2010版乙肝防治指南解读与ADV联合治疗课件.ppt

* 再活动期：部分处于非活动期（1/3）的患者，尽管表现为HBeAg转换（阴性、抗-HBe阳性）但仍有HBV DNA活动性复制、ALT持续或反复异常，称为再活动期（部分是由于前C区与／或BCP变异所导致HBeAg表达水平低下或不表达），成为HBeAg阴性慢性乙型肝炎 。 自发性HBeAg血清学转换主要出现在免疫清除期，年发生率约为2%~15%，其中年龄小于40岁、ALT升高以及感染HBV基因A型和B型者发生率较高[21, 24] 肝硬化高危因素：免疫清除期是肝硬化的高发时期。新指南强调：肝硬化的累积发生率与持续高病毒载量呈正相关，HBV DNA是独立于HBeAg和ALT以外能够独立预测肝硬化发生的危险因素 HCC的高危因素：HBeAg阳性和/或HBV DNA 2,000 IU/mL（相当于104拷贝/mL）是肝硬化和HCC发生的显著危险因素。 （05指南是10的5次方） 05指南；慢性乙型肝炎、代偿期和失代偿期肝硬化的5年病死率分别为0%~2%、14%~20%和70%~86% * * （少了“消除”这个词，目前的治疗条件下追求HBV的彻底清除是很困难的，因此不以“消除”为目标，而更重视HBV的长期抑制？并且是最大限度的。 * 增加：纤维化≥S2，提示对于炎症坏死比较轻小于G2 ，但有明显纤维化≥S2的病人是需要治疗的。 * * * * * * * * * Lamivudine was the first oral agent to be approved for the treatment of chronic hepatitis B, but it soon became apparent that a major disadvantage was the high rate of drug resistance. Clinical endpoints among patients with YMDD mutants occurred at a lower frequency than among patients receiving 安慰剂 Two patients had evidence of YMDD mutants at baseline and five patients had no post-baseline samples, so data on YMDD mutants during therapy were available for 644 patients. At least one post baseline sample with evidence of YMDD mutants was found in 209 (49%) of 430 patients during 拉米夫定 therapy and 11 (5%) of 214 patients receiving 安慰剂. Only 5% of patients without YMDD mutant had detectable HBV DNA breakthrough compared with 62% of patients with YMDD mutant in the 拉米夫定 group. . * 除了贺维力，其它核苷类似物都存在交叉耐药的现象。 A 这是体外实验的结果 M204I/V 位点的变异即YMDD变异 B YMDD 突变株的出现会影响将来的治疗选择，贺维力不会发生YMDD变异，因此保留了未来治疗的选择。 Lamivudine was the first oral agent to be approved for the treatment of chronic hepatitis B, but it soon became apparent that a major disadvantage was the high rate of drug resistance. * 1. Goncalves J, Laeufle R, Avila C. Increased risk with combination of telbivudine and pegylated-interferon alfa-2a in study CLDT600A2406, compared to uncommon rate with telbivudine monotherapy from the Novartis global database. Program and abstracts of the 44th Annual Meeting of the European Association for the