Prognostic Factors in Alcohol-associated Liver Disease Patients Presenting With First Evidence of Ascites.

GOALS: To identify factors associated with transplantation and death in alcohol-associated liver disease (ALD) patients presenting with first evidence of ascites. BACKGROUND: Ascites development is a poor prognostic sign for patients with cirrhosis. Among ALD patients, the baseline factors at time of ascites development that are associated with eventual transplantation or death are currently unknown. STUDY: Adult patients with ascites in the "Evaluating Alcohol Use in Alcohol-related Liver Disease Prospective Cohort Study" (NCT03267069 clinicaltrials.gov) were identified from 2016 to 2020. Demographic, clinical, and laboratory factors at initial ascites presentation were identified as potential predictors of transplant and death as competing risks. RESULTS: A total of 96 patients were identified. Median (interquartile range) follow-up time was 2.00 years (0.87 to 3.85). By last follow-up, 34/96 patients had been transplanted (35.4%) and 11/96 had died (11.4%). Prognostic factors for transplant included age per decade [hazard ratio (HR): 0.52 (95% CI, 0.33 to 0.83)], employed status [HR: 0.35 (95% CI, 0.14 to 0.90)], and sodium [HR: 0.94 (95% CI, 0.90 to 0.99)], whereas prognostic factors for death were body mass index [HR: 1.11 (95% CI, 1.00 to 1.22)], Charlson index [HR: 2.14 [95% CI, 1.13 to 4.08]), Maddrey Discriminant Function >32 (HR: 5.88 (95% CI, 1.18, 29.39)], aspartate aminotransferase [HR: 0.99 (95% CI, 0.98 to 0.997)], and a prior 12-month abstinence period [HR: 5.53 (95% CI, 1.10 to 27.83)], adjusted for age, sex, and ALD subcategory. CONCLUSIONS: Several factors at initial ascites presentation are associated with increased risk of transplantation or death and validation in larger cohorts will allow for improved risk stratification for ALD patients.

Integration of Cirrhosis Best Practices Into Electronic Medical Record Documentation Associated With Reduction in 30-Day Mortality Following Hospitalization.

BACKGROUND: Hospital admissions for patients with cirrhosis continue to increase. In New York City, 25% to 30% of hospitalized cirrhotics are readmitted within 30 days. Rehospitalization is associated with increased mortality, poor quality of life, and financial burden to patients, hospitals, and payers. Preventable readmissions are partially accounted for by a well-documented quality gap between evidence-based guidelines for cirrhosis management and real-world adherence to these recommendations. METHODS: We performed a prospective cohort study that compared outcomes among cirrhotic patients admitted to 4 internal medicine teams over a 6-month period. An electronic medical record (EMR) note template that outlined best-practice measures for cirrhotics was developed. Inpatient providers on 2 teams were instructed to include it in daily progress notes and discharge summaries. The recommended practices included diagnostic paracentesis and diuretics for ascites, rifaximin, and lactulose for hepatic encephalopathy, beta blockers for esophageal varices, and antibiotic prophylaxis for spontaneous bacterial peritonitis. The remaining 2 teams continued the standard of care for cirrhotic patients. The primary outcome was 30-day readmissions. Secondary outcomes included in-hospital mortality, 30-day mortality, length of stay, and adherence to best-practice guidelines. RESULTS: Over a 6-month period, 108 cirrhotic patients were admitted, 83 in the interventional group and 25 in the control group. MELD-Na scores on admission did not differ between the groups (20.1 vs. 21.1, P =0.56). Thirty-day readmissions were not significantly different between the interventional and control groups (19.3% vs. 24%, P =0.61). However, 30-day mortality was significantly lower in the interventional group (8.4% vs. 28%, P =0.01). There was no difference between the 2 groups in in-hospital mortality (4.8% vs. 0%, P =0.27), 90-day mortality (15.7% vs. 28.0%, P =0.17) or length of stay (10.2 vs. 12.6 d, P =0.34). Adherence to best-practice metrics was similar between the groups, except for rates of diagnostic paracentesis, which were higher in the interventional group (98% vs. 80%, P =0.01). CONCLUSION: Implementation of an EMR note template with cirrhosis best practices was associated with lower 30-day mortality and higher rates of diagnostic paracentesis among admitted patients with cirrhosis. These findings suggest that the integration of best-practice measures into the EMR may improve outcomes in hospitalized cirrhotic patients. Larger studies are required to validate these findings.

Mortality, sepsis, and organ failure in hospitalized patients with cirrhosis vary by type of infection.

BACKGROUND AND AIM: Infection is associated with substantial morbidity and mortality in cirrhosis, but presumably, not all infections carry the same risk of mortality. We compared outcomes of different sites of infection in a nationally representative sample of inpatients with cirrhosis. METHODS: We queried the Nationwide Readmissions Database for patients with cirrhosis from 2011 to 2014. Cirrhosis and infection diagnoses were identified by previously used algorithms of ICD-9 codes. The following infections were compared: urinary tract infection (UTI), pneumonia, cellulitis, spontaneous bacterial peritonitis (SBP), and Clostridium difficile infection (CDI). The primary outcome was inpatient mortality. Secondary outcomes included sepsis, any organ failure, multiple organ failures, and 30-day readmission. Outcomes were analyzed using logistic regression and included a priori covariates. RESULTS: A total of 1 798 830 weighted index admissions were identified. Infection was present in 29.2% overall-including UTI (13.7%), pneumonia (8.9%), cellulitis (5.2%), CDI (2.8%), and SBP (2.0%). Mortality was significantly higher in pneumonia (19.6%), SBP (18.6%), and CDI (17.4%) compared with cellulitis (7.6%) and UTI (11.8%). Sepsis, any, and multiple organ failures were most commonly seen in pneumonia, SBP, and CDI. Multivariable analysis demonstrated that pneumonia had the highest associated mortality (odds ratio [OR] 2.73, confidence interval [CI] 2.68-2.80) and multiple organ failures (OR 3.59, CI 3.50-3.68). Significantly increased 30-day readmission was seen only with SBP (24.9%). CONCLUSIONS: Outcomes of inpatients with cirrhosis vary significantly depending on the type of infection. The severity and epidemiology of infection in cirrhosis appears to be shifting with pneumonia, not SBP, having the highest prevalence of multiple organ failures and inpatient mortality.

Black Patients Have Unequal Access to Listing for Liver Transplantation in the United States.

BACKGROUND AND AIMS: The Model for End-Stage Liver Disease score may have eliminated racial disparities on the waitlist for liver transplantation (LT), but disparities prior to waitlist placement have not been adequately quantified. We aimed to analyze differences in patients who are listed for LT, undergo transplantation, and die from end-stage liver disease (ESLD), stratified by state and race/ethnicity. APPROACH AND RESULTS: We analyzed two databases retrospectively, the Center for Disease Control Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) and the United Network for Organ Sharing (UNOS) databases, from 2014 to 2018. We included patients aged 25-64 years who had a primary cause of death of ESLD and were listed for transplant in the CDC WONDER or UNOS database. Our primary outcome was the ratio of listing for LT to death from ESLD-listing to death ratio (LDR). Our secondary outcome was the transplant to listing and transplant to death ratios. Chi-squared and multivariable linear regression evaluated for differences between races/ethnicities. There were 135,367 patients who died of ESLD, 54,734 patients who were listed for transplant, and 26,571 who underwent transplant. Patients were mostly male and White. The national LDR was 0.40, significantly lowest in Black patients (0.30), P < 0.001. The national transplant to listing ratio was 0.48, highest in Black patients (0.53), P < 0.01. The national transplant to death ratio was 0.20, lowest in Black patients (0.16), P < 0.001. States that had an above-mean LDR had a lower transplant to listing ratio but a higher transplant to death ratio. Multivariable analysis confirmed that Black race is significantly associated with a lower LDR and transplant to death ratio. CONCLUSIONS: Black patients face a disparity in access to LT due to low listing rates for transplant relative to deaths from ESLD.

Uncontrolled diabetes mellitus increases risk of infection in patients with advanced cirrhosis.

BACKGROUND: Diabetes mellitus (DM) is common in patients with cirrhosis and is associated with increased risk of infection. AIM: To analyze the impact of uncontrolled DM on infection and mortality among inpatients with advanced cirrhosis. METHODS: This study utilized the Nationwide Inpatient Sample from 1998 to 2014. We defined advanced cirrhosis using a validated ICD-9-CM algorithm requiring a diagnosis of cirrhosis and clinically significant portal hypertension or decompensation. The primary outcome was bacterial infection. Secondary outcomes included inpatient mortality stratified by elderly age (age≥70). Multivariable logistic regression analyzed outcomes. RESULTS: 906,559 (29.2%) patients had DM and 109,694 (12.1%) were uncontrolled. Patients who had uncontrolled DM were younger, had less ascites, but more encephalopathy. Bacterial infection prevalence was more common in uncontrolled DM (34.2% vs. 28.4%, OR 1.33, 95% CI 1.29-1.37, p<0.001). Although uncontrolled DM was not associated with mortality, when stratified by age, elderly patients with uncontrolled DM had a significantly higher risk of inpatient mortality (OR 1.62, 95% CI 1.46-1.81). CONCLUSIONS: Uncontrolled DM is associated with increased risk of infection, and when combined with elderly age is associated with increased risk of inpatient mortality. Glycemic control is a modifiable target to improve morbidity and mortality in patients with advanced cirrhosis.

The North American Consortium for the Study of End-Stage Liver Disease-Acute-on-Chronic Liver Failure Score Accurately Predicts Survival: An External Validation Using a National Cohort.

Acute-on-chronic liver failure (ACLF) carries high short-term mortality. The North American Consortium for the Study of End-Stage Liver Disease (NACSELD)-ACLF score, positive if ≥2 organ failures are present, is a bedside tool that predicts short-term mortality in patients with cirrhosis. However, it was created using major liver referral centers, where a minority of patients with cirrhosis are hospitalized. Therefore, this study used the Nationwide Inpatient Sample, a nationally representative database, from 2005 to 2014 to externally validate the NACSELD-ACLF score in a cohort of patients with decompensated cirrhosis who were identified by a validated algorithm. Organ failures were identified using diagnosis codes. The primary objective was to evaluate the association between the NACSELD-ACLF score and inpatient mortality, whereas secondary objectives compared outcomes depending on presence of infection or hospitalization at a transplant center. Multivariate logistic regression was used to compare outcomes, and area under the curve was calculated. There were 1,523,478 discharges that were included with 106,634 (7.0%) having a positive NACSELD-ACLF score. Patients were a mean 58 years old, and a majority were white men. Infection was present in 33.7% of the sample. Inpatient survival decreased with each organ failure and if infection was present. Patients with the NACSELD-ACLF score had significantly lower inpatient survival on crude (94% versus 48%; P < 0.001) and multivariate analysis (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.07-0.08) and area under the receiver operating characteristic curve 0.77 (95% CI, 0.77-0.78). Liver transplant centers had clinically similar but significantly better survival at each organ failure, in patients with the NACSELD-ACLF score, and on multivariate analysis (OR, 1.17; 95% CI, 1.13-1.22). Using a national cohort, our study validated the NACSELD-ACLF score as an excellent, simple bedside tool to predict short-term survival in patients with decompensated cirrhosis.

Early Paracentesis in High-Risk Hospitalized Patients: Time for a New Quality Indicator.

INTRODUCTION: Symptomatic ascites is the most common indication for hospitalization in patients with cirrhosis. Although guidelines recommend paracentesis for all inpatients with ascites, the timing of paracentesis is likely to be crucial. Performance of an early paracentesis and its relationship to outcomes are unknown, particularly among patients at high risk of spontaneous bacterial peritonitis (SBP). METHODS: We included 75,462 discharges of adult patients with cirrhosis presenting with ascites who underwent paracentesis from the State Inpatient Databases of New York, Florida, and Washington from 2009 to 2013. High-risk patients were identified as having concomitant hepatic encephalopathy or acute kidney injury present on admission. The primary outcome was performance of early paracentesis (within 1 hospital day) with secondary outcomes being inpatient mortality, SBP-related mortality, and 30-day readmission. Multivariable logistic regression models included a priori covariates known to impact outcomes. RESULTS: There were 43,492 (57.6%) patients who underwent early paracentesis. High-risk patients (27,496) had lower rates of early paracentesis (52.8% vs 60.5%, P < 0.001). On multivariable analysis, high-risk patients had significantly decreased odds of undergoing early paracentesis (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.71-0.78, P < 0.001). Early paracentesis was associated with a reduced inpatient all-cause mortality (OR 0.68, 95% CI 0.63-0.73, P < 0.001), SBP-related mortality (OR 0.84, 95% CI 0.73-0.94, P = 0.01), and 30-day readmission (OR 0.87, 95% CI 0.82-0.92, P < 0.001). DISCUSSION: Early paracentesis is associated with reduced inpatient mortality, SBP-related mortality, and 30-day readmission. Given its impact on outcomes, early paracentesis should be a new quality metric. Further education and interventions are needed to improve both adherence and outcomes.

Cirrhosis as a Comorbidity in Conditions Subject to the Hospital Readmissions Reduction Program.

INTRODUCTION: Although the Hospital Readmissions Reduction Program (HRRP) has decreased readmissions in targeted conditions, outcomes in high-risk subgroups are unknown. This study analyzed the impact of cirrhosis as a comorbidity on readmissions in conditions subjected to the HRRP. METHODS: Using a longitudinal analysis of the New York, Florida, and Washington State inpatient databases from 2009 to 2013, adult Medicare beneficiaries with a diagnosis-related group of targeted conditions by the HRRP-pneumonia, congestive heart failure (CHF), and myocardial infarction (MI)-were included. Exclusion criteria included inability to assess for readmission, previous liver transplant, or having a readmission not subject to penalty under the HRRP. A sensitivity analysis used the International Classification of Diseases, 9th Revision, Clinical Modification codes to identify pneumonia, CHF, and MI hospitalizations. The primary outcome was 30-day readmission, with secondary outcomes including 90-day readmission, trends, and cirrhosis-specific risk factors for readmission. RESULTS: Of the 797,432 patients included, 8,964 (1.1%) had cirrhosis. Patients with cirrhosis had significantly higher 30-day readmissions overall (29.3% vs 23.8%, P < 0.001) and specifically for pneumonia and CHF, but not for MI. Thirty-day readmission rates significantly decreased in patients without cirrhosis (annual percent change -1.8%, P < 0.001), but not in patients with cirrhosis (P = 0.39). Similar findings were present for 90-day readmissions. A sensitivity analysis confirmed these findings. On multivariable analysis, cirrhosis was associated with significantly higher 30-day readmissions (odds ratio 1.13, P < 0.001). DISCUSSION: When cirrhosis is comorbid in patients with conditions subjected to the HRRP, readmissions are higher and have not improved. Focused efforts are needed to improve outcomes in cirrhosis and other high-risk comorbidities within the HRRP cohort.

The rise of Clostridioides difficile infections and fall of associated mortality in hospitalized advanced cirrhotics.

BACKGROUND & AIMS: Cirrhotics are at increased risk of Clostridioides difficile infection (CDI) and its associated high morbidity and mortality. However, the impact of CDI in cirrhotics over time remains unclear. This study analyses prevalence and mortality in CDI in hospitalized patients with advanced cirrhosis over 15 years and identifies trends. METHODS: Using the Nationwide Inpatient Sample (NIS) from 1998 to 2014, 3 049 696 weighted patients with advanced cirrhosis (defined as evidence of decompensation or oesophageal varices) were identified using a validated algorithm of ICD-9-CM codes and included in the study. Trends were analysed using Cochran Armitage test and joinpoint regression and compared to the general population. Multivariable logistic regression was performed controlling for risk factors that affect mortality in cirrhotics. RESULTS: CDI prevalence in advanced cirrhotics increased from 0.8% to 2.6%, annual percent change (APC) 8.8% (compared to 7.6% for the general population), while CDI-related mortality decreased from 20.7% to 11.3%, APC -3.4% (compared to -2.0% for the general population), from 1998 to 2014. CDI independently increased mortality in advanced cirrhotics (OR 1.47, P < 0.001) and was associated with acute kidney injury (AKI) (OR 2.09, P < 0.001), which itself significantly increased mortality (OR 4.54, P < 0.001). Hepatic encephalopathy and Hispanic ethnicity were interestingly associated with a lower prevalence of CDI. CONCLUSIONS: CDI is increasingly common in advanced cirrhotics, but on the contrary, its associated mortality is decreasing. Despite improvements in outcomes in patients with advanced cirrhosis, CDI is associated with an increased mortality, driven by AKI, and therefore, requires aggressive identification and therapy.

Portal vein thrombosis prevalence and associated mortality in cirrhosis in a nationally representative inpatient cohort.

BACKGROUND AND AIM: Portal vein thrombosis (PVT) is increasingly common in cirrhotics, but its impact on mortality and outcomes is unclear. Studies evaluating PVT have been limited by small sample size. This study analyzes the trend of the prevalence of PVT and its associated mortality in hospitalized decompensated cirrhotics. METHODS: The Nationwide Inpatient Sample, the largest nationally representative database of hospital discharges, was queried from 1998 to 2014. Inpatients older than 18 years with decompensated cirrhosis were included, while those who received liver transplantation or had hepatocellular carcinoma were excluded. The primary outcomes were the trend in prevalence and associated mortality with PVT. Secondary outcomes included identifying risk factors of PVT and the effect of PVT on complications of portal hypertension. Multivariable logistic regression evaluated the outcomes. RESULTS: A total of 3 045 098 discharges were included, of which 1.5% had PVT. PVT prevalence increased from 0.7% to 2.4%, annual percent change of 9%. Mortality associated with PVT declined from 11.9% to 9.1%, annual percent change of -3.0%. In multivariable analysis controlling for factors associated with mortality in cirrhotics, PVT was associated with an increased risk of mortality (OR 1.12, P < 0.001). Multivariable logistic regression also demonstrated that PVT significantly increased the risk of acute kidney injury (OR 1.75, P < 0.001) and hepatorenal syndrome (OR 1.62, P < 0.001). CONCLUSIONS: The prevalence of PVT is increasing while its associated mortality is decreasing. However, PVT still is associated with risk of mortality and kidney injury, implying a significant impact on cirrhotic outcomes.

NEUTRON RADIOGRAPHY MEASUREMENT OF SALT SOLUTION ABSORPTION IN MORTAR.

Some concrete pavements in the US have recently exhibited premature joint deterioration. It is hypothesized that one component of this damage can be attributed to a reaction that occurs when salt-laden water is absorbed in the concrete and reacts with the matrix. This study examines the absorption of CaCl2 solution in mortar via neutron imaging. Mortar specimens were prepared with water to cement ratios, (w/c), of 0.36, 0.42 and 0.50 by mass and exposed to chloride solutions with concentrations ranging from 0 % to 29.8 % by mass. Depth of fluid penetration and moisture content along the specimen length were determined for 96 h after exposure. At high salt concentration (29.8 %), the sorption rate decreased by over 80 % in all samples. Along with changes in surface tension and viscosity, CaCl2 reacts with the cement paste to produce products (Friedel's salt, Kuzel's salt, or calcium oxychloride) that block pores and reduce absorption.

Disruptive behavior in the workplace: Challenges for gastroenterology fellows.

AIM: To assess first-year gastroenterology fellows' ability to address difficult interpersonal situations in the workplace using objective structured clinical examinations (OSCE). METHODS: Two OSCEs ("distracted care team" and "frazzled intern") were created to assess response to disruptive behavior. In case 1, a fellow used a colonoscopy simulator while interacting with a standardized patient (SP), nurse, and attending physician all played by actors. The nurse and attending were instructed to display specific disruptive behavior and disregard the fellow unless requested to stop the disruptive behavior and focus on the patient and procedure. In case 2, the fellow was to calm an intern managing a patient with massive gastrointestinal bleeding. The objective in both scenarios was to assess the fellows' ability to perform their duties while managing the disruptive behavior displayed by the actor. The SPs used checklists to rate fellows' performances. The fellows completed a self-assessment survey. RESULTS: Twelve fellows from four gastrointestinal fellowship training programs participated in the OSCE. In the "distracted care team" case, one-third of the fellows interrupted the conflict and refocused attention to the patient. Half of the fellows were able to display professionalism despite the heated discussion nearby. Fellows scored lowest in the interprofessionalism portion of post-OSCE surveys, measuring their ability to handle the conflict. In the "frazzled intern" case, 68% of fellows were able to establish a calm and professional relationship with the SP. Despite this success, only half of the fellows were successfully communicate a plan to the SP and only a third scored "well done" in a domain that focused on allowing the intern to think through the case with the fellow's guidance. CONCLUSION: Fellows must receive training on how to approach disruptive behavior. OSCEs are a tool that can assess fellow skills and set a culture for open discussion.

Assessment of Abilities of Gastroenterology Fellows to Provide Information to Patients With Liver Disease.

BACKGROUND & AIMS: Patient education is critical in ensuring patient compliance and good health outcomes. Fellows must be able to effectively communicate with their patients, delivering enough information for the patient to understand their medical problem and maximize patient compliance. We created an objective structured clinical examination (OSCE) with 4 liver disease cases to assess fellows' knowledge and ability to inform standardized patients (SPs) about their clinical condition. METHODS: We developed 4 cases highlighting different aspects of liver disease and created a 4-station OSCE: hepatitis B, acute hepatitis C, new diagnosis of cirrhosis, and an end-stage cirrhotic nontransplant candidate. The SP with hepatitis B was minimizing the fact that she could not read English. The acute hepatitis C SP was a nursing student who is afraid that having hepatitis C might jeopardize her career. The SP with the new diagnosis of alcoholic cirrhosis needed to stop drinking, and the end-stage liver disease patient had to grapple with his advanced directives. Twelve fellows from 4 GI training programs participated. Our focus was to assess the fellows' knowledge about liver diseases and the Accreditation Council for Graduate Medical Education competencies of health literacy, shared decision making, advanced directives, and goals of care. The goal for the fellows was to communicate effectively with the SPs, and acknowledge that each patient had an emotionally charged issue to overcome. The SPs used a checklist to rate fellows' performance. Faculty and the SPs observed the cases and provided feedback. The fellows were surveyed on their performance regarding the case. RESULTS: The majority of fellows were able to successfully summarize findings and discuss a plan with the patient in the new diagnosis of cirrhosis (76.92%) and hepatitis C case (100%), but were less successful in the hepatitis B case (30.77%) and the end-of-life case (41.67%). Overall, a small percentage of fellows reflected that they did a good job (22%-33%), except at the end-of-life case (67%). The fellows' greatest challenge was trying to cover a lot of information in a single outpatient visit. CONCLUSIONS: Caring for patients with liver diseases can be complex and time consuming. The patients and fellows' observations were discordant in several areas: for example, the fellows believed they excelled in the end-of-life case, but the SP thought only a small percentage of fellows were able to successfully summarize and discuss the plan. This discrepancy and others highlight important areas of focus in training programs. OSCEs are important to help the fellows facilitate striking the right balance of information delivery and empathy, and this will lead to better patient education, compliance, rapport, and satisfaction.

Noninvasive Measures of Liver Fibrosis and Severity of Liver Disease.

Determining the degree of fibrosis is an important step in the assessment of disease severity in patients with chronic liver disease. Liver biopsy has been the gold standard for estimating the extent of inflammation and fibrosis, although the procedure has limitations such as sampling error and variability. Noninvasive testing has been shown to be equally predictive in ruling out fibrosis or ruling in advanced fibrosis. Serum biomarkers and imaging-based tests have more limited predictive ability when classifying intermediate stages, but these tools can help identify which patients should receive antiviral treatment sooner and require ongoing cancer surveillance without the need for biopsy. Using a combination of serum markers and imaging tests may also be helpful in providing functional assessment of portal hypertension in patients with chronic liver disease.

The Role of Sarcopenia and Frailty in Hepatic Encephalopathy Management.

Normal regulation of total body and circulating ammonia requires a delicate interplay in ammonia formation and breakdown between several organ systems. In the setting of cirrhosis and portal hypertension, the decreased hepatic clearance of ammonia leads to significant dependence on skeletal muscle for ammonia detoxification; however, cirrhosis is also associated with muscle depletion and decreased functional muscle mass. Thus, patients with diminished muscle mass and sarcopenia may have a decreased ability to compensate for hepatic insufficiency and a higher likelihood of developing physiologically significant hyperammonemia and hepatic encephalopathy.