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.

Non-invasive markers of inflammation in alcohol-associated liver disease: A scoping review.

Clinical manifestations of liver inflammation in alcohol-associated liver disease (ALD) can range from asymptomatic to severe alcoholic hepatitis. While biopsy is the gold standard for identifying liver inflammation, it is an invasive procedure with risks of bleeding, visceral damage, and infection. We aim to establish the state of the current literature on non-invasive markers of inflammation in ALD. We searched Ovid MEDLINE, Embase, and the Cochrane Library for original studies on the association between one or more non-invasive biomarker(s) and histological inflammation or hepatitis in ALD patients. Exclusion criteria were lack of histological data, abstract only, non-English-language articles, and animal studies. Two independent reviewers screened abstracts, reviewed full texts, and extracted data from included papers. Our search identified 8051 unique studies. Title and abstract screening resulted in 563 studies, and full-text screening resulted in 31 studies for final inclusion. The majority were single-center observational cohorts with an average sample size of 124. Review of these studies identified 44 unique biomarkers and 8 calculated scores associated with histological inflammation and/or hepatitis, in addition to a metabolomic panel of 468 metabolites. Six studies examined diagnostic accuracy for histological inflammation and/or hepatitis. The highest area under the receiver operating characteristic curve was 0.932 using a model based on four metabolites. This review highlights the available literature on non-invasive markers of inflammation in ALD. There is a dearth of studies that evaluate the diagnostic accuracy of these biomarkers, and larger studies are needed to confirm findings identified in small cohorts.

Patient Perspectives of High-Quality Care on the Liver Transplant Waiting List: A Qualitative Study.

The prevalence of advanced liver disease and listing for liver transplantation is increasing. Prior assessments of quality of care neither incorporate nor emphasize the patient perspective on quality of care, which may impact clinical outcomes. Our aim was to identify patients' perceptions on what constitutes high quality of care, comparing the findings to existing frameworks and assessments to determine if a patient-derived tool assessing quality of care could facilitate efforts to improve health care. We conducted semistructured interviews of patients wait-listed for liver transplantation, asking patients to describe the quality of their health care with a specific focus on how coordination, communication, office visits, hospitalizations, and cost affect their perceptions of the quality of their care. Data collection conducted concurrently with analyses determined emerging themes and saturation. Themes were mapped to an existing quality-of-care conceptual framework. Qualitative analysis revealed thematic saturation after 15 interviews, and an additional 15 interviews were analyzed that confirmed thematic saturation, maximizing the strength of the results. The 30 patients had a median age of 56 years (range, 32-72 years) and included 15 (50%) men. Although patients believed they received a high quality of care, which was substantiated on current existing measures, a qualitative analysis suggested that patient priorities emphasized 5 themes not currently assessed: managing expectations, providing education, responding to patient needs, executing the care plan efficiently, and utilizing interdisciplinary communication and coordination of care. In conclusion, transplant candidates perceived 5 themes that constitute quality of care, and existing quality-of-care measures do not assess these domains, suggesting a role for creating a patient-derived quality-of-care tool to improve health care and clinical outcomes.

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.

A Call to Standardize Definitions, Data Collection, and Outcome Assessment to Improve Care in Alcohol-Related Liver Disease.

Alcohol-related liver disease (ALD) is highly prevalent and appears to be increasingly reported with worsening mortality; thus, optimizing care in this patient population is imperative. This will require a multidisciplinary, multifaceted approach that includes recognizing alcohol use disorder (AUD) and existing treatments for AUD. We must also acknowledge the full spectrum of ALD clinically and histologically. For example, our current clinical definitions of alcohol-related hepatitis (AH) do not address that >95% of severe AH occurs in the setting of cirrhosis with <60% of liver explants having hepatitis. Given that the majority of ALD studies rely on clinical diagnosis and lack pathologic confirmation, prior data on the efficacy of medical treatment or use of transplantation are likely limited by intertrial and intratrial heterogeneity. Added limitations of the current field include the inconsistent reporting of relapse with the use of varying definitions and unreliable assessments. Moreover, studies fail to consistently capture the data variables that likely influence the main outcomes of interest in this population-mortality and relapse-and a global effort to create a standardized data collection tool moving forward could help effectively and efficiently aid in the advancement of this field. Conclusion: To optimize patient care and make best use of a limited resource, a systematic change in the approach to research in this population must be undertaken that creates consistent definitions for use in future research to generate reliable and reproducible results. With this in mind, we concisely reviewed the literature to summarize the current state of treating and managing ALD, the heterogeneity in definitions, and the significant opportunities for clinical and research improvement.

Evaluation of Alcohol Taxes as a Public Health Opportunity to Reduce Liver Transplant Listings for Alcohol-Related Liver Disease.

BACKGROUND: Alcohol-related liver disease (ALD) is a leading indication for liver transplantation. METHODS: State consumption of spirits, wine, and beer was determined from published sources. Excise and ad valorem alcohol taxes of spirits, wine, and beer were calculated following standard practices and correlated using multiple logistic regression models to 2002 to 2015 ALD transplant listing data from the United Network for Organ Sharing database. RESULTS: 21.22% (29,161/137,440) of transplant listings were for ALD. Increased consumption of spirits was associated with increased ALD transplant listings (odds ratio [OR]: 1.67; 95% CI: 1.12 to 2.49, p = 0.01), but wine and beer consumption did not have a statistically significant association with ALD transplant listings. Spirits excise taxes on- and off-premise were inversely associated with ALD transplant listing (OR: 0.79 and 0.82, respectively, both p < 0.02). Beer and wine taxes were not significantly associated with ALD transplant listings. CONCLUSIONS: Transplant listings for ALD are directly associated with spirit consumption and inversely associated with spirits excise taxes. These findings suggest a possible public health benefit of increasing excise taxes for spirits.

Cost Effectiveness of Gastric Cancer Screening According to Race and Ethnicity.

BACKGROUND & AIMS: There are marked racial and ethnic differences in non-cardia gastric cancer prevalence within the United States. Although gastric cancer screening is recommended in some regions of high prevalence, screening is not routinely performed in the United States. Our objective was to determine whether selected non-cardia gastric cancer screening for high-risk races and ethnicities within the United States is cost effective. METHODS: We developed a decision analytic Markov model with the base case of a 50-year-old person of non-Hispanic white, non-Hispanic black, Hispanic, or Asian race or ethnicity. The cost effectiveness of a no-screening strategy (current standard) for non-cardia gastric cancer was compared with that of 2 endoscopic screening modalities initiated at the time of screening colonoscopy for colorectal cancer: upper esophagogastroduodenoscopy with biopsy examinations and continued surveillance only if intestinal metaplasia or more severe pathology is identified or esophagogastroduodenoscopy with biopsy examinations continued every 2 years even in the absence of identified pathology. We used prevalence rates, transition probabilities, costs, and quality-adjusted life years (QALYs) from publications and public data sources. Outcome measures were reported in incremental cost-effectiveness ratios, with a willingness-to-pay threshold of $100,000/QALY. RESULTS: Compared with biennial and no screening, screening esophagogastroduodenoscopy with continued surveillance only when indicated was cost effective for non-Hispanic blacks ($80,278/QALY), Hispanics ($76,070/QALY), and Asians ($71,451/QALY), but not for non-Hispanic whites ($122,428/QALY). The model was sensitive to intestinal metaplasia prevalence, transition rates from intestinal metaplasia to dysplasia to local and regional cancer, cost of endoscopy, and cost of resection (endoscopic or surgical). CONCLUSIONS: Based on a decision analytic Markov model, endoscopic non-cardia gastric cancer screening for high-risk races and ethnicities could be cost effective in the United States.

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.

Fragmented Care is Prevalent Among Inflammatory Bowel Disease Readmissions and is Associated With Worse Outcomes.

OBJECTIVES: Inflammatory bowel disease (IBD) is a complex chronic disease that often requires a multispeciality approach; thus, IBD patients are prone to care fragmentation. We aim to determine the prevalence of fragmentation among hospitalized IBD patients and identify associated predictors and visit-level outcomes. METHODS: The State Inpatient Databases for New York and Florida were used to identify 90-day readmissions among IBD inpatients from 2009 to 2013. The prevalence of fragmentation, defined as a readmission to a non-index hospital, was reported. Characteristics associated with fragmented care were identified using multivariable logistic regression. Multivariable models were utilized to determine the association between fragmentation and outcomes (in-hospital mortality, readmission length of stay, and inpatient colonoscopy). RESULTS: Among IBD inpatients, 25,241 and 29,033 90-day readmission visits were identified, in New York and Florida, respectively. The prevalence of fragmentation was 26.4% in New York and 32.5% in Florida. Younger age, a non-emergent admission type, public payer or uninsured status, mood disorder, and substance abuse were associated with fragmented care, while female gender and a primary diagnosis of an IBD-related complication had an inverse association. Fragmented inpatient care is associated with a higher likelihood of in-hospital death, higher rates of inpatient colonoscopy, and a longer readmission length of stay. CONCLUSIONS: Over one in four IBD inpatient readmissions are fragmented. Disparities and differences in fragmentation exist and contribute to poor patient outcomes. Additional efforts targeting fragmentation should be made to better coordinate IBD management, reduce healthcare gaps, and promote high-value care.

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.

Timely Use of Probiotics in Hospitalized Adults Prevents Clostridium difficile Infection: A Systematic Review With Meta-Regression Analysis.

BACKGROUND & AIMS: Systematic reviews have provided evidence for the efficacy of probiotics in preventing Clostridium difficile infection (CDI), but guidelines do not recommend probiotic use for prevention of CDI. We performed an updated systematic review to help guide clinical practice. METHODS: We searched MEDLINE, EMBASE, International Journal of Probiotics and Prebiotics, and The Cochrane Library databases for randomized controlled trials evaluating use of probiotics and CDI in hospitalized adults taking antibiotics. Two reviewers independently extracted data and assessed risk of bias and overall quality of the evidence. Primary and secondary outcomes were incidence of CDI and adverse events, respectively. Secondary analyses examined the effects of probiotic species, dose, timing, formulation, duration, and study quality. RESULTS: We analyzed data from 19 published studies, comprising 6261 subjects. The incidence of CDI in the probiotic cohort, 1.6% (54 of 3277), was lower than of controls, 3.9% (115 of 2984) (P < .001). The pooled relative risk of CDI in probiotic users was 0.42 (95% confidence interval, 0.30-0.57; I2 = 0.0%). Meta-regression analysis demonstrated that probiotics were significantly more effective if given closer to the first antibiotic dose, with a decrement in efficacy for every day of delay in starting probiotics (P = .04); probiotics given within 2 days of antibiotic initiation produced a greater reduction of risk for CDI (relative risk, 0.32; 95% confidence interval, 0.22-0.48; I2 = 0%) than later administration (relative risk, 0.70; 95% confidence interval, 0.40-1.23; I2 = 0%) (P = .02). There was no increased risk for adverse events among patients given probiotics. The overall quality of the evidence was high. CONCLUSIONS: In a systematic review with meta-regression analysis, we found evidence that administration of probiotics closer to the first dose of antibiotic reduces the risk of CDI by >50% in hospitalized adults. Future research should focus on optimal probiotic dose, species, and formulation. Systematic Review Registration: PROSPERO CRD42015016395.

Cost Effectiveness of Early Insertion of Transjugular Intrahepatic Portosystemic Shunts for Recurrent Ascites.

BACKGROUND & AIMS: Treatment options for recurrent ascites resulting from decompensated cirrhosis include serial large-volume paracentesis and albumin infusion (LVP+A) or insertion of a transjugular intrahepatic portosystemic shunt (TIPS). Insertion of TIPSs with covered stents during early stages of ascites (early TIPS, defined as 2 LVPs within the past 3 weeks and <6 LVPs in the prior 3 months) significantly improves chances of survival and reduces complications of cirrhosis compared with LVP+A. However, it is not clear if TIPS insertion is cost effective in these patients. METHODS: We developed a Markov model using the payer perspective for a hypothetical cohort of patients with cirrhosis with recurrent ascites receiving early TIPSs or LVP+A using data from publications and national databases collected from 2012 to 2018. Projected outcomes included quality-adjusted life-year (QALY), costs (2017 US dollars), and incremental cost-effectiveness ratios (ICERs; $/QALY). Sensitivity analyses (1-way, 2-way, and probabilistic) were conducted. ICERs less than $100,000 per QALY were considered cost effective. RESULTS: In base-case analysis, early insertion of TIPS had a higher cost ($22,770) than LVP+A ($19,180), but also increased QALY (0.73 for early TIPSs and 0.65 for LVP+A), resulting in an ICER of $46,310/QALY. Results were sensitive to cost of uncomplicated TIPS insertion and transplant, need for LVP+A, probability of transplant, and decompensated QALY. In probabilistic sensitivity analysis, TIPS insertion was the optimal strategy in 59.1% of simulations. CONCLUSIONS: Based on Markov model analysis, early placement of TIPSs appears to be a cost-effective strategy for management of specific patients with cirrhosis and recurrent ascites. TIPS placement should be considered early and as a first-line treatment option for select patients.