European guidance lowers the bar for starting antiviral therapy in chronic HBV
The European Association for the Study of the Liver (EASL) has published its updated clinical practice guideline on the management of hepatitis B virus (HBV) infection. Recommendations for when to start antiviral therapy have been updated to make sure patients who may benefit from antiviral therapy are not left untreated.[30]
All individuals who are hepatitis B surface antigen (HBsAg)-positive with chronic HBV infection and advanced fibrosis or cirrhosis are now candidates for antiviral therapy, provided they have detectable HBV DNA, regardless of serum alanine aminotransferase (ALT) level or level of viremia.
Individuals who do not have advanced fibrosis or cirrhosis are still candidates for antiviral therapy if their HBV DNA level is ≥2000 IU/mL and they have one of the following:
ALT level greater than the upper limit of normal (ULN)
Fibrosis
Risk factors for hepatocellular carcinoma (HCC)
Extrahepatic manifestations
Immunosuppression
Risk for HBV transmission
Individuals with persistent HBV DNA level <2000 IU/mL, persistently normal ALT level, and no signs of fibrosis do not usually require immediate antiviral therapy as these people have a low risk of disease progression and transmission.
In clinical practice, there has been a shift away from basing treatment decisions on the phase of chronic infection toward treatment indications being based on HBV DNA level. The EASL acknowledges this shift in its updated guideline, and presents a more simplified and pragmatic treatment approach that avoids categorizing patients according to traditional disease phases or Hepatitis B e antigen (HBeAg) status. The guideline also emphasizes the importance of consulting an expert when considering stopping antiviral therapy.
This change in practice has been prompted by recent evidence that shows long-term suppression of HBV DNA level is associated with a reduced risk of liver inflammation and fibrosis, thereby preventing disease progression and the development of cirrhosis and HCC, leading to increased survival.
Other major international guidelines currently vary in their recommendations on when to start antiviral therapy. For example, US guidelines still recommend initiating treatment based on the phase of chronic infection.[3] However, these guidelines are currently in the process of being updated. The World Health Organization (WHO) supports the initiation of antiviral therapy in all individuals with a HBV DNA level ≥2000 IU/mL and ALT level above the ULN. The WHO also recommends treatment in all individuals with significant fibrosis, regardless of HBV DNA level.[76]
Approximately 254 million people were living with chronic HBV infection in 2022, globally, with an estimated 1.1 million HBV-related deaths, mostly from cirrhosis and hepatocellular carcinoma.[10]
Summary
Definition
History and exam
Key diagnostic factors
- high risk of exposure
Other diagnostic factors
- asymptomatic
- jaundice
- hepatomegaly
- ascites
- fever/chills
- malaise
- maculopapular or urticarial rash
- right upper quadrant pain
- fatigue
- nausea/vomiting
- arthralgia/arthritis
- anorexia
- dark urine or clay-colored stool
- palmar erythema
- spider angiomata
- splenomegaly
- asterixis
Risk factors
- perinatal exposure in an infant born to a hepatitis B virus (HBV)-infected mother
- high-risk sexual behaviors
- injection drug use
- born in highly endemic region
- family history of hepatitis B virus (HBV) infection, hepatocellular carcinoma (HCC), and/or chronic liver disease
- household contact with hepatitis B virus (HBV) infection
- history of incarceration
- male sex
- living with HIV
- living with hepatitis C
- blood or blood product transfusion
- healthcare workers
- hemodialysis
- solid organ transplantation
Diagnostic tests
1st tests to order
- hepatic panel
- CBC
- basic metabolic panel
- coagulation profile
- serum hepatitis B surface antigen (HBsAg)
- serum antibody to hepatitis B surface antigen (anti-HBs)
- serum antibody to hepatitis B core antigen (anti-HBc)
- serum hepatitis B e antigen (HBeAg)
- serum antibody to hepatitis B e antigen (anti-HBe)
- serum quantitative hepatitis B virus (HBV) DNA
- testing for coinfections
Tests to consider
- abdominal ultrasound
- vibration-controlled transient elastography (VCTE)
- serum liver fibrosis biomarkers
- aspartate aminotransferase-to-platelet ratio index (APRI)
- liver biopsy
- alpha-fetoprotein (AFP)
- CT/MRI abdomen
- drug resistance testing
- hepatitis B virus (HBV) genotype
Treatment algorithm
acute HBV infection
chronic HBV infection and indication for treatment: nonpregnant adult without coinfection or cirrhosis or hepatocellular carcinoma
chronic HBV infection: nonpregnant adult with cirrhosis
chronic HBV infection: nonpregnant adult with hepatocellular carcinoma
chronic HBV infection: nonpregnant adult with HIV coinfection
chronic HBV infection: nonpregnant adult with hepatitis C coinfection
chronic HBV infection: nonpregnant adult with hepatitis D coinfection
chronic HBV infection: pregnant or breastfeeding
chronic HBV infection: children
Contributors
Authors
Jawad Ahmad, MD, FRCP, FAASLD
Professor of Medicine
Division of Liver Diseases
Mount Sinai Hospital
New York
NY
Disclosures
JA declares that he has no competing interests.
Acknowledgements
Dr Jawad Ahmad would like to gratefully acknowledge Dr Sateesh R. Prakash, Dr Siddarth Verma, Dr Smruti R. Mohanty, and Dr Jared Hossack, previous contributors to this topic.
Disclosures
SRP, SV, and JH declare that they have no competing interests. SRM serves as a speaker bureau for Bristol-Myers Squibb regarding the use of entecavir for the treatment of chronic hepatitis B.
Peer reviewers
George Y. Wu, MD, PhD
Chief
Hepatology Section
Department of Medicine
University of Connecticut Health Center
Farmington
CT
Disclosures
GYW is on the medical advisory boards of Gilead Sciences and Bristol-Myers Squibb.
Lucieni Oliveira Conterno, MD, PhD
Director
Clinical Epidemiology Unit
Marilia Medical School
Sao Paulo
Brazil
Disclosures
LOC declares that she has no competing interests.
Mamun-Al-Mahtab, MB BS, MSc, MD
Chairman
Bangladesh Primary Care Research Network
Dhaka
Bangladesh
Disclosures
MAM declares that he has no competing interests.
Peer reviewer acknowledgements
BMJ Best Practice topics are updated on a rolling basis in line with developments in evidence and guidance. The peer reviewers listed here have reviewed the content at least once during the history of the topic.
Disclosures
Peer reviewer affiliations and disclosures pertain to the time of the review.
References
Key articles
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018 Apr;67(4):1560-99.Full text Abstract
European Association for the Study of the Liver. EASL clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2025 Aug;83(2):502-83.Full text Abstract
World Health Organization. Guidelines for the prevention, diagnosis, care and treatment for people with chronic hepatitis B infection. Mar 2024 [internet publication].Full text
Reference articles
A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.
Differentials
- Hepatitis A
- Hepatitis C
- Hepatitis D
More DifferentialsGuidelines
- Clinical practice guidelines on the management of hepatitis B virus infection
- Guidelines for the prevention, diagnosis, care and treatment for people with chronic hepatitis B infection
More GuidelinesPatient information
Hepatitis B: should I have the vaccine?
More Patient information
Log in or subscribe to access all of BMJ Best Practice
Use of this content is subject to our disclaimer