拉米夫定和阿德福韦优化治疗慢性乙型肝炎进展性肝纤维化和代偿期肝硬化患者疗效

One year evaluation of virological response and clinical outcome of lamivudine and adefovir dipivoxil optimized therapy in chronic hepatitis B-related fibrosis and/or compensated cirrhosis

目的观察拉米夫定（LAM）和阿德福韦（ADV）优化治疗乙型肝炎相关肝纤维化和代偿性肝硬化患者的长期疗效。方法208例患者以1：1随机分成LAM和ADV治疗组，根据治疗24周时病毒学应答，完全应答（CR）者（HBVDNA〈60IU／mL）和部分应答（PR）者（HBVDNA60～2000IU／mL）继续单药治疗。对不充分应答（IR）者（HBVDNA〉2000IU／mL）和发生病毒学突破者（HBVDNA比最低值大于1lg）则改为I。AM和ADV联合用药。主要研究终点为48周时的病毒完全应答率，次要研究终点为48周时临床特征的变化。统计学处理采用χ2检验、t检验或Mann-WhitneyU检验。结果24周时LAM组和ADV组病毒CR率分别为56．73％（59例）和35．57％（37例），PR率分别为21．15％（22例）和28．84％（30例），IR率分别为22．11％（23例）和35．57％（37例），60例IR患者中39例改为联合治疗（LAM加ADVl5例；ADV加LAM24例），21例继续单药治疗（LAM组8例和ADV组13例）。24周时获得CR的患者在48周时较PR和IR患者获得更多的CR（P〈0．01）。肝生物化学指标和肝纤维化指标也获得显著改善。结论初始LAM或ADV单药和应答不良加药的优化治疗对慢性乙型肝炎肝硬化患者能快速持续抑制病毒水平。24周时LAM和ADV的病毒早期应答率对预测48周时的病毒应答有重要意义。

Objective To investigate the long-term efficacy of lamivudine（LAM）and adefovir （ADV）combination therapy in chronic hepatitis B related advanced fibrosis and/or compensated cirrhosis. Methods Two hundred and eight eligible Chinese patients were randomly assigned in a 1 ： 1 ratio to receive either LAM or ADV for the first 24 weeks. According to virologic response at 24 weeks, the patients were defined as complete response（CR） （ HBV DNA60 IU/mL）, partial response（HBV DNA 60 - 2 000 IU/mL） （PR）, inadequate response（IR） （HBV DNA〉2 000 IU/mL）and the occurrence o[ virological breakthrough（ HBV DNA greater than the minimum value of lg）. The patients with CR and PR continued monotherapy for 48 weeks while the patients with IR or virological breakthrough switched to combined therapy （ADV was added into LAM initial group, and ADV initial group）. The primary endpoint was the CR in the 48th weeks the secondary endpoint was the clinical outcome in the 48th week. Results 56.73 fro in LAM and 35.57 % in ADV group achieved CR 24 weeks post treatment. The proportion of PS in LAM and ADV group were 21. 15% and 28.84~ in the 24th week, 22.11% in LAM group and 35. 57% in ADV group were IR at 24 weeks and 39 cases of those switching to combination therapy（initial LAM 15 cases add ADV on and initial ADV 24 cases add LAM on）and 21 cases（LAM： 8 and ADV： 13） continued monotherapy to 48 weeks. The patients who gained CR in the 24th week achieved more CVS than those gained PS and IR in the 24th week（P〈0.01 ）. Biochemical response and serum liver fibrosis marks also improved significantly after treatment. Conclusion Initial LAM or ADV monotherapy and then add-on combined therapy in chronic hepatitis B patients with liver cirrhosis can achieve rapid and sustained inhibition of viral replication, improving liver biochemistry and fibrosis.Early virological response in LAM or ADV therapy in the 24th weeks were of great value for virological response prediction in the 48th weeks.