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Int. J. Mol. Sci. 2014, 15(5), 7213-7224; doi:10.3390/ijms15057213
Article

The Association of Il28b Genotype with the Histological Features of Chronic Hepatitis C Is HCV Genotype Dependent

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1 Division of Gastroenterology and Hepatology, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan 20100, Italy 2 INGM, Istituto Nazionale Genetica Molecolare Milano, Milan 20100, Italy 3 Division of Hepatology, Ospedale San Giuseppe IRCCS Multimedica, Università degli Studi di Milano, Milan 20100, Italy 4 Duke Clinical Research Institute, Duke University, Durham, NC 27715, USA 5 Kirby Institute for Infection and Immunity in Society, University of South Wales, Kensington 2033, Australia
* Author to whom correspondence should be addressed.
Received: 25 February 2014 / Revised: 26 March 2014 / Accepted: 28 March 2014 / Published: 25 April 2014
(This article belongs to the collection Molecular Mechanisms of Human Liver Diseases)
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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.
Keywords: interleukin 28B (IL28B) polymorphism; hepatitis C virus (HCV); histology; liver biopsy; fibrosis; necroinflammation; steatosis; natural history interleukin 28B (IL28B) polymorphism; hepatitis C virus (HCV); histology; liver biopsy; fibrosis; necroinflammation; steatosis; natural history
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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D'Ambrosio, R.; Aghemo, A.; De Francesco, R.; Rumi, M.G.; Galmozzi, E.; De Nicola, S.; Cheroni, C.; Clark, P.J.; Ronchi, G.; Lampertico, P.; Colombo, M. The Association of Il28b Genotype with the Histological Features of Chronic Hepatitis C Is HCV Genotype Dependent. Int. J. Mol. Sci. 2014, 15, 7213-7224.

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