Decline of HBV covalently closed circular DNA during telbivudine and lamivudine therapy

Abstract

BACKGROUND AND AIMS: Telbivudine has been shown to have a higher rate of reduction of serum hepatitis B virus (HBV) DNA, normalization of transaminase and histologic improvement than lamivudine in both HBeAg-positive and HBeAg-negative patients [1]. However, the effect of telbivudine therapy on the reduction of covalently closed circular DNA (cccDNA) levels in liver has not been investigated. This study aimed to compare the effect of one year of telbivudine vs. lamivudine therapy on cccDNA levels. PATIENTS AND METHODS: Thirty-eight patients (25 HBeAg-positive and 13 anti-HBe-negative) on 600 mg daily telbivudine and 32 patients (24 HBeAg-positive and 8 anti-HBe-positive) on 100 mg daily lamivudine were recruited These patients were enrolled in the Globe phase 3 trial at our center in Hong Kong. Liver biopsies were taken at baseline and week 52 of therapy. Serum HBV DNA was quantitated by the COBAS Amplicor Monitor Test. Intrahepatic HBV DNA and cccDNA were measured by a previously validated real-time PCR assay [2]. RESULTS: Patients treated with telbivudine had a greater median reduction of serum HBV DNA at week 52 than those treated with lamivudine (6.0 vs. 4.1 log10 copies/mL, respectively, P = 0.041). At week 52, median reduction of intrahepatic total HBV DNA for telbivudine and lamivudine patients were 1.2 and 1.3 log10 copies/cell, respectively (P = 0.973) and for cccDNA were 0.11 and −0.07 log10 copies/cell, respectively (P = 0.217). CONCLUSIONS: There was no significant difference between treatments in the magnitude of the observed reduction in intrahepatic HBV DNA and cccDNA levels even though telbivudine was more potent than lamivudine in the suppression of serum HBV DNA replication. This extends previous findings with no difference observed in the reduction of intrahepatic HBV DNA and cccDNA levels when comparing entecavir vs. lamivudine treatment for 1 year. It may be possible to determine the efficacy of therapeutic treatments using samples obtained after longer treatments. References [1] Lai et al, N Engl J Med (2007) 357: 2576−88. [2] Wong, Yuen, Ngai, Fung, Lai, Antivir Ther (2006) 11: 909–916.