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Background: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent worldwide. Identifying high-risk patients is critical to best utilize limited health care resources. We established a community-based care pathway using 2D ultrasound shear wave elastography (SWE) to identify high risk patients with NAFLD. Our objective was to assess the cost-effectiveness of various non-invasive strategies to correctly identify high-risk patients., Methods: A decision-analytic model was created using a payer's perspective for a hypothetical patient with NAFLD. FIB-4 [≥1.3], NAFLD fibrosis score (NFS) [≥-1.455], SWE [≥8 kPa], transient elastography (TE) [≥8 kPa], and sequential strategies with FIB-4 or NFS followed by either SWE or TE were compared to identify patients with either significant (≥F2) or advanced fibrosis (≥F3). Model inputs were obtained from local data and published literature. The cost/correct diagnosis of advanced NAFLD was obtained and univariate sensitivity analysis was performed., Results: For ≥F2 fibrosis, FIB-4/SWE cost $148.75/correct diagnosis while SWE cost $276.42/correct diagnosis, identifying 84% of patients correctly. For ≥F3 fibrosis, using FIB-4/SWE correctly identified 92% of diagnoses and dominated all other strategies. The ranking of strategies was unchanged when stratified by normal or abnormal ALT. For ≥F3 fibrosis, the cost/correct diagnosis was less in the normal ALT group., Conclusions: SWE based strategies were the most cost effective for diagnosing ≥F2 fibrosis. For ≥F3 fibrosis, FIB-4 followed by SWE was the most effective and least costly strategy. Further evaluation of the timing of repeating non-invasive strategies are required to enhance the cost-effective management of NAFLD., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: SEC reports clinical trial support from Gilead Sciences, Genfit, Boehringer Ingelheim, Allergan, BMS and Sequana and has provided consulting services for Intercept Pharmaceuticals, Eisai, and AstraZeneca and Paladin Labs outside the submitted work. AAS reports research grant support from grants from Gilead Sciences and Intercept Pharmaceuticals and has provided consulting services for Intercept Pharmaceuticals and Gilead Sciences outside the submitted work. MGS reports consulting or speaker services for Intercept Pharmaceuticals, Gilead Sciences, Abbott, Novartis and research and clinical trial support from Gilead Sciences, Intercept, CymaBay, Genkyotex, Novartis, Pfizer, Genfit, GSK, Astra Zeneca outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Introduction: B cells are important regulators of both adaptive and innate immunity. The normal liver contains significant numbers of B cells, and their numbers increase dramatically in immune-mediated liver diseases. Our previous observations suggest a hepatoprotective effect of the antidepressant mirtazapine in human and experimental immune-mediated liver disease. Therefore, we performed a series of experiments to determine the impact of mirtazapine treatment on hepatic B cell homeostasis, as reflected by B cell number, trafficking and phenotype using flow cytometry (FCM) and intravital microscopy (IVM) analysis. Mirtazapine treatment rapidly induced a significant reduction in total hepatic B cell numbers, paralleled by a compositional shift in the predominant hepatic B cell subtype from B2 to B1. This shift in hepatic B cells induced by mirtazapine treatment was associated with a striking increase in total hepatic levels of the chemokine CXCL10, and increased production of CXCL10 by hepatic macrophages and dendritic cells. Furthermore, mirtazapine treatment led to an upregulation of CXCR3, the cognate chemokine receptor for CXCL10, on hepatic B cells that remained in the liver post-mirtazapine. A significant role for CXCR3 in the hepatic retention of B cells post-mirtazapine was confirmed using CXCR3 receptor blockade. In addition, B cells remaining in the liver post-mirtazapine produced lower amounts of the proinflammatory Th1-like cytokines IFNγ, TNFα, and IL-6, and increased amounts of the Th2-like cytokine IL-4, after stimulation in vitro ., Conclusion: Mirtazapine treatment rapidly alters hepatic B cell populations, enhancing hepatic retention of CXCR3-expressing innate-like B cells that generate a more anti-inflammatory cytokine profile. Mirtazapine-induced hepatic B cell shifts could potentially represent a novel therapeutic approach to immune-mediated liver diseases characterized by B cell driven pathology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Almishri, Davis, Shaheen, Altonsy, Jenne and Swain.)

Background: Electronic medical records (EMRs) contain large amounts of rich clinical information. Developing EMR-based case definitions, also known as EMR phenotyping, is an active area of research that has implications for epidemiology, clinical care, and health services research., Objective: This review aims to describe and assess the present landscape of EMR-based case phenotyping for the Charlson conditions., Methods: A scoping review of EMR-based algorithms for defining the Charlson comorbidity index conditions was completed. This study covered articles published between January 2000 and April 2020, both inclusive. Embase (Excerpta Medica database) and MEDLINE (Medical Literature Analysis and Retrieval System Online) were searched using keywords developed in the following 3 domains: terms related to EMR, terms related to case finding, and disease-specific terms. The manuscript follows the Preferred Reporting Items for Systematic reviews and Meta-analyses extension for Scoping Reviews (PRISMA) guidelines., Results: A total of 274 articles representing 299 algorithms were assessed and summarized. Most studies were undertaken in the United States (181/299, 60.5%), followed by the United Kingdom (42/299, 14.0%) and Canada (15/299, 5.0%). These algorithms were mostly developed either in primary care (103/299, 34.4%) or inpatient (168/299, 56.2%) settings. Diabetes, congestive heart failure, myocardial infarction, and rheumatology had the highest number of developed algorithms. Data-driven and clinical rule-based approaches have been identified. EMR-based phenotype and algorithm development reflect the data access allowed by respective health systems, and algorithms vary in their performance., Conclusions: Recognizing similarities and differences in health systems, data collection strategies, extraction, data release protocols, and existing clinical pathways is critical to algorithm development strategies. Several strategies to assist with phenotype-based case definitions have been proposed., (©Seungwon Lee, Chelsea Doktorchik, Elliot Asher Martin, Adam Giles D'Souza, Cathy Eastwood, Abdel Aziz Shaheen, Christopher Naugler, Joon Lee, Hude Quan. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 01.02.2021.)

Introduction and Objectives: Electronic medical records (EMRs), specifically the discharge summary (DS), can improve secondary use data availability and interprofessional communication. We aimed to describe the completeness of our EMRs by assessing the presence of a DS in the EMR. Additionally, we assessed for indicators of a missing DS., Methods: A chart review was conducted on 3,011 non-obstetric adult inpatient charts in Calgary, Alberta. 893 charts were missing an electronic DS. A 10% sample was drawn to evaluate the presence of a paper DS. A Chi-square test, Fisher's test and logistic regression measured the associations between electronic DS absence and i) patient and hospital characteristics, and ii) patient comorbidities., Results: The univariate analyses showed that age, being a surgical patient, a Charlson Comorbidity Index (CCI) of

Background & Aims: In addition to monitoring adverse events (AEs) and post-colonoscopy colorectal cancers (PCCRC), indicators for assessing colonoscopy quality include adenoma detection rate (ADR) and cecal intubation rate (CIR). It is unclear whether there is an association between annual colonoscopy volume and ADR, CIR, AEs, or PCCRC., Methods: We searched publication databases through March 2019 for studies assessing the relationship between annual colonoscopy volume and outcomes, including ADR, CIR, AEs, or PCCRC. Pooled odds ratios (ORs) were calculated using DerSimonian and Laird random effects models. Sensitivity analyses were performed to assess for potential methodological or clinical factors associated with outcomes., Results: We performed a systematic review of 9235 initial citations, generating 27 retained studies comprising 11,276,244 colonoscopies. There was no association between procedural volume and ADR (OR, 1.00; 95% CI, 0.98-1.02 per additional 100 annual procedures). CIR improved with each additional 100 annual procedures (OR, 1.17; 95% CI, 1.08-1.28). There was a non-significant trend toward decreased overall AEs per additional 100 annual procedures (OR, 0.95; 95% CI, 0.90-1.00). There was considerable heterogeneity among most analyses., Conclusions: In a systematic review and meta-analysis, we found higher annual colonoscopy volumes to correlate with higher CIR, but not with ADR or PCCRC. Trends toward fewer AEs were associated with higher annual colonoscopy volumes. There are few data available from endoscopists who perform fewer than 100 annual colonoscopies. Studies are needed on extremes in performance volumes to more clearly elucidate associations between colonoscopy volumes and outcomes., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Emerging technologies for monitoring subclinical liver fibrosis include transient elastography (TE) and shear wave elastography (SWE). A systematic review was conducted to assess the prevalence and report on predictors of liver fibrosis as detected by these technologies in inflammatory arthritis (IA) patients, including rheumatoid arthritis, spondyloarthritis and juvenile idiopathic arthritis., Methods: MEDLINE, EMBASE and Web of Science were searched from inception to 06/27/2016 using search terms for IA or DMARDs and TE/SWE. Studies reporting on prevalence and/or risk factors for liver fibrosis as detected by TE/SWE were included. A meta-analysis was not conducted due to study heterogeneity., Results: Seven cross-sectional and three case-control studies were included. The cut-off values to define liver fibrosis ranged from 5.3-8.6 kPa. The prevalence of liver fibrosis in RA detected by TE/SWE ranged from 3-23%, with higher prevalence found in studies using a 5.3kPa cut-off. In two studies fibrosis was reported in 16-17% of PsA patients with no JIA studies identified. Obesity was the most consistently reported independent predictor of fibrosis in three studies. Liver function tests (LFTs) were found to independently predict increased liver stiffness in one study, while cumulative dose of either methotrexate or leflunomide were predictors in two studies., Conclusions: Methotrexate or leflunomide cumulative dose was not consistently reported as an independent predictor of liver fibrosis; whereas, obesity was more consistently identified. Of note, LFTs did not consistently predict elevated TE/SWE measures. Further studies are needed to evaluate the prevalence and predictors of liver fibrosis and to explore the utility of using TE/SWE in IA patients.

Background: Malnutrition is an important predictor of morbidity and mortality among cirrhotic patients. Our objectives were to assess protein-calorie malnutrition (PCM) in cirrhotic pre-liver transplant patients and to study the correlation between subjective global assessment (SGA) and other objective measures of malnutrition., Methods: We recruited pre-liver transplant adult patients at our center between October 2012 and Oct 2015. Nutrition status was assessed via SGA. PCM was assessed by comparing recommended to actual protein and calorie intake. SGA was correlated with body mass index (BMI), dry BMI, handgrip strength by calibrated dynometer (HGS), and mid-arm circumference (MAC). We used non-parametric statistical methods in our analysis., Results: Seventy patients were included in this study. Majority were males (n = 46, 66%) with a median age of 58 years (IQR: 50-61). Moderate to severe malnutrition was prevalent in our cohort (SGA-A: n = 15 (21.4%), SGA-B: n = 30 (42.9%) and SGA-C: n = 25 (35.7%). There was a significant difference in the recommended calories consumed between SGA groups (A 98.5% vs. C 79.2%, P = 0.03). A similar trend was observed for the recommended protein consumed (A 85.4%, C 62.5%; P = 0.09). SGA correlated with BMI (A = 26.4, C = 22.4; P<0.01), Dry BMI (A = 25.9, C = 20.4; P<0.01), HGS (A = 67.0, C = 47.0 PSI; P = 0.03), and MAC (A = 29.5 cm, C = 22.0 cm; P<0.01). HGS and MAC were strongly correlated (Spearman correlation 0.49, P<0.01)., Conclusions: Cirrhotic patients have significant protein-calorie malnutrition. Multiple malnutrition tools including BMI, dry BMI, HGS and MAC were precisely able to assess malnutrition., (Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: The management of acute biliary diseases often involves endoscopic retrograde cholangiopancreatography (ERCP), but it is not clear whether this technique reduces mortality. We investigated whether mortality from acute biliary diseases that require ERCP has been reduced over time and explored factors associated with mortality., Methods: We conducted a cohort study using the Nationwide Inpatient Sample (1998-2008). We identified hospitalizations for choledocholithiasis, cholangitis, and acute pancreatitis that involved ERCP. Multivariate analyses were used to determine the effects of time period, patient factors, hospital characteristics, features of the ERCP procedure, and types of cholecystectomies on mortality, length of stay, and costs., Results: From 1998 to 2008 there were 166,438 admissions for acute biliary conditions that met the inclusion criteria, corresponding to more than 800,000 patients nationwide. During this interval, mortality decreased from 1.1% to 0.6% (adjusted odds ratio [aOR], 0.7; 95% confidence interval [CI], 0.6-0.8), diagnostic ERCPs decreased from 28.8% to 10.0%, hospitals performing fewer than 100 ERCPs per year decreased from 38.4% to 26.9%, open cholecystectomies decreased from 12.4% to 5.8%, and unsuccessful ERCPs decreased from 6.3% to 3.2% (P < .0001 for all trends). Unsuccessful ERCP (aOR, 1.7; 95% CI, 1.4-2.2), open cholecystectomy (aOR, 3.4; 95% CI 2.7-4.3), cholangitis (aOR, 1.9; 95% CI, 1.5-2.3), older age, having Medicare health insurance, and comorbidity were associated with increased mortality., Conclusions: In-hospital mortality from acute biliary conditions requiring ERCP in the United States has decreased over time. Reductions in the rate of unsuccessful ERCPs and open cholecystectomies are associated with this trend., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Mortality for liver resection has remarkably improved owing to multiple factors. We sought to determine the impact of the various types of fellowship training on patient survival after liver resection., Methods: Patients who underwent hepatic resection between 1995 and 2004 in either the Calgary or Capital health regions (Edmonton) of Alberta, Canada, were identified using ICD-9 and -10 codes. Primary outcomes included in-hospital mortality and patient survival according to surgeon volume and training type (surgical oncology v. hepatobiliary v. others)., Results: A total of 1033 patients underwent hepatic resection. Surgeon volume was not predictive of either in-hospital mortality (adjusted odds ratio 0.63, 95% confidence interval [CI] 0.32-1.20) or patient survival (unadjusted hazard ratio 1.11, 95% CI 0.82-1.51). Nonsignificance was also demonstrated for a surgeon's type of fellowship training., Conclusion: The various modes of fellowship training do not appear to influence inhospital mortality or patient survival after hepatic resection.

Background: Hepatectomy is an accepted standard of care for patients with resectable colorectal liver metastases (CLM). Given that it is unclear whether disparities exist between different patient populations, a population-based analysis was performed to analyze this issue with regards to resection rates and surgical mortality in patients with CLM., Methods: Using the Nationwide Inpatient Sample, characteristics and outcomes of adult patients with a diagnosis of colorectal cancer and colorectal metastases that subsequently underwent a liver resection during the years 1993-2007 were identified. Multivariate analysis was used to determine the effects of demographic and clinical covariables on resection rates and in-hospital mortality., Results: Incident colorectal and liver metastases were identified in 138,565 patients; 3,528 patients (2.6%) underwent subsequent resection. African American and Hispanic race were associated with lower resection rates compared to Caucasian patients (adjusted OR 0.61 (0.52 - 0.71) and 0.81 (0.68 - 0.96) respectively). Medicaid insurance was associated with decreased resection rates compared to private insurance (AOR 0.47 (0.40 - 0.56)). The overall inpatient mortality rate was 3.1%. Multivariate analysis determined that mortality rate was correlated to both insurance status and geographic region., Conclusions: The national resection rate is significantly lower than has been reported by most case series. Race and insurance status appear to be correlated to the likelihood of surgical resection. In-hospital mortality is equivalent to the rates reported elsewhere, but is correlated to insurance status and region.

Background & Aims: The Model for End-Stage Liver Disease (MELD) allocation system for liver transplantation (LT) may present a disadvantage for women by including serum creatinine, which is typically lower in females. Our objectives were to investigate gender disparities in outcomes among LT candidates and to assess a revised MELD, including estimated glomerular filtration rate (eGFR), for predicting waiting list mortality., Methods: Adults registered for LT between 2002 and 2007 were identified using the UNOS database. We compared components of MELD, MDRD-derived eGFR, and the 3-month probability of LT and death between genders. Discrimination of MELD, MELDNa, and revised models including eGFR for mortality were compared using c-statistics., Results: A total of 40,393 patients (36% female) met the inclusion criteria; 9% died and 24% underwent LT within 3 months of listing. Compared with men, women had lower median serum creatinine (0.9 vs. 1.0 mg/dl), eGFR (72 vs. 83 ml/min/1.73 m(2)), and mean MELD (16.5 vs. 17.2; all p <0.0005), but within most MELD strata, had higher bilirubin and INR. After adjusting for relevant covariates including creatinine and body weight, women were less likely than men to receive a LT (hazard ratio [HR] 0.85; 95% CI 0.79-0.87) and had greater 3-month mortality (HR 1.13; 95% CI 1.05-1.21). Revision of MELD and MELDNa to include eGFR did not improve discrimination for 3-month mortality (c-statistics: MELD 0.896, MELD-eGFR 0.894, MELDNa 0.911, MELDNa-eGFR 0.905)., Conclusions: Women are disadvantaged under MELD potentially due to its inclusion of creatinine. However, since including eGFR in MELD does not improve mortality prediction, alternative refinements are necessary., (Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Patients discharged from hospital against medical advice are at risk of adverse health outcomes. The frequency and predictors of self-discharge in cirrhotic patients have not been examined., Methods: By using the 1993-2005 US Nationwide Inpatient Sample, we identified 581,380 cirrhotic patients who had been admitted to hospitals. The proportion discharged against medical advice and predictors of self-discharge were analyzed by using regression models with adjustments for clinical factors, including illness severity., Results: Of the patients with cirrhosis identified, 2.8% left their hospital against medical advice. Self-discharge was most common in patients with alcoholic cirrhosis (4.2%) and hepatitis B or C ( approximately 3%) and least common among those with chronic cholestasis (0.4%). Independent predictors of self-discharge included male sex, younger age, non-private insurance, and admission to urban, nonteaching hospitals. Patients undergoing surgery and those with more comorbidities were less likely to leave against medical advice, whereas those with human immunodeficiency virus, drug and alcohol abuse, or psychosis were more likely to leave against medical advice. Self-discharge was less common among patients with hepatic decompensation (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.76-0.82), primary liver cancer (OR, 0.49; 95% CI, 0.41-0.59), or prior transplantation (OR, 0.37; 95% CI, 0.25-0.55). Length of stay and hospital charges were lower in patients discharged against medical advice (P < .0001)., Conclusions: Approximately 1 in 36 hospitalized cirrhotic patients leave hospital against medical advice. Self-discharge is most common among patients with alcoholic cirrhosis, lower socioeconomic status, psychiatric disorders, substance abuse, and less severe liver disease. These findings might assist in the prevention of self-discharge and, ultimately, improve health outcomes in patients with cirrhosis.

Background & Aims: Management of upper gastrointestinal bleeding (UGIB) often requires urgent endoscopic intervention; limitations in its availability on weekends might be associated with increased mortality, compared with patients admitted on weekdays., Methods: We used the 1993-2005 U.S. Nationwide Inpatient Sample to identify patients hospitalized for UGIB caused by peptic ulceration. Differences in in-hospital mortality between patients admitted on weekends and weekdays were evaluated by using logistic regression models, adjusting for patient and clinical factors including the timing of upper endoscopy., Results: Between 1993 and 2005, there were 237,412 admissions to 3,166 hospitals for peptic ulcer-related UGIB. Compared with patients admitted on a weekday, those admitted on the weekend had an increased risk of death (3.4% vs 3.0%; adjusted odds ratio [OR], 1.08; 95% confidence interval [CI], 1.02-1.15), higher rates of surgical intervention (3.4% vs 3.1%; OR, 1.09; 95% CI, 1.03-1.15), prolonged hospital stays, and increased hospital charges (P < .0001 for all comparisons). Patients admitted on the weekend had a longer mean time to endoscopy (2.21 +/- 0.01 vs 2.06 +/- 0.01 days; P < .0001) and were less likely to undergo endoscopy on the day of admission (30% vs 34%; P < .0001). After adjusting for the timing of endoscopy, weekend admission remained an independent predictor of increased mortality (OR, 1.12; 95% CI, 1.05-1.20)., Conclusions: Patients admitted to hospital on the weekend for peptic ulcer-related hemorrhage have higher mortality and more frequently undergo surgery. Although wait times for endoscopy are prolonged in patients hospitalized on the weekend, this delay does not appear to mediate the weekend effect for mortality.

Background & Aims: Acetaminophen overdose is the most common cause of acute liver failure in the U.S. and other Western countries. Unintentional overdoses, alcohol abuse, and underlying liver disease might increase the risk of hepatotoxicity. In this population-based study, we examined outcomes of acetaminophen overdose, with particular attention to these risk factors., Methods: Patients hospitalized for acetaminophen overdose between 1995 and 2004 were identified retrospectively by using administrative data. Comorbid conditions, suicidal intent, and hepatotoxicity were identified by using International Classification of Diseases-Ninth Revision-Clinical Modification and International Statistical Classification of Diseases and Health-Related Problems, 10th revision diagnostic codes., Results: During the 10-year interval, 1543 patients were hospitalized for acetaminophen overdose; 34% were alcohol abusers, 3% had liver disease, and 13% overdosed unintentionally. Seventy patients (4.5%) developed hepatotoxicity. Unintentional overdoses (odds ratio [OR], 5.18; 95% confidence interval [CI], 3.00-8.95), alcohol abuse (OR, 2.21; 95% CI, 1.30-3.76), underlying liver disease (OR, 3.50; 95% CI, 1.57-7.77), and N-acetylcysteine treatment (OR, 6.75; 95% CI, 2.78-16.39) were independently associated with hepatotoxicity. Fifteen patients (1.0%) died in-hospital; risk factors included older age, unintentional overdoses, alcohol abuse, comorbidities including liver disease, and hepatotoxicity (14% vs 0.3%; P < .0005). During a median follow-up of 5.2 years (range, 1 day-11.0 years), 79 patients (5.1%) died. Approximately half of these deaths were due to preventable conditions including suicide, substance abuse, and trauma., Conclusions: In this population-based study, acetaminophen overdose had a relatively benign short-term course but was associated with substantial long-term mortality caused by preventable conditions. Acetaminophen-related hepatotoxicity is more common in patients with unintentional overdoses, alcohol abuse, and underlying liver disease.

Background & Aims: Esophageal variceal bleeding has a high mortality rate and requires complex management. High provider volume has been associated with improved outcomes for various surgical procedures and medical diagnoses, and volume-based referral has been advocated. The objective of this study was to assess the volume-outcome relationship in patients with esophageal variceal bleeding., Methods: We analyzed the 1998-2005 Nationwide Inpatient Sample to identify patients hospitalized for esophageal variceal bleeding. The effects of hospital volume on in-hospital mortality, length of stay (LOS), and hospital charges were evaluated by using logistic regression models with adjustment for demographic and clinical factors. Hospital volume was classified on the basis of the average annual number of esophageal variceal bleeding admissions during the study interval (low volume, <13; medium volume, 13-25; and high volume, >25)., Results: Between 1998 and 2005, there were 36,807 hospitalizations in 2575 hospitals for esophageal variceal bleeding. The majority of the hospitals were low-volume centers (76%). Overall, in-hospital mortality was 10.9% (95% confidence interval [CI], 10.5%-11.4%), median LOS was 4 days (interquartile range, 2-6), and total per patient charges were $21,144 ($13,240-$36,533). Compared with low-volume centers, admission to a high-volume hospital was associated with an increased risk of death (11.9%; odds ratio, 1.16; 95% CI, 1.03-1.29), prolonged LOS, and increased total charges (P < .005). However, patients admitted to high-volume hospitals were more likely to have negative prognostic characteristics including male gender, non-white race, nonprivate health insurance, alcoholic cirrhosis, hepatic decompensation, and to have been transferred from another institution (P < .05). After adjusting for case mix, volume was not an independent predictor of in-hospital mortality (odds ratio vs low-volume: medium-volume, 0.96; 95% CI, 0.87-1.05; high-volume, 1.03; 95% CI, 0.92-1.15) or LOS; however, medium- and high-volume centers had increased total charges (P < .00005)., Conclusions: The volume-outcome relationship observed for some procedures and conditions does not apply to patients with esophageal variceal bleeding. Therefore, volume-based referral is not indicated to improve short-term outcomes in this condition.