Objective Although most patients with chronic hepatitis B (CHB) reach effective virological suppression with long-term nucleos(t)ide analogues (NA) therapy, some might not need to continue treatment for life. In this randomised, controlled, phase IV trial, we evaluated off-therapy outcomes in patients after discontinuing long-term NA therapy.
Design Patients who had received NA therapy for ≥1 year and achieved virological suppression (hepatitis B e antigen (HBeAg) seroconversion combined with undetectable hepatitis B virus (HBV) DNA ≥12 months in HBeAg-positive patients or undetectable HBV DNA ≥36 months in HBeAg-negative patients) were randomised 2:1 to stop or continue NA therapy for 72 weeks. Sustained disease remission (HBeAg negative, HBV DNA <2000 IU/mL and normal alanine aminotransferase (ALT)) was evaluated at 72 weeks after stopping NA therapy.
Results Among 67 enrolled patients, sustained disease remission was observed in 13/45 (29%) stop versus 18/22 (82%) continue patients. Hepatitis B surface antigen (HBsAg) loss occurred in two patients (one in each group). The median HBsAg decline from randomisation to week 72 was similar in both groups (0.2 (0.0–0.4) vs 0.1 (0.0–0.2) log IU/mL in stop vs continue patients). Among patients who stopped, 15/45 (33%) had virological or biochemical relapse and 17/45 (38%) were retreated according to predefined criteria. A total of 11/18 (61%) pretreatment HBeAg-positive versus 6/27 (22%) HBeAg-negative patients required retreatment (p=0.01). Fourteen (31%) patients developed ALT >10× upper limit of normal (ULN) and another 7 (16%) had ALT >5× ULN. No patients experienced liver decompensation or died.
Conclusion The findings of this prospective study suggest limited benefit of stopping NA therapy in chronic hepatitis B.
Trial registration number NCT01911156.
- viral hepatitis
- nucleos(t)ide analogue
- HBeAg negative
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Correction notice This article has been corrected since it published Online First. The abstract has been corrected.
Contributors HLAJ and BEH: study design and study supervision; JC, KSL: data acquisition; KSL, BEH and HLAJ: analysis and interpretation of data; DKHW, SF, CY and JJF: study clinician advisers and contributed to data interpretation; BEH: study statistician; KSL: drafting of the manuscript; all authors: critical revision and approval of the final manuscript.
Funding This investigator-initiated study was organised and sponsored by University Health Network (Toronto, Canada). Gilead Sciences, Inc. (Foster City, US) has provided funding support and study medication for patients who required but did not have access to tenofovir disoproxil fumarate.
Disclaimer The funding sources did not have any influence on study design, data collection, analysis and interpretation of the data, writing of the report or the decision to submit for publication.
Competing interests BEH has received grants from and is consultant to Intercept Pharmaceuticals. HLAJ has received grants from and is consultant to Abbott, Bristol-Myers Squibb, Gilead Sciences, Merck, Novartis, Roche and Janssen. JJF reports receiving support for research or scientific consulting from Abbott, Abbvie, Contavir, Enanta, Gilead Sciences, Janssen and Roche. SF has received research support from Gilead Sciences and speaking and teaching and/or consulting fees from Gilead Sciences, Merck and AbbVie. DKHW has received speaking and teaching fees from AbbVie and Merck.
Patient consent for publication Not required.
Ethics approval This study was approved by the University Health Network Research Ethics Board (protocol number: 13-6159).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.
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