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

International Journal of Molecular Sciences

Roberta D𠆚mbrosio¹  Alessio Aghemo¹  Raffaele De Francesco²  Maria Grazia Rumi⁴  Enrico Galmozzi¹  Stella De Nicola¹  Cristina Cheroni²  Paul J. Clark³  Guido Ronchi¹  Pietro Lampertico¹ 

[1] Division of Gastroenterology and Hepatology, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan 20100, Italy; E-Mails:;INGM, Istituto Nazionale Genetica Molecolare Milano, Milan 20100, Italy; E-Mails:;Duke Clinical Research Institute, Duke University, Durham, NC 27715, USA; E-Mail:;Division of Hepatology, Ospedale San Giuseppe IRCCS Multimedica, Università degli Studi di Milano, Milan 20100, Italy; E-Mail:

关键词: interleukin 28B (IL28B) polymorphism;    hepatitis C virus (HCV);    histology;    liver biopsy;    fibrosis;    necroinflammation;    steatosis;    natural history;   

DOI  :  10.3390/ijms15057213

来源: mdpi

【 摘 要 】

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.

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.

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© 2014 by the authors; licensee MDPI, Basel, Switzerland