Risk assessment and management of hepatitis B reactivation from direct-acting antivirals for hepatitis C

Although hepatitis B virus (HBV) reactivation has been reported in hepatitis C patients who received interferon therapy, rare cases of HBV reactivation occur in the context of direct-acting antiviral (DAA) agent therapy for treatment of hepatitis C virus (HCV) infection. Recent studies observed that the reactivations were predominantly in hepatitis B surface antigen (HBsAg) positive patients, but reactivation can rarely occur in patients who are HBsAg negative and hepatitis B core antibody (HBcAb) positive. The severity of an HBV flare varies. In some cases, severe liver injury or fulminant hepatic failure may occur. HBV reactivation may occur regardless of HCV genotype and type of DAA regimens. The onset of HBV reactivation can range from 4 to 48 weeks after initiating DAA therapy. These patients may have undetectable levels of HBV deoxyribonucleic acid (DNA) prior to DAA treatment. Pre-emptive antiviral therapy for HBV should be considered in HBsAg-positive patients with high levels of viremia who are not receiving HBV treatment. If HBV DNA viral load is less than the guideline criteria for HBV treatment, one should consider pre-emptive HBV antiviral versus HBV DNA monitoring during DAA therapy. For patients who are HBsAg negative but HBcAb positive, close monitoring of serum alanine aminotransferase (ALT) levels during/post-treatment is highly recommended. The current review summarizes the recommendations of different society guidelines and discusses the appropriate management strategies in various patient profiles.