肝病会议内容_北京小三阳医院汇总.ppt

HBV DNA 检测不到 ALT复常 HBeAg转阴 HBeAg血清学转换 患者比例（%） 替比夫定联合阿德福韦酯治疗YMDD耐药突变HBeAg阳性慢乙肝患者52周疗效 20/38 21/29 9/38 6/38 替比夫定+阿德福韦酯联合治疗YMDD耐药突变HBeAg阳性患者52周疗效 YM Wang, et al. Hepatol Int 2011; 5: 137. PP-05-117. 治疗期间HBV DNA水平下降情况 之前应用拉米夫定治疗 所有患者(HBeAg阳性) 之前应用替比夫定治疗 12周 24周 52周 -3 -4 -5 -6 -7 血清HBV DNA从基线下降的变化平均值 （ log10 copies/ml ） -3.934 -4.943 -4.693 -5.362 -5.072 -4.386 -5.008 -5.595 -5.938 YM Wang, et al. Hepatol Int 2011; 5: 137. PP-05-117. 安全性小结 替比夫定联合阿德福韦治疗52周，没有诱导出现新的变异或阿德福韦酯相关耐药变异（N236T，A181V/T） 联合治疗的耐受性良好，没有患者死亡或因不良事件而停止治疗 不良反应少而轻微，没有患者出现肌病、横纹肌溶解症、乳酸性酸中毒、周围神经病变和肾功能损害 YM Wang, et al. Hepatol Int 2011; 5: 137. PP-05-117. 结论 这是首项在替比夫定或拉米夫定长期单药治疗后出现YMDD变异的代偿性慢性乙肝患者中评估替比夫定与阿德福韦酯联合治疗的研究，证实了这种联合疗法的可行性，也为慢性乙肝患者的优化治疗策略提供了新的有力循证 替比夫定联合阿德福韦酯治疗能快速强效抑制病毒，治疗52周时，超过50%的患者HBV DNA检测不到 替比夫定联合阿德福韦酯治疗安全耐受性良好，没有患者死亡或因不良事件停止治疗 YM Wang, et al. Hepatol Int 2011; 5: 137. PP-05-117. * The main reason was increased rate of pn both as AE and as SAEs. The patients in the combination arm were stopped on the same date, at varying study visits according to their enrollment date The monotherapy arms were stopped at a later date, when the decision was taken to terminate the study. Main messages: - patients have very high viral loads (difficult to treat), number of patients with HBV DNA10 is more than 30% and even 46% in combination arm - the majority of patients are asian - HBV genotype data is not available and pending For all results in the combination arm, the low patient number should be taken into account: only 17 at week 24 and none at week 48. Viral breakhrough* occured in 4/53 telbivudine and 5/53 PegIFN monotherapy patients at last on-treatment visit, none in the combination arm Resistance analysis of the 4 patients in the LDT arm with Viral breakthrough is ongoing. The 总结 该研究获得的安全数据与已知的PEG-IFNα-2a对乙肝患者的安全性数据相一致 PEG-IFNα-2a较大剂量及较长疗程不会增加严重不良事件（SAE）所有治疗组的SAE 因此PEG-IFNα-2a较大剂量及较长疗程的耐受性良好，且对依从性没有影响 对HBeAg-阳性乙肝患者而言，与较低剂量及较短疗程相比，已批准的PEG-IFNα-2a 180 ug /周、持续48周的治疗方案最有效，最能使患者获益 J.D