儿童乙肝的新认识英文

儿童乙肝的新认识英文版当前第1页\共有39页\编于星期六\0点EPIDEMIOLOGY当前第2页\共有39页\编于星期六\0点PrevalenceofChronic

HepatitisBHBsAgPrevalence>8%-High

2-8%-Intermediate<2%-LowImmigrationnumberssummedbycontinentfrom1996-2002~2millionAsians~400,000SouthAmericans~350,000Africans~930,000EuropeansCentersforDiseaseControl.HepatitisBfactsheet.Availableat:/hepatitis.AccessedJanuary31,2006.MahoneyFJ.ClinMicrobiolRev.1999;12:351-366.HepatitisBFoundation.HepatitisBstatistics.Availableat:/hepb/.AccessedJanuary31,2006.当前第3页\共有39页\编于星期六\0点NATURALHISTORYOF

HEPATITISVIRUS INFECTION当前第4页\共有39页\编于星期六\0点NaturalHistoryofHepatitisB当前第5页\共有39页\编于星期六\0点

FACTORSAFFECTINGTHE

CLINICALCOUSEOFHEPATITISVIRUSINFECTIONHostAgeofInfectionVirus:GenotypeMutants/VariantsRouteofInfection

OtherFactors当前第6页\共有39页\编于星期六\0点

-PerinatalTransmission-ChildhoodInfection-Adolescent/AdultOnsetDiseaseAgeofInfectionandOutcome当前第7页\共有39页\编于星期六\0点HBVGENOTYPEAND HBeAgSEROCONVERSION当前第8页\共有39页\编于星期六\0点KaoJH,ChenDS.CurrentHepatitisReport2006(inpress).KaoJH,ChenDS.CurrentHepatitisReport2006WorldwideDistributionofHBVGenotypes.TheSizeoftheCapitalsindicatestheRelativePrevalenceoftheGenotypes当前第9页\共有39页\编于星期六\0点

No.ofChildrenwithChronicHBVInfection

1602386226

HBVGenotypeFollow-up

BBB

BCCC

C

NiYH,ChangMH,etal.Gastroenterology2004;127:1733-8.

当前第10页\共有39页\编于星期六\0点

AgeinYears

HBeAgSeropositivityGenotypeCGenotypeB

NiYH,ChangMH,etal.Gastroenterology2004;127:1733-8.

GenotypeCGenotypeB当前第11页\共有39页\编于星期六\0点HBVGenotypeandClinical CourseinChildrenGenotypeCDelaysHBeAgSeroconversioninChronicHBVInfectioninChildrenGenotypeChanges:RareGenotypeBDominatesinChildrenwithChronicHBVInfectionandHCCinTaiwan

NiYH,ChangMH,etal.Gastroenterology2004;127:1733-8.

当前第12页\共有39页\编于星期六\0点

HBVVARIANTS/ MUTANTS当前第13页\共有39页\编于星期六\0点APointMutationatCodon28(Nucleotide1896)ofHBVPrecoreGeneTGG

TAG(Tryptophan)(StopCodon)LeadingtoHBeAgNegativeStrains当前第14页\共有39页\编于星期六\0点CHANGESOFHBVPRECOREGENE1896IN80HBsAgCARIERCHILDRENChangMH,etal.JHepatol.1998;28:915-22.

当前第15页\共有39页\编于星期六\0点PeakALTlevelsduringfollow-upin3groupswithdifferentpatternsofHBVprecore1896

PeakALTGroup1Group2Group3Total(IU/l)(n=37)(n=22)(n=21)(n=80)Mean136179209167+-SD+-149+-141+-195+-161Group1:Wildtypethroughoutthewholecourse.Group2:MutantafterHBeseroconversionGroup3:MutantbeforeHBeseroconversion.ALTlevelsbetweengroups,p=0.07.ChangMH,etal.JHepatol1998;28:915-22.当前第16页\共有39页\编于星期六\0点ComparisonsofHBVCoreGeneBetween

31ChronicCarriersand12HCCChildrenCodonMutatedCases(No.)inHCCMutatedCases(No.)inChroniccarrierMutationsPvaluePrecore2858%(7)52.2%(12)WX0.73Core218%(1)21.7%(5)SPorA0.32Core6533%(4)17.3%(4)LWorV0.29Core7433%(4)0SG0.0032Core8733%(4)0SG0.0032Core1318%(1)0AD0.16Core14333%(4)4.3%(1)LP0.015Core1478%(1)21.6%(5)TCorS0.32Core15942%(5)0RS0.0006Core18242%(5)4.3%(1)QX0.0035NiYH,etal.Gut2003;52:122-5

当前第17页\共有39页\编于星期六\0点ComparisonsofHBVCoreGeneBetween

31ChronicCarriersand12HCCChildren-SUMMARYCoregenecodon21,65,and147werethecommonestmutationsitesinchildrenwithchronicHBVinfection.AllwerelocatedinHBcAgepitopesofCTL.Codon74,87,and159mutationsarefoundinHCCchildren,butnotinthechronicinfectiongroup.

NiYH,etal.Gut2003;52:122-5

当前第18页\共有39页\编于星期六\0点DISCUSSIONThesemutationsmayhelpHBVtoescapehostimmunepressure,toexpandviralproteins,andfinallybringinthecancerdevelopment.当前第19页\共有39页\编于星期六\0点TREATMENT OFHEPATITISBCURRENTTHERAPYFOR

HEPATITISBISNOT

SATISFACTORY当前第20页\共有39页\编于星期六\0点CURRENTGOALOFANTIVIRAL

THERAPYFORHEAPTITISBReductionofViralReplicationAmeliorationofHepaticDysfunction当前第21页\共有39页\编于星期六\0点HBVAntiviralTherapyIsNotRecommendedinHBeAgNegative&NormalALTSubjects:RelativelyStableCoursewithLowRateofProgression.

HBeAgPositive&NormalALTSubjects:MayProgress,ButNoEffectiveTherapy.当前第22页\共有39页\编于星期六\0点CURRENTAPPROVEDTHERAPY FORHEPATITISBInterferon

Interferon–α*PegylatedInterferon-αNucleosideAnalog

Lamivudine*AdefovirEntecavir

*Approvedforuseinchildren当前第23页\共有39页\编于星期六\0点

Effectsofinterferonin childhoodhepatitisBPlace&ALTHBeAgClearance(%)AuthorsatRx ControlIFNRxBarberanolimit14%(5/37)26%(10/39)Gregorio>1.5xN13%(4/31)38%(24/64)Lainolimit0%(0/30)8%(5/60)Tsai,Hsu>2xN38%(5/13)44%(8/18)Sokal>2xN11%(8/74)26%(18/70)Meta-Ananolimit11%(12/113)23%(29/126)当前第24页\共有39页\编于星期六\0点EfficacyaccordingtobaselineALT11/8843/1839/5833/974/178/1650%24%34%16%23%13%%completevirologicresponse(HBeAg(-),HBVDNA(-)Jonasetal,NEnglJMed2002;346:1706.当前第25页\共有39页\编于星期六\0点Lamivudinepaediatricphase3study(NUC30903)Placebo(n=97)Wk52BaselineNotreatment(n=63)OneyearplacebocontrolledstudyTwoyearfollow-onstudyLamivudine3mg/kg(n=191)Lamivudine3mg/kgHBeAg-veHBeAg+veTreatment(n=213)89%Durabilityofresponseatmonth36

SokalEetal.Hepatology.2006;43:225-32.当前第26页\共有39页\编于星期六\0点LongtermlamivudinetherapyforchildrenwithHBeAg+veCHB(2)Virologicresponseinthetreatmentarm

21%after12+24monthsofRx(n=133)

30%after0+24monthsRx(n=77)*VR=lossofHBeAglossandHBVDNATheincidenceofYMDDmutationswas

64%(66/103)after12+24monthsof lamivudine

49%(34/70)after0+24monthsof lamivudineSokalEetal.Hepatology.2006;43:225-32.当前第27页\共有39页\编于星期六\0点

PREVENTIONOF VIRAL HEPATITIS当前第28页\共有39页\编于星期六\0点当前第29页\共有39页\编于星期六\0点

IMPORTANT

TRANSMISSIONROUTEIN

HYPERENDEMICAREAS:

MOTHERTOCHILD

EFFECTIVEPREVENTION OFHEPATITISB: VACCINATIONIN INFANCY当前第30页\共有39页\编于星期六\0点HEPATITISBVACCINATIONAND

CONTROLOFHEPATITISB

RELATEDLIVERDISEASESAcute/FulminantHepatitisChronicHepatitisLiverCirrhosis?HepatocellularCarcinoma当前第31页\共有39页\编于星期六\0点UniversalHBVVaccinationandDecreased

MortalityfromFulminantHepatitisin

InfantsinTaiwanUniversalHBVVaccinationJuly1984KaoJH,HsuHM,ShauWY,ChangMH,ChenDS.JPediatr.2001;139:349-52.*Theaveragemortalityrateper105infantsMortalityRatio:3.2(p<0.001)1974-1984:5.36*1985-1998:1.71*当前第32页\共有39页\编于星期六\0点

IncidenceRateRatios(IRR)ofHBV-Positivev.s.-NegativeFHFin15YearsoftheUniversalVaccinationProgram(Chenetal.Hepatology2004;39:58-63)

Year1985~99,CaseNo.(Incidenceper105)

P-ValueHBV(+)FHF43

<1Yr33(0.74)

54.2[26.1,123.2]

<0.01

1-15Yr10(0.014)

1-15Yr

<0.01

IRR(1v.s.1-15Y)[95%C.I.]HBV(-)FHF

<1Yr

52

25(0.56)72(0.039)15.2

[8.5,27.2]当前第33页\共有39页\编于星期六\0点ChildhoodHCCMalePredominance:

M/F=3-4:12.HBV,ButNotHCV,Related

>90%HBsAgPositive,86%HBeAgNegative,HBVGenomeIntegrationintoHostGenome,94%MaternalHBsAgPositive

ChangMHetal.Hepatology1991;13:316-20 ChangMHetal.Cancer1989;64:2377-80当前第34页\共有39页\编于星期六\0点EFFECTOFUNIVERSALHEPATITISB VACCINATIONONHCCINTAIWANESECHILDREN,6-9YEARS

BirthHCCIncidence YearinChildren 1974-840.52/105 1984-860.13/105ChangMH,etal.NEnglMed1997;336:1855-9.当前第35页\共有39页\编于星期六\0点IncidenceofHCCinChildrenDiagnosedatAged6to14YearsfromJuly1981toJune2000AccordingtoBirthYearBirthPopulationNo.ofIncidenceR.R.95%

Year* Cases(per105)CI1966-8448,764,7992630.54

1

1984-9417,817,510350.20

0.36