Strong prediction of virological response to combination therapy by IL28B gene variants rs12979860 and rs8099917 in chronic hepatitis C genotype 4

Liver Int. 2014 Jul;34(6):890-5. doi: 10.1111/liv.12321. Epub 2013 Oct 14.

Abstract

Background: A strong association between single nucleotide polymorphisms (SNPs) of IL28B and treatment outcomes of pegylated interferon-α (PEG IFNα) and ribavirin (RBV) has been shown in chronic hepatitis C (CHC) patients with genotype 1.

Aim: This study aimed to assess two SNPs of IL28B, rs12979860 and rs8099917, in predicting sustained virological responses (SVR) to treatment of CHC patients with genotype 4 (HCV-4). The value of rs8099917 was investigated in carriers of unfavourable genotypes of rs12979860.

Methods: This study included 119 CHC patients with HCV-4 receiving combination therapy. Both SNPs of IL28B were determined by real-time detection polymerase chain reaction.

Results: Genotypes CC/CT/TT of rs12979860 were found in 42 (35.3%), 56 (47.1%) and 21 (17.6%) and rs8099917 TT/TG/GG were found in 74 (62.2%), 40 (33.6%) and 5 (4.2%). In carriers of rs12979860 CC and rs8099917 TT, the rate of SVR was 87.5 and 65.7% respectively. In 54 patients heterozygous for the C allele of rs12979860, testing of rs8099917 revealed SVR in 42.3% of carriers of the TT genotype but no such responses in carriers of TG or GG (P < 0.0001, OR = 47.3, 95% CI: 2.33-767.2). By multivariate analysis, predictors of SVR were baseline ALT (P = 0.014, OR = 6.3, 95% CI: 1.45-27.33), rs12979860 CC (P = 0.001, OR = 13.48, 95% CI: 2.95-61.69) and rs8099917 TT (P = 0.027, OR = 7.5, 95% CI: 1.25-44.88).

Conclusion: In CHC genotype 4 patients, favourable genotypes of both SNPs of IL28B are valuable for predicting SVR. Additional genotyping of rs8099917 in carriers of the heterozygous C allele of rs12979860 can improve the prediction of SVR.

Keywords: HCV; IL28B; SVR; genotype 4; rs12979860; rs8099917.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Biomarkers / blood
  • Chi-Square Distribution
  • Drug Therapy, Combination
  • Female
  • Gene Frequency
  • Genotype
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / diagnosis
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics
  • Hepatitis C, Chronic / immunology
  • Heterozygote
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Interferons
  • Interleukins / genetics*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Patient Selection
  • Pharmacogenetics
  • Phenotype
  • Polyethylene Glycols / therapeutic use*
  • Polymorphism, Single Nucleotide*
  • Precision Medicine
  • RNA, Viral / blood
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Viral Load
  • Young Adult

Substances

  • Antiviral Agents
  • Biomarkers
  • interferon-lambda, human
  • Interferon alpha-2
  • Interferon-alpha
  • Interleukins
  • RNA, Viral
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Interferons
  • peginterferon alfa-2b
  • peginterferon alfa-2a