Higher HBeAg‐reversion virological relapse and lower sustained remission after treatment cessation in tenofovir‐treated HBeAg‐positive patients

Abstract A complete investigation of the clinical outcomes after treatment cessation in HBeAg‐positive patients with HBeAg loss is limited. We retrospectively recruited 242 HBeAg‐positive patients with HBeAg loss after a median duration of 37.2 months with tenofovir (TDF, n = 77) or entecavir (ETV, n = 165) treatment. There were 77 (31.8%) patients with sustained virological remission (SVR), 85 (35.1%) with HBeAg‐reversion virological relapse, 80 (33.1%) with HBeAg‐negative virological relapse after treatment cessation, and 23 (9.5%) with HBsAg loss. Clinical data at baseline, on‐treatment and during off‐treatment follow‐up were analyzed. The 3‐year cumulative incidences of overall, HBeAg‐reversion and HBeAg‐negative virological relapse were 70.2%, 54%, and 53.5%, respectively. The common factors associated with HBeAg‐reversion and HBeAg‐negative virological relapse were tenofovir treatment (hazard ratio [HR] = 5.411, p < 0.001; HR = 2.066, p = 0.006, respectively) and HBsAg at end of treatment (EOT) (HR = 1.461, p = 0.001; HR = 1.303, p = 0.019, respectively). The 5‐year cumulative incidence of HBsAg loss in SVR patients was 13.7% and EOT HBsAg was the only associated factor (HR = 0.524, p = 0.024). Compared to that of ETV‐treated patients, TDF‐treated patients had a significantly higher 3‐year cumulative incidence of virological relapse (87.3% vs. 62.8%, p < 0.001), earlier HBeAg‐reversion virological relapse (2.9 vs. 7.8 months, p < 0.001), a higher rate of HBeAg‐reversion virological relapse (53.2% vs. 26.7%) and a lower SVR rate (15.6% vs. 39.4%) ( p < 0.001). In summary, the clinical outcomes after treatment cessation in HBeAg‐positive patients with HBeAg loss were composed of HBeAg‐reversion virological relapse, HBeAg‐negative virological relapse and SVR. TDF was significantly associated with off‐treatment virological relapse. EOT HBsAg plays an important role in HBsAg loss among SVR patients and posttreatment virological relapse.