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

Chronic hepatitis B virus (HBV) infection shows variable progression linked to specific viral mutations. This multi-omics study analyzed 108 patients with chronic HBV, stratified into wild-type, G1896A, A1762T/G1764A, and A1762T/G1764A + G1896A variant groups. Serum proteomics and metabolomics revealed that patients infected with HBV A1762T/G1764A or the double mutants had significantly higher ALT and AST levels, correlating with disease severity. Compared to wild-type, proteomic analysis identified 59, 54, and 79 differentially expressed proteins in the G1896A, double mutant, and combined mutant groups, respectively. Metabolomics showed 201, 242, and 226 altered metabolites in the same groups. Integrated pathway analysis consistently pinpointed cholesterol metabolism as the most disrupted pathway. From this pathway, six key proteins and metabolites emerged as potential combined biomarkers for distinguishing between these HBV variants, linking viral genotype to host molecular response and clinical outcome.