Introduction of nucleos(t)ide analogues (NAs) for oral antiviral therapy has dramatically improved the clinical outcome in patients with chronic hepatitis B (CHB). Although current international guidelines for the management of CHB provide information regarding when to begin the antiviral therapy with NAs, there is no clear consensus on when to stop the treatment, especially for those who respond to the therapy. Hepatitis B surface antigen loss has been regarded as an ideal endpoint of oral antiviral therapy with NAs, however since this is rarely achieved, practical endpoints have been suggested by the international guidelines. Despite the stopping rules recommended by the international guidelines, whether oral antiviral therapy with NAs can be safely discontinued is of major concern. While attention has been drawn to whether antiviral treatment with NAs can be a finite therapy, there is lack of sufficient data on off-treatment durability of highly potent NAs. Based on the available evidences, current guidelines for stopping NA therapy seems to be inadequate in terms of off-treatment durability, with relapse rates of more than 40% for both hepatitis Be antigen (HBeAg)-positive and HBeAg-negative patients. Therefore, further studies are required to accumulate data on off-treatment durability of highly potent NAs, and future studies are warranted to identify adequate predictive markers that could provide supplementary information to guide the timing of stopping NA therapy.
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