WHO Releases New Hepatitis B Guidelines

Chari Cohen, DrPH, MPH

Credit: LinkedIn

The World Health Organization (WHO) has released new guidelines for the prevention, diagnosis, care, and treatment of hepatitis B virus (HBV), making evidence-based recommendations reflecting updated data on antiviral effectiveness, diagnostic performance of tests, and service delivery models.¹

In 2015, the WHO issued the first comprehensive guidelines for chronic hepatitis B. Then, in 2017 and 2021, guidelines on testing for viral hepatitis B and C and guidelines on preventing the mother-to-child transmission of HBV using antiviral prophylaxis in pregnancy were released, respectively. Citing several significant developments since the initial 2015 guidelines were published, investigators called attention to the need for updated evidence-informed recommendations on key priority topics.¹

“These new guidelines are an excellent step forward, opening up more expansive treatment opportunity for people living with hepatitis B and helping us work toward preventing liver damage, liver cancer and premature death,” Chari Cohen, DrPH, MPH, president of the Hepatitis B Foundation, said in a press release.²

Priority areas for recommendations were as follows:

• Expanded treatment eligibility for adults and adolescents and new non-invasive test thresholds for diagnosis of significant fibrosis or cirrhosis
• Expanded antiviral prophylaxis for hepatitis B surface antigen (HBsAg)-positive pregnant women
• HBV diagnostics, including the use of point-of-care HBV viral load and reflex viral load testing, and testing for hepatitis D virus infection
• Approaches for simplified service delivery

Clinical recommendations were developed by a regionally representative and multidisciplinary Guidelines Development Group using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach in accordance with procedures established by the WHO Guidelines Review Committee. Investigators undertook 15 systematic reviews and meta-analyses to address the key research questions, in addition to 2 modeling and cost-effectiveness analyses. The WHO also commissioned various partner organizations to undertake 4 key surveys among populations affected by hepatitis B, healthcare workers, and national hepatitis program managers to assess the acceptability of potential recommendations in the guidelines.¹

The 2024 WHO HBV guideline includes 11 updated chapters with new recommendations, additionally providing updates to existing chapters without new recommendations. It primarily targets national hepatitis program managers and other policy-makers in health ministries, especially in low- and middle-income countries, who are responsible for developing national hepatitis testing and treatment plans, policies, and country-specific guidelines.¹

Expanded eligibility for treatment

The 2024 recommendations provide 4 options for meeting treatment eligibility, applicable to all adults with HBV as well as adolescents ≥ 12 years of age. These include treating all patients with significant fibrosis; with HBV DNA>2000 IU/mL and ALT above the upper limit of normal (ULN); with coinfections, family history of liver cancer or cirrhosis, immune suppression, comorbidities, or extrahepatic manifestations; and where there is no access to HBV DNA, treat those with HBV based on persistently abnormal ALT levels alone.¹

Alternative antiviral regimens for treatment

The existing recommendation for the use of tenofovir disoproxil fumarate or entecavir as the preferred first-line regimen was retained from the 2015 WHO hepatitis B guidelines, although a new recommendation was added for the use of dual regimens with tenofovir/lamivudine or tenofovir/emtricitabine as alternative regimens in settings where access to tenofovir monotherapy is lacking.¹

Expanding access to antiviral prophylaxis for prevention of mother-to-child transmission

The existing recommendation for the use of tenofovir disoproxil fumarate prophylaxis for HBsAg-positive pregnant women with HBV DNA levels ≥200 000 IU/mL or a positive HBeAg was retained from the 2020 WHO guideline. However, to address the continued challenge of accessing HBV DNA and HBeAg serology testing to determine eligibility for antiviral prophylaxis, a new conditional recommendation was added to the 2024 guideline to provide the option of using antiviral prophylaxis for all HBsAg-positive pregnant mothers.¹

Point-of-care and reflex HBV DNA testing

The guideline recommends point-of-care HBV DNA nucleic acid testing assays as an alternative approach to laboratory-based HBV DNA testing to assess treatment eligibility and monitor treatment response. Additionally, reflex HBV DNA testing is recommended as an additional strategy in those with a positive HBsAg test result to promote linkage to care and treatment.¹

HDV infection testing

The WHO recommends universal HDV antibody testing among people with chronic hepatitis B. For settings where this approach may not be feasible due to limited laboratory capacity, testing should be prioritized in specific HBsAg-positive populations or settings with well-established higher prevalence of HDV infection. The WHO recommends a serological assay to detect total anti-HDV followed by a nucleic acid test to detect HDV RNA and active infection among anti-HDV positive individuals. Reflex testing is recommended for anti-HDV antibody testing following a positive HBsAg test result and for HDV RNA testing following a positive anti-HDV antibody test result.¹

Key approaches for delivering high-quality services for hepatitis B care

The guideline promotes 8 key approaches for high-quality health service delivery for hepatitis B care, including strategies to promote uptake of testing and strengthen linkage to care, treatment and prevention; strategies to promote and sustain adherence to long-term antiviral therapy; strategies to promote retention in care; integration of hepatitis testing, care and treatment with other services; decentralization of testing and treatment services at primary health facilities; and community engagement and peer support.¹

References:

1. ^{World Health Organization. Guidelines for the prevention, diagnosis, care and treatment for people with chronic hepatitis B infection. March 2024. https://www.who.int/publications/i/item/9789240090903}
2. ^{Hepatitis B Foundation. WHO announces new guidelines for hepatitis B treatment. March 29, 2024. Accessed April 4, 2024. https://www.hepb.org/news-and-events/news-2/who-announces-new-guidelines-for-hepatitis-b-treatment/}