Application of Metabolomics to Investigate the Process of Human Orthotopic Liver Transplantation: A Proof-of-Principle Study

Olga Hrydziuszko, Michael Silva, Thamara Perera, Douglas Richards, Nick Murphy, Darius Mirza, Mark Viant

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)


To improve the outcome of orthotopic liver transplantation (OLT), knowledge of early molecular events occurring upon ischemia/reperfusion is essential. Powerful approaches for profiling metabolic changes in tissues and biofluids are now available. Our objective was to investigate the applicability of two technologies to a small but well-defined cohort of patients undergoing OLT: consecutive liver biopsies by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and microdialysates of extracellular fluid by coulometric electrochemical array detection (CEAD). FT-ICR MS detected reproducibly more than 4,000 peaks, revealing hundreds of significant metabolic differences between pre- and postreperfusion grafts. These included increased urea production, bile acid synthesis and clearance of preservation solution upon reperfusion, indicating a rapid resumption of biochemical function within the graft. FT-ICR MS also identified successfully the only graft obtained by donation-after-cardiac-death as a "metabolic outlier.'' CEAD time-profile analysis showed that there was considerable change in redox-active metabolites (up to 18 h postreperfusion), followed by their stabilization. Collectively these results verify the applicability of FT-ICR MS and CEAD for characterizing multiple metabolic pathways during OLT. The success of this proof-of-principle application of these technologies to a clinical setting, considering the potential metabolic heterogeneity across only eight donor livers, is encouraging.
Original languageEnglish
Pages (from-to)143-150
Number of pages8
JournalOMICS: A Journal of Integrative Biology
Issue number2
Early online date8 Mar 2010
Publication statusPublished - 1 Apr 2010


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