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Metabolomic profiling predicts graft function after liver transplantation

Researchers found that lactate and choline-derived metabolites predicted poor graft function in both native livers and liver grafts, according to a recently published study.

High-resolution magic-angle-spinning nuclear magnetic resonance (HR-MAS-NMR) appeared to be a valid technique for evaluating graft quality and the consequences of cold ischemia on grafts.

“Evaluation of graft quality is a highly complex daily task for transplant teams, as many factors must be considered,” Francois Faitot, MD, PhD, from the Hopital de Hautepierre, France, and colleagues wrote. “Metabolic biomarkers have been evaluated, but they may provide the unique advantage of informing clinicians on the cellular state and function of a graft. This study demonstrates that metabolomics using HR-MAS-NMR is efficient in predicting EAD and is potentially applicable to daily clinical practice.”

To assess the value of metabolomic profiling using HR-MAS-NMR, Faitot and colleagues evaluated a set of 42 liver grafts at the time of ex vivo preparation and 36 native livers. Additionally, the researchers compared the included liver biopsies with the characteristics of 92 patients not included in the study, which were comparable.

Quantification showed that grafts presenting early allograft dysfunction (EAD) had significantly higher lactate (P < .0001), phosphocholine (P = .006) and taurine levels (P = .011).

Lactate levels (AUROC = 0.906; 95% CI, 0.813-0.999) and phosphocholine levels (AUROC = 0.816; 95% CI, 0.679-0.954) demonstrated high accuracy for predicting EAD. The optimal lactate threshold for predicting EAD was 8.3 mmol/g with a sensitivity of 100% and specificity of 80%, while the optimal phosphocholine threshold was 0.65 mmol/g with a sensitivity of 86% and specificity of 80%.

The researchers developed a metabolomic-defined extended criteria donor (MD-ECD) with the association of high lactate and high phosphocholine levels at the time of preparation. The MD-ECD correlated with a 63% risk of EAD and MD-ECD recipients had a significantly higher risk of 1-year graft loss or patient death than patients without MD-ECD (38% vs. 10%; P = .037).

Metabolomic profiles from native livers did not significantly differ between patients who presented with EAD and those who did not. Additionally, cold ischemia time did not correlate with EAD.

Multivariate analysis for EAD showed that graft lactate levels were an independent predictor of EAD (P = .046).

“We advocate the use of HR-MAS-NMR metabolomics to evaluate the quality of liver grafts after cold storage,” the researchers concluded. “In the case of favorable metabolic profiles, liver transplantation could be safely performed, even with ECD.” – by Talitha Bennett

Disclosure: The authors report no relevant financial disclosures.