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.
Aged
Antiviral Agents
/ administration & dosage
Coinfection
/ drug therapy
Dose-Response Relationship, Drug
Drug Monitoring
/ methods
Drug Therapy, Combination
Duration of Therapy
Female
Hepatitis B virus
/ drug effects
Hepatitis B, Chronic
/ blood
Hepatitis D
/ blood
Hepatitis Delta Virus
/ drug effects
Humans
Lipopeptides
/ administration & dosage
Liver Cirrhosis
/ blood
Liver Function Tests
/ methods
Male
Middle Aged
Patient Acuity
RNA, Viral
/ isolation & purification
Tenofovir
/ administration & dosage
Treatment Outcome
Bulevirtide
Coinfection
Entry inhibitor
HBV
HDV
HDV RNA
Hepatitis delta
Myrcludex-B
NTCP
T cell
Journal
Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
01
05
2019
revised:
15
06
2019
accepted:
08
07
2019
pubmed:
16
7
2019
medline:
15
12
2020
entrez:
15
7
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31302176
pii: S0168-8278(19)30411-8
doi: 10.1016/j.jhep.2019.07.003
pii:
doi:
Substances chimiques
Antiviral Agents
0
Lipopeptides
0
RNA, Viral
0
myrcludex-B
0
Tenofovir
99YXE507IL
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
834-839Informations de copyright
Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.