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1.  APACHE IV Is Superior to MELD Scoring System in Predicting Prognosis in Patients after Orthotopic Liver Transplantation 
This study aims to compare the efficiency of APACHE IV with that of MELD scoring system for prediction of the risk of mortality risk after orthotopic liver transplantation (OLT). A retrospective cohort study was performed based on a total of 195 patients admitted to the ICU after orthotopic liver transplantation (OLT) between February 2006 and July 2009 in Guangzhou, China. APACHE IV and MELD scoring systems were used to predict the postoperative mortality after OLT. The area under the receiver operating characteristic curve (AUC) and the Hosmer-Lemeshow C statistic were used to assess the discrimination and calibration of APACHE IV and MELD, respectively. Twenty-seven patients died during hospitalization with a mortality rate of 13.8%. The mean scores of APACHE IV and MELD were 42.32 ± 21.95 and 18.09 ± 10.55, respectively, and APACHE IV showed better discrimination than MELD; the areas under the receiver operating characteristic curve for APACHE IV and MELD were 0.937 and 0.694 (P < 0.05 for both models), which indicated that the prognostic value of APACHE IV was relatively high. Both models were well-calibrated (The Hosmer-Lemeshow C statistics were 1.568 and 6.818 for APACHE IV and MELD, resp.; P > 0.05 for both). The respective Youden indexes of APACHE IV, MELD, and combination of APACHE IV with MELD were 0.763, 0.430, and 0.545. The prognostic value of APACHE IV is high but still underestimates the overall hospital mortality, while the prognostic value of MELD is poor. The function of the APACHE IV is, thus, better than that of the MELD.
PMCID: PMC3855953  PMID: 24348682
2.  MELD scoring system is useful for predicting prognosis in patients with liver cirrhosis and is correlated with residual liver function: a European study 
Gut  2003;52(1):134-139.
Background: Indices for predicting survival are essential for assessing prognosis and assigning priority for liver transplantation in patients with liver cirrhosis. The model for end stage liver disease (MELD) has been proposed as a tool to predict mortality risk in cirrhotic patients. However, this model has not been validated beyond its original setting.
Aim: To evaluate the short and medium term survival prognosis of a European series of cirrhotic patients by means of MELD compared with the Child-Pugh score. We also assessed correlations between the MELD scoring system and the degree of impairment of liver function, as evaluated by the monoethylglycinexylidide (MEGX) test.
Patients and methods: We retrospectively evaluated survival of a cohort of 129 cirrhotic patients with a follow up period of at least one year. The Child-Pugh score was calculated and the MELD score was computed according to the original formula for each patient. All patients had undergone a MEGX test. Multivariate analysis was performed on all variables to identify the parameters independently associated with one year and six month survival. MELD values were correlated with both Child-Pugh scores and MEGX test results.
Results: Thirty one patients died within the first year of follow up. Child-Pugh and MELD scores, and MEGX serum levels were significantly different among patients who survived and those who died. Serum creatinine, international normalised ratio, and MEGX60 were independently associated with six month mortality while the same variables and the presence of ascites were associated with one year mortality. MELD scores showed significant correlations with both MEGX values and Child-Pugh scores.
Conclusions: In a European series of cirrhotic patients the MELD score is an excellent predictor of both short and medium term survival, and performs at least as well as the Child-Pugh score. An increase in MELD score is associated with a decrease in residual liver function.
PMCID: PMC1773509  PMID: 12477775
cirrhosis; liver function; ascites; creatinine; Child-Pugh score; MELD; MEGX
3.  MELD Scores and Child–Pugh Classifications Predict the Outcomes of ERCP in Cirrhotic Patients With Choledocholithiasis 
Medicine  2015;94(3):e433.
Endoscopic retrograde cholangiopancreatography (ERCP) is challenging in cirrhotic patients with choledocholithiasis. We evaluated the safety and efficacy of ERCP in cirrhotic patients with choledocholithiasis and accessed the model for end-stage liver disease (MELD) scores and Child–Pugh classifications for prediction of morbidity and mortality.
From January 2000 to June 2014, 77 ERCP operations were performed in cirrhotic patients with choledocholithiasis. The data on operative complications were analyzed. MELD scores and Child–Pugh classifications were calculated and associated with operative outcomes and survival. Telephone follow-up was performed to determine survival situations.
No death, perforation, or hemorrhage caused by gastroesophageal varices occurred as a result of the procedure. The rate of intraoperative hemorrhage was 13.0%, and the rate of postoperative morbidity was 27.3% including hemorrhage (18.2%), post-ERCP pancreatitis (6.1%), aggravated infection of the biliary tract (1.3%), hepatic encephalopathy (1.3%), and respiratory failure (1.3%). Four (5.2%) patients had both intraoperative and postoperative hemorrhage. Receiver operating characteristic analysis identified MELD scores higher than 11.5 as the best cutoff value for predicting complication incidence (95% confidence interval = 0.63–0.87). Twenty-one (44.7%) patients with a MELD score above 11.5 developed a complication, and 3 (10%) patients who had a lower MELD score developed a complication (P = 0.001). Both MELD score and Child–Pugh classification had prognostic value in patients without jaundice, although sex may result in different prognostic values based on the 2 scores. The rate of complications was not significantly different among patients with different Child–Pugh classifications. No significant difference was observed in patients with different MELD scores or Child–Pugh classifications in terms of median survival times.
ERCP is an effective and safe procedure in cirrhotic patients with choledocholithiasis. MELD scores can predict the risk of operative complications, but Child–Pugh classification system scores do not predict the risk of complications.
PMCID: PMC4602645  PMID: 25621696
4.  Pretransplant Prediction of Posttransplant Survival for Liver Recipients with Benign End-Stage Liver Diseases: A Nonlinear Model 
PLoS ONE  2012;7(3):e31256.
The scarcity of grafts available necessitates a system that considers expected posttransplant survival, in addition to pretransplant mortality as estimated by the MELD. So far, however, conventional linear techniques have failed to achieve sufficient accuracy in posttransplant outcome prediction. In this study, we aim to develop a pretransplant predictive model for liver recipients' survival with benign end-stage liver diseases (BESLD) by a nonlinear method based on pretransplant characteristics, and compare its performance with a BESLD-specific prognostic model (MELD) and a general-illness severity model (the sequential organ failure assessment score, or SOFA score).
Methodology/Principal Findings
With retrospectively collected data on 360 recipients receiving deceased-donor transplantation for BESLD between February 1999 and August 2009 in the west China hospital of Sichuan university, we developed a multi-layer perceptron (MLP) network to predict one-year and two-year survival probability after transplantation. The performances of the MLP, SOFA, and MELD were assessed by measuring both calibration ability and discriminative power, with Hosmer-Lemeshow test and receiver operating characteristic analysis, respectively. By the forward stepwise selection, donor age and BMI; serum concentration of HB, Crea, ALB, TB, ALT, INR, Na+; presence of pretransplant diabetes; dialysis prior to transplantation, and microbiologically proven sepsis were identified to be the optimal input features. The MLP, employing 18 input neurons and 12 hidden neurons, yielded high predictive accuracy, with c-statistic of 0.91 (P<0.001) in one-year and 0.88 (P<0.001) in two-year prediction. The performances of SOFA and MELD were fairly poor in prognostic assessment, with c-statistics of 0.70 and 0.66, respectively, in one-year prediction, and 0.67 and 0.65 in two-year prediction.
The posttransplant prognosis is a multidimensional nonlinear problem, and the MLP can achieve significantly high accuracy than SOFA and MELD scores in posttransplant survival prediction. The pattern recognition methodologies like MLP hold promise for solving posttransplant outcome prediction.
PMCID: PMC3291549  PMID: 22396731
5.  A comparison of Child-Pugh, APACHE II and APACHE III scoring systems in predicting hospital mortality of patients with liver cirrhosis 
The aim of this study was to assess the prognostic accuracy of Child-Pugh and APACHE II and III scoring systems in predicting short-term, hospital mortality of patients with liver cirrhosis.
200 admissions of 147 cirrhotic patients (44% viral-associated liver cirrhosis, 33% alcoholic, 18.5% cryptogenic, 4.5% both viral and alcoholic) were studied prospectively. Clinical and laboratory data conforming to the Child-Pugh, APACHE II and III scores were recorded on day 1 for all patients. Discrimination was evaluated using receiver operating characteristic (ROC) curves and area under a ROC curve (AUC). Calibration was estimated using the Hosmer-Lemeshow goodness-of-fit test.
Overall mortality was 11.5%. The mean Child-Pugh, APACHE II and III scores for survivors were found to be significantly lower than those of nonsurvivors. Discrimination was excellent for Child-Pugh (ROC AUC: 0.859) and APACHE III (ROC AUC: 0.816) scores, and acceptable for APACHE II score (ROC AUC: 0.759). Although the Hosmer-Lemeshow statistic revealed adequate goodness-of-fit for Child-Pugh score (P = 0.192), this was not the case for APACHE II and III scores (P = 0.004 and 0.003 respectively)
Our results indicate that, of the three models, Child-Pugh score had the least statistically significant discrepancy between predicted and observed mortality across the strata of increasing predicting mortality. This supports the hypothesis that APACHE scores do not work accurately outside ICU settings.
PMCID: PMC156886  PMID: 12735793
6.  The Model for End-stage Liver Disease accurately predicts 90-day liver transplant wait-list mortality in Atlantic Canada 
To determine the generalizability of the predictions for 90-day mortality generated by Model for End-stage Liver Disease (MELD) and the serum sodium augmented MELD (MELDNa) to Atlantic Canadian adults with end-stage liver disease awaiting liver transplantation (LT).
The predictive accuracy of the MELD and the MELDNa was evaluated by measurement of the discrimination and calibration of the respective models’ estimates for the occurrence of 90-day mortality in a consecutive cohort of LT candidates accrued over a five-year period. Accuracy of discrimination was measured by the area under the ROC curves. Calibration accuracy was evaluated by comparing the observed and model-estimated incidences of 90-day wait-list failure for the total cohort and within quantiles of risk.
The area under the ROC curve for the MELD was 0.887 (95% CI 0.705 to 0.978) – consistent with very good accuracy of discrimination. The area under the ROC curve for the MELDNa was 0.848 (95% CI 0.681 to 0.965). The observed incidence of 90-day wait-list mortality in the validation cohort was 7.9%, which was not significantly different from the MELD estimate of 6.6% (95% CI 4.9% to 8.4%; P=0.177) or the MELDNa estimate of 5.8% (95% CI 3.5% to 8.0%; P=0.065). Global goodness-of-fit testing found no evidence of significant lack of fit for either model (Hosmer-Lemeshow χ2 [df=3] for MELD 2.941, P=0.401; for MELDNa 2.895, P=0.414).
Both the MELD and the MELDNa accurately predicted the occurrence of 90-day wait-list mortality in the study cohort and, therefore, are generalizable to Atlantic Canadians with end-stage liver disease awaiting LT.
PMCID: PMC3174075  PMID: 21876856
End-stage liver disease; Liver transplantation; Mortality; Statistical models; Validation study; Wait list
7.  Prediction of Poor Outcome in Patients with Acute Liver Failure—Systematic Review of Prediction Models 
PLoS ONE  2012;7(12):e50952.
Acute liver failure is a rare disease with high mortality and liver transplantation is the only life saving therapy. Accurate prognosis of ALF is crucial for proper intervention.
To identify and characterize newly developed prognostic models of mortality for ALF patients, assess study quality, identify important variables and provide recommendations for the development of improved models in the future.
The online databases MEDLINE® (1950–2012) and EMBASE® (1980–2012) were searched for English-language articles that reported original data from clinical trials or observational studies on prognostic models in ALF patients. Studies were included if they developed a new model or modified existing prognostic models. The studies were evaluated based on an existing framework for scoring the methodological and reporting quality of prognostic models.
Twenty studies were included, of which 18 reported on newly developed models, 1 on modification of the Kings College Criteria (KCC) and 1 on the Model for End-Stage Liver Disease (MELD). Ten studies compared the newly developed models to previously existing models (e.g. KCC); they all reported that the new models were superior. In the 12-point methodological quality score, only one study scored full points. On the 38-point reporting score, no study scored full points. There was a general lack of reporting on missing values. In addition, none of the studies used performance measures for calibration and accuracy (e.g. Hosmer-Lemeshow statistics, Brier score), and only 5 studies used the AUC as a measure of discrimination.
There are many studies on prognostic models for ALF but they show methodological and reporting limitations. Future studies could be improved by better reporting and handling of missing data, the inclusion of model calibration aspects, use of absolute risk measures, explicit considerations for variable selection, the use of a more extensive set of reference models and more thorough validation.
PMCID: PMC3522683  PMID: 23272081
8.  Assessment of the Model for End-stage Liver Disease (MELD) Score in Predicting Prognosis of Patients with Alcoholic Hepatitis 
Traditionally, Maddrey discriminant function (DF) score has been used for stratifying the prognosis of alcoholic hepatitis. Recently, the Model for end-stage liver disease (MELD) score has been applied to alcoholic hepatitis and some investigators consider MELD score as a better prognostic indicator. Another new prognostic approach, Lille model has been also suggested to accurately identify patients at high risk of death. Therefore, this prospective study was aimed to compare MELD, DF, Child–Turcotte–Pugh (CTP) scores and Lille model for predicting the short-term mortality in Indian patients with alcoholic hepatitis.
We calculated the DF, CTP, MELD and Lille scores in patients hospitalized with alcoholic hepatitis & evaluated if the scores predicted in-hospital mortality.
A total of 104 patients were enrolled and thirty-two (30.7%) patients died during the hospitalization (2–30 days). Admission DF score (OR 1.1, P < 0.04), CTP (OR 2, P < 0.05) MELD score (OR 2.2, P < 0.005) and first week MELD score (OR 1.1, P < 0.05) were independently associated with in-hospital mortality. The area under the receiver-operating curve (AUROC) for the admission and day 7 MELD score was significantly higher than CTP score and was comparable to DF score and Lille model (AUC & 95% CI: 0.97 [0.95–1.0], 0.99 [0.99–1.0], 0.91 [0.83–0.91] and 0.92 [0.86–0.98] for MELD at admission & day 7, admission DF and Lille model, respectively). The MELD score >14 at admission and >12 at day 7 had high sensitivity and specificity in predicting short-term mortality (96%, 89% and 95%, 98% respectively). The cutoff of 0.45 for the Lille model was able to identify 79% of the observed deaths, whereas DF score ≥32 for DF were able to identify 85%.
MELD score, as a predictive model for assessment of short-term mortality in alcoholic hepatitis is better than CTP and comparable to DF and Lille model.
PMCID: PMC4017178  PMID: 25755531
DF; CTP; MELD; alcoholic hepatitis; AH, alcoholic hepatitis; HCC, hepatocellular carcinoma; MELD, Model for end-stage liver disease; PVT, portal vein thrombosis; CTP, Child–Turcotte–Pugh score; SBP, spontaneous bacterial peritonitis; HRS, hepatorenal syndrome; AUC, area under the curve; AUROC, area under the receiver-operating curve
9.  Predictors of In-Hospital Mortality in patients with hepatocellular carcinoma and Acute Variceal bleeding 
Electronic Physician  2015;7(6):1336-1343.
Detection of hepatocellular carcinoma (HCC) in cirrhotic patients remains a serious, unsolved problem, and the risk factors for acute variceal bleeding (AVB) in HCC patients remain unclear. This study aimed to determine the in-hospital mortality (IHM) and factors influencing the clinical outcomes of AVB in patients with liver cirrhosis and HCC.
This was a retrospective, non-randomized, clinical study that was conducted in 2014. The study was conducted on 70 patients with liver cirrhosis and HCC presenting by acute upper gastrointestinal bleeding (AUGIH). All patients were examined endoscopically within 24 hours from presentation and bleeding varices accounted for AUGIH. Full medical history, clinical examination, and laboratory and radiologic data were collected from admission charts, and hospital medical records were statistically analyzed with SSPS version 22.
Thirty-two patients (45.7%) survived and 38 died (54.3%). Survivors are more likely to be Child-Pugh class A or B, and the non-survivors were class C. The Model for End-Stage Liver Disease (MELD) was highly predictive of IHM at an optimized cut-off value of ≥ 12.9. Higher esophageal varices grades and presence of active bleeding on index endoscopy were significant (p < 0.01) in the non-survivors compared to survivors. Complications of liver cirrhosis and associated major comorbidity were significantly higher (p < 0.01) in the non-survivors than the survivors. Univariate logistic regression analysis identified higher Grade Esophageal Varices and number of transfused packed red blood cells units as two independent predictors of IHM.
IHM was particularly high (54.3%) among HCC patients with AVB who had MELD score > 12.9, higher grade Esophageal Varices, active bleeding on index endoscopy, more increased needs for blood transfusion, longer hospital stay, decompensated liver disease with major comorbidity.
PMCID: PMC4623792  PMID: 26516439
acute upper gastrointestinal bleeding; MELD score; complications of liver cirrhosis; hepatocellular carcinoma; prognosis
10.  Is an estimated glomerular filtration rate better than creatinine to be incorporated into the end-stage liver disease score? 
World Journal of Hepatology  2012;4(11):291-298.
AIM: To incorporate estimated glomerular filtration rate (eGFR) into the model for end-stage liver disease (MELD) score to evaluate the predictive value.
METHODS: 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].
RESULTS: 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.
CONCLUSION: 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.
PMCID: PMC3536835  PMID: 23293714
Liver cirrhosis; Estimated glomerular filtration rate; End-stage liver disease; Modification of diet in renal disease; Renal function
11.  The refit model for end-stage liver disease-Na is not a better predictor of mortality than the refit model for end-stage liver disease in patients with cirrhosis and ascites 
The modification of the Model for End-Stage Liver Disease (MELD) scoring system (Refit MELD) and the modification of MELD-Na (Refit MELDNa), which optimized the MELD coefficients, were published in 2011. We aimed to validate the superiority of the Refit MELDNa over the Refit MELD for the prediction of 3-month mortality in Korean patients with cirrhosis and ascites.
We reviewed the medical records of patients admitted with hepatic cirrhosis and ascites to the Konkuk University Hospital between January 2006 and December 2011. The Refit MELD and Refit MELDNa were compared using the predictive value of the 3-month mortality, as assessed by the Child-Pugh score.
In total, 530 patients were enrolled, 87 of whom died within 3 months. Alcohol was the most common etiology of their cirrhosis (n=271, 51.1%), and the most common cause of death was variceal bleeding (n=20, 23%). The areas under the receiver operating curve (AUROCs) for the Child-Pugh, Refit MELD, and Refit MELDNa scores were 0.754, 0.791, and 0.764 respectively; the corresponding values when the analysis was performed only in patients with persistent ascites (n=115) were 0.725, 0.804, and 0.796, respectively. The significant difference found among the Child-Pugh, Refit MELD, and Refit MELDNa scores was between the Child-Pugh score and Refit MELD in patients with persistent ascites (P=0.039).
Refit MELD and Refit MELDNa exhibited good predictability for 3-month mortality in patients with cirrhosis and ascites. However, Refit MELDNa was not found to be a better predictor than Refit MELD, despite the known relationship between hyponatremia and mortality in cirrhotic patients with ascites.
PMCID: PMC3992329  PMID: 24757658
Stage Liver Disease; Liver Cirrhosis; Ascites; Mortality; Hyponatremia
12.  Inclusion of Sarcopenia Within MELD (MELD-Sarcopenia) and the Prediction of Mortality in Patients With Cirrhosis 
Limitations of the Model for End-Stage Liver Disease (MELD) score include its failure to assess the nutritional and functional status of cirrhotic patients. Our objectives were to evaluate the impact of sarcopenia in cirrhosis and whether the inclusion of muscularity assessment within MELD could improve the prediction of mortality in patients with cirrhosis.
We included 669 cirrhotic patients who were consecutively evaluated for liver transplantation. Skeletal muscle index at the third lumbar vertebra (L3 SMI) was measured by computed tomography, and sarcopenia was defined using previously published gender and body mass index–specific cutoffs. Using Cox proportional hazards regression, a novel MELD-sarcopenia score was derived.
Sarcopenia was present in 298 patients (45%); sarcopenic patients had shorter median survival than non-sarcopenic patients (20±3 vs. 95±24 months, P<0.001). By Cox regression analysis adjusted for age, gender, and hepatocellular carcinoma, both MELD (hazard ratio (HR) 1.08, 95% confidence interval (CI) 1.06–1.10, P<0.001), and the L3 SMI (HR 0.97, 95% CI 0.96–0.99, P<0.001) were associated with mortality. Overall, the c-statistics for 3-month mortality were 0.82 (95% CI 0.78–0.87) for MELD and 0.85 (95% CI 0.81–0.88) for MELD-sarcopenia (P=0.1). Corresponding figures for 1-year mortality were 0.73 (95% CI 0.69–0.77) and 0.77 (95% CI 0.73–0.80), respectively (P=0.03). The c-statistics for 3-month mortality in patients with MELD<15 (0.85 vs. 0.69, P=0.02) and refractory ascites (0.74 vs. 0.71, P=0.01) were significantly higher for MELD-sarcopenia compared with MELD.
Modification of MELD to include sarcopenia is associated with improved prediction of mortality in patients with cirrhosis, primarily in patients with low MELD scores. External validation of this prognostic index in larger cohorts of cirrhotic patients is warranted.
PMCID: PMC4816259  PMID: 26181291
13.  Development and Validation of a New Prognostic System for Patients with Hepatocellular Carcinoma 
PLoS Medicine  2016;13(4):e1002006.
Prognostic assessment in patients with hepatocellular carcinoma (HCC) remains controversial. Using the Italian Liver Cancer (ITA.LI.CA) database as a training set, we sought to develop and validate a new prognostic system for patients with HCC.
Methods and Findings
Prospective collected databases from Italy (training cohort, n = 3,628; internal validation cohort, n = 1,555) and Taiwan (external validation cohort, n = 2,651) were used to develop the ITA.LI.CA prognostic system. We first defined ITA.LI.CA stages (0, A, B1, B2, B3, C) using only tumor characteristics (largest tumor diameter, number of nodules, intra- and extrahepatic macroscopic vascular invasion, extrahepatic metastases). A parametric multivariable survival model was then used to calculate the relative prognostic value of ITA.LI.CA tumor stage, Eastern Cooperative Oncology Group (ECOG) performance status, Child–Pugh score (CPS), and alpha-fetoprotein (AFP) in predicting individual survival. Based on the model results, an ITA.LI.CA integrated prognostic score (from 0 to 13 points) was constructed, and its prognostic power compared with that of other integrated systems (BCLC, HKLC, MESIAH, CLIP, JIS). Median follow-up was 58 mo for Italian patients (interquartile range, 26–106 mo) and 39 mo for Taiwanese patients (interquartile range, 12–61 mo).
The ITA.LI.CA integrated prognostic score showed optimal discrimination and calibration abilities in Italian patients. Observed median survival in the training and internal validation sets was 57 and 61 mo, respectively, in quartile 1 (ITA.LI.CA score ≤ 1), 43 and 38 mo in quartile 2 (ITA.LI.CA score 2–3), 23 and 23 mo in quartile 3 (ITA.LI.CA score 4–5), and 9 and 8 mo in quartile 4 (ITA.LI.CA score > 5). Observed and predicted median survival in the training and internal validation sets largely coincided. Although observed and predicted survival estimations were significantly lower (log-rank test, p < 0.001) in Italian than in Taiwanese patients, the ITA.LI.CA score maintained very high discrimination and calibration features also in the external validation cohort.
The concordance index (C index) of the ITA.LI.CA score in the internal and external validation cohorts was 0.71 and 0.78, respectively. The ITA.LI.CA score’s prognostic ability was significantly better (p < 0.001) than that of BCLC stage (respective C indexes of 0.64 and 0.73), CLIP score (0.68 and 0.75), JIS stage (0.67 and 0.70), MESIAH score (0.69 and 0.77), and HKLC stage (0.68 and 0.75). The main limitations of this study are its retrospective nature and the intrinsically significant differences between the Taiwanese and Italian groups.
The ITA.LI.CA prognostic system includes both a tumor staging—stratifying patients with HCC into six main stages (0, A, B1, B2, B3, and C)—and a prognostic score—integrating ITA.LI.CA tumor staging, CPS, ECOG performance status, and AFP. The ITA.LI.CA prognostic system shows a strong ability to predict individual survival in European and Asian populations.
Using Italian and Taiwanese cohorts, Alessandro Vitale and colleagues develop and validate a staging system and prognostic model for hepatocellular carcinoma.
Editors' Summary
Primary liver cancer—a tumor that starts when a liver cell acquires genetic changes that allow it and its descendants to divide uncontrollably and move around the body (metastasize)—is the sixth most common cancer and the second leading cause of cancer-related deaths worldwide. Liver cancer kills more than three-quarters of a million people every year, mostly in resource-limited countries. The risk of developing hepatocellular carcinoma (HCC; the most common type of liver cancer) is highest in eastern and southeastern Asia; among wealthier nations, the risk of HCC is particularly high in Italy. HCC can be treated by surgical removal of part of the liver, liver transplantation, ablation (which uses an electric current to destroy the cancer cells), intra-arterial therapies (which deliver drugs directly into the liver), or systemic (whole body) drug therapies. However, the symptoms of HCC, which include weight loss, tiredness, and jaundice, are vague. HCC is therefore rarely diagnosed before the cancer is advanced and has a poor prognosis (likely outcome)—fewer than 5% of patients survive for five or more years after diagnosis.
Why Was This Study Done?
Cancer staging describes the severity of a cancer based on the size and extent of the original tumor and whether the tumor has metastasized. Staging helps doctors estimate the patient’s prognosis and can help them devise a treatment plan that will, hopefully, improve patients’ quality of life and may extend their life expectancy. Several staging systems have been devised for HCC, but prognostic assessment of patients with HCC is controversial. No single prognostic model (a model that allows clinicians to obtain predictions about the likely outcomes of individual patients) has been universally adopted. An ideal model is difficult to achieve as it would need to consider tumor-related, liver-function-related, and patient-related variables, all of which have different impacts on patient prognosis. Here, the researchers use a database created by the Italian Liver Cancer (ITA.LI.CA) group that includes information on more than 5,000 Italians with HCC to develop a new prognostic model to predict individual patient outcomes based on tumor-related, liver-function-related, and patient-related variables.
What Did the Researchers Do and Find?
The researchers first defined ITA.LI.CA stages for HCC using tumor characteristics only. They then used information on 3,628 patients in the ITA.LI.CA database (the “training” set) and statistical modeling to calculate the relative prognostic value of tumor staging, Eastern Cooperative Oncology Group (ECOG) performance status (an indicator of whether patients are able to look after themselves and undertake normal daily activities), liver function (measured using the Child—Pugh score), and alpha-fetoprotein level (a liver tumor marker) in the prediction of the survival of individual patients. Based on these modeling results, they constructed an ITA.LI.CA integrated prognostic score. The researchers report that the observed and predicted median (average) survival times in the training set and in an internal validation cohort of 1,555 additional patients in the ITA.LI.CA database were similar. Moreover, although the observed and predicted survival times were lower in the Italian patients than in 2,651 patients with HCC from Taiwan, the ITA.LI.CA score had high discrimination and calibration features in this external validation cohort as well (the discrimination of a prognostic model indicates its ability to separate patients into groups with different outcomes, the calibration of a prognostic model is the degree of correspondence between predicted and observed outcomes). Finally, the prognostic ability of the new ITA.LI.CA prognostic model was significantly better than that of several other prognostic scoring systems.
What Do These Findings Mean?
These findings introduce a revised staging system for HCC and an integrated prognostic score—the ITA.LI.CA prognostic score—based on this staging system, Child—Pugh score, ECOG performance status, and alpha-fetoprotein level that has a greater ability to predict survival among Italian and Taiwanese patients than previous prognostic models. Because this study was retrospective—previously recorded data, including outcomes, were used to develop the prognostic model—a prospective trial is needed to validate the ITA.LI.CA prognostic score. That is, researchers need to enroll a group of patients, determine their ITA.LI.CA prognostic scores, and then follow the patients to determine their actual outcomes. If validated in this way and in other populations, use of the ITA.LI.CA prognostic score should allow clinicians to provide more accurate prognoses for individual patients, and may be a starting point for evaluating which treatment option is best suited to each patient presenting with HCC.
Additional Information
This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at
This study is further discussed in a PLOS Medicine Perspective by Neehar Parikh and Amit Singal
The US National Cancer Institute provides information about all aspects of cancer, including detailed information for patients and professionals about primary liver cancer and about cancer staging (in English and Spanish)
The American Cancer Society also provides information about liver cancer (including information on support programs and services; available in several languages)
The UK National Health Service Choices website provides information about primary liver cancer (including a video about coping with cancer) and about cancer staging
Cancer Research UK (a not-for-profit organization) provides detailed information about primary liver cancer
The British Liver Trust (a not-for-profit organization) also provides information about liver cancer, including a personal story
MedlinePlus provides links to further resources about liver cancer (in English and Spanish)
PMCID: PMC4846017  PMID: 27116206
14.  A simplified approach to the pooled analysis of calibration of clinical prediction rules for systematic reviews of validation studies 
Clinical Epidemiology  2015;7:267-280.
Estimating calibration performance of clinical prediction rules (CPRs) in systematic reviews of validation studies is not possible when predicted values are neither published nor accessible or sufficient or no individual participant or patient data are available. Our aims were to describe a simplified approach for outcomes prediction and calibration assessment and evaluate its functionality and validity.
Study design and methods:
Methodological study of systematic reviews of validation studies of CPRs: a) ABCD2 rule for prediction of 7 day stroke; and b) CRB-65 rule for prediction of 30 day mortality. Predicted outcomes in a sample validation study were computed by CPR distribution patterns (“derivation model”). As confirmation, a logistic regression model (with derivation study coefficients) was applied to CPR-based dummy variables in the validation study. Meta-analysis of validation studies provided pooled estimates of “predicted:observed” risk ratios (RRs), 95% confidence intervals (CIs), and indexes of heterogeneity (I2) on forest plots (fixed and random effects models), with and without adjustment of intercepts. The above approach was also applied to the CRB-65 rule.
Our simplified method, applied to ABCD2 rule in three risk strata (low, 0–3; intermediate, 4–5; high, 6–7 points), indicated that predictions are identical to those computed by univariate, CPR-based logistic regression model. Discrimination was good (c-statistics =0.61–0.82), however, calibration in some studies was low. In such cases with miscalibration, the under-prediction (RRs =0.73–0.91, 95% CIs 0.41–1.48) could be further corrected by intercept adjustment to account for incidence differences. An improvement of both heterogeneities and P-values (Hosmer-Lemeshow goodness-of-fit test) was observed. Better calibration and improved pooled RRs (0.90–1.06), with narrower 95% CIs (0.57–1.41) were achieved.
Our results have an immediate clinical implication in situations when predicted outcomes in CPR validation studies are lacking or deficient by describing how such predictions can be obtained by everyone using the derivation study alone, without any need for highly specialized knowledge or sophisticated statistics.
PMCID: PMC4404967  PMID: 25931829
clinical prediction rules; derivation; validation; meta-analysis; primary care
15.  Identifying admitted patients at risk of dying: a prospective observational validation of four biochemical scoring systems 
BMJ Open  2013;3(6):e002890.
Risk assessment is an important part of emergency patient care. Risk assessment tools based on biochemical data have the advantage that calculation can be automated and results can be easily provided. However, to be used clinically, existing tools have to be validated by independent researchers. This study involved an independent external validation of four risk stratification systems predicting death that rely primarily on biochemical variables.
Prospective observational study.
The medical admission unit at a regional teaching hospital in Denmark.
Of 5894 adult (age 15 or above) acutely admitted medical patients, 205 (3.5%) died during admission and 46 died (0.8%) within one calendar day.
Main outcome measures
The main outcome measure was the ability to identify patients at an increased risk of dying (discriminatory power) as area under the receiver-operating characteristic curve (AUROC) and the accuracy of the predicted probability (calibration) using the Hosmer-Lemeshow goodness-of-fit test. The endpoint was all-cause mortality, defined in accordance with the original manuscripts.
Using the original coefficients, all four systems were excellent at identifying patients at increased risk (discriminatory power, AUROC ≥0.80). The accuracy was poor (we could assess calibration for two systems, which failed). After recalculation of the coefficients, two systems had improved discriminatory power and two remained unchanged. Calibration failed for one system in the validation cohort.
Four biochemical risk stratification systems can risk-stratify the acutely admitted medical patients for mortality with excellent discriminatory power. We could improve the models for use in our setting by recalculating the risk coefficient for the chosen variables.
PMCID: PMC3693413  PMID: 23794564
Epidemiology; Internal Medicine
16.  Model for End-Stage Liver Disease (MELD) Score as a Predictor and Monitor of Mortality in Patients with Vibrio vulnificus Necrotizing Skin and Soft Tissue Infections 
PLoS Neglected Tropical Diseases  2015;9(4):e0003720.
Vibrio vulnificus necrotizing skin and soft tissue infections (VNSSTIs) usually predispose patients with or without preexisting liver disease to septic shock, and then evolve to multiple organ dysfunction syndrome (MODS), thus resulting in high mortality in humans. However, clinicians do not have a valid prediction model to provide a reliable estimate of case-fatality rate when caring for these acutely and/or critically ill patients.
Methods/Principal Findings
We retrospectively analyzed 39 consecutive patients with VNSSTIs (mean age: 65.7 ± 11.3 years) at our institution between 2007 and 2010. All patients were treated with the same protocol. Demographic and clinical characteristics, disease severity on admission, treatment details, and outcomes were collected for each patient and extracted for analyses. We studied the predictive value of the model for end-stage liver disease (MELD), modified MELD including sodium (MELD-Na), and laboratory risk indicator for necrotizing fasciitis (LRINEC) scores for case-fatality. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed. The mean MELD, MELD-Na and LRINEC scores on admission were 15.1 ± 1.1, 17.7 ± 1.1, and 3.4 ± 0.4 points, respectively. After admission, these patients had temporary or progressive deterioration of nearly all their scores and lab values. The area under the ROC curve for the MELD and ΔMELD scoring models were 0.929 (p = 0.002) and 0.897 (p = 0.005), respectively. An optimal MELD/ΔMELD cutoff value ≥ 20/2 had a good sensitivity and specificity (all > 80%), with a 64/13-fold increased odds for case-fatality. Additionally, the development of severe forms of anemia (p = 0.014) and hypoalbuminemia (p = 0.019) were associated with an increased case-fatality rate.
The MELD/ΔMELD scoring model is an effective risk stratification indicator at the time of admission and also an excellent condition monitor during hospitalization for medical care of acutely and/or critically ill patients with VNSSTIs.
Author Summary
VNSSTIs have increased significantly over the last two decades, with cases now regularly reported globally. Despite advancing antibiotic and infection control practices, these infections are still highly lethal and disabling diseases. They usually predispose patients to septic shock and then evolve to liver dysfunction and MODS, thus resulting in high mortality in humans. However, clinicians do not have a valid prediction model to provide a reliable estimate of case-fatality rate when caring for these acutely and critically ill patients. MELD scoring system was originally developed to assess the short-term prognosis of cirrhotic patients undergoing the transjugular intrahepatic portosystemic shunt procedure. By using the MEGX test, the strong negative association between the scores and the residual liver function has been confirmed. Therefore, it has been validated and applied to a wide spectrum of clinical scenarios in recent years. In this work, we studied the predictive value of the MELD scoring system for case-fatality in patients suffering VNSSTIs. We have found that the MELD scoring system is an effective risk stratification indicator at the time of admission, and also an excellent condition monitor during hospitalization for medical care of acutely and critically ill patients with VNSSTIs.
PMCID: PMC4414517  PMID: 25923115
17.  BLEED-Myocardial Infarction Score: Predicting mid-term post-discharge bleeding events 
World Journal of Cardiology  2013;5(6):196-206.
AIM: To derive and validate a score for the prediction of mid-term bleeding events following discharge for myocardial infarction (MI).
METHODS: One thousand and fifty patients admitted for MI and followed for 19.9 ± 6.7 mo were assigned to a derivation cohort. A new risk model, called BLEED-MI, was developed for predicting clinically significant bleeding events during follow-up (primary endpoint) and a composite endpoint of significant hemorrhage plus all-cause mortality (secondary endpoint), incorporating the following variables: age, diabetes mellitus, arterial hypertension, smoking habits, blood urea nitrogen, glomerular filtration rate and hemoglobin at admission, history of stroke, bleeding during hospitalization or previous major bleeding, heart failure during hospitalization and anti-thrombotic therapies prescribed at discharge. The BLEED-MI model was tested for calibration, accuracy and discrimination in the derivation sample and in a new, independent, validation cohort comprising 852 patients admitted at a later date.
RESULTS: The BLEED-MI score showed good calibration in both derivation and validation samples (Hosmer-Lemeshow test P value 0.371 and 0.444, respectively) and high accuracy within each individual patient (Brier score 0.061 and 0.067, respectively). Its discriminative performance in predicting the primary outcome was relatively high (c-statistic of 0.753 ± 0.032 in the derivation cohort and 0.718 ± 0.033 in the validation sample). Incidence of primary/secondary endpoints increased progressively with increasing BLEED-MI scores. In the validation sample, a BLEED-MI score below 2 had a negative predictive value of 98.7% (152/154) for the occurrence of a clinically significant hemorrhagic episode during follow-up and for the composite endpoint of post-discharge hemorrhage plus all-cause mortality. An accurate prediction of bleeding events was shown independently of mortality, as BLEED-MI predicted bleeding with similar efficacy in patients who did not die during follow-up: Area Under the Curve 0.703, Hosmer-Lemeshow test P value 0.547, Brier score 0.060; low-risk (BLEED-MI score 0-3) event rate: 1.2%; intermediate risk (score 4-6) event rate: 5.6%; high risk (score ≥ 7) event rate: 12.5%.
CONCLUSION: A new bedside prediction-scoring model for post-discharge mid-term bleeding has been derived and preliminarily validated. This is the first score designed to predict mid- term hemorrhagic risk in patients discharged following admission for acute MI. This model should be externally validated in larger cohorts of patients before its potential implementation.
PMCID: PMC3691499  PMID: 23802048
Myocardial infarction; Bleeding; Prediction model; Risk stratification
18.  Score model for predicting acute-on-chronic liver failure risk in chronic hepatitis B 
AIM: To establish a clinical scoring model to predict risk of acute-on-chronic liver failure (ACLF) in chronic hepatitis B (CHB) patients.
METHODS: This was a retrospective study of 1457 patients hospitalized for CHB between October 2008 and October 2013 at the Beijing Ditan Hospital, Capital Medical University, China. The patients were divided into two groups: severe acute exacerbation (SAE) group (n = 382) and non-SAE group (n = 1075). The SAE group was classified as the high-risk group based on the higher incidence of ACLF in this group than in the non-SAE group (13.6% vs 0.4%). Two-thirds of SAE patients were randomly assigned to risk-model derivation and the other one-third to model validation. Univariate risk factors associated with the outcome were entered into a multivariate logistic regression model for screening independent risk factors. Each variable was assigned an integer value based on the regression coefficients, and the final score was the sum of these values in the derivation set. Model discrimination and calibration were assessed using area under the receiver operating characteristic curve and the Hosmer-Lemeshow test.
RESULTS: The risk prediction scoring model included the following four factors: age ≥ 40 years, total bilirubin ≥ 171 μmol/L, prothrombin activity 40%-60%, and hepatitis B virus DNA > 107 copies/mL. The sum risk score ranged from 0 to 7; 0-3 identified patients with lower risk of ACLF, whereas 4-7 identified patients with higher risk. The Kaplan-Meier analysis showed the cumulative risk for ACLF and ACLF-related death in the two risk groups (0-3 and 4-7 scores) of the primary cohort over 56 d, and log-rank test revealed a significant difference (2.0% vs 33.8% and 0.8% vs 9.4%, respectively; both P < 0.0001). In the derivation and validation data sets, the model had good discrimination (C index = 0.857, 95% confidence interval: 0.800-0.913 and C index = 0.889, 95% confidence interval: 0.820-0.957, respectively) and calibration demonstrated by the Hosmer-Lemeshow test (χ2 = 4.516, P = 0.808 and χ2 = 1.959, P = 0.923, respectively).
CONCLUSION: Using the scoring model, clinicians can easily identify patients (total score ≥ 4) at high risk of ACLF and ACLF-related death early during SAE.
PMCID: PMC4507107  PMID: 26217089
Acute-on-chronic liver failure; Chronic hepatitis B; Prediction model; Risk score; Severe acute exacerbation
19.  Comparison of risk adjustment methods in patients with liver disease using electronic medical record data 
BMC Gastroenterology  2017;17:5.
Risk adjustment is essential for valid comparison of patients’ health outcomes or performances of health care providers. Several risk adjustment methods for liver diseases are commonly used but the optimal approach is unknown. This study aimed to compare the common risk adjustment methods for predicting in-hospital mortality in cirrhosis patients using electronic medical record (EMR) data.
The sample was derived from Beijing YouAn hospital between 2010 and 2014. Previously validated EMR extraction methods were applied to define liver disease conditions, Charlson comorbidity index (CCI), Elixhauser comorbidity index (ECI), Child-Turcotte-Pugh (CTP), model for end-stage liver disease (MELD), MELD sodium (MELDNa), and five-variable MELD (5vMELD). The performance of the common risk adjustment models as well as models combining disease severity and comorbidity indexes for predicting in-hospital mortality was compared using c-statistic.
Of 11,121 cirrhotic patients, 69.9% were males and 15.8% age 65 or older. The c-statistics across compared models ranged from 0.785 to 0.887. All models significantly outperformed the baseline model with age, sex, and admission status (c-statistic: 0.628). The c-statistics for the CCI, ECI, MELDNa, and CTP were 0.808, 0.825, 0.849, and 0.851, respectively. The c-statistic was 0.887 for combination of CTP and ECI, and 0.882 for combination of MELDNa score and ECI.
The liver disease severity indexes (i.e., CTP and MELDNa score) outperformed the CCI and ECI for predicting in-hospital mortality among cirrhosis patients using Chinese EMRs. Combining liver disease severity and comorbidities indexes could improve the discrimination power of predicting in-hospital mortality.
PMCID: PMC5219741  PMID: 28061757
Risk adjustment; Electronic medical record; Liver disease; In-hospital mortality
20.  The usefulness of C-reactive protein and neutrophil-to-lymphocyte ratio for predicting the outcome in hospitalized patients with liver cirrhosis 
BMC Gastroenterology  2015;15:146.
The role of clinical parameters such as systemic inflammatory response syndrome (SIRS) criteria in predicting the infection remains unclear in cirrhosis patients. The aim was to evaluate the usefulness of inflammatory markers including C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR) for diagnosis of infection and predicting the outcomes in hospitalized cirrhotic patients.
The study included 184 cirrhotic patients consecutively hospitalized from 2011 to 2012. The presence of overt infection and survival was evaluated. CRP concentration, NLR, Model for End-Stage Liver Disease (MELD) score and the presence of SIRS were assessed.
The main cause of admission was uncontrolled ascites (36.4 %), followed by varix bleeding (23.9 %), and hepatic encephalopathy (13.6 %). Fifty-eight patients (31.5 %) had overt infection during hospitalization and thirty-two patients (17.4 %) expired during the follow up period (median 38 months). Ninety-two patients (52.2 %) fulfilled the SIRS criteria and among them, only 32 patients (38.5 %) had the overt infection. For diagnose of the infection, baseline CRP concentration was a significant factor compared to the presence of SIRS (odds ratio 1.202, P = 0.003). For predicting one-month short-term survival, MELD score, NLR and WBC count were significant factors but in Child-Pugh class C patients, NLR was only an independent factor.
CRP was a significant indicator of infection in hospitalized cirrhotic patients and a NLR was a useful predictor of 1-month survival, particularly in Child–Pugh class C patients. This study suggests that the inflammatory markers such as CRP and NLR can help identify cirrhotic patients at risk of unfavorable outcomes.
PMCID: PMC4619077  PMID: 26498833
C-reactive protein; Liver cirrhosis; Infection; Neutrophil-to-lymphocyte ratio; Survival
21.  Development and Validation of an Index to Predict Personal Prescription Drug Importation by Adults in the United States 
Personal prescription drug importation (PPDI) is prevalent in the United States (U.S.) because of the high cost of U.S. medicines and lower cost of foreign equivalents. The practice carries the risk of exposure to counterfeit, adulterated, and substandard medicines. No known tools are available for predicting person-level PPDI risk. The objective of this study was to develop and validate a predictive PPDI index for policymakers, researchers, and clinicians.
Using 2011 and 2012 National Health Interview Survey (NHIS) data as the development and validation cohorts respectively, we identified predictors, built multivariable logistic regression models, and validated the index by comparing predicted risk of PPDI in the development cohort to the observed risk in the validation cohort. We assessed calibration using the Hosmer-Lemeshow goodness-of-fit test and discrimination with C-statistics. The outcome measure was survey-reported PPDI (1=yes; 0=no).
Key Findings
In the development cohort, prevalence of PPDI in respondents with 0–2, 3, 4, 5–6, or ≥7 risk factors were 0.32%, 0.57%, 1.09%, 2.95%, and 13.67% (C-statistic=0.78), and in the validation cohort, were 0.32%, 0.54%, 0.95%, 2.89%, and 10.80% (C-statistic=0.76). The Hosmer-Lemeshow test indicated absence of a gross lack of fit (P=0.58) in the validation cohort. On the basis of index performance in the validation cohort, if an intervention to reduce importation were applied to all patients with scores of ≥7, it would be applied to 31.1% of patients who engage in PPDI and 0.6% of the overall population.
This predictive index accurately stratifies U.S. adults into groups at differential risk of PPDI and may provide value to those who are responsible for health policy and regulation of pharmaceutical importation.
PMCID: PMC4930104  PMID: 27375777
Modeling; International; Statistics; Health Policy; Pharmaceutical HSR; Regulatory
22.  Model for End-Stage Liver Disease (MELD) Score Measurements on The Daily Basis in Critically Ill Cirrhotic Patients Do Not Provide Additional Prognostic Value 
Mayo Clinic proceedings  2015;90(9):1196-1206.
To determine whether daily measurement of Model for End-Stage Liver Disease (MELD) score adds prognostic value to the initial MELD score in predicting mortality among cirrhotic patients admitted to the intensive care unit (ICU).
We included 830 consecutive cirrhotic patients admitted to a tertiary care ICU between January 1, 2003 and December 31, 2013 who had MELD scores on admission day 1 (MELD-D1). Daily MELD score during the first seven days of ICU admission were retrospectively abstracted. The performances of MELD-D1 to MELD-D7 and changes in MELD score on consecutive days (Δ-MELD) in predicting 90-day mortality were determined using logistic regression.
MELD-D1 was an independent predictor of mortality (adjusted OR 1.07, 95% CI, 1.05-1.10; P<.001), with an area under receiver operating characteristic curve (AUC) 0.72. MELD-D2 to MELD-D7 yielded comparable performance to MELD-D1 with a ∼10% increase in risk of death per each incremental unit of MELD score (range of ORs 1.09-1.11, P<.001, AUCs 0.68-0.72). Δ-MELD-D2 to Δ-MELD-D7 were not independently associated with mortality (P>.05 for all) and did not increase the predictive performance (AUCs) when combined with MELD-D2 to MELD-D7.
Repeating MELD score assessment during the first seven days after ICU admission does not improve the ability of the initial MELD score for predicting 90-day mortality among cirrhotic patients. Our finding does not support the practice of routine daily measurement of the MELD score.
PMCID: PMC4567441  PMID: 26249009
serial MELD scores; delta MELD score; cirrhosis; prognostic performance
23.  The Royal Free Hospital Score: A Calibrated Prognostic Model for Patients With Cirrhosis Admitted to Intensive Care Unit. Comparison With Current Models and CLIF-SOFA Score 
Prognosis for patients with cirrhosis admitted to intensive care unit (ICU) is poor. ICU prognostic models are more accurate than liver-specific models. We identified predictors of mortality, developed a novel prognostic score (Royal Free Hospital (RFH) score), and tested it against established prognostic models and the yet unvalidated Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) model.
Predictors of mortality were defined by logistic regression in a cohort of 635 consecutive patients with cirrhosis admitted to ICU (1989–2012). The RFH score was derived using a 75% training and 25% validation set. Predictive accuracy and calibration were evaluated using area under the receiver operating characteristic (AUROC) and goodness-of-fit χ2 for the RFH score, as well as for SOFA, Model for End-Stage Liver Disease (MELD), Acute Physiology and Chronic Health Evaluation (APACHE II), and Child-Pugh. CLIF-SOFA was applied to a recent subset (2005–2012) of patients.
In-hospital mortality was 52.3%. Mortality improved over time but with a corresponding reduction in acuity of illness on admission. Predictors of mortality in training set, which constituted the RFH score, were the following: bilirubin, international normalized ratio, lactate, alveolar arterial partial pressure oxygen gradient, urea, while variceal bleeding as indication for admission conferred lesser risk. Classification accuracy was 73.4% in training and 76.7% in validation sample and did not change significantly across different eras of admission. The AUROC for the derived model was 0.83 and the goodness-of-fit χ2 was 3.74 (P=0.88). AUROC for SOFA was 0.81, MELD was 0.79, APACHE II was 0.78, and Child-Pugh was 0.67. In 2005–2012 cohort, AUROC was: SOFA: 0.74, CLIF-SOFA: 0.75, and RFH: 0.78. Goodness-of-fit χ2 was: SOFA: 6.21 (P=0.63), CLIF-SOFA: 9.18 (P=0.33), and RFH: 2.91 (P=0.94).
RFH score demonstrated good discriminative ability and calibration. Internal validation supports its generalizability. CLIF-SOFA did not perform better than RFH and the original SOFA. External validation of our model should be undertaken to confirm its clinical utility.
PMCID: PMC3978197  PMID: 24492755
24.  Prediction of Mortality after Emergent Transjugular Intrahepatic Portosystemic Shunt Placement: Use of APACHE II, Child-Pugh and MELD Scores in Asian Patients with Refractory Variceal Hemorrhage 
Korean Journal of Radiology  2009;10(5):481-489.
This study was designed to determine if existing methods of grading liver function that have been developed in non-Asian patients with cirrhosis can be used to predict mortality in Asian patients treated for refractory variceal hemorrhage by the use of the transjugular intrahepatic portosystemic shunt (TIPS) procedure.
Materials and Methods
Data for 107 consecutive patients who underwent an emergency TIPS procedure were retrospectively analyzed. Acute physiology and chronic health evaluation (APACHE II), Child-Pugh and model for end-stage liver disease (MELD) scores were calculated. Survival analyses were performed to evaluate the ability of the various models to predict 30-day, 60-day and 360-day mortality. The ability of stratified APACHE II, Child-Pugh, and MELD scores to predict survival was assessed by the use of Kaplan-Meier analysis with the log-rank test.
No patient died during the TIPS procedure, but 82 patients died during the follow-up period. Thirty patients died within 30 days after the TIPS procedure; 37 patients died within 60 days and 53 patients died within 360 days. Univariate analysis indicated that hepatorenal syndrome, use of inotropic agents and mechanical ventilation were associated with elevated 30-day mortality (p < 0.05). Multivariate analysis showed that a Child-Pugh score > 11 or an MELD score > 20 predicted increased risk of death at 30, 60 and 360 days (p < 0.05). APACHE II scores could only predict mortality at 360 days (p < 0.05).
A Child-Pugh score > 11 or an MELD score > 20 are predictive of mortality in Asian patients with refractory variceal hemorrhage treated with the TIPS procedure. An APACHE II score is not predictive of early mortality in this patient population.
PMCID: PMC2731866  PMID: 19721833
Hepatitis; Viral cirrhosis; Mortality; Prognosis; Transjugular intrahepatic portosystemic shunt (TIPS)
25.  Postoperative resource utilization and survival among liver transplant recipients with Model for End-stage Liver Disease score ≥40: A retrospective cohort study 
Adoption of the Model for End-stage Liver Disease (MELD) score as a marker of chronic liver disease severity has led to shorter wait lists and wait times for liver transplantation, increases in the number of liver transplant procedures and lower mortality. However, given the considerable resource expenditure for patients with significantly elevated MELD score and the high wait list mortality in this group, transplant authorities have set a threshold value for this important metric. This single-centre, retrospective study investigated short- and long-term survival rates, in addition to several important resource-related variables in a group of patients who underwent liver transplantation over a 10-year period.
Cirrhotic patients with Model for End-stage Liver Disease (MELD) score ≥40 have high risk for death without liver transplant (LT).
To evaluate these patients’ outcomes after LT.
The present study analyzed a retrospective cohort of 519 cirrhotic adult patients who underwent LT at a single Canadian centre between 2002 and 2012. Primary exposure was severity of liver disease measured by MELD score at LT (≥40 versus <40). Primary outcome was duration of first intensive care unit (ICU) stay after LT. Secondary outcomes were duration of first hospital stay after LT, rate of ICU readmission, re-LT and survival rates.
On the day of LT, 5% (28 of 519) of patients had a MELD score ≥40. These patients had longer first ICU stays after LT (14 versus two days; P<0.001). MELD score ≥40 at LT was independently associated with first ICU stay after LT ≥10 days (OR 3.21). These patients had longer first hospital stays after LT (45 versus 18 days; P<0.001); however, there was no significant difference in the rate of ICU readmission (18% versus 22%; P=0.58) or re-LT rate (4% versus 4%; P=1.00). Cumulative survival at one month, three months, one year, three years and five years was 98%, 96%, 90%, 79% and 72%, respectively. There was no significant difference in cumulative survival stratified according to MELD score ≥40 versus <40 at LT (P=0.59).
Cirrhotic patients with MELD score ≥40 at LT utilize greater postoperative health resources; however, they derive similar long-term survival benefit from LT.
PMCID: PMC4444027  PMID: 25965438
Cirrhosis; End-stage liver disease; Liver transplant; MELD

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