Meta-analysis: IL28B polymorphisms predict sustained viral response in HCV patients treated with pegylated interferon-α and ribavirin

Aliment Pharmacol Ther. 2012 Jul;36(2):91-103. doi: 10.1111/j.1365-2036.2012.05131.x. Epub 2012 May 16.

Abstract

Background: Interleukin (IL) 28B single nucleotide polymorphisms can predict sustained virological response (SVR) in hepatitis C virus (HCV) patients following pegylated interferon-alpha (PEG IFN-α) and ribavirin treatment.

Aim: To design a meta-analysis to determine IL28B genotypes', rs12979860 CC and rs8099917 TT, correlation with SVR in PEG IFN-α/ribavirin-treated HCV patients.

Methods: Meta-analysis was performed in 17 studies of rs12979860 CC vs. CT/TT and 17 of rs8099917 TT vs. TG/GG. Odds ratios (OR) and confidence intervals (95% CI) were calculated by fixed- or random-effects models. Heterogeneity, sensitivity analysis and publication bias were also assessed.

Results: Of 4252 Asian, Caucasian and African HCV patients analysed for rs12979860, SVR was more frequent in CC (vs. CT/TT; OR = 4.76, 95% CI: 3.15-7.20). Moreover, CC was associated with SVR for HCV genotype-1 or -4 infections (OR(genotype 1) = 5.52, 95% CI: 3.74-8.15; OR(genotype 4) = 8.11, 95% CI: 4.13-15.93), regardless of ethnicity. Of 4549 Caucasian and Asian HCV patients analysed for rs8099917, SVR was more frequent in TT (vs. TG/GG; OR = 3.31, 95% CI: 2.39-4.59). Moreover, TT was associated with SVR for HCV-1 (OR(genotype 1) = 4.28, 95% CI: 2.87-6.38). Rs8099917 TT predictive value was stronger in Asians (OR(Asians) = 8.09, 95% CI: 5.63-11.61; OR(Caucasians) = 3.00, 95% CI: 2.03-4.45). Ethnicity stratification revealed that rs8099917 TT had slight predictive value in Asian HCV-2/3 patients (OR = 1.99, 95% CI: 1.09-3.62).

Conclusions: IL28B rs12979860 CC and rs8099917 TT are strong SVR predictors for PEG IFN-α/ribavirin-treated HCV-1 patients, regardless of ethnicity. In HCV-2/3, rs12979860 CC has no SVR predictive value, but rs8099917 TT was slightly associated with SVR in Asians.

Publication types

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

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Genotype
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepatitis C / drug therapy*
  • Hepatitis C / genetics*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Interferons
  • Interleukins / genetics*
  • Polyethylene Glycols / therapeutic use*
  • Polymorphism, Single Nucleotide*
  • Predictive Value of Tests
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use*
  • Treatment Outcome

Substances

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