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Published on: November 7, 2020
Reduced Histidine Metabolism Is Associated with Early Allograft Dysfunction Following Liver Transplantation
Alissa M Cutrone1,2,3, Thomas Agius2,3, Sofia Baptista1,2,3
1Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Metabolites
|July 27, 2026
Summary
Predicting early allograft dysfunction (EAD) after liver transplant is challenging. Histidine catabolism metabolites, particularly trans-urocanate, show promise as biomarkers for predicting graft function and resilience to injury.
Area of Science:
- Transplantation immunology
- Metabolomics
- Graft viability assessment
Background:
- Early allograft dysfunction (EAD) is a frequent complication post-liver transplant, impacting graft survival.
- Normothermic machine perfusion (NMP) reduces EAD but predicting graft function pre-implantation remains difficult.
- Assessing peri-transplant metabolic profiles may improve prediction of liver graft outcomes.
Purpose of the Study:
- To correlate peri-transplant energetic and metabolic profiles of liver grafts with post-transplant outcomes.
- To identify predictive biomarkers for early graft function in liver transplantation.
- To evaluate metabolic profiles in grafts preserved with static cold storage and NMP.
Main Methods:
- Sequential liver biopsies from 20 transplanted livers (10 immediate graft function [IGF], 10 EAD) were analyzed.
- Metabolomic analysis using liquid chromatography-mass spectrometry was performed pre-implantation and post-reperfusion.
- Energy charge and metabolite concentrations were correlated with EAD using univariate and ROC analyses.
Main Results:
- Hepatic adenine nucleotides and energy charge did not differ between IGF and EAD groups.
- Trans-urocanate and other histidine catabolism metabolites were significantly enriched in IGF grafts.
- Trans-urocanate demonstrated 80% sensitivity and 80% specificity in predicting EAD, outperforming >1600 metabolites.
Conclusions:
- Histidine catabolism is a novel metabolic pathway linked to early liver graft function.
- Trans-urocanate is a potential biomarker for predicting EAD and graft resilience.
- Metabolite-guided strategies, including histidine pathway analysis, may enhance graft viability assessment in the perfusion era.
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