HBeAg-positive patients with HBsAg  < 100 IU/mL and negative HBV RNA have lower risk of virological relapse after nucleos(t)ide analogues cessation

BACKGROUND: Nucleos(t)ide analogues (NAs) cessation is not widely practiced and remains a controversial, but highly relevant subject in patients infected with hepatitis B virus (HBV). We aimed to explore the related factors for safe NAs cessation. METHODS: This is a multicenter prospective cohort study. Overall, 139 initially HBV e antigen (HBeAg)-positive patients meeting the stopping criteria were included in 12 hospitals in China. Enrolled patients ceased NAs and were followed up every 3 months for 24 months or until clinical relapse (CR). RESULTS: The 24 month cumulative rates of virological relapse (VR), CR, HBeAg reversion and HBV surface antigen (HBsAg) loss were 50.4, 24.5, 11.5 and 9.4%, respectively. Patients with end of treatment (EOT) HBsAg < 100 IU/mL plus negative HBV RNA had the lowest 24 month cumulative VR rate (5 vs 58%, p < 0.001). EOT HBsAg ≥ 2 log(10) IU/mL [odds ratio (OR) = 6.686, p = 0.006], EOT positive HBV RNA (OR = 3.453, p = 0.008) and EOT hepatitis B core-related antigen (HBcrAg) ≥ 4log U/mL (OR = 3.702, p = 0.002) were found to independently predict the risk of VR. To predict VR, the area under the receiver-operating characteristic (AUROC) value of the EOT HBsAg < 100 IU/mL plus EOT HBV RNA negative was 0.698 (p < 0.001), which was higher than other parameters alone or combinations. CONCLUSIONS: NAs cessation is suitable only for a small and selected patients. An EOT HBsAg < 100 IU/mL and EOT negative HBV RNA identified a patient with low risk of off-treatment VR.