【摘要】 目的观察恩替卡韦(ETV)联合阿德福韦酯(ADV)治疗拉米夫定(LAM)治疗失败的慢性乙型肝炎(CHB)患者48周的临床疗效和安全性。方法入选我院门诊2008年1月至2014年12月128例LAM治疗失败的CHB患者,选用ETV、ADV挽救治疗,随机分成4组,其中ADV与LAM联用≤12周为A组,共30例;ADV与LAM联用>12周为B组,共35例;单用ETV为C组,共30例;ETV联用ADV为D组,共33例。治疗后每12周检测病毒学指标及肝功能等,治疗48周期间进行安全性评估。结果 D组在治疗12、24、36及48周,HBV DNA转阴率分别为84.8%、93.9%、97.0%、100.0%,各治疗阶段较A组、B组、C组明显提高,差异有统计学意义(P均<0.05);各治疗阶段与A组、B组、C组两两比较差异均有统计学意义(P均<0.008)。而A组、B组、C组各治疗阶段两两比较差异均无统计学意义。D组在治疗12、24、36及48周,ALT复常率均较A组、B组、C组提高,其中12周时与A组、B组、C组两两比较差异均有统计学意义;24、36周时与A组、B组两两比较差异均有统计学意义(P均<0.008);48周时D组ALT转阴率达100%,与A组比较差异有统计学意义(P=0.001);各治疗阶段A组、B组、C组ALT转阴率两两比较,仅36周时A组与C组两两比较差异有统计学意义(P=0.004)。HBe Ag阳性患者中对于HBe Ag转阴率及血清学转换率,各治疗阶段四组应答率均较低,差异无统计学意义(P均>0.05)。未发生与研究药物相关的严重不良反应。结论对于LAM治疗失败的CHB患者ETV联合ADV挽救治疗疗效明显,且安全性好,值得临床推广。更多还原

【Abstract】 Objective To evaluate the efficacy and safety of combined therapy with entecavir(ETV) and adefovir dipivoxol(ADV) in patients with chronic hepatitis B(CHB) failed to lamivudine(LAM) for 48 weeks. Methods A total of 128 cases who were diagnosed with LAM resistant CHB and admitted to the outpatient department of the fifth affiliated hospital of Sun yat-sen university were recruited in this study. The cases received the therapy with ETV and ADV and randomly divided to four groups. The CHB patients were assigned to receive ADV and ETV rescue therapies for 48 weeks, including received ADV and LAM combined therapy(group A, 30 cases) for less than 12 weeks, received ADV and LAM combined therapy(group B, 35 cases) for more than 12 weeks, received ETV(group C, 30 cases) and ADV and ETV combined therapy(group D, 33 cases). The serum chemical index of liver function and virology index of HBV were evaluated at the 12 th week, 24 th week, 36 th week, 48 th week after the treatment. The safety was assessed during the treatment of 48 weeks. Results At the 12 th week, 24 th week, 36 th week, 48 th week after the treatment the rates of serum HBV DNA clearance in group D respectively were 84.8%, 93.9%, 97.0%, 100.0%. Efficacies at every stages were better than that of group A, group B and group C. There were statistically significant differences(P<0.05). It’s the same statistically significant differences between group D and group A, group D and group B, group D and group C(P<0.008). But there were no statistically significant differences among group A, group B and group C. At the 12 th week, 24 th week, 36 th week, 48 th week after the treatment the rates of ALT normalization in group D respectively were better than group A, group B and group C. Efficacies at 12 th week were better than that of group A, group B and group C. Efficacies at 24 th week, 36 th week were better than that of group A, group B. There were statistically significant differences(P<0.008). At the end of 48 weeks, the rates of ALT normalization in group D was 100.0%, there were statistically significant differences between group D and group A(P=0.001). Only at 36 th week, there was statistically significant difference between group A and group C(P=0.004) among group A, group B and group C at every stages. The rates of HBe Ag loss and anti-HBe Ag seroconversion were limited, and there were no statistically significant differences(P>0.05). There was no severe adverse event related to the investigational product in this trial. Conclusion The combined therapy with ETV and ADV is effective and safe for the treatment of patients with chronic hepatitis B failed to LAM, and the clinical application is highly recommended.更多还原