Interferon Gamma Does Not Reverse Fibrosis in Hepatitis C Patients with Advanced Liver Disease

Along with therapies that suppress HCV replication, there is also a need for agents that help retard or reverse liver fibrosis in patients with chronic hepatitis C.

One agent that has been studied for this purpose is interferon gamma-1b (IFN-gamma-1b), a pleiotropic cytokine that displays antiviral, anti-fibrotic, and anti-proliferative activity.

The present placebo-controlled study, reported in the March 2007 issue of Hepatology, included hepatitis C patients with compensated liver disease and Ishak fibrosis scores of 4-6. Most (83.6%) had cirrhosis at baseline (Ishak score 5 or 6).

Participants were randomly assigned to receive subcutaneous injections of IFN-gamma-1b 100 mcg (n = 169), IFN-gamma-1b 200 mcg (n = 157), or placebo (n = 162) 3 times weekly for 48 weeks. Post-treatment liver biopsies were assessed in a blinded fashion for a reduction of 1 or more Ishak points.

 Results

	Among 420 patients with paired pre- and post-treatment liver biopsy results, there was no significant difference in proportions with improved Ishak scores among the 3 treatment groups (12.1%, 12.4%, and 16%, respectively; P>0.05).
	Analysis of IFN-gamma-inducible biomarkers revealed that interferon-inducible T-cell-alpha chemo-attractant (ITAC), an IFN-gamma-inducible CXCR3 chemokine, was an independent predictor of stable or improving Ishak score.
	IFN-gamma-1b was well tolerated overall.
	There was a similar number of deaths in all 3 treatment arms (5, 5, and 4, respectively), mostly due to complications of cirrhosis.

Conclusion

"IFN-gamma-1b therapy was not able to reverse fibrosis in patients with advanced liver disease for 1 year," the authors concluded. "Subgroups of patients with elevated ITAC levels and perhaps less advanced disease may be considered for future studies with IFN-gamma-1b."

PJ Pockros, L Jeffers, N Afdhal, and others. 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 45(3): 569-578. March 2007.