Dynamic Characteristics of Serum Hepatitis B Surface Antigen in Chinese Chronic Hepatitis B Patients Receiving 7 Years of Entecavir Therapy

Abstract

Background: The ultimate goal of hepatitis B treatment is hepatitis B surface antigen (HBsAg) seroclearance. Several factors have been suggested to be associated with the rate of HBsAg reduction in antiviral-naive or lamivudine therapy cohorts. However, there are few studies evaluating the factors during long-term entecavir (ETV) therapy. In the present study, we aimed to evaluate the factors to predict the outcome of ETV therapy for 7 years.

Methods: A total of 47 chronic hepatitis B (CHB) patients treated with ETV monotherapy were included in this study. Liver biochemistry, hepatitis B virus (HBV) serological markers, serum HBV DNA, and HBsAg titers were tested at baseline, 3 months, 6 months, and yearly from 1 to 7. The associations between factors and HBsAg reduction were assessed using multivariate tests with repeated measure analysis of variance.

Results: At baseline, serum HBsAg levels showed a positive correlation with baseline HBV DNA levels (r = 0.625, P < 0.001). The mean HBsAg titers after ETV treatment were significantly lower than the baseline titers (P ranges from 0.025 to 0.000,000,6). The HBsAg reduction rate during the 1st year was greater compared to after 1 year of treatment (P < 0.05). Multivariate test showed that hepatitis B e antigen (HBeAg) seroclearance and/or HBsAg reduction ≥0.5 log10 IU/ml at 6 months had a high negative predictive value (96.77%) for HBsAg seroclearance (P = 0.002, P = 0.012, respectively).

Conclusions: The HBsAg reduction rate during the 1st year was greater than that after 1 year of treatment. Further, HBeAg status and HBsAg levels at month 6 are the optimal factors for the early prediction of HBsAg seroclearance after long-term ETV therapy in CHB patients.

Figure 1

(a) The detectable rates of HBV DNA and (b) mean HBsAg throughout 7-year treatment period. HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen.

Figure 2

Mean serum HBsAg reduction in different patients groups stratified by (A) age and (B) HBeAg seroclearance at 6 months (C) HBsAg reduction≥0.5log₁₀ IU/ml at 6 months. HBsAg: Hepatitis B surface antigen; HBeAg: Hepatitis B e antigen.

Figure 3

Predictive values of HBeAg seroclearance at month 6 (a) and HBsAg reduction ≥0.5 log₁₀ IU/ml within 6 months (b) of entecavir treatment on HBsAg seroclearance. HBeAg: Hepatitis B e antigen; HBsAg: Hepatitis B surface antigen.

Figure 4

Kinetics of serum HBsAg titers and HBV DNA in the four patients who achieved HBsAg seroclearance. HBV: hepatitis B virus; HBsAg: Hepatitis B surface antigen.