World Gastroenterology Organisation

Global Guardian of Digestive Health. Serving the World.


Nucleos(t)ide analogue cessation in HBeAg-negative chronic hepatitis B

Review by Prof. Ahad Eshraghian (Iran)

Study Summary 

Functional cure (loss of HBs Ag) is rarely achieved in patients with chronic HBe Ag-negative hepatitis B. Therefore, lifelong treatment with Nucleos(t)ide analogues (NUCs) is the standard of care in these patients. Hypothetically, stopping NUC treatment may lead to functional cure through a mechanism called autovaccination. In a randomized-controlled trial, patients with HBeAg-negative chronic hepatitis B on continuous long-term NUC treatment, with HBV DNA < 1,000 copies/ml for ≥4 years, were randomized to either stop (Arm A) or continue NUC treatment (Arm B). They were followed for a 96-week observation period with sustained HBsAg loss considered as the primary endpoint. Cessation of NUC treatment was associated with a significantly higher rate of HBsAg loss than continued NUC treatment (10.1 % versus 0).


The study demonstrated that controlled cessation of NUC treatment in HBeAg-negative patients without advanced liver disease was effective in reaching HBS Ag loss that cannot be achieved with long-term NUC treatment. Despite promising results, there are still some concerns about stopping NUCs to achieve functional cure. There were reports of hepatic decompensation, liver failure and even death in some other studies. Furthermore, the study was conducted only among European patients and results cannot be simply generalized to Asian, African and American patients with different HBV genotypes.


van Bömmel F, et al. A multicenter randomized-controlled trial of nucleos(t)ide analogue cessation in HBeAg-negative chronic hepatitis B. J Hepatol. 2023 May;78(5):926-936. doi: 10.1016/j.jhep.2022.12.018. Epub 2023 Mar 28. PMID: 37062574.

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