HEPATITISVIRUSES肝炎病毒.ppt

HEPATITISVIRUSES肝炎病毒￿￿￿￿Still￿waters￿run￿deep.流静水深流静水深,人静心深人静心深￿￿￿￿Where￿there￿is￿life,￿there￿is￿hope有生命必有希望有生命必有希望Hepatitis A virus，HAV甲型肝炎病毒 Biological Properties lpicornavirus, +ssRNA genome小小RNA病毒科病毒科l27 nm in diameter ,non-enveloped icosahedral particle 27nm, 球形，球形， 20面立体对称，面立体对称，无包膜无包膜lone serotype一个血清型一个血清型Feinstone（1973）lStronger 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致病性致病性lspread via the fecal-oral route粪－口途径传播lSource of infection: patient, inapparent infection传染源: 病人、隐性感染者隐性感染者lViral shedding in the stool precedes the onset of symptoms by 14d but stops before the cessation of symptoms lSymptoms–Initial symptoms: fever, fatigue, nausea, loss of appetite, abdominal pain–Jaundice HAV的致病性的致病性粪－口途径传播粪－口途径传播小肠淋巴结中大量增殖小肠淋巴结中大量增殖入血并形入血并形成病毒血成病毒血症症肝脏为最终靶肝脏为最终靶器官（病毒直器官（病毒直接损伤或免疫接损伤或免疫病理作用）病理作用）通过胆汁随粪通过胆汁随粪便排出体外便排出体外lAsymptomatic infections are very common. As already noted, disease in children is generally milder than that in adults and is usually asymptomatic隐性感染多隐性感染多lNo a chronic infection and carrier,not associated with hepatic cancer.无慢性病例和病毒携带者，不与肝癌有关无慢性病例和病毒携带者，不与肝癌有关lComplete recovery:99% 预后好预后好lFulminant hepatitis暴发性肝炎暴发性肝炎: 1~3 / 1000, 80% mortality rate死亡率死亡率 lPregnant women may develop more severe disease. 孕妇感染严重孕妇感染严重Mechanisim of pathogenisis致病机理：lDirectly injury by virus病毒直接损伤病毒直接损伤limmunopathogenesis免疫病理作用免疫病理作用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lanti-HAV IgM 抗－抗－HAV IgMlby an ELISA or radioimmunoassayTreatment and Prevention防治原则lControl the source of infection控制传染源 lCut down the route of transmission切断传播途径lPassive immunization - Normal immunoglobulin 丙种球蛋白lActive immunizations–A killed HAV vaccine–a 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 patient’s bloodlDane particle Dane颗粒颗粒（大球形颗粒）（大球形颗粒）lsmall spherical particle小球形颗粒小球形颗粒ltubulose particle管形颗粒管形颗粒Dane particleComplete particle, infective HBVspherical，double capsid球形,双层衣壳。

outer capsid=envelope外衣壳外衣壳=包膜包膜(脂质双层脂质双层+蛋白质蛋白质) HBsAg等等 inner capsid内衣壳：内衣壳： HBcAg、、HBeAginternal内部： DNA--- circular, double- stranded环状双链环状双链 DNA polymerase 多聚酶HBV的小球形颗粒HBsAg-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 不完不完全双链环状全双链环状DNAfour open reading frames that encode seven polypeptides. 含含4个个ORF,编码编码7个蛋白个蛋白•S HBsAg,Pre-s1,Pre-s2•C HBcAg，，HBeAg•P polymerase多聚酶多聚酶•X HBxAg基因基因Antigen of HBV抗原组成lhepatitis B surface antigenHBsAgHBsAg表面抗原–indicates that virus replication is occurring in the liverindicates that virus replication is occurring in the liver 说明病毒在肝中复制（机体受感染标志）说明病毒在肝中复制（机体受感染标志）–four phenotypesfour phenotypes：：adradr,adw,ayr,ayw,adw,ayr,ayw–antianti－－HBsHBs: :neutralization antibody中和抗体中和抗体lhepatitis B core antigen HBcAgHBcAg核心抗原–not found in bloodnot found in blood一般不能检出一般不能检出–antianti－－HBc nonHBc non－－neutralization antibody非中和抗体非中和抗体–Core IgMCore IgM indicates recent infection. indicates recent infection. 抗－抗－HBc IgMHBc IgM说明说明HBVHBV复制复制–Core IgGCore IgG indicates exposure to HBVindicates exposure to HBVAntigen of outer capsid外衣壳抗原外衣壳抗原Antigens of inner capsid内衣壳抗原内衣壳抗原lhepatitis B e antigenhepatitis B e antigen e抗原HBeAgHBeAg–the best correlate to the presence of infectious virus. the best correlate to the presence of infectious virus. 感染性病毒存在的最有效证据（复制及具传染性的感染性病毒存在的最有效证据（复制及具传染性的标志）标志）–anti-HBeanti-HBe indicates low infectivity in a carrierindicates low infectivity in a carrier 抗抗H HB Be e说明病毒感染性较低（是预后良好的征象）说明病毒感染性较低（是预后良好的征象）lculture培养 lresistance抵抗力 strong resistance to cool,dry, ultraviolet, alcohol inactivate: 100℃ 10minPathogenesis and Immunity lsource of infection传染源 patients or carriers 急性、慢性患者或无症状急性、慢性患者或无症状HBsAgHBsAg携带者携带者lroute of transmission传播途径– sexual routes– parenteral肠胃外的肠胃外的 routesl injection of the virus into the blood stream lcontaminated blood and blood components by transfusion, needle sharing, acupuncture针灸针灸, ear piercing, or tattooing – perinatal围产期围产期 routes lcontact with the mother’s blood at birth and in mother’ milk Pathogenesis of HBV致病性lCell-mediated immunity (liver injury)Cell-mediated immunity (liver injury)lImmune complexes ( HBsAg + anti-HBs) : Immune complexes ( HBsAg + anti-HBs) : development of hypersensitivity reactions development of hypersensitivity reactions (other organs injury(other organs injury）） infants infected perinatally become chronic infants infected perinatally become chronic carrierscarriers Clinical Findings lAcute infection急性感染急性感染lFulminant hepatitis暴发型肝炎暴发型肝炎 lChronic infection 慢性感染慢性感染lPrimary hepatocellular carcinoma （（PHC））原发性肝细胞癌原发性肝细胞癌 Acute infection la long incubation period and an insidious onset lprodromal period前驱期 :fever, malaise不适, anorexia食欲缺乏, nausea, vomiting, abdominal discomfort, chills lclassic icteric黄疸 symptoms of liver damage lRecovery Fulminant hepatitis暴发型肝炎暴发型肝炎 loccurs in approximately 1% of icteric patients and may be fatal 1% 黄疸病人，可致死 lsevere liver damage, such as ascites and bleeding 肝严重受损，腹水，出血Chronic infection lelevated liver enzyme levels 转氨酶水平高l10% of patients with chronic hepatitis may develop cirrhosis and liver failure 10% 可发展为肝硬化和肝衰竭lmajor source for spread of the virus主要传染源lat risk for fulminant disease if they become co-infected with HDV Primary hepatocellular carcinoma （（PHC））原发性肝细胞癌原发性肝细胞癌 lpromoting continued liver repair and cell growth in response to tissue damage lintegrating into the host chromosome and stimulating cell growth directly Laboratory Diagnosis乙肝“两对半”及临床意义 lHBsAg、、 抗抗HBslHBeAg、、 抗抗HBel（HBcAg） 抗抗HBc HBVHBV抗原抗体系统检测临床意义抗原抗体系统检测临床意义HBsAgHBeAg抗-HBe抗-HBc抗-HBs临床意义IgMIgG+-----感染或无症状携带者感染或无症状携带者++ -+--急性乙型肝炎（有急性乙型肝炎（有传染）传染）（大三阳）（大三阳）++--+-慢性乙型肝炎（有传染）慢性乙型肝炎（有传染） （（大三阳）大三阳）+-++-急性肝炎趋向恢复急性肝炎趋向恢复（小三阳）（小三阳）--+-++恢复期（传染性低）恢复期（传染性低）-----+既往感染或接种疫苗既往感染或接种疫苗------未感染，无免疫力未感染，无免疫力Treatment and PreventionlControl the source of infection控制传染源 lCut down the route of transmission切断传播途径lPassive immunization - Hepatitis B immune globulin （HBIg）抗-HBs人血清球蛋白lActive immunizations–HBsAg vaccinelNo 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la member of the flavivirus 黄病毒属成员l40～60nm,spherical球形lan enveloped virion有包膜lGenome: (+)ss RNAPathogenesis and Immunity致病性与免疫性l six genotypes基因型：Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ、Ⅵl transmitted by means similar to HBV 传播途径似HBV–in infected blood （输血后肝炎）lIntravenous drug abusers ltransfusion lorgan recipients lhemophiliacs receiving factors Ⅷ or Ⅸ –sexuallyPathogenesispersistent, chronic hepatitis →cirrhosis肝硬化 ， hepatocellular carcinoma肝癌lacute hepatitis 15% lchronic persistent infection 70% lsevere rapid progression to cirrhosis 15％ Laboratory diagnosislELISA recognition of antibodylgenetic techniques to detect HCV RNATreatment防治原则lNo vaccine尚无可用疫苗lRecombinant IFN-αalone or with ribavirin 病毒唑hepatitis D virus，HDV丁型肝炎病毒la defective virus that acquires an HBsAg coat for transmissionHDV是缺陷病毒，需以是缺陷病毒，需以HBsAg构成其构成其衣壳来传播衣壳来传播lcircular, single-stranded RNA molecules and an internal core δ antigen (HDAg) 单负链环状RNA和和δ 抗原（抗原（HDAg））Pathogenesislspread by the same routes as HBV: blood, semen, and vaginal secretions 传播途径与HBV相同：血液，精液，阴道分泌物lincreases 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 diagnosisldetecting the delta antigen ，，RNA or antibodies病原病原学检查为学检查为HDAg、、抗抗HDV及及HDV-RNAlAnti-HDV IgMlPersistant Anti-HDV IgG chronic infectionTreatment and preventionlno known specific treatment lprevention of infection with HBV prevents HDV infection. hepatitis E virus，HEV戊型肝炎病毒lspherical, non-enveloped, and 27-34 nm 球形，无包膜，la positive-sense, single-strand RNA genome 单正链RNAlspread by the fecal-oral route为粪－口途径传为粪－口途径传播播lsymptoms and course of HEV disease are similar to those of HAV disease 症状病程类似HAVlAcute hepatitis ，mortality rate : 1% to 2% lespecially 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lHEV：EM or IEM电镜或免疫电镜lAnti-HEV IgMlHEV RNA五种肝炎病毒比较HAVHBVHCVHDVHEV病毒结构病毒结构+ssRNAdsDNA+ssRNA-ssRNA+ssRNA传播途传播途径径 粪粪-口口血液、性、垂直传播血液、性、垂直传播粪粪-口口病情病情轻轻偶尔严重偶尔严重 亚临床亚临床,慢慢性多见性多见需需HBV协助协助孕妇重孕妇重慢性及慢性及携带者携带者无无有有无无实验室实验室检查检查抗抗HAV IgMHBsAg-Ab HBcAb HBeAg-Ab 抗抗HCV HCV-RNA抗抗HDV IgM抗抗HEV IgM预防预防疫苗疫苗疫苗疫苗无无同同HBV预防为主预防为主。