Genetic predictors of response to treatment of chronic hepatitis C virus infection in patients from southern Italy

Abstract

Various clinical and genetic factors affect response to antiviral treatment of chronic hepatitis C virus (HCV) infection. The IL28B single-nucleotide polymorphism (SNP) rs12979860 is associated with a sustained viral response (SVR), and the suppressor cytokine signaling 3 (SOCS3) gene is over-expressed in HCV-1b non-responders. The aim of this study was to look for correlations between genetic, clinical and viral factors implicated in response to antiviral treatment in chronic HCV infection. We evaluated 190 controls and 148 HCV-infected patients (102 HCV-1 and 46 HCV-2). Demographic, metabolic and histological features related to antiviral treatment were recorded. Univariate and multivariate analyses were used to identify correlations between the genetic and non-genetic features examined and response to antiviral treatment. IL28B expression was higher in CC SNPs versus other alleles in controls (P=0.01) and this difference was associated with viral infection (HCV vs controls P=0.006), particularly in HCV-2 patients (P=0.003). SOCS3 and IL28B expression was correlated with controls (P=0.011), whereas there was an inverse correlation between the expression of the two genes in HCV patients and HCV-1b non-responders (P=0.014 and P=0.03, respectively). Multivariate analysis showed that the only independent SVR predictive factor was rapid virological response. The frequency of IL28B rs12979860 SNP alleles in controls (C allele=71.1% and T allele= 28.9%) was comparable to that of the HCV population (C allele=66.6% and T allele=33.4%). Rapid virological response seems to be the only significant independent predictor of an SVR to antiviral treatment. The inverse correlation between SOCS3 and IL28B expression in genotype 1b non-responders suggests that SOCS3 may affect IL28B expression thereby influencing response to antiviral therapy.