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

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

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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.

Original languageEnglish
Pages (from-to)834-839
JournalJournal of Hepatology
Volume71
Issue number4
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Hepatitis Delta Virus
Hepatitis B virus
Fibrosis
Safety
Tenofovir
Liver Function Tests
RNA
Bile Acids and Salts
T-Lymphocytes
Christianity
Autoimmune Hepatitis
alpha-Fetoproteins
Portal Hypertension
Therapeutics
Hepatitis B Surface Antigens
myrcludex-B
Alanine Transaminase
Immunoglobulins
Immunoglobulin G
DNA

Keywords

  • Bulevirtide
  • Coinfection
  • Entry inhibitor
  • HBV
  • HDV
  • HDV RNA
  • Hepatitis delta
  • Myrcludex-B
  • NTCP
  • T cell

ASJC Scopus subject areas

  • Hepatology

Cite this

@article{6574fd1b046f423eb48df57ea1ef425c,
title = "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.",
keywords = "Bulevirtide, Coinfection, Entry inhibitor, HBV, HDV, HDV RNA, Hepatitis delta, Myrcludex-B, NTCP, T cell",
author = "Alessandro Loglio and Peter Ferenci and {Uceda Renteria}, {Sara Colonia} and Tham, {Christine Y.L.} and {van B{\"o}mmel}, Florian and Marta Borghi and Heidemarie Holzmann and Riccardo Perbellini and Elena Trombetta and Silvia Giovanelli and Letizia Greco and Laura Porretti and Daniele Prati and Ferruccio Ceriotti and Giovanna Lunghi and Antonio Bertoletti and Pietro Lampertico",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.jhep.2019.07.003",
language = "English",
volume = "71",
pages = "834--839",
journal = "Journal of Hepatology",
issn = "0168-8278",
publisher = "Elsevier B.V.",
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T1 - Excellent safety and effectiveness of high-dose myrcludex-B monotherapy administered for 48 weeks in HDV-related compensated cirrhosis

T2 - A case report of 3 patients

AU - Loglio, Alessandro

AU - Ferenci, Peter

AU - Uceda Renteria, Sara Colonia

AU - Tham, Christine Y.L.

AU - van Bömmel, Florian

AU - Borghi, Marta

AU - Holzmann, Heidemarie

AU - Perbellini, Riccardo

AU - Trombetta, Elena

AU - Giovanelli, Silvia

AU - Greco, Letizia

AU - Porretti, Laura

AU - Prati, Daniele

AU - Ceriotti, Ferruccio

AU - Lunghi, Giovanna

AU - Bertoletti, Antonio

AU - Lampertico, Pietro

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - Bulevirtide

KW - Coinfection

KW - Entry inhibitor

KW - HBV

KW - HDV

KW - HDV RNA

KW - Hepatitis delta

KW - Myrcludex-B

KW - NTCP

KW - T cell

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U2 - 10.1016/j.jhep.2019.07.003

DO - 10.1016/j.jhep.2019.07.003

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JO - Journal of Hepatology

JF - Journal of Hepatology

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