title: The Impact of Ischemia/Reperfusion Injury on Liver Allografts from Deceased after Cardiac Death versus Deceased after Brain Death Donors.
abstract: OBJECTIVE
  The shortage of organs for transplantation has led to increased use of organs procured from donors after cardiac death (DCD). The effects of cardiac death on the liver remain poorly understood, however. Using livers obtained from DCD versus donors after brain death (DBD), we aimed to understand how ischemia/reperfusion (I/R) injury alters expression of pro-inflammatory markers ceramides and influences graft leukocyte infiltration.
  
  
  METHODS
  Hepatocyte inflammation, as assessed by ceramide expression, was evaluated in DCD (n = 13) and DBD (n = 10) livers. Allograft expression of inflammatory and cell death markers, and allograft leukocyte infiltration were evaluated from a contemporaneous independent cohort of DCD (n = 22) and DBD (n = 13) livers.
  
  
  RESULTS
  When examining the differences between transplant stages in each group, C18, C20, C24 ceramides showed significant difference in DBD (p<0.05) and C22 ceramide (p<0.05) were more pronounced for DCD. C18 ceramide is correlated to bilirubin, INR, and creatinine after transplant in DCD. Prior to transplantation, DCD livers have reduced leukocyte infiltration compared to DBD allografts. Following reperfusion, the neutrophil infiltration and platelet deposition was less prevalent in DCD grafts while cell death and recipients levels of serum aspartate aminotransferase (AST) of DCD allografts had significantly increased.
  
  
  CONCLUSIONS
  These data suggest that I/R injury generate necrosis in the absence of a strong inflammatory response in DCD livers with an appreciable effect on early graft function. The long-term consequences of increased inflammation in DBD and increased cell death in DCD allografts are unknown and warrant further investigation.
authors: Liver Transplant Unit, Institute of Liver Studies, King's College Hospital, London, United Kingdom.|Institute of Pharmaceutical Science, Faculty of Life Science & Medicine, King's College London, London, United Kingdom.
authors: Jin
authors: J
authors: Xu
authors: Liver Transplant Unit, Institute of Liver Studies, King's College Hospital, London, United Kingdom.|Department of Transplant Surgery, Emory University, Atlanta, Georgia, United States of America.
authors: Blayne Amir
authors: BA
authors: Sayed
authors: Institute of Pharmaceutical Science, Faculty of Life Science & Medicine, King's College London, London, United Kingdom.|Department of Analytical Chemistry, Nutrition and Food Science, University of Salamanca, Salamanca, Spain.
authors: Ana Maria
authors: AM
authors: Casas-Ferreira
authors: Liver Transplant Unit, Institute of Liver Studies, King's College Hospital, London, United Kingdom.
authors: Parthi
authors: P
authors: Srinivasan
authors: Liver Transplant Unit, Institute of Liver Studies, King's College Hospital, London, United Kingdom.
authors: Nigel
authors: N
authors: Heaton
authors: Liver Transplant Unit, Institute of Liver Studies, King's College Hospital, London, United Kingdom.
authors: Mohammed
authors: M
authors: Rela
authors: Liver Transplant Unit, Institute of Liver Studies, King's College Hospital, London, United Kingdom.
authors: Yun
authors: Y
authors: Ma
authors: Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors: Susan
authors: S
authors: Fuggle
authors: Institute of Pharmaceutical Science, Faculty of Life Science & Medicine, King's College London, London, United Kingdom.
authors: Cristina
authors: C
authors: Legido-Quigley
authors: Liver Transplant Unit, Institute of Liver Studies, King's College Hospital, London, United Kingdom.
authors: Wayel
authors: W
authors: Jassem
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D017209:Apoptosis; D001926:Brain Death; D005260:Female; D006801:Humans; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D008107:Liver Diseases / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015427:Reperfusion Injury; D014019:Tissue Donors; D016896:Treatment Outcome