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Impact of EGF , IL 28B , and PNPLA 3 polymorphisms on the outcome of allograft hepatitis C: a multicenter study
Author(s) -
Mueller Jessica L.,
King Lindsay Y.,
Johnson Kara B.,
Gao Tian,
Nephew Lauren D.,
Kothari Darshan,
Simpson Mary Ann,
Zheng Hui,
Wei Lan,
Corey Kathleen E.,
Misdraji Joseph,
Lee Joon Hyoek,
Lin M. Valerie,
Gogela Neliswa A.,
Fuchs Bryan C.,
Tanabe Kenneth K.,
Gordon Fredric D.,
Curry Michael P.,
Chung Raymond T.
Publication year - 2016
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/ctr.12710
Subject(s) - medicine , cirrhosis , hepatocellular carcinoma , liver transplantation , hepatitis c , gastroenterology , hepatitis c virus , single nucleotide polymorphism , transplantation , genotype , immunology , virus , biology , biochemistry , gene
Hepatitis C virus ( HCV ) infection is accelerated following liver transplantation ( LT ). Single nucleotide polymorphisms ( SNP s) near the epidermal growth factor ( EGF ) (rs4444903), IL 28B (rs12979860), and PNPLA 3 (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 SNP s 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 IL 28B 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 , IL 28B , and PNPLA 3, and donor IL 28B and PNPLA 3 genotypes do not predict adverse outcomes in HCV LT recipients. A potential association exists between donor EGF genotype and cirrhosis.