IL28B alleles associated with poor hepatitis C virus (HCV) clearance protect against inflammation and fibrosis in patients infected with non-1 HCV genotypes

Bochud, Pierre-Yves; Bibert, Stéphanie; Kutalik, Zoltán; Patin, Etienne; Guergnon, Julien; Nalpas, Bertrand; Goossens, Nicolas; Kuske, Lorenz; Müllhaupt, Beat; Gerlach, Tillman; Heim, Markus H; Moradpour, Darius; Cerny, Andreas; Malinverni, Raffaele; Regenass, Stephan; Dollenmaier, Guenter; Hirsch, Hans; Martinetti, Gladys; Gorgiewski, Meri; Bourlière, Marc; ... (2012). IL28B alleles associated with poor hepatitis C virus (HCV) clearance protect against inflammation and fibrosis in patients infected with non-1 HCV genotypes. Hepatology, 55(2), pp. 384-94. Hoboken, N.J.: Wiley Interscience 10.1002/hep.24678

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Genetic polymorphisms near IL28B are associated with spontaneous and treatment-induced clearance of hepatitis C virus (HCV), two processes that require the appropriate activation of the host immune responses. Intrahepatic inflammation is believed to mirror such activation, but its relationship with IL28B polymorphisms has yet to be fully appreciated. We analyzed the association of IL28B polymorphisms with histological and follow-up features in 2335 chronically HCV-infected Caucasian patients. Assessable phenotypes before any antiviral treatment included necroinflammatory activity (n = 1,098), fibrosis (n = 1,527), fibrosis progression rate (n = 1,312), and hepatocellular carcinoma development (n = 1,915). Associations of alleles with the phenotypes were evaluated by univariate analysis and multivariate logistic regression, accounting for all relevant covariates. The rare G allele at IL28B marker rs8099917-previously shown to be at risk of treatment failure-was associated with lower activity (P = 0.04), lower fibrosis (P = 0.02) with a trend toward lower fibrosis progression rate (P = 0.06). When stratified according to HCV genotype, most significant associations were observed in patients infected with non-1 genotypes (P = 0.003 for activity, P = 0.001 for fibrosis, and P = 0.02 for fibrosis progression rate), where the odds ratio of having necroinflammation or rapid fibrosis progression for patients with IL28B genotypes TG or GG versus TT were 0.48 (95% confidence intervals 0.30-0.78) and 0.56 (0.35-0.92), respectively. IL28B polymorphisms were not predictive of the development of hepatocellular carcinoma.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases 04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology
UniBE Contributor:	Gorgievski, Meri, Dufour, Jean-François
ISSN:	0270-9139
Publisher:	Wiley Interscience
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:22
Last Modified:	05 Dec 2022 14:06
Publisher DOI:	10.1002/hep.24678
PubMed ID:	22180014
Web of Science ID:	000299632900007
URI:	https://boris.unibe.ch/id/eprint/7714 (FactScience: 213040)