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."
03/27/07
Reference 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.
