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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Abstract

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
Volume34
Issue number3
Early online date26-Jan-2020
DOIs
Publication statusPublished - 20-Feb-2020

Keywords

  • biomarker
  • cholangiocyte-derived microRNA
  • hepatocyte-derived microRNA
  • miR-122
  • miR-222
  • transplantation
  • TRANSPLANTATION
  • PRESERVATION
  • BIOMARKERS
  • CRITERIA
  • INJURY
  • SERUM
  • RELEASE

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