HEPATITISVIRUSES肝炎病毒.ppt

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 ,non-enveloped icosahedral particle 27nm, 球形， 20面立體對稱，無包膜 one serotype一個血清型,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 抵抗力比腸道病毒強,Pathogenesis致病性,spread via the fecal-oral route糞口途徑傳播 Source of infection: patient, inapparent infection傳染源: 病人、隱性感染者 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,糞口途徑傳播,小腸淋巴結中大量增殖,入血并形成病毒血癥,肝臟為最終靶器官（病毒直接損傷或免疫病理作用）,通過膽汁隨糞便排出體外,Asymptomatic infections are very common. As already noted, disease in children is generally milder than that in adults and is usually asymptomatic隱性感染多 No a chronic infection and carrier,not associated with hepatic cancer.無慢性病例和病毒攜帶者，不與肝癌有關 Complete recovery:99% 預后好 Fulminant hepatitis暴發(fā)性肝炎: 13 / 1000, 80% mortality rate死亡率 Pregnant women may develop more severe disease. 孕婦感染嚴重,Mechanisim of pathogenisis致病機理：,Directly injury by virus病毒直接損傷 immunopathogenesis免疫病理作用,immunity免疫性,無論顯性感染還是隱性感染 均能產生抗-HAV的 IgM和IgG抗體,抗-HAV的IgM在急性期和恢復早期出現(xiàn) 陽性可作為甲肝的確診依據(jù),抗-HAV的IgG在恢復后期出現(xiàn) 有保護作用，維持終身,Laboratory Diagnosis微生物學檢查,anti-HAV IgM 抗HAV IgM by an ELISA or radioimmunoassay,Treatment and Prevention 防治原則,Control the source of infection控制傳染源 Cut down the route of transmission切斷傳播途徑 Passive immunization - Normal immunoglobulin 丙種球蛋白 Active immunizations A killed HAV vaccine a live attenuated HAV vaccine,hepatitis B virus, HBV乙型肝炎病毒,SHAPE AND STRUCTURE 形態(tài)結構,There are 3 particles in patients blood Dane particle Dane顆粒（大球形顆粒） small spherical particle小球形顆粒 tubulose particle管形顆粒,Dane particle,Complete particle, infective HBV spherical，double capsid球形,雙層衣殼。 outer capsid=envelope 外衣殼=包膜(脂質雙層+蛋白質) HBsAg等 inner capsid內衣殼： HBcAg、HBeAg internal內部： DNA- circular, double- stranded環(huán)狀雙鏈 DNA polymerase 多聚酶,HBV的小球形顆粒,HBsAg-containing particles 過剩的衣殼蛋白裝配而成,HBV的管形顆粒,小球形顆粒串聯(lián)而成,Genome of HBV,a circular, double-stranded DNA containing single-strand breaks 不完全雙鏈環(huán)狀DNA four open reading frames that encode seven polypeptides. 含4個ORF,編碼7個蛋白 S HBsAg,Pre-s1,Pre-s2 C HBcAg，HBeAg P polymerase多聚酶 X HBxAg基因,Antigen of HBV抗原組成,hepatitis B surface antigenHBsAg表面抗原 indicates that virus replication is occurring in the liver 說明病毒在肝中復制（機體受感染標志） four phenotypes：adr,adw,ayr,ayw antiHBs:neutralization antibody中和抗體 hepatitis B core antigen HBcAg核心抗原 not found in blood一般不能檢出 antiHBc nonneutralization antibody非中和抗體 Core IgM indicates recent infection. 抗HBc IgM說明HBV復制 Core IgG indicates exposure to HBV,Antigen of outer capsid外衣殼抗原,Antigens of inner capsid內衣殼抗原,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證據(jù)（復制及具傳染性的標志） anti-HBe indicates low infectivity in a carrier 抗HBe說明病毒感染性較低（是預后良好的征象）,culture培養(yǎng) resistance抵抗力 strong resistance to cool,dry, ultraviolet, alcohol inactivate: 100 10min,Pathogenesis and Immunity source of infection傳染源 patients or carriers 急性、慢性患者或無癥狀HBsAg攜帶者 route of transmission傳播途徑 sexual routes parenteral腸胃外的 routes injection of the virus into the blood stream contaminated blood and blood components by transfusion, needle sharing, acupuncture針灸, ear piercing, or tattooing perinatal圍產期 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暴發(fā)型肝炎 Chronic infection 慢性感染 Primary hepatocellular carcinoma （PHC）原發(fā)性肝細胞癌,Acute infection,a long incubation period and an insidious onset prodromal period前驅期 :fever, malaise不適, anorexia食欲缺乏, nausea, vomiting, abdominal discomfort, chills classic icteric黃疸 symptoms of liver damage Recovery,Fulminant hepatitis 暴發(fā)型肝炎,occurs in approximately 1% of icteric patients and may be fatal 1% 黃疸病人，可致死 severe liver damage, such as ascites and bleeding 肝嚴重受損，腹水，出血,Chronic infection,elevated liver enzyme levels 轉氨酶水平高 10% of patients with chronic hepatitis may develop cirrhosis and liver failure 10% 可發(fā)展為肝硬化和肝衰竭 major source for spread of the virus主要傳染源 at risk for fulminant disease if they become co-infected with HDV,Primary hepatocellular carcinoma （PHC） 原發(fā)性肝細胞癌,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“兩對半”及臨床意義,HBsAg、 抗HBs HBeAg、 抗HBe （HBcAg） 抗HBc,HBV抗原抗體系統(tǒng)檢測臨床意義,Treatment and Prevention,Control the source of infection控制傳染源 Cut down the route of transmission切斷傳播途徑 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生物學性狀,a member of the flavivirus 黃病毒屬成員 4060nm,spherical球形 an enveloped virion有包膜 Genome: (+)ss RNA,Pathogenesis and Immunity致病性與免疫性,six genotypes基因型：、 transmitted by means similar to HBV 傳播途徑似HBV in infected blood （輸血后肝炎） Intravenous drug abusers transfusion organ recipients hemophiliacs receiving factors or 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防治原則 No vaccine尚無可用疫苗 Recombinant IFN-alone 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構成其衣殼來傳播 circular, single-stranded RNA molecules and an internal core antigen (HDAg) 單負鏈環(huán)狀RNA和 抗原（HDAg）,Pathogenesis,spread by the same routes as HBV: blood, semen, and vaginal secretions 傳播途徑與HBV相同：血液，精液，陰道分泌物 increases the severity of HBV infections: Fulminant hepatitis 加重HBV感染：爆發(fā)性肝炎 Coinfection聯(lián)合感染 Superinfection重迭感染,Laboratory