DARING-B: discontinuation of effective entecavir or tenofovir disoproxil fumarate long-term therapy before HBsAg loss in non-cirrhotic HBeAg-negative chronic hepatitis B

The remission rates after stopping antivirals in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) vary among studies, while reliable predictors of relapse have not been identified. This prospective study assessed rates and predictors of relapse and retreatment in 57 non-cirrhotic hepatitis B surface antigen (HBsAg)-positive patients with HBeAg-negative CHB who discontinued effective >= 4-year entecavir or tenofovir disoproxil fumarate (TDF) therapy. Methods: A total of 57 patients discontinued therapy after median virological remission of 5.3 years and remained under close follow-up. They were retreated with entecavir/TDF if they fulfilled predetermined criteria. Results: During median follow-up of 18 months, no patient died, developed jaundice or liver decompensation. The cumulative relapse rates varied according to HBV DNA and alanine aminotransferase cutoffs; for HBV DNA >2,000 IU/ml, they were 56%, 70% and 72% at 3, 12 and 18 months after stopping entecavir/TDF. The cumulative probability of retreatment was 18% and 26% at 3 and 12 months being significantly affected only by pretreatment fibrosis severity (adjusted relative hazard: 3.43; P=0.015). Cumulative rates of HBsAg loss were 5%, 16% and 25% at 6, 12 and 18 months being higher in patients with lower HBsAg levels at treatment discontinuation. Conclusions: Our prospective study shows that effective >= 4-year entecavir/TDF therapy can be safely discontinued in non-cirrhotic HBeAg-negative CHB patients. The probability of relapse decreased after month 6. Despite common virological relapses, most patients, particularly those with mild-moderate pretreatment fibrosis, remain without retreatment, at least in the first 18 months, as a substantial proportion of them clear HBsAg and the majority eventually enters into an inactive carrier state.