Cell-free microRNAs as early predictors of graft viability during ex vivo normothermic machine perfusion of human donor livers

Alix P. M. Matton, Jasmijn W. Selten, Henk P. Roest*, Jeroen De Jonge, Jan N. M. IJzermans, Vincent E. De Meijer, Robert J. Porte, Luc J. W. Van der Laan

*Corresponding author for this work

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Background Cell-free microRNAs (miRs) have emerged as early and sensitive biomarkers for tissue injury and function. This study aimed to investigate whether the release of hepatocyte-derived microRNAs (HDmiRs) and cholangiocyte-derived miRs (CDmiRs) correlates with hepato-cholangiocellular injury and function during oxygenated, normothermic machine perfusion (NMP) of human liver grafts.

Methods Donor livers (n = 12), declined for transplantation, were subjected to oxygenated NMP (6 hours) after a period of static cold storage (median 544 minutes (IQR 421-674)). Perfusate and bile samples were analyzed by qRT-PCR for HDmiR-122 and CDmiR-222. Spearman correlations were performed between miR levels and currently available indicators and classic markers.

Results Both HDmiR-122 and CDmiR-222 levels in perfusate at 30 minutes of NMP strongly correlated with hepatocyte injury (peak perfusate AST) and cholangiocyte injury (peak biliary LDH). In bile, only CDmiR-222 correlated with these injury markers. For hepato-cholangiocellular function, both miRs in perfusate correlated with total bilirubin, while HDmiR-122 (in perfusate) and CDmiR-222 (in bile) correlated with bicarbonate secretion. Both the relative ratio of HDmiR-122/CDmiR-222 and AST in perfusate at 30 minutes significantly correlated with cumulative bile production, but only the relative ratio was predictive of histopathological injury after 6 hours NMP.

Conclusion Early levels of HDmiR-122 and CDmiR-222, in perfusate and/or bile, are predictive of excretory functions and hepato-cholangiocellular injury after 6 hours NMP. These miRs may represent new biomarkers for graft viability and function during machine perfusion.

Original languageEnglish
Article number13790
Number of pages10
JournalClinical Transplantation
Issue number3
Early online date26-Jan-2020
Publication statusPublished - 20-Feb-2020


  • biomarker
  • cholangiocyte-derived microRNA
  • hepatocyte-derived microRNA
  • miR-122
  • miR-222
  • transplantation

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