Development of Clinical Criteria for Functional Assessment to Predict Primary Nonfunction of High-Risk Livers Using Normothermic Machine Perfusion.
Publication Date
2018-10ICR Author
Author
Mergental, H
Stephenson, BTF
Laing, RW
Kirkham, AJ
Neil, DAH
Wallace, LL
Boteon, YL
Widmer, J
Bhogal, RH
Perera, MTPR
Smith, A
Reynolds, GM
Yap, C
Hübscher, SG
Mirza, DF
Afford, SC
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Open access location
https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/lt.25291Collections
Licenseref URL
http://creativecommons.org/licenses/by/4.0/Version of record
Subject
Liver
Humans
Reperfusion Injury
Organ Preservation
Tissue and Organ Harvesting
Prognosis
Liver Transplantation
Feasibility Studies
Perfusion
Tissue Survival
Models, Biological
Adult
Aged
Middle Aged
Female
Male
Research team
Clinical Trials & Statistics Unit
Language
eng
Date accepted
2018-05-03
License start date
2018-10
Citation
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 2018, 24 (10), pp. 1453 - 1469