1、HEPATITIS VIRUSES肝炎病毒,HAV甲型肝炎病毒HBV乙型肝炎病毒HCV丙型肝炎病毒HDV丁型肝炎病毒HEV戊型肝炎病毒HFV 已型肝炎病毒HGV 庚型肝炎病毒TTV TT型肝炎病毒,Hepatitis A virus，HAV甲型肝炎病毒,Biological Properties,picornavirus, +ssRNA genome小RNA病毒科27 nm in diameter ,non-enveloped icosahedral particle 27nm, 球形， 20面立体对称，无包膜one serotype一个血清型,Feinstone（1973）,Stronger
2、 than enterovirus, resistant to detergents, acid (pH 1.0 for 2h), 60 for 1h，survive for months in fresh water and salt water 抵抗力比肠道病毒强,Pathogenesis致病性,spread via the fecal-oral route粪口途径传播Source of infection: patient, inapparent infection传染源: 病人、隐性感染者Viral shedding in the stool precedes the onset of
3、 symptoms by 14d but stops before the cessation of symptoms SymptomsInitial symptoms: fever, fatigue, nausea, loss of appetite, abdominal painJaundice,HAV的致病性,粪口途径传播,小肠淋巴结中大量增殖,入血并形成病毒血症,肝脏为最终靶器官（病毒直接损伤或免疫病理作用）,通过胆汁随粪便排出体外,Asymptomatic infections are very common. As already noted, disease in childre
4、n is generally milder than that in adults and is usually asymptomatic隐性感染多No a chronic infection and carrier,not associated with hepatic cancer.无慢性病例和病毒携带者，不与肝癌有关Complete recovery:99% 预后好Fulminant hepatitis暴发性肝炎: 13 / 1000, 80% mortality rate死亡率 Pregnant women may develop more severe disease. 孕妇感染严重
5、,Mechanisim of pathogenisis致病机理：,Directly injury by virus病毒直接损伤immunopathogenesis免疫病理作用,immunity免疫性,无论显性感染还是隐性感染 均能产生抗-HAV的 IgM和IgG抗体,抗-HAV的IgM在急性期和恢复早期出现 阳性可作为甲肝的确诊依据,抗-HAV的IgG在恢复后期出现 有保护作用，维持终身,Laboratory Diagnosis微生物学检查,anti-HAV IgM 抗HAV IgMby an ELISA or radioimmunoassay,Treatment and Prevention
6、防治原则,Control the source of infection控制传染源 Cut down the route of transmission切断传播途径Passive immunization - Normal immunoglobulin 丙种球蛋白Active immunizationsA killed HAV vaccinea live attenuated HAV vaccine,hepatitis B virus, HBV乙型肝炎病毒,SHAPE AND STRUCTURE形态结构,There are 3 particles in patients bloodDane p
7、article Dane颗粒（大球形颗粒）small spherical particle小球形颗粒tubulose particle管形颗粒,Dane particle,Complete particle, infective HBVspherical，double capsid球形,双层衣壳。outer capsid=envelope外衣壳=包膜(脂质双层+蛋白质) HBsAg等 inner capsid内衣壳： HBcAg、HBeAginternal内部： DNA- circular, double- stranded环状双链 DNA polymerase 多聚酶,HBV的小球形颗粒,H
8、BsAg-containing particles 过剩的衣壳蛋白装配而成,HBV的管形颗粒,小球形颗粒串联而成,Genome of HBV,a circular, double-stranded DNA containing single-strand breaks 不完全双链环状DNAfour open reading frames that encode seven polypeptides. 含4个ORF,编码7个蛋白S HBsAg,Pre-s1,Pre-s2C HBcAg，HBeAgP polymerase多聚酶X HBxAg基因,Antigen of HBV抗原组成,hepatit
9、is B surface antigenHBsAg表面抗原indicates that virus replication is occurring in the liver 说明病毒在肝中复制（机体受感染标志）four phenotypes：adr,adw,ayr,aywantiHBs:neutralization antibody中和抗体hepatitis B core antigen HBcAg核心抗原not found in blood一般不能检出antiHBc nonneutralization antibody非中和抗体Core IgM indicates recent infec
10、tion. 抗HBc IgM说明HBV复制Core IgG indicates exposure to HBV,Antigen of outer capsid外衣壳抗原,Antigens of inner capsid内衣壳抗原,hepatitis B e antigen e抗原HBeAgthe best correlate to the presence of infectious virus. 感染性病毒存在的最有效证据（复制及具传染性的标志）anti-HBe indicates low infectivity in a carrier 抗HBe说明病毒感染性较低（是预后良好的征象）,cu
11、lture培养 resistance抵抗力 strong resistance to cool,dry, ultraviolet, alcohol inactivate: 100 10min,Pathogenesis and Immunity source of infection传染源 patients or carriers 急性、慢性患者或无症状HBsAg携带者route of transmission传播途径 sexual routes parenteral肠胃外的 routes injection of the virus into the blood stream contamin
12、ated blood and blood components by transfusion, needle sharing, acupuncture针灸, ear piercing, or tattooing perinatal围产期 routes contact with the mothers blood at birth and in mother milk,Pathogenesis of HBV致病性,Cell-mediated immunity (liver injury)Immune complexes ( HBsAg + anti-HBs) : development of h
13、ypersensitivity reactions (other organs injury） infants infected perinatally become chronic carriers,Clinical Findings,Acute infection急性感染Fulminant hepatitis暴发型肝炎 Chronic infection 慢性感染Primary hepatocellular carcinoma （PHC）原发性肝细胞癌,Acute infection,a long incubation period and an insidious onset prodr
14、omal period前驱期 :fever, malaise不适, anorexia食欲缺乏, nausea, vomiting, abdominal discomfort, chills classic icteric黄疸 symptoms of liver damage Recovery,Fulminant hepatitis暴发型肝炎,occurs in approximately 1% of icteric patients and may be fatal 1% 黄疸病人，可致死 severe liver damage, such as ascites and bleeding 肝严
15、重受损，腹水，出血,Chronic infection,elevated liver enzyme levels 转氨酶水平高10% of patients with chronic hepatitis may develop cirrhosis and liver failure 10% 可发展为肝硬化和肝衰竭major source for spread of the virus主要传染源at risk for fulminant disease if they become co-infected with HDV,Primary hepatocellular carcinoma （PH
16、C）原发性肝细胞癌,promoting continued liver repair and cell growth in response to tissue damage integrating into the host chromosome and stimulating cell growth directly,Laboratory Diagnosis乙肝“两对半”及临床意义,HBsAg、 抗HBsHBeAg、 抗HBe（HBcAg） 抗HBc,HBV抗原抗体系统检测临床意义,Treatment and Prevention,Control the source of infecti
17、on控制传染源 Cut down the route of transmission切断传播途径Passive immunization - Hepatitis B immune globulin （HBIg）抗-HBs人血清球蛋白Active immunizationsHBsAg vaccineNo specific treatment,hepatitis C virus,HCV丙型肝炎病毒,predominant cause of non A non B hepatitis,Biological properties生物学性状,a member of the flavivirus 黄病毒属
18、成员4060nm,spherical球形an enveloped virion有包膜Genome: (+)ss RNA,Pathogenesis and Immunity致病性与免疫性,six genotypes基因型：、 transmitted by means similar to HBV 传播途径似HBVin infected blood （输血后肝炎）Intravenous drug abusers transfusion organ recipients hemophiliacs receiving factors or sexually,Pathogenesis,persisten
19、t, chronic hepatitis cirrhosis肝硬化 ， hepatocellular carcinoma肝癌acute hepatitis 15% chronic persistent infection 70% severe rapid progression to cirrhosis 15,Laboratory diagnosis,ELISA recognition of antibodygenetic techniques to detect HCV RNATreatment防治原则No vaccine尚无可用疫苗Recombinant IFN-alone or with
20、 ribavirin 病毒唑,hepatitis D virus，HDV丁型肝炎病毒,a defective virus that acquires an HBsAg coat for transmissionHDV是缺陷病毒，需以HBsAg构成其衣壳来传播circular, single-stranded RNA molecules and an internal core antigen (HDAg) 单负链环状RNA和 抗原（HDAg）,Pathogenesis,spread by the same routes as HBV: blood, semen, and vaginal sec
21、retions 传播途径与HBV相同：血液，精液，阴道分泌物increases the severity of HBV infections: Fulminant hepatitis 加重HBV感染：爆发性肝炎Coinfection联合感染Superinfection重迭感染,Laboratory diagnosis,detecting the delta antigen ，RNA or antibodies病原学检查为HDAg、抗HDV及HDV-RNAAnti-HDV IgMPersistant Anti-HDV IgG chronic infectionTreatment and prev
22、entionno known specific treatment prevention of infection with HBV prevents HDV infection.,hepatitis E virus，HEV戊型肝炎病毒,spherical, non-enveloped, and 27-34 nm 球形，无包膜，a positive-sense, single-strand RNA genome 单正链RNA,spread by the fecal-oral route为粪口途径传播symptoms and course of HEV disease are similar to those of HAV disease 症状病程类似HAVAcute hepatitis ，mortality rate : 1% to 2% especially serious in pregnant women (mortality rate of approximately 20%)孕妇感染严重,病死率高达20%,Diagnosis 微生物学检查,HEV：EM or IEM电镜或免疫电镜Anti-HEV IgMHEV RNA,五种肝炎病毒比较,
