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Mechanistic Evaluation Of Machine Perfusion Strategies In Donation After Circulatory Death Liver Transplantation (iMAPS)

Liver transplant numbers do not meet the existing needs. Thousands of patients remain on transplant waiting lists worldwide and many die while awaiting a life-saving organ. A key contributor to organ shortage is the discarding of viable organs coming from donors considered high-risk, for fear that they might malfunction after transplantation as a result of a phenomenon called ischaemia reperfusion injury (IRI). Most of the discarded livers are those donated after circulatory death (DCD), only 27% of which are currently utilised in the UK. The quality of DCD organs can be improved by replacing the icebox (static cold storage or SCS), which remains the main approach to preserve the livers after having been retrieved, by strategies that perfuse the livers in a machine (machine perfusion or MP). There are currently 3 MP strategies employed in the clinics: normothermic regional perfusion (NRP) is used in the donors by perfusing the liver with the donor's blood at 37 degrees Celsius, and normothermic (NMP) or hypothermic (HOPE) perfusion are used in the procured livers out of the body (using warm or cold perfusion fluids, respectively). To date, no controlled objective comparisons of these different MP strategies have been undertaken and we do not have a good understanding of their mechanisms of action. Our hypothesis is that the benefits of MP will depend on the capacity of these strategies to improve the damage to the liver cell mitochondria, which constitutes the first event that elicits IRI at the time of transplantation. To determine this, we propose to conduct a randomised clinical trial in which 36 DCD human livers will be allocated to 1 of 3 treatment arms: i) SCS; ii) NRP; and iii) HOPE. This will be followed by a period of time in NMP in order to study the IRI response and determine if the quality of the livers is good enough to proceed to transplantation. Following transplantation, patients will be followed for up to 12 months.


The main objective is to determine the effect of different preservation strategies on the development of mitochondrial damage following reperfusion.


Open-label, prospective, three-arm, phase II randomized clinical trial investigating the effects of 3 different preservation techniques on pre-defined functional and mechanistic endpoints in DCD liver transplantation.


Novel methods of organ preservation and resuscitation have enormous potential for saving the lives of patients awaiting liver transplantation by increasing the number of livers that are successfully transplanted. The greatest benefit is expected to occur in donation after circulatory death (DCD), as only 27% of these livers are currently utilised in the UK. Replacing static cold storage (SCS) by machine perfusion (MP) can improve the utilisation of DCD livers by reducing ischaemia reperfusion injury (IRI)-related complications. Three different MP approaches, differing in the timing when MP is employed and the temperature at which perfusion occurs, have already been implemented clinically. However, they have never been directly compared to each other, and there is a lack of understanding of how they influence the key molecular and cellular events responsible for the initiation and perpetuation of the IRI response in human livers suitable for transplantation. This gap of knowledge hampers an evidence-based adoption of currently available MP systems, as well as the translation of future strategies designed to improve the quality of donated livers.

We intend to address this gap by delivering a clinical trial designed to control the confounders that have limited the generalisability of previous studies.

Project status: Starting

Principal Investigator


  • Niloufar Safinia

    Wellcome Trust Clinical Research Career Development Fellow Honorary Consultant Transplant Hepatologist

  • Miriam Cortes Cerisuelo

    Consultant in Adult and Paediatric Liver Transplantation - King's College Hospital NHS Foundation Trust

  • Wayel  Jassem

    Consultant Liver Transplant Surgeon - King's College Hospital

  • Foad  Rouhani

    Group Leader, The Francis Crick Institute and Honorary Consultant Transplant Surgeon, Kings College Hospital

  • Abdel Douiri

    Chair in Medical Statistics and Clinical Trials


Funding Body: Medical Research Council

Amount: £1,187,317.37

Period: April 2023 - May 2026