HCV Core Gene Polymorphisms Correlate with Liver Fibrosis but Not Sustained Virological Response in Patients with Genotype 1 Infection

Abstract

Amino acid (aa) substitutions in genotype 1 HCV core region (HCV-CR) serve as a negative predictor of treatment responses in Japanese chronic hepatitis C (CHC) patients. Whether this phenomenon could be extrapolated to non-Japanese patients remains unclear. We evaluated the effect of aa substitutions in HCV-CR on clinicopathological features and treatment responses in Taiwanese patients. Clinical and serial virological data were collected from 147 consecutive Taiwanese HCV genotype 1 patients who received pegylated interferon plus ribavirin therapy. Quantification of HCV RNA and sequences of HCV-CR were determined by molecular methods. Of 147 patients, 90 (61.2%) attained rapid virological response (RVR) and 97 (66.0%) attained sustained virological response (SVR). Patients without aa substitutions in HCV-CR (coreWW) had a higher SVR than those with both aa70 and aa91 substitutions (coreMM; 70.5% versus 45.0%; P=0.039). Moreover, coreMM was associated with a higher γ-glutamyl transpeptidase level (P=0.026) as well as more severe liver fibrosis (P=0.027) than coreWW, and patients with aa70 substitution (coreMW) were associated with more severe liver steatosis and fibrosis than those without (P=0.020 and P=0.002, respectively). In multivariate analyses, lower pretreatment body mass index, milder liver fibrosis, 48 weeks of treatment and RVR, but not aa substitutions in HCV-CR, predicted a higher SVR rate. Although aa substitution in genotype 1 HCV-CR is associated with more severe liver fibrosis and might be a negative predictor of SVR in Taiwanese CHC patients with interferon-based therapy, RVR and other clinical factors outweigh its role in predicting SVR.