Immunometabolism of Machine Perfusion Strategies

  • Research type

    Research Study

  • Full title

    Mechanistic Evaluation of Machine Perfusion Strategies in Donation after Circulatory Death Liver Transplantation.

  • IRAS ID

    328606

  • Contact name

    Alberto Sanchez-Fueyo

  • Contact email

    sanchez_fueyo@kcl.ac.uk

  • Sponsor organisation

    King's College London

  • Duration of Study in the UK

    2 years, 8 months, 30 days

  • Research summary

    There are not enough donated livers for everybody who needs one, and as a result, thousands of patients worldwide are waiting for liver transplants, with many dying while waiting for a life-saving organ. One reason for this shortage is that some usable livers from donors who are considered of high risk are being thrown away out of concern that they might not work well after transplantation due to a problem called ischaemia reperfusion injury (IRI).
    The discarded organs are mostly those coming from donors who have died due to cardiac arrest (called 'donation after circulatory death’ or DCD), with only 27% of them being used in the UK. The quality of these DCD organs could be improved by changing how they are preserved after being removed from the donor. The most commonly used strategy is still to remove the livers and put them in an icebox ('static cold storage' or SCS). The alternative approaches, which are more complex and expensive, but that can also improve the quality of the DCD livers, involve using machines to pump fluids through the livers ('machine perfusion' or MP).
    There are three MP methods being used in patients: 1) normothermic regional perfusion (NRP), which involves pumping the donor's blood through the liver after the donor has died but the liver is still in the donor’s body; 2) normothermic machine perfusion (NMP), in which the liver is pumped with blood outside of the donor’s body; and 3) hypothermic machine perfusion (HOPE), which is also used outside of the donor’s body by pumping cold fluid into the liver. HOPE and NRP have been shown to improve how well DCD livers function after transplantation. NMP can also improve the quality of the DCD livers, but its main advantage is that it allows confirming that the donated liver functions well before proceeding with the transplant. Until now, there has not been a proper comparison of these methods, and we do not understand well the mechanisms through which MP improves the quality of the DCD livers.
    Our plan is to conduct a study where 36 DCD human livers will be split into three groups: SCS, NRP, and HOPE. After that, they will be put in NMP to confirm that they are good enough to be transplanted and to study the mechanisms through which NRP, SCS and HOPE work.

  • REC name

    West Midlands - South Birmingham Research Ethics Committee

  • REC reference

    23/WM/0226

  • Date of REC Opinion

    19 Oct 2023

  • REC opinion

    Favourable Opinion