A Genetic Variant in the Interleukin 28B Gene As a Major Predictor for Sustained Virologic Response in Chronic Hepatitis C Virus Infection

Abstract

The IL28B single nucleotide polymorphism (SNP) rs12979860 is a major predictor of treatment outcomes in hepatitis C virus (HCV) infection, but its distribution widely varies among populations and ethnicities. We undertook this study to investigate the distribution of IL28B SNP rs12979860 in Mexican patients with HCV infection and to assess its usefulness in predicting response to pegylated interferon-alpha and ribavirin (PegIFN-α/RVB) therapy. Three hundred and fifty patients with chronic HCV infection were studied. The frequency of sustained virologic response (SVR), non-responders and relapses following a course of standard therapy was longitudinally assessed in 295 of these patients. IL28B SNP rs12979860 was genotyped from genomic DNA using real-time RT-PCR. The number needed to treat (NNT) to achieve a SVR was calculated. Seventy six (22%) patients were CC homozygous, 210 (60%) were heterozygous and 64 (18%) showed TT homozygosity for the IL28B SNP rs12979860. After a standard course of PegIFN-α/RVB, 69% of patients with the CC genotype, 46% of the heterozygous group and 38% of those with the TT genotype (p=0.001) achieved a SVR. Conversely, the percentage of non-responders was 15, 43, and 48% (p<0.0001), respectively. The NNT to achieve a SVR was strongly influenced by the IL28B rs12979860 genotype and ranged from 2-10. The IL-28B rs12979860 CC genotype was found in 22% of Mexican patients chronically infected by HCV. Genotyping IL28B SNP rs12979860 is useful to predict the response to a standard regimen with PegIFN-α/RVB, especially in those infected with HCV genotype1.