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acute liver injury in the context of immune checkpoint inhibitor-related colitis treated with infliximab hao chi zhang外文参考.pdf

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acute liver injury in the context of immune checkpoint inhibitor-related colitis treated with infliximab hao chi zhang外文参考.pdf

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acute liver injury in the context of immune checkpoint inhibitor-related colitis treated with infliximab hao chi zhang外文参考.pdf

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文档介绍:该【acute liver injury in the context of immune checkpoint inhibitor-related colitis treated with infliximab hao chi zhang外文参考 】是由【宝钗文档】上传分享,文档一共【8】页,该文档可以免费在线阅读,需要了解更多关于【acute liver injury in the context of immune checkpoint inhibitor-related colitis treated with infliximab hao chi zhang外文参考 】的内容,可以使用淘豆网的站内搜索功能,选择自己适合的文档,以下文字是截取该文章内的部分文字,如需要获得完整电子版,请下载此文档到您的设备,方便您编辑和打印。(2019)7:47https:///-019-0532-1essAcuteliverinjuryinthecontextofimmunecheckpointinhibitor-relatedcolitistreatedwithinfliximabHaoChiZhang1,WenyiLuo2andYinghongWang3*AbstractBackground:Immunecheckpointinhibitors(ICPIs),usedtotreatdifferentadvancedmalignancies,areassociatedwithawiderangeofimmune-relatedadversereactions(irAEs),:Wedescribeacaseofapatientwithprostateadenocarcinoma,prisedofipilimumabandnivolumab,’sgrade3colitisbecamesteroid-refractory,requiringaone-timeinfusionofinfliximab,monlyininflammatoryboweldisease,asarescuetherapy,,evaluationofthechronologyofevents,andexclusionofothercausesofacutehepatitiswereemployedtomakethefinaldiagnosisofthiseventasinfliximab-:ICPIssuchasCTLA-4andPD-’-associatedhepatotoxicity,,inconjunctionwithpotentialrisksforirAE,theliverprofileshouldbecloselymonitoredduringtreatmentwithICPIaswellaswithanti-TNF-:prostatecancer,immunecheckpointinhibitors,infliximab,liverinjuryBackgroundasanagentforsteroid-refractorycolitissecondarytoICPIImmunecheckpointinhibitors(ICPIs)suchasipilimumab,,inflix-aCTLA-4inhibitor,andnivolumab,aPD-1inhibitor,,plicatedhistorythatpromptedcarefulcanalsobeassociatedwithimmune-relatedadversereac-analysisofthedifferentialdiagnosesforacuteliverinjurytions(irAEs)includingenterocolitis,hepatitis,’-A79-year-oldmanwithahistoryofmetastaticprostatequentbutwell-,treatedwithICPIsipilimumabandnivolu-mab,andenterocolitisasirAEtreatedwithinfliximab,was*Correspondence:******@,HepatologyandNutrition,TheUniversityThepatienthadapastmedicalhistoryincludingofTexasMDAndersonCancerCenter,beBlvd.,Unit1466,Houston,TX77030,-FulllistofauthorinformationisavailableattheendofthearticlecentlyrecoveredfrominfluenzaAH3virusinfection.?TheAuthor(s).(/licenses/by//),whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedyougiveappropriatecredittotheoriginalauthor(s)andthesource,providealinktomonslicense,(/publicdomain/zero//)appliestothedatamadeavailableinthisarticle,(2019)7:,,thepatient’sICPIswerediscon-,-Acontrast-putedtomography(CT)ofthecludedcoloncancerofthepatient’,andstablefind-neoadjuvantchemotherapywithtemsirolimusduringtheingofpriorsmalllow-attenuationliverlesionsthoughtinitialyearofdiagnosis13yearsprior,followedbytobecysts,-,duringFecalcalprotectinwaselevatedat484μg/g(referencewhichtimehewasdiagnosedwithpelviclymphnoderange:≤50μg/g).,heunderwentpalliativeradiotherapygastricbodyandpre-pyloricregion,normal-appearingduo-,andnogastroesophagealvarices;biopsiesrevealedabirateroneacetatewithprednisonebeforethispre--colonoscopyrevealedmilderythemaoftheterminalprogressionofdisease,-appearingrectum;biopsiestreatment(2016–0848)binationregimenofipi-revealeddiffusechronicmucosainjuryandincreasedapop-limumab1mg/kgandnivolumab3mg/kg(forbodytosis(),patiblewithICPI-associatedentero-weightof73kg),().,andthethirdcyclewasad-ministered3weeksthereafter().ShortlyaftertheHepatotoxicityeventthirdcycle,thepatientbegantosufferfromloosebowelFormanagementofgastrointestinalirAE,high-dosemovements,progressingtoacutefrequentnon-bloodyintravenousmethylprednisolone(1mg/kgtwicedaily,fordiarrheacharacterizedasfourepisodesduringthedaybodyweightof67kg)wasstarted(),,delineatingkeypointsrelatedtomedicationadministration,clinicalevents,(2019)7::(Hematoxylinandeosinstain,20×)hcellmetaplasia(yellowarrow).Panelb(Hematoxylinandeosinstain,40×)Increasedapoptosis(whitearrows)regimenwasthentransitionedtoprednisone40mg/ddL(referencerange:–),(refe-forthenext8days().rencerange:–)(;).Thepatient’sliverbiochemicaltestingafterbriefHowever,just4daysafterdischargefromthehospital,hospitalizationpriortodischargeincludedserumALTtherewasrecurrenceofworseningdiarrheaassociated35U/L(referencerange:7–56U/L),AST32U/L(refe-withnauseaandemesisdespitebeingonprednisone40rencerange:15–46U/L),alkalinephosphatase(ALP)60mg/d,whichraisedtheconcernforsteroid-refractoryU/L(referencerange:38–126U/L),--tumornecrosisfactormg/dL(referencerange:–),/(anti-TNF)biologictherapy,infliximab(5mg/kg),(serumALT,AST,alkalinephosphataselevels),displayedindaysrelativetoinfliximabinfusion(linesconnectavailabledatapoints)(2019)7:(totalbilirubin,directbilirubin,albumin,andINR),displayedindaysrelativetoinfliximabinfusion(linesconnectavailabledatapoints),asteroidtaperregimenwasim-,20mg/dLabtestingforliverdiseasewereperformed(Table1).for3days,and10mg/dfor3days().Anti-nuclearantibodytiter,anti-smoothmuscleantibody,Outpatientlabsobtained6daysaftertheinfliximabanti-liver-kidney--administrationrevealedintervalchangeinliverprofile,tiveviralhepatitidesA,B,C,,ASTto51U/L,IgGwaspreviouslypositivepriortoinfliximabadministra-(;).tion,withsubsequentIgMtestingthatwasequivocal;test-At29daysaftertheinitialinfliximabadministration,theingforEBVIgMwasnegativewithpositivenuclearantigenpatientpresentedtotheemergencyroomwithnew-onsetandIgG;andtestingforHSV-1andHSV-2(quantitativejaundicewithoutabdominalpain,nausea,emesis,)werenegative(undetectableviralload).HFEgeneLiverenzymesfrom2dayspriortothispresentationtestingrevealedonemutationofH63D,whichwasnotshowedabruptelevations,withserumALT364U/L,,ALP680U/L,-,AST214U/L,ALP677U/L,,,(;).Thepatientdidnotreportsignificantacetamino-,hehadatemperatureofsub-°C,pulseof80beatsperminute,icreson-119/65mmHg,respiratoryrateof16/min,,--,anon-(2019)7:47Page5of8Table1LaboratorydatabiopsywasperformedthatdemonstratedcholestaticVariableReferenceRange,Resulthepatitiswithbileductinjury,cholestasis,mixedsteato-aAdultssisbutpredominantlymicrovesicularsteatosis().Whitebloodcellcount(per4000–11,0005200Therewerefindingsofmixedinflammatoryinfiltrates,μL)mildportalandperiportalfibrosis,andnoironorα-1–Hemoglobin(g/dL)(fL)82–9887Intravenousmethylprednisolone1mg/kgevery12hPlateletcount(perμL)140,000–440,000208,000wereinitiatedfor48hbeforediscontinuationuponrec-Sodium(mEq/L)136–145143ognitionofhistologyfindingsandlackofimprovementBloodureanitrogen(mg/dL)8–,andCreatinine(mg/dL)–,acutedrug-inducedLactatedehydrogenase(U/L)313–618870liverinjurysecondarytoinfliximabwasdeemedtobeHepatitisAIgMantibodyNegativeNegativethemostlikelycauseofhisabnormalliverbiochemicalHepatitisBsurfaceantigenNon-reactiveNon-<(Negative)<(Negative)(mIU/mL)eofliverinjurymanagementHepatitisBtotalcoreNon-reactiveNon-reactiveBythefourteenthweekpost-infliximabadministration,antibodyserumALThadgraduallyimprovedto51U/L,ASTtoHepatitisBDNA(IU/mL)UndetectedUndetected53U/L,ALPto506U/L,-reactiveNon-reactive(;)’(units)–(Equivocal)CMVIgG(units)–,hepatotoxicityisbeingrecog-–EBVviralcapsidantigenIgGNegativePositivenizedasoneoftheirAEs[113].NewelevationinliverantibodytransaminasesduringtheICPItreatmentshouldpromptin-EBVnuclearanti