Prediction of response to treatment in chronic hepatitis C patients by genetic variation in Interleukin 28B A Thesis Submitted for Partial Fulfillment of the Requirements of the Master Degree of Science (In Microbiology) Submitted By

Abstract

Introduction: Hepatitis C virus (HCV) infection is a global public health problem, affecting 2-3% of the world’s population. Egypt considerthe highest incidence of HCV worldwide (15%), where HCV genotype-4 (HCV-4a)represents 90% of all HCV cases. In 2005, the combination of Pegylated Interferon (PEG-IFN) and Ribavirin (RBV) wasthe standard of care (SOC) treatment, it was only effective in 50% of patients.lately, the United States Food and Drug Administration (FDA) approved direct acting antiviral agents (DAAs) whichincreasedsustained virological response(SVR) to 90%. But due to the high cost and adverse effects of the treatment, it is a compelling reason for the identification of biomarker predictors of disorder response to treatment. One of the most vitalbiomarker predictors is single nucleotide polymorphisms (SNPs) close toInterleukin 28B (IL-28B) gene. This study aimed at assessing whether specific IL-28B gene polymorphisms (SNPs), known as rs12979860 could predict treatment outcomes among chronic HCV-4 patients treated with the Peg-IFN/RBV treatment. Methods:Fifty healthy individuals and 75 chronic HCV-4 Egyptian patients were selected. HCV infected patients submitted to combined PEG-IFN/RBV therapy, 39 of them have SVR while the last 36 did not response. IL-28B rs12979860 SNPs have been carried out within the healthy controls and HCV infected patients by the technique of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The CC genotype of IL-28B rs12979860 was identified in 21 patients, 18 of them achieved SVR, while the CT heterozygous was detected in 43 patients, 20 of them achieved SVR and the TT was found in 11 patients and only one of them was responder. There was a significant association in genotypes distribution of IL-28B rs12979860 between healthy controls and chronic HCV (CHCV) patients (P=0.03). Genotypes were significantly associated with response, genotypes between SVR and NR appeared significant relationship (P=0.000). Also,IL-28B rs12979860 polymorphism was significantly associated with alpha fetoprotein (AFP) (P=0.047). Conclusion: The statistics observed association between IL-28B rs12979860 genotypes in Egyptian HCV G4 and treatment response is an important predictive biomarker for SVR in patients with HCV genotype-4. Also, it is observed thatAFP (cut off 4.5 mg/mL)increases the predictive power of IL28B in response to treatment.

Key words:

Hepatitis C virus (HCV), PEG-IFN/RBV therapy, IL-28B gene, single nucleotide polymorphism (SNP),