Excellent safety and effectiveness of high-dose myrcludex-B monotherapy administered for 48 weeks in HDV-related compensated cirrhosis: A case report of 3 patients.

Abstract

Short-term administration of the entry inhibitor myrcludex-B (MyrB) has been shown to be safe and effective in phase II studies in patients coinfected with hepatitis B virus (HBV) and hepatitis delta virus (HDV). However, its effectiveness and safety are unknown during long-term and high-dose treatment of patients with compensated cirrhosis in real-life settings. Herein, we describe the first 3 European patients with HDV-related compensated cirrhosis who were treated with MyrB 10 mg/day for 48 weeks as a compassionate therapy. Liver function tests, bile acids, and virological markers were monitored every 4 weeks. HBV/HDV-specific T cell quantity (up to 48 and 36 weeks) and HBV RNA levels were also assessed in 2 cases. During MyrB treatment, HDV RNA levels progressively declined from 4.4 and 5.6 logs IU/ml to undetectability in 2 cases, and from 6.8 log copies/ml to 500 copies/ml for the other patient. Alanine aminotransferase normalised after 20, 12 and 28 weeks, respectively. A significant improvement in features of portal hypertension, liver function tests and alpha-fetoprotein levels were documented in 2 cases. In the male patient with histological and clinical stigmata of autoimmune hepatitis, IgG and immunoglobulins rapidly normalised. No significant changes in HBV surface antigen levels and circulating HBV/HDV-specific T cells were demonstrated; HBV DNA and HBV RNA levels remained undetectable throughout the study period. MyrB was well tolerated; patients remained fully asymptomatic despite a significant increase of bile acids. In conclusion, this report shows excellent safety and effectiveness of a 48-week course of MyrB 10 mg/day, combined with tenofovir disoproxil fumarate, for the treatment of HDV-related compensated cirrhosis.

• Authors: Alessandro Loglio, Peter Ferenci, Sara Colonia Uceda Renteria, Christine Y L Tham, Florian van Bömmel, Marta Borghi, Heidemarie Holzmann, Riccardo Perbellini, Elena Trombetta, Silvia Giovanelli, Letizia Greco, Laura Porretti, Daniele Prati, Ferruccio Ceriotti, Giovanna Lunghi, Antonio Bertoletti, Pietro Lampertico
• Journal: Journal of hepatology (J Hepatol) Vol. 71 Issue 4 Pg. 834-839 (10 2019) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 31302176 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antiviral Agents
• Lipopeptides
• RNA, Viral
• myrcludex-B
• Tenofovir

Topics

• Aged
• Antiviral Agents (administration & dosage, adverse effects)
• Coinfection (drug therapy)
• Dose-Response Relationship, Drug
• Drug Monitoring (methods)
• Drug Therapy, Combination
• Duration of Therapy
• Female
• Hepatitis B virus (drug effects, genetics, isolation & purification)
• Hepatitis B, Chronic (blood, physiopathology, therapy)
• Hepatitis D (blood, physiopathology, therapy, virology)
• Hepatitis Delta Virus (drug effects, genetics, isolation & purification)
• Humans
• Lipopeptides (administration & dosage)
• Liver Cirrhosis (blood, therapy, virology)
• Liver Function Tests (methods)
• Male
• Middle Aged
• Patient Acuity
• RNA, Viral (isolation & purification)
• Tenofovir (administration & dosage, adverse effects)
• Treatment Outcome