Until now, the metabolic effects of hepatitis B virus (HBV) replication on the progression of hepatic diseases (hepatitis, cirrhosis, and liver cancer) and liver functions have remained unexplored. Thus, a total of 199 hepatic disease patients with active and inactive HBV were enrolled in this study to explore serum metabolic characteristics using untargeted metabolomics. Multiple analyses, including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), volcano plot and pathway analysis, were used for metabolic data analysis. Additionally, differential metabolites were analysed by commercial databases. A decrease of approximately 0.8-fold in amino acids (L-glutamic acid, D-glutamine and L-tyrosine) and an increase of 2-fold in phosphatidylcholines (PCs) and lysophosphatidylcholines (LPCs) were observed in hepatic disease patients with HBV replication. Moreover, downregulation of arachidonic acid, PC 34:2, sn-glycerol-3-phosphocholine, 1-palmitoylglycerophosphoinositol, and 1-oleoylglycerophosphoinositol by 0.6-fold was also found in the serum of patients with HBV replication. In addition, liver function was significantly different between cirrhosis patients with or without HBV replication (p < .05). In summary, this is the first study to focus on the metabolic changes induced by HBV replication in patients and to compare metabolic alterations in the progression of hepatic disease induced by HBV infection. High levels of amino acid depletion and PC and LPC biosynthesis were primarily observed, which may shed new light on the pathogenesis and treatment of HBV infection.
Keywords: HBV replication; Hepatic diseases; amino acid depletion; phosphatidylcholine biosynthesis; untargeted metabolomics.