Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Tropical Medicine

Ribavirin clearly plays a role in the HCV treatment response. Ribavirin is primarily transported by the equilibrative nucleoside transporter-1 (ENT1) codified by SLC29A1 gene. rs760370 polymorphism at the SLC29A1 gene was suggested to in{uFB02}uence ribavirin activity as part of HCV therapy. A cross-sectional cohort study was conducted in 100 chronic hepatitis C infected patients who had received pegylated interferon (peg-IFN) / ribavirin. The patients were categorized as early virological responders ending with sustained virological response (EVR / SVR 50 patients) or null- responders (NR - 50 patients). rs760370 single nucleotide polymorphism (SNP) at the SLC29A1 gene was examined using TaqMan 5- nuclease assay and also using our newly experimentally designed PCR-based RFLP assay. Allelic frequencies at rs760370 were as follows: A / A genotype (28%), A / G genotype (58%) and G / G genotype (14%) in the studied 100 patients. No association was observed between the 2 groups (NR or EVR / SVR) concerning rs760370 polymorphism (p = 0.5). Significant univariate association was found between EVR/SVR as related to basal activity grade (p = 0.037) and to on-treatment decline in platelets till 12th ws of therapy (p = 0.006). Multivariate logistic regression model conducted to predict responsiveness to Peg - INF / RBV (EVR / SVR) showed that baseline platelet count at cutoff value of 130 x103/mm3 (p = 0.03), ALT level at 12 weeks of therapy (p = 0.027) and hemoglobin reduction {u02C2} 10g/dl within the first 12 weeks of therapy (p = 0.02) were significant. The statistical significance of this model is indicating that the 3 predictors as a set reliably distinguished between SVR and Non-responders (X² = 23.379, p = 0.00003), with predictive values of 90.9% for SVR and 58.8% for non-response to therapy

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