《病毒性肝炎》ppt课件

1、Viral Hepatitis 病 毒 性 肝 炎 吉林大学第一医院感染科“Infectious“SerumViral hepatitisEntericallytransmittedParenterallytransmittedF, G, TTV? otherViral Hepatitis - Historical Perspectives Source ofvirusfecesblood/blood-derivedbody fluidsblood/blood-derivedbody fluidsblood/blood-derivedbody fluidsfecesRoute oftransm

2、issionfecal-oralpercutaneouspermucosalpercutaneouspermucosalpercutaneouspermucosalfecal-oralChronicinfectionnoyesyesyesnoPreventionpre/post-exposureimmunizationpre/post-exposureimmunizationblood donorscreening;risk behaviormodificationpre/post-exposureimmunization;risk behaviormodificationensure saf

3、edrinkingwaterType of HepatitisABCDE病原学Hepatitis A-E virusesNoImageHepatitis A VirusHepatitis A Virus,HAVn分类 嗜肝病毒属Heparnavirusn外形 直径27-28nm 无包膜，球形n基因组：单股线状RNA，7478bpn基因产物：构造蛋白VP1-VP4n 非构造蛋白n抗原抗体系统 1个Laboratory Diagnosis of HAVnAcute infection is diagnosed by the detection of HAV-IgM in serum by EIA.

4、nPast Infection i.e. immunity is determined by the detection of HAV-IgG by EIA. FecalHAVSymptoms01234561224Hepatitis A InfectionTotal anti-HAVTitreALTIgM anti-HAVMonths after exposureTypical Serological CourseNoImageHepatitis B VirusHepatitis B Virusn分类 嗜肝DNA病毒nHBV(Dane颗粒)直径42nm，n基因组为DNA，3200bp，部分双股

5、环状nHBsAg的亚型 adr,adw,ayr,ayw多见。n 我国以adr,adw为主LamivudineLamivudineLamivudineNucleusNucleusCytoplasmCytoplasmHBsAg HBsAg envelopesenvelopesEndoplasmic Endoplasmic reticulumreticulumPartially Partially doubledouble- -stranded DNAstranded DNAPlasma membranePlasma membraneA(n)A(n)( (- -) )- -DNADNAInfecti

6、ous Infectious HBV HBV virionvirionmRNAmRNAcccDNAcccDNADNA DNA polpolRTRTEncapsidated Encapsidated pregenomic pregenomic mRNAmRNAInfectious Infectious HBV HBV virionvirion inhibits RNAinhibits RNA- -dependent DNA dependent DNA polymerase polymerase (reverse (reverse transcriptasetranscriptase) activ

7、ity) activity inhibits formation of the partially doubleinhibits formation of the partially double- -stranded HBV DNAstranded HBV DNA may inhibit completion of doublemay inhibit completion of double- -stranded DNA andstranded DNA andamplification of amplification of cccDNAcccDNA may inhibit completi

8、on of doublemay inhibit completion of double- -stranded DNA andstranded DNA and cccDNAcccDNAformation during initial infectionformation during initial infectionLamivudineLamivudine: mode of action: mode of actionDiagnosis of HBVnA battery of serological tests are used for the diagnosis of acute and

9、chronic hepatitis B infection.nHBsAg - used as a general marker of infection.nHBsAb - used to document recovery and/or immunity to HBV infection. nanti-HBc IgM - marker of acute infection.nanti-HBcIgG - past or chronic infection.nHBeAg - indicates active replication of virus and therefore infectiven

10、ess.nAnti-Hbe - virus no longer replicating. However, the patient can still be positive for HBsAg which is made by integrated HBV.nHBV-DNA - indicates active replication of virus, more accurate than HBeAg especially in cases of escape mutants. Used mainly for monitoring response to therapy.HBV基因组的变异

11、S基因突变：HBsAg-乙型肝炎Pre-C基因突变：HBeAg-乙型肝炎 P基因突变：YMDD变异，出现耐药SymptomsHBeAganti-HBeTotal anti-HBcIgM anti-HBcanti-HBsHBsAg0481216202428323652100Acute Hepatitis B Virus Infection with RecoveryTypical Serologic CourseWeeks after ExposureTitreIgM anti-HBcTotal anti-HBcHBsAgAcute(6 months)HBeAgChronic(Years)ant

12、i-HBe048 12 16 20 24 28 32 3652YearsWeeks after ExposureTitreProgression to Chronic Hepatitis B Virus InfectionTypical Serologic CourseHepatitis C Virusn分类：黄病毒科丙肝病毒属n球形颗粒，直径55nmn基因组单链正股RNA，9400bpn基因型和亚型 6组12基因型n I/1a，II/1b，III/2a，IV/2b，V/3a，4a，4b，4c，4d，5a，and 6a hypervariableregioncapsid envelopepro

13、teinprotease/helicaseRNA-dependentRNA polymerasec225coreE1E2NS2NS333cNS4c-100NS53Hepatitis C VirusSymptomsanti-HCVALTNormal01234561234Hepatitis C Virus InfectionTypical Serologic CourseTitreMonthsYearsTime after ExposureHepatitis D Virusn分类 RNA 缺陷的RNA病毒n基因组 单股环状闭合负链RNA，1780bpn抗原抗体系统 HDAgn Anti-HDnHD

14、VRNA 存在于肝细胞，血液和体液HBsAgRNA antigen antigenHepatitis D (Delta) Virusanti-HBsSymptomsALT ElevatedTotal anti-HDVIgM anti-HDVHDV RNAHBsAgHBV - HDV CoinfectionTypical Serologic CourseTime after ExposureTitreHepatitis E Virusn分类 未定n基因组 单股正链RNA，7500bpNoImageHepatitis E VirusSymptomsALTIgG anti-HEVIgM anti-H

15、EVVirus in stool012345678910111213Hepatitis E Virus InfectionTypical Serologic CourseTiterWeeks after Exposure流行病学传染源：乙肝，丙肝，丁肝病人 乙肝，丙肝，丁肝携带者 nClose personal contact(e.g., household contact, sex contact, child day care centers)nContaminated food, water(e.g., infected food handlers, raw shellfish)nBlo

16、od exposure (rare)(e.g., injecting drug use, transfusion)Hepatitis A Virus Transmission Sexual - sex workers and homosexuals are particular at risk. Parenteral - IVDA, Health Workers are at increased risk. Perinatal - Mothers who are HBeAg positive are much more likely to transmit to their offspring

17、 than those who are not. Perinatal transmission is the main means of transmission in high prevalence populations. Hepatitis B Virus Modes of Transmission Transfusion or transplant from infected donor Injecting drug use Hemodialysis (yrs on treatment) Accidental injuries with needles/sharps Sexual/ho

18、usehold exposure to anti-HCV-positive contact Multiple sex partners Birth to HCV-infected motherRisk Factors Associated with Transmission of HCV Percutanous exposures injecting drug use Permucosal exposures sex contact Hepatitis D Virus Modes of TransmissionnMost outbreaks associated with faecally c

19、ontaminated drinking water.nSeveral other large epidemics have occurred since in the Indian subcontinent and the USSR, China, Africa and Mexico.nIn the United States and other nonendemic areas, where outbreaks of hepatitis E have not been documented to occur, a low prevalence of anti-HEV (2%) has be

20、en found in healthy populations. The source of infection for these persons is unknown. nMinimal person-to-person transmission. Hepatitis E - Epidemiologic Features传播途径总结1 粪口途径2 体液传播3 社区获得性传播4 母婴传播5 性接触传播流行方式1 分发性发病2 流行发病3 季节分布4 地理分布Viral hepatitisPATHOLOGY慢性肝炎分级分期规范 1995年全国肝炎会议方案 炎症活动度（G） 纤维化程度（S）级

21、汇管区及周围 小叶内 级 纤维化程度0 无炎症 无炎症 0 无1 汇管区炎症（CPH ） 变性及少数坏死灶 1 汇管区扩大，纤维化2 轻度PN（轻型CAH） 变性，点灶状坏死 2 汇管区周围纤维化，纤维 或嗜酸小体 隔形成，小叶结构保留3 中度PN（中型CAH） 变形坏死重，或见PN 3 纤维隔伴小叶结构紊乱， 无肝硬化4 重度PN（重型CAH） PN范围广，累及多个 4 早期肝硬化或肯定的 小叶，小叶结构失常 肝硬化Pathology：hepatitis gravis急性重症肝炎： 肝细胞大块坏死8%): 45% of global populationnlifetime risk of i

22、nfection 60%nearly childhood infections commonnIntermediate (2%-7%): 43% of global populationnlifetime risk of infection 20%-60%ninfections occur in all age groupsnLow (2%): 12% of global populationnlifetime risk of infection 20%nmost infections occur in adult risk groupsGlobal Patterns of Chronic H

23、BV InfectionHighModerateLow/NotDetectablebloodsemenurineserumvaginal fluidfeceswound exudatessalivasweattearsbreastmilkConcentration of Hepatitis B Virus in Various Body FluidsSpectrum of Chronic Hepatitis B Diseases1. Chronic Persistent Hepatitis - asymptomatic2.Chronic Active Hepatitis - symptomat

24、ic exacerbations of hepatitis3. Cirrhosis of Liver4. Hepatocellular CarcinomaChronic Hepatitis C InfectionnThe spectrum of chronic hepatitis C infection is essentially the same as chronic hepatitis B infection.nAll the manifestations of chronic hepatitis B infection may be seen, albeit with a lower

25、frequency i.e. chronic persistent hepatitis, chronic active hepatitis, cirrhosis, and hepatocellular carcinoma.Viral Hepatitis：Treatment1 隔离，休憩，对症治疗2 抗病毒治疗TreatmentnInterferon - for HBeAg +ve carriers with chronic active hepatitis. Response rate is 30 to 40%.nLamivudine - a nucleoside analogue rever

26、se transcriptase inhibitor. Well tolerated, most patients will respond favorably. However, tendency to relapse on cessation of treatment. Another problem is the rapid emergence of drug resistance.nSuccessful response to treatment will result in the disappearance of HBsAg, HBV-DNA, and seroconversion

27、 to HBeAg.LamivudineLamivudineLamivudineNucleusNucleusCytoplasmCytoplasmHBsAg HBsAg envelopesenvelopesEndoplasmic Endoplasmic reticulumreticulumPartially Partially doubledouble- -stranded DNAstranded DNAPlasma membranePlasma membraneA(n)A(n)( (- -) )- -DNADNAInfectious Infectious HBV HBV virionvirio

28、nmRNAmRNAcccDNAcccDNADNA DNA polpolRTRTEncapsidated Encapsidated pregenomic pregenomic mRNAmRNAInfectious Infectious HBV HBV virionvirion inhibits RNAinhibits RNA- -dependent DNA dependent DNA polymerase polymerase (reverse (reverse transcriptasetranscriptase) activity) activity inhibits formation o

29、f the partially doubleinhibits formation of the partially double- -stranded HBV DNAstranded HBV DNA may inhibit completion of doublemay inhibit completion of double- -stranded DNA andstranded DNA andamplification of amplification of cccDNAcccDNA may inhibit completion of doublemay inhibit completion

30、 of double- -stranded DNA andstranded DNA and cccDNAcccDNAformation during initial infectionformation during initial infectionLamivudineLamivudine: mode of action: mode of actionAgents approved and in Agents approved and in development for chronic hepatitis Bdevelopment for chronic hepatitis BANTIVI

31、RALANTIVIRALLamivudineLamivudineAdefovir Adefovir dipivoxildipivoxilEntecavir Entecavir Clevudine (LClevudine (L- -FMAU) FMAU) EmtricitabineEmtricitabine(FTC)(FTC)L L- -Fd4CFd4CLDTLDTIMMUNOMODULATIONIMMUNOMODULATIONInterferon Interferon pegpeg- -IFNIFNThymosinThymosin- -a a a a1 1Steroid withdrawal

32、Steroid withdrawal ILIL- -1212Therapeutic vaccinesTherapeutic vaccines拉米夫定延缓乙肝相关肝硬化患者的临床进展拉米夫定延缓乙肝相关肝硬化患者的临床进展及降低肝癌发生率及降低肝癌发生率YF Liaw, JJY Sung, WC Chow, K Shue, O Keene, G Farrell CALM 研讨小组研讨小组.* 覆盖台湾覆盖台湾, 香港香港, 中国大陆中国大陆, 新加坡新加坡, 泰国泰国, 马来西亚马来西亚, 澳澳大利亚大利亚, 新西兰新西兰, 菲律宾等菲律宾等41个地域个地域IFN2a40 kD 支链支链 PEG

33、派罗欣聚乙二醇化干扰素alfa-2a 40KD)佩乐能聚乙二醇化干扰素 alfa-2b 19KD)IFN -2b19 kD 单链单链PEGTreatmentnInterferon - may be considered for patients with chronic active hepatitis. The response rate is around 50% but 50% of responders will relapse upon withdrawal of treatment.nRibavirin - there is less experience with ribavir

34、in than interferon. However, recent studies suggest that a combination of interferon and ribavirin is more effective than interferon alone.Treatmen：hepatitis gravisn出血的防治n肝性脑病的治疗n氨中毒的治疗：低蛋白饮食 乳果糖 诺氟沙星n恢复正常神经递质：左旋多巴n维持氨基酸平衡 补充支链氨基酸n防治脑水肿n、hepatitis gravisn感染的防治n急性肾功不全的继发防治n促进肝细胞再生n肝移植EndemicityDiseas

35、eRatePeak Ageof InfectionTransmission PatternsHighLow to HighEarly childhoodPerson to person;outbreaks uncommonModerateHighLate childhood/ young adultsPerson to person;food and waterborne outbreaksLowLowYoung adultsPerson to person;food and waterborne outbreaksVery lowVery lowAdultsTravelers; outbre

36、aks uncommonGlobal Patterns of Hepatitis A Virus TransmissionnMany cases occur in community-wide outbreaksnno risk factor identified for most casesnhighest attack rates in 5-14 year oldsnchildren serve as reservoir of infectionnPersons at increased risk of infectionntravelersnhomosexual menninjectin

37、g drug users Hepatitis A Vaccination StrategiesEpidemiologic ConsiderationsnPre-exposurentravelers to intermediate and high HAV-endemic regionsnPost-exposure (within 14 days)nRoutinenhousehold and other intimate contactsnSelected situationsninstitutions (e.g., day care centers)ncommon source exposure (e.g., food prepared by infected food handler)Hepatitis A Prevention - Immune GlobulinnHBV-HDV CoinfectionnPre or postexposure prophylaxis to prevent HBV infection.nHBV-HDV Super