医学微生物学课件

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1、单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,,,*,Medical Microbiology,Department of Microbiology, HMU,,,第37章 肝炎病毒,Hepatitis viruses,微生物学教研室 凌 虹,第二篇 致病性细菌,,,教学大纲,掌握内容,肝炎病毒的种类,乙型肝炎病毒形态结构、致病性、预防原则,熟悉内容,丁型肝炎病毒结构特征及致病特点,戊型肝炎病毒传播途径及致病特点,,,问题,肝炎病毒有哪些？,甲型肝炎病毒,的传播方式、致病特点和预防原则,简述,乙型肝炎病毒,的生物学性状、,抗原抗体组成,及检

2、出的意义、传播方式、致病特点及预防原则,丙型肝炎病毒,的生物学特点和致病特点,丁型肝炎病毒,（HDV）的概念,简述,戊型肝炎病毒,传播方式和致病特点,,,肝炎病毒（Hepatitis virus）,以侵害肝脏为主引起病毒性肝炎的病毒,种类：,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,黄热病毒、CMV、EBV、风疹病毒等,,,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,应用免疫电镜技术从急性肝炎患者粪便发现,生物学性状与肠道病毒一致,1982年国际病毒命名委员会将它分类为小核糖核酸病毒科肠道病毒属72型,,,Anti-HAV Prevalence,High,Intermediate,Low,Very Low,Geographic Distribution of HAV infection,,,生物学性状

4、,HAV为球形颗粒，直径27～32nm，无包膜。基因组为线状单正链RNA,,,由VP1～4四种多肽组成,VP1是主要衣壳蛋白和中和抗原，能中和所有HAV,细胞培养：HAV可用猴肾、人胚肾细胞等进行增殖和传代，但不引起CPE,易感动物有黑猩猩、南美洲猴、猕猴等,接种后可出现急性肝炎,抵抗力：较强,对乙醚、酸、热（60,o,C）稳定。高压、紫外、煮沸等可灭活,,,流行,病,病学,传染,源,源,患者,和,和隐,性,性感,染,染者,传播,方,方式,：,：粪－,口,口途,径,径,污染,食,食物,、,、水,源,源、,海,海产,品,品引,起,起暴,发,发或,散,散发,流,流行,隐性,感,感染,率,率高,成人

5、HAV抗,体,体阳,性,性率,高,高达70%—90%,,,致病,性,性,非溶,细,细胞,型,型病,毒,毒，,不,不直,接,接杀,伤,伤细,胞,胞,病毒,复,复制,量,量与,症,症状,严,严重,程,程度,不,不一,致,致，,故,故认,为,为免,疫,疫应,答,答参,与,与损,伤,伤过,程,程,病后,期,期粪,便,便可,检,检出sIgA,抗,抗体,无慢,性,性病,例,例,典型,的,的甲,肝,肝是,自,自限,过,过程,，,，大,约,约三,个,个月,,,甲型,肝,肝炎,血,血清,学,学变,化,化过,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,,,,诊断（,LaboratoryDiagnosis,）,）,Acuteinfectionis diagnosed by thedetectionof HAV-IgM inserumby EIA,PastInfectioni.e.immunity is determined bythedetectionof HAV-IgGby EIA,,,防治原则,加强食品卫,生,生管理，水,源,源,减毒疫苗株H

10、2株和L1株已投放,市,市场,基因工程疫,苗,苗也正在研,究,究之中,应急预防可,用,用丙种球蛋,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,â,*ELISA units,Recommended Doses &Schedulesof HAV Vaccination,,,HapatitisB Virus,1963

13、年Blumberg在多,次,次输血的血,友,友病患者中,发,发现澳抗，1968年,确,确与血清型,肝,肝炎高度相,关,关，1970年Dane在电镜下,看,看到具有传,染,染性的42nm病毒颗,粒,粒,HBV在,亚,亚洲广泛,流,流行，在,中,中国约10%人口,携,携带该病,毒,毒，全球,约,约3.5,亿,亿,,,1983,年,年将HBV及与其,分,分子结构,、,、生物学,特,特性相似,的,的土拨鼠,肝,肝炎病毒(woodchuck hepatitisvirus,WHV)、,地,地松鼠肝,炎,炎病毒(ground squirrelhepatitis virus,GSHV)及鸭肝,炎,炎病毒(du

14、ckhepatits virus,DHV),归,归纳起来,独,独立命名,为,为嗜肝病毒,科,科（Hepadnaviridae,）,）,,,HBsAg Prevalence,³,8% -High,2-7%- Intermediate,<2%- Low,Geographic Distributionof Chronic HBV Infection,,,形态与结,构,构,,,电镜检查,血,血清标本,可,可见小球,形,形颗粒（22nm,）,）、管形,颗,颗粒（22nmx50—700nm,）,）、大球,形,形颗粒（42nm,）,）,,,,,完整的HBV颗粒,亦,亦称Dane颗粒,，,，颗粒直,径,径为4

15、2nm,具有双层,衣,衣壳结构,。,。外壳相,当,当于包膜,，,，由脂质,双,双层和乙,肝,肝表面抗,原,原（HBsAg）,、,、多聚人,血,血清白蛋,白,白受体（PHSA-r）和,前,前S抗原,（,（Pre-S）组,成,成。内部,有,有28nm的核心,，,，表面相,当,当于内衣,壳,壳，含有,乙,乙型肝炎,核,核心抗原,（,（HBcAg）和,乙,乙型肝炎e抗原（HBeAg）。内,部,部有HBV的DNA和DNA多聚酶,,,HBV,基,基因组,DNA是,由,由3.2KB的长,链,链 L（-）和短,链,链 S（+）（约,为,为L链的50%至85%长,）,）组成的,不,不完全双,链,链环状DNA，长

16、,链,链载有病,毒,毒蛋白质,的,的全部密,码,码，有4,个,个开放读,码,码框架(ORF),，,，分别称,为,为S、C,、,、P和X,区,区,,,,,HBV复,制,制周期,,,,,HBVReplication,HBV,2.4KB,3.5KB,Provirus,RT,Replicate,Nuclear,2.1KB,,,抗原组成,HBV表,面,面抗原（HBsAg）,是机体受HBV感,染,染的标志,226AA，由S,基,基因编码,HBsAg有1个,共,共同抗原,决,决定簇a,和,和2组互,相,相排斥的,亚,亚型抗原,决,决定簇d/y和w/r,4种亚型,：,：adr,、,、adw,、,、ayr,、,

17、、 ayw,我国内地,和,和沿海各,省,省汉族主,要,要为adr型，欧,美,美为adw,抗HBs,能与HBV表面结,合,合，使其,失,失去感染,性,性，具有,保,保护作用,,,HBV核,心,心抗原（HBcAg）,在肝细胞,核,核中才能,检,检出,分子量22KD，,由,由C基因,编,编码，病,毒,毒内衣壳,蛋,蛋白,一般方法,在,在血中检,测,测不到,抗HBc,无中和作,用,用,检出高效,价,价抗HBc，特别,是,是抗HBc IgM表示HBV再肝,内,内处于增,殖,殖状态,,,HBVe,抗,抗原（HBeAg,）,）,由PreC和C基,因,因共同编,码,码，15KD,HBcAg在细胞,经,经蛋白酶

18、,降,降解形成,HBV复,制,制及血清,有,有传染性,的,的标志,抗Hbe,对HBV,感,感染有一,定,定保护作,用,用,,,前S抗原,（,（Pre-S Ag）,,前S2蛋,白,白,S +PreS2编码，226+ 55=281AA,前S1,蛋,蛋,白,白,S+PreS2+PreS1,编,编,码,码,，,，226+55+119=400AA,,与HBsAg,、,、HBVDNA,检,检,出,出,相,相,同,同,，,，,都,都,说,说,明,明,病,病,毒,毒,在,在,复,复,制,制,,,Pre-S2,抗,抗,原,原,和,人,人,肝,肝,细,细,胞,胞,表,表,面,面,都,都,具,具,有,有PHSA,受

19、,受,体,体,，,，,通,通,过,过PHSAr,搭,搭,桥,桥,，,，HBV,病,病,毒,毒,易,易,吸,吸,附,附,于,于,肝,肝,细,细,胞,胞,表,表,面,面,部,分,分,解,解,释,释,为,为,什,什,么,么HBV,具,具,有,有,嗜,嗜,肝,肝,细,细,胞,胞,性,性,,抗,前,前S1,和,和,抗,抗,前,前S2,抗,抗,体,体,具,有,有,中,中,和,和HBV,作,作,用,用,，,，,有,有,保,保,护,护,作,作,用,用,,,易,感,感,动,动,物,物,和,和,细,细,胞,胞,培,培,养,养,：,：,只,只,有,有,黑,黑,猩,猩,猩,猩,对,对HBV,易,易,感,感,，,，,体

20、,体,外,外,细,细,胞,胞,培,培,养,养,尚,尚,未,未,成,成,功,功,,,抵,抗,抗,力,力,：,：,强,强,对,低,低,温,温,、,、,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,压,压,蒸,蒸,汽,汽,灭,灭,菌,菌,、,、0.5%,过,过,氧,氧,乙,乙,酸,酸,、,、5%,次,次,氯,氯,酸,酸,钠,钠,、,、3%,漂,漂,白,白,粉,粉,液,液,、,、0.2%,新,新,洁,洁,尔,尔,灭,灭,均,均,可,可,灭,灭,活,活,病,病,毒,毒,，,，,但,但,处,处,理,理,时,时,间,间

21、,要,要,稍,稍,长,长,,,,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,,,传染,源,源：,急,急、,慢,慢性,乙,乙肝,患,患者,及,及无,症,症状,携,携带,者,者,传播,途,途径,：,：非胃,肠,肠道,途,途径,血液,、,、血,制,制品,传,传播,输血,、,、丙,种,种球,蛋,蛋白,医源,性,性传,播,播：,注,注射,（,（吸,毒,毒）,、,、手,术,术、,采,采血,、,、针,刺,刺、,拨,拨牙,、,、内,窥,窥镜,检,检查,、,、纹,身,身等,接触,传,传播,：,：公,共,共卫,生,生洁,具,具、,剃,剃刀,、,、吸,血,血昆,虫,虫,母婴,传,传

26、播,宫内,感,感染,相,相对,少,少（<10%,）,）,母亲HBeAg阳,性,性婴,儿,儿感,染,染机,会,会大,（,（90%,）,）,HBeAg阴,性,性、,抗,抗HBe,阳,阳性,婴,婴儿,感,感染,机,机率,小,小（10%—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,机,机理,尚未,完,完全,明,明了,HBV不,直,直接,损,损害,肝,肝细,胞,胞，,通,通过,宿,宿主,的,的免,疫,疫应,答,答引,起,起肝,细,细胞,的,的损,伤,伤和,破,破坏,,,细胞,免,免疫,损,损伤,细胞,免,免疫,强,强弱,与,与临,床,床

29、过,程,程轻,重,重与,转,转归,密,密切,相,相关,免疫,力,力过,强,强可,出,出现,重,重症,肝,肝炎,，,，过,低,低则,是,是慢,性,性肝,炎,炎,体液,免,免疫,损,损伤,：,：不十,分,分重,要,要,先天,性,性无,丙,丙种,球,球蛋,白,白血,症,症患,者,者乙,肝,肝仍,表,表现,为,为典,型,型的,肝,肝炎,病,病变,抗原,抗,抗体,复,复合,物,物超,敏,敏反,应,应，,造,造成,了,了肝,外,外症,状,状表,现,现,自身,免,免疫,损,损伤,HBV感,染,染后,，,，肝,细,细胞,自,自身,表,表面,抗,抗原,—,—肝特,异,异性,脂,脂蛋,白,白抗,原,原（Liver

30、specificprotein,LSP）暴露,,,HBV与,原,原发,性,性肝,细,细胞,癌,癌,乙肝,患,患者,原,原发,性,性肝,癌,癌发,生,生率,比,比对,照,照高,原发,性,性肝,癌,癌患,者,者有HBV感,染,染标,志,志者,比,比自,然,然人,群,群多,HBV感,染,染者,比,比阴,性,性者,发,发生,原,原发,性,性肝,癌,癌的,危,危险,性,性高217倍,WHV可,诱,诱导,土,土拨,鼠,鼠肝,硬,硬化,及,及原,发,发性,肝,肝癌,新生,土,土拨,鼠,鼠感,染,染WHV,三,三年,后,后100%发,生,生肝,癌,癌,未感,染,染鼠,则,则无,一,一只,发,发生,肝,肝癌,肝

31、癌,细,细胞DNA整,合,合有HBV-DNA,,,,免疫,性,性,体液,免,免疫,HBV的,中,中和,抗,抗体,抗HBs,抗Pre-S2,细胞,免,免疫,CTL是,清,清除,细,细胞,内,内病,毒,毒的,主,主要,机,机制,细胞,免,免疫,处,处于,较,较低,水,水平,则,则易,转,转为,慢,慢性,,,微生,物,物学,检,检查,法,法,病毒,核,核酸,的,的检,测,测,斑点,杂,杂交,法,法，PCR，,极,极敏,感,感的,方,方法,，,，临,床,床常,规,规,对血,清,清病,毒,毒DNA,浓,浓度,可,可做,动,动态,监,监测,HBV抗,原,原、,抗,抗体,的,的检,测,测,最敏,感,感方,法

32、,法是RIA、ELISA,检测,项,项目,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,示机,体,体感,染,染了HBV,急性,乙,乙型,肝,肝炎,潜,潜伏,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,原发,性,性肝,炎,炎

34、,无症,状,状HBsAg,携,携带,者,者,,抗HBs,机体,曾,曾感,染,染过HBV，,并,并获,得,得对HBV的,免,免疫,力,力,,,HBcAg：常,规,规方,法,法难,以,以检,出,出，,临,临床,不,不做,抗HBc,抗HBcIgM,出,出现,于,于急,性,性乙,型,型肝,炎,炎急,性,性期,抗HBcIgG,阳,阳性,表,表示,过,过去,感,感染,过,过HBV,，,，少,数,数也,可,可能,仍,仍有HBV感,染,染,,,HBeAg：体,内,内HBV,复,复制,和,和血,液,液传,染,染性,强,强,急性,乙,乙肝HBeAg呈,短,短暂,阳,阳性,，,，如,持,持续,阳,阳性,提,提示,转

35、,转为,慢,慢性,，,，预,后,后不,良,良,孕妇HBeAg阳,性,性，,新,新生,儿,儿感,染,染率,高,高,,抗Hbe,见于,急,急性,乙,乙肝,的,的恢,复,复期,，,，可,持,持续,较,较长,时,时间,机体,获,获得,一,一定,免,免疫,力,力,,,Pre-S1,、,、Pre-S2和PHSA,受,受体,HBV新,感,感染,的,的标,志,志，,检,检出,表,表示HBV正,在,在复,制,制,,抗Pre-S1、,抗,抗Pre-S2,中和,病,病毒,出现,于,于急,性,性乙,肝,肝恢,复,复早,期,期,消失,较,较快,,,ExamplesofSerologyTest,,,预防,原,原则,要采,

36、取,取切,断,断传,播,播途,径,径为,主,主的,综,综合,性,性措,施,施,自动,免,免疫,：,：HBsAg,疫,疫苗,（,（血,源,源或,重,重组,）,）,被动,免,免疫,：,：乙,肝,肝免,疫,疫球,蛋,蛋白(HBIg),。,。接,种,种者:,医务,人,人员,或,或实,验,验室,工,工作,人,人员,HBsAg、HBeAg阳,性,性母,亲,亲的,新,新生,儿,儿,发现,已,已误,用,用HBsAg,阳,阳性,的,的血,液,液或,血,血制,品,品者,与HBsAg,、,、HBeAg,阳,阳性,者,者有,密,密切,性,性接,触,触者,,,,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,将,将非,甲,甲非,乙,乙型,肝,肝炎,病,病毒,按,按传,播,播途,径,径分,为,为肠,道,道传,播,播的,非,非甲,

39、非,非乙,型,型病,毒,毒和,肠,肠道,外,外传,播,播的,非,非甲,非,非乙,型,型肝,炎,炎病,毒,毒,1989,年,年进,一,一步,将,将前,者,者命,名,名为,戊,戊型,肝,肝炎,病,病毒,（,（HEV,）,），,将,将后,者,者命,名,名为,丙,丙型,肝,肝炎,病,病毒,（,（HCV,）,）,目前,拟,拟将HCV和,庚,庚型,肝,肝炎,病,病毒,（,（HGV,）,）列,入,入黄,病,病毒,科,科（Flavivurus,）,）Hepacivirus,属,属,,,,,生物,学,学性,状,状,HCV属,于,于黄,病,病毒,科,科，,电,电镜,照,照片,不,不清,晰,晰，,似,似球,形,形，

40、,直,直径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,为,为+ssRNA，9.4Kb,,,由于,不,不能,培,培养,，,，故,尚,尚不,能,能进,行,行血,清,清分,型,型,据基,因,因序,列,列同,源,源性,，,，分,为,为I,—,—VI六,个,个基,因,因型,。,。中,国,国和,亚,亚洲,流,流行,多,多Ⅱ,型,型，,欧,欧美,为,为I,型,型,细胞,培,培养,未,未成,功,功,黑猩,猩,猩是,唯,唯一,易,易感,动,动物,,,,,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,基因结,构,构,,,,HepatitisC- Clinical Features,潜伏期,平,平均6-7周,（,（2-26周,）,）,急性表,现,现（黄,疸,疸）,轻,轻微(,<,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,脏,脏疾病,导,导致死,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,杀,杀伤细,胞,胞,病理免,疫,疫和细,胞,胞凋亡,是,是造成,伤,伤害原,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）,从HBV感,染,染者中发现,的,的,,,HDV Prevalence,High,Intermediate,Low,VeryLow,N

55、o Data,Taiwan,Pacific Islands,GeographicDistribution of HDVInfection,,,生物学性状,35～37nm，球形,颗,颗粒,环状单股负,链,链RNA和HDAg（,即,即δ抗原）,1.7Kb,表面为HBV包膜蛋白,（,（HBsAg）,,,HBsAg,RNA,d,antigen,,,HDV为缺,陷,陷病毒,不能独立进,行,行复制，必,须,须在HBV,或,或其它嗜肝DNA病毒,辅,辅助才能增,殖,殖,敏感动物黑,猩,猩猩，土拨,鼠,鼠和北京鸭,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，为诊断,指,指标,H

57、DV IgM和IgG持续存在,，,，提示为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,物学,检,

58、检查,法,法,血清,学,学方,法,法,ELISA检,查,查HDAg或,抗,抗HDV,HDAg,在,在急,性,性期,可,可阳,性,性，,检,检出,率,率低,慢性,感,感染,检,检不,到,到,核酸,分,分子,杂,杂交,法,法,,,HBV-HDVCoinfection,PreorpostexposureprophylaxistopreventHBVinfection.,HBV-HDVSuperinfection,EducationtoreduceriskbehaviorsamongpersonswithchronicHBVinfection.,,,HepatitisD-Prevention,,,He

59、patitisEvirus,，HEV,戊型,肝,肝炎,病,病毒,经肠,道,道传,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,学,学性,状,状,,,HEV呈,球,球形,，,，直,径,径27～38nm,核酸,为,为线,形,形（-）ssRNA,无包,膜,膜，20,面,面体,立,立体,对,对称,现分,类,类于,杯,杯状,病,病毒,只有,一,一个,血,血清,型,型,易感,动,动物,非洲,绿,绿猴,、,、恒,河,河猴,、,、黑,猩,猩猩,,,致病,性,性,粪－,口,口途,径,

60、径传,播,播,水源,污,污染,造,造成,流,流行,，,，极,小,小生,活,活接,触,触导,致,致感,染,染,多感,染,染20—40,岁,岁成,人,人,潜伏,期,期2,—,—9,周,周，,临,临床,表,表现,为,为急,性,性肝,炎,炎，6周,即,即恢,复,复,少数,重,重症,死,死亡,。,。无,慢,慢性,感,感染,病,病例,致病,机,机理,不,不明,免疫,损,损伤,是,是主,要,要机,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,物学,检,检查,法,法,免疫,电,电镜,血清,学,学方,法,法，,检,检测,抗,抗-HEV,HEV核,酸,酸检,测,测,,,,PreventionandControlMeasuresforTravelerstoHEV-EndemicRegions,Avoiddrinkingwater(andbeverageswithice)ofunknownpurity,uncookedshellfish,anduncookedfruit/vegetablesnotpeeledo

62、rpreparedbytraveler.,IGpreparedfromdonorsinWesterncountriesdoesnotpreventinfection.,UnknownefficacyofIGpreparedfromdonorsinendemicareas.,Vaccine?,,,庚型,肝,肝炎,病,病毒,1995,年,年发,现,现,属黄,病,病毒,科,科,核酸为+ssRNA，9.4KB，,编,编码一个ORF,黑猩猩易,感,感,感染世界,分,分布,,,经血或,肠,肠道外,传,传播、,垂,垂直传,播,播和性,传,传播,临床感,染,染,急性和,慢,慢性过,程,程,HGV,常,常与HC

63、V重,叠,叠感染,诊断,血清学,方,方法或PCR,HGV,是,是否嗜,肝,肝仍不,清,清楚,与疾病,关,关系必,须,须将HBV、HDV,、,、HCV感染,排,排除后,才,才可确,认,认,,,,,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?,,,,谢谢观,看,看,/,欢迎下,载,载,BYFAITHI MEANAVISIONOFGOODONECHERISHES ANDTHEENTHUSIASMTHAT PUSHESONETOSEEKITSFULFILLMENTREGARDLESSOFOBSTACLES. BY FAITH IBYFAITH,