IFN-λ gene polymorphisms as predictive factors in chronic hepatitis C treatment-naive patients without access to protease inhibitors

J Med Virol. 2015 Oct;87(10):1702-15. doi: 10.1002/jmv.24227. Epub 2015 May 12.

Abstract

The single nucleotides polymorphisms analyses in the regions near the IL28B gene in patients chronically infected with genotype 1 hepatitis C virus (HCV) are an important predictive factor for sustained virological response (SVR). The aim was to assess the predictive value of the polymorphisms of the IL28B/IFNL3 gene in patients chronically infected with genotype 1 for the viral clearance obtained after initial treatment including admixed populations. A systematic review was conducted, using a meta-analysis in the PubMed, Embase, LILACS, and SCIELO using MesH and DECS in 42 studies. The parameters were IL28B polymorphisms, rs12979860, rs8099917, and rs12980275, SVR ratio, and OR (odds ratio). OR and confidence Interval of 95% (95%CI), were calculated by fixed or random effects models. Heterogeneity, sensitivity analysis, and publication bias were also performed. Significant differences were noted between carriers groups with the major versus minor allele at rs12979860 CC versus CT/TT-genotype (OR = 4.18; 95%CI = 3.37-5.17), rs8099917 TT versus TG/GG-genotype (OR = 4.07; 95%CI = 2.94-5.63), and rs12980275 AA versus AA/AG-genotype (OR = 5.34; 95%CI = 1.60-17.82). There was selection bias in the rs8099917 analysis (Egger's regression P = 0.049), which reversed after performing a sensitivity analysis (P = 0.510). The incorporation of SNP analyses in IL28B/IFNL3 gene during the diagnosis process in Brazil should be used as a complementary tool to determine the appropriate treatment for HCV genotype 1. Here, we confirm that the rs12979860 CC, rs8099917 TT, and rs12980275 AA genotype-carriers have favorable responses to standard therapy, including two studies with Brazilian population, and this information should be considered.

Keywords: chronic hepatitis C; genotype 1; interleukin 28B; meta-analysis; sustained virological response.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Alleles
  • Antiviral Agents / therapeutic use*
  • Brazil
  • Genetic Testing
  • Genotype
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / immunology*
  • Humans
  • Interferons
  • Interleukins / genetics*
  • Interleukins / immunology
  • Male
  • Polymorphism, Single Nucleotide*
  • Protease Inhibitors / therapeutic use

Substances

  • Antiviral Agents
  • interferon-lambda, human
  • Interleukins
  • Protease Inhibitors
  • Interferons