A proof of concept study on real-time LiMAx CYP1A2 liver function assessment of donor grafts during normothermic machine perfusion.
Adult
Aged
Cold Ischemia
Cytochrome P-450 CYP1A2
/ genetics
Graft Survival
Humans
Lactic Acid
/ metabolism
Liver
/ physiology
Liver Diseases
/ pathology
Liver Transplantation
/ methods
Living Donors
Middle Aged
Organ Preservation
/ instrumentation
Perfusion
/ instrumentation
Probability
Proof of Concept Study
Reperfusion Injury
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
06 12 2021
06 12 2021
Historique:
received:
08
07
2021
accepted:
08
11
2021
entrez:
7
12
2021
pubmed:
8
12
2021
medline:
28
1
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34873187
doi: 10.1038/s41598-021-02641-0
pii: 10.1038/s41598-021-02641-0
pmc: PMC8648778
doi:
Substances chimiques
Lactic Acid
33X04XA5AT
CYP1A2 protein, human
EC 1.14.14.1
Cytochrome P-450 CYP1A2
EC 1.14.14.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
23444Informations de copyright
© 2021. The Author(s).
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