Sustained virologic response and IL28B single-nucleotide polymorphisms in patients with chronic hepatitis C treated with pegylated interferon alfa and ribavirin.

Abstract

Hepatitis C virus (HCV) infection is a global health problem which can lead to liver cirrhosis or hepatocellular carcinoma in one-fifth of chronically infected patients. The study group consisted of 123 patients: 90 with HCV mono- and 33 with HIV/HCV co-infection, who were treated with pegylated interferon alfa (Peg-IFN-α) and ribavirin. We analyzed selected pretreatment factors: age, sex, HIV/HCV co-infection, grade of inflammation, necrotic changes and fibrosis in histological analysis of liver bioptates, HCV viral load, HCV genotypes, and single nucleotide polymorphisms (SNPs) of IL28B and tried to find out which of them influence sustained virological response (SVR). The IL28B SNP C/T (rs12979860) was analyzed using Custom(®) SNP Genotyping Assays (Applied Biosystems). Multivariate analysis demonstrated that after adjusting for the other variables three predictors independently influence SVR, namely genotype 3 of HCV, presence of the CC genotype and age >40 years (OR respectively 15.14, 3.62, and 0.36). HCV mono-infected patients were infected with HCV genotype 3 or 4 less frequently (p=0.0001) compared to HIV/HCV co-infected individuals. In patients with HIV/HCV co-infection the CC variant occurred more frequently whereas CT was found less frequently (p=0.001, p=0.0146, respectively). In patients with HIV/HCV co-infection, 3 and 4 genotype of HCV occurred more frequently compared to patients with HCV mono-infection (p=0.0001). These data suggest that age, HCV genotype and IL28B polymorphism are useful for prediction of the response to treatment with Peg-IFN-α and ribavirin. The more frequent occurrence of HCV genotypes 3 or 4 in patients with HIV/HCV co-infection could be associated with the route of transmission.