Higher Off-Therapy Relapse Risk with Tenofovir Alafenamide than Entecavir in Non-cirrhotic HBeAg-Negative Chronic Hepatitis B: Insights from End-of-Treatment qHBsAg Stratification.

BACKGROUND AND AIMS: End-of-treatment (EOT) qHBsAg predicts off-therapy relapse in HBeAg-negative chronic hepatitis B (CHB), but whether its stratifying ability differs between entecavir (ETV) and tenofovir alafenamide (TAF) remains unclear. This study compared 12-month relapse risk across EOT qHBsAg strata after ETV or TAF discontinuation in non-cirrhotic HBeAg-negative CHB patients. METHODS: In this retrospective cohort study, non-cirrhotic HBeAg-negative CHB patients discontinuing ETV or TAF were 1:1 propensity score matched. Virological relapse was assessed by Kaplan-Meier analysis and Cox regression; clinical relapse by cumulative incidence functions with Fine-Gray competing risks regression. Hazard ratios and subdistribution hazard ratios (sHRs) were compared across EOT qHBsAg strata (< 2, 2-3, ≥3 log10 IU/mL). RESULTS: A total of 130 patients (65 per group) were analyzed. Among ETV discontinuers, clinical relapse rates increased progressively with higher EOT qHBsAg (0.0%, 14.6%, and 25.0% for <2, 2-3, and ≥3 log10 IU/mL, respectively). In contrast, TAF discontinuers showed persistently high virological (68.8%-86.3%) and clinical relapse rates (48.5%-57.1%) regardless of EOT qHBsAg level. The relapse risk difference was most pronounced at lower EOT qHBsAg: the sHR for clinical relapse (TAF vs. ETV) reached 5.164 (95% CI 2.131-12.515) at 2-3 log10 IU/mL, with no ETV events at <2 log10 IU/mL. Overall sHR was 5.633 (95% CI 2.801-11.329; p < 0.001). CONCLUSIONS: EOT qHBsAg effectively stratifies clinical relapse risk after ETV discontinuation but shows limited discriminative ability after TAF cessation, where relapse rates remain uniformly high across all qHBsAg levels.