妊娠期肝内胆汁淤积症

IntrahepaticCholestasisofPregnancyLiuWeiDepartmentofOb&Gy

RenJihospitalDefinitionapregnancy-specificliverdisordercharacterizedbymaternalpruritusinthethirdtrimesterraisedserumbileacidsincreasedrateofadversefetalesThereportedincidenceofICPindifferentcountriesthehighestincidenceEtiologyestrogenandprogesteroneAllhormonesaremetabolizedbytheliver,andanexcessofmetabolitesinfluencestheactivityofbiliarycanaliculartransporters.thethirdtrimester

whenestrogen

↑multiplepregnancieswomenwhotakethecombinedoralcontraceptivepillgeneticfactors:

ABCB4environmentalfactors

Selenium(硒)：Glutathioneperoxidase(谷胱甘肽过氧化物酶

)Seasonalvariation:winterInfection:hepatitisCtwinpregnancies(20%-22%)followinginvitrofertilizationtreatment(2.7%vs0.7%)age:>35yearsICPhistoryinpreviouspregnancyafamilyhistoryofICPhistoryofchronichepatology：HepatitisC；gallstonesRiskfactorsHighlevelsofmaternalbileacidsinducevasoconstrictionofhumanplacentalchorionicveins(诱导人胎盘绒毛静脉血管收缩)increasemyometrialsensitivitytooxytocinchronicplacentalinsufficiency

affectplacentaltransport,placentalhormoneproductionSepulvedaWH,GonzalezC,CruzMA,RudolphMI.Vasoconstrictiveeffectofbileacidsonisolatedhumanplacentalchorionicveins.EurJObstetGynecolReprodBiol1991;42:211-215GermainAM,KatoS,CarvajalJA,ValenzuelaGJ,ValdesGL,GlasinovicJC.Bileacidsincreaseresponseandexpressionofhumanmyometrialoxytocinreceptor.AmJObstetGynecol2003;189:577-582SimpsonLL.Maternalmedicaldisease:riskofantepartumfetaldeath.SeminPerinatol2002;26:42-50EtiologyoffetalcomplicationsAdversefetalesPretermlabour:19~60%,lowbirthweightinfant(<2000g)Fetaldistress:22~33%Sudden

Intrauterine

Death(IUD):3.5%orless,around37-39wkTherateofmalformationsorabortionsisnotincreasedinICPthereisa1%-2%increasedriskforeveryµmol/Lofbileacidabove40µmol/L**GlantzA,MarschallHU,MattssonLA.Intrahepaticcholestasisofpregnancy:Relationshipsbetweenbileacidlevelsandfetalcomplicationrates.Hepatology2004;40:467-474Maternaldiseasepruritusapproximately80%ofICPpresentafter30wkofgestation.(reportedasearlyas8wk)thepalmsandthesolesofthefeet,andisworseatnightmostresolvewithin24-48hoursofdelivery,fewwithin1wkormore

mildjaundiceabout15-60%ofICPpresentanaverageof2weeksafterpruritusmostresolvewithinsomedaysofdelivery,fewwilllastmorethanonemonth.palestoolsanddarkurine

othersvomit,anorexia(食欲不振),malaise(全身乏力)

andabdominalpain.subclinicalsteatorrhea(亚临床脂肪泻):vitaminKdeficiencyLaboratoryexamination——Bileacidscholicacid(CA)：highSensitivityandlowSpecificityRadioimmunoassayandresultsinstabilityFastingbloodtest≥10.75μmol/l(Normal:5.61μmol/l)Screeningandfollow-upindicatorstotalserumbileacids(TBA):lowSensitivityandhighSpecificityFastingbloodtest>

10µmol/LToassesstheseverityofthediseaseLaboratoryexamination——liverfunctionSerumaminotransferasesincrease

alaninetransaminase(ALT),aspartatetransaminase(AST)increase2-foldto15-foldmostresolvewithinanaverageof10dofdeliverySerumγ-GTisusuallynormalormodestlyelevatedAlkalinephosphataseisofpoordiagnosticvalue：duetoplacentalandboneproductionLaboratoryexamination——bilirubintotalbilirubinisusuallynormalormodestlyelevatedwithanaveragelevelof30-40µmol/L,PrimarilyisdirectbilirubinAdjunctiveExaminationLiver/gallbladderultrasoundscanNospecificperformanceGallstonesarereportedin13%ofwomenwithICPLiverbiopsy：Lessclinicalusenoevidenceoflivercelldamageonlymildlydilatedbileducts,bilestasisincanaliculi,bileplugsandmildportaltractinflammationThediagnosisofICPBasicpoints

(诊断的基本要点）Themostonsetinthethirdtrimesterofpregnancy,afewinthesecondtrimesterThemainsymptomsispruritus,witnoutrash,afewwithmildjaundiceGenerallyingoodcondition,nosignificantgastrointestinalsymptomsAbnormalliverfunction：alaninetransaminase(ALT)andaspartatetransaminase(AST)mildincreaseIncreaseinserumtotalbilirubin,mainlydirectbilirubinMostresolvequicklyafterdeliveryDiagnosedpoints（确诊要点）cholicacid

Fastingbloodtest≥10.75μmol/l(Normal:5.61μmol/l)

and/ortotalserumbileacidsFastingbloodtest>10µmol/LManifestationMildtypeSeveretypeBileacidstotalserumbileacid10-39µmol/L≥40µmol/Lcholicacid10.75-43µmol/L>43µmol/Lbilirubintotalbilirubin<21µmol/L≥21µmol/Ldirectbilirubin<6µmol/L≥6µmol/LliverfunctionALT<200U/L≥200U/LAST<200U/L≥200U/LClinicalsymptomsmildpruritusseverepruritus、jaundiceandsoonComplicationsNORecurrentICPpregnancyinducedhypertensionsyndromePIHotherNO<34wkofgestationMultiplepregnanciesFetalmonitoringFetalmovementNormal:≥30/12HNST(nonstresstests)33-34wkofgestationQW≥34wkofgestationBIWOCT/CSToxytocinchallengetest(缩宫素激惹实验)/contractionstresstest(宫缩应激实验)everyICPwomenwhowanttohaveavaginallabourmustreceiveOCTSystolictoDiastolic(S/D)≥34wkofgestationQWFetalbiophysicalscore(BPS)Amniocentesis(羊膜腔穿刺)andamnioscope(羊膜镜)Notroutinelymendedonlywhenassessamnioticfluidcolor,fetalmaturityandintrauterineadministration

gestationscreeningHistorytaking:pruritus

determineserumbileacidslevelandfollow-upNormalpregnantwomen:determineSerumbileacidslevelat32-34wkofgestationWomenwithICPriskfactor:determineserumbileacidslevelat28wkofgestation

ifNormal

reviewafter3-4weeksMaternalconditionmonitoringserumbiochemistrymonitoringtotalserumbileacid(µmol/L)scholicacid(µmol/L)ALT(U/L)wkofgestationTreatment10-2010.75-21.5<100<32Revieweveryoneortwoweeks>32Revieweveryweek>20>21.5>100

whateverRevieweveryweekThegoaloftreatmentinICPreducematernalsymptomsimprovefetaleGeneraltreatmentLow-fatdietLeftlateralpositionFetalheartratecountingTIDFetalmovementcountingTIDOxygen30minTIDDrugsTreatment—UDCAursodeoxycholicacid(UDCA,熊去氧胆酸):anon-toxichydrophilicbileacidscompetitivelyinhibittheabsorptionoftoxicendogenousbileacidsintheileumenhancedcholestaticlivercellsecretorycapacityreducetheconcentrationofendogenoushydrophobicbileacidsinthebloodandlivercellscompetitiontoreplacethetoxicbileacidmoleculesinthecellmembraneandorganelles,topreventthedamageofthelivercellsandbileductcellsfromtoxicbileacidsthefirstlineoftreatment.15mg/kgperdayTID,20d.highdoseUDCA:1.5-2g/dnoadverseeffectsinmothersornewbornshavebeenobservedS-Adenosyl-L-methionine(SAMe)theprincipalmethylgroupdonorinvolvedinthesynthesisofphosphatidylcholine

(磷脂酰胆碱合成中的主要甲基供体)

itinfluencesthecompositionandfluidityofhepaticmembranesandhencebiliaryexcretionofhormonemetabolites(影响肝膜的合成和流动性，故利于激素代谢物的胆汁排泄）思美泰

1g/dIntravenousinfusion*12-14d;inseverecase2g/d500mgBIDOralwelltolerated:fewadversematernalorfetaleffectshavebeenreportedCombinationtherapy:severecase:UDCA250mgTIDOral+SAMe500mgBIDIntravenousinfusionDrugsTratment—SAMeDrugsTratment—cholestyramineItbindsbilesaltsandinterruptstheirenterohepaticcirculation(肝肠循环)消胆胺withoutclearevidenceofefficacy8-16g/dmayworsenthemalabsorptionoffat-solublevitamins,especiallyvitaminK(加重脂溶性维生素的吸收不良，特别是维生素K)DrugsTratment—DexamethasoneTopromotefetallungmaturity

<34wkofgestationandestimatedmaypretermdeliverywithin7days5mgIntramuscularinjectionQ12H*2DToinhibitplacentalestrogensynthesisreducingsecretionofdehydroepiandrosterone（脱氢表雄酮）

sulfate(theprecursorofestrogen)fromthefetaladrenalglandsDrugsTratment—others护肝药物：不建议同时使用多种保肝抗炎药物VitaminK:

guardagainstantepartum,postpartumhemorrhageTopicaltreatment:

aqueouscr