Background: Despite its recognized role as a prognostic marker for antiviral treatment, the clinical significance of serum hepatitis B surface antigen (HBsAg) level in the immune-clearance stage of chronic hepatitis B remains unclear. Objectives: To characterize how HBsAg level and various clinical and virological factors are related and analyze the correlation of HBsAg with liver histology. Study design: A total of 198 treatment-naïve HBeAg-positive chronic hepatitis B patients were enrolled. Serum HBV DNA and HBsAg were determined quantitatively. Mutations of precore or basal core promoter (BCP) were also determined. Finally, liver necroinflammation grading and fibrosis stage were evaluated by Knodell score and Ishak score, respectively. Results: Lower HBsAg levels were found in patients with genotype C HBV infection, or in the presence of precore or mutations, or Knodell necroinflammation grading ≥7, or advanced fibrosis (Ishak stage 4-6). HBsAg level displayed a strong correlation with HBV DNA ( r= 0.727, P<. 0.001) and also exhibited a positive correlation with intrahepatic HBcAg expression in either cytoplasm ( r= 0.420, P<. 0.001) or nucleus ( r= 0.401, P<. 0.001). Examining the correlation with advanced liver fibrosis revealed that HBsAg level is a significant factor in univariate analysis and is the only independent factor in multivariate analysis (Coefficient: -0.975, P= 0.039, OR: 0.377, 95% CI: 0.149-0.953). Conclusions: HBsAg level varied with different clinical or virological categories. Lower baseline levels of HBsAg might reflect the status of advanced liver fibrosis in HBeAg positive chronic hepatitis B patients.
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