传染病Viral-hepatitis.ppt

1 Viral hepatitis Tianjin Medical University General Hospital Department of Infectious Diseases 逄崇杰逄崇杰 2 难点难点 HBV形态、基因组结构和编码蛋白形态、基因组结构和编码蛋白 HBV、HCV的发病机制的发病机制 肝炎的临床分类和临床表现（慢肝和重肝）肝炎的临床分类和临床表现（慢肝和重肝）HBV抗原抗原-抗体系统的组成和意义抗体系统的组成和意义 慢性慢性HBV、HCV的治疗的治疗 HBV的母婴阻断的母婴阻断 3 重点和问题重点和问题 定义：定义：病毒性肝炎，病毒性肝炎，Dane颗粒，慢性肝炎，窗口期，颗粒，慢性肝炎，窗口期，cccDNA，胆酶分离，胆酶分离 HBV在人体内的复制过程和发病机制在人体内的复制过程和发病机制 HCV感染易转为慢性的原因感染易转为慢性的原因 HBV抗原抗原-抗体系统的组成和意义抗体系统的组成和意义 各型病毒性肝炎的传播途径各型病毒性肝炎的传播途径 病毒性肝炎的临床分类病毒性肝炎的临床分类 重型肝炎的并发症重型肝炎的并发症 慢性乙肝、丙肝的药物治疗慢性乙肝、丙肝的药物治疗 意外暴露意外暴露HBV后的预防后的预防 4 Introduction Viral hepatitis is a group systemic communicable disease affecting the liver predominantly caused by some kinds of viruses Viral hepatitis may be divided into 5 types according to etiology,that is hepatitis A,B,C,D and E Although the agents can be distinguished by its antigenic properties,the 5 kinds of viruses may produce clinical similar illness 5 Introduction Clinical manifestations are characterized by anorexia,nausea,fatigue,enlarged liver and abnormal liver function,a part of cases may appear jaundice.Hepatitis A and E shows acute hepatitis,fecal-oral route predominantly Hepatitis B,C and D predispose to a chronic hepatitis and is related to liver cirrhosis and hepatic cancer,humoral transmission.6 Introduction Recently,3 kinds of viruses named GBV-C,TTV and SENV are discovered,and not yet considered to relate to viral hepatitis 7 Etiology:Hepatitis A virus(HAV)HAV is one kind of picornavirus（微小RNA病毒科）and used to be classified as enterovirus type 72,but recently,it is considered to be classified as heparnavirus（嗜肝RNA病毒属）Hepatitis A virion is a spherical particle,diameter 2732nm Consists of a genome of linear,single-stranded RNA,7.5kb 8 Etiology:Hepatitis A virus(HAV)Seven gene types,1,2,3,4 types from human body Only one antigen-antibody system.Anti-HAV IgM is diagnostic evidence of recent infection,IgG is protective antibody.During acute stage of infection,HAV can be found in blood and feces of infected human 9 Etiology:Hepatitis B virus(HBV)A kind of hepadnavirus（嗜肝DNA病毒科）19651967,Blumberg and Krugman,hepatitis associated antigen,HAA 1972,hepatitis B surface antigen,HBsAg 1970,Dane particle 1979,genomewide sequence finished 10 Baruch S.Blumberg July 28,1925April 5,2011 After receiving the prize,he was invited to China.“I spoke before several thousand people,”he told The Times in 2002.“I provided them with a copy of the patent,and now Im told that it helped to change the direction of what they were doing and led to the saving of a lot of lives.”“Saving lives”,he said,“is the whole point of his career”,and“This is what drew me to medicine.There is,in Jewish thought,this idea that if you save a single life,you save the whole world,and that affected me.”Nobel Prize in Physiology or Medicine in 1976 11 Etiology:Hepatitis B virus(HBV)Three particles in serum Spherical particles with a diameter of 22nm and tubular particles,composed of HBsAg Large particles with a diameter of 42 nm,named Dane particle.It is a complete infectious HBV particles,consists of an outer protein shell(envelope,contain HBsAg)and an inner body(core,contain HBcAg,HBeAg,HBV-DNA and DNAP)12 large particles spherical particles tubular particles 13 Etiology:Hepatitis B virus(HBV)Hepatitis B virion genome is a small circular,partially double stranded DNA with 3.2kb.HBV DNA is asymmetry in length of two strands:minus strand(long strand,L)has full length.14 15 Etiology:Hepatitis B virus(HBV)Four open reading frames(ORF)S region:include pre-s1,pre-s2 and S gene,encoded pre-s1 protein,pre-s2 protein and S protein C region:included pre-c and C gene,encode HBeAg and HBcAg P region:encoded DNA polymerase X region:encoded HBxAg 16 Etiology:Hepatitis B virus(HBV)Three antigen-antibody system HBsAganti-HBs HBeAganti-HBe HBcAganti-HBc pre-s1,pre-s2anti-pre-s1,anti-pre-s2 17 Etiology:Hepatitis B virus(HBV)HBsAg：疾病早期出现，一般在疾病早期出现，一般在ALT升高前升高前16w，急，急性者持续性者持续5w5m，慢性者可持续多年，慢性者可持续多年 抗抗HBs：HBsAg消失后数周出现，可保持多年消失后数周出现，可保持多年 前前S1，前前S2抗原：抗原：紧随紧随HBsAg出现在血液中，与出现在血液中，与HBV活跃复制有关，也可作为评价药物疗效的指标活跃复制有关，也可作为评价药物疗效的指标 前前S1抗体：抗体：潜伏期出现潜伏期出现 前前S2抗体：抗体：出现于出现于HBV复制终止前后，提示复制终止前后，提示HBV清除清除 18 Etiology:Hepatitis B virus(HBV)HBcAg：肝细胞坏死后释放入血，易与核心抗体形成肝细胞坏死后释放入血，易与核心抗体形成抗原抗体复合物而不易检出抗原抗体复合物而不易检出 抗抗HBc IgM：存在与乙肝急性期及慢乙肝急性发作期，存在与乙肝急性期及慢乙肝急性发作期，HBsAg阳性后阳性后24周出现周出现 抗抗HBc IgG：抗抗HBc IgM下降消失后出现，可持续多下降消失后出现，可持续多年，为年，为HBV既往感染的标志既往感染的标志 窗口期：窗口期：HBV感染时，感染时，HBsAg已消失，抗已消失，抗HBs尚未出尚未出现，血中仅能检出抗现，血中仅能检出抗HBc/抗抗HBe，此期可能有传染性，此期可能有传染性 19 Etiology:Hepatitis B virus(HBV)HBeAg：仅见于HBsAg阳性血清，稍后或同时于HBsAg在血中出现，HBV复制和传染性强的标志 抗抗HBe：紧随HBeAg消失而出现，表示HBV复制减少和传染性减低 前前C区变异：区变异：HBeAg阴性 HBV-DNA：位于HBV核心，与HBeAg同时出现于血中，是HBV感染最直接，特异，灵敏的指标。分为游离型及整合型 HBVDNAP：位于HBV核心，具有逆转录酶特性，是直接反映HBV复制能力的指标 20 乙型肝炎病毒急性感染模式乙型肝炎病毒急性感染模式 10周周 20周周 30周周 2 4 6 8 10 年年 感染感染HBV后时间后时间 21 Etiology:Hepatitis C virus(HCV)HCV is a member of flaviviridae（黄病毒科）HCV genome is a single stranded positive-sense RNA and contains 9.49.6kb The genome contains 3 and 5-non coding region,C region,E region and NS region HCV genome may be d