Premium
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
Author(s) -
Pockros Paul J.,
Jeffers Lennox,
Afdhal Nezam,
Goodman Zachary D.,
Nelson David,
Gish Robert G.,
Reddy K. Rajender,
Reindollar Robert,
RodriguezTorres Maribel,
Sullivan Sarah,
Blatt Lawrence M.,
FarisYoung Sima
Publication year - 2007
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21561
Subject(s) - medicine , gastroenterology , cirrhosis , placebo , fibrosis , cxcr3 , clinical endpoint , alpha interferon , interferon , randomized controlled trial , immunology , pathology , chemokine , inflammation , alternative medicine , chemokine receptor
Interferon‐γ1b (IFN‐γ1b) 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‐γ1b 100 μg (group 1, n = 169), IFN‐γ1b 200 μg (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‐γ–inducible biomarkers revealed that interferon‐inducible T cell–alpha chemoattractant (ITAC), an IFN‐γ–inducible CXCR3 chemokine was an independent predictor of stable or improving Ishak score. IFN‐γ1b 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‐γ1b 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‐γ1b. (H EPATOLOGY 2007;45:569–578.)