Hepatitis C virus survival curve analysis in naïve patients treated with PegInterferon α-2b plus ribavirin. A randomized controlled trial for induction with high doses of PegInterferon and predictability of sustained viral response from early virologic data

Abstract

Aim. To evaluate the significance of induction with high doses of pegylated interferon α-2b (Peg-IFNα-2b) and the predictability of sustained virologic response (SVR) in naïve patients with chronic hepatitis C. Methods. 188 consecutive naïve patients with chronic hepatitis C were enrolled in a randomised controlled clinical trial. Patients were randomised to receive either Peg-IFNα-2b 3.0 mcg/kg QW x 12 weeks followed by 1.5 mcg/kg QW x 36 weeks plus 800-1200 mg ribavirin (Arm A) or Peg-IFNα-2b 1.5 mcg/kg QW x 48 weeks plus 800-1200 mg ribavirin (Arm B). HCV-RNA was obtained at 0, 4, 8, 12, 16, 24, 48 and 72 weeks. Differences between schemes were evaluated by Kaplan-Meier curves. Predictability of SVR was assessed by two-way contingency table analysis and ROC curve analysis. Results. From 176 patients, 75 had genotype 1, 15 genotype 2, 75 genotype 3 and 11 genotype 4. No statistical significance emerged in HCV-RNA positivity, side effects and withdrawals between schemes. Patients with genotype 1 achieved lower SVR (46.6%) in comparison to patients with genotypes 2/3 (94.1%, p<0.001) and 4 (90.9%, p=0.002). The most appropriate time for estimation of SVR for genotype 1 is week 8 (accuracy=0.84, AUC=0.90) while predictability increases with time in genotypes 2/3, reaching maximum accuracy=0.93 and AUC=0.76 at week 16. Conclusion. Induction with high doses of Peg-IFNα-2b does not preclude better outcome and rapid virologic response at 4 weeks of treatment sufficiently predicts SVR. These findings might be useful in an attempt to gain supportive evidence for decision making in difficult-to-treat patients.