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 B
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Open Access
- 1 August 2018
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hepatology
- Vol. 68 (2), 425-434
- https://doi.org/10.1002/hep.29640
Abstract
Hepatitis B surface antigen (HBsAg) loss is a rare event during nucleos(t)ide analogue (Nuc) therapy. Limited data suggest that stopping Nuc therapy may increase HBsAg loss rate in hepatitis B e antigen-negative patients. A large study was conducted to investigate this issue in more detail. Of the 1,075 hepatitis B e antigen-negative patients treated with Nuc for a median of 156 (61-430) weeks, 5 showed HBsAg seroclearance during treatment at an estimated annual incidence of 0.15%. Of the patients who remained HBsAg-seropositive, 691 (52.3 years old, 86% male, 44.6% cirrhosis) had stopped Nuc therapy by the Asian-Pacific Association for the Study of the Liver stopping rule and then were prospectively followed up. Baseline and on-treatment clinical and viral features, treatment duration, consolidation duration, time to undetectable hepatitis B virus DNA, time to normal alanine aminotransferase, end-of-treatment HBsAg, and HBsAg log reduction were compared between patients with and without HBsAg seroclearance after end of treatment. During a median off-therapy follow-up period of 155 (2-614) weeks, HBsAg seroclearance was confirmed in 42 patients. The 6-year cumulative incidence was 13% with an estimated annual incidence of 1.78%. Cox regression analysis showed that shorter time to undetectable hepatitis B virus DNA (1 log(10)), lower end-of-treatment HBsAg level (<100 IU/mL), patients with sustained response, and relapsers not retreated were factors for off-therapy HBsAg seroclearance. Conclusion: The incidence of HBsAg seroclearance after stopping Nuc was much higher than that during therapy and highest in patients without virologic and clinical relapse; patients with clinical relapse who remained untreated had a 7.34 times higher incidence of HBsAg clearance than those who received retreatment, suggesting that transient untreated clinical relapse may drive sufficient immune control to functional cure. (Hepatology 2017).Keywords
Funding Information
- Chang Gung Medical Research Fund (CMRPG1G0061, CMRPG3A0901-3)
- National Science Council (MOST105-2628-B-182-011-MY3)
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