Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/34085
Title: Graft-derived cfDNA Monitoring in Plasma and Bile During Normothermic Machine Perfusion in Liver Transplantation Is Feasible and a Potential Tool for Assessing Graft Viability.
Austin Authors: Cox, Daniel R A ;Lee, Eunice ;Wong, Boris K L;McClure, Tess ;Zhang, Fan;Goh, Su Kah ;Vago, Angela ;Jackett, Louise A ;Fink, Michael A ;Jones, Robert M ;Perini, Marcos V ;Dobrovic, Alexander ;Testro, Adam G ;Starkey, Graham M ;Muralidharan, Vijayaragavan 
Affiliation: Surgery (University of Melbourne)
Hepatopancreatobiliary Surgery
Translational Genomics and Epigenomics Laboratory, Department of Surgery (Austin), University of Melbourne, Melbourne, VIC, Australia.;Liver Transplant Unit, Austin Health, Melbourne, VIC, Australia.
Victorian Liver Transplant Unit
Anatomical Pathology
Issue Date: 30-Oct-2023
Date: 2023
Publication information: Transplantation 2023-10-30
Abstract: Ex vivo normothermic machine perfusion (NMP) is an organ preservation technique that enables an extended assessment of graft suitability before liver transplantation (LT). Established monitoring protocols used during NMP vary significantly in their assessment of transplant suitability when applied to the same grafts. Graft-derived cell-free DNA (gdcfDNA) analysis is an emerging tool for monitoring graft health post-transplantation. We investigated the feasibility of monitoring gdcfDNA during NMP for LT in a proof-of-concept, observational study. Serial plasma and bile samples were collected during NMP for 10 consecutive grafts, at 15 min post-machine reperfusion and then 2-h intervals. Digital polymerase chain reaction was used to quantify gdcfDNA at each time point. Five grafts were suitable for LT, there were no cases of primary nonfunction or death in the recipients. gdcfDNA was quantified in all bile and plasma samples (n > 100). In plasma, gdcfDNA concentrations climbed post-machine reperfusion until 4.25 h (median 2.25 h = 15.98 × 106 copies/mL, 4.25 h = 40.21 × 106 copies/mL). gdcfDNA levels then diverged significantly when comparing the viable and non-viable graft groups (6.25 h, median viable: 117.15 × 106 copies/mL versus non-viable: 16.72 × 106 copies/mL, P = 0.01). These opposing trends correlated in each graft and in all cases with the viable/non-viable outcome. There was a trend of gradual decline in bile gdcfDNA from viable grafts post-machine reperfusion; discarded grafts showed more variable patterns of release. gdcfDNA analysis during NMP is a feasible and potential tool to inform viability assessment during NMP for LT. Bile gdcfDNA monitoring offers the prospect of an objective means to assess the degree of biliary injury associated with organ procurement.
URI: https://ahro.austin.org.au/austinjspui/handle/1/34085
DOI: 10.1097/TP.0000000000004842
ORCID: 
Journal: Transplantation
PubMed URL: 37902630
ISSN: 1534-6080
Type: Journal Article
Appears in Collections:Journal articles

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