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Development of Clinical Criteria for Functional Assessment to Predict Primary Nonfunction of High‐Risk Livers Using Normothermic Machine Perfusion

Increased use of high‐risk allografts is critical to meet the demand for liver transplantation. We aimed to identify criteria predicting viability of organs, currently declined for clinical transplantation, using functional assessment during normothermic machine perfusion (NMP). Twelve discarded hum...

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Autores principales: Mergental, Hynek, Stephenson, Barnaby T. F., Laing, Richard W., Kirkham, Amanda J., Neil, Desley A. H., Wallace, Lorraine L., Boteon, Yuri L., Widmer, Jeannette, Bhogal, Ricky H., Perera, M. Thamara P. R., Smith, Amanda, Reynolds, Gary M., Yap, Christina, Hübscher, Stefan G., Mirza, Darius F., Afford, Simon C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659387/
https://www.ncbi.nlm.nih.gov/pubmed/30359490
http://dx.doi.org/10.1002/lt.25291
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author Mergental, Hynek
Stephenson, Barnaby T. F.
Laing, Richard W.
Kirkham, Amanda J.
Neil, Desley A. H.
Wallace, Lorraine L.
Boteon, Yuri L.
Widmer, Jeannette
Bhogal, Ricky H.
Perera, M. Thamara P. R.
Smith, Amanda
Reynolds, Gary M.
Yap, Christina
Hübscher, Stefan G.
Mirza, Darius F.
Afford, Simon C.
author_facet Mergental, Hynek
Stephenson, Barnaby T. F.
Laing, Richard W.
Kirkham, Amanda J.
Neil, Desley A. H.
Wallace, Lorraine L.
Boteon, Yuri L.
Widmer, Jeannette
Bhogal, Ricky H.
Perera, M. Thamara P. R.
Smith, Amanda
Reynolds, Gary M.
Yap, Christina
Hübscher, Stefan G.
Mirza, Darius F.
Afford, Simon C.
author_sort Mergental, Hynek
collection PubMed
description Increased use of high‐risk allografts is critical to meet the demand for liver transplantation. We aimed to identify criteria predicting viability of organs, currently declined for clinical transplantation, using functional assessment during normothermic machine perfusion (NMP). Twelve discarded human livers were subjected to NMP following static cold storage. Livers were perfused with a packed red cell–based fluid at 37°C for 6 hours. Multilevel statistical models for repeated measures were employed to investigate the trend of perfusate blood gas profiles and vascular flow characteristics over time and the effect of lactate‐clearing (LC) and non‐lactate‐clearing (non‐LC) ability of the livers. The relationship of lactate clearance capability with bile production and histological and molecular findings were also examined. After 2 hours of perfusion, median lactate concentrations were 3.0 and 14.6 mmol/L in the LC and non‐LC groups, respectively. LC livers produced more bile and maintained a stable perfusate pH and vascular flow >150 and 500 mL/minute through the hepatic artery and portal vein, respectively. Histology revealed discrepancies between subjectively discarded livers compared with objective findings. There were minimal morphological changes in the LC group, whereas non‐LC livers often showed hepatocellular injury and reduced glycogen deposition. Adenosine triphosphate levels in the LC group increased compared with the non‐LC livers. We propose composite viability criteria consisting of lactate clearance, pH maintenance, bile production, vascular flow patterns, and liver macroscopic appearance. These have been tested successfully in clinical transplantation. In conclusion, NMP allows an objective assessment of liver function that may reduce the risk and permit use of currently unused high‐risk livers.
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spelling pubmed-66593872019-08-01 Development of Clinical Criteria for Functional Assessment to Predict Primary Nonfunction of High‐Risk Livers Using Normothermic Machine Perfusion Mergental, Hynek Stephenson, Barnaby T. F. Laing, Richard W. Kirkham, Amanda J. Neil, Desley A. H. Wallace, Lorraine L. Boteon, Yuri L. Widmer, Jeannette Bhogal, Ricky H. Perera, M. Thamara P. R. Smith, Amanda Reynolds, Gary M. Yap, Christina Hübscher, Stefan G. Mirza, Darius F. Afford, Simon C. Liver Transpl Original Articles Increased use of high‐risk allografts is critical to meet the demand for liver transplantation. We aimed to identify criteria predicting viability of organs, currently declined for clinical transplantation, using functional assessment during normothermic machine perfusion (NMP). Twelve discarded human livers were subjected to NMP following static cold storage. Livers were perfused with a packed red cell–based fluid at 37°C for 6 hours. Multilevel statistical models for repeated measures were employed to investigate the trend of perfusate blood gas profiles and vascular flow characteristics over time and the effect of lactate‐clearing (LC) and non‐lactate‐clearing (non‐LC) ability of the livers. The relationship of lactate clearance capability with bile production and histological and molecular findings were also examined. After 2 hours of perfusion, median lactate concentrations were 3.0 and 14.6 mmol/L in the LC and non‐LC groups, respectively. LC livers produced more bile and maintained a stable perfusate pH and vascular flow >150 and 500 mL/minute through the hepatic artery and portal vein, respectively. Histology revealed discrepancies between subjectively discarded livers compared with objective findings. There were minimal morphological changes in the LC group, whereas non‐LC livers often showed hepatocellular injury and reduced glycogen deposition. Adenosine triphosphate levels in the LC group increased compared with the non‐LC livers. We propose composite viability criteria consisting of lactate clearance, pH maintenance, bile production, vascular flow patterns, and liver macroscopic appearance. These have been tested successfully in clinical transplantation. In conclusion, NMP allows an objective assessment of liver function that may reduce the risk and permit use of currently unused high‐risk livers. John Wiley and Sons Inc. 2018-10-25 2018-10 /pmc/articles/PMC6659387/ /pubmed/30359490 http://dx.doi.org/10.1002/lt.25291 Text en © 2018 The Authors. Liver Transplantation published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Mergental, Hynek
Stephenson, Barnaby T. F.
Laing, Richard W.
Kirkham, Amanda J.
Neil, Desley A. H.
Wallace, Lorraine L.
Boteon, Yuri L.
Widmer, Jeannette
Bhogal, Ricky H.
Perera, M. Thamara P. R.
Smith, Amanda
Reynolds, Gary M.
Yap, Christina
Hübscher, Stefan G.
Mirza, Darius F.
Afford, Simon C.
Development of Clinical Criteria for Functional Assessment to Predict Primary Nonfunction of High‐Risk Livers Using Normothermic Machine Perfusion
title Development of Clinical Criteria for Functional Assessment to Predict Primary Nonfunction of High‐Risk Livers Using Normothermic Machine Perfusion
title_full Development of Clinical Criteria for Functional Assessment to Predict Primary Nonfunction of High‐Risk Livers Using Normothermic Machine Perfusion
title_fullStr Development of Clinical Criteria for Functional Assessment to Predict Primary Nonfunction of High‐Risk Livers Using Normothermic Machine Perfusion
title_full_unstemmed Development of Clinical Criteria for Functional Assessment to Predict Primary Nonfunction of High‐Risk Livers Using Normothermic Machine Perfusion
title_short Development of Clinical Criteria for Functional Assessment to Predict Primary Nonfunction of High‐Risk Livers Using Normothermic Machine Perfusion
title_sort development of clinical criteria for functional assessment to predict primary nonfunction of high‐risk livers using normothermic machine perfusion
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659387/
https://www.ncbi.nlm.nih.gov/pubmed/30359490
http://dx.doi.org/10.1002/lt.25291
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