Stage of cirrhosis predicts the risk of liver-related death in patients with low model for End-Stage liver disease scores and cirrhosis awaiting liver transplantation

Liver TransplantationVolume 20, Issue 10 p. 1193-1201 Original ArticleFree Access Stage of cirrhosis predicts the risk of liver-related death in patients with low model for End-Stage liver disease scores and cirrhosis awaiting liver transplantation Joel Wedd, Joel Wedd Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, COSearch for more papers by this authorKiran M. Bambha, Kiran M. Bambha Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, COSearch for more papers by this authorMatt Stotts, Matt Stotts Division of Gastroenterology and Hepatology, Saint Louis University, Saint Louis, MOSearch for more papers by this authorHeather Laskey, Heather Laskey Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, COSearch for more papers by this authorJordi Colmenero, Jordi Colmenero Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, CO Liver Transplant Unit, Institute of Digestive Diseases, Hospital Clinic; August Pi i Sunyer Institute for Biomedical Research (IDIBAPS), Barcelona, SpainSearch for more papers by this authorJane Gralla, Jane Gralla Department of Pediatrics, University of Colorado Denver, Aurora, CO Department of Biostatistics and Informatics, University of Colorado Denver, Aurora, COSearch for more papers by this authorScott W. Biggins, Corresponding Author Scott W. Biggins Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, COAddress reprint requests to Scott W. Biggins, M.D., M.A.S., Division of Gastroenterology and Hepatology, University of Colorado Denver, 1635 Aurora Court, Mail Stop B-154, Aurora, CO 80045. Telephone: 720-848-2293; FAX: 303-724-1891; E-mail: scott.biggins@ucdenver.eduSearch for more papers by this author Joel Wedd, Joel Wedd Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, COSearch for more papers by this authorKiran M. Bambha, Kiran M. Bambha Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, COSearch for more papers by this authorMatt Stotts, Matt Stotts Division of Gastroenterology and Hepatology, Saint Louis University, Saint Louis, MOSearch for more papers by this authorHeather Laskey, Heather Laskey Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, COSearch for more papers by this authorJordi Colmenero, Jordi Colmenero Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, CO Liver Transplant Unit, Institute of Digestive Diseases, Hospital Clinic; August Pi i Sunyer Institute for Biomedical Research (IDIBAPS), Barcelona, SpainSearch for more papers by this authorJane Gralla, Jane Gralla Department of Pediatrics, University of Colorado Denver, Aurora, CO Department of Biostatistics and Informatics, University of Colorado Denver, Aurora, COSearch for more papers by this authorScott W. Biggins, Corresponding Author Scott W. Biggins Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, COAddress reprint requests to Scott W. Biggins, M.D., M.A.S., Division of Gastroenterology and Hepatology, University of Colorado Denver, 1635 Aurora Court, Mail Stop B-154, Aurora, CO 80045. Telephone: 720-848-2293; FAX: 303-724-1891; E-mail: scott.biggins@ucdenver.eduSearch for more papers by this author First published: 10 June 2014 https://doi.org/10.1002/lt.23929Citations: 30 Potential conflict of interest: Nothing to report. This work was funded in part by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK076565) and the Agency for Healthcare Research and Quality (DK076565) to Scott W. Biggins and from the National Institutes of Health (5T32DK07038) to Joel Wedd. Jordi Colmenero was supported by a Dr. Juan Rodes Grant from the Spanish Association for the Study of the Liver. See Editorial on Page 1153 AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract The Model for End-Stage Liver Disease (MELD) score has reduced predictive ability in patients with cirrhosis and MELD scores ≤ 20. We aimed to assess whether a 5-stage clinical model could identify liver transplantation (LT) candidates with low MELD scores who are at increased risk for death. We conducted a case-control study of subjects with cirrhosis and MELD scores ≤ 20 who were awaiting LT at a single academic medical center between February 2002 and May 2011. Conditional logistic regression was used to evaluate the risk of liver-related death according to the cirrhosis stage. We identified 41 case subjects who died from liver-related causes with MELD scores ≤ 20 within 90 days of death while they were waiting for LT. The cases were matched with up to 3 controls (66 controls in all) on the basis of the listing year, age, sex, liver disease etiology, presence of hepatocellular carcinoma, and MELD score. The cirrhosis stage was assessed for all subjects: (1) no varices or ascites, (2) varices, (3) variceal bleeding, (4) ascites, and (5) ascites and variceal bleeding. The MELD scores were similar for cases and controls. Clinical states contributing to death in cases were: sepsis 49%, spontaneous bacterial peritonitis 15%, variceal bleeding 24%, and hepatorenal syndrome 22%. In a univariate analysis, variceal bleeding [odds ratio (OR) = 5.6, P = 0.003], albumin (OR = 0.5, P = 0.041), an increasing cirrhosis stage (P = 0.003), reaching cirrhosis stage 2, 3, or 4 versus lower stages (OR = 3.6, P = 0.048; OR = 7.4, P < 0.001; and OR = 4.1, P = 0.008), a sodium level < 135 mmol/L (OR = 3.4, P = 0.006), and hepatic encephalopathy (OR = 2.3, P = 0.082) were associated with liver-related death. In a multivariate model including the cirrhosis stage, albumin, sodium, and hepatic encephalopathy, an increasing cirrhosis stage (P = 0.010) was independently associated with liver-related death. In conclusion, assessing the cirrhosis stage in patients with low MELD scores awaiting LT may help to select candidates for more aggressive monitoring or for living or extended criteria donation. Liver Transpl 20:1193–1201, 2014. © 2014 AASLD. Abbreviations CI confidence interval CTP Child-Turcotte-Pugh IQR interquartile range LT liver transplantation MELD Model for End-Stage Liver Disease Score OR odds ratio TIPS transjugular intrahepatic portosystemic shunt UCH University of Colorado Hospital Predicting the risk of death for patients on the liver transplantation (LT) waiting list is the goal of risk-stratification tools such as the Model for End-Stage Liver Disease (MELD) score, which has been used as the backbone of liver graft allocation in the United States since 2002. There are limitations to the MELD score's predictive ability for certain subpopulations of transplant patients.1-5 Clinical sequelae of portal hypertension such as ascites, varices, and variceal bleeding have been identified as risk factors for death independent of the MELD score, and these clinical parameters may be particularly important for patients with low MELD scores.6-8 D'Amico et al.9, 10 described discrete stages by which patients with cirrhosis can be classified. This unidirectional model was originally created with 4 stages of cirrhosis and then was expanded to 5 stages. Each stage predicts the risk of 1-year mortality. Stage 1 represents patients with cirrhosis who have never had varices, ascites, or variceal bleeding. Stage 2 patients have had documented varices in the past but have not developed variceal bleeding or ascites. Stage 3 patients have had variceal bleeding but have never had ascites. Stage 4 patients have had ascites with or without varices but have never had variceal bleeding. Stage 5 patients have had ascites and variceal bleeding. The novelty and benefit of this staging model in comparison with the Child-Turcotte-Pugh (CTP) score1-5 come from its cumulative nature. Once a patient develops a clinical scenario that places him or her within a particular stage, that patient will always be at that stage or a more advanced stage until transplantation or death. This helps to mitigate some of the subjective nature of clinical scores such as the CTP score that show only a snapshot of a patient's liver disease severity and are thus more likely to vary from one assessment to another. The 1-year mortality rates for cirrhosis stages 1 to 5 in D'Amico et al.'s model were 1%, 3.5%, 15%, 26%, and 30%, respectively. D'Amico et al.'s cirrhosis stage paradigm also describes the risk of advancing from one stage to another. The importance of this classification tool lies in risk stratification for patients who may be underserved by the MELD score. To our knowledge, this paradigm of 5 cirrhosis stages has never been examined exclusively in patients with low MELD scores. The aim of this study was to analyze liver-related mortality risk in patients with low MELD scores on the LT waiting list with particular attention paid to the cirrhosis stage and its constituent variables. We hypothesized that certain patients with low MELD scores may, as a function of the reduced accuracy of the MELD score in the low MELD score range,8, 11 require more frequent monitoring or more aggressive risk-reduction strategies. PATIENTS AND METHODS Selection of Cases and Controls We used a nested case-control design with 1:n matching for cases and controls in this study. In order to identify cases with low MELD scores and liver-related deaths, we queried the University of Colorado Hospital (UCH) LT database for patients who died after they had been listed for LT but who had not yet undergone LT during the period of February 2002 to May 2011. We included all adults who were 18 to 75 years old; had clinical, histological, or radiographic evidence of cirrhosis; were listed for primary LT; and had a laboratory MELD score ≤ 20 within 90 days of death. Controls were identified from the same time period and database used for the cases. We identified all patients listed for primary LT who did not die within 90 days of placement on the waiting list. As many as 3 control subjects were selected at random from the pool of all potential controls for each case subject matched by the following criteria: (1) year of listing (within 4 years), (2) age at listing (within 5 years), (3) sex, (4) liver disease etiology (hepatitis C virus, alcohol, hepatitis C virus with alcohol, other viral etiology, cholestatic/autoimmune etiology, nonalcoholic steatohepatitis/cryptogenic etiology, or other metabolic/genetic etiology), (5) presence of hepatocellular carcinoma, and (6) MELD score at listing (within 2 points of the lowest MELD score within 90 days of the case subject's death). No control subjects were used more than once. This study protocol received a priori approval by our institutional review board. Data Extraction and Definitions We performed identical chart reviews of cases and controls. The observation period for cases was defined as the period between the lowest MELD score within 90 days of death and the death of the subject. For controls, the observation period started at the time of listing and ended 90 days after listing or at LT, whichever happened first. All MELD scores generated for a patient during the observation period were collected. We established baseline MELD scores for both cases and controls. For cases, the baseline MELD score was the lowest MELD score within 90 days of death. For controls, we used the listing MELD score as the baseline. Two independent reviewers assessed charts for the history of varices, variceal bleeding, ascites, hepatic encephalopathy, and transjugular intrahepatic portosystemic shunts (TIPSs) before the baseline MELD score for cases and at the end of the study period for controls (to allow for a full assessment of prevalent conditions). The top 3 causes of liver-related death among cases were also collected by independent chart review. Subjective variables were assessed by 2 independent chart reviewers, with discordant cases adjudicated by an expert reviewer. The presence of ascites was ascertained in accordance with the International Ascites Club12, 13 and was graded as follows: grade 1 (radiographic evidence only), grade 2 (clinically apparent mild to moderate ascites), grade 3 (large ascites and/or paracentesis > 3 L), or refractory (ascites resistant or intractable to medical therapy and requiring repeated large-volume paracentesis or TIPS). Large ascites was defined as physical examination findings describing tense, massive, large, or similarly described ascites or ascites requiring a paracentesis of at least 3 L. For the purpose of data analysis, at least grade 3 or refractory ascites was required for dichotomous variables. The presence of varices was recorded as any grade documented on endoscopy and including esophageal, gastric, rectal, or small/large bowel varices. Variceal bleeding was defined as any chart or procedural documentation implicating varices as the source of gastrointestinal bleeding. Hepatic encephalopathy was retrieved from clinical notes or from documentation of encephalopathy-modifying medications. Medication use, including the use of nonselective beta-blockers, was collected at the time of the lowest MELD score for cases and at the end of the follow-up period for controls. The cirrhosis stage10 was determined at the date of the baseline MELD score for cases and at the end of the observation period for controls. It was determined with any history of varices, variceal bleeding, and ascites as defined previously. The definition of ascites for the assessment of the cirrhosis stage required a history of at least grade 3 or refractory ascites. Two independent reviewers conducted detailed chart reviews to examine causes of death among cases, and they were coded as liver-related or non–liver-related according to a priori defined criteria as follows: bleeding, infection, sepsis, pulmonary complications (including pneumonia and pulmonary edema), acute renal failure, multiorgan failure, and neurological complications resulting from hepatic encephalopathy. A designation as a non–liver-related death required the absence of a dominant liver-associated cause and a clear non–liver-related cause of death such as acute myocardial infarction, accidental trauma-related death, stroke, or complications of procedures not directly related to care for the liver disease. Indeterminate causes of death were adjudicated by a third independent reviewer. Patients with a non–liver-related death or insufficient information to determine the cause of death were excluded. All albumin and sodium laboratory draws were collected during the observation periods. The albumin and sodium levels at the time of the baseline MELD score for cases and the lowest albumin and sodium levels during the controls' observation period were identified and used for analysis. Statistical Analysis The baseline MELD scores for cases and controls were compared with a mixed effects model to allow the matching of cases to controls. Conditional logistic regression (to account for the matching of cases to controls) was conducted for all potential predictors of liver-related death. Variables that were significant in univariate modeling (P ≤ 0.10) were then entered into a multivariate model. Significance in the multivariate model was defined as P < 0.05. The cirrhosis stage was modeled both as a binary variable (eg, stage 5 versus stages 1-4) and as an ordinal variable (stage 1 versus stage 5) tested for trends. Serum sodium was also modeled as both a binary variable (< or ≥135 mEq/L) and as a continuous variable. The baseline characteristics of the cases and the patients excluded for deaths outside our hospital system were compared with the chi-square test or Fisher's exact test as appropriate, with the Cochran-Armitage trend test for stage comparisons, and with the Wilcoxon rank-sum test for comparisons of ages and MELD scores between cases and excluded patients. SAS 9.3 was used for statistical analysis (SAS Institute, Inc. Cary, NC). RESULTS Characteristics of the Study Cohort Figure 1 shows our patient acquisition flow diagram. We identified 1676 patients who were listed for LT between February 2002 and May 2011. The number of individuals who died while they were listed was 321, and 117 of those who died had a MELD score ≤ 20 within 90 days of death. We excluded 71 patients because they died outside the UCH system, and we had insufficient records to assess the cause of death. Two additional patients were excluded because they had experienced non–liver-related deaths (one due to accidental trauma and the other due to postsphincterotomy bleeding after endoscopic retrograde cholangiopancreatography). Three patients were excluded because they lacked suitable controls meeting the a priori matching criteria. Therefore, our study population included 41 case subjects with each matched to as many as 3 control subjects for a total of 66 controls. Figure 1Open in figure viewerPowerPoint Patient acquisition flow diagram. Because cases could have up to 3 matched controls, there were some expected imbalances in the demographics of the cases and controls. The median age at death for the cases and the median age at listing for the controls were 58 years [interquartile range (IQR) = 55-60 years] and 55 years (IQR = 52-57 years), respectively. The cases were 51% male, whereas the controls were 61% male. More cases had reached higher stages of cirrhosis in comparison with controls (66% of cases were stage 3 or higher, whereas 24% of controls were; Table 1). An infection from any source was 1 of the top 3 causes of death for 61% of the cases (Table 2). Sepsis, spontaneous bacterial peritonitis, and pulmonary infections were implicated in the deaths of 49%, 15%, and 20% of the cases, respectively. Gastrointestinal bleeding from any source and variceal bleeding were implicated in the deaths of 29% and 24% of the cases, respectively. Acute renal failure of any cause and hepatorenal syndrome were implicated in the deaths of 32% and 22% of the cases, respectively. Table 1. Cirrhosis Stages for Cases and Controls Stage 1 2 3 4 5 Varices − + + +/− + Variceal bleeding − − + − + Ascites − − − + + Cases [n (%)] 5 (12) 9 (22) 11 (27) 11 (27) 5 (12) Controls [n (%)] 19 (29) 31 (47) 6 (9) 8 (12) 2 (3) Table 2. Disease States Contributing to Liver-Related Deaths Among Cases Contributing Disease State n % Any infection 25 61 Sepsis 20 49 Spontaneous bacterial peritonitis 6 15 Pneumonia/empyema/pulmonary abscess 8 20 Any gastrointestinal bleeding 12 29 Variceal bleeding 10 24 Any acute renal failure 13 32 Hepatorenal syndrome 9 22 NOTE: There were 41 cases; multiple contributing disease states could occur in each individual patient. To examine the potential impact of excluding deaths outside our hospital system with incomplete details about the causes of death, we compared the demographic, laboratory, and clinical data of such patients to our identified cases. Table 3 compares the demographics of the case subjects in our study population to the 71 patients excluded for dying outside our hospital system. Because these patients all had routine care before their deaths, similar data were available for nearly all other data fields in comparison with the cases. There were no significant differences in the baseline characteristics between the case subjects and the patients who were excluded for deaths outside our hospital system. Table 3. Demographic Comparison of Cases and Patients Excluded From the Study Because of Deaths Occurring Outside UCH Characteristic Cases (n = 41) Non-UCH Deaths (n = 71) P Value Sex: male (%) 21 (51) 48 (68) 0.09 Age at death (years)aa The data are presented as medians and IQRs. 58 (55-60) 55 (52-61) 0.27 Etiology [n (%)] Alcohol 10 (24) 14 (20) 0.56 Hepatitis C 12 (29) 22 (31) 0.85 Hepatitis C + alcohol 7 (17) 20 (28) 0.19 Cholestatic/autoimmune 8 (20) 5 (7) 0.07 Other 4 (10) 10 (14) 0.51 Hepatocellular carcinoma [n (%)] 4 (10) 12 (17) 0.30 Baseline MELD scoreaa The data are presented as medians and IQRs.bb Lowest MELD score within 90 days of death. 17 (15-18) 16 (13-18) 0.31 Cirrhosis stage [n (%)] 0.54cc Ordinal variable with a test for trends. 1 5 (12) 10 (14) 2 9 (22) 21 (30) 3 11 (27) 13 (18) 4 11 (27) 20 (28) 5 5 (12) 7 (10) a The data are presented as medians and IQRs. b Lowest MELD score within 90 days of death. c Ordinal variable with a test for trends. In order to evaluate the controls for significant improvements or deterioration after listing, we collected their lowest and highest MELD scores over the observation period. The case and control median baseline MELD scores were 17 (IQR = 15-18) and 16 (IQR = 15-18), respectively (P = 0.19), and this was consistent with effective matching. The median changes between the controls' baseline MELD scores and their highest and lowest MELD scores during the observation period were 0 (IQR = 0-2) and 0 (IQR = 0-2), respectively, and this indicated minimal changes in the controls' MELD scores throughout the observation period. Analysis of Predictors of Deaths With Low MELD Scores Using our 1:n case-control study design, we assessed predictors of liver-related death in univariate analyses and then multivariate analyses. The results of the univariate analysis are shown in Table 4. Statistically significant univariate predictors included prior variceal bleeding [odds ratio (OR) = 5.6, 95% confidence interval (CI) = 1.8-17.7, P = 0.003], prior or current grade 3 or refractory ascites (OR = 4.1, 95% CI = 1.5-11.4, P = 0.008), serum albumin (OR = 0.5, 95% CI = 0.2-1.0, P = 0.041), serum sodium (OR = 0.9, 95% CI = 0.8-1.0, P = 0.051), a serum sodium level < 135 mmol/dL (OR = 3.4, 95% CI = 1.4-8.3, P = 0.006), cirrhosis stages 4 and 5 versus stages 1 to 3 (OR = 4.1, 95% CI = 1.5-11.4, P = 0.008), cirrhosis stages 3 to 5 versus stages 1 and 2 (OR = 7.4, 95% CI = 2.5-21.8, P = <0.001), cirrhosis stages 2 to 5 versus stage 1 (OR = 3.6, 95% CI = 1.0-13.1, P = 0.048), and an increasing stage of cirrhosis as a categorical test for trends (P = 0.003). Prior or current hepatic encephalopathy (OR = 2.3, 95% CI = 0.9-6.0, P = 0.082) also met our threshold for statistical significance in the univariate analysis. Prior or current nonbleeding varices (OR = 1.5, 95% CI = 0.6-3.7, P = 0.36), cirrhosis stage 5 versus cirrhosis stages 1 to 4 (OR = 4.0, 95% CI = 0.7-21.4, P = 0.11), and a history of TIPS placement (OR = 2.3, 95% CI = 0.6-8.4, P = 0.22) did not have a significant association with liver-related death. In a multivariate model including the cirrhosis stage as an ordinal variable tested for trends, serum albumin, serum sodium, and hepatic encephalopathy, only the cirrhosis stage remained significant (P = 0.010; Table 5 and Fig. 2). Table 4. Univariate Analysis of Risk Factors for Liver-Related Mortality Among Patients With Low MELD Scores Listed for LT Variable Cases (n = 41) Controls (n = 66) OR P Value Cirrhosis stages 1-5aa Ordinal variable with a test for trends. — — — 0.003bb Statistically significant in the univariate analysis (P ≤ 0.10). Cirrhosis stage 5 versus stages 1-4 (%) 12 3.0 4.0 0.11 Cirrhosis stages 4 and 5 versus stages 1-3 (%) 39 15 4.1 0.008bb Statistically significant in the univariate analysis (P ≤ 0.10). Cirrhosis stages 3-5 versus stages 1 and 2 (%) 66 24 7.4 <0.001bb Statistically significant in the univariate analysis (P ≤ 0.10). Cirrhosis stages 2-5 versus stage 1 (%) 88 71 3.6 0.048bb Statistically significant in the univariate analysis (P ≤ 0.10). Albumin (g/dL)cc The data are presented as means and standard deviations. 2.5 ± 0.7 2.8 ± 0.6 0.5 0.041bb Statistically significant in the univariate analysis (P ≤ 0.10). Sodium (mmol/L)cc The data are presented as means and standard deviations. 133 ± 4 135 ± 5 0.9 0.051bb Statistically significant in the univariate analysis (P ≤ 0.10). Dichotomous sodium < 135 mmol/L (%) 71 41 3.4 0.006bb Statistically significant in the univariate analysis (P ≤ 0.10). Varices (%) 76 67 1.5 0.36 Variceal bleeding (%) 39 12 5.6 0.003bb Statistically significant in the univariate analysis (P ≤ 0.10). Ascites (%) 39 15 4.1 0.008bb Statistically significant in the univariate analysis (P ≤ 0.10). Hepatic encephalopathy (%) 83 70 2.3 0.08bb Statistically significant in the univariate analysis (P ≤ 0.10). TIPS (%) 17 7.6 2.3 0.22 a Ordinal variable with a test for trends. b Statistically significant in the univariate analysis (P ≤ 0.10). c The data are presented as means and standard deviations. Table 5. Multivariate Analysis of Risk Factors for Liver-Related Mortality Among Patients With Low MELD Scores Listed for LT Variable OR 95% CI P Value Cirrhosis stages 1-5aa Ordinal variable with a test for trends. 0.010 Hepatic encephalopathy 1.8 0.6-5.9 0.31 Continuous sodium (mmol/L) 1.0 0.9-1.1 0.61 Albumin (g/dL) 0.6 0.3-1.4 0.25 a Ordinal variable with a test for trends. Figure 2Open in figure viewerPowerPoint ORs (along with 95% CIs and the P value) for liver-related mortality by cirrhosis stage from a multivariate analysis. The reference is stage 1. Our findings were robust in 3 sensitivity analyses. First, conditional logistic regression was repeated with refractory ascites as the threshold for stage progression, and the cirrhosis stage as an ordinal value tested for trends remained statistically significant (P = 0.046). Second, conditional logistic regression was repeated again after the removal of cases/controls with hepatocellular carcinoma from the analysis. Lastly, in a subgroup analysis of patients who had variceal bleeding, having more than 1 bleed, ever being on nonselective beta-blockers, and undergoing TIPS were not associated with liver-related death (data not shown). In order to investigate nonclinical variables that might explain our findings, we also analyzed available markers of socioeconomic and insurance status in our study population. Two variables of education—whether the subject graduated from high school or obtained a graduate equivalency diploma and whether the subject attended at least some college or technical school—were not significantly associated with death (high school graduation, OR > 999, 95% CI < 0.001 to > 999, P = 0.9932; attending college, OR = 0.5, 95% CI = 0.2-1.2, P = 0.12). The insurance status, coded as private or public insurance, showed a statistically significant protective effect in a univariate analysis (OR = 0.4, 95% CI = 0.2-0.9, P = 0.026); however, when it was included in the multivariate model with the cirrhosis stage, hepatic encephalopathy, serum sodium, and serum albumin, it failed to reach statistical significance (OR = 0.3, 95% CI = 0.1-1.0, P = 0.052), whereas the cirrhosis stage remained statistically significant (P = 0.047). Although the insurance status did not meet our threshold for statistical significance, the numerical value of the OR suggested a protective effect. DISCUSSION This study has examined the role of a new and evolving paradigm for predicting the risk of liver-related death among patients listed for LT with low MELD scores (≤20). Our data suggest that an increasing cirrhosis stage was a major risk factor for 90-day mortality in our study population. After we controlled for several factors through our study design (patient age, sex, liver disease etiology, presence of hepatocellular carcinoma, and MELD score) and developed a multivariate model including the cirrhosis stage, serum sodium, serum albumin, and hepatic encephalopathy, only an increasing cirrhosis stage remained significant as a predictor of death among patients listed for LT with MELD scores ≤ 20. The uniqueness of D'Amico et al.'s model9 is its ability to prognosticate not just mortality but also the risk of a transition to a more advanced stage. Our current study expands on that work through an assessment of cirrhosis stages for patients listed for LT with low MELD scores. The importance of our data is 2-fold. First, our findings have implications for surveillance for patients with low MELD scores while they are awaiting LT. Current United Network for Organ Sharing policy requires updated MELD scores every 3 months for patients with MELD scores from 11 to 18. One hundred seventeen of t