Virological response to antiviral therapy at week 12 indicates a great reduction of intrahepatic hepatitis B virus DNA and cccDNA in HBeAg-positive chronic hepatitis B patients

Abstract

Early virological response is considered to be a predictor for the outcome of anti-hepatitis B virus (HBV) therapy. To analyze its correlation to intrahepatic HBV DNA and covalently closed circular DNA (ccc)DNA, 71 hepatitis B virus e antigen (HBeAg)-positive chronic hepatitis B patients were recruited: 34 patients were treated with lamivudine; 13 with interferon-α2b; and 24 with sequential therapy of lamivudine-interferon-α2b for 48 weeks. Intrahepatic HBV DNA and cccDNA load were measured at the baseline and at Week 48. Fifty-seven patients had virological response at Week 12. Median decreases of serum HBV DNA in patients with or without virological response at Week 12 were 4.0 log10 (max. 6.2, min. 2.2) and 1.1 log10 (max. 2.1, min. 0) (Z = -5.766, P = 0.0000), respectively. At Week 48 they were 4.1 log10 (max. 7.4, min. 1.0) and 2.3 log10 (max. 7.5, min. 0.3) (Z = -2.760, P = 0.006), respectively. For intrahepatic HBV DNA load they were 1.3 log10 (max. 4.3, min. -1.2) and 0.6 log10 (max. 3.5, min. -0.8), respectively, and for HBV cccDNA load they were 1.1 log 10 (max. 4.8, min. -0.5) and 0.5 log10 (max. 3.0, min. -0.8) (Z = -2.097, P = 0.036), respectively at Week 48. Step-wise logistic regression analysis indicated that the baseline intrahepatic HBV DNA load effected virological response at Week 12 [odds ratio (OR) 0.405; 95% confidence interval (CI) 0.174-0.944; P = 0.036] and HBeAg seroconversion at Week 48 (OR 0.292; 95% CI 0.131-0.649; P = 0.003). In conclusion, virological response at Week 12 indicated a great reduction of intrahepatic DNA and cccDNA load in HBeAg-positive CHB patients. The baseline intrahepatic HBV DNA load affected virological response at Week 12 and HBeAg seroconversion at Week 48. © 2010 Blackwell Publishing Ltd.