S2760 Hepatitis B Core-Related Antigen (HBcrAg) as a Novel Marker for Monitoring Antiviral Therapy in Chronic Hepatitis B: A Pilot Study

Introduction: Chronic hepatitis B (CHB) remains a major global health burden, affecting over 400 million people. While quantitative HBV DNA is the gold standard for therapy monitoring, it is costly and technically demanding. Hepatitis B core-related antigen (HBcrAg), a composite marker including HBeAg and HBcAg, is emerging as a cost-effective alternative, correlating with viral replication and intrahepatic cccDNA levels. Methods: A prospective observational study was conducted on 63 patients with CHB receiving long-term NA therapy (entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide) at Max Super Speciality Hospital, Vaishali. Inclusion criteria included adults (>18 years) with documented CHB on therapy for ≥12 months, achievement of undetectable HBV DNA and HBcrAg levels at 2 consecutive time points, and normal liver function tests. Patients meeting these criteria were eligible for therapy discontinuation and followed for 6 months post-treatment with 3 monthly monitoring of HBV DNA, LFTs. Virological relapse was defined as reappearance of HBcrAg and HBV DNA >2000 IU/mL, with or without abnormal LFTs. Results: At baseline (end of treatment), all 63 patients were negative for both HBV DNA and HBcrAg. Over the 6-month post-treatment surveillance period, 5 patients (7.9%) exhibited virological relapse characterized by simultaneous reappearance of HBcrAg and HBV DNA >2000 IU/mL, often accompanied by mild alanine aminotransferase elevations. The remaining 58 patients (92.1%) maintained suppression of both markers and stable liver function. Notably, no patients with sustained HBcrAg negativity experienced relapse, reinforcing its predictive utility. The high negative predictive value of HBcrAg enhances confidence in its role as a marker for treatment cessation. Conclusion: Our findings align with emerging global data supporting HBcrAg as a surrogate marker of intrahepatic cccDNA activity and a useful indicator of viral replication potential. Its strong concordance with HBV DNA and predictive value for post-treatment outcomes underscore its potential as an adjunct or alternative to HBV DNA quantification in therapeutic decision-making. In contrast to HBV DNA testing, HBcrAg assays are more accessible and potentially cost-effective in resource-limited environments. This adds practical value to its utility beyond tertiary care centers. The use of HBcrAg could facilitate broader implementation of standardized treatment withdrawal protocols and contribute to reducing unnecessary prolonged antiviral exposure.