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

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.

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Conflicts of interest Kosh Agarwal has received grants from Abbott and MSD; has served as a consultant for Janssen, Assembly, Arbutus, Immunocore, Roche, BMS, BI, Novartis, Shinoigi, and Sobi; has served as a speaker for Gilead and Sobi; and has served on a data safety monitoring board or advisory board for Drug Farm, NUC-B, and Aligos. James Lok and Ivana Carey have no disclosures to report. Yatin Shivkar, Michael Biermer, and Isabelle Lonjon-Domanec are full-time employees of Janssen Research and Development. Thomas Berg has received grants from Abbvie, BMS, Gilead, MSD/Merck, Humedics, Intercept, Merz, Novartis, and Sequana Medical; has served as a consultant for Abbvie, Alexion, Bayer, Gilead, Eisai, Intercept, Ipsen, Janssen, MSD/Merck, Novartis, Roche, Sequana Medical, and Shionogi; has served as a speaker for Abbvie, Alexion, Bayer, Gilead, Eisai, Intercept, Ipsen, Janssen, MedUpdate GmbH, MSD/Merck, Novartis, and Sequana Medica; has received travel support from Gilead, Abbvie, Intercept, and Janssen; has served on a data safety monitoring board or advisory board for Janssen; and has served as Secretary General of EASL. Please refer to the accompanying ICMJE disclosure forms for further details.