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.
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This study was performed by the Consortium for Organ Preservation in Europe (COPE). We thank the European Commission for their support through the Seventh Framework Programme. The following organisations, groups and individuals also made substantial contributions without which this trial could not have been completed successfully: NHS Blood and Transplant; the Surgical Intervention Trials Unit, University of Oxford; the Clinical Trials and Research Governance unit, University of Oxford; Centre for Evidence in Transplantation, Royal College of Surgeons of England; the Liver Transplant Coordinators, anaesthetists and liver unit physicians at the Queen Elizabeth Hospital, Birmingham, Addenbrooke’s Hospital, Cambridge, King’s College Hospital, London, the Royal Free Hospital London, Hospital Clinic, Barcelona, University Hospitals, Leuven, University Hospital, Essen; M. Soo, S. Morrish, C. Morris, L. Randle, R. Macedo Arantes, R. Morovat, A. Elsharkawy, G. Hirschfield, P. Muiesan, J. Isaac, J. Grayer, B. Buchholz, H. Vilca-Melendez, A. Zamalloa, D. Chasiotis, S. Khorsandi, B. Davidson, D. Sharma, A. Esson, D. Monbaliu, S. Mertens, S. Swoboda, J. Neuhaus, T. Benkö, V. Molina, R. Kumar, A. Bradley, M. Laspeyres, B. Patel, A. Mukwamba, S. Banks, the COPE Transplant Technicians, the Specialist Nurses in Organ Donation and, of course, all of the donors and their families. This study was funded by a European Commission Seventh Framework Programme (FP7) Grant (No 305934).
Nature thanks S. Schneeberger, S. G. Tullius and the other anonymous reviewer(s) for their contribution to the peer review of this work.
Extended data figures and tables
Geometric mean ratio and 95% confidence interval are reported for each subgroup and overall for all groups. DBD group, n = 87 NMP, n = 80 SCS; DCD group, n = 33 NMP, n = 20 SCS.
a, Kaplan–Meier plot for one-year survival of patients with two-sided log-rank test. b, Kaplan–Meier plot for one-year graft survival with two-sided log-rank test.
a, Hepatic artery flow during NMP. b, Portal vein flow during NMP. c, Perfusate pH during NMP. d, Bile production during NMP. a–d, Data are mean ± s.d. of each time point. Actual values are shown in the table. n = 87. Source data
Scatter graph with trend line showing perfusate lactate levels at different time points during NMP for all transplanted livers. n = 94. Source data
a, OrganOx metra (generation 1). The NMP device used in the trial. b, OrganOx metra NMP circuit. The liver is perfused via the hepatic artery and portal vein. It drains via the inferior vena cava to a centrifugal pump through which the perfusate passes, via a heat exchanger/oxygenator, to a reservoir or directly into the hepatic artery. The perfusate in the reservoir drains under gravity into the portal vein.
Clinical Trail Protocol. The full trial protocol for a multicentre randomised controlled trial to compare the efficacy of ex-vivo normothermic machine perfusion with static cold storage in human liver transplantation.
Statistical Analysis Plan. A comprehensive description of the statistical methodology applied to the trial data.
Final Statistical Report. The full report from trial statisticians reporting trial outcomes available at 1 year following completion of recruitment.
Primary Non-Function Serious Adverse Event. Clinical trial source document submitted to the trial Data Monitoring Committee providing a narrative description of the events surrounding the transplantation of a normothermic machine perfused liver which resulted in primary non-function of the organ.
Device Error Serious Adverse Event. Clinical trial source document submitted to the trial Data Monitoring Committee providing a narrative description of the events surrounding the normothermic machine perfusion of a liver in which a device error led to the organ being discarded.
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