We aim to explore the effects of nucleos(t)ide analogues (NUCs) on the changes of HBsAg in chronic hepatitis B (CHB) patients.

A total of 264 CHB patients were enrolled in our study. All of them were treated with NUCs for at least three years. Quantification of HBsAg levels were measured by Elecsys HBsAg II.

Although HBsAg levels were significantly higher in HBeAg seropositive CHB patients at baseline than in HBeAg seronegative CHB patients (3.84 ± 0.82 vs 3.21 ± 0.59 IU/mL), HBsAg levels declined more rapidly in the HBeAg seropositive group (P < 0.001). In HBeAg-positive CHB patients, HBsAg level in the telbivudine (LDT)-treated group was 3.68 ± 0.56 IU/mL after 52-week of treatment, which was significantly higher than that in lamivudine (LAM)-treated group (P = 0.009). Multivariable analyses showed that baseline HBV DNA viral load (OR = 0.75, P = 0.018), baseline ALT level (OR = 0.99, P = 0.015), and baseline HBsAg level (OR = 0.188, P < 0.001) were independent factors that affected HBsAg decline in HBeAg seropositive CHB patients. For HBeAg seronegative CHB patients, the average of serum HBsAg levels in LAM-, LdT-, adefovir (ADV)-, and entecavir (ETV)-treated groups at baseline, 52 weeks, 104 weeks, and 156 weeks were similar. Multivariable analyses showed that only baseline HBV DNA level (OR = 0.56, P = 0.020) and baseline HBsAg level (OR = 0.57, P = 0.012) were independent factors that affected HBsAg decline in HBeAg seronegative patients with CHB. Baseline HBV DNA level (OR = 0.72, P = 0.010) and baseline HBsAg level (OR = 0.19, P < 0.001) were independent factors that affected all CHB patients.

CHB Patients who had received NUCs antiviral treatment showed a slow but significant decrease in serum HBsAg level. Long-term monitoring and continuous antiviral treatment are necessary, especially for those patients with risk factors associated with HBsAg decline.