Amino Acid Substitution in Hepatitis C Virus Core and Genetic Variation in Interleukin 28? Gene and their Correlation to Interferon Treatment Failure in Chronic HCV Egyptian Patients

Hepatitis C virus becomes a one of the top curable chronic diseases worldwide, this was referred to the remarkable efficacy of antiviral therapy, however, many cases showed resistance to interferon/Ribavirin combination therapy. Genetic polymorphism is the major cause of relapse after therapy. To determine whether Hepatitis C virus (HCV) core substitution and IL-28 (rs8099917) play a role in the response to INF/RBV antiviral therapy, 115 HCV chronically infected patients initiated treatment with Peglated INF plus ribavirin (INF/RBV) for 48 weeks were tested for baseline substitution at codon 70 of the viral core protein and for genetic polymorphism in IL-28 rs8099917 (TaqMan Probe assay, Applied Biosystems). In this study, we observed that, TT genotype in IL-28 polymorphism was the favourable genotype as 75 % of this genotype achieved therapeutic success, defined as sustained viral response at 12 weeks of therapy.23.5 % of studied patients presented a mutant HCV core substitution at core position 70, those were resistant to therapy and failed to achieve a viral response. A multivariate analysis revealed three independent predictors of therapeutic success age40years (Pless than0.001), IL-28 rs8099917 genotype (P=0.04) and absence of HCV core substitution at position 70 (Pless than0.001). This study concluded that IL-28 rs8099917 and HCV core mutations can be considered as predictors for therapeutic response to INF/RBV therapy, so those who are affordable should treated with direct acting antiviral drugs (DAAs) rather than INF based therapy to prevent evolution towards end-stage liver disease.