Cholesterol metabolism dysregulated by key HBV mutations revealed through multi-omics profiling

Area of Science:

• Hepatology
• Virology
• Molecular Biology

Background:

• Chronic hepatitis B virus (HBV) infection exhibits diverse clinical outcomes.
• Viral mutations significantly influence HBV pathogenesis and disease progression.
• Understanding host molecular responses to different HBV genotypes is crucial for effective management.

Purpose of the Study:

• To investigate the multi-omics differences in patients with chronic HBV infection based on distinct viral mutations.
• To identify host molecular pathways and potential biomarkers associated with specific HBV genotypes.
• To correlate viral genotype with host response and clinical outcomes.

Main Methods:

• Multi-omics analysis (proteomics and metabolomics) of serum samples from 108 chronic HBV patients.
• Stratification of patients into wild-type, G1896A, A1762T/G1764A, and combined mutant groups.
• Integrated pathway analysis to identify disrupted host molecular pathways.

Main Results:

• Patients with A1762T/G1764A or double HBV mutations showed elevated ALT and AST levels, indicating higher disease severity.
• Proteomic analysis revealed significant differential protein expression across mutant groups compared to wild-type.
• Metabolomics identified numerous altered metabolites, with cholesterol metabolism consistently highlighted as a disrupted pathway across variants.
• Six key proteins and metabolites within the cholesterol pathway were identified as potential biomarkers.

Conclusions:

• Specific HBV mutations (A1762T/G1764A and G1896A) are associated with distinct molecular profiles and clinical severity.
• Cholesterol metabolism is a key host pathway affected by chronic HBV infection and its variants.
• Identified biomarkers hold potential for distinguishing HBV genotypes and predicting clinical outcomes.