Serum Hepatitis B Surface Antigen Levels To Guide The Cessation Of Entecavir In Hepatitis B E Antigen-Negative Chronic Hepatitis B: An Interim Analysis

Abstract

Background: Cessation of nucleoside analogue therapy in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) is controversial. It is uncertain whether serum hepatitis B surface antigen (HBsAg) levels can predict virologic kinetics after treatment cessation. Methods: Entecavir was stopped in HBeAg-negative patients treated for at least 2 years with no co-existing or decompensated liver disease. All patients had undetectable HBV DNA levels on at least 3 separate occasions 6 months apart before treatment cessation. Serum HBsAg (Elecsys II, lower limit of detection 0.05 IU/mL), HBV DNA (Cobas Taqman, lower limit of detection 20 IU/mL) and liver biochemistry were monitored at every 6–12 weeks for 1 year. Entecavir was restarted if virologic relapse, defined as HBV DNA >2,000 IU/mL occurred. The primary endpoint was sustained virologic remission, defined as HBV DNA persistently ≤200 IU/mL. Results: 184 patients (median age 54 years, 67.9% male) were recruited. The median baseline HBsAg level was 892 (range 2.3–24,100) IU/mL. Median duration of entecavir therapy before cessation was 3.05 (range 2.02–5.95) years. At the time of writing, 158 (85.9%) and 104 (56.2%) patients have been followed up for 12 and 24 weeks respectively. The cumulative rates of virologic relapse, calculated using the Kaplan–Meier method, were 11.2% at week 12 and 78.1% at week 24 respectively. Among patients with 24 weeks of follow-up (n = 104), patients achieving sustained virologic remission (n = 9), when compared to patients without virologic remission (n = 93) had a significantly longer median duration of entecavir treatment before therapy cessation (4.05 and 3.03 years respectively, p = 0.007), a higher probability of undetectable viremia at week 12 (88.9% and 17.9% respectively, p<0.001) and a trend towards a lower median baseline HBsAg level (701 and 936 IU/mL respectively, p = 0.088). Conclusion: Base on this interim analysis, a longer duration of prior nucleoside analogue therapy and off-treatment HBV DNA undetectability at week 12 were associated with a higher chance of sustained virologic remission after treatment cessation. Subsequent analysis would determine if baseline and off-treatment HBsAg levels could predict virologic remission after treatment cessation. Acknowledgement: This study was supported by an unrestricted grant from Roche Diagnostics