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1、單擊此處編輯母版標題樣式,單擊此處編輯母版文本樣式,第二級,第三級,第四級,第五級,,,*,Medical Microbiology,Department of Microbiology, HMU,,,第37章 肝炎病毒,Hepatitis viruses,微生物學教研室 凌 虹,第二篇 致病性細菌,,,教學大綱,掌握內容,肝炎病毒的種類,乙型肝炎病毒形態(tài)結構、致病性、預防原則,熟悉內容,丁型肝炎病毒結構特征及致病特點,戊型肝炎病毒傳播途徑及致病特點,,,問題,肝炎病毒有哪些？,甲型肝炎病毒,的傳播方式、致病特點和預防原則,簡述,乙型肝炎病毒,的生物學性狀、,抗原抗體組成,及檢

2、出的意義、傳播方式、致病特點及預防原則,丙型肝炎病毒,的生物學特點和致病特點,丁型肝炎病毒,（HDV）的概念,簡述,戊型肝炎病毒,傳播方式和致病特點,,,肝炎病毒（Hepatitis virus）,以侵害肝臟為主引起病毒性肝炎的病毒,種類：,甲型肝炎病毒（,HAV,）、乙型肝炎病毒（,HBV,）、丙型肝炎病毒（,HCV,）、丁型肝炎病毒（,HDV,）、戊型肝炎病毒（,HEV,）、GBV-C/HGV、TTV,其他病毒,黃熱病毒、CMV、EBV、風疹病毒等,,,Viral Hepatitis - Historical Perspectives,,A,“,Infectious”,“,Serum”,V

3、iral hepatitis,Enterically,transmitted,Parenterally,transmitted,F, G, TTV,? other,E,NANB,B,D,C,,,Hepatitis A virus,1973年Feinstone,應用免疫電鏡技術從急性肝炎患者糞便發(fā)現(xiàn),生物學性狀與腸道病毒一致,1982年國際病毒命名委員會將它分類為小核糖核酸病毒科腸道病毒屬72型,,,Anti-HAV Prevalence,High,Intermediate,Low,Very Low,Geographic Distribution of HAV infection,,,生物學性狀

4、,HAV為球形顆粒，直徑27～32nm，無包膜。基因組為線狀單正鏈RNA,,,由VP1～4四種多肽組成,VP1是主要衣殼蛋白和中和抗原，能中和所有HAV,細胞培養(yǎng)：HAV可用猴腎、人胚腎細胞等進行增殖和傳代，但不引起CPE,易感動物有黑猩猩、南美洲猴、獼猴等,接種后可出現(xiàn)急性肝炎,抵抗力：較強,對乙醚、酸、熱（60,o,C）穩(wěn)定。高壓、紫外、煮沸等可滅活,,,流行,病,病學,傳染,源,源,患者,和,和隱,性,性感,染,染者,傳播,方,方式,：,：糞－,口,口途,徑,徑,污染,食,食物,、,、水,源,源、,海,海產,品,品引,起,起暴,發(fā),發(fā)或,散,散發(fā),流,流行,隱性,感,感染,率,率高,成人

5、HAV抗,體,體陽,性,性率,高,高達70%—90%,,,致病,性,性,非溶,細,細胞,型,型病,毒,毒，,不,不直,接,接殺,傷,傷細,胞,胞,病毒,復,復制,量,量與,癥,癥狀,嚴,嚴重,程,程度,不,不一,致,致，,故,故認,為,為免,疫,疫應,答,答參,與,與損,傷,傷過,程,程,病后,期,期糞,便,便可,檢,檢出sIgA,抗,抗體,無慢,性,性病,例,例,典型,的,的甲,肝,肝是,自,自限,過,過程,，,，大,約,約三,個,個月,,,甲型,肝,肝炎,血,血清,學,學變,化,化過,程,程,,,SourcesofHAVInfection1983-93,PercentageofCases,

6、Source:CDC,ViralHepatitisSurveillanceProgram,Year,Personalcontact,Daycarecenter,Foreigntravel,Outbreak,Druguse,40,30,20,10,0,1983,1984,1985,1986,1987,1988,1989,1990,1991,1992,1993,,,ConcentrationofHAVinVariousBodyFluids,Source:ViralHepatitisandLiverDisease1984;9-22,JInfectDis1989;160:887-890,Feces,S

7、erum,Saliva,Urine,10,0,10,2,10,4,10,6,10,8,10,10,InfectiousDosesperml,,,Age-specificIncidenceofHepatitisA1983-93,Source:CDC,NationalNotifiableDiseasesSurveillanceSystem,Year,ReportedCases(per100,000),1983,1984,1985,1986,1987,1988,1989,1990,1991,1992,1993,0,5,10,15,20,25,5-14years,15-24years,25-39yea

8、rs,0-4years,40+years,,,Endemicity,Disease,Rate,PeakAge,ofInfection,TransmissionPatterns,High,Lowto,High,Early,childhood,Persontoperson;,outbreaksuncommon,Moderate,High,Late,childhood/,youngadults,Persontoperson;,foodandwaterborne,outbreaks,Low,Low,Youngadults,Persontoperson;,foodandwaterborne,outbre

9、aks,Verylow,Verylow,Adults,Travelers;outbreaks,uncommon,GlobalPatternsofHepatitisAVirusTransmission,,,,診斷（,LaboratoryDiagnosis,）,）,Acuteinfectionis diagnosed by thedetectionof HAV-IgM inserumby EIA,PastInfectioni.e.immunity is determined bythedetectionof HAV-IgGby EIA,,,防治原則,加強食品衛(wèi),生,生管理，水,源,源,減毒疫苗株H

10、2株和L1株已投放,市,市場,基因工程疫,苗,苗也正在研,究,究之中,應急預防可,用,用丙種球蛋,白,白,,,Manycasesoccur incommunity-wideoutbreaks,no risk factoridentifiedformostcases,highest attackratesin 5-14 year olds,children serveas reservoir ofinfection,Persons atincreasedriskof infection,travelers,homosexualmen,injectingdrugusers,,HepatitisA

11、Vaccination Strategies,Epidemiologic Considerations,,,Pre-exposure,travelersto intermediateandhighHAV-endemic regions,Post-exposure (within 14days),Routine,householdand otherintimate contacts,Selected situations,institutions (e.g.,day care centers),common source exposure (e.g.,foodprepared by infect

12、edfoodhandler),HepatitisA Prevention,- Immune Globulin,,,Group,Age,No.,Doses,EL.U.* (ml),Schedule,(months),Children and,adolescents,2-18years,3,360 (0.5),0, 1,6-12,Adults,>18 years,2,1,440(1.0),0, 6-12,Doses,HAVRIX,a,*ELISA units,Recommended Doses &Schedulesof HAV Vaccination,,,HapatitisB Virus,1963

13、年Blumberg在多,次,次輸血的血,友,友病患者中,發(fā),發(fā)現(xiàn)澳抗，1968年,確,確與血清型,肝,肝炎高度相,關,關，1970年Dane在電鏡下,看,看到具有傳,染,染性的42nm病毒顆,粒,粒,HBV在,亞,亞洲廣泛,流,流行，在,中,中國約10%人口,攜,攜帶該病,毒,毒，全球,約,約3.5,億,億,,,1983,年,年將HBV及與其,分,分子結構,、,、生物學,特,特性相似,的,的土撥鼠,肝,肝炎病毒(woodchuck hepatitisvirus,WHV)、,地,地松鼠肝,炎,炎病毒(ground squirrelhepatitis virus,GSHV)及鴨肝,炎,炎病毒(du

14、ckhepatits virus,DHV),歸,歸納起來,獨,獨立命名,為,為嗜肝病毒,科,科（Hepadnaviridae,）,）,,,HBsAg Prevalence,3,8% -High,2-7%- Intermediate,<2%- Low,Geographic Distributionof Chronic HBV Infection,,,形態(tài)與結,構,構,,,電鏡檢查,血,血清標本,可,可見小球,形,形顆粒（22nm,）,）、管形,顆,顆粒（22nmx50—700nm,）,）、大球,形,形顆粒（42nm,）,）,,,,,完整的HBV顆粒,亦,亦稱Dane顆粒,，,，顆粒直,徑,徑為4

15、2nm,具有雙層,衣,衣殼結構,。,。外殼相,當,當于包膜,，,，由脂質,雙,雙層和乙,肝,肝表面抗,原,原（HBsAg）,、,、多聚人,血,血清白蛋,白,白受體（PHSA-r）和,前,前S抗原,（,（Pre-S）組,成,成。內部,有,有28nm的核心,，,，表面相,當,當于內衣,殼,殼，含有,乙,乙型肝炎,核,核心抗原,（,（HBcAg）和,乙,乙型肝炎e抗原（HBeAg）。內,部,部有HBV的DNA和DNA多聚酶,,,HBV,基,基因組,DNA是,由,由3.2KB的長,鏈,鏈 L（-）和短,鏈,鏈 S（+）（約,為,為L鏈的50%至85%長,）,）組成的,不,不完全雙,鏈,鏈環(huán)狀DNA，長

16、,鏈,鏈載有病,毒,毒蛋白質,的,的全部密,碼,碼，有4,個,個開放讀,碼,碼框架(ORF),，,，分別稱,為,為S、C,、,、P和X,區(qū),區(qū),,,,,HBV復,制,制周期,,,,,HBVReplication,HBV,2.4KB,3.5KB,Provirus,RT,Replicate,Nuclear,2.1KB,,,抗原組成,HBV表,面,面抗原（HBsAg）,是機體受HBV感,染,染的標志,226AA，由S,基,基因編碼,HBsAg有1個,共,共同抗原,決,決定簇a,和,和2組互,相,相排斥的,亞,亞型抗原,決,決定簇d/y和w/r,4種亞型,：,：adr,、,、adw,、,、ayr,、,

17、、 ayw,我國內地,和,和沿海各,省,省漢族主,要,要為adr型，歐,美,美為adw,抗HBs,能與HBV表面結,合,合，使其,失,失去感染,性,性，具有,保,保護作用,,,HBV核,心,心抗原（HBcAg）,在肝細胞,核,核中才能,檢,檢出,分子量22KD，,由,由C基因,編,編碼，病,毒,毒內衣殼,蛋,蛋白,一般方法,在,在血中檢,測,測不到,抗HBc,無中和作,用,用,檢出高效,價,價抗HBc，特別,是,是抗HBc IgM表示HBV再肝,內,內處于增,殖,殖狀態(tài),,,HBVe,抗,抗原（HBeAg,）,）,由PreC和C基,因,因共同編,碼,碼，15KD,HBcAg在細胞,經,經蛋白酶

18、,降,降解形成,HBV復,制,制及血清,有,有傳染性,的,的標志,抗Hbe,對HBV,感,感染有一,定,定保護作,用,用,,,前S抗原,（,（Pre-S Ag）,,前S2蛋,白,白,S +PreS2編碼，226+ 55=281AA,前S1,蛋,蛋,白,白,S+PreS2+PreS1,編,編,碼,碼,，,，226+55+119=400AA,,與HBsAg,、,、HBVDNA,檢,檢,出,出,相,相,同,同,，,，,都,都,說,說,明,明,病,病,毒,毒,在,在,復,復,制,制,,,Pre-S2,抗,抗,原,原,和,人,人,肝,肝,細,細,胞,胞,表,表,面,面,都,都,具,具,有,有PHSA,受

19、,受,體,體,，,，,通,通,過,過PHSAr,搭,搭,橋,橋,，,，HBV,病,病,毒,毒,易,易,吸,吸,附,附,于,于,肝,肝,細,細,胞,胞,表,表,面,面,部,分,分,解,解,釋,釋,為,為,什,什,么,么HBV,具,具,有,有,嗜,嗜,肝,肝,細,細,胞,胞,性,性,,抗,前,前S1,和,和,抗,抗,前,前S2,抗,抗,體,體,具,有,有,中,中,和,和HBV,作,作,用,用,，,，,有,有,保,保,護,護,作,作,用,用,,,易,感,感,動,動,物,物,和,和,細,細,胞,胞,培,培,養(yǎng),養(yǎng),：,：,只,只,有,有,黑,黑,猩,猩,猩,猩,對,對HBV,易,易,感,感,，,，,體

20、,體,外,外,細,細,胞,胞,培,培,養(yǎng),養(yǎng),尚,尚,未,未,成,成,功,功,,,抵,抗,抗,力,力,：,：,強,強,對,低,低,溫,溫,、,、,干,干,燥,燥,、,、UV,、,、,醚,醚,、,、,氯,氯,仿,仿,、,、,酚,酚,等,等,均,均,有,有,抵,抵,抗,抗,性,性,高,壓,壓,蒸,蒸,汽,汽,滅,滅,菌,菌,、,、0.5%,過,過,氧,氧,乙,乙,酸,酸,、,、5%,次,次,氯,氯,酸,酸,鈉,鈉,、,、3%,漂,漂,白,白,粉,粉,液,液,、,、0.2%,新,新,潔,潔,爾,爾,滅,滅,均,均,可,可,滅,滅,活,活,病,病,毒,毒,，,，,但,但,處,處,理,理,時,時,間,間

21、,要,要,稍,稍,長,長,,,,Incubationperiod:Average60-90days,Range45-180days,Clinicalillness(jaundice):<5yrs,<10%5yrs,30%-50%,Acutecase-fatalityrate:0.5%-1%,Chronicinfection:<5yrs,30%-90%5yrs,2%-10%,Prematuremortalityfromchronicliverdisease:15%-25%,HepatitisB-ClinicalFeatures,,,SpectrumofChronicHepatitisBDisea

22、ses,ChronicPersistentHepatitis-asymptomatic,ChronicActiveHepatitis-symptomaticexacerbationsofhepatitis,CirrhosisofLiver,HepatocellularCarcinoma,,,High(>8%):45%ofglobalpopulation,lifetimeriskofinfection>60%,earlychildhoodinfectionscommon,Intermediate(2%-7%):43%ofglobalpopulation,lifetimeriskofinfecti

23、on20%-60%,infectionsoccurinallagegroups,Low(<2%):12%ofglobalpopulation,lifetimeriskofinfection<20%,mostinfectionsoccurinadultriskgroups,GlobalPatternsofChronicHBVInfection,,,,High,Moderate,Low/NT,blood,semen,urine,serum,vaginalfluid,feces,woundexudates,saliva,sweat,tears,breastmilk,ConcentrationofHe

24、patitisBVirusinVariousBodyFluids,,,,,,ModesofTransmissionofHBV,Sexual,sexualandhomosexualsareparticularatrisk,Parenteral,Intravenousdrugabuse(IVDA),HealthWorkersareatincreasedrisk,Perinatal,MotherswhoareHBeAgpositivearemuchmorelikelytotransmittotheiroffspringthanthosewhoarenot,Perinataltransmissioni

25、sthemainmeansoftransmissioninhighprevalencepopulations,,,傳染,源,源：,急,急、,慢,慢性,乙,乙肝,患,患者,及,及無,癥,癥狀,攜,攜帶,者,者,傳播,途,途徑,：,：非胃,腸,腸道,途,途徑,血液,、,、血,制,制品,傳,傳播,輸血,、,、丙,種,種球,蛋,蛋白,醫(yī)源,性,性傳,播,播：,注,注射,（,（吸,毒,毒）,、,、手,術,術、,采,采血,、,、針,刺,刺、,撥,撥牙,、,、內,窺,窺鏡,檢,檢查,、,、紋,身,身等,接觸,傳,傳播,：,：公,共,共衛(wèi),生,生潔,具,具、,剃,剃刀,、,、吸,血,血昆,蟲,蟲,母嬰,傳,傳

26、播,宮內,感,感染,相,相對,少,少（<10%,）,）,母親HBeAg陽,性,性嬰,兒,兒感,染,染機,會,會大,（,（90%,）,）,HBeAg陰,性,性、,抗,抗HBe,陽,陽性,嬰,嬰兒,感,感染,機,機率,小,?。?0%—15%）,,,*Includessexualcontactwithacutecases,carriers,andmultiplepartners.,Source:CDCSentinelCountiesStudyofViralHepatitis,Heterosexual*,(41%),HomosexualActivity,(9%),HouseholdContact(2%

27、),HealthCareEmployment(1%),Other(1%),Unknown(31%),Injecting,DrugUse,(15%),RiskfactorsforAcuteHepatitisB1992-1993USA,,,Source:CDCViralHepatitisSurveillanceProgram,0-14,15-19,20-29,30-39,40+,0,5,10,15,20,25,RateofReportedHepatitisBbyAgeGroup,USA1990,AgeGroup(years),Rate,(/100,000),,,Exposure,Infection

28、,Death1%,Fulminant,hepatitis,Recovery,90%-95%Immune,AsymptomaticCarrier,PersistentInfection,Chromichepatitis,Chronicactivehepatitis,Cirrhosis,Hepatocellularcarcinoma,,,致病,機,機理,尚未,完,完全,明,明了,HBV不,直,直接,損,損害,肝,肝細,胞,胞，,通,通過,宿,宿主,的,的免,疫,疫應,答,答引,起,起肝,細,細胞,的,的損,傷,傷和,破,破壞,,,細胞,免,免疫,損,損傷,細胞,免,免疫,強,強弱,與,與臨,床,床

29、過,程,程輕,重,重與,轉,轉歸,密,密切,相,相關,免疫,力,力過,強,強可,出,出現(xiàn),重,重癥,肝,肝炎,，,，過,低,低則,是,是慢,性,性肝,炎,炎,體液,免,免疫,損,損傷,：,：不十,分,分重,要,要,先天,性,性無,丙,丙種,球,球蛋,白,白血,癥,癥患,者,者乙,肝,肝仍,表,表現(xiàn),為,為典,型,型的,肝,肝炎,病,病變,抗原,抗,抗體,復,復合,物,物超,敏,敏反,應,應，,造,造成,了,了肝,外,外癥,狀,狀表,現(xiàn),現(xiàn),自身,免,免疫,損,損傷,HBV感,染,染后,，,，肝,細,細胞,自,自身,表,表面,抗,抗原,—,—肝特,異,異性,脂,脂蛋,白,白抗,原,原（Liver

30、specificprotein,LSP）暴露,,,HBV與,原,原發(fā),性,性肝,細,細胞,癌,癌,乙肝,患,患者,原,原發(fā),性,性肝,癌,癌發(fā),生,生率,比,比對,照,照高,原發(fā),性,性肝,癌,癌患,者,者有HBV感,染,染標,志,志者,比,比自,然,然人,群,群多,HBV感,染,染者,比,比陰,性,性者,發(fā),發(fā)生,原,原發(fā),性,性肝,癌,癌的,危,危險,性,性高217倍,WHV可,誘,誘導,土,土撥,鼠,鼠肝,硬,硬化,及,及原,發(fā),發(fā)性,肝,肝癌,新生,土,土撥,鼠,鼠感,染,染WHV,三,三年,后,后100%發(fā),生,生肝,癌,癌,未感,染,染鼠,則,則無,一,一只,發(fā),發(fā)生,肝,肝癌,肝

31、癌,細,細胞DNA整,合,合有HBV-DNA,,,,免疫,性,性,體液,免,免疫,HBV的,中,中和,抗,抗體,抗HBs,抗Pre-S2,細胞,免,免疫,CTL是,清,清除,細,細胞,內,內病,毒,毒的,主,主要,機,機制,細胞,免,免疫,處,處于,較,較低,水,水平,則,則易,轉,轉為,慢,慢性,,,微生,物,物學,檢,檢查,法,法,病毒,核,核酸,的,的檢,測,測,斑點,雜,雜交,法,法，PCR，,極,極敏,感,感的,方,方法,，,，臨,床,床常,規(guī),規(guī),對血,清,清病,毒,毒DNA,濃,濃度,可,可做,動,動態(tài),監(jiān),監(jiān)測,HBV抗,原,原、,抗,抗體,的,的檢,測,測,最敏,感,感方,法

32、,法是RIA、ELISA,檢測,項,項目,HBsAg和,抗,抗-HBs,HBeAg和,抗,抗-Hbe,抗-HBcIgM,和,和抗HBc-IgG,,,Symptoms,HBeAg,anti-HBe,Totalanti-HBc,IgManti-HBc,anti-HBs,HBsAg,0,4,8,12,16,20,24,28,32,36,52,100,TypicalSerologicCourse,WeeksafterExposure,Titre,AcuteHepatitisBVirusInfectionwithRecovery,,,IgManti-HBc,Totalanti-HBc,HBsAg,Acu

33、te,(6months),HBeAg,Chronic,(Years),anti-HBe,0,4,8,12,16,20,24,28,32,36,52,Years,WeeksafterExposure,Titre,ProgressiontoChronicHepatitisBVirusInfection,TypicalSerologicCourse,,,HBsA：表,示,示機,體,體感,染,染了HBV,急性,乙,乙型,肝,肝炎,潛,潛伏,期,期和,急,急性,期,期（70%）,HBV所,致,致的,慢,慢性,肝,肝病,如,如慢,性,性乙,型,型肝,炎,炎、,肝,肝硬,化,化和,原,原發(fā),性,性肝,炎,炎

34、,無癥,狀,狀HBsAg,攜,攜帶,者,者,,抗HBs,機體,曾,曾感,染,染過HBV，,并,并獲,得,得對HBV的,免,免疫,力,力,,,HBcAg：常,規(guī),規(guī)方,法,法難,以,以檢,出,出，,臨,臨床,不,不做,抗HBc,抗HBcIgM,出,出現(xiàn),于,于急,性,性乙,型,型肝,炎,炎急,性,性期,抗HBcIgG,陽,陽性,表,表示,過,過去,感,感染,過,過HBV,，,，少,數(shù),數(shù)也,可,可能,仍,仍有HBV感,染,染,,,HBeAg：體,內,內HBV,復,復制,和,和血,液,液傳,染,染性,強,強,急性,乙,乙肝HBeAg呈,短,短暫,陽,陽性,，,，如,持,持續(xù),陽,陽性,提,提示,轉

35、,轉為,慢,慢性,，,，預,后,后不,良,良,孕婦HBeAg陽,性,性，,新,新生,兒,兒感,染,染率,高,高,,抗Hbe,見于,急,急性,乙,乙肝,的,的恢,復,復期,，,，可,持,持續(xù),較,較長,時,時間,機體,獲,獲得,一,一定,免,免疫,力,力,,,Pre-S1,、,、Pre-S2和PHSA,受,受體,HBV新,感,感染,的,的標,志,志，,檢,檢出,表,表示HBV正,在,在復,制,制,,抗Pre-S1、,抗,抗Pre-S2,中和,病,病毒,出現(xiàn),于,于急,性,性乙,肝,肝恢,復,復早,期,期,消失,較,較快,,,ExamplesofSerologyTest,,,預防,原,原則,要采,

36、取,取切,斷,斷傳,播,播途,徑,徑為,主,主的,綜,綜合,性,性措,施,施,自動,免,免疫,：,：HBsAg,疫,疫苗,（,（血,源,源或,重,重組,）,）,被動,免,免疫,：,：乙,肝,肝免,疫,疫球,蛋,蛋白(HBIg),。,。接,種,種者:,醫(yī)務,人,人員,或,或實,驗,驗室,工,工作,人,人員,HBsAg、HBeAg陽,性,性母,親,親的,新,新生,兒,兒,發(fā)現(xiàn),已,已誤,用,用HBsAg,陽,陽性,的,的血,液,液或,血,血制,品,品者,與HBsAg,、,、HBeAg,陽,陽性,者,者有,密,密切,性,性接,觸,觸者,,,,EliminationofHBVTransmission,

37、PreventperinatalHBVtransmission,Routinevaccination,allinfants,childreninhigh-riskgroups,adolescents,allunvaccinatedchildrenat11-12years,adultsinhigh-riskgroups,,,Vaccine,licensed,HBsAgscreening,ofpregnantwomenrecommended,Infant,immunization,recommended,Adolescentimmunizationrecommended,Declineamongh

38、omosexualmen&HCWs,Declineamonginjecting,drugusers,80,70,60,50,40,30,20,10,0,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,Year,Casesper100,000Population,EstimatedIncidenceofAcuteHepatitisB,USA1978-1995,,,HepatitisCvirus,1978,年,年WHO,將,將非,甲,甲非,乙,乙型,肝,肝炎,病,病毒,按,按傳,播,播途,徑,徑分,為,為腸,道,道傳,播,播的,非,非甲,

39、非,非乙,型,型病,毒,毒和,腸,腸道,外,外傳,播,播的,非,非甲,非,非乙,型,型肝,炎,炎病,毒,毒,1989,年,年進,一,一步,將,將前,者,者命,名,名為,戊,戊型,肝,肝炎,病,病毒,（,（HEV,）,），,將,將后,者,者命,名,名為,丙,丙型,肝,肝炎,病,病毒,（,（HCV,）,）,目前,擬,擬將HCV和,庚,庚型,肝,肝炎,病,病毒,（,（HGV,）,）列,入,入黃,病,病毒,科,科（Flavivurus,）,）Hepacivirus,屬,屬,,,,,生物,學,學性,狀,狀,HCV屬,于,于黃,病,病毒,科,科，,電,電鏡,照,照片,不,不清,晰,晰，,似,似球,形,形，

40、,直,直徑55,～,～65nm,，,，有,脂,脂蛋,白,白包,膜,膜，,包,包膜,上,上有,短,短突,起,起。,核,核酸,為,為+ssRNA，9.4Kb,,,由于,不,不能,培,培養(yǎng),，,，故,尚,尚不,能,能進,行,行血,清,清分,型,型,據(jù)基,因,因序,列,列同,源,源性,，,，分,為,為I,—,—VI六,個,個基,因,因型,。,。中,國,國和,亞,亞洲,流,流行,多,多Ⅱ,型,型，,歐,歐美,為,為I,型,型,細胞,培,培養(yǎng),未,未成,功,功,黑猩,猩,猩是,唯,唯一,易,易感,動,動物,,,,,hypervariable,region,capsid,envelope,protein,p

41、rotease/helicase,RNApolymerase,c22,5’,core,E1,E2,NS2,NS3,33,c,NS4,c-100,NS5,3’,HepatitisCVirusGenome,,,HCV,基,基因結,構,構,,,,HepatitisC- Clinical Features,潛伏期,平,平均6-7周,（,（2-26周,）,）,急性表,現(xiàn),現(xiàn)（黃,疸,疸）,輕,輕微(,<,20%),急性期,死,死亡率,低,低,慢性感,染,染率75%-85%,慢性肝,炎,炎 70%,肝硬化10%-20%,慢性肝,臟,臟疾病,導,導致死,亡,亡 1%-5%,,,Chronic Hepatit

42、isC Infection,ThespectrumofchronichepatitisCinfectionisessentiallythesameaschronic hepatitisB infection,,Allthe manifestations of chronichepatitis Binfection maybeseen, albeitwith alowerfrequency i.e.chronicpersistent hepatitis,chronicactivehepatitis,cirrhosis, andhepatocellularcarcinoma,,,病理,HCV,不,

43、不直接,殺,殺傷細,胞,胞,病理免,疫,疫和細,胞,胞凋亡,是,是造成,傷,傷害原,因,因,,,TransmissionofHCV,Percutaneous,Intravenousdrug abuse,Transfusion,transplant,Therapeutic(contaminated equipment,unsafe injectionpractices),Permucosal,Perinatal,Sexual,,,Sources of InfectionforPersonswith HepatitisC,Sexual15%,Other*5%,Unknown 10%,Injecti

44、ngdruguse60%,Transfusion10%,(before screening),*Nosocomial;Health-carework;Perinatal,Source: Centersfor DiseaseControlandPrevention,,Source: Sentinel Counties,CDC,HCVPrevalencebySelectedGroups, USA,Hemophilia,Injectingdrugusers,Surgeons,PSWs,Hemodialysis,,Average PercentAnti-HCVPositive,Genpopulatio

45、nadults,Militarypersonnel,STDclients,Pregnantwomen,,,Prevalence of HCVInfectionbyAge& Gender,1988-1994 USA,Males,Females,Source: CDC,NHANES III,Total,,,PerinatalTransmission of HCV,Transmissiononlyfrom women HCV-RNApositiveatdelivery,Average rateofinfection 6%,Higher (17%)ifwoman co-infected with HI

46、V,No association with,Deliverymethod,Breastfeeding,Infectedinfantsdowell,Severe hepatitisisrare,,,Household Transmission of HCV,Rarebutnotabsent,Could occurthroughpercutaneous/mucosalexposures to blood,Theoretically through sharing ofcontaminated personal articles(razors,toothbrushes),Contaminatedeq

47、uipment usedforhometherapies,Injections*,Folkremedies,*Reported inU.S.,Serologic Pattern ofAcute HCV Infection,withRecovery,Symptoms+/-,Timeafter Exposure,Titer,anti-HCV,ALT,Normal,0,1,2,3,4,5,6,1,2,3,4,Years,Months,HCVRNA,,,Serologic Pattern ofChronicHCVInfection withProgressionInfection,,Symptoms+

48、/-,Timeafter Exposure,Titer,anti-HCV,ALT,Normal,0,1,2,3,4,5,6,1,2,3,4,Years,Months,HCVRNA,,,Laboratory Diagnosis,HCVantibody- generallyusedtodiagnosehepatitis Cinfection.Notuseful in the acutephase asittakes atleast 4weeks afterinfection before antibody appears.,HCV-RNA- various techniquesareavailab

49、le e.g.PCRandbranchedDNA. May beused todiagnose HCV infectionin the acutephase.However,itsmain use isinmonitoring the responseto antiviraltherapy.,HCV-antigen- anEIAforHCVantigenisavailable. It isused inthesame capacity as HCV-RNA testsbutis mucheasier to carryout.,,,HCVInfection Testing Algorithmfo

50、rDiagnosis ofAsymptomatic Persons,EIAforAnti-HCV,Negative,(non-reactive),STOP,Positive(repeatreactive),OR,RIBAforAnti-HCV,RT-PCR for HCV RNA,Negative,STOP,Additional Laboratory Evaluation(e.g. PCR,ALT),Negative,Positive,Indeterminate,MedicalEvaluation,Positive,NegativePCR,,Normal ALT,PositivePCR,,Ab

51、normalALT,Source:MMWR1998;47(No. RR19),,,RoutineHCVTestingNotRecommended(,Unless RiskFactor Identified),Health-care,emergency medical,andpublic safety workers,Pregnantwomen,Household (non-sexual) contactsof HCV-positivepersons,,,Screeningof blood,organ, tissue donors,High-riskbehavior modification,B

52、loodandbodyfluidprecautions,,Preventionof Hepatitis C,,,EstimatedIncidenceof Acute HCV Infection, 1960-1999 USA,Decline in,transfusion recipients,Decline ininjection,drugusers,Source: Hepatology 2000;31:777-82,Hepatology1997;26:62S-65S,,,PosttransfusionHepatitisC,All volunteer donors,HBsAg,DonorScre

53、eningforHIV Risk Factors,Anti-HIV,ALT/Anti-HBc,Anti-HCV,Improved,HCV Tests,Adapted from HJAlter andTobler and Busch, Clin Chem 1997,,,,Treatment,Interferon- maybe consideredfor patients with chronicactive hepatitis. The response rate isaround 50%but50% of responders will relapseuponwithdrawal oftrea

54、tment.,Ribavirin- there islessexperience with ribavirin than interferon. However, recentstudies suggestthata combinationof interferon and ribavirin ismoreeffectivethaninterferon alone.,,,HepatitisD virus,δ肝炎病毒,（,（Hepatitis,δ,δ virus）,從HBV感,染,染者中發(fā)現(xiàn),的,的,,,HDV Prevalence,High,Intermediate,Low,VeryLow,N

55、o Data,Taiwan,Pacific Islands,GeographicDistribution of HDVInfection,,,生物學性狀,35～37nm，球形,顆,顆粒,環(huán)狀單股負,鏈,鏈RNA和HDAg（,即,即δ抗原）,1.7Kb,表面為HBV包膜蛋白,（,（HBsAg）,,,HBsAg,RNA,d,antigen,,,HDV為缺,陷,陷病毒,不能獨立進,行,行復制，必,須,須在HBV,或,或其它嗜肝DNA病毒,輔,輔助才能增,殖,殖,敏感動物黑,猩,猩猩，土撥,鼠,鼠和北京鴨,等,等,,,,HepatitisD - Clinical Features,Coinfectio

56、n,severe acute disease,low risk of chronicinfection,Superinfection,usually developchronic HDV infection,highriskof severechronic liver disease,may present asan acute hepatitis,,,,HDV Transmission,Percutanous exposures,injectingdruguse,Permucosalexposures,sex contact,,,免疫性,抗HDV,不,不能清除病,毒,毒，為診斷,指,指標,H

57、DV IgM和IgG持續(xù)存在,，,，提示為HDV慢性感,染,染,,,TimeafterExposure,Titer,anti-HBs,Symptoms,ALTElevated,Totalanti-HDV,IgManti-HDV,HDVRNA,HBsAg,SerologicalCourseofAcuteHDVinfection,,,TimeafterExposure,Titer,Jaundice,Symptoms,ALT,Totalanti-HDV,IgManti-HDV,HDVRNA,HBsAg,SerologicalCourseofHDVsuperinfection,,,微生,物,物學,檢,

58、檢查,法,法,血清,學,學方,法,法,ELISA檢,查,查HDAg或,抗,抗HDV,HDAg,在,在急,性,性期,可,可陽,性,性，,檢,檢出,率,率低,慢性,感,感染,檢,檢不,到,到,核酸,分,分子,雜,雜交,法,法,,,HBV-HDVCoinfection,PreorpostexposureprophylaxistopreventHBVinfection.,HBV-HDVSuperinfection,EducationtoreduceriskbehaviorsamongpersonswithchronicHBVinfection.,,,HepatitisD-Prevention,,,He

59、patitisEvirus,，HEV,戊型,肝,肝炎,病,病毒,經腸,道,道傳,播,播的,非,非甲,非,非乙,型,型肝,炎,炎病,毒,毒,疾病,：,：戊,型,型肝,炎,炎,,,GeographicDistributionofHepatitisE,,,生物,學,學性,狀,狀,,,HEV呈,球,球形,，,，直,徑,徑27～38nm,核酸,為,為線,形,形（-）ssRNA,無包,膜,膜，20,面,面體,立,立體,對,對稱,現(xiàn)分,類,類于,杯,杯狀,病,病毒,只有,一,一個,血,血清,型,型,易感,動,動物,非洲,綠,綠猴,、,、恒,河,河猴,、,、黑,猩,猩猩,,,致病,性,性,糞－,口,口途,徑,

60、徑傳,播,播,水源,污,污染,造,造成,流,流行,，,，極,小,小生,活,活接,觸,觸導,致,致感,染,染,多感,染,染20—40,歲,歲成,人,人,潛伏,期,期2,—,—9,周,周，,臨,臨床,表,表現(xiàn),為,為急,性,性肝,炎,炎，6周,即,即恢,復,復,少數(shù),重,重癥,死,死亡,。,。無,慢,慢性,感,感染,病,病例,致病,機,機理,不,不明,免疫,損,損傷,是,是主,要,要機,制,制。,病,病后,有,有一,定,定免,疫,疫力,,,WeeksafterExposure,Titer,Symptoms,ALT,IgGanti-HEV,IgManti-HEV,Virusinstool,0,1,2

61、,3,4,5,6,7,8,9,10,11,12,13,SerologicalCourseofHEVinfection,,,微生,物,物學,檢,檢查,法,法,免疫,電,電鏡,血清,學,學方,法,法，,檢,檢測,抗,抗-HEV,HEV核,酸,酸檢,測,測,,,,PreventionandControlMeasuresforTravelerstoHEV-EndemicRegions,Avoiddrinkingwater(andbeverageswithice)ofunknownpurity,uncookedshellfish,anduncookedfruit/vegetablesnotpeeledo

62、rpreparedbytraveler.,IGpreparedfromdonorsinWesterncountriesdoesnotpreventinfection.,UnknownefficacyofIGpreparedfromdonorsinendemicareas.,Vaccine?,,,庚型,肝,肝炎,病,病毒,1995,年,年發(fā),現(xiàn),現(xiàn),屬黃,病,病毒,科,科,核酸為+ssRNA，9.4KB，,編,編碼一個ORF,黑猩猩易,感,感,感染世界,分,分布,,,經血或,腸,腸道外,傳,傳播、,垂,垂直傳,播,播和性,傳,傳播,臨床感,染,染,急性和,慢,慢性過,程,程,HGV,常,常與HC

63、V重,疊,疊感染,診斷,血清學,方,方法或PCR,HGV,是,是否嗜,肝,肝仍不,清,清楚,與疾病,關,關系必,須,須將HBV、HDV,、,、HCV感染,排,排除后,才,才可確,認,認,,,,,Sourceof,virus,feces,blood/,blood-derived,body fluids,blood/,blood-derived,body fluids,blood/,blood-derived,body fluids,feces,Routeof,transmission,fecal-oral,percutaneous,permucosal,percutaneous,permucos

64、al,percutaneous,permucosal,fecal-oral,Chronic,infection,no,yes,yes,yes,no,Prevention,pre/post-,exposure,immunization,pre/post-,exposure,immunization,blooddonor,screening;,risk behavior,modification,pre/post-,exposure,immunization;,risk behavior,modification,ensuresafe,drinking,water,Summary:,Type of

65、 Hepatitis,A,B,C,D,E,,,Question,Compare HAVandHBV accordingtothefollowing criteria:classification,genome,presenceofenvelope,clinicalfeatures, andtransmissions.,What arethethreeimportant antigens in theHBVparticle?,Whyisthe delta agent found onlyinpersonsinfectedwith HBV?,,,,謝謝觀,看,看,/,歡迎下,載,載,BYFAITHI MEANAVISIONOFGOODONECHERISHES ANDTHEENTHUSIASMTHAT PUSHESONETOSEEKITSFULFILLMENTREGARDLESSOFOBSTACLES. BY FAITH IBYFAITH,