Nucleos(t)ide analogue treatment in hepatitis B: to stop or not to stop?

Monotherapy with a nucleos(t)ide analogue (NA), namely entecavir and tenofovir, represents the mainstay of hepatitis B virus (HBV) treatment, which achieves potent viral suppression and subsequently improved major outcomes, but it rarely leads to functional cure (i.e. 10-year cumulative rate of <3%). Current guidelines recommend NA discontinuation in all chronic hepatitis B patients who achieve HBV surface antigen (HBsAg) loss. Before HBsAg loss, NA discontinuation is recommended with caution only in non-cirrhotics with normal ALT who have remained in long-term on-therapy remission for various periods depending on their initial HBeAg status and agree to close post-treatment monitoring.

This review explores the current landscape of the concept of NA discontinuation, examining benefits, risks, criteria for stopping, and patient selection and monitoring according to international guidelines, and biomarkers that may be helpful in decision-making.

In the absence of novel antivirals leading to HBsAg clearance, accumulating data suggests that stopping NA therapy in carefully selected HBeAg negative patients may increase the probability of HBsAg loss and reduce long-term treatment burden, eventually improving patients' outcome. However, there are risks of post-treatment relapses and flares that need to be considered, while other critical parameters should be fitted to tailor patient selection.