Metabolic characterization of hepatic disease patients with hepatitis B virus DNA replication by untargeted metabolomics

ABSTRACT: Purpose: Worldwide, over 350 million people are chronically infected with the hepatitis B virus (HBV) and are at increased risk of developing progressive hepatic diseases (hepatitis, cirrhosis or liver cancer). Still, the metabolic processes operational during the distinct clinical phases of a chronic HBV infection to liver disease remains unexplored. Thus, the aim of our study was to determine the serum metabolic characteristics of hepatic disease patients with chronic hepatitis B in active and inactive stage and study the influence of active and inactive stage of the chronic hepatitis B virus on the development of liver cancer by untargeted metabolomics. Method: To investigate this, we conducted an untargeted metabolomics approach to determine the metabolic characteristics of 199 human serum samples from hepatic disease patients in active and inactive chronic HBV via UHPLC-Q-TOF/MS, and patients with HBV in active or inactive stage were grouped based on their serum levels of HBV DNA and HBV envelope antigen (HBeAg). Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and volcano plot were used for multivariate analysis. Pathway analysis were conducted according to p-values from pathway enrichment analysis and pathway impact values from pathway topology analysis. In addition, commercial databases were used to identify metabolites from significantly altered metabolic pathways. All samples were analyzed for liver function tests indicated the levels of certain enzymes. Results: Our data provide insight into the metabolic dysregulation experienced during active or inactive stage of the HBV on the development of liver disease, and analysis of serum metabolomic profiles indicated that most of the altered metabolic pathways for chronic hepatitis and cirrhosis patients with active or inactive stage of the HBV were associated with D-Glutamine and D-glutamate metabolism, indicating a strong link to HBV replication (p < 0.05). In addition, liver function analysis showed the enzymes gamma-glutamyl transferase (GGT) were increased concomitant to the progression of hepatitis to cirrhosis induced by chronic HBV (p < 0.05).

ORGANISM(S): Homo Sapiens

SUBMITTER: Jiafu Feng  

PROVIDER: PXD025989 | iProX | Thu May 13 00:00:00 BST 2021

REPOSITORIES: iProX