《病毒性肝炎》PPT課件.ppt

1、Viral Hepatitis,病 毒 性 肝 炎 吉林大學第一醫(yī)院感染科,A,“Infectious”,“Serum”,Viral hepatitis,Enterically transmitted,Parenterally transmitted,F, G, TTV ? other,E,NANB,B,D,C,Viral Hepatitis - Historical Perspectives,Source of,virus,feces,blood/,blood-derived,body fluids,blood/,blood-derived,body fluids,blood/,blood-

2、derived,body fluids,feces,Route of,transmission,fecal-oral,percutaneous,permucosal,percutaneous,permucosal,percutaneous,permucosal,fecal-oral,Chronic,infection,no,yes,yes,yes,no,Prevention,pre/post-,exposure,immunization,pre/post-,exposure,immunization,blood donor,screening;,risk behavior,modificati

3、on,pre/post-,exposure,immunization;,risk behavior,modification,ensure safe,drinking,water,Type of Hepatitis,A,B,C,D,E,病原學,Hepatitis A-E viruses,Hepatitis A Virus,Hepatitis A Virus,HAV,分類 嗜肝病毒屬（Heparnavirus） 形狀 直徑27-28nm 無包膜，球形 基因組：單股線狀RNA，7478bp 基因產(chǎn)物：結構蛋白VP1-VP4 非結構蛋白 抗原抗體系統(tǒng) 1個,Laboratory Diagnosis

4、of HAV,Acute infection is diagnosed by the detection of HAV-IgM in serum by EIA. Past Infection i.e. immunity is determined by the detection of HAV-IgG by EIA.,Fecal HAV,Symptoms,0,1,2,3,4,5,6,12,24,Hepatitis A Infection,Total anti-HAV,Titre,ALT,IgM anti-HAV,Months after exposure,Typical Serological

5、 Course,Hepatitis B Virus,Hepatitis B Virus,分類 嗜肝DNA病毒 HBV(Dane顆粒)直徑42nm， 基因組為DNA，3200bp，部分雙股環(huán)狀 HBsAg的亞型 adr,adw,ayr,ayw多見。 我國以adr,adw為主,Diagnosis of HBV,A battery of serological tests are used for the diagnosis of acute and chronic hepatitis B infection. HBsAg - used as a general marker of infectio

6、n. HBsAb - used to document recovery and/or immunity to HBV infection. anti-HBc IgM - marker of acute infection. anti-HBcIgG - past or chronic infection. HBeAg - indicates active replication of virus and therefore infectiveness. Anti-Hbe - virus no longer replicating. However, the patient can still

7、be positive for HBsAg which is made by integrated HBV. HBV-DNA - indicates active replication of virus, more accurate than HBeAg especially in cases of escape mutants. Used mainly for monitoring response to therapy.,HBV基因組的變異,S基因突變：HBsAg（-）乙型肝炎 Pre-C基因突變：HBeAg（-）乙型肝炎 P基因突變：YMDD變異，出現(xiàn)耐藥,Symptoms,HBeAg

8、,anti-HBe,Total anti-HBc,IgM anti-HBc,anti-HBs,HBsAg,0,4,8,12,16,20,24,28,32,36,52,100,Acute Hepatitis B Virus Infection with Recovery,Typical Serologic Course,Weeks after Exposure,Titre,IgM anti-HBc,Total anti-HBc,HBsAg,Acute (6 months),HBeAg,Chronic (Years),anti-HBe,0,4,8,12,16,20,24,28,32,36,52,Y

9、ears,Weeks after Exposure,Titre,Progression to Chronic Hepatitis B Virus Infection,Typical Serologic Course,Hepatitis C Virus,分類：黃病毒科丙肝病毒屬 球形顆粒，直徑55nm 基因組單鏈正股RNA，9400bp 基因型和亞型 6組12基因型 I/1a，II/1b，III/2a，IV/2b，V/3a，4a，4b，4c，4d，5a，and 6a,hypervariable region,capsid,envelope protein,protease/helicase,RN

10、A-dependent,RNA polymerase,c22,5,core,E1,E2,NS2,NS3,33c,NS4,c-100,NS5,3,Hepatitis C Virus,Symptoms,anti-HCV,ALT,Normal,0,1,2,3,4,5,6,1,2,3,4,Hepatitis C Virus Infection,Typical Serologic Course,Titre,Months,Years,Time after Exposure,Hepatitis D Virus,分類 RNA 缺陷的RNA病毒 基因組 單股環(huán)狀閉合負鏈RNA，1780bp 抗原抗體系統(tǒng) HDA

11、g Anti-HD HDVRNA 存在于肝細胞，血液和體液,HBsAg,RNA, antigen,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,Hepatitis E Virus,分類 未定 基因組 單股正鏈RNA，7500bp,Hepatitis E Virus,Symptoms,ALT,IgG a

12、nti-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,流行病學,傳染源：乙肝，丙肝，丁肝病人 乙肝，丙肝，丁肝攜帶者,Close personal contact(e.g., household contact, sex contact, child day care centers) Contaminated food, water(e.g., infe

13、cted food handlers, raw shellfish) Blood 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 mor

14、e likely to transmit to their offspring 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

15、 injuries with needles/sharps Sexual/household exposure to anti-HCV-positive contact Multiple sex partners Birth to HCV-infected mother,Risk Factors Associated with Transmission of HCV,Percutanous exposures injecting drug use Permucosal exposures sex contact,Hepatitis D Virus Modes of Transmission,M

16、ost outbreaks associated with faecally contaminated drinking water. Several other large epidemics have occurred since in the Indian subcontinent and the USSR, China, Africa and Mexico. In the United States and other nonendemic areas, where outbreaks of hepatitis E have not been documented to occur,

17、a low prevalence of anti-HEV (2%) has been found in healthy populations. The source of infection for these persons is unknown. Minimal person-to-person transmission.,Hepatitis E - Epidemiologic Features,傳播途徑總結,1 糞口途徑 2 體液傳播 3 社區(qū)獲得性傳播 4 母嬰傳播 5 性接觸傳播,流行方式,1 散發(fā)性發(fā)病 2 流行發(fā)病 3 季節(jié)分布 4 地理分布,Viral hepatitis,P

18、ATHOLOGY,慢性肝炎分級分期標準 （1995年全國肝炎會議方案）,Pathology：hepatitis gravis,急性重癥肝炎： 肝細胞大塊壞死50% 亞急性重癥肝炎：肝細胞新舊不等的亞 大塊壞死50% 慢性重癥肝炎： 慢性肝?。愿窝谆蚋斡?化）的背景，出現(xiàn)大塊或亞 大塊新鮮的肝實質(zhì)壞死,Pathology: acute viral hepatitis,急性輕型肝炎 伴橋型壞死的急性肝炎,Pathology：chlostatic hepatitis,淤膽型肝炎： 急性炎癥+膽栓形成，肝細胞內(nèi)膽色素滯留，出現(xiàn)點狀色素顆粒,Viral hepatitis,Pathophysiolo

19、gy,Jaundice,肝細胞性黃疸 肝內(nèi)梗阻性黃疸,Hepatic encephalopathy,氨中毒學說 氨基酸失調(diào)學說 假神經(jīng)遞質(zhì) 其他誘發(fā)因素,other,出血 肝腎綜合征 肝肺綜合征 腹水,Pathogenesis HAV,HAV可能通過免疫介導（不是直接）引起肝細胞損傷,Pathogenesis of HBV,免疫耐受狀態(tài)-無癥狀攜帶者 免疫功能正常-急性肝炎 免疫功能低下，不完全免疫耐受自身抗體-慢性肝炎 免疫過強，CIC，TNF，IL-6-重癥肝炎,Pathogenesis of HCV,HCV直接殺傷 免疫因素 自身免疫 細胞凋亡：Fas Fas-L,Incubation

20、period: viral hepatitis A 30d(5-45) viral hepatitis B 70d(30-180) viral hepatitis C 50d(15-50) viral hepatitis D viral hepatitis E 40d(10-70) CCCCCCC,Viral Hepatitis - Clinical Features,Incubation period: viral hepatitis A 30d(5-45) viral hepatitis B 70d(30-180) viral hepatitis C 50d(15-50) viral he

21、patitis D viral hepatitis E 40d(10-70) CCCCCCC,Viral Hepatitis - Clinical Features,Viral hepatitis:clinical types,1 acute hepatitis 2 chronic hepatitis 3 hepatitis gravis 4 Cholestatic viral hepatitis 5 liver cirrhosis,黃疸前期 1-21天 黃疸期 2-6周 恢復期 4周 丙型肝炎表現(xiàn)較輕 戊型肝炎淤膽癥狀多見，病情較重 急性無黃疸型發(fā)生率高，不容易發(fā)現(xiàn)。,Acute hepat

22、itis,Chronic hepatitis(B,C,D),輕度慢性肝炎 中度慢性肝炎 重度慢性肝炎,Hepatitis gravis,急性重癥肝炎 亞急性重癥肝炎 慢性重癥肝炎,Incubation period:Average 6-7 wks Range 2-26 wks Clinical illness (jaundice):30-40% (20-30%) Chronic hepatitis:70% Persistent infection:85-100% Immunity:No protective antibody response identified,Hepatitis C -

23、Clinical Features,Coinfection severe acute disease. low risk of chronic infection. Superinfection usually develop chronic HDV infection. high risk of severe chronic liver disease. may present as an acute hepatitis.,Hepatitis D - Clinical Features,anti-HBs,Symptoms,ALT Elevated,Total anti-HDV,IgM ant

24、i-HDV,HDV RNA,HBsAg,HBV - HDV Coinfection,Typical Serologic Course,Time after Exposure,Titre,Jaundice,Symptoms,ALT,Total anti-HDV,IgM anti-HDV,HDV RNA,HBsAg,HBV - HDV Superinfection,Typical Serologic Course,Time after Exposure,Titre,Incubation period:Average 40 days Range 15-60 days Case-fatality ra

25、te:Overall, 1%-3%Pregnant women, 15%-25% Illness severity:Increased with age Chronic sequelae:None identified,Hepatitis E - Clinical Features,實驗室檢查,（一）肝功能檢查 血清酶的檢測 血清蛋白的檢測 血清和尿膽色素檢測 凝血酶原時間檢測 血氨濃度檢測,實驗室檢查,（二）肝炎病毒標記物檢測 （三）肝組織學檢查 （四）影象學檢查 （五）血尿常規(guī),Laboratory Diagnosis of HBV,HBV antigen-antibody system.

26、 HBV-DNA - various techniques are available e.g. PCR and branched DNA. May be used to diagnose HBV infection in the acute phase. However, its main use is in monitoring the response to antiviral therapy. HBV DNA-P,Laboratory Diagnosis of HCV,HCV antibody - generally used to diagnose hepatitis C infec

27、tion. Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears. HCV-RNA - various techniques are available e.g. PCR and branched DNA. May be used to diagnose HCV infection in the acute phase. However, its main use is in monitoring the response to antiviral t

28、herapy. HCV-antigen - an EIA for HCV antigen is available. It is used in the same capacity as HCV-RNA tests but is much easier to carry out.,Viral hepatitis:Diagnosis,流行病學資料 臨床資料（癥狀，體征，實驗室檢查） 病原學診斷 病理學診斷,Viral hepatitis:Differential Diagnosis,其他原因引起的黃疸 溶血性黃疸 肝外梗阻性黃疸 其他原因引起的ALT肝炎 其他病毒引起的肝炎 感染中毒性肝炎 藥物

29、引起的肝炎 酒精性肝病 血吸蟲性肝病 其他肝病 PBC，AIH，Wilson 病,Viral hepatitis：Prognosis,Symptomatic Infection,Chronic Infection,Age at Infection,Chronic Infection (%),Symptomatic Infection (%),Birth,1-6 months,7-12 months,1-4 years,Older Children and Adults,0,20,40,60,80,100,100,80,60,40,20,0,Outcome of Hepatitis B Viru

30、s Infection by Age at Infection,Chronic Infection (%),High (8%): 45% of global population lifetime risk of infection 60% early childhood infections common Intermediate (2%-7%): 43% of global population lifetime risk of infection 20%-60% infections occur in all age groups Low (2%): 12% of global popu

31、lation lifetime risk of infection 20% most infections occur in adult risk groups,Global Patterns of Chronic HBV Infection,High,Moderate,Low/Not,Detectable,blood,semen,urine,serum,vaginal fluid,feces,wound exudates,saliva,sweat,tears,breastmilk,Concentration of Hepatitis B Virus in Various Body Fluid

32、s,Spectrum of Chronic Hepatitis B Diseases,1. Chronic Persistent Hepatitis - asymptomatic 2.Chronic Active Hepatitis - symptomatic exacerbations of hepatitis 3. Cirrhosis of Liver 4. Hepatocellular Carcinoma,Chronic Hepatitis C Infection,The spectrum of chronic hepatitis C infection is essentially t

33、he same as chronic hepatitis B infection. All the manifestations of chronic hepatitis B infection may be seen, albeit with a lower frequency i.e. chronic persistent hepatitis, chronic active hepatitis, cirrhosis, and hepatocellular carcinoma.,Viral Hepatitis：Treatment,1 隔離，休息，對癥治療 2 抗病毒治療,Treatment,

34、Interferon - for HBeAg +ve carriers with chronic active hepatitis. Response rate is 30 to 40%. Lamivudine - a nucleoside analogue reverse transcriptase inhibitor. Well tolerated, most patients will respond favorably. However, tendency to relapse on cessation of treatment. Another problem is the rapi

35、d emergence of drug resistance. Successful response to treatment will result in the disappearance of HBsAg, HBV-DNA, and seroconversion to HBeAg.,拉米夫定延緩乙肝相關肝硬化患者的臨床進展及降低肝癌發(fā)生率,YF Liaw, JJY Sung, WC Chow, K Shue, O Keene, G Farrell CALM 研究小組.*,* 覆蓋臺灣, 香港, 中國大陸, 新加坡, 泰國, 馬來西亞, 澳大利亞, 新西蘭, 菲律賓等41個地區(qū),IFN2

36、a,40 kD 支鏈 PEG,派羅欣（聚乙二醇化干擾素alfa-2a 40KD),佩樂能（聚乙二醇化干擾素 alfa-2b 19KD),IFN -2b,19 kD 單鏈PEG,Treatment,Interferon - 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. Ribavirin - there is less expe

37、rience with ribavirin than interferon. However, recent studies suggest that a combination of interferon and ribavirin is more effective than interferon alone.,Treatmen：hepatitis gravis,出血的防治 肝性腦病的治療 氨中毒的治療：低蛋白飲食 乳果糖 諾氟沙星 恢復正常神經(jīng)遞質(zhì)：左旋多巴 維持氨基酸平衡 補充支鏈氨基酸 防治腦水腫 、,hepatitis gravis,感染的防治 急性腎功不全的繼發(fā)防治 促進肝細胞再

38、生 肝移植,Endemicity,Disease,Rate,Peak Age,of Infection,Transmission Patterns,High,Low to,High,Early,childhood,Person to person;,outbreaks uncommon,Moderate,High,Late,childhood/,young adults,Person to person;,food and waterborne,outbreaks,Low,Low,Young adults,Person to person;,food and waterborne,outbre

39、aks,Very low,Very low,Adults,Travelers; outbreaks,uncommon,Global Patterns of Hepatitis A Virus Transmission,Many cases occur in community-wide outbreaks no risk factor identified for most cases highest attack rates in 5-14 year olds children serve as reservoir of infection Persons at increased risk

40、 of infection travelers homosexual men injecting drug users,Hepatitis A Vaccination Strategies Epidemiologic Considerations,Pre-exposure travelers to intermediate and high HAV-endemic regions Post-exposure (within 14 days) Routine household and other intimate contacts Selected situations institutions (e.g., day care centers) common source exposure (e.g., food prepared by infected food handler),Hepatitis A Prevention - Immune Globul