1、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 Mayo TIPS模型 2001年 终末期肝病模型(Model for End-stage Liver Disease，MELD)Combined MELD 2007年 Lille Model 肝功能评估的发展历史肝功能评估的发展历史Child-Turcotte-Pugh肝功能分级肝功能分级指标指标 评分标准评分标准123腹水腹水无无少量少量中等量以上或难治性中等量以上或难治性腹水腹水血清胆红素
2、血清胆红素(umol/L)51血清白蛋白血清白蛋白(g/l)352835 28凝血酶原时间凝血酶原时间(较正较正常延长秒数常延长秒数)or(INR)*13（正常值范围内）（正常值范围内）1.746（延长（延长 6（延长（延长 2秒）秒）2.3肝性脑病肝性脑病无无1-2级级3-4级级*INR,international normalised ratio.估估 计计 生生 存存 率率(%)总积分总积分分组分组一年一年二年二年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:to calculate MELD score directlyLiver Transpl,2003.9:19-20
3、 Kiran M.Banbha,Curr opi org transp 2008,13:227-233RELATIONSHIP BETWEEN MELD AND 3-MONTH MORTALITY IN HOSPITALIZED CIRRHOTIC PATIENTS MELDMORTALITY(%;NUMBER/TOTAL)94(6/148)10-1927(28/103)20-2976(16/21)30-3983(5/6)40100(4/4)Adapted from Wiesner RH,McDiarmid SV,Kamath PS,et al:MELD and PELD:applicatio
4、n of survival models to liver allocation.Liver Transpl 2001;7:567-5802002年年2月月27日：美国器官共享网日：美国器官共享网/全美器全美器官获取和移植网官获取和移植网(Organ Procurement and Transplantation Network,OPTN)确确定定MELD为选择肝移植患者的新标准为选择肝移植患者的新标准 MELD score No.of patients Perioperative mortality,n(%)8 9 1-Year 3-Year 5-YearMELD score surviva
5、l(%)survival(%)survival(%)Perioperative Mortality and long-term survival after Hepatic Resection for HCCJournal Of Gastrointestinal Surgery 2005 Dec;Vol.9(9),pp.1207-15The perioperative mortality for patients with MELD score 9 was significantly greater than that for patients with MELD score 8(0.01).
6、The long-term survival for patients with MELD score 9 was significantly shorter than that for patients with MELD score 8(+1 P-value90 day survival(%)180 day survival(%)1 year survival(%)2 year survival(%)3 year survival(%)Transpl Int,2006 Dec;Vol.19(12),pp.988-94;95.3 90.4 0.000194.9 84.7 0.000191.9
7、 77.8 0.000188.1 72.1 0.000188.1 72.1 0.0001Change in MELD score whilst on the transplant waiting list has a significant effect on survival post-transplantMELD的局限性的局限性没有包括任何没有包括任何临床症状临床症状的判断，也没有考虑到患者的的判断，也没有考虑到患者的生生活质量活质量 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 Four clinical stages
8、 of cirrhosis stage 1:patients without varices or ascites(mortality is about 1%per year)Stage 2:patients with varices but without ascites or bleeding(mortality rate of about 4%per year)Stage 3:patients have ascites with or without esophageal varices that have never bled(mortality rate while remainin
9、g in this stage is 20%per year)Stage 4:with portal hypertensive GI bleeding with or without ascites(1-year mortality rate of 57%)compensated cirrhosis decompensated cirrhosis De Franchis R.J Hepatol 2005;43:pensated cirrhosis拓展为Lille评分0.Stage 3:patients have ascites with or without esophageal varice
10、s that have never bled(mortality rate while remaining in this stage is 20%per year)patients with an HVPG 10mmHg had a 90%probability of not developing clinical decompensation during a follow-up period of up to 4 years血清钠 135mmol/L，586 0.9 78%especially at lower MELD scoressee:Liver Transpl,2003.No h
11、yponatremia Hyponatremia Value可以利用 网站计算Lille模型分值，在所对应的变量空格中填写相应数据即可得到可以利用 网站计算Lille模型分值，在所对应的变量空格中填写相应数据即可得到27(28/103)终末期肝病的肝功能评估3 year survival(%)Mathurin P,Louvet A,Dharancy S.0表明疾病处于相对平稳期或在好转。HVPG patients with an HVPG 10mmHg had a 90%probability of not developing clinical decompensation during a
12、 follow-up period of up to 4 years In compensated cirrhosis,markers of portal hypertension such as varices,splenomegaly,platelet count,gamma globulin level and HVPG were significant mortality predictors DAmico G,J Hepatol 2006;44:217231.MELD 联合血清钠水平联合血清钠水平(SNa)MELD-AS MELD-Na iMELDMELD-AS MELD-AS=ME
13、LD+4.53 X 0,1*+4.46 X 0,1*HEPATOLOGY.2004 Oct;40:802-810*If sodium 135mmol/L,=1;otherwise=0 *If persistent ascites,=1;otherwise=0HEPATOLOGY.2004 Oct;40:802-810MELD-AS CTP MELD MELD-ASALL MELDMELD21 0.789 0.83 0.874 0.696 0.687 0.790 0.586 0.773 0.758Predictors of 180-day Cirrhotic Patient MortalityM
14、ELD-AS may improve predictive accuracy,especially at lower MELD scoresAssociation between serum sodium levels and severity of ascites and complications of cirrhosis血清钠 135mmol/L，Hepatology 2006 Dec;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+
15、1.0 x(140-Na)0.025 MELD(140 Na).Use of the MEL-DNa score may reduce mortality among patients on the waiting list.The difference between the MELD score and the MELD-Na score was often large enough to make a real difference in the probability of receiving a liver transplant and averting deathW.Ray Kim
16、 et al.N Eng J Med 2008;359:1018-26W.Ray Kim et al.N Eng J Med 2008;359:1018-26the expected number of transplantations:67 (58.4%18.5%)+43 (70.4%58.4%)=32 Thus,7%of deaths(32 of 477)that occurred within 3 months after registration on the waiting list might have been preventedPrevalence of Ascites,Sev
17、erity of Liver Failure,Renal Function,and Mortality According to HyponatremiaStatus in Patients Not Transplanted Within 3 Months No hyponatremia Hyponatremia Value (n=160)(n=34)pSerum sodium(mEq/L)138 3 127 4 0.001Clinical ascites 66(41%)34(100%)0.001Total bilirbin(mg/dL)5.3 5.9 11.1 9.1 0.001INR 1.
18、5 0.5 1.9 1.1 0.001MELD score 15.4 5.2 21.1 7.9 0.001Serum creatinine(mg/dL)0.8 0.3 0.8 0.4 0.28Elevated serum creatinine 5(3%)3(9%)0.143-month mortality 7(4%)12(35%)0.001 Hyponatremia was defined as serum sodium 130 mEq/LiMELDiMELD score=MELD+(0.3年龄年龄)-(0.7血清钠血清钠)+100 Liver Transpl 2007 Aug;Vol.13(
19、8),pp.1174-80iMELDMortality in 451 patients with cirrhosis listed for liver transplantation.iMELD MELD3-month6-month12-month 0.76 0.70 0.79 0.71 0.78 0.69 iMELD improves the predictive accuracy of time to death Liver Transpl 2007 Aug;Vol.13(8),pp.1174-80ESTIMATING PROGNOSIS IN PATIENTS WITH PRIMARY
20、BILIARY CIRRHOSIS(PBC)MAYO PBC RISK SCORER=0.871 log(serum bilirubin in mg/dL)2.53 x log(albumin in g/dL)+0.039+(age in years)+2.38 x log(prothrombin time in seconds)+0.859(if edema present)Risk score is translated into a survival function to estimate survival for the individual patient with PBC.Oth
21、er models have emphasized variceal bleeding as an important additional clinical prognosticator.PROGNOSTIC INDEX FOR SURVIVAL AFTER LIVER TRANSPLANTATION IN PATIENTS WITH PBCPI=0.60 x log(serum bilirubin in mg/dL)+0.82 x log(serum urea in mmol/L)+1.14+(transplantation before 1985)0.92(diuretic-respon
22、sive ascites)+1.70 Risk Score 4-Month Survival 9.9 57%酒精性肝病严重程度评估方法 Maddrey判别函数DF=4.6PT延长（秒）TB（mgdl），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AH Phillips M et al.Antioxidants versus corticosteroids in the treatment of severe alcoholic hepatitis a randomized clinical trial.J Hepatol,2006;44:784
23、-790.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：95ECBL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 Mathurin P et al.Early change in bilirubin levels(ECBL)is an important prognostic factor in severe biopsy-proven alcoholic hepatitis(AH)
24、treated by prednisolone.Hepatology,2003;88:1363-1369.Lille 模型 Lille模型于2007年由法国CHRU Lille医院肝病科联合其他四个中心首次提出 计算公式：Lille 积分=3.190.101*年龄(years)+0.147*白蛋白(g/L)0.0165*胆红素(day 7)(mol/L)0.206*(有肾功能不全取1，无肾功能不全取0)0.0065*胆红素(day 0)（mol/L)0.0096*凝血酶原时间(seconds).说明：肾功能不全评价标准：肌酐是否115mol/L 胆红素第0天、第7天分别指类固醇治疗开始时及治疗
25、7天后所测得的胆红素水平 可以利用 网站计算Lille模型分值，在所对应的变量空格中填写相应数据即可得到计算页面 拓展了“non-responder to corticosteroids”（对类固醇治疗无反应患者）定义范畴 以往“non-responder to corticosteroids”是指无ECBL的患者 拓展为Lille评分0.45的患者，Lille评分0.45的患者中有40%对类固醇治疗无反应 Mathurin P,Louvet A,Dharancy S.Treatment of severe forms of alcoholic hepatitis:where are we g
26、oing?J Gastroenterol Hepatol.2008;23 Suppl 1:S60-62.Lille 模型临床应用Lille 模型临床应用 预测ALD患者类固醇治疗后发生感染的风险 Lille评分是类固醇治疗后是否发生感染的独立预测因子（P=.0002)Lille评分 0.45的患者类固醇治疗后发生感染的风险显著低于Lille评分0.45的患者（P=.000001）Louvet A et al.Infection in patients with severe alcoholic hepatitis treated with steroids:early response to therapy is the key factor.Gastroenterology.009;137(2):541-548.
