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1、Hepatitis A virus，HAV 甲型肝炎病毒 Biological Properties lpicornavirus, +ssRNA genome小RNA病毒科 l27 nm in diameter ,non- enveloped icosahedral particle 27nm, 球形， 20面立体对称， 无包膜 lone serotype一个血清型 Feinstone （1973） lStronger than enterovirus, resistant to detergents, acid (pH 1.0 for 2h), 60 for 1h，survive for m
2、onths in fresh water and salt water 抵抗力比肠道病毒强 Pathogenesis致病性 lspread via the fecal-oral route粪口途径传播 lSource of infection: patient, inapparent infection 传染源: 病人、隐性感染者 lViral shedding in the stool precedes the onset of symptoms by 14d but stops before the cessation of symptoms lSymptoms Initial sympt
3、oms: fever, fatigue, nausea, loss of appetite, abdominal pain Jaundice HAV的致病性 粪口途径传播小肠淋巴结中大量增殖 入血并形 成病毒血 症 肝脏为最终靶 器官（病毒直 接损伤或免疫 病理作用） 通过胆汁随粪 便排出体外 lAsymptomatic infections are very common. As already noted, disease in children is generally milder than that in adults and is usually asymptomatic隐性感染多
4、 lNo a chronic infection and carrier,not associated with hepatic cancer.无慢性病例和病毒携带者，不与肝癌有关 lComplete recovery:99% 预后好 lFulminant hepatitis暴发性肝炎: 13 / 1000, 80% mortality rate死亡率 lPregnant women may develop more severe disease. 孕妇感染严重 Mechanisim of pathogenisis致病机理： lDirectly injury by virus病毒直接损伤 li
5、mmunopathogenesis免疫病理作用 immunity免疫性 无论显性感染还是隐性感染 均能产生抗-HAV的 IgM和IgG抗体 抗-HAV的IgM在急性期和恢复早期出现 阳性可作为甲肝的确诊依据 抗-HAV的IgG在恢复后期出现 有保护作用，维持终身 Laboratory Diagnosis微生物学检查 lanti-HAV IgM 抗HAV IgM lby an ELISA or radioimmunoassay Treatment and Prevention 防治原则 lControl the source of infection控制传染源 lCut down the rou
6、te of transmission切断传播途径 lPassive immunization - Normal immunoglobulin 丙种球蛋白 lActive immunizations A killed HAV vaccine a live attenuated HAV vaccine hepatitis B virus, HBV乙型肝炎病毒 SHAPE AND STRUCTURESHAPE AND STRUCTURE 形态结构形态结构 There are 3 particles in patients blood lDane particle Dane颗粒（大球形颗粒） lsma
7、ll spherical particle小球形颗粒 ltubulose particle管形颗粒 Dane particle Complete particle, infective HBV spherical，double capsid球形,双层衣壳。 outer capsid=envelope 外衣壳=包膜(脂质双层+蛋白质) HBsAg等 inner capsid内衣壳： HBcAg、HBeAg internal内部： DNA- circular, double- stranded环状双链 DNA polymerase 多聚酶 HBV的小球形颗粒 HBsAg-containing pa
8、rticles 过剩的衣壳蛋白装配而成 HBV的管形颗粒 小球形颗粒串联而成 Genome of HBV a circular, double-stranded DNA containing single-strand breaks 不完 全双链环状DNA four open reading frames that encode seven polypeptides. 含4个 ORF,编码7个蛋白 S HBsAg,Pre-s1,Pre-s2 C HBcAg，HBeAg P polymerase多聚酶 X HBxAg基因 Antigen of HBV抗原组成 lhepatitis B surfa
9、ce antigenHBsAg表面抗原 indicates that virus replication is occurring in the liver 说明病毒在肝中复制（机体受感染标志） four phenotypes：adr,adw,ayr,ayw antiHBs:neutralization antibody中和抗体 lhepatitis B core antigen HBcAg核心抗原 not found in blood一般不能检出 antiHBc nonneutralization antibody非中和抗体 Core IgM indicates recent infecti
10、on. 抗HBc IgM说明 HBV复制 Core IgG indicates exposure to HBV Antigen of outer capsid外衣壳抗原 Antigens of inner capsid内衣壳抗原 lhepatitis B e antigen e抗原HBeAg the best correlate to the presence of infectious virus. 感染性病毒存在的最有效证据（复制及具传染性的 标志） anti-HBe indicates low infectivity in a carrier 抗HBe说明病毒感染性较低（是预后良好的征象
11、） lculture培养 lresistance抵抗力 strong resistance to cool,dry, ultraviolet, alcohol inactivate: 100 10min Pathogenesis and Immunity lsource of infection传染源 patients or carriers 急性、慢性患者或无症状HBsAg携带者 lroute of transmission传播途径 sexual routes parenteral肠胃外的 routes l injection of the virus into the blood stre
12、am lcontaminated blood and blood components by transfusion, needle sharing, acupuncture针灸, ear piercing, or tattooing perinatal围产期 routes lcontact with the mothers blood at birth and in mother milk Pathogenesis of HBV致病性 lCell-mediated immunity (liver injury) lImmune complexes ( HBsAg + anti-HBs) :
13、development of hypersensitivity reactions (other organs injury） infants infected perinatally become chronic carriers Clinical Findings lAcute infection急性感染 lFulminant hepatitis暴发型肝炎 lChronic infection 慢性感染 lPrimary hepatocellular carcinoma （ PHC）原发性肝细胞癌 Acute infection la long incubation period and
14、an insidious onset lprodromal period前驱期 :fever, malaise不适, anorexia食欲缺乏, nausea, vomiting, abdominal discomfort, chills lclassic icteric黄疸 symptoms of liver damage lRecovery Fulminant hepatitis 暴发型肝炎 loccurs in approximately 1% of icteric patients and may be fatal 1% 黄疸病人，可致死 lsevere liver damage, s
15、uch as ascites and bleeding 肝严重受损，腹水，出血 Chronic infection lelevated liver enzyme levels 转氨酶水平高 l10% of patients with chronic hepatitis may develop cirrhosis and liver failure 10% 可发展为肝硬化和肝衰竭 lmajor source for spread of the virus主要传 染源 lat risk for fulminant disease if they become co-infected with HD
16、V Primary hepatocellular carcinoma （PHC） 原发性肝细胞癌 lpromoting continued liver repair and cell growth in response to tissue damage lintegrating into the host chromosome and stimulating cell growth directly Laboratory Diagnosis 乙肝“两对半”及临床意义 lHBsAg、 抗HBs lHBeAg、 抗HBe l（HBcAg） 抗HBc HBV抗原抗体系统检测临床意义 HBsAgHB
17、eAg抗-HBe抗-HBc抗-HBs临床意义 IgMIgG +- 感染或无症状携带带者 + -+- 急性乙型肝炎（有传传染） （大三阳） +-+- 慢性乙型肝炎（有传传染） （大三阳） +-+- 急性肝炎趋趋向恢复 （小三阳） -+-+ 恢复期（传传染性低） -+ 既往感染或接种疫苗 - 未感染，无免疫力 Treatment and Prevention lControl the source of infection控制传染源 lCut down the route of transmission切断传播途径 lPassive immunization - Hepatitis B immun
18、e globulin （HBIg）抗-HBs人血清球蛋白 lActive immunizations HBsAg vaccine lNo specific treatment hepatitis C virus,HCV 丙型肝炎病毒 predominant cause of non A non B hepatitis Biological properties生物学性状 la member of the flavivirus 黄病毒属成员 l4060nm,spherical球形 lan enveloped virion有包膜 lGenome: (+)ss RNA Pathogenesis an
19、d Immunity 致病性与免疫性 l six genotypes基因型：、 l transmitted by means similar to HBV 传播途径似HBV in infected blood （输血后肝炎） lIntravenous drug abusers ltransfusion lorgan recipients lhemophiliacs receiving factors or sexually Pathogenesis persistent, chronic hepatitis cirrhosis肝硬化 ， hepatocellular carcinoma肝癌 l
20、acute hepatitis 15% lchronic persistent infection 70% lsevere rapid progression to cirrhosis 15 Laboratory diagnosis lELISA recognition of antibody lgenetic techniques to detect HCV RNA Treatment防治原则 lNo vaccine尚无可用疫苗 lRecombinant IFN-alone or with ribavirin 病毒唑 hepatitis D virus，HDV 丁型肝炎病毒 la defec
21、tive virus that acquires an HBsAg coat for transmissionHDV 是缺陷病毒，需以HBsAg构成其 衣壳来传播 lcircular, single-stranded RNA molecules and an internal core antigen (HDAg) 单负链环状RNA 和 抗原（HDAg） Pathogenesis lspread by the same routes as HBV: blood, semen, and vaginal secretions 传播途径与HBV相同：血液，精液，阴道分泌物 lincreases th
22、e severity of HBV infections: Fulminant hepatitis 加重HBV感染：爆发性肝炎 Coinfection联合感染 Superinfection重迭感染 Laboratory diagnosis ldetecting the delta antigen ，RNA or antibodies病原 学检查为HDAg、抗HDV及HDV-RNA lAnti-HDV IgM lPersistant Anti-HDV IgG chronic infection Treatment and prevention lno known specific treatme
23、nt lprevention of infection with HBV prevents HDV infection. hepatitis E virus，HEV 戊型肝炎病毒 lspherical, non-enveloped, and 27-34 nm 球形，无包膜， la positive-sense, single-strand RNA genome 单正链RNA lspread by the fecal-oral route为粪口途径传 播 lsymptoms and course of HEV disease are similar to those of HAV disease
24、 症状病程类似HAV lAcute hepatitis ，mortality rate : 1% to 2% lespecially serious in pregnant women (mortality rate of approximately 20%)孕妇感 染严重,病死率高达20% Diagnosis 微生物学检查 lHEV：EM or IEM电镜或免疫电镜 lAnti-HEV IgM lHEV RNA 五种肝炎病毒比较 HAVHBVHCVHDVHEV 病毒结结构 +ssRNAdsDNA+ssRNA-ssRNA+ssRNA 传传播途 径 粪粪-口 血液、性、垂直传传播 粪粪-口 病情轻轻偶尔严严重 亚临亚临 床,慢 性多见见 需HBV 协协助 孕妇妇重 慢性及 携带带者 无有无 实验实验 室 检查检查 抗HAV IgM HBsAg-Ab HBcAb HBeAg-Ab 抗HCV HCV- RNA 抗HDV IgM 抗HEV IgM 预预防疫苗疫苗无同HBV 预预防为为主