2009恩替卡韦在阿德福韦疗效不佳及耐药患者中的.pptVIP

ADV在核苷初治患者中的疗效数据 指南对于ADV经治患者转换治疗方案的建议 ETV治疗ADV疗效不佳患者临床试验数据 转换治疗时机的探讨 主要内容 * ADV疗效不佳者转换ETV治疗的时机讨论 2008版美国治疗规范对于ADV疗效不佳患者改变治疗方案建议： 24周时HBV DNA104 copies/ml需要改变治疗方案 24周时HBV DNA介于300至104 copies/ml之间的患者继续观察至48周仍未转阴需要改变治疗方案 ADV治疗效果不佳及耐药的患者需要及早转换治疗，以减少乙肝病毒对于肝脏的损伤和耐药的发生率 * 总 结 ADV单药治疗短期疗效较弱，核苷初治HBeAg+患者1年达不可测仅为21%。ADV短期疗效不佳的患者远期治疗耐药较高 ETV与ADV耐药位点无交叉，ETV仍能对ADV耐药株保持敏感性 临床数据显示恩替卡韦抗病毒疗效不受阿德福韦经治或耐药的因素影响 指南建议24周为ADV治疗不佳转换的观察时间点 * 谢 谢！ * * * * ADV治疗48周后，只有小部分的患者能达到HBV DNA不可测。即使在这小部分患者中，也有病毒发生耐药。 * * In case of resistance, an appropriate rescue therapy should be initiated with the most effective antiviral effect and the minimal risk to induce multiple drug-resistant strains. Therefore, adding-on a second drug without cross resistance is the only efficient strategy. Resistance to 替诺福韦 has not been described so far. It is recommended that genotyping and phenotyping be done by an expert laboratory to determine the cross-resistance profile. 恩替卡韦, 替比夫定, 拉米夫定 or emtricitabine* could be added (the safety of these combinations is unknown). Resistance to Adefovir-Switch to 替诺福韦 and add a second drug without cross-resistance -N236T substitution is present, add 拉米夫定, 恩替卡韦 or 替比夫定 or switch to 替诺福韦 plus emtricitabine* (in one tablet). (C1) -A181T/V substitution is present, add 恩替卡韦 (the safety of the 替诺福韦–恩替卡韦 combination is unknown) or switch to 替诺福韦 plus emtricitabine Reference: European Association for the Study of the Liver Journal of Hepatology 50 (2009) 227–242 * * * * Although lamivudine resistant virus remains susceptible to adefovir in vitro, patients who are refractory to lamivudine treatment do not respond as well to adefovir as do patients who are na?ve to nucleoside analogue antivirals. The figure on the right shows the mean change in HBV DNA after 48 weeks of treatment with adefovir 10 mg daily in nucleoside analogue na?ve and lamivudine-refractory patients. Resistance to a second agent may emerge more rapidly in patients who already harbour virus resistant to anoth