Viral Hepatitis (+Antiviral Therapy) HBsAg and HBV DNA levels guiding entecavir cessation in HBeAg-negative chronic hepatitis B

Abstract

Objective: The role of hepatitis B surface antigen (HBsAg) and HBV DNA levels in predicting virologic kinetics after nucleoside analogue cessation has not been well-investigated. Methods: Following APASL guidelines, entecavir was stopped in HBeAg-negative patients treated for ≥2 years and undetectable HBV DNA levels on ≥3 separate occasions 6 months apart before treatment cessation. HBsAg and HBV DNA levels were monitored at every 6–12 weeks for 1 year. Entecavir was restarted if virologic relapse (defined HBV DNA >2,000 IU/mL) occurred. Results: 184 patients (mean age 53.9 years, 67.9% male) were recruited. The mean baseline HBsAg level was 2.86 (SD ± 0.56) log IU/mL. Mean duration of entecavir therapy before cessation was 3.06 (SD ± 0.63) years. At the time of writing, 168 (91.3%) and 119 (72.6%) patients have been followed up for 24 and 36 weeks respectively. Cumulative rates of virologic relapse, calculated using the Kaplan-Meier method, were 75.9% and 86.9% at weeks 24 and 36 respectively. Among patients with at least 24 weeks of follow-up, patients without virologic relapse (n = 25), when compared to patients with virologic relapse (n = 143), had a higher probability of undetectable viremia at week 12 off-treatment (64.0% and 18.2% respectively, p < 0.001). Mean HBsAg levels at entecavir commencement, entecavir cessation and the mean rate of HBsAg reduction during entecavir therapy had no association with virologic relapse (p = 0.738, 0.829 and 0.605 respectively). Off-treatment week-12 HBV DNA levels achieved an AUROC of 0.766 (p < 0.001, 95%CI 0.662–0.869) in predicting virologic relapse. Among patients with HBsAg <1,000 and <500 IU/mL at entecavir cessation, week-12 HBV DNA achieved an AUROC of 0.811 (p = 0.004, 95%CI 0.690–0.931) and 0.868 (p = 0.004, 95%CI 0.736–0.993) respectively. Conclusion: The combination of HBsAg levels at treatment cessation and off-treatment HBV DNA levels could predict virologic remission after entecavir cessation.