Supplementary Material for: Comparison of HBeAg clearance rates between tenofovir alafenamide and entecavir in treatment-naive HBeAg positive chronic hepatitis B patients over 48 to 96 weeks: A retrospective cohort study

Objectives: This retrospective cohort study aimed to compare HBeAg clearance rates at 48 and 96 weeks in treatment-naïve, HBeAg-positive CHB patients receiving TAF versus ETV therapy Patients and Methods: Of 425 initially screened HBeAg-positive CHB patients, 251 were included in the 48-week analysis (ETV: 119; TAF: 132) and 101 in the 96-week analysis (ETV: 41; TAF: 60).PSM was used to balance baseline characteristics. Multivariate cox regression identified factors associated with HBeAg clearance. Results: At 48 weeks, a 1:1 PSM created balanced groups of 77 patients each for the 48-week comparison. the HBeAg clearance rate was significantly higher in the TAF group than in the ETV group: 22.1% versus 6.5% (χ²= 7.636, p= 0.006). The TAF group had significantly lower levels than the ETV group: (ETV: 7.94 (0.85~179.66) vs. TAF: 4.60 (0.20~70.51); p= 0.025). The reduction in HBeAg was also greater in the TAF group: (ETV: -82.10 (-189.65, -5.99) vs. TAF: -149.77 (-267.46, -15.17); p= 0.041). At week 96, 1:2 PSM yielded 66 matched patients (ETV: 24, TAF: 42). The HBeAg clearance rate was significantly higher in the TAF group (13/42, 31.0%) than in the ETV group (2/24, 8.3%) (χ²= 4.450, p = 0.035). qHBeAg levels were significantly lower in the TAF group (2.85 (0.33~33.38)) than in the ETV group (57.35 (4.78~257.45)) (p=0.001). The TAF group also showed a greater magnitude of reduction from baseline: (ETV: -81.66 (-170.58~ -1.13) vs. TAF: -260.66 (-398.15 ~ -50.31), p< 0.001). Multivariate cox analysis identified TAF treatment, baseline anti-HBe positivity , and lower baseline qHBeAg as independent predictors of HBeAg clearance. Conclusions: For HBeAg-positive CHB patients, TAF demonstrated superior efficacy to ETV in achieving HBeAg clearance over 48-96 weeks. This effect was more pronounced in patients with lower baseline qHBeAg levels or already existing anti-HBe positivity.