Reactivation of Occult HBV Infection in Patients Cured of HCV With Direct-Acting Antivirals

Abstract

The era of hepatitis C virus (HCV) treatment with direct-acting antiviral (DAA) therapy has remarkably improved liver-related morbidity and overall mortality with patients achieving rapid and sustained clearance of HCV infection. The initial DAA clinical trials excluded patients with hepatitis B virus (HBV) co-infection, and thus potential complications were unforeseen until case reports of HBV reactivation associated with DAA therapy began to emerge. A recent United States Food and Drug Administration (FDA) drug safety communication has brought public attention to the issue of HBV reactivation in patients treated with DAA for HCV co-infection. Reactivation of HBV is well known to occur with a variety of immune-suppressive therapies notably in the context of cancer, rheumatologic treatments, and organ transplantation. While HBV reactivation in the setting of DAA therapy remains rare, the severity of hepatitis can be profound and deadly. Early recognition and treatment are keys to improving patient outcomes. Therefore, it is currently recommended to screen all patients for current or prior HBV infection prior to starting DAA therapy. If either hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (anti-HBc) is positive, HBV DNA should be obtained. With active viremia, prophylactic therapy should be started with DAA treatment with an agent with a high barrier for resistance. If there is no evidence of active viremia, the risks and benefits of prophylactic therapy should be weighed. Those with positive HBsAg should consider prophylactic therapy. Those with an isolated anti-HBc in the absence of HBsAg have an option of monitoring their liver enzymes, HBV DNA, and HBsAg at regular intervals during DAA therapy. If prophylactic HBV therapy is initiated, it should be continued for at least 3 months after DAA therapy is complete. After this period, the risks and benefits of continuing their HBV therapy should be re-addressed.