Hep B

National Viral Hepatitis
Control Program
Operational Guidelines
2018
National Viral Hepatitis
Control Program
Operational Guidelines
ACRONYMS
ALF Acute Liver Failure
ART Anti-Retroviral Therapy
B.Sc Bachelor of Science
BCC Behaviour Change Communication
CBO Community Based Organization
CDSCO Central Drugs Standard Control Organization
CoE Centre of Excellence
CST Care, Support and Treatment
CT Computed Tomography
DAA Directly acting anti-viral
DMLT Diploma in Medical Laboratory Technology
DOEACC Department of Electronics and Accreditation of Computer Courses
DVHMU District Viral Hepatitis Control Management Unit
EQA External Quality Assessment
EQC External Quality Control
FEFO First Expiry First Out
FSSAI Food Safety and Standards Authority of India
FSW Female Sex Worker
GoI Government of India
HAV Hepatitis A Virus
HBV Hepatitis B Virus
HBsAg Hepatitis B surface antigen
HCC Hepatocellular Carcinoma
HCV Hepatitis C Virus
HDV Hepatitis D Virus
HEV Hepatitis E Virus
HIV Human Immunodeficiency Virus
HR Human Resource
ICMR Indian Council of Medical Research
ICTC Integrated Counselling and Testing Centre
ICU Intensive Care Unit
IDSP Integrated Disease Surveillance Program
IEC Information, Education and Communication
IQC Internal Quality Control
IQ Installation Qualification
M&E Monitoring and Evaluation
MLT Medical Laboratory Technology
MoHFW Ministry of Health and Family Welfare
MO Medical Officer
MRI Magnetic Resonance Imaging
MSM Men who have sex with men
MTC Model Treatment centre
NACO National AIDS Control Organization
NACP National AIDS Control Program
NAT Nucleic Acid Testing
NCDC National Centre for Disease Control
NGO Non Governmental Organization
NHM National Health Mission
NVHMU National Viral Hepatitis Control Management Unit
OQ Operational Qualification
OST Opioid Substitution Therapy
PHC Primary Health Centre
PIP Program Implementation Plan
PQ Performance Qualification
PT Proficiency Testing
PWID People Who Inject Drugs
RNA Ribonucleic Acid
RUP Reuse Prevention
SACS State AIDS Control Society
SDG Sustainable Development Goal
SGPGI Sanjay Gandhi Post-graduate Institute
SVHMU State Viral Hepatitis Control Management Unit
STI Sexually Transmitted Infection
SVR Sustained Virological Response
TC Treatment Centre
TG Transgender
TTIs Transfusion Transmitted Infections
UIP Universal Immunization Program
WHA World Health Assembly
WHO World Health Organization
CONTENTS
CHAPTER 1:
BACKGROUND 22
Epidemiology of Viral Hepatitis 22
Global 22
India 22
CHAPTER 2:
INTRODUCTION TO THE PROGRAM 24
Aims 24
Components 25
Activities 26
Targets for the initiative 27
CHAPTER 3:
PROGRAM MANAGEMENT 29
National Program Steering Committee 30
National Viral Hepatitis Control Management Unit (NVHMU) 30
State Viral Hepatitis Control Management Unit (SVHMU) 32
District Viral Hepatitis Control Management Unit (DVHMU) 33
CHAPTER 4:
SERVICE DELIVERY : SYNERGIES WITH THE EXISTING PROGRAMS
AND RELEVANT MINISTRIES 34
Universal Immunization Program 34
National AIDS Control Program (NACP) 35
Safety of blood and blood products 35
Harm reduction in key populations 36
Injection safety and infection control 36
Integrated Disease Surveillance Programme 36
National program for Surveillance of Viral Hepatitis 37
Swachh Bharat Mission- Urban & Rural 37
Ministry of Drinking Water and Sanitation 37
Food Safety and Standards Authority of India (FSSAI) 37
CHAPTER 5:
SERVICE DELIVERY: NEW INTERVENTIONS- DIAGNOSIS AND MANAGEMENT
OF VIRAL HEPATITIS WITH FOCUS ON TREATMENT OF HEPATITIS B & C 38
Laboratories Services 38
Centre of Excellence for laboratory testing 39
State Laboratories 39
District Laboratories 40
Laboratories below district level 41
Sample Transportation for HBV/HCV Quantitative NAT testing 41
Human Resource in Laboratories 41
Approach to Diagnosis of Viral Hepatitis 42
TREATMENT SITES 43
Model Hepatitis Treatment Centre 43
Hepatitis Treatment Centre 44
Selection criteria and steps for setting up a centre 44
Human Resource for the Treatment Sites 45
Approach to providing Treatment 45
Monitoring and Evaluation of the Treatment sites 48
Recording tools 48
CHAPTER 6:
SUPPLY CHAIN MANAGEMENT 50
CHAPTER 7:
TRAININGS 51
CHAPTER 8:
MONITORING AND EVALUATION 52
Record keeping 52
Indicators 52
CHAPTER 9:
PATTERN OF ASSISTANCE AND FLOW OF FUNDS 53
CHAPTER 10:
BIBLIOGRAPHY 54
Annexure 1:
FEASIBILITY VISIT FOR SETTING HEPATITIS
TREATMENT CENTRE 55
Annexure 2:
MONITORING AND EVALUATION INDICATORS 57
Annexure 3:
TERMS OF REFERENCE OF HUMAN RESOURCE 59
Annexure 4:
SUMMARY OF FINANCIAL ALLOCATIONS 64
Annexure 5:
PATIENT ENTRY AND SERVICE AVAILABILITY
AT VARIOUS LEVELS OF HEALTH CARE 65
LIST OF CONTRIBUTORS 66
ChapteR 1
Background
Introduction
The global hepatitis report, 2017 by WHO, provides the baseline statistics on Hepatitis B virus (HBV) and
Hepatitis C virus (HCV) infection, including mortality and coverage levels of key interventions. (1) Hepatitis B
and C, the two main types of the five different hepatitis infections (A,B,C,D,E), are responsible for 96% of overall
viral hepatitis related mortality.
Epidemiology of Viral Hepatitis
Global
Viral hepatitis is now recognized as a major public health challenge that requires an urgent response. Viral
Hepatitis caused 1.34 million deaths in 2015, a number comparable to deaths caused by tuberculosis and higher
than those caused by HIV. (1)
It is estimated that worldwide, Hepatitis A Virus (HAV) infections caused approximately 11,000 deaths in 2015
(accounting for 0.8% of the mortality from viral hepatitis). (2)
It is estimated that 325 million people worldwide are living with chronic HBV or HCV infection. Approximately,
1.75 million people were estimated to be newly infected with HCV in 2015, increasing the total number of
people living with Hepatitis C to 71 million. (1)
Every year, there are an estimated 20 million Hepatitis E Virus (HEV) infections worldwide leading to an
estimated 3.3 million symptomatic cases of acute hepatitis E. It is estimated that Hepatitis E caused 44,000
deaths in 2015 (accounting for 3.3% of mortality due to viral hepatitis). (1)
India
Viral hepatitis is increasingly being recognized as a public health problem in India. HAV and HEV are important
causes of acute viral hepatitis and Acute Liver Failure (ALF). Due to paucity of data, the exact burden of disease
for the country is not established. However, available literature indicates a wide range and suggests that HAV is
responsible for 10-30% of acute hepatitis and 5-15% of acute liver failure cases in India. It is further reported that
HEV accounts for 10-40% of acute hepatitis and 15-45% of acute liver failure. (3)
22 National Viral Hepatitis Control Program – Operational Guidelines

Hepatitis B surface Antigen (HBsAg) positivity in the general population ranges from 1.1% to 12.2%, with
an average prevalence of 3-4%. Anti-Hepatitis C virus (HCV) antibody prevalence in the general population
is estimated to be between 0.09-15%. (3) Based on some regional level studies, it is estimated that in India,
approximately 40 million people are chronically infected with Hepatitis B and 6-12 million people with
Hepatitis C. (4) Chronic HBV infection accounts for 40% of Hepato-cellular Carcinoma (HCC) and 20-30% cases
of cirrhosis in India. (3) Chronic HCV infection accounts for 12-32% of HCC and 12-20% of cirrhosis. (3)
Population based syndromic and health facility based surveillance of viral hepatitis is mandated under the
Integrated Disease Surveillance Programme (IDSP).
A systematic review of available information from published studies and from large unpublished reliable
datasets, to assess the prevalence of chronic HCV infection in the Indian population has recently been done to
assess the prevalence of overall HCV infections, and by age, sex, risk factors and place in the country. This meta-
analysis data estimated that India (current population approx. 1.3 billion) has 5.2-13 million anti-HCV positive
persons. As the data on HCV viremia amongst the anti-HCV positive persons were not available, data from
elsewhere was used to estimate that India has about 3 million to 9 million persons with active HCV infections. (5)
All key and bridge population groups under the NACP for HIV infections are specially vulnerable to viral hepatitis
infections too. There include groups like recipients of multiple blood/blood products transfusion, patients on
hemodialysis, People Who Inject Drugs, MSM, femalesex workers, sexual partners of infected people, prisoners,
migrants and truckers etc. Also, high risk population for viral hepatitis include close first degree relatives and
family members: mother, siblings, spouse and children, of persons affected with viral hepatitis. The other
populations for both hepatitis B and C include those who have received blood or blood products specially before
implementation of hepatitis C testing at a large scale in India; i.e. before 2001. Such population groups shall be
treated as key populations or high-risk groups (HRGs) under the National Viral Hepatitis Control Program.
Hepatitis B and C infections have long gestation periods before the disease progresses to advanced stages
resulting in liver cirrhosis and liver cancer, resulting in mortality if treatment is not provided in time. Intervene
to prevent advancement of the disease is particularly more challenging because during the gestation period, the
disease does not manifest itself through any specific symptoms.
Recent advances in diagnostics have now made it possible to diagnose people carrying viral hepatitis infections
through point-of-care rapid diagnostic kits. Several new technologies and platforms are also now available for
conducting confirmatory tests through viral load testing. Reliable treatment of viral hepatitis B & C is now
possible with new medicines. Diagnostics and treatment services have so far been available only through the
private sector in India. In absence of a public health initiative, such incidence of disease leads to high out of
pocket expenditure.
The Government of India has, hence, decided to launch a new National Viral Hepatitis Control Program
(NVHCP) for prevention and control of viral hepatitis, with a view to provide free of charge screening, diagnosis,
treatment & counselling services to all, and specially to people belonging to high-risk groups.
National Viral Hepatitis Control Program – Operational Guidelines 23

ChapteR 2
Introduction to the Program
India is committed to progressively move towards elimination of viral hepatitis B and C and control other virus
induced hepatitis. This is in line with our global commitment towards achieving Sustainable development
goal (SDG) goal 3; target 3.3 which aims to “By 2030, end the epidemics of AIDS, tuberculosis, malaria and
neglected tropical diseases and combat hepatitis, water borne diseases and other communicable diseases” The
Government of India is a signatory to the resolution 69.22 endorsed in the WHO Global Health Sector Strategy
on Viral Hepatitis 2016-2021 at 69th WHA towards ending viral hepatitis by 2030.
In India, the estimated burden of hepatitis is very high, necessitating focus on prevention and control measures
to mitigate morbidity and mortality arising out of hepatitis. (6)
There are several components that exist in the different programs of Government of India, such as Immunization
for Hepatitis B; Swachh Bharat Mission; Safety of blood and blood products; Safe drinking water and sanitation,
which are directly or indirectly related to the response to viral hepatitis.
The sequel of chronic hepatitis which includes cirrhosis and HCC poses long term burden on the health system.
A recent cost benefit analysis of treating hepatitis C infection demonstrated that curing the HCV with 12-24
weeks of directly acting antivirals (DAAs) is substantially more cost effective than managing the sequels and
has better health outcomes. (7) Unsafe injection practices during health care or otherwise, remain a risk and
have potential to transmit the HBV and HCV infection. Use of Reuse Prevention (RUP) syringes is a critical
intervention to interrupt the chain of such transmission. India manufactures RUPs for injection in therapeutic
care and mandating its use in public and private sector offers a new opportunity to address unsafe injections.
With the view to address the existing gaps in current programs, the program proposes to address management
of all types of viral hepatitis. The advent of newer and safe drugs for treatment of Hepatitis C ensuring cure
makes it easier to combat it. Similarly, the available drugs for hepatitis B treatment are quite potent and safe and
keep the virus suppressed for prolonged periods, reducing the risk of cirrhosis and liver cancer.
Aim
1. Combat hepatitis and achieve country wide elimination of Hepatitis C by 2030
2. Achieve significant reduction in the infected population, morbidity and mortality associated with
Hepatitis B and C viz. Cirrhosis and Hepato-cellular carcinoma (liver cancer)
3. Reduce the risk, morbidity and mortality due to Hepatitis A and E.

Key Objectives:
1. Enhance community awareness on hepatitis and lay stress on preventive measures among general
population especially high-risk groups and in hotspots.
2. Provide early diagnosis and management of viral hepatitis at all levels of healthcare
3. Develop standard diagnostic and treatment protocols for management of viral hepatitis and its
complications.
4. Strengthen the existing infrastructure facilities, build capacities of existing human resource and raise
additional human resources, where required, for providing comprehensive services for management of
viral hepatitis and its complications in all districts of the country.
5. Develop linkages with the existing National programmes towards awareness, prevention, diagnosis and
treatment for viral hepatitis.
6. Develop a web-based “Viral Hepatitis Information and Management System” to maintain a registry of
persons affected with viral hepatitis and its sequelae.
Components
The key components include:
1. Preventive component: This remains the cornerstone of the NVHCP. It will include
a. Awareness generation
b. Immunization of Hepatitis B (birth dose, high risk groups, health care workers)
c. Safety of blood and blood products
d. Injection safety, safe socio-cultural practices
e. Safe drinking water, hygiene and sanitary toilets
2. Diagnosis and Treatment:
a. Screening of pregnant women for HBsAg to be done in areas where institutional deliveries are < 80% to
ensure their referral for institutional delivery for birth dose Hepatitis B vaccination.
b. Free screening, diagnosis and treatment for both hepatitis B and C would be made available at all levels
of health care in a phased manner.
c. Provision of linkages, including with private sector and not for profit institutions,for diagnosis
and treatment.
d. Engagement with community/peer support to enhance and ensure adherence to treatment and
demand generation.
3. Monitoring and Evaluation, Surveillance and Research
Effective linkages to the surveillance system would be established and operational research would be
undertaken through Department of Health Research (DHR). Standardised M&E framework would be
developed and an online web based system established.
4. Training and capacity Building: This would be a continuous process and will be supported by NCDC,
ILBS and state tertiary care institutes and coordinated by NVHCP. The hepatitis induction and update
programs for all level of health care workers would be made available using both, the traditional cascade
model of training through master trainers and various platforms available for enabling electronic,
e-learning and e-courses.

Activities
The main activities of the program would include the following:
Program Management
Prevention Diagnosis and Monitoring & Training and

Treatment Evaluation, Capacity
Awareness Surveillance Building
generation & Diagnosis/Screening & Research
behaviour change - serological tests Standardized
communication Hepatitis training modules for
Confirmation - information and all cadres of health
Immunization for molecular tests management portal care workers &
hepatitis B – birth (where required) program managers
dose, high risk Standardized M&E
groups, health Treatment of framework and Digital &
care workers uncomplicated web based portal conventional
cases - at treatment training program
centres, drug Indicator based
Provision of
dispensation monitoring of
safe blood and E learning
upto HWC the program
blood products
Induction &
Treatment of Surveillance
Injection Safety by refresher trainings
complicated of acute viral
Use of only RUP
cases at model hepatitis, chronic
syringes in all Facilitation through
treatment centres viral hepatitis and
government HCFs tele-consulting
it’s sequelae
Laboratory capacity
Safe socio-cultural
building and quality Review Meetings
practices
assurance
External Reviews
Referral and
linkages
Standard treatment
protocols for
viral hepatitis
Uninterrupted
supply of drugs
Training of health
care staff
leverage capacities
through PPP models

Targets for the NVHCP
The National Viral Hepatitis Control program has the following cumulative physical targets for the first three
years:
1. Program Management:
a. National Viral Hepatitis Management Unit (NVHMU): To establish a NVHMU in the first year.
b. State Viral Hepatitis Management Unit (SVHMU) - To establish a State Viral Hepatitis Management
Unit in the first year within existing state health governance structure i.e. State Health Society. This
would be structured on similar lines as the NVHMU.
2. Prevention:
a. Develop and implement the protocol for ante-natal screening of pregnant women for Hepatitis B; and
start screening in the first year.
b. Develop and implement tracking mechanism to ensure institutional delivery for all Hepatitis B carrier
pregnant women.
c. Increase Hepatitis B zero dose immunization to over 90%
d. Implement safe injection practices in government systems immediately
e. Blood safety targets
f. To develop institutional mechanism for periodic testing of drinking water sources in coordination
with Department of Drinking Water and Sanitation (DoDWS).
g. Improved IEC for prevention and checking transmission
3. Diagnosis & Treatment
A. Diagnosis:
a. Set up the National Reference Laboratory by the end of first year.
b. Establish State level reference laboratories in each state by the end of first year.
c. Develop District Diagnostics centres with viral load testing capabilities by the end of first year.
d. Start first line diagnosis through Rapid Diagnostic Kits at all levels by the end of first year.
e. Test 1.6 lakh individuals in the first year, 10.1 lakh in second year and 30.1 lakh in the third year for
Hepatitis C.
f. Start screening people belonging to high-risk groups for Hepatitis B in first year.
g. Encourage opportunistic screening for HBV and HCV of patients visiting health care facilities
B. Treatment:
a. Establish at least one Model Hepatitis Treatment Centre in each state\UT in the first year in an
institution identified by the respective state\UT government. Increase the number of such centres if
required (on the basis of need assessment) in consultation with the concerned state\UT government,
in subsequent years.
b. Establish at least one Treatment Centre at district level in the public sector, preferably in a medical
college or the District Hospital, by the end of second year to offer access to quality assured management
of Viral Hepatitis.
c. Number of new hepatitis C cases to be treated across the country: over 3 lakh patients in 3 years
d. Start treatment for Hepatitis B for people needing treatment, by the end of first year

4. Training:
a. Ensure all trainings to operationalize state reference laboratories and Model Treatment Centres by the
end of first year.
b. To develop capacities of state\UT teams for training of personnel at the district laboratories and
treatment centres.
c. To develop IT driven institutional mechanisms for offering online counselling and courses to personnel
at all levels. The program will also explore facilitation through tele consulting where required.
d. To develop capacities of functionaries in Community Health Centre, Primary Health Centre and
Health and Wellness Centre (CHC, PHC and HWCs) to implement diagnostic and treatment support
protocol appropriate at that level
5. Monitoring and Evaluation, Surveillance and Research:
a. To develop and operationalize the Viral Hepatitis Information Management System (VHIMS) for
i. Maintaining a registry of patients
ii. Tracking of patients for ensuring treatment adherence and compliance.
iii. Developing dashboards and reports for monitoring of the Program.
b. Co-ordinate with the National Viral Hepatitis Surveillance Program
i. Surveillance of acute viral hepatitis
ii. Surveillance of chronic viral hepatitis
iii. Surveillance of sequelae of chronic viral hepatitis
c. Research: Identify evidence based operational research and implement in collaboration with DHR

Chapter 3
Program Management
The NVHCP will be coordinated by the units at the centre and the states.
1. National Viral Hepatitis management unit (NVHMU)
2. State Viral Hepatitis management unit (SVHMU)
3. District Viral Hepatitis management unit (DVHMU)
Organizational Structure
National
program steering
committee
National Viral Hepatitis Technical National

Management Unit (NVHMU) Resource Groups level
State program
steering committee
Model Rx State State level

Centre SVHMU
Laboratory
TC Pvt. lab
Treatment District Reagent Rental

DVHMU PPP model
Centre Lab District level
Pvt. Lab
CHC, PHC HWC

Sub District level
Diagnostics (RDTs)
Drug dispensation

The laboratory and treatment site should preferably be co-located. The NVHCP envisages a service delivery
mechanism in subsequent years where there will be co-location of district labs and treatment centres with due
considerations to capacity in different domains and move towards PHC for screening and drug dispensation.
National Program Steering Committee:

There will be a National Program Steering Committee headed by Secretary Health & Family Welfare. The
Committee shall inter alia include
1. Secretary, Department of Health Research (DHR)

2. DGHS,
3. Mission Director, National Health Mission
4. Director General, National AIDS Control Organisation
5. Representative of RCH, Immunization division, IDSP, NHM Policy, and IEC divisions in the Ministry of
Health and Family Welfare.
6. NCDC representative
7. Principal Secretaries from 2 states nominated by the Secretary Health & Family Welfare, Government of
India
8. Mission directors from 2 states, nominated by the Secretary Health & Family Welfare, Government of
India
9. Director, ILBS
10. ED, NHSRC
11. 2-3 eminent persons from academic institution across the country,
12. Representatives of Swachh Bharat Mission for both urban and rural sectors
13. Representative from Ministry of Drinking water and sanitation,
14. Representatives of the community ( like PWID, haemophiliacs, PLHIV, FSW, MSM)
15. Development partners like UNICEF and WHO.
The Joint Secretary looking after the NVHCP shall be the convenor of the Committee.
The Steering Committee shall monitor & provide guidance for implementation of the Program and shall meet
as often as necessary, but at least once every 6 months..
Key Functions of the Program Steering Committee

1. Monitor the progress of the National Program
2. Advise on the newer interventions over the process of implementation
3. Guide on the external evaluation process
National Viral Hepatitis Control Management Unit

The NVHMU established at the Centre with in the NHM and will be responsible for implementation of program
and activities of the Program. The NVHMU will be headed by a Joint Secretary who will report to the Mission
Director (NHM). It will have following wings, namely –
1. Prevention unit ( Will perform the functions of IEC, coordination and linkage with other programs)
2. Diagnosis and Treatment unit
3. Surveillance , monitoring and Evaluation
4. Training and capacity building

Appropriate number of consultants with needed competencies will be engaged to support the NVHMU. The
support will be provided through the NVHMU budget under the NHM. The key functions of NVHMU will
include procurement and supply chain management, training and capacity building, development of guidelines
for the use in the program, collaboration with existing programs and divisions of GoI [like UIP, safety of
blood and blood products, IDSP, Indian Council of Medical Research (ICMR) etc] and overall implementation,
supervision, monitoring and evaluation.
Roles and Responsibilities of National Viral Hepatitis Control Management Unit (NVHMU) in
the Centre
»» Provide technical assistance for facilitating the implementation of the ‘National Viral Hepatitis Control
Program’ and achieving the yearly physical and financial targets at various levels.
»» Development of Standard Treatment Protocols and Standard Diagnostic Protocols for Acute and Chronic
Hepatitis under the guidance of a “Inter-Ministerial Task Force” and the “Technical Working Group”.
»» Provide normative guidance (technical and operational) and standard operating procedures, biomedical
waste management and bio-safety guidelines for the various points of service delivery.
»» Development of standardised Training manuals for all cadres of health care providers including doctors,
pharmacist, data managers, peer supporters, ANM, Para-medical professionals etc
»» Collaboration and coordination with the other existing national health programs/schemes at the national
level (like Universal Immunization Program; Injection Safety; Safety of Blood and blood products;
Integrated Disease Surveillance Programme (IDSP); National AIDS Control Program (NACP); Harm
reduction in key population; Surveillance of Viral Hepatitis; Swachh Bharat Mission; Safe drinking water
and sanitation Program; Biomedical waste management).
»» Coordinate with IDSP at the Central Surveillance Unit (CSU) for epidemic/outbreak investigation as and
when required.
»» Facilitate all work related to External Quality Assessment (EQA) with the designated laboratory
periodically
»» Budgeting and financial planning for the NVHCP including maintaining expenditure Control Register,
manage records with respect to finance and accounts, reconcile head-wise expenditure for the NVHCP at
the national level.
»» Responsible for providing inputs for preparing the Program Implementation Plan for the states with
respect to the NVHCP and appraising the PIPs received from the states.
»» Regular monitoring of the functioning of State and District Laboratory network under the NVHCP and
with IDSP through Central, State and District Surveillance Unit.
The key functions of NVHMU will include

»» Awareness generation
»» Procurement and supply chain management,
»» Training and capacity building,
»» Development of guidelines for the use in the program,
»» Collaboration with existing programs and divisions of GoI [like UIP, safety of blood and blood
products, IDSP, Indian Council of Medical Research (ICMR) etc] and
»» Discussions with states and guidance to formulate State PIP to meet annual targets
»» Overall implementation, supervision, monitoring and evaluation

State Viral Hepatitis Control Management Unit (SVHMU)
A State Viral Hepatitis management unit for coordination shall be set up in all the states and UTs, within the
existing state health governance structure i.e. the State Health Society with dedicated nodal officer and required
essential manpower for the program. This will be guided by a state program steering committee and supported
by technical experts ( in synchronization with the NVHMU structure) involved in the program implementation.
The SVHMU shall be responsible for planning, implementation, monitoring and reporting of all the Program
activities in the state\UT. This will include supply chain management and distribution within the state, training
and capacity building, integration with existing programs and divisions at the state level (like UIP, safety of
blood and blood products, ICMR etc.), coordination with the NVHMU and the laboratory and treatment sites at
all levels, establishing supervision, monitoring and evaluation framework for viral hepatitis at the state level.
Roles and Responsibilities of the State Viral Hepatitis Management Unit in the State
1. Budgeting and financial planning for the prevention and control of viral hepatitis at the state and district
level. Responsible for preparing the Program Implementation Plan (PIP) for the respective state for the
NVHCM.
2. To submit evidence based proposal during the state PIP development
3. Provide technical assistance for facilitating the implementation of program for achieving the yearly
physical and financial targets at various service delivery components.
4. Ensure that the normative guidance, guidelines and standard operating procedures provided by the centre
are followed at the point of service delivery.
5. Ensure implementation of standard operating procedures, diagnosis & treatment guidelines and quality
control measures.
6. Collaboration and coordination with the other existing national health programs/schemes at the state
level (like UIP; Injection safety; Safety of blood and blood products; Integrated disease surveillance
program; State aids control society; Harm reduction in key population and Surveillance of viral hepatitis;
Swachh Bharat mission; Safe drinking water and sanitation program; Biomedical waste management).
7. Coordinate with NVHMU and state and district level to help in capacity building under the NVHCP.
8. Collect, collate and analyse the state and district level data on components of the NVHCP on regular basis
and send the same to the NVHMU.
9. Coordinate and collaborate with other ministries at the state level for better synergy in implementing the
NVHCP
10. Supervise through on site visits and provide technical support for strengthening of state and District
Hepatitis units under the program;
11. Regular monitoring of the functioning of State and district level facilities for diagnosis and treatment.
12. Maintain expenditure control register, manage records with respect to finance and accounts, reconcile
head-wise expenditure.
Key Functions of the SVHMU

1. Identify a nodal person for Viral Hepatitis related program activities in the state and district
2. Develop State PIP for submission to NVHMU to set targets for the state
3. Identify the service delivery sites and regularly monitor them
4. Conduct state level review meeting and field visits to monitor the program implementation at state
level
5. Ensure coordination with other program of GoI
6. Ensure that the data is analysed at state level for better program planning and regularly reported to
centre.

District Viral Hepatitis Control Management Unit (DVHMU)
A district Viral Hepatitis management unit for coordination shall be set up in all the districts, within the existing
health governance structure.
The state government will designate a program officer at the district level from available manpower as the
nodal person to supervise and facilitate the logistics, supply chain, outreach, training etc.
Roles and Responsibilities of the District Viral Hepatitis Management Unit (DVHMU)
1. To ensure that the district labs and treatment centres are functional
2. To identify sites for service delivery
3. To ensure training of the personnel
4. To establish referral networks both for diagnostics and treatment wherever required
5. To ensure linkages with existing program NVHCPs to achieve the set targets.
6. To assist in distribution of IEC material at the facilities
7. To ensure data recording, and reporting from the service delivery units on a real time basis as far as
possible

ChapteR 4
Service Delivery : Synergies with the
existing programs and relevant ministries
Service Delivery Component will include the following two aspects:

1. Synergies with the existing programs and relevant ministries of Government of India
2. New Interventions- Diagnosis and Management of Viral Hepatitis with focus on treatment of
Hepatitis B&C
The delivery of services for the components already existing shall be done through the currently established
channels like the UIP; Injection safety; Safety of blood and blood products; IDSP; State AIDS control society
(SACS); Harm reduction in key population; Surveillance of viral hepatitis; Swachh Bharat Mission; Safe drinking
water and sanitation program; Biomedical waste management). These synergies will be established to ensure
that there is no duplication of resources and efforts and the plan under the Viral Hepatitis is aligned with the
respective, existing components. This will largely be done by NVHMU and SVHMU at their respective levels of
administrative control.
Universal Immunization Program

Hepatitis B vaccine was universalised nationwide in 2011.. The UIP schedule recommends hepatitis B birth dose
to all infants within 24 hours, followed by three doses at 6, 10 and 14 weeks to complete the schedule.
The hepatitis-B birth dose coverage among the total live births was 45% in 2015 and 60% in 2016. Missed
opportunity is about 40% which need to be addressed. The coverage amongst institutional deliveries for
Hepatitis -B birth dose was reported to be 76.36% as of December 2017.
India’s target for Hepatitis B immunization

S.No. Country Targets (to be provided by UIP) Baseline (2016-17) 2019-20
1. Coverage of Birth Dose of Hepatitis B ( All deliveries) 90%
2. Coverage with three doses of Hepatitis B vaccine in infants (B3). 95%
3. Routine Hepatitis B vaccination among health-care workers. N/A Will be made
Available
The NVHMU and SVHMU will therefore integrate with the UIP for the following:
A) Strengthen routine immunization services to achieve and sustain the desired coverage of the timely birth
dose followed by three doses of hepatitis B vaccine

B) Coordinate with the Universal immunization programme for mandatory immunization of all healthcare
workers. Provision of vaccination for health care workers should be followed one month later by testing for
protective hepatitis B antibody levels (anti HBs>10 IU/ml). This approach will not only provide protection to
the healthcare workers against contracting hepatitis B accidentally, but will also help detect and support the
positive HCWs.
National AIDS Control Program (NACP)

There are certain population groups like recipients of multiple blood / blood products transfusion, patients on
hemodialysis, PWID, MSM, female sex workers, sexual partners of infected people, prisoners etc which are at a
higher vulnerability to get infection with hepatitis B and hepatitis C.
The NVHMU will coordinate with NACP for surveillance of hepatitis in key populations, establishing linkages
for testing and care for hepatitis C infected PLHIV and vaccination of the vulnerable population. The SVHMU
will coordinate in a similar manner with the state machinery for executing the same.
Safety of blood and blood products

HBV and HCV can be transmitted through contaminated blood and blood products and hence the need
for strengthening blood safety. Ensuring availability of safe blood and blood products is one of the critical
interventions for reducing transmission. One of the ways to ensure safety of blood& blood products is by
increasing voluntary blood donations (100%). Blood Banks are regulated by an Act of parliament namely “The
Drugs and Cosmetics Act (1940)” and the regulations therein. As per the requirements of the Act, it is mandatory
to screen every unit of blood for HBV and HCV along with other transfusion transmitted infections (TTIs)
before transfusion, in all licensed blood banks. Screening for HCV was made mandatory and introduced in 2001
across blood banks in India.
NVHMU, SVHMU and DVHMU will establish linkages with the existing system of NACPat the central and state
level, for the following
1. To review and strengthen national policies and practices on blood safety those promote rational use of
blood and blood products, and move towards 100% voluntary blood donation.
2. Setting up a mechanism for follow up of individuals detected positive on screening, their counselling,
confirmatory testing and linkages to care and support services for viral hepatitis.
3. Strengthen systems for surveillance, hemo-vigilance and monitoring of the incidence and prevalence of
viral hepatitis infections in blood donors, and monitor the risk of post-transfusion hepatitis.
4. Establish mechanisms for counselling of HBsAg and anti-HCV reactive blood donors for referral and
follow-up to confirm the presence of infection by confirmatory tests & provide treatment for Hepatitis B
and C where necessary.
5. Developing/updating training modules with SACS, State Blood Transfusion Council and blood cells
on safety of blood and blood products with special focus on prevention of Viral Hepatitis through
transfusion of blood and blood products and linkages for those screened positive.
Country Target
S.No. Indicator ( from NACP and NHM)* Target
1. % of blood donations that are voluntary 80% by 2020
2. % of donated blood units screened for Hepatitis B and C 100% by 2018
* To be monitored and submitted to the NVHCP twice every year (as absolute numbers
as well as percentage)

Harm reduction in key populations
Targeted Interventions (TI) for key and bridge populations has been the core prevention strategy under NACP in
India. Key population include female sex workers (FSW), men who have sex with men (MSM), transgender (TG)&
people who inject drugs (PWID), while bridge populations include migrants & truckers.
TIs are implemented as NGO/CBO led peer outreach model to provide a package of prevention services including
behavioural change communication, condom promotion, prevention and management of sexually transmitted
infections (STI), community mobilization and enabling environment, and linkages to HIV testing, care, support
& treatment. Needle syringe exchange program and opioid substitution therapy are provided for prevention
of HIV among PWID. Since the mode of transmission of Hepatitis B and Hepatitis C are largely similar to HIV/
AIDS, NVHMU and SVHMU will coordinate with NACP for including prevention/management of hepatitis B
and C in the package of prevention services for the key and bridge population.
In addition to the key population under NACP, there are other focus groups that need to be attended to under
the NVHCP. These focus groups include close first degree relatives and family members of infected person:
mother, siblings, spouse and children. The other populations for both hepatitis B and C include those who
have received blood or blood products specially before implementation of hepatitis C testing at a large scale in
India; i.e. before 2001., recipients of multiple blood transfusion, person exposed to unsafe injection practices
by informal health care providers, etc . Identification of hot spots of hepatitis B and C should also be one of the
priorities of the NVHCU.
Injection safety and infection control
S.No. Targets WHO Regional Action Plan for Viral Hepatitis in South-East Asia:2016–2021
1. By 2020, 50% of all injections are administered with safety engineered devices.
Country Target
S.No. Indicator
1. By 2020, 100% of injection devices are safety engineered devices in India.
Unsafe health care practices by health care providers/ traditional healers/ quacks pose a major challenge and
risk for transmission of HBV and HCV. There are gaps in implementation of bio-medical waste management
rules, leading to sharps injuries and increased risk of infections.
NVHMU and SVHMU will integrate with the national and state regulatory bodies to strengthen the infection
prevention and control practices in healthcare settings (public and private), including in laboratories, dental
clinics, endoscopy clinics and haemodialysis units etc. Coordinate with the Pradhan Mantri National Dialysis
Program for making special emphasis on the component of injection safety and infection control in their
program module. NVHMU and SVHMU will also coordinate with the regulatory body towards effective
roll-out of re-use prevention (RUP) syringes, addressing prescriber practices and community preference for
injections while respecting the socio-cultural practices like tattooing, religious ceremonies (e.g. mundans),
ear/body piercing etc. States need to identify CBOs/NGOs and incentivise them for training on prevention of
HAV and HEV during mass religious activities; and mundan ceremonies and community barbers for HBV and
HCV. NVHMU and SVHMU will coordinate with the Ministry of Environment & Forestry and pollution control
board (at national and state level) for capacity building for effective implementation of the bio-medical waste
management rules.
Integrated Disease Surveillance Programme

The NVHMU and SVHMU will integrate with the IDSP

• To provide technical support for outbreak investigation and reporting and monitoring of outbreaks of
viral hepatitis, specially hepatitis E and A.
• Assisting in rapid response team activities during outbreaks.
• Ensure linkages with the laboratory and treatment facilities of those affected in the outbreak with the
disease.
• To involve all structures up to PHC level
National program for Surveillance of Viral Hepatitis:

The initiative will integrate with the National Program for Surveillance of Viral Hepatitis such that the sentinel
sites for surveillance are co-located and function with MTC. This will ensure that all those found positive in
surveillance can be linked for further testing and treatment.
S.No. Targets WHO Regional Action Plan for Viral Hepatitis in South-East Asia:2016–2021
1. Have effective outbreak response and surveillance systems in place to monitor HAV and HEV outbreaks and
outcomes by 2020
The NVHCP will undertake surveillance of acute, chronic hepatitis as well as their sequel over the next three
years. It will also have estimates for the disease burden for Hepatitis B and C in the country.
Swachh Bharat Mission- Urban & Rural

Swachh Bharat Mission, an initiative of Ministry of Housing and Urban Affairs, Government of India in
urban areas has the objective of improving the sanitation by eliminating open defecation, eradicating manual
scavenging, managing municipal solid waste through modern and scientific techniques, generating awareness
about sanitation especially in context of viral hepatitis A and E (relating to contamination of water and food),
and effecting behaviour change regarding healthy sanitation practices will play a vital role in achieving the
objective of preventing and controlling viral hepatitis especially in context of hepatitis A and hepatitis E which
are largely spread through faecal oral route and there prevalence can certainly reduced significantly by efforts
towards improved sanitation. NVHMU and SVHMU will therefore establish linkages with Swachh Bharat
Mission through meetings and consultations with the officials of Ministry of Housing and Urban Affairs at
the national and state level so as to achieve the objectives of the mission and indirectly help reduce the burden
of hepatitis A and E. NVHMU and SVHMU will also work towards ensuring training of each facility towards
cleanliness and environmental hygiene.
The Swachh Bharat Mission in rural areas implemented through Ministry of Drinking Water and Sanitation
will also be involved in a similar manner.
Ministry of Drinking Water and Sanitation

NVHMU and SVHMU will also establish linkages with the Ministry of Drinking Water and Sanitation for
strategizing towards provision of clean drinking water and sanitation. This will further help in reducing
the burden of Hepatitis A and E. Advocate for and communicate the importance of safe water, hygiene and
sanitation and improve access to safe sanitation facilities. Educate the public on safe disposal of human faeces.
Food Safety and Standards Authority of India (FSSAI)

Ensure inter-sectoral collaboration with FSSAI for access to safe food through enforcement mechanisms at
national, state and district levels. To promote and advocate for safe food to reduce the burden of hepatitis
amongst general population and food business operators.

ChapteR 5
Service Delivery: New Interventions- Diagnosis
and Management of Viral Hepatitis with
focus on treatment of Hepatitis B&C
There will be need to establish implementation mechanism and service delivery points for interventions like
diagnosis and treatment, surveillance and awareness generation. The service delivery for these will happen at
facilities identified for each type of services, based on evidence and existing capacities. Additional staff wherever
required for each service delivery type is proposed. The various components of service delivery under this head
will include:
A. Laboratory services
B. Treatment services
Laboratories Services
Laboratory services are necessary for screening, confirmation and monitoring the response and outcomes of
treatment. A tiered mechanism as shown in figure below reflects on the facilities being offered at various levels.
To facilitate the same, the program will strengthen the state, district, up to PHC laboratories in a phased manner.
In the first year, the focus will be on laboratory which will be designated as sentinel sites to be used for both
testing and training. Some of the state medical college laboratories will also be engaged for the same. All efforts
will be made to cascade these trainings and capacities to below district level labs ( for screening) in a time bound
manner, to strengthen them to provide quality assured testing for viral hepatitis.
Procurement of services using the reagent rental model, existing facilities and PPP models for molecular testing
will be explored to enhance access to them in a quality assured manner.

Network of Laboratories under the National Viral Hepatitis Control Program
CoE RDT, ELISA/CLIA, RT-PCR, Sequencing
Sentinel site RDT, ELISA/CLIA, RT-PCR
State RDT, ELISA/CLIA, access to RT-PCR*
District RDT, ELISA, access to RT-PCR*
RDT for HBV & HCV, referral for

PHC /HWC/SC
confirmation*
*If samples are to be transported, they need to be collected, packaged and transported
within six hours of collection under suitable environmental conditions.
Centre of Excellence for laboratory testing

Centre of Excellence (CoE) will be situated at National Centre for Disease Control (NCDC).
Roles and Responsibilities

• All samples will be archived. A subset will be sequenced to determine the genotype and maintain a
national database on the virus genotypes circulating in the population.
• Capacity building of the sentinel sites for onward training of the state labs nominated.
• Formulation and dissemination of guidelines as part of the NVHCP
• Supervision of all the laboratory activities under the NVHCP
• Provide technical assistance for implementation of the NVHCP
• Building capacities at national and state level under the NVHCP
• Facilitate all work related to EQA/proficiency testing (PT) with the designated PT provider(s) and
the participating labs
• Undertake review of literature and stay up-to-date on current trends in health systems
strengthening with regard to the NVHCP for prevention and control of viral hepatitis.
State Laboratories
It is targeted to strengthen state laboratories under the program. State Laboratories under the NVHCP will be
selected by the state based on the burden of disease according to available evidence in form of studies, outbreaks,
case reports, blood bank data etc.
In the first year, State Laboratories will be co-located in those Microbiology labs which are also the sentinel site
labs under the National Program on Surveillance of Viral Hepatitis. State laboratories will build the capacity of
the district laboratories in a time bound manner (based on the operational guidelines on the laboratory services
for viral hepatitis NVHCP).Some of the state labs will be identified and their capacity built for HBV DNA / HCV
RNA testing. It is proposed to adopt a reagent rental model for molecular testing wherever feasible. Sample
transportation is envisaged to meet economies of scale. However, looking at the diversity of the country, the
NVHCP will explore public private partnership models in hard to reach areas and use of existing infrastructure
and equipment to facilitate access to HCV RNA testing in a cost efficient manner.

1. The laboratory will be required to ensure that the samples are collected from all the HCFs in the
geographical area linked to that State lab. These samples should be logged in and stored as per the
prescribed guidelines for subsequent testing.
2. Testing of the samples for viral hepatitis as per the prescribed guidelines for testing
3. Some of the state labs will be identified and their capacity strengthened to perform serological and NAT
tests. Testing will be done of the samples received from the co-located treatment sites and other state and
district laboratories
4. Ensuring a referral mechanism to the treatment centre
5. Storing of the plasma for viral load NAT
6. To develop a repository of panel members to be used for evaluation purpose.
7. Follow a common plan, standard operating procedures (SOPs) and recording/reporting forms for carrying
out the activity.
8. The state lab has to ensure that the equipment for the activity are satisfactorily installed by the
supplier, facilitate the necessary Installation Qualification (IQ), Operational Qualification (OQ) and the
Performance Qualification (PQ) and ensure that the supplier performs the requisite calibration and
maintenance of the equipment at specified intervals as per the work order. Ensure on site training by the
vendor on the equipment installed before signing of the certificate for satisfactory installation as this is
linked to financial obligations of the centre and subject to accountability of all concerned.
9. The state lab needs to ensure that all records pertaining to testing, equipments, manpower, facility etc. are
maintained as per the guidelines.
10. Shall ensure quality management systems in pre-analytic, analytic and post-analytic processes of testing.
11. Shall follow the protocols on sample rejection as prescribed by CoE.
12. Shall maintain minimum performance standards for the laboratory to be functional at all times
13. Participate in external quality assessment scheme (EQAS) mandated by CoE.
14. Shall prepare its own IQC panel which will include weakly positive and negative controls.
15. Shall monitor the IQC results regularly and Levy-Jennings charts will be prepared and reviewed
every month.
16. Shall ensure that the samples for EQAS are sent to the designated laboratory in proper packaging, and
controlled temperature and humidity conditions in cold chain as per the prescribed guidelines.
17. Samples received at the testing laboratories will be stored in adherence to the protocols as specified in this
programme Guidelines.
18. Shall follow the standardized testing algorithm
19. Training and Capacity building of the district labs
District Laboratories
These laboratories would be co- located with the Treatment Centres at the district hospitals. The capacities of
these labs will be strengthened in a phased manner. The state laboratories will train the district laboratories in
carrying out serological testing for viral hepatitis (immuno-assays/rapid Tests). These laboratories will perform
the testing and would be linked to other treatment centres in the district, sub-district levels in the region. Each
treatment centre would be linked to HBV DNA/HCV RNA estimating laboratories in the Government or private
sector. This can be done by using existing machines in the system, reagent rental or PPP model in hard to reach
areas as detailed earlier. Cartridge based nucleic acid amplification testing will also be explored.

1. Sample collection and serological testing under the NVHCP
2. Molecular testing where feasible
3. Sample transportation for molecular testing, where necessary

Functions at the District Laboratory
1. Undertake testing for screening and diagnosis
2. Undertake molecular testing where feasible and transport the sample for molecular testing where
necessary
Laboratories below district level

At all levels below district, provision for screening by using rapid diagnostic tests (RDTs) will be done for
screening of HBV/HCV
1) Sample collection and serological testing under the NVHCP

2) Establish referral mechanisms for confirmation and treatment
At all levels below district level, provision for screening by using RDTs will be done for HBV/HCV screening
Sample Transportation for HBV/HCV Quantitative NAT testing

Hub and spoke model will be followed for the collection, storage and transport of the samples for viral load NAT,
where required. These samples will travel from the district lab/ state lab to the identified laboratories for DNA/
RNA/NAT testing. (Refer to the National Laboratory Guidelines for Viral Hepatitis Testing)Other options like
use of CBNAAT and PPP will also be explored.
The program will endeavor to set up a network of laboratories for drug resistance testing in the future.
Human Resource in Laboratories

To facilitate the diagnosis and laboratory monitoring of treatment, the NVHCP will strengthen the laboratories
to deliver services as per the national guidelines. The laboratories so strengthened should have the following
manpower.
S No Manpower at state laboratories

1 Technical officer – 1
2 Data entry operator – 1
3 Laboratory technician – 1
S No Manpower at district laboratories

1 Laboratory technician -1
The NVHCP will evaluate and provide the same on a need based approach. The staff should be recruited by the
institution as per the norms and procedures followed for recruitment of contractual staff as per the guidelines
of the National Health Mission (NHM). The terms of reference of the human resource are available in Annexure
3. The remuneration for all these staff shall be in accordance to the state NHM norms. There should be an in-
built system of appraisal of such staff from time to time.
(Detailed operational guidelines on the laboratory services for viral hepatitis have been developed and should be
referred to for manpower, pattern of assistance, etc).

Approach to Diagnosis of Viral Hepatitis
A patient with acute or chronic viral hepatitis infection may present at a healthcare setting with or without
jaundice. The patient may be referred by a treating doctor/health worker/mid level provider for investigations
after taking a written informed consent with a complete test requisition form.
Testing for HBV in pregnant women- In states where institutional deliveries are less than 80%, screening of all
pregnant women should be carried out for HBsAg detection. Institutional delivery of HBsAg positive pregnant
women must be mandated to prevent transmission to the child by giving birth dose Hepatitis B vaccine. A birth
dose of HBIG as per requirement will be given to the new born at the district level.
Self-presenting asymptomatic individuals at high risk may be provided access to testing by a defined mechanism
in the health care facility.
The algorithms to be followed for diagnosis are as under:
Testing algorithm for Diagnosis of Viral Hepatitis in jaundiced patients

Specimen: Serum/Plasma*
HAV HEV HBV HCV
IgM Anti
IgM Anti IgM Anti HBsAg
HBc
Anti HCV
HAV HEV
Reactive Non-reactive Reactive Non-reactive Reactive Non-reactive

Reactive Non-reactive Reactive Non-reactive
Report : Report : Report : Report : If HbsAg is Reactive and lgM anti HBc is Non- Report:
Report:
HAV HAV HEV HEV reactive: HBV positive HCV Ab
HCV Ab
Positive Negitive Positive Negitive Positive#
If lgM Anti HBc is Reactive and HBsAg is Non- Negative#
reactive: HBV positive
If both Reactive: HBV positive
If both Non-reactive: HBV negative
* Serum samples to be used for serological and biochemical testing, to be aliquoted and stored at -20 0 C for
retesting for quality purposes, dispute etc.
# All HCV antibody (Ab) positive to be referred to treatment centre. Plasma samples to be collected and
aliquoted in 3 sterile cryo vials. One vial to be used for quantitative hepatitis C RNA estimation and two
archived at -80 0 C for quality assurance.

Testing algorithm for Diagnosis of Viral Hepatitis in suspected patients
)without jaundice(
HBV HCV
HBsAg Anti HCV
Reactive Non-Reactive Reactive Non-Reactive
Report: Report: Report: Report:

HBV HBV HCV Ab HCV Ab
Positive Negative Positive# Negative
# All HCV antibody (Ab) positive to be referred to treatment centre. Plasma samples to be collected and
archived at -80 0 C for quality assurance
Treatment Sites
The services under the hepatitis treatment initiative will be delivered through the designated treatment sites
that are located within an existing health facility, such as district hospitals and state medical colleges. It will
utilize the current health care system. However, the extent of services can be graded upon the availability of
the expertise in the selected sites. There will be a few sites that will be labelled as Model Hepatitis Treatment
centres (MTC). These will also act as places for referral and mentoring of the other treatment centres (TC). The
Model Hepatitis Treatment centre will 3-4 per state and can be located in the district hospital or co-located with
the sentinel sites. All the diagnosis and treatment centres will have the capacity to differentiate whether the
patient has advanced liver disease or not. They would deliver the DAA in uncomplicated cases (and few other
scenarios as per the national technical guidelines). Selection of the other treatment sites will be based on the
concurrence of states after due considerations on existing capacities. They could be situated in any competent
health care facility like the medical colleges, district hospitals etc. However, the cases that need more specialized
care will be referred to higher centre that have the requisite capacity and experience to manage the complicated
cases ( e.g. decompensated cirrhosis, thalassemics with HCV infection, and HCV infection in renal impairment
etc). These health care facilities with specialized services for diagnosis and management (like availability of
Gastro-enterologist /hepatologist, fibroscan, Doppler, CT scan, MRI scan etc)are termed as Model Treatment
centre. Hence, the MTC will perform all the functions of a treatment centre, will also receive in-referrals and
also be the centres for training, mentoring and conducting operational research under the NVHCP.
Model Hepatitis Treatment Centre

1. To ensure screening/ diagnosis in suspected cases of hepatitis B and hepatitis C infection
2. Treatment &management of viral hepatitis

3. In referrals for cases screened / diagnosed elsewhere, for the management of hepatitis
4. Management of complicated cases referred from other treatment centres. Prescription and dispensation
for the first month shall be done at the MTC and if the patient is stable, he can be transferred out to the
nearest dispensing site for regular follow up. In case of any adverse event, s/he may come back to MTC.
5. Management of cases under special categories as per national guidelines(e.g.: paediatric patients,
thalassemics, patient with treatment failure etc. )
6. Ensure compliance and completion of treatment
7. Training and mentoring of other treatment sites
8. Operational research
Key Functions of MTC
1. Screening / Diagnosis of Suspected cases

2. Management of uncomplicated cases
3. Ensure that national guidelines and protocols are adhered to
4. Mange the complicated cases referred from Treatment centres
5. Maintain the data base and ensure timely reporting
6. Undertake training and mentoring of the Treatment centres in their region ( as defined by NVHMU
and SVHPU)
7. Participate in operational research as per the program needs
Hepatitis Treatment Centre

1. To ensure Screening/ Diagnosis in suspected cases of Hepatitis B/C Infection
2. Treatment and Management of uncomplicated Hepatitis B/C infection
3. In referrals for cases screened / diagnosed elsewhere, for the management of hepatitis and prescription
with drugs to be dispensed after first month from site nearest to patient convenience
4. Out referrals to MTC for clinical management as per national treatment guidelines.
Key Functions of a Treatment Centre
1. Screening / Diagnosis of Suspected cases

2. Management of uncomplicated cases
3. Ensure that national guidelines and protocols are adhered to
4. Referrals for complicated cases to MTC
5. Maintain the data base and ensure timely reporting
Selection criteria and steps for setting up a centre
Each site will be selected by the state, based on the burden of disease according to available evidence in form
of studies, outbreaks, case reports, blood bank data and existing capacities. Once the sites are identified and
proposed, a joint team will visit the facility and assess its feasibility for delivery of services, adequacy of needed
space and man power and willingness of the institute to set up such centre. The team that will undertake the
feasibility visit should ideally comprise of the state and district officials of the NVHCP, central unit officials and
other invited partners. The report of feasibility visit should be prepared, signed and kept with the state officials.
The format for feasibility visit is attached as annexure 1. Attempts will be made to provide services till PHC.

Inclusion criteria for consideration as a potential treatment site include:
1. Established evidence of case load for viral hepatitis infection or its sequel
2. Evidence of high hepatitis burden in catchment area
3. Commitment and willingness of the state government to have a treatment site and consequent
agreement to follow the SOP and protocols under the NVHCP
4. Availability of required infrastructure and existing capacities.
5. Availability of appropriate and optimum human resource for clinical and laboratory management, as well
as other services routinely.
Human Resource for the Treatment Sites
The services will be delivered through the existing health system and the institution will have to nominate a
nodal officer who would be responsible for the day to day functioning of the centres. Ideally, this could be the
Head of department of Internal Medicine/Gastro-enterology/Hepatology (or a person deputed /nominated by
head of the institution) in tertiary centres and the physician in district hospitals and elsewhere. The patients
should be seen by the attending physician from the system and the documentation of the patient data and
management should be recorded in the formats that are made available under the program.
To assist the delivery of services in a uni-flow system and to ensure efficacy, the treatment centres will be
provided the following staff under the program in a phased manner:
Staffing provided by the program (contractual staff)
The treatment centres so established should have the following manpower

S No Model Treatment centres
1 Medical officer – 1
2 Pharmacist -1
4 Peer support -1
S No Treatment centres
1 Pharmacist -1
3 Peer support -1
The NVHCP will evaluate and provide the same on a need based approach. Since the Model treatment centres
will also undertake additional tasks like training, mentoring, operational research and conducting review
meetings with state and NVHMU, they will be provided one contractual position of level of medical officer
(MO).
Approach to providing Treatment
The following sections and figure below elaborate on the flow of patient at the treatment centre and also can be
used to guide the smooth functioning of the staff.
There are two components:

1. Enrolment of the patient into care
2. Follow up visits of the patient

Enrolment of the patient: The patients who present to the centre could either have a definite diagnosis or might
have suspected infection. In case the person is found to have hepatitis C infection by the anti-HCV test (from a
government facility), they should be confirmed with HCV RNA as per the diagnosis algorithm in the national
guidelines. Every person who has a detectable HCV RNA is eligible to receive treatment after taking consent.
Patient presents to the Treatment centre
Treatment naiive Treatment experienced
Refer to Model Treatment Centre. If already

at MTC, to be managed case by case
Patient is referred from other health care provider or Refer to Model Treatment Centre. If already
presents due to suspicion/ perceived risk by self at MTC, to be managed case by case
Get a anti HCV done, and if positive get a HCV viral load done Refer to sections on laboratory above
Patient has a positive anti-HCV and a recent HCV Viral load that is detectable. Peer supporter enters the
details in HCV Treatment register and makes the HCV Treatment card
Doctor: Confirms the status, Examine the patient, Advises Baseline investigations and gives the
necessary forms. Peer supporter guides the patient to laboratory
Lab technician: draws the blood, performs the tests/ ensures transport and ensures that the reports
are generated and sent to the clinician at the treatment centre. Keeps close coordination with the peer
supporter and pharmacist. Ensures that test results are updated in records
Doctor reviews the case with clinical assessment and investigation, evaluates for the presence or
absence of cirrhosis (usingnon invasive criteria), prescribes the medicines as per the guidelines and send
to pharmacist. In case of specific situations*, refers the patient to MTC
Pharmacist dispenses the medicines as prescribed (28 days) and updates the drug stock and dispensing
register, gives a follow up date, reinforces adherence to treatment. Does pill count in follow up
Patient leaves the centre with clear

Data manager enters the data into the excel sheet
instruction for follow up
SVR done after completion of 12 weeks

of treatment
* Thesespecific situations are described in the treatment guidelines and include retreatment cases/
pregnant women/patients with decompensated cirrhosis, malignancy, renal insufficiency etc.
Every patient found anti HCV positive is registered in care for onward enrolment and has to be confirmed
with a detectable HCV viral load for being eligible for treatment. Cases where anti-HCV is positive but no HCV
viral RNA is detected do not have an active HCV infection and do not need treatment. Sequential entries for
all the registration are to be maintained in the hepatitis C Treatment Register. Once confirmed, the testing and
treatment card for the patient is made. It is made in two sets: one to be kept at the centre and other given to
the patient. The centre should take an address proof (Aadhaar card as UID is mandatory) from the patient. The
confidentiality of the information provided by the patient is to be protected at all cost. Any divulgence of such
information will have penal implication as per law for anyone responsible for such divulgence. The testing and
treatment card will capture patient demographic information diagnosis and treatment details.

The sections on name and demographic details are filled by the peer supporter while enrolling. The section on
the clinical parameters and the laboratory investigations are filled by the treating doctor. The service provider
signs the card at the respective places mentioned.
The data entry operator maintains the digitize format of the same.
The details are also entered at each visit as and when they are advised. The follow up entries help in monitoring
the disease progress, counselling of the patient for regular treatment, review of adherence of the patient to
therapy. The drugs will be dispensed for 28 days. However, the pharmacist should ensure that the patient is
given a follow-up day after 25 days. This will ensure that the patient does not land in a situation where s/he is
out of drug stock. At every visit, the pharmacist should also count the remaining drugs (pill count) to have an
idea if any doses have been missed. The patient should be instructed to bring the bottle of DAA with her/him at
every visit so that the pharmacist can perform pill count, collect the old bottle and issue a new one.
The complicated cases, as defined in the technical guidelines, should be referred to the MTC. At the MTC, the
drugs should be dispensed and once the patient is stable and the treating doctor is confident that the patient can
be managed at the nearest treatment site, then the drug dispensation can be done at the nearest site. However,
the patient should be referred back to MTC in case it is deemed necessary for appropriate management.
The uncomplicated cases, as defined in the technical guidelines, should be initiated treatment at the treatment
centre. Once the patient is stable and the treating doctor is confident that the patient can be managed at the
nearest treatment site, then the drug dispensation can be done at the nearest site. However, the patient should
be referred back in case it is deemed necessary for appropriate management.
Summary of the key actions to be undertaken for patient management and record maintenance and the
responsible person.
Visit Number Key activity (but not limited to( Responsible person
First visit and baseline, after Ascertain Diagnosis of active Hepatitis C Attending doctor
confirmation of active hepatitis C )anti HCV as well as HCV RNA(
infection Enter patient details in Hepatitis C Treatment Peer Supporter
Register and demographic details in treatment
card
Take a detailed history and examination Attending Doctor
Categorize presence/Absence of Cirrhosis and fill Attending Doctor
relevant section in Treatment card
Select Regimen and start treatment Attending Doctor
Explain patient on adherence and follow up date Peer supporter and
pharmacist
Dispense prescribed medicines Pharmacist
Get the baseline investigations done and furnish Doctor, Lab technician
report to centre
Follow up visit Educate on adherence and regular follow up Doctor ,Peer supporter
and pharmacist
Check for any side effects Attending Doctor
Get any investigations needed as per technical Attending Doctor
guidelines, prescribe the medicines
Update investigations in treatment card Lab technician, Doctor
End of Treatment Counsel on Treatment completion and need for Doctor, peer supporter
weeks of completing treatment 12 SVR after
Recheck the contact details including phone Peer supporter
For all visits Update the record from the register and card to Data entry operator
the excel based sheet

Ideally, there should be no expiry at any centre. However, in the event there is expiry of some medicines under
the program, they should be discarded as per the hospital policy. The process should be documented with details
on the quantity of drug, batch number and should be signed by three regular government employees including
the nodal officer of the centre. In case there is no institutional policy for discarding the medicines, from the
central and state unit for viral hepatitis under NHM must be sought through a written communication clearly
mentioning the absence of such institutional policy. Justifications and reasons for the same must be recorded in
writing and kept for review by supervising authorities
Monitoring and Evaluation of the Treatment sites
The treatment sites and the laboratory will be reviewed regularly by the nodal officers for the site level day to
day functioning. In addition, the district/state and National officials will also undertake supervisory site visits
for supportive supervision and mentoring. The suggested frequency of the monitoring and mentoring visits are:
Level Frequency of visit

National Annual
State Quarterly
District Once monthly
During the visits, the officials should try and provide on spot trouble shooting wherever needed, should provide
clarification, assess the HR availability and required infrastructure, check the completeness and quality of
records and reports submitted and randomly check the drug stocks ( physical stocks versus the reported stocks)
Additionally, review meetings will be conducted that will provide a platform for experience sharing and review
the progress.
Recording tools
The following recording tools are to be used under the program:

1. Site Feasibility Form:
2. Patient Treatment card :
a. To be maintained at centre
b. Patient Treatment card ( for the patient to retain)
3. Hepatitis C Treatment register:
4. Drug stock and dispensing register:
5. Excel based tool for comprehensive record in the documents above.
(Detailed operational guidelines on the care, support and Treatment services for hepatitis C services have
been developed and should be referred to for details on site selection, manpower, pattern of assistance, patient
management and M & E etc. A detailed guidance on operational issues for management of hepatitis B will be issued
subsequently.)

Level Screening Confirmation Treatment of Treatment of
uncomplicated cases Complicated case
Health and Wellness Introduced
centres in phased
manner
PHC Y
CHC Y Y In phased manner after
assessing capacity
District Hospital Y Y Y
Medical Colleges and Y Y Y Y
specialised centres ( MTC)
States will select the number and locations of sites based on capacity assessment and feasibility visits and
propose in the State PIP. The services shall be scaled up till PHC
The treatment centres so established should have the following manpower

S No Model Treatment centres
1 Medical officer – 1
2 Pharmacist -1
4 Peer support -1

ChapteR 6
Supply Chain Management
There will be central procurement of diagnostic equipment, kits and drugs at the national level so as to ensure
quality and advantage of economies of scale. These would be provided directly under intimation of the state
programme management unit. Each centre will have to generate demand based in the consumption as per the
given targets annually.
Once the kits/drugs are provided, a lead time of at least 12 weeks to raise the demand to the central agency will
be required to ensure no disruption to supply chain.
The nodal officer in the SVHMU/DVHMU will monitor the same monthly with the facility.
10% buffer to account for quality control/wastage. Supply will be monitored by the centre/state. Supply to the
point of consignee periodically in atleast 2 lots per year.
At the time of receipt of the consignment, the nodal officer will keep the receipt in original; will get the stock
verified after that sign on the receipt of the consignment. The receipt in original will be sent to the state
coordination unit for onward transmission to the NVHMU after keeping due record at all level. For serological
tests, equipment will be available in the designated labs. Consumables will be procured locally/through state
depending upon the state policy

Chapter 7
Trainings
Trainings are important for any new initiative as well as for building capacity of the service delivery points for
effective implementation. To ensure standardized and uniform quality of service delivery, there will be capacity
building of different cadres of staff in the NVHCP, using standardized training modules and facilitator guides.
The trainings for building capacities of the human resource under the NVHCP will be planned by NVHMU
and conducted by identified institutions like model treatment centres and state laboratories using both
conventional and digital technology. An ongoing mentoring through digital platform for case discussion and
to address various technical issues will be undertaken by Centre of Excellence and the Institute of Liver and
Biliary Sciences (ILBS) to maintain and improve quality of care. The training approach will be in hub and spoke
model where National Institutes will impart training to trainers and develop Training modules. There should
be special trainings conducted for sensitization on confidentiality and respecting the status of a positive patient.
1st Year
0-3 months •• Identification of the sentinel site labs and Model Treatment Centres
•• Identification of the regular officers for carrying out the NVHCP
•• Recruitment of Human Resource
•• Capacity building of the 15 sentinel site labs and Model Treatment Centre by CoE
3-6 months •• Capacity Building of the 50 state labs. (Minimum of 4 persons/lab to be trained)
•• Training of 15 Model Treatment Centres (All cadre of staff) (15X5=75-minimum persons
trained)
6-12 months •• Cascade training of identified district/sub-district upto level of PHC labs for viral
hepatitis testing. The training of trainers will be in a tiered cascade mechanism.
Standardized training modules will be shared
•• Training of the treatment centres (All cadre of staff) (Minimum of 4 persons/centre to be
trained)
2st Year
>12months-24months •• Capacity Building of the Treatment Centres (other than the MTC) and other districts/
CHC/PHC labs for viral hepatitis testing
•• (Minimum of 2 persons/lab to be trained at district level)
•• (Minimum of 2 persons/treatment site to be trained)

ChapteR 8
Monitoring and Evaluation
Data management
Timeliness is a key feature of an efficient delivery system. A computerized data management system under the
‘Integrated Initiative for Prevention and Control of Viral Hepatitis’ would facilitate automated data transfer,
data validation, monitoring and evaluation. Data should therefore, be entered in standard data formats at the
source, in software capable of handling multilevel entries and validation. Standard formats for recording and
reporting will be prescribed by the NVHMU. The data needs to be shared by all the service delivery points,
maintaining confidentiality.
Review meetings of the SVHMU officials will be organized on a quarterly basis to assess physical and financial
progress, discuss constraints in implementation of the NVHCP and identify solutions to key barriers and bottle
necks. Key gaps identified during the implementation of the NVHCP will also be addressed through planned
operational research.
In addition to the data collected from the service delivery points in the newer activities (diagnosis and management
of viral hepatitis, etc.), the NVHCP will also coordinate with the existing programs and schemes that contribute
towards the response to viral hepatitis and this would be compiled for monitoring a comprehensive program
update at national level as well as for fulfilling the international commitments and reporting.
Record keeping
Proper record keeping of client results is vital for providing quality service, tackling the medico-legal issues,
and operational research. As per the guidelines, all documents must be stored for at least 5 years or as per state/
institutional guidelines whichever is longer.
Indicators
The NVHCP has some components that involve coordination with other existing programs and schemes, and
there are few interventions that are new and will be directly implemented under the aegis of NHM. These have
been discussed in the respective sections and the relevant targets have been enlisted there. A compiled table for
the indicators is attached in Annexure 3.
Independent evaluation of the NVHCP will also be planned and organized by National Program Management
Unit. Key gaps identified during implementation of the NVHCP and innovative interventions would also be
planned through operational research and will follow the established procedures under the guidance from the
NVHMU.

Chapter 9
Pattern of Assistance and Flow of Funds
Data management
The states will need to factor in their budget proposal in the Programme implementation plan based on the
annexure 4.
The flow of funds will be in the mechanisms prescribed under NHM

ChapteR 10
Bibliography
1. World Health Organization. WHO Global Hepatitis Report. 2017.
2. World Health Organization media centre. Hepatitis A fact sheet in world health
organization media centre. [Online] 2016. http://www.who.int/mediacentre/.
3. MoHFW, WHO, ILBS. Technical Consultation: World Hepatitis Day . New Delhi : s.n., 2014.
4. MoHFW-WHO-ILBS.Third GoI-WHO-ILBS National Technical Consultation on Viral Hepatitis-

Towards a National Action Plan for Viral Hepatitis (NAP-VH) . New Delhi : s.n., 2016.
5. Goel, Amit. Hepatitis C Virus Infection in India:A Systematic Review of Seroprevalence

Data. Dept of gastroenterology, SGPGI, WHO India Country Office. 2017.
6. Central Bureau of Health Intelligence, Ministry of Health and Family

Welfare. National Health Profile. New Delhi : s.n., 2016.
7. Cost-effectiveness of Hepatitis C Treatment using generic direct-acting antivirals

available in India. Aggarwal, R, et al., et al. s.l. : PLOS One, 2017, Vol. 12. e0176503.
8. Prevalence of Hepatitis A virus, Hepatitis B virus, Hepatitis C virus, Hepatitis D virus and
Hepatitis E virus as causes of acute viral hepatitis in north India: A Hospital based study. Jain,
Prakash P, et al., et al. 2013, Indian Journal of Medical Microbiology, Vol. 31, pp. 261-5.
9. National Strategic Plan for HIV/AIDS 2017-2024;NACO MoHFW

Annexure 1: Feasibility Visit for Setting Hepatitis Treatment Centre
Checklist for Feasibility of Hepatitis Treatment Center

1 Name of the town / District/ City:
2 Type of Hospital: ( Medical College/ District Hospital / Other tertiary care)
3 Name of the Medical Superintendent or IC of the institution
4 Names of the identified Nodal officer by Institute
5 Date of Feasibility Visit
6 Members of the Visiting Team
a
b
c
d
7 Complete postal address of the Hospital with Pin Code
8 Contact details of the Nodal person ( mobile and email )
BACKGROUND INFORMATION
1 Is the Institution willing to set up a center for hepatitis treatment Yes No
2 Is the In-charge keen on establishing services? Yes No
a Willing to allocate necessary space Yes No
b Willing to have nodal person for treatment and lab services Yes No
c Integrate the functioning and follow the National guidelines Yes No
and protocols , including recording and reporting
3 What is the annual OPD of the hospital
4 Is there super-speciality( Gastroenterology/ Hepatology) Yes No
5 How many cases of acute hepatitis are seen annually ( explore last years report)
6 How many cases of hepatitis B and C are seeking care ( explore previous reports)
7 Is there a blood bank in institute? What is sero-positivity for hepatitis Yes No
B and hepatitis C in last three years ( record year wise)
8 If this is a district hospital, where are patients referred
or usually go for complicated cases?
9 Do you have a HIV related service?
a ICTC Yes No
b ART center Yes No
c Opioid Substitution Center Yes No
d Involvement with Prison Yes No
8 Is the institution implementing any other program under NHM? Please mention name(s) Yes No
INFRASTRUCTURE
1 Location of the proposed centre ( is it in vicinity to OPD services) Yes No
Is there an ICU Yes No
2 Number of rooms
a Doctors Yes No
b Pharmacist Yes No
c Data Entry Operators Yes No
d Drug Storage & Pharmacist Yes No
e Lab Technician Yes No
f Peer supporter Yes No
3 Is institution willing to provide necessary furniture ( chairs, tables, Almirah etc) Yes No
4 Will the center have access to internet Yes No

HUMAN RESOURCES
1 Does the institution have the required capacity to manage chronic hepatitis Cases? Yes No
a Gastroenterologist/Hepatologist Yes No
c Physician ( Internal Medicine) Yes No
d Pediatrician Yes No
e Microbiologist Yes No
f Pathologist Yes No
g Obstetrician Yes No
h Others (Mention)
LABORATORY CAPACITY / INVESTIGATIONS FACILITY
1 Does the institute have a capacity to do HCV RNA Yes No
2 Does the Institution have facility to do HCV Screening Yes No
test (immunoassay - please specify)
3 Are the following investigation routinely available Yes No
a Complete Blood Count / Hemogram Yes No
b Renal Function test Yes No
c Liver Function Test (please ask for each test) Yes No
d Blood Sugar Yes No
e INR Yes No
f Platelet count Yes No
g Pregnancy Test Yes No
h X Ray Yes No
I Ultra Sound abdomen with Doppler Yes No
J Fibroscan Yes No
k CT scan
l MRI
m Endoscopy
n Liver Biopsy Yes No
o Others
S No Key Issues Identified Follow-up Actions suggested
FINAL RECOMMENDATION OF THE TEAM (Please tick)

Recommended to Select Site for Opening Hepatitis Treatment Site
Not Recommended to Select Site for Opening Hepatitis Treatment Site
Signature of the Feasibility Visit Team: 1……………………………………………
2……………………………………………
3……………………………………………
4…………………………………………….

Annexure 2: Monitoring and Evaluation Indicators
Table 1: Monitoring Indicators for Diagnosis and Management of Viral Hepatitis

Achievement Source of
Sl. No. Base line reporting/data/
Indicator Target Target Target verification
Year 1 Year 2 Year 3 and level
Input indicators
1. National Program Management Unit
N/A Yes Yes Yes NHM
established
2. Number of states in which State Program NHM/ State
Management Unit has been established N/A 30 30 30 Health
Machinery
3. Cumulative number of state labs strengthened NVHMU/
to carry out testing under the initiative 10 60 65 State Health
Machinery
4. Cumulative number of district labs
strengthened to carry out testing under the 0 300 600
initiative
5. Cumulative number of treatment sites NVHMU/
strengthened under the initiative N/A 15 60 100 State Health
Machinery
6. Are operational guidelines for the initiative Program
developed? N/A Yes Documents at
NHM
7. Are standard laboratory guidelines for Program
diagnosing of Viral Hepatitis developed under N/A Yes Documents at
the initiative? NHM
8. Are standard treatment guidelines for Viral Program
Hepatitis developed under the initiative? N/A Yes √ √ documents at
NHM
9. Is there a standard Training curriculum Program
developed for the initiative? N/A yes √ √ Documents at
NPMU
Process Indicators
1. % of State laboratory sites which have been Training report;
trained on the SOPs for labs with respect to 0 100% 100% 100% NPMU and
diagnosis of Viral Hepatitis under the initiative SPMU
2. % of Treatment sites which have been
trained on the SOPs on Management of Viral Training report;
N/A 100% 100% 100%
Hepatitis with focus on Hepatitis C under the NPMU/ SPMU
initiative
Output Indicators
1 Number of new serological tests done for 30.1 Compiled
N/A 1.6 lakh 10.1lakh
diagnosing viral hepatitis lakh facility report
2 Number of new patients initiated on treatment Compiled
N/A 1 lakh 1lakh 1 lakh
of hepatitis C facility report

Table 2: Monitoring Indicators - Integration with other programs and Ministries/Departments
Target Source
Frequency of
(Information
S.N0. Indicator Year 3 reporting to
Year 1 Year 2 to be collected
(2020) NPMU
by NPMU-VH)
1. Proportion(%) of infants (<12 months
Immunization
of age) who received the third dose of 95% 95% >95% Bi annually
Program
hepatitis B
2. Proportion (%) of newborns who have
Immunization
benefited from timely birth dose of 95% 95% >95% Bi annually
Program
hepatitis vaccine
3. Routine Hepatitis B vaccination among Available
health-care workers. (for all
N/A
who
need it)
4. Number of needles–syringes
distributed per person who injects As per NACO NACO Annually
drugs
5. Is Vaccination for Hepatitis B available Currently No; Policy decision
NACO Bi annually
to key populations by NACO
Proportion of NACO and
blood units 100% 100% NHM ( to report Bi annually
6. screened for TTIs (HBV and HCV) as % and
Proportion of all blood donations that numbers to
80% NPMU –VH) Bi annually
are voluntary
7. Proportion of health-care facilities
(sampled) where all injections are safe 50% Survey Year 3
( RUP)
Viral Hepatitis Control Program – Operational Guidelines

Annexure 3: Terms of Reference of Human Resource
Laboratory In-charge (State Lab)
Designated Microbiologist of the Institution, or Pathologist in the absence of Microbiologist

Job Responsibilities
1. Supervises the work of laboratory personnel
2. Verification and signing of reports generated in the laboratory
3. Ensuring that all job responsibilities are adhered to, by all laboratory personnel
4. Management of funds with relation to laboratory
5. Ensure participation in and review of EQA
6. Ensure training and competence of all the laboratory personnel
7. Ensuring timely reporting of data.
Technical officer (State Lab)

Qualification: MSc Medical Microbiology with 1 year experience in clinical laboratory services. Candidates
with PhD Medical Microbiology from recognized university with 3 months experience in clinical laboratory
services will be preferred.
1. Supervises the work of Laboratory technician under the guidance of the Laboratory In-charge.
2. Molecular testing where available
3. Preparation of SOPs and work instructions.
4. Verification of reports generated in testing laboratory
5. Preparation of quality control (QC) samples
6. Preparation & distribution of proficiency panels (PT) panels
7. Inventory and financial document management in lab.
8. Maintaining and monitoring timely calibration / verification of all devices and ensuring that all
monitoring and measurements are done with devices having valid verification / calibration status.
9. Adherence to Bio-safety guidelines.
10. Maintenance of records and logs in laboratory.
11. Disposition of nonconforming products in her area of operation.
12. Help in the conduct of teaching and training programs.
13. Participate in surveillance activities of programme, through NCDC
14. Onsite field visit to district lab for mentoring and quality assurance.
15. Reporting to laboratory In-charge
16. Any other duty assigned by laboratory In-charge

Laboratory Technician (State/District Laboratory):
Qualification: DMLT two year course or certificate in MLT for one year or B.Sc in MLT from
recognized university.
1. Collect / receive specimens in the laboratory.
2. Assist in sample transportation to referral laboratory as and when required.
3. Performs tests for hepatitis markers and preparation of reports.
4. Storage and maintenance of serum samples as per guidance.
5. Confirmation of reference samples from state medical college labs and compilation of reports.
6. Perform regular internal quality control testing, EQA and their documentation
7. To maintain essential records in the laboratory
8. Inventory preparation for equipment and reagents.
9. Indent for supplies to the Laboratory through Lab In charge and ensure sufficient stock of Laboratory
consumables is available.
10. Participate in trainings and workshops conducted.
11. Assist in molecular testing of samples where required.
12. To maintain cleanliness in and safety and follow proper biomedical waste disposals.
13. Any other work/ activity assigned from time to time.
Data Entry Operator (State laboratory):

Qualification: The Data Entry Operator should be a graduate with Diploma in Computer Applications (from a
recognized institute or university) or ‘O’ Level course from DOEACC. S/he has to undergo training under the
initiative in monitoring and evaluation tools (M & E) of the initiative aimed to build the capacity of the person
in recording data, preparing and sending reports and maintaining records properly.
Job responsibilities of Data Entry Operator:

1. S/he has to work under the guidance and supervision of nodal officer (Microbiologist)
2. Ensure that all data recording and reporting is updated for all activities under the initiative, including
surveillance of viral hepatitis, if the lab is also participating in the surveillance program for viral hepatitis
3. Print and share all circulars/information sent by NHM/States to the Nodal Officer and maintain a file for
orders/communication
4. Maintain the attendance register for the staff and get it verified by the nodal officer (daily/ end
of the month)
5. Maintain the personnel file/s including the bio-data of the staff, copies of certificates, appointment letters,
contractual service agreement, performance appraisal report, training details, remuneration etc
6. Prepare and send all the monthly reports prescribed by the initiative after approval of Nodal Officer
7. Assist in analysis of data under the supervision of the Nodal Officer
8. Any other duty assigned by nodal officer.

Terms of Reference for various staff at Treatment site
1. Nodal Officer
1. Overall responsibility of the functioning of the centre, reporting to state / central unit, participation
in review meeting, coordinate and develop referral system and linkages with other departments of the
hospital
2. Ensure that patient are not discriminated in the hospital and are not denied admission/ care.
3. Ensure that all ethical practices including confidentiality are maintained.
4. Ensure availability of adequate stock of quality drugs as per defined targets at all times
5. Ensure reporting of any short expiry drug in a timely manner to allow timely relocation and avoid
financial loss
6. All administrative matters relating to the centre including sanctioning of leave of contractual staff,
annual performance appraisal of the staff etc as per guidelines
7. Ensure adherence to the highest standards of quality and excellence in patient care
8. Ensure that all staff should be entering data electronically
9. Review and monitor the functioning of the centre periodically and in depth and ensure submission of
reports as required.
10. Act as Focal point for interaction with central unit/ State program management officials etc
2. Medical officer ( MO) of Model Treatment Centre ( MTC)
Qualification: The MO should be a Medical graduate (MBBS) with 5 years of experience in clinical care preferably
related to infectious diseases. S/he must be registered in the concerned state Medical Council.
1. S/he is the functional team leader of the centre under the overall guidance of the Nodal officer. The
MO has to supervise the administrative and medical functions of the centre on a day- to- day basis and
provide leadership to staff to work as a cohesive team and deliver the services effectively
2. S/he should examine the patients, advise required investigations, review the investigations and prescribe
the treatment.
3. Refer difficult/ complicated cases to the Nodal Officer or other specialist for further expert opinion and
interventions including admission and inpatient care, if required
4. Monitor the consumption and availability of drugs, and alert the concerned authorities in case of
impending shortage well in advance so as to enable adequate replenishment without disruption of
services
5. S/he must ensure that all records, registers, cards are updated on a daily basis and reports are sent to the
concerned authorities on time. All reports should be checked by the MO before taking approval from the
Nodal Officer for sending them to the concerned authorities
6. S/he has to ensure that the guidelines for running and maintaining the centre are abided by.
7. Facilitate and coordinate trainings in the centre.
8. Ensure that a daily due list is prepared for the patients expected to visit and a follow up action is taken to
contact the defaulting patients.
9. Any other duty assigned by Nodal Officer/ Programme.

3. Pharmacist
Qualification: The pharmacist should hold a Degree in Pharmacy from a recognized institute. If candidate with
degree is not available, diploma holder in pharmacy with 3 years of experience in health care institution can be
considered. S/he must be registered in the concerned state pharmacy council.
Job responsibilities of Pharmacist:

1. S/he has to work under the guidance and supervision of nodal officer/MO
2. Dispense drugs with proper counselling / interaction with patient
3. Advise the patients and family about the importance of adherence during each visit
4. Counsel the patient on possible drug toxicities and report the same, if significant
5. Do pill count and report any adverse effects of drugs Also, confirm the next visit date and inform the
patient
6. Maintenance of the drug stores
7. Maintain and update drug stock and drug dispensing registers regularly every day. Inform the concerned
medical and nodal officer in case of any discrepancy. Duly take signature of nodal officer every
fortnightly in the stock register
8. Ensure that the centre has enough stock of drugs for at least 3 months and inform the concerned
authority about any near expiry or excess stocks well in time for relocation to other sites and ensure FEFO
protocol is followed
9. Physical verification of the drugs under the supervision of the nodal officer and/or the MO
10. Besides all the above, any other duty assigned by nodal officer.
In case pharmacist is not available/on leave, the nodal officer in consultation with the head of institute will
make any alternative arrangement so that the functioning does not suffer and regular staff of the facility must
also be integrated for service delivery.
4. Data entry operator
Qualification: The Data entry operator should be a graduate with Diploma in Computer Applications (from
a recognized institute or university) or ‘O’ Level course from DOEACC. S/he has to undergo training under
the initiative in monitoring and evaluation tools (M & E) of the programme aimed to build the capacity of the
person in recording data, preparing and sending reports and maintaining records properly.

1. S/he has to work under the guidance and supervision of MO and/or nodal officer
2. Ensure that all data recording and reporting is updated
3. Print and share all circulars/information sent by central unit/States to the Nodal Officer/MO and
maintain a file for the important orders/communication
4. Maintain the attendance register for the centre staff and get it verified by the nodal officer everyday and
by the Nodal Officer at the end of the month
5. Maintain the HR file including the bio-data of the staff, copies of certificates, appointment letters,
6. Prepare and send all the monthly reports prescribed by central unit after approval of Nodal Officer

5. Peer supporter
Qualification: The peer supporter should be a person preferably with or recovered from the disease (hepatitis B
or hepatitis C), with a minimum of intermediate (12th) level education. S/he must also have sound knowledge of
the local language and working knowledge of English.
Job responsibilities of peer supporter:

1. S/he has to work under the guidance and supervision of nodal officer /MO
2. Be the first interface with patient at centre
3. Ensure entries in the visit register
4. Be a peer educator for patients at centre and provide psycho-social support to newly registered patients
5. Provide assistance to patients enrolled at the centre, within the hospital (OP and IP)
6. Discuss the importance of adherence to treatment and need of viral load at 12 weeks post treatment
(SVR) with the patients , Keep track of drug adherence of patients , counselling them on the importance of
regularity of visits and timely investigations
7. Follow up the patients and assist in patient retrieval, where necessary and as far as possible
8. Undertake data entry in absence of the data entry operator
9. Any other duty related to the initiative assigned by nodal officer/MO

Annexure 4: Summary of financial allocations
S. Type of facility Areas covered Unit Cost for the facility Remarks
No (Rs)
1. State Coordination Manpower As described in the table To be adapted as per
unit above state need.
Other grant to state 12.87 lakhs As per need
-Equipment (one time grant
for computer set ,printer, (2.7 lakhs for small
photocopier and scanner) states- Goa, Uttarakhand
Other administrative , Sikkim and Tripura)
expenses (meeting/travel/
contingency)
2. State Laboratory Manpower as per the state 17.24 lakhs Refer to national
NHM norms and other laboratory guidelines on
administrative expenses( viral hepatitis testing for
meeting/travel/contingency) more details
3. Model Treatment Human resource as per 21.72 lakhs Refer to operational
Centre the state norms (described guidelines for roll out of
above), contingency, grant- Hepatitis C treatment for
in-aid, meetings and training more details
cost
4. Treatment Centres Human resource as per 5.335 lakhs Refer to operational
the state norms (described guidelines for roll out of
above), contingency, grant- Hepatitis C treatment for
in-aid, meetings and training more details
cost
5. Procurement Test kits and Drugs – to be centrally procured.
6. District lab Need based provision of one lab technician at state
NHM norms

Annexure 5: Patient entry and service availability at various levels of
health care
Level Patient Diagnostics Management

entry Screening ( Diagnosis( Advanced Uncomplicated Complicated
RDT) ELISA/ diagnostics
CLIA; LFT; / Quality
molecular Control
H &WC
Below
PHC  (Dispensing)
District
CHC  (Dispensing)
District District
level Level
State MTC/
Level State lab

List of Contributors
1. Mr Manoj Jhalani, Additional Secretary & Mission Director, NHM, MoHFW

2. Dr Manohar Agnani, Joint Secretary, MoHFW
3. Mr Lav Agarwal, Joint Secretary, MoHFW
4. Mr Vikas Sheel, Joint Secretary, MoHFW
5. Dr S.K. Sarin, Director, ILBS, Delhi
6. Dr S.K. Singh, Director, NCDC, DteGHS, MoHFW
7. Dr Sandhya Kabra, Additional Director, NCDC, DteGHS, MoHFW
8. Dr Partha Rakshit, Deputy Director, NCDC, DteGHS, MoHFW
9. Dr Hema Gogia, Deputy Assistant Director, NCDC, DteGHS, MoHFW
10. Dr Preeti Madan, EIS Officer, NCDC
11. Dr Nicole Seguy, Team leader Communicable Diseases, WHO India
12. Dr Vimlesh Purohit, National Professional Officer, WHO India
13. Dr Rekha Jain, Consultant
14. Technical Resource Groups on
• Care Support and Treatment
• Laboratory Services
• Surveillance
15. Representatives from community and civil society
16. Members of the working groups for preparation of National Action Plan-Viral Hepatitis

Technical Guidelines for
Diagnosis & management of Hepatitis B
2019
FOREWORD
The National Viral Hepatitis Control Programme, a new initiative under the National Health Mission, marks
the beginning of the nation’s journey to control Viral Hepatitis and thereby reducing mortality and morbidity
attributed to it. It is envisioned that this programme wilt reach large number of persons possible harboring the
infection.
This document provides implementation strategies for treatment of Hepatitis B on how to reverse this alarming
trend of Viral Hepatitis B, describing a number of high-impact interventions and opportunities for their scaled-
up implementation.
The recommendations in these guidelines promote the use of simple, non-invasive diagnostic tests to assess
the stage of tiver disease and eligibility for treatment; prioritize treatment for those with most advanced liver
disease and at greatest risk of mortality and recommend the preferred use of nucleos(t) ide with a high barrier
to drug resistance for first and second-tine treatment.
I hope that these Technical and Operational Guidelines with inputs from stalwarts from across the country
will enable effective roll out of Hepatitis B diagnosis and management in India. I wish National Viral Hepatitis
Control Programme all success.
Preface
Viral hepatitis is a public health problem in India. Hepatitis A and E, which are water and foodbome infections, are often
the cause for sporadic cases or outbreaks of viral hepatitis in India. Hepatitis B and C infections can lead to chronicity and
thereafter sequelae like cirrhosis and hepatocellular carcinoma, which account for majority of hepatitis B and C related
deaths.
Hepatitis B virus (HBV) infection is a significant health problem in India. Since India has one-fifth of the world’s population,
it possibly accounts for a large proportion of the worldwide HBV burden. It is estimated that 15 - 25% of these chronic
hepatitis B cases are likely to suffer from cirrhosis and liver cancer and may die prematurely.
The Government of India launched National Viral Hepatitis Control Program (NVHCP) on the World Hepatitis Day (28th
July 2018) with provision of free diagnosis and treatment for viral hepatitis through the National Health Mission.
Horizontal transmission in childhood and Mother to Child transmission of HBV are considered to be the most common
mode of transmission. However, the HBV infection is both preventable by a very effective vaccine as well as treatable with
oral drugs. The hepatitis B vaccine has been incorporated in the current Universal Immunization Program; the first dose is
given as early as possible after birth, preferably within 24 hours for preventing perinatal HBV transmission.
The NVHCP entails free diagnostics and treatment of chronic hepatitis B and it is important to have standard diagnostic
algorithm and treatment protocols that are followed across the country. These guidelines provide this standardization in
a public health approach. This guidance d(])cument is the collective effort of the members of Technical Resource Group on
care and support for viral hepatitis, with representation of clinicians, laboratorians and program managers from across
the country, representing different sectors (government, private, academic institutes, community members, development
partners). The group has taken into considerations the latest available evidence and global guidelines, and adapted them
to the Indian context.
I hope; these guidelines will offer the needed technical guidance for delivering quality treatment and services for successful
implementation of the program.
Office
Department of Hepatology, Room
Number 6, D Block, Nehru Hospital,
Postgraduate Institute of Medical
Education and Research, Chandigarh
Secretary General, Indian National Association for the Study of the Liver (INASL) 160012, India
Editor-in-Chief, Journal of Clinical & Experimental Hepatology (JCEH) Email: [email protected] Tel:
Past President, International Society for Hepatic Encephalopathy & Nitrogen Metabolism +911722756335, +917087009337,
(ISHEN) +919914209337 (PA).
ACRONYMS
AFP Alfa Feto Protein
AIDS Acquired Immuno Deficiency Syndrome
ALP Alkaline Phosphatase
ALT Alanine amino transferase
Anti-HBc Antibody to Hepatitis B core antigen
Anti-HBe Antibody to Hepatitis B envelope antigen
APRI AST to Platelet Ratio Index
ARVs Anti Retro Virals
AST Aspartate aminotransferase
CBC Complete Blood cell Count
CD4 Cluster of Differentiation 4
CEMRI Contrast Enhanced Magnetic Resonance Imaging
CHB Chronic Hepatitis B
d4T Stavudine
DCV Daclatasvir
ddI Didanosine
DDIs Drug Drug Interactions
DNA Deoxyribo Nucleic Acid
Department of Electronics and Accreditation of Computer
DOEACC
Courses
DPT Diptheria Pertussis Tetanus
EASL European Association for Study of the Liver
eGFR estimated Glomerular Filtration Rate
HBIG Hepatitis B Immuno Globulin
HBsAg Hepatitis B Surface Antigen
HBeAg Hepatitis B envelope Antigen
HCVcAg Hepatitis C Virus core Antigen
Hib Haemophilus influenzae type b
HR Human Resource
ICTC Integrated Counseling and Testing Centre
IDSP Integrated Disease Surveillance Programme
INR International normalized ratio
IP In Patient
LDV Ledipasvir
MO Medical Officer
MTC Model Treatment Centres
NAs Nucleos(t)ide analogues
NITs Non Invasive Tests
NPMU Non Steroidal Anti Inflammatory Drug
NSAID National Viral Hepatitis Management Unit
NVP Nevirapine
OP Out Patient
PCR Polymerase Chain Reaction
PEG Pegylated Interferon
PLHIV People Living with HIV
PMU Program Management Unit
QC Quality Control
RAS Resistance-Associated Substitution
RBV Ribavarin
RNA Ribo-nucleic acid
SoE Statement of Expenditure
SOF Sofosbuvir
SOP Standard Operating Procedure
SPMU State Surveillance Officer
SSO State Viral Hepatitis Management Unit
TAF Tenofovir Alafenamide Fumarate
TB Tuberculosis
TC Treatment Centre
TDF Tenofovir Disoproxil Fumarate
TG Transgender
TPCT Tri Phasic Computerised Tomography
UID Unique Identification
ULN Upper limit of normal
USG Ultra Sono Graphy
VEL Velpatasvir
CONTENTS
Background 12
Hepatitis B Virus 18
Diagnosis of Hepatitis 19
Whom to Treat 22
Treatment: What to treat with? 23
Referral to Model Treatment Centers 24
Hepatitis B infection and Pregnancy 24
Chronic Hepatitis B in Children and Adolescents 25
Organization of Services 27
Laboratory Services 27
Whom To Test 28
Treatment Services 28
Objectives and functions of the Treatment Sites 28
Selection criteria and steps for setting up a Treatment Site 30
Infrastructure 30
Human Resource 31
Training 35
Logistics 36
Financial management 36
Patient Flow at the Treatment Centers 37
Monitoring and Evaluation of Hepatitis B Treatment 40
Introduction 40
Objectives of the Monitoring and Evaluation framework 40
Monitoring Indicators 41
Data Sources 41
Recording and Reporting at various levels and flow of information 41
Review meetings & Supervisory visits 42
Evaluation 43
Annexures 44
Annexure 1: Assessing severity of liver disease 44
Annexure 2: Summary Guidance for the Model Treatment Center (MTC) 46
for some special situations
Response to Treatment 46
Virological responses 46
Use of TAF in Chronic Hepatitis B 47
Entecavir Dose in Renal Impairment 47
Use of Pegylated Interferon 47
Monitoring Patients for HCC, with a family history of HBV related HCC 47
Annexure 3: Site Feasibility Checklist 50
Annexure 4: Hepatitis B Care Register 52
Annexure 5: Hepatitis B Treatment Register 53
Annexure 6: Testing & Treatment Card 56
Monthly Report 58
Annexure 8: Drug Stock Register 59
Annexure 9 :Drug Dispensation Register 59
Annexure 10: Supervisory Checklist 60
References 62
List of Contributors 63
Background

12 Diagnosis & management of Hepatitis B
global
Epidemiology of Viral Hepatitis Global Viral hepatitis is now recognized as a major public health challenge
that requires an urgent response. Viral Hepatitis caused 1.34 million deaths in 2015, a number comparable to
deaths caused by tuberculosis and higher than those caused by HIV. (1) It is estimated that worldwide, Hepatitis
A Virus (HAV) infections caused approximately 11,000 deaths in 2015 (accounting for 0.8% of the mortality
from viral hepatitis). (2) It is estimated that 325 million people worldwide are living with chronic HBV or HCV
infection. Approximately, 1.75 million people were estimated to be newly infected with HCV in 2015, increasing
the total number of people living with Hepatitis C to 71 million. (1) Every year, there are an estimated 20 million
Hepatitis E Virus (HEV) infections worldwide leading to an estimated 3.3 million symptomatic cases of acute
hepatitis E. It is estimated that Hepatitis E caused 44,000 deaths in 2015 (accounting for 3.3% of mortality due
to viral hepatitis). (1)
India
Viral hepatitis is increasingly being recognized as a public health problem in India. HAV and HEV are important
causes of acute viral hepatitis and Acute Liver Failure (ALF). Due to paucity of data, the exact burden of disease
for the country is not established. However, available literature indicates a wide range and suggests that HAV is
responsible for 10-30% of acute hepatitis and 5-15% of acute liver failure cases in India. It is further reported that
HEV accounts for 10-40% of acute hepatitis and 15-45% of acute liver failure. (3)
Hepatitis B surface Antigen (HBsAg) positivity in the general population ranges from 1.1% to 12.2%, with
an average prevalence of 3-4%. Anti-Hepatitis C virus (HCV) antibody prevalence in the general population
is estimated to be between 0.09-15%. (3) Based on some regional level studies, it is estimated that in India,
approximately 40 million people are chronically infected with Hepatitis B and 6-12 million people with Hepatitis
C. (4) Chronic HBV infection accounts for 40% of Hepato-cellular Carcinoma (HCC) and 20-30% cases of cirrhosis
in India. (3) Chronic HCV infection accounts for 12-32% of HCC and 12-20% of cirrhosis. (3) Population based
syndromic and health facility based surveillance of viral hepatitis is mandated under the Integrated Disease
Surveillance Programme (IDSP). A systematic review of available information from published studies and from
large unpublished reliable datasets, to assess the prevalence of chronic HCV infection in the Indian population
has recently been done to assess the prevalence of overall HCV infections, and by age, sex, risk factors and place
in the country. This meta-analysis data estimated that India (current population approx. 1.3 billion) has 5.2-13
million anti-HCV positive persons. As the data on HCV viremia amongst the anti-HCV positive persons were
not available, data from elsewhere was used to estimate that India has about 3 million to 9 million persons
with active HCV infections. (5) All key and bridge population groups under the NACP for HIV infections are
especially vulnerable to viral hepatitis infections too. There include groups like recipients of multiple blood/
blood products transfusion, patients on hemodialysis, People Who Inject Drugs, MSM, female sex workers,
sexual partners of infected people, prisoners, migrants and truckers etc. Also, high risk population for viral
hepatitis include close first degree relatives and family members: mother, siblings, spouse and children, of
persons affected with viral hepatitis. The other populations for both hepatitis B and C include those who have
received blood or blood products especially before implementation of hepatitis C testing at a large scale in India;
i.e. before 2001. Such population groups shall be treated as key populations or high-risk groups (HRGs) under
the National Viral Hepatitis Control Program. Hepatitis B and C infections have long gestation periods before
the disease progresses to advanced stages resulting in liver cirrhosis and liver cancer, resulting in mortality
if treatment is not provided in time. Intervene to prevent advancement of the disease is particularly more
challenging because during the gestation period, the disease does not manifest itself through any specific
symptoms. Recent advances in diagnostics have now made it possible to diagnose people carrying viral hepatitis
infections through point-of-care rapid diagnostic kits. Several new technologies and platforms are also now
available for conducting confirmatory tests through viral load testing. Reliable treatment of viral hepatitis B & C
is now possible with new medicines. Diagnostics and treatment services have so far been available only through
the private sector in India. In absence of a public health initiative, such incidence of disease leads to high out of
pocket expenditure. The Government of India has, hence, launched National Viral Hepatitis Control Program
(NVHCP) for prevention and control of viral hepatitis, with a view to provide free of charge screening, diagnosis,
treatment & counseling services to all, and specially to people belonging to high-risk groups.

13
Introduction to the Programme
India is committed to progressively move towards elimination of viral hepatitis B and C and control other virus
induced hepatitis. This is in line with our global commitment towards achieving Sustainable development
goal (SDG) goal 3; target 3.3 which aims to “By 2030, end the epidemics of AIDS, tuberculosis, malaria and
neglected tropical diseases and combat hepatitis, water borne diseases and other communicable diseases” The
Government of India is a signatory to the resolution 69.22 endorsed in the WHO Global Health Sector Strategy
on Viral Hepatitis 2016-2021 at 69th WHA towards ending viral hepatitis by 2030. In India, the estimated
burden of hepatitis is very high, necessitating focus on prevention and control measures to mitigate morbidity
and mortality arising out of hepatitis. (6) There are several components that exist in the different programs
of Government of India, such as Immunization for Hepatitis B; Swachh Bharat Mission; Safety of blood and
blood products; Safe drinking water and sanitation, which are directly or indirectly related to the response to
viral hepatitis. The sequel of chronic hepatitis which includes cirrhosis and HCC poses long term burden on the
health system. A recent cost benefit analysis of treating hepatitis C infection demonstrated that curing the HCV
with 12-24 weeks of directly acting antivirals (DAAs) is substantially more cost effective than managing the
sequels and has better health outcomes. (7) Unsafe injection practices during health care or otherwise, remain
a risk and have potential to transmit the HBV and HCV infection. Use of Reuse Prevention (RUP) syringes is
a critical intervention to interrupt the chain of such transmission. India manufactures RUPs for injection in
therapeutic care and mandating its use in public and private sector offers a new opportunity to address unsafe
injections.
With the view to address the existing gaps in current programs, National Viral Hepatitis Control Program
(NVHCP) was launched in July, 2018 on the occasion of the World Hepatitis Day, with the focus to integrate the
existing programs towards awareness, prevention and treatment for viral hepatitis (A, B, C, D & E). The program
proposes to address management of all types of viral hepatitis. The advent of newer and safe drugs for treatment
of Hepatitis C ensuring cure makes it easier to combat it. Similarly, the available drugs for hepatitis B treatment
are quite potent and safe and keep the virus suppressed for prolonged periods, reducing the risk of cirrhosis and
liver cancer. The technical guideline on diagnosis and management of viral hepatitis with focus on management
of Hepatitis C were published in 2018. The current guidelines are focusing on diagnosis and management of
Hepatitis B along with the operational component of implementing the same under the program.
Aim
1. Combat hepatitis and achieve country wide elimination of Hepatitis C by 2030
2. Achieve significant reduction in the infected population, morbidity and mortality associated with Hepatitis
B and C viz. Cirrhosis and Hepato-cellular carcinoma (liver cancer)
3. Reduce the risk, morbidity and mortality due to Hepatitis A and E.
Key Objectives:
1. Enhance community awareness on hepatitis and lay stress on preventive measures among general
population especially high-risk groups and in hotspots.
2. Provide early diagnosis and management of viral hepatitis at all levels of healthcare
3. Develop standard diagnostic and treatment protocols for management of viral hepatitis and its
complications.
4. Strengthen the existing infrastructure facilities, build capacities of existing human resource and raise
additional human resources, where required, for providing comprehensive services for management of
viral hepatitis and its complications in all districts of the country.
5. Develop linkages with the existing National programmes towards awareness, prevention, diagnosis and
treatment for viral hepatitis.
6. Develop a web-based “Viral Hepatitis Information and Management System” to maintain a registry of
persons affected with viral hepatitis and its sequelae.

Components
The key components include:
1. Preventive component: This remains the cornerstone of the NVHCP. It will include
a. Awareness generation
b. Immunization of Hepatitis B (birth dose, high risk groups, health care workers)
c. Safety of blood and blood products d. Injection safety, safe socio-cultural practices
d. Safe drinking water, hygiene and sanitary toilets
2. Diagnosis and Treatment:

a. Screening of pregnant women for HBsAg to be done in areas where institutional deliveries are < 80% to
ensure their referral for institutional delivery for birth dose Hepatitis B vaccination.
b. Free screening, diagnosis and treatment for both hepatitis B and C would be made available at all levels of
health care in a phased manner.
c. Provision of linkages, including with private sector and not for profit institutions, for diagnosis and
treatment.
d. Engagement with community/peer support to enhance and ensure adherence to treatment and demand
generation.
3. Monitoring and Evaluation, Surveillance and Research Effective linkages to the surveillance system would
be established and operational research would be undertaken through Department of Health Research (DHR).
Standardised M&E framework would be developed and an online web based system established.
4. Training and capacity Building:
This would be a continuous process and will be supported by NCDC, ILBS and state tertiary care institutes and
coordinated by NVHCP. The hepatitis induction and update programs for all level of health care workers would
be made available using both, the traditional cascade model of training through master trainers and various
platforms available for enabling electronic, e-learning and e-courses.

15
Activities
The main activities of the program would include the following:
Program Management
Prevention Diagnosis and Treatment Monitoring & Evaluation Training and Capacity
Surveillance & Research Building
Awareness generation Diagnoisis/Screening –
& behaviour change serological tests
communication
Hepatitis information and Standardized training
management portal modules for all cadres
Immunization for hepatitis Confirmation – molecular of health care workers &
B – birth dose, high tests (where required)
program managers.
risk groups, health care Standardized M&E
workers Treatment of framework and web
uncomplicated cases – at based portal Digital & conventional
Provision of safe blood treatment centres, drug training program
and blood products dispensation upto HWC Indicator based
monitoring of the E learning
Injection Safety by Use of Treatment of complicated program
only RUP syringes in all cases at model
government HCFs Induction & refresher
treatment centres Surveillance of acute training
viral hepatitis, chronic
Safe socio-cultural Laboratory capacity viral hepatitis and it’s
practices sequelae Facilitation through tele-
building and quality consulting
assurance
Review Meetings
Referral and linkages
External Reviews
Targets for the NVHCP

The National Viral Hepatitis Control program has the following cumulative physical targets for the first
three years:
1. Program Management:
a. National Viral Hepatitis Management Unit (NVHMU): To establish a NVHMU in the first year.
b. State Viral Hepatitis Management Unit (SVHMU) - To establish a State Viral Hepatitis Management Unit
in the first year within existing state health governance structure i.e. State Health Society. This would be
structured on similar lines as the NVHMU.
2. Prevention:
a. Develop and implement the protocol for ante-natal screening of pregnant women for Hepatitis B; and start
screening in the first year.
b. Develop and implement tracking mechanism to ensure institutional delivery for all Hepatitis B carrier
pregnant women.
c. Increase Hepatitis B zero dose immunization to over 90%
d. Implement safe injection practices in government systems immediately
e. Blood safety targets
f. To develop institutional mechanism for periodic testing of drinking water sources in coordination with
Department of Drinking Water and Sanitation (DoDWS).

g. Improved IEC for prevention and checking transmission
3. Diagnosis & Treatment
A. Diagnosis:
a. a. Set up the National Reference Laboratory by the end of first year.
b. Establish State level reference laboratories in each state by the end of first year.
c. Develop District Diagnostics centres with viral load testing capabilities by the end of first year.
d. Start first line diagnosis through Rapid Diagnostic Kits at all levels by the end of first year.
e. Test 1.6 lakh individuals in the first year, 10.1 lakh in second year and 30.1 lakh in the third year for Hepatitis
C.
f. Start screening people belonging to high-risk groups for Hepatitis B in first year.
g. Encourage opportunistic screening for HBV and HCV of patients visiting health care facilities
B. Treatment:
a. Establish at least one Model Hepatitis Treatment Centre in each state\UT in the first year in an institution
identified by the respective state\UT government. Increase the number of such centres if required (on the
basis of need assessment) in consultation with the concerned state\UT government, in subsequent years.
b. Establish at least one Treatment Centre at district level in the public sector, preferably in a medical college
or the District Hospital, by the end of second year to offer access to quality assured management of Viral
Hepatitis.
c. Number of new hepatitis C cases to be treated across the country: over 3 lakh patients in 3 years
d. Start treatment for Hepatitis B for people needing treatment, by the end of first year
4. Training:
a. Ensure all trainings to operationalize state reference laboratories and Model Treatment Centres by the end
of first year.
b. To develop capacities of state\UT teams for training of personnel at the district laboratories and treatment
centres.
c. To develop IT driven institutional mechanisms for offering online counselling and courses to personnel at
all levels. The program will also explore facilitation through tele consulting where required.
d. To develop capacities of functionaries in Community Health Centre, Primary Health Centre and Health
and Wellness Centre (CHC, PHC and HWCs) to implement diagnostic and treatment support protocol
appropriate at that level
5. Monitoring and Evaluation, Surveillance and Research:

a. To develop and operationalize the Viral Hepatitis Information Management System (VHIMS) for
i. Maintaining a registry of patients
ii. Tracking of patients for ensuring treatment adherence and compliance.
iii. Developing dashboards and reports for monitoring of the Program.

b. Co-ordinate with the National Viral Hepatitis Surveillance Program
i. Surveillance of acute viral hepatitis
ii. Surveillance of chronic viral hepatitis
iii. Surveillance of sequelae of chronic viral hepatitis
c. Research: Identify evidence based operational research and implement in collaboration with DHR

17
Hepatitis B
Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV). It is a major
public health problem worldwide including India. HBV is spread predominantly by per-cutaneous or mucosal
exposure to infective blood and various body fluids. Common modes of transmission of infection include
perinatal mother to child transmission, infected needles, transfusion of infected blood and blood products and
sexual mode.
Hepatitis B can be either acute or chronic, and the associated illness ranges in severity from asymptomatic to
symptomatic, progressive disease. The risk of complication correlates with the age of acquisition of infection i.e.
neonate acquiring infection from mother has nearly 90% chance of developing chronicity. People with chronic
hepatitis B are at increased risk of developing hepatic decompensation, cirrhosis, and hepatocellular carcinoma.
Chronic hepatitis B (CHB) – defined as persistence of hepatitis B surface antigen (HBsAg) for six months or more
after acute infection with HBV– is a major public health problem. Based on the prevalence of HBsAg, different
areas of the world are classified as high (≥8%), intermediate (2-7%) or low (<2%)HBVendemicity. Published
literature suggests that India falls under the category of intermediateendemicity zone.
Viral hepatitis B is preventable through the intramuscular administration of a safe and effective vaccine.
Prevention of perinatal /vertical transmission is possible through hepatitis B vaccination at birth. In India,under
Universal immunization program(UIP), hepatitis B immunization includes birth dose for hepatitis B vaccine
andsubsequentthree doses of vaccine at 6, 10 and 14 weeks. Health care workers and high-risk groups by virtue
of their occupation and behavior are more vulnerable to acquiring infection.
Routine assessment of HBsAg-positive persons is needed to guide HBV management and indicate the need for
treatment. This generally includes assessment of: measuring aminotransferase levels to help determine liver
inflammation and stage of liver fibrosis by non-invasive tests (NITs) such as aspartate aminotransferase (AST)-
to-platelet ratio index (APRI). Serum HBV DNA levels/viral load quantified by real-time polymerase chain
reaction (PCR) correlate with disease progression and are used for decisions to treat and subsequent monitoring.
Since majority of infected people remain asymptomatic, and often present with advanced disease, early diagnosis
is critical to timely initiation and scale up of treatment for viral hepatitis B. Inadequate public and health-care
provider awareness; the asymptomatic nature of infection during the early stages, lifelong treatment and access
to quality diagnostics are some of the challenges to scaling up management of viral hepatitis B.
Antiviral agents active against HBV are available, and have been shown to suppress HBV replication, prevent
progression to cirrhosis, and reduce the risk of HCC and liver-related deaths. However, currently available
treatments fail to eradicate the virus in most of those treated, necessitating potentially lifelong treatment. These
drugs need to be made available and used such that timely intervention will prevent the onset of advanced liver
disease.
Prevention strategies including needle exchange in people who injects drugs (PWID), barrier contraception
need to be promoted in key affected populations, including persons who inject drugs, men who have sex with
men (MSM), and sex workers; prevention of HBV transmission through immunization of health care workers
need to be ensured in health-care settings. Voluntary blood donation and universal screening of blood and
blood products for transfusion will also help in prevention strategies.
In view of the above, it is pertinent to address all aspects of HBV prevention, care and treatment of persons with
CHB infection under the NVHCP. This will provide opportunities to save lives improve clinical outcomes of
persons living with CHB, reduce HBV incidence and transmission, and stigma due to disease.
Hepatitis B Virus
HBV, a double-stranded DNA virus, belongs to the family of hepadnaviruses. Perinatal transmission and
occasionally horizontal transmission early in life are most common in high prevalence areas. Sexual contact

and percutaneous transmission also contribute to the transmission of HBV.
The disease can manifest both in acute and chronic forms and varies from asymptomatic to symptomatic
progressive disease.
The spectrum of disease and natural history of chronic HBV infection are diverse. In some people, CHB is
inactive and does not lead to significant liver disease. In others, it may cause progressive liver fibrosis, leading
to cirrhosis with end-stage liver disease, and a markedly increased risk of hepatocellular carcinoma (HCC),
independent of the presence of cirrhosis – usually many years after initial infection. Longitudinal studies of
untreated persons with CHB show an 8–20% cumulative risk of developing cirrhosis over five years. In those
with cirrhosis, there is an approximately 20% annual risk of hepatic decompensation and the annual incidence
of hepatitis B-related HCC is high, ranging from <1% to 5%. Untreated patients with decompensated cirrhosis
have a poor prognosis, with 15–40% survival at five years. Several host and viral factors, especially coinfections
with HIV, HCV and hepatitis D virus (HDV), together with other cofactors such as alcohol use, may increase the
rate of disease progression and risk of developing HCC.
The detailed guidelines for the natural history, phases of chronic HBV infection and co-morbidities have been
address in the National guidelines for Diagnosis and management of viral hepatitis, 2018 by NVHCP, NHM and
should be referred to.
Diagnosis of Hepatitis
Chronic HBV infection is a dynamic process reflecting the interaction between HBV replication, hepatocytes
and the host’s immune response. The natural history of chronic HBV infection has been schematically divided
into four phases, as depicted in figure below, taking into account the presence of HBeAg, HBV DNA levels,
alanine aminotransferase (ALT) values and eventually the presence or absence of liver inflammation. The risk
of progression to cirrhosis and HCC is variable and is affected by the host’s immune response.
HBsAg
HBeAg(+) HBeAg(-) / anti-HBe(+)
HBV DNA
109-1012 IU/mL >2000-<109 IU/mL <2000 IU/mL >2000 IU/mL <2000 IU/mL
ALT
Minimal disease HBeAg+CHB Inactive carrier HBeAg-CHB Occult infection
Immune-tolerant Immune-reactive Immune-control Immune-reactive Immune-control

Phases of Infection
Source: Santantonio T, Fasano M, Current concepts on management of chronic hepatitis B.

http//dx.doi.org/10.5772/54759

19
Clinical progression along with associated serological events in acute HBV infection
Incubation Prodrome, Convalescence

period acute disease Early Late
Important HBsAg Anti-HBs
diagnostic tests IgM anti-HBc IgG anti-HBc
1 2 3 4 5 6 7 8
DNA polymerase
Relative HBV particles

Anti-HBc
concentration
of reactants
HBsAg
Anti-HBs
HBeAg
Level of Anti-HBe
detection
Months after
exposure 1 2 3 4 5 6 7 8
ALT
Symptoms
Source: Karen C. Carroll, Stephen A. Morse, Timothy Meitzner, Steve Miller: Jawetz, Melnick,
and Adelberg’s Medical Microbiology, 27th Edition, Mc-Graw Hill Education.
Interpretation of HBV markers

The following table depicts the combination of various serological markers of hepatitis B and the
interpretation of these findings.
Table 1: Common serologic patterns of hepatitis B infection and their interpretation
HBsAg Total anti-HBc IgM anti-HBc Anti-HBs Interpretation

- - Never exposed
- + - + Past natural
infection, cleared,
immunity achieved
- + - - Past natural
infection, cleared,
anti-HBs has
waned over time
- + - - Immunity due
to vaccination
- - - + Recent infection,
recovered,
immunity achieved
- + + + Acute infection,
ongoing
+ + - - Chronic infection
(ongoing)

Testing algorithm for Diagnosis of Viral Hepatitis in suspected patients (without jaundice)
Specimen:Serum/Plasma*
HAV HEV HBV HCV
IgM ANTI IgM ANTI

HAV HEV HBsAg IgM Anti Anti HCV
HBc
Reactive NonReactive Reactive NonReactive Reactive NonReactive

Reactive NonReactive Reactive NonReactive
Report: Report: Report: Report: • If HbsAg is Reactive and Igm anti Hbc Report: Report:
HAV HAV HEV HEV in Non-eactive: HBV positive HCV ab HCV ab
Positive Negative Positive Negative • If IgM Anti HBc is Reactive and HBsAg #Positive Negative#
is Non-reactive: HBV positive
• If both Reactive: HBV positive
• If both Non-reactive: HBV negative
*Serum samples to be used for serological and biochemical testing, to be aliquoted and stored at -200 C for retesting for
quality purposes, dispute etc.
#All HCV antibody (AB) positive to be referred to treatment centre. Plasma samples to be collected and aliquoted in 3
sterile cryo vials. One vial to be used for quantitative hepatitis hepatitis C RNA estimation and two archived at-800 C
for quality assurance

(without jaundice)
HBV HCV
HBsAg Angi HCV
:Report :Report :Report :Report

HBV HBV HBV HBV
Positive Negative Positive Negative
* Serum samples to be used for serological and biochemical testing, to be aliquoted and stored at -200 C for
#All HCV antibody (Ab) positive to be referred to treatment centre. Plasma samples to be collected and aliquoted
in 3 sterile cryo vials. One vial to be used for quantitative hepatitis C RNA estimation and two archived at -800 C

21
Whom to Treat
The persistence of HBsAg beyond 6 months defines the person to have a chronic hepatitis B.There is no need
to confirm with second HBsAg test in completely asymptomatic patients or those with features of fibrosis/
cirrhosis/HBV flare. Those with acute hepatitis or a recent risk factor (180 days) for HBV infection should
undergo a repeat HBsAg testing after 6 months to confirm chronicity.
The decision to identify the people who need treatment rely upon the presence of cirrhosis, fibrosis, levels of
liver enzymes and platelet count. The HBeAg is not required for assessing the eligibility to initiate treatment
and hence will not be used in the program.
The persistently elevated ALT under the program is defined as at least 2 values four weeks apart in the last 6
months, which are above the upper limit of normal.
The extent of fibrosis / cirrhosis can be established using several methods. It is recommended to use the non-
invasive techniques (NIT) like APRI and FIB-4 for assessing the extent of fibrosis. An APRI score of 2 or more
or a FIB-4 more than or equal to 3.25 is suggestive of cirrhosis. The APRI score more than 1.5 or FIB-4 score
more than 1.45 correlates with significant fibrosis (Stage F2). Transient elastography(FibroScan) may be done
in settings where they are available and cost is not a major constraint (Conditional recommendation).A mean
cut-off of ≥12.5 kPa may be used to diagnose cirrhosis and ≥8.0 to diagnose significant fibrosis.The details on
evaluating the status of cirrhosis can be seen in Annexure 1 that details on the assessment of the severity of
liver disease
Based on the various parameters, the following algorithms should be used to identify people who need treatment.
Chronic Hepatitis B Infection : Whom To Treat
HBsAg Fibrosis/age ALT HBV DNA
Cirrhosis or Irrespective of age, ALT, HBeAg or DNA Treatment

APRI z2/Fib-4 Recommended
z3.25 Irrespective of age, HBeAg
Treatment
>20,000 Recommended
Persistently Particularly if age >30 Treatment

Recommended if,
elevated APRI>1.5 or fib-4>
>20,000 1.45 or Plstelets
<100 x101/mm1
Treatment
Recommended if,
HBsAg +ve >2000 APRI>1.5 or fib-4>
1.45 or Plstelets
<100 x101/mm1
Non-cirrhotic
Population
No treatment
Normal recommended
(<Lab’s cut-off) >2000
HBsAg-ve No Treatment
Required
HBsAg, hepatitis B surface antigen; HBeAg, hepatitis B e-Antigen; APRI, AST to platelets ratio index; FIB-4,
fibrosis-4

Treatment: What to treat with?
There are various antiviral agents recommended for treatment of CHB. The details are described in the
National Treatment guidelines. However, the following table summarizes the recommendations:
Table 2: Recommended drugs for the treatment of CHB and their doses in adults
Drug Dose
1 Tenofovir disoproxil fumarate (TDF) 300 mg once daily
2 Entecavir (adult with compensated liver disease and lamivudine naive) 0.5 mg once daily
3 Entecavir (adult with decompensated liver disease) 1 mg once daily

4 Tenofovir alafenamide fumarate (TAF) 25 mg once daily
Table 3: Recommended drugs for the treatment of CHB and their doses in children
Drug Dose
Tenofovir (in children 12 years of age and older, 300 mg once daily
and weighing at least 35kg)
Entecavir (in children 2 years of age or older and Recommended once-daily dose of oral solution (mL)
weighing at least 10kg. the oral solution should be
Body weight (kg) Treatment –naïve persons*
given to children with a body weight up to 30kg)
10 to 11 3
> 11 to 14 4
> 14 to 17 5
> 17 to 20 6
> 20 to 23 7
> 23 to 26 8
> 26 to 30 9
>30 10
*Children with body weight more than 30 kg should receive 10 mL (0.5 mg) of oral solution or one 0.5 mg tablet
once daily.
Selection of antiviral drug for CHB:

•• In all adults, adolescents and children aged 12 years or older in whom antiviral therapy is indicated, the nucleotide
analogues (NAs) which have a high barrier to drug resistance (Tenofovir or Entecavir) are recommended.
•• In woman of childbearing age,Tenofovir may be preferred as the drug of choice in the

eventuality of a pregnancy. Entecavir is not recommended in pregnancy.
•• Tenofovir is preferred in patients who have been exposed to lamivudine

who have a potential for Entecavir resistance.
•• Entecavir is recommended in children aged 2–11 years.
•• Entecavir may be preferred over Tenofovir in:Age > 60 years; bone disease due to chronic steroid use
or use of other medications that worsen bone density, history of fragility fracture, osteoporosis; altered
renal function with eGFR<60 mL/min/1.73 m2 or albuminuria >30 mg/ 24 hr or moderate dipstick
proteinuria or Low phosphate (<2.5 mg/dL) or in patient on hemodialysis ( Ref: EASL guidelines).
•• TAF is the drug of choice in patients with reduced renal function or bone
disease bone toxicities, where entecavir is contraindicated.
Drugs with a low barrier to resistance (lamivudine, adefovir or telbivudine) are available but not
recommended as they lead to drug resistance.
The formulations for children are not currently approved, as and when they become available and
approved, the above recommendation will be useful.

23
Monitoring the Treatment
The disease is complex and has sequelae, resolution as well as drugs side effects. Hence, three types of
monitoring is necessitated
1. Monitoring for disease progression and treatment response in persons with CHB prior to, during and post-
treatment
2. Monitoring for tenofovir or entecavir side-effects
3. Monitoring for hepatocellular carcinoma
Baseline Investigations: At first visit, we need to do complete blood counts (CBC), HBsAg, APRI, LFT (at least
ALT & AST), ultrasound (USG) of abdomen and HBV DNA.. There should be baseline HIV screening where
possible of all people testing positive for HBsAg or anti-HCV.
Follow up Investigations: The person should be followed up regularly and the ALT levels have to be monitored
every six months. The HBV DNA should be done for each person every year. The APRI/FIB-4 scoring should
be done every 6 months and hence the lab investigations needed should be accordingly undertaken. Renal
function tests should be monitored every six months, or earlier if deemed necessary by the treating physician
for monitoring drug toxicity.
Referral to Model Treatment Centers

Majority of patients will be covered with these regimens recommended in these guidelines. However, a
few cases might need some variants from these regimes (like patientsneeding TAF, patients needing and
eligible for pegylated interferon, patients with malignancy on chemotherapy, patients with family history of
cirrhosis or HCC attributable to HBV infection, patients with virological failure, acute liver failure and acute
liver injury and jaundice/flare up cases, reactivation cases etc). These special cases will be a very small
fraction of the overall disease burden and have to be managed at the Model Treatment Center. A summary
guidance for MTC is enclosed as Annexure 2
Hepatitis B infection and Pregnancy

Perinatal transmission is the major route of HBV transmission, In the absence of prophylaxis, a large
proportion of viraemic mothers, especially those who are seropositive for HBeAg, transmit the infection
to their infants at the time of, or shortly after birth. The risk of perinatal infection is also increased if the
mother has acute hepatitis B in the second or third trimester of pregnancy or within two months of delivery.
Although HBV can infect the fetus in utero, this appears to be uncommon and is generally associated with
antepartum hemorrhage and placental tears. The risk of developing chronic infection is 90% following
perinatal infection (up to 6 months of age) but decreases to 20–60% between the ages of 6 months and 5
years.
All pregnant women with HBV should be evaluated for the need of treatment for hepatitis B and any
associated liver disease, and given advice about prevention of transmission. Only a proportion of those with
hepatitis B virus infection (pregnant or otherwise) need treatment.
Hepatitis B in a pregnant woman is not a reason for considering termination of pregnancy. Similarly, the
need for caesarean delivery should be decided based on obstetric indications, and not on the presence of
HBV infection.
Administration of hepatitis B vaccine to pregnant women with HBV provides no benefit either to the mother
or the baby.
Care of the baby

Immunoprophylaxis of hepatitis B virus infection
The newborn baby should be administered a timely first dose (the ‘birth dose’) of hepatitis B vaccine

(monovalent) as soon as possible after birth, ideally within 24 hours. Even within this time duration, the
earlier it can be administered, the better. If, for some reason, the birth dose is not administered within 24
hours, it should still be administered as soon as it is possible and not omitted. This dose is administered
intramuscularly in the anterolateral aspect of mid-thigh. This birth dose must be followed by timely
administration of 3-doses of hepatitis B-containing vaccine [e.g. monovalent hepatitis B vaccine, tetravalent
combination vaccine with DPT (DPT-Hep B) or a pentavalent vaccine (DPT+HepB+Hib). The hepatitis B
vaccine birth dose followed by these three doses is the most effective method for prevention of mother-to-
child transmission of hepatitis B.
Hepatitis B immunoglobulin (HBIG) may provide some additional protection in situations where
risk of transmission is particularly high – i.e. babies born to mothers with hepatitis B who also have
detectableHBeAg and/or high viral load. However, additional benefit provided by it, over properly-
administered hepatitis B vaccine (as described above) is small. Also, HBIG is costly and has limited
availability. Under the program, HBIG will be made available and should be administered for preventing
mother to child transmission of HBV (0.5 ml or 100 international units, intramuscular), this should be done
as soon after birth as possible (and within 12-24 hours) and in anterolateral aspect of mid-thigh other than
the one in which hepatitis B vaccine has been administered.
Data on benefit and risks of administering anti-hepatitis B drugs to the pregnant women for prevention of
mother-to-child transmission are unclear.
Breast-feeding
A mother who has hepatitis B may breast-feed her baby, unless there is an exuding injury or disease of the
nipple or surrounding skin. The advantages of breast-feeding far outweigh the risk, if any, of transmission of
hepatitis B to a baby who has received hepatitis B vaccine.
Timing of testing
If it is felt that the baby needs to be tested for hepatitis B, this should be done only after 1 year of age. Any
positivity before this age is difficult to interpret and may resolve spontaneously over time.
HBV Infection in Pregnancy
All pregnant women with HBV should be evaluated for the need of treatment for hepatitis B and any
associated liver disease, and given advice about prevention of transmission. Only a proportion of those
with hepatitis B virus infection (pregnant or otherwise) need treatment as detailed in above section.
Hepatitis B in a pregnant woman is not a reason for considering termination of pregnancy. Similarly,
the presence of HBV infection is not an indication for caesarean delivery, which should be based on
obstetric indications only.
Administration of hepatitis B vaccine to pregnant women with HBV provides no benefit either to the
mother or the baby.
Chronic Hepatitis B in Children and Adolescents

CHB is usually benign and asymptomatic in children. In addition, there are low curative response rates with
both NAs (necessitating long-term therapy) and IFN treatment, and concerns over long-term safety and risks of
drug resistance. For these reasons, a conservative approach to treatment is generally indicated, unless there are
other criteria for treatment, such as cirrhosis or evidence of severe ongoing necro-inflammatory disease on liver
biopsy. Although the majority of children will not require antiviral therapy, early identification and monitoring
of children at risk for progression of liver disease guided by liver histology and a family history of HCC remains
important. The use of NITs and identification of appropriate cut-offs have not yet been defined in children. Only
conventional IFN, lamivudine and adefovir have been evaluated for safety and efficacy, but children generally
have a similar response as adults. IFN cannot be used in infants aged less than 1 year. The FDA has approved

25
tenofovir for use in adolescents and children above the age of 12 years for HBV treatment. Therefore, treatment
options for children below 12 years, and especially below 2 years, remain limited. Studies with NAs are ongoing
to better define treatment strategies.
Co-morbidities
HBV with HCV co-infection
Persons with HBV/HCV co-infection It is important to check for the presence of HBV infection before starting
HCV treatment. HBV and HCV co-infection may result in an accelerated disease course; HCV is considered to
be the main driver of disease. Persons co-infected with HBV and HCV can be treated with antiviral therapy for
HCV; SVR rates are likely to be similar to those in HCV-mono infected persons. During treatment and after
HCV clearance, there is a risk of reactivation of HBV, and this may require treatment with concurrent anti-HBV
antiviral therapy. DDIs must be checked before initiating treatment.
HIV and Hepatitis B Co-infection

The natural history of both diseases is affected when a person is co-infected with both HIV and Hep B and this
has implications on management of both diseases. Current evidence suggests that human immunodeficiency
virus (HIV) infection has an adverse impact on HBV-related liver disease progression, with higher serum HBV
DNA polymerase activity, lower rates of loss of serum hepatitis B e antigen, and increased risk of cirrhosis,
liverrelated mortality, and hepatocellular carcinoma at lower CD4 T-cell counts. HBV infection is more likely
to be chronic in those with HIV infection. In some cohorts, liver disease has emerged as a leading cause of
death in HIV-infected persons co-infected with either hepatitis B or C, as mortality due to other HIV-related
conditions has declined following the introduction of antiretroviral therapy (ART). Similarly, the HBV infection
also negatively impacts the progression of HIV infection leading to faster immune deterioration and higher
mortality. Other studies have suggested that HBV is associated with a rapidly progressive course of HIV infection
. A retrospective analysis indicated that the risk of death in 64 individuals co-infected with HIV and HBV was
approximately two-fold higher than that in individuals with HIV mono infection. Prospective observational
cohort among those with primary HIV infection showed that HBV coinfection is an independent predictor of
immunologic deterioration in such group of patients. In another large prospective multicentre cohort by Chun
et al among 2352 (PLHIV) with sero-conversion window of less than 3 years, co-infected persons with Hepatitis
B were associated with two times higher risk of AIDS/death, higher among HBV co-infected patients compared
to HBV mono-infected patients The HIV-Hepatitis co-infected persons show faster CD4 decline, slower CD4
recovery following ART, increased incidence of AIDS and non-AIDS events, increased rate of ARV toxicity and
increased chances of Immune reconstitution hepatitis. In one of the large cohort studies of more than 5000
co-infected persons, the relative risk of liver related deaths was found to be 17 times higher than those with
HBV mono-infected patients. Other challenges among co-infected include cross-resistance between HIV and
HBV drugs, increased liver injury, either due to direct hepatotoxicity or to ART-related immune-reconstitution
hepatitis, with elevation of ALT; if ART does not cover both HIV and HBV infections adequately, fulminant
hepatitis is an eventuality. Evaluation of HIV and HBV Co-infected Persons The risk of HBV infection may
be higher in HIV-infected adults, and therefore all persons newly diagnosed with HIV should be screened for
HBsAg. Those found positive for HBsAg should be evaluated further following the guidelines for evaluation
of those with HBV Infection. Besides routing clinical evaluation, one should look for sign of cirrhosis and
hepatic decompensation like ascites and pedal oedema. The lab investigations, besides routine haemogram and
biochemistry, should specifically include Liver Function Test (LFT), prothrombin time, AFP, ultrasound and
upper gastrointestinal endoscopy. The virological examination should include HBeAg, Anti-HBe antibody and
HBV DNA quantitative (Real-Time PCR).
Assessment of severity of fibrosis : The assessment of degree of fibrosis and cirrhosis is important.
Treatment of HIV and HBV Co-infected patients

All HIV positive patients with HBV co-infection should start dual anti HIV & HBV therapy with tenofovir

based ART regimen irrespective of CD4 count, HBV viral load or status of liver disease e.g., ALT level or fibrosis
stage. In HBV and HIV co-infected adults and adolescents, tenofovir + lamivudine + efavirenz as a fixed-dose
combination is recommended as the preferred option to initiate ART under the National AIDS Control Program.
This three drug combination includes the drugs with efficacy against hepatitis B. Stopping Tenofovir based ART
should be avoided in HIV + HBV co-infection for concern of severe hepatitis flare and decompensated following
HBV reactivation. This treatment strategy has achieved high rates of HBV DNA suppression (90%), HBeAg loss
(46%) and HBsAg loss (12%) in HBeAg-positive patients after 5 years of treatment, without evidence of resistance,
and reduced progression to cirrhosis with no significant differences in response in those with or without HIV
co-infection . To date, no viral resistance to tenofovir in vivo has been described, although resistant strains have
been identified in vitro. Although the risk of developing cirrhosis is negligible in HBV-HIV-co-infected persons
on long-term tenofovir combined with lamivudine therapy, the risk of HCC persists, but is low. If ARVs need
to be changed because of HIV drug resistance or some drug toxicity, then tenofovir and lamivudine should be
continued together with the new ARV drugs unless TDF is specifically contraindicated due to its toxicity.
Prevention of HBV infection
The risk of HBV infection may be higher in HIV-infected adults, and therefore all persons newly diagnosed
with HIV should be screened for HBsAg and immunized if HBsAg is negative. Those already infected with HBV
(HBsAg positive) do not benefit from HBV vaccine. PLHIV who have already suffered from HBV in the past and
have developed protective titre of Anti-HBs antibody (>10 mIU/mL) also do not require HBV vaccine. Response
to HBV vaccine is lower in persons with HIV or with a low CD4 count, and a meta-analysis has shown that a
schedule of four double (40 μg) doses of the vaccine provides a higher protective anti-HBs titre than the regular
three 20 μg dose schedule Besides this, all infants born to HBV positive women need to be immunized within 24
hours of birth (Dose - 0) followed by 6, 10 & 14 weeks (dose – 10 µg IM) and HBIG – (0.5 ml or 100 international
units, intramuscular), this should be done as soon after birth as possible (and within 12-24 hours) and in a limb
other than the one in which hepatitis B vaccine has been administered.
HBV and HDV co-infection

HDV a defective RNA virus infects persons who are infected with HBV since they require HBV to complete
its life cycle. Prevention and control of HDV requires prevention of HBV infection through hepatitis B
immunization, although there is no protection against HDV for those already HBV infected. Management of
HBV will automatically prevent or manage co-infection as well as super-infection.
HBV and Tuberculosis co-infection

Groups at increased risk of infection with HBV are also at risk of infection with TB, largely because they
live in regions of the world that are endemic for both infections. Drug-induced liver injury with elevation of
aminotransferases is three- to six fold higher in persons co-infected with HBV, HCV or HIV who are receiving
anti-tuberculosis drugs, due to hepatotoxicity with isoniazid, rifampicin and pyrazinamide.
Organization of Services
The diagnosis and management of hepatitis B infection requires availability of appropriate , quality assured
testing for screening, confirmed diagnosis and monitoring of treatment,and at the same time, since the
treatment is life long, it also demands that the treatmentbe efficacious and at the same time accessible for a
chronic disease management, with strong linkages and referral mechanisms. The organization of laboratory
services and the treatment services therefore, needs to be extremely strategically organized and coordinated.
Laboratory Services
A variety of tests are required to establish a diagnosis of viral hepatitis and its further management. These
include platelet count, estimation of liver enzymes and specific serological tests and molecular tests (HBV DNA
and HCV RNA). The initiative envisages a tiered network of existing laboratories taking into account their

27
existing competencies and capacities in order to attain a quality assured test result.
The specific tests for viral hepatitis offered in the NVHCP across public health laboratories are summarized
below.
CoE
Sentinel Site
State
District
PHC level
Whom To Test
Diagnostic serologic testing for hepatitis B will be available to all people who would access the testing sites.
However, theinitial focus would remain on testing specific population groups that remain more vulnerable to
acquiring infection. These include the key populations under the NACP, and PLHA. It is important to screen
them and vaccinate those who are not found to be infected with hepatitis B.
A large number of adults who get infected will clear the infection and a small proportion will remain
chronically infected. Therefore, it becomes important to link those who are identified while routine screening
for other purposes (eg, pre-operative screening, the persons screening positive in blood banks for donations).
The transmission of mother to child also accounts for the major mode of transmission of hepatitis B.
Screeningof pregnant women , including ‘direct in labour’ pregnant women remain important to ensure that
they get diagnosed and appropriate management can be offered to them as well for preventing mother to child
transmission of HBV. Family members / siblings of the infected person and their sexual partners should also be
offered testing for hepatitis B infection.
Treatment Services
The services will be delivered through designated treatment sites that are located within an existing public
health facility, including tertiary care facilities followed by district hospitals. The extent of services will depend
upon the availability of the expertise and resources in the selected sites. There will be some sites that will be
identified as Model Treatment Centers (MTC). These will also act as places for referral, capacity building and
mentoring for the other treatment centers (TC). Selection of the Model treatment Center sites will be done by the
central unit for viral hepatitis, with concurrence of states being the implementing agency.
The NVHCP has already rolled out the treatment of Hepatitis C. The sites that have been identified as MTC and
TC for the hepatitis C, will also be delivering the services for hepatitis B. The human resources provided by the
program for hepatitis C will also be delivering the services for hepatitis B under same pattern of assistance.
Objectives and functions of the Treatment Sites

The management of hepatitis C has been simplified over the last few years since the introduction of DAAs.
However, the treatment for hepatitis B remains a life long treatment for most individuals who need treatment.
The main objective of the treatment site under the NVHCP is to enhance the access to treatment for hepatitis B

and C.
Model Treatment Centre(MTC) and Treatment Centre (TC): The treatment for hepatitis B will involve management
of patients that present with a range of clinical presentations, cirrhotic and non-cirrhotic, treatment naive or
treatment experienced, special situations like renal impairment etc. Hence, to effectively manage the patients
with HBV infection, it is planned to have a tiered approach for service delivery.
Organization of services - Treatment

Establish MTC/TC for Treatment of Hep B&B; Refer
complicated casesto specialcenters identified as MTC
Medical
Phased Colleges
scale up and Tertiary Centers
Establish Treatment centers for Treatment of

HepB & C; Refer complicated
District Hospitals
casesto specialcenter identified
Secondary care
TC-uncomplicated cases; Drug dispesing

Sub District Level sites: for hep B: CHC, PHC- evidence
based (Parent center to monitor and report)
All the treatment centers will have the capacity to initiate / dispense the treatment for hepatitis B as per the
national technical guidelines. They could be situated in public health care facilities like the medical colleges,
district hospitals etc. However, the cases that need more specialized care will be referred to higher center that
have the requisite capacity and experience to manage the complicated cases (e.g. decompensated cirrhosis,
thalessemicsetc.). These health care facilities with specialized services for diagnosis and management (like
availability of Gastroenterologist/hepatologist, Doppler, CT scan, MRI scan etc.) are termed as Model Treatment
center. Hence, the MTC will perform all the functions of a treatment center, will also receive in-referrals and
also be the centers for training, mentoring and conducting operational research under the initiative.
To minimize the travel costs, the treatment center can undertake the analysis of data and identify places where
there is clustering of cases for hepatitis B treatment. They can identify these sites as Drug Dispensing Units(DDU)
under them, in consultation with the state NVHCP. The DDU would be established in a phased manner. DDUs
will cater to cohort of patients who are stable (as per the treating physician) for dispensing of drugs. Such patients
can therefore be followed up at MTC/TC every 3-6 monthly. Once the DDU are planned, a detailed SOP for the
drug supply, eligibility and reporting will have to be ensured. There should be no minimum number of patients
for cohort and willingness of the patient to be linked to DDU should be considered before deciding so.
As the complications of chronic viral hepatitis are vast, the scope of initiative will be restricted to the treatment
of the hepatitis B infection and ensure linkages to the other programs and schemes for managing the sequel of
chronic hepatitis. Such schemes include (but not limited to) - Ayushman Bharat, NHPS, state specific schemes
for patient support etc
Functions of the Model Treatment Center:

1. To ensure Screening/ Diagnosis in suspected cases of Hepatitis B &C Infection
2. Treatment & Management of Hepatitis B &C infection
3. In referrals for cases screened / diagnosed elsewhere, for the management of viral hepatitis
4. Management of complicated cases referred from other treatment centers.

29
5. Management of cases under special categories as per national guidelines (eg: thalassemics, patient with
treatment failure, etc.)
Functions of the Treatment Center:

1. To ensure Screening/ Diagnosis in suspected cases of Hepatitis B &C Infection
2. Treatment and Management of uncomplicated Hepatitis B &C infection
4. Out referrals to MTC for clinical management of hepatitis as per national treatment guidelines.
Functions of Drug Dispensing Units

1. 1) To ensure Screening/ Diagnosis in suspected cases of Hepatitis B &C Infection
2. To dispense the drugs to stable patients transferred from the MTC/TC.
3. Encourage testing of partners and at risk people for acquiring infection with Hep B & C
4. Out referrals to MTC/TC for clinical management of hepatitis as per national treatment guidelines and for
regular annual monitoring for people at their center
5. Ensure compliance to treatment, regular adherence support.
Selection criteria and steps for setting up a Treatment Site

Each site will be selected by the state, based on the burden of disease according to available evidence in form
of studies, outbreaks, case reports, blood bank data etc. Once the sites are identified and proposed, a joint team
will visit the facility and assess its feasibility for delivery of services, adequacy of needed space and manpower
and willingness of the institute to set up such center. The team that will undertake the feasibility visit should
ideally comprise of the state and district officials of the initiative, central unit officials and other invited
partners. The report of feasibility visit should be prepared, signed and kept with the state officials. The format
for feasibility visit is attached as Annexure 3

1. 1. Established evidence of case load for Viral hepatitis B &/or C infection or its sequel
2. Evidence of highviral hepatitis burden in catchment area
3. Commitment and Willingness of the Institute to have a center and consequent agreement to follow the
SOP and protocols under the initiative
4. Availability of required infrastructure
5. Availability of appropriate human resource for clinical and laboratory management, as well as other
services routinely.
Infrastructure
The institution will be responsible for providing essential infrastructure for setting up the center. The
institution should identify adequate space from where the services can be delivered, preferably in vicinity of
OPD services. It should be clearly displayed at several places in the hospital for the ease of access by the patients
especially in the blood bank premises, STI clinics, HIV/ICTC centers etc. There should be services available
every day preferably, and have definite timings displayed boldly across the facility. It will be the responsibility
of the institution to provide basic furniture like chairs, tables, cabinet/almirah etc., space for storage of drugs,
and have necessary electrical and other fixtures. It has to be noted that no separate allocation will be made for

infrastructure and state has to bear the costs if any.
Human Resource
nodal officer who would be responsible for the day to day functioning of the centers. Ideally, this could be the
Head of department of Internal Medicine/Gastroenterology/Hepatology (or a person deputed /nominated by
HOD) in tertiary centers and the physician in district hospitals and elsewhere. The attending physician should
see the patients from the system and the documentation of the patient data and management should be recorded
in the formats that are made available under the program. To assist the delivery of services in a uniflow system
and to ensure efficacy, the treatment centers will be provided the following staff under the program in a phased
manner:Staffing provided by the program
Staffing provided by the program
S No Model Treatment centers

1 Medical Officer – 1
2 Pharmacist -1
3 Data Entry Operator – 1
4 Peer Support -1
S No Treatment centers
1 Pharmacist -1
3 Peer Support -1
Since the Model Treatment centers will also undertake additional tasks like training, mentoring, operational
research and conducting review meetings with state and central unit, they will be provided one contractual
position of level of Medical Officer(MO).
To facilitate the diagnosis and laboratory monitoring of treatment, the initiative will strengthen the laboratories
to deliver services as per the national guidelines. The laboratories so established (preferably in the same institute
as the treatment center) will have the following manpower that the program will provide in a phased manner,
as per the level of facility.
S No Manpower at State laboratories

1 Technical Officer – 1
3 Laboratory Technician – 1
S No Treatment centers
The staff should be recruited by the institution as per the norms and procedures followed for recruitment of
contractual staff as per the guidelines of the National Health Mission (NHM). The remuneration for all these
staff shall be in accordance to the state NHM norms. There should be an in-built system of appraisal of such
staff from time to time. It is of utmost importance that the centers identified as MTC and TC deliver the services
for both hepatitis B and C

1. Nodal Officer
a. Overall responsibility of the functioning of the centre, reporting to state / central unit, participation in

31
review meeting, coordinate and develop referral system and linkages with other departments of the hospital
b. Ensure that patient are not discriminated in the hospital and are not denied admission/ care.
c. Ensure that all ethical practices including confidentiality are maintained.
d. Ensure availability of adequate stock of quality drugs as per defined targets at all times
e. Ensure reporting of any short expiry drug in a timely manner to allow timely relocation and avoid financial
loss
f. All administrative matters relating to the center including sanctioning of leave of contractual staff, annual
performance appraisal of the staff etc. as per guidelines
g. Ensure adherence to the highest standards of quality and excellence in patient care
h. Review and monitor the functioning of the center periodically and in depth and ensure submission of
i. Act as Focal point for interaction with central unit/ State program management officials etc.
2. Medical officer (MO) of Model Treatment Center ( MTC)

related to infectious diseases. S/he must be registered in the concerned state Medical Council. A candidate with
higher education will be preferred.
a. S/he is the functional team leader of the center under the overall guidance of the Nodal officer. The MO
has to supervise the administrative and medical functions of the center on a day- to- day basis and provide
leadership to staff to work as a cohesive team and deliver the services effectively
b. S/he should examine the patients, advise required investigations, review the investigations and prescribe
the treatment.
c. Refer difficult/ complicated cases to the Nodal Officer or other specialist for further expert opinion and
d. Monitor the consumption and availability of drugs, and alert the concerned authorities in case of impending
shortage well in advance so as to enable adequate replenishment without disruption of services
e. S/he must ensure that all records, registers, cards are updated on a daily basis and reports are sent to the
f. S/he has to ensure that the guidelines for running and maintaining the center are abided by.
g. Facilitate and coordinate trainings in the center.
h. Ensure that a daily due list is prepared for the patients expected to visit and a follow up action is taken to
i. Any other duty assigned by Nodal Officer/ NVHCP.
3. Pharmacist
considered. S/he must be registered in the concerned state pharmacy council.Basic Knowledge of computers is
desirable.

a. S/he has to work under the guidance and supervision of nodal officer/MO
b. Dispense drugs with proper counseling / interaction with patient
c. Advise the patients and family about the importance of adherence during each visit

d. Counsel the patient on possible drug toxicities and report the same, if significant
e. Do pill count and report any adverse effects of drugs Also, confirm the next visit date and inform the patient
f. Maintenance of the drug stores
g. Maintain and update drug stock and drug dispensing registers regularly every day. Inform the concerned
medical and nodal officer in case of any discrepancy. Duly take signature of nodal officer every fortnightly
in the stock register
h. Ensure that the center has enough stock of drugs for at least 3 months and inform the concerned authority
about any near expiry or excess stocks well in time for relocation to other sites and ensure FEFO protocol
is followed
i. Physical verification of the drugs under the supervision of the nodal officer and/or the MO
j. Besides all the above, any other duty assigned by nodal officer.


3. Print and share all circulars/information sent by central unit/States to the Nodal Officer/MO and maintain
a file for the important orders/communication
4. Maintain the attendance register for the center staff and get it verified by the nodal officer everyday and by
the Nodal Officer at the end of the month
contractual service agreement, performance appraisal report, training details, remuneration etc.
5. Peer supporter
or hepatitis C), with a minimum of intermediate (12th) level education. S/he must also have sound knowledge
of the local language and working knowledge of English.

a. S/he has to work under the guidance and supervision of nodal officer /MO
b. Be the first interface with patient at center
c. Ensure entries in the visit register
d. Be a peer educator for patients at center and provide psycho-social support to newly registered patients
e. Provide assistance to patients enrolled at the center, within the hospital (OP and IP)
f. Discuss the importance of adherence to treatment and need of viral load at 12 weeks post treatment

33
(SVR) with the patients, Keep track of drug adherence of patients , counseling them on the importance of
g. Follow up the patients and assist in patient retrieval, where necessary and as far as possible
h. Any other duty related to the initiative assigned by nodal officer/MO
Terms of Reference for various staff of the Laboratories

Microbiologist designated by Institution, or Pathologist in the absence of Microbiologist
a. Supervises the work of Laboratory personnel
b. Verification and signing of reports generated in the laboratory
c. Ensuring that all job responsibilities are adhered to by all the laboratory personnel
d. Management of funds with relation to laboratory
e. Ensure participation in and review of EQA
f. Ensure training and competence of all the laboratory personnel

Qualification: MSc Medical Microbiology with 1-year experience in clinical laboratory services. Candidates
with PhD Medical Microbiology from recognized university with 3 months experience in clinical laboratory
services will be preferred.
a. Supervises the work of Laboratory technician under the guidance of the Laboratory In-charge.
b. Molecular testing where available
c. Preparation of SOPs and work instructions.
d. Verification of reports generated in testing laboratory
e. Preparation of quality control (QC) samples
f. Preparation anddistribution of proficiency panels (PT) panels
g. Inventory and financial document management in lab.
h. Maintaining and monitoring timely calibration / verification of all devices and ensuring that all monitoring
and measurements are done with devices having valid verification / calibration status.
i. Adherence to Biosafety guidelines.
j. Maintenance of records and logs in laboratory.
k. Disposition of nonconforming products in her area of operation.
l. Help in the conduct of teaching and training programs.
m. Participate in surveillance activities of programme, through NCDC
n. Onsite field visit to district lab for mentoring and quality assurance.
o. Reporting to laboratory In-charge
p. Any other duty assigned by laboratory In-charge

Qualification: DMLT two-year course or certificate in MLT for one year or B.Sc in MLT from recognized
university.

a. Collect / receive specimens in the laboratory.
b. Assist in sample transportation to referral laboratory as and when required.
c. Performs tests for hepatitis markers and preparation of reports.
d. Storage and maintenance of serum samples as per guidance.
e. Confirmation of reference samples from state medical college labs and compilation of reports.
f. Perform regular internal quality control testing ,EQA and their documentation
g. To maintain essential records in the laboratory
h. Inventory preparation for equipment and reagents.
i. Indent for supplies to the Laboratory through Lab In charge and ensure sufficient stock of Laboratory
j. Participate in trainings and workshops conducted.
k. Assist in molecular testing of samples where required.
l. To maintain cleanliness in and safety and follow proper biomedical waste disposals.
m. Any other work/ activity assigned from time to time.
Data Entry Operator(State laboratory):


1. S/he has to work under the guidance and supervision of nodal officer ( Microbiologist)
2. Ensure that all data recording and reporting is updated for all activities under the program, including
surveillance of viral hepatitis, if the lab is also participating in the surveillance program for viral hepatitis
3. Print and share all circulars/information sent by central unit/States to the Nodal Officer and maintain a file
for the important orders/communication
4. Maintain the attendance register for the program staff and get it verified by the nodal officer ( daily/ end of
the month )
5. Maintain the HR file including the bio-data of the staff, copies of certificates, appointment letters, contractual
service agreement, performance appraisal report, training details, remuneration etc
Training
Trainings are important for any new initiative as well as for building the capacity of the service delivery points
for an effective implementation. To ensure standardized and uniform quality of service delivery, there will
be capacity building of the different cadres of staff in the program, using standardized training modules and
facilitator guides. The following table summarizes the proposed trainings.

35
Table 4: Trainings proposed for various health care workers under NVHCP
Cadre of Health Number Responsible agency Remark
care worker of days
Multi-specialty 1 Institutional nodal person with Sensitization about
team at Institute head of institution and SPMU program and its
contents/approach
Medical Officers 3 Central unit for standardized manual; Induction training

SPMU for implementation and monitoring
Medical Officers 2 Central unit for standardized manual; Refresher trainings as

SPMU for implementation and monitoring deemed necessary
Pharmacist 2 Central unit for standardized manual;

Peer supporter 1 Central unit for standardized manual;
Lab technicians 5 Central unit for standardized manual; Also include EQA
Technical Officer labs 3 Central unit for standardized manual; Also include EQA
Data Entry Operator 2 Central and state unit
Logistics
The drugs provided for the treatment centers will be provided through the state as per the laid down
procedures and as per the list of drugs indicated in the treatment algorithm in the technical guidelines for
clinical management of hepatitis. It will be ensured that no stock out/expiry happens in any circumstance,
once the center starts functioning. A provision of 10% buffer stock needs to be maintained all the time as per
the laid down procedure. These drugs should be kept under safe custody and proper storage conditions shall be
maintained. The nodal person of the center should undertake physical verification of the stocks periodically
and the stock registers should be regularly updated and duly signed by the pharmacist and nodal officer.
Financial management
The treatment center will be provided funds as per the pattern of assistance under the initiative through the
state management unit of the NHM. The institute must handle the funds allocated for the purpose it is meant
for and generate a statement of expenditure (SOE) from time to time as per the policy and procedures laid
down by the state.
Table 5A and 5B below details the pattern of assistance:
Table 5A:Pattern of assistance for Model Treatment Centers
Budget Head Number Total (Annual), in INR Remarks
Nodal Officer 1 Regular cadre From Regular cadre
Medical Officer 1 As per state NHM
Pharmacist 1 norms for each
personnel.
Data Entry operator 1
Peer support 1
Total (HR)
Grant-in-aid for Hepatitis A and 100,000 To be provided
Hepatitis E case management from SPMU
Meeting/ Training 6 128,000
Contingency ( photocopy/internet/ 300,000
communication/ Resistance testing in selected
cases/ Printing M & E tools/ Tablets for M & E
if needed) any other operational costs etc.)

Table 5B:Pattern of assistance for Treatment Centers
Budget Head Number Total (Annual), in INR Remarks
Human Resource
Pharmacist 1 As per state NHM
Data Entry operator 1 norms for each
personnel.
Peer support 1
Total (HR)
Grant-in-aid for Hepatitis A and 100,000 To be provided
Hepatitis E case management from SPMU
Contingency ( photocopy/internet/ 50,000
communication/ Resistance testing
in selected cases/ Printing M & E
tools/ Tablets for M & E if needed)
any other operational costs etc.)
Patient Flow at the Treatment Centers

The following sections elaborate on the flow of patient at the treatment center and also can be used to guide the
smooth functioning of the staff.

1. Enrollment of the patient into care
Enrollment of the patient: The patients who present to the center could either have a definite diagnosis or
might have suspected infection. In case the person is found to have hepatitis B infection by the HBsAg (from a
government facility), they should be confirmed with another HBsAg,if needed, at least after 6 months as per
the diagnosis algorithm in the national guidelines.

37
Patient presents to the Treatment center
Refer to Model Treatment Center. If already

Patient is referred from other health care provider or Patient has a positive HBsAg / viral load
presents due to suspicion/ perceived risk by self result from outside laboratory
Get HBsAg done, and if positive enroll in care. Peer supporter makes entry in Hepatitis B pre treatment
register and sends to doctor
Doctor undertakes detailed history, examination and requests necessary investigation. Peer supporter
guides the patient to laboratory
Lab technician: draws the blood, performs the tests/ensures transport (as per guidelines) and ensures
that the reports are generated and sent to the clinician at the treatment center. Keeps close coordination
with the peer supporter and pharmacist. Ensures that test results are updated in records
absence of cirrhosis ( usingnon invasive criteria), prescribes the medicines as per the guidelines and
send to pharmacist. In case of specific situations*, refers the patient to MTC. Doctor fills the relevant
sections of treatment card.
Data entry operator enters the data into the excel Patient leaves the center with clear
sheet, maintains a line list of the patients instruction for follow up
Follow up visits
Every patient found HBsAg positive ( without acute features like jaundice) is registered in care. There is no need
to confirm with second HBsAg test in completely asymptomatic patients or those with features of fibrosis/
cirrhosis/HBV flare. Those with acute hepatitis or a recent risk factor (within 180 days) for HBV infection should
undergo a repeat HBsAg testing after 6 months to confirm chronicity.
Once enrolled, each patient has to undergo clinical and laboratory assessment to determine the eligibility for
treatment with antivirals. All the patients who are HBsAgpositive have to be enrolled in the Hepatitis B Care
register ( Annexure4). Once a person becomes eligible and started the treatment, the name is transferred to the
hepatitis B Treatment register(Annexure5).This means that those people who are not yet eligible for treatment
should be followed in the Hepatitis B Care register. Once the treatment starts, the entry are only to be made in
the Hepatitis B Treatment register.
The Hepatitis B testing and treatment card will capture patient demographic information diagnosis and
treatment details (Annexure 6).

signs the card at the respective places mentioned.
The data entry operator maintains the digitize format of the same.
The details are also entered at each visit as and when they are advised. The follow up entries help in monitoring
the disease progress, counseling of the patient for regular treatment, review of adherence of the patient to
therapy.
Follow up: The drugs will be dispensed for 30 days for initial 6-12 months. The first follow up date should be
given after 25 days and then after every 30 days. This is to ensure that the patient will always have a buffer stock
for 5 days and will not miss the dose in case s/he misses the scheduled appointment. Once the treating doctor is
confident that the patient has been stabilized, the drug dispensation can be done for upto 3 months. The patient
should be instructed to bring the bottle of medicines with her/him at every visit so that the pharmacist can
perform pill count, collect the old bottle and issue a new one. Since this is a life long treatment once started, each
staff interacting with the patient should provide counseling on the need for regular treatment.
The complicated cases, , should be referred to the MTC. At the MTC, the drugs should be dispensed and once the
patient is stable and the treating doctor is confident that the patient can be managed at the nearest treatment
site, then the drug dispensation can be done at the nearest site. However, the patient should be referred back to
MTC in case it is deemed necessary for appropriate management.
The uncomplicated cases, should be initiated treatment at the treatment center. Once the patient is stable and
the treating doctor is confident that the patient can be managed at the nearest treatment site, then the drug
dispensation can be done at the nearest site. However, the patient should be referred back in case it is deemed
necessary for appropriate management.
Table 6:Summary of the key actions to be undertaken for patient management, record maintenance and the
responsible person.
Visit Number Key activity ( but not limited to) Responsible person
Ascertain Diagnosis of Chronic HBV infection Attending doctor
Enter patient details in Hepatitis B Peer Supporter
Enrollment Register and demographic
details in treatment card
Take a detailed history and examination Attending Doctor
First visit and baseline, Categorize presence/Absence of Cirrhosis Attending Doctor
after confirmation of and fill relevant section in Treatment card
Chronic HBV infection Select Regimen and start treatment Attending Doctor
Explain patient on adherence Peer supporter and pharmacist
and follow up date
Get the baseline investigations done and Lab technician, Doctor
)furnish report to center ( treatment site
Educate on treatment adherence Doctor ,Peer supporter
and regular follow up and pharmacist
Check for any side effects Attending Doctor, pharmacist
Follow up visit Get any investigations needed as per Attending Doctor
technical guidelines, prescribe the medicines
Recheck the contact details including Peer supporter / data entry operator
phone number and pincode / post office
Update the record from the register Data entry operator
For all visits
and card to the excel based sheet

39
Ideally, there should be no expiry at any center. However, in the event there is expiry of some medicines under
the nodal officer of the center. In case there is no institutional policy for discarding the medicines, from the
Monitoring and Evaluation of Hepatitis B Treatment

Introduction
A robust monitoring and evaluation framework is vital for the program. The day to day operations of the
program rely on the system established for monitoring and evaluation since Hepatitis B treatment is a lifelong
treatment. The effective functioning of M&E systems relies on the ownership and responsibility of stakeholders
regarding the information they provide to the systems, the feedback and it’s use for policy making.In addition
to the dat a collected from the service delivery points (diagnosis and management of viral hepatitis, etc.), the
NVHCP will also coordinate with the existing programs and schemes that contribute towards the response to
viral hepatitis B and this would be compiled for monitoring a comprehensive program update at national level.
Objectives of the Monitoring and Evaluation framework

• Guide monitoring of the Hepatitis B management at all levels-national, state & district
• To identify the core indicators for Hepatitis B that will allow key stakeholders in country to evaluate and
measure NVHCP in all its components of Hepatitis B management.
• To facilitate collection and analysis of standardized data through appropriate reporting mechanisms at all
levels.
• Enhance the availability and quality of data by using the required reporting formats with relevant data
field.
• To build capacity of the Viral Hepatitis Management Units at National, State and district level and the
service delivery points to regularly and systematically track progress of implementation and adherence of
treatment of Hepatitis B under NVHCP.
Timeliness is a key feature of an efficient delivery system. A computerized data management system under the
‘National Viral hepatitis Control Program’ would facilitate automated data transfer, data validation, monitoring
and evaluation. Data will therefore, be entered in standard data formats at the source, in software capable of
handling multilevel entries and validation. Standard formats for recording and reporting prescribed by the
NVHMU are annexed. The relevant data of the service delivery points needs to be shared within the centre,
maintaining confidentiality.
In addition to the data collected from the service delivery points (diagnosis and management of viral hepatitis,
etc.), the NVHCP will also coordinate with the existing programs and schemes that contribute towards the
response to viral hepatitis B and this would be compiled for monitoring a comprehensive program update at
national level.

Monitoring Indicators
S Indicator Baseline Target for Source of
No Year 1 reporting and level
Input indicators
1 Number of sites offering 0 650 Reports from SVHMU
treatment for Hepatitis B
2 Are National guidelines and SOPs developed N/A Yes NVHMU
?for management of Hepatitis B
3 Is there a standard Training curriculum N/A Yes NVHMU
?developed for management of Hepatitis B
Process Indicators
4 of State laboratory sites which have been % N/A 100% NVHMU and SVHMU
trained on the SOPs for labs with respect to
diagnosis of Hepatitis B under the program
5 of Treatment sites which have been % N/A 100% NVHMU and SVHMU
trained on the SOPs on Management
of Hepatitis B under theprogram
Output Indicators
6 Total number of patients eligible for N/A NVHMU and SVHMU
treatment for Hepatitis B put on treatment
7 Proportion of newborns who received % NVHMU, SVHMU with
birth dose of Hepatitis B vaccine inputs prom Universal
Immunization Program
Data Sources
TData sources will include State and District health units, service delivery points and healthcare-facilities.
The NVHCP has some components that involve coordination with other existing programs and schemes.
Data will be obtained from the respective programs/schemes/ministries for data triangulation and relevant
intervention.
Data Storage
Proper record keeping of client results is vital. As per the guidelines, all documents must be stored for at least 5
years or as per state/ institutional guidelines whichever is longer.
Recording and Reporting at various levels and flow of information

Every health facility/service delivery point needs a system of recording the required data. Making records
system systematically & regularly will help to follow up on defaulters, loss to follow up, treatment interruption
and solve issues of non-adherence. Data generated & collected at service delivery point i.e. treatment site and
state and district laboratory will be sent to the DVHMU, SVHMU and NVHMU through monthly reports. At
State & National level, the data will be aggregated and analyzed, and feedback will be provided.

41
Responsibility of reporting, flow of information and frequency of monthly format reporting
Level Reporting Person Reporting to Frequency Submission

form Responsible of date by
for reporting submission
SVHMU Consolidated Program I/C; NVHMU Monthly 10th of every
report of or state nodal month
the state officer
DVHMU Consolidated Program I/C; SVHMU Monthly 7th of every month
report of the or district
district including nodal officer
district hospitals,
sub-district
hospitals,
CHC,PHC,
SC, H&WC
Model Monthly report Nodal Officer SVHMU Monthly 5th of every month
Treatment of TC/MTC
Centre
Treatment SVHMU (through DVHMU Monthly 5th of every month
centre if treatment centre
is located at district
)hospital/sub-district level
State Monthly report Nodal officer of SVHMU Monthly 5th of every month
Laboratory state laboratory
District Monthly report Nodal officer DVHMU Monthly 5th of every month
Laboratory of district
laboratory
DVHMU SVHMU Monthly 7th of every month
Review meetings & Supervisory visits

The treatment sites and the laboratory will be reviewed regularly by the nodal officers for site level day to day
functioning.
In addition, the district/state and national officials will also undertake supervisory site visits for supportive
supervision and mentoring according to the supervisory checklist in the annexure. Review meetings of the
SVHMU officials will be organized on a quarterly basis to assess physical and financial progress, discuss
constraints in implementation of the NVHCP and identify solutions to key barriers and bottle necks. Key
gaps identified during the implementation of the NVHCP will also be addressed through planned operational
research.
The suggested frequency of the monitoring and supervisory visits is:
Frequency of visit to the treatment sites

National Annual
State Quarterly

Evaluation
The purpose of the evaluation is to examine NVHCP in the context of the health system and its broader
surroundings. The evaluation looks at the program’s strengths and weaknesses, the efficiency and
effectiveness of its activities and its impact on disease. It also assesses the program’s capacity to adapt to
new demands, both those generated from health sector reform and decentralization, as well as those arising
in response to the population’s need for access to new drugs and technologies.
Outcome of the program will be assessed through framework of evaluation. It is envisaged that the
program will undergo process evaluation, mid-term evaluation and end evaluation. It will be carried out by
independent agency. The evaluation will be conducted in two stages after two to three years of roll out of the
program. Panel of institutions will be identified to conduct evaluation.The evaluationresults will be used to
maintain, correct, or modify program activities.

43
Annexure 1: Assessing severity of liver disease
A full assessment should include
»» Clinical evaluation for features of cirrhosis and evidence of decompensation, and
»» Measurement of serum bilirubin, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST),
alkaline phosphatase (ALP), and prothrombin time; as well as full blood count, including platelet count.
»» Other routine investigations include ultrasonography and alpha-fetoprotein (AFP) measurement for periodic
surveillance for HCC, and endoscopy for varices in persons with cirrhosis.
Liver enzymes: Aminotransferase levels may fluctuate with time, and single measurements of ALT and AST do not
indicate disease stage. Usually, the ALT concentrations are higher than those of AST, but with disease progression
to cirrhosis, the AST/ALT ratio may be reversed. Tests of liver synthetic function and/or portal hypertension
include serum albumin, bilirubin, platelet count and prothrombin time. A progressive decline in serum albumin
concentrations, rise in bilirubin and prolongation of the prothrombin time are characteristically observed as
decompensated cirrhosis develops.
Liver biopsy: Liver biopsy has been used to ascertain the degree of necro-inflammation and fibrosis, and to help
guide the decision to treat. There are several established methods of scoring histology and measuring activity
(necroinflammation) separately from stage (fibrosis). However, limitations of biopsy include sampling error,
subjectivity in reporting, high costs, the risks of bleeding and pneumothorax, discomfort to the patient, and the
need for training and infrastructure. The pathological features of CHB on liver biopsy depend upon the stage of
the disease, host immune response and degree of virus replication.
Metavir Stage F0 F1 F2 F3 F4
Definition No Fibrosis Portal fibrosis Portal Numerous septa Cirrhosis

without septa fibrosis without cirrhosis
with septa
Non-invasive tests (NITs): Though liver biopsy remains the gold standard, non-invasive methods for assessing
the stage of liver disease are supplanting it due to the limited availability and accessibility to liver biopsy and
have been validated in adults with CHB. Blood and serum markers for fibrosis, including APRI and FIB-4, or
transient elastography (FibroScan) are performed to rule out advanced fibrosis.
APRI (AST-to-platelet ratio index) and FIB 4 are recommended as the preferred non-invasive tests (NIT) to assess
for the presence of cirrhosis (APRI score >2: FIB 4 >3.25 in adults).Transient elastography (e.g. FibroScan) may be
the preferred NITs in settings where they are available and cost is not a major constraint.
APRI and FIB-4 can be readily calculated by the following formulae
APRI = * (AST/ULN) x 100) / platelet count (109/L)
FIB-4 = (age (yr) x AST (IU/L)) / (platelet count (109/L x [ALT (IU/L)1/2])
For APRI, ULN signifies the upper limit of normal for AST in the laboratory where these investigations were
undertaken. For example, in a patient with an AST of 92 IU/L (where laboratory ULN for AST is 40 IU/L) and a
platelet count of 80x109/L, the APRI would be: (92/40) x100/80 = 2.87. This value is >2 and is consistent with the
presence of cirrhosis.
The optimal cut-off values for different NITs that correlate with specific stages of liver fibrosis have been derived
and validated in case of APRI and FIB-4. APRI and FIB-4 use two cut-off points for diagnosing specific fibrosis
stages, as the use of a single cut-off would result in suboptimal sensitivity and specificity. A high cut-off with
high specificity (i.e. fewer false-positive results) is used to diagnose persons with fibrosis (i.e. greater than or equal
to a particular stage [e.g. ≥F2]), and a low cut-off with high sensitivity (i.e. fewer false-negative results) to rule out
the presence of a particular stage of fibrosis. Some persons will fall in the indeterminate range of test results (i.e.
their score will be between the low and the high cut-off) and will need future re-testing and evaluation.

APRI (low APRI (high FIB-4 Transient elastography
cut-off) cut-off) (FibroScan)*
Cirrhosis 1.0 2.0 - kPa >11–14
)METAVIR F4(
Significant fibrosis 0.5 1.5 )low( 1.45 kPa 8.5–7>
)METAVIR ≥F2( )high( 3.25
There are no validated exact cut-offs for specific stages of fibrosis with FibroScan. This table presents the range of
kPa may be used 12.5 stages of fibrosis in CHB. A mean cut-off of and ≥F2 the most commonly used cut-offs for F4
.to diagnose cirrhosis and guide treatment decisions, after taking into account key limitations
Reference:Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection., WHO,(
)2015
Ascertaining the Degree of Cirrhosis

The degree of cirrhosis is important to be ascertained before the treatment is initiated. The Child–Pugh
score is a system for assessing the degree of liver disease, and classified patients as Class A, B, or C based on
clinical and laboratory criteria. Those with Class C have the most severe liver disease. Some HCV regimens
are contraindicated among persons with Child-Pugh Class B and C or decompensated cirrhosis.
The following table depicts the Child Pugh Score:
Points 1 2 3
Encephalopathy None )Minimal (Grade 1 or 2 )Advanced (Grade 3 or 4
Ascites Absent Controlled Refractory
Total bilirubin )2<( 34< )3–2( 51–34 )3>( 51>
)μmol/L) (mg/dL(
)Albumin (g/dL 3.5> 3.5–2.8 2.8<
Prothrombin time or <1.7 4< or 1.7–2.3 6–4 or >2.3 6>
prolongation (seconds) or INR
Child–Pugh Class A: 5-6 points
Child–Pugh Class B: 7-9 points
Child–Pugh Class C: 10-15 points

45
Annexure 2: Summary Guidance for the Model Treatment Center (MTC)
for some special situations
The MTC will have cases that are complicated or have special needs, and will be referred from the treatment
centers. Some of these include patients with suspected treatment failure, patients where TAF is indicated,
patients with malignancy etc. Hence, some information that could be used by the MTC is summarized below.
However, with growing evidence and newer established modalities, the MTC will be expected to provide the
approved management modalities.
Response to Treatment
Responses can be divided into virological, serological, biochemical, and histological. All responses can be
estimated at several time points during and after therapy. The definitions of virologicalresponses vary according
to the timing (on or after therapy) and type of therapy.
Virological responses:
(1) NA therapy
Virological response during NA is defined as undetectableHBV DNA by a sensitive polymerase chain reaction
(PCR) assay with a limit of detection of 20 IU/ml. Primary nonresponseis defined by a less than one log10
decrease of serum HBV DNA after 3 months of therapy. Partial virologicalresponse is defined as a decrease in
HBV DNA of morethan 1 log10 IU/ml but detectable HBV DNA after at least12 months of therapy in compliant
patients. Virologicalbreakthrough is defined as a confirmed increase in HBVDNA level of more than 1 log10 IU/
ml compared to the nadir(lowest value) HBV DNA level on-therapy; it may precede abiochemical breakthrough,
characterized by an increase inALT levels.HBVresistance to NA(s) is characterised by selectionof HBV variants
with amino acid substitutions that conferreduced susceptibility to the administered NA(s).
However the program advocates the HBV DNA monitoring on a yearly basis. However, as and when the clinician
feels a justifiable need the same may be recommended more than once in a year with appropriate documentation
and signature of the nodal officer at the MTC.
In patients who discontinue NA, sustained off-therapyvirological response could be defined as serum HBV DNA
levels <2,000 IU/ml for at least 12 months after the endof therapy.
(2) PegIFN-alfa therapy

Virological response is defined as serum HBV DNA levels <2,000 IU/ml. It is usually evaluated at 6 months and
atthe end of therapy.
Sustained off-therapy virological response is defined as serum HBV DNA levels <2,000 IU/ml for at least12
months after the end of therapy.
Serologic Response
Serological responses for HBeAg are HBeAg loss and HBeAgseroconversion, i.e., HBeAg loss and development of
anti-HBe(only for HBeAg-positive patients).
Serological responses for HBsAg are HBsAg loss and HBsAgseroconversion,i.e., HBsAg loss and development of
anti-HBs (for allpatients).
Biochemical Response
Biochemical response is defined as a normalization of ALTlevels based on the traditional ULN (<40 IU/L).
Since ALT activityoften fluctuates over time, a minimum follow-up of at least1 year post-treatment with ALT

determinations at least every3 months is required to confirm sustained off-treatment biochemicalresponse. It
should be noted that the rates of sustainedoff-treatment biochemical responses may sometimes be difficultto
evaluate, as transient ALT elevations before long-term biochemicalremission may occur in some CHB patients
within thefirst year after treatment discontinuation. In such cases, additionalclose ALT follow-up of at least 2
years after ALT elevationseems to be reasonable in order to confirm sustained offtherapybiochemical remission.
Histological Response
Histological response is defined as a decrease in necroinflammatory activity (by P2 points in histologic activity
index orIshak’s system) without worsening in fibrosis compared to pretreatment histological findings.
Use of TAF in Chronic Hepatitis B

Minimal rates of renal function decline have been reported during long-term therapy with ETV and TDF, but
the nephrotoxic potential is higher for TDF. Cases of Fanconisyndromeassociated with TDF therapy and rescued
after a switch to ETVhave been reported. In addition, studies using sensitive markers of glomerular and tubular
kidney function and of bone mineral density have also reported chronic tubular damage and decline ofeGFR
and bone mineral density in TDF treated patients.
Therefore, it seems appropriate for now to monitor all CHBpatients treated with TDF therapy for adverse renal
effects withserum creatinine (eGFR). Moreover, CHB patients at high renal risk undergoing any NA therapy
should be monitored with serum creatinine (eGFR) levels. Thefrequency of renal monitoring can be every 3
months during the first year and every 6 months thereafter, if no deterioration.
Closer renal monitoring is required in patients who developcreatinine clearance <60 ml/min or serum phosphate
levels<2 mg/dl.
In CHB patients with deteriorating renal function or low eGFR (<60mL/min/1.73 M2), albuminuria and/or
osteopenia/osteoporosis, chronic steroid use, particularly in older age (>60 years)should also be considered
when choosing NA therapy. In such subgroups of CHB patients, entecavir represent suitable choice. TAF should
be used in patients with previous exposure to nucleoside analogues, such as, lamuvidine or telbuvidine..
Entecavir Dose in Renal Impairment

Usual daily dose (0.5 mg)
• CrCl ≥50 mL/min: No dosage adjustment required
• CrCl 30-49 mL/min: Reduce to 0.5 mg q48hr
• CrCl 10-29 mL/min: Reduce to 0.5 mg q72hr
• CrCl<10 mL/min, hemodialysis, or CAPD: Reduce to 0.5 mg q7days
Use of Pegylated Interferon

The Nuceotide Analogues are the mainstay of the treatment under the National Program. The two with high
genetic barrier to resistance, namely tenofovir and entecavir are recommended.
PegIFNa can be considered as an initial treatment option for patients with mild to moderate HBeAgpositiveor
negative CHB.The standard duration of PegIFNa therapy is 48 weeks. The extension of the duration of
PegIFNatherapy beyond week 48 may be beneficial in selected HBeAgnegativeCHB patients.
Only patients with mild to moderate CHB with compensated cirrhosis but no portal hypertension should be
considered for PegIFNa therapy.
HBeAg loss with HBV DNA <2,000 IU/ml at 6 months post-treatment was achieved in ~23% in a meta-
analysis of three large trials. In initiallyHBeAg-positive CHB patients with sustained virologicalresponses,

47
HBsAg loss rates increase after the end of PegIFNa therapy. HBsAgloss is uncommon during PegIFNa therapy
in HBeAgnegativeCHB patients, however the rate of HBsAg loss progressivelyincreases after PegIFNa
discontinuation, from 3% at month 6% to9% at year 3 to 12% at year 5.
All CHB patients treated with PegIFNa should be followed with periodical assessments of at least completeblood
count, ALT, TSH, serum HBV DNA and HBsAg levels. HBeAg-positive CHB patients treated with PegIFNashould
be also followed with periodical assessments of
HBeAg and anti-HBe.CHB patients with virological response after PegIFNatherapy should remain under long-
term follow-up because of the risk of relapse.
However, the since the selection of patient is critical to the successful outcome to therapy with Peg IFN, it is
recommended that this drug should not be used at any site other than MTC that has the required expertise. Also,
the selection of eligible patients for Peg IFN should be done on case to case basis by a committee of three experts
and one program person from the SVMHU/NVMHU. These committees shall be constituted by the program as
it evolves.
Monitoring Patients for HCC, with a family history of HBV related HCC
Chronic HBV infection leads to an increased risk of death from liver cirrhosis and/or liver cancer. In resource-
limited and high HBV-burden settings, persons are often diagnosed with HBV only when they present for the
first time with HCC. While the majority of these (80–90%) have cirrhosis at the time of diagnosis of HCC, it
may sometimes occur without the presence of cirrhosis; this is especially true for HCC due to HBV. A further
major challenge with HCC is that it is rapidly progressive, and may be asymptomatic until it presents clinically
at an advanced stage. Treatment options for advanced HCC are limited and overall survival is extremely poor.
The prognosis of HCC is affected by the size and number of tumours, and the underlying liver function, and is
improved if treatment can be commenced at an early stage of the disease, when the tumour is small. Surveillance
is therefore required to detect HCC at an early stage (tumour size <3 cm in diameter) and increase the chances
of effective treatment. Effective surveillance programmes require a means for implementing such treatment
for small HCC in LMICs, recognizing that access to liver transplantation or resection remains limited, even in
high-income settings. These treatments would include alcohol injection or radiofrequency ablation of small
tumours. Current surveillance tools include ultrasound and/or alpha-fetoprotein (AFP) measurement, but there
is no consensus on the best strategy or frequency of monitoring for HCC in persons with CHB, although existing
evidence suggests that semi-annual surveillance detects HCC at an earlier stage and improves survival.
Who should be screened for HCC?

Evidence from longitudinal studies shows that the most important risk factors for development of HCC
(associated with an approximately four-fold increased risk) are the presence of cirrhosis, HBeAg positivity and
a family history of HCC. Global experts opined that the majority of persons (80–90%) also have cirrhosis at
the time of diagnosis of HCC and therefore recommended that those with cirrhosis as well as those with a
family history of HCC are the most important high-risk groups to target for screening. Although age >40 years
is associated with an increased risk of HCC in Asian populations, these experts considered that the optimal age
at which surveillance for HCC should commence cannot yet be established with certainty, as the incidence of
HCC varies with age according to region, and occurs at a younger mean age in Africans compared to Asians
(see http://globocan.iarc.fr/ia/World/ atlas.html, IARC GLOBOCAN). Therefore, no specific age threshold for
screening was recommended.
Risk calculators have been developed, which provide an easy-to-use formula to predict the risk of HCC from
models that include age, sex, levels of albumin, bilirubin and ALT, HBeAg status, HBV DNA levels and presence
of cirrhosis. These models were derived largely from longitudinal cohort data of Asian patients and have not
been extensively validated in non-Asians. The evidence was rated as being of high-to-moderate quality (due to
imprecision or limitations in the outcome assessment). More limited data were available in HBV/HIV-coinfected

patients, but low CD4+ cell count and longer cumulated time with detectable HIV RNA were associated with an
increased risk of developing HCC.
Cumulative incidence of hepatocellular carcinoma (HCC) according to family history of HCC, baseline HBV
DNA level and HBeAg status ( Ref WHO guidelines, 2015)
(%) Cumulative incidence Adjusted HR (95% CI)

NO family history 7.5 Reference
Family history of HCC 15.8 )1.63-3.72( 2.46
NO family history 2.5 Reference
HBV DNA <10 000 copies/mL
HBeAg positive 40 )22.86-90.63( 45.52
Family history of HCC
HBeAg positive 19.1 )9.31-20.77( 13.91
No family history
HBeAg negative 17.6 )4.52-21.37( 9.90
HBV DNA >10 000 copies/mL
HBeAg negative 10.3 )3.02-6.50( 4.43
No family history
HBV DNA >10 000 copies/mL
HBeAg negative 5.4 NS
HBV DNA <10 000 copies/mL
All data among HBsAg-positive persons with CHB
HR hazard ratio, CI confidence interval

49
Annexure 3 Site Feasibility Checklist
National Viral Hepatitis Control Program

a
b
c
d
1 Is the Institution willing to set up a center for hepatitis treatment Yes No Yes No
2 Is the In-charge keen on establishing services? Yes No Yes No
a Willing to allocate necessary space Yes No Yes No
b Willing to have nodal person for treatment and lab services Yes No Yes No
c Integrate the functioning and follow the National guidelines and Yes No
protocols , including recording and reporting Yes No
3 What is the annual OPD of the hospital Yes No
4 Is there super-specialty( Gastroenterology/ Hepatology) Yes No Yes No
5 )How many cases of acute hepatitis are seen annually ( explore last years report Yes No
6 )How many cases of hepatitis B and C are seeking care ( explore previous reports Yes No
B and hepatitis C in last three years ( record year wise) Yes No
8 If this is a district hospital, where are patients referred or usually go for Yes No
complicated cases?
A ICTC Yes No
B ART center Yes No
C Opioid Substitution Center Yes No
D Involvement with Prison Yes No
10 )Is the institution implementing any other program under NHM? Please mention name(s Yes No
INFRASTRUCTURE
1 Location of the proposed centre ( is it in vicinity to OPD services) Yes No Yes No
2 Is there an ICU Yes No Yes No
3 Number of rooms Yes No
A Doctors Yes No Yes No
B Pharmacist Yes No Yes No
C Data Entry Operators Yes No Yes No
D Drug Storage & Pharmacist Yes No Yes No
E Lab Technician Yes No Yes No
F Peer supporter Yes No Yes No
4 Is institution willing to provide necessary furniture ( chairs, tables, Almirahetc) Yes No Yes No
5 Will the center have access to internet

HUMAN RESOURCES
1 Does the institution have the required capacity to manage chronic Yes No
hepatitis Cases? Yes No
a Gastroenterologist/Hepatologist Yes No Yes No
b Physician ( Internal Medicine) Yes No Yes No
c Pediatrician Yes No Yes No
d Microbiologist Yes No Yes No
e Pathologist Yes No
f Obstetrician Yes No
g )Others (Mention
)test (immunoassay - please specify
A Complete Blood Count / Haemogram Yes No
B Renal Function test Yes No
C )Liver Function Test (please ask for each test Yes No
D Blood Sugar Yes No
E INR Yes No
F Platelet count Yes No
G Pregnancy Test Yes No
H X Ray Yes No
J Fibroscan Yes No
K CT scan Yes No
l MRI Yes No
M Endoscopy Yes No
N Liver Biopsy Yes No
O Others Yes No
Final Recommendation of the Team (Please Tick)

……………………………………………Signature of the Feasibility Visit Team: 1
……………………………………….……2
……………………………………….……3
.……………………………………………4

51
52
Annexure 4: Hepatitis B Care Register
Register for work up of any suspect of Hepatitis B
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Confirmed

HBsAg test
Sex Date Place Is patient If the regimen has

Patient’s Preg-nant eligible for Date of Date of
Date of hosp. NVHCP )(Y/N Base-line Base-line Follow changed-Date of
.S. No name and Age / M / F treatment eligibility for initiation of
1st visit .reg. no ID *APRI score FIB4 up HBV change and the

address TG If yes, date at time of treatment treatment
Reasons for change
? enrolment
Annexure 5: Hepatitis B Treatment Register
Month: Year:
1 2 3 4 5 6 7 8 9 10 11 12 13
Guardian / Liver cirrhosis
Patient’s Patient’s
Date of Treatment status at
first Sex address Prior
S. start of Registration supporter’s registration Platelet Regimen
name Age M/F/ and treatment HBV VL APRI score
.N Hep B Number name and (no cirrhosis, count started
and TG contact history
treatment contact compensated,
surname number
number )decompensated
0 12 24 0 12 24 0 12 24
Y
M M M M M M M M M
36 48 60 36 48 60 36 48 60
N M M M M M M M M M
0 12 24 0 12 24 0 12 24
Y
M M M M M M M M M
36 48 60 36 48 60 36 48 60
N M M M M M M M M M
0 12 24 0 12 24 0 12 24
Y
M M M M M M M M M
36 48 60 36 48 60 36 48 60
N M M M M M M M M M
0 12 24 0 12 24 0 12 24
Y
M M M M M M M M M
36 48 60 36 48 60 36 48 60
N M M M M M M M M M
Y 0 12 24 0 12 24 0 12 24
M M M M M M M M M
36 48 60 36 48 60 36 48 60
N M M M M M M M M M
Y 0 12 24 0 12 24 0 12 24
M M M M M M M M M
36 48 60 36 48 60 36 48 60
N M M M M M M M M M
Y 0 12 24 0 12 24 0 12 24
M M M M M M M M M
36 48 60 36 48 60 36 48 60
N M M M M M M M M M

53
54
Annexure 5: Hepatitis B Treatment Register
Month: Year:
1 2 3 4 5 6 7 8 9 10 11 12 13
Guardian / Liver cirrhosis
Patient’s Patient’s

Date of Treatment status at
first Sex address Prior
S. start of Registration supporter’s registration Platelet Regimen
name Age M/F/ and treatment HBV VL APRI score
.N Hep B Number name and (no cirrhosis, count started
and TG contact history
treatment contact compensated,
surname number

number )decompensated
Y 0 12 24 0 12 24 0 12 24
M M M M M M M M M
36 48 60 36 48 60 36 48 60
N M M M M M M M M M
Y 0 12 24 0 12 24 0 12 24
M M M M M M M M M
36 48 60 36 48 60 36 48 60
N M M M M M M M M M
Y 0 12 24 0 12 24 0 12 24
M M M M M M M M M
36 48 60 36 48 60 36 48 60
N M M M M M M M M M
16 18 19
Follow up visits: ● 1st row, write patient outcome: on treatment (OT) if patient picked up
ART drugs; stopped (ST) if ART was stopped by the doctor; missing (MIS) if the patient
If the Regimen has )missed the scheduled visit but came back within a week; lost to follow-up (LFU
Date and
,been changed reason for if the patient did not come till the end of month; restart (RS) if treatment was restarted after an
stopping interruption; transferred out (TR); dead (D); REF: If patient was referred to TC/MTC
Treatment )2nd row: write compliance to treatment based on pill count ( pill taken actually/pills prescribed *100 ●
Date of New M M M M M M M M M M M M M M M M M M M M M M M M M M M
*Reason Week2
change Regimen 1 2 3 4 5 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69

55
Annexure 6: Testing & Treatment Card
Patient Testing & Treatment Card

Hospital Registration Number
NVHCP ID
………/..……/.…… Date of starting DAA
Basic Demographic Information
Name Age Gender M F
TG
/Father’s name/Mother’s Name
Guardian’s name
Address
Home & street address

State
District
Village/Town/city
Pincode /Post office
Contact Number
Consent for communication: Y N
Date of HBsAg Rapid ELISA Other
testing
Result of HBsAg
Whether sample Y N Condition of storage Duration of Storage
is being stored
Whether sample is Y N Date of transport If sample received for viral load
being transported in optimum conditions
Date of HBVDNA Result of HBV DNA
testing
Is there Cirrhosis No If yes then Decompensated
at Registration Yes Compensated
)Criteria for Evaluating cirrhosis (At least one
Ultrasound Date___/_____/___
Fibroscan )LSM Value ( in kPa( Date___/_____/___
*APRI Score
*FIB-4 ALT___________ ALT___________ Platelet Count Age
Date___/_____/___
Score____________
If decompensated cirrhosis, select basis
CP Score Variceal bleed Ascites Encephalopathy
Drug Prescribed
Patient not treated but transferred to higher centre Y N
Reasons for transfer
Place Date
The centre must do both APRI and FIB 4 scoring*

Date of Hemoglobin Platelet ALT AST S.Bilirubin S.Albumin INR HBV Other Remarks
visit count )(T/D/I DNA )(USG
Follow up visits
S.No .Visit No Date of Any new Any other Any Next Signature Signature Patients
visit complaints medications remarks Follow of Doctor of /signature
or side- up Date pharmacist Thumb
effects impression
Outcome of treatment
On Treatment
Loss to follow up
Death
Missed
Interruption
Restart

57
Monthly Report

Monthly Report-Hepatitis B
.S.No
1 Name of Centre
2 .Code No
3 Name of District
4 Name of State
5 Name of Site-Incharge
6 Report for the period
7 Total Number of patients found positive for Hepatitis B registering in Care
7.1 Total number of patients screened for HBsAg in that month
7.2 Total Number of patients found positive for HBsAg in that month
7.3 Total number of patients found eligible for treatment of Hepatitis B in that month
8 Initiation of Treatment for Hepatitis B
8.1 Total number of patients eligible for treatment for
Hepatitis B put on treatment in that month
8.2 Total number of patients ever started on treatment
for Hepatitis B at the starting of the month
9 Treatment Outcomes for Hepatitis B
9.1 Total number of patients put on treatment for Hepatitis B continuing
treatment as recorded through follow up visits in that month
10 Regimen status
10.1 Cumulative number of Hepatitis B patients onRegimen 1
at the end of the month
10.2 Cumulative number of Hepatitis B patients on Regimen 2
10.3 Cumulative number of Hepatitis B patients on Regimen 3
11 Treatment Outcome
11.1 "Cumulative number of patients who "transferred out
11.2 "Cumulative number of patients who "transferred in
11.3 The number of all patients whose treatment status in this
month is “stopped treatment” due to medical reasons
11.4 )Cumulative Number of patients who are lost to follow-up (LFU
11.5 The number of patients who missed their doses in this month
11.6 Total number of patients Referred to Higher center for further management
Drug Stock
Generic Opening Stock Add expiry Consumption Expiry Stock on Amt required Issues
Drug Stock Received date during the during last day of for 3 months comment
name during month the month the month based on
month existing stock
Was there a stock out in this month Yes No

Reasons for the stock out
Signature of the nodal officer

Annexure 7: Patient’s Referral Register

Patient’s Referral Register
.S.No Hospital Reg No
Date NVHCP Unique Id
State District Block/CHC PHC/Sub-centre
Name & Address Age Sex
Brief History of illness Phone/Mobile
Tested for Suspected for
Reasons for referral
Referred by Referred to
Signature Signature
Mobile No Mobile No
Designation Designation
Annexure 8: Drug Stock Register
.Dte Opening Stock Received Stock Stock Stock Balance Rem-

Stock Transferred Dispensed /Expired Stock ark
out (consumpt- Discard-
)ion ed
Qty. Batch Expiry Manu-
(No of .No Dte facturing
)tablets Date
Annexure 9 :Drug Dispensation Register
S.No. Patient Patient No. of tablets dispensed Patient’s

name Registration Signature
No. Regimen 1 Regimen 2 Regimen 3

59
Annexure 10: Supervisory Checklist
Supervisory Checklist for Treatment Site

.S.No Head Response
1 :Name of the State/ District/ City/ town
2 Type of Hospital: ( Medical College/
)District Hospital / Other tertiary care
3 Name of the Medical Superintendent
or IC of the institution
4 Names of the identified Nodal officer by
healthcare facility for treatment
5 Date of Supervisory Visit
.i
.ii
.iii
7 Complete postal address of the
Hospital with Pin Code
8 Contact details of the Nodal person
) ( mobile and email
9 Number of human resource available S.No. Name Designation
with designation under the program I
II
III
IV
10 Number of human resource trained with )S.No. Name Trained (Y/N
Designation under the program I
II
III
IV
11 How many cases have been identified
for Viral hepatitis in the FY
A
B
C
E
12 How many cases were treated/managed
for viral hepatitis in the FY
A
B
C
E
13 Is the record being maintained as
per the NVHCP guidelines
A Patient treatmentCard Y/N If no then why?
C Stock for drugs ?Y/N If no then why?
14 Has there been stock out of the drugs Y/N
?in the last three months
15 ?If Yes, then when and why
16 How many patients diagnosed with Hepatitis B put Current FY Previous FY
on each regimen in that FY and the previous FY

Regimen I
Regimen II
17 How many patients put on treatment have Current FY Previous FY
successfully completed treatment
Regimen I
Regimen II
18 Are the sanctioned positions under the ?Y/N If No then why
NVHCP for the treatment site filled
Positions ?Y/N If No then why
A ?Y/N If No then why
B ?Y/N If No then why
C ?Y/N If No then why
D
.S.No Key Issues Identified Follow up Action recommended
Name of the supervisory visit officer Signature

1
2
3
4

61
REFERENCES
1. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection. WHO 2015
2. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection:
recommendations for a public health approach – 2nd ed. WHO, 2016
3. Guidelines for the screening care and treatment of persons with chronic hepatitis C infection. Updated
version, April 2016, WHO
4. WHO Global Disease estimates 2016; WHO 2016
5. Central Bureau of Health Intelligence, Ministry of Health and Family Welfare. National Health Profile. New
Delhi : s.n., 2016.
6. Cost-effectiveness of Hepatitis C Treatment using generic direct-acting antivirals available in India.
Aggarwal, R, et al., et al. s.l. : PLOS One, 2017, Vol. 12. e0176503.
7. Prevalence of Hepatitis A virus, Hepatitis B virus, Hepatitis C virus, Hepatitis D virus and Hepatitis E virus as
causes of acute viral hepatitis in north India: A Hospital based study. Jain, Prakash P, et al., et al. 2013, Indian
Journal of Medical Microbiology, Vol. 31, pp. 261-5.
8. WHO guidelines on hepatitis B and C testing, WHO, Feb 2017
9. World Health Organization media centre. Hepatitis A fact sheet in world health organization media centre.
[Online] 2016. http://www.who.int/mediacentre/.
10. Harrison’s Principles of Internal Medicine, 19th edition
11. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents; Downloaded
from https://aidsinfo.nih.gov/guidelines on 6/27/2018
12. Colin JF, Cazals-Hatem D, Loriot MA, Martinot-Peignoux M, Pham BN, Auperin A, et al. Influence of human
immunodeficiency virus infection on chronic hepatitis B in homosexual men. Hepatology. 1999;29(4):1306–
10.133
13. Konopnicki D, Mocroft A, de Wit S, Antunes F, Ledergerber B, Katlama C, et al. Hepatitis B and HIV:
prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in
the EuroSIDA cohort. AIDS. 2005;19(6):593–601.
14. Thio CL, Seaberg EC, Skolasky R Jr, et al. HIV-1, hepatitis B virus, and risk of liver-related mortality in the
Multicenter Cohort Study (MACS). Lancet 2002;360:1921-1926.
15. Thio CL. Hepatitis B and human immunodeficiency virus co-infection. Hepatology. 2009;49(5 Suppl):S138–45.
16. Santantonio T, Fasano M,Current concepts on management of chronic hepatitis B. http//dx.doi.
org/10.5772/54759
17. : Karen C. Carroll, Stephen A. Morse, Timothy Meitzner, Steve Miller: Jawetz, Melnick, and Adelberg’s Medical
Microbiology, 27th Edition, Mc-Graw Hill Education.
18. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection , European
Association for the Study of the Liver, Journal of Hepatology 2017 vol. 67 j 370–398
19. National guidelines for Diagnosis and management of Viral hepatitis, 2018. NVHCP, MoH& FW
20. National laboratory testing guidelines for viral hepatitis, 2018, NVHCP, MoH& FW
21. Operational guidelines for the National Viral Hepatitis Control Program, 2018. MoH& FW
22. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection, 2015

LIST OF CONTRIBUTORS
Mr Abou Mere - Representative, Community Organisation
Dr Akash Shukla, Sion Hospital, Mumbai
Dr Amit Goel, SGPGI, Lucknow
Dr C. E. Eapen - Hepatologist, CMC, Vellore
Dr Ekta Gupta, Microbiologist, ILBS, New Delhi
Dr G. Kausalya, Sr CMO(SAG), CHEB
Dr Gourdas Choudhuri, Gastroenterologist, Fortis, Gurgaon
Dr Hema Gogia - Deputy Assistant Director, NCDC, Delhi
Dr Inderprakash, Advisor, DGHS
Mr K Narendran – Office of the DGC(I)
Dr Mamta Manglani - Paediatrichemato-oncologist, LTMMC & GH, Sion, Mumbai
Sh. Manoj Jhalani, Addl. Secretary & Mission Director (NHM), MoHF
Dr Manoj Kumar, Hepatologist, ILBS, New Delhi
Mr Mehmood Pracha - Senior Advocate, Delhi
Dr Mohd. Shaukat - Advisor, Dte GHS, MoHFW, Delhi
Dr Narayanasamy K - Hepatologist, MMC, Chennai
Dr Nicole Seguy - CD team leader, WHO (India)
Dr Partha Rakshit - Deputy Director, NVHCP, MoHFW
Dr Praveen Malhotra - Gastroenterologist, PGIMS, Rohtak
Dr Preeti Madan - EIS Officer Cohort 5, NCDC, Delhi
Dr R. K. Dhiman - Gastroenterologist, PGIMER, Chandigarh
Dr R. S. Gupta - DDG CST, NACO, Delhi
Dr Rakesh Aggarwal - Gastroenterologist, SGPGI, Lucknow
Dr Rohan Malik – Paediatrician, AIIMS, New Delhi
Dr S K Sarin, Director, ILBS, New Delhi
Dr S.Venkatesh, DGHS, MoHFW
Dr Samir R. Shah - Hepatologist, Global Hospital, Mumbai
Dr Sandhya Kabra - Additional Director, NVHCP, MoHFW
Dr Srijaya S - Gastroenterologist, GMC, Trivandrum
Dr T. Jiten Singh - Physician, RIMS, Imphal
Sh. Vikas Sheel, Joint Secretary, NVHCP, MoHFW
Dr Vimlesh Purohit - NPO (HIV & Hepatitis), WHO (India)

63
Notes

Notes

65
Notes

National Laboratory
Guidelines for
Testing of Viral Hepatitis
2018
National laboratory guidelines Final_26 July.indd 1 7/31/2018 12:41:10 PM

National Laboratory
Guidelines for
Testing of Viral Hepatitis

Preface
Viral hepatitis is a global problem of huge dimensions, which also leads to significant morbidity and
mortality in India. Infection with the blood-borne hepatitis B and C viruses can result in chronic
infection in a proportion of cases, from where it can progress to cirrhosis or even liver cancer. There is
an effective preventive vaccine against hepatitis B, while effective antiviral drugs have become available
against hepatitis C. Hepatitis A and E viruses are transmitted through the faeco-oral route and have
the potential to cause large outbreaks. Infection by hepatitis E may be especially life-threatening in
pregnant women.
A clinical suspicion of any of these types of viral hepatitis can only be confirmed by virus-specific
laboratory tests. The development of these National Laboratory Guidelines for Viral Hepatitis Testing
is an important step towards defining the approach and procedures for the performance of these tests.
A robust, multi-tiered network of testing laboratories is necessary for the success of any national-level
programme that seeks to reduce the burden and alleviate the adverse impact of an infectious disease.
These laboratories, which are really the driving engines of the programme, should be capable of
providing quality-assured and timely reports for the accurate diagnosis of the infection, in order to
initiate appropriate treatment if available, and to monitor the response of the patient to treatment.
Detection of the specific viral aetiology of hepatitis is become increasingly crucial, especially since the
availability of a diverse group of effective direct-acting antivirals (DAAs) against the hepatitis C virus,
which can elicit a sustained virological response (SVR).
The National Laboratory Guidelines for Viral Hepatitis Testing provide background information on the
various hepatitis viruses, along with the details of their genomes and antigens, as well as the antibodies
produced in response to them, which can all be targeted for detecting these viruses. They also include
the principles of the laboratory tests used for this purpose. Most importantly, practical guidance and
algorithms for viral hepatitis testing are also included. All stages of the process have been covered,
starting from proper sample collection and transport (the pre-analytical stage), to the actual performance
of the test and its quality control (the analytical stage), to the generation of reports and safe disposal of
biomedical waste (the post-analytical stage). Quality assurance, one of the most important aspects for
generating confidence in the results of the laboratories among patients and treating physicians, is also
dealt with in adequate detail. Ethical issues like informed consent and ensuring the confidentiality of
patient information have been given due importance.
Treating the testing laboratory as the living heart of this programme, these guidelines are intended
to help support and sustain the elimination viral hepatitis as a public health threat by 2030 (reducing
new infections by 90% and mortality by 65%), as envisaged by the WHO under its Global Health Sector
Strategy (GHSS) on Viral Hepatitis 2016–2021. With adequate infrastructure, capacity building and
training of manpower for the network of viral hepatitis testing laboratories in concordance with the
requirements of these guidelines, India should be well on its way to achieve the target it has set for itself.

ABBREVIATIONS
AND ACRONYMS

ALT Alanine Aminotransferase
APRI Aminotransferase/Platelet Ratio Index
AST Aspartate Aminotransferase
CI Confidence Interval
CLIA Chemiluminescence Immunoassay
DAA Direct-Acting Antiviral
DBS Dried Blood Spot
ECL Electrochemiluminescence Immunoassay
EIA Enzyme Immunoassay
ELISA Enzyme-Linked Immunosorbent Assay
EQAS External Quality Assessment Scheme
HBeAg Hepatitis B e Antigen
HBIG Hepatitis B Immunoglobulin
HBsAg Hepatitis B surface Antigen
HCVcAg Hepatitis C Virus Core Antigen
IVD In Vitro Diagnostic (Medical Device)
LoD Limit Of Detection
M&E Monitoring And Evaluation
MSM Men Who Have Sex With Men
MTCT Mother-To-Child Transmission
PEG-IFN Pegylated Interferon
PHC Primary Health Care
PMTCT Prevention Of Mother-To-Child Transmission
PPV Positive Predictive Value
PST Plasma Separator Tube
QA Quality Assurance
QC Quality Control
QI Quality Improvement
RDT Rapid Diagnostic Test
RNA Ribonucleic Acid
STI Sexually Transmitted Infection

GLOSSARY OF TERMS
1. Hepatitis A total antibody: Measures combined IgG and IgM (Anti-HAV).

2. Hepatitis A IgM: Test diagnosis of acute hepatitis A (IgM Anti-HAV).
3. Hepatitis B surface antigen (HBsAg): HBV envelope protein often produced in excess and detectable
in the blood in acute and chronic HBV infection.
4. Hepatitis B core antigen (HBcAg): HBV core protein. The core protein is coated with HBsAg and
therefore not found free in serum. It is found freely in the hepatocytes.
5. Hepatitis B e antigen (HBeAg): Viral protein found in the high replicative phase of HBV. HBeAg
is usually a marker of high levels of replication with wild-type virus but is not essential for viral
replication.
6. Hepatitis B surface antibody (anti-HBs): Antibody to HBsAg. Develops in response to hepatitis B
vaccination and during recovery from hepatitis B, denoting past infection and immunity.
7. Hepatitis B core antibody (anti-HBc): Antibody to HBV core (capsid) protein. Anti-HBc antibodies are
non- neutralizing antibodies and are detected in both acute and chronic infection.
8. Anti-HBc IgM. Subclass of anti-HBc: Detected in acute/recent HBV infection but can be detected by
sensitive assays in chronic HBV infection.
9. HBV e antibody (anti-HBe): Antibody to HBeAg. Detected in persons with lower levels of HBV
replication but also in HBeAg-negative disease (i.e. HBV that does not express HBeAg).
10. HBV DNA: HBV viral genomes that can be detected and quantified in plasma by nucleic acid testing
(NAT).
11. Anti-HCV antibody: Antibody to HCV, which can be detected in the blood usually within two or
three months of HCV infection or exposure. The terms HCV antibody and anti-HCV antibody are
equivalent, but in these guidelines, HCV antibody is used throughout.
12. Hepatitis E IgM: IgM antibody to hepatitis E virus (anti HEV IgM).
13. HCV RNA: HCV viral RNA that can be detected and quantified in serum by nucleic acid testing
(NAT).
14. HCV core antigen (HCVcAg): Nucleocapsid peptide 22 [p22] of HCV, which is released into plasma
during viral assembly and can be detected from early on and throughout the course of infection.
15. Chronic HBV infection: Persistence of HBsAg for at least six months. The persistence of HBsAg in
two specimens six months apart is frequently used in clinical practice to confirm chronic hepatitis B
infection.
16. Chronic HCV infection: The presence of viraemic HCV RNA or HCVcAg in association with positive
serology for HCV antibody.
17. Viraemic infection: Hepatitis B or C infection associated with presence of virus in the blood (as
measured by HBV DNA or HCV RNA), and often referred to as active, ongoing or current infection.
18. Occult HBV infection: HBsAg negative but HBV DNA positive, although at very low levels (invariably
<200 IU/mL). Most are also anti-HBc positive.

19. Cirrhosis: An advanced stage of liver disease characterized by extensive hepatic fibrosis, nodularity
of the liver, alteration of liver architecture and disrupted hepatic circulation.
20. Decompensated cirrhosis: Clinical features are portal hypertension (ascites, variceal haemorrhage
and hepatic encephalopathy), coagulopathy, or liver insufficiency (jaundice). Other clinical features
of advanced liver disease/cirrhosis may include – hepatomegaly, splenomegaly, pruritus, fatigue,
arthralgia, palmar erythema and oedema.
21. Hepatocellular carcinoma (HCC): Primary cancer of the liver arising from the hepatocytes and may
be a complication of chronic hepatitis B or C infection.
22. Hepatitis C qualitative PCR: It is a very sensitive assay and will detect the presence of hepatitis C RNA
and indicates ongoing viral replication.
23. Hepatitis C quantitative PCR: It is used to measure the viral RNA titres (viral load) and for
monitoring response to antiviral therapy.
24. HCV sustained virological response (SVR): Undetectable HCV RNA in the blood at defined time point
after the end of treatment, usually at 12 or 24 weeks (SVR12 or 24).
25. HCV non-response: Detectable HCV RNA and no significant drop in HCV RNA titres in the blood
throughout treatment.
26. Serological assays: Assays that detect the presence of either antigens or antibodies, typically in
serum or plasma but also in capillary/venous whole blood and oral fluid. These include rapid
diagnostic tests (RDTs), and laboratory-based immunoassays, e.g. enzyme immunoassays (EIAs),
chemiluminescence immunoassays (CLIAs), and electrochemiluminescence immunoassays (ECLs).
27. Rapid diagnostic test (RDT): Immunoassays that detect antibodies or antigens and can give a result in
less than 30 minutes. Most RDTs can be performed with capillary whole blood collected by finger-
stick sampling.
28. Enzyme immunoassay (EIA): Laboratory-based serological immunoassays that detect antibodies,
antigens, or a combination of both.
29. Nucleic acid testing (NAT): A molecular technology, for example, polymerase chain reaction (PCR)
or nucleic acid sequence-based amplification (NASBA) that can detect very small quantities of viral
nucleic acid (RNA or DNA), either qualitatively or quantitatively.
30. Multiplex or multi-disease testing: Refers to testing using one specimen in the same test device (or
reagent cartridge) that can detect other infections (e.g. HIV, syphilis, hepatitis C, hepatitis B).
31. Testing algorithm: The combination and sequence of specific assays used within hepatitis B and C
testing strategies.
32. Key populations: Groups of people who, due to specific high-risk behaviours, are at increased risk for
HIV infection irrespective of the epidemic type or local context. This may also apply to HBV and/
or HCV infection. Key populations often have legal and social issues related to their behaviors that
increase their vulnerability to HIV, HBV and HCV infection. These guidelines refer to the following
groups as key populations: men who have sex with men (MSM); people who inject drugs (PWID).

CONTENTS

Chapter 1 : Introduction to viral hepatitis 14
Hepatitis A 16
Hepatitis B 18
Hepatitis C 21
Hepatitis D 25
Hepatitis E 26
Chapter 2 : Organization of laboratory services for diagnosis of viral hepatitis 28
Chapter 3: Approach to diagnosis of viral hepatitis 30
Chapter 4: Laboratory tests 34
Chapter 5 : Specimen collection, storage, transportation 44
Chapter 6 : Quality management system 52
References 61
Annexure 1: Consent form 62
Annexure 2: Parameters in the test kit for quality assured test result 63
List of contributors 64

1
C H A P T E R
Introduction to viral hepatitis

The laboratory plays a crucial role in the diagnosis and management of patients towards combating viral
hepatitis. The guideline has been developed to provide a framework for implementing priority activities for
strengthening laboratory capacity mandated in the national initiative. The purpose of the national guideline
is to ensure the delivery of effective, efficient, accessible, equitable and quality laboratory services towards
management of viral hepatitis.
Viral hepatitis
Viral hepatitis is primary inflammation of the liver due to infiltration of hepatocytes with viral infected cells
leading to parenchymal necrosis in portal and peri-portal areas. Almost all cases of viral hepatitis are caused
by one of five viral agents: hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), the HBV-
associated delta agent or hepatitis D virus (HDV) and hepatitis E virus (HEV). HAV and HEV are transmitted
enterically by the fecal-oral route while the others are transmitted usually by per-mucosal or per-cutaneous
route. The salient features of viral hepatitis are described in the following table 1:
Table 1: Salient features of viral hepatitis.

Virus A* B C D E
Nucleic acid RNA DNA RNA RNA RNA
Size 27-32 nm 27-42 nm 50-80nm 35-37 nm 32–34 nm
Family Picornaviridae Hepadnaviridae Flaviviridae Unclassified Hepeviridae
Genus Hepatovirus Orthohepadna Hepacivirus Deltavirus Hepevirus
virus
Genome Positive sense Partial dsDNA Positive sense Negative sense Positive sense
+ssRNA +ssRNA −ssRNA +ssRNA
Spread
Faecal-oral Yes No No No Yes
Blood/blood Rare Yes Yes Yes No
products
Vertical (Mother No Yes Rare Occasional No
to child)
Saliva Yes Yes Yes ? No ?
Sexual Rare Yes Yes (rare) Rare No
Incubation period Short (15- Long (30- Long (15- Long (30- Short (14-
45 days) 180 days) 160 days) 180 days 60 days)
Age Young Any Any Any Any
Carrier state No Yes Yes ? Noa
Severity/ Mild; acute Occasionally Subclinical; Exacerbates Normal patients,
Chronicity severe; 5–10% 70% chronic symptoms of HBV; mild; pregnant
chronic chronic w/ HBV women, severe;
acutea
Liver cancer No Yes Yes Yes No
Immunization
Passive Available Available: No No No
Active (licensed) Available. Available None available None available None available
Vaccine in India
*Single serotype.
a
Chronic hepatitis in immunosuppressed patients.
National Laboratory Guidelines for Testing of Viral Hepatitis 15

Viruses that are infrequently associated with hepatitis are Epstein Barr virus, herpes simplex virus,
cytomegalovirus, measles virus, yellow fever virus etc.
Two different patterns of viral hepatitis are recognized: acute viral hepatitis with rapid onset of infection and,
usually, rapid resolution; and chronic viral hepatitis, which is asymptomatic and often detected on routine blood
tests or during screening for infection. The enterically transmitted forms of viral hepatitis are self-limited and
do not cause chronic hepatitis (rarely, acute hepatitis A serves as trigger for the onset of autoimmune hepatitis
in genetically susceptible patients and hepatitis E can cause chronic liver disease in immunosuppressed hosts).
HBV, HCV and HDV may cause acute or chronic disease.
Hepatitis A
HAV presents with non-specific constitutional symptoms of low grade fever, anorexia, nausea and vomiting,
fatigue, malaise, arthralgia, myalgia, headache, photophobia, pharyngitis, cough and coryza may precede onset
of jaundice by 1-2 weeks.
Fig. 1: Structure of hepatitis A virus.
5' Open reading frame (ORF) 3'
Non-coding Non-coding
Translation
Structural Non-Structural
NH2 COOH
P1 P2 P3
VP1, VP2, 2A,2B,2C (diffrent 3D RNA polymerase

VP3, VP4 from other
(viral capsid) picornaviruses)
Fig. 2: Genome of hepatitis A virus
Source: Kumar and Clark’s Medicine.
16 National Laboratory Guidelines for Testing of Viral Hepatitis

Virus In Blood
Virus In feces
Aminotransterases
Symptoms/jaundice
Relative concentration of anti-HAV
IgM
IgG
Level of detection
0 2 4 6 8 10 12
Weeks after exposure
Fig. 3: Summary of immunological and biological events
The early antibody response is predominantly of the IgM class and persists for several (about 3 months) rarely
for 6-12 months, followed by IgG. Detection of IgM anti-HAV antibody indicates acute/recent infection whereas
the presence of HAV total antibody in the absence of HAV IgM indicates previous infection or immunity. In
an infant less than 18 months of age, a positive antibody test result may indicate passive transfer of maternal
antibody.
An HAV total antibody test detects both IgG and IgM; when used in combination with the HAV IgM antibody
test, it is an effective way to determine current or previous infection and test for immunity before vaccination.

Hepatitis B
The disease can manifest both in acute and chronic forms and varies from asymptomatic to symptomatic
progressive disease.
Structure
The small (3.2 kb), partially double-stranded, relaxed circular (rc) DNA features four open reading frames
encoding seven proteins: HBeAg (HBV e antigen, secreted dimeric protein), HBcAg (HBV core antigen, viral
capsid protein), HBV Pol/RT (polymerase, reverse transcriptase activity), PreS1/PreS2/HBsAg (large, medium,
and small surface envelope glycoproteins), and HBx (HBV x antigen, regulator of transcription required for the
initiation of infection).
Envelope HBsAg sub-determinants include a common group reactive antigen- ‘a’ shared by all HBsAg isolates
and one of several subtype-specific antigens-d or yw or r -as well as other specificities. Hence the surface protein
has four subtypes: adw, adr, ayw and ayr. Hepatitis B isolates fall into one of at least eight subtypes and 10
genotypes (A-J). Geographic distribution of genotypes and subtypes varies.
Fig. 4: Structure of hepatitis B virus Fig. 5: Genome of hepatitis B virus
Source: Mandell, Douglas, and Bennett’s Principles The viral DNA is partially double-stranded (red incomplete
and Practice of Infectious Diseases, Updated Edition. circle and purple circle). The long strand encodes seven
Thio, Chloe Lynne; Hawkins, Claudia. Published proteins from four overlapping reading frames [S, surface
January 1, 2015. Pages 1815-1839.e9. 2015. (Pre-S1, Pre-S2, S)-green; c, core (Pre-C, C)-pink; P,
polymerase (P)-blue; and X gene (X)]-yellow.

HBV is not usually directly cytopathic (although high replication levels in immunosuppressed individuals can
lead to direct toxicity) and liver damage is produced by the host’s immune response.
The following figure 6 indicates the clinical progression along with associated serological events in acute HBV
infection.
Incubation Incubation Convalescence

period period Early Late
Important HBsAg Anti-HBs
diagnostic tests lgM anti-HBc lgG anti-HBc
1 2 3 4 5 6 7 8
DNA polymerase
Relative HBV particles Anti-HBc

concentration
of reactants
HBsAg
Anti-HBs
HBeAg
Level of Anti-HBe
detection
Months after
oxposure 1 2 3 4 5 6 7 8
ALT
Symptoms
Fig. 6: Clinical progression along with associated serological events in acute HBV infection
Source: Karen C. Carroll, Stephen A. Morse, Timothy Meitzner, Steve Miller: Jawetz,
Melnick, and Adelberg’s Medical Microbiology, 27th Edition, Mc-Graw Hill Education.
Chronic HBV infection is a dynamic process reflecting the interaction between HBV replication, hepatocytes and
the host’s immune response and not all patients with chronic HBV infection have chronic hepatitis (CHB). The
natural history of chronic HBV infection has been schematically divided into four phases taking into account
the presence of HBeAg, HBV DNA levels, alanine aminotransferase (ALT) values and eventually the presence
or absence of liver inflammation. The risk of progression to cirrhosis and HCC is variable and is affected by the
host’s immune response.

HBsAg
HBeAg(+) HBeAg(-)/ anti-HBe(+)
HBV DNA
109-1012 IU/mL >2000-<10 IU/mL

9
<2000 IU/mL >2000 IU/mL <2000 IU/mL
ALT
Minimal disease HBeAg+CHB Inactive carrier HBeAg-CHB Occult infection
Immune-tolerant Immune-tolerant Immune-Control Immune-reactive Immune-control
Phases of Infection
Fig. 7: Serological markers in different phases of chronic hepatitis B virus infection

Source: Santantonio T, Fasano M,Current concepts on management of chronic hepatitis B.
http//dx.doi.org/10.5772/54759.
Interpretation of HBV markers

Table 2: Commonly encountered serology patterns of hepatitis B infection.
HBsAg Anti-HBs Anti-HBc HBeAg Anti-HBe Interpretation
+ – IgM + – Acute hepatitis B , high infectivity *
+ - IgG + - Chronic hepatitis B , high infectivity *
+ - IgG - + 1. Late acute or chronic hepatitis B, low infectivity
2. HBe Ag negative(“precore- mutant”)
hepatitis B ( chronic or rarely acute)
+ + + IgM +/- 1. HBsAg of one subtype and
heterotypic anti-HBs (common)
2. Process of seroconversion from
HBsAg to anti-HBs (rare)
- – IgM +/- +/- 1. Acute Hepatitis B*
2. Anti-HBc “window”
- - IgG - +/- 1. Low level Hepatitis B carrier
2. Hepatitis B in remote past
- + IgG - +/- Recovery from Hepatitis B
- + - - - 1. Immunization with HBsAg(after vaccination)
2. Hepatitis B in the remote past
3. False Positive
*IgM Anti-HBc may reappear during acute reactivation of chronic Hepatitis B
Source: Harrison’s Principles of Internal Medicine, 20th edition
HBV molecular variants

Hepatitis B viral mutants can emerge as a result of selection pressure from either immune response (vaccination)
or treatment options (antiviral therapy).
The commonly seen variants are:
1. Escape mutants
2. Pre-core mutant
3. YMDD (tyrosine-methionine-aspartate-aspartate) mutant.

Thus HBV has significant genomic diversity and are associated with antiviral therapy response, vaccine escape,
diagnostic failure, liver fibrosis progression and HCC development.
Hepatitis C
HCV infection usually resolves spontaneously in 15 to 45% patients and progresses to chronic infection in 55 to
85% patients.
Structure
It is a single-stranded, positive sense RNA virus of the Flaviviridae family. The genome is approximately 10 kb
in length, encoding a poly-protein product consisting of structural (capsid and envelope) and non-structural
viral proteins.
Fig. 8: Structure of hepatitis C virus

Source: Virology Journal; December 2017, 14:88| Cite as; Hepatitis C virus management:
potential impact of nanotechnology.
500 1000 1500 2000 2500 3000

AA
Envelope Helicase RNA-dopendent
Serine
Core glycoproteins protease RNApolymerase
5’ C E1 E2 NS2 Ns3 NS4B NS5A NS5B 3’
p7 NS4A
Conserved Hypervariable
region region
Fig. 9: Organization of the HCV genome and its associated amino acid proteins
Source: Harrison’s Principles of Internal Medicine, 20th edition.
The HCV genome consists of seven functional regions- the core, the envelope, including the E1 and E2 regions,
and the nonstructural region, including NS2, NS3, NS4, and NS5.
Comparisons of sub-genomic regions, such as E1, NS4 or NS5, have allowed variants to be classified into major
genotypes with many subtypes. The term genotype refers to different genetic variations or strains of hepatitis C
(HCV). The variance in genetic differences is approximately one third between the different genotypes. There are
six distinct major genotypes and a minor genotype 7 and more than 50 subtypes within the genotypes of HCV
have been identified. Within each genotype are further divisions called subtypes (for example 1a and 1b) and
intra-genotypic variations are referred to as quasi-species and differ in sequence homology by only a few percent.

As the HCV virus replicates rapidly, it constantly changes and mutates. The process of constant mutation helps
the virus escape the body’s immune response, and may lead to the development of chronic HCV disease.
Infections are usually asymptomatic, about 10% of patients having a mild illness with constitutional features,
with jaundice and a rise in serum aminotransferases. Most patients will not be diagnosed until they present,
years later, with evidence of the disease only being discovered following a routine biochemical test when mild
elevations in the aminotransferases (usually ALT) are noticed (50%). The elevation in ALT may be minimal and
fluctuating and some patients have a persistently normal ALT (25%), the disease being detected by checking
HCV antibodies (e.g. in blood donors).
Events
ALT
anti-HCV
HCV
+ + + + + + + + RNA
SYMPTOMS
// Months // Year
0 3 mo 6 mo 9 mo 12 mo 5 yr 10 yr 15 yr 20 yr 25 yr
Acute Chronic active

hepatitis hepatitis Cirrhosis HCC
Fig. 10: Clinical and serology events associated with HCV infection
Source: Karen C. Carroll, Stephen A. Morse, Timothy Meitzner, Steve Miller: Jawetz,
Melnick, and Adelberg’s Medical Microbiology, 27th Edition, Mc-Graw Hill Education.
The diagnosis of HCV infection is made by detection of anti-HCV antibodies using immunoassays followed by
detection of HCV RNA in serum or plasma. Current HCV RNA assays express HCV RNA titres in international
units per mL (IU/mL).
The assessment of the disease progression and its management takes into consideration platelet count, serum
aminotransferases and other non-invasive tests.
A reactive HCV antibody result indicates one of the following:

1. Current HCV infection
2. Past HCV infection that has resolved
3. False positive.
A reactive HCV antibody result should be followed by testing for HCV RNA using NAT (RT-PCR) for confirmation
of hepatitis C infection.
If HCV RNA is detected, results indicate current/active HCV infection. If HCV RNA is not detected, results
indicate either past, resolved infection or false HCV antibody positivity. Regardless of serology for HCV antibody,
patients with detectable HCV RNA should be considered to have active HCV infection and should be referred for
further medical evaluation.
HCV RNA can be detected within a few days of exposure. ALT elevation is usually seen after HCV RNA is
detectable in blood. Sero-conversion usually occurs after 8-9 weeks of infection and about 90% of patients are

positive for anti-HCV antibodies within 5 months. Anti-HCV antibody test results may be negative in early
acute hepatitis C and in profoundly immunosuppressed patients (HCV RNA testing in serum or plasma should
be part of the initial evaluation).
Counseling messages for screening test results: All patients should be provided information in language
understood by them on the meaning of their test results by the attending clinicians/trained health care workers/
peer counselors.
Providing Pre- test information:

Information to be provided through material such as posters, brochures, websites and short video clips shown
in waiting rooms. This would include information on viral hepatitis and the benefits of testing for hepatitis B or
C; the meaning of a positive and negative test result; a brief description of prevention options; confidentiality
of the test result; the practical implications of a positive test result, including the when and where of treatment
available.
Post- test counselling and linkages to treatment services for a reactive hepatitis C screening test:
• Explain the meaning of the reactive antibody test and counsel on the need for diagnostic testing
(hepatitis C RNA test) to confirm a diagnosis of chronic hepatitis and other tests for staging of liver
disease.
• Explain that the patient may be chronically infected or have cleared the virus in the past.
• Provide basic hepatitis C disease, prevention and treatment information. Make an active referral to the
viral hepatitis treatment units for confirmation of diagnosis.
• Discuss the importance of minimizing risk behaviors to avoid transmitting hepatitis C infection to others,
and encourage notification and screening of needle sharing and sexual partners.
• Encourage and offer HBV and HCV testing for family members, including children, and sexual partners
after confirmation.
• Discuss healthy life practices, including stopping or reducing alcohol intake and getting vaccinated
against hepatitis A and B, if appropriate.
Adherence counselling by trained pharmacist:

1. Inform patients about common side effects;
2. Pill count- the total number of pills/doses dispensed and the total number of pills/doses returned at
monthly visits for each drug for the entire treatment duration for all patients;
3. Patient self-reports, it helps to determine reasons for non-adherence.
Post-test information/counselling for a non-reactive hepatitis C screening test:

• Explain the meaning of the non-reactive antibody test, ensuring that the patient understands a negative
antibody test does not protect him/her from future infection in the event of risk taking behaviours.
• Discuss that if the patient was recently exposed (6 months), he/she may be in a window period and
recommend repeat screening in 6 months, and provide information on hepatitis C prevention, risk and
harm reduction.
• Encourage the patient to make healthy choices and to get vaccinated against hepatitis A and B, if
appropriate.
It is important to counsel the patient at every human interface in the initiative. Laboratory workforce, if
required, need to impart pre-test information and post-test counselling and therefore need to be trained on the
same. Moreover, special trainings need to be conducted for sensitization on confidentiality and respecting the
status of a positive patient.
The following table 3 summarizes the interpretation of HCV markers with further actions to be taken:

Table 3: Interpretation of HCV markers
TEST OUTCOME INTERPRETATION FURTHER ACTIONS
HCV antibody No HCV antibody Sample can be reported as non-reactive for
(Anti-HCV) detected HCV antibody. No further action required.
Non-reactive If recent exposure in person tested is
suspected, NAT test for HCV RNA.*
HCV antibody Presumptive A repeatedly reactive result is consistent with current
(Anti-HCV) HCV infection HCV infection, or past HCV infection that has resolved,
or biologic false positivity for HCV antibody. NAT
Reactive
Test for HCV RNA to identify current infection.
HCV antibody reactive, Current HCV infection Provide person tested with appropriate counseling and
HCV R NA detected link person tested to medical care and treatment.
HCV antibody reactive, No current HCV No further action required in most cases.
HCV RNA not detected infection If distinction between true positivity and biologic false positivity
for HCV antibody is desired, and if sample is repeatedly reactive
in the initial test, test with another HCV antibody assay.
In certain situations§, follow up with HCV RNA
testing and appropriate counseling.
* If the person tested is immune-compromised, consider testing for HCV RNA.
§ If the person tested is suspected of having HCV exposure within the past 6 months, or has clinical evidence
of HCV disease, or if there is concern regarding the handling or storage of the test specimen.
Source: CDC MMWR - Testing for HCV Infection: An Update of Guidance for Clinicians and Laboratorians (May 2013).
Direct acting antiviral agents (DAAs)

Treatment for HCV infection is undergoing a revolution, with treatments changing from interferon-based
regimes to all-oral combination regimes using directly acting antiviral agents. DAAs are molecules that target
specific non-structural proteins of the virus and results in disruption of viral replication and infection. There
are four classes of DAAs which are defined by their mechanism of action and therapeutic target. The four classes
are non-structural proteins 3/4A (NS3/4A) protease inhibitors (PIs), NS5B nucleoside polymerase inhibitors
(NPIs), NS5B non-nucleoside polymerase inhibitors (NNPIs) and NS5A inhibitors.
Fig. 11: Mechanism of action of direct acting antivirals for hepatitis C virus.
NS5A: non-structural protein 5A; NS5B: non-structural protein 5B; NNPI: non-nucleoside polymerase inhibitor.
Source: Clinical Pharmacology & Therapeutics. Au J, Pockros PJ. Novel Therapeutic Approaches for Hepatitis C.
Clin Pharmacol Ther 2014; 95:78. Macmillan Publishers Ltd. www.nature.com/clpt.

Hepatitis D
Hepatitis D virus (HDV or delta virus) is a satellite virus, which is dependent on HBV for the production of
envelope proteins. It is an incomplete RNA particle enclosed in a shell of HBsAg. The virus is unable to replicate
on its own but is activated by the presence of HBV. Natural HDV infections occur as either a co-infection with
HBV or a super-infection of HBV carriers. HDV can cause severe acute and chronic liver diseases in HBV-infected
individuals; most of the HBV carriers super-infected with HDV become carriers of both HBV and HDV.
Fig. 12: Structure of hepatitis D virus.

• Co-infection of HDV and HBV is clinically indistinguishable from an acute icteric HBV infection, but
a biphasic rise of serum aminotransferases may be seen. Diagnosis is confirmed by finding serum IgM
anti-HDV in the presence of IgM anti-HBc. IgM anti-delta appears at 1 week and disappears by 5–6 weeks
(occasionally 12 weeks), when serum IgG anti-delta is seen. The HDV RNA is an early marker of infection.
The infection may be transient but the clinical course is variable.
• Super-infection results in an acute flare-up of previously quiescent chronic HBV infection. A rise in serum
AST or ALT may be the only indication of infection. Diagnosis is made by finding HDV RNA or serum IgM
anti-HDV at the same time as IgG anti-HBc. Active HBV DNA synthesis is reduced by delta super-infection
and patients are usually negative for HBeAg with low HBV DNA.
Acute hepatic failure can follow both types of infection but is more common after co-infection. HDV RNA in the
serum and liver can be measured and is found in acute and chronic HDV infection.
Co-existent acute Hepatitis B

and Hepatitis D.
Acute hepatitis D
superimposed on a chronic
HBV infection.
Acute hepatitis D progressing

to chronic hepatitis,
superimposed on a chronic
HBV infection.
Fig. 13: Serologic patterns of type D hepatitis after co-infection or super-infection of

a person with HBV infection.

When HDV infection is suspected in HBV-positive individuals, laboratory testing can be used for diagnosis,
differentiating co-infection from super-infection, and determining if the HDV infection is active or resolved.
The total HDV antibody assay is generally the initial test.
Diagnosed HBV
Infection
HDV Ab- HDV infection unlikely
HDV Ab
HBV with HDV

HBc IgM Ab+
coinfection
Monitor theraphy
therapy with
with
HDV Ab+ HBV DNA and HDV
RNA
HBc IgM Ab- HBV with HDV
superinfection
Fig. 14: Approach to detect HDV in HBV diagnosed individual.
Hepatitis E
HEV infection is usually an acute self-limiting disease.
Structure
Hepatitis E virus (HEV) is an RNA virus and is a 27- to 34-nm, icosahedral capsid, non-enveloped, HAV-like
virus with a 7200-nucleotide, single-strand, positive-sense RNA genome HEV has three open reading frames
(ORF) (genes), the largest of which, ORF1, encodes nonstructural proteins involved in virus replication. A
middle-sized gene, ORF2, encodes the nucleo-capsid protein– the major structural protein, and the smallest,
ORF3, encodes a structural protein whose function remains undetermined. All HEV isolates appear to belong
to a single serotype despite genomic heterogeneity of up to 25% and the existence of four genotypes (genotypes
1 to 4 [HEV1, HEV2, HEV3, and HEV4]). Genotypes 1 and 2 appear to be more virulent, whereas genotypes 3 and
4 are more attenuated and account for subclinical infections.
Fig. 15: Hepatitis E virus genome.

Source: Nassim Kamar et al. Clin. Microbiol. Rev. 2014; 27: 116-138.

Human infection with HEV has two distinct epidemiological patterns. In areas of poor sanitation and hygiene,
genotypes HEV1 and HEV2 are transmitted between humans by the fecal-oral route, usually via contaminated
water, is usually a self-limiting illness which last a few weeks and results in frequent sporadic cases and occasional
large outbreaks.
In developed countries, genotypes HEV3 and HEV4 are transmitted zoonotically from animal reservoirs, with
sporadic cases. Moreover, HEV 3 infection in immune-compromised patients in developed countries causes
chronic infection with rapidly progressive cirrhosis (in organ transplant recipients, patients with hematological
malignancy requiring chemotherapy, and individuals with HIV). HEV also causes extra-hepatic manifestations,
including a number of neurological syndromes and renal injury.
HEV (Stool)
HEV RNA (serum)
Clinical symptoms
IgG anti-HEV antibody
Alanine aminotransferase (ALT)
1000 ALT
900
800
700
600
(U/liter)
500
400
300
200 IgM anti-HEV antibody
100
0
normal(or undetectable)
0 2 4 6 8 10 12 16 20 24 48
Weeks After Composure
Fig. 16: Course of acute hepatitis E virus infection.

Source: Lisa J Krain et al. Clin.Microbiol.Rev.2014:27:139-165.
HEV infections can be diagnosed by measuring anti-HEV antibodies, HEV RNA or viral capsid antigen in blood
or stool.
HEV infection can be diagnosed either indirectly by detecting serum anti-HEV antibodies or directly by detecting
the HEV RNA in blood or other body fluids. Following an incubation period of 2 to 6 weeks, an initial short-lived
IgM response is followed by longer-lasting IgG antibodies. The presence of anti-HEV IgM is a marker of acute
infection. The presence of anti-HEV IgG alone is a marker of past infection. HEV RNA becomes detectable in
early phase of the disease and is undetectable in blood in about 3 weeks after the onset of symptoms but can be
detected in feces for another 2 weeks.

2
C H A P T E R
Organization of laboratory
services for diagnosis
of viral hepatitis

A variety of tests are required to establish a diagnosis of viral hepatitis and its further management. These
include platelet count, estimation of liver enzymes and specific serological tests and molecular tests (HBV DNA
and HCV RNA). The initiative envisages a tiered network of existing laboratories taking into account their
existing competencies and capacities in order to attain a quality assured test result.
The specific tests for viral hepatitis offered in the initiative across public health laboratories are summarized
below.
Figure17 : Tiered laboratory network and the available tests.

*If samples are to be transported, they need to be collected, packaged and transported
within six hours of collection under suitable environmental conditions.
To effectively deliver the services, the following pattern of assistance will be provided to the state
laboratories under the initiative-
Table 4: Pattern of assistance for state laboratories.

Budget head Number Total (Annual), in INR Remarks
Human Resource
Coordinator 1 Regular cadre From Regular cadre
(Microbiologist)
Technical officer 1 As per state NHM norms for each
Data Entry operator 1 personnel. To be transferred
from SVHMU of NHM
Laboratory technician 1
Equipment (computer, 100,000
printer, scanner)
Consumables 500,000
To be transferred from
SVHMU to state lab
For district laboratories under the initiative, there is provision for only one laboratory technician subject to
projection from the state in PIP.

3
C H A P T E R
Approach to diagnosis
of viral hepatitis

A patient with acute or chronic viral hepatitis infection may present at a health care
setting with or without jaundice. The patient may be referred by a treating doctor for
investigations after taking a written informed consent (Annexure 1) with a complete
test requisition form.
Testing for HBV in pregnant women: In states where institutional deliveries are less
than 90%, screening of all pregnant women should be carried out for HBsAg detection.
Institutional delivery of HBsAg positive pregnant women must be mandated to prevent
transmission to the child by giving birth dose hepatitis B vaccine.
Self-presenting asymptomatic individuals at high risk may be provided access to testing

by a defined mechanism in the health care facility.
The algorithms to be followed for diagnosis are in the

following pages:

32
Testing algorithm for the diagnosis of viral hepatitis in jaundiced patients.
National laboratory guidelines Final_26 July.indd 32

HAV HEV HBV HCV
IgM Anti
IgM Anti IgM Anti HBsAg Anti HCV
HBc
HAV HEV
National Laboratory Guidelines for Testing of Viral Hepatitis

Report : Report : Report : Report : If HbsAg is Reactive and lgM anti HBc is Non- Report: Report:
HAV HAV HEV HEV reactive: HBV positive HCV Ab HCV Ab
Positive Negative Positive Negative Positive# Negative#
If lgM Anti HBc is Reactive and HBsAg is Non-
* Serum samples to be used for serological and biochemical testing, to be aliquoted and stored at -20 0 C for retesting for quality purposes, dispute etc.
#All HCV antibody (Ab) positive to be referred to treatment centre. Plasma samples to be collected and aliquoted in 3 sterile cryo vials. One vial to be
used for quantitative hepatitis C RNA estimation and two archived at -80 0 C for quality assurance
Fig. 18a: Testing algorithm for the diagnosis of viral hepatitis in jaundiced patients.
7/31/2018 12:41:20 PM
Testing algorithm for the diagnosis of viral hepatitis in patients without jaundice.
National laboratory guidelines Final_26 July.indd 33

HBV HCV
HBsAg Anti HCV

#All HCV antibody (Ab) positive to be referred to treatment centre. Plasma samples to be collected and
archived at -80 0 C for quality assurance
Fig. 18b: Testing algorithm for the diagnosis of viral hepatitis in patients without jaundice.
National Laboratory Guidelines for Testing of Viral Hepatitis

33
7/31/2018 12:41:20 PM
4
C H A P T E R
Laboratory tests

Immunoassays – detect antibodies to the virus or a viral antigen in the
host.
Immunoassays may be available as rapid diagnostic tests (RDTs) which are simple, rapid, low cost and do not
require extensive laboratory infrastructure. They are less technically intensive and equipment independent.
In comparison, enzyme linked immunosorbent assay (ELISA) and chemiluminescence immunoassay (CLIA)
are useful for high-volume clinical laboratories due to high throughput but technically intensive, equipment
dependent and require appropriate laboratory infrastructure.
Rapid diagnostic tests

Rapid diagnostic tests (RDTs) are single-use disposable assays that are provided in simple-to-use formats that
generally require no additional reagents except those supplied in the test kit. They are read visually and can give
a simple qualitative result ≤ 30 minutes.
Most RDTs can be performed using venous/capillary whole blood, serum or plasma. They detect antigens and/
or antibodies by often using an in-vitro diagnostics (IVD) device. They are based on immunologic principles
like particle agglutination, lateral flow immunoassay, immune-filtration etc. Positive test result is indicated by
clumping/dot/line visible to the naked eye.
The lateral flow immunoassay (LFI) is a test based on the principles of immune-chromatography for the
qualitative detection of antibody/antigen.
i. The required volume of whole blood/serum/plasma is added to the specimen well. This is the sample-
loading pad/ adsorbent pad, which acts as the first stage of the absorption process, and in some cases
contains a filter, to ensure the accurate and controlled flow of the sample.
ii. Then the analyte to be detected reacts with the conjugate (particle coated with antibody/antigen). If the
analyte is present, the immobilized conjugated antibodies and labels (visible indicator system) will bind to
the target and continue to migrate along the test. LFI utilize colloidal gold nanoparticles, latex microspheres,
carbon, or coloured latex nanoparticles.
iii. The complex with the analyte then migrates upward along the membrane by capillary action, and reacts
with polyclonal antibodies, which are pre-coated on the test line region in the reaction membrane/detection
membrane.
iv. Ensure validity of the test by observing the control as per kit literature
Fig. 19: Schematic representation of lateral flow immunoassay.
National Guidelines for Diagnosis & Management of Viral Hepatitis 35

The visual readout is interpreted as specified in the kit literature. The invisibility of the control line indicates
insufficient specimen volume or incorrect procedure techniques. The presence of one coloured (red/blue) line
in the control region indicates a negative result, and the presence of two distinct lines in both the control and
test regions indicates a positive result. In case of absence of control the test is invalid and needs to be repeated.
Immuno-filtration assays (IFAs) also known as immune-

concentration or flow through assays use nitrocellulose
(NC) membranes or glass fiber filters as a solid phase with
large surface that allows the flow of the sample. The sample
passing through the membrane gets concentrated and
accelerates the binding of antigens and antibodies. The solid
support immobilizes or captures the analyte to be detected,
along with a proper signal reporting system in a typical
sandwich reaction. The testing process involves multiple
steps that include drop-wise addition of buffer, samples, and
conjugates. Recombinant and synthetic antigens are used to
provide better, stable, and sensitive test systems. The assay
includes a built-in control to verify the correct protocol. The
control mainly uses antihuman immunoglobulin that binds
any immunoglobulin in the sample and produces a separate
indicator when all reagents are added appropriately.
It is important to determine the extent to which the tests are

able to identify the likely presence or absence of a disease/
condition of interest so that their findings encourage
appropriate decision making. Adequacy and usefulness of
screening tests are determined and described by sensitivity,
specificity and predictive value of these tests. All four metrics
should be regarded as important when describing and assessing Fig.20: Schematic presentation of
a screening test’s adequacy and usefulness. (Annexure 2) Immuno-concentration technique.
Enzyme linked immunosorbent assay (ELISA) / Enzyme immunoassay (EIA)

ELISA is a plate based assay technique which is used for detecting and quantifying substances such as peptides,
proteins, antigens, antibodies and hormones. An enzyme conjugated with an antibody reacts with colourless
substrate to generate a coloured product. Such substrate is called chromogenic substrate. A number of enzymes
have been used for ELISA such as glucose oxidase, alkaline phosphatase, and beta galactosidase. Specific
substrates such as TMB (for peroxidase); paranitrophenyl phosphate (for alkaline phosphatase); are used, which
are hydrolyzed to give coloured end product.
Materials needed in ELISA testing:
A. Pipettes, washer system, ELISA plate reader: Readers, washers and pipette are available as manual or
automated system. One of the main factors affecting equipment selection is the number and types of test
samples being run.
B. Reagents needed for the testing: Concluded in the kit (coated plates, sample diluents, controls, wash
concentrate, conjugate, substrate, stop solution).

Fig.21: General procedure of ELISA.
Fig. 22 : Types of ELISA.

Fig. 23: Indirect ELISA.
Advantages Disadvantages
High sensitivity - more than one labeled secondary Possibility of background noise - secondary
antibody can bind the primary antibody antibody may be cross-reactive
Economical - fewer labeled antibodies are needed Longer procedure than direct ELISA technique - additional
incubation step for secondary antibody needed
Greater flexibility - different primary antibodies can
be used with a single labeled secondary antibody
Best for: determining total antibody concentration in samples.
Fig. 24: Sandwich ELISA.
High sensitivity - 2-5 times more sensitive Antibody optimization can be difficult - cross-reactivity
than direct or indirect ELISA may occur between the capture and detection antibodies.
High specificity - two antibodies are Needs a standardized ELISA kit or tested antibody pair.
involved in capture and detection
Flexibility - both direct and indirect
detection can be used
Best for: analysis of complex samples, since the antigen does not need
to be purified prior to measurement.

Antibody capture ELISA is similar to sandwich ELISA but in the first step, anti-Ig (M or G) is coated on the plate.
Antibody capture ELISAs is particularly sensitive in demonstrating IgM responses early in illness. Reasons for
this increase in sensitivity are: specific antibody isotypes in the patient’s specimen are bound to the solid phase
by the capture antibody allowing the specific antibody-antigen reaction to occur in the absence of competing
isotypes.
Fig. 25: Competitive ELISA (for antigen detection).
Main advantage - no sample processing is required Same limitations as base ELISA - as each ELISA
and crude or impure samples can be used technique can be adapted to a competitive format
More robust - less sensitive to sample dilution and
sample matrix effects than the sandwich ELISA
More consistent - less variability between
duplicate samples and assays
Maximum flexibility - it can be based on
direct, indirect or sandwich ELISA
Best for: commonly used when only one antibody is available for the antigen of interest. It is also suitable for
detecting small antigens that cannot be bound by two different antibodies such as in the sandwich ELISA technique.
The EIA results have also been interpreted in the form of signal (or sample) to cut-off ratio (s/co ratio) to express
the results quantitatively. S/co ratio of EIA for HCV could serve as an important tool in notifying the blood
donors of their HCV status in resource poor setting where there is absence of supplemental testing. Algorithms
derived on the basis of s/co ratio could also be used for guiding the blood donors for further referral and for
re-entry purposes.

Newer techniques
It may use fluorogenic, electro-chemiluminescent and quantitative PCR reporters to create quantifiable signals.
These new reporters can have various advantages, including higher sensitivities and multiplexing.
Chemiluminescence immunoassay (CLIA)

CLIA is an immunoassay technique where the label, i.e. the true “indicator” of the analytic reaction, is a
luminescent molecule. The resultant potential energy in the atom gets released in the form of light, which is
measured in terms of Relative Light Units (RLU). In spectrophotometry, luminescence has an advantage over
absorbance in that the former is an absolute measure whereas the latter is relative.
Fig. 26: Chemiluminescence Assays.
Chemiluminescent methods can be direct—using luminophore markers—or indirect—using enzyme markers.

Either method may be competitive or non-competitive.
CLIA analysers are useful for the detection of serological markers of hepatitis viruses B virus (HBV), hepatitis
C virus (HCV), hepatitis A virus (HAV) and hepatitis E virus (HEV). CLIA has advantages of being more reliable,
precise, technically simple, shorter execution times (30–40 minutes) and high-speed throughput. It provides
univocal recognition of patient and quality control samples and of specific and common reagents resulting in
complete control of the analytical process CLIAs have higher analytical sensitivity and improved diagnostic
sensitivity and specificity as compared to conventional EIAs.

Table 5: Interpretation of individual serology test results in the diagnosis of acute and chronic
viral hepatitis.
MARKER INTERPRETATION
IgM Antibody to hepatitis A •• Positive result indicates a current or recent HAV infection
(Anti-HAV IgM or
•• A negative result indicates absence of infection. May be negative in early
HAV IgM Ab)
infection (if collected within five to seven days after onset of symptoms)
•• Present for three to six months after onset of acute infection

Total Antibody to hepatitis A •• Positive result indicates past infection and immunity to
(IgM and IgG) HAV (in the absence of HAV IgM antibody)
(Anti-HAV or HAV Ab) •• Individuals given serum immune globulin for HAV prophylaxis
may test as positive for at least six months
Hepatitis B surface •• Presence indicates that a person has HBV infection and is infectious
antigen (HBsAg)
•• First marker to appear in an acute infection
•• Disappearance indicates recovery from infection
•• Used to diagnose an acute or chronic infection
•• Persistence for > 6 months indicates chronic infection (carrier)
•• Individuals tested within 72 hours after administration of the vaccine

may test as positive (see anti-HBs, anti-HBc IgM and HBeAg.)
Antibody to hepatitis •• Presence indicates resolution and immunity against
B surface antigen HBV infection or response to vaccination.
(Anti-HBs or HBs Ab)
•• Levels of 10MIU/mL (10 IU/L) are usually considered protective
•• Routine monitoring of levels in individuals who have received the

complete course of vaccine is not considered necessary
•• Some individuals, e.g., healthcare workers, who are believed to have

been exposed to the virus by a needle injury, should have their anti-
HBs levels tested to determine whether they require administration of
hepatitis B immune globulin (HBIG) and hepatitis B vaccine booster
•• Positive result in individuals with recent acute HBV

infection Indicates convalescence
•• Usually NOT detected when HBsAg is also present
•• In some cases of chronic hepatitis B infection, both HBsAg and anti-HBs can
be detected. These antibodies are heterotypic and likely not protective
•• Antibody levels may decline with time

IgM antibody to hepatitis •• Primarily be used if there is a high index of suspicion to indicate that the patient
B core antigen is in the early convalescence “window period” (two to 16 weeks post infection)
(Anti-HBc IgM or when HBsAg has disappeared and anti-HBs levels are not yet detectable
HBc IgM Ab)
•• Positive result usually indicates HBV infection within the
preceding 4 to 6 months (ie, acute infection).
•• Usually detectable for three to 12 months.

Hepatitis B e antigen •• Presence indicates active viral replication and high infectivity. Marker of active
(HBeAg) HBV replication and of infectivity. However, the absence of HBeAg in a person
who is HBsAg-positive does not imply that the individual is NOT infectious.
•• Can be used to monitor therapy of patients with chronic HBV infection

Antibody to hepatitis •• Appears as HBeAg disappears
B e antigen
•• In chronic hepatitis B infection, a positive result indicates
(Anti-HBe or HBe Ab)
resolving, or response to therapy or minimal liver disease
•• However, individuals who are HBsAg-positive and have anti-

HBe present must still be considered infectious
Total antibody to hepatitis •• A positive result indicates past or current HBV infection
B core antigen (Anti-
HBc or HBc Ab) •• Usually persists for life
•• This antibody is absent in individuals who are

immune solely as a result of vaccination
•• Up to 10% false-positive rate has been described in individuals with no

documented infection to HBV. If uncertain, presence of one other marker, e.g.,
anti-HBs or anti-HBe would confirm previous exposure with HBV. Alternatively
a negative repeat test later may indicate an earlier false-positive result.
Antibody to hepatitis D virus •• Presence coincident with the presence of HBsAg indicates past
(Anti-HDV or HBV Ab) or current HBV/HDV co-infection or super-infection.
HDV Ab, total •• Antibodies appear late during the course of acute infection
HDV IgM •• Presence coincident with the presence of HBsAg indicates past or current
HBV/HDV co-infection or super-infection. A negative result coincident
with the presence of HDV total antibody indicates resolved infection.
Antibody to hepatitis C •• Presence of antibody can be due to acute or chronic infection.
(Anti-HCV or HCV Ab) It may represent only evidence of an infection with HCV
•• Presence of antibody does not imply immunity to HCV
•• Presence (with detectable HCV RNA) indicates current infection. A

positive result coincident with a negative HCV RNA test may indicate
a resolved infection or a false-positive antibody screening test.
IgM Antibody to hepatitis •• Positive result indicates a current or recent HEV infection.
E virus (Anti-HEV IgM
or HEV IgM Ab) •• A negative result indicates absence of infection. May be negative in early
infection (if collected within five to seven days after onset of symptoms)
Present for three to six months after onset of acute infection
Nucleic acid testing

Nucleic acid testing (NAT) are highly sensitive and specific in detecting the presence of viral nucleic acid (HBV
DNA or HCV RNA). It is an important tool to confirm diagnosis, identify individuals with high viral loads, which
may suggest high infectivity, to monitor disease progression and the efficacy of antiviral therapies, to detect
drug resistant mutants, and to identify relapse after the discontinuation of an antiviral therapy.
Laboratory-based technologies for NAT require sophisticated equipment, rigorous laboratory conditions and
specimen collection, and highly trained staff who can perform precision steps and avoid contamination. In
addition to NAT assays that target a single virus, multiplex NAT screening assays have been developed, which
can detect DNA or RNA from multiple viruses simultaneously.
Currently, viral load is measured using international units per milliliter (IU/mL). However, in the past it was
measured in copies per milliliter (copies/mL). In order to convert copies into international units, there are about
5.6 copies in one international unit, so 5 000 copies/mL equals about 893 IU/mL.
Hepatitis B quantitative DNA PCR plays a critical role in determining the phase of infection, deciding the
treatment, and detecting responses to antiviral therapy. Assay range - 10 IU/mL to 1.0 x 109 IU/mL, HBV DNA
detected below 10 IU/mL will be reported as "<10 IU/mL". Reported in two formats: IU/mL and Log10 IU/mL.

Methods to detect HCV RNA are based on an adaptation of the reverse-transcriptase polymerase chain reaction
(RT-PCR). Transcription mediated amplification (TMA) or a signal amplification strategy that involves the use
of enzymatically labeled branched nucleotide (bDNA) are available.
Genotyping
Genotyping is useful for investigating outbreaks and for understanding the epidemiology and virological
features of this virus. Accurate classification of genotypes and subtypes of HCV is important for correct
stratification of groups and accurate analysis of data related to efficacy and resistance of new HCV drugs. It is
also essential for the implementation of therapeutic procedures, the production of effective vaccines, and the
improvement of diagnostic tests.
Many genotyping methods targeting different regions of the HCV genome have been developed, such as
restriction fragment length polymorphism, line probe assay, TaqMan PCR, liquid microarray, sequencing and
solid-phase electrochemical array.
Genotyping by Nucleotide Sequencing: A few sequencing-based and several non-sequencing-based HCV

genotyping assays are available and are used for routine determination of the HCV genotype and selected
subtypes. The non-sequencing-based HCV genotyping assays are mainly founded on reverse hybridization
or real-time PCR. Since both assay groups belong to DNA probe-based technologies, they occasionally fail to
provide unambiguous results, particularly when the genetic diversity of the target is high, as in the case of HCV.
Even with the last versions of commercial non-sequencing-based HCV genotyping assays, the HCV genotype/
subtype fails to be assigned in 5 to 10% of patients and sometimes misclassifies the HCV genotypes/subtypes
with clinical consequences such as treatment failure.
Laboratories may use the more accurate, Sanger sequencing of a carefully selected, usually relatively short
part of the HCV genome using sequencing-based assays or in-house sequencing protocols. This is very labour-
intensive and time-consuming, however, it is the preferred method for population screening.
Next generation sequencing

Next-generation sequencing (NGS) is a high-throughput genome sequencing which has revolutionized the
study of genomics and molecular biology. NGS platforms perform sequencing of millions of small fragments of
DNA in parallel. Bioinformatics analyses are used to piece together these fragments by mapping the individual
reads. For example, by using NGS, an entire human genome can be sequenced within a single day.
It is a rapid and cost-effective method for generating the whole HCV genome to accurately and simultaneously
determine HCV genotypes/subtypes, RASs (resistance associated substitutions), and quasi species diversity and
to allow comprehensive viral strain analysis.

5
C H A P T E R
Specimen collection, storage,

transportation

Appropriate specimen management impacts patient care in several very important ways. Nothing is more
important to the effectiveness of a laboratory than a specimen that has been appropriately selected, collected,
and transported. It influences therapeutic decisions, hospital infection control, patient length of stay, overall
hospital costs and directly affects patient care and patient outcome.
All standard precautions must be followed during specimen collection, storage and transport.
Test requisition form

The Test Requisition Form (TRF) – printed or computer-generated form, should be dated and provide the
following information:
1. Patient’s full name
2. Patient’s age and gender
3. Patient’s hospital/medical record number (inpatient or outpatient identification number)
4. The department or location where the specimen was collected
5. Ordering physician information
6. Type of specimen provided
7. A unique identification number
8. An accessioning number
9. Date and time of specimen collection (critical information)
10. Specific test(s) required
11. Written informed consent taken
12. Any other information, if needed
Supplemental information, if it can be provided, would be helpful for the laboratory:

• Relevant clinical information regarding patient’s condition; clinical diagnosis, relevant patient history e.g.
H/o repeated blood transfusion, dialysis, thalassemia
• Special procedures used in obtaining the specimen
• Drugs/Antimicrobial agents, if any, that the patient is receiving
All primary specimen containers are labeled with at least two patient-specific identifiers. Examples of acceptable
identifiers include, but are not limited to: patient’s name, date of birth, hospital number, requisition number,
accession number, unique random number, and the date and time of collection
A location (e.g. hospital room number) is not an acceptable identifier. Identifiers may preferably be in a machine
readable format, such as a barcode.
Aseptically collected fresh serum/plasma sample that is clear, non-haemolysed, or non-lipemic is the preferred
specimen for testing. Serum can be stored at room temperature if the assay is performed within 8 hours of
collection. If the assay cannot be completed within 8 hours, the specimen should be refrigerated at 2 –8 ˚C. The
specimens can be stored up to 7 days at 2– 8 ˚C, and for 1 month at -20 ˚C. In case the specimen is to be stored
beyond 30 days, temperature of storage should be at least -80 ˚C. Repeated freeze-thaw of specimens should
be avoided.

The following equipment are needed for routine venipuncture:
• Evacuated collection tubes - the tubes are designed to fill with a predetermined volume of blood by
vacuum. The rubber stoppers are colour coded according to the additive that the tube contains. Various
sizes are available. Blood should NEVER be poured from one tube to another since the tubes can have
different additives or coatings.
• Needles - the gauge number indicates the bore size: the larger the gauge number, the smaller the needle
bore. Needles are available for evacuated systems and for use with a syringe, single draw or butterfly
system.
• Holder/Adapter – use with the evacuated collection system.
• Tourniquet – Wipe off with alcohol and replace frequently.
• Alcohol wipes – 70% isopropyl alcohol. (Povidone-iodine wipes/swabs - used if blood culture is to be
drawn).
• Gauze sponges – for application on the site from which the needle is withdrawn.
• Adhesive bandages/tape – protects the venipuncture site after collection.
• Needle disposal unit – needles should NEVER be broken, bent, or recapped. Needles should be placed in a
proper disposal unit IMMEDIATELY after their use.
• Gloves – can be made of latex, rubber, vinyl; worn to protect the patient and the phlebotomist.
• Syringes – may be used in place of the evacuated collection tube for special circumstances.
Phlebotomy: Procedural steps

Before carrying out phlebotomy, technicians must wash their hands with soap and water and then dry with a
single-use towel. An alternative would be to cleanse the hands with 3 mL of alcohol rub, starting with the palm
of the hand, rubbing it into the fingertips and all over the hands until the alcohol dries out.
Put on well-fitting latex, rubber or vinyl gloves. Then

1. Patient ID
2. Explain the procedure and purpose to the patient.
3. Assess patient’s condition and position the patient sitting or lying down. (Never allow the patient to
sit upright on a high stool or standing due to the possibility of syncope).
4. Check the requisition form for requested tests, patient information and any special requirements.
5. Select suitable site for venipuncture
6. Assemble and prepare equipment required (order of draw)
7. Prepare patient and venipuncture site. Apply the tourniquet: clean the site with a swab soaked with
70% alcohol for 30 seconds, then allow it to dry. The cleaning is done in concentric circles starting
from the site of puncture.
8. Perform venipuncture.
9. Collect sample/s in the appropriate container/s.
10. While the tube fills, remove the tourniquet and apply a dry swab/cotton on the puncture wound
with pressure to contain the bleeding.
11. Assess for any possible complications.
12. Tubes with anticoagulants should be gently and completely inverted (end over end) four to six times
after collection.
13. Label collection tubes.
14. Send samples to lab with requisition form immediately.

Phlebotomy– infection prevention and control practices:
• MUST carry out hand hygiene (use soap and water or alcohol rub), and wash/rub carefully, including
wrists and spaces between the fingers for at least 30 seconds (follow WHO hand hygiene procedure)
• MUST use one pair of non-sterile gloves per procedure or patient
• MUST use a single-use device for blood sampling and drawing
• MUST disinfect the skin at the venipuncture site
• MUST discard the used device (a needle and syringe is a single unit) immediately into a puncture proof
sharps container
• MUST seal the sharps container with a tamper-proof lid
• MUST place laboratory sample tubes in a sturdy rack (before injecting into the rubber stopper)
• MUST immediately report any incident or accident linked to a needle or sharp injury, and seek assistance;
start PEP as soon as possible.
Table 6: Recommended order of draw for plastic vacuum tubes.

Order Type of tube/ Additivec Mode of action Uses
of use usual colour
a b
1 Blood culture Broth mixture Preserves viability of Microbiology – aerobes,

bottle (yellow-black micro-organisms anaerobes, fungi
striped tubes)
2 Non-additive tube Serum
3 Coagulation tubed Sodium citrate Forms calcium salts Coagulation tests
(light blue top) to remove calcium (prothrombin time),
requires full draw
4 Clot activator Clot activator Blood clots, and the Chemistries, immunology
(red top) serum is separated and serology, blood
by centrifugation bank (cross-match)
5 Serum separator None Contains a gel at the Chemistries, immunology
tube (red-grey bottom to separate and serology
tiger top or gold) blood from serum
on centrifugation
6 Sodium heparin Sodium heparin or Inactivates thrombin For lithium level use
(dark green top) lithium heparin and thromboplastin sodium heparin, for
ammonia level use either
7 PST (light green top) Lithium heparin Anticoagulants with lithium, Chemistries
anticoagulant and separates plasma with
a gel separator PST gel at bottom of tube
8 EDTA (purple top) EDTA Forms calcium salts Haematology, Blood
to remove calcium bank (cross-match)
requires full draw
9 Blood tube (pale Acid-citrate- Complement inactivation HLA tissue typing, paternity
yellow top) dextrose (ACD, testing, DNA studies
ACDA or ACDB)
10 Oxalate/fluoride Sodium fluoride and Antiglycolytic agent Glucoses, requires
(light grey top) potassium oxalate preserves glucose full draw (may cause
up to five days haemolysis if short draw)
a “1” indicates draw first, and “10” draw last (if used).
b Verify with local laboratory in case local colour codes differ.
c Gently invert tubes with additives to mix thoroughly; erroneous test results may
be obtained when blood is not thoroughly mixed with the additive.
d If a routine coagulation assay is the only test ordered, then a single light blue top tube may be drawn. If there is a concern
about contamination by tissue fluids or thromboplastins, then a non-additive tube can be drawn before the additive
tube. The PST tube contains lithium heparin anticoagulant and a gel separator; if used, draw in the order shown.

Table 7: Elements of quality assurance in phlebotomy.
Element Notes
Education and Education and training is necessary for all staff carrying out phlebotomy. It should
training include an understanding of anatomy, awareness of the risks from blood exposure,
and the consequences of poor infection prevention and control.
Standard operating SOPs are required for each step or procedure. They should be written and be readily
procedures (SOPs) available to health workers.
Correct identification Identification should be through matching to the laboratory request form. After samples
of the patient have been taken from a patient, a system of identification and tracking is essential to
ensure that the sample is correctly matched with the result and with the patient or donor.
The condition The condition of the sample should be such that the quality of the results is satisfactory.
of the sample
Safe transportation Making safe transportation of blood or blood products part of best practices will improve
the quality of results from laboratory testing.
An incident A system is required for reporting all adverse events. A log book or register should be
reporting system established with accurate details of the incident, possible causes and management
of adverse events.
Specimen collection for NAT testing

Specimen type: Plasma is the standard specimen type used for the detection and quantitation of HBV DNA
or HCV RNA. The volume of plasma required varies by test and platform used. Methods that use automated
extraction platforms may require a larger sample volume. Although serum may be an approved specimen
type for certain platforms, testing of serum using most quantitative assays generally results in viral loads
significantly less than those measured in plasma. Therefore, plasma is generally recommended for quantitative
NAT and results are reported as plasma viral load.
Collection tubes and anticoagulants: Nearly all methods require that plasma specimens be collected in tubes
containing specific anticoagulants. In general, EDTA is the anticoagulant of choice; acid citrate dextrose (ACD) is
acceptable in some situations. The higher volume of anticoagulant in ACD tubes results in a viral load decrease
of 15%.
Sample collection for quantitative detection of plasma HCV RNA levels-

• Collect 4-5 mL whole blood in EDTA, ACD or EDTA evacuated tube with clot activator gel
• Centrifuge within 6 hours of draw and transfer 2 mL plasma to a sterile, screw top tube.
• If the specimen was collected in PPT, the entire tube can be shipped frozen following centrifugation.
• If shipped (at 2 –8 ˚C), separated plasma fraction must arrive within 24 hours of draw.
Sample collection for quantitative detection of serum HCV RNA levels

• Collect 4-5 mL whole blood in red-top or SST.
• Centrifuge within 6 hours of draw and transfer 2 mL serum to a sterile, screw top tube.
• If the specimen was collected in SST, the entire tube can be shipped frozen following centrifugation.
• If shipped ambient, separated serum fraction must arrive within 24 hours of draw.
This is not the preferred method for HCV RNA estimation.

Storage of Specimen in laboratory and during transport
For immunoassays, separated serum/plasma should remain at room temperature for no longer than eight
hours. After that they need to be stored at 2 – 8 ˚C. If assays are not completed within 48 hours or the separated
serum/plasma need to be stored beyond 48 hours, store at - 20 ˚ C for up to one month and below - 80 ˚C for long
durations of storage. Repeated freeze-thaw should be avoided as it causes marked reduction in values.
For NAT testing, the laboratory should follow the directions in the assay manufacturer’s product insert for
specimen collection, transport and storage. When EDTA is used, whole blood can be collected in tubes with or
without a gel separator. For RNA targets such as HCV, whole blood samples should be centrifuged and, in case
of a non-gel separator tube, the plasma removed to a secondary tube within six hours of phlebotomy. Plasma
separated in a gel separator tube may be transported to the laboratory in situ. Plasma samples are stable for up
to five days at 2 – 8 ˚C and longer if frozen at -20 ˚C or -80 ˚C or lower. The laboratory should validate the effects
on analytical results of in situ freezing of the plasma sample in gel separator tubes and freeze thaw cycles of
plasma stored in secondary tubes.
Blood scheduled for DNA analysis can be stored at room temperature for up to 24 hours or at 2– 8 ˚C for up to
72 hours prior to DNA extraction.
Polypropylene and polyethylene tubes are associated with DNA adsorption. Polyallomer tubes and some
specially designed polypropylene tubes have been shown to be appropriate for storing DNA.
“Frost free” freezers are not suitable for the storage of serum/plasma samples. Freeze/thaw cycles allow the
temperature of the sample to increase and then drop (is cycled several times per day in this variety of freezer –
allowing the sample to refreeze), causing degradation of nucleic acid targets and other analytes.
Specimen labeling and requisition submission for NAT

1. Collection time: The laboratory should determine a mechanism to ensure that the time of collection
is accurately recorded.
2. Specimen labeling: Unique ID number – 15-digit Unique Infant code, to be allocated on the
following basis:
»» First three digits: RNA/DNA
»» Next two digits: state code
»» Next three digits: district code
»» Next two digits: testing centre number
»» Next two digits: year
»» Next three digits: serial number of the patient at the testing laboratory
3. Written informed consent must be obtained.
Specimen Transport/Shipment
Diagnostic samples are shipped as “Clinical Samples, Biological Substance Category B (UN3373)”. They DO NOT
need to be shipped as “Infectious Agent”. Proper labeling includes the “Biological Substance – Category B” label
(replaces Diagnostic Sample label), the UN 3373 label, and proper dry ice labeling (UN 1845). Dangerous goods
and dry ice shipping regulations must be followed for any diagnostic sample.
Refer to the following for regulated shipping instructions:
a) Guidelines for the Safe Transport of Infectious Substances and Diagnostic Specimens, (World Health
Organization)

b) The IATA Dangerous Goods Regulations, (International Air Transport Association)
1. The culture or specimen should be placed in a screw-capped tube or leak-proof container that is
clearly labeled.
2. The lid is then sealed with waterproof tape. This tube is wrapped in absorbent packing material and
inserted in a secondary shipping tube/ziplock bag that has soft packing in the bottom to protect the
specimen tube from breakage.
3. The requisition form or paperwork accompanying the specimen is wrapped around the outside of
this secondary container or is written on the outside of the secondary container.
4. The secondary container is then placed in a sturdy shipping container and labeled for mailing and
marked with a biosafety notice.
5. Both the shipper and consignee’s name, address, and telephone number must be on the outer
package and should also be on the inner containers.
Fig. 27: Packaging and shipping of specimens.

Source: Image courtesy of Centres for Disease Control and Prevention.
http://www.cdc.gov/vhf/ebola/pdf/ebola-lab-guidance.pdf.

Unacceptable samples (Specimen rejection criteria)
The following criteria are used to consider a sample is unacceptable and will be rejected, as it may lead to
erroneous results.. The laboratory staff will notify the clinician who has requested the tests.
• Incompletely filled or no specimen identify on the request form
• Specimen without accompanying request form
• Inappropriate specimen
• Specimen without any label/ inadequate labeling
• Discrepancy in patient’s identity between the request form and specimen label
• Inappropriate specimen containers
• Inappropriate volume of plasma/blood
• Using the wrong collection tube, for example, wrong use of container/preservative/anticoagulant
• Specimens not meeting the stability or storage requirements
• Specimen is haemolysed, lipaemic or contaminated
Specimen referral network is a coordinated system that allows a health facility or laboratory lacking capacity to
perform tests to safely send a patient’s specimen to another or higher-level laboratory with capacity to perform
the requested tests. The aim is safe, efficient handling and analysis of specimens to obtain reliable results
without delays to provide optimal care to the patients at the referring facility. Prior to initiating the specimen
transport system, workers must be trained on specimen referral and biosafety, and standard transportation
containers with packaging be provided.
In the “hub-and-spoke” design/model, the patients’ samples (blood, serum, plasma) are shipped/ couriered
from “spoke” collection facilities (DH, state) to the core testing laboratory placed at the “hub” (regional/CoE)
of the network. The integrated specimen referral and transport system is designed to serve multiple disease
programs (such as Hepatitis, HIV, TB etc.) and in order to further improve the delivery of laboratory services, the
testing capacities of the specimen transport hubs are being strengthened to allow them to conduct testing (as
immunoassays and NAT testing) for multiple health programmes. An electronic reporting system is established
to deliver real-time notification of test results to the treating clinician, regional focal person, and the national
programme/CoE. In this manner the patient does not move but the specimen moves and test results can be
available easily at lesser equipped labs.

6
C H A P T E R
Quality management system

A laboratory consists of numerous processes in which inputs are turned into outputs through one or more
process steps. The core process of the laboratory is the primary process consisting of three stages: the pre-
analytical stage (the sample is collected, received at the laboratory, registered and processed), the analytical
stage (the actual laboratory test is performed and the result is recorded), and the post-analytical stage (the result
is authorized, reported and archived and the sample is discarded/archived).
A Quality Management System (QMS) affects each single process of the laboratory and consists of several layers.
A QMS can be described as a set of building blocks, called quality system essentials (QSEs) needed to control,
assure and manage the quality of the laboratory’s processes. Quality can be assured by ensuring that all the
processes related to the QSEs perform correctly.
Organization Personnel Equipment
Purchasing Process Information

and control management
inventory
documents Occurence
Assessment
and management
records
Process Customer facilites

improvement service and safety

The laboratory should have a written quality management/quality control (QM/QC) programme. The
programme must ensure quality throughout the pre-analytic, analytic, and post-analytic (reporting) phases
of testing, including patient identification and preparation; specimen collection, identification, preservation,
transportation, and processing; and accurate, timely result reporting. The programme must be capable of
detecting problems in the laboratory's systems, and identifying opportunities for system improvement. The
laboratory must be able to develop plans of corrective action based on data from its QM system.
Specimen collection and handling

Specimen collection manual: There are written procedures describing methods for patient identification, patient
preparation, specimen collection and labeling, specimen preservation, and conditions for transportation, and
storage before testing, consistent with good laboratory practice.
There should be written criteria for the rejection of unacceptable specimens, instructions for the special handling
of sub-optimal specimens, and records of disposition of all unacceptable specimens in the patient report and in
the quality management records. If there is a problem with a specimen, there must be a mechanism to notify
clinical personnel responsible for patient care. If the treating physician desires the result, then the laboratory
must note the condition of the specimen on the report.
Standard operating procedure (SOP) manual: The SOP should be used by personnel at the workbench and must
include the following elements, when applicable to the test procedure:
1. Principle and clinical significance
2. Requirements for patient preparation; specimen collection, labeling, storage, preservation,
transportation, processing, and referral; and criteria for specimen acceptability and rejection
3. Step-by-step performance of the procedure, including test calculations and interpretation of results
4. Preparation of, solutions, calibrators, controls, reagents and other materials used in testing
5. Calibration and calibration verification procedures
6. The analytic measurement range for test results for the test system, if applicable. The analytic
measurement range may not apply to qualitative or semi-quantitative tests.
7. Quality Control (QC) procedures
8. Corrective action to take when calibration or quality control results fail to meet the laboratory's
criteria for acceptability
9. Limitations in the test methodology, including interfering substances
10. Reference intervals (normal values)
11. Critical or urgent test results
12. The laboratory's system for entering results in the patient record and reporting patient results
including, when appropriate, the procedure for reporting critical results
13. Pertinent literature references
14. Description of the course of action to take if a test system becomes inoperable
Electronic (computerized) manuals may also be used. There is no requirement for paper copies to be available for
the routine operation of the laboratory, so long as the electronic versions are readily available to all personnel.
However, procedures must be available to laboratory personnel when the electronic versions are inaccessible
(e.g. during laboratory information system or network downtime); Electronic versions of procedures must be
subjected to proper document control (i.e. only authorized persons may make changes, changes are dated/
signed (manual or electronic), and there are records of the review.

Inventory/Commodities/Reagents
Reagents, controls, calibrators and test kits must be stored and handled as recommended by the manufacturer
to prevent environmentally induced alterations that could affect reagent stability and test performance. If there
are multiple components of a reagent kit, the laboratory must use components of reagent kits only within the
kit lot unless otherwise specified by the manufacturer.
If the manufacturer defines a required storage temperature range, the temperature of storage areas must be
monitored and recorded daily (at least twice in a day). The identity of the individual recording the temperature(s)
must be recorded (initials of the individual are adequate). Prepared reagents must be properly stored, mixed,
when appropriate, and discarded when stability parameters are exceeded.
If the laboratory identifies a problem with a reagent that was used for patient testing (e.g. expired vial or reagent
subjected to unacceptable storage conditions, etc.), the laboratory must evaluate the potential impact on
patient test results and maintain records of the evaluation and actions taken. If ambient storage temperature
is indicated, there must be records that the defined ambient temperature is maintained and corrective action
taken when tolerance limits are exceeded.
Records of the commodities (reagents/test kits, calibrators, controls, chemicals, and consumables must be
maintained in a log (paper or electronic), with the following elements:
1. Content and quantity, concentration or titer
2. Storage requirements
3. Date received, prepared, or reconstituted by laboratory
4. Expiration date
5. Batch/Lot number
New reagent lots and shipments must be checked against old reagent lots or with suitable reference material
before or concurrently with being placed in service. The purpose of this check is to confirm that the use of new
reagent lots and shipments do not affect patient results.
For qualitative tests, minimum cross-checking includes retesting at least one positive and negative sample with
known reactivity against the new reagent lot. A weakly positive sample should also be used in systems where
patient results are reported in that method. Examples of suitable reference materials for qualitative tests include:
1. Positive and negative patient samples tested on a previous lot;
2. Previously tested proficiency testing materials;
3. External QC materials tested on the previous lot.
For quantitative tests, patient specimens should be used to compare a new lot against the old lot. Manufactured
materials, such as proficiency testing (PT) or QC materials may be affected by matrix interference between
different reagent lots, even if results show no change following a reagent lot change. The use of patient samples
confirms the absence of matrix interference. Other than patient samples, the following materials may be used:
1. Reference materials or QC products provided by the manufacturer with method specific and reagent
lot specific target values;
2. Proficiency testing materials with peer group established means;
3. QC materials with peer group established means based on inter-laboratory comparison that is
method specific and includes data from other laboratories;
4. Third party general purpose reference materials. If the material is referenced to, in the package
insert , it has to be run along with the patient specimens

5. QC material used to test the current lot is adequate alone to check a new shipment of the same
reagent lot, as there should be no change in potential matrix interactions between the QC material
and different shipments of the same lot number of reagents.
Instruments and equipment

Instrument/equipment performance verification: The performance of all instruments and equipment should
be verified upon installation and after major maintenance or service to ensure that they run according to
expectations.
There must be written procedures for start-up, operation and shutdown of instruments and equipment,
as applicable and should include a procedure for emergency shutdown and for handling workload during
instrument downtime. These procedures must readily be available to the operator in the immediate vicinity
of the instrument. Instructions are provided for minor troubleshooting and repairs of instruments (such as
manufacturer's service manual).
Appropriate maintenance and function checks should be performed and records maintained for all instruments
(e.g. analysers) and equipment (e.g. centrifuges) following a defined schedule, at least as frequent as specified
by the manufacturer. These may include (but are not limited to) cleaning, electronic, mechanical and
operational checks. Function checks should be designed to detect drift, instability, or malfunction, before the
problem is allowed to affect test results. The defined tolerance limits must follow the manufacturer's specified
limits. Function checks must be within the defined tolerance limits prior to use for testing patient samples.
For equipment that has no standard frequency or requirement for maintenance and function checks, each
laboratory should establish a schedule and procedure that reasonably reflects the workload and specifications
of its equipment.
Calibration is the set of operations that establish, under specified conditions, the relationship between reagent
system/instrument response and the corresponding concentration/activity values of an analyte. Calibration
procedures are usually specified in the manufacturer's instructions, but may also be established by the laboratory.
Calibration verification denotes the process of confirming that the current calibration settings for each analyte
remain valid for a test system. If the manufacturer provides a calibration validation or verification process, it
should be followed. Other techniques include: 1) assay of the current method calibration materials as unknown
specimens, and determination that the correct target values are recovered, and 2) assay of matrix-appropriate
materials with target values that are specific for the test system.
The laboratory must follow the manufacturer’s instructions for calibration, calibration verification, and related
functions. Calibration must be performed, at minimum, following the manufacturer's instructions, including
the number, type, and concentration of calibration materials and criteria for acceptable performance.
Materials for calibration verification must have a matrix appropriate for the clinical specimens assayed by that
method, and target values appropriate for the measurement system. Suitable materials include:
1. Calibrators used to calibrate the analytical system
2. Materials provided by the vendor for the purpose of calibration verification
3. Previously tested unaltered patient specimens
4. Primary or secondary standards or reference materials with matrix characteristics and target values
appropriate for the method
5. Proficiency testing material or PT validated material with matrix characteristics and target values
appropriate for the method
In general, routine control materials are not suitable for calibration verification, except in situations where the
material is specifically designated by the test manufacturer as suitable for verification of the calibration process.

Required frequency of calibration verification
The Laboratory must calibrate a test system when it is first placed in service and perform calibration verification
as follows:
1. A change of reagent lots
2. If QC materials reflect an unusual trend or shift, or are outside of the laboratory's acceptable limits,
and other means of assessing and correcting unacceptable control values fail to identify and correct
the problem
3. After major maintenance or service
4. When recommended by the manufacturer
5. At least every six months
The system must be recalibrated when calibration verification fails to meet the established criteria of the
laboratory.
Temperature-dependent equipment (e.g. refrigerators, freezers, incubators) containing reagents and/or patient
specimens must be monitored daily, as equipment failures could affect accuracy of patient test results. Items
such as water baths and heat blocks used for procedures need only be checked on days of patient testing. If specific
instruments, equipment, kits, or supplies have specified ambient temperature ranges for proper operation or use,
there must be records that the specified ambient temperature is maintained and corrective action taken when
tolerance limits are exceeded. Acceptable ranges must be defined for all temperature-dependent equipment and
environments in accordance with the manufacturer’s instructions. There must be evidence of corrective action
taken if acceptable temperature ranges are exceeded. Stored reagents, controls, calibrators etc. must be checked
to confirm the accuracy or quality of the material before use and records maintained.
Appropriate thermometric standard device of known accuracy (certified to meet NPL/International Standards
or traceable to NPL/international Standards) if used must be recalibrated, recertified, or replaced prior to
the date of expiration of the guarantee of calibration. All non-certified thermometers that are in use must
be checked against a certified calibrated thermometric standard device before initial use and as defined by
laboratory policy (at least annually). If digital or other displays of temperatures on equipment are used for daily
monitoring, the laboratory must verify that the readout is accurate. The display must be checked initially and
periodically thereafter as per the manufacturer’s instructions.
Automatic and adjustable pipetting devices must be checked at defined intervals (at least annually) for
accuracy and reproducibility, and results recorded. Pipette checks may be done gravimetrically. This consists
of transferring a number of measured samples of water from the pipette to a balance. Each weight is recorded,
the weights are converted to volumes, and then means (for accuracy) and standard deviation/coefficient of
variation (SD/CV - for imprecision) are calculated.
Spectrophotometer including ELISA plate readers wavelength calibration, absorbance and linearity must be
checked at least annually (or as often as specified by the manufacturer), with appropriate solutions, filters or
emission line source lamps, and the results recorded. For procedures using calibration curves, all the curves are
rerun at defined intervals and/or verified after servicing or recalibration of instruments.
Instrument/Equipment records: Instrument and equipment maintenance, function check, performance

verification, and service and repair records (or copies) must be available to, and usable by, the technical staff
operating the equipment to detect trends or malfunctions. Retention period of equipment records is for at least
five years after the equipment has been decommissioned/replaced.

Quality control
Quality Control (QC) in the laboratory is a procedure that verifies the attainment of the intended quality of
results. QC materials are processed similar to a patient sample to monitor the ongoing performance of the entire
analytic process. Control specimens are tested in the same manner, at the time of and by the same personnel as
patient samples. It is implicit in quality control that patient test results will not be reported when controls yield
unacceptable results.
The laboratory must define the number and type of quality control used and the frequency of testing in its
quality control procedure. Control testing is not required on days when patient testing is not performed.
Controls must be run prior to reporting patient results, after a change of analytically critical reagents, major
preventive maintenance, or change of a critical instrument component. Daily quality control must be run as
follows:
1. Quantitative tests – two controls at different concentrations at least daily, with each run (of which
one must be a low positive).
2. Qualitative tests – a negative control and a positive control at least daily and with each run. For RDT
they are run with each new kit or may be run every week if the kit is used beyond a week.
For immunoassays, appropriate controls must be used in each run or batch of samples. Appropriate controls for
screening assays should consist of at least one positive control. If a single calibrator is used, the control must be
at or near the declared cutoff value(s). Controls must be run with each batch to verify the calibration.
Controls should verify assay performance at relevant decision points. The selection of these points may be
based on clinical or analytical criteria. If an internal quality control process (e.g. electronic/procedural/built-
in) is used then an external control material must be used to meet daily quality control requirements, as per
a documented individualized quality control plan (QCP) approved by the laboratory in charge. Acceptability
limits must be defined for all control materials and standards. These controls must be appropriate for the range
of sensitivities tested and should, ideally, focus on result ranges that are near clinical decision points.
For quantitative tests, a valid acceptable range must be established or verified for each lot of control material.
For unassayed controls, the laboratory must establish a valid acceptable range by repetitive analysis in runs
that include previously tested control material. The laboratory must use statistical methods such as calculating
SD and CV monthly to detect problems, evaluate analytic imprecision/ variance and to monitor trends over
time in numeric QC data (quantitative data should be plotted as Levey-Jennings charts. Testing and supervisory
staff must review quality control data on days when controls are run prior to reporting patient results. The
laboratory in charge must review QC data for omissions, outliers, trends and their follow-up, at least monthly,
as specified in the laboratory QC policy. There must be evidence of corrective action when control results exceed
defined acceptability limits.
For single use test devices, appropriate QC materials (both positive and negative) are analyzed with each:
• Change of reagent lot number
• New shipment
• Change in storage conditions
• Replacement of a critical part or following any major preventive maintenance in cartridge based
equipment
Controls for molecular testing must assess adequacy of extraction and amplification, e.g., positive and negative
controls that go through the entire testing process.

1. An extraction control must be used for each run (positive controls fulfill this requirement).
2. If the samples from an extraction batch are tested over multiple amplification runs, each
amplification run (as defined by the laboratory) must have its own amplification control. A single
extraction control need only be tested in one of the amplification runs.
Qualitative cut-off: For qualitative tests that use a cut-off value to distinguish positive from negative, the cut-
off value is established initially when the test is placed in service, and verified every six months thereafter.
If the value of a calibrator or calibration verification material is near that of the cut-off, then the process of
calibration or calibration verification is satisfied. Verification of the cut-off should also be performed at changes
of lots of analytically critical reagents; after replacement of major instrument components, after major service
to the instrument, and when QC materials reflect an unusual trend or shift, or are outside of the laboratory's
acceptable limits, and other means of accessing and correcting unacceptable control values fail to identify and
correct the problem. Appropriate materials for establishment and verification of the cut-off are identical to
those recommended for calibration verification. A low-positive control that is close to the limit of detection (cut
off) can satisfy this requirement, but must be external to the kit (e.g. weak-positive patient sample or reference
material prepared in appropriate matrix).
Quality Control materials may be procured commercially or prepared in-house. Positive/Reactive, weakly
reactive and negative/nonreactive controls are all used in test systems. In general, calibrators should not be
used as QC materials. If calibrators are used as controls, then different preparations should be used for these two
functions. If a calibrator obtained from an outside supplier is used as a control, it must be a different lot number
from that used to calibrate the method.
The results of all controls must be recorded. When a QC result is unacceptable, patient test results obtained
since the last acceptable test run must be re-evaluated to determine if there is a significant clinical difference
in patient/client results. Re-evaluation may or may not include re-testing patient samples, depending on the
circumstances. Even if patient samples are no longer available, test results can be re-evaluated to search for
evidence of an out-of-control condition that might have affected patient results.
The laboratory must have a written procedure for investigation and corrective action when data from QC
precision statistics change significantly from previous data. Records of investigation and corrective actions
taken must be maintained.
Quality assurance
External assessment of quality assurance is an essential component of each clinical laboratory’s overall quality
assurance programme.
Laboratories must participate in the appropriate required proficiency testing (PT) / EQA (when available) for
all patient tests. The laboratory should have written procedures for proficiency testing including procedures
for the proper handling, analysis, review and reporting of proficiency testing materials. There must be written
procedure(s) for investigation and correction of problems that are identified by unacceptable proficiency testing
results. The laboratory should also have procedure(s) for investigation of results that, although acceptable, show
bias or trends suggesting a problem. The laboratory must integrate all proficiency testing samples within the
routine laboratory workload, and those samples are analysed by personnel who routinely test patient/client
samples, using the same primary method systems as for patient/client/donor samples. If the laboratory uses
multiple methods for an analyte, proficiency samples should be analysed by the primary method.
For tests for which PT/EQA is not available, the laboratory must implement, at least semi-annually an alternative
assessment procedure for the affected analytes. (Split sample analysis with reference or other laboratories, split
samples with an established in-house method, assayed materials, clinical validation by chart review, or other
suitable and documented means.) It is the responsibility of the laboratory in-charge to define such alternative
assessment procedures and the criteria for successful performance in accordance with good clinical and
scientific laboratory practice.

In summary, for the validity, reproducibility, and reliability of an assay, blank reagents, cut-off, calibrators,
and controls (high positive, low positive, and negative) must be tested in parallel with patient samples with
every assay. Most commercially available kits provide these reagents; however, additional controls may be
tested. Additional external or in-house-pooled standard controls with known titers add to the rigorousness
and validity of the testing conditions, method and test results. In order to ensure the validity of in-house
controls, they should be tested over a period of several assay runs to establish a laboratory reference range that
could be used to validate a test run. Every kit has its own reference range for all of its blank reagents, cut-off
calibrators, and controls. Patient test results should not be released until the blank reagent, control, and cutoff
calibrator parameters are within acceptable ranges. If any parameters are outside of the acceptable range, the
test run should be deemed invalid and repeated. Each new lot of kits should be tested (in tandem) and validated
before routine use. Periodic review of test results will help to identify, investigate, and troubleshoot any testing
anomaly or unusual result patterns.
Reporting of results
The laboratory must report reference (normal) intervals or interpretations with patient results, where such exist.
This is essential to allow proper interpretation of patient data. Age- and/or gender-specific reference ranges
(normal values) or interpretive ranges must be reported with patient test results, as applicable. In addition, the
use of high and low flags is recommended.
The laboratory must have written procedures for immediate notification of a clinician when results of designated
tests exceed established "critical" values that are important for prompt patient management decisions. Critical
results with their values should be defined by the laboratory in charge, in consultation with the clinicians served.
Records of notification should be maintained. These records must include: date, time, responsible laboratory
individual, person notified and test results. Any problem encountered in accomplishing this task should be
investigated to prevent recurrence.
In summary, QMS requires laboratories to:

1. Maintain optimal patient specimen integrity and identification throughout testing process
2. Specify responsibilities and qualification for personnel performing the test
3. Establish and follow written Quality Control (QC) procedures
4. Have comprehensive Quality Assurance (QA) programme in place
5. Participate in proficiency testing programme for each analyte, or test

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Hepatitis E Virus Infection (American Society for Microbiology) Lisa J. Krain et al. Clin. Microbiol.
Rev. 2014;27:139-165
3. Clinical relevance of hepatitis B virus variants Shan Gao, Zhong-Ping Duan, and Carla S Coffin.
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(Fourth edition)
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virus mutations: Recent advances. Ivana Lazarevic. World Journal Gastroenterol. 2014 June 28; 20(24):
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Rodden, et al. Journal of Laboratory Automation 2015, Vol. 20(5) 519– 538
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(*European Association for the Study of the Liver) Journal of Hepatology 2017 vol. 67 j 370–398
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the Liver) journal of hepatology (2018), https://doi.org/10.1016/j.Jhep.2018.03.026
9. Expanded Classification of Hepatitis C Virus Into 7 Genotypes and 67 Subtypes: Updated Criteria and
Genotype Assignment Web Resource Donald B Smith, Jens Bukh, Carla Kuiken, A Scott Muerhoff,
Charles M Rice, Jack T Stapleton, and Peter Simmonds Emerg Microbes Infect. 2017 Nov; 6(11): e95.
Published online 2017 Nov 1. doi: 10.1038/emi.2017.77
10. Global health sector strategy on viral hepatitis 2016-2021, Authors: WHO Publication date: June 2016.
11. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection
Authors: WHO Publication date: March 2015
12. Guidelines for the screening care and treatment of persons with chronic hepatitis C infection.
Updated version, April 2016, WHO
13. Guidelines on hepatitis B and C testing Authors: WHO, Publication date: February 2017
14. Harrison’s Principles of Internal Medicine, Twentieth Edition by J. Larry Jameson ), Anthony S.
Fauci, Dennis L. Kasper, Stephen L. Hauser , Dan L. Longo , Joseph Loscalzo. New York: McGraw Hill
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15. Hepatitis Delta: Epidemiology, Diagnosis and Management 36 Years after Discovery Mazen
Noureddin and Robert Gish, Current Gastroenterology Report 2014; 16(1): 365.Published online 2013
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16. ISO 15189:2012 Medical laboratories - Requirements for quality and competence
17. Jawetz, Melnick, & Adelberg’s. Medical Microbiology. 27th edition by Karen C. Carroll, Jeffery A.
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Annexure 1: Consent form
INDIVIDUAL’S CONSENT FORM FOR TESTING AND MANAGEMENT OF VIRAL HEPATITIS
I, ______________________________________________ (full name), daughter/son of _______________________

____________________ (full name) age ________ resident of (address) ____________________________________
_____________________ have read/have been read over and explained (circle appropriate) the accompanying
guidance and have understood the information provided to me related to the investigations and proposed
management required (if available)
I understand that the purpose of these tests is to:
• Establish my Viral Hepatitis status,

• Evaluate the presence of liver disease which may be associated with Hepatitis infection.
• I can allow the program to archive my specimen for further molecular testing related to viral hepatitis
only in the interest of public health, provided that any information/data/detail relating to or emanating
from my molecular sample shall not be divulged to any third party under any circumstances. A breach of
this condition shall automatically forfeit my consent and the program’s right to retain such information
and shall further render them liable to penal action and compensation.
I understand that if a diagnosis of Chronic Hepatitis B/C is confirmed, I will be offered treatment as per the
provisions in the initiative. I give my consent to the proposed management offered by the initiative subject to
strict protection of my information.
Patient’s Signature: _________________________________ DATE: ____________
Staff member name obtaining consent: __________________________________________
Staff signature: ___________________________________ DATE: ____________

Annexure 2: Parameters in the test kit for quality
assured test result
It is important to determine the extent to which tests are able to identify the likely presence or absence of
a disease/condition of interest so that their findings encourage appropriate decision making. Adequacy and
usefulness of screening tests are determined and described by the sensitivity, specificity, and predictive values
of these tests. All four metrics should be regarded as important when describing and assessing a screening test’s
adequacy and usefulness.
Status of person
according to “gold standard”
Has the Does not have
condition the condition
a b
Row entries for
Positive True positive False positive determining positive
Result from predictive value
screening test c d
Negative False negative True negative Row entries for
determining negative
predictive value
Column entries Column entries

for determining for determining
sensitivity specificity
Fig. A1: Diagram demonstrating the basis for deriving sensitivity, specificity,
and positive and negative predictive values.
Sensitivity= [a/(a+c)]×100
Specificity= [d/(b+d)]×100
Positive predictive value (PPV) = [a/(a+b)]×100
Negative predictive value (NPV) = [d/(c+d)] ×100
When kit inserts refer to sensitivity, specificity, and predictive values to describe the characteristics of a
screening test, they are cited as percentages or as decimal fractions, and preferably with accompanying 95%
confidence interval.
Sensitivity and specificity indicate the concordance of a test/effectiveness of a test with respect to a chosen
referent, while PPV and NPV, respectively, indicate the likelihood that a test can successfully identify whether
people do or do not have a target condition, based on their test results. Predictive values are more relevant than
sensitivity and specificity when people are being screened.


1. Dr Lalit Dar, AIIMS, Delhi
2. Dr Priya Abraham, CMC, Vellore
3. Dr Ekta Gupta, ILBS, Delhi
4. Dr Srikala Baliga, Kasturba Medical College, Mangalore
5. Dr Sujata Baveja, Lok Manya Tilak Municipal Medical College, Mumbai
6. Dr Thasneem Banu S., Madras Medical College, Chennai
7. Dr Rekha Jain, Microbiologist, Mumbai
8. Dr Margaret Yhome, Naga Hospital Authority, Kohima
9. Dr Anita Desai, National Institute of Mental Health & Neurosciences, Bangalore
10. Dr Praveen Malhotra, PGIMS, Rohtak
11. Mr Mehmood Pracha, Sr. Advocate
12. Dr Sandhya Kabra, NCDC, Delhi
13. Dr Partha Rakshit, NCDC, Delhi
14. Dr Preeti Madan, EIS Officer, NCDC, Delhi
15. Dr Vimlesh Purohit, NPO, WHO Country Office, India
16. Dr Hema Gogia, NCDC, Delhi
17. Dr Daniel Garcia, CDC, India
18. Dr Mayank Dwivedi, CDC, India
19. Dr Indranil Roy, CDC, India
20. Mr Sella Senthila, CDSCO, India
21. Dr Sujeet Sinha, NHSRC

National Guidelines for
Diagnosis & Management

of Viral Hepatitis
2018
National Guidelines for
Diagnosis & Management

of Viral Hepatitis
Preface
Viral hepatitis is increasingly being recognized as a public health problem in India. While hepatitis
A and E – that are water and foodborne infections – are often the cause for sporadic or outbreaks
of hepatitis in India and recover completely with no clinical sequelae, hepatitis B and C can lead to
chronic infection and thereafter sequelae like cirrhosis and hepatocellular carcinoma.
Viral hepatitis is a leading cause of death in the world, which is comparable to that of HIV, tuberculosis
and malaria. Cirrhosis and hepatocellular carcinoma, which are the sequelae of chronic hepatitis B and
C, accounted for more than 90% of all hepatitis B and C related deaths. Further, mortality from HBV-
and HCV-associated cirrhosis and hepatocellular carcinoma is still increasing because of poor access
to treatment. While prevention can reduce the rate of new infections, treatment eliminates existing
infections; thus combining both prevention and treatment makes hepatitis B and C elimination
feasible long term goal.
The Government of India has decided to launch the National Viral Hepatitis Control Program with
provision of free diagnosis and treatment for viral hepatitis through the National Health Mission.
Consequently, it is of utmost importance to have standard national guidelines that are robust, evidence
based, and simple to be followed at the decentralized level. It should also enable the service providers to
decide on the assessment of patient, treatment options, managing special situation ( like co-infections),
parameters for timely referrals and quality service delivery. The current guidelines are a outcome for
the collective effort of the members of Technical Resource Group on hepatitis Treatment, constituted
by the MoH & FW, and that had representations of clinicians and program managers from across the
country, representing different sectors (government, private sector, academic institutes, community
members, development partners). The group has taken into considerations the latest available evidence,
global guidelines (such as EASL, WHO etc) and adapted them to the Indian context taking relevant
considerations from with the extensive experience of delivering services in the state of Punjab.
I hope, these guidelines will offer the needed guidance for delivering quality treatment and services in
a public health approach.
ACRONYMS
AFP Alfa Feto Protein
AIDS Acquired Immuno Deficiency Syndrome
ALT Alanine amino transferase
AntiHBc Antibody to Hepatitis B core antigen
AntiHBe Antibody to Hepatitis B envelope antigen
APRI AST to Platelet Ratio Index
ARVs Anti Retro Virals
AST Aspartate aminotransferase
CBC Complete Blood cell Count
CD4 Cluster of Differentiation 4
CEMRI Contrast Enhanced Magnetic Resonance Imaging
d4T Stavudine
DCV Daclatasvir
ddI Didanosine
DDIs Drug Drug Interactions
DNA Deoxyribo Nucleic Acid
DOEACC Department of Electronics and Accreditation of Computer Courses
DPT Diptheria Pertussis Tetanus
EASL European Association for Study of the Liver
eGFR estimated Glomerular Filtration Rate
HBIG Hepatitis B Immuno Globulin
HBsAg Hepatitis B Surface Antigen
HBeAg Hepatitis B envelope Antigen
HCVcAg Hepatitis C Virus core Antigen
Hib Haemophilus influenzae type b
HR Human Resource
ICTC Integrated Counseling and Testing Centre
IDSP Integrated Disease Surveillance Programme
INR International normalized ratio
IP In Patient
LDV Ledipasvir
MO Medical Officer
MTC Model Treatment Centres
NAs Nucleos(t)ide analogues
NITs Non Invasive Tests
NSAID Non Steroidal Anti Inflammatory Drug
NVHMU National Viral Hepatitis Management Unit
NVP Nevirapine
OP Out Patient
PEG-IFN Pegylated Interferon
PLHIV People Living with HIV
PMU Program Management Unit
QC Quality Control
RAS Resistance-Associated Substitution
RBV Ribavarin
RNA Ribo-nucleic acid
SoE Statement of Expenditure
SOF Sofosbuvir
SSO State Surveillance Officer
SVHMU State Viral Hepatitis Management Unit
TAF Tenofovir Alafenamide Fumarate
TB Tuberculosis
TC Treatment Centre
TDF Tenofovir Disoproxil Fumarate
TG Transgender
TPCT Tri Phasic Computerised Tomography
UID Unique Identification
ULN Upper limit of normal
USG Ultra Sono Graphy
VEL Velpatasvir
CONTENTS
SECTION 1:
GUIDELINES FOR DIAGNOSIS AND MANAGEMENT OF VIRAL HEPATITIS 14
Introduction 15
Estimating the problem statement 15
Hepatitis A Infection 16
Clinical presentation 16
Laboratory Diagnosis 17
Management 18
Hepatitis B Infection 18
Clinical Presentation 18
Acute Hepatitis 18
Chronic Hepatitis 19
Assessment and Staging of HBV Chronic infection 22
Management 23
Whom To Treat 23
When To Stop Treatment 26
Monitoring 27
Special Situations 29
Pregnancy 29
Co-morbidities 30
Hepatitis C Infection 32
Clinical Course of Hepatitis C Infection 33
Whom To Test 34
Treatment of Viral Hepatitis C in Adults 34
Clinical Assessment before Initiating Treatment 35
Assessment of Degree of Fibrosis 35
Baseline and follow-up Investigations 35
Whom To Treat 36
What Regimen To Use 36
Side Effects of Drugs Used in Treatment 38
Drug Interactions with DAA 39
Special Situations and co-morbidities 39
Treatment of Patients with Decompensated Cirrhosis 39
Management of Treatment Experienced Patients 40
People who inject drugs 40
Persons with HIV/HCV Co-infection 41
Management of Cirrhotic Patients after HCV clearance in SVR 12 43
Persons with chronic kidney disease 43
Persons with HBV/HCV co-infection 43
Persons with TB/HCV co-infection 43
Women of child-bearing age 44
Hepatitis E 44
Clinical Presentation 44
Management of Viral Hepatitis E 44
Special Situations 45
SECTION 2:
OPERATIONAL GUIDELINES TO ROLL OUT TREATMENT OF HEPATITIS C 48
Introduction 49
Organization of Services 49
Guidelines for the Organization of Services 49
Objectives and functions of the Treatment Sites 49
Selection criteria and steps for setting up a Treatment Site 50
Infrastructure 50
Human Resource 50
Training 55
Logistics 56
Financial management 56
Patient Flow at the Treatment Centers 57
Monitoring and Evaluation of the Treatment sites 59
Recording tools 60
Reporting tools 60
Annexure 1: Assessing severity of liver disease 62

Annexure 2: Algorithm for the Laboratory Diagnosis of Viral Hepatitis 64
Annexure -3: Drug interactions between DAA and some commonly
prescribed medications. 65
Annexure 4: Feasibility Visit for Setting Hepatitis Treatment Center 66
Annexure 5: Patient Testing &Treatment Card 68
Annexure 6: Hepatitis C Treatment Register 69
Annexure 7a: DAA Stock register 70
Annexure 7b: Drug Dispensation Register 71
Annexure 8: Monthly reporting format 72
Annexure 9: Consent form 75
References 76
List of Contributors 78
SECTION 1
GUIDELINES FOR DIAGNOSIS
AND MANAGEMENT OF
VIRAL HEPATITIS
14 National Guidelines for Diagnosis & Management of Viral Hepatitis

Introduction
Viral hepatitis is recognized as a public health problem globally. Various etiological agents (Hepatitis A, B, C, D
and E viruses) have been implicated that can lead to acute, chronic or sequel of chronic infection. While hepatitis
A and E are often the cause for sporadic or outbreaks of hepatitis, hepatitis B and C can either clear spontaneously
or can lead to chronic infection and there after sequelae like cirrhosis and hepatocellular carcinoma (HCC).
Viral hepatitis is increasingly being recognized as a public health problem in India.
Hepatitis A Virus (HAV) and Hepatitis E Virus (HEV) are important causes of acute viral hepatitis and acute liver
failure (ALF). Due to paucity of data, the exact burden of disease for the country is not established. However,
available literature indicates a wide range and suggests that HAV is responsible for 10-30% of acute hepatitis and
5-15% of acute liver failure cases in India. It is further reported that HEV 10-40% of acute hepatitis and 15-45%
of acute liver failure.
Hepatitis B surface antigen (HBsAg) positivity in the general population ranges from 1.1% to 12.2%, with an
average prevalence of 3-4%. Anti-Hepatitis C virus (HCV) antibody prevalence in the general population is
estimated to be between 0.09-15%. It is estimated that there are 40 million people chronically infected with
Hepatitis B Virus (HBV) and based on some regional level studies, it is estimated that there are 6-12 million
people with Hepatitis C in India. Chronic HBV infection accounts for 40-50% of HCC and 20-30% cases of
cirrhosis in India. Chronic HCV infection accounts for 12-32% of hepatocellular carcinoma (HCC) and 12-20%
of cirrhosis.
Population based syndromic and health facility based surveillance of viral hepatitis is mandated under the
Integrated Disease Surveillance Program (IDSP).
Recently, a meta-analysis of studies on hepatitis C prevalence was undertaken by SGPGI, Lucknow. The study
documented the pooled prevalence of Hepatitis C amongst various sub populations.
This meta-analysis concluded that based on the above studies, it can be estimated that India (current population
= ~1.3 billion) has 5.2 to 13 million anti-HCV positive persons. The data on HCV viremia rates among anti-HCV
antibody positive persons were not available. Hence it is difficult to arrive at a conclusion on this. However,
using data from elsewhere that 60%-70% of anti-HCV persons have HCV viremia, it can be estimated that India
as ~3 million to ~9 million persons with active HCV infection.
Estimating the problem statement

There are a few estimates that are available from global publications. However, it is assumed that these estimates
are likely to change, as data sets and evidence increase across India.

Table 1: WHO Global Disease estimates 2016 viral hepatitis could be contributing to
nearly 2.85% of all deaths in India:
Hepatitis Numbers in thousands Total ( in thousands)
a. Acute hepatitis A 5.0
b. Acute hepatitis B 43.3
78.7
c. Acute hepatitis C 1.1
d. Acute hepatitis E 29.2
Liver cancer Numbers in thousands Total ( in thousands)

a. Liver cancer secondary 15.3
to hepatitis B
20.1
b. Liver cancer secondary 4.9
to hepatitis C
Cirrhosis of the liver Numbers in thousands Total ( in thousands)

a. Cirrhosis due to hepatitis B 141.8
173.6
b. Cirrhosis due to hepatitis C 31.9
Estimated Total Deaths ( All causes) 9559.1

% of deaths attributed to viral hepatitis 2.85%
Similarly, the Global Burden of diseases in 2016, suggests that the mortality attributable to viral hepatitis in
India could be 1.18% of all deaths. The National Health Profile 2016 identified viral hepatitis to contribute to 3%
of all deaths related to communicable diseases in India in 2015.
Acute viral hepatitis is a systemic infection affecting the liver predominantly. Almost all cases of acute viral
hepatitis are caused by one of five viral agents: HAV, HBV, HCV, the HBV-associated delta agent or hepatitis
D virus (HDV) and HEV. All these human hepatitis viruses are RNA viruses, except for hepatitis B, which is
a DNA virus but replicates like a retrovirus. Although these agents can be distinguished by their molecular
and antigenic properties, all types of viral hepatitis produce clinically similar illnesses. These range from
asymptomatic and inapparent to fulminant and fatal acute infections common to all types, on the one hand,
and from subclinical persistent infections to rapidly progressive chronic liver disease with cirrhosis and even
hepatocellular carcinoma, common to the blood borne types (HBV, HCV, and HDV), on the other.
Hepatitis A Infection
HAV is a non-enveloped RNA virus belonging to the picornavirus family, with 4 genotypes belonging to one
serotype.
This agent is transmitted almost exclusively by the fecal-oral route. It is an outbreak prone disease with an
incubation period of around 4 weeks. Person to person spread of HAV is enhanced by poor personal hygiene
and overcrowding. Excretion in the stool occurs for only 7-14 days after the onset of the clinical illness and is
diagnostic of an acute HAV infection. No carrier state has been identified. Inactivated attenuated vaccine, which
is safe, immunogenic and effective, is available.
Clinical presentation
The incubation period for HAV ranges from 15-45 days. The prodromal symptoms of acute viral hepatitis
are systemic and quite variable. Constitutional symptoms of low grade fever, anorexia, nausea and vomiting,

fatigue, malaise, arthralgias, myalgias, headache, photophobia, pharyngitis, cough and coryza may precede
onset of jaundice by 1-2 weeks.
Dark urine and clay colored stools may be noticed by the patient from 1-5 days before the onset of clinical
jaundice. With the onset of clinical jaundice, the constitutional prodromal symptoms usually diminish. The
liver becomes enlarged and tender and may be associated with right upper quadrant pain and discomfort.
During recovery phase the constitutional symptoms disappear, but usually some liver enlargement and
abnormalities in liver biochemical tests are still evident.
Laboratory Diagnosis
HAV has an incubation period of ~4 weeks. Its replication is limited to the liver, but the virus is present in liver,
bile, stools and blood during late incubation period and acute pre-icteric / pre-symptomatic phase of illness.
In acute hepatitis with clinical jaundice, the serum bilirubin levels are above 2.5mg/dL and serum alanine
aminotransferase (ALT) is more than 10 times the upper limit of normal.
Jaundice
ALT IgG Anti-HAV

IgM Anti-HAV
Fecal HAV
0 4 8 12 16 20
Weeks after exposure
Fig.1: Laboratory Markers of HAV Infection
Source: Faud AS, Kasper DL, Braunveld E, Hauser SL, Longo DL, Jameson JL, Loscalzo J, Harrison’s
Principles of Internal medicine, 19th Edition: http://www.accessmedicine.com
Detection of anti- HAV antibody in serum/plasma is important in diagnosis of infection, as HAV is present in
blood transiently during the incubation period.
IgM antibodies against HAV are generally detectable 5-10 days before onset of symptoms and can persist for up
to 6 months. Anti-HAV IgM antibodies indicate acute infection.
IgG antibodies against HAV becomes the predominant antibody during convalescence and remains detectable
indefinitely. Anti-HAV total antibodies (IgG and IgM) or specific IgG (but anti-HAV IgM negative) indicate
immunity to hepatitis A either because of past infection or vaccination.

The serum aminotransferases, aspartate aminotransferase (AST) and ALT increase to a variable degree during
prodromal phase of illness and precede the rise in bilirubin levels.
Yellowish discoloration of sclera (jaundice) and skin is usually visible when serum bilirubin value is >2.5 mg/dL.
Management
There is no role for antiviral drugs in therapy for HAV infection. Virtually all previously healthy patients
with hepatitis A recover completely with no clinical sequelae. The case fatality is very-very low (~0.1%) but is
increased in advanced age and in the presence of underlying debilitating diseases.
Infection in the community is best prevented by improving social conditions especially overcrowding and poor
sanitation.
Hepatitis B Infection
HBV, a double-stranded DNA virus, belongs to the family of hepadnaviruses. HBV infection is a global public
health problem. Perinatal transmission and occasionally horizontal transmission early in life are most common
in high prevalence areas. Sexual contact and percutaneous transmission also contribute to the transmission of
HBV.
Clinical Presentation
The spectrum of clinical manifestations of HBV infection varies in both acute and chronic disease. During the
acute phase, manifestations range from subclinical or anicteric hepatitis to icteric hepatitis and, in some cases,
fulminant hepatitis. The incubation period for HBV varies from 30-180 days. In chronic phase, manifestations
range from an asymptomatic carrier state to chronic hepatitis, cirrhosis, and HCC. Extra-hepatic manifestations
can also occur with both acute and chronic infection.
Acute Hepatitis:
Approximately 70 percent of patients with acute HBV infection have subclinical or anicteric hepatitis, while 30
percent develop icteric hepatitis. The disease may be more severe in patients co-infected with other hepatitis
viruses or with underlying liver disease.
Fulminant hepatitis B is unusual, occurring in approximately 0.1 to 0.5 percent of patients; it is believed to be
due to massive immune-mediated lysis of infected hepatocytes. A serum sickness-like syndrome may develop
during the prodromal period, followed by constitutional symptoms, anorexia, nausea, jaundice, and right upper
quadrant discomfort. The symptoms and jaundice generally disappear after one to three months, but some
patients have prolonged fatigue even after normalization of serum aminotransferase concentrations.
The complete eradication of HBV rarely occurs after recovery from acute HBV infection and that latent
infection can maintain the T cell response for decades following clinical recovery, thereby keeping the virus
under control.
The rate of progression from acute to chronic hepatitis B in immunocompetent persons is determined primarily
by the age at infection. The rate is approximately 90 percent for a perinatally acquired infection, 20 to 50 percent
for infections between the age of one and five years, and less than 5 percent for an adult-acquired infection.
Treatment for acute HBV is mainly supportive. In addition, appropriate measures should be taken to prevent
infection in exposed contacts.

The decision to hospitalize patients should be taken on a case-to-case basis. Patients, who have a coagulopathy,
are deeply jaundiced, or encephalopathy should generally be hospitalized. Hospitalization might also be
considered in patients who are older, have significant comorbidities, cannot tolerate oral intake, or have poor
social support systems.
In acute cases, the patients who have fulminant hepatitis or hepatitis B with underlying cirrhosis should be
considered for antiviral treatment.
Chronic Hepatitis:
A history of acute hepatitis is elicited in only a small percentage of patients with chronic HBV infection. In low
or intermediate prevalence areas, approximately 30 to 50 percent of patients with chronic HBV infection have
a past history of acute hepatitis; such a history is lacking in the remaining patients in these areas and in the
majority of patients in high prevalence areas (predominantly perinatal infection).
Many patients with chronic HBV are asymptomatic (unless they have decompensated cirrhosis or have
extrahepatic manifestations), while others have nonspecific symptoms such as fatigue. Some patients experience
exacerbations of the infection which may be asymptomatic, mimic acute hepatitis, or manifest as hepatic failure.
Physical examination may be normal, or there may be stigmata of chronic liver disease. Jaundice, splenomegaly,
ascites, peripheral edema, upper gastrointestinal bleed and encephalopathy may be present in patients with
decompensated cirrhosis. Laboratory tests may be normal, but most patients have a mild to moderate elevation
in serum AST and ALT. During exacerbations, the serum ALT concentration may be as high as 50 times the upper
limit of normal, and alfa-fetoprotein (AFP) concentrations as high as 1000 ng/mL may be seen. A progression
to cirrhosis is suspected when there is evidence of hypersplenism (decreased hemoglobin, white blood cell and/
or platelet counts) or impaired hepatic synthetic function (hypoalbuminemia and/or prolonged prothrombin
time/ international normalized ratio (INR).
Extrahepatic manifestations — Extrahepatic manifestations, which are thought to be mediated by circulating

immune complexes, occur in 10 to 20 percent of patients with chronic HBV infection. As mentioned above,
acute hepatitis may be heralded by a serum sickness-like syndrome manifested as fever, skin rashes, arthralgia,
and arthritis, which usually subsides with the onset of jaundice. The two major extrahepatic complications of
chronic HBV are polyarteritis nodosa and glomerular disease.
Natural Course and Phases of Chronic Hepatitis B Infection

The natural course of chronic HBV infection is determined by the interplay between virus replication and the
host immune response. Other factors that may play a role in the progression of HBV-related liver disease include
gender, alcohol consumption, and concomitant infection with other hepatitis virus(es). The outcome of chronic
HBV infection depends upon the severity of liver disease at the time HBV replication is arrested.

Immune active Inactive Immune escape/
Phase Immune Tolerant
(clearance) (immune control) Reactivation
HBeAg
HBeAg/Anti HBe Anti HBe Positive
positive
HBVDA HBV DNA

2x109IU/ml cirrhosis
2x104IU/ml HCC
ALT Level
ALT
Liver histology
Minimal
minimal Active Hepatitis Minimal/ Inactive Active Hepatitis
Inflammation
inflammation
AGE 20 35 60 35+
This phase seen in With increased immune HBeAg remains Progression from
HBV transmission response HBV DNA level negative in HBeAg negative
at birth/1-2 years decreases. 70-85% with inactive phase to
of life. low viral load HBeAg negative
Liver enzymes fluctuate. <2 x 103 IU/mL hepatitis B with
HBeAg +ve and with persistently mutation in core
high viral load Active inflammation in normal liver or core promoter
(107 IU/mL) but liver enzymes but region of HBV
no elevation of ending in HBeAg hepatitis activity genome resulting
transaminases and negative and may continue in in HBeAg negative
minimal activity HBeAb +ve some but with continued
in liver as there is (HBeAg seroconversion) HBV replication and
no immunological Fibrosis/ progression in liver
response. Ongoing activity could cirrhosis noted in disease.
progress those who had
to fibrosis and liver progressed in
cirrhosis immune active
with HCC. phase
Fig.2: Natural History of Chronic HBV Infection

Modified from: Hepatitis B Virus Infection, Yun-Fan Liaw, Chia-Ming Chu, Lancet 2009; 373 : 582-92

Replicative phase: Immune tolerance — In patients with a perinatally acquired HBV infection, the initial phase is
characterized by high levels of HBV replication—the presence of hepatitis B e antigen (HBeAg) and high levels of
HBV DNA in serum—but no evidence of active liver disease as manifested by lack of symptoms, normal serum
ALT concentrations, and minimal changes on liver biopsy.
The immune tolerance phase usually lasts 10 to 30 years, during which there is a very low rate of spontaneous
HBeAg clearance.
Replicative phase: Immune clearance — The transition from the immune tolerance to the immune clearance
phase occurs during the second and third decades in patients with perinatally acquired HBV infection. During
the immune clearance phase, spontaneous HBeAg clearance increases to an annual rate of 10 to 20 percent.
HBeAg seroconversion is frequently, but not always, accompanied by biochemical exacerbations (abrupt
increases in serum ALT). Exacerbations are believed to be due to a sudden increase in immune-mediated lysis of
infected hepatocytes. They are often preceded by an increase in serum HBV DNA and a shift of HBcAg (hepatitis
B core antigen) from nuclear to cytoplasmic sites within hepatocytes, suggesting that immune clearance may
be triggered by an increase in viral load or a change in the presentation of viral antigens. How these changes
occur is not known.
Most exacerbations are asymptomatic and are discovered during routine follow-up. However, some are
accompanied by symptoms of acute hepatitis and may lead to the incorrect diagnosis of acute hepatitis B in
patients who are not previously known to have chronic HBV infection. Exacerbations may be associated with
an elevation in the IgM anti-HBc titer, which may lead to misdiagnosis of acute HBV infection and an increase
in the serum alpha-fetoprotein concentration, which may raise concerns about the diagnosis of HCC.
Patients with severe exacerbations should be referred to specialized centers for liver transplantation and receive
treatment with nucleos(t)ide analogues (NAs).
Not all exacerbations lead to HBeAg sero-conversion and clearance of HBV DNA from the serum, a phenomenon
termed abortive immune clearance. These patients may develop recurrent exacerbations with an intermittent
disappearance of serum HBV DNA with or without a transient loss of HBeAg. Such repeated episodes of hepatitis
may increase the risk of developing cirrhosis and HCC.
Low or non-replication phase/inactive carrier state — Patients in the low or non-replicating phase/inactive
carrier state are HBeAg negative and anti-HBe positive. In some patients, HBV DNA is undetectable in serum
by polymerase chain reaction assays, and liver disease is in remission as evidenced by normal serum ALT
concentrations and the resolution of necro-inflammation in liver biopsies. HBeAg-negative patients with a
persistently normal serum ALT can still have significant histologic inflammation and/or fibrosis.
Because of the fluctuating nature of chronic HBV infection, patients should not be categorized as inactive
carriers unless there are at least three ALT levels and two to three HBV DNA levels over a 12-month period
of observation. Studies suggest that combined quantification of HBsAg level and HBV DNA at a single time
point may help in differentiating inactive carrier phase versus HBeAg-negative chronic hepatitis. HBsAg <1000
international units/mL in an HBeAg-negative patient with serum HBV DNA <2000 international units/mL
identifies the inactive carrier phase with a high diagnostic accuracy (94 percent).
HBeAg-negative chronic hepatitis — Some patients continue to have moderate levels of HBV replication and
active liver disease (elevated serum ALT and chronic inflammation on liver biopsies), but remain HBeAg
negative. Such patients are said to have HBeAg-negative chronic hepatitis. They have a residual wild-type virus
or HBV variants that cannot produce HBeAg due to precore or core promoter genetic variations.
Patients with HBeAg-negative chronic hepatitis are older and have more advanced liver disease. They also tend
to have fluctuations in HBV DNA and ALT levels.

Resolution of chronic HBV infection — Some patients with chronic HBV infection become HBsAg negative.
The annual rate of delayed clearance of HBsAg has been estimated to be 0.5 to 2 percent in Western patients
and much lower (0.1 to 0.8 percent) in Asian countries In most reports, patients who cleared HBsAg appeared
to have a good prognosis. In the absence of other causes of liver injury, progression to cirrhosis and hepatic
decompensation after HBsAg clearance is rare. However, the risk of hepatocellular carcinoma remains, and
surveillance should continue in those who have HCV or hepatitis D virus (HDV) co-infection, cirrhosis, or are
older than 50 years at the time of HBsAg clearance.
Laboratory testing during the acute phase reveals elevations in the concentration of alanine and aspartate
aminotransferase levels (ALT and AST); values up to 1000 to 2000 international units/L are typically seen during
the acute phase with ALT being higher than AST. The serum bilirubin concentration may be normal in patients
with anicteric hepatitis. The prothrombin time is the best indicator of prognosis. In patients who recover, the
normalization of serum aminotransferases usually occurs within one to four months. A persistent elevation of
serum ALT for more than six months indicates a progression to chronic hepatitis.
Assessment and Staging of HBV Chronic infection

Routine assessment of HBsAg-positive persons is needed to guide management and indicate the need for
treatment. This generally includes assessment of:
1. Serological markers of HBV infection ;
2. Measurement of HBV DNA levels; and
3. Assessing severity of liver disease by
a. Liver enzymes
b. Non-invasive tests (NITs) such as aspartate aminotransferase (AST)-to-platelet ratio index (APRI),
FIB-4, transient elastography (FibroScan).
c. Liver biopsy, if available
Serological markers of HBV infection

Chronic Hepatitis B (CHB) infection is defined as the persistence of HBsAg for more than 6 months. Previous
HBV infection is characterized by the presence of antibodies (anti-HBs and anti-HBc). Immunity to HBV
infection after vaccination is characterized by the presence of only anti-HBs.
HBeAg: It also needs to be established whether the person is in the HBeAg-positive or HBeAg-negative phase
of infection (please see the table above), though both require lifelong monitoring, as the condition may change
over time. In persons with CHB, a positive HBeAg result usually indicates the presence of active HBV replication
and high infectivity. Spontaneous improvement may occur following HBeAg-positive sero-conversion (anti-
HBe), with a decline in HBV replication, and normalization of ALT levels. This confers a good prognosis and
does not require treatment. HBeAg can also be used to monitor treatment response, as HBeAg (anti-HBe) sero-
conversion in HBeAg-positive persons with a sustained undetectable HBV DNA viral load may be considered a
potential stopping point of treatment. However, this is infrequent even with potent NAs therapy. Some HBeAg-
negative persons have active HBV replication but are positive for anti-HBe and do not produce HBeAg due to the
presence of HBV variants or pre-core mutants.

Measurement of HBV DNA levels
Plasma HBV DNA concentrations quantified by real-time polymerase chain reaction (PCR) correlate with disease
progression and are used to differentiate active HBeAg-negative disease from inactive chronic infection, and for
decisions to treat and subsequent monitoring. HBV DNA concentrations are also used for optimal monitoring of
response to antiviral therapy, and a rise may indicate the emergence of resistant variants.
Plasma HBV DNA levels should be expressed in IU/mL to ensure comparability; values given as copies/mL can
be converted to IU/mL by dividing by a factor of 5 to approximate the conversion used in the most commonly
used assays (i.e. 10,000 copies/mL = 2000 IU/mL; 100,000 copies/mL = 20,000 IU/mL; 1 million copies/mL =
200,000 IU/mL). The same assay should be used in the same patient to evaluate the efficacy of antiviral therapy.
Assessing severity of liver disease

• Clinical evaluation for features of cirrhosis and evidence of decompensation, and
• Measurement of serum bilirubin, albumin, ALT, AST, alkaline phosphatase (ALP), and prothrombin time;
as well as full blood count, including platelet count.
• Other routine investigations include ultrasonography and alpha-fetoprotein (AFP) measurement for
periodic surveillance for HCC, and endoscopy for varices in persons with cirrhosis.
Please refer to Annexure 1 for details on assessing severity of liver disease ( fibrosis and cirrhosis)
Please refer to Annexure 2 for the algorithm for laboratory diagnosis of Viral hepatitis
Management
Whom To Treat
It is critical to evaluate the patient carefully as treatment of hepatitis B is life-long in most cases. The clinical
spectrum and phases of the chronic hepatitis B pose difficulty in deciding on whom to treat.
Table 2: Whom to treat and whom to monitor

WHOM TO TREAT WHOM NOT TO TREAT
As a priority, all adults, adolescents Antiviral therapy is not recommended and can be deferred in
and children with CHB and evidence of persons without evidence of cirrhosis, and with persistently
compensated or decompensated cirrhosis normal ALT levels and low levels of HBV replication (HBV
should be treated, regardless of ALT levels, DNA <2000 IU/mL), regardless of HBeAg status or age.
HBeAg status or HBV DNA levels
•• Where HBV DNA testing is not available: Treatment
can be deferred in HBeAg-positive persons aged 30
years or less and persistently normal ALT levels.
Treatment is recommended for adults with CHB Continued monitoring is necessary in all persons with
who do not have evidence of cirrhosis, but are CHB, but in particular those who do not currently meet
aged more than 30 years (in particular), and have the recommended criteria for whom to treat or not treat,
persistently abnormal ALT levels and evidence to determine if antiviral therapy may be indicated in the
of high-level HBV replication (HBV DNA >20 future to prevent progressive liver disease. These include
000 IU/mL), regardless of HBeAg status. persons without cirrhosis aged 30 years or less, with HBV
DNA levels >20 000 IU/mL but persistently normal ALT;

Non-Cirrhotic HBeAg positive Chronic HBV infected patient
VIRAL HBV DNA HBV DNA HBV DNA

LOAD < 2000 IU/mL < 2000-20,000 IU/mL > 20,000 IU/mL
ALT Any Any ALT-2x ULN or N ALT>2x ULN
• If elevated ALT, • If elevated ALT,

exclude other exclude other • Observe for
causes causes 3 months, if
• Assess fibrosis • Assess fibrosis • Assess fibrosis no concerns
noninvasively noninvasively noninvasively of hepatic
Fibrosis • Monitor 3 monthly • Monitor 3 monthly • Monitor 3 monthly decompensation
• Individualize liver • Individualize liver • Individualize liver • Treat if no
biopsy@ biopsy@ biopsy@ seroconversion
• Treat if moderate to • Treat if moderate to • Treat if moderate to • Obtain histology
severe inflammation severe inflammation severe inflammation or assess
or significant or significant or significant fibrosis non-
fibrosis.$ fibrosis. $ fibrosis. $ invasively. $
@Biopsy if non-invasive tests suggest evidence of significant fibrosis, ALT persistently elevated, Age>35 yr or family h/o
HCC or cirrhosis.$
• Moderate to severe inflammation on liver biopsy means either Hepatic activity index by Ishak activity score >3/18 or
METAVIR activity score A2 or A3
• Significant fibrosis on liver biopsy means F >2 by METAVIR fibrosis score or Ishak fibrosis stage > 3
• Liver stiffness > 8 kPa (by Fibroscan) or APRI > 1.5 indicates significant fibrosis; Liver stiffness > 11 kPa (by Fibroscan)
or APRI > 2.0 indicates cirrhosis
Fig.3: Treatment indications for non-cirrhotic HBeAg positive chronic HBV infected patients
Non-Cirrhotic HBeAg negative Chronic HBV infected patient
VIRAL HBV DNA < 2000 IU/mL HBV DNA > 2000 IU/mL
LOAD
ALT ALT > ULN ALT > ULN ALT-2x ULN or N ALT>2x ULN
• If elevated ALT, • Assess fibrosis • Observe for 3

exclude other causes noninvasively months, if no
• Assess fibrosis • Monitor ALT 3-6 • Assess fibrosis concerns of hepatic
noninvasively monthly and DNA noninvasively decompensation
Fibrosis • Monitor 3 monthly 6-12 monthly • Individualize liver • Treat if no
• Individualize liver • Individualize liver biopsy@ seroconversion
biopsy@ biopsy@ • Treat if moderate • Obtain histology
• Treat if moderate to • Treat if moderate to severe or assess fibrosis
severe inflammation to severe inflammation or non-invasively. $
or significant inflammation or significant fibrosis.*
fibrosis.$ significant fibrosis.$
@Biopsy if non-invasive tests suggest evidence of significant fibrosis, ALT persistently elevated, Age>35 yr or family h/o
HCC or cirrhosis.$
• Moderate to severe inflammation on liver biopsy means either Hepatic activity index by Ishak activity score >3/18 or
METAVIR activity score A2 or A3
• Significant fibrosis on liver biopsy means F >2 by METAVIR fibrosis score or Ishak fibrosis stage > 3
• Liver stiffness > 8 kPa (by Fibroscan) or APRI > 1.5 indicates significant fibrosis; Liver stiffness > 11 kPa (by Fibroscan)
or APRI > 2.0 indicates cirrhosis
Fig.4 :Treatment indications for non-cirrhotic HBeAg-negative chronic HBV-infected patients
Reference: SK Sarin et al, Asian-Pacific clinical practice guidelines on the management of Hepatitis B:
A 2015 update; Hepatol Int (2016) 10:1-98

There are various antiviral agents recommended for treatment of CHB. The section below deals with these
drugs and their dosages in adults and children.
Table 3: Recommended drugs for the treatment of CHB and their doses in adults
Drug Dose
1 Tenofovir disoproxil fumarate (TDF) 300 mg once daily
2 Entecavir ( adult with compensated liver disease and lamivudine naive) 0.5 mg once daily
3 Entecavir ( adult with decompensated liver disease) 1 mg once daily
4 Tenofovir alafenamide fumarate ( TAF) 25 mg once daily
Table 4: Recommended drugs for the treatment of CHB and their doses in children
Drug Dose
Tenofovir (in children 12 300 mg once daily
years of age and older, and
weighing at least 35kg)
Entecavir (in children 2 years Recommended once-daily dose of oral solution (mL)
of age or older and weighing Body weight (kg) Treatment –naïve persons*
at least 10kg. the oral solution
should be given to children with 10 to 11 3
a body weight up to 30kg) >11 to 14 4
>14 to 17 5
>17 to 20 6
>20 to 23 7
>23 to 26 8
>26 to 30 9
>30 10
*Children with body weight more than 30 kg should receive 10mL (0.5mg) of oral solution or
one 0.5 mg tablet once daily
Selection of antiviral drug for CHB:

• In all adults, adolescents and children aged 12 years or older in whom antiviral therapy is indicated, the
NAs which have a high barrier to drug resistance (tenofovir or entecavir) are recommended.
• In woman of childbearing age Tenofovir may be preferred as the drug of choice in the eventuality of a
pregnancy. Entecavir is not recommended in pregnancy.
• Tenofovir is preferred in patients who have been exposed to lamivudine who have a potential for
Entecavir resistance.
• Entecavir is recommended in children aged 2–11 years.
• Entecavir may be preferred over Tenofovir in:

Age > 60 years; bone disease due to chronic steroid use or use of other medications that worsen bone density,
history of fragility fracture, osteoporosis; altered renal function with eGFR < 60 mL/min/1.73 m2 or albuminuria
> 30 mg/ 24 hr or moderate dipstick proteinuria or Low phosphate (<2.5 mg/dL) or in patient on hemodialysis
(Ref: EASL guidelines)
• Tenofovir alafenamide fumarate ( TAF) is the drug of choice in patients with reduced renal function or
bone disease bone toxicities, where entecavir is contraindicated
• Drugs with a low barrier to resistance (lamivudine, adefovir or telbivudine) are available but not
recommended as they lead to drug resistance.
• Despite the inconvenience of injections and side effects PegIFN may be considered in a sub group of non
cirrhotics where a finite therapy might achieve a sustained response.
Key points in counseling and preparing the patient prior to initiation of therapy
Preparing to start treatment: Patients should be counseled about the indications for treatment, including
the likely benefits and side-effects, willingness to commit to long-term treatment, and need to attend for
follow-up monitoring both on and off therapy; the importance of full adherence for treatment to be both
effective and reduce the risk of drug resistance; and cost implications.
Measurement of baseline renal function and assessment of baseline risk for renal dysfunction should be
considered in all persons prior to initiation of antiviral therapy
When To Stop Treatment

All persons with cirrhosis based on clinical evidence (or APRI score >2 in adults) require lifelong treatment with
NAs, and should not discontinue antiviral therapy because of the risk of reactivation, which can also cause
severe acute-on-chronic liver injury.
The discontinuation of treatment of Hepatitis B is usually not recommended and should be done at specialized
centers under the guidance of the necessary expertise
Decision to discontinue therapy requires careful consideration on the risk of virological relapse, decompensation
and death on discontinuation versus the financial implication of continued cost of medications and monitoring.
All patients with cirrhosis should not discontinue antiviral therapy because of the risk of reactivation which
may potentially lead to decompensation and death.
Discontinuation may be considered in patients without cirrhosis:

• With persistent HBsAg loss after one year of consolidation treatment (regardless of prior HBeAg status or
availability of HBV DNA levels)
• HBeAg loss and sero-conversion to Anti-HBe after completion of one year (preferably 3 years) of
additional treatment with persistently normal ALT levels and undetectable HBVDNA levels.
• Careful long term monitoring for reactivation with serial 3-6 monthly HBeAg, ALT and HBVDNA levels is
mandatory in those who have discontinued treatment for consideration of retreatment.
Relapse may occur after stopping therapy with NAs. Retreatment is recommended if there are consistent signs
of reactivation (HBsAg or HBeAg becomes positive, ALT levels increase, or HBV DNA becomes detectable again)

Monitoring
The disease is complex and has sequelae, resolution as well as drugs side effects. Hence, three types of monitoring
is necessitated
• Monitoring for disease progression and treatment response in persons with CHB prior to, during and
post-treatment
• Monitoring for tenofovir or entecavir side-effects
• Monitoring for hepatocellular carcinoma
Table 5: Monitoring : Parameters and frequency

Interval 3 Months 6 Months 9 Months 12 Months
(Months)
HBeAg/Anti HBe √ √ √ √ √ √ √ √ √ √ √
HBVDNA √ √ √ √ √ √ √ √ √ √ √
ALT √ √ √ √ √ √ √ √ √ √ √ √
AST √ √
CBC (Platelet) √ √ √
APRI/FIB4/ √ √ √
Fibro Scan
USG √ √ √ √
Serum Creatinine √
eGFR √
Phosphate √
Urine Protein: √
Creatinine Ratio
Not on Treatment
Treatment
Discontinue Treatment
Monitoring for those:

Not on Treatment:
Frequent monitoring with monthly ALT and 3 monthly HBeAg/Anti HBeAg and HBVDNA quantitative would
be required in those with fluctuating ALT and HBV DNA 2000-20,000 IU/mL, who are as yet not on treatment.
In active chronic B with persistently normal ALT and HBV DNA <20,000IU/mL, may be monitored annually
On Treatment:
More frequent 3-6 monthly assessment is required initially in those with advanced liver disease in the first year.
Discontinued Treatment:
Careful long term monitoring for reactivation with serial 3-6 monthly HBeAg, ALT and HBVDNA levels is
mandatory in those who have discontinued treatment for consideration of retreatment.

Monitoring for disease progression and treatment response in persons with CHB prior to,
during and post-treatment
It is recommended that the following be monitored at least annually:
--ALT levels (and AST for APRI), HBsAg, HBeAg, and HBV DNA levels (where HBV DNA testing is available)
--Non-invasive tests (APRI score, FIB-4 or FibroScan) to assess for the worsening of fibrosis/presence of cirrhosis,
in those without cirrhosis at baseline
--If on treatment, adherence should be monitored regularly and at each visit.
More frequent monitoring is needed

• In persons who do not yet meet the criteria for antiviral therapy: More frequent monitoring for disease
progression may be indicated in: persons who have intermittently abnormal ALT levels or HBV DNA
levels that fluctuate between 2000 IU/mL and 20 000 IU/mL (where HBV DNA testing is available) and in
HIV co-infected persons.
• In persons on treatment or following treatment discontinuation: More frequent on-treatment
monitoring (at least every 3 months for the first year) is indicated in: persons with more advanced disease
(compensated or decompensated cirrhosis); during the first year of treatment to assess treatment response
and adherence; where treatment adherence is a concern; in HIV co-infected persons and in persons after
discontinuation of treatment.
Monitoring for tenofovir and entecavir toxicity

Measurement of baseline renal function and assessment of baseline risk for renal dysfunction should be
considered in all persons prior to initiation of antiviral therapy. Renal function should be monitored annually
in persons on long-term tenofovir or entecavir therapy, and growth monitored carefully in children.
Measurement of baseline renal function includes: serum creatinine (Cr) levels, and calculation of creatinine
clearance (CrCl)/estimated glomerular filtration rate (eGFR) using the Cockcroft–Gault (CG)
CG formula: eGFR = (140 – age) x (weight in kg) x 0.85 (if female) / (72xCr in mg/dL)
Table 6: Recommended dosage of Tenofovir in adults with renal impairment

CrCl (mL/min) Dose
30-49 300 mg every 48h
10-29 300 mg twice weekly (every 72-96 hours)
<10 and not on Haemodialysis No recommendation
On Haemodialysis 300 mg every7d
Monitoring for hepatocellular carcinoma (HCC)

Routine surveillance for HCC with abdominal ultrasound and alpha-fetoprotein testing every six months is
recommended for:
• Persons with cirrhosis, regardless of age or other risk factors
• Persons with a family history of HCC
• Persons aged over 40 years (lower age may apply according to regional incidence of HCC), without clinical
evidence of cirrhosis (or based on APRI score ≤2), and with HBV DNA level >2000 IU/mL (where HBV DNA
testing is available).

Special Situations
Pregnancy
Care of the pregnant woman
All pregnant women with HBV should be evaluated for the need of treatment for hepatitis B and any associated
liver disease, and given advice about prevention of transmission. Only a proportion of those with hepatitis B
virus infection (pregnant or otherwise) need treatment.
Hepatitis B in a pregnant woman is not a reason for considering termination of pregnancy. Similarly, the need for
caesarean delivery should be decided based on obstetric indications, and not on the presence of HBV infection.
Administration of hepatitis B vaccine to pregnant women with HBV provides no benefit either to the mother
or the baby.
Care of the baby
Immunoprophylaxis of hepatitis B virus infection
The newborn baby should be administered a timely first dose (the ‘birth dose’) of hepatitis B vaccine
(monovalent) as soon as possible after birth, ideally within 24 hours. Even within this time duration, the earlier
it can be administered, the better. If, for some reason, the birth dose is not administered within 24 hours, it
should still be administered as soon as it is possible and not omitted. This dose is administered intramuscularly
in the anterolateral thigh. This birth dose must be followed by timely administration of 3-doses of hepatitis
B-containing vaccine [e.g. monovalent hepatitis B vaccine, tetravalent combination vaccine with DPT (DPT-
Hep B) or a pentavalent vaccine (DPT+Hep B+Hib)]. The hepatitis B vaccine birth dose followed by these three
doses is the most effective method for prevention of mother-to-child transmission of hepatitis B.
Hepatitis B immunoglobulin (HBIG) may provide some additional protection in situations where risk of
transmission is particularly high – i.e. babies born to mothers with hepatitis B who also have detectable
detectable HBeAg and/or high viral load. However, additional benefit provided by it, over properly-administered
hepatitis B vaccine (as described above) is small. Also, HBIG is costly and has limited availability. If a decision is
taken to administer HBIG (0.5 ml or 100 international units, intramuscular), this should be done as soon after
birth as possible (and within 12-24 hours) and in a limb other than the one in which hepatitis B vaccine has been
administered.
Data on benefit and risks of administering anti-hepatitis B drugs to the pregnant women for prevention of
mother-to-child transmission are unclear.
Breast feeding
A mother who has hepatitis B may breast feed her baby, unless there is an exuding injury or disease of the nipple
or surrounding skin. The advantages of breast feeding far outweigh the risk, if any, of transmission of hepatitis
B to a baby who has received hepatitis B vaccine.
Timing of testing
If it is felt that the baby needs to be tested for hepatitis B, this should be done only after 1 year of age. Any
positivity before this age is difficult to interpret and may resolve spontaneously over time.

Co-morbidities
HIV and Hepatitis B Co-infection
The natural history of both diseases is affected when a person is co-infected with both HIV and Hep B and this
has implications on management of both diseases. Current evidence suggests that human immunodeficiency
virus (HIV) infection has an adverse impact on HBV-related liver disease progression, with higher serum HBV
DNA polymerase activity, lower rates of loss of serum hepatitis B e antigen, and increased risk of cirrhosis, liver-
related mortality, and hepatocellular carcinoma at lower CD4 T-cell counts. HBV infection is more likely to be
chronic in those with HIV infection. In some cohorts, liver disease has emerged as a leading cause of death in
HIV-infected persons co-infected with either hepatitis B or C, as mortality due to other HIV-related conditions
has declined following the introduction of antiretroviral therapy (ART).
Similarly, the HBV infection also negatively impacts the progression of HIV infection leading to faster immune
deterioration and higher mortality. Other studies have suggested that HBV is associated with a rapidly
progressive course of HIV infection . A retrospective analysis indicated that the risk of death in 64 individuals
co-infected with HIV and HBV was approximately two-fold higher than that in individuals with HIV mono
infection. Prospective observational cohort among those with primary HIV infection showed that HBV co-
infection is an independent predictor of immunologic deterioration in such group of patients. In another large
prospective multicentre cohort by Chun et al among 2352 (PLHIV) with sero-conversion window of less than
3 years, co-infected persons with Hepatitis B were associated with two times higher risk of AIDS/death, higher
among HBV co-infected patients compared to HBV mono-infected patients
The HIV-Hepatitis co-infected persons show faster CD4 decline, slower CD4 recovery following ART, increased
incidence of AIDS and non-AIDS events, increased rate of ARV toxicity and increased chances of Immune
reconstitution hepatitis. In one of the large cohort studies of more than 5000 co-infected persons, the relative
risk of liver related deaths was found to be 17 times higher than those with HBV mono-infected patients.
Other challenges among co-infected include cross-resistance between HIV and HBV drugs, increased liver
injury, either due to direct hepatotoxicity or to ART-related immune-reconstitution hepatitis, with elevation
of ALT; if ART does not cover both HIV and HBV infections adequately, fulminant hepatitis is an eventuality.
Evaluation of HIV and HBV Co-infected Persons
The risk of HBV infection may be higher in HIV-infected adults, and therefore all persons newly diagnosed with
HIV should be screened for HBsAg. Those found positive for HBsAg should be evaluated further following the
guidelines for evaluation of those with HBV Infection. Besides routing clinical evaluation, one should look for
sign of cirrhosis and hepatic decompensation like ascites and pedal oedema.
The lab investigations, besides routine haemogram and biochemistry, should specifically include Liver
Function Test (LFT), prothrombin time, AFP, ultrasound and upper gastrointestinal endoscopy. The virological
examination should include HBeAg, Anti-HBe antibody and HBV DNA quantitative (Real-Time PCR).
Assessment of severity of fibrosis : The assessment of degree of fibrosis and cirrhosis is important. Please refer
to Annexure 1 for details.

Treatment of HIV and HBV Co-infected patients
All HIV positive patients with HBV co-infection should start dual anti HIV & HBV therapy with tenofovir
based ART regimen irrespective of CD4 count, HBV viral load or status of liver disease e.g., ALT level or fibrosis
stage. In HBV and HIV co-infected adults and adolescents, tenofovir + lamivudine + efavirenz as a fixed-dose
combination is recommended as the preferred option to initiate ART under the National AIDS Control Program.
This three drug combination includes the drugs with efficacy against hepatitis B.
Stopping Tenofovir based ART should be avoided in HIV + HBV co-infection for concern of severe hepatitis flare
and decompensated following HBV reactivation.
This treatment strategy has achieved high rates of HBV DNA suppression (90%), HBeAg loss (46%) and HBsAg
loss (12%) in HBeAg-positive patients after 5 years of treatment, without evidence of resistance, and reduced
progression to cirrhosis with no significant differences in response in those with or without HIV co-infection
. To date, no viral resistance to tenofovir in vivo has been described, although resistant strains have been
identified in vitro. Although the risk of developing cirrhosis is negligible in HBV-HIV-co-infected persons on
long-term tenofovir combined with lamivudine therapy, the risk of HCC persists, but is low.
If ARVs need to be changed because of HIV drug resistance or some drug toxicity, then tenofovir and lamivudine
should be continued together with the new ARV drugs unless TDF is specifically contraindicated due to its
toxicity.
Prevention of HBV infection

The risk of HBV infection may be higher in HIV-infected adults, and therefore all persons newly diagnosed
with HIV should be screened for HBsAg and immunized if HBsAg is negative. Those already infected with HBV
(HBsAg positive) do not benefit from HBV vaccine. PLHIV who have already suffered from HBV in the past and
have developed protective titre of Anti-HBs antibody (>10 mIU/mL) also do not require HBV vaccine.
Response to HBV vaccine is lower in persons with HIV or with a low CD4 count, and a meta-analysis has shown
that a schedule of four double (40 μg) doses of the vaccine provides a higher protective anti-HBs titre than the
regular three 20 μg dose schedule
Besides this, all infants born to HBV positive women need to be immunized within 24 hours of birth (Dose - 0)
followed by 6, 10 & 14 weeks (dose – 10 µg IM) and HBIG – (0.5 ml or 100 international units, intramuscular), this
should be done as soon after birth as possible (and within 12-24 hours) and in a limb other than the one in which
hepatitis B vaccine has been administered.

HBsAg Positive
CIRRHOSIS
• Clinical criteriab
• NITs (APRI score >2
in adults or FibroScan)
Yes No
AGEc AGE≤30
>30 Years years
ASSESSMENT FOR TREATMENT
(in Particulary)
ALTd,e ALTd,e ALTd,e ALTd,e

Persistently Intermittently Persistently Persistently
abnormal abnormal normal normal
HBV DNA HBV DNA HBV DNA HBV DNA

> 20,000 IU/ 2000 - < 2000 IU/ml < 2000 IU/ml
ml 20,000 IU/ml
INITIATE NA THERAPY DEFER TREATMENT AND MONITOR

AND MONITOR
• Tenofovir or entecavir
• Entecavir in children
aged 2-11 years
NIT : non-invasive tests, ALT alanine aminotransferase, APRI aspartase aminotransferase-to-platelet ratio index
a Defined as persistence of hepatitis B surface antigen (HBsAg) for six months or more. The algorithm does
not capture all potential scenarios, but the main categories for treatment or monitoring. Recommendations
for settings without access to HBV DNA testing are provided in the relevant chapters.
b Clinical features of decompensated cirrhosis: Portal hypertension (ascites, variceal haemorrhage and hepatic
encephalopathy), coagulopathy, or liver insufficiency (jaundice). Other clinical features of advanced liver disease/
cirrhosis may include: hepatomegaly, splenomegaly, pruritus, fatigue, arthralgia, palmar erythema, and oedema.
c The age cut-off of >30 years is not absolute, and some persons with CHB less
than 30 years may also meet criteria for antiviral treatment.
d ALT levels fluctuate in persons with chronic hepatitis B and require longitudinal monitoring to determine the trend. Upper
limits for normal ALT have been defined as below 30 U/L for men and 19 U/L for women, though local laboratory normal
ranges should be applied. Persistently normal/abnormal may be defined as three ALT determinations below or above the upper
limit of normal, made at unspecified intervals during a 6–12–month period or predefined intervals during 12-month period.
e Where HBV DNA testing is not available, treatment may be considered based on persistently
abnormal ALT levels, but other common causes of persistently raised ALT levels such as
impaired glucose tolerance, dyslipidaemia and fatty liver should be excluded.
Fig. 5: Algorithm on the management of persons with chronic hepatitis B infectiona

Modified from WHO guidelines 2015
Hepatitis C Infection
Hepatitis C virus, which, before its identification was labeled "non-A, non-B hepatitis," is a linear, single-stranded
enveloped RNA virus belonging to the flavivirus family.

Clinical Course of Hepatitis C Infection
Hepatitis C infection is usually acquired through infected syringes and needles, and transfusion of infected
blood. Sexual transmission of HCV occurs infrequently in heterosexual couples. It is reported to be more
common in HIV-positive persons, particularly in MSM. The risk of transmission of HCV from a mother to her
child occurs in 4–8% of births to women with HCV infection, and in 10.8–25% of births to women with HIV and
HCV co-infection.
HCV causes both acute and chronic hepatitis. Acute hepatitis is often clinically mild and marked by fluctuating
elevations of serum aminotransferase levels; >50% likelihood of chronicity, leading to cirrhosis in >20%.
Chronic infection with HCV is usually clinically silent, and is only very rarely associated with life-threatening
disease. Spontaneous clearance of acute HCV infection occurs within six months of infection in 15–45% of
infected individuals in the absence of treatment. Almost all the remaining 55–85% of persons will harbor HCV
for the rest of their lives (if not treated) and are considered to have chronic HCV infection.
Left untreated, chronic HCV infection can cause liver cirrhosis, liver failure and HCC. Of those with chronic
HCV infection, the risk of cirrhosis of the liver is 15–30% within 20 years. The risk of HCC in persons with
cirrhosis is approximately 2–4% per year.
As illustrated in figure 6, following an initial eclipse phase of 1–2 weeks when no virological or serological
markers of infection may be detected, the natural course of HCV infection is characterized by the appearance of
HCV RNA, then HCV core p22 Ag in the absence of an antibody response for a further 6–10 weeks. During this
serological window, it has been shown that free (i.e. not complexed with antibody) HCV core antigen (HCVcAg)
can be detected in a proportion of individuals. Following the development of the antibody response, HCVcAg
becomes complexed with these antibodies specific for HCV.
A Serological Window
Sero-con
version
Virus
clearance
Waning
anti-HCV
Seroreversion B Serological Window Seroconversion/actual phase
chronic
phase
Anti-HCV
HCV
RNA Anti-HCV
HCV RNA
Eclipse phase
Eclipse phase
HCV Ag
HCV Ag
0 1 2 3 4 5 6 months 12 24 decades 0 1 2 3 4 5 6 months 12 24 decades
Fig.6: Approximate Time course of virological and immunological markers of HCV infection with
(A) Self-resolving HCV infection, and (B) Chronic HCV infection
Ref: WHO guidelines; Feb. 2017

The standard method of diagnosis is by detection of anti-HCV antibody. Third generation immunoassays,
which incorporate proteins from the core, NS3, and NS5 regions, can detect anti-HCV antibodies usually within
6 - 8 weeks of infection, i.e., from the initial phase of elevation of aminotransferases. Both rapid diagnostic
tests (RDTs) and Immunoassays are available, with comparable sensitivity and specificity. This test does not
differentiate between current and past infection. The test may also be false positive in some situations and the
diagnosis of an individual patient should be confirmed by HCV RNA detection prior to considering treatment.
Since anti-HCV antibodies from an infected mother may persist in children <18 months of age, HCV RNA
detection is also used to diagnose HCV infection in this age group (after 2 months of age)
Window period. Assays designed solely to detect antibodies to HCV inevitably have a window period of
infectivity in early infection, during which antibodies may be undetectable. HCV RNA is typically not used to
determine exposure to HCV, in spite of its short window period (1–2 weeks after the onset of acute infection)
primarily because of cost. There are some situations with occult HCV infection, i.e. HCV RNA detectable in the
absence of any serological markers (i.e. HCV seronegative), which may be due to underlying immunosuppression
in, for example, HIV-infected populations.
Screening for HCV infection is done using serological testing for antibodies to HCV. If positive, a Nucleic Acid
Test (NAT) for HCV RNA is needed to confirm chronic HCV infection. It is important to consider the possibility
of infection with other blood borne viruses in persons infected with HCV, and to offer screening for HBV and
HIV in addition to HCV. Screening for other infections, for example tuberculosis (TB), is also indicated in some
groups at risk, such as people living with HIV, prisoners and People who inject drugs (PWID).
The algorithm for the diagnosis of Hepatitis C infection is enclosed as Annexure 2
Whom To Test
Diagnostic serologic testing for HCV will be available to all people who would access the testing sites. However,
the initial focus would remain on testing specific population groups that have been documented to have a
higher positivity rates in different studies across India.
These focus or priority populations for testing will include but not limited to:
1. People who inject drugs ( PWID)
2. Men who have sex with men
3. Female sex workers
4. People who received blood transfusion before routine testing for hepatitis C
5. People who need frequent blood transfusion, such as, thalessemic and dialysis patients
6. People living with HIV
7. Inmates of prisons and other closed settings
Treatment of Viral Hepatitis C in Adults

The spectrum of disease in persons infected with HCV extends from mild fibrosis to cirrhosis and HCC.
Compensated cirrhosis may progress over time to decompensated cirrhosis associated with ascites, oesophageal
and gastric varices, and eventually to liver failure, renal failure and sepsis, all of which are life-threatening. HCC
may also occur at a rate of 2–4% per year in persons with cirrhosis. The diagnosis of decompensated liver disease
is based on both clinical examination and laboratory monitoring, and therefore a careful medical examination
of patients must be made prior to commencing therapy. The stage of disease may be assessed by liver biopsy or
by using a variety of non-invasive methods.
Chronic HCV infection is the leading cause for end-stage liver disease (cirrhosis) and its complications including
development of ascites, variceal bleeding, severe infections, etc, HCC and liver-related deaths worldwide. There

is substantial economic burden if HCV patients are not treated. HCV is a major cause of morbidity globally, with
estimated 495,000 deaths; in India, HCV infection was estimated to be responsible for 37,000 deaths in the year
2015.
The availability of highly effective DAAs has however changed the HCV treatment paradigm, leading to hope
of elimination of this infection as a public health threat by the year 2030. In a recent study, this has been
demonstrated that the treatment with generic DAAs available in India will improve patient outcomes, provide
a good value for money within 2 years, and be ultimately cost-saving. Therefore, HCV treatment should be a
priority from a public health as well an economic perspective. Treating HCV-infected persons could prevent
decompensated cirrhosis, HCC and liver-related mortalities. Treating all persons with HCV along with preventive
measures will ultimately eliminate HCV infection from India.
Staging of HCV infection is important as it identifies patients with advanced disease, a group that requires
enhanced monitoring and prioritization for treatment before the onset of decompensated cirrhosis. In many
high-income countries, all persons with chronic HCV infection who do not have a contraindication for therapy
are considered to be suitable for treatment (although many are not able to access treatment because of eligibility
restrictions placed by third- party payers to reduce costs).
Clinical Assessment Before Initiating Treatment

A number of clinical considerations are important for the management of persons with chronic HCV infection.
Pre-treatment evaluation of the risk of adverse events should be based on the patients clinical details,
concomitant medications, and knowledge of treatment regimen to be administered.
A detailed history for alcohol consumption as well as any other medications that the patient might be taking
should be taken. An alcohol intake assessment should be done for all persons with HCV infection followed by
the offer of a behavioral alcohol reduction intervention for persons with moderate-to-high alcohol intake.
The risk of cirrhosis and HCC varies, depending upon certain patient characteristics or behaviors. For example,
men, persons who consume excess alcohol, persons with HBV or HIV co-infection and immunosuppressed
individuals are all at higher risk of developing cirrhosis or HCC. Disease associated with HCV infection is not
confined to the liver. Extrahepatic manifestations of HCV include cryoglobulinaemia, glomerulonephritis,
thyroiditis and Sjogren syndrome, insulin resistance, type 2 diabetes, and skin disorders such as porphyria
cutanea tarda and lichen planus. Persons with chronic HCV infection are more likely to develop cognitive
dysfunction, fatigue and depression. These outcomes may be associated with replication of the virus in the
brain; however, the causal link between these manifestations and chronic HCV infection is not certain.
Assessment of Degree of Fibrosis

Assessing the degree of liver fibrosis is an important step in the clinical management of persons with HCV
infection. Persons with cirrhosis are at increased risk of HCC and death due to liver failure. Furthermore, the
selection of treatment regimens can depend on the presence or absence of cirrhosis.
Please refer to Annexure 1 for assessment of degree of fibrosis and cirrhosis
Baseline and follow-up Investigations

The directly acting antivirals are much better tolerated by patients, as they have fewer adverse events and thus
less need for early discontinuation of therapy. However, there remains the need for laboratory monitoring in
patients with cirrhosis, those with significant comorbidities and those treated with ribavirin therapy. A summary
monitoring schedule framework for the treatment of patients is shown in Table below. If blood parameters
become abnormal on therapy, increased monitoring and dose adjustment may be required. Clinical judgement
based on the patient’s clinical details such as presence of HIV co-infection, cirrhosis or renal impairment,
potential Drug –Drug Interactions and clinical well-being during treatment may necessitate more frequent
monitoring

Table 7: Monitoring schedule framework for the treatment of patients
Time Regimen: Only DAAs Regimen: DAAs and Ribavirin
(non-cirrhotic usually) (cirrhotic usually)
CBC, Adherence and HCV CBC, Adherence and HCV RNA
S.Creatinine, LFT side effects RNA S.Creatinine , LFT side effects
Baseline Yes Yes Yes Yes
Week 1 Yes Yes
Week 2 Yes Yes
Week 4 Yes Yes Yes Yes
Week 8 Yes Yes
Week 12 Yes Yes
Week 12 after Yes Yes Yes
completion of
treatment ( SVR-12)
CBC, complete blood counts; LFT, liver function tests; SVR, sustained viral response
Whom To Treat
Any individual diagnosed to have infection with hepatitis C virus (viremia +) needs treatment. The duration
of treatment will depend on the several situations such as, cirrhosis versus non-cirrhosis, presence of
decompensation (ascites, variceal bleeding, hepatic encephalopathy, or infection(s), treatment naïve versus
treatment experienced (to peg IFN, DAAs, etc).
What Regimen To Use

DAAs are the recommended first line treatment in India. The combination of the DAAs and the duration of
treatment will depend on presence or absence of cirrhosis and on the genotype of the virus.
The following algorithm will provide guidance on selection of regimen and the duration in treatment naïve
hepatitis C patient .
Person with confirmed HCV infection (detected HCV RNA)
Undertake baseline investigations – APRI,FIB-4 and

Elastography (if available)
Patient does not Patient has Cirrhosis

have Cirrhosis (compensated, Child-Pugh A)
Treat with SOF + Treat with SOF +

DCV for 12 weeks VEL for 12 weeks
Perform HCV RNA 12 weeks after completion of the treatment
HCV RNA not detected HCV RNA detected
Treatment completed Refer to higher center for further management

SOF, sofosbuvir; DCV, daclatasvir; VEL, velpatasvir
Fig. 7: Algorithm for guidance on selection of regimen and duration of treatment in
hepatitis C naïve patient .

Table 8: Regimens recommended
Regime Category of patients Regime recommended Duration of
type Treatment
I Patient without cirrhosis(uncomplicated) Sofosbuvir(400mg) & Daclatasvir(60mg)* 84 days (12 wks)
II Patient with cirrhosis- Sofosbuvir(400mg) + Velpatasvir(100mg) 84 days(12 wks)
compensated (Child-Pugh A)
III Patient with cirrhosis- decompensated Sofosbuvir(400mg) + Velpatasvir 84 days(12 wks)
(Child-Pugh B and C)** (100mg) & Ribavirin(600-1200mg**)
In Ribavirin intolerant patients - 168days ( 24 wks)
Sofosbuvir(400mg) + Velpatasvir(100mg)
*dose adjustments in PLHIV, renal insufficiency, etc. ** Refer to the Model Treatment Center (MTC)
Table 9: Dosage of recommended DAA

Name of drug Dosage
Sofosbuvir 400 mg once a day
Daclatasvir 60mg once a day
Sofosbuvir + Velpatasvir Sofosbuvir(400mg) + Velpatasvir (100mg) once a day
Ribavirin 800-1200 mg (to be decided based on weight, hemoglobin
level, renal function and presence of cirrhosis)
Counseling Messages for Screening Test Results:

All patients should be provided information on the meaning of their test results by the attending clinicians/
trained health care workers/peer counselors:
Providing Pre-test information: through media such as posters, brochures, websites and short video clips shown
in waiting rooms. This would include information on viral hepatitis and the benefits of testing for hepatitis B or
C; the meaning of a positive and negative test result; a brief description of prevention options; confidentiality
of the test result; the practical implications of a positive test result, including the when and where of treatment
available.
Post-test information/counseling for a non-reactive hepatitis C screening test:

»» Explain the meaning of the non-reactive antibody test, ensuring that the patient understands a
negative antibody test does not protect him/her from future infection in the event of risk taking
behaviors.
»» Discuss that if the patient was recently exposed (6 months), he/she may be in a window period and
recommend repeat screening in 6 months, and provide information on hepatitis C prevention, risk
and harm reduction.
»» Encourage the patient to make healthy choices and to get vaccinated against hepatitis B, if appropriate.
Post- test counseling and linkages to treatment services for a reactive hepatitis C
screening test:
»» Explain the meaning of the reactive antibody test and counsel on the need for diagnostic testing
(hepatitis C RNA test) to confirm a diagnosis of chronic hepatitis and other tests for staging of liver
disease.
»» Explain that the patient is most likely chronically infected and provide basic hepatitis C disease and
treatment information. Make an active referral to the viral hepatitis treatment units.
»» Discuss the importance of minimizing risk behaviors to avoid transmitting hepatitis C infection to
others, and encourage notification and screening of needle sharing and sexual partners.
»» Encourage and offer HBV and HCV testing for family members, including children, and sexual partners.
»» Discuss healthy liver practices, including stopping or reducing alcohol intake and getting vaccinated
against hepatitis A and B, if appropriate.

Adherence counseling by trained pharmacist: 1) Pill count: the total number of pills/doses dispensed and the
total number of pills/doses returned at monthly visits for each drug for the entire treatment duration for all
patients; 2) Patient self-reports: it helps to determine reasons for non-adherence
Though the majority of patients can be initiated the treatment for hepatitis C, there are several situations in
which it is recommended to refer the patient to a specialized center. These include:
a. Patients with decompensated cirrhosis
b. Treatment experienced patients
c. Patients on chemotherapy with deranged liver enzymes
d. Patient with impaired renal function
e. Patient with HCC
f. Paediatric patients
g. Thalassemic patients
Side Effects of Drugs Used in Treatment

New DAA regimens are well tolerated by patients. Certain regimens have been shown to be safe for use in
patients with decompensated liver cirrhosis and those who have undergone liver transplantation. However,
close monitoring is required in these patients and it is recommended that such regimens be undertaken only in
units with the expertise to manage these patients and treat complications if they arise.
Daclatasvir: The common adverse reactions associated with this drug are fatigue, headache and nausea, seen in
studies that have either used the drug in combination with sofosbuvir with or without ribavirin.
Sofosbuvir with or without ledipasvir: Both drugs have been well tolerated by patients. They are reasonably well
accepted by patients, with low rates of discontinuation in clinical studies. Fatigue, headache, insomnia and nausea
are the most common adverse events reported. Recent evidence has emerged of significant bradyarrhythmias
associated with sofosbuvir in patients also taking amiodarone and therefore it is contraindicated in these
patients.
Sofosbuvir with Velpatasvir: Both drugs have been well tolerated by patients. Headache, fatigue, anemia, nausea,
insomnia, diarrhea, weakness, rash and depression are the most common adverse events reported, which are at
as similar frequency to placebo-treated patients.
Dose adjustment of ribavirin

Anaemia is a common, predictable side-effect of ribavirin therapy and dose adjustment is often required.
Patients whose haemoglobin level falls below 10 g/dL should have their ribavirin dose reduced from
800–1200 mg/day (depending on the patient’s weight and HCV genotype) to 600 mg/day. A patient whose
haemoglobin level falls below 8.5 g/dL should discontinue ribavirin therapy.
For patients with a history of stable cardiovascular disease, dose reduction of ribavirin is required if the
haemoglobin decreases by ≥2 g/dL during any 4-week period. In addition, for these patients, if the haemoglobin
remains <12 g/dL after 4 weeks on a reduced dose, the patient should discontinue combination therapy.
The dose of ribavirin in patients with renal failure must also be adjusted; patients with an eGFR <50 mL/
min/1.73 m2 should not be treated with ribavirin and those on haemodialysis must have the dose lowered
to 200 mg per day or take it three times per week. Increased monitoring is required in this group. Among
patients with decompensated cirrhosis, ribavirin dosing should either be weight-based or started at an
initial dose of 600 mg and increased as tolerated.

Drug Interactions with DAA
The following tables provide common drug interactions of the commonly used DAA.
Therapy with DAAs: contraindications/warnings
There are few contraindications to treatment with DAAs. The cytochrome P450 (CYP)/P-glycoprotein (P-gp)
inducing agents, such as carbamazepine and phenytoin, are contraindicated with all regimens. Simultaneous
use lead to significantly reduced concentrations of DAAs, which may lead to virological failure.
Other concomitant medicine-related interactions are discussed in table ….. The University of Liverpool website,
www.hep-druginteractions.org, is a good resource for checking for drug interactions with DAA.
Sofosbuvir should be used with caution in patients with severe renal impairment (eGFR <30 ml/min/1.73 m2)
at MTC .
Table 10: Contraindications to therapy with Ribavirin

Absolute Contraindication Relative Contraindication
•• Pregnancy or unwillingness •• Abnormal haematological indices:
to use contraception
»» Hemoglobin <10 g/dL
•• Breastfeeding women
»» Neutrophil count <1.5x109/L
•• Severe concurrent medical disease,
including severe infections »» Platelet count <90x109/L
•• Poorly controlled cardiac failure •• Serum creatinine >1.5 mg/dL
•• Chronic obstructive pulmonary disease •• Haemoglobinopathies (sickle cell

disease or thalassaemia)
•• Previous ribavirin hypersensitivity
•• Significant coronary artery disease
•• Co-administration of didanosine
Annexure-3 highlights drug interactions between DAA and some commonly prescribed medications. The
University of Liverpool website, www.hep-druginteractions.org, is a good resource for checking for drug
interactions with DAAs.
Special Situations and co-morbidities

Treatment of Patients with Decompensated Cirrhosis
DAAs can cause severe complications when prescribed to persons with decompensated cirrhosis (presence of
ascites, jaundice, history of hepatic encephalopathy and variceal bleed or Child-Pugh score ≥7 [Class B and C],
http://www.hepatitisc.uw.edu/page/clinical-calculators/ctp). Therefore, they should be used only in settings
where specialized care for managing such cases is available. Therefore refer all these patients to a specialized
center for further evaluation, HCV genotype estimation should be done in all patients. Following regimens
would be used to treat these patients (Table 11).
Table 11: DAAs in the Treatment of Decompensated Cirrhosis *

All Genotype
Ribavirin tolerant Daily fixed-dose combination of SOF (400 mg) +
VEL (100 mg) + weight-based RBV** x 12 weeks
Ribavirin intolerant Daily fixed-dose combination of SOF (400
mg) + VEL (100 mg) x 24 weeks
SOF: sofosbuvir; VEL: velpatasvir; RBV: ribavirin. * to be managed at model treatment center (MTC), **Ribavirin
should be administered orally with food twice daily, with the dose determined according to body weight (1000
mg daily in patients with a body weight of <75 kg and 1200 mg daily in patients with a body weight ≥75 kg).
Ribavirin should be started at lower dose (600 mg perday) then gradually increase to the máximum tolerated dose.

Management of Treatment Experienced Patients
Refer all these patients to a specialized center for further evaluation, especially analysis for resistance associated
substitutions (RAS), endoscopy, imaging (TPCT, CEMR, etc), etc. HCV genotype estimation should be done in all
patients. These patients would be treated by regimens as shown in Table 12.
Table 12: DAAs in the Management of Treatment Experienced Cirrhotic and Non-cirrhotic
Patients.
Treatment No cirrosis / Non-Genotype 3 Genotype 3
failure Compensated
regimen cirrhosis
Peg IFN+RBV No cirrhosis Daily fixed-dose combination Daily fixed-dose combination
Or SOF+RBV of SOF (400 mg) + VEL of SOF (400 mg) + VEL
(100 mg) x 12 weeks (100 mg) x 12 weeks
Compensated cirrhosis Daily fixed-dose combination Daily fixed-dose combination of
of SOF (400 mg) + VEL SOF (400 mg) + VEL (100 mg) +
(100 mg) x 12 weeks weight-based ribavirin* x 12 weeks
SOF+DCV/LDV No cirrhosis Daily fixed-dose combination Daily fixed-dose combination of
(100 mg) + weight-based weight-based ribavirin x 24 weeks
ribavirin x 24 weeks
Compensated cirrhosis Daily fixed-dose combination Daily fixed-dose combination of
(100 mg) + weight-based weight-based ribavirin x 24 weeks
ribavirin x 24 weeks
SOF: sofosbuvir; RBV: ribavirin, VEL: velpatasvir.
*Ribavirin should be administered orally with food twice daily, with the dose determined according to body weight
(1000 mg daily in patients with a body weight of <75 kg and 1200 mg daily in patients with a body weight ≥75 kg).
Ribavirin should be started at lower dose (600 mg perday) then gradually increase to the maximum tolerated dose.
Reference Gane EJ, Shiffman ML, Etzkorn K, Morelli G, Stedman CAM, Davis MN, Hinestrosa F, Dvory-Sobol H, Huang KC,
Osinusi A, McNally J, Brainard DM, McHutchison JG, Thompson AJ, Sulkowski MS; GS-US-342-1553 Investigators. Sofosbuvir
velpatasvir with ribavirin for 24 weeks in hepatitis C virus patients previously treated with a direct-acting antiviral
regimen. Hepatology. 2017 Oct;66(4):1083-1089. doi: 10.1002/hep.29256. Epub 2017 Aug 26. PubMed PMID: 28498551.
People who inject drugs

Globally, approximately 67% of PWID have evidence of anti-HCV antibodies. PWID are at increased risk of
HCV-related disease and transmission, as well as for all-cause morbidity and mortality, and therefore require
specialized care and should be considered as a priority for HCV treatment. In reality, many PWID with HCV
infection are unaware that they are infected and HCV treatment rates among them are very low. This is due to
a number of reasons, including the criminalization of drug use, as well as discrimination and stigma in health
care settings. When caring for PWID, the central tenets of respect and non-discrimination should be followed,
and additional adherence and psychological support given as required.
Screening
As a population with a high prevalence of HCV infection, all PWID should be offered screening for HCV as
an integral component of a comprehensive package of harm reduction interventions. Repeated screening is
required in individuals at ongoing risk of reinfection, and the possibility of reinfection after spontaneous
clearance or successful treatment should also be considered. Those who have been previously infected should
be re-tested at least annually using HCV RNA testing, as the antibody remains positive after the first infection.
HCV case-finding and treatment in specialist drug dependency services has also been shown to be cost-effective
in high-income settings. The higher the treatment rates, the more cost-effective HCV case-finding becomes, as
more of those identified will be treated, and a greater population impact would be seen. Screening for HBV and
HIV is also recommended in PWID.

Care
Treatment of HCV in PWID requires integration of services, as other health care needs, including treatment for
HIV and TB as well as drug and alcohol dependency, are often also present. Harm reduction strategies, including
the provision of OST and sterile injection equipment, are required in order to prevent acquisition of HCV and
other blood borne viruses such as HBV and HIV.
At all times, avoidance of discrimination or stigmatization of PWID is essential. Care should be given only with
informed consent. Moreover, acceptability of services is a vital component of health care, and peer interventions
may help with reducing injecting drug use and promoting safer injection practices. PWID are at risk of infection
with HBV and should be vaccinated using the rapid vaccination regimen.
Interventions in PWID offer important area of synergies with the National AIDS Control Programme (NACP)
and the different intervention can be delivered using the targeted interventions.
Persons with HIV/HCV Co-infection

Persons with HIV/HCV co-infection generally have more rapid progression of liver fibrosis, especially those
with a CD4 cell count of <200 cells/mm3. Furthermore, even among patients in whom ART leads to successful
control of HIV infection (i.e. undetectable HIV viral load), the risk of hepatic decompensation among co-infected
patients is higher than among patients with HCV mono infection. For these reasons, all persons with HIV/HCV
co-infection should be considered for HCV treatment.
Evaluation of HIV and HCV Co-infected persons

The assessment of those with HCV/HIV includes clinical evaluation – history, physical examination for jaundice,
hepato-splenomegaly, ascites, cirrhosis/decompensation and laboratory tests including LFT, prothrombin time,
complete haemogram, AFP, etc. Other tests required are abdominal ultrasound, endoscopy, assessment of liver
fibrosis (APRI/FIB 4/fibro-Scan- please refer Annexure 1, and HCV RNA quantitative assay.
Treatment of HIV and HCV Co-infection

In the past, treatment of HIV and HCV co-infected persons with interferon and ribavirin combination therapy
was difficult, as many patients had to discontinue treatment due to side-effects such as depression or weight
loss as well as severe anaemia, thrombocytopenia and neutropenia. Furthermore, SVR rates in patients with
co-infection were lower than among HCV-mono infected patients.
Outcomes of HCV therapy with DAAs in persons with HIV co-infection are comparable to those with HCV
mono infection. Thus, DAA therapy has substantially simplified the treatment of persons with HIV and HCV
co-infection.
There are fewer Drug-Drug Interactions (DDIs) between DAAs and ARV medicines, and SVR rates with DAA-
based therapy among persons with HIV co-infection are higher than 95%, even for those with prior HCV
treatment failure or advanced fibrosis. Therefore, there is no longer a need to consider HIV/HCV co-infected
patients as a special, difficult-to treat patient population. The need to check for DDIs between HIV and HCV
medications, however, needs to be emphasized.
It is advisable to first initiate treatment for HIV and achieve HIV suppression before starting HCV treatment,
although there are some circumstances where it may make sense to treat HCV infection first and then initiate
therapy for HIV. This could include persons with moderate-to-severe fibrosis at risk of rapid liver disease
progression if the HIV infection is not associated with significant immunosuppression at the time of treatment.
Also, in view of the short duration of HCV treatment, the risk of DDIs between HCV and HIV medicines and the
increased risk of ART-related hepatotoxicity in the presence of HCV infection, treating HCV infection first can
simplify subsequent ART depending on the regimen available locally.

Potential harmful effects of ARV drugs include their hepatotoxic effects. Several studies have shown that
hepatotoxicity as a result of ART may be worsened in the presence of concomitant HCV infection. However,
the highest rates of hepatotoxicity have been observed with ARV drugs that are no longer commonly used or
recommended, including stavudine (d4T), didanosine (ddI), nevirapine (NVP) or full-dose ritonavir (600 mg twice
a day) . For most HIV/HCV co-infected persons, including those with cirrhosis, the benefits of ART outweigh
concerns regarding drug-induced liver injury. Raised liver enzymes may be the result of ART-induced drug
toxicity and/ or opportunistic infections, making interpretation of liver enzyme elevations more problematic
than for patients with HCV infection alone. ALT and AST should be monitored at 1 month after ART initiation
and then every 3–6 months. A significant elevation of AST/ALT should prompt careful evaluation for other
causes of liver function impairment (e.g. alcoholic hepatitis, hepatobiliary disease), and may require short-term
interruption of the ART regimen or specific drug suspected of causing the elevation.
Daclatasvir is associated with significant drug interactions with many NNRTIs and PIs, and its concomitant
use requires caution, dose adjustments or consideration of alternative DAAs. The dose of daclatasvir will be 30
mg with ATV/r and 90 mg with EFV. Ledipasvir (LDV) and sofosbuvir have shown reduced potential for drug
interactions with ARV drugs due to their use of different metabolic pathways. A complete list of drug-drug
interactions is available at www.hep-druginteractions.org.
Table 13: Drug Interactions Between Direct-Acting Antivirals and Antiretroviral Drugs
Selected Daclatasvir Sofosbuvir Ledipasvir/ Sofosbuvir/
HIV Drugs Sofosbuvir Velpatasvir
3TC √ √ √ √
ABC √ √ √ √
FTC √ √ √ √
TDF √ √
√ √
Monitor for TDF toxicity. Monitor for TDF toxicity.
Unboosted ATV √ √ √ √
ATV/r or ATV/c √ √ √
↓ DCV dose to √ If a PI/r or PI/c is If a PI/r or PI/c is
30 mg/day used with TDF, ↑ used with TDF, ↑
DRV/r or DRV/c √ √ TDF concentrations TDF concentrations
are expected. If co- are expected. If co-
LPV/r administration is administration is
√ √ necessary, monitor necessary, monitor
for TDF-associated for TDF-associated
toxicities.* toxicities.*
EFV √
↑ DCV dose to √ X
√
90 mg/day
If used with TDF, monitor
NVP √
for TDF toxicity.
↑ DCV dose to √ X
90 mg/day
RAL √ √ √ √
ATV/r = atazanavir/ritonavir; ATV/c = atazanavir/cobicistat; DAA = direct-acting antiviral agents; DRV = darunavir;
DRV/r = darunavir/ritonavir;; DTG = dolutegravir; DSV = dasabuvir; EFV = efavirenz; FTC = emtricitabine; LPV/r =
lopinavir/ritonavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase
inhibitor; NVP = nevirapine; PI = protease inhibitor; RAL = raltegravir; RPV = rilpivir; RTV = ritonavir; TAF = tenofovir
alafenamide; TDF = tenofovir disoproxil fumarate;
*Consider alternative HCV or ART to avoid increases in TDF exposure. If co-administration is necessary, monitor patient
for TDF-associated adverse reactions.
Key to Symbols:
√ = ARV agents that can be used concomitantly
X = ARV agents not recommended
( Ref: Guidelines for the Use of Anti-retroviral Agents in HIV-1-Infected Adults and Adolescents; Downloaded from
https://aidsinfo.nih.gov/guidelines on 6/27/2018)

Management of Cirrhotic Patients after HCV clearance in SVR 12
HCV infection can be considered cured in non-cirrhotic patients who have achieved a SVR 12 after 12 weeks of
completing the treatment. Thus no follow-up is required.
Patients with a history of excessive alcohol drinking, obesity, type 2 diabetes, hypertension etc should be
periodically subjected to a thorough clinical assessment as needed.
In patients with cirrhosis who have achieved cured (successful treatment), long-term post-SVR follow-up
studies have demonstrated that there is a persistence of risk of developing HCC, although it is significantly
reduced compared to untreated patients or patients who did not achieve an SVR. Thus, HCC surveillance in
these patients must be indefinite. These patients with liver cirrhosis who have achieved SVR should remain
under surveillance for HCC every 6 months by ultrasound, and for oesophageal varices by endoscopy if varices
were present at pre-treatment endoscopy.
There is increased risk of reinfection (1-8%) following successful HCV among patients at high risk, such as
PWIDs or men who have sex with men, etc. Thus the risk of reinfection should be explained to the patient
in order to positively modify risk behavior. Following SVR 12, the monitoring for HCV reinfection should be
recommended in these patients with ongoing risk behavior. If reinfection is identified during post-SVR follow-
up, then retreatment is indicated.
Persons with chronic kidney disease

There is an unmet need for DAA treatment in patients with severe renal disease (eGFR <30 mL/min/1.73 m2)
and those requiring haemodialysis. Sofosbuvir, which is used in many approved regimens, does not have the
safety and efficacy data to support its use in these situations.
Patients receiving ARV drugs in combination with tenofovir and sofosbuvir may require enhanced renal
monitoring.
Given the complex management needs for this group, these patients should be referred to higher and specialized
center for appropriate management.
Persons with HBV/HCV co-infection

It is important to check for the presence of HBV infection before starting HCV treatment. HBV and HCV
co-infection may result in an accelerated disease course; HCV is considered to be the main driver of disease.
Persons co-infected with HBV and HCV can be treated with antiviral therapy for HCV; SVR rates are likely to
be similar to those in HCV-mono infected persons. During treatment and after HCV clearance, there is a risk of
reactivation of HBV, and this may require treatment with concurrent anti-HBV antiviral therapy. DDIs must be
checked before initiating treatment.
Persons with TB/HCV co-infection

People at increased risk of infection with HCV are also often at increased risk of infection with TB. Therefore,
screening for active TB should be part of the clinical evaluation of patients being considered for HCV treatment.
If the patient does not have any one of the following symptoms – current cough, fever, weight loss or night
sweats – TB can be reasonably excluded; otherwise, the patient should undergo further investigations for TB or
other diseases.
Most of the DAAs interact with metabolic pathways in the liver, which increases and/or decreases the drug
level of DAAs when co-administered with antimicrobial medicines such as rifabutin, rifampin and rifapentine.
Therefore, concurrent treatment of HCV infection and TB should be avoided. Active TB should generally be
treated before commencing therapy for HCV. Furthermore, in persons with HCV infection being treated for
TB, it is important to monitor liver function tests, as the risk of anti-mycobacterial -induced hepatotoxicity is

higher in patients with TB/HCV co-infection than in those with TB mono infection, although the risk of severe
hepatotoxicity is rare.
Concurrent treatment of HCV infection and multidrug-resistant TB is particularly complicated because of many
DDIs between DAAs and second-line antimicrobials. There are limited data on the management of persons co-
infected with HCV, HIV and TB, but such cases need sound clinical judgement in order to reduce the additive
side-effects, pill burden and DDIs. Baseline liver function tests for individuals with chronic liver disease are
encouraged prior to initiating treatment for latent TB infection. For individuals with abnormal baseline test
results, routine periodic laboratory testing should be carried out during the treatment of latent TB infection.
Women of child-bearing age

None of the DAAs have been evaluated among pregnant women. Thus, women with childbearing potential
should be counseled that they require effective contraception during treatment and for six months after
completion of therapy. Safety of DAAs in pregnancy has not been established. Ribavirin is associated with fetal
abnormalities. DAAs are thus contraindicated in pregnant women and those with child bearing potential unless
effective contraception (i.e. two forms of contraception) can be guaranteed during treatment and, for women
taking ribavirin, for 6months after completing therapy. Pre-treatment pregnancy tests should be conducted
prior to treatment initiation.
Hepatitis E
Hepatitis E virus (HEV) is a non-enveloped single stranded RNA virus belonging to Hepevirus. This agent is
transmitted almost exclusively by the fecal oral route. It is an outbreak prone disease with an incubation period
of around 2-10 weeks.
Clinical Presentation
The illness usually begins after the incubation period of 14-70 days as an acute viral syndrome with mild fever,
marked loss of appetite, aversion to food, upper abdominal discomfort ,nausea and/vomiting. Within a few
days of onset of these non-specific symptoms jaundice can appear with the resolution of these non-specific
symptoms. Jaundice usually persists for 1-6 weeks and then gradually resolves. In children, most HEV infections
occur without any symptom or as a mild illness without jaundice. In contrast, in adults, acute hepatitis E may
have a prolonged cholestatic phase with significant itching. Acute liver failure may be seen in a small proportion
(0.4-5%) which is higher in pregnant women normally within a week of onset of symptoms.
Cases of hepatitis E are not clinically distinguishable from other types of acute viral hepatitis. Diagnosis is
strongly suspected in appropriate epidemiologic settings e.g. occurrence of several cases in localities in known
disease-endemic areas, in settings with risk of water contamination, if the disease is more severe in pregnant
women and if hepatitis A has been excluded.
Definitive diagnosis of hepatitis E infection is based on the detection of specific IgM antibodies to the virus in
a person’s blood. In acute hepatitis with clinical jaundice, the serum bilirubin levels are above 2.5mg/dL and
serum ALT is more than 10 times the upper limit of normal.
Management of Viral Hepatitis E

There is no specific treatment capable of altering the course of acute hepatitis E. As the disease is usually
self-limiting, hospitalization is generally not required. Hospitalization is required for people with fulminant
hepatitis and symptomatic pregnant women.

Immunosuppressed people with chronic hepatitis E benefit from specific treatment using ribavirin, an antiviral
drug. In some specific situations, interferon has also been used successfully.
Special Situations
Certain population sub-groups are at a higher risk for severe disease following HEV infection. These include
pregnant women, persons with pre-existing liver disease and persons with immunosuppression. During HEV
epidemics, fulminant hepatitis occurs with a disproportionately high rate among pregnant women. Overall
case-fatality rates from hepatitis E have ranged from 0.1% to 4%; however, case-fatality rates among pregnant
women are much higher, being 10%-25%.
It is important to recognize patients with acute hepatitis E occurring in these special situations as sick patients
who need hospitalization.
Management of acute viral hepatitis during pregnancy
The patient is preferably managed in a hospital with ICU facilities and blood banking to provide adequate blood
product support, in addition to Obstetric services.
• Monitor blood pressure, exclude toxaemia of pregnancy.
• Permit oral intake, maintain adequate hydration.
• Monitor closely for development of signs of acute liver failure.
Premature induction of labor has no proven role in preventing or treating ALF.
If spontaneous premature rupture of membranes or premature labor occur, one should: Give vitamin K (10 mg
IV, repeat after 24 h), monitor fetal heart rate, arrange blood (may need if postpartum bleeding occurs). If the
fetus is >34-36 weeks, consider induction of labour, otherwise manage conservatively. For premature rupture of
membranes, give antibiotic prophylaxis.
In case of intrauterine death, induction of labor (misoprostol or oxytocin) should be considered in a patient not
in acute liver failure. However, if the mother has acute liver failure, labour should not be induced.
Oxytocin should be used after delivery, to prevent post-partum bleeding. If bleeding occurs, use oxytocin
infusion; if needed, ergometrine or misoprostol can be used. Use blood transfusion, if necessary.
For baby, assess for hypothermia and hypoglycaemia, and treat if present. Administer vitamin K, give normal
vaccines and initiate breast feeding (if the mother can nurse).
Diagnosis and management of acute liver failure

Acute liver failure: Definition
Acute liver failure (ALF) is defined as a severe injury to a previously normal liver, presenting initially as jaundice,
and then altered mental state (hepatic encephalopathy) within 4 weeks of the onset of jaundice. Hepatic
encephalopathy manifests as mental changes, restlessness, reversal of sleep pattern, altered consciousness and/
or persistent vomiting. It is often associated with cerebral edema, which may manifest as slowed heart rate, high
blood pressure and irregular respiration. Less commonly, coagulopathy may develop with bleeding from one or
more body sites.
ALF can be complicated by secondary bacterial infection (leading to sepsis), renal failure, multi-organ failure,
and carries a high risk of death.

How to suspect
The development of one or more of the following should lead to suspicion of impending acute liver failure, or
of severe acute hepatitis:
• Severe or persistent nausea and vomiting
• Mental state changes: excessive sleepiness, irritability, agitation, disorientation, confusion, abnormal
behaviour or decreased level of consciousness
• Spontaneous bleeding (nasal, oral, vaginal, diarrhoea, vomiting)
• Repeated episodes of hypoglycemia
• Fever not possible to manage with tepid sponging
• Dehydration or inability to maintain oral hydration, or not passing urine
Differential diagnosis
In such patients, other diseases (e.g. severe malaria, dengue infection, leptospirosis, other less common systemic
infections, sepsis, cholangitis, liver abscess, drug toxicity) may need to be excluded by clinical or laboratory
evaluation.
Management
Patients with manifest or suspected ALF should be hospitalized. Hospitalization may also be considered in
persons with acute hepatitis who are at high risk of developing ALF (e.g. pregnant women with hepatitis E in the
last trimester, or those with underlying chronic liver dysfunction). The patient is preferably managed in ICU or
high dependency unit.
Treatment should focus on:

a. General care of seriously ill or unconscious patient, including
i. Close observation and monitoring of vital signs, changes in sensorium and bleeding, urine output, etc
ii. Quiet surroundings; head of the bed elevated at ~30O with head in neutral position
iii. Nil by mouth, maintenance of fluid and electrolyte balance by intravenous route, while avoiding over-
hydration and hyponatremia (these can worsen cerebral edema)
iv. Steps to prevent bed sores and corneal injury
v. Monitoring of blood sugar, and prevention and treatment of hypoglycaemia

b. Treatment of symptoms, including
i. Fever: Sponging, paracetamol if needed
ii. Vomiting: Domperidone
iii. Itching: Calamine lotion

c. Patients with encephalopathy should receive lactulose (via nasogastric tube – thin tube, placed gently
to avoid injury and bleeding) 30 ml 2-3 times per day initially, later adjusted to produce 2-3 soft stools
daily (avoid diarrhea). Mannitol (0.5-1.0 g/Kg IV) may be considered in case of prominent cerebral edema,
provided urine output is good. In such patients, transfer to a hospital with intensive care facilities may need
consideration.
d. Vitamin K may be administered if coagulopathy is prominent (10 mg IV/d X 3 days)
e. Prevention and treatment of complications

i. Bacterial infections: consider prophylactic antibiotic, look for and treat early.
ii. Stress ulcers/bleeding: H2 receptor antagonist or proton pump inhibitor
iii. Bleeding: blood or fresh frozen plasma transfusion
iv. Seizures: diazepam
v. Shock: IV fluids
vi. Hypoxia: Oxygen
The following should be avoided or used with caution:

a. Invasive procedures that carry the risk of bleeding
b. Hepatotoxic drugs
c. Drugs that increase the risk of bleeding (e.g. aspirin, NSAIDs)
d. Sedative drugs
e. Corticosteroids
Specific anti-viral agents have no role in management, except possibly in case of acute severe hepatitis B.
Referral of a Patient with Acute Liver Failure to a Tertiary Care Center

When to refer?
• When the patient develops any degree of alteration in sensorium and INR is above 1.5
Where to refer?
• Transfer the patient to a specialized intensive care with the skills to provide airway and ventilator
management (tertiary care unit)
• Facility for liver transplantation is available (if patient is willing)
How to transport the patient?

• Transfer without delay along with a trained health care personnel
• Detailed discussion between the transferring and receiving physicians/team is essential before the
transfer
• In the scenario of an evolving hepatic encephalopathy - intubate and sedate to ensure a controlled
and safe transfer
• Appropriate fluids should be available for ongoing volume resuscitation
• Patient should be maintained normoglycaemic
• Vasopressors should be drawn-up and available.
• Mannitol should be available for management of raised intracranial pressure during transit.

SECTION 2
OPERATIONAL GUIDELINES*
TO ROLL OUT TREATMENT
OF HEPATITIS C
(*Operational guidelines for roll out of treatment of hepatitis B will be disseminated subsequently)

Introduction
The Government of India has decided to launch the integrated initiative for Prevention and Control of Viral
Hepatitis with provision of free treatment for hepatitis C through the National Health Mission. To roll out the
treatment for hepatitis C with a public health approach, the present section has been developed for facilitating
the operationalization of the treatment of Hepatitis C across the country and intends to address the operational
aspects of the same.
Organization of Services
The services will be delivered through designated treatment sites that are located within an existing public
health facility, including tertiary care facilities followed by district hospitals. The extent of services will depend
upon the availability of the expertise and resources in the selected sites. There will be 15 sites that will be
identified as Model Treatment centers (MTC). These will also act as places for referral, capacity building and
mentoring for the other treatment centers (TC). Selection of the Model treatment Center sites will be done by
the central unit for viral hepatitis, with concurrence of states being the implementing agency.
Guidelines for the Organization of Services

Objectives and functions of the Treatment Sites
The management of hepatitis C has been simplified over the last few years since the introduction of Directly
Acting Antivirals. The main objective of the treatment site under the initiative is to enhance the access to
treatment for hepatitis C.
Model Treatment Centre (MTC) and Treatment Centre (TC): The treatment for hepatitis C will also involve
management of patients that present with a range of clinical presentations, cirrhotic and non-cirrhotic,
treatment naive or treatment experienced, special situations like renal impairment etc. Hence, to effectively
manage the patients with HCV infection, it is planned to have a tiered approach for service delivery. All the
treatment centers will have the capacity to deliver the DAA in uncomplicated cases (and few other scenarios
as per the national technical guidelines). They could be situated in public health care facilities like the medical
colleges, district hospitals etc. However, the cases that need more specialized care will be referred to higher
centre that have the requisite capacity and experience to manage the complicated cases (e.g. decompensated
cirrhosis, thalessemics with HCV infection, HCV infection in renal impairment etc.). These health care facilities
with specialized services for diagnosis and management (like availability of Gastroenterologist/hepatologist,
Doppler, CT scan, MRI scan etc.) are termed as Model Treatment center. Hence, the MTC will perform all the
functions of a treatment centre , will also receive in-referrals and also be the centers for training, mentoring and
conducting operational research under the initiative.
As the complications of chronic viral hepatitis are vast, the scope of initiative will be restricted to the use of
directly acting antivirals in treatment of hepatitis C as per the prescribed regimens.
Functions of the Model Treatment Center:

1. To ensure Screening/ Diagnosis in suspected cases of Hepatitis C Infection
2. Treatment & Management of Hepatitis C infection
4. Management of complicated cases referred from other treatment centers.
5. Management of cases under special categories as per national guidelines( eg: thalassemics, patient
with treatment failure etc. )

Functions of the Treatment Center :

1. To ensure Screening/ Diagnosis in suspected cases of Hepatitis C Infection
2. Treatment and Management of uncomplicated Hepatitis C infection
3. In referrals for cases screened/diagnosed elsewhere, for the management of viral hepatitis.
4. Out referrals to MTC for clinical management of hepatitis as per national treatment guidelines.
Selection criteria and steps for setting up a Treatment Site

Each site will be selected by the state, based on the burden of disease according to available evidence in form of
studies, outbreaks, case reports, blood bank data etc. Once the sites are identified and proposed, a joint team will
visit the facility and assess its feasibility for delivery of services, adequacy of needed space and man power and
willingness of the institute to set up such center. The team that will undertake the feasibility visit should ideally
comprise of the state and district officials of the initiative, central unit officials and other invited partners. The
report of feasibility visit should be prepared, signed and kept with the state officials. The format for feasibility
visit is attached as Annexure 4

1. Established evidence of case load for Viral hepatitis C infection or its sequel
2. Evidence of high hepatitis burden in catchment area
3. Commitment and Willingness of the Institute to have a center and consequent agreement to follow
the SOP and protocols under the initiative
4. Availability of required infrastructure
5. Availability of appropriate human resource for clinical and laboratory management, as well as other
services routinely.
Infrastructure
The institution will be responsible for providing essential infrastructure for setting up the center. The
institution should identify adequate space from where the services can be delivered, preferably in vicinity of
OPD services. It should be clearly displayed at several places in the hospital for the ease of access by the patients
especially in the blood bank premises, STI clinics, HIV/ICTC centres etc. There should be services available
every day preferably, and have definite timings displayed boldly across the facility. It will be the responsibility
of the institution to provide basic furniture like chairs, tables, cabinet/almirah etc., space for storage of drugs,
and have necessary electrical and other fixtures. It has to be noted that no separate allocation will be made for
infrastructure and state has to bear the costs if any.
Human Resource
nodal officer who would be responsible for the day to day functioning of the centers. Ideally, this could be the
Head of department of Internal Medicine/Gastroenterology/Hepatology (or a person deputed /nominated by
HOD) in tertiary centers and the physician in district hospitals and elsewhere. The patients should be seen by
the attending physician from the system and the documentation of the patient data and management should be
recorded in the formats that are made available under the program. To assist the delivery of services in a uniflow
system and to ensure efficacy, the treatment centers will be provided the following staff under the program in
a phased manner:

Staffing provided by the program
Table 14: Staff at the treatment sites.

S No Model Treatment centers S No Treatment centers
1 Medical Officer – 1 1 Pharmacist -1
2 Pharmacist -1 2 Data Entry Operator – 1
3 Data Entry Operator – 1 3 Peer Support -1
4 Peer Support -1
Since the Model Treatment centers will also undertake additional tasks like training, mentoring, operational
research and conducting review meetings with state and central unit, they will be provided one contractual
position of level of Medical Officer( MO).
To facilitate the diagnosis and laboratory monitoring of treatment, the initiative will strengthen the laboratories
to deliver services as per the national guidelines. The laboratories so established (preferably in the same institute
as the treatment center) will have the following manpower that the program will provide in a phased manner,
as per the level of facility.
Table 15: Staff at the state laboratory.

S No Manpower at State laboratories
1 Technical Officer – 1
3 Laboratory Technician – 1
Table 16: Staff at the district laboratory.

S No Manpower at District laboratories
The staff should be recruited by the institution as per the norms and procedures followed for recruitment of
contractual staff as per the guidelines of the National Health Mission (NHM). The remuneration for all these
staff shall be in accordance to the state NHM norms. There should be an in-built system of appraisal of such
staff from time to time.
1. Nodal Officer
a. Overall responsibility of the functioning of the centre, reporting to state / central unit, participation in
review meeting, coordinate and develop referral system and linkages with other departments of the hospital
b. Ensure that patient are not discriminated in the hospital and are not denied admission/ care.
c. Ensure that all ethical practices including confidentiality are maintained.
d. Ensure availability of adequate stock of quality drugs as per defined targets at all times
e. Ensure reporting of any short expiry drug in a timely manner to allow timely relocation and avoid financial
loss
f. All administrative matters relating to the centre including sanctioning of leave of contractual staff, annual
performance appraisal of the staff etc. as per guidelines
g. Ensure adherence to the highest standards of quality and excellence in patient care
h. Review and monitor the functioning of the centre periodically and in depth and ensure submission of
i. Act as Focal point for interaction with central unit/ State program management officials etc.

2. Medical officer ( MO) of Model Treatment Center ( MTC)
related to infectious diseases. S/he must be registered in the concerned state Medical Council. A candidate with
higher education will be preferred.
a. S/he is the functional team leader of the centre under the overall guidance of the Nodal officer. The MO
has to supervise the administrative and medical functions of the centre on a day- to- day basis and provide
leadership to staff to work as a cohesive team and deliver the services effectively
b. S/he should examine the patients, advise required investigations, review the investigations and prescribe
the treatment.
c. Refer difficult/ complicated cases to the Nodal Officer or other specialist for further expert opinion and
d. Monitor the consumption and availability of drugs, and alert the concerned authorities in case of impending
shortage well in advance so as to enable adequate replenishment without disruption of services
e. S/he must ensure that all records, registers, cards are updated on a daily basis and reports are sent to the
f. S/he has to ensure that the guidelines for running and maintaining the centre are abided by.
g. Facilitate and coordinate trainings in the centre.
h. Ensure that a daily due list is prepared for the patients expected to visit and a follow up action is taken to
i. Any other duty assigned by Nodal Officer/ Initiative.
3. Pharmacist
considered. S/he must be registered in the concerned state pharmacy council.

a. S/he has to work under the guidance and supervision of nodal officer/MO
b. Dispense drugs with proper counseling / interaction with patient
c. Advise the patients and family about the importance of adherence during each visit
d. Counsel the patient on possible drug toxicities and report the same, if significant
e. Do pill count and report any adverse effects of drugs Also, confirm the next visit date and inform the patient
f. Maintenance of the drug stores
g. Maintain and update drug stock and drug dispensing registers regularly every day. Inform the concerned
medical and nodal officer in case of any discrepancy. Duly take signature of nodal officer every fortnightly
in the stock register
h. Ensure that the centre has enough stock of drugs for at least 3 months and inform the concerned authority
about any near expiry or excess stocks well in time for relocation to other sites and ensure FEFO protocol
is followed
i. Physical verification of the drugs under the supervision of the nodal officer and/or the MO
j. Besides all the above, any other duty assigned by nodal officer.


3. Print and share all circulars/information sent by central unit/States to the Nodal Officer/MO and
4. Maintain the attendance register for the centre staff and get it verified by the nodal officer everyday
and by the Nodal Officer at the end of the month
contractual service agreement, performance appraisal report, training details, remuneration etc.
5. Peer supporter
or hepatitis C) , with a minimum of intermediate (12th) level education. S/he must also have sound knowledge
of the local language and working knowledge of English.

a. S/he has to work under the guidance and supervision of nodal officer /MO
b. Be the first interface with patient at centre
c. Ensure entries in the visit register
d. Be a peer educator for patients at centre and provide psycho-social support to newly registered patients
e. Provide assistance to patients enrolled at the centre, within the hospital (OP and IP)
f. Discuss the importance of adherence to treatment and need of viral load at 12 weeks post treatment
(SVR) with the patients , Keep track of drug adherence of patients , counseling them on the importance of
g. Follow up the patients and assist in patient retrieval, where necessary and as far as possible
h. Any other duty related to the initiative assigned by nodal officer/MO
Terms of Reference for various staff of the Laboratories

Designated Microbiologist of the Institution, or Pathologist in the absence of Microbiologist
a. Supervises the work of Laboratory personnel
b. Verification and signing of reports generated in the laboratory
c. Ensuring that all job responsibilities are adhered to by all the laboratory personnel
d. Management of funds with relation to laboratory

e. Ensure participation in and review of EQA
f. Ensure training and competence of all the laboratory personnel
Qualification: MSc Medical Microbiology with 1 year experience in clinical laboratory services. Candidates with
PhD Medical Microbiology from recognized university with 3 months experience in clinical laboratory services
will be preferred.
a. Supervises the work of Laboratory technician under the guidance of the Laboratory In-charge.
b. Molecular testing where available
c. Preparation of SOPs and work instructions.
d. Verification of reports generated in testing laboratory
e. Preparation of quality control (QC) samples
f. Preparation & distribution of proficiency panels (PT) panels
g. Inventory and financial document management in lab.
h. Maintaining and monitoring timely calibration / verification of all devices and ensuring that all monitoring
and measurements are done with devices having valid verification / calibration status.
i. Adherence to Biosafety guidelines.
j. Maintenance of records and logs in laboratory.
k. Disposition of nonconforming products in her area of operation.
l. Help in the conduct of teaching and training programs.
m. Participate in surveillance activities of programme, through NCDC
n. Onsite field visit to district lab for mentoring and quality assurance.
o. Reporting to laboratory In-charge
p. Any other duty assigned by laboratory In-charge
Qualification: DMLT two year course or certificate in MLT for one year or B.Sc in MLT from recognized university.
a. Collect / receive specimens in the laboratory.
b. Assist in sample transportation to referral laboratory as and when required.
c. Performs tests for hepatitis markers and preparation of reports.
d. Storage and maintenance of serum samples as per guidance.
e. Confirmation of reference samples from state medical college labs and compilation of reports.
f. Perform regular internal quality control testing ,EQA and their documentation
g. To maintain essential records in the laboratory
h. Inventory preparation for equipment and reagents.
i. Indent for supplies to the Laboratory through Lab In charge and ensure sufficient stock of Laboratory
j. Participate in trainings and workshops conducted.
k. Assist in molecular testing of samples where required.
l. To maintain cleanliness in and safety and follow proper biomedical waste disposals.
m. Any other work/ activity assigned from time to time.

Data Entry Operator( State laboratory):

1. S/he has to work under the guidance and supervision of nodal officer ( Microbiologist)
2. Ensure that all data recording and reporting is updated for all activities under the program,
including surveillance of viral hepatitis, if the lab is also participating in the surveillance program
for viral hepatitis
3. Print and share all circulars/information sent by central unit/States to the Nodal Officer and
4. Maintain the attendance register for the program staff and get it verified by the nodal officer ( daily/
end of the month )
Training
Trainings are important for any new initiative as well as for building the capacity of the service delivery points
for an effective implementation. To ensure standardized and uniform quality of service delivery, there will
be capacity building of the different cadres of staff in the program, using standardized training modules and
facilitator guides. The following table summarizes the proposed trainings.
Table 17: Proposal for trainings.

Cadre of Health Number Responsible agency Remark
care worker of days
multi-specialty team 1 Institutional nodal person with head Sensitization about
at Institute of institution and SVHMU program and its
contents/approach
Medical Officers 3 NVHMU for standardized manual; SVHMU Induction training
for implementation and monitoring
Medical Officers 2 NVHMU for standardized manual; SVHMU Refresher trainings
for implementation and monitoring as deemed
necessary
Pharmacist 2 NVHMU for standardized manual; SVHMU
Peer supporter 1 NVHMU for standardized manual; SVHMU
Lab technicians 3 NVHMU for standardized manual; SVHMU Also include EQA
Technical Officer labs 3 NVHMU for standardized manual; SVHMU Also include EQA
Data Entry Operator 2 NVHMU and SVHMU

Logistics
The drugs provided for the treatment centers will be provided through the state as per the laid down
procedures and as per the list of drugs indicated in the treatment algorithm in the technical guidelines for
clinical management of hepatitis. It will be ensured that no stock out/expiry happens in any circumstance,
once the center starts functioning. A provision of 10% buffer stock needs to be maintained all the time as per
the laid down procedure. These drugs should be kept under safe custody and proper storage conditions shall
be maintained. The nodal person of the center should undertake physical verification of the stocks periodically
and the stock registers should be regularly updated and duly signed by the pharmacist and nodal officer.
Financial management
The treatment center will be provided funds as per the pattern of assistance under the initiative through the
state management unit of the NHM. The institute must handle the funds allocated for the purpose it is meant
for and generate a statement of expenditure (SOE) from time to time as per the policy and procedures laid down
by the state.
Table 18A and 18B below details the pattern of assistance:
Table 18A:Pattern of assistance for Model Treatment Centers.

Budget Head Number Total (Annual), Remarks
in INR
Medical Officer 1 As per state NHM
Pharmacist 1 norms for each
personnel. To be
Data Entry operator 1 transferred from
Peer support 1 SVHMU of NHM
Total (HR)
Grant-in-aid for Hepatitis A and 100,000
Hepatitis E case management
Contingency ( photocopy/internet/ SVHMU to MTC
communication/ Resistance testing in selected
cases/ Printing M & E tools/ Tablets for M & E
300,000
if needed) any other operational costs etc.)
Table 18B:Pattern of assistance for Treatment Centers.

Budget head Number Total (Annual), Remarks
in INR
Human Resource
Pharmacist 1 As per state NHM norms
Data Entry operator 1 for each personnel.
Peer support 1 SVHMU of NHM
Total (HR)
Grant-in-aid for Hepatitis A and 100,000
Hepatitis E case management
Contingency ( photocopy, internet/ To be transferred from
communication/ Resistance testing SVHMU to TC
in selected cases/ Printing M & E
50,000
tools/ Tablets for M & E if needed)
any other operational costs etc)

Patient Flow at the Treatment Centers
The following sections elaborate on the flow of patient at the treatment center and also can be used to guide the
smooth functioning of the staff.

1. Enrollment of the patient into care
Enrollment of the patient: The patients who present to the center could either have a definite diagnosis or might
have suspected infection. In case the person is found to have hepatitis C infection by the anti-HCV test (from a
government facility), they should be confirmed with HCV RNA as per the diagnosis algorithm in the national
guidelines. Every person who has a detectable HCV RNA is eligible to receive treatment after taking consent
(annexure 9)
Patient presents to the Treatment center
Refer to Model Treatment Center. If already

Patient is referred from other health care provider or Refer to Model Treatment Center. If already
presents due to suspicion/ perceived risk by self at MTC, to be managed case by case
Get a anti HCV done, and if positive get a HCV viral load done
Patient has a positive anti-HCV and a recent HCV Viral load that is detectable. Peer supporter enters the
details in HCV Treatment register and makes the HCV Treatment card
Doctor: Confirms the status, Examine the patient, Advises Baseline investigations and gives the
necessary forms. Peer supporter guides the patient to laboratory
Lab technician: draws the blood, performs the tests/ ensures transport and ensures that the reports
are generated and sent to the clinician at the treatment center. Keeps close coordination with the peer
supporter and pharmacist. Ensures that test results are updated in records
absence of cirrhosis (using non-invasive criteria), prescribes the medicines as per the guidelines and
send to pharmacist. In case of specific situations*, refers the patient to MTC
Patient leaves the center with clear

Data manager enters the data into the excel sheet
instruction for follow up
SVR done after completion of 12 weeks

of treatment
* These specific situations are described in the treatment guidelines and include retreatment cases/
pregnant women/patients with decompensated cirrhosis, malignancy, renal insufficiency etc
Fig.8: Patient Flow at the Treatment Centers

Every patient found anti HCV positive is registered in care for onward enrolment and has to be confirmed
with a detectable HCV viral load for being eligible for treatment. Cases where anti-HCV is positive but no
HCV viral RNA is detected do not have an active HCV infection and do not need treatment. Sequential
entries for all the registration are to be maintained in the hepatitis C Treatment Register (Annexure 6).
Once confirmed, the testing and treatment card for the patient is made. It is made in two sets: one to be
kept at the center and other given to the patient. The center should take an address proof (Aadhaar card
as UID is mandatory) from the patient. The confidentiality of the information provided by the patient is
to be protected at all cost. Any divulgence of such information will have penal implication as per law for
anyone responsible for such divulgence. The testing and treatment card will capture patient demographic
information diagnosis and treatment details (Annexure 5).
signs the card at the respective places mentioned. The data entry operator maintains the digitize format
of the same.
The details are also entered at each visit as and when they are advised. The follow up entries help in
monitoring the disease progress, counseling of the patient for regular treatment, review of adherence of the
patient to therapy. The drugs will be dispensed for 28 days. However, the pharmacist should ensure that the
patient is given a follow-up day after 25 days. This will ensure that the patient does not land in a situation
where s/he is out of drug stock. At every visit, the pharmacist should also count the remaining drugs (pill
count) to have an idea if any doses have been missed. The patient should be instructed to bring the bottle
of DAA with her/him at every visit so that the pharmacist can perform pill count, collect the old bottle and
issue a new one.
The complicated cases, as defined in the technical guidelines, should be referred to the MTC. At the MTC,
the drugs should be dispensed and once the patient is stable and the treating doctor is confident that the
patient can be managed at the nearest treatment site, then the drug dispensation can be done at the nearest
site. However, the patient should be referred back to MTC in case it is deemed necessary for appropriate
management.
The uncomplicated cases, as defined in the technical guidelines, should be initiated treatment at the
treatment center. Once the patient is stable and the treating doctor is confident that the patient can be
managed at the nearest treatment site, then the drug dispensation can be done at the nearest site. However,
the patient should be referred back in case it is deemed necessary for appropriate management.

Table 19: Summary of the key actions to be undertaken for patient management and record
maintenance and the responsible person.
Visit Number Key activity ( but not limited to) Responsible person
Ascertain Diagnosis of active Hepatitis Attending doctor
C ( anti HCV as well as HCV RNA)
Enter patient details in Hepatitis C Treatment Peer Supporter
Register and demographic details in treatment card
First visit and Take a detailed history and examination Attending Doctor
baseline, after Categorize presence/Absence of Cirrhosis Attending Doctor
confirmation of and fill relevant section in Treatment card
active hepatitis
C infection Select Regimen and start treatment Attending Doctor
Explain patient on adherence and follow up date Peer supporter and pharmacist
Get the baseline investigations done Doctor, Lab technician
and furnish report to center
Educate on adherence and regular follow up Doctor ,Peer supporter and pharmacist
Check for any side effects Attending Doctor
Follow up visit
Get any investigations needed as per technical Attending Doctor
guidelines, prescribe the medicines
Counsel on Treatment completion and need for Doctor, peer supporter
End of Treatment SVR after 12 weeks of completing treatment
Recheck the contact details including phone Peer supporter
Update the record from the register and Data entry operator
For all visits
card to the excel based sheet
Ideally, there should be no expiry at any center. However, in the event there is expiry of some medicines under
the nodal officer of the center. In case there is no institutional policy for discarding the medicines, from the
Monitoring and Evaluation of the Treatment sites

The treatment sites and the laboratory will be reviewed regularly by the nodal officers for the site level day to
day functioning. In addition, the district/state and National officials will also undertake supervisory site visits
for supportive supervision and mentoring. The suggested frequency of the monitoring and mentoring visits are:
Table 20: Frequency of visit to the treatment sites.

National Annual
State Quarterly

During the visits, the officials should try and provide on spot trouble shooting wherever needed, should provide
clarification, assess the HR availability and required infrastructure, check the completeness and quality of
records and reports submitted and randomly check the drug stocks ( physical stocks vs the reported stocks)
Additionally, review meetings will be conducted that will provide a platform for experience sharing and review
the progress.
Recording tools
The following recording tools are to be used under the program:
1. Site Feasibility Form: Annexure 4
2. Patient Treatment card : Annexure 5
a. to be maintained at center
b. Patient Treatment card ( for the patient to retain)
3. Hepatitis C Treatment register: Annexure 6
4. Drug stock and dispensing register: Annexure 7a and 7b
5. Excel based tool for comprehensive record in the documents above.
Reporting tools
There will be a monthly report that each laboratory and treatment center will have to collate and submit to
the state and national officials. The reporting will be in a standard format that will be developed by NCDC and
initially, it will be paper / excel based and later there will be plan to digitalize the same.
The monthly reporting format is attached as Annexure 8
Information from the prescribed records and registers is compiled and used in filling up various monitoring
reports which are forwarded to State Surveillance Officer (SSO) and other officials at state (NHM) and central
level at central unit. Monthly reports from centres should be forwarded by 5thof every month to SSO and other
state level officers by email. The reports at the state level should be compiled into a state report, the facility level
reports have to be checked and feedback should be provided to centers.
The responsibility of information collection, reporting, management and analysis rests at four levels:
1. The treatment sites for creation and maintenance of patient records and files, operational information and
reporting to state and NCDC through monthly reports and special studies
2. State NHM, SSO and Program management unit for analysis and consolidation of information, quality
control, assessments, supportive supervision and guidance, feedback and dissemination of information to
state-level stakeholders; for Programme Implementation Plans (PIPs)
3. Central unit for compilation of reports, analysis, evaluation and dissemination of information back to State
NHM and to national and international stakeholders for advocacy and planning.
Responsibility of reporting, flow of information and frequency of reporting is summarized below:

Table 21: Flow of information and frequency of reporting.
Level Reporting Person responsible Reporting to Frequency of Submission
form for reporting Submission date by
Facility Monthly Report Nodal Officer SVHMU for Monthly 5th of every
(Treatment) of Center Hepatitis and SSO month
State PMU Consolidated SSO / Program I/C Central unit Monthly 10th of every
report of the state month
Independent evaluation of the program will also be planned and organized by National Program Management
Unit. Key gaps identified during implementation of the program and innovative interventions would also be
planned through operational research and will follow the established procedures under the guidance from the
central unit.
Table 22: Monitoring Indicators for the Hepatitis C initiative.

S Indicator Baseline Target for Source of reporting/data
No Year 1 / verification and level
Input indicators
1 Number of Treatment sites 0 15 Reports from centers
approved for Hepatitis C
2 Are National guidelines N/A Yes Program Documents;
and SOPs developed? At NVHMU
3 Is there a standard Training N/A Yes Program Documents;
curriculum developed? At NVHMU
Process Indicators
4 % of Treatment sites 0 80% Report from treatment center
with 100% manpower as
mentioned in the program
5 Number of Persons receiving NA 100,000 Analysis report at central unit
treatment for HCV in the country
6 Number of functional Treatment 0 15 Monthly Reports from
sites in country who are managing Treatment site
Hepatitis C under the program
Outcome indicators
% of patients who achieved
SVR 12 (Treatment completed)

Annexure 1: Assessing severity of liver disease

»» Clinical evaluation for features of cirrhosis and evidence of decompensation, and
»» Measurement of serum bilirubin, albumin, alanine aminotransferase (ALT), aspartate aminotransferase
(AST), alkaline phosphatase (ALP), and prothrombin time; as well as full blood count, including platelet
count.
»» Other routine investigations include ultrasonography and alpha-fetoprotein (AFP) measurement for
periodic surveillance for HCC, and endoscopy for varices in persons with cirrhosis.
Liver enzymes: Aminotransferase levels may fluctuate with time, and single measurements of ALT and AST
do not indicate disease stage. Usually, the ALT concentrations are higher than those of AST, but with disease
progression to cirrhosis, the AST/ALT ratio may be reversed. Tests of liver synthetic function and/or portal
hypertension include serum albumin, bilirubin, platelet count and prothrombin time. A progressive decline in
serum albumin concentrations, rise in bilirubin and prolongation of the prothrombin time are characteristically
observed as decompensated cirrhosis develops.
Liver biopsy: Liver biopsy has been used to ascertain the degree of necro-inflammation and fibrosis, and to help
guide the decision to treat. There are several established methods of scoring histology and measuring activity
(necroinflammation) separately from stage (fibrosis). However, limitations of biopsy include sampling error,
subjectivity in reporting, high costs, the risks of bleeding and pneumothorax, discomfort to the patient, and the
need for training and infrastructure. The pathological features of CHB on liver biopsy depend upon the stage of
the disease, host immune response and degree of virus replication.
Table 23: Metavir staging for liver biopsy.

Metavir Stage F0 F1 F2 F3 F4
Definition No Fibrosis Portal fibrosis Portal fibrosis Numerous septa Cirrhosis
without septa with septa without cirrhosis
Non-invasive tests (NITs): Though liver biopsy remains the gold standard, non-invasive methods for assessing
the stage of liver disease are supplanting it due to the limited availability and accessibility to liver biopsy and
have been validated in adults with CHB. Blood and serum markers for fibrosis, including APRI and FIB-4, or
transient elastography (FibroScan) performed to rule out advanced fibrosis.
APRI (AST-to-platelet ratio index) and FIB 4 are recommended as the preferred non-invasive tests (NIT) to assess
for the presence of cirrhosis (APRI score >2: FIB 4 >3.25 in adults). Transient elastography (e.g. FibroScan) may be
the preferred NITs in settings where they are available and cost is not a major constraint.
APRI and FIB-4 can be readily calculated by the following formulae

APRI = * (AST/ULN) x 100) / platelet count (109/L)
FIB-4 = (age (yr) x AST (IU/L)) / (platelet count (109/L x [ALT (IU/L)1/2])

For APRI, ULN signifies the upper limit of normal for AST in the laboratory where these investigations were
undertaken. For example, in a patient with an AST of 92 IU/L (where laboratory ULN for AST is 40 IU/L) and a
platelet count of 80x109/L, the APRI would be: (92/40)x100/80 = 2.87. This value is >2 and is consistent with the
presence of cirrhosis.
The optimal cut-off values for different NITs that correlate with specific stages of liver fibrosis have been derived
and (in the case of APRI and FIB-4) also validated. APRI and FIB-4 use two cut-off points for diagnosing specific
fibrosis stages, as the use of a single cut-off would result in suboptimal sensitivity and specificity. A high cut-off
with high specificity (i.e. fewer false-positive results) is used to diagnose persons with fibrosis (i.e. greater than or
equal to a particular stage [e.g. ≥F2]), and a low cut-off with high sensitivity (i.e. fewer false-negative results) to rule
out the presence of a particular stage of fibrosis. Some persons will fall in the indeterminate range of test results
(i.e. their score will be between the low and the high cut-off) and will need future re-testing and evaluation.
APRI APRI FIB-4 Transient elastography

(low cut-off) (high cut-off) (FibroScan)*
Cirrhosis 1.0 2.0 - >11–14 kPa
(METAVIR F4)
Significant fibrosis 0.5 1.5 1.45 (low) >7–8.5 kPa
(METAVIR ≥F2) 3.25 (high)
*There are no validated exact cut-offs for specific stages of fibrosis with FibroScan. This table presents the range
of the most commonly used cut-offs for F4 and ≥F2 stages of fibrosis in CHB. A mean cut-off of 12.5 kPa may be
used to diagnose cirrhosis and guide treatment decisions, after taking into account key limitations. (Reference :
Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection., WHO, 2015)
Ascertaining the Degree of Cirrhosis
The degree of cirrhosis is important to be ascertained before the treatment is initiated. The Child–Pugh
Score is a system for assessing the degree of liver disease, and classified patients as Class A, B, or C based on
clinical and laboratory criteria. Those with Class C have the most severe liver disease. Some HCV regimens are
contraindicated among persons with Child-Pugh Class B and C or decompensated cirrhosis.
The following table depicts the Child Pugh Score:
Table 24: The Child Pugh Score.

Points 1 2 3
Encephalopathy None Minimal (grade 1 or 2) Advanced (grade 3 or 4)
Ascites Absent Controlled Refractory
Total bilirubin <34 (<2) 34–51 (2–3) >51 (>3)
(μmol/L) (mg/dL)
Albumin (g/dL) >3.5 2.8–3.5 <2.8
Prothrombin time <4 or <1.7 4–6 or 1.7–2.3 >6 or >2.3
(seconds) or PT-INR
Child–Pugh Class A: 5-6 points
Child–Pugh Class B: 7-9 points
Child–Pugh Class C: 10-15 points

Annexure 2: Algorithm for the Laboratory Diagnosis of Viral Hepatitis
Testing algorithm for Diagnosis of Viral Hepatitis in jaundiced patients

HAV HEV HBV HCV
IgM Anti
IgM Anti IgM Anti HBsAg
HBc
Anti HCV
HAV HEV

Report : Report : Report : Report : If HbsAg is Reactive and lgM anti HBc is Non- Report: Report:
HAV HAV HEV HEV reactive: HBV positive HCV Ab HCV Ab
Positive Negitive Positive Negitive Positive# Negative#
If lgM Anti HBc is Reactive and HBsAg is Non-
in 3 sterile cryo vials. One vial to be used for quantitative hepatitis C RNA estimation and two archived at -80 0 C
Fig.9: Testing algorithm for Diagnosis of Viral Hepatitis in jaundiced patients

(without jaundice)
HBV HCV
HBsAg Anti HCV

* Serum samples to be used for serological and biochemical testing, to be aliquoted and stored at -200 C for
in 3 sterile cryo vials. One vial to be used for quantitative hepatitis C RNA estimation and two archived at -800 C
Fig.10: Testing algorithm for Diagnosis of Viral Hepatitis in suspected patients (without jaundice)

Annexure -3: Drug interactions between DAA and some commonly
prescribed medications
Table 25: Drug interactions between DAA and some commonly prescribed medications.
Sofosbuvir Daclatasvir Sofosbuvir/ Sofosbuvir/
Ledispavir Valpatasvir
Immunosuppressants
Azathioprine No interaction No interaction No interaction No interaction
Cyclosporine No interaction No interaction No interaction No interaction
Everolimus No interaction Potential interaction Potential interaction Potential interaction
Mycophenolate No interaction No interaction No interaction No interaction
Sirolimus No interaction No interaction No interaction No interaction
Tacrolimus No interaction No interaction No interaction No interaction
Antiretrovirals
Zidovudine No interaction No interaction No interaction No interaction
Tenofovir No interaction No interaction Potential interaction Potential interaction
Lamivudine No interaction No interaction No interaction No interaction
Efavirenz No interaction Potential interaction* Potential interaction Significant interaction
Nevirapine No interaction Potential interaction No interaction Significant interaction
Abacavir No interaction No interaction No interaction No interaction
Protease inhibitors No interaction No interaction No interaction No interaction
Lipid lowering drugs
Statins No interaction Potential interaction Potential interaction Potential interaction
Fibrates No interaction No interaction Potential interaction Potential interaction
Ezetimibe No interaction No interaction No interaction No interaction
Cardiovascular drugs
Amiodarone Significant interaction Significant interaction Significant interaction Significant interaction
Digoxin No interaction Potential interaction Potential interaction Potential interaction
Clopidogrel No interaction Potential interaction No interaction No interaction
Dabigatran No interaction Potential interaction Potential interaction Potential interaction
Atenolol No interaction No interaction No interaction No interaction
Propranolol No interaction No interaction No interaction No interaction
Carvidolol Potential interaction Potential interaction Potential interaction Potential interaction
Amlodipine No interaction Potential interaction Potential interaction Potential interaction
Diltiazem No interaction Potential interaction Potential interaction Potential interaction
Nifedipine No interaction Potential interaction No interaction No interaction
Enalapril No interaction No interaction No interaction No interaction

Annexure 4: Feasibility Visit for Setting Hepatitis Treatment Center

a
b
c
d
1 Is the Institution willing to set up a center for hepatitis treatment Yes No
2 Is the In-charge keen on establishing services? Yes No
a Willing to allocate necessary space Yes No
b Willing to have nodal person for treatment and lab services Yes No
c Integrate the functioning and follow the National guidelines Yes No
and protocols , including recording and reporting
3 What is the annual OPD of the hospital
4 Is there super-speciality( Gastroenterology/ Hepatology) Yes No
5 How many cases of acute hepatitis are seen annually ( explore last years report)
6 How many cases of hepatitis B and C are seeking care ( explore previous reports)
B and hepatitis C in last three years ( record year wise)
8 If this is a district hospital, where are patients referred
or usually go for complicated cases?
a ICTC Yes No
b ART center Yes No
c Opioid Substitution Center Yes No
d Involvement with Prison Yes No
8 Is the institution implementing any other program under NHM? Please mention name(s) Yes No
INFRASTRUCTURE
1 Location of the proposed centre ( is it in vicinity to OPD services) Yes No
Is there an ICU Yes No
2 Number of rooms
a Doctors Yes No
b Pharmacist Yes No
c Data Entry Operators Yes No
d Drug Storage & Pharmacist Yes No
e Lab Technician Yes No
f Peer supporter Yes No
3 Is institution willing to provide necessary furniture ( chairs, tables, Almirah etc) Yes No
4 Will the center have access to internet Yes No

HUMAN RESOURCES
1 Does the institution have the required capacity to manage chronic hepatitis Cases? Yes No
a Gastroenterologist/Hepatologist Yes No
c Physician ( Internal Medicine) Yes No
d Pediatrician Yes No
e Microbiologist Yes No
f Pathologist Yes No
g Obstetrician Yes No
h Others (Mention)
test (immunoassay - please specify)
a Complete Blood Count / Hemogram Yes No
b Renal Function test Yes No
c Liver Function Test (please ask for each test) Yes No
d Blood Sugar Yes No
e INR Yes No
f Platelet count Yes No
g Pregnancy Test Yes No
h X Ray Yes No
J Fibroscan Yes No
k CT scan
l MRI
m Endoscopy
n Liver Biopsy Yes No
o Others
FINAL RECOMMENDATION OF THE TEAM (Please tick)

Signature of the Feasibility Visit Team: 1……………………………………………
2……………………………………………
3……………………………………………
4…………………………………………….

Annexure 5: Patient Testing & Treatment Card
PATIENT TESTING & TREATMENT CARD
Registration Details
Hospital ID Number Patient ID under program

Date of starting DAA : …./….…/……….
Basic Demographic Information
Name : …………………………………………………. Age : ……………………… Gender : M F

TG
Address Contact number
Aadhaar Number
Date of Anti-HCV testing Rapid ELISA Other

Date of HCV Viral Load Result
Previous Exposure to Hepatitis C Treatment Yes No
If yes, details
DAA Interferon
Details
Is there Cirrhosis at Registration No Compensated Decompensated
Criteria for evaluating cirrhosis ( At least one)
…/..……/..… :Date
Ultrasound
Fibroscan .……………………… )LSM Value (in kPa …/..……/..… :Date
APRI* ……Score …………… Platelet Count ..………AST …/..……/..… :Date
FIB-4* ………ALT .…………… AST ..……… Age /..……/..… :Date

……Score ……………………… Platelet Count
If Decompensated cirrhosis, select basis
CP Score Variceal Bleed Ascites

Encephalopathy
Regimen Prescribed Duration of Treatment
12 weeks 24 weeks
Patient not treated at this center but transferred to higher center

Date …………………………..Place………………………
*mandatory. The center must do both APRI and FIB-4 scoring.

Baseline and Follow Up Investigations
S No Date Hemoglobin Platelet ALT AST S. S INR HCV Viral Other-1 (USGetc)
of Count Bilirubin Albumin Load
Visit
1
2
3
4
5
Follow Up Visits
Visit Date Pills Left Any New Any other Any Next Signature Signature of Patient’s
Number of Complaints or medications Remark Follow of Doctor Pharmacist Signature/
Visit side effects up date Thumb
Impression
1
2
3
4
5
Treatment Outcomes
Failure
SVR Achieved (write
( Date) HCV RNA Lost to Follow up Death Other
Relapse
quantity)
Annexure 6: Hepatitis C Treatment Register
Month: Year:
12 Follow
up Date
1 2 3 4 5 6 7 8 9 10 11 13 14 15 16 17
and status
(Months)
S. 1 2 3 4 5 6
Date of HCV RNA testing*
Date of ANTI-HCV testing
Date of start of treatment
No.
Prior treatment history
Guardian / Care Giver
Registration Number
Due Date of SVR 12

Pre Treatment HCV
Date of completion
Regimen started *
name and contact
Remarks, if any**
Patient’s address
Name of Patient
Contact number
number, if any
Result of SVR
SVR Done on
Sex M/F/ TG
of Treatment
RNA Level
District
I, II, III
Age
1 Y
N
2 Y
N
3 Y
N
*HCV RNA is done only if ANTI-HCV is positive. In case HCV RNA is not
detectable, please put a line across the rest of the fields from 10-16
** In the remarks, please mention the status of patient ( died, lost to follow up, stop treatment due to
medical reasons, transferred out, referred to higher center). For any of these, also mention date.

Annexure 7a: DAA Stock register
Important: Separate page to be maintained for each drug.
Summary should be filled on the last day of the month.
Name of the drug / Regimen __________________________________________
A B C D E F
Stock Received Stock
Date Opening Stock Stock
transferred Balance Remarks
batch Expiry Manufacturing dispensed expired /
Stock Quantity out stock
number date date (consumption) discarded
officially
Monthly summary:
Stock at the start of the month / Opening Stock (A): Reusable stock returned during the month (D):
Stock received during the month (B): Stock dispensed (consumed) during the month (E):
Stock transferred out officially during the month (C): Stock expired/discarded during the month (F)
Stock at the end of the month (F) = (A+B) − (C+D+E):

Annexure 7b: Drug Dispensation Register
Important: Separate page to be maintained for each day. Date: ______/______/______
Patient
Number of Tablets Dispensed
Signature
Patient
Regimen 1
Regimen 2
Regimen 3
SI. No. Patient Name Registration
Number
Total tablets Dispensed
* Specify other drugs used.
Signature of the pharmacist/drug dispenser: ___________________________________

Annexure 8: Monthly reporting format
1.Name of Centre 2. Code Number
3. Name of the District
4. Name of the State
5. Name of the Site Incharge
6. Report for the period

month year
7. Number of Hepatitis C infected people seeking adult adult children total
care at the treatment center (Registering in Care) male female <18 years
7.1 Cumulative number of persons registered in Hepatitis C care at
the beginning of this month
7.2 Number of new persons registered in during this month
7.3 Cumulative number of persons registered at the end of this
month = 7.1 + 7.2
adult adult children total
8. Initiation of Treatment
male female <18years
8.1 Cumulative number of patients ever started on Treatment
(Number at the beginning of this month)
8.2 Number of new patients started on Treatment during this month
8.3 Number of patients on Treatment "transferred in" during this
month
8.4 Cumulative number of patients ever received Treatment
(Number at the end of this month) = 8.1+ 8.2 + 8.3
9. Treatment status (at the end of the month) out adult adult children total
of all patients ever started on treatment (8.4) male female <18years
9.1 Cumulative number of patients who have completed treatment
9.2 Cumulative number of patients who are currently taking
treatment ( 9.2=9.1-( 9.3+9.4+9.5+9.7+9.8)
9.3 Cumulative number of patients who "transferred out"
9.4 The number of all patients whose treatment status in this month
is “stopped treatment” due to medical reasons
9.5 Cumulative Number of patients who are lost to follow-up (LFU)
9.6 The number of patients who did not return to the (Defaulter) and
missed their doses in this month
9.7 Total number of patients Referred to Higher center for further
management
9.8 number of deaths reported
10. Sustained Virologic Response adult adult children total
male female <14 years
10.1 Cumulative number of patients who are eligible for SVR ( i.e
have completed 12 weeks after end of treatment)have completed
12 weeks treatment ( Out of 9.1)
10.2 Cumulative number of patients who have undergone SVR out
of the eligible patient ( out of 10.1)
10.3 Cumulative number of undetectable HCV RNA ( out of 10.2)

11. REGIMENS AT THE END OF THE MONTH
Regimen a) Number of ADULTS b) Number of CHILDREN
alive and on treatment alive and on treatment
Others
Total number of patients
12. DRUG STOCKS

12.1 Drug Stock Status (use separate sheet if required)
Generic a) Opening b) Stock Add expiry d) Consumption e) Expiry f) stock g) Amt. h) Issues /
Drug Name stock received date during the month during the on last reqst for Comments
during month day 3 mo.
month of the based on
month existing
stock
Other
12.2 Was there a stock-out of DAA this month? Yes No
Signature of Nodal Officer:
Date:
Addendum for Lost to Follow up

S No Reason for lost to follow up Number of Patients
Total*
*Total should match 9.5
Addendum for Deaths

S No Reason for Death Number of Patients
1 Liver related causes
2 Due to causes not related to liver disease
Total*
*Total should match 9.8

Guidance on Monthly report:
1. Section 7 captures all the registrations at the treatment center. It will come from the hepatitis C
Treatment Register.
2. Out of all the registrations, there will be a significant proportion that will have undetectable viral
load and will not need treatment. The section 8 captures the details on those who were started
treatment. This will also come from hepatitis C Treatment Register.
3. Section 9.3 to 9.8 will be taken from Remarks column of the hepatitis C Treatment Register
4. Section 11 will come from hepatitis C Treatment Register or from drug dispensing register
5. Section 12 will come from drug stocks register

Annexure 9: Consent form
INDIVIDUAL’S CONSENT FORM FOR TESTING AND MANAGEMENT OF VIRAL HEPATITIS
I, ______________________________________________ (full name), daughter/son of _______________________

____________________ (full name) age ________ resident of (address) ____________________________________
_____________________ have read/have been read over and explained (circle appropriate) the accompanying
guidance and have understood the information provided to me related to the investigations and proposed
management required (if available)
I understand that the purpose of these tests is to:

• Establish my Viral Hepatitis status,
• Evaluate the presence of liver disease which may be associated with Hepatitis infection.
• I can allow the program to archive my specimen for further molecular testing related to viral hepatitis
only in the interest of public health, provided that any information/data/detail relating to or emanating
from my molecular sample shall not be divulged to any third party under any circumstances. A breach of
this condition shall automatically forfeit my consent and the program’s right to retain such information
and shall further render them liable to penal action and compensation.
I understand that if a diagnosis of Chronic Hepatitis B/C is confirmed, I will be offered treatment as per the
provisions in the initiative. I give my consent to the proposed management offered by the initiative subject to
strict protection of my information.
Patient Signature: _________________________________ DATE: ____________
Staff member name obtaining consent: ______________________________________
Staff signature: ___________________________________ DATE: ____________

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3. Colin JF, Cazals-Hatem D, Loriot MA, et al. Influence of human immunodeficiency virus infection on
chronic hepatitis B in homosexual men. Hepatology 1999;29:1306-1310.
4. Colin JF, Cazals-Hatem D, Loriot MA, Martinot-Peignoux M, Pham BN, Auperin A, et al. Influence of
human immunodeficiency virus infection on chronic hepatitis B in homosexual men. Hepatology.
1999;29(4):1306–10.133
5. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection:
recommendations for a public health approach – 2nd ed. WHO, 2016
6. Cost-effectiveness of Hepatitis C Treatment using generic direct-acting antivirals available in India.
Aggarwal, R, et al., et al. s.l. : PLOS One, 2017, Vol. 12. e0176503.
7. Easterbrook P, Sands A, Harmanci H. Challenges and priorities in the management of HIV/HBV and
HIV/HCV coinfection in resource-limited settings. Semin Liver Dis. 2012;32(2):147-57
8. Eskild A, Magnus P, Petersen G, Sohlberg C, Jensen F, Kittelsen P, Skaug K.Hepatitis B antibodies
in HIV-infected homosexual men are associated with more rapid progression to AIDS. AIDS. 92
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9. Gane EJ, Shiffman ML, Etzkorn K, Morelli G, Stedman CAM, Davis MN, Hinestrosa F, Dvory-Sobol
H, Huang KC, Osinusi A, McNally J, Brainard DM, McHutchison JG, Thompson AJ, Sulkowski MS;
GS-US-342-1553 Investigators. Sofosbuvir velpatasvir with ribavirin for 24 weeks in hepatitis C virus
patients previously treated with a direct-acting antiviral regimen. Hepatology. 2017 Oct;66(4):1083-
1089. doi: 10.1002/hep.29256. Epub 2017 Aug 26. PubMed PMID: 28498551.
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gastroenterology,SGPGI, WHO India Country Office. 2017.
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Updated version, April 2016, WHO
13. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents;
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14. Harrison’s Principles of Internal Medicine, 19th edition
15. Hawkins C, Christian B, Ye J, Nagu T, Aris E, Chalamilla G, et al. Prevalence of hepatitis B co-
infection and response to antiretroviral therapy among HIV-infected patients in Tanzania. AIDS.
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Lancet Infect Dis. 2007;7(6):402–9.

17. Ioannou GN, Bryson CL, Weiss NS, Miller R, Scott JD, Boyko EJ. The prevalence of cirrhosis and
hepatocellular carcinoma in patients with human immunodeficiency infection. Hepatology.
2013;57:249-257.
18. Konopnicki D, Mocroft A, de Wit S, Antunes F, Ledergerber B, Katlama C, et al. Hepatitis B and
HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased
mortality in the EuroSIDA cohort. AIDS. 2005;19(6):593–601.
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HIV Ther. 2003;8:77–84.
20. Prevalence of Hepatitis A virus, Hepatitis B virus, Hepatitis C virus, Hepatitis D virus and Hepatitis E
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22. Standard Operating Procedure, Mukh Mantri Punjab Hepatitis C Relief Fund: http://pbhealth.gov.in/
mmphcrf.htm
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25. Wandeler G, Gsponer T, Bihl F, Bernasconi E, Cavassini M, Kovari H, et al. Hepatitis B virus infection
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2012;18:883-890


Dr R. K. Dhiman - Gastroenterologist, PGIMER, Chandigarh
Dr Rakesh Aggarwal - Gastroenterologist, SGPGI, Lucknow
Dr C. E. Eapen - Hepatologist, CMC, Vellore
Dr Samir R. Shah - Hepatologist, Global Hospital, Mumbai
Dr Narayanasamy K - Hepatologist, MMC, Chennai
Dr Praveen Malhotra - Gastroenterologist, PGIMS, Rohtak
Dr Mamta Manglani - Paediatric hemato-oncologist, LTMMC & GH, Sion, Mumbai
Dr Srijaya S - Gastroenterologist, GMC, Trivandrum
Dr T. Jiten Singh - Physician, RIMS, Imphal
Dr Mohd. Shaukat - Advisor, Dte GHS, MoHFW, Delhi
Mr Mehmood Pracha - Senior Advocate, Delhi
Dr Sujeet Kumar Singh - Director, NCDC, Delhi
Dr R. S. Gupta - DDG CST, NACO, Delhi
Dr Sandhya Kabra - Additional Director, NCDC, Delhi
Mr Sella Senthilm - Assistant Drug Controller, Office of DCG(I), Delhi
Mr Abou Mere - Representative, Community Organisation
Dr Aparajita Ravi Sondh - State Surveillance Officer, IDSP, Haryana
Dr Nicole Seguy - CD team leader, WHO (India)
Dr Vimlesh Purohit - NPO (HIV & Hepatitis), WHO (India)
Dr Rekha Jain – Consultant, Delhi
Dr Partha Rakshit - Deputy Director, NCDC, Delhi
Dr Hema Gogia - Deputy Assistant Director, NCDC, Delhi
Dr Preeti Madan - EIS Officer Cohort 5, NCDC, Delhi


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National Viral Hepatitis

Epidemiology of Viral Hepatitis

22 National Viral Hepatitis Control Program – Operational Guidelines

National Viral Hepatitis Control Program – Operational Guidelines 23

24 National Viral Hepatitis Control Program – Operational Guidelines

National Viral Hepatitis Control Program – Operational Guidelines 25

Prevention Diagnosis and Monitoring & Training and

26 National Viral Hepatitis Control Program – Operational Guidelines

National Viral Hepatitis Control Program – Operational Guidelines 27

28 National Viral Hepatitis Control Program – Operational Guidelines

National Viral Hepatitis Technical National

Model Rx State State level

Treatment District Reagent Rental

CHC, PHC HWC

National Viral Hepatitis Control Program – Operational Guidelines 29

National Program Steering Committee:

1. Secretary, Department of Health Research (DHR)

Key Functions of the Program Steering Committee

National Viral Hepatitis Control Management Unit

30 National Viral Hepatitis Control Program – Operational Guidelines

The key functions of NVHMU will include

National Viral Hepatitis Control Program – Operational Guidelines 31

Key Functions of the SVHMU

32 National Viral Hepatitis Control Program – Operational Guidelines

National Viral Hepatitis Control Program – Operational Guidelines 33

Service Delivery Component will include the following two aspects:

Universal Immunization Program

India’s target for Hepatitis B immunization

34 National Viral Hepatitis Control Program – Operational Guidelines

National AIDS Control Program (NACP)

Safety of blood and blood products

National Viral Hepatitis Control Program – Operational Guidelines 35

Injection safety and infection control

Integrated Disease Surveillance Programme

36 National Viral Hepatitis Control Program – Operational Guidelines

National program for Surveillance of Viral Hepatitis:

Swachh Bharat Mission- Urban & Rural

Ministry of Drinking Water and Sanitation

Food Safety and Standards Authority of India (FSSAI)

National Viral Hepatitis Control Program – Operational Guidelines 37

38 National Viral Hepatitis Control Program – Operational Guidelines

CoE RDT, ELISA/CLIA, RT-PCR, Sequencing

Sentinel site RDT, ELISA/CLIA, RT-PCR

State RDT, ELISA/CLIA, access to RT-PCR*

District RDT, ELISA, access to RT-PCR*

RDT for HBV & HCV, referral for

Centre of Excellence for laboratory testing

Roles and Responsibilities

National Viral Hepatitis Control Program – Operational Guidelines 39

Roles and Responsibilities

40 National Viral Hepatitis Control Program – Operational Guidelines

Laboratories below district level

Roles and Responsibilities

1) Sample collection and serological testing under the NVHCP

Sample Transportation for HBV/HCV Quantitative NAT testing

Human Resource in Laboratories

S No Manpower at state laboratories

S No Manpower at district laboratories

National Viral Hepatitis Control Program – Operational Guidelines 41