Urinary metabolomics analysis identifies key biomarkers of different stages of nonalcoholic fatty liver disease

Abstract

AIMTo identify a panel of biomarkers that can distinguish between non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), and explore molecular mechanism involved in the process of developing NASH from NAFLD.METHODSBiomarkers may differ during stages of NAFLD. Urine and blood were obtained from non-diabetic subjects with NAFLD and steatosis, with normal liver function (n = 33), from patients with NASH, with abnormal liver function (n = 45), and from healthy age and sex-matched controls (n = 30). Samples were subjected to metabolomic analysis to identify potential non-invasive biomarkers. Differences in urinary metabolic profiles were analyzed using liquid chromatography tandem mass spectrometry with principal component analysis and partial least squares-discriminate analysis.RESULTSCompared with NAFLD patients, patients with NASH had abnormal liver function and high serum lipid concentrations. Urinary metabonomics found differences in 31 metabolites between these two groups, including differences in nucleic acids and amino acids. Pathway analysis based on overlapping metabolites showed that pathways of energy and amino acid metabolism, as well as the pentose phosphate pathway, were closely associated with pathological processes in NAFLD and NASH.CONCLUSIONThese findings suggested that a panel of biomarkers could distinguish between NAFLD and NASH, and could help to determine the molecular mechanism involved in the process of developing NASH from NAFLD. Urinary biomarkers may be diagnostic in these patients and could be used to assess responses to therapeutic interventions.

Urine Metabolomics Analysis in Patients With Normoalbuminuric Diabetic Kidney Disease

“…It can systematically and comprehensively analyze the metabolites, thus obtaining a large amount of metabolite data and identifying differential metabolites ( Johnson et al, 2016 ). It has been widely used in the research of many diseases, such as lung cancer ( Seow et al, 2019 ), pancreatic cancer ( Shu et al, 2018 ), prostate cancer ( Jayaraman et al, 2018 ), heart disease ( Li et al, 2016 ), and liver disease ( Dong et al, 2017 ). Recently, the metabolomics related to the occurrence and development of DKD has attracted much attention ( Rhee, 2015 ).…”

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

“…A Chinese urinary metabolomics study compared NAFL patients with normal liver function with NASH patients with abnormal liver function. Many discriminating metabolites were reported (Table 4) [190], although none displayed a large fold-change or was seen as highly specific to NASH. An elegant study was reported containing several large clinical cohorts containing biopsy-proven NASH patients that also had liver fat determined by CT. Serum metabolomics identified the top metabolite associated with liver fat as a mass of 202.1185 + .…”

“…As the BA pattern appeared to be dependent upon the status of the gut microbiota, the data obtained were not useful for evaluation as biomarkers of NAFLD. [203] [190] Human Several large clinical cohorts with CT-defined liver fat plus NASH patients.…”

Accurate non‐invasive diagnosis and staging of non‐alcoholic fatty liver disease using the urinary steroid metabolome

“…Untargeted urinary metabolic profiling in small numbers of patients has been explored, 18,19 but its diagnostic ability has not been interrogated in detail. Volatile organic compound generated via the gut microbiome and excreted in the urine have been examined in a very small exploratory pilot study with AUC ROC values of 0.73 (0.45‐0.92) to distinguish advanced disease 20 …”