IL28B polymorphism is associated with treatment response in patients with genotype 4 chronic hepatitis C

被引:147
作者
Asselah, Tarik [1 ,2 ]
De Muynck, Simon [1 ,2 ]
Broet, Philippe [3 ,4 ]
Masliah-Planchon, Julien [5 ,6 ]
Blanluet, Maud [5 ,6 ]
Bieche, Ivan [5 ,6 ]
Lapalus, Martine [1 ,2 ]
Martinot-Peignoux, Michelle [1 ,2 ]
Lada, Olivier [1 ,2 ]
Estrabaud, Emilie [1 ,2 ]
Zhang, Qian [1 ,2 ]
El Ray, Ahmed [7 ]
Vidaud, Dominique [5 ,6 ]
Ripault, Marie-Pierre [1 ,2 ]
Boyer, Nathalie [1 ,2 ]
Bedossa, Pierre [8 ]
Valla, Dominique [1 ,2 ]
Vidaud, Michel [5 ,6 ]
Marcellin, Patrick [1 ,2 ]
机构
[1] Beaujon Hosp, INSERM, U773, CRB3, F-92110 Clichy, France
[2] Univ Paris 07, AP HP, Hepatol Dept, Clichy, France
[3] Grp Hosp Antoine Beclere Bicetre Paul Brousse, AP HP, Le Kremlin Bicetre, France
[4] Univ Paris 11, INSERM, UMR669, Villejuif, France
[5] Beaujon Hosp, Dept Biochem & Mol Genet, F-92110 Clichy, France
[6] Univ Paris 05, INSERM, UMR745, Paris, France
[7] Theodor Bilharz Res Inst, Giza, Egypt
[8] Beaujon Hosp, Dept Pathol Anat, F-92110 Clichy, France
关键词
Genetic; Personalised medicine; Interferon; Prediction; Companion diagnostic; PEGYLATED INTERFERON; GENETIC-VARIATION; PLUS RIBAVIRIN; EXPRESSION; SIGNATURE; FIBROSIS; THERAPY; ALPHA;
D O I
10.1016/j.jhep.2011.09.008
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: Polymorphisms in the region of the interleukin (IL)28B gene have been associated with pegylated-interferon (PEG-IFN) and ribavirin treatment response mainly in genotype 1 HCV infections. However, there are few data on HCV genotype 4 (HCV-4) infection. We evaluated, in a unique well-characterized cohort of HCV-4 patients, the association of IL28B polymorphism with response to treatment or liver disease severity. Methods: This study included 164 HCV-4 patients from different ethnic groups (Egyptian, European, and Sub-Saharan African). Among these patients, 82 were studied for response and 160 for disease severity. Free DNA extracted from all the 164 patient's serum samples was analyzed by direct sequencing of the SNP rs12979860 of IL28B. Genetic and bio-clinical features from patients having sustained virological response (43 SVR patients) and from those who did not respond to treatment or had a relapse after the end of the treatment (39 NR patients) were compared. IL28B polymorphism was compared between the 78 patients with mild fibrosis (Metavir score F0-F1) and the 82 with advanced fibrosis (F2-F4). Results: Our data showed a better treatment response rate of the C allele of the IL28B gene SNP rs12979860 (p = 0.0008). The response rates were 81.8%, 46.5%, and 29.4% for genotype CC, CT, and TT, respectively. No significant relationship was found between rs12979860 and the severity of the disease. Conclusions: The SNP rs12979860 is strongly associated with SVR in patients infected with HCV-4, but not with liver disease severity. Analysis of IL28B genotype might be used to guide treatment for these patients. (C) 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:527 / 532
页数:6
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