IL28B rs12979860 gene polymorphism and sofosbuvir-based therapy response in HCV-infected Pakistani patients

Abstract

Objectives: Interleukin-28B (IL-28B) gene polymorphisms play an important role in response prediction of direct-acting antivirals (DAAs) treatment, including Sofosbuvir and Daclatasvir with or without Ribavirin. The purpose of this study was to assess the IL-28B polymorphism SNP (rs12979860) and other clinical factors as response predictors for the sustained virological response (SVR) in chronic HCV-infected patients taking DAA therapy. Methods: A cross-sectional and observational study was carried out among 104 HCV-infected patients who completed a course of Sofosbuvir and Daclatasvir along with Ribavirin. Patients were classified according to their response to therapy. Genotyping of IL-28B was determined through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay, and HCV genotyping was identified by PCR method. We analyzed the response prediction of IL-28 gene polymorphism among patients receiving DAA therapy. Results: Overall, IL-28B CC, CT, and TT genotypes were found in 56 (53.8%), 22 (21.2%), and 26 (25.0%) patients, respectively. Higher early virological response (EVR) and SVR were observed in patients with the rs12979860 CC alleles (82.1% and 75%) as compared to CT/TT alleles (54.2% and 20.8%). IL-28B CC genotype (OR=0.14; 95% CI=0.04-0.44; p=0.001) and EVR (OR=0.20; 95% CI=0.05-0.71; p=0.013) remained significantly associated with SVR in the multivariate regression analysis. However, the FIB-4 score (OR=4.24; 95% CI=1.46-11.75; p=0.008) is a strong predictor of non-SVR. Conclusion: The antiviral efficacy of triple therapy (sofosbuvir, daclatasvir, and ribavirin) is influenced by the variability of the IL-28B gene, as well as the EVR and FIB-4 score. These variables also play a significant role in predicting the treatment response of patients with chronic HCV infection in Pakistan.