Solute Carrier Gene Polymorphism (SLC29A1) in Relation to Treatment Outcome and Hematological Changes in Chronic Hepatitis C Patients Treated With Direct Acting Antivirals Plus Ribavirin

Direct-acting antiviral agents (DAAs) are safe and effective in eradicating hepatitis C virus (HCV) infection. Ribavirin is still used as an important part of modern HCV therapy. Main protein involved in ribavirin cellular uptake is encoded by solute carrier family 29, member1 (SLC29A1), which has a role in ribavirin uptake into erythrocytes. To evaluate the association of SLC29 Agene polymorphism (rs760370) with hematological changes and sustained virological response (SVR) in Egyptian chronic HCV patients treated with DAAs. Sixty chronic HCV infected patients receiving DAAs with ribavirin (group I; triple therapy) were classified as group Ia is associated with hematologic complication, group Ib without complications. Sixty chronic HCV infected patients receiving DAAs without ribavirin were included in (group II; dual therapy). Liver tests, complete blood counts, hemolytic markers (indirect bilirubin, reticulocytic count and LDH), HCV RNA level and SLC29A1 (rs760370) using allelic discrimination real time PCR were done for all subjects. Median age of the enrolled patients was 37 years old with female majority (69 patients). Patients carrying GG genotype had increased a significant risk of hemoglobin decline ≥ 2 g/dL as compared to AA genotype. Similar results were obtained in the dominant model which also had increased risk for Hb decline (OR = 4.26, 95% CI: 1.34-13.55, and p = 0.011), changes in reticulocyte count and platelet count (p = 0.022, and 0.020 respectively). Also, patients with dominant genetic models had an increase in SVR in patients receiving triple therapy. Regarding the change in hematological parameters revealed a highly significant decrease in delta Δ Hb, RBCs count and MCHC (p < 0.001) in group 1 compared to group 2 plus a statistically significant increase in delta Δ AST level, indirect bilirubin and LDH in group 1 compared to group 2 p-value (p = 0.019, p < 0.001, p < 0.001) respectively. SNP rs760370A > G at SLC29A1 gene influences the severity of ribavirin-induced anemia, possibly mirroring erythrocyte uptake of ribavirin and that increases SVR in chronic hepatitis C patients receiving DAAs and ribavirin.