HBsAg ≤ 135 IU/mL or HBcrAg ≤ 3.6 logU/mL was associated with HBsAg loss after nucleos(t)ide analogue cessation

Abstract Background Since hepatitis B surface antigen (HBsAg) loss is rarely achieved with nucleos(t)ide analogue (NA) treatment, most patients require life-long NA treatment. Previous studies have shown that a proportion of patients remained virological response after NA cessation. Whether NA discontinuation can increase HBsAg loss rate is still under controversial. This study was conducted to assess the cumulative rate of HBsAg loss and identify predictors of HBsAg loss after NA discontinuation Methods In this multicenter prospective study, initially HBV e antigen (HBeAg)-positive patients without cirrhosis who met the stopping criteria were included from 12 hospitals in China. Enrolled patients stopped NA and were followed up with clinical and laboratory assessments every 3 months for 24 months after NA cessation or until clinical relapse (CR) occured. Results Overall 158 patients were divided into two groups. Group A included patients with HBsAg positive when NA cessation (n=139) and Group B included patients with HBsAg negative when NA cessation (n=19). In Group A, the 12-month and 24-month cumulative rates of HBsAg loss were 4.3% and 9.4%, respectively. End of treatment (EOT) HBsAg (hazard ratio (HR) = 0.152, P < 0.001) and EOT hepatitis B core-related antigen (HBcrAg) (HR = 0.257, P = 0.001) were associated with HBsAg loss. The area under the receiver operating characteristic value of the EOT HBsAg and HBcrAg were 0.952 (P < 0.001) and 0.765 (P< 0.001), respectively. Patients with EOT HBsAg ≤ 135 IU/mL (59.2% vs 1.3%, P < 0.001) or HBcrAg ≤ 3.6 logU/mL (17% vs 5.4%, P = 0.027) had higher 24-month cumulative HBsAg loss rate. In Group B, none of patients had virological relapse after NA cessation. Only 1 (5.3%) patient had HBsAg reversion. Conclusions EOT HBsAg ≤ 135 IU/mL or HBcrAg ≤ 3.6 logU/mL can identify patients with more chance to be HBsAg loss after NA cessation. Patients with HBsAg negative when NA cessation have favorable clinical outcomes and HBsAg loss was durable in most cases.