Front Med (Lausanne). 2026 Sep 16;13:1926645. doi: 10.3389/fmed.2026.1926645. eCollection 2026.
ABSTRACT
BACKGROUND: Chronic hepatitis B (CHB) frequently coexists with metabolic dysfunction-associated fatty liver disease (MAFLD), yet the impact of MAFLD on hepatitis B virus (HBV) replication remains incompletely understood. We aimed to investigate the association between MAFLD and HBV DNA levels and to provide biological context through integrative transcriptomic analyses.
METHODS: We analyzed a large retrospective cohort of patients with CHB and assessed the association between MAFLD and serum HBV DNA levels using linear regression models. HBV DNA was analyzed as a continuous outcome after log10 transformation. To provide molecular context for the clinical findings, weighted gene co-expression network analysis (WGCNA) was performed in an independent HBV liver transcriptomic dataset to identify HBV-associated host co-expression modules. These modules were subsequently characterized in independent liver transcriptomic datasets representing distinct metabolic and histological liver contexts using single-sample gene set enrichment analysis (ssGSEA).
RESULTS: MAFLD was independently associated with lower circulating HBV DNA levels. This association varied across MAFLD phenotypes, with the lowest HBV DNA levels observed in overweight- or obesity-related MAFLD. Transcriptomic analyses identified HBV-associated host co-expression programs linked to lipid and cholesterol metabolism, inflammatory signaling, and antiviral responses. Cross-cohort analyses further showed that selected modules varied across distinct metabolic and fibrotic liver contexts.
CONCLUSIONS: MAFLD is associated with reduced HBV DNA levels in patients with CHB, especially in overweight- or obesity-related MAFLD. The transcriptomic findings provide complementary biological context for this clinical association and highlight metabolic and immune pathways that warrant further mechanistic investigation.
PMID:42818704 | PMC:PMC13623727 | DOI:10.3389/fmed.2026.1926645