IL28B rs12979860 gene polymorphism and sofosbuvir-based therapy response in HCV-infected Pakistani patients
Maleha Asim1, Anoshia Javed1, Ammarah Saeed2, Bushra Adeel3, Shazia Siddique4, Saddaf Ayub51Department of Biochemistry, Islamic International Dental College, Riphah International University, Islamabad, Pakistan2Department of Medicine, PAF unit 2, Fazaia Medical College, Air University, Islamabad, Pakistan
3Department of Pathology, Rashid Latif Medical College, Lahore, Pakistan
4Department of Biochemistry, Sahiwal Medical College, Sahiwal, Pakistan
5Department of Biochemistry, Islamic International Medical College, Riphah International University, Rawalpindi, Pakistan
INTRODUCTION: 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.
DISCUSSION AND 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.
Manuscript Language: English