终末期肝病的肝功能评估

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,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,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,Child-Turcotte-Pugh,肝功能分级,指标,评分标准,1,2,3,腹水,无,少量,中等量以上或难治性腹水,血清胆红素,(umol/L),51,血清白蛋白,(g/l),35,2835,28,凝血酶原时间,(,较正常延长秒数,),or(INR)*,13,（正常值范围内）,1.7,46,（延长,6,（延长,2,秒）,2.3,肝性脑病,无,1-2,级,3-4,级,*INR, international normalised ratio.,估 计 生 存 率,(%),总积分,分组,一年,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:,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 2008,13:227-233,RELATIONSHIP BETWEEN,MELD,AND,3-MONTH,MORTALITY IN HOSPITALIZED,CIRRHOTIC PATIENTS,MELD,MORTALITY (%; NUMBER/TOTAL),9,4 (6/148),10-19,27 (28/103),20-29,76 (16/21),30-39,83 (5/6),40,100 (4/4),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 Transplantation 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-Year,MELD,score,survival (%) survival (%) survival (%),Perioperative Mortality and,long-term survival,after,Hepatic Resection,for HCC,Journal Of Gastrointestinal Surgery 2005 Dec; Vol. 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 ( +1 P-value,90 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 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,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 remaining 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; 43:167176,.,HVPG,patients with an,HVPG,10mmHg had a 90% probability,of not developing clinical 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-AS,MELD-Na,iMELD,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-AS,ALL MELD,MELD21,0.789 0.83 0.874,0.696 0.687 0.790,0.586 0.773 0.758,Predictors 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,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) .,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 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 registration 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) p,Serum sodium (mEq/L),138,3 127,4 0.001,Clinical ascites,66 (41%) 34 (100%) 0.001,Total bilirbin (mg/dL),5.3,5.9 11.1,9.1 0.001,INR,1.5,0.5 1.9,1.1 0.001,MELD score,15.4,5.2 21.1,7.9 0.001,Serum creatinine (mg/dL),0.8,0.3 0.8,0.4 0.28,Elevated serum creatinine,5 (3%) 3 (9%) 0.14,3-month mortality,7 (4%) 12 (35%) 0.001,Hyponatremia was defined as serum 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,MELD,3-month,6-month,12-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. 1174-80,ESTIMATING PROGNOSIS IN PATIENTS WITH,PRIMARY BILIARY CIRRHOSIS,(,PBC,),MAYO PBC RISK SCORE,R = 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. Other models have emphasized variceal bleeding as an important additional clinical prognosticator.,PROGNOSTIC INDEX FOR SURVIVAL AFTER LIVER TRANSPLANTATION IN PATIENTS WITH PBC,PI,= 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,（,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,AH,Phillips 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：,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,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,医院肝病科联合其他四个中心首次提出,计算公式：,Lille,积分,= 3.19,0.101 *,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, 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.,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,.,谢 谢,