UNLABELLED: Background & Aims: This study investigated the off-therapy relapse in hepatitis B e antigen (HBeAg)-negative non-cirrhotic patients who discontinued tenofovir alafenamide (TAF) or entecavir (ETV). METHODS: Non-cirrhotic HBeAg-negative patients who discontinued TAF or ETV were enrolled. The propensity score -matching method at a ratio of 1:1 and Cox proportional hazard model were performed to analyze factors associated with virological relapse and clinical relapse. RESULTS: A total of 62 patients were analyzed. The cumulative rates of virological relapse at 12-month after discontinuing TAF and ETV were 80.4% and 60.0%, respectively. The respective rates of clinical relapse at 12-month were 48.7% and 21.1%. Multivariable Cox regression analysis showed that discontinuation of TAF (vs ETV, HR=2.279
p=0.005) and HBsAg levels at EOT (HR=1.540
p=0.005) were independently associated with virological relapse. Discontinuation of TAF (vs ETV, HR=3.003
p=0.011) was independently associated with clinical relapse. HBsAg levels at EOT (<
3 vs. ≥ 3 log10 IU/ml) had significant interactions with the treatment regimen (TAF vs ETV) in terms of the risk of clinical relapse after treatment cessation (p for interaction <
0.05). CONCLUSIONS: Patients who discontinued TAF had a higher risk of virological relapse and clinical relapse than those who discontinued ETV. HBsAg levels at EOT may be an appropriate predictor to distinguish the different risks of clinical relapse between patients who have discontinued TAF or ETV.