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 11 TH
Sleisenger and Fordtran’s EDITION

Gastrointestinal
and Liver Disease
PATHOPHYSIOLOGY | DIAGNOSIS | MANAGEMENT

EDITORS ASSOCIATE EDITORS

MARK FELDMAN, MD RAYMOND T. CHUNG, MD
Chairman of Internal Medicine Director of Hepatology, Vice Chief, Gastroenterology
Texas Health Presbyterian Hospital Dallas Division of Gastroenterology
Clinical Professor of Internal Medicine Massachusetts General Hospital and Harvard Medical School
University of Texas Southwestern Medical School Associate Member, Broad Institute
Dallas, Texas Boston, Massachusetts

LAWRENCE S. FRIEDMAN, MD DAVID T. RUBIN, MD

Professor of Medicine Joseph B. Kirsner Professor of Medicine
Harvard Medical School Chief, Section of Gastroenterology, Hepatology, and Nutrition
Professor of Medicine Department of Medicine
Tufts University School of Medicine University of Chicago
Boston, Massachusetts Chicago, Illinois
The Anton R. Fried, MD, Chair
Department of Medicine
Newton-Wellesley Hospital C. MEL WILCOX, MD, MSPH
Newton, Massachusetts Division of Gastroenterology and Hepatology
Assistant Chief of Medicine University of Alabama at Birmingham
Massachusetts General Hospital Birmingham, Alabama
Boston, Massachusetts

LAWRENCE J. BRANDT, MD
Professor of Medicine and Surgery
Albert Einstein College of Medicine
Emeritus Chief
Division of Gastroenterology
Montefiore Medical Center
Bronx, New York
Elsevier
1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA 19103-2899

SLEISENGER AND FORDTRAN’S GASTROINTESTINAL AND LIVER DISEASE,

ELEVENTH EDITION ISBN: 978-0-323-60962-3
Volume 1: 978-0-323-76078-2
Volume 2: 978-0-323-76077-5

Copyright © 2021 by Elsevier, Inc. All rights reserved.

No part of this publication may be reproduced or transmitted in any form or by any means, electronic or
mechanical, including photocopying, recording, or any information storage and retrieval system, without
permission in writing from the publisher. Details on how to seek permission, further information about the
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Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions.

This book and the individual contributions contained in it are protected under copyright by the Publisher
(other than as may be noted herein).

Notice

Practitioners and researchers must always rely on their own experience and knowledge in evaluating
and using any information, methods, compounds or experiments described herein. Because of rapid
advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages
should be made. To the fullest extent of the law, no responsibility is assumed by Elsevier, authors, editors
or ­contributors for any injury and/or damage to persons or property as a matter of products liability,
negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas
contained in the material herein.

Previous editions copyrighted 2016, 2010, 2006, 2002, 1998, 1993, 1989, 1983, 1978, and 1973.

Library of Congress Control Number: 2020934045

Senior Content Strategist: Nancy Duffy

Senior Content Development Specialist: Dee Simpson
Publishing Services Manager: Julie Eddy
Senior Project Manager: Cindy Thoms
Design Direction: Patrick Ferguson

Printed in Canada

Last digit is the print number: 9 8 7 6 5 4 3 2 1

We dedicate this 11th edition to you, our readers, as you
were always central in our thoughts as we wrote, edited,
and produced this textbook. We hope our book meets
your educational needs.
 Contributors

Nezam H. Afdhal, MD, DSc Bruce R. Bacon, MD William Bernal, MD

Senior Physician in Hepatology Professor of Internal Medicine Professor
Department of Gastroenterology Division of Gastroenterology and Liver Intensive Therapy Unit
Beth Israel Deaconess Medical Center Hepatology King’s College Hospital
Boston, Massachusetts, United States Saint Louis University School of London, United Kingdom
Medicine
Rakesh Aggarwal, MD, DM Adil E. Bharucha, MBBS, MD
St. Louis, Missouri, United States
Director Professor of Medicine
Jawaharlal Institute of Postgraduate William F. Balistreri, MD Division of Gastroenterology and
Medical Education and Research Director, Pediatric Liver Care Center Hepatology
Puducherry, India Gastroenterology, Hepatology, and Mayo Clinic
Nutrition Rochester, Minnesota, United States
Taymeyah Al-Toubah, MPH
Cincinnati Children’s Hospital Medical
Gastroenterology and Oncology Taft P. Bhuket, MD
Center
H. Lee Moffitt Cancer Center Associate Clinical Professor of Medicine
Cincinnati, Ohio, United States
Tampa, Florida, United States Division of Gastroenterology
Todd H. Baron, MD University of California, San Francisco
Jaime Almandoz, MD
Professor of Medicine San Francisco, California
Assistant Professor
Division of Gastroenterology and Chief of Gastroenterology and
Department of Internal Medicine,
Hepatology ­Hepatology
­Division of Endocrinology
University of North Carolina Director of Endoscopy
University of Texas Southwestern
Chapel Hill, North Carolina, United Alameda Health System
Dallas, Texas, United States
States Oakland, California, United States
Ashwin N. Ananthakrishnan, MD, MPH
Bradley A. Barth, MD, MPH Yangzom D. Bhutia, DVM, PhD
Associate Professor of Medicine
Professor Assistant Professor
Harvard Medical School
Department of Pediatrics Cell Biology and Biochemistry
Division of Gastroenterology
University of Texas Southwestern Texas Tech University Health Sciences
Massachusetts General Hospital
Dallas, Texas, United States Center
Boston, Massachusetts, United States
Lubbock, Texas, United States
Lee M. Bass, MD
Karin L. Andersson, MD, MPH
Associate Professor of Pediatrics J. Andrew Bird, MD
Assistant Professor of Medicine
Gastroenterology, Hepatology, and Associate Professor
Harvard Medical School
Nutrition Pediatrics, Division of Allergy and
Hepatologist
Ann and Robert H. Lurie Children’s Immunology
Division of Gastroenterology
Hospital of Chicago University of Texas Southwestern
Massachusetts General Hospital
Northwestern University Feinberg Medical Center
Boston, Massachusetts, United States
School of Medicine Director
Farshid Araghizadeh, MD, MBA Chicago, Illinois, United States Food Allergy Center
Colon and Rectal Surgeon Children’s Medical Center
Alex S. Befeler, MD
Texas Digestive Disease Consultants Dallas, Texas, United States
Professor of Internal Medicine
(TDDC) and The GI Alliance (TGIA)
Medical Director of Liver Boris Blechacz, MD, PhD
Dallas–Fort Worth, Texas, United States
Transplantation Clinical Associate Professor of Internal
Louis J. Aronne, MD Department of Internal Medicine Medicine
Sanford I. Weill Professor of Metabolic Saint Louis University Gastroenterology and Hepatology
Research St. Louis, Missouri, United States Palmetto Health—University of South
Department of Medicine Carolina
Mark Benson, MD
Weill Cornell Medicine Columbia, South Carolina, United States
Associate Professor of Medicine
New York, New York, United States
Section of Gastroenterology and Diego V. Bohórquez, PhD
Fernando Azpiroz, MD, PhD Hepatology Assistant Professor
Chief University of Wisconsin School of Departments of Medicine and
Department of Gastroenterology Medicine and Public Health Neurobiology
University Hospital Vall d’Hebron Madison, Wisconsin, United States Duke University Medical Center
Professor of Medicine Durham, North Carolina, United States
Universitat Autònoma de Barcelona
Barcelona, Spain

vi
 Contributors vii

Jan Bornschein, MD Eugene B. Chang, MD Paul A. Dawson, PhD

Translational Gastroenterology Unit Martin Boyer Professor Professor 

John Radcliffe Hospital Department of Medicine Pediatrics— Gastroenterology,

Oxford University Hospitals University of Chicago Hepatology, and ­Nutrition
Oxford, United Kingdom Chicago, Illinois, United States Emory University
Atlanta, Georgia, United States
Christopher L. Bowlus, MD Joseph G. Cheatham, MD
Professor and Chief Associate Professor of Medicine Gregory de Prisco, MD
Division of Gastroenterology and Department of Medicine Diagnostic Radiologist
Hepatology Uniformed Services University Department of Radiology
University of California Davis Bethesda, Maryland Baylor University Medical Center
Sacramento, California, United States Program Director Director of Medical Education
Gastroenterology Fellowship American Radiology Associates
Lawrence J. Brandt, MD
Naval Medical Center San Diego Dallas, Texas, United States
Professor of Medicine and Surgery
San Diego, California, United States
Albert Einstein College of Medicine Jill K. Deutsch, MD
Emeritus Chief Shivakumar Chitturi, MD Clinical Fellow
Division of Gastroenterology Associate Professor Department of Internal Medicine
Montefiore Medical Center Australian National University Section of Digestive Diseases
Bronx, New York, United States Senior Staff Hepatologist Yale New Haven Hospital—Yale
The Canberra Hospital University School of Medicine
Robert Scott Bresalier, MD
Australian Capital Territory, Australia New Haven, Connecticut, United States
Professor of Medicine
Lydia and Birdie J Resoft Distinguished Daniel C. Chung, MD Kenneth R. DeVault, MD
Professor in GI ­Oncology Associate Professor of Medicine Professor of Medicine
Gastroenterology, Hepatology, and Harvard Medical School Mayo Clinic College of Medicine
Nutrition Division of Gastroenterology Jacksonville, Florida, United States
The University of Texas MD Anderson Massachusetts General Hospital
Adrian M. Di Bisceglie, MD
Cancer Center Medical Co-Director
Professor of Internal Medicine
Houston, Texas, United States Center for Cancer Risk Analysis
Department of Internal Medicine
Massachusetts General Hospital Cancer
Simon J.H. Brookes, PhD Saint Louis University
Center
Professor St. Louis, Missouri, United States
Boston, Massachusetts, United States
Human Physiology
John K. DiBaise, MD
College of Medicine, Flinders University Raymond T. Chung, MD
Professor of Medicine
Adelaide, South Australia, Australia Director of Hepatology, Vice Chief,
Division of Gastroenterology and
Gastroenterology
Alan L. Buchman, MD, MSPH Hepatology
Division of Gastroenterology
Professor of Clinical Surgery Mayo Clinic
Massachusetts General Hospital and
University of Illinois at Chicago Scottsdale, Arizona, United States
Harvard Medical School
Medical Director
Associate Member, Broad Institute Philip G. Dinning, PhD
Intestinal Rehabilitation and Transplant
Boston, Massachusetts, United States Flinders Medical Centre
Center
Human Physiology
Chicago, Illinois, United States Marcello Costa, MD
Flinders University
Matthew Flinders Distinguished
Ezra Burstein, MD, PhD Adelaide, South Australia, Australia
Professor and Professor of
Professor
Neurophysiology J. Marcus Downs, MD
Departments of Internal Medicine and
Physiology Program Director
Molecular Biology
Flinders University Colon and Rectal Surgery
UT Southwestern Medical Center
Adelaide, South Australia, Australia Texas Health Resources
Dallas, Texas, United States
Clinical Professor of Surgery
Thomas G. Cotter, MD
Andres F. Carrion, MD Colon and Rectal Surgery
Gastroenterology Fellow
Assistant Professor of Clinical Medicine University of Texas Southwestern
Section of Gastroenterology,
Program Director, Transplant Medical School
Hepatology, and Nutrition
Hepatology Fellowship Dallas, Texas, United States
University of Chicago Medicine
Division of Gastroenterology and
Chicago, Illinois, United States Douglas A. Drossman, MD
Hepatology
Professor Emeritus of Medicine and
University of Miami Albert J. Czaja, MD
Psychiatry
Miami, Florida, United States Professor Emeritus of Medicine
Division of Digestive Disease and
Gastroenterology and Hepatology
Scott Celinski, MD Nutrition
Mayo Clinic College of Medicine and
Surgical Oncologist University of North Carolina
Science
Department of Surgery President
Rochester, Minnesota, United States
Baylor University Medical Center Center for Education and Practice of
Dallas, Texas, United States Brian G. Czito, MD Biopsychosocial Care
Professor Chapel Hill, North Carolina
Francis K.L. Chan, MBChB(Hons), MD,
Radiation Oncology President
DSc
Duke University Medical Center Drossman Gastroenterology PLLC
Professor of Medicine
Durham, North Carolina, United States Durham, North Carolina, United States
Department of Medicine and
Therapeutics
Chinese University of Hong Kong
Hong Kong, China
viii Contributors

Kerry B. Dunbar, MD, PhD Michael B. Fallon, MD Alexander C. Ford, MBChB, MD

Section Chief, VA Gastroenterology Professor of Medicine Professor of Gastroenterology
Section Gastroenterology, Hepatology, and and Honorary Consultant
Department of Medicine– Nutrition ­Gastroenterologist
Gastroenterology and Hepatology University of Arizona Leeds Institute of Medical Research
VA North Texas Healthcare System– Chair St. James’s University of Leeds
Dallas VA Medical Center Department of Internal Medicine Leeds Gastroenterology Institute
Associate Professor of Medicine University of Arizona—Phoenix Leeds Teaching Hospitals Trust
Department of Medicine–Division of Phoenix, Arizona, United States Leeds, West Yorkshire, United Kingdom
Gastroenterology and Hepatology
Geoffrey C. Farrell, MD John S. Fordtran, MD
University of Texas Southwestern
Professor, Hepatic Medicine Internal Medicine, Division of
Medical School
Australian National University Gastroenterology
Dallas, Texas, United States
Senior Staff Hepatologist Baylor University Medical Center
John E. Eaton, MD The Canberra Hospital Dallas, Texas, United States
Assistant Professor of Medicine Australian Capital Territory, Australia
Chris E. Forsmark, MD
Department of Internal Medicine
Jordan J. Feld, MD, MPH Professor and Chief
Division of Gastroenterology and
Associate Professor of Medicine Division of Gastroenterology,
Hepatology
University of Toronto Hepatology, and Nutrition
Mayo Clinic
Research Director University of Florida
Rochester, Minnesota, United States
Toronto Centre for Liver Disease Gainesville, Florida, United States
Steven A. Edmundowicz, MD Senior Scientist
Lawrence S. Friedman, MD
Professor of Medicine Sandra Rotman Centre for Global
Professor of Medicine
Interim Director, Division of Health
Harvard Medical School
Gastroenterology and Hepatology Toronto General Hospital
Professor of Medicine
University of Colorado Anschutz Toronto, Ontario, Canada
Tufts University School of Medicine
Medical Campus
Mark Feldman, MD Boston, Massachusetts
Aurora, Colorado, United States
Chairman of Internal Medicine The Anton R. Fried, MD, Chair
David E. Elliott, MD, PhD Texas Health Presbyterian Hospital Department of Medicine
University of Iowa Carver College of Dallas Newton-Wellesley Hospital
Medicine Clinical Professor of Internal Medicine Newton, Massachusetts
Department of Internal Medicine University of Texas Southwestern Assistant Chief of Medicine
Division of Gastroenterology and Medical School Massachusetts General Hospital
Hepatology Dallas, Texas, United States Boston, Massachusetts, United States
Iowa City VAHCS
Nielsen Q. Fernandez-Becker, MD Scott Fung, MD
Department of Internal Medicine
Clinical Associate Professor of Medicine Associate Professor
Veterans Administration Health Care
Division of Gastroenterology and Department of Medicine
System
Hepatology University of Toronto
Iowa City, Iowa, United States
Stanford University Staff Hepatologist
B. Joseph Elmunzer, MD, MSc Redwood City, California, United States University Health Network
Peter B. Cotton Professor of Medicine Toronto General Hospital
Paul Feuerstadt, MD
and Endoscopic ­Innovation Toronto, Ontario, Canada
Attending Physician
Division of Gastroenterology and
Gastroenterology Vadivel Ganapathy, PhD
Hepatology
Gastroenterology Center of Connecticut Professor
Medical University of South Carolina,
Hamden, Connecticut Cell Biology and Biochemistry
Charleston
Assistant Clinical Professor of Medicine Texas Tech University Health Sciences
Charleston, South Carolina, United
Gastroenterology Center
States
Yale University School of Medicine Lubbock, Texas, United States
Charles O. Elson, MD New Haven, Connecticut, United States
Professor of Medicine and Microbiology John J. Garber, MD
Peter Fickert, Prof Instructor in Medicine
Basil I. Hirschowitz Chair in
Division of Gastroenterology and Harvard Medical School
Gastroenterology
Hepatology Assistant in Medicine
University of Alabama at Birmingham
Medical University of Graz Division of Gastroenterology
Birmingham, Alabama, United States
Graz, Austria Massachusetts General Hospital
Grace H. Elta, MD Boston, Massachusetts, United States
Robert E. Fleming, MD
Professor Emeritus
Professor of Pediatrics Praveen Ramakrishnan Geethakumari,
Formerly the H. Marvin Pollard
Saint Louis University School of MD, MS
Collegiate Professor
Medicine Assistant Professor
Division of Gastroenterology
St. Louis, Missouri, United States Division of Medical Oncology
University of Michigan
Ann Arbor, Michigan, United States Department of Internal Medicine
University of Texas Southwestern
Medical Center
Dallas, Texas, United States
 Contributors ix

Marc G. Ghany, MD, MHSc David J. Hass, MD M. Nedim Ince, MD

Liver Diseases Branch Associate Clinical Professor of Medicine University of Iowa Carver College of 

National Institute of Diabetes and Division of Digestive Diseases Medicine

Digestive and Kidney ­Diseases Yale University School of Medicine Iowa City, Iowa, United States
National Institutes of Health New Haven, Connecticut, United States Department of Internal Medicine
Bethesda, Maryland, United States Division of Gastroenterology and
David M. Hockenbery, MD
Hepatology
Pere Ginès, MD, PhD Member
Iowa City VAHCS
Chairman Clinical Research
Department of Internal Medicine
Liver Unit Fred Hutchinson Cancer Research
Veterans Administration Health Care
Hospital Clinic Barcelona Center
System
Full Professor of Medicine Professor of Medicine
Iowa City, Iowa, United States
University of Barcelona Division of Gastroenterology
Principal Investigator University of Washington Rachel B. Issaka, MD, MAS
Institut d’Investigacions Biomediques Seattle, Washington, United States Assistant Member
August Pi i Sunyer (IDIBAPS) Clinical Research and Public Health
Christoph Högenauer, MD
Barcelona, Spain Science Divisions
Associate Professor of Medicine
Fred Hutchinson Cancer Research Center
Robert E. Glasgow, MD Department of Internal Medicine
Assistant Professor
Professor and Vice Chairman Medical University of Graz
Department of Medicine, Division of
Surgery Graz, Austria
Gastroenterology
University of Utah
Jacinta A. Holmes, MBBS, PhD University of Washington
Salt Lake City, Utah, United States
Division of Gastroenterology Seattle, Washington, United States
Gregory J. Gores, MD Massachusetts General Hospital
Johanna C. Iturrino, MD
Executive Dean for Research, Professor Boston, Massachusetts, United States
Assistant Professor of Medicine
of Medicine Gastroenterology
Harvard Medical School
Division of Gastroenterology and St. Vincent’s Hospital
Beth Israel Deaconess Medical Center
Hepatology University of Melbourne
Boston, Massachusetts, United States
Mayo Clinic Fitzroy, Victoria, Australia
Rochester, Minnesota, United States Theodore W. James, MD
Colin W. Howden, MD
Fellow
Peter H.R. Green, MD Hyman Professor of Medicine
Division of Gastroenterology
Phyllis and Ivan Seidenberg Professor of Division of Gastroenterology
University of North Carolina
Medicine University of Tennessee Health Science
Chapel Hill, North Carolina, United
Columbia University Medical Center Center
States
New York, New York, United States Memphis, Tennessee, United States
Harry L.A. Janssen, MD, PhD
David A. Greenwald, MD Patrick A. Hughes, PhD
Professor of Medicine
Director of Clinical Gastroenterology Centre for Nutrition and
Gastroenterology and Hepatology
and Endoscopy Gastrointestinal Diseases
University of Toronto
Division of Gastroenterology Adelaide Medical School
Toronto, Ontario, Canada
Mount Sinai Hospital University of Adelaide
New York, New York, United States South Australian Health and Medical Dennis M. Jensen, MD
Research Institute Professor of Medicine
C. Prakash Gyawali, MD, MRCP
Nutrition and Metabolism Professor of Medicine–Gastrointestinal
Professor of Medicine
Adelaide, South Australia, Australia David Geffen School of Medicine at
Division of Gastroenterology
UCLA
Department of Medicine Sohail Z. Husain, MD
Staff Physician
Washington University in St. Louis Professor of Pediatrics
Medicine-Gastrointestinal
St. Louis, Missouri, United States Division of Gastroenterology,
VA Greater Los Angeles Healthcare
Hepatology, and Nutrition
Hazem Hammad, MD System
Stanford University School of Medicine
Assistant Professor of Medicine Key Investigator
Stanford, California, United States
Division of Gastroenterology and Director, Human Studies Core and
Hepatology Christopher D. Huston, MD Gastrointestinal Hemostasis Research
University of Colorado Anschutz Professor Unit
Medical Campus Medicine, Microbiology, and Molecular CURE Digestive Diseases Research
Aurora, Colorado, United States Genetics Center
University of Vermont College of Los Angeles, California, United States
Heinz F. Hammer, MD
Medicine
Associate Professor of Medicine Pamela J. Jensen, MD
Attending Physician
Department of Internal Medicine Department of Pathology
Medicine and Infectious Diseases
Medical University Texas Health Presbyterian Hospital
Fletcher Allen Health Care
Graz, Austria Dallas
Burlington, Vermont, United States
Dallas, Texas, United States
Stephen A. Harrison, MD
Visiting Professor of Hepatology
Radcliffe Department of Medicine
University of Oxford
Oxford, United Kingdom
x Contributors

D. Rohan Jeyarajah, MD Jonathan D. Kaunitz, MD Brian E. Lacy, MD, PhD

Chair of Surgery Professor of Medicine and Surgery Senior Associate Consultant
Assistant Chair of Clinical Sciences UCLA School of Medicine Division of Gastroenterology
Head of Surgery Attending Gastroenterologist Mayo Clinic
TCU and UNTHSC School of West Los Angeles Veterans Affairs Jacksonville, Florida, United States
Medicine Medical Center
Anne M. Larson, MD
Fort Worth, Texas Los Angeles, California, United States
Professor of Medicine
Director, Gastrointestinal Services
Laurie Keefer, PhD Division of Gastroenterology/
Methodist Richardson Medical Center
Professor Hepatology
Director, HPB/UGI Fellowship
Medicine and Psychiatry University of Washington
Associate Program Director, General
Icahn School of Medicine at Mount Sinai Seattle, Washington, United States
Surgery Residency Program
New York, New York, United States
Methodist Richardson Medical Center James Y.W. Lau, MD
Richardson, Texas, United States Ciarán P. Kelly, MD Professor of Surgery
Professor of Medicine Department of Surgery
Peter J. Kahrilas, MD
Gastroenterology The Chinese University of Hong Kong
Gilbert H. Marquardt Professor of
Harvard Medical School Director
Medicine
Fellowship Program Director Endoscopy Centre
Feinberg School of Medicine
Gastroenterology Prince of Wales Hospital
Northwestern University
Beth Israel Deaconess Medical Center Hong Kong, China
Gastroenterology and Hepatology
Boston, Massachusetts, United States
Northwestern Medicine Ryan Law, DO
Chicago, Illinois, United States Sahil Khanna, MBBS, MS Assistant Professor
Associate Professor of Medicine Division of Gastroenterology
Vishal Kaila, BS, MD
Gastroenterology and Hepatology University of Michigan
Resident
Mayo Clinic Ann Arbor, Michigan, United States
Internal Medicine
Rochester, Minnesota, United States
Texas Health Presbyterian Benjamin Lebwohl, MD, MS
Dallas, Texas, United States Arthur Y. Kim, MD Assistant Professor of Medicine and
Associate Professor of Medicine Epidemiology
Patrick S. Kamath, MD
Harvard Medical School Columbia University Medical Center
Professor of Medicine
Division of Infectious Diseases New York, New York, United States
Division of Gastroenterology and
Massachusetts General Hospital
Hepatology Anthony J. Lembo, MD
Boston, Massachusetts, United States
Consultant Professor of Medicine
Gastroenterology and Hepatology Kenneth L. Koch, MD Department of Medicine
Mayo Clinic College of Medicine and Professor of Medicine Beth Israel Deaconess Medical Center
Science Department of Medicine Boston, Massachusetts, United States
Rochester, Minnesota, United States Section on Gastroenterology and
Cynthia Levy, MD
Hepatology
Gilaad G. Kaplan, MD, MPH Professor of Medicine
Wake Forest University School of
Professor of Medicine Division of Hepatology
Medicine
University of Calgary University of Miami
Winston-Salem, North Carolina, United
Calgary, Alberta, Canada Miami, Florida, United States
States
Purna Kashyap, MBBS Blair Lewis, MD
Benjamin Kulow, MD
Associate Professor of Medicine Medical Director
Colon and Rectal Surgeon
Physiology and Biomedical Engineering Carnegie Hill Endoscopy
Saint Luke’s Health System
Mayo Clinic Clinical Professor of Medicine
Kansas City, Missouri, United States
Rochester, Minnesota, United States Mount Sinai Medical Center
Rekha B. Kumar, MD, MS New York, New York, United States
Jennifer Katz, MD
Assistant Professor of Medicine
Assistant Professor of Medicine James H. Lewis, MD
Endocrinology, Diabetes, and
Division of Gastroenterology Professor of Medicine
Metabolism
Montefiore Medical Center Director of Hepatology
Weill Cornell Medical College
Bronx, New York, United States Division of Gastroenterology
Attending Physician
Georgetown University Medical Center
David A. Katzka, MD Endocrinology, Diabetes, and
Washington, DC, United States
Professor of and Consultant in Medicine Metabolism
Gastroenterology New York Presbyterian Hospital Rodger A. Liddle, MD
Mayo Clinic New York, New York, United States Professor of Medicine
Rochester, Minnesota, United States Department of Medicine
Vidhya Kunnathur, MD
Duke University Medical Center
Debra K. Katzman, MD, FRCPC Assistant Professor
Durham, North Carolina, United States
Professor of Pediatrics Division of Digestive Diseases
Department of Pediatrics University of Cincinnati Steven D. Lidofsky, MD, PhD
The Hospital for Sick Children and Cincinnati, Ohio, United States Professor of Medicine
University of Toronto University of Vermont
Joann Kwah, MD
Toronto, Ontario, Canada Director of Hepatology
Assistant Professor of Medicine
University of Vermont Medical Center
Albert Einstein College of Medicine
Burlington, Vermont, United States
Gastroenterology
Montefiore Medical Center
Bronx, New York, United States
 Contributors xi

Keith D. Lindor, MD Ricard Masia, MD, PhD Frederick H. Millham, MD, MBA
Senior Advisor and Professor Associate Director, Translational Chair, Surgery 

Office of the University Provost Pathology South Shore Hospital

Arizona State University Medicine Surface Oncology Weymouth, Massachusetts
Gastroenterology and Hepatology Cambridge, Massachusetts, United States Associate Professor of Surgery (Part
Mayo Clinic Hospital Time)
Joel B. Mason, MD
Phoenix, Arizona, United States Harvard Medical School
Professor of Medicine and Nutrition
Boston, Massachusetts, United States
Mark E. Lowe, MD, PhD Divisions of Gastroenterology and
Harvey R. Colton Professor of Pediatric Clinical Nutrition Ginat W. Mirowski, DMD, MD
Science and Vice Chair Tufts University Adjunct Clinical Professor
Department of Pediatrics Director Department of Oral Pathology,
Washington University School of Vitamins and Carcinogenesis Laboratory Medicine, and Radiology
Medicine USDA Human Nutrition Research Indiana University School of Dentistry
St. Louis, Missouri, United States Center at Tufts University Professor of Clinical Dermatology
Boston, Massachusetts, United States (Clinical Track)
Cara L. Mack, MD
Department of Dermatology
Professor of Pediatrics Jeffrey B. Matthews, MD
Indiana University School of Medicine
University of Colorado School of Dallas B. Phemister Professor and
Indianapolis, Indiana, United States
Medicine Chairman
Children’s Hospital Colorado Department of Surgery Joseph Misdraji, MD
Aurora, Colorado, United States The University of Chicago Medicine Associate Professor of Pathology
Chicago, Illinois, United States Harvard Medical School
Ryan D. Madanick, MD
Associate Pathologist
Assistant Professor of Medicine Craig J. McClain, MD
Massachusetts General Hospital
Division of Gastroenterology and Professor of Medicine and Pharmacology
Boston, Massachusetts, United States
Hepatology and Toxicology
University of North Carolina School of Vice President for Health Affairs and Daniel S. Mishkin, MD, CM
Medicine Research Chief of Gastroenterology
Chapel Hill, North Carolina, United University of Louisville Atrius Health
States Director Boston, Massachusetts, United States
Gastroenterology
Willis C. Maddrey, MD Bijal Modi, MD
Robley Rex VA Medical Center
Special Assistant to the President Department of Internal Medicine
Louisville, Kentucky, United States
Professor of Internal Medicine Division of Hematology and Oncology
Arnold N. and Carol S. Ablon Stephen A. McClave, MD Texas Health Presbyterian Hospital
Professorship in Biomedical Science Professor and Director of Clinical Dallas
Adelyn and Edmund M. Hoffman Nutrition Dallas, Texas, United States
Distinguished Chair in Medical Department of Medicine
John Magaña Morton, MD, MPH, MHA
Science University of Louisville School of
Vice Chair for Quality
University of Texas Southwestern Medicine
Department of Surgery
Medical Center Louisville, Kentucky, United States
Chief
Dallas, Texas, United States
Shilpa Mehra, MD Bariatric and Minimally Invasive Surgery
Matthias Maiwald, MD, PhD Assistant Professor of Medicine Yale School of Medicine
Senior Consultant in Microbiology Department of Medicine Department of Surgery
Department of Pathology and Division of Gastroenterology New Haven, Connecticut, United States
Laboratory Medicine Albert Einstein College of Medicine
William Conan Mustain, MD
KK Women’s and Children’s Hospital, Bronx, New York, United States
Assistant Professor of Surgery
Singapore
Megha S. Mehta, MD Division of Colon and Rectal Surgery
Adjunct Associate Professor
Assistant Professor of Pediatrics University of Arkansas for Medical
Department of Microbiology and
University of Texas Southwestern Sciences
Immunology
Medical Center Little Rock, Arkansas, United States
Yong Loo Lin School of Medicine
Dallas, Texas, United States
National University of Singapore Filipe Gaio Nery, MD
Adjunct Associate Professor Shivang S. Mehta, MD Physician
Duke-NUS Graduate Medical School Pediatric Gastroenterology Fellow Departamento de Anestesiologia,
Singapore, Singapore Department of Pediatric Cuidados Intensivos e Emergência
Gastroenterology Centro Hospitalar do Porto–Hospital
Lawrence A. Mark, MD, PhD
University of Texas Southwestern Santo António, Porto
Associate Professor of Clinical
Medical Center Researcher, EPIUnit
Dermatology
Dallas, Texas, United States Instituto de Saúde Pública, Universidade
Department of Dermatology
do Porto, Porto
Indiana University School of Medicine Joanna M.P. Melia, MD
Researcher, Ciências Médicas
Indianapolis, Indiana, United States Assistant Professor of Medicine
Instituto de Ciências Biomédicas de Abel
Johns Hopkins University School of
Paul Martin, MD, FRCP, FRCPI Salazar
Medicine
Chief, Division of Gastroenterology and Porto, Portugal
Baltimore, Maryland, United States
Hepatology
University of Miami
Miami, Florida, United States
xii Contributors

Siew C. Ng, MBBS (Lond), PhD (Lond) Patrick R. Pfau, MD Christopher K. Rayner, MBBS, PhD
Professor of Medicine Professor, Chief of Clinical Professor
Department of Medicine and Gastroenterology Adelaide Medical School
Therapeutics Section of Gastroenterology and University of Adelaide
State Key Laboratory of Digestive Hepatology Consultant Gastroenterologist
Disease University of Wisconsin School of Department of Gastroenterology and
LKS Institute of Health Science Medicine and Public Health Hepatology
The Chinese University of Hong Kong Madison, Wisconsin, United States Royal Adelaide Hospital
Hong Kong, China Adelaide, South Australia, Australia
Angela K. Pham, MD
Mark L. Norris, BSc (Hon), MD Clinical Assistant Professor Ahsan Raza, MD
Associate Professor of Pediatrics Gastroenterology, Hepatology, and General and Colorectal Surgery
Pediatrics Nutrition Rapides Surgical Specialists
Children’s Hospital of Eastern Ontario University of Florida Alexandria, Louisiana, United States
University of Ottawa Gainesville, Florida, United States
Miguel D. Regueiro, MD
Ottawa, Ontario, Canada
Kimberly L. Pham, MD Chair and Professor of Medicine
John O’Grady, MD, FRCPI St. George’s University Grenada Department of Gastroenterology and
Professor West Indies, Grenada Hepatology
Institute of Liver Studies Cleveland Clinic, Digestive Disease and
Daniel S. Pratt, MD
King’s College Hospital Surgery Institute
Clinical Director, Liver Transplantation
London, United Kingdom Cleveland, Ohio, United States
Division of Gastroenterology
Manisha Palta, MD Massachusetts General Hospital John F. Reinus, MD
Associate Professor Assistant Professor of Medicine Professor of Medicine
Radiation Oncology Harvard Medical School Department of Medicine
Duke University Boston, Massachusetts, United States Albert Einstein College of Medicine
Durham, North Carolina, United States Medical Director of Liver
David O. Prichard, MB, BCh, PhD
Transplantation
Stephen J. Pandol, MD Gastroenterologist
Montefiore-Einstein Center for
Professor Gastroenterology and Hepatology
Transplantation
Medicine Mayo Clinic
Montefiore Medical Center
Cedars-Sinai Medical Center Rochester, Minnesota
Bronx, New York, United States
Los Angeles, California, United States
Michael Quante, PD, Dr
David A. Relman, MD
John E. Pandolfino, MD, MSCI Technische Universität München
Thomas C. and Joan M. Merigan
Hans Popper Professor of Medicine II Medizinische Klinik
Professor
Feinberg School of Medicine Klinikum rechts der Isar
Departments of Medicine and
Northwestern University München, Germany
Microbiology and Immunology
Division Chief
Eamonn M.M. Quigley, MD Stanford University
Gastroenterology and Hepatology
Professor of Medicine and Chief, Stanford, California
Northwestern Medicine
Gastroenterology and Hepatology Chief of Infectious Diseases
Chicago, Illinois, United States
David M. and Lynda K. Underwood Veterans Affairs Palo Alto Health Care
Darrell S. Pardi, MD, MS Center for Digestive Disorders System
Vice Chair Houston Methodist Hospital Palo Alto, California, United States
Division of Gastroenterology and Weill Cornell Medical College
Arvind Rengarajan, MD
Hepatology Houston, Texas, United States
Barnes-Jewish Hospital
Associate Dean
Balakrishnan S. Ramakrishna, MBBS, Department of Internal Medicine
Mayo School of Graduate Medical
MD, DM, PhD Washington University in St. Louis
Education
Head St. Louis, Missouri, United States
Mayo Clinic
Institute of Gastroenterology
Rochester, Minnesota, United States Joel E. Richter, MD
SRM Institutes for Medical Science
Professor and Director
Michelle Pearlman, MD Chennai, Tamil Nadu, India
Division of Digestive Diseases and
Professor of Medicine
Mrinalini C. Rao, PhD Nutrition
Department of Internal Medicine,
Professor University of South Florida
Division of Digestive and Liver
Department of Physiology and Director
Diseases
Biophysics Joy McCann Culverhouse Center for
University of Texas Southwestern
University of Illinois at Chicago Swallowing Disorders
Dallas, Texas, United States
Chicago, Illinois, United States University of South Florida
Vyjeyanthi S. Periyakoil, MD Tampa, Florida, United States
Satish S.C. Rao, MD, PhD
Director, Palliative Care Education and
Professor of Medicine Sumera H. Rizvi, MD
Training
Harold J. Harrison, MD, Distinguished Assistant Professor of Medicine
Department of Medicine
University Chair in Gastroenterology Division of Gastroenterology and
Stanford University School of Medicine
Medicine-Gastroenterology/Hepatology Hepatology
Stanford, California, United States
Augusta University Mayo Clinic
Augusta, Georgia, United States Rochester, Minnesota, United States
 Contributors xiii

Syed Mujtaba Rizvi, MD Jayashree Sarathy, PhD Vijay H. Shah, MD

Assistant Professor Associate Professor Professor 

Division of Medical Oncology Department of Biological Sciences Medicine, Physiology, and Cancer Cell
Department of Internal Medicine Program Director of Master of Science Biology
UT Southwestern Medical Center in Integrative Physiology Chair
Dallas, Texas, United States Benedictine University Division of Gastroenterology and
Lisle, Illinois Hepatology
Eve A. Roberts, MD, PhD
Visiting Research ­Professor Associate Chair of Research Medicine
Adjunct Professor
Department of Physiology and Mayo Clinic College of Medicine and
Pediatrics, Medicine, and Pharmacology
­Biophysics Science
and Toxicology
University of Illinois at Chicago Rochester, Minnesota, United States
University of Toronto
Chicago, Illinois, United States
Adjunct Scientist G. Thomas Shires, MD
Genetics and Genome Biology Program George S. Sarosi Jr., MD John P. Thompson Chair
Hospital for Sick Children Research Robert H. Hux MD Professor and Vice Surgical Services
Institute Chairman for Education Texas Health Presbyterian Hospital
Associate Department of Surgery Dallas
Division of Gastroenterology, University of Florida College of Dallas, Texas, United States
Hepatology, and Nutrition Medicine
Maria H. Sjogren, MD, MPH
The Hospital for Sick Children Staff Surgeon
Senior Hepatologist
Toronto, Ontario, Canada Surgical Service
Department of Medicine
Associate Fellow NF/SG VAMC
Walter Reed National Medical Center
History of Science and Technology Gainesville, Florida, United States
Bethesda, Maryland, United States
Program
Thomas J. Savides, MD
University of King’s College Phillip D. Smith, MD
Professor of Clinical Medicine
Halifax, Nova Scotia, Canada Professor of Medicine and Microbiology
Division of Gastroenterology
University of Alabama at Birmingham
Martin D. Rosenthal, MD University of California San Diego
Birmingham, Alabama, United States
Assistant Professor La Jolla, California, United States
Surgery Elsa Solà, MD, PhD
Lawrence R. Schiller, MD
University of Florida Liver Unit
Attending Physician
Gainesville, Florida, United States Hospital Clinic
Gastroenterology Division
Associate Professor
Marc E. Rothenberg, MD, PhD Baylor University Medical Center
University of Barcelona
Professor of Pediatrics Dallas, Texas, United States
Researcher
Cincinnati Children’s Hospital Medical
Mitchell L. Schubert, MD Institut d’Investigacions Biomediques
Center
Professor of Medicine and Physiology August Pi i Sunyer (IDIBAPS)
Cincinnati, Ohio, United States
Virginia Commonwealth University Barcelona, Spain
Jayanta Roy-Chowdhury, MBBS Health System
Rhonda F. Souza, MD
Professor Chief, Division of Gastroenterology,
Co-Director, Center for Esophageal
Departments of Medicine and Genetics Hepatology, and Nutrition
Diseases
Director, Genetic Engineering and Gene McGuire Veterans Affairs Medical
Department of Medicine
Therapy Core Facility Center
Baylor University Medical Center
Albert Einstein College of Medicine Richmond, Virginia, United States
Co-Director, Center for Esophageal
New York, New York, United States
Cynthia L. Sears, MD Research
Namita Roy-Chowdhury, PhD Professor of Medicine and Oncology Baylor Scott and White Research
Professor Johns Hopkins University School of Institute
Departments of Medicine and Genetics Medicine Dallas, Texas, United States
Albert Einstein College of Medicine Baltimore, Maryland, United States
Cedric W. Spak, MD, MPH
New York, New York, United States
Joseph H. Sellin, MD Clinical Assistant Professor
David T. Rubin, MD Professor Emeritus Infectious Diseases
Joseph B. Kirsner Professor of Medicine Division of Gastroenterology Baylor University Medical Center
Chief, Section of Gastroenterology, Baylor College of Medicine Staff Physician
Hepatology, and Nutrition Chief of Gastroenterology Infectious Diseases
Department of Medicine Ben Taub General Hospital Texas Centers for Infectious Disease
University of Chicago Houston, Texas, United States Associates
Chicago, Illinois, United States Dallas, Texas, United States
M. Gaith Semrin, MD, MBBS
Associate Professor Stuart Jon Spechler, MD
Pediatric Gastroenterology and Chief, Division of Gastroenterology
Nutrition Co-Director, Center for Esophageal
UT Southwestern Medical Center Research
Children Medical Center Dallas Department of Medicine
Dallas, Texas, United States Baylor University Medical Center at Dallas
Co-Director, Center for Esophageal
Research
Baylor Scott and White Research Institute
Dallas, Texas, United States
xiv Contributors

James E. Squires, MD, MS Jan Tack, MD, PhD Dominique Charles Valla, MD
Assistant Professor Head, Division of Gastroenterology and Professor of Hepatology
Department of Pediatrics Hepatology Liver Unit
UPMC Children’s Hospital of Leuven University Hospitals Hôpital Beaujon, APHP,
Pittsburgh Professor of Medicine Clichy-la-Garenne
Pittsburgh, Pennsylvania, United States Translational Research Center for France
Gastrointestinal Disorders (TARGID) CRI, UMR1149
Neil H. Stollman, MD
Department of Clinical and Inserm and Université de Paris
Associate Clinical Professor
Experimental Medicine Paris, France
Department of Medicine, Division of
University of Leuven
Gastroenterology John J. Vargo II, MD, MPH
Leuven, Belgium
University of California San Francisco Associate Professor of Medicine
San Francisco, California Nicholas J. Talley, MD, PhD Gastroenterology and Hepatology
Chief Distinguished Laureate Professor Cleveland Clinic
Division of Gastroenterology Faculty of Health and Medicine Cleveland, Ohio, United States
Alta Bates Summit Medical Center University of Newcastle, Australia
Santhi Swaroop Vege, MD
Oakland, California, United States Newcastle, New South Wales, Australia
Professor of Medicine and Director
Sarah E. Streett, MD Jarred P. Tanksley, MD, PhD Pancreas Group
Clinical Associate Professor Resident Gastroenterology and Hepatology
Director IBD Education Radiation Oncology Mayo Clinic
Division of Gastroenterology and Duke University Rochester, Minnesota, United States
Hepatology Durham, North Carolina, United States
Axel von Herbay, MD
Stanford University
Narci C. Teoh, MD Professor of Pathology
Redwood City, California, United States
Professor of Medicine Faculty of Medicine
Jonathan R. Strosberg, MD Australian National University University of Heidelberg
Associate Professor Senior Staff Hepatologist Heidelberg Hans Pathologie
Gastrointestinal Oncology The Canberra Hospital Hamburg, Germany
Moffitt Cancer Center Australian Capital Territory, Australia
Margaret von Mehren, MD
Tampa, Florida, United States
Dawn M. Torres, MD Professor
Frederick J. Suchy, MD Program Director GI Fellowship Department of Hematology/Oncology
Children’s Hospital Colorado Department of Medicine Fox Chase Cancer Center
Professor of Pediatrics and Associate Walter Reed National Military Medical Philadelphia, Pennsylvania, United
Dean for Child Health Research Center States
Pediatrics Associate Professor of Medicine
David Q.-H. Wang, MD, PhD
University of Colorado School of Department of Medicine
Professor of Medicine
Medicine Uniformed Services University of the
Departments of Medicine and Genetics
Aurora, Colorado, United States Health Sciences
Director, Molecular Biology and Next
Bethesda, Maryland, United States
Aravind Sugumar, MD Generation Technology Core
Instructor Kiran Turaga, MD, MPH Marion Bessin Liver Research Center
Gastroenterology and Hepatology Associate Professor Albert Einstein College of Medicine
Cleveland Clinic Foundation Department of Surgery Bronx, New York, United States
Cleveland, Ohio, United States The University of Chicago
Sachin Wani, MD
Chicago, Illinois, United States
Shelby Sullivan, MD Associate Professor of Medicine
Associate Professor of Medicine Richard H. Turnage, MD Division of Gastroenterology and
Director, Gastroenterology Metabolic Executive Associate Dean for Clinical Hepatology
and Bariatric Program Affairs University of Colorado Anschutz
Division of Gastroenterology and Professor of Surgery Medical Campus
Hepatology University of Arkansas for Medical Aurora, Colorado, United States
University of Colorado Anschutz Sciences Medical Center
Frederick Weber, MD
Medical Campus University of Arkansas for Medical
Clinical Professor
Aurora, Colorado, United States Sciences
Division of Gastroenterology and
Little Rock, Arkansas, United States
Gyongyi Szabo, MD, PhD Hepatology
Mitchell T. Rabkin, MD Chair Michael F. Vaezi, MD, PhD, MS University of Alabama Birmingham
Chief Academic Officer Professor of Medicine and Birmingham, Alabama, United States
Beth Israel Deaconess Medical Center ­Otolaryngology
Barry K. Wershil, MD
and Beth Israel Lahey Health Division of Gastroenterology and
Professor
Faculty Dean for Academic Affairs ­Hepatology
Pediatrics
Harvard Medical School Vanderbilt University
Northwestern University Feinberg
Boston, Massachusetts, United States Director
School of Medicine
Center for Swallowing and Esophageal
Chief, Division of Gastroenterology,
Disorders
Hepatology, and Nutrition
Vanderbilt University Medical Center
Pediatrics
Director
Ann & Robert H. Lurie Children’s
Clinical Research
Hospital of Chicago
Vanderbilt University Medical Center
Chicago, Illinois, United States
Nashville, Tennessee, United States
 Contributors xv

David C. Whitcomb, MD, PhD Christopher G. Willett, MD Anahit A. Zeynalyan, MD

Professor Professor and Chairman Resident 

Medicine, Cell Biology and Molecular Radiation Oncology Internal Medicine

Physiology, and Human Genetics Duke University Baylor University Medical Center
University of Pittsburgh and UPMC Durham, North Carolina, United States Dallas, Texas, United States
Pittsburgh, Pennsylvania, United States
Joseph C. Yarze, MD
C. Mel Wilcox, MD, MSPH Assistant Professor of Medicine
Division of Gastroenterology and Harvard Medical School
­Hepatology Associate Physician
University of Alabama at Birmingham Division of Gastroenterology
Birmingham, Alabama, United States Massachusetts General Hospital
Boston, Massachusetts, United States
 Foreword

Even attempting to write a Foreword for the 11th edition been in the recent past and what we hope (and expect) to achieve
of Sleisenger and Fordtran’s Gastrointestinal and Liver Disease: in the future.
Pathophysiology/Diagnosis/Management, a textbook that has served A trusted book provides a helpful guide that is readily available
for many decades to prepare readers to respond to challenges at moments of uncertainty. A comparison of an individual chapter
presented by patients with gastrointestinal and liver disease, is from a past edition and what we have now further validates the
a daunting task and yet a great pleasure. Just having achieved an conclusion that progress is being made, and the future of our spe-
11th edition of a textbook is, in and of itself, a remarkable accom- cialty is encouraging. The three senior editors and three associate
plishment. Generations of gastroenterologists and hepatologists editors of the 11th edition are foremost authorities and widely
have relied on Sleisenger and Fordtran to provide comprehensive, recognized for their abilities to identify topics of interest and
up-to-date, reliable information. to persuade experts in these areas to share their knowledge. To
The 11th edition is a welcome addition to the previous editions, write an updated review of one’s field can be a Herculean task that
which have been widely acclaimed as important go-to sources requires not only knowledge but also courage. The editors have
of information regarding the broad array of disorders affecting surely succeeded. The careful selection of authors of individual
the gastrointestinal tract and the liver. Over the past half cen- chapters allows each to bring his or her own style regarding what
tury, these volumes have been mainstays in the libraries of those to emphasize; to lay out what we know, as well as what we need to
engaged in these fields. Since its inception 10 editions ago, this know, to diagnose and effectively treat specific problems; and to
now classic textbook has tracked the evolution of thinking in mul- provide suggestions and guidance as to how to manage patients
tiple areas and has served readers well. These days, there are ever- while integrating new observations into practice.
expanding ways for those of us interested in gastroenterology and With regard to the liver section, the current state of knowl-
hepatology to be stimulated, informed, educated, and refreshed. edge about hepatitis-inducing viruses and drug-induced liver dis-
Lectures, conversations with colleagues, and attendance at local, eases and the tsunami of interest in the many consequences of the
regional, and national meetings have their roles, and we all learn effects of excessive fat in the liver in the causation of chronic liver
from our patients. Perusal of relevant articles in medical journals diseases are breathtaking. These achievements have been well-
is increasingly difficult in an era in which the number of available chronicled journeys with opportunities (and hope) for even more
journals has increased remarkably. The practicing clinician, given effective therapeutic agents in the near future. Just one edition
present-day time constraints, will more than ever find this text- ago, we were on the threshold of having effective, widely appli-
book reliable, informative, and useful. In these two volumes are cable treatments for the several types of viral hepatitis; much of
overviews of what is known now and glimpses of what the future what we hoped for has been achieved. It is now likely that there
is likely to bring. A blend of skill, knowledge, practical experi- will be discovery of therapeutic approaches that will favorably
ence, and the ability to teach is required of the authors in order affect the broad array of fat-related liver injuries, including their
to achieve these goals. Overall, these efforts have been successful association with cardiovascular disorders. Widely available access
in presenting accurate and comprehensive updates in our fields of to advanced endoscopy has changed the approach to the evalua-
interest and serve us well as a look to our past, provide reflections tion and treatment of many disorders of the gastrointestinal tract,
regarding our present, and delineate problems yet to be solved. bile ducts, and pancreas. Furthermore, who could have foreseen
We are fortunate to live in exciting and rapidly changing just a few years ago how advances in biological therapies and
times in gastroenterology and hepatology. The sheer volume minimally invasive surgery would so redirect our treatments of
of new ideas presented in multiple journals is stimulating and a broad array of disorders or how important the gut microbiome
often overwhelming. Each of us must evaluate and assimilate would be in the pathogenesis of many disorders. Once we under-
new information while making efforts to appropriately incor- stand how to favorably alter the gut microbiome, major leaps for-
porate the new advances into our practices. To stay up to date ward can be expected.
and achieve our goals requires considerable effort and dedica- What is next? Gene editing and an understanding of intesti-
tion (Even COVID-19 is mentioned several times throughout nal microbiota, now in their infancy, will receive much deserved
the book.). There is comfort in having available a reliable and attention in the next few years. With each passing year, advances in
trusted guide to refresh and stimulate us. manipulation of the human genome and intestinal microbiota are
The 11th edition of Sleisenger and Fordtran provides a firm, becoming more precise and require constant, thoughtful oversight
authoritative platform regarding what is established knowledge to ensure that we do what we should do and not just what we can
and identifies where progress is being made to prepare us to do. In this edition, we have blueprints and predictions of the future
be better armed for the foreseeable future. We all need to be for many aspects of our specialty. It is important to discard old
informed of the likely validity and usefulness of new observa- ideas that have not proved effective while constantly re-examining
tions. It is vital that we recognize the degree of certainty of the the basis for what we think we know and appropriately altering
data that led to our conclusions. There have been (and will be) what we do.
definite game-changing advances and also many seemingly good We all marvel when we see what has been (and is) happening
ideas and approaches that turn out to be sidesteps. New concepts in medicine and the effects of these advances in gastroenterology
must be recognized, double-checked, processed, and then incor- and hepatology. Surely, the best is yet to come, and we all hope
porated into our thinking, subsequently affecting our actions. that what we are learning and applying now will stimulate us to
The breadth of subjects covered in depth in these two vol- create an even better future.
umes is impressive. I had the honor to write the Foreword to the
9th edition published in 2010. When comparing the expansion of Willis C. Maddrey, MD
knowledge from then to now, one can appreciate where we have Dallas, Texas
xvi
 The Sleisenger and Fordtran Editors

Mark Feldman, MD Lawrence S. Friedman, MD Lawrence J. Brandt, MD

Editions 5-11 Editions 7-11 Editions 8-11

Raymond T. Chung, MD David T. Rubin, MD C. Mel Wilcox, MD

Edition 11 Edition 11 Edition 11

Marvin H. Sleisenger, MD John S. Fordtran, MD Bruce F. Scharschmidt, MD

Editions 1-7 Editions 1-5 Editions 5-6

xvii
 Preface

Nearly a half century ago, in the summer of 1971, Drs. Marvin As one looks back 50 years, the advances made in our field
H. Sleisenger in San Francisco and John S. Fordtran in Dallas as a result of rigorous basic science and clinical research have
embarked on a new venture: planning, writing, and editing the been truly remarkable, and the future holds even greater prom-
inaugural edition of a new textbook for gastroenterologists. ise of discovery. Featured advances discussed in the 11th edition
The book received widespread praise for incorporating state- include improved diagnosis and treatment of chronic hepatitis B
of-the-art descriptions of the pathophysiology of the d ­ isorders and C; evolution in the diagnosis and treatment of Helicobacter
­discussed—a first for a medical textbook. Since the a­ uspicious pylori infection and the resulting benefits on the prevention and
debut of Gastrointestinal Disease: Pathophysiology/Diagnosis/ treatment of peptic ulcer disease and gastric neoplasia; improve-
Management, subsequent editions have been published every ments in the prevention of colorectal cancer through screening
4 to 5 years, and we are pleased that the 11th edition of this and surveillance; new approaches to the recognition and treat-
venerable textbook continues the tradition and standards set ment of Barrett esophagus and consequent prevention of esopha-
by the founding editors. To be sure, innumerable enhance- geal adenocarcinoma; the expanding use of biologic agents and
ments have been made since the 1st edition, such as the addi- novel small molecules to treat and prevent recurrences of IBD;
tion of chapters on liver diseases, the availability of the book recognition of an increasing number of immune and autoimmune
online and on hand-held devices, the introduction of monthly diseases affecting not only the stomach and hepatobiliary system
updates to bring attention to important new developments but also the pancreas and intestine; improvements in the ability
that occur between editions, the incorporation of videos of to risk stratify and treat patients with GI bleeding; and continuing
new diagnostic and therapeutic procedures, and the participa- progress in hepatic, pancreatic, and small bowel transplantation.
tion of authors from around the world to give the book a truly There have been remarkable advances in our understanding the
international flavor. gut microbiome, which is becoming the focus of interest in diverse
In the summer of 2017, the current editors met with the fields, such as IBS, IBD, obesity, hepatic encephalopathy, and oth-
publisher and reviewed the prior (10th) edition of the book ers, including non-GI disorders. We are particularly pleased to
in great detail. Most importantly, the core group of 3 senior have completely redesigned the section on IBD by reorganizing
editors invited 3 associate editors (Drs. Raymond T. Chung, and updating the discussions of pathophysiology, clinical presen-
David T. Rubin, and C. Mel Wilcox) to join them in order to tation, and management, all of which are evolving rapidly.
facilitate critical review of the chapters, to help select the most Sadly, the original co-founder of this textbook, Dr. Marvin H.
expert authors, and to provide greater content expertise. Each Sleisenger, passed away on October 19, 2017, at the age of 93.
associate editor worked closely with a senior editor. The result, Marvin will be greatly missed, and we trust that this 11th edition
we hope, is an easily readable, carefully edited, highly accurate, would have met with his approval and commendation.
and thorough review of the state of the art of gastrointestinal
and liver disease. The target audience is primarily practicing Mark Feldman, MD
gastroenterologists and hepatologists (adult and pediatric) and Lawrence S. Friedman, MD
trainees in gastroenterology. We hope the book will also be Lawrence J. Brandt, MD
useful to general internists, other specialists, and students at
all levels.

xviii
 Acknowledgments

The editors and associate editors of the 11th edition of Sleisenger thank Dr. Willis C. Maddrey of the University of Texas South-
& Fordtran’s Gastrointestinal and Liver Disease are most grateful western for his eloquent Foreword, the second time he has been
to the more than 230 authors from countries in North America, called on to do this honor for Sleisenger & Fordtran. We remem-
Europe, Asia, and Australia who contributed their knowledge, ber with affection Dr. Marvin H. Sleisenger, who passed away as
expertise, and wisdom to the pages of the book. We are also the 11th edition of the book he co-­created was being prepared,
appreciative of the talented staff at Elsevier who helped bring and pay tribute to Dr. John S. Fordtran for his continuing inspi-
this book to life, particularly Nancy Duffy, Dolores Meloni, and ration and contributions. We are deeply appreciative of the love
Deidre Simpson. A special call out goes to Cindy Thoms, who and support of our spouses: Barbara Feldman, Mary Jo Cappuc-
oversaw production of the book. We are most thankful to our cilli, Lois Brandt, Kim Wilcox, Diane Abraczinskas, and Rebecca
assistants, Sherie Strang, Alison Sholock, Amy Nash, and Amy Rubin. Finally, we thank our readers, to whom the book is dedi-
Majkowski, for outstanding secretarial support. We want to cated, for their confidence and trust in this textbook.

xix
 Abbreviation List

AASLD American Association for the Study of Liver ESR Erythrocyte sedimentation rate
Diseases EUS Endoscopic ultrasonography
ACG American College of Gastroenterology FDA U.S. Food and Drug Administration
ACTH Corticotropin FNA Fine-needle aspiration
AE Angioectasia GAVE Gastric antral vascular ectasia
AFP Alpha fetoprotein GERD Gastroesophageal reflux disease
AGA American Gastroenterological Association GGTP Gamma glutamyl transpeptidase
AIDS Acquired immunodeficiency syndrome GI Gastrointestinal
ALF Acute liver failure GIST GI stromal tumor
ALT Alanine aminotransferase GU Gastric ulcer
AMA Antimitochondrial antibodies H & E Hematoxylin and eosin
ANA Antinuclear antibodies H2RA Histamine-2 receptor antagonist
ANCA Antineutrophil cytoplasmic antibodies HAV Hepatitis A virus
APACHE Acute physiology and chronic health HBV Hepatitis B virus
­examination
HCC Hepatocellular carcinoma
APC Argon plasma coagulation
HCG Human chorionic gonadotropin
ASGE American Society for Gastrointestinal Endoscopy
HCV Hepatitis C virus
AST Aspartate aminotransferase
HDL High-density lipoprotein
ATP Adenosine triphosphate
HDV Hepatitis D virus
BICAP Bipolar electrocoagulation
HELLP Hemolysis, elevated liver enzymes, low platelets
BMI Body mass index
HEV Hepatitis E virus
BRBPR Bright red blood per rectum
Hgb Hemoglobin
CBC Complete blood count
HHT Hereditary hemorrhagic telangiectasia
CCK Cholecystokinin
HIV Human immunodeficiency virus
CEA Carcinoembryonic antigen
HLA Human leukocyte antigen
CDI Clostridioides difficile infection
HPV Human papillomavirus
CF Cystic fibrosis
HSV Herpes simplex virus
CFTR Cystic fibrosis transmembrane conductance
­regulator Hp Helicobacter pylori
CMV Cytomegalovirus IBD Inflammatory bowel disease
CNS Central nervous system IBS Irritable bowel syndrome
CO2 Carbon dioxide ICU Intensive care unit
COX Cyclooxygenase IMA Inferior mesenteric artery
CT Computed tomography IMT Intestinal microbiota transplantation
CTA Computed tomography angiography INR International normalized ratio
DAA Direct-acting antiviral agent IV Intravenous
DIC Disseminated intravascular coagulation IVIG Intravenous immunoglobulin
DILI Drug-induced liver injury LDH Lactate dehydrogenase
DNA Deoxyribonucleic acid LDL Low-density lipoprotein
DU Duodenal ulcer LGI Lower gastrointestinal
DVT Deep vein thrombosis LGIB Lower gastrointestinal bleed
EBV Epstein-Barr virus LLQ Left lower quadrant
EGD Esophagogastroduodenoscopy LT Liver transplantation
EGF Epidermal growth factor LUQ Left upper quadrant
EMG Electromyography MELD Model for end-stage liver disease
ERCP Endoscopic retrograde cholangiopancreatography MEN Multiple endocrine neoplasia

xxv
xxvi Abbreviation List

MHC Major histocompatibility complex SBP Spontaneous bacterial peritonitis

MRA Magnetic resonance angiography SIBO Small intestinal bacterial overgrowth
MRCP Magnetic resonance cholangiopancreatography SLE Systemic lupus erythematosus
MRI Magnetic resonance imaging SOD Sphincter of Oddi dysfunction
NAFLD Nonalcoholic fatty liver disease TB Tuberculosis
NASH Nonalcoholic steatohepatitis TG Triglyceride(s)
NG Nasogastric TIPS Transjugular intraheptic portosystemic shunt
NPO Nil per os (nothing by mouth) TNF Tumor necrosis factor
NSAID(s) Nonsteroidal anti-inflammatory drug(s) TNM Tumor node metastasis
O2 Oxygen TPN Total parenteral nutrition
PBC Primary biliary cholangitis UC Ulcerative colitis
PCR Polymerase chain reaction UDCA Ursodeoxycholic acid
PET Positron emission tomography UGI Upper gastrointestinal
PPI Proton pump inhibitor UGIB Upper gastrointestinal bleed
PSC Primary sclerosing cholangitis UGIS Upper gastrointestinal series
PSE Portosystemic encephalopathy UNOS United Network for Organ Sharing
PUD Peptic ulcer disease US Ultrasonography
RA Rheumatoid arthritis USA United States of America
RLQ Right lower quadrant VLDL Very-low-density lipoprotein
RNA Ribonucleic acid WBC White blood cell
RUQ Right upper quadrant WHO World Health Organization
SBO Small bowel obstruction ZES Zollinger-Ellison syndrome
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