1、Medical MicrobiologyDepartment of Microbiology, HMU2021/9/101第37章 肝炎病毒Hepatitis viruses微生物學(xué)教研室 凌 虹第二篇 致病性細(xì)菌2021/9/102 教學(xué)大綱掌握內(nèi)容肝炎病毒的種類 乙型肝炎病毒形態(tài)結(jié)構(gòu)、致病性、預(yù)防原則熟悉內(nèi)容丁型肝炎病毒結(jié)構(gòu)特征及致病特點(diǎn)戊型肝炎病毒傳播途徑及致病特點(diǎn)2021/9/103問題肝炎病毒有哪些？甲型肝炎病毒的傳播方式、致病特點(diǎn)和預(yù)防原則簡(jiǎn)述乙型肝炎病毒的生物學(xué)性狀、抗原抗體組成及檢出的意義、傳播方式、致病特點(diǎn)及預(yù)防原則丙型肝炎病毒的生物學(xué)特點(diǎn)和致病特點(diǎn)丁型肝炎病毒（HDV）的概

2、念簡(jiǎn)述戊型肝炎病毒傳播方式和致病特點(diǎn)2021/9/104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(fēng)疹病毒等 2021/9/105Viral Hepatitis - Historical PerspectivesA“Infectious”“Serum”Viral hepatitisEntericallytransmittedParenterallytransmittedF, G

3、, TTV? otherENANBBDC2021/9/106Hepatitis A virus1973年Feinstone應(yīng)用免疫電鏡技術(shù)從急性肝炎患者糞便發(fā)現(xiàn)生物學(xué)性狀與腸道病毒一致1982年國(guó)際病毒命名委員會(huì)將它分類為小核糖核酸病毒科腸道病毒屬72型2021/9/107Anti-HAV PrevalenceHighIntermediateLowVery LowGeographic Distribution of HAV infection2021/9/108生物學(xué)性狀HAV為球形顆粒，直徑2732nm，無包膜。基因組為線狀單正鏈RNA2021/9/109由VP14四種多肽組成VP1是主要衣

4、殼蛋白和中和抗原，能中和所有HAV細(xì)胞培養(yǎng)：HAV可用猴腎、人胚腎細(xì)胞等進(jìn)行增殖和傳代，但不引起CPE易感動(dòng)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(qiáng)對(duì)乙醚、酸、熱（60oC）穩(wěn)定。高壓、紫外、煮沸等可滅活2021/9/1010流行病學(xué)傳染源患者和隱性感染者傳播方式：糞口途徑污染食物、水源、海產(chǎn)品引起暴發(fā)或散發(fā)流行 隱性感染率高成人HAV抗體陽(yáng)性率高達(dá)70%90%2021/9/1011致病性非溶細(xì)胞型病毒，不直接殺傷細(xì)胞病毒復(fù)制量與癥狀嚴(yán)重程度不一致，故認(rèn)為免疫應(yīng)答參與損傷過程病后期糞便可檢出sIgA抗體無慢性病例典型的甲肝是自限過程，大約三個(gè)月2021/9/1012 甲型肝

5、炎血清學(xué)變化過程2021/9/1013Sources of HAV Infection 1983-93Percentage of CasesSource: CDC, Viral Hepatitis Surveillance ProgramYearPersonal contactDay care centerForeign travelOutbreakDrug use403020100198319841985198619871988198919901991199219932021/9/1014Concentration of HAV in Various Body Fluids Source:V

6、iral Hepatitis and Liver Disease 1984;9-22J Infect Dis 1989;160:887-890FecesSerumSalivaUrine1001021041061081010Infectious Doses per ml2021/9/1015Age-specific Incidence of Hepatitis A 1983-93Source: CDC, National Notifiable Diseases Surveillance SystemYearReported Cases (per 100,000)19831984198519861

7、9871988198919901991199219930510152025 5-14 years 15-24 years 25-39 years 0-4 years 40+ years 2021/9/1016EndemicityDiseaseRatePeak Ageof InfectionTransmission PatternsHighLow to HighEarly childhoodPerson to person;outbreaks uncommonModerateHighLate childhood/ young adultsPerson to person;food and wat

8、erborne outbreaksLowLowYoung adultsPerson to person;food and waterborne outbreaksVery lowVery lowAdultsTravelers; outbreaks uncommonGlobal Patterns of Hepatitis A Virus Transmission2021/9/1017診斷（Laboratory Diagnosis）Acute infection is diagnosed by the detection of HAV-IgM in serum by EIAPast Infecti

9、on i.e. immunity is determined by the detection of HAV-IgG by EIA 2021/9/1018防治原則加強(qiáng)食品衛(wèi)生管理，水源減毒疫苗株H2株和L1株已投放市場(chǎng)基因工程疫苗也正在研究之中應(yīng)急預(yù)防可用丙種球蛋白2021/9/1019Many cases occur in community-wide outbreaksno risk factor identified for most caseshighest attack rates in 5-14 year oldschildren serve as reservoir of inf

10、ectionPersons at increased risk of infectiontravelershomosexual meninjecting drug users Hepatitis A Vaccination StrategiesEpidemiologic Considerations2021/9/1020Pre-exposuretravelers to intermediate and high HAV-endemic regionsPost-exposure (within 14 days)Routinehousehold and other intimate contact

11、sSelected situationsinstitutions (e.g., day care centers)common source exposure (e.g., food prepared by infected food handler)Hepatitis A Prevention - Immune Globulin2021/9/1021GroupAgeNo.DosesEL.U.* (ml)Schedule(months)Children and adolescents2-18 years3360 (0.5)0, 1, 6-12Adults18 years21,440 (1.0)

12、0, 6-12DosesHAVRIX*ELISA unitsRecommended Doses & Schedules of HAV Vaccination2021/9/1022Hapatitis B Virus1963年Blumberg在多次輸血的血友病患者中發(fā)現(xiàn)澳抗，1968年確與血清型肝炎高度相關(guān)，1970年Dane在電鏡下看到具有傳染性的42nm病毒顆粒HBV在亞洲廣泛流行，在中國(guó)約10%人口攜帶該病毒，全球約3.5億2021/9/10231983年將HBV及與其分子結(jié)構(gòu)、生物學(xué)特性相似的土撥鼠肝炎病毒(woodchuck hepatitis virus,WHV)、地松鼠肝炎病毒(gr

13、ound squirrel hepatitis virus,GSHV)及鴨肝炎病毒(duck hepatits virus,DHV)歸納起來獨(dú)立命名為嗜肝病毒科（Hepadnaviridae）2021/9/1024HBsAg Prevalence8% - High 2-7% - Intermediate 2% - LowGeographic Distribution of Chronic HBV Infection2021/9/1025形態(tài)與結(jié)構(gòu)2021/9/1026電鏡檢查血清標(biāo)本可見小球形顆粒（22nm）、管形顆粒（22nmx50700nm）、大球形顆粒（42nm）2021/9/1027完

14、整的HBV顆粒亦稱Dane顆粒，顆粒直徑為42nm具有雙層衣殼結(jié)構(gòu)。外殼相當(dāng)于包膜，由脂質(zhì)雙層和乙肝表面抗原（HBsAg）、多聚人血清白蛋白受體（PHSA-r）和前S抗原（Pre-S）組成。內(nèi)部有28nm的核心，表面相當(dāng)于內(nèi)衣殼，含有乙型肝炎核心抗原（HBcAg）和乙型肝炎e抗原（HBeAg）。內(nèi)部有HBV的DNA和DNA多聚酶2021/9/1028HBV 基因組DNA是由3.2KB的長(zhǎng)鏈 L（-）和短鏈 S（+）（約為L(zhǎng)鏈的50%至85%長(zhǎng)）組成的不完全雙鏈環(huán)狀DNA，長(zhǎng)鏈載有病毒蛋白質(zhì)的全部密碼，有4個(gè)開放讀碼框架(ORF)，分別稱為S、C、P和X區(qū)2021/9/10292021/9/10

15、30HBV復(fù)制周期2021/9/10312021/9/1032HBV Replication HBV2.4 KB3.5 KBProvirusRTReplicateNuclear2.1 KB2021/9/1033 抗原組成HBV表面抗原（HBsAg）是機(jī)體受HBV感染的標(biāo)志226AA，由S基因編碼HBsAg有1個(gè)共同抗原決定簇a和2組互相排斥的亞型抗原決定簇d/y和w/r4種亞型：adr、adw、ayr、 ayw我國(guó)內(nèi)地和沿海各省漢族主要為adr型，歐美為adw 抗HBs能與HBV表面結(jié)合，使其失去感染性，具有保護(hù)作用2021/9/1034HBV核心抗原（HBcAg）在肝細(xì)胞核中才能檢出分子量2

16、2KD，由C基因編碼，病毒內(nèi)衣殼蛋白一般方法在血中檢測(cè)不到抗HBc無中和作用檢出高效價(jià)抗HBc，特別是抗HBc IgM表示HBV再肝內(nèi)處于增殖狀態(tài)2021/9/1035HBVe抗原（HBeAg）由PreC和C基因共同編碼，15KDHBcAg在細(xì)胞經(jīng)蛋白酶降解形成HBV復(fù)制及血清有傳染性的標(biāo)志抗Hbe對(duì)HBV感染有一定保護(hù)作用2021/9/1036前S抗原（Pre-S Ag）前S2蛋白S + PreS2編碼，226 + 55=281AA前S1蛋白S + PreS2 + PreS1編碼，226 + 55 + 119 = 400AA與HBsAg、HBV DNA檢出相同，都說明病毒在復(fù)制2021/9/

17、1037Pre-S2抗原和人肝細(xì)胞表面都具有PHSA受體，通過PHSAr搭橋，HBV病毒易吸附于肝細(xì)胞表面部分解釋為什么HBV具有嗜肝細(xì)胞性抗前S1和抗前S2抗體具有中和HBV作用，有保護(hù)作用2021/9/1038易感動(dòng)物和細(xì)胞培養(yǎng)：只有黑猩猩對(duì)HBV易感，體外細(xì)胞培養(yǎng)尚未成功2021/9/1039抵抗力：強(qiáng)對(duì)低溫、干燥、UV、醚、氯仿、酚等均有抵抗性高壓蒸汽滅菌、0.5%過氧乙酸、5%次氯酸鈉、3%漂白粉液、0.2%新潔爾滅均可滅活病毒，但處理時(shí)間要稍長(zhǎng)2021/9/1040Incubation period:Average 60-90 daysRange 45-180 daysClinic

18、al illness (jaundice):5 yrs, 10%5 yrs, 30%-50%Acute case-fatality rate:0.5%-1%Chronic infection:8%): 45% of global populationlifetime risk of infection 60%early childhood infections commonIntermediate (2%-7%): 43% of global populationlifetime risk of infection 20%-60%infections occur in all age grou

19、psLow (2%): 12% of global populationlifetime risk of infection 20%most infections occur in adult risk groupsGlobal Patterns of Chronic HBV Infection2021/9/1043 HighModerateLow/NTbloodsemenurineserumvaginal fluidfeceswound exudatessalivasweattearsbreastmilkConcentration of Hepatitis B Virus in Variou

20、s Body Fluids2021/9/1044 Modes of Transmission of HBVSexual sexual and homosexuals are particular at riskParenteral Intravenous drug abuse (IVDA), Health Workers are at increased riskPerinatalMothers who are HBeAg positive are much more likely to transmit to their offspring than those who are not Pe

21、rinatal transmission is the main means of transmission in high prevalence populations2021/9/1045傳染源：急、慢性乙肝患者及無癥狀攜帶者傳播途徑：非胃腸道途徑血液、血制品傳播輸血、丙種球蛋白醫(yī)源性傳播：注射（吸毒）、手術(shù)、采血、針刺、撥牙、內(nèi)窺鏡檢查、紋身等接觸傳播：公共衛(wèi)生潔具、剃刀、吸血昆蟲母嬰傳播宮內(nèi)感染相對(duì)少（10%）母親HBeAg陽(yáng)性嬰兒感染機(jī)會(huì)大（90%）HBeAg陰性、抗HBe陽(yáng)性嬰兒感染機(jī)率小（10%15%）2021/9/1046* Includes sexual contact wi

22、th acute cases, carriers, and multiple partners. Source: CDC Sentinel Counties Study of Viral HepatitisHeterosexual* (41%)Homosexual Activity (9%)Household Contact (2%)Health Care Employment (1%)Other (1%)Unknown (31%)InjectingDrug Use(15%)Risk factors for Acute Hepatitis B1992-1993 USA2021/9/1047So

23、urce: CDC Viral Hepatitis Surveillance Program0-1415-1920-2930-3940+0510152025Rate of Reported Hepatitis B by Age Group USA 1990Age Group (years)Rate (/100,000)2021/9/1048ExposureInfectionDeath 1%FulminanthepatitisRecovery90% - 95% ImmuneAsymptomatic CarrierPersistent InfectionChromic hepatitisChron

24、ic active hepatitisCirrhosisHepatocellular carcinoma2021/9/1049致病機(jī)理尚未完全明了HBV不直接損害肝細(xì)胞，通過宿主的免疫應(yīng)答引起肝細(xì)胞的損傷和破壞2021/9/1050細(xì)胞免疫損傷細(xì)胞免疫強(qiáng)弱與臨床過程輕重與轉(zhuǎn)歸密切相關(guān)免疫力過強(qiáng)可出現(xiàn)重癥肝炎，過低則是慢性肝炎體液免疫損傷：不十分重要先天性無丙種球蛋白血癥患者乙肝仍表現(xiàn)為典型的肝炎病變抗原抗體復(fù)合物超敏反應(yīng)，造成了肝外癥狀表現(xiàn)自身免疫損傷HBV感染后，肝細(xì)胞自身表面抗原肝特異性脂蛋白抗原（Liver specific protein, LSP）暴露2021/9/1051HBV與原

25、發(fā)性肝細(xì)胞癌乙肝患者原發(fā)性肝癌發(fā)生率比對(duì)照高原發(fā)性肝癌患者有HBV感染標(biāo)志者比自然人群多HBV感染者比陰性者發(fā)生原發(fā)性肝癌的危險(xiǎn)性高217倍WHV可誘導(dǎo)土撥鼠肝硬化及原發(fā)性肝癌新生土撥鼠感染W(wǎng)HV三年后100%發(fā)生肝癌未感染鼠則無一只發(fā)生肝癌肝癌細(xì)胞DNA整合有HBV-DNA2021/9/1052免疫性體液免疫HBV的中和抗體抗HBs抗Pre-S2細(xì)胞免疫CTL是清除細(xì)胞內(nèi)病毒的主要機(jī)制細(xì)胞免疫處于較低水平則易轉(zhuǎn)為慢性2021/9/1053微生物學(xué)檢查法病毒核酸的檢測(cè)斑點(diǎn)雜交法，PCR，極敏感的方法，臨床常規(guī)對(duì)血清病毒DNA濃度可做動(dòng)態(tài)監(jiān)測(cè)HBV抗原、抗體的檢測(cè)最敏感方法是RIA、ELISA檢

26、測(cè)項(xiàng)目HBsAg和抗-HBsHBeAg和抗-Hbe抗-HBcIgM和抗HBc-IgG2021/9/1054SymptomsHBeAganti-HBeTotal anti-HBcIgM anti-HBcanti-HBsHBsAg0481216202428323652100Typical Serologic CourseWeeks after ExposureTitreAcute Hepatitis B Virus Infection with Recovery2021/9/1055IgM anti-HBcTotal anti-HBcHBsAgAcute(6 months)HBeAgChronic

27、(Years)anti-HBe0481216202428323652YearsWeeks after ExposureTitreProgression to Chronic Hepatitis B Virus InfectionTypical Serologic Course2021/9/1056HBsA：表示機(jī)體感染了HBV急性乙型肝炎潛伏期和急性期（70%）HBV所致的慢性肝病如慢性乙型肝炎、肝硬化和原發(fā)性肝炎無癥狀HBsAg攜帶者抗HBs機(jī)體曾感染過HBV，并獲得對(duì)HBV的免疫力2021/9/1057HBcAg：常規(guī)方法難以檢出，臨床不做抗HBc抗HBc IgM出現(xiàn)于急性乙型肝炎急性期抗

28、HBc IgG陽(yáng)性表示過去感染過HBV，少數(shù)也可能仍有HBV感染2021/9/1058HBeAg：體內(nèi)HBV復(fù)制和血液傳染性強(qiáng)急性乙肝HBeAg呈短暫陽(yáng)性，如持續(xù)陽(yáng)性提示轉(zhuǎn)為慢性，預(yù)后不良孕婦HBeAg陽(yáng)性，新生兒感染率高抗Hbe見于急性乙肝的恢復(fù)期，可持續(xù)較長(zhǎng)時(shí)間機(jī)體獲得一定免疫力2021/9/1059Pre-S1、Pre-S2和PHSA受體HBV新感染的標(biāo)志，檢出表示HBV正在復(fù)制抗Pre-S1、抗Pre-S2中和病毒出現(xiàn)于急性乙肝恢復(fù)早期消失較快2021/9/1060Examples of Serology Test2021/9/1061預(yù)防原則要采取切斷傳播途徑為主的綜合性措施自動(dòng)免疫

29、：HBsAg疫苗（血源或重組）被動(dòng)免疫：乙肝免疫球蛋白(HBIg)。接種者:醫(yī)務(wù)人員或?qū)嶒?yàn)室工作人員HBsAg、HBeAg陽(yáng)性母親的新生兒發(fā)現(xiàn)已誤用HBsAg陽(yáng)性的血液或血制品者與HBsAg、HBeAg陽(yáng)性者有密切性接觸者2021/9/1062Elimination of HBV TransmissionPrevent perinatal HBV transmissionRoutine vaccination all infantschildren in high-risk groupsadolescentsall unvaccinated children at 11-12 yearsadu

30、lts in high-risk groups2021/9/1063VaccinelicensedHBsAg screeningof pregnant women recommendedInfantimmunizationrecommendedAdolescent immunization recommendedDecline among homosexual men & HCWsDecline among injectingdrug users80706050403020100787980818283848586878889909192939495YearCases per 100,000

31、PopulationEstimated Incidence of Acute Hepatitis B, USA 1978-1995 2021/9/1064Hepatitis C virus1978年WHO將非甲非乙型肝炎病毒按傳播途徑分為腸道傳播的非甲非乙型病毒和腸道外傳播的非甲非乙型肝炎病毒1989年進(jìn)一步將前者命名為戊型肝炎病毒（HEV），將后者命名為丙型肝炎病毒（HCV）目前擬將HCV和庚型肝炎病毒（HGV）列入黃病毒科（Flavivurus）Hepacivirus屬2021/9/10652021/9/1066生物學(xué)性狀HCV屬于黃病毒科，電鏡照片不清晰，似球形，直徑5565 nm，有脂

32、蛋白包膜，包膜上有短突起。核酸為+ssRNA，9.4Kb2021/9/1067由于不能培養(yǎng)，故尚不能進(jìn)行血清分型據(jù)基因序列同源性，分為I VI六個(gè)基因型。中國(guó)和亞洲流行多型，歐美為I 型細(xì)胞培養(yǎng)未成功黑猩猩是唯一易感動(dòng)物2021/9/1068 hypervariableregioncapsidenvelopeproteinprotease/helicaseRNA polymerasec225coreE1E2NS2NS333cNS4c-100NS53Hepatitis C Virus Genome2021/9/1069 HCV基因結(jié)構(gòu)2021/9/1070 Hepatitis C - Clini

33、cal Features潛伏期 平均6-7周（2-26周）急性表現(xiàn)（黃疸） 輕微(20%)急性期死亡率 低慢性感染率75%-85%慢性肝炎70% 肝硬化10%-20%慢性肝臟疾病導(dǎo)致死亡1%-5%2021/9/1071Chronic Hepatitis C InfectionThe spectrum of chronic hepatitis C infection is essentially the same as chronic hepatitis B infectionAll the manifestations of chronic hepatitis B infection may

34、be seen, albeit with a lower frequency i.e. chronic persistent hepatitis, chronic active hepatitis, cirrhosis, and hepatocellular carcinoma2021/9/1072病理HCV不直接殺傷細(xì)胞病理免疫和細(xì)胞凋亡是造成傷害原因2021/9/1073Transmission of HCVPercutaneous Intravenous drug abuseTransfusion, transplant Therapeutic (contaminated equipme

35、nt, unsafe injection practices)PermucosalPerinatalSexual2021/9/1074Sources of Infection forPersons with Hepatitis CSexual 15%Other* 5%Unknown 10%Injecting drug use 60%Transfusion 10%(before screening)*Nosocomial; Health-care work; PerinatalSource: Centers for Disease Control and Prevention2021/9/107

36、5Source: Sentinel Counties, CDCHCV Prevalence by Selected Groups, USAHemophiliaInjecting drug usersSurgeons, PSWsHemodialysis Average Percent Anti-HCV PositiveGen population adultsMilitary personnelSTD clientsPregnant women2021/9/1076Prevalence of HCV Infection by Age & Gender, 1988-1994 USAMalesFem

37、alesSource: CDC, NHANES IIITotal2021/9/1077Perinatal Transmission of HCVTransmission only from women HCV-RNA positive at deliveryAverage rate of infection 6%Higher (17%) if woman co-infected with HIVNo association withDelivery methodBreastfeedingInfected infants do wellSevere hepatitis is rare2021/9

38、/1078Household Transmission of HCVRare but not absentCould occur through percutaneous/mucosal exposures to bloodTheoretically through sharing of contaminated personal articles (razors, toothbrushes)Contaminated equipment used for home therapiesInjections*Folk remedies79*Reported in U.S.Serologic Pat

39、tern of Acute HCV Infection with RecoverySymptoms +/-Time after ExposureTiteranti-HCVALTNormal01234561234YearsMonthsHCV RNA 2021/9/1080Serologic Pattern of Chronic HCV Infection with Progression InfectionSymptoms +/-Time after ExposureTiteranti-HCVALTNormal01234561234YearsMonthsHCV RNA 2021/9/1081La

40、boratory DiagnosisHCV antibody - generally used to diagnose hepatitis C infection. Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears.HCV-RNA - various techniques are available e.g. PCR and branched DNA. May be used to diagnose HCV infection in the acu

41、te phase. However, its main use is in monitoring the response to antiviral therapy.HCV-antigen - an EIA for HCV antigen is available. It is used in the same capacity as HCV-RNA tests but is much easier to carry out.2021/9/1082HCV Infection Testing Algorithmfor Diagnosis of Asymptomatic PersonsEIA fo

42、r Anti-HCVNegative (non-reactive)STOPPositive (repeat reactive)ORRIBA for Anti-HCVRT-PCR for HCV RNANegativeSTOPAdditional Laboratory Evaluation (e.g. PCR, ALT)NegativePositiveIndeterminateMedical EvaluationPositiveNegative PCR, Normal ALTPositive PCR, Abnormal ALTSource: MMWR 1998;47 (No. RR 19)202

43、1/9/1083Routine HCV Testing Not Recommended (Unless Risk Factor Identified) Health-care, emergency medical, and public safety workers Pregnant women Household (non-sexual) contacts of HCV-positive persons2021/9/1084Screening of blood, organ, tissue donorsHigh-risk behavior modificationBlood and body

44、 fluid precautions Prevention of Hepatitis C2021/9/1085Estimated Incidence of Acute HCV Infection, 1960-1999 USADecline intransfusion recipientsDecline in injection drug usersSource: Hepatology 2000;31:777-82 Hepatology 1997;26:62S-65S 2021/9/1086Posttransfusion Hepatitis C All volunteer donorsHBsAg

45、Donor Screening for HIV Risk FactorsAnti-HIVALT/Anti-HBcAnti-HCVImproved HCV TestsAdapted from HJ Alter and Tobler and Busch, Clin Chem 19972021/9/1087TreatmentInterferon - may be considered for patients with chronic active hepatitis. The response rate is around 50% but 50% of responders will relaps

46、e upon withdrawal of treatment.Ribavirin - there is less experience with ribavirin than interferon. However, recent studies suggest that a combination of interferon and ribavirin is more effective than interferon alone.2021/9/1088Hepatitis D virus肝炎病毒（Hepatitis virus）從HBV感染者中發(fā)現(xiàn)的2021/9/1089HDV Preval

47、enceHighIntermediateLowVery LowNo DataTaiwanPacific IslandsGeographic Distribution of HDV Infection2021/9/1090生物學(xué)性狀3537nm，球形顆粒環(huán)狀單股負(fù)鏈RNA和HDAg（即抗原） 1.7Kb表面為HBV包膜蛋白（HBsAg）2021/9/1091HBsAgRNAd antigen2021/9/1092HDV為缺陷病毒不能獨(dú)立進(jìn)行復(fù)制，必須在HBV或其它嗜肝DNA病毒輔助才能增殖敏感動(dòng)物黑猩猩，土撥鼠和北京鴨等2021/9/1093Hepatitis D - Clinical Feat

48、uresCoinfectionsevere acute diseaselow risk of chronic infectionSuperinfectionusually develop chronic HDV infectionhigh risk of severe chronic liver diseasemay present as an acute hepatitis2021/9/1094 HDV TransmissionPercutanous exposuresinjecting drug usePermucosal exposuressex contact2021/9/1095免疫

49、性抗HDV 不能清除病毒，為診斷指標(biāo)HDV IgM和IgG持續(xù)存在，提示為HDV慢性感染2021/9/1096Time after ExposureTiteranti-HBsSymptomsALT ElevatedTotal anti-HDVIgM anti-HDVHDV RNAHBsAgSerological Course of Acute HDV infection2021/9/1097Time after ExposureTiterJaundiceSymptomsALTTotal anti-HDVIgM anti-HDVHDV RNAHBsAgSerological Course of

50、HDV superinfection2021/9/1098微生物學(xué)檢查法血清學(xué)方法ELISA檢查HDAg或抗HDVHDAg在急性期可陽(yáng)性，檢出率低慢性感染檢不到核酸分子雜交法2021/9/1099HBV-HDV CoinfectionPre or postexposure prophylaxis to prevent HBV infection.HBV-HDV SuperinfectionEducation to reduce risk behaviors among persons with chronic HBV infection. Hepatitis D - Prevention2021/9/10100Hepatitis E virus，HEV戊型肝炎病毒經(jīng)腸道傳播的非甲非乙型肝炎病毒疾病：戊型肝炎2021/9/10101Geographic Distribution of Hepatitis E2021/9/10102生物學(xué)性狀2021/9/10103