Final results of a double-blind, placebo-controlled trial of the antifibrotic efficacy of interferon-γ1b in chronic hepatitis C patients with advanced fibrosis or cirrhosis

✍ Scribed by Paul J. Pockros; Lennox Jeffers; Nezam Afdhal; Zachary D. Goodman; David Nelson; Robert G. Gish; K. Rajender Reddy; Robert Reindollar; Maribel Rodriguez-Torres; Sarah Sullivan; Lawrence M. Blatt; Sima Faris-Young

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 383 KB
• Volume: 45
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.21561

✦ Synopsis

Interferon-␥1b (IFN-␥1b

) 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-␥1b 100 g (group 1, n ‫؍‬ 169), IFN-␥1b 200 g (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-␥-inducible biomarkers revealed that interferon-inducible T cell-alpha chemoattractant (ITAC), an IFN-␥inducible CXCR3 chemokine was an independent predictor of stable or improving Ishak score. IFN-␥1b 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-␥1b 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-␥1b. (HEPATOLOGY 2007