Metabolic Profiling of Human Liver Fibrosis

Jose Manuel Morales¹, Beatriz Martinez-Granados, Juan del Olmo², Bernardo Celda, Jose Manuel Rodrigo^1,2, Daniel Monleon³

Liver fibrosis is characterized by the replacement of liver tissue by fibrous scar tissue as well as regenerative nodules, leading to progressive loss of liver function and to altered liver metabolism. Cirrhosis is the end-stage of this reaction and it represents a major change in the tissue. Global metabolic profiles, which are affected by many physiological and pathological processes, may reflect accurately the presence of a particular disease state. The aim of this study is to demonstrate the applicability of 1H HR-MAS NMR spectroscopy biochemical profile determination in human liver needle biopsy as support for the assessment of chronic liver disease stage. Metabolic profiles of chronic liver disease biopsies provided differential patterns between cirrhosis and non cirrhosis and allow the determination of progressive metabolic alterations associated to chronic hepatic disease. In this work, we report that metabolic alterations associated to liver disease stage affect essential metabolic processes beyond lipid metabolism. Early stages of chronic liver disease seem to have important metabolic consequences including increased glutamate and decreased glutamine and glucose. Overall, this work suggests that the additional information obtained by NMR metabolomics applied to needle biopsies of human liver may be useful for assessing metabolic alterations and liver dysfunction in chronic liver disease.