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dc.contributor.authorMergental, H
dc.contributor.authorStephenson, BTF
dc.contributor.authorLaing, RW
dc.contributor.authorKirkham, AJ
dc.contributor.authorNeil, DAH
dc.contributor.authorWallace, LL
dc.contributor.authorBoteon, YL
dc.contributor.authorWidmer, J
dc.contributor.authorBhogal, RH
dc.contributor.authorPerera, MTPR
dc.contributor.authorSmith, A
dc.contributor.authorReynolds, GM
dc.contributor.authorYap, C
dc.contributor.authorHübscher, SG
dc.contributor.authorMirza, DF
dc.contributor.authorAfford, SC
dc.date.accessioned2019-12-10T11:19:30Z
dc.date.issued2018-10
dc.identifier.citationLiver 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
dc.identifier.issn1527-6465
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3453
dc.identifier.eissn1527-6473
dc.identifier.doi10.1002/lt.25291
dc.description.abstractIncreased 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.
dc.formatPrint
dc.format.extent1453 - 1469
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectLiver
dc.subjectHumans
dc.subjectReperfusion Injury
dc.subjectOrgan Preservation
dc.subjectTissue and Organ Harvesting
dc.subjectPrognosis
dc.subjectLiver Transplantation
dc.subjectFeasibility Studies
dc.subjectPerfusion
dc.subjectTissue Survival
dc.subjectModels, Biological
dc.subjectAdult
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.titleDevelopment of Clinical Criteria for Functional Assessment to Predict Primary Nonfunction of High-Risk Livers Using Normothermic Machine Perfusion.
dc.typeJournal Article
dcterms.dateAccepted2018-05-03
rioxxterms.versionofrecord10.1002/lt.25291
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfLiver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
pubs.issue10
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit
pubs.publication-statusPublished
pubs.volume24
pubs.embargo.termsNot known
pubs.oa-locationhttps://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/lt.25291
icr.researchteamClinical Trials & Statistics Uniten_US
dc.contributor.icrauthorYap, Christinaen


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