传染病学肝炎.ppt

* 22 22 22 * 22 22 22 * 23 23 23 * 28 28 28 * Table 6. Definition of Response to Antiviral Therapy of Chronic Hepatitis B Category of response Biochemical (BR) Decrease in serum ALT to within the normal range Virologic (VR) Decrease in serum HBV DNA to undetectable levels by PCR assays, and loss of HBeAg in patients who were initially HBeAg positive Primary non-response Decrease in serum HBV DNA by 2 log10 IU/ml after at least 24 weeks of therapy (not applicable to interferon therapy) Virologic relapse Increase in serum HBV DNA of 1 log10 IU/ml after discontinuation of treatment in at least two determinations more than 4 weeks apart Histologic (HR) Decrease in histology activity index by at least 2 points and no worsening of fibrosis score compared to pre-treatment liver biopsy Complete (CR) Fulfill criteria of biochemical and virological response and loss of HBsAg 在抗病毒应答定义中没有包括血清学应答 Management of Hepatitis B, it was proposed that responses to antiviral therapy of chronic hepatitis B be categorized as biochemical (BR), virologic (VR), or histologic (HR), Standardized definitions of primary nonresponse, breakthrough and relapse were also proposed. * 乙肝治疗的长期目标是防止或减少肝硬化和肝癌，最终延长生存期。在通向长期目标的旅程上，不同的时间有不同的治疗终点，首先是HBV DNA消失，接下来是HBeAg消失，Anti-HBe的血清转换，而现有的临床试验表明，获得HBeAg消失或血清转换的病人，组织学将获得明显改善。再接下来是表面抗原消失，表面抗原的血清转换，最终达到避免肝硬化、肝癌，乙肝病人的寿命延长的目的。 需要强调的是，在所有的抗病毒药物的临床试验中，核苷类似物与干扰素的治疗终点是不同的。 * TH:辅助T细胞；Tc:细胞毒T细胞；NK：自然杀伤细胞 cccDNA：共价闭环DNA，是HBV－DNA转录成RNA中间体的模板，结构稳定不易被降解 干扰素抑制前基因mRNA的形成，拉米呋啶则抑制前基因mRNA转录成新的病毒DNA单链 干扰素除直接的抗病毒作用外，更重要的是调节人体自身免疫功能，激活机体特异、非特异免疫细胞，增强受感染肝细胞的MHC表达，从而免疫清除受感染的肝细胞，即彻底清除cccDNA 拉米呋啶则不能够清除cccDNA * * Results from Week 0 to Week 52 have been converted from Abbott pg/mL to Chiron MEq/mL. At Week 260: Median HBV DNA non-variant: 2.3 MEq/mL Median HBV DNA YMDD variant: 107.5 MEq/mL * Key Message: Both non-variant and variant patients had median ALT’s below baseline and below the ULN by Week 12. Non variant patients: Median ALT