Open AccessEarly reduced liver graft survival in hepatitis C recipients identified by two combined genetic markers
Author(s) -
Romagnoli Renato,
Martini Silvia,
Tandoi Francesco,
Dell Olio Dominic,
Magistroni Paola,
Bertinetto Francesca E.,
Dametto Ennia,
Rizzetto Mario,
Salizzoni Mauro,
Amoroso Antonio
Publication year - 2016
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/tri.12795
Subject(s) - medicine , interleukin 28b , human leukocyte antigen , hepatitis c , liver transplantation , genotype , concomitant , allele , proportional hazards model , immunology , gastroenterology , transplantation , hepatitis c virus , antigen , gene , biology , genetics , virus , ribavirin
Summary HLA and IL ‐28B genes were independently associated with severity of HCV ‐related liver disease. We investigated the effects of these combined genetic factors on post‐transplant survival in HCV ‐infected recipients, aiming to provide new data to define the optimal timing of novel antiviral therapies in the transplant setting. HLA ‐A/B/ DRB 1 alleles and IL ‐28B rs12979860 (C > T) polymorphism frequencies were determined in 449 HCV viremic recipients and in their donors. Median follow‐up was 10 years; study outcome was graft survival. HLA ‐ DRB 1*11 phenotype and IL ‐28B C/C genotype were significantly less frequent in recipients than donors (27.8% vs. 45.9% and 27.4% vs. 44.9%, respectively, P < 0.00001). Ten‐year graft survival was better in patients with HLA ‐ DRB 1*11 ( P = 0.0183) or IL ‐28B C/C ( P = 0.0436). Conversely, concomitant absence of HLA ‐ DRB 1*11 and IL ‐28B C/C in 228 (50.8%) predicted worse survival ( P = 0.0006), which was already evident at the first post‐transplant year ( P = 0.0370). In multivariable Cox analysis, absence of both markers ranked second as risk factor for survival ( HR = 1.74), following donor age ≥ 70 years ( HR = 1.77). In the current era of direct‐acting antiviral agents, the negative effects of this common immunogenetic profile in HCV ‐infected recipients could be most effectively neutralized by peri‐transplant treatment. This should be particularly relevant in countries where elderly donors represent an unavoidable resource.