病毒性肝炎的诊断与治疗课件.ppt
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1、病 毒 性 肝 炎Viral Hepatitis,Viral Hepatitis,Etiology and Epidemiology(病原学和流行病学) Pathogenesis and pathology(发病机制和病理) Clinical manifestation(临床表现) Laboratory findings(实验室检查) Diagnosis(诊断) Treatment (治疗) Prevention(预防),肝 炎,以肝脏炎症和功能障碍为特征的疾病非感染性 中毒性:酒精、药物、化学、生物 免疫性:自身免疫性肝病-自身免疫性肝炎 原发性胆汁性肝硬化 原发性硬化性胆管炎感染性寄生虫、
2、原虫:血吸虫、肝吸虫、阿米巴病、疟疾细菌: 伤寒、败血症病毒: YFV, CMV, EBV, HSV secondary effect Hepatitis viruses Viral Hepatitis,病毒性肝炎,由肝炎病毒所致以肝脏炎症和肝细胞坏死为特征的一组感染性疾病 传播途径 消化道、血液或体液 临床特点 疲乏、食欲减退、肝(脾)大、肝功异常 部分病例出现黄疸 无症状感染常见,肝炎病毒,Hepatitis A virus (HAV) 甲型肝炎 Hepatitis B virus (HBV) 乙型肝炎 Hepatitis C virus (HCV) 丙型肝炎 Hepatitis D vi
3、rus (HDV) 丁型肝炎 Hepatitis E virus (HEV) 戊型肝炎 - Hepatitis G virus /GB virus-C (HGV/GBV)? Transfusion transmitted virus (TTV)?,病毒性肝炎的类型,病毒性肝炎 分型,病 因 Hepatitis A、B、 C、 D、E 甲、乙、丙、丁、戊型 肝炎临 床 急性、 慢性、重型、 淤胆型、 肝炎后肝硬化,病毒性肝炎在我国危害极大,病毒性肝炎在我国各类传染病中发病率最高,我国乙肝病毒感染者近1亿 7.18%,乙型肝炎患者近3千万,每年近 30万人 死于肝炎或肝癌,Viral Hepati
4、tis,Etiology and Epidemiology (病原学和流行病学) Pathogenesis and pathology(发病机制和病理) Clinical manifestation(临床表现) Laboratory findings(实验室检查) Diagnosis(诊断) Treatment (治疗) Prevention(预防),Hepatitis A - HAV,27-32nm, non-enveloped spherical particle7.5Kb single-stranded, positive RNA virusPicornaviridae family h
5、eparnavirus,Etiology,Etiology,Hepatitis A virus (HAV),One serotype, one antigen-antibody system HAAg Anti-HAV: anti-HAV IgM - marker for acute HAV infection(3-6 m) anti-HAV IgG - indicator of immunity to HAVStrong resistance, alive very long at low temperature Inactivated by heating to 80oC 5 min or
6、 100oC 1 min ultraviolet light formalin solution,Etiology,Etiology,Hepatitis A is a highly contagious disease,Source of infection: early phase of acute illness or subclinical patients HAV in the stool: 1 to 2 weeks before or after the onset of illness Rout of transmission: fecal - oral Susceptibilit
7、y: all non-immune peopleCharacterizations: epidemic in the developing countries, peak at Spring highest attack rates in 5-14 year olds,Etiology,Epidemiology,Hepatitis A is extremely common in developing nations,usually spread by fecal - oral routeClose personal contact: sporadic forms(e.g., househol
8、d contact, child day care centers ,sex contact,)Contaminated food, water: epidemic or outbreaks(e.g., infected food handlers, raw shellfish)Blood exposure ( very rare)(e.g., injecting drug use, transfusion),How is Hepatitis A Spread?,Epidemiology,Hepatitis B - HBV,42nm, enveloped spherical particleT
9、hree forms: Big spherical(Dane particle): 42nm Small spherical: 22nm spherical Filamentary: 22nm/100-1000nm Hepadnaviridae family which include HBV, WHV, GSHV, DHBV,Etiology,Etiology,Danes particle,HBsAg,HBcAg,HBV DNA,DNAP,Hepatitis B virus,HBsAg major envelope polypeptide,HBsAg middle envelope poly
10、peptide,HBsAg large envelope polypeptide,HBcAg polypeptide,HBV DNA polymerase,HBV terminal protein,HBV plus strand RNA primer,HBV DNA,HBV genome is a 3.2Kb partially double-stranded DNA with 4 promoters/4 ORFs,Figure . Genome of Hepatitis B Virus,Hepatitis B virus (HBV),10 antigenic subtypes(mainly
11、adw, adr, ayw, ayr) 4 antigen antibody system HBsAg anti-HBs HBeAg anti-HBe HBcAg anti-HBc(Ig M & Ig G) HBxAg anti-HBx Partially double-stranded DNA (HBV DNA)Very strong resistance Inactivation needs 10010 or 6510h,Etiology,Etiology,Extracellular,Intracellular,Endocytosis,Fusion,with,NUCLEUS,ENDOPLA
12、SMICRETICULUM,GOLGI,APPARATUS,3.5kb RNA,2.4kb RNA,0.7kb RNA,HBcAg,Pol,HBeAg,HBsAg (P43/GP46),HBsAg (P25/GP28,GP33/GP36),HBxAg,TRANSPORT,VESICLE,HBV,Nucleocapsid,DNA,RNA,HBeAg (P22),HBeAg(P18),HBsAg (P25,P31,P43),22nm particle,plasma membrane,Receptor,2.1kb RNA,HBV is replicate through reverse transc
13、ription,Source of infection: acute and chronic patients, or chronic “carriers” Rout of transmission: Parenteral rout(e.g blood, maternal-infant) Susceptibility: all anti-HBs (-) personsCharacterizations: epidemic in Asia, Africa and Far East higher risk in early childhood,Etiology,Epidemiology,Hepat
14、itis B is a serious public health problem in the world,China is a high prevalence area HBsAg positive rate: 7.18%,乙型肝炎是血源传播性疾病,经血途径传播 经输血或血液制品:已较少发生 经皮肤黏膜传播主要发生于: 使用未经严格消毒的医疗器械 侵入性诊疗操作和手术 以及静脉内滥用毒品等 其他:如修足、纹身、扎耳环孔、共用剃须刀 医务人员工作中的意外暴露 母婴传播:围生 (产) 期传播 性接触传播:,日常工作或生活接触一般不会传染HBV 同一办公室工作 (包括共用计算机等办公用品) 握手
15、、拥抱 同住一宿舍 同一餐厅用餐 共用厕所等经吸血昆虫 (蚊、臭虫等) 传播: 未被证实,HBV不经呼吸道和消化道传播,Hepatitis C - HCV,first virus identified by molecular biology technique (1989, HCV cDNA)40-60nm, double-shelled spherical particle9.6Kb single-stranded, positive RNA virusFlaviviridae family,Etiology,Etiology,Envelope 1 & 2 protein complex,
16、Nucleocapsid (core) protein,RNA genome,HCV RNA genome organization and polyprotein maturation,RNA:,Proteins:,Hypothetical model of the HCV viral life cycle,Nucleus,NS3-5B complex,NS2,(+) RNA,(+) RNA,(-) RNA,TranslationProcessing,RNA replication,ER,Golgi,Progeny virus release,HCV virus attachment Int
17、ernalization,Core,E1,E2,p7,Virionmorphogenesis,HCV is replicates by RNA-dependent RNA polymerase,HCV Infection: Worldwide Prevalence,全球HCV的感染率约为3,估计约1.7亿人感染了HCV 我国一般人群抗-HCV阳性率为3.2(1992年)(目前应该是低于该水平:估计约1%),丙型肝炎:全球性健康问题,Hepatitis C virus (HCV),There are at least 6 major genotypes and more than 50 subt
18、ypes (the virus mutates rapidly especially at envelope coding region)One antigen-antibody system HCAg: very low in serum, detectable in liver Anti-HCV: marker for HCV infectionHCV RNA: indicator for infectious(active infection) weak resistance, inactivated by 10% chlorid formalin solution(1:1000) 6
19、h heating to 60oC 10 h,Etiology,Etiology,Transmission of HCV resembles Hepatitis B, spreading through parenteral route, especially by blood & blood products transfusion or IVDUThe mode of infection for those patients, who have no risk factors such as transfusion or drug abuse, is uncertain - family
20、spread is possible but rare (through sharing razors,tooth brushes - sexual transmission is believed to be low - perinatal spread is also unusual (transmission rate of mother to baby is lower than HBV),Etiology,Epidemiology,There are 170 millions current HCV infected patients in the world,Hepatitis D
21、 - HDV,35-37nm spherical particle 1.7Kb single-stranded negative RNA folded itself and appears rod-like,Etiology,Etiology,HBsAg,RNA,HDV antigen,Surface: HBsAgCore: HDAg & HDV RNA,Defective virus requires the presence of HBV for its replication,one antigen-antibody system HDAg: Anti-HDV: anti-HDV IgM
22、 anti-HDV IgG,HDV RNA滚环式复制,环状基因组RNA,RNAP,重复抗基因组分子,裂解,正股RNA分子,环化,抗基因组RNA,转录,环状基因组RNA,自我剪切,图 HDV RNA滚环式复制 G:基因组RNA,AG:抗-基因组RNA,X:G和AG分子链被RNA自身裂解点,Co-infection: at the same time as HBV infection Super-infection: after HBV infection The risk factors for HDV infection are similar to those for HBV infecti
23、on (blood or blood products, IVDU),Etiology,Etiology,Epidemiology,HDV only infects people who also have hepatitis B,Hepatitis D is the rarest form of viral hepatitis,Hepatitis E - HEV,27-34nm, non-enveloped spherical particle7.6Kb single-stranded positive RNACalicivirdae family,Etiology,Etiology,Tra
24、nsmission mode of HEV infection is similar to that of HAV infection (fecal oral)Most outbreaks associated with faecally contaminated drinking water. Minimal person-to-person transmissionThe disease has been reported almost exclusively in developing countries,Etiology,Etiology,Epidemiology,Hepatitis
25、E is a enterically transmitted non-A non-B hepatitis,Hepatitis G Virus(HGV),History: 1996(GBV-C/HGV)Family: UnknowGenome/protein: 9.7Kb single-stranded, positive RNA One ORF- multiple proteinsReplication: RNA dependent RNA polymeraseTransmission: Similar to HCV HGV - ? - viral hepatitis,Summary (Tra
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