Interferon-gamma with peginterferon alpha-2a and ribavirin in nonresponder patients with chronic hepatitis C (ANRS HC16 GAMMATRI)

J Gastroenterol Hepatol. 2013 Feb;28(2):329-34. doi: 10.1111/jgh.12060.

Abstract

Background and aim: Interferon-gamma-1b (IFN-γ-1b) improves alpha interferon (IFN-α) inhibition of hepatitis C virus (HCV) replication in replicon system. We described virological response after addition of IFN-γ to a combination of ribavirin/peginterferon (PEG-IFN)-α-2a or α-2b.

Methods: In this non-comparative, multicenter trial, patients chronically infected by HCV who were nonresponders to a previous treatment by PEG-IFN and ribavirin were restarted on a regimen of PEG-IFN-α-2a (180 μg/week) + ribavirin (1000-1200 mg/day) for 16 weeks. If HCV-RNA decreased less than 2 log(10) copies/mL (nonresponders), and if PEG-IFN-α-2a and ribavirin dosages were unchanged while tolerance was good, IFNγ-1b (100 μg three times per week) was added for the last 32 weeks of treatment. Virological response was evaluated at week 28 (12 weeks after initiation of IFN-γ-1b).

Results: Among the 48 patients started on dual therapy, 23 patients (47%) were nonresponders at week 12 and received IFN-γ-1b from week 16 onward. Their mean HCV-RNA (log(10) IU/mL) was 6.83 at baseline, 5.81 at week 12, and 5.63 at week 28. No patient reached undetectable HCV-RNA at week 28 (upper bound of 95% confidence interval: 14.8%); none had a decrease > 1 log(10) IU/mL. One case of grade 4 neutropenia was reported.

Conclusion: Among the strictly selected nonresponders, IFN-γ-1b (at a dosage of 100 μg thrice a week) in combination with PEG-IFN-α-2a and ribavirin failed to show virological efficacy.

Trial registration: ClinicalTrials.gov NCT00148863.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Biomarkers / blood
  • Chi-Square Distribution
  • Drug Therapy, Combination
  • Female
  • France
  • Hepatitis C / genetics
  • Hepatitis C, Chronic / diagnosis
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferon-alpha / adverse effects
  • Interferon-alpha / therapeutic use*
  • Interferon-gamma / adverse effects
  • Interferon-gamma / therapeutic use*
  • Male
  • Middle Aged
  • Pilot Projects
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / therapeutic use*
  • RNA, Viral / blood
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • Ribavirin / adverse effects
  • Ribavirin / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Viral Load

Substances

  • Antiviral Agents
  • Biomarkers
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • interferon gamma-1b
  • Polyethylene Glycols
  • Ribavirin
  • Interferon-gamma
  • peginterferon alfa-2a

Associated data

  • ClinicalTrials.gov/NCT00148863