妊娠期肝內(nèi)膽汁淤積癥

IntrahepaticCholestasisofPregnancyLiuWeiDepartmentofOb&Gy

RenJihospitalDefinitionapregnancy-specificliverdisordercharacterizedbymaternalpruritusinthethirdtrimesterraisedserumbileacidsincreasedrateofadversefetalesThereportedincidenceofICPindifferentcountriesthehighestincidenceEtiologyestrogenandprogesteroneAllhormonesaremetabolizedbytheliver,andanexcessofmetabolitesinfluencestheactivityofbiliarycanaliculartransporters.thethirdtrimester

whenestrogen

↑multiplepregnancieswomenwhotakethecombinedoralcontraceptivepillgeneticfactors:

ABCB4environmentalfactors

Selenium(硒)：Glutathioneperoxidase(谷胱甘肽過氧化物酶

)Seasonalvariation:winterInfection:hepatitisCtwinpregnancies(20%-22%)followinginvitrofertilizationtreatment(2.7%vs0.7%)age:>35yearsICPhistoryinpreviouspregnancyafamilyhistoryofICPhistoryofchronichepatology：HepatitisC；gallstonesRiskfactorsHighlevelsofmaternalbileacidsinducevasoconstrictionofhumanplacentalchorionicveins(誘導(dǎo)人胎盤絨毛靜脈血管收縮)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(亞臨床脂肪瀉):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

(診斷的基本要點(diǎn)）Themostonsetinthethirdtrimesterofpregnancy,afewinthesecondtrimesterThemainsymptomsispruritus,witnoutrash,afewwithmildjaundiceGenerallyingoodcondition,nosignificantgastrointestinalsymptomsAbnormalliverfunction：alaninetransaminase(ALT)andaspartatetransaminase(AST)mildincreaseIncreaseinserumtotalbilirubin,mainlydirectbilirubinMostresolvequicklyafterdeliveryDiagnosedpoints（確診要點(diǎn)）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(縮宮素激惹實(shí)驗(yàn))/contractionstresstest(宮縮應(yīng)激實(shí)驗(yàn))everyICPwomenwhowanttohaveavaginallabourmustreceiveOCTSystolictoDiastolic(S/D)≥34wkofgestationQWFetalbiophysicalscore(BPS)Amniocentesis(羊膜腔穿刺)andamnioscope(羊膜鏡)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,熊去氧膽酸):anon-toxichydrophilicbileacidscompetitivelyinhibittheabsorptionoftoxicendogenousbileacidsintheileumenhancedcholestaticlivercellsecretorycapacityreducetheconcentrationofendogenoushydrophobicbileacidsinthebloodandlivercellscompetitiontoreplacethetoxicbileacidmoleculesinthecellmembraneandorganelles,topreventthedamageofthelivercellsandbileductcellsfromtoxicbileacidsthefirstlineoftreatment.15mg/kgperdayTID,20d.highdoseUDCA:1.5-2g/dnoadverseeffectsinmothersornewbornshavebeenobservedS-Adenosyl-L-methionine(SAMe)theprincipalmethylgroupdonorinvolvedinthesynthesisofphosphatidylcholine

(磷脂酰膽堿合成中的主要甲基供體)

itinfluencesthecompositionandfluidityofhepaticmembranesandhencebiliaryexcretionofhormonemetabolites(影響肝膜的合成和流動性，故利于激素代謝物的膽汁排泄）思美泰

1g/dIntravenousinfusion*12-14d;inseverecase2g/d500mgBIDOralwelltolerated:fewadversematernalorfetaleffectshavebeenreportedCombinationtherapy:severecase:UDCA250mgTIDOral+SAMe500mgBIDIntravenousinfusionDrugsTratment—SAMeDrugsTratment—cholestyramineItbindsbilesaltsandinterruptstheirenterohepaticcirculation(肝腸循環(huán))消膽胺withoutclearevidenceofefficacy8-16g/dmayworsenthemalabsorptionoffat-solublevitamins,especiallyvitaminK(加重脂溶性維生素的吸收不良，特別是維生素K)DrugsTratment—DexamethasoneTopromotefetallungmaturity

<34wkofgestationandestimatedmaypretermdeliverywithin7days5mgIntramuscularinjectionQ12H*2DToinhibitplacentalestrogensynthesisreducingsecretionofdehydroepiandrosterone（脫氫表雄酮）

sulfate(theprecursorofestrogen)fromthefetaladrenalglandsDrugsTratment—others護(hù)肝藥物：不建議同時(shí)使用多種保肝抗炎藥物VitaminK:

guardagainstantepartum,postpartumhemorrhageTopicaltreatment:

aqueouscr