Titre
Ip-10 Is Associated With Il28b Variation And Predicts The First Phase Decline Of Hcv Rna And Outcome Of Therapy In Chronic Hepatitis C
Type
abstract de conférence/colloque
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Série
Hepatology
Auteur(s)
Lagging, M.
Auteure/Auteur
Askarieh, G.
Auteure/Auteur
Bochud, P.Y.
Auteure/Auteur
Bibert, S.
Auteure/Auteur
Negro, F.
Auteure/Auteur
Missale, G.
Auteure/Auteur
Ferrari, C.
Auteure/Auteur
Neumann, A. U.
Auteure/Auteur
Pawlotsky, J.-M.
Auteure/Auteur
Haagmans, B. L.
Auteure/Auteur
Schalm, S. W.
Auteure/Auteur
Zeuzem, S.
Auteure/Auteur
Soderholm, J.
Auteure/Auteur
Westin, J.
Auteure/Auteur
Lindh, M.
Auteure/Auteur
Hellstrand, K.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
Titre du livre ou conférence/colloque
61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases
Adresse
Boston, United-States, October 29-November 2, 2010
ISBN
0270-9139
Statut éditorial
Publié
Date de publication
2010
Volume
52
Première page
766A
Peer-reviewed
Oui
Langue
anglais
Notes
Publication type : Meeting Abstract
Résumé
High systemic levels of IP-10 at onset of combination therapy for chronic hepatitis C mirror intrahepatic mRNA levels and predict a slower first phase decline in HCV RNA as well as poor outcome. Recently several genome wide association studies have revealed that single nucleotide polymorphisms (SNPs) on chromosome19 within proximity of IL28B predict spontaneous clearance of HCV infection and as therapeutic outcome among patients infected with HCV genotype 1, with three such SNPs being highly predictive: rs12979860, rs12980275, and rs8099917. In the present study, we correlated genetic variations in these SNPs from 253 Caucasian patients with pretreatment plasma levels of IP-10 and HCV RNA throughout therapy within a phase III treatment trial (HCV-DITTO). The favorable genetic variations in all three SNPs (CC, AA, and TT respectively) was significantly associated with lower baseline IP-10 (CC vs. CT/TT at rs12979860: median 189 vs. 258 pg/mL, P=0.02, AA vs. AG/GG at rs12980275: median 189 vs. 258 pg/mL, P=0.01, TT vs. TG/GG at rs8099917: median 224 vs. 288 pg/mL, P=0.04), were significantly less common among HCV genotype 1 infected patients than genotype 2/3 (P<0.0001, P<0.0001, and P=0.01 respectively) and had significantly higher baseline viral load than carriers of the SNP genotypes (6.3 vs. 5.9 log 10 IU/mL, P=0.0012, 6.3 vs. 6.0 log 10 IU/mL, P=0.026, and 6.3 vs. 5.8 log 10 IU/mL, P=0.0003 respectively). Among HCV genotype 1 infected homozygous or heterogeneous carriers of the favorable C, A, and T genotypes, lower baseline IP-10 was significantly associated with greater decline in HCV-RNA day 0-4, which translated into increased rates of achieving SVR among homozygous patients with baseline IP-10 below 150 pg/mL (85%, 75%, and 75% respectively). In a multivariate analysis among genotype 1 infected patients, both baseline IP-10 and the SNPs were significant independent predictors of SVR. Conclusion: Baseline plasma IP-10 is significantly associated with IL28B variations, and augments the predictiveness of the first phase decline in HCV RNA and final treatment outcome.
PID Serval
serval:BIB_D3CAEF61A5CE
Date de création
2011-04-18T14:02:37.437Z
Date de création dans IRIS
2025-05-20T23:22:51Z