Hepatitis B reactivation during or after direct acting antiviral therapy - implication for susceptible individuals

Introduction: The FDA issued a warning following 24 cases of HBV reactivation during DAA therapy for HCV, including individuals with inactive, occult and past HBV infection. Clinical presentations ranged from asymptomatic fluctuations in HBV DNA to fulminant hepatic failure, liver transplantation and death. The mechanism is unknown. Areas covered: HCV/HBV coinfection is common, particularly in regions endemic for HBV. HCV and HBV utilize host factors to support replication; both viruses evade/impair host immunity. Clinical presentations of HBV reactivation during DAAs are summarized. Other causes of HBV reactivation are revisited and recent data regarding HBV reactivation are presented. Expert opinion: HBV reactivation during DAAs for HCV occurs, with life-threatening consequences in some individuals. The risk of HBV reactivation is observed in all HBV stages. The rapid removal of HCV likely alters and liberates host-viral +/- viral-viral interactions that lead to increased HBV replication. As immune reconstitution occurs with HCV removal, host recognition of HBV DNA likely ensues followed by vigorous host immune responses leading to liver injury (HBV flare). These cases highlight the importance of HBV testing prior to initiating DAA therapy, the need for close monitoring of HBV during therapy and timely administration of anti-HBV therapy to prevent serious sequelae.