KINETICS AND PREDICTION OF HBSAG SEROCLEARANCE DURING LONG- TERM TREATMENT WITH NUCLEOS( T) IDE ANALOGUES IN PATIENTS WITH CHRONIC HEPATITIS

초록

Background: Serum Hepatitis B Surface Antigen (HBsAg) seroclearance is the ultimate goal in the treatment of chronic hepatitis B (CHB) patients, but is a rare event. The factors influencing HBsAg seroclearance remain unclear. This study aims to investigate the long-term kinetics of HBsAg levels according to different nucleos(t)ide analogues (NUCs) and identify predictors of functional cure (HBsAg seroclearance). Methods: We conducted a retrospective observational study of patients treated with one of the following NUCs: entecavir (ETV), tenofovir disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF), or besifovir (BSV). The patients were enrolled from 2007 to 2023 and were followed-up for at least one year and HBsAg levels were quantified every 6-12 months. Results: A total of 539 CHB patients treated with first-line NAs were included, with a follow-up duration of 61.5 months. Baseline HBV DNA and HBsAg level were significantly higher in HBeAg patients compared to HBeAg negative patients (3.72 ± 0.81 vs 3.02 ± 0.99 IU/mL). During follow-up, 24 patients (4.4%) achieved functional cure within 44 months and 33 patients (6.1%) achieved significant HBsAg reduction ( > 2 log10 IU/mL). The firstyear mean HBsAg log reduction was 0.21 log IU/mL, significantly higher than reductions in the second (0.10 log10IU/mL, p = 0.017) and third (0.06 log IU/mL, p =0.004) years. All four NA groups showed consistent reductions in HBsAg levels throughout without significant difference within 3 years of treatment but a significant decrease was observed in TAF treated patient after 3 years of treatment compared to other types of NUCs. The first-year HBsAg reduction rate was positively associated with baseline HBsAg levels (p =0.013). Key predictors for functional cure included lower baseline HBsAg levels ( < 3 log IU/mL) and a higher first-year HBsAg reduction rate of ≥ 1 log IU/mL (both, p <0.001). The estimated time for functional cure in TAF, TDF and ETV treated patients were 67.3, 71.4, 94.3 months, respectively. None of the patients who achieved functional cure developed hepatocellular carcinoma (HCC), while 34 patients (8.1%) among those who did not achieved functional cure progressed to HCC. Conclusion: Consistent HBsAg reduction was observed throughout treatment with no significant differences among the four NUCs. However, further decrease in HBsAg level can be expected in TAF treated patients after a prolonged treatment duration compared to other treatment groups. Low baseline HBsAg levels and higher reduction rates of HBsAg in the first year of treatment, may be reliable factors in predicting HBsAg seroclearance.