Allograft TNFβ and IL16 polymorphisms influence HCV recurrence and severity after liver transplantation

Abstract

Hepatitis C (HCV) recurrence after liver transplantation is universal although severity varies. We explored whether certain donor cytokine gene polymorphisms may be useful markers of susceptibility to severe recurrence. Allograft tumor necrosis factor (TNF) β and interleukin (IL) 16 gene polymorphisms were correlated with 1-yr clinical outcome among HCV+ recipients. Recipients of donor TNFβ2,2 (n = 8) experienced less recurrence (50% vs. 71 %, P < 0.05), less fibrosis (25% vs. 76%, P < 0.01), and less rejection (25% vs. 71%, P < 0.01) than donor TNFβ1,1 (n = 19). Recipients of donor TNFβ1,2 (n = 27) demonstrated an intermediate picture with less fibrosis (56%, P < 0.01) and less rejection (37%, P < 0.01) than TNFβ1,1. Recipients with donor IL16TC (n = 22) showed less recurrence (65% vs. 78%, P = 0.05), less fibrosis (53% vs. 67%, P = 0.06), and less rejection (41% vs. 55%, P = 0.06) than IL16TT (n = 32) genotype. Recipients of the combination TNFβ2,2/IL16TC donor genotype had the most benign clinical outcome with less recurrence (33% vs. 75%, P < 0.01), no fibrosis (0% vs. 50%, P < 0.001), and fewer rejections (33% vs. 75%, P < 0.01) than donor TNFβ1,1/IL16TT genotype. In vitro production of cytokines correlated with genotype. Release of soluble TNFβ for TNFβ1,1 vs. TNFβ1,2 and TNFβ2,2 was 4803 ± 2142 pg/mL vs. 5629 ± 3106 (P = not significant [ns]) and 7180 ± 3005 (P = ns). Release of soluble IL16 for IL16TT vs. IL16TC was 437 ± 86 pg/mL vs. 554 ± 39 (P = 0.06). In conclusion, allograft TNFΒ and IL16 gene polymorphisms may be useful markers to predict the severity of disease recurrence among HCV+ patients after liver transplantation. © 2006 AASLD.