Liver Transplantation Biomarkers in the Metabolomics Era

Abstract

The term biomarker usually refers to the biochemical molecules used in basic and clinical research, and also in the clinical practice, as surrogate markers that offer the advantage of being an objective, quantifiable, and reproducible measure. Themost common applications of biomarkers include diagnosis, screening and monitoring of disease, assessment of response during therapy, risk assessment, and prognosis. Metabolomics or metabonomics enables the determination of hundreds of small molecules at the same time, which provides more comprehensive information than the determination of a single biomarker. Using metabolomics as an approach for searching biomarkers is supported by its capabilities to detect subtle metabolic changes triggered by external stimuli or perturbation. Metabolome changes are quite dynamic compared to genomics and transcriptomics, or even proteomics. Therefore, such metabolite alterations are found early in different samples, like tissues, cell lysates, blood, serum, plasma, feces, urine, etc. Application of metabolomics in liver transplantation is still in its early stages and has focused mainly on studying three aspects: post-reperfusion damage and rejection and dysfunction of the organ. In the current era when lack of organs suitable for transplantation is the most important limiting factor, the existence of an accepted functional assessment of grafts before transplantation would help to not only recover initially discarded organs but to also assess the therapies used to improve the quality of these organs. Different metabolic approaches have been used to search for objective markers of graft function and quality, but further analytical and clinical validation in multicentre studies is mandatory before they are incorporated into clinical routines.