Genetic Determinants of Spontaneous Hepatitis B Surface Antigen Seroclearance and Its Associated Viral Markers

BACKGROUND: Chronic hepatitis B virus (HBV) rarely leads to spontaneous hepatitis B surface antigen (HBsAg) seroclearance. However, host genetics contributing to this outcome remain poorly understood. We investigate genetic variants associated with HBsAg seroclearance and related viral markers. METHODS: ) were tested for association with spontaneous HBsAg seroclearance. The top variants (p < 0.05) were evaluated in an independent Taiwan Biobank (TWB) cohort, comprising 11,340 HBsAg-positive participants and 54,072 HBsAg-negative but anti-hepatitis B core antigen (anti-HBc) positive participants. RESULTS: ) and rs446717 (OR = 1.03, 95% CI = 1.00-1.06, p = 0.04) were observed for early HBsAg seroclearance. CONCLUSIONS: Although host genetic factors may influence HBV replication through immune-mediated mechanisms, their impact on HBsAg levels is limited by its dual origin from cccDNA and integrated HBV DNA. These findings enhance understanding of host genetic contributions to HBV traits, though further research is needed to clarify their role in HBsAg seroclearance and guiding immunomodulatory therapies.