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/DRB1 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-DRB1*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-DRB1*11 (P = 0.0183) or IL-28B C/C (P = 0.0436). Conversely, concomitant absence of HLA-DRB1*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

Early reduced liver graft survival in hepatitis C recipients identified by two combined genetic markers

ROMAGNOLI, Renato
First
;
MARTINI, Silvia;TANDOI, FRANCESCO;BERTINETTO, FRANCESCA;RIZZETTO, Mario;SALIZZONI, Mauro;AMOROSO, Antonio
Last
2016

Abstract

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/DRB1 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-DRB1*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-DRB1*11 (P = 0.0183) or IL-28B C/C (P = 0.0436). Conversely, concomitant absence of HLA-DRB1*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
29
10
1070
1084
http://www.blackwellpublishing.com/journal.asp?ref=0934-0874&site=1
HCV recurrence; HLA-DRB1*11; IL-28B C/C; Liver transplantation; Post-transplant outcome; Transplantation
Romagnoli, Renato; Martini, Silvia; Tandoi, Francesco; Dell Olio, Dominic; Magistroni, Paola; Bertinetto, Francesca; Dametto, Ennia; Rizzetto, Mario; Salizzoni, Mauro; Amoroso, Antonio
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1568865
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