Mechanistic Evaluation of Machine Perfusion Strategies in Donation After Circulatory Death Liver Transplantation
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 the doctors do not understand well the mechanisms through which MP improves the quality of the DCD livers. The iInvestigators plan 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.
• DCD category III donors considered for abdominal organs-only retrieval.
• Donor age ≥18 years.
• Retrieval procedure allocated to KCH or UHB NORS teams.
• Donor liver accepted for a patient at KCH or UHB transplant waiting list via the standard offering process.
• Functional donor warm ischaemia (defined as a period between the systolic blood pressure \<50mmHg and aortic cold flush) ≤30 minutes.
• Donor BMI \<35kg/m2.
• Predicted cold ischaemic time \<8 hours.
• Donor family has given consent to use donated liver for research.
⁃ Transplant recipient inclusion criteria
• Recipients 18 years of age or older.
• Listed on an elective transplant waiting list.
• First liver transplantation.
• Suitable to receive a DCD graft based on the liver listing MDT.
• Willingness to consent for the study participation.