An integrated perfusion machine preserves injured human livers for 1 week

• Published in: Nature biotechnology Vol. 38; no. 2; pp. 189 - 198
• Main Authors: Eshmuminov, Dilmurodjon, Becker, Dustin, Bautista Borrego, Lucia, Hefti, Max, Schuler, Martin J., Hagedorn, Catherine, Muller, Xavier, Mueller, Matteo, Onder, Christopher, Graf, Rolf, Weber, Achim, Dutkowski, Philipp, Rudolf von Rohr, Philipp, Clavien, Pierre-Alain
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-02-2020; Nature Publishing Group
• Subjects: 631/61; 692/308; 692/308/575; 692/699/1503/1607; Adenosine Triphosphate - metabolism; Agriculture; Alarmins - metabolism; Animals; Automation; Bile; Bioinformatics; Biological products; Biomarkers - metabolism; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedicine; Biotechnology; Cellular manufacture; Cellular structure; Coagulation; Dextrose; Electrolytes - metabolism; Epoprostenol; Glucagon; Glucose; Glucose - metabolism; Hematocrit; Hemodynamics; Hemolysis; Humans; In vivo methods and tests; Insulin; Life Sciences; Liver; Liver - injuries; Liver - physiopathology; Metabolism; Oxygen - metabolism; Oxygen Consumption; Oxygenation; Perfusion; Perfusion - instrumentation; Physiology; Portal Vein - metabolism; Preservation, Biological; Process engineering; Reperfusion; Surgical apparatus & instruments; Swine; Transplantation; Veins & arteries; Viability
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/s41587-019-0374-x

The ability to preserve metabolically active livers ex vivo for 1 week or more could allow repair of poor-quality livers that would otherwise be declined for transplantation. Current approaches for normothermic perfusion can preserve human livers for only 24 h. Here we report a liver perfusion machine that integrates multiple core physiological functions, including automated management of glucose levels and oxygenation, waste-product removal and hematocrit control. We developed the machine in a stepwise fashion using pig livers. Study of multiple ex vivo parameters and early phase reperfusion in vivo demonstrated the viability of pig livers perfused for 1 week without the need for additional blood products or perfusate exchange. We tested the approach on ten injured human livers that had been declined for transplantation by all European centers. After a 7-d perfusion, six of the human livers showed preserved function as indicated by bile production, synthesis of coagulation factors, maintained cellular energy (ATP) and intact liver structure.
Livers are stored long term in a sophisticated perfusion system.