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Case Reports
. 2022 Feb;76(2):464-469.
doi: 10.1016/j.jhep.2021.10.012. Epub 2021 Oct 23.

Safety and effectiveness of up to 3 years' bulevirtide monotherapy in patients with HDV-related cirrhosis

Alessandro Loglio  1 , Peter Ferenci  2 , Sara Colonia Uceda Renteria  3 , Christine Y L Tham  4 , Caroline Scholtes  5 , Heidemarie Holzmann  6 , Florian van Bömmel  7 , Marta Borghi  1 , Riccardo Perbellini  1 , Alessandro Rimondi  8 , Elisa Farina  8 , Elena Trombetta  9 , Maria Manunta  10 , Laura Porretti  9 , Daniele Prati  10 , Ferruccio Ceriotti  3 , Fabien Zoulim  5 , Antonio Bertoletti  4 , Pietro Lampertico  11
Affiliations
Case Reports

Safety and effectiveness of up to 3 years' bulevirtide monotherapy in patients with HDV-related cirrhosis

Alessandro Loglio et al. J Hepatol. 2022 Feb.

Abstract

The entry inhibitor bulevirtide (BLV) received conditional approval from the EMA in July 2020 for the treatment of adult patients with compensated chronic hepatitis delta. However, the effectiveness and safety of BLV administered as monotherapy beyond 48 weeks in difficult-to-treat patients with HDV-related cirrhosis is presently unknown. Herein, we describe the first patients with HDV-related compensated cirrhosis who were treated with BLV (10 mg/day as a starting dose) for up to 3 years on a compassionate use program. Patients were also monitored for HBcrAg and HBV RNA levels, and HDV- and HBV-specific T-cell markers. In the patient who stopped BLV at week 48, after achieving a virological and biochemical response, the initial virological and biochemical rebound was followed by alanine aminotransferase normalization coupled with low HDV RNA and HBsAg levels. In the 2 patients treated continuously for 3 years, virological and biochemical responses were maintained throughout the treatment period even after dose reduction. In a patient with advanced compensated cirrhosis, liver function tests significantly improved, esophageal varices disappeared, and histological/laboratory features of autoimmune hepatitis resolved. Overall, no safety issues were recorded, as bile salt increase was asymptomatic. While serum HBV RNA levels remained undetectable in all patients, HBV core-related antigen levels showed a progressive, yet modest decline during long-term BLV treatment. No HDV-specific interferon-γ-producing T cells were detected, neither after HDV reactivation (after BLV withdrawn in Patient 1) nor during 3 years of BLV treatment. In conclusion, this report shows that continuous administration of BLV monotherapy for 3 years leads to excellent virological and clinical responses in patients with HDV-related cirrhosis who had contraindications to interferon-based therapies.

Keywords: Bulevirtide; Entry inhibitor; HBV; HBV-RNA; HBcrAg; HDV; HDV-RNA; T-cell.

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Conflict of interest statement

Conflict of interest Alessandro Loglio: travel grant for MYR Pharma, speaker bureau for Gilead Sciences. Peter Ferenci: advisor and speaker bureau for Gilead Sciences, GSK, MSD, Abbvie; Florian van Bömmel: research grants from Gilead Sciences Inc., MYR Pharma and Roche Diagnostics, speaker and advisor for Gilead Sciences, Roche, Janssen, Abbvie, MSD and BMS; Antonio Bertoletti advisor for Gilead, Spring-Bank, Vir, Simcere; he is also Scientific Founder of LION TCR pte.; Fabien Zoulim: advisor for Aligos, Antios, Arbutus, Assembly, Gilead, GSK, MYR Pharma, Roche; Pietro Lampertico: advisor and speaker bureau for BMS, Roche, Gilead Sciences, GSK, MSD, Abbvie, Janssen, Arrowhead, Alnylam, Eiger, MYR Pharma, Antios, Aligos. The other authors declare that they have no competing interests. Please refer to the accompanying ICMJE disclosure forms for further details.

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