IL28B polymorphisms leading to poor response to treatment are associated with low necroinflammatory activity and slow fibrosis progression in HCV genotype non-1-infected patients

Détails

ID Serval
serval:BIB_951F83DED325
Type
Actes de conférence (partie): contribution originale à la littérature scientifique, publiée à l'occasion de conférences scientifiques, dans un ouvrage de compte-rendu (proceedings), ou dans l'édition spéciale d'un journal reconnu (conference proceedings).
Sous-type
Abstract (résumé de présentation): article court qui reprend les éléments essentiels présentés à l'occasion d'une conférence scientifique dans un poster ou lors d'une intervention orale.
Collection
Publications
Institution
Titre
IL28B polymorphisms leading to poor response to treatment are associated with low necroinflammatory activity and slow fibrosis progression in HCV genotype non-1-infected patients
Titre de la conférence
46th Annual Meeting of the European Association for the Study of the Liver (EASL)
Auteur(s)
Bochud P.Y., Bibert S., Kutalik Z., Goossens N., Muellhaupt B..., Gerlach T..., Heim M., Moradpour D., Cerny A., Malinverni R., Dufour J.F., Negro F.
Adresse
Berlin, Germany, March 30-April 3, 2011
ISBN
0168-8278
Statut éditorial
Publié
Date de publication
2011
Peer-reviewed
Oui
Volume
54
Série
Journal of Hepatology
Pages
S539
Langue
anglais
Notes
Publication type : Meeting Abstract
Résumé
Background and Aims: Genetic polymorphisms near IL28Bhave been associated with spontaneous and treatment-inducedclearance of hepatitis C virus (HCV). This is believed to proceed viathe appropriate activation of innate and adaptive immune responsestargeting infected hepatocytes. Intrahepatic inflammation is thereflection of the host cell immune response, but its relationshipwith IL28B polymorphisms has yet to be fully appreciated.Methods: We analyzed the association of IL28B polymorphismswith Metavir activity (≥1) and fibrosis scores (≥2) in 1114 HCVinfectedCaucasian patients enrolled in the Swiss Hepatitis C CohortStudy (629, 127, 268 and 110 infected with HCV genotype 1, 2, 3and 4, respectively). In a subgroup of 915 patients with an estimateddate of infection, the association between IL28B polymorphismsand fibrosis progression rate (FPR > median) was assessed. Singlenucleotide polymorphisms (SNPs) of interest were extracted froma dataset generated in a genome-wide association study and/orgenotyped by TaqMan assay. Associations of alleles with differentdegrees of activity and fibrosis were evaluated using an additivemodel of inheritance by multivariate logistic regression, accountingfor all relevant covariates.Results: The rare G allele at marker rs8099917 was associated withlower activity (P = 0.008) and fibrosis (P = 0.01), as well as slower FPR(P = 0.02). Most striking associations were observed among patientsinfected with non-1 genotypes (P = 0.002 for activity, P = 0.002 forfibrosis and P = 0.005 for FPR). In genotype 1-infected patients, theassociation with activity was observed only in the recessive model(P = 0.04), whereas other associations were not significant (P = 0.7for fibrosis and P = 0.4 for FPR).Conclusions: In chronic hepatitis C, IL28B polymorphisms linkedwith a poor virological response to therapy are also associated withreduced intrahepatic necroinflammation and slower liver diseaseprogression. These observations underscore the role played by thehost immune response in clearing HCV, especially in patients withHCV genotypes non-1.
Mots-clé
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Web of science
Création de la notice
03/01/2012 14:25
Dernière modification de la notice
20/08/2019 15:57
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