AIM: To evaluate the efficacy and safety of entecavir (ETV) in hepatitis Be antigen (HBeAg)-positive chronic hepatitis B (CHB) patients who had not received a nucleoside analogue and who had failed in lamivudine (LVD) therapy. METHODS: Sixty-one patients were divided into three groups. Forty-two patients who had not received a nucleoside analogue were randomized into two groups: group A (n = 21) received LVD 100 mg/d and group B (n = 21) received ETV 0.5 mg/d. The remaing 19 patients treated with LVD (n = 19), who switched to ETV 1.0 mg/d served as group C. All patients were treated for 48 wk. HBV DNA levels were measured with polimerase-chain-reaction (PCR) analysis. Liver function tests, HBV serology and safety assessments were also conducted. RESULTS: Signifi cantly more patients in group B (52.1% and 71.4%) had undetectable HBV DNA levels than in groups A (35.8% and 38%; P < 0.0001) and C (10.6% and 21.1%, P < 0.0001) at wk 24 and 48, respectively. At wk 48, ALT levels were normalized in more patients in group B (85.7%) than in groups A (76.2%) and C (74%). CONCLUSION: ETV had a signif icantly higher response rate than LVD in patients with HBeAg-positive CHB who had not previously received a nucleoside analogue; ETV can effectively inhibit the replication of HBV DNA and normalize the levels of ALT in refractory CHB patients treated with LVD; and ETV is safe in clinical application. AIM: To evaluate the efficacy and safety of entecavir (ETV) in hepatitis Be antigen (HBeAg) -positive chronic hepatitis B (CHB) patients who had not received a nucleoside analogue and who had failed in lamivudine (LVD) therapy. METHODS: Sixty -one patients were divided into three groups. Forty-two patients who had not received a nucleoside analogue were randomized into two groups: group A (n = 21) received LVD 100 mg / d and group B (n = 21) received ETV 0.5 mg / d. The remaing 19 patients treated with LVD (n = 19), who switched to ETV 1.0 mg / d served as group C. All patients were treated for 48 weeks. HBV DNA levels were measured with polimerase-chain- reaction PCR: analysis of liver function tests, HBV serology and safety assessments were also conducted. RESULTS: Signifi cantly more patients in group B (52.1% and 71.4%) had undetectable HBV DNA levels than in groups A (35.8% and 38%; P <0.0001) and C (10.6% and 21.1%, P <0.0001) at wk 24 and 48, respectively. At wk 48, ALT levels were normali Zed in more patients in group B (85.7%) than in groups A (76.2%) and C (74%). CONCLUSION: ETV had a signif icantly higher response rate than LVD in patients with HBeAg-positive CHB who had not received received a nucleoside analogue; ETV can effectively inhibit the replication of HBV DNA and normalize the levels of ALT in refractory CHB patients treated with LVD; and ETV is safe in clinical application.