Outcomes of DCD liver transplantation using organs treated by hypothermic oxygenated perfusion before implantation. 2019

Andrea Schlegel, and Xavier Muller, and Marit Kalisvaart, and Beat Muellhaupt, and M Thamara P R Perera, and John R Isaac, and Pierre-Alain Clavien, and Paolo Muiesan, and Philipp Dutkowski
NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, United Kingdom; Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Zurich, Switzerland.

Donation after circulatory death (DCD) liver transplantation is known for potentially worse outcomes because of higher rates of graft non-function or irreversible cholangiopathy. The impact of machine liver perfusion techniques on these complications remains elusive. We aimed to provide data on 5-year outcomes in patients receiving DCD liver transplants, after donor organs had been treated by hypothermic oxygenated perfusion (HOPE). Fifty HOPE-treated DCD liver transplants performed in Zurich between 2012 and 3/2017 were matched with 50 primary donation after brain death (DBD) liver transplants, and with 50 untreated DCD liver transplants in Birmingham. Match factors focussed on short cold ischaemia, comparable recipient age and low recipient laboratory model for end-stage liver disease scores. Primary endpoints were post-transplant complications, and non-tumour-related patient death or graft loss. Despite extended donor warm ischaemia, HOPE-treated DCD liver transplants achieved similar overall graft survival, compared to standard DBD liver transplants. Particularly, graft loss due to any non-tumour-related causes occurred in 8% (4/50) of cases. In contrast, untreated DCD livers resulted in non-tumour-related graft failure in one-third (16/50) of cases (p = 0.005), despite significantly (p <0.001) shorter functional donor warm ischaemia. Five-year graft survival, censored for tumour death, was 94% for HOPE-treated DCD liver transplants vs. 78% in untreated DCD liver transplants (p = 0.024). The 5-year outcomes of HOPE-treated DCD liver transplants were similar to those of DBD primary transplants and superior to those of untreated DCD liver transplants, despite much higher risk. These results suggest that a simple end-ischaemic perfusion approach is very effective and may open the field for safe utilisation of extended DCD liver grafts. Machine perfusion techniques are currently being introduced into the clinic, with the aim of optimising injured grafts prior to implantation. While short-term effects of machine liver perfusion have been frequently reported in terms of hepatocellular enzyme release and early graft function, the long-term benefit on irreversible graft loss has been unclear. Herein, we report on 5-year graft survival in donation after cardiac death livers, treated either by conventional cold storage, or by 1-2 h of hypothermic oxygenated perfusion (HOPE) after cold storage. Graft loss was significantly less in HOPE-treated livers, despite longer donor warm ischaemia times. Therefore, HOPE after cold storage appears to be a simple and effective method to treat high-risk livers before implantation.

UI MeSH Term Description Entries
D007036 Hypothermia, Induced Abnormally low BODY TEMPERATURE that is intentionally induced in warm-blooded animals by artificial means. In humans, mild or moderate hypothermia has been used to reduce tissue damages, particularly after cardiac or spinal cord injuries and during subsequent surgeries. Induced Hypothermia,Mild Hypothermia, Induced,Moderate Hypothermia, Induced,Targeted Temperature Management,Therapeutic Hypothermia,Hypothermia, Therapeutic,Induced Mild Hypothermia,Induced Mild Hypothermias,Induced Moderate Hypothermia,Induced Moderate Hypothermias,Mild Hypothermias, Induced,Moderate Hypothermias, Induced,Targeted Temperature Managements
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009926 Organ Preservation The process by which organs are kept viable outside of the organism from which they were removed (i.e., kept from decay by means of a chemical agent, cooling, or a fluid substitute that mimics the natural state within the organism). Organ Preservations,Preservation, Organ,Preservations, Organ
D009927 Tissue and Organ Procurement The administrative procedures involved with acquiring TISSUES or organs for TRANSPLANTATION through various programs, systems, or organizations. These procedures include obtaining consent from TISSUE DONORS and arranging for transportation of donated tissues and organs, after TISSUE HARVESTING, to HOSPITALS for processing and transplantation. Organ Procurement,Organ Procurement Systems,Organ Shortage,Tissue Procurement,Tissue Shortage,Donor Cards,Organ Donation,Required Organ Donation Request,Required Request,Tissue Donation,Donor Card,Organ Donations,Organ Procurement System,Organ Procurements,Required Requests,Shortage, Tissue,Tissue Donations,Tissue Procurements,Tissue Shortages
D010477 Perfusion Treatment process involving the injection of fluid into an organ or tissue. Perfusions
D011379 Prognosis A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations. Prognostic Factor,Prognostic Factors,Factor, Prognostic,Factors, Prognostic,Prognoses
D005260 Female Females
D005500 Follow-Up Studies Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. Followup Studies,Follow Up Studies,Follow-Up Study,Followup Study,Studies, Follow-Up,Studies, Followup,Study, Follow-Up,Study, Followup
D006084 Graft Rejection An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. Transplant Rejection,Rejection, Transplant,Transplantation Rejection,Graft Rejections,Rejection, Graft,Rejection, Transplantation,Rejections, Graft,Rejections, Transplant,Rejections, Transplantation,Transplant Rejections,Transplantation Rejections

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