传染病学英文版课件：viral hepatitis2

ViralhepatitissynopsisViralhepatitisisagroupsystemicinfectionaffectingtheliverpredominantlycausedby5kindsofvirusesatleastViralhepatitismaybedividedinto5typesaccordingtoetiology,thatishepatitisA,B,C,DandEAlthoughtheagentscanbedistinguishedbyitsantigenicproperties,the5kindsofvirusesmayproduceclinicalsimilarillnessSynopsisClinicalmanifestationsarecharacterizedbyanorexia,nausea,lassitude,enlargedliverandabnormalliverfunction,apartofcasesmayappearjaundice.SubclinicalinfectioniscommonHepatitisAandEshowsacutehepatitis,hepatitisB,CandDpredisposetoachronichepatitisandisrelatedtolivercirrhosisandhepaticcancerThecourseofacutehepatitisisabout2-4monthsgenerally.Recently,2kindsofvirusesnamedHGVandTTVarediscoveredandconsideredtorelatetoviralhepatitisEtiologyHepatitisAvirus(HAV)HAVisonekindofpicornavirusandusedtobeclassifiedasenterovirustype72,butrecently,itisconsideredtobeclassifiedasheparnavirusHepatitisAvirionisanakedsphericalparticle,diameter27nmConsistsofagenomeoflinear,single-strandedRNA,7.5kb.Thegenomemaybedividedinto3codingregion:P1region(encodingstructuralprotein),P2andP3regions(encodingnon-structureprotein)Duringacutestageofinfection,HAVcanbefoundinbloodandfecesofinfectedhumanandprimatesMarmosetandchimpanzeearesusceptibleanimalsEtiologyHepatitisAvirus(HAV)HAVcannotcausecytopathy,replicatewithincytoplasmaofhepatocytesandviabillaredischargedwithfeces7genetypes,1,2,3,7typesfromhumanbodyOnlyoneantigen-antibodysystem.Anti-HAVIgMisdiagnosticevidenceofrecentinfection,IgGisprotectiveantibody.ResistanceofHAV:56°C,30min,usuallytemperature1week,dryfecesat25°C30days,freshwater,seawater,shellfishorsoilforseveralmonths.70%alcoholat25°C,3min,100°C,5minandultraviolet,1minHAVEtiologyHepatitisBvirus(HBV)HBVisakindofhepadnavirusThreeparticlesinserum:

sphericalparticlesandtubularparticleswithadiameterof20nm,composedofHBsAg

largeparticleswithadiameterof42nm,namedDaneparticle.Itconsistsofanouterproteinshell(envelope,containHBsAg)andaninnerbody(core,containHBcAg,HBeAg,HBV-DNAandDNAP)EtiologyHepatitisBvirus(HBV)HepatitisBviriongenomeisasmallcircular,partiallydoublestrandedDNAwith3200nucleotideslong.HBVDNAisasymmetryinlengthoftwostrands:minusstrand(longstrand,L)hasfulllength.Fouropenreadingframes(ORF)codedontheminusstrand:C,S,X,andPregionHBV大球形颗粒管形颗粒小球形颗粒EtiologyHepatitisBvirus(HBV)Fouropenreadingframes(ORF)Sregion:includepre-s1,pre-s2andSgene,encodedpre-s1protein,pre-s2proteinandHBsAg.Pre-s1protein+pre-s2protein+HBsAg—largeproteinPre-s2protein+HBsAg—middleprotein

HBsAg—majorproteinCregionincludedpre-candCgene,encodeHBeAgand

HBcAg

XregionencodedHBxAg

PregionencodedDNApolymerase

etiologyThreeantigen-antibodysystem

HBsAg--anti-HBssystem:IncludeHBsAg,anti-HBs,pre-s1,s2antigenandanti-pres1,s2HBsAgappears1-2weeks(lateto11-12weeks)afterexposure,persistsfor1-6weeks(even5months)inacutehepatitisB.Inchronicpatientsorcarrier,HBsAgpersistmanyyearsHBsAg

antigencitybutnoinfectivityHBsAgisthemarkerofinfectivityHBsAgcanbefoundinhumorsandsecretions:salive,urine,semina,tears,sweatandbreastmilk10subtypeofHBsAg,4majorsubtypes:adr,adw,ayr,ayw.Anti-HBsappearafterHBsAgdisappearseveralweeks(ormonths)anti-HBsisprotectiveantibody,canpersistformanyyearspre-s1andpre-s2antigensappearfollowingHBsAg.Theyarethemarkerofinfectivity.Anti–pres2hastheactionofclearingvirusEtiologyHBcAg—anti-HBcsystemHBcAgcanbefoundinthenucleioflivercells,nofreeHBcAginserumHBcAgisthemarkerofreplicationofHBVThestagecalledwindowphaseAnti-HBc

IgMisamarkerofacuteinfectionandacuteattackofchronicinfectionofHBV.Anti-HBc

IgGisthemarkerofpastinfection,hightitermeanslowlevelreplicationofHBVEtiologyHBeAg—anti-HBesystemHBeAgisasoliableantigenHBeAgisareliableindicatorofactivereplicationofHBVAnti-HBeisamarkerofreducedinfectivity.IfexistlongmaybeamarkerofintegrationofHBVintolivercellEtiologyThemarkerofmolecularbiologyofHBVHBV-DNAThedirectindicatorofHBVinfectionCanintegrateintothegenomeofhepatocytesHBVDNApolymerasePossessestheabilityofreversetranscriptaseandtheindicatoroftheabilityofreplicationofHBVEtiologyHBxAg

Relatedtochronicity,activityofhepatitisBorlivercancerResistance

Resistanttoheatingandcommondisinfections.ChimpanzeeissusceptibletoHBVEtiologyHepatitisCvirus(HCV)HCVisamemberofflavivirusfamily.HCVgenomeisasinglestrandedpositive-senseRNAandcontains9.4kbThegenomecontains5’-noncodingregion,Cregion,EregionandNSregionHCVgenomemaybedividedintomanytypesandsubtypes.ResistanceAntigen-antibodysystemTheconcentrationofHCVinbloodislow,HCVAghasnotbedetected,anti-HCVistheindicatorofinfectionandthemarkerofinfectivityHCV-RNA

HCV-RNAmaybedetectedfrombloodorlivertissue,it’sthedirectevidenceofinfectivityHCVEtiologyHepatitisDvirus(HDV)HDV(Deltahepatitisvirus)isakindofdefectivevirusHDVisfoundinthenucleiofinfectedhepatocytesandreplicateHDVgenomeisacircularsinglestrandRNAandcontains1.7kbThereplicationofHDVdependsonHBVorotherhepadnavirus,coatedbyHBsAginbloodHDVhasoneantigen-antibodysystemNofreeHDAgisdetectedinblood,it’sinthenucleiofhepatocytes;anti-HDVcanbedetectedbyRIAorELISAinserumHBVandHDVco-infectionorsuperinfectionmaymakethediseaseexacerbationandmayleadtofulminanthepatitisHDVRNAmaybedetectedfromlivercells,bloodorhumor.ResistanceEtiologyHepatitisEvirus(HEV)HEVisamemberofcalicivirusfamily.HEVisasphericalnuenveloped

icosahedralparticles.HEVgenomeisasinglestrand,positive–senseRNA(7.5kb),includestructureandnon-structureregionThreeORFORF-1:encodingnon-structureproteinORF-2:encodingneucleocapsideproteinORF-3:encodingapartofneucleocapsideprotein2subtypeofHEVfounded:BurmasubtypeandMexicosubtype;orepidemicstrainandsporadicstrainHEVreplicationwithinhepatocytesandviabilltractisdischargedMonkeysandchimpanzeearesusceptibletoHEVOneantigen-antibodysystemHGV,TTVHEVEpidemiologySourceofinfectionHepatitisAandE:patientswithacutehepatitisandpersonwithsublinicalinfectionHepatitisB,CandD:patientswithacute,chronichepatitisB,C,andDandcarriersRouteoftransmissionHepatitisAandE:fecal-oralroutepredominantlyEpidemiologyRouteoftransmissionHepatitisB,C,andD:humoraltransmission(parenteraltransmission)Mathertoinfenttransmission(verticaltransmission)SexualcontacttransmissionInsecttransmissionEpidemiologySusceptibilityandimmunityofpopulationHepatitisAMostadulthasanti-HAVduetocovertinfection.Infentunder6monthacquiredantibodyfrommother.YoungchildrenissusceptibleHepatitisBInfentsaresusceptibletoHBafterboring.HBVinfectiondevelopedininfentschildrenandteenagesHepatitisCPopulationiscommonsusceptible.Anti-HCVisnotprotectiveantibody.HepatitisDCommonsusceptibleHepatitisECommonsusceptible.Childrenappearcovertinfection,adultshowovertinfectionEpidemicfeatureSporadicoccurrenceHepatitisA:sporadicoccurrencemayseenindevelopingcountriesofhighepidemicareaHepatitisB:sporadicoccurrenceismajormodeofonsetforHB.,thereisfamilyclusteringphenomenonwhichisrelatedwithverticalinfectionHepatitisC:non-transfusionHCiscalledsporadicHCbymothertoinfantorlifeCONTACTTRASMISSIONHepatitisE:innon-epidemicarea,HEissporadicoccurrenceOutbreakepidemicDuetofoodandwaterarecontaminatedleadtooutbreakofHAandHESeasonaldistributionHA:mostcasesdevelopedinautumnandwinterHE:mostcasesdevelopedinsummerandautumnGeographicdistributionHA:geographicdistributionisnotobviousHB:maybedividedintothreeareasHighepidemicarea:HBsAgcarrierrateis8-20%Moderateepidemicarea:HBsAgcarrierrateis2-7%Lowepidemicarea:HBsAgcarrierrateis0.2-0.5%HC:nodifferentinfectionrateHD:worldwidedistributionHE:developingcountriesaremajorepidemicareassuchasAsia,AfricapathogenesisHepatitisA:HAVinvadeintohumanbodybymouthandcauseviremia.Afteroneweek,theHAVreachlivercellsreplicatewithin.Thenenterintestienwithbillandappearinfeces.someonebelievethatdamageoflivercellsmaybecausedbyimmuneresponse.Dueto:HAVdoesnotcausecytopathyAfterHAVreplicatinganddischarging,livercellsdamagebeginAnimalexperimentprovedthatimmunecomplexmayattendthepathogenesisofHAComplementlevelreducethepathogenesismaybefollowing:activatedTcellsecreteγ-INFthatpromotetherepresentationofHLA-Ⅰantigenonthelivercells,CTLmaykillthetargetcellinfectedwithHAVHepatitisB:HBVinvadeintothehumanbodybyskinandmucosa,viabloodflowentertheliverandotherorganssuchaspancreas,billduct,vessels,WBC,bonemarrow,glomerularbasementmembransHBcAg,HBsAg,HBeAgandHLA-ⅠappearonthelivercellsinfectedwitharerecognizedbyCTLsimultaneouslyandleadtothecytolysisoflivercellsHelpTcellareactivatedbythereceptorofHLA-ⅡonitssurfacecombingwithHBsAg,HBcAgandHLA-ⅡantigenontheBcellspromoteBcelltoreleaseanti-HBsandclearHBVTherepresentationofHBcAgonthelivercellsmaycausecytopethyHighdegreerepresentationofHBsAgwithinlivercellsbutthesecretionisnotenoughleadtoground-glass-likechangeoflivercellsAntigen-antibodycomplexprecipitatedonthewallofbloodvesselsandglomerularbasementmembranscausingnephritisornodusepolyarteritis,fever,rushandarthralgiacalledserumsick-likereactionTNF,IL-1,IL-6mayplayrolesinpathogenesisChronicityofhepatitisBisrelatedtoimmunetolerance,immunesuppressandgeneticfactorsHBVinfectionisrelatedtoHCCcloselyHepatitisCIssimilartothatofHB.CTLandsomecytokinesplayanimportantactionThechronicityisrelatedtothevariabilityofgeneHCVinfectionisrelatedtoHCCcloselybutHCVdoesnotintegratetolivercells,sofromHCVinfectiontoHCCmayberelatedtochronicinflammationandcirrhosisPathologyDegenerationNecrosisRegenerationInfiltrationofinflammatorycellsHyperplasiaofinterstitialcellsAcuteviralhepatitisThedegenerationoflivercellsinclude

ballooningdegeneration,fattydegeneration,

acidophilicdegenerationCellnucleusvacuolardegenerationFocalorspottynecrosisandregenerationTheinfiltrationofmononuclearcell,plasmocyte,lymphocyteinportalareaCholestasisandformofbilethrombasinbilecapillariesofliverPiecemealnecrosis

ChronicviralhepatitisMildchronichepatitisG1-2,S0-2Degeneration,spotty,focalnecrosis,acidophilicbodyPortalmayhaveornotheinfiltrationofinflammationcell,mildPNorenlargedThestructureisintactModeratechronichepatitis(CAH)Portalareahaveobviousinflammation,withmoderatePNSevereinflammationwithBNofintralobuleFormfibrousseptum,mostthestructureoflobulereservedSeverechronichepatitisPortalareahassevereinflammationwithseverePNBNofextensiverangeinvolvingseverallobulusMuchmorefibrousseptumsdistortionoflobulestructureorformearlylivercirrhosisFulminantviralhepatitis(hepatitisgravis)Acutehepatitisgravis:livercellsshowmassivenecrosisincludinggreatamongoflivercells.Necrosisandreticular

fibernetworkcollapse,sotheliverisgreatlyreduceinsize-acuteyellowhepaticetrophy

SubacutehepatitisgravisExceptmassivenecrosis,thereareball-likeregenerationoflivercellsNewconnectivetissuewhichformfibrousbandandseparatethelivercellsregeneratedformingpseudolobuliBilecapillarieshyperplasiaChronic

hepatitisgravis:baseonthepathologicchangesofchronichepatitisorlivercirrhosis,therearemassiveorsubmassivenecrosisoflivercellsCholestaticviralhepatitisTherearethechangesofacutehepatitisThereisobviouscholestasisInseverecases,thelivercellsmayappearglandularductlikePortalareashowsedemeandsmallbileductisdilationpathophysiologyJaundicethejaundiceismainlyhepatocyticjaundiceandpartobstructivejaundiceHepaticencephalopathy

RetentionoftoxicmaterialleadtopoisoningofCNSImbalanceofaminoacidFalseneurotransmitterhypothesisOtherevokedfactorsHemorrageDeficiencyofmanykindsofbloodcoagulatingfactors,DIC,thrombucytopenialeadtohemorrageAcuterenalfailure(hepatic-renalsyndrome)HepatopulmonarysyndromeAscites

ClinicalmanifestationIncubationperiodHA15-45days30daysHB30-180days70daysHC15-150days

50daysHDsimilartoHBHE10-70days40daysClinicaltypesAcute

viralhepatitisAcuteictericviralhepatitisAcuteanictericviralhepatitisChronicviralhepatitisMildchronicviralhepatitisModeratechronicviralhepatitisSeverechronicviralhepatitisHepatitisgravisAcutehepatitisgravisSubacutehepatitisgravisChronichepatitisgravisCholestaticviralhepatitisAcuteviralhepatitisAcuteictericviralhepatitis

thecausemaybe2-4monthsanddividedthreeperiodsPreictericperiodInHA,HE,theonsetisabruptwithfever;butHB,HC,theonsetisinsidious.Theinitialsymptoms:lossofappetite,nausea,vomitinglassitude,abdominalpainanddiarrhea.Theendoftheperiod,theurinedarkens.Afewpatients,especialchildren,fever,headache,upperrespiratorytractsymptomearemainmanifestationsThedurationofthisperiodvariesfrom1-21days,average5-7daysIctoricperiodTheurinedeepenscontinuouslyandjaundiceappearsontheskinandsclerawithin2weeksSubjectivesymptomsisabatePruritusmayappearabout1weekLiverpalpable7%,spleenpalpable20%Theperiodlasts2-6weeksConvalscentperiodThejaundicedisappeargradually,symptomsabateordisappearLiverandspleenretract,liverfunctionreturntonormalTheperiodlasts2weeksto4months,average1monthAbout10%ofHBand50%ofHCwillbecomechronichepatitisAcutehepatitisD:Co-infectionwithHBVSuper-infectionwithHBVAcutehepatitisEissimilartoacutehepatitisA,butcholestasisisobviousandsymptomsandsignsissevere.IfwomenwithpregnancysufferfromtheHE－－fulminanthepatitisIfHBsuper-infectHEVorHCV－－fulminanthepatitisAcuteanicterichepatitisAllof5kindsofhepatitisviruscancauseacuteanicterichepatitis.Thistypeismostcommon.ImportantsourceofinfectionChronicviralhepatitisOnlyappearinHBV,HCVandHDVinfectionMildchronichepatitisThecourseismorethanhalfyearFatigue,dizziness,digestivetractsymptoms,dullpainofliver,enlargedlivertendernessorspleentenderness,lowerdegreeoffever,ALT↑,thepathologychangehasonlymildThecoursemaypersistmanyyearsModerateThecourse→halfyearThesymptomareobviousSpidernevus,liverpalms,hepaticfaceDysfunctionofliverAccompanythelesionsofotherorgansandpresenceofautoantibodyReversetheratioofalbumin/globulinBiopsyshowthechangesofmildCAHSevereExceptsymptomsandsignsmentioned,thebiopsyshowthechangesofearlycirrhosisandclinicalmanifestationsofcompensatorycirrhosisHepatitisgravis

Alloffivekindsofhepatitisviruscancausethistypeofhepatitis.Theincidenceisonly0.2-0.5%,butthemortalityisthehighest.AcutehepatitisgravisTheonsetmaybegininatypicalacuteicterichepatitis,butwithin10daysJaundicedeepensrapidlyVomitisfrequentObviousanorexiaHemorrhageThelivershrinksinsizeToxicintestinaltympeniceProthrombintimeisprolongedAscitesappearAcuterenalfailureHepaticencephalopathySubacutehepatitisgravis

ThecourseofAIHismorethan10daysThehepaticencephalupathyappearlaterThecoursemaybeseveralmonthsThepostnecroticcirrhosismaydevelopChronichepatitisgravisBasedonchronichepatitisorcirrhosisdevelopedsubacutehepaticnecroticCholestatichepatitisIntrahepaticcholestaticjaundiceforalongtime(2-4monthsorlonger)PruritusPalefecesHepatomogaly

SubjectivesymptomsisslightCourse2-6monthsRecoveryiscompleteManifostationsofhepatitisforspecialpopulationCharacteristicsofhepatitisforchildCharacteristicsofhepatitisforthesenilityThecharacterofhepatitisofpregnancyperiodLaboratoryexaminationLiverfunctionSerumtransaminaseALT(alaninetransferase)↑AST(aspartasetransferase)↑ALP(Alkalinephosphatase)↑inchronichepatitisLDH(Lactatedehydrogenase)↑SerumproteinAlbumin↓InchronichepatitisIg↑↑The

ratioofA/G↓BilirubinUrobilinogen↑inearlystageofAIHUrobilinogenandurobilin↑inictericstageUrobilinispositiveandurobilinogenmaybenegativeincholestatichepatitisInAIH,thedirectivebilirubinandindirectivebilirubin↑ProthrombintimemaybeprolongedespeciallyinfulminanthepatitisBloodamoniaexaminationDetectionofthemarkersofhepatitisvirusHepatitisASerologicmarkerAnti-HAVIgM:recentinfectionAnti-HAVIgG:pastinfectionMarkeroffecesHAVparticlesmaybedetectedbyRIAorIEMIsolationofHAVmayusetissuecultureoranimalinoculationHepatitisBSero-immunologicmarkerHBsAganti-HBsHBcAganti-HBcHBeAganti-HbeMolecularbiologicalmarkerDNApHBVDNAImmunetissuechemistryexaminationHepatitisCSerologicalmarkerAnti-HCVIgMAnti-HCVIgGMolecularbiologicmarkerHCVRNAmaybedetectivebyRT-PCR1-2weeksafterinfectionofHCVQualityofHCVRNAImmunetissuechemistrymethoddetectHCAgwithinlivercellsHepatitisDHDAganti-HDVHDVRNAHepatitisEAnti-HEVIgG,Anti-HEVIgmRT-PCRHEVparticais:IFIEMUltra-soundexaminationLiverbiopsyOtherlaboratoryexamination

BloodroutineUrineroutineComplicationandprognosiHBInfectionofbiliarytract,pancreatitis,gastro-enteritisDiabetesHemolyticanemia,aplasticanemiaMyocarditis,polyarteritis,nodoseGlomerulo-nephritis,renaltubular,acidosisSkin:allergicpurpureCirrhosisHCCDiagnosisEpidemiologicaldataHA,HE:food,water,seasonal,ageHB,HC:

bloodandbloodproducttransfusion,contacthistory,inoculationhistoryClinicaldiagnosisAcutehepatitisChronichepatitisDegreeofdamageofliverItemmildmoderatesevere

ALT(u)<3X

3-10X