A randomized trial of normothermic preservation in liver transplantation

Abstract

Liver transplantation is a highly successful treatment, but is severely limited by the shortage in donor organs. However, many potential donor organs cannot be used; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively. Normothermic machine perfusion maintains the liver in a physiological state, avoids cooling and allows recovery and functional testing. Here we show that, in a randomized trial with 220 liver transplantations, compared to conventional static cold storage, normothermic preservation is associated with a 50% lower level of graft injury, measured by hepatocellular enzyme release, despite a 50% lower rate of organ discard and a 54% longer mean preservation time. There was no significant difference in bile duct complications, graft survival or survival of the patient. If translated to clinical practice, these results would have a major impact on liver transplant outcomes and waiting list mortality.

Improvement of Normothermic Ex Vivo Machine Perfusion of Rat Liver Grafts by Dialysis and Kupffer Cell Inhibition With Glycine

“…This is in line with our results because ALT seems to level out during perfusion of normal and DCD livers under optimized conditions with a more apparent effect in marginal grafts. This effect is also observed during clinical application of NEVLP …”

“…Ravikumar et al and Goldaracena et al demonstrated the safety and feasibility of NEVLP in phase 1 clinical trials in Europe and North America . A multicenter phase 3 randomized controlled clinical trial recently compared NEVLP to static cold storage . Normothermic conditions offer the chance for pharmacologic interventions that are dependent on an active metabolism of the graft .…”

Reply

“…Watson et al reported 1 liver with a perfusate ALT level of 9490 U/L at 2 hours of NMP, which developed primary nonfunction after transplantation. In contrast with this, Nasralla et al recently reported a liver with perfusate transaminases >20,000 U/L during NMP (using the OrganOx perfusion device), which was successfully transplanted . These data highlight the difficulty in comparing studies with different devices, timing, and settings.…”

Gene Silencing With siRNA (RNA Interference): A New Therapeutic Option During Ex Vivo Machine Liver Perfusion Preservation

“…However, at this time, perfusion at cold temperatures lacks a reliable method to assess the energy (adenosine triphosphate) status of the liver, and a consensus regarding a biomarker profile of useable HMP livers has not been reached . At normothermic perfusion temperatures, even with extended preservation times, a marked decrease (~50%) in peak ALT was observed in treated livers compared with static cold storage grafts . In addition to HMP, normothermic machine perfusion (NMP) allows for viability assessment of the organ prior to transplantation.…”