严重乙肝相关肝病发病机理和治疗（英文版）

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1、HBV-associatedSevereLiverDiseases:ProgressonPathogenesisandTreatmentYumingWangInstituteforInfectiousDiseasesofPLASouthwestHospitalThirdMilitaryMedicalUniversityChongqing,P.R.ChinaTheProgressofPathogenesisViralFactorsEvidencefortheroleofviralfactorsLong-termfollow-upstudiesdemonst

2、ratedthecloserelationshipbetweendiseaseseverityandviralfactorsNAhasbeenshowedtobeeffectiveinpreventionandtreatmentofhepatitisexacerbationHBVmutationandgenotypesarecloselyrelatedtodiseaseseverityImmunesuppressedALF:overwhelmingviralreplicationandimmuneparalysisHBVmutationandgenotyp

3、ingiscloselyrelatedtodiseaseseverityPrecore(G1896A)mutation/core-promoter(G1762T/G1764A)mutationsPreS2mutationsHBVgenotypesFig.FrequenciesofPrecore/C-promotermutationscomparedbetweenpts.withFHandself-limitedacutehepatitiswhowereinfectedwithHBV/BjorCeOzasaA,etal.Hepatology.2006,44:

4、326-334OutcomeofacutehepatitisBvirusinfectionPtswithFHwereolder(>34y)FHwasfrequent(13%)andassociatedwithBjandCeLackofHBeAgHighreplicationduetoprecoremutationOzasaA,etal.Hepatology.2006,44:326-334PathogenesisofSpecialFulminantHepatitis----Immunosuppression-inducedALF(FibrosingChola

5、staticHepatitis,FCH)Fig.HepatitisreactivationafterchemotherapyTimeafterexposure(w)0481216202428323652100chemotherapyChronichepatitisLivercirrhosisALTRecoverAcutehepatitisHBVDNAImmuno-suppressionImmuno-reboundALFDeathMeulemanP,etal.JVirol,2006,80(6):2797-2807.Actuallythereare2kinds

6、ofresponses:immunereboundandimmuneparalysisOcamaP,etal.AmJMed,2005,118,Dec:e15-1413.e22Fig.OverwhelmingHBVinfectionwithimmnosuppressionA-DALFafterchemotherapyin1caseofnon-HodgkinlymphomaE,FacasewithCHBHBsAgHBcAgExtensivePositiveHBsAgExtensivehepatocyteinjuryandinflamationSeverearc

7、hitecturaldisruptionwithfibrosisandnecrosisHBcAgWhydothepts.intolerancestagehavenoFCHmanifestations?Immunetolerance≠immuneparalysisImmunetolerance：virusandhosthavearelationshipofmutuallyrestrictionimmuneparalysis:hostlosesitsrestrictiontothevirusMedicalstrategyfortwocategoriesofAL

8、FImmunesuppressioninducedALF-Inhi