Impact of EGF , IL 28B , and PNPLA 3 polymorphisms on the outcome of allograft hepatitis C: a multicenter study

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.