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A proof of concept study on real-time LiMAx CYP1A2 liver function assessment of donor grafts during normothermic machine perfusion
No single reliable parameter exists to assess liver graft function of extended criteria donors during ex-vivo normothermic machine perfusion (NMP). The liver maximum capacity (LiMAx) test is a clinically validated cytochromal breath test, measuring liver function based on 13CO2 production. As an inn...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8648778/ https://www.ncbi.nlm.nih.gov/pubmed/34873187 http://dx.doi.org/10.1038/s41598-021-02641-0 |
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author | Schurink, Ivo J. de Haan, Jubi E. Willemse, Jorke Mueller, Matteo Doukas, Michael Roest, Henk de Goeij, Femke H. C. Polak, Wojciech G. Ijzermans, Jan N. M. Dutkowski, Philipp van der Laan, Luc J. W. de Jonge, Jeroen |
author_facet | Schurink, Ivo J. de Haan, Jubi E. Willemse, Jorke Mueller, Matteo Doukas, Michael Roest, Henk de Goeij, Femke H. C. Polak, Wojciech G. Ijzermans, Jan N. M. Dutkowski, Philipp van der Laan, Luc J. W. de Jonge, Jeroen |
author_sort | Schurink, Ivo J. |
collection | PubMed |
description | No single reliable parameter exists to assess liver graft function of extended criteria donors during ex-vivo normothermic machine perfusion (NMP). The liver maximum capacity (LiMAx) test is a clinically validated cytochromal breath test, measuring liver function based on 13CO2 production. As an innovative concept, we aimed to integrate the LiMAx breath test with NMP to assess organ function. Eleven human livers were perfused using NMP. After one hour of stabilization, LiMAx testing was performed. Injury markers (ALT, AST, miR-122, FMN, and Suzuki-score) and lactate clearance were measured and related to LiMAx values. LiMAx values ranged between 111 and 1838 µg/kg/h, and performing consecutive LiMAx tests during longer NMP was feasible. No correlation was found between LiMAx value and miR-122 and FMN levels in the perfusate. However, a significant inverse correlation was found between LiMAx value and histological injury (Suzuki-score, R = − 0.874, P < 0.001), AST (R = − 0.812, P = 0.004) and ALT (R = − 0.687, P = 0.028). Furthermore, a significant correlation was found with lactate clearance (R = 0.683, P = 0.043). We demonstrate, as proof of principle, that liver function during NMP can be quantified using the LiMAx test, illustrating a positive correlation with traditional injury markers. This new breath-test application separates livers with adequate cytochromal liver function from inadequate ones and may support decision-making in the safe utilization of extended criteria donor grafts. |
format | Online Article Text |
id | pubmed-8648778 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-86487782021-12-08 A proof of concept study on real-time LiMAx CYP1A2 liver function assessment of donor grafts during normothermic machine perfusion Schurink, Ivo J. de Haan, Jubi E. Willemse, Jorke Mueller, Matteo Doukas, Michael Roest, Henk de Goeij, Femke H. C. Polak, Wojciech G. Ijzermans, Jan N. M. Dutkowski, Philipp van der Laan, Luc J. W. de Jonge, Jeroen Sci Rep Article No single reliable parameter exists to assess liver graft function of extended criteria donors during ex-vivo normothermic machine perfusion (NMP). The liver maximum capacity (LiMAx) test is a clinically validated cytochromal breath test, measuring liver function based on 13CO2 production. As an innovative concept, we aimed to integrate the LiMAx breath test with NMP to assess organ function. Eleven human livers were perfused using NMP. After one hour of stabilization, LiMAx testing was performed. Injury markers (ALT, AST, miR-122, FMN, and Suzuki-score) and lactate clearance were measured and related to LiMAx values. LiMAx values ranged between 111 and 1838 µg/kg/h, and performing consecutive LiMAx tests during longer NMP was feasible. No correlation was found between LiMAx value and miR-122 and FMN levels in the perfusate. However, a significant inverse correlation was found between LiMAx value and histological injury (Suzuki-score, R = − 0.874, P < 0.001), AST (R = − 0.812, P = 0.004) and ALT (R = − 0.687, P = 0.028). Furthermore, a significant correlation was found with lactate clearance (R = 0.683, P = 0.043). We demonstrate, as proof of principle, that liver function during NMP can be quantified using the LiMAx test, illustrating a positive correlation with traditional injury markers. This new breath-test application separates livers with adequate cytochromal liver function from inadequate ones and may support decision-making in the safe utilization of extended criteria donor grafts. Nature Publishing Group UK 2021-12-06 /pmc/articles/PMC8648778/ /pubmed/34873187 http://dx.doi.org/10.1038/s41598-021-02641-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Schurink, Ivo J. de Haan, Jubi E. Willemse, Jorke Mueller, Matteo Doukas, Michael Roest, Henk de Goeij, Femke H. C. Polak, Wojciech G. Ijzermans, Jan N. M. Dutkowski, Philipp van der Laan, Luc J. W. de Jonge, Jeroen A proof of concept study on real-time LiMAx CYP1A2 liver function assessment of donor grafts during normothermic machine perfusion |
title | A proof of concept study on real-time LiMAx CYP1A2 liver function assessment of donor grafts during normothermic machine perfusion |
title_full | A proof of concept study on real-time LiMAx CYP1A2 liver function assessment of donor grafts during normothermic machine perfusion |
title_fullStr | A proof of concept study on real-time LiMAx CYP1A2 liver function assessment of donor grafts during normothermic machine perfusion |
title_full_unstemmed | A proof of concept study on real-time LiMAx CYP1A2 liver function assessment of donor grafts during normothermic machine perfusion |
title_short | A proof of concept study on real-time LiMAx CYP1A2 liver function assessment of donor grafts during normothermic machine perfusion |
title_sort | proof of concept study on real-time limax cyp1a2 liver function assessment of donor grafts during normothermic machine perfusion |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8648778/ https://www.ncbi.nlm.nih.gov/pubmed/34873187 http://dx.doi.org/10.1038/s41598-021-02641-0 |
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