title: Criteria for viability assessment of discarded human donor livers during ex vivo normothermic machine perfusion.
abstract: Although normothermic machine perfusion of donor livers may allow assessment of graft viability prior to transplantation, there are currently no data on what would be a good parameter of graft viability. To determine whether bile production is a suitable biomarker that can be used to discriminate viable from non-viable livers we have studied functional performance as well as biochemical and histological evidence of hepatobiliary injury during ex vivo normothermic machine perfusion of human donor livers. After a median duration of cold storage of 6.5 h, twelve extended criteria human donor livers that were declined for transplantation were ex vivo perfused for 6 h at 37 °C with an oxygenated solution based on red blood cells and plasma, using pressure controlled pulsatile perfusion of the hepatic artery and continuous portal perfusion. During perfusion, two patterns of bile flow were identified: (1) steadily increasing bile production, resulting in a cumulative output of ≥ 30 g after 6 h (high bile output group), and (2) a cumulative bile production <20 g in 6 h (low bile output group). Concentrations of transaminases and potassium in the perfusion fluid were significantly higher in the low bile output group, compared to the high bile output group. Biliary concentrations of bilirubin and bicarbonate were respectively 4 times and 2 times higher in the high bile output group. Livers in the low bile output group displayed more signs of hepatic necrosis and venous congestion, compared to the high bile output group. In conclusion, bile production could be an easily assessable biomarker of hepatic viability during ex vivo machine perfusion of human donor livers. It could potentially be used to identify extended criteria livers that are suitable for transplantation. These ex vivo findings need to be confirmed in a transplant experiment or a clinical trial.
authors.affiliation: Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Sutton
authors.affiliation: Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Sanna
authors.initials: S
authors.lastname: op den Dries
authors.affiliation: Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Negin
authors.initials: N
authors.lastname: Karimian
authors.affiliation: Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Pepijn D
authors.initials: PD
authors.lastname: Weeder
authors.affiliation: Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Marieke T
authors.initials: MT
authors.lastname: de Boer
authors.affiliation: Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Janneke
authors.initials: J
authors.lastname: Wiersema-Buist
authors.affiliation: Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Annette S H
authors.initials: AS
authors.lastname: Gouw
authors.affiliation: Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Henri G D
authors.initials: HG
authors.lastname: Leuvenink
authors.affiliation: Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Ton
authors.initials: T
authors.lastname: Lisman
authors.affiliation: Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Porte
mesh_terms: D000368:Aged; D001646:Bile / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001784:Blood Gas Analysis; D003710:Demography; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014019:Tissue Donors; D014021:Tissue Preservation
chemical_list: D015415:Biomarkers