核苷(酸)单药与联合治疗失代偿期乙型肝炎肝硬化疗效的比较  

Comparing the efficacy of monotherapy versus combination therapy of nucleos(t)ide analogues for decompensated HBV liver cirrhosis

作　　者：欧阳颖[1] 刘伟[1] 陈玉涵[1] 魏飞立 李磊[1] 范春蕾[1] 董培玲[1] 张斌[1] 陈德喜 李鹏[1] 

机构地区：[1]首都医科大学附属北京佑安医院肝病消化中心,100069 [2]北京市肝病研究所病毒实验室

出　　处：《北京医学》2011年第12期966-969,共4页Beijing Medical Journal

基　　金：首都科技发展基金(2007-1021);中国科学院病原微生物与免疫学重点实验室开放基金(2009CASPMI-004)

摘　　要：目的比较核苷(酸)单药与联合治疗对失代偿期乙型肝炎肝硬化患者的疗效。方法回顾性分析130例核苷(酸)单药或联合治疗失代偿期乙型肝炎肝硬化患者的临床资料。单药组111例,其中恩替卡韦组(ETV)25例,阿德福韦酯组(ADV)45例,拉米夫定组(LAM)41例;联合组[替比夫定(LDT)+ADV]19例。于治疗后4、12、24、48周观察患者丙氨酸氨基转移酶(ALT)水平、Child评分、HBVDNA变化,48周累积肝癌发生率、耐药发生率、乙肝病毒e抗原(HBeAg)阴转率及平均住院次数等。结果 4周时各组患者ALT水平较基线水平显著下降(P<0.05)。ETV组、LDT+ADV组12周,LAM组24周,ADV组48周时HBVDNA水平较基线明显降低(P<0.05);LDT+ADV组4周时HBVDNA阴转率显著高于单药组(P<0.05)。LDT+ADV组24周、各单药组48周时Child评分较基线明显下降(P<0.05)。LDT+ADV组48周HBeAg阴转率(15.8%)高于LAM组(4.9%)及ADV组(4.4%),P<0.05。48周LAM、ADV组累积耐药率分别为24.4%、6.7%,ETV组及LDT+ADV组无耐药发生。结论失代偿期乙型肝炎肝硬化患者,LDT联合ADV治疗抑制病毒快、耐药率低,可成为失代偿期乙型肝炎肝硬化患者优化的抗病毒治疗方案之一。Objective To compare the efficacy of monotherapy versus combination therapy with nucleos （t）ide analogues for decompensated HBV liver cirrhosis patients. Methods Antiviral therapy was retrospectively analyzed in 130 decompensated HBV liver cirrhosis patients, which included 111 patients treated with nucleos （t）ide monotherapy （25 patients with entecavir 0.5 mg/d,45 with adefovir lO mg/d and 41 with lamivudine 100 mg/d） and 19 patients with combination therapy of telbivudine 600 mg/d and adefovir 10 mg/d. ALT level, CPS score and HBV DNA level at week 4, 12, 24, 48, and HBeAg loss rate, incidence of HCC, average times of hospitalization, drug resistance rate and so on at week 48 were analyzed. Results ALT levels decreased significantly at week 4. HBV DNA levels decreased significantly at week 12 in combination group and entecavir monotherapy group, at week 24 in lamivudine monotherapy group and at week 48 in adefovir monotherapy group （all P 〈 0.05）. At week 4, more patients in combination group had HBV DNA〈500 eopies/ml than those in monotherapy group （P 〈 0.05）. CPS scores decreased significantly from baseline to week 48 in each monotherapy group and to week 24 in combination group （P 〈 0.05 ）. At week 48, the rate of HBeAg loss was higher in combination group （15.8%） than that in lamivudine group（4.9%） or adefovir group（4.4%）, both P 〈 0.05. There was no significant difference in combination group and each monotherapy group. Cumulative rates of HBV resistance in lamivudine group and adefovir group were 24.4% and 6.7%, respectively, at week 48. No HBV resistance was detected in ETV or combination group. Conclusion Combination therapy of telbivudine and adefovir for decompensated HBV cirrhosis had rapid HBV DNA suppression, high rate of HBeAg loss, low rate of resistance, which is potential to be one of the optimal regimens for decompensated HBV cirrhosis.

关 键 词：乙型肝炎 肝硬化 核苷(酸)类似物 联合治疗 

分 类 号：R512.62[医药卫生—内科学] R575.2[医药卫生—临床医学]