Abstract
OBJECTIVE: Although nucleos(t)ide analogues (NUCs) are effective in the treatment of chronic hepatitis B (CHB), the optimal duration of therapy and the criteria for safe cessation remain unclear. The aim of this study was to assess the rate of hepatitis B surface antigen (HBsAg) loss after treatment cessation in HBeAg-negative, non-cirrhotic patients and to determine the proportion of patients who could be followed without treatment. METHODS: This prospective study was conducted from April 2022 to August 2024. A total of 46 non-cirrhotic, HBeAg-negative, HBV DNA-negative, and non-coinfected patients who had been on nucleos(t)ide analogue therapy for more than three years and were HBV DNA-negative for at least three years were included. Treatment cessation was performed in 23 of these patients, while the remaining 23 patients who continued treatment formed the control group. Patients in the treatment discontinuation group were followed monthly for the first six months and then every three months over a 24-month period. RESULTS: At the end of the 24-month follow-up, HBsAg loss was observed in 3 (13%) patients in the treatment discontinuation group, whereas 69.6% of patients had HBV DNA levels < 2000 IU/mL and remained in treatment-free follow-up. No HBsAg loss was observed in the control group. There were no significant predictors of the need for re-treatment when comparing patients who maintained treatment-free follow-up and those who required re-treatment (p > 0.05). However, virologic relapse was significantly higher in the first three months after treatment discontinuation among patients who had been previously treated with tenofovir (p < 0.001). Additionally, the cumulative clinical relapse rate was significantly higher in the tenofovir group compared to the control group (p = 0.009). CONCLUSIONS: In this study, the rate of HBsAg loss at 24 months following treatment discontinuation was 13%. The cumulative rate of clinical relapse was significantly higher in patients who had been treated with tenofovir before treatment cessation. These findings suggest that treatment cessation may be a viable option for certain patients, though careful monitoring is essential, particularly in those who have previously received tenofovir-based therapies. CLINICAL TRIAL: This study was a prospective study involving treatment discontinuation. Although it was not registered in a public clinical trial database, it was conducted with approval of the institutional ethics committee (Approval No: GOKAE-0111) and in accordance with relevant regulations. GRAPHICAL ABSTRACT: [Image: see text]