title: Early reduced liver graft survival in hepatitis C recipients identified by two combined genetic markers.
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.
authors.affiliation: Liver Transplantation Center, General Surgery Unit 2U, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
authors.forename: Renato
authors.identifier: http://orcid.org/0000-0001-8340-8885
authors.initials: R
authors.lastname: Romagnoli
authors.affiliation: Liver Transplantation Center, Gastrohepatology Unit, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Martini
authors.affiliation: Liver Transplantation Center, General Surgery Unit 2U, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Tandoi
authors.affiliation: Regional Transplantation Center - Piedmont, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
authors.forename: Dominic
authors.initials: D
authors.lastname: Dell Olio
authors.affiliation: Regional Transplantation Center - Piedmont, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.|Immunogenetics Laboratory, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Magistroni
authors.affiliation: Regional Transplantation Center - Piedmont, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.|Immunogenetics Laboratory, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
authors.forename: Francesca E
authors.initials: FE
authors.lastname: Bertinetto
authors.affiliation: Regional Transplantation Center - Piedmont, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.|Immunogenetics Laboratory, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
authors.forename: Ennia
authors.initials: E
authors.lastname: Dametto
authors.affiliation: Liver Transplantation Center, Gastrohepatology Unit, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Rizzetto
authors.affiliation: Liver Transplantation Center, General Surgery Unit 2U, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Salizzoni
authors.affiliation: Regional Transplantation Center - Piedmont, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy. antonio.amoroso@unito.it.|Immunogenetics Laboratory, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy. antonio.amoroso@unito.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Amoroso
mesh_terms: D000368:Aged; D000483:Alleles; D001706:Biopsy; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006085:Graft Survival; D006680:HLA Antigens / Q000235:genetics; D016174:Hepacivirus; D006526:Hepatitis C / Q000601:surgery*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D017093:Liver Failure / Q000401:mortality / Q000601:surgery*; D016031:Liver Transplantation / Q000379:methods*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012086:Reoperation; D000095022:Interferon Lambda
chemical_list: D005819:Genetic Markers; D006680:HLA Antigens; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: HCV recurrence; HLA-DRB1*11; IL-28B C/C; liver transplantation; post-transplant outcome