title: Analysis of ischemia/reperfusion injury in time-zero biopsies predicts liver allograft outcomes.
abstract: Ischemia/reperfusion injury (IRI) that develops after liver implantation may prejudice long-term graft survival, but it remains poorly understood. Here we correlate the severity of IRIs that were determined by histological grading of time-zero biopsies sampled after graft revascularization with patient and graft outcomes. Time-zero biopsies of 476 liver transplants performed at our center between 2000 and 2010 were graded as follows: nil (10.5%), mild (58.8%), moderate (26.1%), and severe (4.6%). Severe IRI was associated with donor age, donation after circulatory death, prolonged cold ischemia time, and liver steatosis, but it was also associated with increased rates of primary nonfunction (9.1%) and retransplantation within 90 days (22.7%). Longer term outcomes in the severe IRI group were also poor, with 1-year graft and patient survival rates of only 55% and 68%, respectively (cf. 90% and 93% for the remainder). Severe IRI on the time-zero biopsy was, in a multivariate analysis, an independent determinant of 1-year graft survival and was a better predictor of 1-year graft loss than liver steatosis, early graft dysfunction syndrome, and high first-week alanine aminotransferase with a positive predictive value of 45%. Time-zero biopsies predict adverse clinical outcomes after liver transplantation, and severe IRI upon biopsy signals the likely need for early retransplantation.
authors.affiliation: Departments of Surgery, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Ali
authors.forename: Susan E
authors.initials: SE
authors.lastname: Davies
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Brais
authors.forename: Lucy V
authors.initials: LV
authors.lastname: Randle
authors.forename: John R
authors.initials: JR
authors.lastname: Klinck
authors.forename: Michael E D
authors.initials: ME
authors.lastname: Allison
authors.forename: Yining
authors.initials: Y
authors.lastname: Chen
authors.forename: Laura
authors.initials: L
authors.lastname: Pasea
authors.forename: Simon F J
authors.initials: SF
authors.lastname: Harper
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Pettigrew
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D064591:Allografts; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D050377:Cold Ischemia / Q000009:adverse effects; D005260:Female; D006085:Graft Survival; D006801:Humans; D053208:Kaplan-Meier Estimate; D016031:Liver Transplantation / Q000009:adverse effects* / Q000401:mortality; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D015427:Reperfusion Injury / Q000097:blood / Q000209:etiology / Q000401:mortality / Q000473:pathology*; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D014019:Tissue Donors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D000410:Alanine Transaminase