Hepatitis viruses.

Presentation on theme: "Hepatitis viruses."— Presentation transcript:

1 Hepatitis viruses

2 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 其他病毒如黄热病毒、CMV、EBV、风疹病毒等也可引起肝炎，但不列为肝炎病毒

3 Viral Hepatitis - Historical Perspectives
Enterically transmitted “Infectious” A E Viral hepatitis NANB Parenterally transmitted “Serum” B D C F, G, TTV ? other 2

4 Hepatitis A virus 1973年Feinstone应用免疫电镜技术从急性肝炎患者粪便悬液中发现
生物学性状与肠道病毒一致，故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

5 Geographic Distribution of HAV infection
Anti-HAV Prevalence High Intermediate Low Very Low 16

6 生物学性状 HAV为球形颗粒，直径27～32nm，无包膜。基因组为线状单正链RNA

7 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（60oC）稳定。高压、紫外、煮沸等可灭活

8 致病性 传染源为患者和隐性感染者 传播方式是粪－口途径。HAV污染食物、水源、海产品等引起暴发或散发流行
病毒进入机体经过两次病毒血症，到达肝脏，在肝细胞增殖致病

9 非溶细胞型病毒，不直接杀伤细胞，患者症状高峰是潜伏期末和症状出现初期，与病毒复制高峰时间不相符，说明病毒复制量与症状严重程度不一致，故认为免疫应答参与损伤过程
发病后期粪便中可检出sIgA抗体。出现病毒的特异细胞免疫应答 典型的甲肝是自限过程，大约三个月，无慢性病例

10 Hepatitis A - Clinical Features
Incubation period: Average 30 days Range days Jaundice by <6 yrs, <10% age group: yrs, 40%-50% >14 yrs, 70%-80% Complications: Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis Chronic sequelae: None 7

11 Hepatitis A Infection Typical Serological Course ALT Total anti-HAV
Symptoms ALT Total anti-HAV Titre IgM anti-HAV Fecal HAV 1 2 3 4 5 6 12 24 Months after exposure 9

12 Hepatitis A Virus Transmission
Close personal contact (e.g., household contact, sex contact, child day care centers) Contaminated food, water (e.g., infected food handlers, raw shellfish) Blood exposure (rare) (e.g., injecting drug use, transfusion) 11

13 Sources of HAV Infection 1983-93
40 30 Personal contact Percentage of Cases 20 Day care center 10 Foreign travel Drug use Outbreak 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 Year Source: CDC, Viral Hepatitis Surveillance Program 14

14 Concentration of HAV in Various Body Fluids
Feces Serum Saliva Urine 100 102 104 106 108 1010 Infectious Doses per ml Source: Viral Hepatitis and Liver Disease 1984;9-22 J Infect Dis 1989;160: 10

15 Age-specific Incidence of Hepatitis A 1983-93
25 20 15 5-14 years Reported Cases (per 100,000) 15-24 years 25-39 years 10 0-4 years 5 40+ years 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 Year Source: CDC, National Notifiable Diseases Surveillance System 13

16 Global Patterns of Hepatitis A Virus Transmission
Disease Peak Age Endemicity Rate of Infection Transmission Patterns High Low to Early Person to person; High childhood outbreaks uncommon Moderate High Late Person to person; childhood/ food and waterborne young adults outbreaks Low Low Young adults Person to person; food and waterborne outbreaks Very low Very low Adults Travelers; outbreaks uncommon 15

17 诊断（Laboratory Diagnosis）
Acute infection is diagnosed by the detection of HAV-IgM in serum by EIA. Past Infection i.e. immunity is determined by the detection of HAV-IgG by EIA.

18 防治原则 加强食品卫生管理，水源保护。但HAV感染以隐性感染和无黄疸型病毒例占多数，故对传染源较难控制
我国已批准将减毒疫苗株H2株和L1株投放市场试用 应急预防可用丙种球蛋白 基因工程疫苗也正在研究之中

19 Hepatitis A Vaccination Strategies Epidemiologic Considerations
Many cases occur in community-wide outbreaks no risk factor identified for most cases highest attack rates in 5-14 year olds children serve as reservoir of infection Persons at increased risk of infection travelers homosexual men injecting drug users 18

20 Hepatitis A Prevention - Immune Globulin
Pre-exposure travelers to intermediate and high HAV-endemic regions Post-exposure (within 14 days) Routine household and other intimate contacts Selected situations institutions (e.g., day care centers) common source exposure (e.g., food prepared by infected food handler) 27

21 Recommended Doses & Schedules of HAV Vaccination
HAVRIXâ No. Doses Schedule Group Age Doses EL.U.* (ml) (months) Children and adolescents 2-18 years 3 360 (0.5) 0, 1, 6-12 Adults >18 years 2 1,440 (1.0) 0, 6-12 *ELISA units 26

22 Hapatitis B Virus 1963年Blumberg在多次输血的血友病患者中发现澳抗，1968年确与血清型肝炎高度相关，1970年Dane在电镜下看到具有传染性的42nm病毒颗粒 HBV在亚洲广泛流行，在中国约10%人口携带该病毒，全球约3.5亿

23 1983年将HBV及与其分子结构、生物学特性相似的土拨鼠肝炎病毒(woodchuck hepatitis virus,WHV)、地松鼠肝炎病毒(ground squirrel hepatitis virus,GSHV)及鸭肝炎病毒(duck hepatits virus,DHV)归纳起来独立命名为嗜肝病毒科（Hepadnaviridae）

24 Geographic Distribution of Chronic HBV Infection
HBsAg Prevalence ³8% - High 2-7% - Intermediate <2% - Low 36

25 形态与结构 28

26 电镜检查血清标本可见小球形颗粒（22nm）、管形颗粒（22nmx50—700nm）、大球形颗粒（42nm）

27 完整的HBV颗粒亦称Dane颗粒，颗粒直径为42nm
具有双层衣壳结构。外壳相当于包膜，由脂质双层和乙肝表面抗原（HBsAg）、多聚人血清白蛋白受体（PHSA-r）和前S抗原（Pre-S）组成。内部有28nm的核心，表面相当于内衣壳，含有乙型肝炎核心抗原（HBcAg）和乙型肝炎e抗原（HBeAg）。内部有HBV的DNA和DNA多聚酶

28 HBV 基因组 DNA是由3.2KB的长链 L（-）和短链 S（+）（约为L链的50%至85%长）组成的不完全双链环状DNA，长链载有病毒蛋白质的全部密码，有4个开放读码框架(ORF)，分别称为S、C、P和X区

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32 HBV: Replication Nuclear 2.1 KB 2.4 KB HBV 3.5 KB Provirus Replicate
RT

33 抗原组成 HBV表面抗原（HBsAg），是机体受HBV感染的标志。226AA，由S基因编码。HBsAg有一个共同抗原决定簇a和二组互相排斥的亚型抗原决定簇d/y和w/r。因此， HBsAg可分为adr、adw、ayr和 ayw4种亚型。我国内地和沿海各省汉族主要为adr型，欧美为adw HBsAg刺激机体产生的抗HBs，能与HBV表面结合,使其失去感染性，具有防御HBV感染的作用

34 HBV核心抗原（HBcAg），在肝细胞核中才能检出。分子量22KD，由C基因编码，是病毒的内衣壳蛋白。通常被HBsAg或与抗HBc抗体结合成免疫复合物，一般方法在血中检测不到，只能在肝细胞内检出。是致敏CTL作用的靶抗原 抗HBc无中和作用，检出高效价抗HBc，特别是抗HBc IgM表示HBV再肝内处于增殖状态

35 HBVe抗原（HBeAg），由PreC和C基因共同编码， 15KD，是HBcAg在细胞经蛋白酶降解形成。是HBV复制及血清有传染性的标志
抗HBe对HBV感染有一定保护作用

36 前S抗原（Pre-S Ag），目前认为，HBsAg由三种蛋白组成。病毒小球颗粒只有主要蛋白，而大球形颗粒和管形颗粒里则有300—400分子的主要蛋白和40—80分子的中等蛋白和大分子蛋白
主要蛋白：S基因编码，226AA 中等蛋白：S + PreS2编码， =281AA，称前S2蛋白或抗原 大分子蛋白：S + PreS2 + PreS1编码， = 400AA，称前S1蛋白或抗原

37 Pre-S2抗原和人肝细胞表面都具有PHSA受体，通过PHSAr搭桥，HBV病毒易吸附于肝细胞表面，这也可以部分解释为什么HBV具有嗜肝细胞性
Pre-S抗原的出现与HBsAg、HBV DNA的检出意义相同，都说明病毒在复制 抗前S1和抗前S2抗体具有中和血循环内的HBV作用，故具有阻止HBV侵入肝细胞的免疫防御作用

38 易感动物和细胞培养：只有黑猩猩对HBV易感，体外细胞培养尚未成功

39 抵抗力：认为抵抗力相当强 对低温、干燥、UV、醚、氯仿、酚等均有抵抗性 高压蒸汽灭菌、0.5%过氧乙酸、5%次氯酸钠、3%漂白粉液、0.2%新洁尔灭均可灭活病毒，但处理时间要稍长

40 Hepatitis B - Clinical Features
Incubation period: Average days Range days Clinical illness (jaundice): <5 yrs, <10% yrs, 30%-50% Acute case-fatality rate: 0.5%-1% Chronic infection: <5 yrs, 30%-90% yrs, 2%-10% Premature mortality from chronic liver disease: 15%-25% 29

41 Spectrum of Chronic Hepatitis B
Chronic Persistent Hepatitis - asymptomatic Chronic Active Hepatitis - symptomatic exacerbations of hepatitis Cirrhosis of Liver Hepatocellular Carcinoma

42 Global Patterns of Chronic HBV Infection
High (>8%): 45% of global population lifetime risk of infection >60% early childhood infections common Intermediate (2%-7%): 43% of global population lifetime risk of infection 20%-60% infections occur in all age groups Low (<2%): 12% of global population lifetime risk of infection <20% most infections occur in adult risk groups 35

43 Concentration of Hepatitis B Virus in Various Body Fluids
High Moderate Low/NT blood semen urine serum vaginal fluid feces wound exudates saliva sweat tears breastmilk 1 1 1

44 Modes of Transmission of HBV
Sexual sexual and homosexuals are particular at risk. Parenteral Intravenous drug abuse (IVDA), Health Workers are at increased risk. Perinatal Mothers who are HBeAg positive are much more likely to transmit to their offspring than those who are not. Perinatal transmission is the main means of transmission in high prevalence populations. 2 2 2

45 传染源：急、慢性乙肝患者及无症状携带者 传播途径：非胃肠道途径 血液、血制品传播：输血、丙种球蛋白 医源性传播：注射（吸毒）、手术、采血、针刺、拨牙、内窥镜检查、纹身等 母婴传播：发生在围产期，通过产道或吞入羊水等因素。宫内感染相对少（<10%）。母亲HBeAg阳性婴儿感染机会大（90%），HBeAg阴性、抗HBe阳性婴儿感染机率小（10%—15%） 接触传播：公共卫生洁具、剃刀、吸血昆虫

46 Risk factors for Acute Hepatitis B 1992-1993 USA
Heterosexual* (41%) Injecting Drug Use (15%) Homosexual Activity (9%) Household Contact (2%) Health Care Employment (1%) Unknown (31%) Other (1%) * Includes sexual contact with acute cases, carriers, and multiple partners. Source: CDC Sentinel Counties Study of Viral Hepatitis 3 3 3

47 Rate of Reported Hepatitis B by Age Group USA 1990
25 20 Rate (/100,000) 15 10 5 0-14 15-19 20-29 30-39 40+ Age Group (years) Source: CDC Viral Hepatitis Surveillance Program 32

48 Exposure Recovery 90% - 95% Immune Infection Asymptomatic Carrier Persistent Infection Chromic hepatitis Death 1% Fulminant hepatitis Chronic active hepatitis Cirrhosis Hepatocellular carcinoma

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50 Symptoms of Acute Infection

51 Development of the chronic HBV carrier state

52 致病机理 尚未完全明了。一般认为HBV不直接损害肝细胞，而产通过宿主的免疫应答引起肝细胞的损伤和破坏，出现相应临床表现
细胞免疫损伤：以抗原特异CTL为主。直接杀伤或释放淋巴因子间接杀伤肝细胞。细胞免疫强弱与临床过程轻重与转归密切相关。免疫力过强可出现重症肝炎，过低则是慢性肝炎

53 体液免疫损伤：并不十分重要，因为先天性无丙种球蛋白血症患者的乙肝仍表现为典型的肝炎病变。抗原抗 体复合物导致的超敏反应，造成了肝外症状表现，如关节炎、皮疹、肾小球肾炎等
自身免疫损伤：HBV感染后，肝细胞自身表面抗原—肝特异性脂蛋白抗原（Liver specific protein, LSP）暴露，自身抗体加重肝细胞损伤

54 HBV与原发性肝细胞癌 乙肝患者原发性肝癌发生率比对照高。原发性肝癌患者血清中，有HBV感染标志者比自然人群多。HBV感染者比阴性者发生原发性肝癌的危险性高217倍 与HBV分子生物学相似的WHV在其宿主土拨鼠中可诱导肝硬化及原发性肝癌。新生土拨鼠感染WHV三年后100%发生肝癌，未感染鼠则无一只发生肝癌 肝癌细胞DNA整合有HBV-DNA

55 免疫性 体液免疫：有免疫防御作用的有抗HBs和抗Pre-S2，是HBV的中和抗体
细胞免疫：CTL是清除细胞内病毒的主要机制，如细胞免疫处于较低水平则易转为慢性

56 微生物学检查法 病毒核酸的检测：斑点杂交法，PCR，极敏感的方法，临床常规。对血清病毒DNA浓度可做动态监测 HBV抗原、抗体的检测
最敏感方法是RIA、ELISA 检测的项目主要是HBsAg和抗-HBs、HBeAg和抗-HBe、以及抗-HBcIgM和抗HBc-IgG

57 Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course Symptoms HBeAg anti-HBe Total anti-HBc Titre anti-HBs HBsAg IgM anti-HBc 4 8 12 16 20 24 28 32 36 52 100 Weeks after Exposure 30

58 Progression to Chronic Hepatitis B Virus Infection
Typical Serologic Course Acute (6 months) Chronic (Years) HBeAg anti-HBe HBsAg Total anti-HBc Titre IgM anti-HBc 4 8 12 16 20 24 28 32 36 52 Weeks after Exposure Years 31

59 HBsA：表示机体感染了HBV。阳性见于
急性乙型肝炎潜伏期和急性期（70%） HBV所致的慢性肝病如慢性乙型肝炎、肝硬化和原发性肝炎 无症状HBsAg携带者 抗HBs：表示机体曾感染过HBV，并获得对HBV的免疫力

60 HBcAg：常规方法难以检出，临床不做 抗HBc 抗HBc IgM出现于急性乙型肝炎急性期 抗HBc IgG阳性表示过去感染过HBV，少数也可能仍有HBV感染

61 HBeAg：HBeAg阳性是体内有HBV复制和血液传染性强的标志

62 Pre-S1、Pre-S2和PHSA受体：HBV新感染的标志，检出表示HBV正在复制

63 Examples of Serology Test

64 预防原则 要采取切断传播途径为主的综合性措施 自动免疫：HBsAg疫苗（血源或重组） 被动免疫：乙肝免疫球蛋白(HBIg)。接种者:
医务人员或实验室工作人员 HBsAg、HBeAg阳性母亲的新生儿 发现已误用HBsAg阳性的血液或血制品者 与HBsAg、HBeAg阳性者有密切性接触者

65 Elimination of HBV Transmission
Strategy Prevent perinatal HBV transmission Routine vaccination all infants children in high-risk groups adolescents all unvaccinated children at years adults in high-risk groups 5 5 5

66 Estimated Incidence of Acute Hepatitis B, USA 1978-1995
80 HBsAg screening of pregnant women recommended Vaccine licensed 70 Infant immunization recommended 60 50 Cases per 100,000 Population Adolescent immunization recommended 40 30 20 Decline among homosexual men & HCWs Decline among injecting drug users 10 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 Year 6 6 6

67 Hepatitis C virus 1978年WHO将非甲非乙型肝炎病毒按传播途径分为肠道传播的非甲非乙型病毒和肠道外传播的非甲非乙型肝炎病毒 1989年进一步将前者命名为戊型肝炎病毒（HEV），将后者命名为丙型肝炎病毒（HCV） 目前拟将HCV和庚型肝炎病毒（HGV）列入黄病毒科（Flavivurus）Hepacivirus属

68 14 14 14

69 生物学性状 HCV属于黄病毒科，电镜照片不清晰，似球形，直径55～65 nm，有脂蛋白包膜，包膜上有短突起。核酸为+ssRNA，9.4Kb

70 由于不能培养，故尚不能进行血清分型。据基因序列同源性，现分为I — VI六个基因型。中国和亚洲流行多Ⅱ型，欧美为I 型
细胞培养未成功。黑猩猩是唯一易感动物

71 Hepatitis C Virus Genome
capsid envelope protein protease/helicase RNA polymerase c22 33c c-100 5’ 3’ core E1 E2 NS2 NS3 NS4 NS5 hypervariable region 7 7 7

72 Hepatitis C - Clinical Features
潜伏期 平均6-7周（2-26周） 急性表现（黄疸） 轻微(<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% 慢性肝脏疾病导致死亡 1%-5%

73 Chronic Hepatitis C Infection
The spectrum of chronic hepatitis C infection is essentially the same as chronic hepatitis B infection. All the manifestations of chronic hepatitis B infection may be seen, albeit with a lower frequency i.e. chronic persistent hepatitis, chronic active hepatitis, cirrhosis, and hepatocellular carcinoma.

74 病理 HCV不直接杀伤细胞，故其致病机理被认是病理免疫和细胞凋亡是造成伤害的原因

75 Transmission of HCV Percutaneous Permucosal Intravenous drug abuse
Transfusion, transplant Therapeutic (contaminated equipment, unsafe injection practices) Permucosal Perinatal Sexual

76 Sources of Infection for Persons with Hepatitis C
Injecting drug use 60% Sexual 15% Transfusion 10% (before screening) Other* 5% Unknown 10% *Nosocomial; Health-care work; Perinatal Source: Centers for Disease Control and Prevention Source: Sentinel Counties, CDC

77 HCV Prevalence by Selected Groups, USA
Hemophilia Injecting drug users Hemodialysis STD clients Gen population adults Surgeons, PSWs Pregnant women Military personnel Average Percent Anti-HCV Positive

78 Prevalence of HCV Infection by Age & Gender, 1988-1994 USA
Males Total Females Source: CDC, NHANES III

79 Perinatal Transmission of HCV
Transmission only from women HCV-RNA positive at delivery Average rate of infection 6% Higher (17%) if woman co-infected with HIV No association with Delivery method Breastfeeding Infected infants do well Severe hepatitis is rare

80 Household Transmission of HCV
Rare but not absent Could occur through percutaneous/mucosal exposures to blood Theoretically through sharing of contaminated personal articles (razors, toothbrushes) Contaminated equipment used for home therapies Injections* Folk remedies *Reported in U.S.

81 Serologic Pattern of Acute HCV Infection
with Recovery anti-HCV Symptoms +/- HCV RNA Titer ALT Normal 1 2 3 4 5 6 1 2 3 4 Months Years Time after Exposure

82 Serologic Pattern of Chronic HCV Infection with Progression Infection
anti-HCV Symptoms +/- HCV RNA Titer ALT Normal 1 2 3 4 5 6 1 2 3 4 Months Years Time after Exposure

83 Laboratory Diagnosis HCV 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 acute 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.

84 HCV Infection Testing Algorithm for Diagnosis of Asymptomatic Persons
Negative (non-reactive) STOP EIA for Anti-HCV Positive (repeat reactive) OR Negative RIBA for Anti-HCV RT-PCR for HCV RNA Negative Indeterminate Positive Positive STOP Additional Laboratory Evaluation (e.g. PCR, ALT) Medical Evaluation Negative PCR, Normal ALT Positive PCR, Abnormal ALT Source: MMWR 1998;47 (No. RR 19)

85 Routine 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 persons

86 Prevention of Hepatitis C
Screening of blood, organ, tissue donors High-risk behavior modification Blood and body fluid precautions 15 15 15

87 Estimated Incidence of Acute HCV Infection, 1960-1999 USA
Decline in injection drug users Decline in transfusion recipients Source: Hepatology 2000;31:777-82 Hepatology 1997;26:62S-65S

88 Posttransfusion Hepatitis C
All volunteer donors HBsAg Donor Screening for HIV Risk Factors Anti-HIV ALT/Anti-HBc Anti-HCV Improved HCV Tests Adapted from HJ Alter and Tobler and Busch, Clin Chem 1997

89 Treatment Interferon - may be considered for patients with chronic active hepatitis. The response rate is around 50% but 50% of responders will relapse 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.

90 Hepatitis D virus 又称δ肝炎病毒（Hepatitis δ virus） 从HBV感染者中发现的

91 Geographic Distribution of HDV Infection
Taiwan Pacific Islands HDV Prevalence High Intermediate Low Very Low No Data 24 24 24

92 生物学性状 HDV为直径35～37nm的球形颗粒，核心含有环状单股负链RNA和HDAg（即δ抗原），表面为HBV包膜蛋白（HBsAg）包裹。HDV RNA全长为1.7Kb

93 d antigen HBsAg RNA 19 19 19

94 HDV为缺陷病毒，不能独立进行复制，必须在HBV或其它嗜肝DNA病毒辅助才能增殖
敏感动物黑猩猩，土拨鼠和北京鸭等

95 Hepatitis D - Clinical Features
Coinfection severe acute disease. low risk of chronic infection. Superinfection usually develop chronic HDV infection. high risk of severe chronic liver disease. may present as an acute hepatitis. 20 20 20

96 HDV Transmission Percutanous exposures injecting drug use
Permucosal exposures sex contact 21 21 21

97 免疫性 抗HDV 不能清除病毒，为诊断指标 抗HDV IgM感染2周后产生。如HDV IgM和IgG持续存在，提示为HDV慢性感染

98 Serological Course of Acute HDV infection
Symptoms ALT Elevated anti-HBs Titer IgM anti-HDV HDV RNA HBsAg Total anti-HDV Time after Exposure 22 22 22

99 Serological Course of HDV superinfection
Jaundice Symptoms Total anti-HDV ALT Titer HDV RNA HBsAg IgM anti-HDV Time after Exposure 23 23 23

100 微生物学检查法 血清学方法：ELISA检查HDAg或抗HDV。HDAg在急性期可阳性，检出率低。慢性感染检不到 核酸分子杂交法

101 Hepatitis D - Prevention
HBV-HDV Coinfection Pre or postexposure prophylaxis to prevent HBV infection. HBV-HDV Superinfection Education to reduce risk behaviors among persons with chronic HBV infection. 25 25 25

102 Hepatitis E virus 戊型肝炎病毒（Hepatitis E virus，HEV），所致的疾病称为戊型肝炎。是经肠道传播的非甲非乙型肝炎病毒

103 Geographic Distribution of Hepatitis E
30 30 30

104 生物学性状

105 HEV呈球形，直径27～38nm，核酸为线形（-）ssRNA，无包膜，表面呈现锯齿状，20面体立体对称。现分类于杯状病毒
只有一个血清型。但基因序列有差异 易感动物是非洲绿猴、恒河猴、黑猩猩

106 致病性 主要通过粪－口途径传播，主要因水源污染造成流行，极小生活接触导致感染
多感染20—40岁成人，潜伏期2—9周，临床表现为急性肝炎，6周即恢复。少数重症死亡。无慢性感染病例 致病机理不明，免疫损伤是主要机制。病后有一定免疫力

107 Serological Course of HEV infection
Symptoms ALT IgG anti-HEV IgM anti-HEV Titer Virus in stool 1 2 3 4 5 6 7 8 9 10 11 12 13 Weeks after Exposure 28 28 28

108 微生物学检查法 免疫电镜 血清学方法，检测抗-HEV HEV核酸检测

109 Prevention and Control Measures for Travelers to HEV-Endemic Regions
Avoid drinking water (and beverages with ice) of unknown purity, uncooked shellfish, and uncooked fruit/vegetables not peeled or prepared by traveler. IG prepared from donors in Western countries does not prevent infection. Unknown efficacy of IG prepared from donors in endemic areas. Vaccine? 31 31 31

110 庚型肝炎病毒 近年来新发现的一些肝炎病毒，研究较多的是庚型肝炎病毒（HGV）
HGV是1995年发现，属黄病毒科，核酸为+ssRNA，9.4KB，编码一个ORF。黑猩猩易感

111 HGV感染世界分布，主要经血或肠道外传播、垂直传播和性传播。受血者、接触血源的医务工作者和静脉注射吸毒者是高危人群
临床感染可表现为急性和慢性过程。HGV常与HCV重叠感染。病后抗HGV E2具有一定保护作用 诊断主要是血清学方法或PCR。HGV是否嗜肝仍不清楚，因为与疾病关系必须将HBV、HDV、HCV感染排除后才可确认

112 Summary: Type of Hepatitis
B C D E Source of feces blood/ blood/ blood/ feces virus blood-derived blood-derived blood-derived body fluids body fluids body fluids Route of fecal-oral percutaneous percutaneous percutaneous fecal-oral transmission permucosal permucosal permucosal Chronic no yes yes yes no infection Prevention pre/post- pre/post- blood donor pre/post- ensure safe exposure exposure screening; exposure drinking immunization immunization risk behavior immunization; water modification risk behavior modification 3

113 Question Examples Compare HAV and HBV according to the following criteria: classification, genome, presence of envelope, clinical features, and transmissions. What are the three important antigens in the HBV particle? Why is the delta agent found only in persons infected with HBV?

114 问题 肝炎病毒有哪些？ 简述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、抗原抗体组成及检出的意义
乙型肝炎病毒的传播方式和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