美国肝病研究学会慢性乙型肝炎临床实践指南：最新建议(译文)

33AASLDPRACTICEGUIDELINEChronicHepatitisB:UpdateofRecommendationsAnnaS.F.Lok1andBrianJ.McMahon2_____________________________________________________________Anestimated350millionpersonsworldwideand1.25millionintheUnitedStatesareinfectedwithhepatitisBvirus(HBV).HepatitisBcarriersareatriskfordevelopmentofcirrhosisandhepatocellularcarcinoma(HCC).ThenaturalhistoryofchronicHBVinfectionisvariable.PersonswithchronicHBVinfectionneedlifelongmonitoringtodetermineifandwheninterventionwithantiviraltherapyisneededandtoobserveforserioussequelae.Theseguidelinesweredevelopedundertheauspicesof,andapprovedby,thePracticeGuidelinesCommitteeoftheAmericanAssociationfortheStudyofLiverDiseases.TheoriginalguidelineswerepublishedinHEPATOLOGY2001;34:1225–1241.1Inlightofrecentprogress,particularlyinthetreatmentofchronichepatitisB,theseguidelineswereupdatedinSeptemberof2003.Acompleteversionoftheupdatedguidelines,includingareviewofrecentlypublishedliter-ature,canbefoundattheAASLDwebsite,(random-izedcontrolledtrials),II-1(controlledtrialswithoutrandomization),II-2(cohortorcase-controlanalyticstudies),II-3(multipletimeseries,dramaticuncontrolledexperiments),andIII(opinionsofrespectedauthorities,descriptiveepidemiology).SummaryofRecentLiteratureontheTreatmentofChronicHepatitisBLamivudineApprovedforUseinChildren.Inacontrolledtrialthatinvolved286childrenaged2to17years,randomizedtolamivudine(3mg/kg/dupto100mg/d)orplacebo,hepatitisBeantigen(HBeAg)seroconversionwasobservedin22%lamivudine-treatedchildrenversus13%placebocontrols_____________________Abbreviations:HBV,hepatitisBvirus;HCC,hepatocellularcarcinoma;HBeAg,hepatitisBeantigen;ALT,alanineaminotransferase;IFN-_,interferonalfa;HBsAg,hepatitisBsurfaceantigen.Fromthe1DivisionofGastroenterology,UniversityofMichiganMedicalCenter,AnnArbor,MI;andthe2ViralHepatitisProgram,AlaskaNativeMedicalCenterandArcticInvestigationsProgram,CentersforDiseaseControl,Anchorage,AK.ReceivedDecember8,2003;acceptedDecember9,2003.A.S.F.L.servesontheadvisoryboardofGileadSciences,GlaxoSmithKline,Idenix,andXTLBiopharmaceuticals,ShealsoreceivesresearchsupportfromBristol-MyersSquibb,GileadSciences,GlaxoSmithKline,Idenix,Roche,andSchering.B.J.M.hasreceivedresearchsupportgrantsfromGlaxoSmithKlineforHepatitisAvaccinestudiesinthepast.HecurrentlyreceivesaresearchgrantfromPrometheus.Hisspouseowns100sharesofGlaxoSmithKlineinherindividualretirementaccount.Addressreprintrequeststo:AnnaS.F.Lok,M.D.,DivisionofGastroenterology,UniversityofMichiganMedicalCenter,3912TaubmanCenter,AnnArbor,MI48109-0362.E-mail:[e-mail];fax:[phone].ThisisaUSgovernmentwork.Therearenorestrictionsonitsuse.PublishedonlineinWileyInterScience().DOI10.1002/hep.2011034(P=.06),whileHBeAglosswasobservedin26%and15%,respectively(P=0.03).2HBeAgserocon-versionratewashigheramongchildrenwithelevatedalanineaminotransferase(ALT)levels.Lamivu-dine-resistantmutationwasdetectedin19%oftreatedchildrenduringthe1-yearperiod.DurabilityofHBeAgSeroconversion.AmongpatientswhoexperiencedHBeAgseroconversionduringlamivudinetreatment,thedurabilityofresponseaftercessationoftherapyhasrangedfrom38%to77%.3–5The3-yearcumulativerelapseratevariedfrom36%to54%,withmostoftherelapsesoccurringduringthefirstyearposttreatment.LamivudineResistance.Theriskofdevelopinglamivudineresistanceincreaseswiththedurationoftherapy.InastudyfromAsia,genotypicresistanceincreasedfrom14%inyear1to38%,49%,66%,and69%after2,3,4,and5years,respectively,oftreatment.6Long-termfollow-upstudiesshowedthatovertime,theinitialbenefitisnegatedinpatientswithlamivudine-resistantmutants.Inonestudythatcomparedliverhistologyin63patientspriortoandafter3yearsoflamivudinetreatment,necroinflam-matoryscoreswereimprovedin77%andworsenedin5%ofpatientswithoutlamivudine-resistantmutants,butimprovedinonly45%andworsenedin14%ofthosewithlamivudine-resistantmutants.7Forpatientswithconfirmedlamivudine-resistance,theoptionsincludecontinuinglamivudinetreatmentaslongasbenefittothepatient(basedonclinicalassessment,ALT,andHBVDNAlevels)ismaintained;discontinuingtreatmentandmonitoringforhepatitisflares;orswitchingtootherantiviralagentssuchasadefovir,whichareeffectiveinsuppressinglamivudine-resistantHBV.TworecentreportsfromAsiasuggestthatdiscontinuationoflamivudineinpatientswithresistantmutantsisnotassociatedwithincreasedfrequencyofhepatitisflaresordecompensation,comparedwiththosewhocontinuedtoreceivelamivudine.8,9Thus,stoppinglamivudineisareasonableoptionforimmunocompetentpatientswithoutcirrhosis,aslongastheyarecloselymonitored;butpatientswithunderlyingcirrhosisorimmunosuppressionshouldbeswitchedtoadefovirbeforestoppinglamivudine.AdefovirDipivoxilAdefovirdipivoxilisanorallybioavailableprodrugofadefovir,anucleotideanalogofadenosinemonophosphatethatinhibitsbothHBVreversetranscriptaseandDNApolymeraseactivity.Adefovirhasbeenshowntobeeffectiveinsuppressingnotonlywild-typeHBVbutalsolamivudine-resistantHB