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      From “Gut Feeling” to Objectivity: Machine Preservation of the Liver as a Tool to Assess Organ Viability

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          Abstract

          Purpose of Review

          The purpose of this review was to summarise how machine perfusion could contribute to viability assessment of donor livers.

          Recent Findings

          In both hypothermic and normothermic machine perfusion, perfusate transaminase measurement has allowed pretransplant assessment of hepatocellular damage. Hypothermic perfusion permits transplantation of marginal grafts but as yet has not permitted formal viability assessment. Livers undergoing normothermic perfusion have been investigated using parameters similar to those used to evaluate the liver in vivo. Lactate clearance, glucose evolution and pH regulation during normothermic perfusion seem promising measures of viability. In addition, bile chemistry might inform on cholangiocyte viability and the likelihood of post-transplant cholangiopathy.

          Summary

          While the use of machine perfusion technology has the potential to reduce and even remove uncertainty regarding liver graft viability, analysis of large datasets, such as those derived from large multicenter trials of machine perfusion, are needed to provide sufficient information to enable viability parameters to be defined and validated .

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          Most cited references64

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          Liver Transplantation After Ex Vivo Normothermic Machine Preservation: A Phase 1 (First-in-Man) Clinical Trial.

          The number of donor organs suitable for liver transplantation is restricted by cold preservation and ischemia-reperfusion injury. We present the first patients transplanted using a normothermic machine perfusion (NMP) device that transports and stores an organ in a fully functioning state at 37°C. In this Phase 1 trial, organs were retrieved using standard techniques, attached to the perfusion device at the donor hospital, and transported to the implanting center in a functioning state. NMP livers were matched 1:2 to cold-stored livers. Twenty patients underwent liver transplantation after NMP. Median NMP time was 9.3 (3.5-18.5) h versus median cold ischaemia time of 8.9 (4.2-11.4) h. Thirty-day graft survival was similar (100% NMP vs. 97.5% control, p = 1.00). Median peak aspartate aminotransferase in the first 7 days was significantly lower in the NMP group (417 IU [84-4681]) versus (902 IU [218-8786], p = 0.03). This first report of liver transplantation using NMP-preserved livers demonstrates the safety and feasibility of using this technology from retrieval to transplantation, including transportation. NMP may be valuable in increasing the number of donor livers and improving the function of transplantable organs.
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            First Comparison of Hypothermic Oxygenated PErfusion Versus Static Cold Storage of Human Donation After Cardiac Death Liver Transplants: An International-matched Case Analysis.

            Exposure of donor liver grafts to prolonged periods of warm ischemia before procurement causes injuries including intrahepatic cholangiopathy, which may lead to graft loss. Due to unavoidable prolonged ischemic time before procurement in donation after cardiac death (DCD) donation in 1 participating center, each liver graft of this center was pretreated with the new machine perfusion "Hypothermic Oxygenated PErfusion" (HOPE) in an attempt to improve graft quality before implantation.
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              HOPE for human liver grafts obtained from donors after cardiac death.

              Due to ethical rules in most countries, long ischemia times are unavoidable prior to organ procurement of donors without a heartbeat, which can cause early graft failure after liver transplantation or late biliary strictures. Hypothermic oxygenated machine perfusion, used prior to graft implantation, may rescue these high risk organs. Eight patients with end stage liver diseases received human livers, obtained after controlled cardiac death (Maastricht category III), with a median donor warm ischemia time of 38 min, followed by a standard cold flush and static storage at 4 °C. Hypothermic oxygenated perfusion (HOPE) was applied for 1-2h prior to implantation through the portal vein. The HOPE-perfusate was cooled at 10 °C and oxygenated (pO2 60 kPa) using an ECOPS device (Organ Assist®). Perfusion pressure was maintained below 3 mmHg. Each machine perfused liver graft disclosed excellent early function after transplantation. The release of liver enzymes and kidney function, as well as ICU and hospital stays were comparable or better than in matched liver grafts from brain death donors. No evidence of intrahepatic biliary complications could be documented within a median follow up of 8.5 months. This is the first report on cold machine perfusion of human liver grafts obtained after cardiac arrest and subsequent transplantation. Application of HOPE appears well tolerated, easy-to-use, and protective against early and later injuries. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                cjew2@cam.ac.uk
                Journal
                Curr Transplant Rep
                Curr Transplant Rep
                Current Transplantation Reports
                Springer International Publishing (Cham )
                2196-3029
                20 January 2018
                20 January 2018
                2018
                : 5
                : 1
                : 72-81
                Affiliations
                [1 ]ISNI 0000000121885934, GRID grid.5335.0, Department of Surgery, , University of Cambridge School of Clinical Medicine, ; Cambridge, UK
                [2 ]ISNI 0000 0001 2116 3923, GRID grid.451056.3, The National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre and the NIHR Blood and Transplant Research Unit (BTRU) at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT), ; Cambridge, UK
                [3 ]ISNI 0000 0001 0668 7884, GRID grid.5596.f, Laboratory of Abdominal Transplant Surgery, Department of Microbiology and Immunology, , KU Leuven, ; Leuven, Belgium
                [4 ]ISNI 0000 0004 0626 3338, GRID grid.410569.f, Department of Abdominal Transplant Surgery, , University Hospitals Leuven, ; Leuven, Belgium
                Article
                178
                10.1007/s40472-018-0178-9
                5843692
                29564205
                774e0f76-98ae-435d-bfce-a2cffb222d50
                © The Author(s) 2018

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                Funding
                Funded by: University of Cambridge
                Categories
                Machine Preservation of the Liver (C Miller and C Quintini, Section Editors)
                Custom metadata
                © Springer International Publishing AG, part of Springer Nature 2018

                liver transplantation,organ preservation,normothermic perfusion,viability assessment,machine perfusion

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