The Association of IL28B Genotype With the Histological Features of Chronic Hepatitis C Is HCV Genotype Dependent

Int J Mol Sci. 2014 Apr 25;15(5):7213-24. doi: 10.3390/ijms15057213.

Abstract

The interleukin 28B (IL28B) rs12979860 polymorphism is associated with treatment outcome in hepatitis C virus (HCV) genotype 1 and 4 patients. Its association with the histological features of chronic hepatitis C and disease severity needs further clarifications. To assess the correlation between IL28B genotype, HCV genotype and liver biopsy findings in untreated patients.

Materials and methods: Pre-treatment liver biopsies from 335 HCV Caucasian patients (59% males, age 50 years) enrolled in the MIST study were staged for fibrosis and inflammation according to the METAVIR and the Ishak scoring systems; steatosis was dichotomized as <5% or ≥5%. IL28B was typed by Taqman Single Nucleotide Polymorphism (SNP) genotyping assay. HCV genotype was 1 in 151 (45%), 2 in 99 (30%), 3 in 50 (15%) and 4 in 35 (10%) patients. IL28B genotype was CC in 117 (34%), CT in 166 (49%) and TT in 52 (15%). At univariate analysis, the IL28B CC genotype was associated with severe portal inflammation in HCV-1 patients (CC vs.

Ct/tt: 86% vs. 63%, p = 0.005), severe lobular inflammation in HCV-2 patients (CC vs.

Ct/tt: 44% vs. 23%, p = 0.03), and less fatty infiltration in HCV-1 patients (CC vs.

Ct/tt: 72% vs. 51%, p = 0.02). Despite the lack of any association between IL28B and fibrosis stage, in HCV-3 patients IL28B CC correlated with METAVIR F3-F4 (CC vs.

Ct/tt: 74% vs. 26%, p = 0.05). At multivariate analysis, the genotype CC remained associated with severe portal inflammation in HCV-1, only (Odds Ratio (OR): 95% Confidence Interval (CI): 3.24 (1.23-8.51)). IL28B genotype is associated with the histological features of chronic hepatitis C in a HCV genotype dependent manner, with CC genotype being independently associated with severe portal inflammation.

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • Fatty Liver / complications
  • Female
  • Genotype
  • Hepacivirus / genetics*
  • Hepacivirus / isolation & purification
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / pathology*
  • Hepatitis C, Chronic / virology
  • Humans
  • Inflammation / complications
  • Interferons
  • Interleukins / genetics*
  • Liver / pathology*
  • Liver / virology*
  • Liver Cirrhosis / complications
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Young Adult

Substances

  • IFNL3 protein, human
  • Interleukins
  • Interferons