Hepatitis A virus，HAV 甲型肝炎病毒,Biological Properties,picornavirus, +ssRNA genome小RNA病毒科 27 nm in diameter ,non-enveloped 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,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,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: 13 / 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 patients 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,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 antiHBs:neutralization antibody中和抗体 hepatitis 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 infection. 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,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 mothers 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,HBsAg、 抗HBs HBeAg、 抗HBe （HBcAg） 抗HBc,HBV抗原抗体系统检测临床意义,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,hepatit