联合抗病毒治疗透析HCV的meta(2011)

JournalofViralHepatitis,2011,18,e263–e269doi:10.1111/j.1365-2893.2010.01405.x

CombinedantiviraltherapyofhepatitisCvirusindialysispatients:meta-analysisofclinicaltrials

DivisionofNephrologyandDialysis,MaggioreHospital,IRCCS

Foundation,Milano,Italy;andDivisionofHepatology,SchoolofMedicine,UniversityofMiami,Miami,FL,USA

2

F.Fabrizi,1,2V.Dixit,2P.Martin2andP.Messa1

1

ReceivedAugust2010;acceptedforpublicationSeptember2010

SUMMARY.Theef cacyandsafetyofcombinedinterferon

(IFN)plusribavirininpatientsonlong-termdialysisandchronichepatitisCremainsunclear,althoughanumberofsmallclinicaltrialshaveaddressedthisissue.Weevaluatedtheef cacyandsafetyofcombinationantiviraltherapy(conventionalorpegylatedinterferonplusribavirin)indialysispatientswithchronichepatitisCbyperformingasystematicreviewoftheliteraturewithameta-analysisofclinicaltrials.Theprimaryoutcomewassustainedvirologi-calresponse(SVR)(asameasureofef cacy);thesecondaryoutcomewasdrop-outrate(asameasureoftolerability).WeusedtherandomeffectsmodelofDerSimonianandLaird,withheterogeneityandsensitivityanalyses.Weidenti ed10clinicalstudies(151uniquepatients),one(10%)ofwhichwasacontrolledclinicaltrial.Most(97.4%)patientswereonlong-termhaemodialysis.ThesummaryestimateforSVR

anddrop-outratewas56%[95%Con denceIntervals(95%CI)28–84]and25%(95%CI,10–40),respectively.Themostfrequentsideeffectsrequiringinterruptionoftreatmentwereanaemia(26%)andheartfailure(9%).Theseresultsoccurredirrespectiveoftypeofinterferon(conventionalorpeg-IFN,peg-IFNalfa-2aoralfa-2b),trialdesign(controlledorcohortstudy),orclinicalcharacteristicsofpatients(na ¨ve,nonrespondersorrelapsers)http://doc.guandang.netbinationantiviraltherapy(interferonplusribavirin)givesencouragingresultsintermsofef cacyandsafetyamongdialysispatientsevenifthelimitednumberofpatientsenrolledinourmeta-analysishampersde nitiveconclusions.

Keywords:dialysis,hepatitisC,interferon,meta-analysis,ribavirin.

INTRODUCTION

ChronichepatitisCvirus(HCV)infectionremainsprevalentinthehaemodialysispopulationdespiteeliminationofHCVfromthebloodsupply,re ecting,inpart,nosocomialspreadwithinhaemodialysisunits[1,2].AlthoughthereisincreasingconcernaboutthedetrimentaleffectofHCVinfectiononsurvivalinpatientswithchronickidneydisease(CKD),therapyofhepatitisCinthispopulationremainschallenging.

ThetreatmentofHCVinpatientsonchronichaemodial-ysisispredicatedonthepremisethatHCVisassociatedwithdecreasedpatientsurvival.Theassociationbetweenanti-HCVpositiveserologicstatusanddiminishedsurvivalinthe

Abbreviations:CKD,chronickidneydisease;EBR,end-of-treatmentbiochemicalresponse;HCV,hepatitisCvirus;IFN,interferon;OTR,on-treatmentresponse;PCR,polymerasechainreaction;RR,relativerisk;SBR,sustainedbiochemicalresponse;SVR,sustainedvirologi-calresponse.

Correspondence:DrFabrizioFabrizi,DivisioneNefrologica,OspedaleMaggiore,Pad.Croff,ViaCommenda15,20122,Milano,Italy.E-mail:fabrizi@policlinico.mi.it

dialysispopulationisalreadyestablished[3]evenifanaccurateassessmentofthenaturalhistoryofHCVinthesepatientsisdif cult[1].Arecentmeta-analysis(sevenobservationalstudiesenrolling11589patientsonmainte-nancedialysis)showedthatthesummaryestimateforadjustedrelativerisk(RR)ofall-causemortalitywithanti-HCVwas1.34witha95%con denceintervalof1.13–1.59[3].Liverdysfunctionhasbeenimplicatedinalowersur-vivalofseropositivepatients;thesummaryestimateforRRofliver-relatedmortalitywithanti-HCVwas3.75(95%CI,1.93;17.99)[3].Theseresultsareconsistentwithevidencefromothersources.Alargesurveyofpatientsondialysisinthreecontinentsreportedanassociationbetweenanti-HCVpositiveserologicstatusandincreasedmortality(RR,1.17;P£0.02)[reviewedinref.4].

Ithadbeensuggestedthatmono-therapywithconven-tionalorpeg-IFNyieldsinferiorresponsesindialysispatientswithchronichepatitisC[4,5].Experiencewithcombinedantiviraltherapy[interferon(IFN)plusribavirin]inpatientswithCKDandhepatitisCislimited.Theprimarygoalofourstudywastosynthesizetheavailableevidenceonthetoler-abilityandef cacyofcombinedantiviraltherapy(conven-tionalorpeg-IFNplusribavirin)inCKDpatientswith

Ó2010BlackwellPublishingLtd

e264F.Fabrizietal.

chronichepatitisCbyperformingasystematicreviewoftheliteraturewithameta-analysisofclinicaltrials.Theguide-linesreportedinthePRISMAstatementwerefollowed[6].

PATIENTSANDMETHODSSearchstrategyanddataextraction

ElectronicsearchesoftheNationalLibraryofMedicineMEDLINEdatabase,CurrentContentsandmanualsearchesofselectedspecialtyjournalswereperformedtoidentifyallpertinentliterature.Ithadbeenpreviouslydemonstratedthatanelectronicsearchalonemaynotbesensitiveenough[7].FourMEDLINEdatabaseengines(Ovid,PubMed,Embase,andGratefulMed)wereused.ThekeywordsÔhepatitisCÕ,Ôribavi-rinÕ,ÔinterferonÕ,andÔdialysisÕwereused.Referencelistsfromqualitativetopicreviewsandpublishedclinicaltrialswerealsosearched.Allarticleswereidenti edbyasearchfromJanuary1998toJune2010.Dataextractionwasconductedindependentlybytwoinvestigators(F.F.,V.D),andconsensuswasachievedforalldata.Studieswerecomparedtoeliminateduplicatereportsforthesamepatients,whichincludedcon-tactwithinvestigatorswhennecessary.Eligibilityandexclusioncriteriawerepre-speci ed.

Criteriaforinclusion

Tobeincludedinthismeta-analysis,aclinicaltrialhadtoful lcertaincriteria.Ithadtobepublishedinapeer-reviewedjournal,reporttheresultsofcombinedantiviraltherapyandusethesustainedvirologicalresponse(SVR)asaclinicalendpoint.Thedecisionastotheinclusionorexclusionofclinicaltrialswasnotrelatedtoresults.Patientswhounderwentprimaryantiviraltherapy(na ¨vepatients)orthosewhohadalreadycompletedanantiviralcourse(non-responderorrelapserpatients)wereenrolled.Antiviraltherapybasedonconventional(orpegylated)IFNplusribavirinwasconsidered.

Ineligiblestudies

Studieswereexcludediftheyreportedinadequatedataontreatmentormeasuresofresponse.ClinicaltrialsincludinghepatitisBsurfaceantigen–positivepati …… 此处隐藏：23248字，全部文档内容请下载后查看。喜欢就下载吧 ……