Efficacy and safety of boceprevir-based triple therapy in HCV cirrhotic patients awaiting liver transplantation (ANRS HC29 BOCEPRETRANSPLANT)

Clin Res Hepatol Gastroenterol. 2017 Feb;41(1):56-65. doi: 10.1016/j.clinre.2016.06.006. Epub 2016 Aug 20.

Abstract

Background and aims: In this French multicentre, open-label study, we analyzed the efficacy, safety and patient-reported outcomes of a boceprevir-based triple therapy in HCV genotype 1 cirrhotic patients awaiting liver transplantation (LT).

Methods: Patients received PEG-IFN/ribavirin (RBV) for 48 weeks (W) and boceprevir from W4 to W48 or until LT.

Results: Fifty-one patients (80% males, median age: 56 years) were included. Fifty-seven percent had hepatocellular carcinoma and 43% end-stage liver disease. At enrolment, the median MELD score was 9 (range: 6-18); the Child-Pugh score was A in 65%, B in 35% and C in 2%. Therapy was discontinued because of severe adverse events (SAEs) in 39% of cases and virological inefficacy in 24%. 16% of patients had undetectable HCV RNA 24 weeks after the end of treatment (SVR24). LT was performed in 18 patients (35%). HCV RNA was undetectable in 16.6% at LT. Seven patients (14%) died and three deaths were attributed to treatment. SAEs (n=129) were observed in 84% of patients. Twenty-four percent of patients developed severe infections. Albumin<35g/L was independently associated with severe infection. Compared with baseline values, a significant decrease (P=0.02) of the physical dimension of health-related quality of life was observed between W4 and W24. The mean (95% CI) number of self-reported symptoms doubled during treatment (from 6.3 [4.8-7.7] to 11.8 [9.3-14.3]; P<0.001).

Conclusions: The safety of the PEG-IFN/RBV/boceprevir combination is poor in patients awaiting LT, with a high risk of severe infection. Moreover, the limited efficacy confirms the indication for IFN-free combinations in these patients.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • Carcinoma, Hepatocellular / complications
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / mortality
  • Drug Therapy, Combination
  • Female
  • France
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / diagnosis
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / mortality
  • Humans
  • Interferon-alpha / therapeutic use
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / mortality
  • Liver Cirrhosis / virology
  • Liver Neoplasms / complications
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / mortality
  • Liver Transplantation*
  • Male
  • Middle Aged
  • Proline / analogs & derivatives*
  • Proline / therapeutic use
  • Quality of Life
  • Retrospective Studies
  • Ribavirin / therapeutic use
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Interferon-alpha
  • Ribavirin
  • N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide
  • Proline