阿德福韦酯治疗HBeAg阳性慢性乙型肝炎的疗效和安全性研究

目的评价一种国产阿德福韦酯用于治疗HBeAg阳性慢性乙型肝炎患者的疗效和安全性。方法采用多中心、随机、双盲、安慰剂对照的临床试验,选择HBeAg阳性的慢性乙型肝炎患者211例,按1∶1的比例随机分为阿德福韦酯组和拉米夫定组。完成12周治疗后均进入阿德福韦酯开放治疗期。完成12周和48周治疗时,检测血清HBVDNA及ALT水平。结果治疗12周时阿德福韦酯组（107例）血清HBVDNA水平平均下降2.94log10拷贝/ml,77.6%的受试者血清HBVDNA水平下降≥2log10拷贝/ml或血清HBVDNA≤104拷贝/ml,ALT均值下降76.9IU/L;而安慰剂组（104例）血清HBVDNA水平平均下降0.57log10拷贝/ml,血清HBVDNA水平下降≥2log10拷贝/ml或血清HBVDNA≤104拷贝/ml的受试者比例仅为13.5%,ALT均值下降20.9IU/L。两组血清HBVDNA水平下降值和血清ALT下降值比较,差异均有统计学意义（P〈0.05）。治疗48周时,阿德福韦酯组血清HBVDNA水平平均下降3.54log10拷贝/ml,ALT均值下降100.6IU/L;安慰剂组血清HBVDNA水平平均下降3.28log10拷贝/ml,ALT均值下降92.7IU/L;两组血清HBVDNA水平下降值和血清ALT下降值比较,差异无统计学意义（P〉0.05）。阿德福韦酯组不良事件发生率与安慰剂组相比,差异无统计学意义（P〉0.05）。结论阿德福韦酯治疗HBeAg阳性慢性乙型肝炎可在病毒学及生化学方面取得较好疗效,且安全性良好。

Treatment of HBeAg-positive chronic hepatitis B patients with adefovir dipivoxil: A double-blinded,randomized, placebo-controlled clinical trial

Objective To investigate the efficacy and safety of adefovir dipivoxil （ ADV） for adult HBeAg-positive chronic hepatitis B patients. Methods This study was a multicenter,double-blinded,randomized （ 1∶ 1） and placebo-controlled clinical trial and 211 chronic hepatitis B patients with positive serum HBeAg were included. After 12-week of double-blinded dosing phase,all subjects was swithed to open-labelled ADV treatment. Serum HBV DNA and ALT levels were monitored,and safety assessments were also conducted during the trial. Results The mean reduction of HBV DNA from baseline at week 12 was significantly greater in ADV group compared with placebo group （ 2. 94 log10 copies/ml vs. 0. 57 log10 copies/ml,P = 0. 000）. The percentage of patients whose serum HBV DNA decrease ≥2 log10 copies/ml or whose serum HBV DNA≤10^4 copies/ml was significantly higher in ADV group than in placebo group （ 77. 6% vs. 13. 5%）. The mean reduction of ALT levels from baseline at week 12 was also significantly greater in ADV group compared with placebo group （ 76. 9 IU/L vs. 20. 9 IU/L）. At week 48,the mean decrease of HBV DNA levels from baseline in the two groups were 3. 54 log10 copies/ml and 3. 28 log10 copies/ml respectively. The mean reduction of ALT levels from baseline at week 48 was in the two groups were 100. 6 IU/L and 92. 7 IU/L. There was no significant difference between the two groups in the incidence of adverse events. There was no severe adverse event related to the investigational product in thetrial. Conclusions ADV trialed in this study is effective and safe for HBeAg-positive chronic hepatitis B patients.