Abstract:

The difference of serum metabolome between hepatitis B virus (HBV) infected patients and healthy controls was explored for the potential metabolite biomarkers of HBV disease using serum metabolomics approach. Totally 30 HBV infected patients and 35 healthy controls were enrolled. Gas chromatography-time-of-flight mass spectrometry (GC-TOFMS), pattern recognition by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were applied in each group. Several metabolites which were different between the two groups based on variable importance in projection (VIP) value, non-parametric test and screening in databases were identified. Ten variables that were significantly different were considered as the potential biomarkers, among which five variables (citric acid, aconitic acid, glutamine, N,N-dimethylglycine and malonic acid) showed good correlation with HBV patients. The area under the receiver operating characteristic curve was 0.975, with good specificity and sensitivity. A panel of metabolite markers composed of citric acid, aconitic acid, glutamine, N,N-dimethylglycine and malonic acid from GC-TOFMS were selected to discriminate HBV subjects from their healthy counterparts. These biochemical changes provide a novel molecular diagnostic approach which could be helpful to further understand the pathogenesis and identify the therapeutic target of HBV disease.

Key words: gas chromatography-mass spectrometry (GC-MS), hepatitis B virus (HBV), metabolomics, orthogonal partial least squares-discriminant analysis (OPLS-DA), potential biomarkers