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1、Introduction,HBV基因组结构,pre-s1,pre-s2,S,P,C,pre-c,X,HBV DNA 3.2 kb,pre-S1 pre-S1蛋白 pre-S2 pre-S2蛋白 S HBsAg pre-C HBeAg C HBcAg P DNAP X HBxAg,编码,HBsAg,pre-S2,pre-S1,IgM anti-HBc,Total anti-HBc,HBsAg,Acute (6 months),HBeAg,Chronic (Years),anti-HBe,0,4,8,12,16,20,24,28,32,36,52,Years,Source: CDC and Pre
2、vention,Titer,Weeks of Exposure,慢性乙肝的病毒标志,transmitting,Perinatal, percutaneous and sexual exposure Close person-to-person contact (open cuts and sores, especially among children in hyperendemic areas) Risk of developing CHB after acute exposure: 90% in newborns 25-30% in infants and children under 5
3、 5% in adults,Groups at high risk for HBV infection who should be screened,Individuals born in areas of high or intermediate prevalence rates for HBV including immigrants and adopted children -Asia: All countries -Africa: All countries -south pacific islands: All countries -Middle East (except Cypru
4、s and Israel) -European Mediterranean: Malta and Spain -The Arctic (indigenous populations of Alaska, Canada and Greenland) -South America: Ecuador, Guyana, Suriname, Venezuela and Amazon regions of Bolivia, Brazil, Colombia and Peru -Eastern Europe: All countries except Hungary -Caribbean: Antigua
5、and Barbuda, Dominica, Granada, Haiti, Jamaica, St. Kitts and Nevis, St. Lucia, and Turks and Caicos -Central America: Guatemala and Honduras,Other groups recommended for screening -U.S. born persons not vaccinated as infants whose parents were born in regions with high HBV endemicity (8%) -Househol
6、d and sexual contacts of HBsAg-positive persons -Persons who have ever injected drugs -Persons with multiple sexual parteners or history of STD -Men who have sex with men -Inmates of correctional facilities -Individuals with chronically elevated ALT or AST -Patients undergoing renal dialysis -All pr
7、egnant women -Persons needing immunosuppressive therapy,Recommendations for infected persons regarding prevention of transmission of HBV to others,Persons who are HBsAg-positive should: -Have sexual contacts vaccinated -Use barrier protection during sexual intercourse if partner not vaccinated or na
8、turally immune -Not share toothbrushes or razors -Cover open cuts and scratches -Clean blood spills with detergent or bleach -Not donate blood, organs or sperms Children and adults who are HBsAg-positive: -Can participate in all activities including contact sports -Should not be excluded from daycar
9、e or school participation and should not be isolated from other children -Can share food, utensils or kiss others,Counseling and Prevention of Hepatitis B,No effective specific dietary measures Alcohol (20g/d in F; 30g/d in M): a risk factor for cirrhosis Sexual and household contacts of carriers: H
10、BV vaccination Newborns of HBV (+) mothers: HBIG and HBV vaccine Those remain a risk for HBV infection: tested for response to vaccine Postvaccination testing: 9-15 m in infants of carrier mothers and 1-2m after the last dose in others hemodialysis patients: follow-up testing of vaccine responders a
11、nnually HBcAb (+) donor organs for HBV seronegative recipients: Non-hepatic solid organs transplatation: 6-12 m prophylactic therapy Liver transplantation: life-long antiviral therapy,HBV感染病程和预后,围产期感染：大部份HBeAg(+)者高DNA，ALT正常免疫耐受 多在青春期发展为HBeAg(+)的慢乙肝 HBeAg血清学转换 伴ALT升高者，HBeAg清除率约每年8-12% HBeAg的清除往往伴随ALT
12、的升高 67-80%患者HBeAg转换后HBV DNA检测不出，ALT正常，肝活检炎症及坏死程度轻微 4-20%患者可出现一次或多次的HBeAg逆转 发生转换后约10-30%可伴有HBV DNA及ALT升高 HBeAg的清除可减少肝硬化发生，提高生存率 多数HBeAg(-) CHB者存在Pre-C/C 区变异 HBsAg血清学转换 0.5%HBsAg(+) 者可有HBsAg清除，多数产生HBsAb 半数者仍HBV DNA(+) 预后改善 有报道数年后进展为HCC者（年龄大，转换前已有肝硬化）,HBV相关疾病的危险因素,肝硬化 年龄、基因型C、高HBV DNA水平、嗜酒、HCV/HDV/HIV共
13、同感染 HCC 男性、家族史、年龄(感染超过40年)、HBeAg复燃、肝硬化、genotype C、C区变异、HCV共同感染、黄曲霉素、嗜酒,HBV感染者的评价与对策,HBV慢性感染者评估,初始评价 询问病史及体格检查 肝病及HCC家族史 实验室检查：血小板、肝功能、PT HBV检查：HBeAg/HBeAb, HBV DNA 排除共同感染：HCV/HDV/HIV HCC筛查：AFP、B超 有指征者肝活检,HBV感染路线图,HBsAg(+),HBeAg(+),HBeAg(-),ALT1ULN,ALT1-2ULN,ALT2ULN,3-6mo ALT 6-12mo HBeAg,3mo ALT 6mo
14、 HBeAg Consider bx if persistent or age40,Rx as needed,1-3mo ALT, HBeAg Treat if persistent Liver bx optitional Immediate Rx if jaundice or decompensated,*HCC surveillance if indicated,ALT1-2ULN HBV DNA 2,000-20,000IU/mL,ALT2ULN HBV DNA 20,000IU/mL,ALT1ULN HBV DNA 2,000IU/mL,Treat if persistent Live
15、r bx optitional,3 mo ALT 352(26):2682-95.,pegIFN-2a treatment in HBeAg(-) patients,Marcellin P, et al. N Engl J Med. 2004 351(12):1206-17,干扰素的副作用,流感样症状 胃肠道症状 脱发 骨髓抑制 肝功能异常，甚至肝衰竭 精神症状 自身免疫性疾病,干扰素不良反应及处理,Hoofnagle JH. N Engl J Med 1997; 336:347-356,干扰素治疗的禁忌证,核 苷 类 药 物,种类,拉米夫定 lamivudine 阿德福韦 Adefovir 恩替卡韦 entecavir 替比夫定 telbivudine 替诺福韦 tenofovir 恩曲他宾 entricitabine 克拉夫定 clevudine,HBsAg 衣壳,部分双链 DNA,拉米夫定 阿德福韦 恩替卡韦,A(n),有感染性的乙肝病毒颗粒,(-)-DNA,有感染性的乙肝病毒颗粒,mRNA,cccDNA,DNA多聚酶,RT,被包裹的 前基因组 mRNA,核苷(酸)类似物的作用机制,Predictors of response in HBeAg(+) patients,拉 米 夫 定,拉米夫定治疗HBeAg阳性慢乙肝5年结果,Guan, et al. 2002,拉米夫定
