Pilot, open, randomized, prospective trial for normothermic machine perfusion evaluation in liver transplantation from older donors.

Ex-situ normothermic machine perfusion (NMP) might minimize ischemia/reperfusion injury (IRI) of liver grafts. Twenty primary liver transplants recipients of older grafts (≥70 years) were randomized 1:1 to NMP or cold storage (CS). The primary study endpoint was to evaluate graft and patient survival at 6 months posttransplantation. The secondary endpoint was to evaluate: IRI by means of peak transaminases within 7 days after surgery; incidence of biliary complications at month 6, and evaluation of liver and bile duct biopsies. Liver and bile duct biopsies were collected at bench surgery, end of ex-situ NMP, and end of transplant surgery. Interleukin 6, 10 and TNF-α perfusate concentrations were tested during NMP. All grafts were successfully transplanted. Median (IQR) posttransplant AST peak was 709 (371-1575) and 574 (377-1162) UI/L, for NMP and CS respectively (p=0.597). One hepatic artery thrombosis in the NMP group and one death in the CS group were observed. 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 increased volume density of autophagic vacuoles at the end of transplantation in NMP versus CS patients (p