1、1,Viral hepatitis,Tianjin Medical University General HospitalDepartment of Infectious Diseases逄崇杰,第一页，共九十四页。,2,难点(ndin),HBV形态、基因组结构和编码蛋白HBV、HCV的发病机制肝炎的临床(ln chun)分类和临床(ln chun)表现（慢肝和重肝）HBV抗原-抗体系统的组成和意义慢性HBV、HCV的治疗HBV的母婴阻断,第二页，共九十四页。,3,重点(zhngdin)和问题,定义：病毒性肝炎，Dane颗粒，慢性肝炎，窗口期，cccDNA，胆酶分离HBV在人体内的复制过程和发
2、病机制(jzh)HCV感染易转为慢性的原因HBV抗原-抗体系统的组成和意义各型病毒性肝炎的传播途径病毒性肝炎的临床分类重型肝炎的并发症慢性乙肝、丙肝的药物治疗意外暴露HBV后的预防,第三页，共九十四页。,4,Introduction,Viral hepatitis is a group systemic communicable disease affecting the liver predominantly caused by some kinds of virusesViral hepatitis may be divided into 5 types according to etio
3、logy,that is hepatitis A,B,C,D and EAlthough the agents can be distinguished by its antigenic properties,the 5 kinds of viruses may produce clinical similar illness,第四页，共九十四页。,5,Introduction,Clinical manifestations are characterized by anorexia,nausea,fatigue,enlarged liver and abnormal liver functi
4、on,a part of cases may appear jaundice.Hepatitis A and E shows acute hepatitis,fecal-oral route predominantlyHepatitis B,C and D predispose to a chronic hepatitis and is related to liver cirrhosis and hepatic cancer,humoral transmission.,第五页，共九十四页。,6,Introduction,Recently,3 kinds of viruses named GB
5、V-C,TTV and SENV are discovered,and not yet considered to relate to viral hepatitis,第六页，共九十四页。,7,Etiology:Hepatitis A virus(HAV),HAV is one kind of picornavirus（微小(wixio)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）He
6、patitis A virion is a spherical particle,diameter 2732nmConsists of a genome of linear,single-stranded RNA,7.5kb,第七页，共九十四页。,8,Etiology:Hepatitis A virus(HAV),Seven gene types,1,2,3,4 types from human bodyOnly one antigen-antibody system.Anti-HAV IgM is diagnostic evidence of recent infection,IgG is
7、protective antibody.During acute stage of infection,HAV can be found in blood and feces of infected human,第八页，共九十四页。,9,Etiology:Hepatitis B virus(HBV),A kind of hepadnavirus（嗜肝DNA病毒科）19651967,Blumberg and Krugman,hepatitis associated antigen,HAA1972,hepatitis B surface antigen,HBsAg1970,Dane particl
8、e1979,genomewide sequence finished,第九页，共九十四页。,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 dir
9、ection 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 P
10、hysiology or Medicine in 1976,第十页，共九十四页。,11,Etiology:Hepatitis B virus(HBV),Three particles in serum Spherical particles with a diameter of 22nm and tubular particles,composed of HBsAgLarge particles with a diameter of 42 nm,named Dane particle.It is a complete infectious HBV particles,consists of a
11、n outer protein shell(envelope,contain HBsAg)and an inner body(core,contain HBcAg,HBeAg,HBV-DNA and DNAP),第十一页，共九十四页。,12,large particles,tubular particles,第十二页，共九十四页。,13,Etiology:Hepatitis B virus(HBV),Hepatitis B virion genome is a small circular,partially double stranded DNA with 3.2kb.HBV DNA is
12、asymmetry in length of two strands:minus strand(long strand,L)has full length.,第十三页，共九十四页。,14,第十四页，共九十四页。,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 proteinC region:included pre-c and C gene,en
13、code HBeAg and HBcAgP region:encoded DNA polymeraseX region:encoded HBxAg,第十五页，共九十四页。,16,Etiology:Hepatitis B virus(HBV),Three antigen-antibody systemHBsAganti-HBsHBeAganti-HBeHBcAganti-HBcpre-s1,pre-s2anti-pre-s1,anti-pre-s2,第十六页，共九十四页。,17,Etiology:Hepatitis B virus(HBV),HBsAg：疾病早期出现，一般在ALT升高前16w，急
14、性者持续5w5m，慢性者可持续多年抗HBs：HBsAg消失后数周出现，可保持多年前S1，前S2抗原：紧随HBsAg出现在血液中，与HBV活跃复制有关(yugun)，也可作为评价药物疗效的指标前S1抗体：潜伏期出现前S2抗体：出现于HBV复制终止前后，提示HBV清除,第十七页，共九十四页。,18,Etiology:Hepatitis B virus(HBV),HBcAg：肝细胞坏死后释放入血，易与核心抗体形成抗原抗体复合物而不易检出抗HBc IgM：存在与乙肝急性期及慢乙肝急性发作期，HBsAg阳性后24周出现抗HBc IgG：抗HBc IgM下降消失后出现，可持续多年，为HBV既往感染的标志(
15、biozh)窗口期：HBV感染时，HBsAg已消失，抗HBs尚未出现，血中仅能检出抗HBc/抗HBe，此期可能有传染性,第十八页，共九十四页。,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HBe：紧随HBeAg消失(xiosh)而出现，表示HBV复制减少和传染性减低前C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
16、复制能力的指标,第十九页，共九十四页。,20,乙型肝炎病毒(bngd)急性感染模式,10周,20周,30周,2 4 6 8 10 年,感染(gnrn)HBV后时间,第二十页，共九十四页。,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 9.49.6kbThe genome contains 3 and 5-non coding region,C region,E region and NS regionHCV genome may be divided into many types and subtypes,第二十一页，共九十四页。,22,Etiology:Hepatitis C virus(HCV),Antigen-antibody system The concentration of HCV in blood is low,HCV Ag has not be
