Impact of EGF, IL28B, and PNPLA3 polymorphisms on the outcome of allograft hepatitis C: a multicenter study

被引:2
作者
Mueller, Jessica L. [1 ,2 ]
King, Lindsay Y. [1 ,2 ]
Johnson, Kara B. [1 ,2 ]
Gao, Tian [3 ]
Nephew, Lauren D. [4 ]
Kothari, Darshan [2 ,5 ]
Simpson, Mary Ann [6 ]
Zheng, Hui [7 ]
Wei, Lan [8 ]
Corey, Kathleen E. [1 ,2 ]
Misdraji, Joseph [9 ]
Lee, Joon Hyoek [10 ]
Lin, M. Valerie [1 ,2 ]
Gogela, Neliswa A. [1 ,2 ]
Fuchs, Bryan C. [2 ,8 ]
Tanabe, Kenneth K. [2 ,8 ]
Gordon, Fredric D. [2 ,6 ]
Curry, Michael P. [2 ,5 ]
Chung, Raymond T. [1 ,2 ]
机构
[1] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, 55 Fruit St, Boston, MA 02114 USA
[2] Harvard Univ, Sch Med, Boston, MA USA
[3] Boston Med Ctr, Dept Med, Div Gastroenterol, Boston, MA USA
[4] Univ Penn Hlth Syst, Dept Med, Div Gastroenterol, Philadelphia, PA USA
[5] Beth Israel Deaconness Med Ctr, Dept Med, Div Gastroenterol, Boston, MA USA
[6] Lahey Hosp & Med Ctr, Dept Med, Div Gastroenterol, Burlington, MA USA
[7] Massachusetts Gen Hosp, Ctr Biostat, 55 Fruit St, Boston, MA 02114 USA
[8] Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, 55 Fruit St, Boston, MA 02114 USA
[9] Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA
[10] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Med, Seoul, South Korea
关键词
cirrhosis; hepatitis C virus; single nucleotide polymorphism; sustained virological response; transplantation; GROWTH-FACTOR GENE; LIVER-TRANSPLANTATION; HEPATOCELLULAR-CARCINOMA; FIBROSIS PROGRESSION; ANTIVIRAL THERAPY; RECIPIENT IL28B; FUNCTIONAL POLYMORPHISM; VIRUS; DONOR; ASSOCIATION;
D O I
10.1111/ctr.12710
中图分类号
R61 [外科手术学];
学科分类号
摘要
Hepatitis C virus (HCV) infection is accelerated following liver transplantation (LT). Single nucleotide polymorphisms (SNPs) near the epidermal growth factor (EGF) (rs4444903), IL28B (rs12979860), and PNPLA3 (rs738409) loci are associated with treatment response, fibrosis, and hepatocellular carcinoma in non-transplant hepatitis C, but allograft population data are limited. We sought to determine the role of these SNPs in 264 patients with HCV who underwent LT between 1990 and 2008. Genotypes were determined from donor wedge/allograft biopsies and recipient explants. Cox proportional hazards model was used to assess time to cirrhosis, liver-related death, and retransplantation, adjusting for donor age and sustained virological response (SVR). Over a median follow-up of 6.3 yr, a trend toward increased progression to graft cirrhosis was observed among recipients of an EGF non-AA vs. AA donor liver (adjusted HR 2.01; 95% CI 0.93-4.34; p = 0.08). No other genotypes predicted cirrhosis development or graft survival. The CC IL28B variant in both recipients and donors was associated with increased rate of SVR (R-CC/D-CC 8/12[67%], R-non-CC/D-CC or R-CC/D-non-CC 23/52[44%], R-non-CC/D-non-CC 12/45[27%], p linear trend = 0.009). Recipient EGF, IL28B, and PNPLA3, and donor IL28B and PNPLA3 genotypes do not predict adverse outcomes in HCV LT recipients. A potential association exists between donor EGF genotype and cirrhosis.
引用
收藏
页码:452 / 460
页数:9
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