阿德福韦酯联合拉米夫定治疗拉米夫定耐药慢性乙型肝炎疗效观察

目的探讨阿德福韦酯(ADV)联合拉米夫定(LAM)治疗拉米夫定耐药慢性乙型肝炎(CHB)患者的临床疗效及安全性。方法选择拉米夫定耐药的HBeAg阳性慢性乙型肝炎患者102例随机分为3组,ADV+LAM组(A组)38例,给予ADV 10 mg/d联合LAM 100 mg/d口服;ADV组(B组)42例,ADV 10 mg/d口服;LAM组(C组)22例,LAM 100 mg/d口服,分别于完成24、48和72周治疗时,观察血清HBV DNA水平、HBV血清学标志、肝功能及不良反应。结果治疗24、48、72周A、B组HBV DNA水平较C组均显著下降(P<0.01),HBV DNA阴转率较C组显著升高(P<0.01),治疗治疗24、48、72周A组和72周B组ALT复常率较C组均显著升高(P<0.01);治疗48、72周A组HBV DNA水平较B组显著下降(P<0.05),治疗72周HBV DNA阴转率和ALT复常率较B组显著升高(P<0.01)。三组血清HBeAg阴转率及血清转换率间差异无统计学意义(P>0.05)。治疗期间A组新的变异率低于C组(P<0.05),均未发现与药物相关的严重不良反应。结论阿德福韦酯联合拉米夫定治疗拉米夫定耐药慢性乙型肝炎患者具有显著的抗病毒和临床疗效,且安全性良好。

Observation on Efficacy of Adefovir Dipivoxil Combined with Lamivudine for Chronic Hepatitis B Patients with Lamivudine Resistant

Objective To study the therapeutic effect and safety of adefovir dipivoxil（ADV）combined with lamivudine（LAM）for chronic hepatitis B（CHB）patients with lamivudine-resistant.Methods The 102 cases of HBeAg positive CHB patients with LAM resistant were randomly divided into three groups;ADV combined with LAM group（group A,n=38）was treated with ADV 10 mg and LAM 100 mg once daily by orally taken;ADV group（group B,n=42）was given ADV 10 mg/d;LAM group（group C,n=22）was given LAM 100mg/d.After 24,48 and 72-weeks of treatment,serum HBV DNA levels,HBV serologic marker and liver function tests were measured respectively,and safety assessments were also conducted.Results At 24,48 and 72 weeks,the mean reduction and negative rate of HBV DNA were significantly greater in group A and B compared with that in group C（P0.01）.The ALT normalization of group A at 24,48 and 72 weeks and group B at 72 weeks were significantly higher than that of group C（P0.01）.The mean reduction of HBV DNA at 48 and 72 weeks,HBV DNA negative rate and ALT normalization at 72 weeks were significantly greater in group A than group B（P0.01）.There were no significant different among the three groups in the negative rate and seroconversion rate of HBeAg（P0.05）.During the treatment,the new resistance mutation rate was lower in group A than group C（P0.05）,and there was no severe adverse event related to the investigational product.Conclusion ADV combined with LAM is effective and safe for CHB patients with lamivudine-resistant.