替比夫定联合阿德福韦酯治疗替比夫定耐药慢性乙型肝炎的临床疗效观察

Effect of telbivudine and adefovir dipivoxil combination therapy fochronic hepatitis B patients with resistance to telbivudine

目的:评价替比夫定联合阿德福韦酯治疗发生替比夫定耐药突变的慢性乙型肝炎患者的疗效及安全性。方法:31例经耐药突变检测后确认发生替比夫定基因耐药的患者加用阿德福韦酯治疗。观察加用阿德福韦酯治疗后的不同时间阶段即第12、24、36、48周时乙型肝炎病毒核酸(HBV-DNA)水平下降幅度以及HBV-DNA转阴、谷丙转氨酶(ALT)复常、乙型肝炎E抗原(HBe Ag)转换率。结果:与基线相比,HBV-DNA在联合治疗12周后下降(1.89±1.19)log10 copies/ml(P=0.033),54.8%的患者发生HBV-DNA转阴,32.0%的患者ALT复常。随着治疗时间延长,病毒学和生物化学应答逐渐升高,治疗48周时,74.2%患者发生HBV-DNA转阴,64.0%患者发生ALT复常,3例(9.7%)患者发生HBe Ag转阴。结论:替比夫定治疗慢性乙型肝炎出现rt M204I基因变异后加用阿德福韦酯是安全有效的拯救治疗策略。

Objective To investigate the effect of adding on adefovir dipivoxil（ ADV） in chronic hepatitis B（ CHB） patients with genotypic resistance to telbivudine（ Ld T）. Method Thirty- one CHB patients with genotypic resistance to Ld T were enrolled,and thereafter treated with combination of Ld T and ADV for 48 weeks. HBV- DNA,ALT,and HBV markers were measured at 12,24,36,and 48 weeks. Results Ld T plus ADV led to rapid decreases in viral loads and viral replications were suppressed with（ 1. 89 ± 1. 19） log 10 copies / ml reductions at 12 weeks（ P = 0. 033）. Virological and biochemical response was54. 8% and 32. 0% at 12 weeks,respectively. The cumulative rates of virological response,ALT normalization,and HBe Ag loss were increased to 74. 2%,64. 0%,and 9. 7%. Conclusion It is safety and efficient for the rescue strategy of Ld T and ADV combination therapy for chronic hepatitis B patients with genotypic resistance to Ld T.