[医药卫生]斯崇文-慢性乙肝.ppt

耐药的处理:联合治疗抑或换药? 联合阿德福韦酯治疗或换为阿德福韦酯单药治疗 在拉米夫定耐药的代偿期肝病患者中，表现出相同的短期疗效1 然而，在现有的拉米夫定治疗中加入阿德福韦酯，在长期治疗中减少了阿德福韦酯耐药的发生 恩替卡韦对于拉米夫定耐药株同样保持活性 (换药) 在48周时，病毒载量平均下降5.11 log10 拷贝/mL 在48周时，基因型耐药发生率为7% 1. Zoulim et al. EASL 2005. Abstract 545. 2. Maynard et al. J Hepatol. 2005. 42:279-281. 3. Peters et al. Gastroenterology. 2004;126:91-101. 4. Xiong. EASL 2005. Abstract 36. 5. Sherman et al. AASLD 2004. Abstract 1152. 1年 2年 3年 在435 460i研究中，非阿德福韦酯耐药的患者 0/131 2*/144 0/76 * 2位患者开始时采用拉米夫定和阿德福韦酯联合治疗，随后撤掉拉米夫定，在阿德福韦酯单药治疗期间出现阿德福韦酯耐药 延缓耐药发生的一线治疗策略； 代偿期肝病患者 单药治疗 阿德福韦酯 – 拉米夫定 – 恩替卡韦 – Peg干扰素 如需长期治疗 (大多数病例): 阿德福韦酯可作为首选 肝硬化，失代偿期肝病或肝移植的患者 联合治疗 核苷酸类似物 + 核苷类似物 小结 耐药角度考虑，阿德福韦酯长期治疗的优势： 基因耐药出现较晚 与其它核苷类药交叉耐药少 与拉米夫定序贯治疗选择多药联合耐药毒株的机会少 长期、序贯单药治疗方案选择出多药联合耐药毒株 联合治疗耐药发生的潜在危险性低 同时联合：有不同交叉耐药特点的药物联合，耐药发生率低 可作为一线治疗和治疗失败后的选择 在临床研究中需要进一步评估 总 结 * * * * * * * * * * The study enrolled 184 patients; randomized in a 2:1 ratio ADV or placebo for the first 48 weeks. After 48 weeks, ADV patients were re-randomized to either continue ADV or go to placebo in the second 48 weeks. A total of 80 patients received ADV for 96 weeks. Patients who complete the 96 week study may continue in a long-term study for an additional 3 years. * Message: Long-term treatment with ADV up to 192 weeks resulted in continuous and sustained suppression of HBV DNA and ALT normalisation in the majority of HBeAg-negative patients. Information: This is a cohort of patients originally randomized to receive ADV 10 mg in the first year of study 438 (see previous 3 slides) who received ADV 10 mg for 192 weeks. These results were generated using Kaplan Meier estimates i.e., this demonstrates the percentage of patients that have achieved the event by a time-point. The analysis does not account for patients that subsequently lose the endpoint. The Roche Monitor Amplicor PCR assay used was to evaluate HBV DNA (LLQ = 1,000 copies/mL). Serum ALT concentrations were assessed at a central laboratory (Covance). The upper limit