A Polymorphism Near IL28B Is Associated With Spontaneous Clearance of Acute Hepatitis C Virus and Jaundice

被引:270
作者
Tillmann, Hans L. [1 ]
Thompson, Alex J.
Patel, Keyur
Wiese, Manfred
Tenckhoff, Hannelore [4 ]
Nischalke, Hans D. [5 ]
Lokhnygina, Yuliya
Kullig, Ulrike [6 ]
Goebel, Uwe
Capka, Emanuela [7 ]
Wiegand, Johannes [4 ]
Schiefke, Ingolf [8 ]
Guethoff, Wolfgang [9 ]
Gruenfreiff, Kurt
Koenig, Ingrid
Spengler, Ulrich [5 ]
McCarthy, Jeanette [2 ]
Shianna, Kevin V. [3 ]
Goldstein, David B. [3 ]
McHutchison, John G.
Timm, Joerg [10 ]
Nattermann, Jacob [5 ]
机构
[1] Duke Univ, Duke Clin Res Inst, Div Gastroenterol, GI Hepatol Res Program, Durham, NC 27706 USA
[2] Duke Univ, Inst Genom Sci & Policy, Ctr Genom Med, Durham, NC USA
[3] Duke Univ, Ctr Human Genome Variat, Durham, NC USA
[4] Univ Leipzig, Klin & Poliklin Gastroenterol & Rheumatol, Leipzig, Germany
[5] Univ Bonn, Dept Internal Med, D-5300 Bonn, Germany
[6] Krankenhaus Dresden Friedrichstadt, Med Klin 3, Dresden, Germany
[7] Klinikum Chemnitz, Med Klin 2, Chemnitz, Germany
[8] Klinikum St Georg, Leipzig, Germany
[9] Klinikum Ernst Von Bergmann, Potsdam, Germany
[10] Univ Klin Essen, Inst Virol, Essen, Germany
基金
英国医学研究理事会;
关键词
Chronic Hepatitis C Virus Infection; Liver; Genetic Variance; Prediction; SINGLE-SOURCE OUTBREAK; GENETIC-VARIATION; AMERICAN PATIENTS; RIBAVIRIN; PEGINTERFERON; MULTICENTER; GENOTYPE-1; INFECTION; GERMANY; HOST;
D O I
10.1053/j.gastro.2010.07.005
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
BACKGROUND & AIMS: A single nucleotide polymorphism (SNP) upstream of the IL28B gene has been associated with response of patients with chronic hepatitis C to therapy with pegylated interferon and ribavirin and also with spontaneous clearance of acute hepatitis C in a heterogeneous population. We analyzed the association between IL28B and the clinical presentation of acute hepatitis C virus (HCV) infection in a homogeneous population. METHODS: We analyzed the SNP rs12979860 in 190 women from the German anti-D cohort (infected with HCV genotype 1b via contaminated rhesus prophylaxis) and its association with spontaneous clearance. Clinical data were available in 136 women with acute infection who were also evaluated for IL28B genotype. Based on results of a TaqMan polymerase chain reaction assay, the rs12979860 SNP genotypes studied were C/C, C/T, or T/T. RESULTS: Spontaneous clearance was more common in patients with the C/C genotype (43/67; 64%) compared with C/T (22/90; 24%) or T/T (2/33; 6%) (P < .001). Jaundice during acute infection was more common among patients with C/C genotype (32.7%) than non-C/C patients (with C/T or T/T) (16.1%; P = .032). In C/C patients, jaundice during acute infection was not associated with an increased chance of spontaneous clearance (56.3%) compared with those without jaundice (60.6%). In contrast, in non-C/C patients, jaundice was associated with a higher likelihood of spontaneous clearance (42.9%) compared with those without jaundice (13.7%). CONCLUSIONS: The SNP rs12979860 upstream of IL28B is associated with spontaneous clearance of HCV. Women with the C/T or T/T genotype who did not develop jaundice had a lower chance of spontaneous clearance of HCV infection.
引用
收藏
页码:1586 / +
页数:8
相关论文
共 21 条
[1]   Impact of aboriginal ethnicity on HCV core-induced IL-10 synthesis: Interaction with IL-10 gene polymorphisms [J].
Aborsangaya, Koko Bate ;
Dembinski, Iga ;
Khatkar, Suresh ;
Alphonse, Martin Prince ;
Nickerson, Peter ;
Rempel, Julia D. .
HEPATOLOGY, 2007, 45 (03) :623-630
[2]   How to Use an Article About Genetic Association B: Are the Results of the Study Valid? [J].
Attia, John ;
Ioannidis, John P. A. ;
Thakkinstian, Ammarin ;
McEvoy, Mark ;
Scott, Rodney J. ;
Minelli, Cosetta ;
Thompson, John ;
Infante-Rivard, Claire ;
Guyatt, Gordon .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2009, 301 (02) :191-197
[3]   Correlates of hepatitis C virus (HCV) RNA negativity among HCV-seropositive blood donors [J].
Busch, MP ;
Glynn, SA ;
Stramer, SL ;
Orland, J ;
Murphy, EL ;
Wright, DJ ;
Kleinman, S .
TRANSFUSION, 2006, 46 (03) :469-475
[4]   Peginterferon and ribavirin treatment in African American and Caucasian American patients with hepatitis C genotype 1 [J].
Conjeevaram, Hari S. ;
Fried, Michael W. ;
Jeffers, Lennox J. ;
Terrault, Norah A. ;
Wiley-Lucas, Thelma E. ;
Afdhal, Nezam ;
Brown, Robert S. ;
Belle, Steven H. ;
Hoofnagle, Jay H. ;
Kleiner, David E. ;
Howell, Charles D. .
GASTROENTEROLOGY, 2006, 131 (02) :470-477
[5]   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
[6]   Factors associated with spontaneous clearance of hepatitis C virus among illicit drug users [J].
Grebely, Jason ;
Raffa, Jesse D. ;
Mmath, Calvin Lai ;
Krajden, Mel ;
Conway, Brian ;
Tyndall, Mark W. .
CANADIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 2007, 21 (07) :447-451
[7]   Peginterferon Alfa-2a (40 kd) and ribavirin for Black American patients with chronic HCV genotype 1 [J].
Jeffers, LJ ;
Cassidy, W ;
Howell, CD ;
Hu, S ;
Reddy, KR .
HEPATOLOGY, 2004, 39 (06) :1702-1708
[8]   Replicated Association Between an IL28B Gene Variant and a Sustained Response to Pegylated Interferon and Ribavirin [J].
McCarthy, Jeanette J. ;
Li, Josephine H. ;
Thompson, Alexander ;
Suchindran, Sunil ;
Lao, Xiang Qian ;
Patel, Keyur ;
Tillmann, Hans L. ;
Muir, Andrew J. ;
McHutchison, John G. .
GASTROENTEROLOGY, 2010, 138 (07) :2307-2314
[9]   PHARMACOGENOMIC ANALYSIS REVEALS IMPROVED VIROLOGIC RESPONSE IN ALL IL-28B GENOTYPES IN NAIVE GENOTYPE 1 CHRONIC HCV PATIENTS TREATED WITH GI-5005 THERAPEUTIC VACCINE PLUS PEG-IFN/RIBAVIRIN [J].
McHutchison, J. G. ;
Thompson, A. J. ;
Jacobson, I. M. ;
Boyer, T. D. ;
Schiff, E. R. ;
Everson, G. T. ;
Vierling, J. M. ;
Shiffman, M. L. ;
Brown, R. S. ;
Di Bisceglie, A. M. ;
Gordon, S. C. ;
Lee, W. M. ;
Guo, Z. ;
King, T. H. ;
Armstrong, B. ;
Rodell, T. C. ;
Apelian, D. .
JOURNAL OF HEPATOLOGY, 2010, 52 :S457-S457
[10]   Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites [J].
Muir, AJ ;
Bornstein, JD ;
Killenberg, PG ;
Fowler, F ;
Gilliam, J ;
Harlan, W ;
Hayes, J ;
Marcuard, S ;
McCone, J ;
Medoff, J ;
Mertesdorf, J ;
Newton, D ;
Pancotto, F ;
Poleynard, G ;
Riely, C ;
Strohecker, J ;
Werth, T ;
Williams, D .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (22) :2265-2271