Using early viral kinetics to predict antiviral outcome in response-guided pegylated interferon plus ribavirin therapy among patients with hepatitis C virus genotype 1

Abstract

HCV kinetics during treatment demonstrated strong association with the antiviral outcome of patients treated with pegylated interferon (Peg-IFN) plus ribavirin. However, the relationship between HCV kinetics and pre-treatment factors remains unclear. Of 547 patients with HCV genotype 1 treated with Peg-IFN alfa-2b plus ribavirin, 401 completed the response-guided therapy and were assessed for per protocol analysis. The sustained virologic response (SVR) rate was 53% for all patients, 60% for those with genotype TT, and 19% for those with genotype TG/GG according to IL28B (rs8099917) single nucleotide polymorphisms. The SVR rates increased with HCV decrease at week 4; 4% (2/56) with <1 log10 decrease, 13% (7/56) with 1-2 log10 decrease, 51% (44/87) with 2-3 log10 decrease, 64% (56/87) with 3-4 log10 decrease, 88% (72/82) with more than 4 log10 decrease but with detectable HCV RNA and 100% (33/33) with undetectable HCV RNA (p<0.001). Similarly, SVR rates increased step-by-step in proportion to HCV decrease in both IL28B TT and TG/GG groups, showing almost the same SVR rates for the same conditions. In multivariate analysis, age (p=0.005) and the magnitude of HCV decrease at week 4 (p<0.001) but not IL28B were associated with SVR. Advanced liver fibrosis (p=0.004) and the magnitude of HCV decrease at week 4 (p<0.001) but not IL28B were associated with non-response. The magnitude of the HCV decrease at week 4 seems to be the most reliable marker for predicting antiviral outcome after starting Peg-IFN plus ribavirin therapy.