Beneficial IL28B genotype associated with lower frequency of hepatic steatosis in patients with chronic hepatitis C

被引:80
作者
Tillmann, Hans L. [1 ,2 ]
Patel, Keyur [1 ,2 ]
Muir, Andrew J. [1 ,2 ]
Guy, Cynthia D. [4 ]
Li, Josephine H. [3 ]
Lao, Xiang Qian [3 ]
Thompson, Alexander [1 ,2 ]
Clark, Paul J. [1 ,2 ]
Gardner, Stephen D. [5 ]
McHutchison, John G. [6 ]
McCarthy, Jeanette J. [3 ]
机构
[1] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27705 USA
[2] Duke Univ, Med Ctr, Div Gastroenterol, Durham, NC 27705 USA
[3] Duke Univ, Med Ctr, Inst Genome Sci & Policy, Durham, NC 27705 USA
[4] Duke Univ, Med Ctr, Div Pathol, Durham, NC 27705 USA
[5] GlaxoSmithKline Res & Dev Ltd, Res Triangle Pk, NC USA
[6] Gilead Sci Inc, Foster City, CA 94404 USA
基金
美国国家卫生研究院;
关键词
Chronic hepatitis C; Genetic; Lipids; IL28B; Steatosis; INTERFERON-ALPHA; LIPID-METABOLISM; VIRUS; THERAPY;
D O I
10.1016/j.jhep.2011.03.015
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: IL28B polymorphisms have been associated with both treatment induced and spontaneous clearance of hepatitis C virus (HCV). We previously found that LDL cholesterol levels were higher in chronic hepatitis C (CHC) patients with the CC genotype at the rs12979860 polymorphism, located proximal to the IL28 gene. Here we analyzed the association of steatosis with IL28B genotype in treatment naive patients with CHC. Methods: Two independent cohorts of 145 genotype 1 infected patients from an antifibrotic study and 180 genotype 1 patients from Duke were analyzed for the presence and severity of steatosis in relation to the rs12979860 polymorphism at the IL28B locus. TaqMan assay based genotyping classified three groups CC, CT, and TT. Results: CC genotype was associated with a lower prevalence of steatosis. In the antifibrotic study, steatosis was found in 47.6% (50/105) of IL28B non-CC vs. 22.5% (9/40; p = 0.008) in CC patients. Similarly, steatosis was found in 67.4% (89/132) of non-CC patients compared to only 39.6% (19/48; p = 0.001) of CC patients in the Duke cohort. Conclusions: IL28B CC genotype is associated with less pronounced disturbances of lipid metabolism, as reflected both in serum lipoprotein levels and hepatic steatosis, in HCV infection. (C) 2011 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.
引用
收藏
页码:1195 / 1200
页数:6
相关论文
共 22 条
[1]  
Andrade RJ, 2000, ALIMENT PHARM THER, V14, P929
[2]   THE HISTOLOGICAL FEATURES OF CHRONIC HEPATITIS-C AND AUTOIMMUNE CHRONIC HEPATITIS - A COMPARATIVE-ANALYSIS [J].
BACH, N ;
THUNG, SN ;
SCHAFFNER, F .
HEPATOLOGY, 1992, 15 (04) :572-577
[3]  
BALAGOPAL A, 2010, GASTROENTEROLOGY
[4]  
Brunt EM, 1999, AM J GASTROENTEROL, V94, P2467, DOI 10.1111/j.1572-0241.1999.01377.x
[5]   Screening for IL28B gene variants identifies predictors of hepatitis C therapy success [J].
Doehring, Alexandra ;
Hofmann, Wolf Peter ;
Schlecker, Christina ;
Zeuzem, Stefan ;
Susser, Simone ;
Geisslinger, Gerd ;
Sarrazin, Christoph ;
Loetsch, Joern .
ANTIVIRAL THERAPY, 2010, 15 (08) :1099-1106
[6]   EFFECT OF INTERFERON ON PLASMA-LIPOPROTEINS AND ON THE ACTIVITY OF POST-HEPARIN PLASMA LIPASES [J].
EHNHOLM, C ;
AHO, K ;
HUTTUNEN, JK ;
KOSTIAINEN, E ;
MATTILA, K ;
PIKKARAINEN, J ;
CANTELL, K .
ARTERIOSCLEROSIS, 1982, 2 (01) :68-73
[7]   miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting [J].
Esau, C ;
Davis, S ;
Murray, SF ;
Yu, XX ;
Pandey, SK ;
Pear, M ;
Watts, L ;
Booten, SL ;
Graham, M ;
McKay, R ;
Subramaniam, A ;
Propp, S ;
Lollo, BA ;
Freier, S ;
Bennett, CF ;
Bhanot, S ;
Monia, BP .
CELL METABOLISM, 2006, 3 (02) :87-98
[8]   Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance [J].
Ge, Dongliang ;
Fellay, Jacques ;
Thompson, Alexander J. ;
Simon, Jason S. ;
Shianna, Kevin V. ;
Urban, Thomas J. ;
Heinzen, Erin L. ;
Qiu, Ping ;
Bertelsen, Arthur H. ;
Muir, Andrew J. ;
Sulkowski, Mark ;
McHutchison, John G. ;
Goldstein, David B. .
NATURE, 2009, 461 (7262) :399-401
[9]   A predictive model of response to peginterferon ribavirin in chronic hepatitis C using classification and regression tree analysis [J].
Kurosaki, Masayuki ;
Matsunaga, Kotaro ;
Hirayama, Itsuko ;
Tanaka, Tomohiro ;
Sato, Mitsuaki ;
Yasui, Yutaka ;
Tamaki, Nobuharu ;
Hosokawa, Takanori ;
Ueda, Ken ;
Tsuchiya, Kaoru ;
Nakanishi, Hiroyuki ;
Ikeda, Hiroki ;
Itakura, Jun ;
Takahashi, Yuka ;
Asahina, Yasuhiro ;
Higaki, Megumu ;
Enomoto, Nobuyuki ;
Izumi, Namiki .
HEPATOLOGY RESEARCH, 2010, 40 (03) :251-260
[10]   PATHOLOGICAL DIAGNOSIS OF CHRONIC HEPATITIS-C - A MULTICENTER COMPARATIVE-STUDY WITH CHRONIC HEPATITIS-B [J].
LEFKOWITCH, JH ;
SCHIFF, ER ;
DAVIS, GL ;
PERRILLO, RP ;
LINDSAY, K ;
BODENHEIMER, HC ;
BALART, LA ;
ORTEGO, TJ ;
PAYNE, J ;
DIENSTAG, JL ;
GIBAS, A ;
JACOBSON, IM ;
TAMBURRO, CH ;
CAREY, W ;
OBRIEN, C ;
SAMPLINER, R ;
VANTHIEL, DH ;
FEIT, D ;
ALBRECHT, J ;
MESCHIEVITZ, C ;
SANGHVI, B ;
VAUGHAN, RD .
GASTROENTEROLOGY, 1993, 104 (02) :595-603