AGA Releases Clinical Practice Update on HBV Reactivation Prevention, Treatment

The American Gastroenterological Association (AGA) has released a clinical practice guideline update on the prevention and treatment of hepatitis B virus (HBV) reactivation in at-risk individuals.1

Published in Gastroenterology, the new guideline addresses research published since the first iteration was released in 2014 and provides 4 key clinical recommendations regarding the role of antiviral prophylaxis and monitoring without antiviral prophylaxis for management of HBV reactivation based on the balance between desirable and undesirable effects, patient values, costs, and health equity considerations.1,2

“Since that publication, multiple novel classes of immunosuppressive therapies have been developed and approved for clinical use,” Yngve Falck-Ytter, MD, a professor of medicine at Case Western University, and colleagues wrote.1 “In addition, interventional therapies, such as transcatheter arterial chemoembolization that can induce an immuno-suppressed state, and thus are relevant to potential HBV reactivation, have also been recognized.”

According to the World Health Organization, an estimated 254 million people were living with chronic hepatitis B infection in 2022, with 1.2 million new infections occurring each year. Although acute hepatitis B is a short-term illness that is rarely fatal, HBV can reactivate due to a variety of immune-modulating exposures, including multiple drug classes and disease states.3

Intended for frontline healthcare practitioners tasked with the prevention and management of HBV reactivation in their clinical practice, policymakers, and patients with exposures that increase their risk of HBV reactivation, the guideline was developed by a panel of 7 committee members, including 5 hepatologists; a senior Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodologist; and a junior GRADE methodologist.1

The panel conducted a systematic evidence review to identify new studies published since the release of the first version of the guideline in 2014. They then used the Evidence to Decision framework to develop recommendations regarding the role of antiviral prophylaxis and monitoring without antiviral prophylaxis for the management of HBV reactivation, defined as the de novo appearance of HBV-DNA in a patient with previously undetectable HBV- DNA or a 10-fold increase in HBV-DNA value compared with baseline.1

In total, the panel agreed upon 4 recommendations intended to serve as a benchmark for high-quality HBV care and improve the delivery and management of related healthcare services.1

Recommendation 1: Antiviral Prophylaxis in High-Risk Individuals

For individuals at high risk of HBVr, defined as > 10% risk, the AGA strongly recommends antiviral prophylaxis over monitoring alone with a moderate certainty of evidence. The recommendation assumes the use of antivirals with a high barrier to resistance and asserts that antiviral prophylaxis should be started before the start of medications that impose risk of HBV reactivation and should be continued for ≥ 6 months after discontinuation of risk-imposing therapy.1

Recommendation 2: Antiviral Prophylaxis in Moderate-Risk Individuals

For individuals at moderate risk of HBV reactivation, defined as 1-10% risk, the AGA conditionally recommends antiviral prophylaxis over monitoring alone with a moderate certainty of evidence. Like the recommendation in high-risk individuals, this recommendation assumes the use of antivirals with a high barrier to resistance.1

Investigators noted patients who value avoiding the long-term use of antiviral therapy and the cost associated with its use and place a lower value on avoiding the small risk of reactivation may reasonably select active monitoring over antiviral prophylaxis, with careful consideration of feasibility and likelihood of adherence to long-term monitoring. According to the guideline, monitoring should be performed at 1- to 3-month intervals and must include an assessment of hepatitis B viral load in addition to an assessment of alanine aminotransferase.1

Recommendation 3: Monitoring Alone in Moderate-Risk Individuals

For individuals at low risk of HBV reactivation, defined as <1% risk, the AGA conditionally recommends monitoring alone over using antiviral prophylaxis with a moderate certainty of evidence.1

The recommendation assumes regular and sufficient follow-up that ensures continued monitoring but recognizes that patients who value avoiding the small risk of reactivation and place a lower value on the burden and cost of antiviral therapy may reasonably select antiviral therapy.1

Recommendation 4: Monitoring Alone in Individuals at Potential Risk

For individuals at risk of HBV reactivation, the AGA strongly recommends testing for hepatitis B with a moderate certainty of evidence.1

The guideline asserts that stratifying screening practices by the magnitude of HBV reactivation risk is no longer needed, given universal Centers for Disease Control and Prevention screening guidance for hepatitis B for all adults ≥ 18 years of age by testing for HBsAg, anti-HBs, and total anti-HBc. Instead, the panel suggests it is reasonable to test initially for serologic markers alone followed by viral load testing if HBsAg and/or anti-HBc is positive.1

References

1. Ali FS, Nguyen MH, Hernaez R, et al. AGA Clinical Practice Guideline on the Prevention and Treatment of Hepatitis B Virus Reactivation in At-Risk Individuals. Gastroenterology. doi:10.1053/j.gastro.2024.11.008
2. Reddy KJ, Beavers KL, Hammond SP, et al. American Gastroenterological Association Institute Guideline on the Prevention and Treatment of Hepatitis B Virus Reactivation During Immunosuppressive Drug Therapy. Gastroenterology. doi:10.1053/j.gastro.2014.10.039
3. World Health Organization. Hepatitis B. April 9, 2024. Accessed January 23, 2025. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b