were even increased. However, during further follow-up we workers (HW)
documented a continuous decrease in the majority of cytokines. For Alessandra Mangia1, Valeria Piazzolla1, Maria Squillante1,
25 cytokines, including IL-6 and IL-2, levels were significantly lower Giovanna Cocomazzi1, Vito Ciciriello1, Vincenzo Giambra2,
at month 6 compared to the time of TIPS insertion (FDR < 0.05; Nicola Serra3. 1Liver Unit, IRCCS “Casa Sollievo della Sofferenza”, San
figure). Moreover, 7 of the 30 cytokines (including IL-2), which were Giovanni Rotondo, Italy; 2ISBREMIT, IRCCS “Casa Sollievo della
elevated prior to TIPS, did not show any statistical difference anymore Sofferenza”, San Giovanni Rotondo, Italy; 3University “Federico II”, Public
compared to healthy controls. When correlating cytokine changes Health, Napoli
with the clinical status, IL-6 appeared to be of particular interest: Email: [email protected]
Decrease in IL-6 was associated with a significant improvement in
MAMC and numerical increase in HGS and BMI. Background and aims: Patients with advanced liver disease have
well recognized deficiencies in innate and humoral immunity. Phase
3 trials on both BNT162b2 and mRNA-1273 included an extremely
limited number of pts with liver diseases. Real life data on vaccine
response in cirrhotics are lacking. To characterize the longitudinal
anti-SARS-CoV-2 response in LC as compared to an age and gender
matched HW population.
Method: In pts with established diagnosis of LC ± portal hyperten-
sion, levels of binding antibodies at baseline before the first
BNT162b2 dose, 7 and 31 days after the first dose and 90 and 180
Figure: Decrease in SI after TIPS. days after the second dose were evaluated and compared to HW
levels at similar time-points. Semiquantitative serological testing for
Conclusion: Decreasing portal hypertension via TIPS insertion leads IgG antibodies anti S1 domain was performed by anti-SARS-CoV-2
to a significant improvement of SI over time, which is associated with QuantiVac ELISA (EUROIMMUN); cut-off for positivity = 32.5 BAU/ml.
a favorable clinical outcome. Swab test was performed in suspected cases by RT-PCR kit (ROCHE
Diagnostics). Micro neutralization test using wild type virus is
FRI486 ongoing. LC pts were matched 3:1 with HW. Both pts and HW had
RWE evaluating patients with cirrhosis and features of portal received BNT162b2 vaccine.
hypertension reveals significant comorbidities Results: Among 207 LC pts identified so far, 178 have results currently
Philip Ambery1, Peter Greasley2, Daniel Pettersen2, Nerissa Lee3, available at the different time-points. After a careful analysis of the
Steven Kiddle4, Phillip Hunt5, Victoria Parker6. 1Astrazeneca, Late swab tests results, 28 pts COVID experienced were identified. Of 150
CVRM clinical research, Gothenburg, Sweden; 2Astrazeneca, Early CVRM, SARS-CoV-2 naive, 86 (58%) were male, mean age 65.4 ± 4. Pts with
Gothenburg, Sweden; 3University of Bristol, United Kingdom; HCV etiology were 67%, pts with portal hypertension 29%. Geometric
4
Astrazeneca, Health Data Science, Cambridge, United Kingdom; Mean of anti-SARS-CoV-2 antibody levels overall and by gender
5
Astrazeneca, Epidemiology, Washington, United States; 6Astrazeneca, among LC pts and HW in the Table. Higher levels of anti-SARS-CoV-2
Early CVRM, United Kingdom were observed in HW as compared LC at d7 ( p = 0.007) and d31 ( p =
Email: [email protected] 0.063), as well as at d90 ( p = 0.0049) and d180 ( p = 0.039). At d180,
Background and aims: Development of portal hypertension is the number of pts with results lower than the assay’s threshold was
associated with high risk of variceal haemorrhage, ascites, enceph- higher among LC than in HW (5 vs 0, P = 0.0028). Irrespective of age,
alopathy and death. In over 100, 000 individuals identified with female pts were more likely to have higher anti-SARS-CoV-2 levels as
portal hypertension we identify significant comorbidities that should compared to male at late time points.
be addressed to improve outcomes in this vulnerable population.
Method: Individuals with features of portal hypertension were
identified using the TriNetX federated health records. Three groups of
patients were identified, Group 1 with confirmed variceal haemor-
rhage (19, 454 in total, of which 12, 968 were incident), Group 2 with
varices but no haemorrhage (43, 583 in total, of which 30, 083 were
incident), and Group 3 with portal hypertension but no diagnosed
varices (48, 496 in total, of which 31, 611 were incident). Significant
comorbidities were identified across all 3 groups.
Results: Higher rates of ischaemic heart disease (IHD), heart failure
and chronic kidney disease (CKD) were found in Group 3 versus the
other two groups:

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POSTER PRESENTATIONS
Conclusion: Pts with LC showed an initial response to SARS-CoV-2 FRI489
vaccination weaker than that of HW. An earlier antibody decline was Blunted cardiovascular effects of beta-blockers in patients with
also observed. The number of pts with absent anti-SARS-CoV-2 after cirrhosis: relation to severity?
180 days was higher than in HW. This ongoing study highlights the Puria Nabilou1, Karen Danielsen1, Nina Kimer2, Jens Hove3,4,
need of a possibly more intensive vaccination schedule in LC as Flemming Bendtsen1,4, Søren Møller4,5. 1Hvidovre Hospital, Gastro
compared to HW. Unit, Medical Division, Hvidovre, Denmark; 2University of Copenhagen,
Bridge Translational Excellence Program, Novo Nordisk Center for Basic
FRI488 Metabolic Research; 3Hvidovre Hospital, Department of Cardiology,
A simple model for predicting survival in cirrhotic patients Hvidovre, Denmark; 4Hvidovre Hospital, Department of Clinical
undergoing portosystemic shunt embolization Medicine, Hvidovre, Denmark; 5Hvidovre Hospital, Department og
Won-Mook Choi1, Seungbong Han2, Young Seok Kim3, Clinical Physiology and Nuclear Medicine, Center for Functional and
Dong Hyun Sinn4, Dong Il Kwon5, Young-Suk Lim1. 1Asan Medical Diagnostic Imaging and Research, Hvidovre, Denmark
Center, University of Ulsan College of Medicine, Department of Email: [email protected]
Gastroenterology, Seoul, Korea, Rep. of South; 2Korea University College
of Medicine, Department of Biostatistics, Seoul, Korea, Rep. of South; Background and aims: Patients with cirrhosis and portal hyperten-
3
Soonchunhyang University Bucheon Hospital, Division of sion are at high risk of developing complications such as variceal
Gastroenterology and Hepatology, Bucheon, Korea, Rep. of South; hemorrhage, ascites, and cardiac dysfunction known as cirrhotic
4
Samsung Medical Center, Department of Medicine, Seoul, Korea, Rep. of cardiomyopathy. Since non-selective betablockers may aggravate
South; 5Asan Medical Center, University of Ulsan College of Medicine, hemodynamic complications we investigated the effect of real-time
Department of Radiology, Seoul, Korea, Rep. of South propranolol infusion on cardiac function in patients with varying
Email: [email protected] degrees of cirrhosis.
Method: Thirty-eight patients with Child-Pugh A (n = 17), B (n = 17)
Background and aims: Portosystemic shunt embolization (PSSE) is and C (n = 4) had liver vein catherization and cardiac magnetic
an effective treatment for hepatic encephalopathy and gastric varix in resonance imaging performed. We assessed the effect of real-time
patients with portosystemic shunt. However, some of the patients propranolol infusion on the hepatic venous pressure gradient, cardiac
rapidly progress to hepatorenal syndrome and hepatic failure after index, stroke volume, ejection fraction, heart rate, and contractility. 19
PSSE. The aim of this study was to develop a prognostic model for patients were classified responders to beta-blocker therapy.
predicting survival in patients treated with PSSE. Results: When pooling Child-Pugh B & C patients, the decrease in
Method: We included 188 patients with portosystemic shunt who cardiac index by beta-blockade was blunted, compared to Child-Pugh
received PSSE for gastric varix or recurrent hepatic encephalopathy to A patients (−8.5% vs. −20.5%, p = 0.043).
develop a prediction model for 1-year mortality using a Cox The effect of NSBB on portal pressure was inversely correlated to the
proportional-hazard model incorporating significant prognostic changes on left atrium since the left atrial volume changed by 4 ml ±
factors, which was validated in a separate cohort of 184 patients. 18 in the responders compared to 15 ml ± 11 in the non-responders
Results: Using multivariable analysis, baseline serum levels of total ( p = 0.03). Finally, baseline ejection fraction correlated inversely with
bilirubin, albumin, and international normalized ratio (INR) were the the decrease in portal pressure r = −0.39, p = 0.02.
independent prognostic factors that were significantly associated
with the 1-year survival of the patients. An Albumin-Bilirubin-INR
(ABI) score was developed assigning 1 point for ≥1.5 mg/dL of total
bilirubin, <3.0 g/dL of albumin, and ≥1.5 for INR, respectively. Time-
dependent area under the curve of the ABI score for predicting
6-month and 1-year survival were 0.851 (95% confidence interval
[CI], 0.778–0.923) and 0.857 (95% CI, 0.793–0.921) in the develop-
ment cohort and 0.777 (95% CI, 0.664–0.829) and 0.727 (95% CI,
0.624–0.829) in the validation cohort, which was comparable to the
MELD score and the Child-Pugh score, indicating excellent discrim-
ination performance. The ABI score showed a batter calibration
performance than other scores, especially in patients at high-risk.

Conclusion: We found a blunted effect of beta-blockade on cardiac

index in patients with advanced cirrhosis compared to patients with
early cirrhosis indicating impaired compensatory cardiac reserve and
underlying cirrhotic cardiomyopathy with disease progression. The
differential effects of beta-blockade on the left atrium may predict
the beta-blocker response on portal pressure but further studies are
warranted on this matter.

Conclusion: The novel ABI score, which is easier to calculate than

MELD or Child-Pugh scores, may help identify a proper indication for
PSSE in cirrhotic patients with portosystemic shunt.

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 POSTER PRESENTATIONS
FRI490 Background and aims: Ascites formation is a common manifestation
Gender affects the association between serum creatinine levels of cirrhosis decompensation and heralds a poor prognosis. Refractory
and clinical response to terlipressin in patients with hepatorenal ascites (RA) denotes a worsened state of this condition, where
syndrome type of acute kidney injury pharmacotherapies are ineffective or induce significant side-effects.
R. Todd Frederick1, Chris Pappas2, Khurram Jamil3. 1California Pacific The current definition of RA remains largely unaltered through the
Medical Center, Department of Transplant, San Francisco, United States; past 25 years, and rests on a panel of diagnostic criteria including the
2
Orphan Therapeutics, LLC, Longboat Key; 3Mallinckrodt introduction of intensive diuretic therapy and a modest salt-
Pharmaceuticals, Hampton, United States restrictive diet, and evaluations of renal sodium excretion, weight
Email: [email protected] loss, ascites recurrence rate, and diuretic-induced complications.
Further, the traditional binary RA classification may be too simplistic
Background and aims: Hepatorenal syndrome (HRS)-acute kidney
as a predictive measure. We aim to develop a prediction model that
injury (AKI) is a rare and serious complication of cirrhosis, with
relies on easily obtainable ascites-related variables and predicts one-
serum creatinine (SCr) used diagnostically. Women generally have year mortality more accurately than the traditional RA classification.
less muscle mass and consequently lower SCr levels than men with
Method: We included 478 patients from the placebo-groups of trials
similar renal function. Terlipressin more effectively reverses HRS for the treatment of cirrhotic ascites. The outcome was mortality
when started at lower SCr levels. The largest randomized, prospective
hazard during one year of follow-up. Fractional polynomials were
database of placebo-controlled studies in patients ( pts) with HRS-AKI
included to investigate the functional form of continuous variables.
was examined to assess a gender-based impact on treatment We used Cox regression with stepwise backward variable selection of
response.
ascites-related predictors of mortality. Candidate variables were: age,
Method: Pooled data from 3 phase III US studies (OT-0401, REVERSE, sex, serum sodium, ascites discomfort score, and a categorical
CONFIRM) were used; pts with HRS-AKI were treated with
variable based on ascites accumulation and diuretic treatment
terlipressin plus albumin (terli) or placebo plus albumin ( pbo).
(ascites accumulation with no, moderate, and intensive diuretic
Associations between baseline (BL) SCr (SCr upon treatment treatment, and no ascites accumulation with any diuretic treatment).
initiation) and clinical response (complete response [CR]: HRS
We compared the final model’s discriminative ability (Harrell’s C
reversal, SCr [1.5 or less] or partial response [PR]: at least 30% index) with that of the traditional RA classification.
improvement in SCr) stratified by treatment and gender were Results: The final prediction model included age, serum sodium, and
assessed. Overall response rate (ORR) comprised pts with a CR or
the categorical accumulation/diuretics variable. The CIRrhotic Ascites
PR; p values were calculated using a Fisher’s exact test. Severity (CIRAS) score was computed as 0.041* (age-56)-0.078*
Results: Males in the terli group with BL SCr <3 had significant
(serum sodium-137) and then add 0.718 if ascites accumulation and
improvements in CR and ORR, relative to pbo, while females did not
no diuretics, or add 0.407 if ascites accumulation and intensive
(Figure). Among pts with a BL SCr of 3–5, both males and females had diuretic treatment, or subtract 0.270 if no ascites accumulation and
a significant improvement in ORR (terli vs pbo); however, only males
any diuretic treatment.
had significant improvements in CR. Across genders, pts with a BL SCr The CIRAS score had a C index for one-year mortality of 0.70 (95% CI:
>5 demonstrated limited response to treatment.
0.64–0.75) which was statistically significantly better than the
traditional RA classification with a C index of 0.60 (95% CI: 0.55–
0.65) ( p < 0.001, Figure).
BL SCr <3 BL SCr 3–5 BL SCr >5

Parameter, p p p
n (%) Terli Pbo value Terli Pbo value Terli Pbo value

Male 74 47 112 96 27 22
HRS 36 (48.6) 13 (27.7) 0.024 35 (31.3) 11 (11.5) <0.001 2 (7.4) 1 (4.5) 1.000
Reversal
ORR 42 (56.8) 15 (31.9) 0.009 54 (48.2) 24 (25.0) <0.001 5 (18.5) 3 (13.6) 0.715
Female 52 37 71 46 16 8
HRS 26 (50.0) 12 (32.4) 0.129 16 (22.5) 5 (10.9) 0.141 2 (12.5) 0
Reversal
ORR 27 (51.9) 13 (35.1) 0.135 24 (33.8) 6 (13.0) 0.016 3 (18.8) 0 0.526

Conclusion: Pts in the terli group had a greater clinical response vs

pbo for BL SCr of <5. Males were more likely to have a CR and ORR
than females, especially those with BL SCr 3–5. Despite matched SCr,
females had a lower response than males, likely reflecting more
advanced renal dysfunction upon treatment initiation. New guidance
recommending initiation of vasoconstrictor treatment based on SCr
change from BL rather than absolute cut-offs may improve outcomes Conclusion: The novel CIRAS score combining age, serum sodium,
for female pts. Additional biomarkers to evaluate renal dysfunction diuretic treatment, and ascites accumulation has better discrimina-
should also be evaluated. tive ability than the traditional RA classification during a one-year
follow-up. These findings warrant validation in external cohorts.
FRI491
A novel cirrhotic ascites severity score predicts one-year mortality FRI492
better than the classification into refractory or diuretic- A network meta-analysis of numbers needed to treat to prevent
responsive ascites an episode of overt hepatic encephalopathy in patients with
Rasmus Hvidbjerg Gantzel1,2, Niels Kristian Aagaard1, cirrhosis treated for at least 6 months with lactulose alone, or
Hendrik Vilstrup1,2, Hugh Watson1,3, Peter Jepsen1,2, lactulose plus rifaximin-alpha
Henning Grønbæk1,2. 1Aarhus University Hospital, Department of Juha Halonen1, Roland Henrar1, Eric Ngonga Kemadjou2. 1Norgine Ltd,
Hepatology and Gastroenterology, Århus N, Denmark; 2Aarhus Harefield, United Kingdom; 2JB Medical Ltd, Little Cornard, Sudbury,
University, Department of Clinical Medicine, Århus N, Denmark; United Kingdom
3 Email: [email protected]
Virology, Evotec ID, Lyon, France
Email: [email protected] Background and aims: Overt hepatic encephalopathy (OHE) occurs
in 30–40% of patients with cirrhosis during their clinical course.

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POSTER PRESENTATIONS
Frequent hospitalisations and high mortality make prevention of OHE transjugular intrahepatic portosystemic shunt (TIPS) and balloon-
essential. Current treatment options for OHE include nonabsorbable occluded antegrade or retrograde transvenous obliteration (BA-RTO)
disaccharides (e.g. lactulose) and antibiotics (e.g. rifaximin-alpha are potential treatment options. Our study is the first to assess and
550 mg). We conducted a network meta-analysis (NMA) of data from compare TIPS vs. BA-RTO for the management of ectopic varices.
a previously published literature review (Hudson M, Schuchmann Method: This is a retrospective cohort study at a tertiary liver center.
M. Eur J Gastroenterol Hepatol 2019;31:434–50) to determine the All interventional radiology procedures performed for bleeding
comparative long-term efficacy, in terms of number needed to treat varices between 2006 and 2020 were identified. Only patients
(NNT) to prevent an additional OHE episode, of lactulose versus undergoing TIPS and BA-RTO for bleeding ectopic varices were
placebo and lactulose + rifaximin-alpha versus placebo. included. Demographics, pre-procedural data and outcome data was
Method: Literature searches were previously conducted in PubMed collected and compared between BA-RTO and TIPS groups.
of titles and abstracts only, with language restricted to English and Results: Eleven patients undergoing BA-RTO were compared to seven
the data range unrestricted up to the cut-off date (05 March 2018), patients undergoing TIPS. In 6 of the BA-RTO patients, TIPS was
using the following search terms: ‘hepatic encephalopathy + rifax- deemed unfeasible. Mean age at procedure was 55.6 ± 10.0. 55.6%
imin’ and ‘hepatic encephalopathy + lactulose’. Randomized con- were men and 83.3% were white. There were 8 rectal varices, 7
trolled trials (RCTs) with long-term (>/ = 6 months) effectiveness peristomal, one duodenal, one cecal and one superior mesenteric.
endpoints for lactulose and/or rifaximin-alpha were selected for NNT The mean MELD-Na prior to procedures was 20.8 ± 10.4 in the BA-
analysis if statistically significant between-group differences were RTO group vs. 19.0 ± 6.4 in the TIPS groups (p = 0.69). In the BA-RTO
reported in the rate of OHE recurrence. In this analysis, we conducted vs. TIPS groups, respectively, the mean MELD-Na at 30 days after
an indirect treatment comparison analysis using the odds ratio (OR) procedure was 18.8 ± 9.9 vs 21.7 ± 5.5 ( p = 0.67) and at 90 days after
for OHE recurrence for NNT mapping. The NMA was conducted using procedure was 18.0 ± 4.2 vs 24.0 ± 7.5 ( p = 0.39). Rebleeding rates
the Mantel-Haenszel approach, with placebo used as the reference during admission were 9.1% for BA-RTO vs. 14.3% for TIPS ( p = 1.00).
treatment and only the fixed effect analysis considered. The mean length of stay for BA-RTO vs. TIPS was 10.6 ± 8.9 vs. 7.9 ± 8.1
Results: A total of 570 articles, including 201 with primary clinical days ( p = 0.41), mean paracenteses 90 days prior and after procedure
data, were identified. Long-term treatment was reported in 8 articles were 1.9 ± 3.6 vs. 0.0 ± 0.0 ( p = 0.12) and 2.0 ± 3.9 vs. 0.0 ± 0.0 ( p =
for lactulose alone and in 19 articles for rifaximin-alpha, alone or in 0.082), in the BA-RTO vs TIPS groups, respectively. The rates of hepatic
combination with lactulose. NNTs were calculated from 4 studies. encephalopathy in the BA-RTO vs TIPS groups at 90 days before and
When the ORs for the relative efficacy of each treatment versus each after the procedure were 45.4% vs. 57.1% (p = 1.00) and 28.6% vs 33.3%
of the remaining treatments were calculated, the ORs (95% ( p = 1.00), respectively. The mortality rates were 27.3% vs 28.6% ( p =
confidence intervals) for lactulose versus placebo and lactulose + 1.00) in the BA-RTO vs TIPS groups.
rifaximin-alpha versus placebo were 0.276 (0.164–0.466) and 0.081 Conclusion: Our results demonstrate that both TIPS and BA-RTO are
(0.042–0.158), respectively. The resulting NNTs were lower for effective treatment modalities for bleeding ectopic varices, with
lactulose + rifaximin-alpha versus placebo (2.28) than for lactulose comparable post-procedure outcomes. Patients undergoing BA-RTO
versus placebo (3.46; Figure). had a higher MELD at procedure but lower MELD at 30 and 90 day
post-procedure and less HE though no differences were significant.
BA-RTO is an excellent option for bleeding ectopic varices, primarily
rectal and peristomal, and especially in patients not candidates for
TIPS.

FRI494
Identification of potential new serum biomarkers for clinically
significant portal hypertension by proteomic profiling of
circulating extracellular vesicles
̵ Novak2,
Frane Pastrovic1, Grgur Salai2,3, Stela Hrkač2, Ruder
Lovorka Grgurević , Marko Žarak , Kristian Podrug5,
2,4 1

́
Tajana Filipec Kanizaj6, Tomislav Bokun1,7, Ivica Grgurevic1,7,8 .
1
University Hospital Dubrava, Zagreb, Croatia; 2Center for Translational
and Clinical Research, Department of Proteomics, School of Medicine,
University of Zagreb; 3Teaching Institute of Emergency Medicine of the
City of Zagreb; 4Department of Anatomy, “Drago Perovic”, School of
Medicine, University of Zagreb; 5University Hospital Centre Split,
University of Split School of Medicine, Croatia; 6KB Merkur; 7University
Conclusion: This NMA based on NNTs demonstrated that, in of Zagreb Faculty of Pharmacy and Biochemistry; 8School of Medicine,
comparison with placebo, lactulose + rifaximin-alpha may be more University of Zagreb, Zagreb
effective than lactulose alone in preventing OHE recurrence. Email: [email protected]

FRI493 Background and aims: Portal hypertension (PH) is a driving force for
Transjugular intrahepatic portosystemic shunt versus balloon- the progression of chronic liver disease. Complications from PH
occluded transvenous obliteration for the management of ectopic develop when hepatic venous pressure gradient (HVPG) exceeds
varices 10 mmHg, defining the presence of clinically significant portal
hypertension (CSPH). However, measuring HVPG is invasive
Ranya Selim1, Jenna Yousif2, Daniel Hillman3, Scott Schwartz3,
method, with limited availability. Thus, reliable non-invasive tools
Kylie Springer4, Dilip Moonka1. 1Henry Ford Hospital, Gastroenterology
would be welcome alternative. Circulating extracellular vesicles
and Hepatology, United States; 2Wayne State University School of
(ECV) originating from the cells are valuable source of information
Medicine, United States; 3Henry Ford Hospital, Radiology, United States;
4 pertaining the ongoing pathophysiological process including the
Henry Ford Hospital, Biostatistics, United States
molecules which might serve as the biomarkers. In this study we
Email: [email protected]
aimed to identify potential new serum biomarkers for CSPH in
Background and aims: Bleeding ectopic or non-gastroesophageal patients with compensated advanced chronic liver disease (cACLD)
varices occur uncommonly in the setting of portal hypertension. Both by proteomic profiling of serum ECV.

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 POSTER PRESENTATIONS
Method: Severity of PH was assessed by HVPG measurement that and decompensated cirrhosis (41%). Overall and transplant-free
served as the reference standard. Serum samples were pooled based survival at 12-months were 68% and 41% respectively. The majority
on HVPG measurement in two groups: with and without CSPH. ECV of deaths occurred early after the index admission, with a 45-day
were isolated from the serum pools using ultracentrifugation and overall survival of 80%. The most common cause of deaths was
vesicle membranes were lysed by sonication. ECV protein cargo was complications of end-stage liver disease and multiorgan failure (75%).
analyzed by Liquid Chromatography-Mass spectrometry (LC-MS). No deaths were recorded in patients receiving LT. In the multivariable
Samples were analyzed in triplicates and proteins identified with at analysis, increasing age ( per 5-year increase, HR 1.3 (CI 1.1–1.7),
least one peptide were considered relevant for analysis. Functional p = 0.04), increasing MELD score ( per 5 points, HR 1.5 (CI 1.1–1.7),
enrichment analysis of the isolated proteins was conducted using p = 0.02), current smoking (HR 8.7 (CI 3.4–21.9), p < 0.01) and acute
FunRich 3.1.3 analysis tool. kidney injury (AKI) (HR 2.9 (CI 1.2–7.0), p = 0.01) were associated with
Results: A total of 48 patients were included (30 in the CSPH group a significantly increased risk of death. After bootstrapping and
and 18 in the non-CSPH group, 75% males; median age: 59, 9 ± 9, 8 correcting for MELD score and age, a current smoker had 8.7 times the
years; majority with alcoholic (48%) and non-alcoholic fatty liver hazard of death of a non- or ex-smoker and AKI was associated with a
disease (23%)). LC-MS analysis of ECV content resulted in identifica- 2.9-fold increase in the hazard of death (Figure).
tion of 733 proteins (38 distinctive for CSPH, and 75 for non-CSPH
group), that were furtherly classified based on their cellular origin
and function. Proteins involved in platelet degranulation, integrin-
mediated signaling pathway, receptor mediated endocytosis and
regulation of cholesterol efflux were more represented, whereas
those involved in opsonization, phagocytosis, complement activa-
tion, immune and inflammatory response were less represented in
the CSPH group. Among the individual proteins that showed the most
significant difference between the studied groups phospholipid
transfer protein and beta-2-glycoprotein 1 were more represented,
whereas complement C1q, C1r and C1s subcomponents and annexin
A2 were less represented in the CSPH group.
Conclusion: Results of this study provide additional insights into
pathophysiological processes taking place along the development of
PH in patients with cACLD. Distinctive protein profiles are identified
between the patients with respect to the presence of CSPH. Several
individual proteins are identified that should be furtherly studied as
Figure: Multivariable Cox regression of overall patient survival showing
the potential non-invasive biomarkers of CSPH. survival estimates by smoking and AKI status (age and MELD scores held
at mean values).
FRI495
Factors influencing survival in cirrhotic patients with hepatic Conclusion: Cirrhotic patients with HH continue to have a poor 12-
hydrothorax month survival despite current treatments and a high-risk of
Sarah Romero1, Andy Lim2, Gurpreet Singh3, Chamani Kodikara1, treatment-related complications. LT assessment should be consid-
Rachel Shingaki-Wells1, Lynna Chen3, Samuel Hui1, ered in all cases. Current smoking and episodes of AKI are potential
Marcus Robertson1,2. 1Monash Health-Clayton Hospital Main Entrance, modifiable factors affecting survival.
Gastroenterology, Clayton, Australia; 2Monash University Clayton
Campus; 2Department of Medicine, School of Clinical Sciences, Clayton, FRI496
Australia; 3Austin Hospital, Gastroenterology & Liver Transplantation, Hepatic venous pressure gradient (HVPG) measured at events is
Heidelberg, Australia lower in non-alcoholic fatty liver disease (NAFLD) associated
Email: [email protected] cirrhosis as compared to alcoholic cirrhosis
Lubomir Skladany1, Daniela Jancekova1, Michal Žilinčan2,
Background and aims: Hepatic hydrothorax (HH) remains a Stanislav Okapec2, Janka Vnencakova1,
challenging complication of cirrhosis with limited treatment Svetlana Adamcova Selcanova1, Michal Kukla3, Tomáš Koller4. 1
options. We sought to identify factors associated with mortality in F.D.Roosevelt Teaching Hospital, HEGITO (Div Hepatology,
hospitalised patients with confirmed HH treated with current Gastroenterology and Liver Transplant) of the Dept Internal Medicine 2,
standards-of-care. Banská Bystrica, Slovakia; 2F.D.Roosevelt Teaching Hospital, Radiology,
Method: We performed a retrospective multi-center cohort study of Banská Bystrica, Slovakia; 3Faculty of Medicine, Jagiellonian University
cirrhotic patients with HH admitted to 3 tertiary hospitals (2010– Medical College, Gastroenterology, Krakow, Poland; 4University Hospital
2018). HH was defined as pleural effusion in the absence of of Bratislava, Faculty of Medicine Comenius University, Div
cardiopulmonary disease. The primary outcomes were overall and Gastroenterology Hepatology of Dept Internal Medicine 5, Bratislava,
transplant-free survival at 12-months after the index admission. Cox Slovakia
proportional hazards analysis was used to determine factors Email: [email protected]
associated with the primary outcomes.
Results: 84 patients were included. Mean age 58.3 ± 11.5 years and Background and aims: In our region, alcohol-associated liver disease
54.8% were male. The median Model for End-stage Liver Disease (ALD) and NAFLD are the most prevalent and the fastest-growing
(MELD) score was 29 (IQR 25–33). Management of patients aligned cirrhosis etiologies, respectively. We have recently demonstrated,
with AASLD guidelines. Diuretics alone achieved resolution of HH in that a natural history of cirrhosis differs in NAFLD as compared to
only 12% patients. At least 1 thoracocentesis was performed in 73.8% ALD. HVPG is a strong surrogate of cirrhosis severity but its value in
patients, of which 15% were complicated by pneumothorax. Within NAFLD is yet to be clarified.
12-months of the index admission, 33% patients received liver We aimed to compare HVPG in NAFLD with ALD according to the
transplantation (LT) and 11.9% had transjugular intrahepatic porto- indication (compensated and decompensated disease) with a
systemic shunt (TIPS) insertion, none of whom subsequently particular focus on variceal bleeding (VB) and refractory ascites (RA).
required LT. At least 1 hospital readmission was required in 63 Method: In our hospital system, we have retrospectively identified
(75%) patients, most commonly due to recurrent hydrothorax (38%) patients who underwent HVPG measurement and scrutinized them

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POSTER PRESENTATIONS
against our RH7 cirrhosis registry (NCT04767945). Then we retrieved VATI did not. Similarly, when adjusting for age and MELD, SATI (aOR =
patients’ etiologies-ALD, NAFLD and other (viral [VIR], autoimmune 0.98, 95%CI 0.97–0.99) and SMI (aOR = 0.94, 95%CI 0.88–0.99) were
[AI])-as well as indications for HVPG measurement-VB, RA (or associated with mortality, but not PMI or VATI.
hydrothorax), liver resection, differential diagnosis with transjugular Conclusion: We have shown that SATI is associated with mortality
liver biopsy, or implantation of TIPSS. We excluded patients with independently of HVPG. Future larger studies should review the
other etiologies, malignancies, and those with less than 6months of strength of this association separately for males and females and
follow-up. propose cut-offs.
Results: We enrolled 220 patients. Cirrhosis was due to NAFLD and
ALD in 52 and 128 pts (VIR and AI in 26 and 14), respectively. Patients FRI498
with NAFLD vs. ALD had similar age (60.4 vs. 56.9), a higher Association of low mechano-energitic efficiency and prognosis in
proportion of females 67.3 vs. 31.2), lower MELD scores (13.0 vs. liver cirrhosis
16.0), and a lower white blood cell count (4.9 vs. 6.15). Overall, the Sannia Sjöstedt1, Signe Wiese2, Flemming Bendtsen3,4,
median HVPG in NAFLD and ALD (VIR and AI) was 14.0 and 18.0 (12.5 Søren Møller1,4. 1Hvidovre Hospital, Department of Clinical Physiology
and 10.0) mmHg (P-value for trend <0.001), respectively. In 30 and 19 and Nuclear Medicine, Hvidovre, Denmark; 2Gastro Unit, Medical
(17 and 8) compensated pts, HVPG was 11.5 and 10.0 (12.0 and 6.5) Division, Hvidovre; 3Hvidovre Hospital, Gastro Unit, Medical Division,
mmHg ( p = 0.4). Among decompensated pts with VB, in 16 and 51 (7 Hvidovre; 4Copenhagen University, Department of Clinical Medicine,
and 5) the HVPG was 15.5 and 19.0 (13.0 and 18.0) mmHg, Faculty of Health Sciences, Copenhagen, Denmark
respectively ( p = 0.02). In 6 and 31 (2 and 1) of pts with RA, the Email: [email protected]
median HVPG was 16.5 and 19.0 (16.0 and 16.0) (p = 0.75).
Background and aims: In cirrhosis, cardiac systolic dysfunction as
Transplant-free survival at 3 and 6 months did not differ between
part of cirrhotic cardiomyopathy (CCM) affects development of
NAFLD and ALD (84.6 vs. 85.2, and 82.7 vs. 75.8%).
complications and course of the disease and prognosis. Myocardial
Conclusion: Overall, and in decompensated cirrhosis, the NAFLD
mechano-energetic efficiency (MEE) is an estimate of left ventricular
etiology was associated with lower values of HVPG compared with
performance and reduced MEE is associated with poor prognosis in
ALD, likely reflecting a lower HVPG threshold for VB in NAFLD.
heart failure patients. In this study we aimed to investigate the
FRI497 relation of MEE to patient characteristics and its impact on survival in
Low subcutaneous adipose tissue is associated with mortality patients with cirrhosis.
independently from portal hypertension in patients with Method: We included 283 patients with cirrhosis of different severity
cirrhosis according to the Child-Pugh classifications (A/B/C: 106/87/90). All
patients had a liver vein catheterization and a hemodynamic
Xun Zhao1, Balqis Alabdulkarim1, Dana Kablawi1, Marc Deschenes1,
investigation performed including determination of cardiac output
Philip Wong1, Tianyan Chen1, Benjamin Rehany1,
(CO), stroke volume, and heart rate (HR). These data were used to
Mohamed Abu-Nada1, David Valenti1, Ali Bessissow1,
assess MEE, which was defined as (stroke volume/HR)*1.666.
Giada Sebastiani1, Amine Benmassaoud1. 1McGill University Health
Results: Eighty-nine percent of the patients had portal hypertension
Centre Glen Site (MUHC), Montréal, Canada
(Hepatic venous pressure gradient >5 mmHg) and 80% indications of
Email: [email protected]
a hyperdynamic circulatory state with increased CO and HR. There
Background and aims: Sarcopenia and adipopenia are associated was no difference in MEE in Child-Pugh class C patients (2.03) vs
with worse outcomes in patients with cirrhosis. To this date, it is Child-Pugh class A (1.98) and B (2.05) patients. In Child-Pugh class C
unclear if muscle and adipose tissue mass predict mortality patients, low MEE was associated with a poorer prognosis (median
independently of portal hypertension. The aim of our study was to survival 886 days vs 2693 days).
investigate whether body composition could predict mortality while
adjusting for the severity of portal hypertension by using the gold
standard, the Hepatic Venous Pressure Gradient (HVPG).
Method: This was a single center retrospective cohort study of adult
patients with cirrhosis who underwent HVPG measurement between
November 2012 and June 2020 and had available cross-sectional
imaging at the 3rd lumbar vertebrae (L3). Participants were excluded
if HVPG was not reliable or if imaging was performed more than 12
months before or 1month after HVPG. Body composition was
determined using CoreSlicer, a dedicated radiology software. Total
psoas muscle index (PMI), total skeletal muscle index (SMI),
subcutaneous and visceral adipose tissue indeces (SATI, VATI) were
calculated at L3 by measuring their respective areas and dividing by
the height squared ((in cm2/m2). Factors associated with death were
assessed using univariate and multivariate logistic regression.
Results: We included a total of 81 patients (mean age 60.2years, 62%
males, 31% with non-alcoholic fatty liver disease, 20% with alcohol-
related liver disease and 17.3% with viral hepatitis, 52% with HVPG
above 10 mmHg, 54% with decompensated cirrhosis at baseline, and
median MELD 13). During follow-up, 27 (33.3%) patients died. Figure: Kaplan-Meier plot showing differences in survival in liver cirrhosis
Patients who died were older (64.6 yrs vs 58 yrs, p = 0.018), had patients classified as Child C stratified by MEE (low MEE below the
higher HVPG (13.7 mmHg vs 9.2 mmHg, p = 0.004), lower muscle median value and high MEE above the median value). A significantly
mass (PMI: 4.5 vs 5.6, p = 0.002; SMI: 41.3 vs 48.5, p = 0.002), lower poorer survival is seen in patients with low MEE.
SATI (45.6 vs 74.2, p = 0.002), and tended to have a higher MELD (15.3
Conclusion: In our study, MEE does not seem to be associated with
vs 12.9, p = 0.067). Sex, BMI and VATI were not associated with
severity of the liver disease, but in patients with advanced disease
mortality. On separate models for each compartment, after adjusting
low MEE is associated with a poorer prognosis. The prognostic impact
for age and HVPG, SATI (aOR = 0.98, 95%CI 0.96–0.99) was the only
of MEE should be further investigated in future prospective studies.
body compartment associated with mortality whereas PMI, SMI and

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 POSTER PRESENTATIONS
FRI499 FRI500
Long term albumin administration is associated with reduced Improved survival rates in hepatic encephalopathy after a decade
healthcare resource use in patients with uncomplicated cirrhotic of clinical practice with the addition of rifaximin-alpha to
ascites: results from a simulation model lactulose: a real-world data meta-analysis
Kris Bennett1,2, Elisabet Viayna3, Murat Gunal4, Duncan Stacey5, Juha Halonen1, Roland Henrar1. 1Norgine Ltd, Harefield, United
Anne Davis6, David Southern7, Matthew Cramp1. 1University Hospitals Kingdom
Plymouth NHS Trust, South West Liver Unit, Plymouth, United Kingdom; Email: [email protected]
2
University Hospitals Plymouth NHS Trust, South West Liver Unit,
Background and aims: Hepatic encephalopathy (HE) is a frequent
Plymouth, United Kingdom; 3Grifols S.A., Sant Cugat del Valles̀ , Spain;
4 complication of liver cirrhosis with a high risk of both short-term and
Simarter, Instanbul, Turkey; 5Grifols UK, Cambridge, United Kingdom;
6 long-term mortality [1]. Real-world longitudinal data on mortality
Employed by Grifols SSNA, NC, United States; 7SSB Research Ltd., United
rates in HE are scarce. This meta-analysis of two available studies
Kingdom
compared the survival rates attained over approximately one decade.
Email: [email protected]
Method: In HE, real-world mortality rates over 5 years were initially
Background and aims: Decompensated cirrhosis is associated with reported in patients with alcohol-related liver cirrhosis [1] and more
high rates of complications and costs. The ANSWER trial showed that recently in patients with HE who received combination treatment
long-term human albumin infusions (LTA; 40 g twice/week for 2 with rifaximin-alpha plus lactulose [2, 3]. Our meta-analysis
weeks, 40 g/week thereafter) added to standard medical treatment calculated survival rates at 1, 12 and 60 months in the first study,
(SMT) led to significant reduction of complications and mortality in and at 12, 36 and 60 months in the more recent study. Survival rates at
patients with uncomplicated ascites. We developed a discrete event 12 and 60 months were compared between studies using two-sided
simulation (DES) model to estimate economic and clinical impacts of t-tests, assuming equal variance.
LTA in patients with cirrhosis and uncomplicated ascites in the UK. Results: The first study (conducted in 1993–2006) included 169
Real-world rates of hospital visits, treatments, and complications in patients with HE and survival rates at 1, 12 and 60 months were 55%,
the UK are used as model inputs. The potential benefit of LTA is 36% and 15%, respectively. The more recent study (conducted in
modelled on data from the ANSWER trial. 2014–2019) included 136 patients with HE and survival rates after 12,
Method: We developed a DES model using Simul8 Professional 2021 36 and 60 months were 72%, 49% and 35%, respectively. Survival rates
software to simulate individual patients’ disease course by tracking were significantly higher in the more recent study in comparison
health events (treatments, complications, hospitalizations, death) with the previous study at both 12 months (72% vs 36%; p = 0.029)
over time. We compared outputs for 2 patient cohorts: 1) SMT only, 2) and 60 months (35% vs 15%; p < 0.001). In the more recent study, all
SMT + LTA per ANSWER protocol. Model inputs for the SMT cohort patients received lactulose plus rifaximin-alpha 550 mg; in the
were health event probabilities retrieved from Hospital Episode previous study, treatments were not reported but were likely to
Statistics for 10 UK hospitals between Apr-2016 and Mar-2020. This consist of lactulose alone. Notably, the number needed to treat to
real-world data gathered from 873 cirrhotic patients with uncompli- prevent an HE death, when comparing the more recent study versus
cated ascites comprised 12-month rates for hospital visits, cirrhosis the previous study, was 2.8 at 12 months and 4.9 at 60 months.
complications, treatments, and death. These were transformed into Conclusion: Direct comparison of the two studies is limited by
costs using NHS tariffs. Reduction in health event probabilities for the different countries and by expected clinical improvements over a
SMT + LTA cohort was based on ANSWER trial data. decade. Nevertheless, these real-world results suggest that treating
Results: A hypothetical cohort of 100 patients with cirrhosis and patients with a combination of rifaximin-alpha 550 mg twice daily
uncomplicated ascites was simulated over 12 months, first with all plus lactulose, rather than lactulose alone, may improve both 1-year-
patients treated with SMT, and then with 30% of patients treated with and 5-year survival rates in HE in current clinical practice.
SMT + LTA; 30% was felt to represent an achievable patient volume for
References
administering LTA in cirrhotic cohorts. In our model, the use of LTA
decreased hospital admissions by 12.6% and reduced incidence of Jepsen P, et al. Hepatology 2010;51 (5):1675–82.
Hudson M, et al. Frontline Gastroenterol 2017;8 (4):243–51.
cirrhosis-related complications. The development of refractory Hudson M, et al. Gut 2021;70 (S3):A41–2.
ascites decreased from 37% to 30% in the LTA group. In the model,
SMT + LTA in 30 out of 100 patients with uncomplicated cirrhotic FRI501
ascites may save up to £264, 589/year in total healthcare costs. Risk prediction of hepatic encephalopathy after molecular
targeted therapy for hepatocellular carcinoma in patients with
cirrhosis
Kisako Fujiwara1, Takayuki Kondo1, Sae Yumita1, Takamasa Ishino1,
Keita Ogawa1, Miyuki Nakagawa1, Hidemi Unozawa1,
Terunao Iwanaga1, Takafumi Sakuma1, Naoto Fujita1,
Hiroaki Kanzaki1, Keisuke Koroki1, Kazufumi Kobayashi1,
Soichiro Kiyono1, Masato Nakamura1, Naoya Kanogawa1,
Tomoko Saito1, Sadahisa Ogasawara1, Shingo Nakamoto1,
Tetsuhiro Chiba1, Jun Kato1, Naoya Kato1. 1Graduate School of Medicine,
Chiba University, Department of Gastroenterology, Chiba, Japan
Email: [email protected]
Background and aims: The management of hepatic encephalopathy
Figure: Graphical representation of the discrete event simulation model. (HE) during treatment for advanced hepatocellular carcinoma is
crucial because it may cause interruption of molecular targeted
Conclusion: Our DES model suggests that, if outcomes reported in therapy. However, the incidence of HE and the risk of its development
the ANSWER trial translate to similar real-world benefits in UK has not been sufficiently clarified. In this study, we investigated the
patients, the use of LTA in cirrhotic uncomplicated ascites could lead incidence and risk factors of HE in cirrhotic patients with advanced
to cost-savings, even when administered to a proportion of those hepatocellular carcinoma after the first-line chemotherapy.
eligible. Method: This retrospective study enrolled 316 cirrhotic patients with
advanced hepatocellular carcinoma diagnosed by contrast-enhanced

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S615

POSTER PRESENTATIONS
computed tomography (Child-Pugh A 242 cases/B 74 cases) who
received molecular targeted agents as first-line chemotherapy
between July 2009 and February 2019 and measured ammonia
levels　before ( pre-treatment) and 1 week after treatment ( post-
treatment). We examined the incidence and predictors of HE within 2
weeks after treatment.
Results: Incidence of HE: Pre-treatment serum ammonia levels
elevated significantly compared to post-treatment (56.9 ± 30.6 vs.
79.9 ± 48.3 μmol/L, P < 0.001), and hepatic encephalopathy was
observed in 14 patients (4.4%) within 2 weeks after chemotherapy.
Risk factors for the development of HE: Multivariate analysis showed
that higher pre-treatment ammonia levels (Odds ratio 1.022 [1.008–
1.036], P = 0.002) and the greater maximum diameter of portosys-
temic shunts (Odds ratio 1.094 [1.014–1.179], P = 0.020) were
significant predictive factors for the development of HE.
Predictive model for the development of HE using a decision-tree-
based approach: The final selected tree-discriminated cases were
classified according to the following 3 subpopulations; low-risk
group (ammonia levels <73 μmol/L; development of HE, 0.9%), Results: A total of 1118 cACLD patients were enrolled in training
intermediate-risk group (ammonia levels ≥73 μmol/L and portosys- cohort and validation cohort. In training cohort, multivariate analysis
temic shunt diameter <6.2 mm; development of HE, 4.2%), and high- revealed that liver stiffness measurement (LSM), platelet count (PLT),
risk group (ammonia levels ≥73 μmol/L and portosystemic shunt albumin, alanine aminotransferase (ALT) and varices were the
diameter ≥6.2 mm; development of HE, 20%). independent risk factors for hepatic decompensation. The novel
Conclusion: The development of HE after molecular targeted therapy CHESS criteria was produced, and <−4.4, −4.4 to −3.1 and >−3.1
could be clearly risk-segmented according to the ammonia level and indicated the low risk, medium risk, and high risk of decompensa-
the diameter of portosystemic shunts. Therefore, treatment for HE tion, with a 3 year-time-dependent area under the curve (tAUC) of
should be considered in cases with higher ammonia levels and large 0.851 (0.800–0.901) (Figure 1 A). In validation cohort, the 3 year-tAUC
portosystemic shunt before molecular targeted therapy. of ABC model was 0.843 (0.742–0.943) (Figure 1 B).
Conclusion: The ABC model can stratify the risk of decompensation
FRI502 in cACLD. HVPG evaluation can be waived in both low risk and high
ABC: a novel algorithm to stratify decompensation risk in patients risk cACLD patients as they can be managed by Baveno VI criteria and
with cACLD (CHESS2102): an international, multicenter cohort non-selective β-blockers intervention, respectively, and the remain-
study ing medium risk patients need further HVPG evaluation.
Chuan Liu1, Jia Li2, Yu Jun Wong3, Qing Xie4, Masashi Hirooka5,
Hirayuki Enomoto6, Tae Hyung Kim7, Amr Hanafy8, Zhujun Cao4, FRI503
Lili Zhao2, Yanna Liu1, Yifei Huang1, Xiaoguo Li1, Ning Kang1, Quantitative parameters of esophageal varices based on
Yohei Koizumi5, Yoichi Hiasa5, Takashi Nishimura6, Hiroko Iijima6, computed tomography may be used for predicting severe varices
Young Kul Jung7, Hyung Joon Yim7, Xin Li9, Qing-Lei Zeng10, in patients with liver cirrhosis
Xiaolong Qi1. 1The First Hospital of Lanzhou University, CHESS Center, Shang Wan1, Bin Song1. 1West China Hospital, West China School of
Institute of Portal Hypertension, China; 2Department of Gastroenterology Medicine, Sichuan University, Radiology, Cheng Du, China
and Hepatology, Tianjin Second People’s Hospital, Tianjin, China; Email: [email protected]
3
Department of Gastroenterology & Hepatology, Changi General Hospital, Background and aims: Esophageal varices (EV) are the most
Singapore; 4Department of infectious disease, Ruijin hospital, Shanghai common complication in patients with portal hypertension resulted
Jiao Tong university school of medicine, Shanghai, China; 5Department of from liver cirrhosis, and the subsequent variceal bleeding is the
Gastroenterology and Metabology, Ehime University Graduate School of leading cause of death in those patients. The invasive procedure of
Medicine; 6Department of Internal Medicine, Division of endoscopy is now regarded as the reference standard for evaluation
Gastroenterology and Hepatology, Hyogo College of Medicine, of EV, however, the utility of it is limited due to the invasive nature
Nishinomiya, Japan; 7Division of Gastroenterology and Hepatology, Korea and the high-cost effectiveness. Thus, in this study, we aimed to
UniversityAnsan Hospital, Ansan-si, Gyeonggi-do, Republic of Korea; assess whether the quantitative computed tomography (CT)-derived
8
Division of Gastroenterology, Hepatology and Endoscopy, Internal parameters can noninvasively predict the severity of EV and the risk
Medicine, Zagazig University Faculty of Medicine, Egypt; 9Department of of esophageal variceal bleeding (EVB).
radiology, Tianjin second people’s hospital, Tianjin, China; 10Department Method: In this retrospective study, a total of 145 endoscopically
of Infectious Diseases and Hepatology, The First Affiliated Hospital of confirmed EV patients were included and were divided into a
Zhengzhou University, Zhengzhou, 450052, China conspicuous (mild-to-moderate EV, n = 39) and a non-conspicuous
Email: [email protected] EV group (severe EV, n = 106), a bleeding (n = 89) and a non-bleeding
Background and aims: Liver-related death is preceded by clinical group (n = 56). EV grade (EVG), EV diameter (EVD), cross-sectional
decompensation; therefore, the risk stratification of decompensation surface area (CSA), EV volume (EVV), spleen volume (SV), splenic vein
in compensated advanced chronic liver disease (cACLD) is extraor- (SNV), portal vein (PV), diameter of left gastric vein (DLGV), and the
dinary significant. This study intended to investigate a novel opening type of LGV were measured independently using 3D-slicer.
algorithm to stratify the decompensation risk in patients with cACLD. Univariate and multivariate logistic analysis were used to determine
Method: The international, multicenter study included two cohorts the independent factors and the receiver operating characteristic
from January 2009 to August 2020. In training cohort, the unfavorable (ROC) curves were performed to evaluate the diagnostic performance.
Baveno VI criteria patients were used to develop the novel CHESS Results: The difference of EVG, EVD, CSA, EVV, DLGV, SNV between the
criteria to stratify decompensation risk. The Algorithm based on conspicuous and non-conspicuous EV group were statistically signifi-
Baveno VI criteria plus CHESS criteria (ABC model) was validated in cant (p < 0.05), area under the curves (AUCs) of them for predicting
validation cohort. severe EV were 0.72, 0.772, 0.704, 0.768, 0.707, 0.65, with correspond-
ing sensitivities of 70.3%, 63.5%, 50%, 74.3%, 52.7%, 48.6%, specificities

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 POSTER PRESENTATIONS
of 71.4%, 85.7%,100%, 71.4%, 81%, 81% respectively. EVG, CSA (odds ratio
(OR):3.258, 95% confidence interval (CI):1.597–6.647; OR:1.029, 95%
CI:1.008–1.050) were found to be independent predictive factors.
However, there was no significant difference of the included
parameters between the bleeding and non-bleeding group (p > 0.05).

Figure: Probabilistic Sensitivity analysis of incremental Costs versus

Incremental QALYS of GORE® VIATORR® TIPS Endoprosthesis versus LVP;
CE threshold 30, 000 Euros.

Conclusion: From the Spanish healthcare perspective, this economic

analysis suggests that the GORE® VIATORR® Device was cost saving
and cost-effective at two years compared to LVP. Cost-savings were
primarily driven by reduced LVP sessions and decreased inpatient
hospital stay. Based on this economic evaluation the consideration of
the GORE® VIATORR® Device in refractory ascites is cost-saving to the
hospital provider and may improve patient health-related quality of
life. Further long term studies are required in providing health
economic evidence in this space.

FRI505
Conclusion: CT can be used as a noninvasive method to effectively Factor VIII/protein C ratio does not reflect coagulation but is
predict the severity of esophageal varices, which may reduce the linked to pathophysiological mechanisms driving disease
invasive screening of endoscopy and be used as a supplementary progression in patients with advanced chronic liver disease
procedure in patients with portal hypertension. Lorenz Balcar1,2, Bernhard Scheiner1,2, Rafael Paternostro1,2,
Benedikt Simbrunner1,2, Lukas Hartl1,2, Mathias Jachs1,2,
FRI504 David JM Bauer1,2, Albert Stättermayer1,2, Georg Semmler1,2,
A cost-effectiveness evaluation of the GORE® VIATORR® TIPS Matthias Pinter2, Peter Quehenberger3, Michael Trauner2,
Endoprosthesis versus large volume paracentesis in the Thomas Reiberger1,2, Ton Lisman4, Mattias Mandorfer1,2. 1Medical
management of portal hypertension complications in the Spanish University of Vienna, Vienna Hepatic Hemodynamic Lab, Division of
healthcare system Gastroenterology and Hepatology, Department of Internal Medicine III,
Mitesh Nakum1, Thomas Wiersma2, Francesca Di Stasi3. 1W. L. Gore & Vienna, Austria; 2Medical University of Vienna, Division of
Associates (UK) Ltd., Health Economics, United Kingdom; 2W.L. Gore & Gastroenterology and Hepatology, Department of Internal Medicine III,
Associates B.V., Tilburg, Netherlands; 3W.L. Gore & Associati Srl, Verona, Vienna, Austria; 3Medical University of Vienna, Department of
Italy Laboratory Medicine, Vienna, Austria; 4University Medical Center
Email: [email protected] Groningen, Surgical Research Laboratory and Section of Hepatobiliary
Surgery and Liver Transplantation, Department of Surgery, Groningen,
Background and aims: The GORE® VIATORR® TIPS Endoprosthesis is
Netherlands
widely used in patients for the treatment of portal hypertension and
Email: [email protected]
its complications such as refractory ascites in Spain, however little is
known about the cost-effectiveness of the GORE® VIATORR® Device Background and aims: We and others have demonstrated that the
in the Spanish healthcare system. The aim of this analysis was to ratio of procoagulant factor VIII to anticoagulant protein C (FVIII/PC)
establish the cost-effectiveness of the GORE® VIATORR® Device is a versatile predictor of hepatic decompensation/liver-related death
versus large volume paracentesis (LVP) in refractory ascites with the in patients with advanced chronic liver disease (ACLD). Of note, the
Spanish healthcare system. association between FVIII/PC and thrombomodulin-modified throm-
Method: A published markov model1 was updated to simulate bin generation assay (TM-TGA) results is confounded by liver disease
economic outcomes at two years from the Spanish healthcare severity.
perspective. Clinical parameters were derived from an updated To substantiate the notion that FVIII/PC is unrelated to coagulation
published literature review2. Costing information was gathered from potential and provide an alternative explanation for its prognostic
national tariffs, existing literature and expert opinion. Uncertainty value, we investigated its association with (i) bleeding and throm-
was tested using deterministic and probabilistic sensitivity analyses. botic events, and (ii) key pathophysiological mechanisms promoting
Results: The GORE® VIATORR® Device was estimated to be cost- liver disease progression.
saving by 21, 493 Euros versus LVP over the time frame of the analysis. Method: In cohort (i) including ACLD patients undergoing HVPG
The GORE® VIATORR® Device also resulted in +0.60 QALYs versus LVP measurement at the Vienna Hepatic Hemodynamic Lab with
and so was cost-effective. Savings with the GORE® VIATORR® Device information on FVIII/PC (n = 576), we evaluated the development of
was from reduced LVP resource utilisation costs and reduced major bleeding as well as arterial/venous thrombotic events
inpatient stay. The GORE® VIATORR® Device also remained over (Schulman S, et al, J Thromb Haemost 2010) during follow-up.
98% cost-effective in a probabilistic sensitivity analysis versus LVP Moreover, incidence of ACLF was assessed. In cohort (ii), associations
(see figure below). between FVIII/PC and pathophysiology-oriented biomarkers were
assessed in 142 patients from the prospective VIenna CIrrhosis Study
(VICIS).

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S617

POSTER PRESENTATIONS
Results: (i) During a follow-up of 31.8 (IQR:12.0–60.3) months, major the impact of the transmembrane 6 superfamily 2 (TM6SF2)
bleedings were observed in 44 (7.6%) patients and bleedings were rs58542926 and membrane-bound O-acyltransferase domain-contain-
attributed to portal hypertension in 35 (6.3%) of the first bleeding ing 7 (MBOAT7) rs641738 single nucleotide variants (SNV) in patients
events. Non-malignant thrombotic events were diagnosed in 50 who have already progressed to ACLD are unknown.
(8.7%) patients. FVIII/PC was associated with neither the incidence of Method: The impact of TM6SF2/MBOAT7 variants on liver-related
major bleedings (hazard ratio [HR]: 1.03[95%CI:0.98–1.09];p = 0.272), events was evaluated in 938 ACLD (as defined by HVPG ≥6mmHg;
nor the occurrence of thrombotic events (HR: 1.03[95%CI:0.98–1.09]; viral hepatitis and alcohol-related or non-alcoholic fatty liver disease)
p = 0.269). However, it predicted ACLF (adjusted HR: 1.10[95%CI:1.02– patients undergoing HVPG-measurement at the Vienna Hepatic
1.19];p = 0.015) in decompensated patients, independently of CLIF-C Hemodynamic Lab.
ACLF-D. Results: Mean age was 55 ± 11 years, mean HVPG was 15 ± 7 mmHg
(ii) As demonstrated in the attached Figure, FVIII/PC showed and mean MELD was 11 ± 5 points. The main etiologies were viral
moderate to strong correlations with HVPG (Spearman’s ρ = 0.442; hepatitis (n = 495, 53%) alcohol-related liver disease (n = 342, 37%)
p < 0.001), von Willebrand factor (ρ = 0.628;p < 0.001), serum sodium and non-alcoholic fatty liver disease (n = 101, 11%).
(ρ = − 0.487;p < 0.001), and renin (ρ = 0.450;p < 0.001), as well as While 754 (80%) patients harboured the TM6SF2 wild-type (C/C), 174
associations with systemic inflammation: C-reactive protein (ρ = (19%) and 10 (1%) patients had one or two T-alleles, respectively.
0.230;p = 0.006), interleukin-6 (ρ = 0.381;p < 0.001), and procalcito- Patients with at least one TM6SF2 T-allele had more pronounced
nin (ρ = 0.257;p = 0.002). Finally, it also strongly correlated with the portal hypertension (HVPG: 16 ± 7 vs. 15 ± 7 mmHg; p = 0.031),
enhanced liver fibrosis (ELF) test, as an indicator of fibrogenesis/ higher gamma-glutamyl transferase levels (123 vs. 97 U × L−1; p =
matrix remodelling (ρ = 0.613;p < 0.001). 0.002), and more commonly hepatocellular carcinoma (HCC, 17% vs.
12%; p = 0.049). Patients with at least one MBOAT7 T-allele also tended
to have a higher HCC prevalence at baseline (14% vs. 10%; p = 0.051),
while other baseline characteristics were comparable.
In univariable Cox regression analyses, carriers of the TM6SF2 T-allele
showed a trend towards an increased risk for decompensation/liver-
related death during follow-up (hazard ratio [HR]: 1.26 [95%
confidence interval (95%CI): 0.98–1.62]; p = 0.072); in the viral
hepatitis subgroup, the association attained statistical significance
(HR: 1.53 [95%CI: 1.03–2.29]; p = 0.036). After adjusting for age,
HVPG, MELD, and albumin levels, neither the TM6SF2 nor the MBOAT7
genotype had an effect on decompensation/liver-related death
during follow-up.
These results were unaffected by restricting our analysis to patients at
increased risk of hepatic decompensation/liver-related death, i.e.,
those with clinically significant portal hypertension.
Conclusion: While SNVs in TM6SF2 and MBOAT7 modulate the risk of
progression to ACLD, both genotypes had no independent impact on
liver-related outcomes in ACLD patients but were potential risk
factors for HCC development. Thus, these variants have limited value
for risk stratification in patients with ACLD as HCC screening is
warranted anyway.

Conclusion: Baseline FVIII/PC was associated with neither throm- FRI507

botic events nor major bleedings during follow-up, i.e., the clinical Hepatocellular carcinoma and number of elastic bands per
correlates of coagulation. Hence, results from previous studies on session are strong predictors of bleeding after prophylactic
FVIII/PC require reinterpretation. However, FVIII/PC was associated endoscopic variceal bleeding
with key pathophysiological mechanisms involved in disease Renato Medas1, Rodrigo Liberal1, Tiago Ribeiro1, João Afonso1,
progression, including those promoting further decompensation Rosa Coelho1, Hélder Cardoso1, Guilherme Macedo1. 1Centro
and ACLF, which may explain its prognostic utility. Hospitalar Universitário São João, Gastrenterology and Hepatology,
Porto, Portugal
FRI506 Email: [email protected]
Prognostic impact of variants in TM6SF2 and MBOAT7 in patients
Background and aims: Endoscopic variceal band ligation (EVL) is
who have progressed to advanced chronic liver disease
considered a standard care for high-risk varices treatment in
Lorenz Balcar1,2, Bernhard Scheiner1,2, Markus Urheu1, cirrhosis. Despite being globally safe, procedure-related bleeding is
Patrick Weinberger1, Rafael Paternostro1,2, Benedikt Simbrunner1,2, a potential complication, with an estimated incidence up to 15% in
Georg Semmler1,2, Nicole Auer1, Claudia Willheim1, Matthias Pinter1, some series, requiring hospitalization and blood transfusion.
Michael Trauner1, Thomas Reiberger1,2, Mattias Mandorfer1,2, However, risk factors associated with this serious complication are
Albert Stättermayer1,2. 1Medical University of Vienna, Division of not well established. The aim of our study was to evaluate factors
Gastroenterology and Hepatology, Department of Internal Medicine III, associated with increased risk for upper gastrointestinal bleeding
Vienna, Austria; 2Medical University of Vienna, Vienna Hepatic (UGIB) within 30 days after prophylactic EVL.
Hemodynamic Lab, Division of Gastroenterology and Hepatology, Method: We performed a single center retrospective study in a
Department of Internal Medicine III, Vienna, Austria tertiary hospital during a 6-year period (between 09/2015 and 09/
Email: [email protected] 2021). All patients with clinically significant portal hypertension due
Background and aims: Genome-wide association studies revealed to liver cirrhosis, submitted to prophylactic EVL, were considered
genetic variants that modulate the susceptibility for (advanced) eligible for the study. After EVL, all patients received oral proton
chronic liver disease (A)CLD. We have previously shown that a pump inhibitor and sucralfate, according to an internal protocol.
PNPLA3 variant promotes hepatic decompensation/death in ACLD, Statistical analysis was performed with SPSS®v.25.0.
while HSD17B13 did not impact prognosis at this stage. Importantly,

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 POSTER PRESENTATIONS
Results: A total of 871 prophylactic EVL procedures, performed in 281
patients were analysed. Most procedures were primary prophylaxis
(70.3%). 79.9% of patients were male (79.9%) and median age was 60
years (IQR 54–68). Alcohol was the main etiology for cirrhosis (57.9%),
followed by hepatitis C virus (14.9%). UGIB 30-days after EVL occurred
in 21 cases (2.4% of all EVLs) within a median time of 9 days (IQR 8–
17) after index procedure. In 15 patients (68.2%) ligation ulcers were
identified as the potential source of bleeding. On univariate analysis
the number of elastic bands per session, platelets, albumin, total
bilirubin, sodium, hepatocellular carcinoma (HCC) and portal venous
thrombosis were associated with increased risk of UGIB 30-days after
EVL. After multivariate logistic regression, only the number of elastic
bands applied per session [above 7] (odds ratio [OR] 4.76, 95%
confidence interval [CI] 1.97–13.02, p = 0.001), presence of HCC (OR
3.79, 95% CI 1.16–9.02, p = 0.006) and sodium (OR 0.86, 95% CI 0.78–
0.95, p = 0.002) reached statistical significance. Age, sex, cirrhosis
etiology, high-risk varices, concomitant gastric varices, ligation
system, creatinine, international normalized ratio, antiplatelet and
anticoagulant therapy were not associated with increased risk of
bleeding after EVL.
Conclusion: Our study describes a relative low incidence of post-EVL
Conclusion: In patients with cirrhosis treated with TIPS, simultan-
UGIB in accordance with previous reports, reinforcing EVL as a safe
eous large SPSS embolization reduced the risk for overt HE without
procedure for prophylaxis of variceal bleeding. The number of elastic
increasing other complications. Simultaneous large SPSS emboliza-
bands applied per session, serum sodium and presence of HCC, rather
tion should therefore be considered for prophylaxis of post-TIPS HE.
than platelets or coagulopathy, are predictors of bleeding after
prophylactic EVL in patients with liver cirrhosis. These data suggest
FRI509
that prophylactic administration of blood or coagulation products are
Use of second-harmonic generation microscopy for automated
not necessary. In addition, a minimal EVL strategy should be
detection of septa and nodules in needle liver biopsies of NASH
considered in selected patients.
cirrhosis
FRI508 Mazen Noureddin1, Dean Tai2, Elaine Chng2, Yayun Ren2, Pol Boudes3,
Simultaneous large spontaneous portosystemic shunt Harold Shlevin3, Stephen Harrison4, Guadalupe Garcia-Tsao5,
embolization for the prevention of overt hepatic encephalopathy Naga Chalasani6, Zachary Goodman7. 1Division of Digestive and Liver
after TIPS: a randomized controlled trial Diseases, Comprehensive Transplant Center, Cedars-Sinai Medical
Yong Lv1, Hui Chen1, Bohan Luo1,2, Wei Bai1,2, Kai Li1, Center, United States; 2HistoIndex Pte. Ltd., Singapore; 3Galectin
Therapeutics, United States; 4Pinnacle Clinical Research, San Antonio, TX,
Zhengyu Wang1,2, Dongdong Xia1,2, Wengang Guo1,2, Xiaomei Li1,2,
Jie Yuan1,2, Zhanxin Yin1,2, Daiming Fan1, Guohong Han1,2. 1National USA; 5Section of Digestive Diseases, Yale University and CT-VA Healthcare
System, Connecticut, USA; 6Division of Gastroenterology and Hepatology,
Clinical Research Center for Digestive Diseases and Xijing Hospital of
Digestive Diseases, Fourth Military Medical University, Department of Department of Medicine, Indiana University School of Medicine, USA;
7
Liver Diseases and Digestive Interventional Radiology, Xi’an; 2Xi’an Inova Fairfax Hospital, Falls Church, Virginia, USA
Email: [email protected]
International Medical Center Hospital of Digestive Diseases, Department
of Liver Diseases and Digestive Interventional Radiology, Xi’an, China Background and aims: Cirrhosis, previously considered irreversible,
Email: [email protected] is now recognized as capable of regression or progression. Most
Background and aims: Large spontaneous portosystemic shunt staging systems oversimplify all degrees of cirrhosis into one
(SPSS) is associated with increased risk of hepatic encephalopathy category. Portal hypertension, defined by hepatic venous pressure
(HE) in patients undergoing transjugular intrahepatic portosystemic gradient (HVPG), correlates with key histological features of cirrhotic
shun (TIPS). This study aimed to evaluate whether prophylactic liver biopsies, including septa and nodules, which might make a
biopsy an acceptable surrogate for clinical outcome. Using second
embolization of large SPSS at the time TIPS creation could reduce the
incidence of post-TIPS HE in patients with cirrhosis and variceal harmonic generation/two-photon excitation fluorescence (SHG/
bleeding. TPEF), this exploratory analysis aims to develop an artificial
intelligence (AI) tool based on septa and nodule microscopy for use
Method: From June 2014 to August 2017, 56 patients with cirrhosis
and large SPSS planning to undergo elective TIPS for the prevention of in natural history monitoring and evaluate treatment response in
cirrhotic NASH trials.
variceal bleeding were randomly assigned (1:1) to receive TIPS alone
(TIPS group, n = 29) or TIPS plus simultaneous SPSS embolization Method: 25 liver biopsies from 15 NASH patients with compensated
(TIPS+E group, n = 27). The primary endpoint was overt HE. cirrhosis were included from a phase 2a trial. Digitized images
stained with Sirius red and immunostain for smooth muscle actin
Results: TIPS placement and SPSS embolization was successful in all
patients. During a median follow-up of 59.0 months in the TIPS group were used by an expert pathologist to identify all septa and cirrhotic
nodules. 2 image algorithms were developed to automatically detect
and 45.3 months in the TIPS+E group, the primary endpoint was met
in 15 patients (51.7%) in the TIPS group and 6 patients (22.2%) in the septa and nodules based on pathologist’s annotations, named qSepta
TIPS+E group ( p = 0.045). The 2-year cumulative incidence of overt and qNodules, respectively. Agreement between the algorithm
detection results and annotations were determined, and the images
HE was significantly lower in the TIPS+E group (21.2% vs 48.3%; HR:
0.38, 95%CI, 0.15–0.97; p = 0.043) compared with TIPS group. The were rotated to establish repeatability.
incidence of recurrent bleeding (18.5% vs 27.6%, p = 0.627), shunt Results: Concordance between the pathologist annotations and
dysfunction (14.8% vs 17.2%, p = 0.995), death (40.7% vs 31.0%, p = algorithm identification was determined after excluding technical
0.632) and other adverse events was not significantly different artifacts. 284 septa were annotated by the pathologist (“true septa”)
and 294 septa were detected from the SHG/TPEF images using qSepta
between the 2 groups.
algorithm. Comparing the qSepta results versus true septa, 91% of the
true septa were detected by the algorithm and 85% of the algorithm

Journal of Hepatology 2022 vol. 77(S1) | S389–S664 S619

POSTER PRESENTATIONS
detection results were true septa. 587 nodules were annotated from Results: Fifty-one patients (31 male, median age 62 (56–67) years,
25 H&E images by the pathologist. 525 nodules were detected from Child Pugh A 12 (23%), B 28 (55%) C 11 (22%) were included. Median
the SHG/TPEF images using qNodules. Comparing the qNodules hepcidin (nmol/L) in the peripheral vein was 2.2 (0.5–7.6) and in the
results and true nodules, 82% of the true nodules were detected by hepatic vein 2.1 (0.5–9.2) with a positive correlation between both
the algorithm and 95% of the algorithm detection results were true (rho Spearman 0.85, p < 0.001). 31 and 36% of the patients had levels
nodules. The repeatability of qSepta and qNodules were 95% and 99% of hepcidin ≤0.5 nmol/l (lower limit of detection) in peripheral and
respectively. hepatic vein respectively. Those with hepcidin >0.5 nmol/l had vs
those below: greater MELD [16 (11–19) vs 10 (19–12) and Ferritin
(229 (154–473) vs 37 (26–80)]. No differences were observed
according to CRP & leukocytes. Hepcidin was higher in patients
with more severe liver disease [MELD: r = 0.436, p = 0.003; Child B&C
vs A: 2.7 (0.5–11.8) nmol/l vs 0.5 (0.5–3.3) nmol/l p = 0.05]. No
relevant association to HVPG.
Conclusion: No significant differences in peripheral and hepatic vein
can be observed, suggesting that the liver remains a main source of
hepcidin production even in end-stage liver disease. Increased levels
of hepcidin are associated to more severe liver disease and ferritin
and have no relevant association to portal hypertension.

FRI511
Effect of thrombocytopenia and platelet transfusion on outcomes
of acute variceal bleeding: a real world experience
Sagnik Biswas1, Manas Vaishnav1, Piyush Pathak1,
Aditya Vikram Pachisia1, Rithvik Golla1, Amit Goel2, Dr. Shalimar1.
1
All India Institute of Medical Sciences, New Delhi, Gastroenterology and
Human Nutrition, New Delhi, India; 2Sanjay Gandhi Post Graduate
Institute of Medical Sciences, Gastroenterology, Lucknow, India
Email: [email protected]
Background and aims: Thrombocytopenia is a feature of portal
hypertension. In patients with thrombocytopenia and acute variceal
bleeding (AVB), platelet transfusion is recommended by few guide-
lines and is common in routine clinical practice. However, the effect
of thrombocytopenia and platelet transfusion on acute variceal
bleeding (AVB) outcomes is unclear. We aimed to assess the outcomes
in AVB patients with thrombocytopenia and the effect of platelet
Figure: Examples of septa and nodules detection. transfusion on rebleeding and mortality.
Method: Prospectively maintained database of the patients who
Conclusion: qSepta and qNodules algorithms can accurately detect
presented with AVB were reviewed to study their outcome. Patients
septa and nodules in NASH cirrhotic patients. This can be used to
were grouped as platelet count <20, 000/mm3, 20, 000–50, 000/mm3
develop more sophisticated algorithms to correlate with HVPG and
and >50, 000/mm3. The outcomes were assessed as the risk of
study the natural history of NASH cirrhosis and treatment response.
rebleeding at days 5 and 42, and risk of death at day 42 from the onset
FRI510 of AVB. Outcomes were compared among patients with and without
Hepcidin is higher in patients with