Higher lifetime chance of spontaneous surface antigen loss in hepatitis B carriers with genotype C infection

Summary Background Clearance of hepatitis B surface antigen (HBsAg) indicates clinical control of hepatitis B virus (HBV) infection. However, little is known about the impact of viral genomic variations on HBsAg loss. Methods We explored the association between viral genomic factors and HBsAg loss in 2121HBeAg‐negative patients. HBV pre‐core stop codon (1896) and basal core promoter (BCP) (1762/1764) sequences were determined in patients with HBV DNA ≥200 IU/mL (N = 1693). The effect of HBV genotype on HBsAg loss was further validated in the whole cohort of 3445 HBsAg carriers. Results The cumulative lifetime (age 28–75 years) incidence of HBsAg loss was 50.4% in 2121 HBeAg‐negative patients. We found that genotype C, but not pre‐core stop codon or BCP mutants, was associated with HBsAg loss. Compared to genotype B patients, genotype C patients had higher lifetime chance of HBsAg loss, with hazard ratio of 1.8 (95% confidence interval: 1.4–2.4). Multivariable analysis showed that male sex, elevated ALT levels, lower serum HBV DNA and HBsAg levels, and genotype C infection were associated with higher chance of HBsAg loss independently. We then performed sensitivity analysis, which re‐included HBeAg‐positive, cirrhotic and treatment‐experienced patients, and confirmed the robustness of our results in 3445 HBsAg carriers. Conclusion Genotype C infection, compared to genotype B, is associated with a higher lifetime chance of HBsAg loss in Asian HBV carriers.