Limited sustained response after stopping nucleos(t)ide analogues in patients with chronic hepatitis B: results from a randomised controlled trial (Toronto STOP study)
- 28 August 2019
- Vol. 68 (12), 2206-2213
- https://doi.org/10.1136/gutjnl-2019-318981
Abstract
ObjectiveAlthough 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.DesignPatients 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 ResultsAmong 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.ConclusionThe findings of this prospective study suggest limited benefit of stopping NA therapy in chronic hepatitis B.Trial registration numberNCT01911156.Keywords
Funding Information
- University Health Network (N/A)
This publication has 19 references indexed in Scilit:
- Stopping nucleos(t)ide analogue treatment in Caucasian hepatitis B patients after HBeAg seroconversion is associated with high relapse rates and fatal outcomesAlimentary Pharmacology & Therapeutics, 2018
- Eight-year survival in chronic hepatitis B patients under long-term entecavir or tenofovir therapy is similar to the general populationJournal of Hepatology, 2018
- Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidanceHepatology, 2018
- Incidence and predictors of hepatitis B surface antigen seroclearance after cessation of nucleos(t)ide analogue therapy in hepatitis B e antigen–negative chronic hepatitis BHepatology, 2017
- DARING-B: Discontinuation of Effective Entecavir or Tenofovir Disoproxil Fumarate Long-Term Therapy before HBsAg Loss in Non-Cirrhotic HBeAg-Negative Chronic Hepatitis BAntiviral Therapy, 2017
- Long-term response after stopping tenofovir disoproxil fumarate in non-cirrhotic HBeAg-negative patients – FINITE studyJournal of Hepatology, 2017
- EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infectionJournal of Hepatology, 2017
- Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 updateHepatology International, 2015
- Specific and Nonhepatotoxic Degradation of Nuclear Hepatitis B Virus cccDNAScience, 2014
- Long-term hepatitis B surface antigen (HBsAg) kinetics during nucleoside/nucleotide analogue therapy: Finite treatment duration unlikelyJournal of Hepatology, 2012