兒童乙肝的新認(rèn)識(shí)英文

兒童乙肝的新認(rèn)識(shí)英文版現(xiàn)在是1頁(yè)\一共有39頁(yè)\編輯于星期日EPIDEMIOLOGY現(xiàn)在是2頁(yè)\一共有39頁(yè)\編輯于星期日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.現(xiàn)在是3頁(yè)\一共有39頁(yè)\編輯于星期日NATURALHISTORYOF

HEPATITISVIRUS INFECTION現(xiàn)在是4頁(yè)\一共有39頁(yè)\編輯于星期日NaturalHistoryofHepatitisB現(xiàn)在是5頁(yè)\一共有39頁(yè)\編輯于星期日

FACTORSAFFECTINGTHE

CLINICALCOUSEOFHEPATITISVIRUSINFECTIONHostAgeofInfectionVirus:GenotypeMutants/VariantsRouteofInfection

OtherFactors現(xiàn)在是6頁(yè)\一共有39頁(yè)\編輯于星期日

-PerinatalTransmission-ChildhoodInfection-Adolescent/AdultOnsetDiseaseAgeofInfectionandOutcome現(xiàn)在是7頁(yè)\一共有39頁(yè)\編輯于星期日HBVGENOTYPEAND HBeAgSEROCONVERSION現(xiàn)在是8頁(yè)\一共有39頁(yè)\編輯于星期日KaoJH,ChenDS.CurrentHepatitisReport2006(inpress).KaoJH,ChenDS.CurrentHepatitisReport2006WorldwideDistributionofHBVGenotypes.TheSizeoftheCapitalsindicatestheRelativePrevalenceoftheGenotypes現(xiàn)在是9頁(yè)\一共有39頁(yè)\編輯于星期日

No.ofChildrenwithChronicHBVInfection

1602386226

HBVGenotypeFollow-up

BBB

BCCC

C

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

現(xiàn)在是10頁(yè)\一共有39頁(yè)\編輯于星期日

AgeinYears

HBeAgSeropositivityGenotypeCGenotypeB

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

GenotypeCGenotypeB現(xiàn)在是11頁(yè)\一共有39頁(yè)\編輯于星期日HBVGenotypeandClinical CourseinChildrenGenotypeCDelaysHBeAgSeroconversioninChronicHBVInfectioninChildrenGenotypeChanges:RareGenotypeBDominatesinChildrenwithChronicHBVInfectionandHCCinTaiwan

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

現(xiàn)在是12頁(yè)\一共有39頁(yè)\編輯于星期日

HBVVARIANTS/ MUTANTS現(xiàn)在是13頁(yè)\一共有39頁(yè)\編輯于星期日APointMutationatCodon28(Nucleotide1896)ofHBVPrecoreGeneTGG

TAG(Tryptophan)(StopCodon)LeadingtoHBeAgNegativeStrains現(xiàn)在是14頁(yè)\一共有39頁(yè)\編輯于星期日CHANGESOFHBVPRECOREGENE1896IN80HBsAgCARIERCHILDRENChangMH,etal.JHepatol.1998;28:915-22.

現(xiàn)在是15頁(yè)\一共有39頁(yè)\編輯于星期日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.現(xiàn)在是16頁(yè)\一共有39頁(yè)\編輯于星期日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

現(xiàn)在是17頁(yè)\一共有39頁(yè)\編輯于星期日ComparisonsofHBVCoreGeneBetween

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

NiYH,etal.Gut2003;52:122-5

現(xiàn)在是18頁(yè)\一共有39頁(yè)\編輯于星期日DISCUSSIONThesemutationsmayhelpHBVtoescapehostimmunepressure,toexpandviralproteins,andfinallybringinthecancerdevelopment.現(xiàn)在是19頁(yè)\一共有39頁(yè)\編輯于星期日TREATMENT OFHEPATITISBCURRENTTHERAPYFOR

HEPATITISBISNOT

SATISFACTORY現(xiàn)在是20頁(yè)\一共有39頁(yè)\編輯于星期日CURRENTGOALOFANTIVIRAL

THERAPYFORHEAPTITISBReductionofViralReplicationAmeliorationofHepaticDysfunction現(xiàn)在是21頁(yè)\一共有39頁(yè)\編輯于星期日HBVAntiviralTherapyIsNotRecommendedinHBeAgNegative&NormalALTSubjects:RelativelyStableCoursewithLowRateofProgression.

HBeAgPositive&NormalALTSubjects:MayProgress,ButNoEffectiveTherapy.現(xiàn)在是22頁(yè)\一共有39頁(yè)\編輯于星期日CURRENTAPPROVEDTHERAPY FORHEPATITISBInterferon

Interferon–α*PegylatedInterferon-αNucleosideAnalog

Lamivudine*AdefovirEntecavir

*Approvedforuseinchildren現(xiàn)在是23頁(yè)\一共有39頁(yè)\編輯于星期日

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)現(xiàn)在是24頁(yè)\一共有39頁(yè)\編輯于星期日EfficacyaccordingtobaselineALT11/8843/1839/5833/974/178/1650%24%34%16%23%13%%completevirologicresponse(HBeAg(-),HBVDNA(-)Jonasetal,NEnglJMed2002;346:1706.現(xiàn)在是25頁(yè)\一共有39頁(yè)\編輯于星期日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.現(xiàn)在是26頁(yè)\一共有39頁(yè)\編輯于星期日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.現(xiàn)在是27頁(yè)\一共有39頁(yè)\編輯于星期日

PREVENTIONOF VIRAL HEPATITIS現(xiàn)在是28頁(yè)\一共有39頁(yè)\編輯于星期日現(xiàn)在是29頁(yè)\一共有39頁(yè)\編輯于星期日

IMPORTANT

TRANSMISSIONROUTEIN

HYPERENDEMICAREAS:

MOTHERTOCHILD

EFFECTIVEPREVENTION OFHEPATITISB: VACCINATIONIN INFANCY現(xiàn)在是30頁(yè)\一共有39頁(yè)\編輯于星期日HEPATITISBVACCINATIONAND

CONTROLOFHEPATITISB

RELATEDLIVERDISEASESAcute/FulminantHepatitisChronicHepatitisLiverCirrhosis?HepatocellularCarcinoma現(xiàn)在是31頁(yè)\一共有39頁(yè)\編輯于星期日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*現(xiàn)在是32頁(yè)\一共有39頁(yè)\編輯于星期日

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]現(xiàn)在是33頁(yè)\一共有39頁(yè)\編輯于星期日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現(xiàn)在是34頁(yè)\一共有39頁(yè)\編輯于星期日EFFECTOFUNIVERSALHEPATITISB VACCINATIONONHCCINTAIWANESECHILDREN,6-9YEARS

BirthHCCIncidence YearinChildren 1974-840.52/105 1984-860.13/105ChangMH,etal.NEnglMed1997;336:1855-9.現(xiàn)在是35頁(yè)\一共有39頁(yè)\編輯于星期日IncidenceofHCCinChildrenDiagnosedatAged6to14YearsfromJuly1981toJune2000AccordingtoBirthYearBirthPopulationNo.ofIncidenceR.R.95%

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

1

1984-9417,817,510350.20

0.36