Transcript 肝炎病毒
HEPATITIS VIRUSES 肝炎病毒 HAV甲型肝炎病毒 HBV乙型肝炎病毒 HCV丙型肝炎病毒 HDV丁型肝炎病毒 HEV戊型肝炎病毒 HFV 已型肝炎病毒 HGV 庚型肝炎病毒 TTV TT型肝炎病毒 Hepatitis A virus，HAV 甲型肝炎病毒 Biological Properties picornavirus, +ssRNA genome小RNA病毒科 27 nm in diameter ,nonenveloped icosahedral particle 27nm, 球形， 20面立体对称， 无包膜 one serotype一个血清型 Feinstone （1973） Stronger than enterovirus, resistant to detergents, acid (pH 1.0 for 2h), 60℃ for 1h，survive for months in fresh water and salt water 抵抗力比肠道病毒强 Pathogenesis致病性 spread via the fecal-oral route粪－口途径传播 Source of infection: patient, inapparent infection 传染源: 病人、隐性感染者 Viral shedding in the stool precedes the onset of symptoms by 14d but stops before the cessation of symptoms Symptoms – Initial symptoms: 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 通过胆汁随粪 便排出体外 肝脏为最终靶 器官（病毒直 接损伤或免疫 病理作用） Asymptomatic 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 No 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 Complete recovery:99% 预后好 Fulminant hepatitis暴发性肝炎: 1~3 / 1000, 80% mortality rate死亡率 Pregnant women may develop more severe disease. 孕妇感染严重 Mechanisim of pathogenisis致病机理： Directly injury by virus病毒直接损伤 immunopathogenesis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 anti-HAV IgM 抗－HAV IgM by an ELISA or radioimmunoassay Treatment and Prevention 防治原则 Control the source of infection控制传染源 Cut down the route of transmission切断传播途径 Passive immunization - Normal immunoglobulin 丙种球蛋白 Active immunizations – A killed HAV vaccine – a live attenuated HAV vaccine hepatitis B virus, HBV乙型肝炎病毒 SHAPE AND STRUCTURE 形态结构 There are 3 particles in patient’s blood Dane particle Dane颗粒（大球形颗粒） small spherical particle小球形颗粒 tubulose 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 particles 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 Antigen of outer capsid外衣壳抗原 hepatitis B surface 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 – anti－HBs:neutralization antibody中和抗体 Antigens of inner capsid内衣壳抗原 hepatitis B core antigen HBcAg核心抗原 – not found in blood一般不能检出 – anti－HBc non－neutralization antibody非中和抗体 – Core IgM indicates recent infection. 抗－HBc IgM 说明HBV复制 – Core IgG indicates exposure to HBV hepatitis 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） culture培养 resistance抵抗力 strong resistance to cool,dry, ultraviolet, alcohol inactivate: 100℃ 10min Pathogenesis and Immunity source of infection传染源 patients or carriers 急性、慢性患者或无症状HBsAg携带者 route of transmission传播途径 – sexual routes – parenteral肠胃外的 routes injection of the virus into the blood stream contaminated blood and blood components by transfusion, needle sharing, acupuncture针灸, ear piercing, or tattooing – perinatal围产期 routes contact with the mother’s blood at birth and in mother’ milk Pathogenesis of HBV致病性 Cell-mediated immunity (liver injury) Immune complexes ( HBsAg + anti-HBs) : development of hypersensitivity reactions (other organs injury） infants infected perinatally become chronic carriers Clinical Findings Acute infection急性感染 Fulminant hepatitis暴发型肝炎 Chronic infection 慢性感染 Primary hepatocellular carcinoma （PHC）原发性肝细胞癌 Acute infection a long incubation period and an insidious onset prodromal period前驱期 :fever, malaise不适, anorexia食欲缺乏, nausea, vomiting, abdominal discomfort, chills classic icteric黄疸 symptoms of liver damage Recovery Fulminant hepatitis 暴发型肝炎 occurs in approximately 1% of icteric patients and may be fatal 1% 黄疸病人，可致死 severe liver damage, such as ascites and bleeding 肝严重受损，腹水，出血 Chronic infection elevated liver enzyme levels 转氨酶水平高 10% of patients with chronic hepatitis may develop cirrhosis and liver failure 10% 可发展为肝硬化和肝衰竭 major source for spread of the virus主要传 染源 at risk for fulminant disease if they become co-infected with HDV Primary hepatocellular carcinoma （PHC） 原发性肝细胞癌 promoting continued liver repair and cell growth in response to tissue damage integrating into the host chromosome and stimulating cell growth directly Laboratory Diagnosis 乙肝“两对半”及临床意义 抗HBs HBeAg、 抗HBe （HBcAg） 抗HBc HBsAg、 HBV抗原抗体系统检测临床意义 HBsAg HBeAg 抗-HBe 抗-HBc 抗-HBs 临床意义 IgM IgG + - - - - - 感染或无症状携带者 + + - + - - + + - - + - + - + - - + - + + 急性乙型肝炎（有传染） （大三阳） 慢性乙型肝炎（有传染） （大三阳） 急性肝炎趋向恢复 （小三阳） 恢复期（传染性低） - - - - - + - + - 既往感染或接种疫苗 未感染，无免疫力 Treatment and Prevention Control the source of infection控制传染源 Cut down the route of transmission切断传播途径 Passive immunization - Hepatitis B immune globulin （HBIg）抗-HBs人血清球蛋白 Active immunizations –HBsAg vaccine No 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 a member of the flavivirus 黄病毒属成员 40～60nm,spherical球形 an enveloped virion有包膜 Genome: (+)ss RNA Pathogenesis and Immunity 致病性与免疫性 six genotypes基因型：Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ、Ⅵ transmitted by means similar to HBV 传播途径似HBV – in infected blood （输血后肝炎） Intravenous drug abusers transfusion organ recipients hemophiliacs receiving factors Ⅷ or Ⅸ – sexually Pathogenesis persistent, chronic hepatitis →cirrhosis肝硬化 ， hepatocellular carcinoma肝癌 acute hepatitis 15% chronic persistent infection 70% severe rapid progression to cirrhosis 15％ Laboratory diagnosis ELISA recognition of antibody genetic techniques to detect HCV RNA Treatment防治原则 No vaccine尚无可用疫苗 Recombinant IFN-αalone or with ribavirin 病毒唑 hepatitis D virus，HDV 丁型肝炎病毒 a defective virus that acquires an HBsAg coat for transmissionHDV 是缺陷病毒，需以HBsAg构成其 衣壳来传播 circular, single-stranded RNA molecules and an internal core δ antigen (HDAg) 单负链环状RNA 和δ 抗原（HDAg） Pathogenesis spread 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 increases the 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 detecting the delta antigen ，RNA or antibodies病原 学检查为HDAg、抗HDV及HDV-RNA Anti-HDV IgM Persistant Anti-HDV IgG chronic infection Treatment and prevention no known specific treatment prevention of infection with HBV prevents HDV infection. hepatitis E virus，HEV 戊型肝炎病毒 spherical, non-enveloped, and 27-34 nm 球形，无包膜， a positive-sense, single-strand RNA genome 单正链RNA spread by the fecal-oral route为粪－口途径 传播 symptoms and course of HEV disease are similar to those of HAV disease 症状病程类似HAV Acute hepatitis ，mortality rate : 1% to 2% especially 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 HEV：EM or IEM电镜或免疫电镜 Anti-HEV IgM HEV RNA 五种肝炎病毒比较 HAV 病毒结构 +ssRNA 传播途 径 病情 HBV HCV HDV HEV dsDNA +ssRNA -ssRNA +ssRNA 粪-口 血液、性、垂直传播 轻 粪-口 慢性及 携带者 无 偶尔严重 亚临床,慢 需HBV 孕妇重 性多见 协助 有 无 实验室 检查 抗HAV IgM HBsAg-Ab HBcAb 预防 疫苗 抗HCV HCV-RNA 抗HDV IgM 抗HEV IgM 无 同HBV 预防为主 HBeAg-Ab 疫苗