Long-TermManagementoftheSuccessful

AdultLiverTransplant

(2012PracticeGuideline)

感染內(nèi)科科內(nèi)業(yè)務(wù)學(xué)習(xí)陳洪濤

2016-03-17編輯pptBackground------中國(guó)肝移植現(xiàn)狀編輯pptBackground------中國(guó)肝移植現(xiàn)狀編輯pptBackground------中國(guó)肝移植現(xiàn)狀編輯pptBackground------中國(guó)肝移植現(xiàn)狀編輯pptBackground------中國(guó)肝移植現(xiàn)狀編輯pptBackground------中國(guó)肝移植現(xiàn)狀編輯pptBackground------中國(guó)肝移植現(xiàn)狀編輯pptBackground------中國(guó)肝移植現(xiàn)狀編輯pptBackground------中國(guó)肝移植現(xiàn)狀Survival

>85%,

4years

>75%,

5yearsRecurrence

8%,

4years編輯pptBackground------中國(guó)肝移植現(xiàn)狀

杭州標(biāo)準(zhǔn)編輯pptBackground------美國(guó)肝移植現(xiàn)狀

編輯pptBackground------美國(guó)肝移植現(xiàn)狀

Characteristicsof

adultlivertransplantrecipients,2002&2012編輯pptBackground編輯pptLiver

Transplantation

(LT)asaTreatmentforEnd-stageLiverDisease/MortalityAfterLT/MorbidityAfterLTComplicationsofPortalHypertensionAfterLTLiverTests/VascularThrombosisImmunosuppressionLateRejectionPromotingHealthAfterLTBoneHealth.

Contents編輯pptSystemicDiseaseNutritionandObesityOncologyReproductiveHealthInfectiousDiseaseImmunizationsHepatitis（Viral,

PBC/PSC,

AIH,

ALD,

NASH/NAFLD）

Contents編輯ppt

Recommendations

and

Rationales

MorbidityAfterLT編輯pptClinicalfeaturesofliverfailureandportalhypertensionresolverapidlyafterLT.Theexceptionissplenomegaly,whichmaypersistforyearsVaricealhemorrhageisveryunusualunlessthepatienthasanoccludedportalvein.ThelateemergenceofhepaticencephalopathysuggeststhedevelopmentofclandestinecirrhosisorapersistentportosystemicshuntLate-onset

ascitesorperipheraledemamayindicatestenosisoftheinferiorvenacavaorportalveinanastomosis.

Recommendations

and

Rationales

ComplicationsofPortalHypertensionAfterLT編輯ppt

Recommendations

and

Rationales

LIVERTESTS編輯ppt

Recommendations

and

Rationales

VascularThrombosisHepaticarterythrombosis(HAT)orstenosismaypresentclinicallyafter3months,as:intrahepaticnon-anastomoticstricturesand/orsterileorinfectedfluidcollectionswithintheliver,sometimesreferredtoasbilomasischemiccholangiopathyorbiliarycastsyndrome.編輯ppt

Recommendations

and

Rationales

Immunosuppression

thetargetlevelsafter3months,

wholebloodtroughlevelsTacrolimus

---5to10ng/mLCyclosporine---100to150ng/mLSirolimus

---5ng/mL.編輯ppt

Recommendations

and

Rationales

LateRejectionCellularrejection(alsoknownasacutecellularrejectionandlate-onsetrejection)

Livertests

nonspecificabnormalitieswitharise

inserumbilirubinandaminotransferasesHistologically,cellularrejectionischaracterizedbythetriadofinflammatorybileductdamage,subendothelialinflammationoftheportal,central,orperivenularveins,andapredominantlylymphocyticportalinflammatoryinfiltratewithneu-trophilsandeosinophilsinadditionDuctopenicrejection(alsoknownasvanishingbileductsyndrome)編輯ppt

Recommendations

and

Rationales

LateRejectionCellularrejection--RiskfactorsReductionofimmunosuppression(whetheriatro-genicorduetononcompliance).Pre-LTautoimmuneliverdisease.Concurrentadministrationofinterferon(forHCVtreatment).Thedifferentialdiagnosisincludesinfection,recurrentanddenovoautoimmunedisease,anddrugtoxicity編輯ppt

Recommendations

and

Rationales

LateRejectionCellularrejection--TreatmentMild:

anincreaseinmaintenancelevelsofimmunosuppressionModerateorsevere:

ashortcourseofincreasedimmunosuppression(eg,methylpredni-soneat500mg/dayorprednisoloneat200mg/dayfor3days)followedbyanincreaseinthebaselineimmunosuppressionOnlyapproximatelyhalfofpatients,withapproximately25%developingafurtherepisodeofcellularrejectionand25%developingductopenicrejection.編輯ppt

Recommendations

and

Rationales

LateRejectionDuctopenicrejection--RiskfactorsRecurrentandunresponsivecellularrejection.Transplantationforautoimmunedisease.Exposuretointerferon

Lossofapreviousgrafttoductopenicrejection.Thedifferentialdiagnosisincludesrecurrentdisease(PBCorPSC)anddrugtoxicity.編輯ppt

Recommendations

and

Rationales

LateRejectionDuctopenicrejection–Treatmentncreasedimmunosuppression,andanincreaseinorswitchtotacrolimusmaybeeffectiveinsomeearlycases.whenfewerthan50%oftheportaltractscontainbileducts,theconditionprogressestograftfailure.編輯pptRecommendations

and

RationalesPromotingHealthAfterLTFrequenthandwashingreducestheriskofinfectionwithpathogensacquiredbydirectcontact,includingClostridiumdifficile,community-acquiredviralinfections,andpathogensfoundinsoil

Shoes,socks,long-sleeveshirts,andlongpantsshouldbewornforactivitiesthatwillinvolvesoilexposureandtickexposureandalsotoavoidunnecessarysunexposureDuringperiodsofmaximalimmunosuppression,LTrecipientsshouldavoidcrowdstominimizeexposurestorespiratoryillnessesWorkinhigh-riskareas,suchasconstruction,animalcaresettings,gardening,landscaping,andfarming,shouldbereviewedwiththetransplantteam編輯pptRecommendations

and

RationalesPromotingHealthAfterLTLTrecipientsshouldavoidtheconsumptionofwaterfromlakesandriversLTrecipientsshouldavoidunpasteurizedmilkproductsandrawandundercookedeggsandmeats

LTrecipientsshouldavoidhigh-riskpets

AllLTrecipientsshouldbeeducatedabouttheimportanceofsunavoidanceandsunprotectionthroughtheuseofasunblockwithasunprotectionfactorofatleast15andprotectiveclothing.Theyshouldbeencouragedtoexaminetheirskinonaregularbasisandreportanysuspiciousorconcerninglesionstotheirphysiciansthesustainedcessationofsmokingisthemostimportantpre-ventativeintervention編輯pptRecommendations

and

RationalesBoneHealth編輯pptRecommendations

and

RationalesBoneHealthInthefirst5yearsaftertransplantation,screeningbyBMDshouldbedoneyearlyforosteopenicpatientsandevery2to3yearsforpatientswithnormalBMD;thereafter,screen-ingdependsontheprogressionofBMDandonriskfactorsIfosteopenicbonediseaseisconfirmedorifatraumaticfracturesarepresent,thenpatientsshouldbeassessedforriskfactorsforboneloss;inparticular,thisshouldincludeanassessmentofcalciumintakeand25-hydroxy-vitaminDlevels,anevaluationofgonadalandthyroidfunction,afullmedicationhistory,andthoracolumbarradiographyTheosteopenicLTrecipientshouldperformregularweight-bearingexerciseandreceivecalciumandvitaminDsupplements

編輯pptRecommendations

and

RationalesSystemicDiseaseKidneyDisease

UrinaryproteinquantificationusingtheconcentrationratioofproteintocreatinineinaspoturinespecimenshouldbeevaluatedatleastonceyearlyThereductionorwithdrawalofCNI-associatedimmunosuppressionisanappropriateresponsetothedevelopmentofCKDinLTrecipientsMetabolicSyndromeMetabolicSyndrome編輯pptRecommendations

and

RationalesSystemicDiseaseMetabolicSyndromeThetreatmentofDMafterLTshouldaimforanHBA1ctargetgoalof<7.0%withacombinationoflifestylemodificationsandpharmacologicalagentsasappropriateMetforminorsulfonylureasmaybeusedinLTrecipientswithnormalrenalfunction,whereassulfonylureassuchasglipizideandglimepiridearepreferableifthereisanydeteriorationofrenalfunction

Considerationcanbegiventotheconversionofimmunosuppressionfromtacrolimustocyclosporine

inLTrecipientswithpoorglycemiccontrol編輯pptRecommendations

and

RationalesSystemicDiseaseHypertensionThetreatmentofhypertensionshouldaimforatargetgoalof130/80mmHgwithacombinationoflifestylemodificationsandpharmacologi-calagentsasappropriateamlodipineandnifedipinemaybemoreeffectiveinLTrecipientsbecausetheycounteractthevasoconstrictiveeffectofCNIs

non-dihydropyridinecalciumchannelblockers(verapamilanddiltiazem)shouldbeusedwithcautionbecausetheymayincreasethebioavailabilityofCNIssignificantlyAngiotensin-convertingenzymeinhibitors,angiotensinreceptorblockers,anddirectrenininhibitorsshouldbeusedasfirst-lineantihypertensivetherapyinLTrecipientswithDM,CKD,and/orsignificantproteinuria編輯pptRecommendations

and

RationalesSystemicDiseaseHyperlipidemia

編輯pptRecommendations

and

RationalesONCOLOGY

編輯pptRecommendations

and

RationalesONCOLOGY

AllLTrecipientsshouldseeadermatologistaftertransplantationtoassesscutaneouslesions,withatleastanannualevaluationbyaderma-tologist5yearsormoreaftertransplantationPatientswithPSCandinflammatoryboweldiseaseorotherestablishedriskfactorsforcolorectalcancershouldundergoanannualscreeningcolonoscopywithbiopsies.Colectomy,includingcontinence-preservingpouchoperations,shouldbeconsideredwhencolonicbiopsyrevealsdysplasia編輯pptRecommendations

and

RationalesONCOLOGY

ForpatientswithoutpriorHCCwhodeveloprecurrentcirrhosisoftheallograft,surveillancefordenovoHCCshouldbeundertakenwithabdominalimagingevery6to12monthsAnimmunosuppressantregimenthatincludessirolimus(startedseveralweeksaftertrans-plantation)shouldbeconsideredforpatientsundergoingtransplantationforHCCResectionorablationisusuallythetreatmentofchoiceforasolitaryextrahepaticmetastasisoranintrahepaticrecurrenceofHCC編輯pptRecommendations

and

RationalesREPRODUCTIVEHEALTHthefemaleLTrecipientspostponeconceptionuntilAtleast1yearafterLT.Allograftfunctionisstable.Medicalcomorbiditiessuchasdiabetesandhypertensionarewellcontrolled.

Immunosuppressionisatalowlevel.編輯pptRecommendations

and

RationalesREPRODUCTIVEHEALTHTheidealimmunosuppressionforpregnancyistacrolimusmonotherapy,whichshouldbemaintainedattherapeuticlevelsthroughoutpregnancy;cyclosporine,azathioprine,andprednisonemayalsobeusediftheyarenecessary

AllograftfunctionandCNIserumlevelsaremonitoredevery4weeksuntil32weeks,thenevery2weeks,andthenweeklyuntildelivery編輯pptRecommendations

and

RationalesINFECTIOUSDISEASE編輯pptRecommendations

and

RationalesINFECTIOUSDISEASECMVThetreatmentofLTrecipientswithCMVshouldbemaintaineduntilviremiaandallsymptomshaveresolvedProphylaxisagainstCMVshouldberesumedwheneverLTrecipientsreceiveanti-lymphocytetherapyforthetreatmentofrejectionandshouldbecontinuedfor1to3monthsafterthetreatmentofrejectionResistantvirusshouldbesuspectedinpatientswithahistoryofprolongedganciclovirorvalganciclovirexposurewhohaveapersistentorprogressiveinfectiondespitetreatmentwithhigh-doseintravenousganciclovir

Insuchinstances,genotypicassaysshouldbeperformed,andconsiderationshouldbegiventotheinitiationoffoscarnetwithorinsubstitutionforganciclovir編輯pptRecommendations

and

RationalesINFECTIOUSDISEASEEBV/PTLDPTLDshouldbeconsideredinLTrecipients(especiallyhigh-riskindividuals)whopresentwithunexplainedfever,lymphadenopathy,orcytopeniasAlthoughEBVmaybeassociatedwiththede-velopmentofPTLD,thedetectionofEBVviremiaisnotdiagnosticforPTLD;ahistopathologicaldiagnosisisrequired編輯pptRecommendations

and

RationalesINFECTIOUSDISEASE

FungalInfectionsRiskfactorspre-operativefungalcolonization,massivetransfusionrequirements(>40Uofbloodproducts),Choledocho-jejunostomy,reoperation,retransplantation,hepaticironoverload,renalreplacementtherapyextendedintervalsofintensivecare編輯pptRecommendations

and

RationalesINFECTIOUSDISEASE

FungalInfectionsBloodculturesaremosthelpfulforthediagnosisofCandidabloodstreaminfectionsandBlastomycesCryptococcalantigentestingofcerebrospinalfluidorbloodismosthelpfulforthediagnosisofCryptococcusUrinaryhistoplasmosisandBlastomycesantigensareusefulforthediagnosisofdisseminatedhistoplasmosisandblastomycosis,respectively

編輯pptRecommendations

and

RationalesINFECTIOUSDISEASE

PneumocystisjiroveciiAllLTrecipientsshouldreceiveprophylaxisagainstP.jiroveciiwithtrimethoprim-sulphame-thoxazole(singlestrengthdailyordoublestrength3timesperweek)foraminimumof6to12monthsaftertransplantation(grade1,levelA).Atovaquoneanddapsonearethepreferred