摘要
目的评价国产阿德福韦酯片(ADV)10 mg/d 治疗拉米夫定(LAM)失效的 HBeAg 阳性慢性乙型肝炎患者的疗效和安全性。方法随机、有限的(12周)双盲、安慰剂对照、多中心临床研究。筛选合格的慢性乙型肝炎患者按照2:1的随机比例,分为 ADV+LAM→ADV 组:ADV 10 mg/d联合 LAM 100 mg/d,治疗12周后改为单用 ADV 10 mg/d 治疗36周,共41例;安慰剂+LAM→ADV组:安慰剂10 mg/d 联合 LAM 100 mg/d,治疗12周后,改为单用 ADV 10 mg/d,治疗36周,共18例。结果 12周双盲治疗结束时,ADV+LAM→ADV 组患者血清中 HBV DNA 水平与基线相比的平均下降量(2.69 lg 拷贝/ml)、HBV DNA<5 lg 拷贝/ml 的患者比例(92.7%)、与基线相比下降≥2lg 拷贝/ml 的患者比例(78.1%)明显高于安慰剂+LAM→ADV 组(1.06 lg 拷贝/ml、33.3%、27.85),P=0.00。两组患者继续治疗,病毒学、血清学和生化学应答均有进一步改善。两组的不良事件发生率及其种类差异无统计学意义。治疗48周内未发现 rtN236T 和 rtA181V 突变。结论 ADV10 mg/d 具有明显抗 LAM 失效的 HBV 株复制作用,且随着治疗时间延长作用增强,其安全性与安慰剂相似。
Objective To evaluate the efficacy and safety of adefovir dipivoxil （ADV） in treating patients with lamivudine （LAM） refractory HBeAg-positive chronic hepatitis B. Methods It is a randomized, double-blind, placebo-controlled, muhicenter study. 226 eligible patients with HBeAg-positive chronic hepatitis B were randomized （ randomization ratio was 2： 1 ） into two groups. One group received ADV 10 mg/d and LAM 100 mg/d for 12 weeks and followed by ADV 10 mg/d for 36 weeks （ ADV ＋ LAM→ADV group） ; the other received placebo and LAM 100 mg/d for 12 weeks and followed by ADV 10 mg/d for 36 weeks （placebo ＋ LAM→ADV group）. The primary efficacy measure was virological response. The secondary efficacy measure was serological response （HBeAg loss rate and HBeAg seroconversion rate） and ALT normalization rate. Results After 12 weeks of therapy, mean reduction of HBV DNA level, the percentage of patients with HBV DNA lower than 5 lg copies/ml and the percentage of patients with HBV DNA level decrease of more than 2 lg copies/ml in patients of ADV ＋ LAM→ADV group were significantly higher than those in patients of placebo ＋ LAM→ADV group （2. 69 lg copies/ml vs. 1.06 lg copies/ml, 92.7% vs. 33. 3%, 78. 1% vs. 27. 8% ）, all the P values were 0. 00. HBV DNA undetectable （ 〈 3 lg copies/ml） rate and serological response （HBeAg loss rate and HBeAg seroconversion rate） in patients of ADV ＋ LAM→ADV group was slightly higher than those in patients of placebo ＋ LAM→ADV group （12.2% vs 5.6%, 5.1% vs 0,4. 9% vs 0）, but did not reach statistical significance. Much more patients in both treatment arms achieved virological response, serological response and ALT normalization after another 36 weeks of therapy. The overall safety profile of ADV was similar to that of placebo, rtN236T and rtA181V mutation was not found in this 48-week study. Conclusion ADV is an effective and well-tolerated treatment option for patients with LAM refractory HBeAg-positive chronic hepatitis B.
出处
《中华内科杂志》
CAS
CSCD
北大核心
2007年第4期294-297,共4页
Chinese Journal of Internal Medicine
关键词
肝炎
乙型
慢性
肝炎E抗原
乙型
阿德福韦酯
Hepatitis B, chronic
Hepatitis B e antigens
Adefovir dipivoxil
