Evolution of liver transplant organ allocation policy: Current limitations and future directions

Since the adoption of the model for end-stage liver disease(MELD) score for organ allocation in 2002, numerous changes to the system of liver allocation and distribution have been made with the goal of decreasing waitlist mortality and minimizing geographic variability in median MELD score at time of transplant without worsening post-transplant outcomes. These changes include the creation and adoption of the MELD-Na score for allocation, Regional Share 15, Regional Share for Status 1, Regional Share 35/National Share 15, and, most recently, the Acuity Circles Distribution Model. However, geographic differences in median MELD at time of transplant remain as well as limits to the MELD score for allocation, as etiology of liver disease and need for transplant changes. Acute-onchronic liver failure(ACLF) is a subset of liver failure where prevalence is rising and has been shown to have an increased mortality rate and need for transplantation that is under-demonstrated by the MELD score. This underscores the limitations of the MELD score and raises the question of whether MELD is the most accurate, objective allocation system. Alternatives to the MELD score have been proposed and studied, however MELD score remains as the current system used for allocation. This review highlights policy changes since the adoption of the MELD score, addresses limitations of the MELD score, reviews proposed alternatives to MELD, and examines the specific implications of these changes and alternatives for ACLF.     

Scoring systems predict the prognosis of acute-on-chronic hepatitis B liver failure: an evidence-based review

Acute-on-chronic hepatitis B liver failure is a devastating condition that is associated with mortality rates of over 50% and is consequent to acute exacerbation of chronic hepatitis B in patients with previously diagnosed or undiagnosed chronic liver disease. Liver transplantation is the definitive treatment to lower mortality rate, but there is a great imbalance between donation and potential recipients. An early and accurate prognostic system based on the integration of laboratory indicators, clinical events and some mathematic logistic equations is needed to optimize treatment for patients. As parts of the scoring systems, the MELD was the most common and the donor-MELD was the most innovative for patients on the waiting list for liver transplantation. This review aims to highlight the various features and prognostic capabilities of these scoring systems.     

Relationship between model for end-stage liver disease score and left ventricular function in patients with end-stage liver disease

BACKGROUND:Decreased cardiac contractility has been observed in cirrhosis,suggesting a latent cardiomyopathy in these patients.This study was designed to evaluate left ventricular structure and function in patients with end-stage liver disease by the model for end-stage liver disease(MELD) scoring system. METHODS:We recruited 82 patients(72 male,10 female; mean age 50.3±8.9 years)with end-stage liver disease who underwent orthotopic liver transplantation between January 2002 and May 2008.Seventy-eight patie...     

多种肝功能评分系统预测血浆置换治疗肝衰竭患者预后的价值探讨

目的：探讨终末期肝病模型（MELD）和MELD-Na评分系统及Child-Pugh分级系统对血浆置换治疗的肝衰竭患者预后的价值。方法回顾性分析我院2005年1月至2012年9月收治的238例乙型肝炎肝衰竭患者的临床资料,应用MELD、MELD-Na和Child-Pugh评分系统判断患者在观察3个月期内的预后情况。结果在3个月的观察期内,本组患者生存145例,死亡93例（39.1%）;生存患者入院时凝血酶原时间、INR、血清总胆红素、血清钠和肌酐水平分别为（19.6±3.7）秒、（1.6±2.2）、（199.8±50.6）μmol/L、（137.6±7.7） mmol/L和（127.3±10.8）μmol/L,与死亡患者比[分别为（25.3±5.8）秒、（2.3±1.5）、（332.7±120.9）μmol/L、（127.0±14.6） mmol/L和（210.7±75.3）μmol/L],均有显著性统计学差异（P〈0.01）;生存患者MELD、MELD-Na和Child-Pugh计分分别为（19.3±6.9）、（21.1±4.6）和（11.4±2.3）,均显著低于死亡患者[分别为（29.2±13.4）、（32.4±5.7）和（15.2±6.7）,P〈0.05];MELD-Na和MELD评分系统在预测肝衰竭近期病死率方面优于Child-Pugh分级计分。结论MELD、MELD-Na评分系统和Child-Pugh分级系统对于肝衰竭患者的病情判断均有较好的价值,但MELD和MELD-Na评分系统对肝衰竭预后判断的价值更高。     

239例肝硬化失代偿期患者的短期预后评估

目的评价终末期肝病模型（MELD）、MELD-Na、Child—Turcotte—Pugh（CTP）和包含血肌酐值的CTP（CrCTP）评分对肝硬化患者短期预后的评估意义。方法回顾性收集自2005年1月-2007年12月我院收治的239例肝硬化失代偿期患者的病例资料,分别应用CTP、CrCTP、MELD和MELD—Na模型进行评分,并了解其3个月内的病死率。以受试者工作特征曲线（ROC）下面积（AUC）衡量各评分系统预测肝硬化失代偿期患者短期预后的能力,并运用Z检验比较各系统的预测能力。结果30例患者在3个月内死亡。死亡组患者的CTP、CrCTP、MELD和MELD—Na分值（分别为11．47±2．46、12,47±2．05、19．70±6．71、27．97±10．79）与生存组（分别为8．73±2．03、8．95±2．13、10．92±4．74、14．48±6．55）相比差异有统计学意义（P〈0．001）。CTP、CrCTP、MELD和MELD-Na评分对肝硬化失代偿期患者3个月预后评估的ROC曲线下面积分别为0．799、0．822、0．873、0．870。结论CTP、CrCTP、MELD和MELD-Na模型均可有效预测我国肝硬化失代偿期患者的短期预后;MELD评分在判断肝硬化失代偿期患者的短期预后方面优于CTP;在CTP中引入血肌酐值即CrCTP评分可以提高对肝硬化失代偿患者短期预后的判断准确性;MELD-Na模型未显示比MELD更佳的预测能力。     

Prognostic models for acute liver failure

BACKGROUND:Acute liver failure (ALF) remains a dramatic and unpredictable disease with high morbidity and mortality. Early and accurate prognostic assessment of patients with ALF is critically important for optimum clinical pathway. DATA SOURCES:Five English-language medical databases,MEDLINE,ScienceDirect,OVID,Springer Link and Wiley Interscience were searched for articles on acute liver failure, prognosis,and related topics. RESULTS:Multi-variable prognostic models including the King's College Hospital cr...     

Child-Pugh-Turcott versus Meld score for predicting survival in a retrospective cohort of black African cirrhotic patients

AIM： To compare the performance of the Child-Pugh- Turcott （CPT） score to that of the model for end-stage liver disease （MELD） score in predicting survival of a retrospective cohort of 172 Black African patients with cirrhosis on a short and mid-term basis.
METHODS： Univariate and multivariate （Cox model） analyses were used to identify factors related to mortality. Relationship between the two scores was appreciated by calculating the correlation coefficient. The Kaplan Meier method and the log rank test were used to elaborate and compare survival respectively. The Areas Under the Curves were used to compare the performance between scores at 3, 6 and 12 mo.
RESULTS： The study population comprised 172 patients, of which 68.9% were male. The mean age of the patient was 47.5 ± 13 years. Hepatitis B virus infection was the cause of cirrhosis in 70% of the cases. The overall mortality was 31.4% over 11 years of follow up. Independent factors significantly associated with mortality were： CPT score （HR = 3.3, 95% CI [1.7-6.2]） （P 〈 0.001） （stage C vs stage A-B）; Serum creatine （HR = 2.5, 95% CI [1.4-4.3]） （P = 0.001） （Serum creatine 〉 1.5 mg/dL versus serum creatine 〈 1.5 mg/dL）; MELD score （HR = 2.9, 95% CI [1.63-5.21]） （P 〈 0.001） （MELD 〉 21 vs MELD 〈 21）. The area under the curves （AUC） that predict survival was 0.72 and 0.75 at 3 mo （P = 0.68）, 0.64 and 0.62 at 6 mo （P = 0.67）, 0.69 and 0.64 at 12 mo （P = 0.38） respectively for the CPT score and the MELD score.
CONCLUSION： The CPT score displays the same prognostic significance as does the MELD score in black African patients with cirrhosis. Moreover, its handling appears less cumbersome in clinical practice as compared to the latter.     

Applicability of MELD as a short-term prognostic indicator in patients with chronic liver disease: an Indian experience

Background: The model for end‐stage liver disease (MELD), which employs objective variables, statistical weighting and a continuous scale, has replaced the Child–Turcotte–Pugh (CTP) classification as the scoring system of choice in several liver transplant centers. However, the predictive ability of MELD has never been prospectively evaluated in India. The aim of this study was to examine the MELD score, the CTP score and the recently proposed modified CTP score in Indian patients with liver cirrhosis to determine their correlation and compare their prognostic significance for short‐term survival. Methods: A total of 76 patients with cirrhosis (mean age 46.97 years) were prospectively evaluated and followed up for 6 months. MELD score, CTP score and modified CTP score were calculated at baseline. The correlation between variables was evaluated by Pearson's correlation test. Receiver‐operating characteristic (ROC) curves were used to determine the cutoff values for each score with the best sensitivity and specificity in discriminating between patients who survived and those who died. Results: Alcoholic liver disease was the most common (50%) etiology of cirrhosis. MELD score and CTP score showed very good correlation (Pearson correlation r = 0.983). ROC curve showed area under curve (c‐statistics) for MELD score, CTP score and modified CTP score as 0.764, 0.804 and 0.817, respectively. Conclusion: The MELD score was not found to be superior to CTP score and modified CTP score for short‐term prognostication of patients with cirrhosis in this study.     

终末期肝病模型联合总胆汁酸对亚急性肝衰竭患者预后的评估

目的探讨终末期肝病模型（MELD）联合血清总胆汁酸（TBA）的检测对于判断亚急性肝衰竭患者预后的意义。方法亚急性肝衰竭患者110例,测定血清肌酐（CR）,TBil,凝血酶原时间国际标准化比值（INR）,TBA,根据公式计算MELD值,单一评估MELD,TBA及二者联合对亚急性肝衰竭患者预后的判断价值。结果恶化死亡组的MELD值及TBA均明显高于好转治愈组（P〈0.05）,MELD值、TBA值各组间病死率的比较具有统计学意义（P〈0.01）。将MELD值≥30,TBA值≥200联合判断患者病死率的敏感性和特异性分别为67.65%,97.37%,MELD值与TBA值呈正相关（r=0.9903,P〈0.01）。结论 MELD分值联合TBA可以提高亚急性肝衰竭患者预后判断的准确性     

Prediction of the prognosis of patients with acute-on-chronic hepatitis B liver failure using the model for end-stage liver disease scoring system and a novel logistic regression model

Summary. The objective of this study was to determine the predictive value of the model for end‐stage liver disease (MELD) scoring system in patients with acute‐on‐chronic hepatitis B liver failure (ACLF‐HBV), and to establish a new model for predicting the prognosis of ACLF‐HBV. A total of 204 adult patients with ACLF‐HBV were retrospectively recruited between July 1, 2002 and December 31, 2004. The MELD scores were calculated according to the widely accepted formula. The 3‐month mortality was calculated. The validity of the MELD model was determined by means of the concordance (c) statistic. Clinical data and biochemical values were included in the multivariate logistic regression analysis based on which the regression model for predicting prognosis was established. The receiver‐operating characteristic curves were drawn for the MELD scoring system and the new regression model and the areas under the curves (AUC) were compared by the z‐test. The 3‐month mortality rate was 57.8%. The mean MELD score for the patients who died was significantly greater than those who survived beyond 3 months (28.7 vs 22.4, P = 0.003). The concordance (c) statistic (equivalent to the AUC) for the MELD scoring system predicting 3‐month mortality was 0.709 (SE = 0.036, P < 0.001, 95% confidence interval 0.638–0.780). The independent factors predicting prognosis were hepatorenal syndrome (P < 0.001), liver cirrhosis (P = 0.009), HBeAg (P = 0.013), albumin (P = 0.028) and prothrombin activity (P = 0.011) as identified in multivariate logistic regression analysis. The regression model that was constructed by the logistic regression analysis produced a greater prognostic value (c = 0.891) than the MELD scoring system (z = 4.333, P < 0.001). The MELD scoring system is a promising and useful predictor for 3‐month mortality of ACLF‐HBV patients. Hepatorenal syndrome, liver cirrhosis, HBeAg, albumin and prothrombin activity are independent factors affecting the 3‐month mortality. The newly established logistic regression model appears to be superior to the MELD scoring system in predicting 3‐month mortality in patients with ACLF‐HBV.     

Preliminary clinical experience in liver retransplantation

BACKGROUND: The past several decades have witnessed increasingly successful rates of liver transplantation. However, retransplantation remains the only choice for patients with irreversible graft failure after primary transplantation. This article aimed to summarize our clinical experience in liver retransplantation. METHODS: From June 2002 to December 2005, a total of 185 cases of liver transplantation including 8 cases of retransplantation were performed in our hospital. The clinical data were analyzed retrospectively. RESULTS: The rate of liver retransplantation was 4.32%. Retransplantation was indicated for the following reasons: biliary complication (3 cases), chronic rejection (2), hepatic artery thrombosis (1), uncontrollable acute rejection (1) and hepatitis B recurrence (1). The mean model of end-stage liver disease (MELD) scores before primary transplantation and retransplantation were 15.6 and 23.9, respectively (P<0.05). The MELD score reflected the severity of liver disease more precisely than the Child classification. The mean interval between the first and second transplantation was 316 days (78-725 days). The first three patients, with mean interval of 101 days, died of severe infection combined with multiple organ failure after retransplantation. The patients who underwent retransplantation more than six months after the first transplant had better outcomes. The one-year survival rate for retransplantation in our group was 62.5%. CONCLUSIONS: Liver retransplantation is the only means of saving the patient with hepatic allograft failure. Understanding of the indications for retransplantation,careful selection of operation timing, excellent surgical skills and meticulous postoperative management all contribute to the success of each case of retransplantation.     

中性粒细胞与淋巴细胞比值联合序贯器官功能衰竭评分对老年脓毒症患者预后的预测作用

目的探讨中性粒细胞与淋巴细胞比值(NLR)联合序贯器官功能衰竭评分(SOFA)对老年脓毒症患者预后的预测作用。方法回顾性分析解放军第305医院2017年1月至2019年8月收治的124例老年脓毒症患者的临床资料,根据预后情况,分为存活组(58例)和死亡组(66例)。比较2组患者性别、年龄、基础病、原发疾病及NLR、SOFA评分,多因素logistic回归分析影响患者预后的危险因素,绘制受试者工作特征(ROC)曲线,分析危险因素对老年脓毒症患者预后的预测作用。结果2组患者性别组成、年龄、基础病及原发疾病差异无统计学意义,但存活组NLR及SOFA评分明显低于死亡组(P<0.001),且NLR及SOFA评分均为老年脓毒症患者预后的独立危险因素(NLR:OR=1.163,95%CI 1.090~1.241,P<0.001;SOFA评分:OR=1.406,95%CI 1.199~1.649,P<0.001)。NLR预测老年脓毒症患者预后的ROC曲线下面积(AUC)为0.918(95%CI 0.872~0.964,P<0.001),最佳截断值30.68(灵敏度86.2%,特异度81.8%);SOFA预测效能的AUC为0.844(95%CI 0.771~0.916,P<0.001),最佳截断值12.5(灵敏度81.0%,特异度80.3%)。当两者联合预测时,AUC为0.964(P<0.001),优于任何一项指标单独预测的效果。结论NLR和SOFA评分是预测老年脓毒症患者死亡的独立危险因素,尤其两者联合预测死亡风险时,可明显提高对老年脓毒症预后判断的准确性,为临床工作提供一定指导。     

终末期肝病模型对失代偿期肝硬化患者预后的回顾性分析

目的:应用受试者运行曲线(ROC)比较终末期肝病模型(MELD)及Child-Pugh分级(CTP)对失代偿期肝硬化患者短期生存率的预测能力.方法:对171例住院的失代偿期肝硬化患者进行回顾性分析,按MELD模型及Child-Pugh分级评分.根据MELD分值分为4组(MELD≤9,10≤MELD≤19,20≤MELD≤29,MELD≥30),Child-Pugh分级分成A级、B级及C级3组,计算各组患者1 mo及3 mo的死亡率;应用ROC曲线评价每一预测模型对于失代偿期肝硬化患者短期生存率的预测结果.结果:MELD≤9,10≤MELD≤19,20≤MELD≤29,MELD≥30患者1 mo的死亡率分别为10.6%,23.9%,68.0%及75.0%,3 mo的死亡率分别为10.6%,28.4%,80.0%及84.4%;Child- Pugh A级,B级及C级1 mo的死亡率分别为9.7%,21.1%及44.9%,3 mo死亡率分别为9.7%,23.9%及52.2%;MELD分值能够预测失代偿期肝硬化患者短期生存率(ROC曲线下面积1 mo及3 mo分别为0.832和0.844),优于Child-Pugh分级(ROC曲线下面积1 mo及3 mo分别为0.768和0.772).结论:MELD模型及Child-Pugh分级能够预测失代偿期肝硬化患者短期生存率,而且MELD模型的预测能力优于Child-Pugh分级.     

Multicenter study of plasma diafiltration in patients with acute liver failure

Plasma diafiltration (PDF) is a blood purification therapy in which simple plasma exchange (PE) is performed using a selective membrane plasma separator while the dialysate flows outside the hollow fibers. A prospective, multicenter study was undertaken to evaluate the changes in bilirubin, IL-18, and cystatin C, as well as the 28-day and 90-day survival rates, with the use of PDF according to the level of severity as measured by the Model for End-Stage Liver Disease (MELD) score. Twenty-one patients with liver failure were studied: 10 patients had fulminant hepatitis and PDF therapies were performed 28 times; 11 had acute liver failure with the therapy performed 96 times. Levels of total bilirubin, IL-18, and cystatin C decreased significantly after treatment. The 28-day survival rate was 70.0% and that at 90 days was 16.7%. According to the severity of the MELD score, each of the results compared well with the use of Molecular Adsorbent Recirculating System or Prometheus therapy. In conclusion, PDF appears to be one of the most useful blood purification therapies for use in cases of acute liver failure in terms of medical economics and the removal of water-soluble and albumin-bound toxins.     

Major adverse events, pretransplant assessment and outcome prediction

Liver cirrhosis and portal hypertension pose enormous loss of lives and resources throughout the world, especially in endemic areas of chronic viral hepatitis. Although the pathophysiology of cirrhosis is not completely understood, the accumulating evidence has paved the way for better control of the complications, including gastroesophageal variceal bleeding, hepatic encephalopathy, ascites, hepatorenal syndrome, hepatopulmonary syndrome and portopulmonary hypertension. Modern pharmacological and interventional therapies have been designed to treat these complications. However, liver transplantation (LT) is the only definite treatment for patients with preterminal end-stage liver disease. To pursue successful LT, the meticulous evaluation of potential recipients and donors is pivotal, especially for living donor transplantation. The critical shortage of cadaveric donor livers is another concern. In many Asian countries, cultural and religious concerns further limit the number of the donors, which lags far behind that of the recipients. The model for end-stage liver disease (MELD) scoring system has recently become the prevailing criterion for organ allocation. Initial results showed clear benefits of moving from the Child–Turcotte–Pugh-based system toward the MELD-based organ allocation system. In addition to the MELD, serum sodium is another important prognostic predictor in patients with advanced cirrhosis. The incorporation of serum sodium into the MELD could enhance the performance of the MELD and could become an indispensable strategy in refining the priority for LT. However, the feasibility of the MELD in combination with sodium in predicting the outcome for patients on transplant waiting list awaits actual outcome data before this becomes standard practice in the Asia–Pacific region.     

Evidence-based incorporation of serum sodium concentration into MELD

BACKGROUND & AIMS: Serum sodium (Na) concentrations have been suggested as a useful predictor of mortality in patients with end-stage liver disease awaiting liver transplantation. METHODS: We evaluated methods to incorporate Na into model for end-stage liver disease (MELD), using a prospective, multicenter database specifically created for validation and refinement of MELD. Adult, primary liver transplant candidates with end-stage liver disease were enrolled. RESULTS: Complete data were available in 753 patients, in whom the median MELD score was 10.8 and sodium was 137 mEq/L. Low Na (<130 mEq/L) was present in 8% of patients, of whom 90% had ascites. During the study period, 67 patients (9%) died, 243 (32%) underwent transplantation, 73 (10%) were withdrawn, and 370 were still waiting. MELD score and Na, at listing, were significant (both, P < .01) predictors of death within 6 months. After adjustment for MELD score and center, there was a linear increase in the risk of death as Na decreased between 135 and 120 mEq/L. A new score to incorporate Na into MELD was developed: "MELD-Na" = MELD + 1.59 (135 - Na) with maximum and minimum Na of 135 and 120 mEq/L, respectively. In this cohort, "MELD-Na" scores of 20, 30, and 40 were associated with 6%, 16%, and 37% of risk of death within 6 months of listing, respectively. If this new score were used to allocate grafts, it would affect 27% of the transplant recipients. CONCLUSIONS: We demonstrate an evidence-based method to incorporate Na into MELD, which provides more accurate survival prediction than MELD alone.     

Model for end-stage liver disease combined with serum prealbumin to predict the prognosis of patients with decompensated liver cirrhosis

OBJECTIVE: To evaluate the prognostic value of model for end-stage liver disease (MELD) combined with serum prealbumin (PA) in patients with decompensated liver cirrhosis. METHODS: A total of 252 patients were enrolled in the study and followed 1 year. PA was measured and MELD score was calculated on the first day of admission. Analysis of variance (anova ) was used to assess correlation between PA level and MELD score. Multivariable Cox proportional hazards model was used to screen the prognosis related factors. Kaplan–Meier survival curves were drawn. RESULTS: Of the 252 patients, 28 died within 3 months, 58 within 6 months and 91 within 1 year. Serum PA level in dead patients was significantly lower than that in survival patients (P < 0.005) and decreasing with increasing of MELD score. Cox analysis showed that MELD score > 18 (RR = 2.749) and PA < 70 mg/L (RR = 2.412) were independent prognosis risk factors. The risk ratio of MELD score combined with PA level (1.854, P < 0.01) was higher than that of MELD score alone (1.054, P < 0.05). Kaplan–Meier survival curve analysis showed that MELD score ≤ 18 combined with PA ≥ 70 mg/L could clearly discriminate patients who would survive or die within 6 month and 1 year follow up. CONCLUSION: MELD score ≤ 18 combined with PA ≥ 70 mg/L could predict the 6-month and 1-year prognosis of patients with decompensated liver cirrhosis, and was superior to that of MELD score alone.     

终末期肝病模型对肝硬化患者预后评估价值的研究进展

客观、准确地判断肝硬化患者的病情及预后有助于指导临床医生选择正确的治疗方案。终末期肝病模型（MELD）是目前被广泛认可的评估终末期肝病严重程度的评分体系。近年来各种基于MELD评分发展而来的新评分系统不断涌现。加入新的变量例如血清钠可进一步提高MELD的预测能力,此文就MELD的研究现状作一综述。