• Sousa Da SilvaRichard XRXDepartment of Surgery and Transplantation, Swiss HPB and Transplant Center Zurich, University Hospital Zurich, Zurich, Switzerland.Wyss Zurich Translational Center, ETH Zurich and University of Zurich, Zurich, Switzerland., Bautista BorregoLuciaLDepartment of Surgery and Transplantation, Swiss HPB and Transplant Center Zurich, University Hospital Zurich, Zurich, Switzerland.Wyss Zurich Translational Center, ETH Zurich and University of Zurich, Zurich, Switzerland., Daniela Lenggenhager, Florian Huwyler, Jonas Binz, Leandro Mancina, Eva Breuer, Kendra Wernlé, Max Hefti, Matteo Mueller, Leslie Cunningham, Michelle L De Oliveira, Henrik Petrowsky, Achim Weber, Philipp Dutkowski, Waldemar Hoffmann, Anurag Gupta, Mark W Tibbitt, Bostjan Humar, and Pierre-Alain Clavien.
• Department of Surgery and Transplantation, Swiss HPB and Transplant Center Zurich, University Hospital Zurich, Zurich, Switzerland.
• Ann. Surg. 2023 Nov 1; 278 (5): 669675669-675.

ObjectiveTo develop a protocol for the defatting of steatotic liver grafts during long-term ex situ normothermic machine perfusion.BackgroundDespite the alarming increase in donor organ shortage, the highly prevalent fatty liver grafts are often discarded due to the risk of primary nonfunction. Effective strategies preventing such outcomes are currently lacking. An exciting new avenue is the introduction of ex situ normothermic machine perfusion (NMP), enabling a liver to remain fully functional for up to 2 weeks and providing a unique window of opportunity for defatting before transplantation.MethodsOver a 5-year period, 23 discarded liver grafts and 28 partial livers from our resection program were tested during ex situ normothermic machine perfusion. The steatosis degree was determined on serial biopsies by expert pathologists, and triglyceride contents were measured simultaneously.ResultsOf 51 liver grafts, 20 were steatotic, with up to 85% macrovesicular steatosis, and were perfused for up to 12 days. Ten livers displayed marked (5 of which almost complete) loss of fat, while the other 10 did not respond to long-term perfusion. Successful defatting was related to prolonged perfusion, automated glucose control, circadian nutrition, and L-carnitine/fenofibrate supplementation. Pseudopeliotic steatosis and the associated activation of Kupffer/stellate cells were unexpected processes that might contribute to defatting. Synthetic and metabolic functions remained preserved for most grafts until perfusion ended.ConclusionEx situ long-term perfusion effectively reduces steatosis while preserving organ viability and may in the future allow transplantation of primarily unusable high-risk grafts, significantly increasing the number of organs available for transplantation.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

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