Non-targeted Serum Metabolomics Identifies Candidate Biomarkers Panels Associated with Nonalcoholic Fatty Liver Disease: A Pilot Study in Russian Male Patients

Aims: The aim of the present study was to explore changes in the serum metabolome of patients with NAFLD relative to healthy controls to identify biomarkers associated with steatosis or Non-Alcoholic Steatohepatitis (NASH). Background: The serum metabolome reflects changes at the organismal level. This is especially important in Non-Alcoholic Liver Disease (NAFLD), where changes in hormones, cytokines, enzymes and other metabolic alterations can affect the liver, as well as adipose tissue, skeletal muscle and other systems. Objective: The objectives were to conduct non-targeted serum metabolomics, data processing, and identification of candidate biomarkers, as well as panels and assessment of their prognostic value. Materials and Methods: Non-targeted metabolomic analysis of blood serum samples from 21 male patients with NAFLD (simple steatosis or NASH) and seven male Control group was performed using gas chromatography-mass spectrometry. Results: A total of 319 serum metabolites were detected in NAFLD and Control groups, several of which differed significantly between groups. The most discriminating biomarkers were 3-hydroxybutyric acid, 2-hydroxybutyric acid, 2,3-dihydroxybutyric acid, arabitol and 3-methyl-2-oxovaleric acid. Using a panel of three, four or more markers could distinguish patients with NAFLD from controls, and patients with NASH from those with simple steatosis. Conclusion: We identified candidate biomarkers for simple steatosis and NASH. Since NAFLD is a multifactorial disease, it is preferable to use a marker panel rather than individual metabolites. Markers may not only result from dysregulation of metabolic pathways in patients with NAFLD, they may also reflect adaptive responses to disease, including functional changes in the intestinal microbiota.