乙肝治疗策略.ppt
121.Torresi et al.，Antiviral Chemotherapy for the reatment of Hepatitis B Virus Infections；Gastroenterology.2000;118:S83S1032.Perrillo et al.，Occurrence of Hepatocellular Carcinoma and Decompensation in Western EuropeanPatients With Cirrhosis Type B；Hepatology 2001;33:424432肝癌肝癌 (HCC)(HCC)肝硬化肝硬化肝功能衰竭肝功能衰竭慢性乙肝慢性乙肝肝移植肝移植30%30%1 15%-10%5%-10%1 123%23%在确诊肝硬在确诊肝硬化后化后5 5年内年内2 2急性恶化急性恶化34慢性乙型肝炎防治指南 Chinese Hepatology,Dec 2005,Vol 10,No.4：348357慢性慢性HBVHBV携带者携带者慢性乙型肝炎慢性乙型肝炎（HBeAg+/-)HBeAg+/-)非活动性非活动性HBsAgHBsAg携携带者带者HBsAgHBsAg+HBeAgHBeAg+/-+/-+/-+/-HBeAbHBeAb-/+-/+-/+-/+ALTALT正常正常异常异常正常正常HBV DNA HBV DNA*（拷贝（拷贝/mL)/mL)肝组织学肝组织学正常正常/轻度异常轻度异常不同程度异常不同程度异常正常正常/轻度异常轻度异常*PCRPCR检测方法检测方法5慢性乙型肝炎防治指南 Chinese Hepatology,Dec 2005,Vol 10,No.4：348357Keeffe EB,el at.,July 2006;Clinical Gastroenterology and Hepatology2006;4:936962美国消化协会乙肝治疗规范美国消化协会乙肝治疗规范-建议暂不治疗建议暂不治疗 ALT ALT 正常，肝活检正常，肝活检 Knodell HAI 4Knodell HAI 4-治疗治疗 ALT ALT异常，异常，HBV DNA 10HBV DNA 105 5拷贝拷贝/mL(HBeAg/mL(HBeAg阳性）阳性）ALT ALT异常，异常，HBV DNA 10HBV DNA 104 4拷贝拷贝/mL(HBeAg/mL(HBeAg阴性）阴性）ALT ALT正常，肝活检正常，肝活检 Knodell HAI Knodell HAI 4 46 Lok AS,McMahon BJ.Hepatology.2007;45:507-539.7Yang et al.Chinese J Dig Dis.2002;3:150.8分层：ALT 0.5-1 x ULN,ALT 1-2 x ULNALT 2-6 x ULN,ALT 6 x ULNYuen MF et al.Gut 2005;54:1610随访月数随访月数并发症危险率并发症危险率 (%)(%)ALTALT与肝脏并发症与肝脏并发症u3,233 名中国慢性乙肝患者ALT 2-6 X ULNALT 1-2 X ULNALT 6 X ULN010203003060901201501809*Chen CJ,et al.,Risk of Hepatocellular Carcinoma Across a Biological Gradient of Serum Hepatitis B Virus DNA Level;JAMA 2006;295:6573基线人群特征：基线人群特征：HBeAg(-),ALT正常,进入研究时无肝硬化(n=2,925)HBV DNAHBV DNA10103 3 10104 4如何控制如何控制?.14.14.12.12.1.1.08.08.06.06.04.04.02.020 00 01 12 23 34 45 56 67 78 89 91010 1111 1212 1313HCCHCC累积发生率累积发生率随访时间（年）随访时间（年）基线基线HBV DNAHBV DNA水平水平10610104 410105 510103 310104 430030010103 33003001061041051031043001033001011从而改善生活质量和延从而改善生活质量和延长存活时间长存活时间1.Liaw Y-F,et al.J Gastroenterol Hepatol.2005;25:472-89.2.慢性乙型肝炎防治指南 Chinese Hepatology,Dec 2005,Vol 10,No.4：3483573.Lok A.Viral Hepatitis Summit.24-26 August 2006,Cleveland,Ohio,USA12持续的持续的HBV DNA抑制抑制ALT防止肝病进展防止肝病进展为肝硬化、肝衰竭为肝硬化、肝衰竭或肝癌或肝癌减少死亡减少死亡或进行肝移植或进行肝移植Keeffe EB,el at.,A Treatment Algorithm for the Management of Chronic Hepatitis B Virus Infection in the United States:An Update,16 July 2006;Clinical Gastroenterology and Hepatology2006;4:936962131415中国乙肝指南中国乙肝指南:干扰素疗程固定干扰素疗程固定 抗病毒药物抗病毒药物 HBeAg(+):1HBeAg(+):1年年 HBV DNAHBV DNA转阴、转阴、ALTALT复常且发生复常且发生e e抗原血清转换后继续抗原血清转换后继续治疗治疗1212月（月（22年年 ）HBeAg(-):1HBeAg(-):1年年 HBV DNAHBV DNA转阴、转阴、ALTALT复常后继续治疗复常后继续治疗1818月月 （2.52.5年年 ）美国消化协会乙肝治疗规范美国消化协会乙肝治疗规范:抗病毒药物抗病毒药物 HBeAg(+):1HBeAg(+):1年年HBV DNAHBV DNA转阴、且发生转阴、且发生e e抗原血清转换后继续治疗抗原血清转换后继续治疗6-126-12月（月（1.51.5年年 ）HBeAg(-)HBeAg(-)：长期治疗：长期治疗慢性乙型肝炎防治指南 Chinese Hepatology,Dec 2005,Vol 10,No.4：348357Keeffe EB,el at.,A Treatment Algorithm for the Management of Chronic Hepatitis B Virus Infection in the United States:An Update,16 July 2006;Clinical Gastroenterology and Hepatology2006;4:93696216疾病进展患者的比例疾病进展患者的比例 月月安慰剂安慰剂 (n=215)(n=215)ITT 人群人群拉米夫定拉米夫定(n=436)(n=436)p=0.001安慰剂安慰剂P=0.00121%9%Liaw et al,N Engl J Med 2004,351:1521-1531.安慰剂安慰剂肝脏失代偿肝癌自发性细菌性腹膜炎出血食管静脉曲张肝病相关的死亡17安慰剂安慰剂 (n=215)(n=215)拉米夫定拉米夫定 (n=436)(n=436)诊断诊断HCCHCC的比例的比例诊断时间（月）诊断时间（月）拉米夫定拉米夫定安慰剂安慰剂P=0.047Liaw et al,N Engl J Med 2004,351:1521-1531.5%10%18*Patients with child-Turcotte-Pugh A cirrhosisIncidence of HCCp105105 copies/ml(virologic breakthrough)HBV DNA 105 copies/ml(maintained virologic response)62154877231111025719287No.at risk19Di Marco V et al.Antivir Ther.2005;10(3):431-9 2021Keeffe EB,el at.,A Treatment Algorithm for the Management of Chronic Hepatitis B Virus Infection in the United States:An Update,16 July 2006;Clinical Gastroenterology and Hepatology2006;4:93696222232425262728293031Keeffe EB,el at.,A Treatment Algorithm for the Management of Chronic Hepatitis B Virus Infection in the United States:An Update,16 July 2006;Clinical Gastroenterology and Hepatology2006;4:9369622006美国消化协会最新乙肝治疗规范3233343536恩替卡韦治疗核苷初治患恩替卡韦治疗核苷初治患者达到者达到300 300 拷贝拷贝/mL/mL恩替卡韦治疗恩替卡韦治疗2-32-3年队列年队列:核苷初治患者达到核苷初治患者达到HBV DNAHBV DNA不可测水平比例不可测水平比例%患者出现患者出现HBV DNA 300 Copies/mLHBV DNA 300 Copies/mL1010202030304040505070706060808090901001000 00 05050100100150150治疗治疗 (周周)N=319N=319N=345N=345核苷初治HBeAg(-)核苷初治 HBeAg(+)Colonno.RJ,et al.Assessment at Three Years Shows High Barrier to Resistance Is Maintained In Entecavir-Treated Nucleoside-Nave Patients while Resistance Increases Over Time In Lamivudine-Refractory Patient.Hepatology Vol44 Issue S1 229A(abstract 110);37拉米夫定拉米夫定2929月月耐药(中位数)vs 2424周周病毒载量4848周周HBV DNAHBV DNAn=114 原发HBeAg()阿德福韦阿德福韦144144周周耐药 vs 4848周周病毒载量2424周周HBV DNAHBV DNAn=159 HBeAg(+)Yuen MF,et al.Hepatology 2001;34(4):785791Locarnini S,et al.J Hepatol 2005;42(Suppl 2):17(Abstract 36)8 81212323264640 020204040606080801001002002003 log3 log4 log4 log4 log%耐药耐药4 4262667670 020204040606080801001003 log6 log6 log%耐药耐药*对当前可靠资料的总结对当前可靠资料的总结非来自头对头研究非来自头对头研究381年耐药年耐药(%)24周周HBV DNAHBeAg(+)HBeAg()Lai CL,et al.Hepatology 2005;42(suppl 1):232A233A(Abstract 92)GLOBE研究研究20%7%6%0%7%5%
