Ex vivo machine perfusion: current applications and future directions in liver transplantation

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SYSTEMATIC REVIEWS AND META-ANALYSES

Ex vivo machine perfusion: current applications and future directions in liver transplantation Julian Michelotto 1 & Joseph M. G. V. Gassner 1 & Simon Moosburner 1 & Vanessa Muth 1 & Madhukar S. Patel 2 & Markus Selzner 2 & Johann Pratschke 1 & Igor M. Sauer 1 & Nathanael Raschzok 1,2 Received: 26 June 2020 / Accepted: 21 July 2020 # The Author(s) 2020

Abstract Background Liver transplantation is the only curative treatment option for end-stage liver disease; however, its use remains limited due to a shortage of suitable organs. In recent years, ex vivo liver machine perfusion has been introduced to liver transplantation, as a means to expand the donor organ pool. Purpose To present a systematic review of prospective clinical studies on ex vivo liver machine perfusion, in order to assess current applications and highlight future directions. Methods A systematic literature search of both PubMed and ISI web of science databases as well as the ClinicalTrials.gov registry was performed. Results Twenty-one articles on prospective clinical trials on ex vivo liver machine perfusion were identified. Out of these, eight reported on hypothermic, eleven on normothermic, and two on sequential perfusion. These trials have demonstrated the safety and feasibility of ex vivo liver machine perfusion in both standard and expanded criteria donors. Currently, there are twelve studies enrolled in the clinicaltrials.gov registry, and these focus on use of ex vivo perfusion in extended criteria donors and declined organs. Conclusion Ex vivo liver machine perfusion seems to be a suitable strategy to expand the donor pool for liver transplantation and holds promise as a platform for reconditioning diseased organs. Keywords Machine perfusion . Liver transplantation . Clinical application . Systematic literature review

Abbreviations EAD Early allograft dysfunction PNF Primary nonfunction DBD Donation after brain death DCD Donation after circulatory death IRI Ischemia-reperfusion injury Julian Michelotto and Joseph M. G. V. Gaßner contributed equally to this work. * Nathanael Raschzok [email protected] 1

2

Charité – Universitätsmedizin Berlin, Department of Surgery, Experimental Surgery, corporate member of Freie Universität Berlin, Humboldt- Universität zu Berlin and Berlin Institute of Health, Campus Charité Mitte | Campus Virchow-Klinikum, Berlin, Germany Department of Surgery, Abdominal Transplant and HPB Surgery, Ajmera Family Transplant Centre, Toronto General Hospital, Toronto, ON, Canada

SCS HMP HOPE D-HOPE HLS pSCS NEVLP

Static cold storage Hypothermic machine perfusion Hypothermic oxygenated machine perfusion Dual hypothermic oxygenated machine perfusion Hospital length of stay post-Static cold storage Normothermic ex vivo liver machine perfusion

Introduction Liver transplantation is the only curative treatment option for acute liver failure and advanced hepatobiliary malignancies. Unfortunately, this therapy is limited by the supply of suitable donor livers for transplantatio