Pilot, Open, Randomized, Prospective Trial for Normothermic Machine Perfusion Evaluation in Liver Transplantation From Older Donors

Liver Transpl. 2019 Mar;25(3):436-449. doi: 10.1002/lt.25362.

Abstract

Ex situ normothermic machine perfusion (NMP) might minimize ischemia/reperfusion injury (IRI) of liver grafts. In this study, 20 primary liver transplantation recipients of older grafts (≥70 years) were randomized 1:1 to NMP or cold storage (CS) groups. The primary study endpoint was to evaluate graft and patient survival at 6 months posttransplantation. The secondary endpoint was to evaluate liver and bile duct biopsies; IRI by means of peak transaminases within 7 days after surgery; and incidence of biliary complications at month 6. Liver and bile duct biopsies were collected at bench surgery, end of ex situ NMP, and end of transplant surgery. Interleukin (IL) 6, IL10, and tumor necrosis factor α (TNF-α) perfusate concentrations were tested during NMP. All grafts were successfully transplanted. Median (interquartile range) posttransplant aspartate aminotransferase peak was 709 (371-1575) IU/L for NMP and 574 (377-1162) IU/L for CS (P = 0.597). There was 1 hepatic artery thrombosis in the NMP group and 1 death in the CS group. In NMP, we observed high TNF-α perfusate levels, and these were inversely correlated with lactate (P < 0.001). Electron microscopy showed decreased mitochondrial volume density and steatosis and an increased volume density of autophagic vacuoles at the end of transplantation in NMP versus CS patients (P < 0.001). Use of NMP with older liver grafts is associated with histological evidence of reduced IRI, although the clinical benefit remains to be demonstrated.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Allografts / blood supply
  • Allografts / pathology
  • Allografts / ultrastructure
  • Biopsy
  • Cold Ischemia / adverse effects
  • Delayed Graft Function / epidemiology
  • Delayed Graft Function / etiology
  • Delayed Graft Function / prevention & control
  • Donor Selection
  • End Stage Liver Disease / mortality
  • End Stage Liver Disease / surgery*
  • Female
  • Graft Survival
  • Humans
  • Liver / blood supply
  • Liver / pathology
  • Liver / ultrastructure
  • Liver Transplantation / adverse effects
  • Liver Transplantation / methods*
  • Male
  • Microscopy, Electron
  • Middle Aged
  • Organ Preservation / instrumentation
  • Organ Preservation / methods*
  • Perfusion / instrumentation
  • Perfusion / methods*
  • Pilot Projects
  • Prospective Studies
  • Reperfusion Injury / etiology
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Survival Analysis
  • Treatment Outcome