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

Abstract

Background: 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. ©2018 International Medical Press.