γ-glutamyltransferase and rapid virological response as predictors of successful treatment with experimental or standard peginterferon-α-2b in chronic hepatitis C non-responders

Background: High-dose peginterferon-α (PegIFN-α) induction and prolongation of therapy may be an option to improve sustained virological response (SVR) rates among hepatitis C virus (HCV) non-responders, although a higher and a longer dosing of PegIFN-α may intensify side effects. Methods: We randomized 53 patients, who previously failed with standard IFN-α ± ribavirin, to a high-dose induction and an extended regimen with PegIFN-α-2b [3.0 μg/kg once weekly (q.w.) 12 weeks → 2.0 μg/kg q.w. 12 weeks → 1.5 μg/kg q.w. 48 weeks] or a standard regimen (1.5 μg/kg q.w. 48 weeks). All patients received daily weight-based ribavirin (800-1200 m/day). The short-form 36 health survey was used to evaluate health-related quality of life (HRQL). Results: Intention-to-treat analysis showed no significant difference in SVR rate (44% vs. 37%, P = 0.62) and relapse rate (9% vs. 31%, P = 0.17) between experimental and standard treatment. Overall, 80% of the [positive predictive value (PPV)] patients with rapid virological response (RVR, HCV-RNA negativity at week 4) achieved SVR. No significant dose-related differences in HRQL were seen between both groups. At baseline, genotype 2 or 3 [odds ratio (OR): 7.4, 95% confidence interval (CI): 1.4-33.3, P = 0.01] and γ-glutamyltransferase (GGT) levels <2 × ULN (upper limit of normal) (OR: 6.76, 95% CI: 1.5-31.3, P = 0.009) were significantly associated with SVR. Multivariate logistic regression at week 4 showed that only baseline GGT <2 × ULN (OR: 7.3, 95% CI: 1.4-38.5, P = 0.01) and RVR (OR: 15.6, 95% CI: 3.2-76.9, P < 0.001) were independently predictive for SVR. Conclusion: Retreatment with PegIFN-α-2b and ribavirin for a minimum of 48 weeks should be considered in all patients unresponsive to previous IFN-based therapies. Baseline GGT values and RVR are highly predictive for retreatment outcome.

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