Screening for mitochondrial function before use-routine liver assessment during hypothermic oxygenated perfusion impacts liver utilizationResearch in context
Janina Eden,
Eva Breuer,
Dominique Birrer,
Matteo Müller,
Matthias Pfister,
Hemma Mayr,
Keyue Sun,
Jeannette Widmer,
Florian Huwyler,
Udo Ungethüm,
Bostjan Humar,
Anurag Gupta,
Stefanie Schiess,
Martin Wendt,
Franz Immer,
Andreas Elmer,
David Meierhofer,
Andrea Schlegel,
Philipp Dutkowski
Affiliations
Janina Eden
Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
Eva Breuer
Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
Dominique Birrer
Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
Matteo Müller
Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
Matthias Pfister
Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
Hemma Mayr
Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
Keyue Sun
Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
Jeannette Widmer
Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
Florian Huwyler
Department of Mechanical and Process Engineering, ETH Zurich, Zurich, Switzerland
Udo Ungethüm
Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
Bostjan Humar
Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
Anurag Gupta
Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
Stefanie Schiess
Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
Martin Wendt
Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
Franz Immer
Swisstransplant, The Swiss National Foundation for Organ Donation and Transplantation, Effingerstrasse 1, Bern 3011, Switzerland
Andreas Elmer
Swisstransplant, The Swiss National Foundation for Organ Donation and Transplantation, Effingerstrasse 1, Bern 3011, Switzerland
David Meierhofer
Max Planck Institute for Molecular Genetics, Mass Spectrometry Facility, Berlin 14195, Germany
Andrea Schlegel
Transplantation Center, Digestive Disease and Surgery Institute and Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
Philipp Dutkowski
Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland; Corresponding author. Department of Surgery & Transplantation, University Hospital Zurich, Switzerland.
Summary: Background: To report on a concept of liver assessment during ex situ hypothermic oxygenated perfusion (HOPE) and its significant impact on liver utilization. Methods: An analysis of prospectively collected data on donation after circulatory death (DCD) livers, treated by HOPE at our institution, during a 11-year period between January 2012 and December 2022. Findings: Four hundred and fifteen DCD Maastricht III livers were offered during the study period in Switzerland, resulting in 249 liver transplants. Of those, we performed 158 DCD III liver transplants at our institution, with 1-year patient survival and death censored graft survival (death with functioning graft) of 87 and 89%, respectively, thus comparable to benchmark graft survivals of ideal DBD and DCD liver transplants (89% and 86%). Correspondingly, graft loss for primary non-function or cholangiopathy was overall low, i.e., 7/158 (4.4%) and 11/158 (6.9%), despite more than 82% of DCD liver grafts ranked high (6–10 points) or futile risk (>10 points) according to the UK-DCD score. Consistently, death censored graft survival was not different between low-, high-risk or futile DCD III livers. The key behind these achievements was the careful development and implementation of a routine perfusate assessment of mitochondrial biomarkers for injury and function, i.e., release of flavin mononucleotide from complex I, perfusate NADH, and mitochondrial CO2 production during HOPE, allowing a more objective interpretation of liver quality on a subcellular level, compared to donor derived data. Interpretation: HOPE after cold storage is a highly suitable and easy to perform perfusion approach, which allows reliable liver graft assessment, enabling surgeons to make a fact based decision on whether or not to implant the organ. HOPE-treatment should be combined with viability assessment particularly when used for high-risk organs, including DCD livers or organs with relevant steatosis. Funding: This study was supported by the Swiss National Foundation (SNF) grant 320030_189055/1 to PD.
