替比夫定与拉米夫定长期治疗慢性乙型肝炎患者疗效与安全性的随机对照研究

Efficacy and safety of long-term therapy with telbivudine compared to lamivudine in patients with chronic hepatitis B:a randomized controlled study

目的：比较替比夫定与拉米夫定长期治疗慢性乙型肝炎患者的疗效及安全性。方法：2004年3月至2005年2月符合入选标准的39例慢性乙型肝炎患者纳入研究。39例患者随机分为2组进入双盲治疗：替比夫定组（22例）,男18例,女4例,平均年龄（30.9±7.8）岁,口服替比夫定600mg,1次/d,治疗104周;拉米夫定组（17例）,男13例,女4例,平均年龄（30.4±8.5）岁,口服拉米夫定100mg,1次/d,治疗104周。104周后2组患者均进入替比夫定开放治疗,口服替比夫定600mg,1次/d,继续治疗104周。每8周检测患者血清HBV DNA水平、完全应答率和ALT水平,观察2组患者治疗104周后HBeAg血清转换情况、治疗期间病毒学反弹率及替比夫定的不良反应。结果：双盲治疗阶段,替比夫定组和拉米夫定组患者治疗52周和104周时HBV DNA的完全应答率分别为72.2%（16/22）、77.3%（17/22）和47.1%（8/17）、47.1%（8/17）;ALT的复常率分别为100%（22/22）、86.4%（19/22）和82.3%（14/17）、76.5%（13/17）。替比夫定组治疗60周、104周和第3年HBV DNA反弹率分别为4.5%（1/22）、18.2%（4/22）和28.6%（6/21）,第4年未增加反弹的病例;拉米夫定组治疗52周、104周HBV DNA的反弹率分别为23.5%（4/17）和41.2%（7/17）。2组共有4例耐药者加用阿德福韦酯联合治疗8～24周后HBV DNA下降至可检测值下限。双盲治疗阶段替比夫定组有5例患者发生9例次肌酸激酶（CK）升高（1065～4915U/L）,但无肌肉症状;开放治疗阶段有6例患者发生9例次CK升高（1036～45984U/L）,均出现肌肉症状。结论：替比夫定对慢性乙型肝炎患者的疗效优于拉米夫定;患者对替比夫定的耐受性较好。

Objective：To compare the efficacy and safety of long-term treatment with tebivudine versus lamivudine in patients with chronic hepatitis B. Methods：Thirty-nine patients with chronic hepatitis B in accordance with inclusion criteria were enrolled in the study from March 2004 to February 2005. Thirty-nine patients were randomly divided into two groups and received double-blind therapy：the tebivudine group （22 cases） and the lamivudine group （17cases）. The tebivudine group comprised 18 men and 4 women with average age of （30.9±7.8） years and the patients were given tebivudine 600mg once daily for 104 weeks. The lamivudine group comprised 13 men and 4 women with average age of （30.4±8.5）years and the patients were given lamivudine 100mg once daily for 104 weeks. After 104 weeks,all patients in the two groups received open-label tebivudine therapy and were given tebivudine 600mg once daily for another 104 weeks. The serum HBV DNA levels,complete response rates and ALT levels were measured every 8 weeks. The Seroconversion of HBeAg after 104 weeks of therapy and the viral breakthrough rates as well as the adverse reactions of tebivudine during the treatment were observed in the two groups. Results：In the tebivudine and lamivudine groups at weeks 52 and 104 of the double-blind therapy,the complete response rates of HBV DNA were 72.2%（16/22）and 77.3%（17/22）,47.1%（8/17）and 47.1%（8/17）,respectively; the ALT normalization rates were 100%（22/22）and 86.4%（19/22）,82.3%（14/17）and 76.5%（13/17）,respectively. The HBV DNA breakthrough rates were respectively 4.5%（1/22）,18.2%（4/22）,and 28.6%（6/21） in the tebivudine group at weeks 60,104 and in year 3,but there was no increase in cases of breakthrough in year 4; the HBV DNA breakthrough rates were 23.5%（4/17）and 41.2%（7/17）respectively at weeks 52 and 104 in the lamivudine group. The levels of HBV DNA in 4 patients with lamivudine resistance in the two groups decreased to the lower limit of detectable value after treatment combined with adefovir for 8-24 weeks. Five patients experienced 9 episodes of elevated creatine kinase （CK） levels [（1 065-4 915 ）U/L] without muscle symptoms in the tebivudine group during the double-blind therapy; and 6 patients experienced 9 episodes of elevated CK levels [（1 036～45 984）U/L] with muscle symptoms during the open-label tebivudine therapy. Conclusion：Telbivudine is more effective than lamivudine in the treatment of patients with chronic hepatitis B,and the drug is well tolerated.