Background: Nucleos(t)ide analog therapy (NA) is the standard of care for patients with chronic hepatitis B infection. However, NA rarely leads to HBsAg seroclearance, which is considered as a ‘functional cure' and is associated with improved clinical outcomes. However, the optimal duration of NA therapy remains unclear and stopping NA as a strategy to cure HBV is controversial. The kinetics of HBsAg decline on NA has not been well studied in clinical trials but may help predict the duration of therapy required to achieve HBV cure.
Purpose: The aim of this study was to determine the rate of HBsAg decline in CHB patients on NA in order to predict time to functional cure.
Methods: Consecutive adult patients with CHB attending the Toronto General Hospital Liver Clinic from 2018-2022 who received NA as per current treatment guidelines were included. Baseline demographic, clinical and laboratory data including liver panel, quantitative HBsAg levels (Abbott Architect, LLOQ 0.02 IU/ml), and HBV DNA (RT PCR, LLOQ 10 IU/ml) were collected every 6 months during followup. Baseline quantitative HBsAg was compared with HBsAg level at the time of seroclearance or at last followup for kinetics analysis annd to estimate the rate of HsAg loss.
Results: Of 371 consecutive patients were treated with NA (TDF 90%, ETV 10%), the majority was male (67%), Asian (92%) with a mean age 57 yrs. The mean baseline HBsAg was 6754.6 IU/ml. Patients were divided into 3 categories according to HBsAg levels: low <1000 IU/ml, 167 (45%) patients; intermediate 1000-10,000 IU/ml, 161(44%) patients; and high >10,000 IU/ml, 43 (11%) patients. The average decline in HBsAg was 1031.7 IU/mL/year over an average treatment duration of 5.83 years. The mean annual rate of decline in HBsAg differed according to baseline HBsAg levels: low group declined by 50.4 IU/ml; intermediate 446.8 IU/ml; and high 9851.5 IU/ml, (p<0.05). HBsAg seroclearance was observed in 53 (14%) patients after a mean duration of 11 years of NA. Those with low HBsAg were more likely to achieve HBsAg seroclearance.
Conclusions: In this retrospective cohort study, the annual rate of quantitative HBsAg decline was slow but measurable at 1034.7 IU/ml. The magnitude of HBsAg decline correlated with baseline HBsAg level in treated CHB patients. HBsAg seroclearance increases with prolonged duration of NA and was greatest among those with low HBsAg levels at baseline. These data demonstrate the utility of HBsAg kinetics and can be used to predict time to functional cure for those currently receiving NA, but further studies are required.