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

  • Author Footnotes
    † Contributed equally as first authors.
    Andrea Schlegel
    Footnotes
    † Contributed equally as first authors.
    Affiliations
    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
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  • Author Footnotes
    † Contributed equally as first authors.
    Xavier Muller
    Footnotes
    † Contributed equally as first authors.
    Affiliations
    Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Zurich, Switzerland
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  • Marit Kalisvaart
    Affiliations
    NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, United Kingdom
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  • Beat Muellhaupt
    Affiliations
    Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
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  • M. Thamara P.R. Perera
    Affiliations
    NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, United Kingdom
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  • John R. Isaac
    Affiliations
    NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, United Kingdom
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  • Author Footnotes
    ‡ Contributed equally as senior authors.
    Pierre-Alain Clavien
    Correspondence
    Corresponding author. Address: Department of Surgery, Swiss HPB and Transplantation Centre, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland; Tel.: +41 44 255 3300; fax: +41 44 255 4999.
    Footnotes
    ‡ Contributed equally as senior authors.
    Affiliations
    Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Zurich, Switzerland
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  • Author Footnotes
    ‡ Contributed equally as senior authors.
    Paolo Muiesan
    Footnotes
    ‡ Contributed equally as senior authors.
    Affiliations
    NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, United Kingdom
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  • Author Footnotes
    ‡ Contributed equally as senior authors.
    Philipp Dutkowski
    Footnotes
    ‡ Contributed equally as senior authors.
    Affiliations
    Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Zurich, Switzerland
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  • Author Footnotes
    † Contributed equally as first authors.
    ‡ Contributed equally as senior authors.
Published:October 17, 2018DOI:https://doi.org/10.1016/j.jhep.2018.10.005

      Highlights

      • End-ischemic HOPE protected against arterial and biliary complications, resulting in significantly less graft loss.
      • Equivalent outcomes were achieved with HOPE as with primary DBD liver transplants.
      • HOPE after cold storage is a simple and effective method to treat high-risk DCD livers prior to implantation.

      Background & Aims

      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).

      Methods

      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.

      Results

      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).

      Conclusions

      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.

      Lay summary

      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.

      Graphical abstract

      Keywords

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