Ivo J Schurink, Stefan H Luijmes, Jorke Willemse, Femke H C de Goeij, Puck C Groen, Efrayim H Küçükerbil, Roberto Broere, Marco M Pascale, Robert J Porte, Andrei N Tintu, Luc J W van der Laan, Wojciech G Polak, Jeroen de Jonge
{"title":"Assessment of Ex Situ Liver Function by Indocyanine Green Clearance During Clinical Normothermic Machine Perfusion of Extended Criteria Grafts.","authors":"Ivo J Schurink, Stefan H Luijmes, Jorke Willemse, Femke H C de Goeij, Puck C Groen, Efrayim H Küçükerbil, Roberto Broere, Marco M Pascale, Robert J Porte, Andrei N Tintu, Luc J W van der Laan, Wojciech G Polak, Jeroen de Jonge","doi":"10.1097/TP.0000000000005350","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Normothermic machine perfusion (NMP) enables pretransplantation assessment of donor liver viability to increase donor liver utilization. However, unambiguous objective criteria to determine integrated liver function during NMP to decide upon acceptance are still lacking. This study investigates whether the indocyanine green (ICG) elimination test can be applied to assess liver function during NMP.</p><p><strong>Methods: </strong>Donor livers underwent dual-hypothermic oxygenated machine perfusion and NMP. The ICG elimination test was improved during an optimization phase (n = 10) and tested against current functional perfusion parameters and posttransplantation outcomes in clinically perfused livers (n = 32).</p><p><strong>Results: </strong>The ICG plasma disappearance rate (PDR) during NMP was dependent on perfusion blood flow and liver weight. The corrected PDR (NMP-PDR) was correlated to the hepatic extraction rate (R = 0.923; P > 0.001) and ATP content in liver biopsies at 2 h of NMP (R = 0.692; P = 0.027). In the clinical phase, the length of the functional warm ischemia time in the donation process was inversely correlated to the NMP-PDR (P = 0.042). Both individual acceptance criteria (lactate clearance, ability of self-regulate pH, Δbicarbonate, and ΔpH) and overall hepatocellular and cholangiocellular acceptance criteria were correlated to the NMP-PDR. The NMP-PDR was higher in the cohort accepted for transplantation (n = 18; 18.1%/L·kg [14.0% to 22.7%/L·kg]) than in the nontransplanted cohort (n = 14; 11.8%/L·kg [8.8% to 12.9%/L·kg]; P < 0.0001). Furthermore, the NMP-PDR correlated with the liver graft assessment following transplantation at 7 d score posttransplantation (R = -0.551; P = 0.027).</p><p><strong>Conclusions: </strong>We demonstrate that the NMP-PDR correlates with both liver function during NMP and short-term posttransplantation outcomes. This simple objective test has the potential to increase donor liver utilization rate, while preventing hepatocellular dysfunction posttransplantation.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.3000,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Transplantation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/TP.0000000000005350","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Normothermic machine perfusion (NMP) enables pretransplantation assessment of donor liver viability to increase donor liver utilization. However, unambiguous objective criteria to determine integrated liver function during NMP to decide upon acceptance are still lacking. This study investigates whether the indocyanine green (ICG) elimination test can be applied to assess liver function during NMP.
Methods: Donor livers underwent dual-hypothermic oxygenated machine perfusion and NMP. The ICG elimination test was improved during an optimization phase (n = 10) and tested against current functional perfusion parameters and posttransplantation outcomes in clinically perfused livers (n = 32).
Results: The ICG plasma disappearance rate (PDR) during NMP was dependent on perfusion blood flow and liver weight. The corrected PDR (NMP-PDR) was correlated to the hepatic extraction rate (R = 0.923; P > 0.001) and ATP content in liver biopsies at 2 h of NMP (R = 0.692; P = 0.027). In the clinical phase, the length of the functional warm ischemia time in the donation process was inversely correlated to the NMP-PDR (P = 0.042). Both individual acceptance criteria (lactate clearance, ability of self-regulate pH, Δbicarbonate, and ΔpH) and overall hepatocellular and cholangiocellular acceptance criteria were correlated to the NMP-PDR. The NMP-PDR was higher in the cohort accepted for transplantation (n = 18; 18.1%/L·kg [14.0% to 22.7%/L·kg]) than in the nontransplanted cohort (n = 14; 11.8%/L·kg [8.8% to 12.9%/L·kg]; P < 0.0001). Furthermore, the NMP-PDR correlated with the liver graft assessment following transplantation at 7 d score posttransplantation (R = -0.551; P = 0.027).
Conclusions: We demonstrate that the NMP-PDR correlates with both liver function during NMP and short-term posttransplantation outcomes. This simple objective test has the potential to increase donor liver utilization rate, while preventing hepatocellular dysfunction posttransplantation.
期刊介绍:
The official journal of The Transplantation Society, and the International Liver Transplantation Society, Transplantation is published monthly and is the most cited and influential journal in the field, with more than 25,000 citations per year.
Transplantation has been the trusted source for extensive and timely coverage of the most important advances in transplantation for over 50 years. The Editors and Editorial Board are an international group of research and clinical leaders that includes many pioneers of the field, representing a diverse range of areas of expertise. This capable editorial team provides thoughtful and thorough peer review, and delivers rapid, careful and insightful editorial evaluation of all manuscripts submitted to the journal.
Transplantation is committed to rapid review and publication. The journal remains competitive with a time to first decision of fewer than 21 days. Transplantation was the first in the field to offer CME credit to its peer reviewers for reviews completed.
The journal publishes original research articles in original clinical science and original basic science. Short reports bring attention to research at the forefront of the field. Other areas covered include cell therapy and islet transplantation, immunobiology and genomics, and xenotransplantation.