Study of Interleukin-28B Polymorphism as a Predictive Factor for the Treatment Response of Interferon in Egyptian Patients with Chronic Hepatitis C Virus

Abstract

The highest prevalence of Hepatitis C virus (HCV) infection is reported in Egypt with a high burden of morbidity and mortality due to progress to cirrhosis and hepatocellular carcinoma (HCC). the natural course of infection, patient response to antiviral therapy as well as the clinical outcome of HCV-induced liver disease were all linked to gene polymorphisms in inflammatory cytokines producing genes. It was evident that host genetic factors determine the treatment induced viral clearance as well as spontaneous response. The documented association between IL28B genotypes with the treatment efficacy of pegylated interferon-alpha (PEG-IFN)/ ribavirin (RBV) antiviral therapy in patients infected with HCV genotype 1 or 4 has motivated the current study that was conducted in the Oncology Diagnostic Unit, Faculty of Medicine, Ain Shams University The aim of this study was to determine the prevalence of different type of single nucleotide polymorphism in gene IL28B and analyze the impact of this IL-28B polymorphism on early treatment response, sustained virological response (SVR) as well as late virological response (LVR) in Egyptian patients with HCV. Fifty Egyptians patients with HCV genotype 4 treated with PEG-IFN/ RBV were assessed at 12 and 24 weeks of therapy, the polymorphisms of rs8099917 (G/T) and of rs12979860 of IL28B gene were determined using TaqMan-based quantitative polymerase chain reaction. Although the TT genotype was the most frequent (58%) among rs12979860 of IL28B gene, the highest SVR was achieved for patients with favorable CC genotype (86%) in contrast to CT and TT genotypes. A high significant association was observed between the positivity of T allele and LVR to INF/RBV. No significant associations were detected between the positivity of C allele and either SVR or LVR or the positivity of T allele and SVR. Among IL28b (rs8099917 G/T) genotypes TT genotype was the most predominant genotype (64%). TT and GT genotypes showed high tendency for response to INF/RBV at 12 weeks (p=0.04). HCV patients who were negative for G allele showed a significantly higher tendency to respond at 12 weeks. No significant associations were detected between the positivity of T allele and either SVR or LVR or between positivity of G allele and late viral response at 24 weeks. It was evident from the current study results that IL 28b polymorphism is highly associated with SVR to therapy in the Egyptian population infected with HCV genptype 4.