Urinary Metabolomic Profiling in Chronic Hepatitis B Viral Infection Using Gas Chromatography/Mass Spectrometry

Abstract

Background: Chronic hepatitis B (CHB) can lead to cirrhosis and hepatocellular carcinoma. The metabolomic<br />profiling has been shown to be associated with pathogenic mechanisms in many medical conditions including<br />CHB. The purpose of this study was to investigate the urine metabolomic profiles in CHB patients by gas<br />chromatography/mass spectrometry (GC/MS). Methods: Urine samples were collected from CHB patients (n = 20)<br />and normal control subjects (n = 20). Metabolite profiles were assessed using GC/MS in conjunction with multivariate<br />statistical analysis, in order to identify biomarker metabolites. Pathway analysis was performed by MetaboAnalyst<br />3.0 and KEGG database.Results: Twelve out of 377 metabolites were shown to be significantly different between the<br />CHB and normal control groups (p < 0.05). These include palmitic acid, stearic acid, oleic acid, benzoic acid, butanoic<br />acid, cholesterol, glycine, 3-heptanone, 4-heptanone, hexanal, 1-tetradecanol and naphthalene. Multivariate statistical<br />analysis constructed using these expressed metabolites showed CHB patients can be discriminated from healthy controls<br />with high sensitivity (95%) and specificity (85%). All the metabolic perturbations in this disease are associated with<br />pathways of fatty acid, amino acid, bile acid and gut microbial metabolism. Conclusion: CHB patients have a specific<br />urinary metabolomic profile. The abnormalities of fatty acid, amino acid, bile acid, and gut microbial metabolism lead<br />to the development of disease progression. GC/MS-based assay is a promising tool for the metabolomic study in CHB.