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Abstract Hepatitis C virus (HCV) becomes one of the top curable chronic diseases worldwide; however, many cases showed resistance to interferon/Ribavirin combination therapy. Genetic polymorphism is the major cause of relapse after therapy. To determine whether HCV core substitution and IL-28B (rs8099917 and rs12979860) play a role in the response to INF/RBV antiviral therapy; 50 HCV chronically infected patients who initiated treatment with Pegylated INF plus ribavirin (INF/RBV) for 48 weeks were tested for genetic polymorphism in IL-28B rs8099917 and rs12979860 to determine their effects on virological response of the INF/RBV regimen. The response to treatment was assessed at 12 weeks after therapy to determine the achievement of sustained viral response (SVR), patient was considered as a responder if he achieved reduction by two folds of the HCV_RNA viral load; otherwise, it was considered as non-responder. Also patients were assessed at 24 weeks after therapy to evaluate their late response (LVR) to INF/RBV. In addition; liver function tests were evaluated to determine hepatic status and severity of infection. In the current study, among IL28b (rs8099917 G/T) genotypes TT genotype was the most predominant genotype among the HCV genotype 4 infected patients (64%) followed by GT genotype (32%), however GG genotype were minor group (4%). TT and GT genotypes showed high tendency for response to INF/RBV at 12 weeks (p=0.04). Although; the majority of patients who had achieved LVR were of TT genotype (66%) followed by GT genotype (50%), no significant association was observed between IL28b (rs8099917 G/T) genotype and LVR to INF/RBV (p=0.09). However 100% of GG genotype didn‟t response to therapy. HCV patients who were negative for G allele “TT genotype” showed a significantly higher tendency to respond at 12 weeks compared to G positive group [p=0.02]. On contrary, no significant associations were detected between the positivity of T allele and either SVR or LVR (p>0.05). Likewise, significance could not reached between positivity of G allele and late viral response at 24 weeks (p>0.05). Considering the distribution of rs12979860 C/T genotypes among HCV-4 infected patients as well their response to INF/RBV at 12 weeks; 58% of patients were of TT genotype, followed by 28% of CC, while CT genotypes accounts the least percentage (14%). No significant association was observed between the genotype and response to therapy at 12 weeks (p=0.06). Although; the majority (86%) of CT genotype patients didn‟t response to therapy at 24 weeks, the majority of CC (86%) genotype respond to INF/RBV and TT genotype showed equal distribution among responders and non-responders. A high significant association was observed between the positivity of T allele and LVR to INF/RBV. On contrary, no significant associations were detected between the positivity of C allele and either SVR or LVR (p>0.05). Likewise, significance could not reached between positivity of T allele and SVR (p>0.05). However; no significant difference was detected between different genotypes of each studied polymorphism and the severity of infection. In conclusion; IL28B polymorphism rs12979860 was found to be excellent biomarkers for prediction of therapeutic response to PEGINF/RBV therapies in Egyptians with chronic HCV genotype4. |