Association of interferon-λ4-ss469415590 genotype with virologic response of interferon-alpha2b among chronic Hepatitis C patients attending a tertiary care hospital of D I Khan, KP, Pakistan

Abstract

Introduction: Hepatitis C virus (HCV) infection remains a hazard to universal public health. Treatment with interferon (IFN) plus ribavirin produces a sustained virologic response in about 50% patients after 6 months. Data regarding association of interferon with genotypes of virus and humans are still deficient. Objective: To determine IFNL4-ss469415590 genotype in Hepatitis C patients and its association with virologic response to Interferon-alpha2b and Ribavirin treatment.
Materials & Methods: A cross sectional descriptive study was carried out from January 2012 to December 2014 in a tertiary care hospital of DI Khan, KP, on 165 chronic Hepatitis C patients enrolled through non-probability sampling after obtaining informed consent. Patients were given 300 IU of IFN-a-2a subcutaneously three times every week. Daily dose of ribavirin 1000 mg/day for a pre-treatment weight <75 kg or 1200 mg/day for weight >75 kg was also added. Relevant hematological, PCR and genotyping tests for HCV were done. Quantitative PCR tests were performed before treatment and at 1 month, 3 months and 6 months post-treatment for each patient. Taqman assay-based SNP genotyping was done for detection of the allelic variants at rs368234815. Real time PCR was used to amplify patients’ DNA and SNP analysis for single nucleotide mutation using PCR thermal cycler SDS7000.
Results: At rs368234815, 85(51.5%) were Responders. Genotype 3a(51%) and 2b(20%) were the predominant genotypes. Among responders, 43(50.6%) patients were having TT genotype, 28(33%) GT and 07(8.2%) GG genotype. Among 80(48.5%) non-responders, 15(18.8%) had TT genotype, 52(65%) GT and 11(13.7%) GG genotype. TT genotype presence displayed a significant association (p=0.003) with treatment result i.e. TT > GT >GG.
Conclusion: The TT genotype at SNP rs368234815 offers improved virologic response to interferon in combination with ribavirin in chronic Hepatitis C patients when compared to other genotypes.