Navigating the Latest Hepatitis B Virus Reactivation Guidelines

Hepatitis B virus (HBV) infection is a global health concern with an estimated 254 million people with chronic HBV infection. The utilization of immunosuppressive therapies (ISTs) is increasing and expanding continuously with new agents being implemented across multiple medical disciplines. The occurrence of HBV reactivation (HBVr) during or after IST varies from 15% to 50% in HBsAg-positive individuals and can be higher than 75% after stem cell transplantation. HBVr is gaining increasing significance in contemporary clinical practice. The American Gastroenterological Association (AGA) in 2025, the European Association for the Study of the Liver (EASL) in 2025, and the Asian Pacific Association for the Study of the Liver (APASL) in 2021, published their most recent clinical guidelines as major societies in the area, which enables us to better predict and manage HBVr. This narrative review focuses on comparing these three current guidelines, highlighting key similarities and differences to provide valuable guidance for practitioners navigating the complex, sometimes conflicting recommendations, thereby aiding clinicians in their decision-making. The risk of HBVr during IST has been stratified into three categories in all three guidelines: high (>10%), moderate (1-10%), and low (<1%). The effectiveness of prophylaxis scales with baseline risk for HBV reactivation. Prophylaxis is clearly cost-effective for high-risk patients, potentially beneficial for those at moderate risk, and generally may not be justified for low-risk individuals. Entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) are all highly effective in preventing HBV reactivation during immunosuppression and all are considered to be economically viable options for HBVr high risk patients. When selecting among these agents, safety considerations-particularly renal and bone toxicity-and insurance coverage remain the primary factors directing clinical decision-making.