MicroRNA profiles in graft preservation solution are associated with early allograft dysfunction after liver transplantation

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J.W. Selten, C.J. Verhoeven, H.P. Roest, R.W.F. de Bruin, J. de Jonge, J.N.M Ijzermans, L.J.W. van der Laan

Chair(s): dr. Martin. J. Hoogduijn, wetenschappelijk medewerker, Erasmus MC & prof. dr. Cees. van Kooten, onderzoeker, LUMC

Wednesday 9 march 2016

15:30 - 15:40h at Zaal 5 & 6

Categories: Parallelsessie (basaal)

Parallel session: Parallelsessie IV - Basaal

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Introduction:
Early allograft dysfunction (EAD) after liver transplantation (LT) is associated with inferior patient and graft survival and is more prevalent with increasing cold ischemia times and decreased initial graft quality. However, the possibility of predicting EAD and hereby minimizing the clinical consequences, remains difficult in practice. Recent animal and human studies highlight the potential of hepatocyte-derived microRNAs (HDmiRs) in serum as sensitive, stable an specific biomarkers of liver injury. The aim of this study is to investigate whether HDmiRs in cell-free graft preservation solution are predictive of the development of EAD after liver transplantation.

Methods:
Graft preservation solutions of 83 prospective liver grafts at the end of cold ischemia time were analyzed after heparinase treatment. RT-qPCR was performed for four miRNAs, including miRNA-122 and miR-148a. MircoRNA profiles were compared between patients who developed EAD or primary non-function (PNF) (n=48) with the patients without EAD or PNF (n=35).

Results:
In our cohort, EAD was associated with grafts from donation after cardiac death (DCD) donors, higher donor age (>65), male donors and female recipients (p=0.004; p=0.037; p=0.03; p=0.03). Levels of miR-122 were shown to be higher in preservation solution samples from EAD/PNF grafts (p<0.005), and from DCD donors (p=0.001). Higher levels of miR-122 in preservation solution during transplantation was associated with increased levels of ASAT and ALAT (

Conclusion:
This study demonstrates that HDmiRs in graft preservation solutions may successfully be applied to assess the liver function following transplantation. Increased levels of miR-122 and miR-148a are related to the development of EAD/PNF and long term graft and patient survival. Further research is required for the predictive value of tissue-specific HDmiRs and graft function in perfusion liquids during machine preservation.