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1、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,MELD,(Model for End-stage Liver Disease)(终末期肝病模型),MELD = 9.57 log e(creatine mg/dl) + 3.78 log e（积分）
2、(bilirubin mg/dl) +11.20 log e (INR) + 6.4 3 (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: http:/www.mayo.edu/int-med/gi/model/mayomodl-5-unos.htm to calculate MELD score directly,Liver Transpl,2003.9:19-20,Kiran M.Banbha,Curr opi org transp 2008,13:227-23
3、3,RELATIONSHIP BETWEEN MELD AND 3-MONTH MORTALITY IN HOSPITALIZED CIRRHOTIC PATIENTS,Adapted from Wiesner RH, McDiarmid SV, Kamath PS, et al :MELD and PELD: application of survival models to liver allocation. Liver Transpl 2001;7:567-580,2002年2月27日：美国器官共享网/全美器官获取和移植网(Organ Procurement and Transplant
4、ation Network, OPTN)确定MELD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 survival (%) survival (%) survival (%),Perioperative Mortality and long-term survival after Hepatic Resection for HCC,Journal Of Gastrointestinal Surgery 2005 Dec; Vol.
5、 9 (9), pp. 1207-15,The perioperative mortality for patients with MELD score 9 was significantly greater than that for patients with MELD score 8 (0.01).,The long-term survival for patients with MELD score 9 was significantly shorter than that for patients with MELD score 8 (0.01). .,37 0 (0),45 13
6、(29),8 89 63 51,9 46 34 23,Outcome post-transplant dependent on MELD between listing and transplant,MELD +1 MELD +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 0.0001,94.9 84.7
7、0.0001,91.9 77.8 0.0001,88.1 72.1 0.0001,88.1 72.1 0.0001,Change in MELD score whilst on the transplant waiting list has a significant effect on survival post-transplant,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,Four clinical stages of cirrhosis,s
8、tage 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 remaining in
9、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; 43:167176.,HVPG,patients with an HVPG 10mmHg had a 90% probability of not developing clinical
10、 decompensation during a 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(SNa),MELD-ASMELD-Nai
11、MELD,MELD-AS,MELD-AS = MELD + 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 =0,HEPATOLOGY. 2004 Oct; 40:802- 810,MELD-AS,CTP MELD MELD-ASALL MELDMELD21,0.789 0.83 0.874,0.696 0.687 0.790,0.586 0.773 0.758,Predictor
12、s of 180-day Cirrhotic Patient Mortality,MELD-AS may improve predictive accuracy,especially at lower MELD scores,Association 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 130mm
13、ol/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 +1.0 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 probabili
14、ty of receiving a liver transplant and averting death,W.Ray Kim et al.N Eng J Med 2008;359:1018-26,W.Ray Kim et al.N Eng J Med 2008;359:1018-26,the 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 registrat
15、ion on the waiting list might have been prevented,Prevalence of Ascites, Severity 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 0.001Clin
16、ical ascites 66 (41%) 34 (100%) 0.001Total bilirbin (mg/dL) 5.3 5.9 11.1 9.1 0.001INR 1.5 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 s
17、erum sodium 130 mEq/L,Liver Transplantation,Vol 11,No3 ,2005: pp336-343,iMELD,iMELD score=MELD + (0.3年龄) - (0.7血清钠) + 100,Liver Transpl 2007 Aug; Vol. 13 (8), pp. 1174-80,iMELD,Mortality in 451 patients with cirrhosis listed for liver transplantation.,iMELD MELD3-month6-month12-month,0.76,0.70,0.79,
18、0.71,0.78,0.69,iMELD improves the predictive accuracy of time to death,Liver Transpl 2007 Aug; Vol. 13 (8), pp. 1174-80,ESTIMATING PROGNOSIS IN PATIENTS WITH PRIMARY 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 year
19、s) + 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. Other models have emphasized variceal bleeding as an important additional clinical prognosticator.PROGNOSTIC INDEX FOR S
20、URVIVAL 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-responsive 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），D
21、F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AHPhillips M et al. Antioxidants versus corticosteroids in the treatment of severe alcoholic hepatitis a randomized clinical trial. J Hepatol, 2006; 44:784-790.,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
22、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) treated by prednisolone. Hepatology, 2003; 88:1363-1369.,Lille 模型,Lille模型于2007年由法国CHRU Lille
23、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7天后所测得的胆红素水平可以利用http:/ 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,http:/计算页面,拓展
24、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 going?J Gastroenterol Hepatol. 2008;23 Suppl 1:S60-62.,Lill
25、e 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.,谢 谢,
