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

ABSTRACT

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.

KEYWORDS:

• Direct acting antiviral (DAA) therapy
• HBV flare
• HBV reactivation
• Hepatitis B virus (HBV)
• Hepatitis C virus (HCV) coinfection

Article highlights

• HCV/HBV coinfection is common, particularly in areas where HBV is endemic

• Newer direct-acting antiviral agents (DAAs) are extremely effective in eradicating HCV (>95%) but have no activity against HBV, in contrast to IFN-based therapy

• In vitro studies and in vivo studies have suggested viral interference between HCV and HBV replication, most likely mediated by host factors, although some studies have demonstrated inhibitory effects of viral proteins on the other virus

• DAA therapy has been associated with HBV reactivation in HCV patients infected with HBV and HCV patients with a history of past HBV infection

• HBV reactivation during DAA therapy occurred during therapy and was associated with a more severe clinical phenotype, including fulminant liver failure requiring liver transplantation and death

• All HCV patients should be assessed for HBV coinfection or HBV past infection, and should undergo regular monitoring of HBV DNA and ALT during DAA therapy

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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Funding

This paper has not been funded.