Hyporesponsiveness to PegIFNα2B plus ribavirin in patients with hepatitis C-related advanced fibrosis

Background & Aims

The success of pegylated-interferon (PegIFN)/ribavirin (Rbv) therapy of chronic hepatitis C is compromised by liver fibrosis. Whether fibrosis equally affects the two PegIFNα-based therapies is unknown. To assess the response to the two PegIFN regimens in patients with different degree of liver fibrosis.

Methods

A sub-analysis of the MIST study: 431 consecutive naïve patients randomly assigned, based on HCV genotype, to receive either (A) PegIFNα2a 180μg/wk plus daily Rbv 800–1200mg or (B) PegIFNα2b 1.5μg/kg/week plus daily Rbv 800–1200mg, were stratified according to Ishak staging (S) into mild (S0–S2) or moderate (S3, S4) fibrosis and cirrhosis (S5, S6).

Results

In A the sustained virological response (SVR) rates were not significantly influenced by fibrosis stage (71% in S0–S2, 66% in S3, S4, 53% in S5, S6, p=0.12), compared to B where the SVR rates differed according to fibrosis stage (65%, 46%, and 38%, p=0.004, respectively). This was even more so in HCV-1/4 patients treated with PegIFNα2b where the SVR rates were twice as many in S0–S2 vs. S⩾3 (44% vs. 22%, p=0.02), while in A the SVR rates were similar between the two fibrosis subgroups (S0–S2: 47% vs. S⩾3: 48%, p=0.8). By logistic regression analysis genotype 1/4 and lack of rapid virological response were independent predictors of treatment failure in both treatment groups, while S⩾3 fibrosis was associated to PegIFNα2b treatment failure, only (OR 2.83, 95% CI 1.4–5.68, p=0.004).

Conclusions

Liver fibrosis was an independent moderator of treatment outcome in patients receiving PegIFNα2b, not in those receiving PegIFNα2a.

Abbreviations: HCV, hepatitis C virus, PegIFN, pegylated-interferon, Rbv, ribavirin, Peg, polyethylene glycol, SVR, sustained virological response, RVR, rapid virological response, cEVR, complete early virological response, ETR, end of treatment response, S, Ishak fibrosis score, ITT, intention-to-treat

Keywords: Hepatitis C virus, Liver fibrosis, Pegylated interferon, Ribavirin, Sustained virological response