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Research Article| Volume 68, ISSUE 4, P699-706, April 2018

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Impact of real-time metabolomics in liver transplantation: Graft evaluation and donor-recipient matching

Published:November 27, 2017DOI:https://doi.org/10.1016/j.jhep.2017.11.022

      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

      Keywords

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