终末期肝病的肝功能评估[1]

肝硬化患者肝脏储备功能的研究进展上海交通大学医学院附属仁济医院上海市消化疾病研究所邱德凯•1964年Child-Turcotte肝功能分级•1973年Child-Turcott-Pugh(CTP)•1997年UNOS成人(18岁)肝病严重程度分级•2000年MayoTIPS模型•2001年终末期肝病模型(ModelforEnd-stageLiverDisease，MELD)CombinedMELD2007年LilleModel肝功能评估的发展历史Child-Turcotte-Pugh肝功能分级指标评分标准123腹水无少量中等量以上或难治性腹水血清胆红素(umol/L)3434~5151血清白蛋白(g/l)3528~3528凝血酶原时间(较正常延长秒数)or(INR)*1~3（正常值范围内）1.74~6（延长2秒）1.7~2.36（延长2秒）2.3肝性脑病无1-2级3-4级*INR,internationalnormalisedratio.估计生存率(%)总积分分组一年二年6A(轻度)90-100857-9B(中度)70~8060≥10C(重度)40~4535MELD(ModelforEnd-stageLiverDisease)(终末期肝病模型)MELD=9.57loge(creatinemg/dl)+3.78loge（积分）(bilirubinmg/dl)+11.20loge(INR)+6.43(肝硬化病因：胆汁性或酒精性0，其余为1）(6-40)若MELD积分相同则：△MELD（30d内积分的差值）0表明疾病在进展；0表明疾病处于相对平稳期或在好转。see::19-20KiranM.Banbha,Curropiorgtransp2008,13:227-233RELATIONSHIPBETWEENMELDAND3-MONTHMORTALITYINHOSPITALIZEDCIRRHOTICPATIENTSMELDMORTALITY(%;NUMBER/TOTAL)94(6/148)10-1927(28/103)20-2976(16/21)30-3983(5/6)40100(4/4)AdaptedfromWiesnerRH,McDiarmidSV,KamathPS,etal:MELDandPELD:applicationofsurvivalmodelstoliverallocation.LiverTranspl2001;7:567-5802002年2月27日：美国器官共享网/全美器官获取和移植网(OrganProcurementandTransplantationNetwork,OPTN)确定MELD为选择肝移植患者的新标准MELDscoreNo.ofpatientsPerioperativemortality,n(%)≤8≥91-Year3-Year5-YearMELDscoresurvival(%)survival(%)survival(%)PerioperativeMortalityandlong-termsurvivalafterHepaticResectionforHCCJournalOfGastrointestinalSurgery2005Dec;Vol.9(9),pp.1207-15TheperioperativemortalityforpatientswithMELDscore≥9wassignificantlygreaterthanthatforpatientswithMELDscore≤8(0.01).Thelong-termsurvivalforpatientswithMELDscore≥9wassignificantlyshorterthanthatforpatientswithMELDscore≤8(0.01)..370(0)4513(29)≤8896351≥9463423Outcomepost-transplantdependenton△MELDbetweenlistingandtransplant△MELD≤+1△MELD+1P-value90daysurvival(%)180daysurvival(%)1yearsurvival(%)2yearsurvival(%)3yearsurvival(%)TransplInt,2006Dec;Vol.19(12),pp.988-94;95.390.40.000194.984.70.000191.977.80.000188.172.10.000188.172.10.0001ChangeinMELDscorewhilstonthetransplantwaitinglisthasasignificanteffectonsurvivalpost-transplantMELD的局限性没有包括任何临床症状的判断，也没有考虑到患者的生活质量对于合并有严重的门脉高压、顽固性腹水以及肝性脑病的病人，在实行器官分配原则时，应当增加除MELD之外的其它附加条件Fourclinicalstagesofcirrhosis•stage1:patientswithoutvaricesorascites(mortalityisabout1%peryear)•Stage2:patientswithvaricesbutwithoutascitesorbleeding(mortalityrateofabout4%peryear)•Stage3:patientshaveasciteswithorwithoutesophagealvaricesthathaveneverbled(mortalityratewhileremaininginthisstageis20%peryear)•Stage4:withportalhypertensiveGIbleedingwithorwithoutascites(1-yearmortalityrateof57%)compensatedcirrhosisdecompensatedcirrhosisDeFranchisR.JHepatol2005;43:167–176.HVPG•patientswithanHVPG10mmHghada90%probabilityofnotdevelopingclinicaldecompensationduringafollow-upperiodofupto4years•Incompensatedcirrhosis,markersofportalhypertensionsuchasvarices,splenomegaly,plateletcount,gammaglobulinlevelandHVPGweresignificantmortalitypredictorsD’AmicoG,JHepatol2006;44:217–231.MELD联合血清钠水平(SNa)•MELD-AS•MELD-Na•iMELDMELD-ASMELD-AS=MELD+4.53X[0,1]*+4.46X[0,1]**HEPATOLOGY.2004Oct;40:802-810*Ifsodium135mmol/L,=1;otherwise=0**Ifpersistentascites,=1;otherwise=0HEPATOLOGY.2004Oct;40:802-810MELD-ASCTPMELDMELD-ASALLMELDMELD21MELD210.7890.830.8740.6960.6870.7900.5860.7730.758Predictorsof180-dayCirrhoticPatientMortalityMELD-ASmayimprovepredictiveaccuracy,especiallyatlowerMELDscoresAssociationbetweenserumsodiumlevelsandseverityofascitesandcomplicationsofcirrhosis血清钠135mmol/L，Hepatology2006Dec;Vol.44(6),pp.1535-42.发生腹水的概率要比血钠水平正常的患者高；血清钠130mmol/L，更容易出现肝性脑病、自发性细菌性腹膜炎、肝肾综合征。MELD-Na•MELD-Na=MELD+1.0x(140-Na)−0.025×MELD×(140−Na).•UseoftheMEL-DNascoremayreducemortalityamongpatientsonthewaitinglist.•ThedifferencebetweentheMELDscoreandtheMELD-NascorewasoftenlargeenoughtomakearealdifferenceintheprobabilityofreceivingalivertransplantandavertingdeathW.RayKimetal.NEngJMed2008;359:1018-26W.RayKimetal.NEngJMed2008;359:1018-26theexpectednumberoftransplantations:67×(58.4%−18.5%)+43×(70.4%−58.4%)=32Thus,7%ofdeaths(32of477)thatoccurredwithin3monthsafterregistrationonthewaitinglistmighthavebeenpreventedPrevalenceofAscites,SeverityofLiverFailure,RenalFunction,andMortalityAccordingtoHyponatremiaStatusinPatientsNotTransplantedWithin3MonthsNohyponatremiaHyponatremiaValue(n=160)(n=34)pSerumsodium(mEq/L)138±3127±40.001Clinicalascites66(41%)34(100%)0.001Totalbilirbin(mg/dL)5.3±5.911.1±9.10.001INR1.5±0.51.9±1.10.001MELDscore15.4±5.221.1±7.90.001Serumcreatinine(mg/dL)0.8±0.30.8±0.40.28Elevatedserumcreatinine5(3%)3(9%)0.143-monthmortality7(4%)12(35%)0.001Hyponatremiawasdefinedasserumsodium≤130mEq/LLiverTransplantation,Vol11,No3,2005:pp336-343iMELDiMELDscore=MELD+(0.3×年龄)-(0.7×血清钠)+100[LiverTranspl]2007Aug;Vol.13(8),pp.1174-80iMELDMortalityin451patientswithcirrhosislistedforlivertransplantation.iMELDMELD3-month6-month12-month0.760.700.790.710.780.69iMELDimprovesthepredictiveaccuracyoftimetodeathLiverTranspl2007Aug;Vol.13(8),pp.1174-80ESTIMATINGPROGNOSISINPATIENTSWITHPRIMARYBILIA