终末期肝病的肝功能评估课件

肝硬化患者

肝脏储备功能的研究进展

邱德凯

终末期肝病的肝功能评估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终末期肝病的肝功能评估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)<3434~51>51血清白蛋白(g/l)>3528~35<

28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）1.7~2.3>6（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)40~4535终末期肝病的肝功能评估MELD(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:

tocalculateMELDscoredirectlyLiverTranspl,2003.9:19-20

KiranM.Banbha,Curropiorgtransp2008,13:227-233终末期肝病的肝功能评估RELATIONSHIPBETWEENMELDAND3-MONTHMORTALITYINHOSPITALIZEDCIRRHOTICPATIENTS

MELDMORTALITY(%;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;7:567-580终末期肝病的肝功能评估终末期肝病的肝功能评估2002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

终末期肝病的肝功能评估MELDscore

No.ofpatientsPerioperativemortality,n(%)≤8

≥9

1-Year3-Year5-YearMELDscoresurvival(%)survival(%)survival(%)

PerioperativeMortalityandlong-termsurvivalafterHepaticResectionforHCCJournalOfGastrointestinalSurgery2005Dec;Vol.9(9),pp.1207-15TheperioperativemortalityforpatientswithMELDscore≥9wassignificantlygreaterthanthatforpatientswithMELDscore≤8(<0.01).Thelong-termsurvival

forpatientswithMELDscore≥9

wassignificantlyshorterthanthatforpatientswithMELDscore≤8(<0.01).

.370(0)

4513(29)≤8

896351≥9

463423终末期肝病的肝功能评估Outcomepost-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-transplant终末期肝病的肝功能评估MELD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终末期肝病的肝功能评估Fourclinicalstagesofcirrhosis

stage1:patientswithoutvaricesorascites(mortalityisabout1%peryear)Stage2:patientswithvaricesbutwithoutascitesorbleeding(mortalityrateofabout4%peryear)Stage3:patientshaveasciteswithorwithoutesophagealvaricesthathaveneverbled(mortalityratewhileremaininginthisstageis20%peryear)Stage4:withportalhypertensiveGIbleeding

withorwithoutascites(1-yearmortalityrateof57%)compensatedcirrhosisdecompensatedcirrhosisDeFranchisR.JHepatol2005;43:167–176.终末期肝病的肝功能评估HVPG

patientswithanHVPG

<10mmHghada90%probability

ofnotdevelopingclinicaldecompensation

duringafollow-upperiodofupto4yearsIncompensatedcirrhosis,markersofportalhypertensionsuchasvarices,splenomegaly,plateletcount,gammaglobulinlevelandHVPGweresignificantmortalitypredictors D’AmicoG,JHepatol2006;44:217–231.终末期肝病的肝功能评估MELD联合血清钠水平(SNa)MELD-ASMELD-NaiMELD终末期肝病的肝功能评估MELD-AS

MELD-AS=MELD+4.53X[0,1]*+4.46X[0,1]**

HEPATOLOGY.2004Oct;40:802-810*Ifsodium<135mmol/L,=1;otherwise=0**Ifpersistentascites,=1;otherwise=0终末期肝病的肝功能评估HEPATOLOGY.2004Oct;40:802-810MELD-AS

CTPMELDMELD-ASALLMELDMELD<21MELD>21

0.7890.830.874

0.6960.6870.790

0.5860.7730.758Predictorsof180-dayCirrhoticPatientMortalityMELD-ASmayimprovepredictiveaccuracy,especiallyatlowerMELDscores终末期肝病的肝功能评估Associationbetweenserumsodiumlevelsandseverityofascitesandcomplicationsofcirrhosis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。终末期肝病的肝功能评估MELD-NaMELD-Na=MELD+1.0x(140-Na)−0.025×MELD×(140−Na).UseoftheMEL-DNascoremayreducemortalityamongpatientsonthewaitinglist.ThedifferencebetweentheMELDscoreandtheMELD-NascorewasoftenlargeenoughtomakearealdifferenceintheprobabilityofreceivingalivertransplantandavertingdeathW.RayKimetal.NEngJMed2008;359:1018-26终末期肝病的肝功能评估W.RayKimetal.NEngJMed2008;359:1018-26theexpectednumberoftransplantations:67×(58.4%−18.5%)+43×(70.4%−58.4%)=32Thus,7%ofdeaths(32of477)thatoccurredwithin3monthsafterregistrationonthewaitinglistmighthavebeen

prevented终末期肝病的肝功能评估PrevalenceofAscites,SeverityofLiverFailure,RenalFunction,andMortalityAccordingtoHyponatremia

StatusinPatientsNotTransplantedWithin3Months

NohyponatremiaHyponatremia

Value

(n=160)(n=34)pSerumsodium(mEq/L)138±3127±4<0.001Clinicalascites66(41%)34(100%)<0.001Totalbilirbin(mg/dL)5.3±5.911.1±9.1<0.001INR

1.5±0.51.9±1.1<0.001MELDscore15.4±5.221.1±7.9<0.001Serumcreatinine(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:pp336-343终末期肝病的肝功能评估iMELDiMELDscore=MELD+(0.3×年龄)-(0.7×血清钠)+100

[LiverTranspl]2007Aug;Vol.13(8),pp.1174-80终末期肝病的肝功能评估iMELDMortalityin451patientswithcirrhosislistedforlivertransplantation.

iMELDMELD3-month6-month12-month0.76

0.700.79

0.710.78

0.69iMELDimprovesthepredictiveaccuracyoftimetodeath

LiverTranspl2007Aug;Vol.13(8),pp.1174-80终末期肝病的肝功能评估ESTIMATINGPROGNOSISINPATIENTSWITHPRIMARYBILIARYCIRRHOSIS(PBC)MAYOPBCRISKSCORER=0.871log(serumbilirubininmg/dL)–2.53xlog(albumining/dL)+0.039+(ageinyears)+2.38xlog(prothrombintimeinseconds)+0.859(ifedemapresent)RiskscoreistranslatedintoasurvivalfunctiontoestimatesurvivalfortheindividualpatientwithPBC.Othermodelshaveemphasizedvaricealbleedingasanimportantadditionalclinicalprognosticator.PROGNOSTICINDEXFORSURVIVALAFTERLIVERTRANSPLANTATIONINPATIENTSWITHPBCPI=0.60xlog(serumbilirubininmg/dL)+0.82xlog(serumureainmmol/L)+1.14+(transplantationbefore1985)–0.92(diuretic-responsiveascites)+1.70

RiskScore

4-MonthSurvival<8.691%8.6-9.978%>9.957%终末期肝病的肝功能评估酒精性肝病严重程度评估方法Maddrey判别函数DF=4.6×PT延长（秒）＋TB（mg／dl），DF有助于判断AH患者的预后，DF大于32者8周内死亡率高达50%以上，DF大于32者又称重症AHPhillipsMetal.Antioxidantsversuscorticosteroidsinthetreatmentofseverealcoholichepatitis–arandomizedclinicaltrial.JHepatol,2006;44:784-790.终末期肝病的肝功能评估酒精性肝病严重程度评估方法TB水平早期变化模式（ECBL）定义：激素治疗第7天的TB水平低于第1天临床意义：95％ECBL患者在治疗期间可获得持续的肝功能改善。6个月时，ECBL患者生存率为82.8％，显著高于无ECBL患者的23％。多因素分析表明，ECBL、年龄、DF和肌酐都是独立的预测参数，而ECBL预测价值最大MathurinPetal.Earlychangeinbilirubinlevels(ECBL)isanimportantprognosticfactorinseverebiopsy-provenalcoholichepatitis(AH)treatedbyprednisolone.Hepatology,2003;88:1363-1369.终末期肝病的肝功能评估Lille模型Lille模型于2007年由法国