乙肝與乙肝病毒

1、Epidemic jaundice described by Hippocrates in 5th century BCJaundice reported among recipients of human serum and yellow fever vaccines in 1930s and 1940sAustralian antigen described in 1965Serologic tests develope

2、d in 1970s,Hepatitis B,Hepatitis B Virus,Hepadnaviridae family (DNA)Numerous antigenic componentsHumans are only known hostMay retain infectivity for at least 1 month at room temperature,>200 million carriers wo

3、rldwideEstablished cause of chronic hepatitis and cirrhosisHuman carcinogen - cause of up to 80% of hepatocellular carcinomas,Hepatitis B Virus Infection,,,HBsAg,,HBcAg,HBeAg,,,,,,,,,,,,Hepatitis B Virus,Hepatitis B

4、Clinical Features,Incubation period 6 weeks to 6 months (average 120 days)Nonspecific prodrome of fever, malaise, headache, myalgiaIllness not specific for hepatitis BAt least 50% of infections asymptomatic,Fulmina

5、nt hepatitisHospitalizationCirrhosisHepatocellular carcinomaDeath,Hepatitis B Complications,Chronic Hepatitis B Virus Infection,Chronic viremiaResponsible for most mortalityOverall risk 10%Higher risk with earl

6、y infection,,Risk of Chronic HBV Carriage by Age of Infection,Hepatitis B Epidemiology,ReservoirHuman. EndemicTransmissionBloodborneSubclinical cases transmit Communicability1-2 months before

7、 and after onset of symptomsChronic carriers,,Hepatitis B Perinatal Transmission*,If mother positive for HBsAg and HBeAg70%-90% of infants infected90% of infected infants become chronic carriersIf po

8、sitive for HBsAg only20% of infants infected90% of infected infants become chronic carriers,*in the absence of postexposure prophylaxis,,,High (>8%): 45% of global populationlifetime risk of infection >60%earl

9、y childhood infections commonIntermediate (2%-7%): 43% of global populationlifetime risk of infection 20%-60%infections occur in all age groupsLow (<2%): 12% of global populationlifetime risk of infection <2

10、0%most infections occur in adult risk groups,Global Patterns of Chronic HBV Infection,Hepatitis B – United States, 1978-2000,Total infections 80,000/yrCurrent carriers >1 millionNew carriers

11、 >5,000Deathfulminant hepatitis 200liver cancer 1,500cirrhosis 4,000,HBV Disease Burden in the United States*,*1999 estimates,Age of Infection of Acute and Chronic He

12、patitis B Virus Infection,Acute infection,Chronic infection,CDC Sentinel Sites. 1989 data.,Risk Factors for Hepatitis B,CDC Sentinel Sites. 1992-1993 data.,Hepatitis B Virus Infection by Duration of High Risk Behavior,

13、,,,,,,,,Strategy to Eliminate Hepatitis B Virus Transmission - United States,Prevent perinatal HBV transmissionRoutine vaccination of all infantsVaccination of children in high-risk groupsVaccination of adolescentsVa

14、ccination of adults in high-risk groups,1965Discovery of Australian antigen1973Successful HBV infection of chimpanzees1981Licensure of plasma-derived vaccine1986Licensure of recombinant vaccine1991Unive

15、rsal infant vaccination1996Universal adolescent vaccination,Hepatitis B Vaccine,Hepatitis B Vaccine,CompositionRecombinant HBsAgEfficacy95% (Range, 80%-100%)Duration ofImmunity>15 yearsSchedule3 Dos

16、esBooster doses not routinely recommended,Hepatitis B Vaccine Formulations,Recombivax HB (Merck)- 5.0 mcg/0.5 ml (pediatric)- 10 mcg/1 ml (adult)- 40 mcg/1 ml (dialysis)Engerix-B (GSK)- 10 mcg/0.5 ml (pediatric)

17、- 20 mcg/1 ml (adult),Recommended Dose of Hepatitis B Vaccine,Infants and children20 years,Recombivax HBDose (mcg)0.5 ml (5)0.5 ml (5)1.0 ml (10),Engerix-BDose (mcg)0.5 ml (10)0.5 ml (10)1.0 ml (20),Hepa

18、titis B VaccineLong-term Efficacy,Immunologic memory established following vaccinationExposure to HBV results in anamnestic anti-HBs responseChronic infection rarely documented among vaccine responders,,Hepatitis B

19、Vaccine,Routine booster doses are NOT routinely recommended for any group,Hepatitis B Vaccine Recommendations,Indications for Hepatitis B Vaccine,InfantsAdolescents 11-12 years of ageSelected adults,DosePrimary 1Pr

20、imary 2Primary 3,Usual Age 0-2 months* 1- 4 months6-18 months,Minimum Interval ---1 month2 months,Hepatitis B VaccineRoutine Infant Schedule,*ACIP prefers the first dose of hepatitis B vaccine be give

21、n soon after birth and before hospital discharge.,Third Dose of Hepatitis B Vaccine,Minimum of 2 months after second dose, andAt least 4 months after first dose, andFor infants, at least 6 months of age,,Very Low Bir

22、thweight Infants,Infants <2000 grams respond poorly to vaccine Delay first dose until chronological age 1 month if mother HBsAg negativeBirth dose and HBIG if mother HBsAg positive,COMVAX,Hepatitis B-Hib combinati

23、onUse when either antigen is indicatedCannot use <6 weeks of ageNot licensed for use if mother HBsAg+,Hepatitis B VaccineAdolescent Vaccination,Routine vaccination recommended through age 18yearsIntegrate into r

24、outine adolescent immunization visitFlexible schedules,DosePrimary 1Primary 2Primary 3,Minimum Interval --- 1 month 2 months*,Usual Interval ---1 month5 months,Hepatitis B VaccineAdolescent an

25、d Adult Schedule,*third dose must be separated from first dose by at least 4 months,Alternative Adolescent Vaccination Schedule,Two 10 mcg doses of Recombivax HB separated by 4-6 monthsMay only be used for adolescents

26、 11-15 years of ageOnly applies to Merck hepatitis B vaccine,Adult Hepatitis B Vaccine Candidates,Men who have sex with menHeterosexual with multiple partnersPersons diagnosed with an STDProstitutesInjection drug

27、usersMale prison inmatesPersons receiving dialysisHealth care workers,Adult Hepatitis B Vaccine Candidates,Staff of institutions for developmentally disabledAlaskan Natives, Pacific IslandersImmigrants/refugees* Ad

28、optees, orphans, unaccompanied minors*Household members and sexual partners of HBV carriers Extended travel to areas of high endemicityRecipients of certain blood products,,*from countries of high or intermediate HBV

29、endemnicity,Prevaccination Serologic Testing,Not indicated before routine vaccination of infants or childrenMay be considered when vaccinating adolescents in groups with high rates of HBV infectionAlaskan NativesPaci

30、fic IslandersChildren of immigrants from endemic countriesFamily members of HBV carriers,Postvaccination Serologic Testing,Not routinely recommended following vaccination of infants, children, adolescents, or most adul

31、tsRecommended for:Infants born to HBsAg+ womenDialysis patientsImmunodeficient personsCertain health care workers,Postvaccination Serologic Testing,Health care workers who have contact with patients or blood should

32、 be tested for antibody after vaccination.,Management of Nonresponse to Hepatitis B Vaccine,Complete a second series of three dosesShould be given on the usual schedule of 0, 1 and 6 monthsRetest 1 to 2 months after

33、completing the second series,,Persistent Nonresponse to Hepatitis B Vaccine,<5% of vaccinees do not develop anti-HBs after 6 valid dosesMay be nonresponder or "hyporesponder"Check HBsAg statusIf expose

34、d, treat as nonresponder with post exposure prophylaxis,,Prevention of Perinatal Hepatitis B Virus Infection,Begin treatment within 12 hours of birthHepatitis B vaccine (first dose) and HBIG at different sitesComplet

35、e vaccination series at 6 months of ageTest for response at 9-15 months of age,Twinrix,Combination hepatitis B (adult dose) and hepatitis A vaccine (pediatric dose)Schedule: 0, 1, 6-12 monthsApproved for persons &

36、gt;18 years,Hepatitis B VaccineAdverse Reactions,Pain at injection siteMild systemic complaints(fatigue, headache)Temperature >37.7 CSevere systemic reactions,Adults13%-29%11%-17%1%rare,Infants and Chi

37、ldren3%-9%0%-20%0.4%-6%rare,Hepatitis B VaccineContraindications and Precautions,Severe allergic reaction to a vaccine component or following a previous doseModerate or severe acute illness,,National Immunizat