Final results of a double-blind, placebo-controlled trial of the antifibrotic efficacy of interferon-gamma1b in chronic hepatitis C patients with advanced fibrosis or cirrhosis

Hepatology. 2007 Mar;45(3):569-78. doi: 10.1002/hep.21561.


Interferon-gamma1b (IFN-gamma1b) is a pleiotropic cytokine that displays antifibrotic, antiviral, and antiproliferative activity. A total of 502 patients with compensated liver disease and an Ishak fibrosis score of 4-6 were randomized in a double-blind, placebo-controlled study, and 488 of these patients received subcutaneous injections of IFN-gamma1b 100 microg (group 1, n=169), IFN-gamma1b 200 microg (group 2, n=157), or placebo (group 3, n=162) 3 times a week for 48 weeks. Most patients (83.6%) had cirrhosis at baseline (Ishak score=5 or 6). Posttreatment liver biopsies were assessed in a blinded fashion for a reduction of 1 or more Ishak points (primary endpoint). Four hundred twenty patients with pretreatment and posttreatment liver biopsies were evaluable and showed no improvement in Ishak score between the 3 treatment groups (12.1%, 12.4%, and 16% of patients in groups 1, 2, and 3, respectively; P>0.05). Analysis of IFN-gamma-inducible biomarkers revealed that interferon-inducible T cell-alpha chemoattractant (ITAC), an IFN-gamma-inducible CXCR3 chemokine was an independent predictor of stable or improving Ishak score. IFN-gamma1b was well tolerated. There were similar numbers of deaths in all 3 arms (5, 5, and 4, respectively), and most were related to complications of cirrhosis.

Conclusion: IFN-gamma1b therapy was not able to reverse fibrosis in patients with advanced liver disease for 1 year. Subgroups of patients with elevated ITAC levels and perhaps less advanced disease may be considered for future studies with IFN-gamma1b.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Biomarkers / analysis
  • Clinical Trials, Phase II as Topic
  • Disease Progression
  • Double-Blind Method
  • Female
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferon-gamma / adverse effects
  • Interferon-gamma / therapeutic use*
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / etiology
  • Male
  • Middle Aged
  • Prospective Studies
  • RNA, Viral / metabolism
  • Recombinant Proteins


  • Antiviral Agents
  • Biomarkers
  • RNA, Viral
  • Recombinant Proteins
  • Interferon-gamma