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Ischemia-Reperfusion Injury in Marginal Liver Grafts and the Role of Hypothermic Machine Perfusion: Molecular Mechanisms and Clinical Implications

1
Department of Surgery and Transplantation, University Hospital RWTH Aachen, 52074 Aachen, Germany
2
Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum—Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany
3
Department of Hepatology and Gastroenterology, Campus Charité Mitte | Campus Virchow-Klinikum—Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany
4
Department of Gastroenterology, Metabolic Disorders and Intensive Care, University Hospital RWTH Aachen, 52074 Aachen, Germany
5
Department of Transplant Surgery, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic
6
Department of General, Visceral and Transplantation Surgery, University of Heidelberg, 69120 Heidelberg, Germany
7
The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, UK
*
Author to whom correspondence should be addressed.
First two and last two authors contributed equally to this manuscript.
J. Clin. Med. 2020, 9(3), 846; https://doi.org/10.3390/jcm9030846
Received: 13 February 2020 / Revised: 9 March 2020 / Accepted: 11 March 2020 / Published: 20 March 2020
Ischemia-reperfusion injury (IRI) constitutes a significant source of morbidity and mortality after orthotopic liver transplantation (OLT). The allograft is metabolically impaired during warm and cold ischemia and is further damaged by a paradox reperfusion injury after revascularization and reoxygenation. Short-term and long-term complications including post-reperfusion syndrome, delayed graft function, and immune activation have been associated with IRI. Due to the current critical organ shortage, extended criteria grafts are increasingly considered for transplantation, however, with an elevated risk to develop significant features of IRI. In recent years, ex vivo machine perfusion (MP) of the donor liver has witnessed significant advancements. Here, we describe the concept of hypothermic (oxygenated) machine perfusion (HMP/HOPE) approaches and highlight which allografts may benefit from this technology. This review also summarizes clinical applications and the main aspects of ongoing randomized controlled trials on hypothermic perfusion. The mechanistic aspects of IRI and hypothermic MP—which include tissue energy replenishment, optimization of mitochondrial function, and the reduction of oxidative and inflammatory damage following reperfusion—will be comprehensively discussed within the context of current preclinical and clinical evidence. Finally, we highlight novel trends and future perspectives in the field of hypothermic MP in the context of recent findings of basic and translational research. View Full-Text
Keywords: ischemia-reperfusion injury; extended criteria donation; machine perfusion; HOPE; hypothermic machine perfusion ischemia-reperfusion injury; extended criteria donation; machine perfusion; HOPE; hypothermic machine perfusion
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Czigany, Z.; Lurje, I.; Schmelzle, M.; Schöning, W.; Öllinger, R.; Raschzok, N.; Sauer, I.M.; Tacke, F.; Strnad, P.; Trautwein, C.; Neumann, U.P.; Fronek, J.; Mehrabi, A.; Pratschke, J.; Schlegel, A.; Lurje, G. Ischemia-Reperfusion Injury in Marginal Liver Grafts and the Role of Hypothermic Machine Perfusion: Molecular Mechanisms and Clinical Implications. J. Clin. Med. 2020, 9, 846.

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