The Impact of Organic Anion-Transporting Polypeptide (OATP) Variants on the Side Effects of Direct-Acting Antivirals in Hepatitis C Patients

Abstract

Background Organic anion-transporting polypeptides (OATPs) are responsible for the cellular uptake of a broad range of endogenous compounds and xenobiotics in multiple tissues. The aim of our study was to determine whether variations in OATP1B1 and OATP1B3 affect the side effects experienced by hepatitis C patients treated with direct-acting antivirals (DAAs). Methods This study included 199 hepatitis C patients treated with DAAs. Ledipasvir/sofosbuvir or ombitasvir/paritaprevir/ritonavir ± dasabuvir and 162 control individuals without hepatitis C. Treatment-related side effects were recorded. The OATP1B1 gene variations c.388A>G and c.521T>C and the OATP1B3 gene variations c.334T>G and c.699G>A were analyzed via the polymerase chain reaction-restriction fragment length polymorphism method. Allele/genotype combinations of OATP1B1 and OATP1B3 haplotypes were evaluated. Results Side effects were observed in 53 (26.6%) of 199 hepatitis C patients. There were skin mucosal lesions in 19 patients (36%), fatigue in 18 patients (34%), pruritus in 11 patients (20.5%), and other in five patients (9.5%). There was a significant relationship between the c.334T>G variant and side effects (p = 0.030). The frequency distribution of the c.334T>G variant was in Hardy-Weinberg equilibrium. The frequencies of the patient group and the control group were 65.3% and 63%, respectively. We found a significant difference between the patient and control groups in terms of the haplotype ratios of c.388A>G and c.521T>C (p = 0.036). Conclusions We found a significant relationship between the c.334T>G variant in OATP1B3 and DAA-related side effects in hepatitis C patients.

Keywords: direct-acting antiviral agents; gene; hepatitis c virus; oatps; variants.