Quantitative HBsAg Distribution and Eligibility for Cure-Directed Bepirovirsen Therapy in Chronic Hepatitis B

Bepirovirsen achieved a functional cure in 19–20% of nucleos(t)ide analogue (NUC)-treated participants in the phase 3 B-Well trials. These trials enrolled patients with baseline quantitative hepatitis B surface antigen (qHBsAg) levels >100–≤ 3000 IU/mL, but the potential reach of this treatment in routine care remains uncertain. We evaluated 706 patients with chronic hepatitis B monoinfection at a German tertiary-care center. qHBsAg levels were ≤100, >100–≤1000, >1000–≤3000, and >3000 IU/mL in 145/706 (20.5%), 175/706 (24.8%), 142/706 (20.1%), and 244/706 (34.6%) patients, respectively. Overall, 317/706 (44.9%) patients fell within the B-Well qHBsAg window. Of these, 109/317 (34.4%) were receiving NUC therapy; among the remaining 208 untreated patients, 23/208 (11.1%) met an operationalized EASL 2025 indication for NUC initiation. The primary implementation scenario therefore comprised 132/706 (18.7%) patients. Excluding patients with identifiable B-Well trial exclusion proxies in a sensitivity analysis reduced this number to 102/706 (14.4%). Applying stratum-specific B-Well response rates of 26.0% and 7.3% yielded hypothetical functional cure rates of 17.2% (approximately 23 modeled functional cures) in the primary scenario and 16.1% (approximately 16 modeled functional cures) in the restricted scenario. These findings estimate the potential clinical reach of bepirovirsen and associated hypothetical functional cure outcomes at our center, highlighting the absence of current NUC therapy as a key factor limiting its implementation.