Abstract
BACKGROUND: The kinetics of serum hepatitis B surface antigen (HBsAg) levels during long-term nucleos(t)ide analogue (NA) therapy remains unclear. We delineated the kinetics of HBsAg and analyzed its association with long-term treatment outcomes. METHODS: We enrolled 912 treatment-naïve patients with chronic hepatitis B (CHB) who had received NA therapy for >12 months and analyzed the kinetic patterns through group-based trajectory models (GBTMs). RESULTS: The median treatment duration for the entire cohort was 60.3 months. GBTMs revealed 4 patterns in patients achieving HBsAg loss (groups 1-4) in the study population and in patients achieving HBsAg <100 IU/mL among those with HBeAg-negative CHB with baseline HBsAg ≥100 IU/mL (groups A-D). Patients in groups 1 and A had the highest rates of HBsAg loss (22.2%, 6/27) and of achieving HBsAg <100 IU/mL (47.5%, 56/118), respectively. HBsAg <40 IU/mL and <400 IU/mL at 12 months of treatment predicted group 1 and group A membership among all patients and those with HBeAg-negative CHB, respectively. Multivariable Cox regression analysis identified HBsAg trajectory group (group 1 vs groups 3 and 4: hazard ratio [HR], 179.46; P < .001; group 2 vs groups 3 and 4: HR, 24.34; P < .001) and HBsAg decline (HR, 82.14; P < .001) as independent predictors of both HBsAg loss and achieving HBsAg <100 IU/mL. CONCLUSIONS: Serum HBsAg trajectories and decline can predict HBsAg loss and the achievement of HBsAg <100 IU/mL in patients with CHB receiving long-term NA therapy.