Original Model For End-stage Liver Disease Research Articles

Revising model for end-stage liver disease from calendar-time cross-sections with correction for selection bias

BackgroundEurotransplant liver transplant candidates are prioritized by Model for End-stage Liver Disease (MELD), a 90-day waitlist survival risk score based on the INR, creatinine and bilirubin. Several studies revised the original MELD score, UNOS-MELD, with transplant candidate data by modelling 90-day waitlist mortality from waitlist registration, censoring patients at delisting or transplantation. This approach ignores biomarkers reported after registration, and ignores informative censoring by transplantation and delisting.MethodsWe study how MELD revision is affected by revision from calendar-time cross-sections and correction for informative censoring with inverse probability censoring weighting (IPCW). For this, we revised UNOS-MELD on patients with chronic liver cirrhosis on the Eurotransplant waitlist between 2007 and 2019 (n = 13,274) with Cox models with as endpoints 90-day survival (a) from registration and (b) from weekly drawn calendar-time cross-sections. We refer to the revised score from cross-section with IPCW as DynReMELD, and compare DynReMELD to UNOS-MELD and ReMELD, a prior revision of UNOS-MELD for Eurotransplant, in geographical validation.ResultsRevising MELD from calendar-time cross-sections leads to significantly different MELD coefficients. IPCW increases estimates of absolute 90-day waitlist mortality risks by approximately 10 percentage points. DynReMELD has improved discrimination over UNOS-MELD (delta c-index: 0.0040, p < 0.001) and ReMELD (delta c-index: 0.0015, p < 0.01), with differences comparable in magnitude to the addition of an extra biomarker to MELD (delta c-index: ± 0.0030).ConclusionCorrecting for selection bias by transplantation/delisting does not improve discrimination of revised MELD scores, but substantially increases estimated absolute 90-day mortality risks. Revision from cross-section uses waitlist data more efficiently, and improves discrimination compared to revision of MELD exclusively based on information available at listing.

The Model for End-stage Liver Disease 3.0 is not superior to the Model for End-stage Liver Disease-Na in predicting survival: A retrospective cohort study.

The Model for End-stage Liver Disease (MELD) 3.0 yields high prognostic performance for patients with end-stage liver disease (ESLD). However, its prognostic performance for patients with alcohol-related liver disease (ARLD) has limited results. The aim of this study was to perform such an evaluation among Chinese patients. Patients hospitalized with ARLD in one institution between 2015 and 2018 were retrospectively included and followed up for 12 months. The original MELD, MELD-Na, MELD 3.0, and modified Maddrey discriminant function (MDF) scores were calculated for each patient at baseline. Their prognostic performances for 1-year survival were assessed. Time-dependent receiver operating characteristic curves were constructed, and AUCs were calculated for each scoring system. Among the 576 patients included in our analysis, 209 patients had alcoholic hepatitis (AH). By the 1-year follow-up, 14.8% (84/567) of all the patients and 23.4% (49/209) of those with AH had died. Overall, patients who had died had higher MELD, MELD-Na, MELD 3.0, and MDF scores (all p < 0.001) than those who had not. The same was true in the AH subgroup (MELD: p < 0.001, MELD-Na: p < 0.001, MELD 3.0: p = 0.007, MDF: p = 0.017). The AUC of the MELD 3.0 for prediction of 1-year survival among patients with ARLD was 0.682, lower than that of the original MELD (0.728, p < 0.001) and MELD-Na (0.735, p < 0.001). Moreover, in the AH subgroup, the AUC for the prediction of 1-year survival was lower than that in the MELD-Na subgroup (0.634 vs. 0.708, p < 0.001). The MELD 3.0 was not superior to the original MELD or the MELD-Na in predicting the mortality of patients with ARLD.

Revising the MELD Score to Address Sex-Bias in Liver Transplant Prioritization for a German Cohort.

(1) Background: Prioritization of patients for liver transplantation in Germany relies on the MELD (model for end-stage liver disease) scoring system that does not consider the patient's sex. Many studies have shown that women are disadvantaged by the MELD score. Using a large patient cohort from a German liver transplant centre, we investigated options to reduce gender inequality in the patient prioritization for liver transplantation. (2) Methods: We calculated female-as-male MELD scores in our cohort by substituting the serum creatinine of a female patient with that of their male equivalent to test for the fairness of the scores. We investigated the effects of the female-as-male scores compared to the original MELD score of 1759 patients listed for liver transplantation. (3) Results: Serum creatinine sex correction (female-as-male) for MELD scores added up to 5.4 points in females, while the median changed by +1.6 points for females. We identified 72 females with an original MELD score < 20, for whom the adjusted female-as-male MELD score would be >20, thus giving them a better chance to receive a liver transplant. (4) Conclusions: Mathematical conversion of female to male creatinine concentrations identified disadvantages in liver transplantation prioritization for females and ascertained MELD 3.0 as having high potential to compensate for these inequalities.

The Effect of Model for End-Stage Liver Disease 3.0 on Disparities between Patients with and without Hepatocellular Carcinoma in Korea.

The model for end-stage liver disease (MELD) 3.0 has recently been suggested for determining liver allocation. We aimed to apply MELD 3.0 to a Korean population and to discover differences between patients with and without hepatocellular carcinoma (HCC). This study is a retrospective study of 2203 patients diagnosed with liver cirrhosis at Severance Hospital between 2016-2022. Harrell's concordance index was used to validate the ability of MELD scores to predict 90-day survival. During a mean follow-up of 12.9 months, 90-day survival was 61.9% in all patients, 50.4% in the HCC patients, and 74.8% in the non-HCC patients. Within the HCC patients, the concordance index for patients on the waitlist was 0.653 using MELD, which increased to 0.753 using MELD 3.0. Among waitlisted patients, the 90-day survival of HCC patients was worse than that of non-HCC patients with MELD scores of 31-37 only (69.7% vs. 30.0%, p=0.001). Applying MELD 3.0, the 90-day survival of HCC patients was worse than that of non-HCC patients across a wider range of MELD 3.0 scores, compared to MELD, with MELD 3.0 scores of 21-30 and 31-37 (82.0% vs. 72.5% and 72.3% vs. 24.3%, p=0.02 and p<0.001, respectively). MELD 3.0 predicted 90-day survival of the HCC patients more accurately than original MELD score; however, the disparity between HCC and non-HCC patients increased, particularly in patients with MELD scores of 21-30. Therefore, a novel exception score is needed or the current exception score system should be modified.

From Child-Pugh to MELD score and beyond: Taking a walk down memory lane

The Child-Turcotte-Pugh (CTP) and the MELD (Model for End-Stage Liver Disease) scores were designed to predict the outcome of decompressive therapy for portal hypertension. They were prospectively validated to predict mortality risk in patients with a wide spectrum of liver disease etiology and severity. Unlike the CTP score, the MELD score was derived from prospectively gathered data. Its calculation was based on serum bilirubin, serum creatinine, international normalized ratio (INR) and etiology of liver disease. Instituting a continuous disease severity score that de-emphasizes waiting time resulted in better categorization of waiting patients and enhanced transparency. The US instituted the MELD system in 2002 and soon thereafter, MELD-based liver allocation was adopted throughout the world including Latin America. The most significant impact of MELD-based policies has been the reduction of waiting-list mortality. In the years after implementation of the MELD system, several options have been proposed to improve the MELD score's accuracy. Adding serum sodium (MELD-Na) increased the accuracy of the score in predicting waiting list mortality, thus completing the original MELD score as a prognostic model in liver allocation. On the 20th anniversary of the creation of MELD score we present a brief account of its development, its use to stratify patients on the waiting list for liver transplantation as well as its adoption as liver allocation system .

Applying the original model for end-stage liver disease score rather than the model for end-stage liver disease-Na score for risk stratification prior to transjugular intrahepatic portosystemic shunt procedures.

The model for end-stage liver disease (MELD) score can be used to predict survival of patients undergoing transjugular intrahepatic portosystemic shunt procedures (TIPS). The effect of hyponatremia on survival resulted in the development of the MELD-Na score. The aim of this study is to compare the prognostic value of MELD and MELD-Na scores in predicting post-TIPS outcomes. A retrospective chart review was performed on consecutive patients with cirrhosis who underwent TIPS placement from 2012 to 2017. Indications for TIPS were either refractory ascites or variceal bleeding. Primary outcomes analyzed were death or liver transplantation. Follow-up data were censored at 1 year. Eighty-three patients underwent TIPS. There was no difference in MELD or MELD-Na score between indication groups. However, the delta MELD (MELD-Na subtracted by MELD score) was higher in those with refractory ascites. There was no difference in outcomes of death or liver transplantation between the MELD and MELD-Na at 1 year. (area under the curve 0.79 vs 0.72, respectively, P = 0.119). In patients with a MELD-Na greater than 18, higher delta MELD was protective (hazard ratio 0.74, P < 0.05). There was no prognostic difference using either score despite a higher delta MELD in those with refractory ascites. The decision to pursue TIPS should utilize the original MELD score, as the MELD-Na score alone may exclude patients with refractory ascites who may benefit from TIPS.

Role of biomarkers as predictors of acute kidney injury and mortality in decompensated cirrhosis

Evidence suggests that novel biomarkers predict acute kidney injury (AKI) development and outcome earlier than serum creatinine. The aim of this study was to determine the incidence and prognosis of AKI in decompensated cirrhotic patients, and also assess the usefulness of plasma cystatin C, urine neutrophil gelatinase associated lipocalin (NGAL), tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) in early prediction of AKI and mortality. Single-center, prospective observational study enrolling decompensated cirrhotic patients without AKI at the time of admission. Of 111 patients with decompensated cirrhosis, 45 (40.5%) developed AKI while hospitalized. Even with 53.3% being transient (stage 1), mortality was significantly higher in AKI than non-AKI patients (46.5% vs. 25%, p = 0.02). Plasma cystatin C and urine NGAL, but not urine [TIMP-2]·[IGFBP7] at the time of admission were found to be independent early predictors of AKI. Substitution of cystatin C for creatinine significantly improved the model for end-stage liver disease (MELD) score accuracy for mortality prediction. The incidence of AKI is high and is associated with high mortality in decompensated cirrhotic patients. Plasma cystatin C and urine NGAL are useful for early detection of AKI. MELD-cystatin C, rather than original MELD, improves predictive accuracy of mortality.

A New Recalibrated Four-Category Child-Pugh Score Performs Better than the Original Child-Pugh and MELD Scores in Predicting In-Hospital Mortality in Decompensated Alcoholic Cirrhotic Patients with Acute Variceal Bleeding: a Real-World Cohort Analysis.

There currently is no consensus on how to accurately predict early rebleeding and death after a major variceal bleed. This study investigated the relative predictive performances of the original Child-Pugh (CP), model for end-stage liver disease (MELD) and a four-category recalibrated Child-Pugh (rCP). This prospective study included all adult patients admitted to Groote Schuur Hospital with acute esophageal variceal bleeding secondary to alcoholic cirrhosis, between January 2000 and December 2017. CP and rCP grades and MELD score were calculated on admission, and the predictive ability in discriminating in-hospital rebleeding and death was compared by area under receiver-operating characteristic (AUROC) curves. During the study period, 403 consecutive adult patients were treated for bleeding esophageal varices of whom 225 were secondary to alcoholic cirrhosis. Twenty-four (10.6%) patients were CP grade A, 88 (39.1%) grade B and 113 (50.2%) grade C on hospital admission. MELD scores ranged from 6 to 40. Thirty-one (13.8%) patients rebleed, and 41 (18.2%) patients died. There was no difference in the discriminatory capacity of the CP (AUROC 0.59, 95% CI 0.50-0.670) and MELD (AUROC 0.62, 95% CI 0.51-0.73) to predict rebleeding (p = 0.72), or between the Child-Pugh (AUROC 0.75, 95% CI 0.71-0.81) and MELD (AUROC 0.71, 95% CI 0.62-0.80) to predict death (p = 0.35). The rCP classification (A-D) had a significantly improved discriminatory capacity (AUROC 0.83 95% CI 0.77-0.89) compared to the CP score (A-C) and MELD to predict death (p = 0.004). A recalibrated Child-Pugh score outperforms the original Child-Pugh grade and MELD score in predicting in-hospital death in patients with bleeding esophageal varices secondary to alcoholic cirrhosis.

Utility of MELD scoring system for assessing the prognosis of acute fatty liver of pregnancy

ObjectiveTo evaluate the value of Model for end-stage liver disease (MELD) in assessing the prognosis of acute fatty liver of pregnancy (AFLP). Study designThis was a retrospective study. From January 2010 to July 2018, data of 53 women diagnosed with AFLP in the third affiliated hospital of Sun Yat-Sen University were collected. Blood samples were collected on admission and MELD score was calculated. The MELD score was calculated by using the original MELD formula as shown: 9.57 log (creatinine) + 3.78 log (bilirubin) + 11.20 log (international normalized ratio, INR) + 6.43. The perinatal outcomes were documented. ResultsNine women were excluded as they were transfered to our hospital after delivery in other hospitals. The remaining 44 women had average age of 28.8 ± 5.2 years. The MELD score showed good performance in predicting most of the perinatal complications of AFLP with all the area under the receiver operating characteristic (ROC) curves (AUC) > 0.8, including ascites (AUC: 0.91, 95% CI: 0.78–0.98), wound seroma (AUC: 0.91, 95% CI: 0.78–0.93), hepatic encephalopathy (AUC: 0.93, 95% CI: 0.82–0.99), DIC (AUC: 0.87, 95% CI: 0.74–0.95), sepsis (AUC: 0.93, 95% CI: 0.82–0.99), renal insufficiency (AUC: 0.94, 95% CI: 0.82–0.99) and stillbirth (AUC: 0.85, 95% CI: 0.71–0.94). Nearly all the maternal complications were more frequently happened in MELD score ≥30 group (P < 0.05). ConclusionMELD scoring system may be a suitable method for assessing the prognosis of AFLP.

Defining a liver transplant benefit threshold for model for end stage liver disease

Background: Priority on the liver transplant (LT) waiting list is largely determined by the Model for End-stage Liver Disease (MELD) score. Prior studies have explored variation in transplant benefit – the difference between post-transplant survival versus survival on the waiting list – based on MELD. Serum sodium was recently added to the MELD score to improve survival prediction. We sought to define the MELD-Na threshold that corresponded to survival benefit for liver transplantation. Methods: Data on adult LT candidates listed 6/2013-12/2015 were identified from the UNOS registry. Patients with MELD ≥ 12 were included. Six-month survival after listing was analyzed using multivariable Cox proportional hazards regression. MELD and MELD-Na scores at listing were examined as piecewise-constant time-varying covariates for patients undergoing LT. Transplant benefit was defined as hazard ratio (HR) of death <1 with receipt of transplantation. Results: 12,243 patients with a median age of 56 years were included; 7,800 (63%) were male and 8,747 were white (71%). The most common etiology of liver disease was alcoholic cirrhosis (3,906, 32%). Using the original MELD score, 73% of patients were expected to derive benefit from transplantation with a MELD threshold of >18. Similarly, assessing the transplant benefit according to MELD-Na, 72% of patients had an expected transplant benefit with a threshold MELD-Na > 20 (Figure). Of note, transplant benefit was not consistent between MELD and MELD- Na prediction for 14% of patients. Specifically, the MELD-NA score resulted in a higher estimation of survival benefit for transplantation versus MELD alone. Conclusion: Transition from MELD to MELD-Na did not define a more precise range at which patients benefited from transplantation. The population for whom transplantation was predicted to improve survival did change, however.

Remodeling the model for end-stage liver disease for predicting mortality risk in critically ill patients with cirrhosis and acute kidney injury.

Serum creatinine measurement demonstrates a poor specificity and sensitivity for the early diagnosis of acute kidney injury (AKI) in patients with cirrhosis. The existing model for end‐stage liver disease (MELD) score reveals multiple pitfalls in critically ill patients with cirrhosis and acute kidney injury (CAKI). The aim of this study was to re‐evaluate the role of creatinine values in the existing MELD score and to develop a novel score for CAKI, named the “acute kidney injury–model for end‐stage liver disease score” (AKI‐MELD score). We extracted 651 CAKI from the Multiparameter Intelligent Monitoring in Intensive Care database. A time‐dependent Cox regression analysis was performed for developing remodeled MELD scores (Reweight‐MELD score, Del‐Cr‐MELD score, and AKI‐MELD score). The area under the receiver operating characteristic curve provided the discriminative power of scoring models related to outcome. The hazard ratio of creatinine was 1.104 (95% confidence interval [CI], 0.945‐1.290; P = 0.211). Reweight‐MELD score and Del‐Cr‐MELD score (decreasing the weight of creatinine) were superior to the original MELD score (all P < 0.001). The new AKI‐MELD score consists of bilirubin, the international normalized ratio, and the ratio of creatinine in 48 hours to creatinine at admission. It had competitive discriminative ability for predicting mortality (area under the receiver operating characteristic curve, 0.720 [95% CI, 0.653‐0.762] at 30 days, 0.688 [95% CI, 0.630‐0.742] at 90 days, and 0.671 [95% CI, 0.612‐0.725] at 1 year). Further, AKI‐MELD score had significantly higher predictive ability in comparison with MELD score, MELD‐Na score, and Updated MELD score (all P < 0.001). Conclusion: The predictive value of creatinine for CAKI should be re‐evaluated. AKI‐MELD score is a potentially reliable tool to determine the prognosis for mortality of CAKI. (Hepatology Communications 2017;1:748–756)

Mortality in hepatectomy: Model for End-Stage Liver Disease as a predictor of death using the National Surgical Quality Improvement Program database

The predictive value of the Model for End-stage Liver Disease (MELD) for mortality after hepatectomy is unclear. This study aimed to evaluate whether MELD score predicts death after hepatectomy and to identify the most useful score type for predicting mortality. We hypothesized that an increase in this score is correlated with 30-day mortality in patients undergoing hepatic resection. The American College of Surgeons National Surgical Quality Improvement Program database was queried for hepatectomy. Original MELD, United Network of Organ Sharing-modified MELD (uMELD), integrated MELD (i-MELD), and sodium-corrected MELD (MELD-Na) scores were calculated. Mortality was analyzed by multivariate logistic regression. MELD types were compared using receiver operating characteristic (ROC) curves. From 2005 to 2011, 11,933 hepatic resections were performed, including 7,519 partial, 2,104 right, and 1,210 left resections, and 1,100 trisectionectomies. The mean duration of stay was 8.4 ± 22.0 days, and there were 275 deaths (2.4%). The 30-day mortality rates were 1.8%, 6.9%, 15.4%, and 25% according to uMELD strata of 0-9, 10-19, 20-29, and ≥ 30, respectively. Multivariate analysis revealed that increasing MELD stratum was independently associated with higher mortality (P < .001) for all MELD types. The uMELD had the largest effect size (odds ratio [OR], 1.16; 95% CI, 1.10-1.20), whereas i-MELD had the narrowest CI (OR, 1.13; 95% CI, 1.10-1.17) and largest area under the ROC curve. The postoperative 30-day mortality after hepatectomy increases with increasing MELD score across all MELD types. There is a 16% increase in the odds of mortality for each point increase in uMELD.

MELD score for prediction of survival after emergent TIPS for acute variceal hemorrhage: derivation and validation in a 101-patient cohort

Background and rationale for the study. The Model for End Stage Liver Disease (MELD) score has not been derived and validated for the emergent transjugular intrahepatic portosystemic shunt (TIPS) population. We sought to identify predictive factors for survival among emergent TIPS patients, and to substantiate MELD for outcomes prognostication in this population.Results. 101 patients with acute life threatening variceal hemorrhage underwent emergent TIPS (defined by failed endoscopic therapy for active bleeding, acute hemoglobin drop, ≥ 2-unit transfusion requirement, and/or vasopressor need) at between 1998-2013. Demographic, clinical, laboratory, and procedure parameters were analyzed for correlation with mortality using Cox proportional hazards regression to derive the prognostic value of MELD constituents. Area under receiver operator characteristic (AUROC) curves was used to assess the capability of MELD prediction of mortality. TIPS were created 119 ± 167 h after initial bleeding events. Hemodynamic success was achieved in 90%. Median final portosystemic pressure gradient was 8 mmHg. Variceal rebleeding incidence was 21%. The four original MELD components showed significant correlation with mortality on multivariate Cox regression: baseline bilirubin (regression coefficient 0.366), creatinine (0.621), international normalized ratio (1.111), and liver disease etiology (0.808), validating the MELD system for emergent cases. No other significant predictive parameters were identified. MELD was an excellent predictor of 90-day mortality in the emergent TIPS population (AUROC = 0.842, 95% CI 0.755-0.928).Conclusions. Based on independent derivation of prognostic constituents and confirmation of predictive accuracy, MELD is a valid and reliable metric for risk stratification and survival projection after emergent TIPS.

A novel integrated Model for End‐Stage Liver Disease model predicts short‐term prognosis of hepatitis B virus‐related acute‐on‐chronic liver failure patients

A considerable proportion of chronic hepatitis B (CHB) or hepatitis B virus (HBV)-related cirrhotic patients develop acute-on-chronic liver failure (ACLF) with high short-term mortality. It remains difficult to accurately predict short-term prognosis in ACLF patients. The aim of the study is to develop a new prognostic model by assessing new objective variables. A total of 432 HBV-ACLF patients were recruited into a retrospective observational cohort study including one training and validation cohort. Cox proportional hazard analysis was performed in the training cohort to develop the prognostic model. The performance of the new model was tested in the validation cohort by a receiver-operator curve (ROC). During follow up, 241 deaths were reported, with a high 3-month mortality of 48.4%. On multivariate analysis, age, hepatic encephalopathy (HE) and Model for End-Stage Liver Disease (MELD) score were found to be significantly associated with 3-month mortality. The integrated MELD (iMELD) model had a higher area under the ROC than the original MELD, Sequential Organ Failure Assessment (SOFA), Chronic Liver Failure-SOFA and Child-Turcotte-Pugh score (0.853 vs 0.743 vs 0.726 vs 0.764 vs 0.592) in predicting 3-month mortality. In the validation sample of 212 patients, iMELD remained better than the other models. HBV-ACLF patients are characterized by high short-term mortality, but steady long-term survival. A modified MELD model by incorporating age and HE score has better predictive value of 3-month mortality than other conventional models.

A New Formula as a Predictive Score of Post–Liver Transplantation Outcome: Postoperative MELD-Lactate

IntroductionLiver transplantation (OLT) involves a 5% to 10% 30-day mortality rate. Multiple scores have been used as predictors of early postoperative mortality, such as the original Model for End-stage Liver Disease (MELD) and MELD sodium. Investigations have been conducted over the last 5 years to find new predictors of early post-OLT mortality. ObjectiveThe aim of this study was to develop a new mathematical model to predict the individual chance of 30-day mortality after OLT. MethodsThe study was conducted on 58 patients submitted to OLT at the University Hospital, between October 2008 and March 2012. The 29 latest survivor and 29 latest nonsurvivor cases were selected. Arterial blood sodium, lactate, international normalized ratio, total bilirubin, and creatinine values were determined 1 hour after the end of surgery. The MELD original equation, MELD sodium, and new MELD lactate were also elaborated. The results were analyzed by the Mann-Whitney and Wilcoxon tests. The level of significance was set at .05. ResultsThe new formula elaborated was as follows: MELD lactate = 5.68 × loge (lactate) + 0.64 × (Original MELD) + 2.68. The MELD lactate values were significantly higher than the MELD sodium and original MELD values (P < .05). The area under the receiver operating characteristic curve of MELD lactate in predicting the outcome of patients submitted to OLT was 0.80, as opposed to 0.71 for the original MELD and 0.72 for MELD sodium (P < .05). ConclusionThe postoperative MELD lactate score proved to be more specific and sensitive than the original MELD and MELD sodium as a predictive model of the outcome of patients submitted to OLT.

Tu1027 A New Formula As a Predictive Score of Post-Liver Transplantation Outcome: Postoperative MELD Lactate

Introduction. Liver transplantation (OLT) involves a 5% to 10% 30-day mortality rate. Multiple scores have been used as predictors of early postoperative mortality, such as the original Model for End-stage Liver Disease (MELD) and MELD sodium. Investigations have been conducted over the last 5 years to find new predictors of early post-OLT mortality. Objective. The aim of this study was to develop a new mathematical model to predict the individual chance of 30-day mortality after OLT. Methods. The study was conducted on 58 patients submitted to OLT at the University Hospital, between October 2008 and March 2012. The 29 latest survivor and 29 latest nonsurvivor cases were selected. Arterial blood sodium, lactate, international normalized ratio, total bilirubin, and creatinine values were determined 1 hour after the end of surgery. The MELD original equation, MELD sodium, and new MELD lactate were also elaborated. The results were analyzed by the Mann-Whitney and Wilcoxon tests. The level of significance was set at .05. Results. The new formula elaborated was as follows: MELD lactate ¼ 5.68 � loge (lactate) þ 0.64 � (Original MELD) þ 2.68. The MELD lactate values were significantly higher than the MELD sodium and original MELD values (P < .05). The area under the receiver operating characteristic curve of MELD lactate in predicting the outcome of patients submitted to OLT was 0.80, as opposed to 0.71 for the original MELD and 0.72 for MELD sodium (P < .05). Conclusion. The postoperative MELD lactate score proved to be more specific and sensitive than the original MELD and MELD sodium as a predictive model of the outcome of patients submitted to OLT.

Clinical applications of the Model for End-Stage Liver Disease (MELD) in hepatic medicine.

The Model for End-Stage Liver Disease (MELD) score incorporates serum bilirubin, creatinine, and the international normalized ratio (INR) into a formula that provides a continuous variable that is a very accurate predictor of 90-day mortality in patients with cirrhosis. It is currently utilized in the United States to prioritize deceased donor organ allocation for patients listed for liver transplantation. The MELD score is superior to other prognostic models in patients with end-stage liver disease, such as the Child–Turcotte–Pugh score, since it uses only objective criteria, and its implementation in 2002 led to a sharp reduction in the number of people waiting for liver transplant and reduced mortality on the waiting list without affecting posttransplant survival. Although mainly adopted for use in patients waiting for liver transplant, the MELD score has also proved to be an effective predictor of outcome in other situations, such as patients with cirrhosis going for surgery and patients with fulminant hepatic failure or alcoholic hepatitis. Several variations of the original MELD score, involving the addition of serum sodium or looking at the change in MELD over time, have been examined, and these may slightly improve its accuracy. The MELD score does have limitations in situations where the INR or creatinine may be elevated due to reasons other than liver disease, and its implementation for organ allocation purposes does not take into consideration several conditions that benefit from liver transplantation. The application of the MELD score in prioritizing patients for liver transplantation has been successful, but further studies and legislation are required to ensure a fair and equitable system.

Is an estimated glomerular filtration rate better than creatinine to be incorporated into the end-stage liver disease score?

To incorporate estimated glomerular filtration rate (eGFR) into the model for end-stage liver disease (MELD) score to evaluate the predictive value. From January 2004 to October 2008, the records of 4127 admitted cirrhotic patients were reviewed. Patients who survived and were followed up as outpatients were defined as survivors and their most recent available laboratory data were collected. Patients whose records indicated death at any time during the hospital stay were defined as non-survivors (in-hospital mortality). Patients with incomplete data or with cirrhosis due to a congenital abnormality such as primary biliary cirrhosis were excluded; thus, a total of 3857 patients were enrolled in the present study. The eGFR, which was calculated by using either the modification of diet in renal disease (MDRD) equation or the chronic kidney disease epidemiology collaboration (CKD-EPI) equation, was incorporated into the MELD score after adjustment with the original MELD equation by logistic regression analysis [bilirubin and international normalized ratio (INR) were set at 1.0 for values less than 1.0]. Patients defined as survivors were significantly younger, had a lower incidence of hepatoma, lower Child-Pugh and MELD scores, and better renal function. The underlying causes of cirrhosis were very different from those in Western countries. In Taiwan, most cirrhotic patients were associated with the hepatitis virus, especially hepatitis B. There were 16 parameters included in univariate logistic regression analysis to predict in-hospital mortality and those with significant predicting values were included in further multivariate analysis. Both 4-variable MDRD eGFR and 6-variable MDRD eGFR, rather than creatinine, were significant predictors of in-hospital mortality. Three new equations were constructed (MELD-MDRD-4, MELD-MDRD-6, MELD-CKD-EPI). As expected, original MELD score was a significant predictor of in-hospital mortality (odds ratio = 1.25, P < 0.001). MELD-MDRD-4 excluded serum creatinine, with the coefficients refit among the remaining 3 variables, i.e., total bilirubin, INR and 4-variable MDRD eGFR. This model represented an exacerbated outcome over MELD score, as suggested by a decrease in chi-square (2161.45 vs 2198.32) and an increase in -2 log (likelihood) (2810.77 vs 2773.90). MELD-MDRD-6 included 6-variable MDRD eGFR as one of the variables and showed an improvement over MELD score, as suggested by an increase in chi-square (2293.82 vs 2198.32) and a decrease in -2 log (likelihood) (2810.77 vs 2664.79). Finally, when serum creatinine was replaced by CKD-EPI eGFR, it showed a slight improvement compared to the original MELD score (chi-square: 2199.16, -2 log (likelihood): 2773.07). In the receiver-operating characteristic curve, the MELD-MDRD-6 score showed a marginal improvement in area under the curve (0.909 vs 0.902), sensitivity (0.854 vs 0.819) and specificity (0.818 vs 0.839) compared to the original MELD equation. In patients with a different eGFR, the MELD-MDRD-6 equation showed a better predictive value in patients with eGFR ≥ 90, 60-89, 30-59 and 15-29. Incorporating eGFR obtained by the 6-variable MDRD equation into the MELD score showed an equal predictive performance in in-hospital mortality compared to a creatinine-based MELD score.

Prioritization for liver transplantation

There are three possible policies for prioritization for liver transplantation: medical urgency, utility and transplant benefit. The first is based on the severity of cirrhosis, using Child-Turcotte-Pugh score and, more recently, the Model for End-stage Liver Disease (MELD) score, or variants of MELD, for allocation. Although prospectively developed and validated, the MELD score has several limitations, including interlaboratory variations for measurement of serum creatinine and international normalized ratio of prothrombin time, and a systematic adverse female gender bias. Adjustments to the original MELD equation and new scoring systems have been proposed to overcome these limitations; incorporation of serum sodium improves its predictive accuracy. The MELD score poorly predicts outcomes after liver transplantation due to the absence of donor factors incorporated into the scoring system. Several utility models are based on donor and recipient characteristics. Combined poor recipient and donor characteristics lead to very poor outcomes, which in a utility system would be considered unacceptable. Finally, transplant benefit models rank patients according to the net survival benefit that they would derive from transplantation. However, complex statistical models are required, and unmeasured characteristics may unduly affect the models. Well-designed prospective studies and simulation models are necessary to establish the optimal allocation system in liver transplantation.

An integrated MELD model including serum sodium and age improves the prediction of early mortality in patients with cirrhosis

The Model for End-Stage Liver Disease (MELD) is widely used to predict the short-term mortality in patients with cirrhosis, but potential limitations of this score have been reported. The aim of this study was to improve the score's prognostic accuracy by assessing new objective variables. Data of 310 consecutive patients with cirrhosis who underwent elective transjugular intrahepatic portosystemic shunt placement between July 1995 and March 2005 were analyzed retrospectively. Bivariate and multivariate analyses were performed by proportional hazard Cox regression models. The area under the receiver operating characteristic curve (auROC) and the likelihood ratio test were used to evaluate the performance of the models for predicting early mortality. Findings were validated in a cohort of 451 consecutive patients with cirrhosis on waiting list for liver transplantation. Bivariate analyses showed that the following variables correlated with time to death: age, serum bilirubin, serum creatinine, international normalized ratio of prothrombin time, serum albumin, serum sodium, and MELD. Multivariate analysis revealed that MELD, serum sodium, and age were independently associated with the risk of death. The integrated MELD model (iMELD, incorporating serum sodium and age) was better than original MELD in predicting 12-month mortality: auROC increased by 13.4% and the likelihood ratio statistic from 23.5 to 48.2. The improved accuracy of iMELD was confirmed in the validation sample of 451 patients with cirrhosis on the waiting list for liver transplantation by increasing auROC (+8%) and likelihood ratio statistic (from 41.4 to 82.0). This study shows that in patients with cirrhosis, serum sodium and age are predictors of mortality independent of the MELD score. The incorporation of these variables into the original MELD formula improves the predictive accuracy of time to death.