Criteria for viability assessment of discarded human donor livers during ex vivo normothermic machine perfusion.

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 vi...

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Main Authors: Michael E Sutton, Sanna op den Dries, Negin Karimian, Pepijn D Weeder, Marieke T de Boer, Janneke Wiersema-Buist, Annette S H Gouw, Henri G D Leuvenink, Ton Lisman, Robert J Porte
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0110642
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spelling doaj-857a103b814f476eba0ddbadfb88cec22021-03-04T08:50:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01911e11064210.1371/journal.pone.0110642Criteria for viability assessment of discarded human donor livers during ex vivo normothermic machine perfusion.Michael E SuttonSanna op den DriesNegin KarimianPepijn D WeederMarieke T de BoerJanneke Wiersema-BuistAnnette S H GouwHenri G D LeuveninkTon LismanRobert J PorteAlthough 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.https://doi.org/10.1371/journal.pone.0110642
collection DOAJ
language English
format Article
sources DOAJ
author Michael E Sutton
Sanna op den Dries
Negin Karimian
Pepijn D Weeder
Marieke T de Boer
Janneke Wiersema-Buist
Annette S H Gouw
Henri G D Leuvenink
Ton Lisman
Robert J Porte
spellingShingle Michael E Sutton
Sanna op den Dries
Negin Karimian
Pepijn D Weeder
Marieke T de Boer
Janneke Wiersema-Buist
Annette S H Gouw
Henri G D Leuvenink
Ton Lisman
Robert J Porte
Criteria for viability assessment of discarded human donor livers during ex vivo normothermic machine perfusion.
PLoS ONE
author_facet Michael E Sutton
Sanna op den Dries
Negin Karimian
Pepijn D Weeder
Marieke T de Boer
Janneke Wiersema-Buist
Annette S H Gouw
Henri G D Leuvenink
Ton Lisman
Robert J Porte
author_sort Michael E Sutton
title Criteria for viability assessment of discarded human donor livers during ex vivo normothermic machine perfusion.
title_short Criteria for viability assessment of discarded human donor livers during ex vivo normothermic machine perfusion.
title_full Criteria for viability assessment of discarded human donor livers during ex vivo normothermic machine perfusion.
title_fullStr Criteria for viability assessment of discarded human donor livers during ex vivo normothermic machine perfusion.
title_full_unstemmed Criteria for viability assessment of discarded human donor livers during ex vivo normothermic machine perfusion.
title_sort criteria for viability assessment of discarded human donor livers during ex vivo normothermic machine perfusion.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2014-01-01
description 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.
url https://doi.org/10.1371/journal.pone.0110642
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