We investigated the incidence and predictors of post-treatment hepatitis B virus (HBV) relapse and hepatitis B surface antigen (HBsAg) loss. After cessation of nucleoside analogue (NA) treatment in hepatitis B e antigen (HBeAg)-negative patients with cirrhosis. The rates of HBsAg loss and hepatocellular carcinoma (HCC) development in HBeAg-negative patients with cirrhosis who continued NA treatment were compared with those who discontinued treatment. Patients with compensated cirrhosis who had discontinued NA treatment for at least 12 months (discontinuing group; n=73) and patients who continued entecavir treatment for at least 4 years (continuing group; n=158) were recruited. Serum HBsAg levels were analysed at the end of treatment (discontinuing group) or at 2.5-3 years of treatment (continuing group). In the discontinuing group, the 6-year cumulative incidence of post-treatment virological relapse and HBsAg loss were 56.3% and 46.7%, respectively. The end-of-treatment HBsAg level of 300 IU/mL was a cut-off value for subsequent post-treatment HBsAg loss and sustained response. In the continuing group, HBsAg loss occurred in five of 158 patients. Cox regression analysis showed that HBsAg levels in the discontinuing group were independent predictors for HBsAg loss in all patients and 104 propensity score (PS)-matched patients. There was no significant difference in HCC development between the groups in all patients and 104 PS-matched patients. Two patients experienced post-treatment alanine aminotransferase flare with hepatic decompensation, and neither of them died after retreatment. In conclusion, HBeAg-negative patients with cirrhosis who discontinued NA treatment might have a higher rate of HBsAg loss and their risk of developing HCC did not increase compared with those who continued entecavir treatment.

The predictors of hepatitis B virus (HBV) relapse and HBsAg loss after cessation of nucleos(t)ide analogues (NA) in HBeAg-negative patients with end-of-treatment HBsAg ≤ 200 IU/mL remains unclear. The study recruited 119 chronic hepatitis B (CHB) patients who achieved end-of-treatment HBsAg ≤ 200 IU/mL, were treated with lamivudine (n = 34) and entecavir (n = 85). The 5-year rates of post-treatment virological relapse, clinical relapse, and HBsAg loss at 60 months were 39.4%, 27.6%, and 45.9%, respectively. Cox regression analysis revealed that HBV DNA at entry and end-of-treatment HBsAg levels were independent predictors of virolgical and clinical relapse. HBV genotype C and end-of-treatment HBsAg were independent factors of HBsAg loss. Patients with a combination of end-of-treatment HBsAg < 50 IU/mL and HBV DNA < 2 × 105 IU/mL at entry experienced the lowest virological and clinical relapse rates (5% and 0% at 60 months, respectively). In contract, patients with a combination of end-of-treatment HBsAg ≥ 50 IU/mL and HBV DNA ≥ 2 × 105 IU/mL at entry experienced high virological and clinical relapse (80.7% and 71.5% at 60 months, respectively). No patients experienced hepatic decompensation when clinical relapse occurred after timely retreatment. A combination of HBV DNA levels at entry and end-of-treatment HBsAg levels was useful for predicting the post-treatment HBV relapse in HBeAg-negative patients with HBsAg ≤ 200 IU/mL.

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