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

Yimin Chen1, Peixia Lin1, Jiaxin Jin1

  • 1Department of Infectious Diseases, Affiliated Hospital of Jiaxing University, Jiaxing 314001, China.

Iscience
|May 11, 2026
PubMed

Insights

Chronic hepatitis B virus (HBV) infection progression varies with viral mutations. This study links specific HBV mutations to altered cholesterol metabolism and identifies potential biomarkers for disease stratification.

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.

Keywords:
Health sciences

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