1、Laboratory diagnosis of Viral Hepatitis,谭龙益,History of Human Hepatitis,500 B.C. written accounts of jaundice in Babylonia400 B.C.Hippocrates describes “epidemic jaundice”1883jaundice noted to occur after inoculation of human sera1941 post-vaccination jaundice occurs in 28,000 U.S. soldiers infectiou
2、s hepatitis designated Hepatitis A; serum hepatitis designated Hepatitis B,1962 Hepatitis B Surface Antigen identified1973 Hepatitis A identified by electron microscopyMid-1970s Hepatitis D recognizedMid-1970s Non-A, Non-B hepatitis describedMid-1980s epidemics of “non-hepatitis A” enteric hepatitis
3、1989 Hepatitis C cloned and serological tests developed1990 Hepatitis E cloned and characterized,HFV or 1995 HGV1997 TTV SEN-V2006 NF-V,Other Viruses Causing Hepatitis,Hepatitis G and GB TT Virus post-transfusional hepatitis in JapanSanban, Yonban, TLMV Giant Cell Hepatitis paramyxovirus; Herpes Vir
4、usesHSV Cytomegalovirus Epstein Barr Virus,Rift Valley Fever VirusYellow Fever VirusLassa VirusMarburg VirusEbola VirusAdenoviuresEnteorvirusesCoxsackie VirusesSARS,肝炎病毒的定义及种类,Viral hepatitis hepatitis Virus,Hepatitis A virus HAV HBV HCV HDV HEV,Hepatitis F virus HFV HGV,TTVSENNV-F,Hepatitis F Virus
5、,Hepatitis F Virus,血清,血清,急性肝炎,急性肝炎,急性肝炎,GB agent,HGV,1966年Deinhardt,G. Barker,两株RNA病毒,GB virus type AGBV/A,GB virus type BGBV/B,肝炎病人GB virus type C GBV-C,1995年,急、慢性非甲戊型肝炎病人,hepatitis G virusHGV,Hepatitis Gvirus (HGV) Science. 1996 Jan 26;271(5248):505-8. An RNA virusentire genome (9392 nucleotides)e
6、ncoding a polyprotein of 2873 amino acids. from the plasma of a patient with chronic hepatitis.,GBV-C感染的流行病学,GBV-C感染与人类疾病的关系前瞻性和回顾性研究单独感染：不引起急、慢性肝炎之间的联系与其它肝炎病毒共感染：不影响肝炎的发生和发展过程长期携带GBV-C病毒：不增加肝癌等疾病发生风险 不增加其它临床疾病的发生和发展主要在外周血淋巴细胞中复制。,GBV-C与HIV共感染对HIV感染者的影响,C型GB病毒/庚型肝炎病毒对HIV LTR启动子活性的调控作用研究 ,E2 envelope
7、 protein of GBV-C/HGV,J Phys Chem B. 2009 May 21;113(20):7383-91,Synthetic peptides of hepatitis G virus (GBV-C/HGV) in the selection of putative peptide inhibitors of the HIV-1 fusion peptide.Herrera E, Gomara MJ, Mazzini S, Ragg E, Haro I.,Torque teno viruses (TTV),transfusion-transmitted virus (T
8、TV),3.8 kb DNA virus ，6 genotypes. transmit ： parenteral routes. globally ， healthy ，various disease groups. liver tropism liver diseases. multiplies in bone marrow cells and PBMCs,TT virus,Primi D, Sortini A. Identification and characterization of SENvirus, a family of novel DNA viruses Antiviral T
9、her 2000;5(suppl 1):6.7.,SEN virus,a novel DNA virus3,900 nucleotides. 8 genotypes，coinfected with HCV or HIV. NANE hepatitis。,Yeh CT, Tsao ML, Lin YC, Tseng IC: Identification of a novel single-stranded DNA fragment associated with human hepatitis. J. Infect. Dis.193(8),10891097 (2006).,NVF,Hepatit
10、is A Virus,Hepatitis A Virus,Naked RNA virus4 genotypesOne serotype,Clinical,virological,and serological events associated with viral hepatitis A,Symptoms,Jaundice,HAV in feces,Hepatitis C Virus,RNA病毒 9600nt基因型多,基因组容易变异,易转变为慢性肝炎,Hepatitis C VirusFate of Acute Infection,15%,Chronic,85%,Spontaneousres
11、olution,Clinical and serological events associated with viral hepatitis C,HCV感染的实验室诊断,Anti-HCV IgG：感染后持续存在 主要诊断依据HCV RNA： 病毒复制水平，疗效观察基因型：治疗依据HCV AgAnti-HCV (+) HCV RNA(-)Anti-HCV(-) HCV RNA(+),Prognostic Tests,Genotyp genotype 1 and 4 have a worse prognosis overall and respond poorly to interferon t
12、herapy. Viral Load patients with high viral load are thought to have a poorer prognosis.,Hepatitis D (Delta) Virus,anti-HBs,Symptoms,ALT Elevated,Total anti-HDV,IgM anti-HDV,HDV RNA,HBsAg,HBV - HDV Coinfection,Typical Serologic Course,Time after Exposure,Titre,Jaundice,Symptoms,ALT,Total anti-HDV,Ig
13、M anti-HDV,HDV RNA,HBsAg,HBV - HDV Superinfection,Typical Serologic Course,Time after Exposure,Titre,Hepatitis E Virus,Symptoms,ALT,IgG anti-HEV,IgM anti-HEV,Virus in stool,0,1,2,3,4,5,6,7,8,9,10,11,12,13,Hepatitis E Virus Infection,Typical Serologic Course,Titer,Weeks after Exposure,Biological Feat
14、ures of HBV,20nm spherical filamentous Noninfectious subviral particles,42 nmDane particle,139147 common“ a” antigen determinant122134 subtype determinant “ d/r”159160 subtype determinant “ w/r”,four subtypes: adw、adr、ayw 、ayr,blood,HBV CORF,Hepatocyte: Nucleus Cytoplasm Membrance,HBV,Clinical fearu
15、res of HBV Infection,HBV,Questions,1 Modes of transmission,2 Mechanism of tropism toward hepatocytes,3 Pathogenesis,Laboratory diagnosis of HBV infection,(三),Main marker of HBV infection,HBV DNA,HBV Antigen and Antibody,Viremia,HBV DNA测定,Acute Hepatitis B,Chronic HBV Infection(1),HBV DNAHBV复制增殖的敏感指标
16、,特殊模式,HBsAg（） Anti-HBs（）,“window”期消失,两种或以上血清型,抗原变异,HBeAg（） Anti-HBe（）,“window”期消失,两种或以上血清型,抗原变异,Anti-HBs(+)、Anti-HBe(+)、Anti-HBc(+)HBV 感染后，已恢复，无传染性。Anti-HBe(+)、Anti-HBc(+)HBV感染恢复期？HBsAg变异？HBV DNA？,五个指标全部阳性两个或两个以上血清学先后或同时感染。多个基因位点发生突变。,单一Anti-HBc（）感染早期，HBsAg浓度较低感染恢复期，Anti-HBs浓度低于检测限。需要：Anti-HBc IgM或HBV DNA,Thanks a lot,
