One-year treatment of entecavir results in reduction in intrahepatic covalently closed circular DNA level

Abstract

BACKGROUND: Two phase 3, multicenter, double-blind trials on HBeAg-positive and HBeAg-negative patients demonstrate that, compared with lamivudine, entecavir is superior in inducing histologic improvement, serum HBV DNA suppression and transaminase normalization. Since intrahepatic HBV DNA and covalently closed circular (ccc) DNA are important for control of viral replication, the efficacy of entecavir vs. lamivudine in achieving suppression of these entities should be studied. METHODS AND PATIENTS: The patients involved in this study were recruited from patients participating in the two phase 3 entecavir trials at our center in Hong Kong. Forty chronic hepatitis B patients (14 HBeAg-positive and 26 anti-HBe-positive) were randomized to receive either entecavir (0.5 mg once daily) or lamivudine (100 mg once daily). Paired liver biopsy and serum samples were collected both at baseline and week 48 of treatment. Total intrahepatic HBV DNA and cccDNA were measured by the Invader® assay.1 Serum HBV DNA was measured by the COBAS Amplicor HBV Monitor Test. RESULTS: This is an interim report for the 14 HBeAg-positive patients. (The findings of the 26 anti-HBe-positive patients will be analyzed later.) For the 14 HBeAg-positive patients, 7 were randomized to receive entecavir, while the rest received lamivudine. CONCLUSION: The preliminary results of this study showed that 1 year of entecavir was superior to lamivudine in suppression of total intrahepatic and ccc DNA in liver biopsies. The addition of the data from the 26 anti-HBe patients may confirm these results.