Metabolic profile of chronic liver disease by NMR spectroscopy of human biopsies

Abstract

Abstract. Among the different processes occurring during the evolution of liver disease, fibrosis has a predominant role. Liver fibrosis mechanisms are fairly constant irrespective of the underlying etiology. Cirrhosis is the end-stage of this reaction. Metabolic profiles, which are affected by many physiological and pathological processes, may provide further insight into the metabolic consequences of this severe liver disease. The aim of this study was to demonstrate the applicability of 1 H high resolution magic angle spinning (HR-MAS) NMR spectroscopy in the biochemical profile determination of human liver needle biopsy samples for the characterization of metabolic alterations related to the severity of liver disease. We recorded and analyzed HR-MAS spectra of 68 liver tissue samples obtained by needle biopsy from patients with chronic liver disease. Multivariate analysis was applied to these data to obtain discrimination patterns and to reveal relevant metabolites. The metabolic characterization of liver tissue from needle biopsies by HR-MAS NMR spectroscopy provided differential patterns for cirrhotic and non-cirrhotic chronic liver disease tissue. Metabolites closely related to the liver metabolism such as some fatty acids, glucose and amino acids show differences between the two groups. Phospholipid precursors, which have been previously correlated with hepatic lesions also show differences. Furthermore, the correlation between histologically assessed liver disease stages and the levels of the most discriminative metabolites show that liver dysfunction is present at the initial stages of chronic hepatic lesions. 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. IntroductionThe liver is among the most metabolically diverse organs of the body and is involved in many critical metabolic processes (1). One of its major roles is storing endogenous fuels of the body. In addition, the liver acts as a major distribution center for exogenous energy supplies. The liver may be affected by many pathological aggressions. Liver dysfunction results in a variety of clinical signs and symptoms. However, some of these pathologies pose a diagnostic challenge as many different diseases show similar clinical signs (2-4). Moreover, liver biopsy assessment involves some degree of complication because of the proliferation of different grading and staging schemes (5-7). Metabolic alterations produced by liver disease may help clinicians better characterize the disease. Among the different processes occurring during the evolution of liver disease, fibrosis takes a predominant role. 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 (8-11). Liver fibrosis induction mechanisms are fairly constant irrespectivel...

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