Incidence and predictors of HBsAg seroclearance after cessation of nucleos(t)ide analogue therapy in HBeAg negative chronic hepatitis B

Abstract

Hepatitis B s 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 (HBeAg) negative patients. A large study was conducted to investigate this issue in more detail. Of the 1075 HBeAg-negative patients treated with Nuc for 156 (61-430) weeks, 6 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% males, 44.6% cirrhosis) had stopped Nuc therapy by Asian-Pacific stopping rule and then were prospectively followed-up. Baseline and on treatment clinical and viral features, treatment duration, consolidation duration, time to undetectable HBV DNA, time to normal ALT, end of treatment (EOT) HBsAg and HBsAg log reduction were compared between patients with and without HBsAg seroclearance after EOT. 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 HBV DNA (<12wks), greater HBsAg reduction during therapy (>1 log₁₀), lower EOT 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 was highest in patients without virologic and clinical relapse. Patients with clinical relapse who remain untreated had 7.34 times higher incidence of HBsAg clearance than those received re-treatment, suggesting that transient untreated clinical relapse may drive sufficient immune control to functional cure. This article is protected by copyright. All rights reserved.

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