The effect of genetic variations on ribavirin pharmacokinetics and treatment response in HCV-4 Egyptian patients receiving sofosbuvir/daclatasvir and ribavirin

Abstract

Purpose: This study aimed to investigate the effect of single nucleotide polymorphisms (SNPs) of genes involved in ribavirin (RBV) transport (SLC28A2 gene, ABCB1 gene and ABCB11 gene) on the clinical outcome and pharmacokinetics of ribavirin in HCV- 4 Egyptian patients.

Method: 100 patients treated with sofosbuvir/daclatasvir and ribavirin for 12 weeks. The SNP genotyping was performed by real-time PCR using high resolution melting analysis. Ribavirin plasma trough concentrations were determined at week 4 of therapy using a liquid chromatography/tandem mass spectrometry (LC-MS/MS). For clinical outcomes, sustained virological response (SVR), liver function tests (ALT and AST), total bilirubin, albumin, serum creatinine, hemoglobin, leukocyte count, and platelet count were measured.

Results: Concerning RBV pharmacokinetics, ABCB1 2677 G > T SNP and ABCB11 1331 T > C SNP were statistically associated with RBV C_trough levels after 4 weeks of therapy. ABCB11 1331 T > C SNP revealed significant association with clinical outcomes (SVR). SLC28A2-146 A > T SNP has not showed any statistically significant association with RBV plasma levels or response.

Conclusion: SNP genotyping for ABCB1 and ABCB11 genes can help in better personalized medicine for maximizing response for ribavirin as explored by the significant association between polymorphism in ABCB1 and ABCB11 genes and ribavirin pharmacokinetics and the significant association of ABCB11 1331 T > C SNP with clinical response.

Keywords: ABCB1; ABCB11; Hepatitis C; Pharmacokinetics; Ribavirin; SNP.