終末期肝病的肝功能評估課件

肝硬化患者

肝臟儲備功能的研究進(jìn)展

邱德凱

終末期肝病的肝功能評估1964年

Child-Turcotte肝功能分級1973年Child-Turcott-Pugh(CTP)1997年UNOS

成人(>18歲)肝病嚴(yán)重程度分級2000年MayoTIPS模型2001年終末期肝病模型(ModelforEnd-stageLiverDisease，MELD)CombinedMELD2007年LilleModel肝功能評估的發(fā)展歷史終末期肝病的肝功能評估Child-Turcotte-Pugh肝功能分級指標(biāo)評分標(biāo)準(zhǔn)123腹水無少量中等量以上或難治性腹水血清膽紅素(umol/L)<3434~51>51血清白蛋白(g/l)>3528~35<

28凝血酶原時(shí)間(較正常延長秒數(shù))or(INR)*1~3（正常值范圍內(nèi)）<1.74~6（延長<2秒）1.7~2.3>6（延長

2秒）>2.3肝性腦病無1-2級3-4級*INR,internationalnormalisedratio.估計(jì)生存率(%)總積分分組一年二年<6A(輕度)90-100857-9B(中度)70~8060

≥10C(重度)40~4535終末期肝病的肝功能評估MELD(ModelforEnd-stageLiverDisease)(終末期肝病模型)MELD=9.57

loge(creatinemg/dl)+3.78

loge（積分）

(bilirubinmg/dl)+11.20

loge(INR)+6.43

(肝硬化病因：膽汁性或酒精性0，其余為1）(6-40)若MELD積分相同則：

△MELD（30d內(nèi)積分的差值）>0表明疾病在進(jìn)展；

0表明疾病處于相對平穩(wěn)期或在好轉(zhuǎn)。see:

tocalculateMELDscoredirectlyLiverTranspl,2003.9:19-20

KiranM.Banbha,Curropiorgtransp2008,13:227-233終末期肝病的肝功能評估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終末期肝病的肝功能評估終末期肝病的肝功能評估2002年2月27日：美國器官共享網(wǎng)/全美器官獲取和移植網(wǎng)(OrganProcurementandTransplantationNetwork,OPTN)確定MELD為選擇肝移植患者的新標(biāo)準(zhǔn)

終末期肝病的肝功能評估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終末期肝病的肝功能評估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終末期肝病的肝功能評估MELD的局限性沒有包括任何臨床癥狀的判斷，也沒有考慮到患者的生活質(zhì)量

對于合并有嚴(yán)重的門脈高壓、頑固性腹水以及肝性腦病的病人，在實(shí)行器官分配原則時(shí)，應(yīng)當(dāng)增加除MELD之外的其它附加條件終末期肝病的肝功能評估Fourclinicalstagesofcirrhosis

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

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

patientswithanHVPG

<10mmHghada90%probability

ofnotdevelopingclinicaldecompensation

duringafollow-upperiodofupto4yearsIncompensatedcirrhosis,markersofportalhypertensionsuchasvarices,splenomegaly,plateletcount,gammaglobulinlevelandHVPGweresignificantmortalitypredictors D’AmicoG,JHepatol2006;44:217–231.終末期肝病的肝功能評估MELD聯(lián)合血清鈉水平(SNa)MELD-ASMELD-NaiMELD終末期肝病的肝功能評估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終末期肝病的肝功能評估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終末期肝病的肝功能評估Associationbetweenserumsodiumlevelsandseverityofascitesandcomplicationsofcirrhosis血清鈉

<135mmol/L，

Hepatology2006Dec;Vol.44(6),pp.1535-42.

發(fā)生腹水的概率要比血鈉水平正常的患者高；血清鈉<130mmol/L，

更容易出現(xiàn)肝性腦病、自發(fā)性細(xì)菌性腹膜炎、肝腎綜合征。終末期肝病的肝功能評估MELD-NaMELD-Na=MELD+1.0x(140-Na)?0.025×MELD×(140?Na).UseoftheMEL-DNascoremayreducemortalityamongpatientsonthewaitinglist.ThedifferencebetweentheMELDscoreandtheMELD-NascorewasoftenlargeenoughtomakearealdifferenceintheprobabilityofreceivingalivertransplantandavertingdeathW.RayKimetal.NEngJMed2008;359:1018-26終末期肝病的肝功能評估W.RayKimetal.NEngJMed2008;359:1018-26theexpectednumberoftransplantations:67×(58.4%?18.5%)+43×(70.4%?58.4%)=32Thus,7%ofdeaths(32of477)thatoccurredwithin3monthsafterregistrationonthewaitinglistmighthavebeen

prevented終末期肝病的肝功能評估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終末期肝病的肝功能評估iMELDiMELDscore=MELD+(0.3×年齡)-(0.7×血清鈉)+100

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

iMELDMELD3-month6-month12-month0.76

0.700.79

0.710.78

0.69iMELDimprovesthepredictiveaccuracyoftimetodeath

LiverTranspl2007Aug;Vol.13(8),pp.1174-80終末期肝病的肝功能評估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%終末期肝病的肝功能評估酒精性肝病嚴(yán)重程度評估方法Maddrey判別函數(shù)DF=4.6×PT延長（秒）＋TB（mg／dl），DF有助于判斷AH患者的預(yù)后，DF大于32者8周內(nèi)死亡率高達(dá)50%以上，DF大于32者又稱重癥AHPhillipsMetal.Antioxidantsversuscorticosteroidsinthetreatmentofseverealcoholichepatitis–arandomizedclinicaltrial.JHepatol,2006;44:784-790.終末期肝病的肝功能評估酒精性肝病嚴(yán)重程度評估方法TB水平早期變化模式（ECBL）定義：激素治療第7天的TB水平低于第1天臨床意義：95％ECBL患者在治療期間可獲得持續(xù)的肝功能改善。6個(gè)月時(shí)，ECBL患者生存率為82.8％，顯著高于無ECBL患者的23％。多因素分析表明，ECBL、年齡、DF和肌酐都是獨(dú)立的預(yù)測參數(shù)，而ECBL預(yù)測價(jià)值最大MathurinPetal.Earlychangeinbilirubinlevels(ECBL)isanimportantprognosticfactorinseverebiopsy-provenalcoholichepatitis(AH)treatedbyprednisolone.Hepatology,2003;88:1363-1369.終末期肝病的肝功能評估Lille模型Lille模型于2007年由法國