Incidence and determinants of achieving HBsAg <100 IU/mL in HBeAg-negative CHB patients with nucleos(t)ide analogue treatment

Quantitative hepatitis B serum antigen (HBsAg) level <100 IU/mL has been proposed as one of the key criteria for partial cure for chronic hepatitis B (CHB) and as an important threshold for stopping nucleos(t)ide analogues (NAs) with a finite therapeutic strategy. We investigated the incidence and associated factors of HBsAg<100 IU/mL in hepatitis B e antigen (HBeAg)-negative CHB patients initiating NAs therapy. A total of 996 HBeAg-negative CHB patients with baseline HBsAg>100 IU/mL initiating first-line NAs treatment from five hospitals in China were retrospectively included. Cumulative incidence and associated factors of HBsAg<100 IU/mL were assessed using Kaplan-Meier and Cox regression analyses, respectively. During a median follow-up of 28.8 months, 69 patients (6.9%) achieved HBsAg<100 IU/mL, with a 5-year cumulative incidence of 13.97% (95%CI: 10.42%-17.38%). Among them, 94.2% (65/69) achieved both HBsAg<100 IU/mL and undetectable HBV DNA, with a 5-year incidence of 13.15% (95%CI: 9.66%-16.50%). Baseline HBsAg<1000 IU/mL (aHR = 19.66, 95%CI: 8.84-43.71, P<0.001) and HBV DNA<10,000 IU/mL (aHR = 2.47, 95%CI: 1.48-4.13, <i>P</i> = 0.001) were independently associated with a high chance of achieving HBsAg<100 IU/mL. Patients with both baseline HBsAg<1000 IU/mL and HBV DNA<10,000 IU/mL had a 5-year incidence of 58.73% for achieving HBsAg<100 IU/mL, whereas the 5-year incidence was only 3.91% in patients with HBsAg≥1000 IU/mL and HBV DNA≥10,000 IU/mL. Few HBeAg-negative CHB patients achieved HBsAg<100 IU/mL with NAs treatment. A combination of baseline HBsAg and HBV DNA levels can help identify HBeAg-negative CHB patients who are more likely to achieve HBsAg <100 IU/mL with NAs and may benefit from a finite therapeutic strategy.