文献抄读ppt参考课件.pptVIP

* 常见不良反应：流感样症状、血细胞减少 丙型肝炎通用方法为干扰素、利巴韦林 基因1型中是48周，基因2、3型为24周，若有快速反应应答，时间可以减半 * 长效的更容易出现粒细胞减少,甚至缺乏,难以继续使用. * 外文也有用促红素和粒细胞刺激因子联合应用 * 甲状腺炎、肖格伦综合症、狼疮样综合症、溶血性贫血、血小板减少性紫癜 文献抄读 标题： 聚乙二醇干扰素α2a单独应用之前聚乙二醇干扰素α2b与利巴韦林联合应用导致丙肝患者重度血小板减少症 * 什么是聚乙二醇干扰素？ 聚乙二醇（PEG）技术又成为聚乙二醇技术，聚乙二醇干扰素（或PEG干扰素），就是通过最新的一种生物技术在干扰素分子上安装了一个无活性的聚乙二醇分子，这样不仅使干扰素的分子量得到了增加，延缓了干扰素的吸收，而且聚乙二醇分子还可以保护干扰素与分解酶的直接接触，降低其清除速度，这就象给超人穿了一件防护衣，不仅药物浓度得以维持在一个平稳水平，而且由于清除减慢，用药的周期也得以大幅延长，血药浓度维持在一个比较理想的水平，疗效也大幅提高。用药间期从普通干扰素的每周三次延长到聚乙二醇干扰素的每周一次，患者的用药依从性也可以得到明显改善。另外，通过采用聚乙二醇技术，减少免疫系统与干扰素的直接接触，产生干扰素抗体的机会也就更少了，因此疗效也更好。正是聚乙二醇干扰素在用药便利性和患者顺应性以及疗效的上飞跃才使聚乙二醇干扰素成为乙肝抗病毒治疗的一个新的里程碑。 * 聚乙二醇干扰素 优点：半衰期长，每周只需用药一次 缺点：屏蔽受体，阻碍特异结合，抗病毒作 用降低 * Five nucleoside/nucleotide analogues have been licensed since 1998. Lamivudine, an L-nucleoside, is limited by the development of resistance in 76% of patients after 5 years of therapy. Telbivudine, another L-nucleoside, is more potent than lamivudine but resistance still develops in 25% of HBeAg-positive and 11% HBeAg-negative patients after 2 years. Adefovir, an acyclic phosphonate, is relatively weak, but is effective against lamivudine- and telbivudine- resistant mutations, for which it should be used in combination (add-on therapy) rather than substituted. Resistance to adefovir develops slowly, rising to 29% for HBeAg-negative patients by year 5, but more rapidly when used alone for lamivudine-resistant HBV. Currently the two first line nucleoside/nucleotides are entecavir and tenofovir. Entecavir, a cyclopentane (D-nucleoside), is very potent, with 94% of patients having undetectable HBV DNA after 5 years. Resistance develops in only 1.2% of treatment-na?ve patients. Tenofovir, another acyclic nucleotide, is more potent with less renal toxicity compared to adefovir. It is effective against lamivudine-resistant mutations when used alone. No resistance to tenofovir has been described after its use for 3 years or longer, often for patients with human immunodeficiency virus/HBV co-infect