Exploring the Relationship Between Hepatitis B e Antigen (HBeAg) Positivity and Viral Load Among Asymptomatic HBV-Infected Individuals

Background: Hepatitis B virus (HBV) infection presents a significant global health challenge, with many infected individuals being asymptomatic and possibly undergoing active viral replication without clinical detection. While hepatitis B e antigen (HBeAg) is commonly viewed as a marker of viral replication and infectivity, recent evidence indicates that substantial viral replication can occur in HBeAg-negative individuals due to mutations. Hence, assessing the link between HBeAg status and HBV DNA levels is crucial for accurate disease evaluation. Therefore, the present study aimed to evaluate the association between HBeAg status and HBV DNA viral load among asymptomatic HBV-infected individuals to improve the assessment of viral replication and disease status. Methods: A cross-sectional observational study was conducted at a tertiary care hospital in Pune, India, from June 2024 to April 2025. On the basis of sample size estimation study recruited 100 patients incidentally found to be HBV surface antigen (HBsAg) positive during routine health screening. A total of 68 individuals blood samples were analyzed for HBeAg detection and HBV DNA viral load testing, as the remaining 32 samples were not processed due to inadequate sample availability. Statistical comparisons between viral load, HBeAg-reactive, and HBeAg-nonreactive groups were performed. Results: Among 68 tested asymptomatic HBV-infected individuals, 10.6% were HBeAg-reactive, while 89.4% were HBeAg-nonreactive. The HBeAg-reactive group showed significantly higher HBV DNA levels indicating active viral replication. Differences in hematological and biochemical parameters were noted, with most HBeAg-nonreactive individuals having low to moderate viral loads, although some had elevated HBV DNA levels suggesting ongoing replication despite HBeAg negativity. Conclusion: HBeAg positivity remains a strong indicator of high viral replication in asymptomatic HBV infection. Reliance on HBeAg status alone may underestimate disease activity in HBeAg-negative individuals with elevated viral loads. Hence, HBeAg status and HBV DNA quantification are essential for optimal clinical management of asymptomatic HBV carriers.