阿德福韦酯治疗拉米夫定耐药的HBeAg阳性慢性乙型肝炎的临床研究
[A clinical study of adefovir dipivoxil in treating lamivudine refractory HBeAg-positive chronic hepatitis B].
作者信息
Zhao Hong, Zhang Yue-xin, Chen Xin-yue, Wang Lei, Tang Xiao-ping, Si Chong-wen
机构信息
Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China.
出版信息
Zhonghua Nei Ke Za Zhi. 2007 Apr;46(4):294-7.
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, multicenter 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 l g copies/ml and the percentage of patients with HBV DNA level decrease of more than 2 l g 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 (<3l g 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.
目的
评估阿德福韦酯（ADV）治疗拉米夫定（LAM）耐药的HBeAg阳性慢性乙型肝炎患者的疗效和安全性。
方法
这是一项随机、双盲、安慰剂对照、多中心研究。226例符合条件的HBeAg阳性慢性乙型肝炎患者被随机（随机化比例为2:1）分为两组。一组接受ADV 10 mg/d和LAM 100 mg/d治疗12周，随后接受ADV 10 mg/d治疗36周（ADV + LAM→ADV组）；另一组接受安慰剂和LAM 100 mg/d治疗12周，随后接受ADV 10 mg/d治疗36周（安慰剂 + LAM→ADV组）。主要疗效指标为病毒学应答。次要疗效指标为血清学应答（HBeAg消失率和HBeAg血清学转换率）和ALT复常率。
结果
治疗12周后，ADV + LAM→ADV组患者的HBV DNA水平平均下降值、HBV DNA低于5 log拷贝/ml的患者百分比以及HBV DNA水平下降超过2 log拷贝/ml的患者百分比均显著高于安慰剂 + LAM→ADV组（2.69 log拷贝/ml对1.06 log拷贝/ml，92.7%对33.3%，78.1%对27.8%），所有P值均为0.00。ADV + LAM→ADV组患者的HBV DNA不可测（<3 log拷贝/ml）率和血清学应答（HBeAg消失率和HBeAg血清学转换率）略高于安慰剂 + LAM→ADV组（12.2%对5.6%，5.1%对0，4.9%对0），但未达到统计学意义。在另外36周的治疗后，两个治疗组中更多患者实现了病毒学应答、血清学应答和ALT复常。ADV的总体安全性与安慰剂相似。在这项48周的研究中未发现rtN236T和rtA181V突变。
结论
对于LAM耐药的HBeAg阳性慢性乙型肝炎患者，ADV是一种有效且耐受性良好的治疗选择。
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