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1、HBV 治疗疗:用什么开始?This program is supported by educational grants Treatment:What to Start?幻灯目录录 HBV治疗目标 已经公认的HBV治疗 病人的入选标准 初开始治疗方案:干扰素和核苷类 选择核苷类 选择干扰素类 其他考虑 Treatment:What to Start?HBV 治疗疗目标标，病人评评估和入选选 Treatment:What to Start?HBV的治疗疗目标标 HBV感染不能完全清除达到“治愈”治疗目标 预防或逆转因严重肝损害导致的综合症及死亡 对IHBeAg-阳性和HBeAg-阴性病人 治疗
2、目的是降低复制使病毒量HBV DNA 20,000 20,000 2,000ALT,x ULN*2 1 1疾病程度Moderate/severe necroinflammation and/or significant fibrosis 一线方案ADV,ETV,pegIFN ETV,TDF,pegIFNETV,TDF,pegIFN1.Lok A,et al.Hepatology.2007;45:507-539.2.Keeffe EB,et al.Clin Gastroenterol Hepatol.2008;6:1315-1341.3.EASL HBV Guidelines.J Hepatol
3、ogy.2009;50:227-242.*Persistent(3-6 mos).TDF not FDA approved at time of publication.Criteria for HBV DNA,ALT and disease stage/grade must all be met If not,guidelines recommend monitoring and consideration of treatment based on individuals age,health status,and stage of infection/ Treatment:What to
4、 Start?HBeAg-阴性患者的启动动治疗疗AASLD 20071US Algorithm 20082EASL 20093HBV DNA,IU/mL 20,000 2000 2000ALT,x ULN*1 to 2 1 1疾病程度Moderate/severe necroinflammation and/or significant fibrosis 一线治疗ADV,ETV,pegIFN ETV,TDF,pegIFNETV,TDF,pegIFN*Persistent(3-6 mos).TDF not FDA approved at time of publication.Consider
5、liver biopsy if 2000 IU/mL and treat if moderate/severe inflammation and/or fibrosis found.Criteria for HBV DNA,ALT and disease stage/grade must all be met If not,guidelines recommend monitoring and consideration of treatment based on individuals age,health status,and stage of infection/disease1.Lok
6、 A,et al.Hepatology.2007;45:507-539.2.Keeffe EB,et al.Clin Gastroenterol Hepatol.2008;6:1315-1341.3.EASL HBV Guidelines.Journal of Hepatology.2009;50:227- Treatment:What to Start?某些可以考虑虑HBV治疗疗的情况 不管HBV DNA和ALT水平如何 迅速发生肝坏死的病人 肝硬化失代偿期 DNA 2,000 IU/mL,ALT水平忽略不计 肝硬化失代偿经病例证实 肝移植后HBV感染 HBV携带者免疫抑制或cytotoxi
7、c chemotherapyLok A,et al.Hepatology.2007;45:507-539.Keeffe EB,et al.Clin Gastroenterol Hepatol.2008;6:1315-1341.EASL HBV Guidelines.Journal of Hepatology.2009;50:227242.Sorrell MF,et al.Ann Intern Med.2009;150:104- Treatment:What to Start?HBeAg状态态和治疗疗反应应关系HBeAg 状态态基线线病毒量HBV DNA 测测不到病毒抑制持久性阳性Higher高
8、Less少Higher*高阴性Lower低More多低Lower*After Treatment:What to Start?一线线核苷类和干扰扰素的选择选择Nucleos(t)idesInterferon-Based TherapyFeatureProConProConAdministrationOralLong term/indefiniteFinite durationSubcutaneousAntiviral activityHighLow durable rates DNA suppressionResistanceVery low resistanceNoAdverse event
9、sMinimalRare renal tox with nucleotideSubstantial*HBeAg loss and clearanceHBeAg loss over timeLower rates vs IFNHigher rates vs nucles(t)idesHBeAg loss HBV DNA suppressionHBsAg loss and clearanceHigher and earlier eventsLow ratesHigh rates(select populations)Low rates in general patient groupsOtherA
10、nti HIV(TDF)May induce HIV resistance(TDF/ETV)Anti HCV/HDV*Prolonged treatment not feasible.Newer vs older nucles(t) Treatment:What to Start?选择选择一线线核苷类似物 Treatment:What to Start?选择选择影响因素 对治疗反应好的相关因素 高ALT 低 HBV DNA 特殊病人群体 老年人 优先治疗 HIV 合并感染 没有HCV合并感染 Treatment:What to Start?疗疗效(稳稳定性=耐药药屏障)考虑选择虑选择起始药药物
11、的几个问题问题安全性 Treatment:What to Start?有效性(Potency) Treatment:What to Start?治疗疗1年HBV DNA测测不到*By PCR-based assay(LLD 50 IU/mL)except for some LAM studies.Lok A,et al.Hepatology.2007;45:507-539.EASL HBV Guidelines.Journal of Hepatology.2009;50:227-242.Not head-to-head trials;different patient populations
12、and trial designsHBeAg 阳性HBeAg 阴性Undetectable*HBV DNA(%)100806040200LAMADVETVLdTTDF40-4413-2167607660-7351-63908891100806040200LAMADVETVLdTTDF Treatment:What to Start?HBeAg-阳性病人1年治疗疗后发发生HBeAg 下降/血清逆转转HBeAg Loss/Seroconversion(%)Lau GK,et al.N Engl J Med.2005;352:2682-2695.Marcellin P,et al.N Engl J
13、Med.2003;348:808-816 Chang TT,et al.N Engl J Med.2006;354:1001-1010.Lai CL,et al.N Engl J Med.2007;357:2576-2588.Marcellin P,et al.N Engl J Med.2008;359:2442-2455.Not head-to-head trials;different patient populations and trial designsHBeAg LossHBeAg Seroconversion100806040200LAMADVETVLdTTDF322422262
14、212-18212321100806040200LAMADVETVLdTTDFNR Treatment:What to Start?Years of TherapyPatients(%)HBeAg-阳性病人巩固治疗疗 HBeAg血清逆转转*With sustained undetectable HBV DNA.Chang TT,et al.N Engl J Med.2006;354:1001-1010.Lai CL,et al.N Engl J Med.2007;357:2576-2588.Marcellin P,et al.N Engl J Med.2003;348:808-816.Marc
15、ellin P,et al.N Engl J Med.2008;359:2442-2455.Lok AS,et al.Gastroenterology.2003;125:1714-1722.Leung NW,et al.Hepatology.2001;33:1527-1532.Dienstag JL,et al.Hepatology.2003;37:748-755.Marcellin P,et al.Hepatology.2008;48:750-758.Liaw YF,et al.Gastroenterology.2009;136:486-495.Gane E,et al.AASLD 2008
16、.Abstract 729.Heathcote E,et al.AASLD 2008.Abstract 158.Not head-to-head trials;different patient populations and trial designs1008060402001234522122123 21293129274037475048LAMADVETVLdTTDF Treatment:What to Start?HBeAg-阳性治疗疗后逐渐渐HBsAg 丢丢失Not head-to-head trials;different patient populations and trial designsYear12345LAM1-C or D 基线低HBV DNA(baseline and on treatment)基线高ALT(baseline)特殊人群 年轻人 将来有生育欲望的年轻女性 病人自己选择 没有HIV合并感染 合并HCV感染 Treatment:What to Start?培干扰扰素治疗疗相关的副作用 Patients should be carefully mon
