傳染病學Chapter25 肝炎病毒

Chapter25Hepatitisviruses

EBvirusCMVRubellavirusyellowfevervirushepatitisvirusesTypeofHepatitisVirusesitemHAVHBVHCVHDVHEVClassificationPicorna-viridaeHepadna-viridaeFlavi-viridaeDefectivevirusHepeviridaeDiameter(nm)274255-653632Nucleicacid+ssRNADsDNA+ssRNA-ssRNA+ssRNA

Sourceofvirusfecesblood/blood-derivedbodyfluidsblood/blood-derivedbodyfluidsblood/blood-derivedbodyfluidsfecesRouteoftransmissionfecal-oralBloodtransfusion,VerticalBloodtransfusion,Verticalfecal-oralChronicInfectionCarcinomaNoNoYesYesYesYesYes------NoNoPrevention

inactivatedvaccineAttenuatedlivingvaccine

subunitvaccineblooddonorscreening;riskbehaviormodification

AbriskbehaviormodificationensuresafedrinkingwaterTypeofHepatitisVirusesABCDEBloodtransfusion,VerticalSection1HepatitisAvirus(HAV)HAV:APicornavirus,nowclassifiedasaHeptoVirus,FormerlyknownasEnteroVirus72.I.BIOLOGICALPROPERTIESShape:sphericalSize:27~32nm

Symmetry:icosahedralNon-enveloped+ssRNA,7500bp

OneserotypeHepatitisAVirus

Chimpanzeeandmarmosetaresusceptible.

Culture:Difficult,noCPE,growslowly. Stable:resistanceto60℃4h,pH=3.

inactivatedat100℃5min.

Sourceofinfection:Patients,subclinicalinfectedPersons.

Transmission:fecal-oralroute.(fromfecallycontaminatedwaterorfood).

Childrenarethemostfrequentlyinfectedgroup.Pathogenicmechanism:

HAVMouthIntestineBloodLiverPathogenesisDiagrammaticRepresentationCLINICALFEATURES

IncubationPeriod:

Average30daysRange15-50daysJaundicebyagegroup:<6yrs<10%6-14yrs40%-50%>14yrs70%-80%

Outcome:FulminanthepatitisAcutehepatitis

Chronicsequel:NoneSHANGHAI1988Over300,000peoplewereinfectedwiththevirusresultedfromeatingclamsobtainedfromapollutedwaterMICROBIALDETECTION

Detectanti-HAVIg:AcuteinfectionisdiagnosedbythedetectionofHAV-IgMinserum.PastInfectioni.e.immunityisdeterminedbythedetectionofHAV-IgG.CONTROL

γ-Globulinforurgentprevention.

Vaccine:InCHINA,attenuatedlivingvaccinesarecommonlyused. InUSA,Inactivatedvaccinesarecommonlyusedattenuatedlivingvaccine

Section2HepatitisBvirus(HBV)HepatitisBvirus(HBV)

Globally,morethan370millionpeoplearechronicallyinfectedwithHBVandabout75%ofthemareAsian.ⅠBiologicalproperties1.Threedifferentparticles:

Daneparticle:intactvirion,42nm,infectious.Smallsphericalparticle:22nm,carryHBsAg.Tubularparticle:consistsofHBsAg.

2.structure:

Core:1)

incompletecirculardsDNA(3200bp):thelongstrandiscomplete,variablelengthoftheshortstrand.2)DNApolymerase

layercapsids:innercapsid:icosahedral,carryHBcAg(HBeAg)outercapsid:carryHBsAg,pre-SAg.innercapsiddsDNApolymerasePreS2PreS13.GeneandencodedproteinsS,C,P,Xregions,locatedinthelongstrand.Sregion:HBsAg,Pre-S1protein,Pre-S2protein.Cregion:HBcAg,HBeAg.Pregion:DNApolymerase(bothRNA-dependentandDNA-dependentactivity).Xregion:Xprotein.mainproteinofHBsAg:HBsAg

middleprotein:HBsAg+PreS2AgLargeprotein:HBsAg+PreS2+PreS14.Replication:TherearesomeparallelsbetweentheHBVandtheretroviruses.(reversetranscription)5.Ags&Abs

1)HBsAg:4subtypes:adr,adw,ayr,ayw;aywpredominatesinN.Europe,N.AmericaandAustralia;

adrinChinaandJapan

HBsAg(+):

indicatesthatthepatientisinfectedwithHBV,eitherasarecentacuteinfectionorasacarrier;

anti-HBs:

protective.pre-S1Agandpre-S2Ag:

*berelatedtotheadsorptionofvirus;*enhancetheantigenicityofSprotein.anti-pre-S1:protective,neutralizingAbanti-pre-S2:protective,neutralizingAb2)HBcAg:

noteasilydetectiveinserumanti-HBc:notprotective

anti-HBc(+):

viralmultiplication,activeinfection,infectious.

3)HBeAg:

CgeneandpreCgeneencodeHBeAgproteinLiesininnercapsidAndeasilydetectedinserumvariableHBeAg(+):

viralmultiplication,activeinfection,infectious.

anti-HBe（+）:

viralmultiplicationandactiveinfectionarereduced,haslessinfectiousHBxAg:

associatedwithcancer.6.Cannotgrowinanycellculture.7.Resistancestable60℃1h,100℃10min.Ⅱ.Pathogenesis&immunity1.Sourceofinfection:patients,HBsAg-carrier(WhohasHBsAgpersistingintheirbloodforatleast6months).2.Transmissionway:①Bybloodorbloodproducts;②Verticaltransmission:frommothertochild(duringbirthorbreastfeeding);③Sexualtransmission.ConcentrationofHepatitisBVirusinVariousBodyFluidsHighModerateLow/NotDetectablebloodsemenurineserumvaginalfluidfeceswoundexudatessalivasweattearsBreast

milk3.Mechanismofpathogenesis:

1)immunopathologicalreactions:*Cell–mediatedhypersensitivity*Antibody-mediatedhypersensitivity*Autoimmuneinjury(LSP)

2)immunetolerance

lowcytoimmunityandhumoralimmunity----immunetolerance----HBVcarrierorchronicinfection3)Variation

“a”epitopemutation---diagnosticescape

HBVpreCmutation----HBeAgnegative----immunalescape

Cmutation---HBcAgvariation---CTLescapemutantPmutation---drugresistance4)HBVandhepatocellularcarcinomaⅢ.Microbiologicaldetection

1.DetectAgs&Abs:

HBsAg,anti-HBs,anti-HBc,HBeAg,anti-HBe.HBsAg-usedasageneralmarkerofinfection:patients,HBV-carrierHBsAb

-usedtodocumentrecoveryand/orimmunitytoHBVinfection.

anti-HBcIgM-markerofacuteinfection.anti-HBc

IgG-pastorchronicinfection.HBeAg-indicatesactivereplicationofvirusandthereforeinfectiveness.Anti-HBe-viralmultiplicationandactiveinfectionarereduced,haslessinfectious2.HBVDNA

HBV-DNA-indicatesactivereplicationofvirus,moreaccuratethanHBeAgespeciallyincasesofescapemutants.Usedmainlyformonitoringresponsetotherapy.3.SeraDNApolymerase

Ⅳ.ControlVaccination-highlyeffectiverecombinantvaccinesarenowavailable.Vaccinecanbegiventothosewhoare:1)Healthcareworkers2)Sexualpartnersofchroniccarriers3)InfantsofHBVcarriermothersSerumderived-preparedfromHBsAgpurifiedfromtheserumofHBVcarriers

Recombinant

HBsAg

-madebygeneticengineeringinyeastsHepatitisBImmunoglobulin-HBIgmaybeusedtoprotectpersonswhoareexposedtohepatitisB.Othermeasures-screeningofblooddonors,bloodandbodyfluidprecautions.Ⅴ.TreatmentInterferon

-forHBeAg+carrierswithchronicactivehepatitis.Responserateis30to40%.Lamividine-anucleosideanaloguereversetranscriptaseinhibitor.

SuccessfulresponsetotreatmentwillresultinthedisappearanceofHBsAg,HBV-DNA,andseroconversiontoHBeAg.

Section3HepatitisCvirus(HCV)

HepatitisCvirus(HCV)

+ssRNA,lipo-enveloped.Cannotculture.

easyvariation.Transmission:transmittedmainlybybloodandbloodproducts.HCViscloselyrelatedtohepatoma.

Microbiologicaldetection:

Detectanti-HCV;DetectviralRNA:RT-PCR.Control:Neitheractivenorpassiveimmunizationisavailable.

Section4HepatitisDvirus(HDV)HepatitisDvirus(HDV)

1.Spherical,35-37nm.2.–ssRNA,circle,1700bp.

OutercapsidisHBsAg.

3.Oneserotype.4.Defectivevirus.HBsAg

antigenRNA5.HumanandchimpanzeearesusceptibletoHDV.6.Transmission:sameasHBV.7.Infeciousmode:CoinfectionSuperinfection8.DetectHDAg&anti-HDV.Coinfection:

OccurswhenapersonbecomesinfectedsimultaneouslywithHBVandHDV.Themostcommonoutcomeiscompleterecoveryandclearanceofbothviruses.Inlessthan5%ofcases,patientsdevelopchronicinfections.Inabout1%ofcases,infectionresultsinfulminanthepatitis.

Superinfection:

OccurswhenapersonwhoisalreadyseropositiveforHBVbecomesinfectedwithHDV.Itisassociatedwithmoresevereclinicaloutcomesthanco-infectionwithHDV.Fulminanthepatitisdevelopsinabout5%ofcases.80-90%ofinfectionswillbecomechronic,increasingtheratewithwhichpatientsdevelopcirrhosis.Thechanceofdevelopinghepatocellularcarcinoma(livercancer)alsoincreases.

Section5HepatitisEvirus(HEV)HepatitisEVirus1Spherical,27-38nm,non-enveloped.2+ssRNA,7.5kb.3Notstable.4culture.:difficult5Transmission:fecal-oralroute.6Mainlyinvolveyounganda