Highlights
- •Real-time metabolomics by HR-MAS-NMR accurately predicts early allograft dysfunction.
- •Lactate and phosphocholine content are highly predictive biomarkers of early allograft dysfunction.
- •Livers from patients with sarcopenia and cirrhosis have low lactate and phosphocholine content.
- •Metabolic adaptation in these patients may lead to poor short-term outcomes.
Background & Aims
There is an emerging need to assess the metabolic state of liver allografts especially
in the novel setting of machine perfusion preservation and donor in cardiac death
(DCD) grafts. High-resolution magic-angle-spinning nuclear magnetic resonance (HR-MAS-NMR)
could be a useful tool in this setting as it can extemporaneously provide untargeted
metabolic profiling. The purpose of this study was to evaluate the potential value
of HR-MAS-NMR metabolomic analysis of back-table biopsies for the prediction of early
allograft dysfunction (EAD) and donor-recipient matching.
Method
The metabolic profiles of back-table biopsies obtained by HR-MAS-NMR, were compared
according to the presence of EAD using partial least squares discriminant analysis.
Network analysis was used to identify metabolites which changed significantly. The
profiles were compared to native livers to identify metabolites for donor-recipient
matching.
Results
The metabolic profiles were significantly different in grafts that caused EAD compared
to those that did not. The constructed model can be used to predict the graft outcome
with excellent accuracy. The metabolites showing the most significant differences
were lactate level >8.3 mmol/g and phosphocholine content >0.646 mmol/g, which were
significantly associated with graft dysfunction with an excellent accuracy (AUROClactates = 0.906; AUROCphosphocholine = 0.816). Native livers from patients with sarcopenia had low lactate and glycerophosphocholine
content. In patients with sarcopenia, the risk of EAD was significantly higher when
transplanting a graft with a high-risk graft metabolic score.
Conclusion
This study underlines the cost of metabolic adaptation, identifying lactate and choline-derived
metabolites as predictors of poor graft function in both native livers and liver grafts.
HR-MAS-NMR seems a valid technique to evaluate graft quality and the consequences
of cold ischemia on the graft. It could be used to assess the efficiency of graft
resuscitation on machine perfusion in future studies.
Lay summary
Real-time metabolomic profiles of human grafts during back-table can accurately predict
graft dysfunction. High lactate and phosphocholine content are highly predictive of
graft dysfunction whereas low lactate and phosphocholine content characterize patients
with sarcopenia. In these patients, the cost of metabolic adaptation may explain the
poor outcomes.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: November 27, 2017
Accepted:
November 15,
2017
Received in revised form:
November 9,
2017
Received:
June 15,
2017
Identification
Copyright
© 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
