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1、HEPATITIS VIRUSES肝炎病毒HAV甲型肝炎病毒甲型肝炎病毒HBV乙型肝炎病毒乙型肝炎病毒HCV丙型肝炎病毒丙型肝炎病毒HDV丁型肝炎病毒丁型肝炎病毒HEV戊型肝炎病毒戊型肝炎病毒HFV 已型肝炎病毒已型肝炎病毒HGV 庚型肝炎病毒庚型肝炎病毒TTV TT型肝炎病毒型肝炎病毒Hepatitis A virus，HAV甲型肝炎病毒Biological Properties lpicornavirus,+ssRNAgenome小小RNA病毒科病毒科l27nmindiameter,non-envelopedicosahedralparticle 27nm, 球形，球形， 20面立体对称，
2、面立体对称，无包膜无包膜loneserotype一个血清型一个血清型Feinstone1973lStrongerthanenterovirus,resistanttodetergents,acid(pH1.0for2h),60for1h，surviveformonthsinfreshwaterandsaltwater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lSourceofinfection:patient,inapparentinfection传染源:病人、隐性感染者隐性感染者lViralsheddin
3、ginthestoolprecedestheonsetofsymptomsby14dbutstopsbeforethecessationofsymptomslSymptomsInitialsymptoms:fever,fatigue,nausea,lossofappetite,abdominalpainJaundiceHAV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 i
4、nfections 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爆发
5、性肝炎爆发性肝炎: 13 / 1000, 80% mortality rate死亡率死亡率 lPregnant women may develop more severe disease.l 孕妇感染严重孕妇感染严重Mechanisimofpathogenisis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 阳性可作为甲肝确实诊依据 抗-HAV的IgG在恢复后期出现
6、有保护作用，维持终身 Laboratory Diagnosis微生物学检查lanti-HAVIgM抗抗HAV IgMlbyanELISAorradioimmunoassayTreatment and Prevention防治原那么防治原那么lControlthesourceofinfection控制传染源lCutdowntherouteoftransmission切断传播途径lPassiveimmunization-Normalimmunoglobulin丙种球蛋白lActiveimmunizationsAkilledHAVvaccinealiveattenuatedHAVvaccinehep
7、atitis B virus, HBV乙型肝炎病毒SHAPE AND STRUCTURE形态结构There are 3 particles in patients bloodDane particle Dane颗粒大球形颗粒颗粒大球形颗粒small spherical particle小球形颗粒小球形颗粒tubulose particle管形颗粒管形颗粒DaneparticleCompleteparticle,infectiveHBVspherical，doublecapsid球形,双层衣壳。outercapsid=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) HB
8、sAg等等 innercapsid内衣壳：内衣壳： HBcAg、HBeAginternal内部：DNA- circular, double- stranded环状双链环状双链DNApolymerase多聚酶HBV的小球形颗粒HBsAg-containingparticles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 HBVa 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 seve
9、n polypeptides. 含含4个个ORF,编码编码7个蛋白个蛋白S HBsAg,Pre-s1,Pre-s2C HBcAg，HBeAgP polymerase多聚酶多聚酶X HBxAg基因基因Antigen of HBV抗原组成lhepatitis B surface antigenHBsAghepatitis B surface antigenHBsAg外表抗原外表抗原lindicates that virus replication is occurring in the indicates that virus replication is occurring in the liv
10、erliverl 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lfour phenotypesfour phenotypes：adr,adw,ayr,aywadr,adw,ayr,aywlantiantiHBs:neutralization antibodyHBs:neutralization antibody中和抗体中和抗体lhepatitis B core antigen HBcAghepatitis B core antigen HBcAg核心抗原核心抗原lnot found in bloodnot found in blood一般不能检出一般不能检出lantiant
11、iHBc nonHBc nonneutralization antibodyneutralization antibody非中和抗非中和抗体体lCore IgM indicates recent infection. Core IgM indicates recent infection. 抗抗HBc IgMHBc IgM说明说明HBVHBV复制复制lCore IgG indicates exposure to HBVCore IgG indicates exposure to HBVAntigen of outer capsid外衣壳抗原外衣壳抗原Antigens of inner caps
12、id内衣壳抗原内衣壳抗原lhepatitis B e antigen ehepatitis B e antigen e抗原抗原HBeAgHBeAglthe best correlate to the presence of the best correlate to the presence of infectious virus. infectious virus. 感染性病毒存在的最有效感染性病毒存在的最有效证据复制及具传染性的标志证据复制及具传染性的标志lanti-HBe indicates low infectivity in a anti-HBe indicates low infe
13、ctivity in a carriercarrierl 抗抗HBeHBe说明病毒感染性较低是预后良好的说明病毒感染性较低是预后良好的征象征象lculture培养lresistance抵抗力strongresistancetocool,dry,ultraviolet,alcoholinactivate:100 10minPathogenesis and Immunity source of infection传染源传染源 patients or carriers 急性、慢性患者或无病症急性、慢性患者或无病症HBsAg携带者携带者route of transmission传播途径传播途径 sex
14、ual routes parenteral肠胃外的肠胃外的 routes injection of the virus into the blood stream contaminated 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 contact with the mothers blood at birth and in mother milk Pathogenesis of HBV致
15、病性lCell-mediated immunity (liver injury)lImmune complexes ( HBsAg + anti-HBs) : development of hypersensitivity reactions (other organs injuryl infants infected perinatally become chronic carriers Clinical Findings lAcute infection急性感染急性感染lFulminant hepatitis爆发型肝炎爆发型肝炎 lChronic infection 慢性感染慢性感染lPr
16、imary hepatocellular carcinoma PHC原发性肝细胞癌原发性肝细胞癌 Acute infection lalongincubationperiodandaninsidiousonsetlprodromalperiod前驱期:fever,malaise不适,anorexia食欲缺乏,nausea,vomiting,abdominaldiscomfort,chillslclassicicteric黄疸symptomsofliverdamagelRecoveryFulminant hepatitis爆发型肝炎爆发型肝炎 loccursinapproximately1%of
17、ictericpatientsandmaybefatal1%黄疸病人，可致死lsevereliverdamage,suchasascitesandbleeding肝严重受损，腹水，出血Chronic infection lelevatedliverenzymelevels转氨酶水平高l10%ofpatientswithchronichepatitismaydevelopcirrhosisandliverfailurel10%可开展为肝硬化和肝衰竭lmajorsourceforspreadofthevirus主要传染源latriskforfulminantdiseaseiftheybecomec
18、o-infectedwithHDVPrimary hepatocellular carcinoma PHC原发性肝细胞癌原发性肝细胞癌 lpromotingcontinuedliverrepairandcellgrowthinresponsetotissuedamagelintegratingintothehostchromosomeandstimulatingcellgrowthdirectlyLaboratory Diagnosis乙肝乙肝“两对半及临床意义两对半及临床意义 lHBsAg、 抗抗HBslHBeAg、 抗抗HBelHBcAg 抗抗HBc HBVHBV抗原抗体系统检测临床意义抗
19、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 PreventionlControlthesourceofinfection控制传染源lCutdowntherout
20、eoftransmission切断传播途径lPassiveimmunization-HepatitisBimmuneglobulinHBIg抗-HBs人血清球蛋白lActiveimmunizationslHBsAgvaccinelNospecifictreatmenthepatitis C virus,HCV丙型肝炎病毒predominant cause of non A non B hepatitis Biological properties生物学性状lamemberoftheflavivirus黄病毒属成员l4060nm,spherical球形lanenvelopedvirion有包膜l
21、Genome:(+)ssRNAPathogenesis and Immunity致病性与免疫性lsixgenotypes基因型：、ltransmittedbymeanssimilartoHBVl传播途径似HBVlininfectedblood输血后肝炎lIntravenousdrugabusersltransfusionlorganrecipientslhemophiliacsreceivingfactorsorlsexuallyPathogenesispersistent,chronichepatitiscirrhosis肝硬化，hepatocellularcarcinoma肝癌lacute
22、hepatitis15%lchronicpersistentinfection70%lsevererapidprogressiontocirrhosis15Laboratory diagnosislELISArecognitionofantibodylgenetictechniquestodetectHCVRNAlTreatment防治原那么lNovaccine尚无可用疫苗lRecombinantIFN-aloneorwithribavirinl病毒唑hepatitis D virus，HDV丁型肝炎病毒ladefectivevirusthatacquiresanHBsAgcoatfortra
23、nsmissionHDV是缺陷病毒，需以HBsAg构成其衣壳来传播lcircular,single-strandedRNAmoleculesandaninternalcoreantigen(HDAg)单负链环状RNA和抗原HDAgPathogenesislspreadbythesameroutesasHBV:blood,semen,andvaginalsecretions传播途径与HBV相同：血液，精液，阴道分泌物lincreasestheseverityofHBVinfections:Fulminanthepatitis加重HBV感染：爆发性肝炎Coinfection联合感染Superinf
24、ection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
25、毒lspherical,non-enveloped,and27-34nm球形，无包膜，lapositive-sense,single-strandRNAgenome单正链RNAlspreadbythefecal-oralroute为粪口途径传播lsymptomsandcourseofHEVdiseasearesimilartothoseofHAVdiseasel病症病程类似HAVlAcutehepatitis，mortalityrate:1%to2%lespeciallyseriousinpregnantwomen(mortalityrateofapproximately20%)孕妇感染严重,
26、病死率高达20%Diagnosis 微生物学检查lHEV：EMorIEM电镜或免疫电镜lAnti-HEVIgMlHEVRNA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
