AIM:To evaluate the effects of antiviral agents and HBV genotypes on intrahepatic covalently closed circular DNA (ccc DNA) in HBeAg-positive chronic hepatitis B patients. METHODS:Seventy-one patients received lamivudine (n = 35), or sequential therapy with lamivudine-interferon alpha 2b (IFN-α 2b, n = 24) for 48 wk, or IFN-α 2b (n = 12) for 24 wk. All subjects were followed up for 24 wk. Intrahepatic ccc DNA was measured quantitatively by PCR. HBV genotypes were analyzed by PCR-RFLP. RESULTS:Sequential lamivudine-INF-α therapy, lamivudine and INF-α monotherapy reduced ccc DNA of 1.7 log, 1.4 log and 0.8 log, respectively (P < 0.05). Seventeen out of the 71 patients developed HBeAg seroconversion, the reduction of ccc DNA in the HBeAg seroconversion patients was more significant than that in the HBeAg positive patients (3.0 log vs 1.6 log, P = 0.0407). Twenty-four weeks after antiviral therapy withdrawal, 16 patients had a sustained virological response, the baseline intrahepatic ccc DNA in the patients with a sustained virological response was significantly lower than that in the patients with virological rebound (4.6 log vs 5.4 log, P = 0.0472). HBV genotype C accounted for 85.9% (n = 61), and genotype B for 14.1% (n = 10), respectively, in the 71 patients. There was no significant difference in the change of ccc DNA level between HBV genotypes C and B (2.1 log vs 1.9 log). CONCLUSION:Forty-eight week sequential lamivudine-INF-α therapy and lamivudine monotherapy reduce ccc DNA more significantly than 24-wk INF-α monotherapy. Low baseline intrahepatic ccc DNA level may predict the long-term efficacy of antiviral treatment. HBV genotypes C and B have no obvious influence on ccc DNA load. AIM: To evaluate the effects of antiviral agents and HBV genotypes on intrahepatic covalently closed circular DNA (ccc DNA) in HBeAg-positive chronic hepatitis B patients. METHODS: Seventy-one patients received lamivudine (n = 35), or sequential therapy with lamivudine -interferon alpha 2b (IFN-α 2b, n = 24) for 48 wk, or IFN-α 2b (n = 12) for 24 wk. All subjects were subsequently up for 24 weeks. Intrahepatic ccc DNA was measured quantitatively by PCR. HBV genotypes were analyzed by PCR-RFLP. RESULTS: Sequential lamivudine-INF-α therapy, lamivudine and INF-α monotherapy reduced ccc DNA of 1.7 log, 1.4 log and 0.8 log respectively (P <0.05) patients developed HBeAg seroconversion, the reduction of ccc DNA in the HBeAg seroconversion patients was more significant than that in the HBeAg positive patients (3.0 log vs 1.6 log, P = 0.0407). Twenty-four weeks after antiviral therapy withdrawal, 16 patients had a sustained virological response, the baseline intrahepatic cc c DNA in the patients with a sustained virological response was significantly lower than that in the patients with virological rebound (4.6 log vs 5.4 log, P = 0.0472). HBV genotype C accounted for 85.9% (n = 61), and genotype B for There was no significant difference in the change of ccc DNA level between HBV genotypes C and B (2.1 log vs 1.9 log). CONCLUSION: Forty-eight week sequential lamivudine- INF-α therapy and lamivudine monotherapy reduce ccc DNA more significantly than 24-wk INF-α monotherapy. Low baseline intrahepatic ccc DNA level may predict the long-term efficacy of antiviral treatment. HBV genotypes C and B have no obvious influence on ccc DNA load.