Impact of donor and recipient IL28B rs12979860 genotypes on hepatitis C virus liver graft reinfection

被引：82

作者：

Lange, Christian M. ^{[1
,5
]}

Moradpour, Darius ^{[5
]}

Doehring, Alexandra ^{[2
]}

Lehr, Hans-Anton ^{[5
]}

Muellhaupt, Beat ^{[6
]}

Bibert, Stephanie ^{[5
]}

Bochud, Pierre-Yves ^{[5
]}

Antonino, Anca T. ^{[5
]}

Pascual, Manuel ^{[5
]}

Farnik, Harald ^{[1
]}

Shi, Ying ^{[1
]}

Bechstein, Wolf Otto ^{[3
]}

Moench, Christian ^{[3
]}

Hansmann, Martin-Leo ^{[4
]}

Sarrazin, Christoph ^{[1
]}

Loetsch, Joern ^{[2
]}

Zeuzem, Stefan ^{[1
]}

Hofmann, Wolf-Peter ^{[1
]}

机构：

[1] Klinikum JW Goethe Univ Frankfurt Main, Med Klin 1, D-60590 Frankfurt, Germany

[2] Klinikum JW Goethe Univ Frankfurt Main, Pharmazentrum Frankfurt ZAFES, Inst Klin Pharmakol, D-60590 Frankfurt, Germany

[3] Klinikum JW Goethe Univ Frankfurt Main, Klin Allgemein Viszeral & Transplantat Chirugie, D-60590 Frankfurt, Germany

[4] Klinikum JW Goethe Univ Frankfurt Main, Senckenberg Inst Pathol, D-60590 Frankfurt, Germany

[5] Univ Lausanne, CHU Vaudois, CH-1010 Lausanne, Switzerland

[6] Univ Zurich, Div Gastroenterol & Hepatol, CH-8091 Zurich, Switzerland

来源：

JOURNAL OF HEPATOLOGY | 2011年 / 55卷 / 02期

基金：

瑞士国家科学基金会;

关键词：

HCV; Interferon-alpha; Interferon-lambda; Liver transplantation; Reinfection; Ribavirin; Single nucleotide polymorphism; ALPHA-2B PLUS RIBAVIRIN; GENETIC-VARIATION; PEGINTERFERON ALPHA-2A; INITIAL TREATMENT; INTERLEUKIN; 28B; THERAPY; INTERFERON-ALPHA-2B; COMBINATION; INFECTION; VARIANTS;

D O I：

10.1016/j.jhep.2010.10.037

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background & Aims: Recent studies have described a major impact of genetic variations near the IL28B gene on the natural course and outcome of antiviral therapy in chronic hepatitis C. We therefore, aimed to explore the impact of donor and recipient genotypes of these polymorphisms on hepatitis C virus (HCV) liver graft reinfection. Methods: Donor and recipient genotypes of IL28B rs12979860C>T single nucleotide polymorphism were determined in 91 patients with HCV liver graft reinfection, 47 of whom were treated with pegylated interferon-alpha (PEG-IFN-alpha) and ribavirin. IL28B genetic polymorphisms were correlated with the natural course and treatment outcome of recurrent hepatitis C. Results: Patients requiring liver transplantation due to end-stage chronic hepatitis C appeared to be selected toward the adverse genotypes rs12979860 CT/TT compared to non-transplanted HCV-infected patients (p = 0.046). Patients with the donor genotype rs12979860 CC had higher peak ALT and HCV RNA serum concentrations than those with CT/TT (p = 0.04 and 0.06, respectively). No association was observed between ALT/HCV RNA serum concentrations and recipient genotypes (p >0.3). More important, donor IL28B rs12979860 CC vs. CT/TT genotypes were associated with rapid, complete early, and sustained virologic response (RVR, cEVR, SVR) to treatment with PEG-IFN-alpha and ribavirin (p = 0.003, 0.0012, 0.008, respectively), but weaker associations of recipient genotypes with RVR, cEVR, and SVR were observed as well (p = 0.0046, 0.115, 0.118, respectively). Conclusions: We provide evidence for a dominant, but not exclusive impact of the donor rather than the recipient IL28B genetic background on the natural course and treatment outcome of HCV liver graft reinfection. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

引用

页码：322 / 327

页数：6

共 25 条

[1] Amino Acid Substitution in Hepatitis C Virus Core Region and Genetic Variation Near the Interleukin 28B Gene Predict Viral Response to Telaprevir with Peginterferon and Ribavirin [J].