Metabolomics

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Metabolic characterization of the natural progression of chronic hepatitis B (Biogenic amine and Acyl-carnitine assays).


ABSTRACT: Background: Worldwide, over 350 million people are chronically infected with the hepatitis B virus (HBV) and are at increased risk of developing progressive liver diseases. The confinement of HBV replication to the liver, which also acts as the central hub for metabolic and nutritional regulation, emphasizes the interlinked nature of host metabolism and the disease. Still, the metabolic processes operational during the distinct clinical phases of a chronic HBV infection—immune tolerant, immune active, inactive carrier, and HBeAg-negative hepatitis phases—remains unexplored.

Methods: To investigate this, we conducted a targeted metabolomics approach on serum to determine the metabolic progression over the clinical phases of chronic HBV infection, using patient samples grouped based on their HBV DNA, alanine aminotransferase, and HBeAg serum levels.

Results: Our data illustrate the strength of metabolomics to provide insight into the metabolic dysregulation experienced during chronic HBV. The immune tolerant phase is characterized by the speculated viral hijacking of the glycerol-3-phosphate–NADH shuttle, explaining the reduced glycerophospholipid and increased plasmalogen species, indicating a strong link to HBV replication. The persisting impairment of the choline glycerophospholipids, even during the inactive carrier phase with minimal HBV activity, alludes to possible metabolic imprinting effects. The progression of chronic HBV is associated with increased concentrations of very long chain triglycerides together with citrulline and ornithine, reflective of a dysregulated urea cycle peaking in the HBV envelope antigen-negative phase.

Conclusions: The work presented here will aid in future studies to (i) validate and understand the implication of these metabolic changes using a thorough systems biology approach, (ii) monitor and predict disease severity, as well as (iii) determine the therapeutic value of the glycerol-3-phosphate–NADH shuttle.

The Oxylipin assay and the Lipid assays for this study can be found in the MetaboLights studies MTBLS253 and MTBLS279 respectively.

INSTRUMENT(S): Xevo TQ MS

SUBMITTER: Michael van Vliet  

PROVIDER: MTBLS280 | MetaboLights | 2016-06-06

REPOSITORIES: MetaboLights

Dataset's files

Source:
Action DRS
MTBLS280 Other
01_acylcarnitines.zip Other
01_amines.zip Other
02_acylcarnitines.zip Other
02_amines.zip Other
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Publications

Metabolic characterization of the natural progression of chronic hepatitis B.

Schoeman Johannes C JC   Hou Jun J   Harms Amy C AC   Vreeken Rob J RJ   Berger Ruud R   Hankemeier Thomas T   Boonstra Andre A  

Genome medicine 20160610 1


<h4>Background</h4>Worldwide, over 350 million people are chronically infected with the hepatitis B virus (HBV) and are at increased risk of developing progressive liver diseases. The confinement of HBV replication to the liver, which also acts as the central hub for metabolic and nutritional regulation, emphasizes the interlinked nature of host metabolism and the disease. Still, the metabolic processes operational during the distinct clinical phases of a chronic HBV infection-immune tolerant, i  ...[more]

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