TY - JOUR
T1 - Safety and effectiveness of up to 3 years’ bulevirtide monotherapy in patients with HDV-related cirrhosis
AU - Loglio, Alessandro
AU - Ferenci, Peter
AU - Uceda Renteria, Sara Colonia
AU - Tham, Christine Y.L.
AU - Scholtes, Caroline
AU - Holzmann, Heidemarie
AU - van Bömmel, Florian
AU - Borghi, Marta
AU - Perbellini, Riccardo
AU - Rimondi, Alessandro
AU - Farina, Elisa
AU - Trombetta, Elena
AU - Manunta, Maria
AU - Porretti, Laura
AU - Prati, Daniele
AU - Ceriotti, Ferruccio
AU - Zoulim, Fabien
AU - Bertoletti, Antonio
AU - Lampertico, Pietro
N1 - Funding Information:
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.
Funding Information:
This work was supported by a grant from “Ricerca Corrente RC2021/105-01”, Italian Ministry of Health , and by a grant from the French National Research Agency Investissements d’Avenir Progam (CirB-RNA project-ANR-17-RHUS-0003).
Funding Information:
This work was supported by a grant from ?Ricerca Corrente RC2021/105-01?, Italian Ministry of Health, and by a grant from the French National Research Agency Investissements d'Avenir Progam (CirB-RNA project-ANR-17-RHUS-0003).
Publisher Copyright:
© 2021 European Association for the Study of the Liver
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Bulevirtide
KW - Entry inhibitor
KW - HBcrAg
KW - HBV
KW - HBV-RNA
KW - HDV
KW - HDV-RNA
KW - T-cell
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UR - http://www.scopus.com/inward/citedby.url?scp=85120726167&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2021.10.012
DO - 10.1016/j.jhep.2021.10.012
M3 - Article
AN - SCOPUS:85120726167
VL - 76
SP - 464
EP - 469
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 2
ER -