Analysis of ischemia/reperfusion injury in time-zero biopsies predicts liver allograft outcomes

Liver Transpl. 2015 Apr;21(4):487-99. doi: 10.1002/lt.24072.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Alanine Transaminase / blood
  • Allografts
  • Biomarkers / blood
  • Biopsy
  • Cold Ischemia / adverse effects
  • Female
  • Graft Survival
  • Humans
  • Kaplan-Meier Estimate
  • Liver Transplantation / adverse effects*
  • Liver Transplantation / mortality
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Reperfusion Injury / blood
  • Reperfusion Injury / etiology
  • Reperfusion Injury / mortality
  • Reperfusion Injury / pathology*
  • Retrospective Studies
  • Risk Factors
  • Severity of Illness Index
  • Time Factors
  • Tissue Donors
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers
  • Alanine Transaminase