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Interferon-Induced Gene Expression Is a Stronger Predictor of Treatment Response than IL28B Genotype in Patients with Hepatitis C

Dill, M. T. and Duong, F. H. and Vogt, J. E. and Bibert, S. and Bochud, P. Y. and Terracciano, L. and Papassotiropoulos, A. and Roth, V. and Heim, M. H.. (2010) Interferon-Induced Gene Expression Is a Stronger Predictor of Treatment Response than IL28B Genotype in Patients with Hepatitis C. Gastroenterology, Vol. 140, H. 3 , S. 1021–1031.

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Official URL: http://edoc.unibas.ch/dok/A5841009

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Abstract

BACKGROUND and AIMS: The host immune response during the chronic phase of hepatitis C virus infection varies among individuals-some patients have a no interferon (IFN) response in the liver whereas others have full activation IFN-stimulated genes (ISGs). Pre-activation of this endogenous IFN system is associated with non-response to pegylated IFN? (pegIFN?) and ribavirin. Genome-wide association studies have associated allelic variants near the IL28B (IFN?3) gene with treatment response. We investigated whether IL28B genotype determines the constitutive expression of ISGs in the liver and compared the abilities of ISG levels and IL28B genotype to predict treatment outcome. METHODS: We genotyped 109 patients with chronic hepatitis C for IL28B allelic variants and quantified the hepatic expression of ISGs and of IL28B. Decision tree ensembles, in the form of a random forest classifier, were used to calculate the relative predictive power of these different variables in a multivariate analysis. RESULTS: The minor IL28B allele was significantly associated with increased expression of ISG. However, stratification of the patients according to treatment response revealed increased ISG expression in non-responders, irrespective of IL28B genotype. Multivariate analysis of ISG expression, IL28B genotype, and several other factors associated with response to therapy identified ISG expression as the best predictor of treatment response. CONCLUSIONS: IL28B genotype and hepatic expression of ISGs are independent predictors of response to treatment with pegIFN? and ribavirin in patients with chronic hepatitis C. The most accurate prediction of response was obtained with a 4-gene classifier comprising IFI27, ISG15, RSAD2, and HTATIP2.
Faculties and Departments:05 Faculty of Science > Departement Mathematik und Informatik > Informatik > Datenanalyse (Roth)
03 Faculty of Medicine > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Molekulare Neurowissenschaften (Papassotiropoulos)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Molekulare Neurowissenschaften (Papassotiropoulos)
03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Molekulare Pathologie (Terracciano)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Molekulare Pathologie (Terracciano)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Hepatology Laboratory (Heim)
UniBasel Contributors:Heim, Markus H. and Terracciano, Luigi M. and Papassotiropoulos, Andreas and Roth, Volker and Vogt, Julia
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Saunders
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Apr 2015 09:14
Deposited On:11 Oct 2012 15:23

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