Cessation of nucleos(t)ide analogues therapy in chronic hepatitis B: a systematic review and meta-analysis

Backgroud: To address the possibility of safe cessation of nucleos(t)ide analogues (NAs) therapy in chronic hepatitis B (CHB) and to identify factors associated with off-NAs virological relapse (VR). Methods: A published work search was performed to identify all published studies including patients who ceased NAs and were followed for ≥12 months. A meta-analysis was performed. Results: Twenty-six studies involving 2573 patients who discontinued NAs were included. The pooled rate of off-NAs VR was 0.63, being lower in initially hepatitis B e antigen (HBeAg)-positive than HBeAg-negative patients (0.57 versus 0.62, P = 0.732). The pooled rates of VR were 0.47, 0.55, 0.61, 0.51, 0.73 and 0.64 at 6, 12, 24, 36, 48 and 60 months after NAs cessation, respectively, being relatively lower in initially HBeAg-positive (0.31, 0.45, 0.55, 0.44, 0.48, 0.52) than HBeAg-negative patients (0.50, 0.55, 0.69, 0.57, 0.53, 0.68) ( P = 0.405). The pooled rate of biochemical relapse was 0.44, being lower in initially HBeAg-positive than HBeAg-negative patients (0.43 versus 0.48, P = 0.554). The pooled rates of hepatitis B surface antigen (HBsAg) loss and seroconversion was 0.09 and 0.06, respectively. The pooled rates of VR at 12 months after NAs cessation were significantly different between duration of on-NAs virological response ≤24 months and >24 months in all patients (0.55 versus 0.41, P = 0.011), initially HBeAg-positive patients (0.59 versus 0.41, P = 0.031), and initially HBeAg-negative patients (0.53 versus 0.37, P = 0.025). Conclusions: Safe cessation of NAs therapy seems to be feasible in a substantial proportion of CHB patients. On-NAs virological response >24 months reduces the risk of off-NAs VR. Stopping NAs treatment may have an impact on long-term HBsAg decline and HBsAg clearance.