2025中国多学科专家共识：肝豆状核变性的孤儿、抗铜药物和其他非药物管理（英文）解读

Interpretationof2025ChineseMultidisciplinaryExpertConsensus:OrphanDrugs,Anti-copperDrugsandNon-pharmacologicalManagementofWilsonDisease

1.BackgroundoftheConsensus

Wilsondisease(WD),alsoknownashepatolenticulardegeneration,isanautosomalrecessiveinheriteddisorderofcoppermetabolismclassifiedasararedisease.ChinahasthelargestnumberofWDpatientsworldwideduetoitslargepopulationbase,buttherewerestillproblemssuchasinconsistentdiagnosisandtreatmentnorms,lowaccessibilityoforphandrugs,andinadequateattentiontonon-pharmacologicalmanagementinpreviousclinicalpractice.The2025ChineseMultidisciplinaryExpertConsensus,releasedinEnglish,systematicallysortedoutthemanagementstrategiesforWDfromthedimensionsoforphandrugs,anti-copperpharmacologicaltreatmentandnon-pharmacologicalintervention,whichprovidesclearguidanceforclinicalmultidisciplinarycollaboration.Thispaperinterpretsthecorecontentoftheconsensus.

2.CoreDefinitionandPositioningofWDOrphanDrugs

TheconsensusfirstclarifiesthepositioningofWD-relatedorphandrugsinChina'srarediseasemanagementsystem.AsaregisteredrarediseaseinChina,WDmeetsallthecriteriafororphandrugdesignation.Theconsensuspointsoutthatcurrentlyapprovedanti-copperdrugsforWDincludebothtraditionaldrugsanddesignatedorphandrugs:trientinetetrahydrochlorideisthemainorphandrugforWDofficiallyapprovedformarketinginChinainrecentyears,whichhasbeenincludedinthefirstbatchoforphandrugcatalogsandmedicalinsurancecoveragethroughpolicysupport.TheconsensusemphasizesthatthecoregoaloforphandrugmanagementforWDistoimprovetheaccessibilityandavailabilityofdrugs,andputsforwardmulti-levelguaranteestrategiesincludingimprovingmedicalinsurancereimbursement,expandingcharitabledonationprojects,andencouragingdomesticgenericdrugresearchanddevelopment,tosolvetheproblemof"difficultandexpensiveaccesstodrugs"forWDpatients.

Inaddition,theconsensusalsoclarifiestheunmetclinicalneedsofWDorphandrugs.Atpresent,thereisstillalackoftargetedgenetherapydrugsandnewmechanismanti-copperdrugsforWDinChina.TheconsensuscallsforincreasingpolicysupportfortheresearchanddevelopmentofWDorphandrugs,toenrichtheclinicaltreatmentchoicesinthefuture.

3.UpdateofAnti-copperDrugManagementRecommendations

3.1Stratifiedrecommendationforfirst-linedrugs

Theconsensusupdatesthestratifiedtreatmentstrategyforanti-copperdrugs.FortheinitialtreatmentofsymptomaticWDpatients:penicillamineisstillarecommendedfirst-linedrugformostpatientswithhepaticWD,butitisnotrecommendedasthepreferredfirst-linedrugforpatientswithsevereneurologicalWDduetotheriskofearlyworseningofneurologicalsymptoms.Trientine(orphandrug)isrecommendedasthefirst-linechoiceforpatientswithneurologicalWD,anditisalsothepreferredalternativeforpatientswhocannottoleratetheadversereactionsofpenicillamine(suchashypersensitivity,bonemarrowsuppression,andautoimmuneinjury).Zincpreparations(suchaszincgluconateandzincsulfate)arestillrecommendedasthefirst-linetreatmentforpre-symptomaticWDpatientsandlong-termmaintenancetreatmentafterde-coppertreatment,withgoodsafetyandtolerance.

3.2Doseadjustmentandadversereactionmanagement

Theconsensusrefinesthedoseadjustmentprinciplefordifferentpopulations.Foradultpatients,therecommendedstartingdoseofpenicillamineis750-1000mg/d,dividedinto2-4dosestakenonanemptystomach;thestartingdoseoftrientineis750-1500mg/d;thedoseofzincpreparationis75-150mg/dofelementalzinc.Forchildren,pregnantwomenandpatientswithliverandkidneyfunctioninjury,theconsensusgivespersonalizeddoseadjustmentrecommendations,emphasizingclosemonitoringof24-hoururinarycopper,serumcopperandceruloplasminlevelstoadjustthetreatmentplan.Forcommonadversereactionssuchasearlyneurologicalworsening,theconsensusgivescleartreatmentrecommendations:reducethestartingdose,combinewithsymptomaticintervention,andavoidblinddrugwithdrawal.

3.3Principleoflong-termmedication

TheconsensusreaffirmsthatWDrequireslifelonganti-coppertreatment,andrandomdrugwithdrawalwillleadtoirreversibleliverandnerveinjury,evenlife-threateningacuteliverfailure.Itisnotrecommendedtostopdrugduringpregnancyaslongastheconditionisstable,onlyadjustthedosetoensurethesafetyofmotherandchild.

4.NewProgressinNon-pharmacologicalManagement

4.1Dietarycoppermanagement

Theconsensusupdatesthelow-copperdietrecommendation,correctingthepreviousmisunderstandingof"completeavoidanceofcopper".ItisrecommendedthatthedailytotalcopperintakeofWDpatientsshouldbecontrolledbelow1.5mg,avoideatinghigh-copperfoodssuchasanimaloffal,shellfish,nuts,chocolate,ediblefungiandwildvegetables,andpatientsinareaswithhighcoppercontentindrinkingwaterneedtousereverseosmosiswaterpurifierstoreducecopperintake.Atthesametime,itisnotrecommendedtoexcessivelyrestrictcopperintakeleadingtomalnutrition,andindividualizeddietaryguidanceshouldbegivenaccordingtothepatient'sconditionandnutritionalstatus.

4.2Otherlifestyleandcomplicationmanagement

TheconsensusrecommendsthatWDpatientsavoidusingcoppertablewareandcookingutensils,avoidtakinghealthproductsandtraditionalChinesemedicinewithunknowningredientsthatmaycontainhighcopper,andavoiddrinkingalotofalcohol.Forpatientswithseverecomplicationssuchasacuteliverfailureanddecompensatedcirrhosis,theconsensusclarifiestheindicationoflivertransplantation,andemphasizesthatlivertransplantationisaneffectivelife-savingtreatmentforpatientswithend-stageliverdiseasecausedbyWD.Forpatientswithneurologicaldysfunction,theconsensusrecommendsearlyaccesstorehabilitationinterventiontoimprovethequalityoflife.Inaddition,theconsensusemphasizestheimportanceofgeneticcounselingandprenataldiagnosisforWDfamilies,whichcaneffectivelyreducethebirthrateofchildrenwithWD.PsychologicalinterventionforpatientswithWDcombinedwithanxietyanddepressionisalsoinclu