A case of HBV-induced liver failure in the REEF-2 phase II trial: Implications for finite treatment strategies in HBV 'cure'

J Hepatol. 2022 Jul;77(1):245-248. doi: 10.1016/j.jhep.2022.03.006. Epub 2022 Mar 28.


Nucleoside analogues are the mainstay of treatment for patients with chronic HBV infection but have no direct effect on covalently closed circular DNA. Long-term HBV viral suppression is now routine, but the desirable endpoint of functional cure is rarely achieved. Newer therapies, targeting other aspects of the replicative life cycle of HBV, present opportunities to deliver finite therapy and HBV 'cure'. This is an area of keen focus for the HBV community. We describe a severe case of hepatitis B reactivation, occurring shortly after the withdrawal of a nucleoside analogue within the protocol of a clinical trial (REEF-2). Despite best supportive care and prompt re-introduction of tenofovir, the patient developed subacute liver failure, requiring emergency orthotopic liver transplantation. As we strive to achieve HBV cure, this case highlights the potential risks of finite therapy and highlights the need for improved biomarker-driven strategies and re-evaluation of study protocols.

Keywords: HBV; discontinuation; liver failure; nucleoside analogue.

Publication types

  • Case Reports
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • DNA, Viral
  • Hepatic Insufficiency*
  • Hepatitis B virus / genetics
  • Hepatitis B, Chronic* / complications
  • Hepatitis B, Chronic* / drug therapy
  • Humans
  • Liver Failure*
  • Male
  • Middle Aged
  • Nucleosides / pharmacology
  • Tenofovir / pharmacology
  • Tenofovir / therapeutic use


  • Antiviral Agents
  • DNA, Viral
  • Nucleosides
  • Tenofovir