A randomized trial of normothermic preservation in liver transplantation.
Nasralla D, Coussios CC, et al.Nature 2018; 557(7703): 50-56.
Aims
To determine the efficacy of normothermic machine perfusion (NMP) compared to conventional static cold storage (SCS) in liver transplantation.
Interventions
Livers were randomised to receive either NMP where following removal from the donor, the liver was attached to the OrganOx metra NMP device and perfused throughout the duration of preservation and removed from the device when the transplanting surgeon was ready to implant it, versus SCS where the organ retrieval, storage and the transplant were conducted according to standard practice.
Participants
220 DBD or DCD adult donor livers were transplantated into adult patients awaiting a liver-only transplant.
Outcomes
The primary outcome measured was the difference between the two treatment arms in the peak level of serum aspartate transaminase. Secondary measured outcomes included early allograft dysfunction, biliary strictures on magnetic resonance imaging scan of the biliary tree, hospital stay, graft and patient survival, perfusion characteristics indicative of organ quality and adverse events.
Follow-up
12 months
CET Conclusions
This is a well written report of a well-conducted multinational RCT in liver transplantation. It was not possible to blind the investigators to the intervention given its specific nature. Apart from this, the trial was adequately randomised, withdrawals are clearly described, and the data analysis is presented as both ITT and per protocol with appropriate statistical tests. The study showed a significant difference in its primary outcome, namely a 50% reduction in peak AST during the first 7 days after transplantation when NMP was used. The improvement was greater for DCD than DBD livers, and each was independently significantly improved over their cold stored counterparts. NMP-preserved livers also had lower rates of EAD, which was also a reflection of bilirubin levels. NMP was associated with a 20% reduction in post-reperfusion syndrome. The NMP arm had a 50% lower discard rate than the SCS arm, potentially because clinicians could assess viability during perfusion. An adaptation to surgical practice also occurred during the trial, resulting in a longer average preservation time for NMP livers (11 h 54 versus 7 h 45). The lower discard rate, and longer preservation times only strengthen the case for the benefit of NMP over static cold storage.One organ was discarded due to a malfunction of the device resulting in hypoperfusion. There was no significant difference seen in the low rates of biliary strictures, primary non-function and 1-year graft loss. Median ICU stay, and in-hospital stay were similar between the two groups. This trial has provided excellent evidence of the real-world applicability and potential impact of NMP in clinical liver transplantation. The technique provided improved early graft function alongside increased organ utilization. Some information has also been gathered on which perfusion parameters may be used to assess organ quality.
Data analysis
Available case analysis
Trial registration
ISRCTN - 39731134