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.

Multimodal multidisciplinary management of alcohol use disorder in liver transplant candidates and recipients.

Alcohol-related liver disease (ALD) is the most common indication for liver transplantation (LT) in the United States. The judicious allocation of organs and improvement in outcomes requires identification and monitoring of patients with ALD at high-risk for relapse post-transplantation. The controversial movement toward early LT for severe alcohol-related hepatitis (SAH) has also raised concern for alcohol relapse. While LT cures ALD, treatment of alcohol use disorder (AUD) must be included in the care plan to prevent a return to drinking and subsequent graft ALD. Patients with underlying AUD must be recognized, offered brief interventions and referred for multimodal multidisciplinary treatment that includes medications and psychotherapies along with sober support groups, family engagement, and a new dedication to healthy living in order to help sustain remission. Such comprehensive care will increase LT candidacy in patients with ALD while optimizing clinical outcomes of patients transplanted with AUD.

Identification of Quantifiable Predictors of Relapse in Patients with Alcohol-Associated Liver Disease.

Abstinence in patients with alcohol-associated liver disease (ALD) reduces mortality. Most predictors of relapse are not quantifiable, preventing objective analysis of relapse risk and targeted intervention to improve clinical outcomes. We prospectively enrolled patients with ALD from November 2016 to December 2019 and administered a survey with two previously published scales to assess insight into alcohol-use disorder (Hanil Alcohol Insight Scale [HAIS]) and social support (Community Assessment Inventory Scale [CAIS]). Relapse was assessed using surveys and metabolite testing. Unadjusted and prespecified adjusted regression analyses identified predictors of relapse. We enrolled 81% of eligible patients (n = 136), of whom 58 had follow-up data available at the time of analysis. Over a median follow-up of 1 year (interquartile range: 0.5-1.4), 10 patients relapsed (17%). Patients who relapsed were more likely to continue drinking despite either a diagnosis of liver disease or a decompensating event, and were less likely to have been transplanted (all P < 0.05). In unadjusted regression, the HAIS and the "support inside the home" subcategory of the CAIS were predictive of relapse, with odds ratio (OR) = 0.84 (95% confidence interval 0.72-0.97) and 0.85 (0.74-0.97). In adjusted regression, the HAIS was no longer significant, with adjusted OR = 0.70 (0.49-1.00, P = 0.05), whereas the "support inside the home' subcategory of CAIS remained significant, with adjusted OR = 0.69 (0.51-0.92, P = 0.01). Conclusions: Risk factors for relapse in patients with ALD were identified and quantified prospectively, suggesting opportunities to objectively identify patients at risk for relapse as well as to intervene to prevent relapse.

Osseointegration Pharmacology: A Systematic Mapping Using Artificial Intelligence.

Clinical performance of osseointegrated implants could be compromised by the medications taken by patients. The effect of a specific medication on osseointegration can be easily investigated using traditional systematic reviews. However, assessment of all known medications requires the use of evidence mapping methods. These methods allow assessment of complex questions, but they are very resource intensive when done manually. The objective of this study was to develop a machine learning algorithm to automatically map the literature assessing the effect of medications on osseointegration. Datasets of articles classified manually were used to train a machine-learning algorithm based on Support Vector Machines. The algorithm was then validated and used to screen 599,604 articles identified with an extremely sensitive search strategy. The algorithm included 281 relevant articles that described the effect of 31 different drugs on osseointegration. This approach achieved an accuracy of 95%, and compared to manual screening, it reduced the workload by 93%. The systematic mapping revealed that the treatment outcomes of osseointegrated medical devices could be influenced by drugs affecting homeostasis, inflammation, cell proliferation and bone remodeling. The effect of all known medications on the performance of osseointegrated medical devices can be assessed using evidence mappings executed with highly accurate machine learning algorithms.

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.

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.

Quality improvement initiative increases total paracentesis and early paracentesis rates in hospitalised cirrhotics with ascites.

OBJECTIVE: Early paracentesis (EP) for rapid diagnosis of spontaneous bacterial peritonitis is considered best practice in the care of admitted patients with cirrhosis and ascites, but inpatient paracentesis is frequently not performed or delayed. We developed a quality improvement (QI) initiative aimed at increasing the proportion of admitted patients with cirrhosis who undergo paracentesis and EP. DESIGN: Pre-post study of a QI initiative. SETTING: A tertiary care hospital in a major metropolitan area. PATIENTS: Hospitalised patients with cirrhosis and ascites. INTERVENTIONS: We targeted care providers in the emergency department (ED) by raising awareness of the importance of EP, developing criteria to identify patients at highest risk of SBP who were prioritised for EP by ED providers and restructuring the ED environment to enable timely paracentesis. RESULTS: 76 patients meeting inclusion criteria were admitted during the postintervention 9-month study period. Of these, 91% (69/76) underwent paracentesis during admission versus 71 % (77/109) preintervention (p=0.001). 81% (56/69) underwent EP within 12 hours of presentation or after a predefined acceptable reason for delay versus 48% (37/77) preintervention (p=0.001). There were no significant differences in in-hospital mortality or length of stay before and after intervention. CONCLUSION: A multidisciplinary QI intervention targeting care in the ED successfully increased the proportion of patients with cirrhosis and ascites undergoing diagnostic paracentesis during admission and EP within 12 hours of presentation.

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.

Inflammatory bowel disease readmissions are associated with utilization and comorbidity.

OBJECTIVES: Hospital care accounts for up to one-third of the cost of inflammatory bowel disease (IBD) management. A select group of patients with IBD is responsible for a large proportion of this utilization, demonstrating the burden of frequent hospitalizations. We aim to better understand the burden of 30-day readmissions among patients with IBD using a national hospital database. STUDY DESIGN: Retrospective cohort study of state-specific inpatient databases. METHODS: The State Inpatient Databases for New York and Florida were used to identify patients with IBD hospitalized between 2009 and 2013. The prevalence of 30-day IBD-specific readmission was determined. The association between 30-day readmission and visit outcomes, specifically length of stay and a composite of comorbid conditions (venous thromboembolism, pneumonia, sepsis, Clostridium difficile infection, enteral and parenteral nutrition, and blood transfusion), was analyzed using multivariable logistic regression. RESULTS: Patients with IBD accounted for 35,514 and 39,506 inpatient stays in New York and Florida, respectively. Of these stays, 13.7% to 16.2% resulted in a 30-day readmission. On multivariable analysis, 30-day readmissions were associated with a longer length of stay than index hospitalizations by 1.00 day (adjusted regression coefficient, 1.00; 95% CI, 0.73-1.26) and a higher likelihood of having a comorbid condition (adjusted odds ratio, 1.83; 95% CI, 1.68-1.99) in New York. Similar associations were confirmed in Florida. CONCLUSIONS: Nearly 1 in 7 hospitalizations of patients with IBD lead to a 30-day readmission. These IBD-specific readmissions are associated with increased utilization and comorbidity. Patients at risk for readmission need to be targeted to improve outcomes and IBD care quality.

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.

Systematic review with meta-analysis on transplantation for alcohol-related liver disease: Very low evidence of improved outcomes.

BACKGROUND: Alcohol-related liver disease (ALD) is a leading cause of liver failure and indication for liver transplantation that arises in the setting of alcohol use disorder (AUD). Previous reviews of transplantation for ALD are limited in scope of outcomes and type of ALD studied. A comprehensive systematic review could improve use of transplantation in ALD and improve future research. We hypothesize that while transplanting ALD may improve mortality and relapse, findings will be limited by pre-specified causes of heterogeneity - assessment and treatment of AUD, definition of ALD, spectrum of ALD studied, assessment and rates of relapse, and study quality and bias. AIM: To optimize liver transplantation for ALD, understanding existing research to guide future research, we conducted a systematic review with meta-analysis. METHODS: We conducted a systematic review, comparing liver transplant to no-transplant in patients with ALD, with a primary outcome of both short- and long-term mortality and relapse. We performed a comprehensive search of MEDLINE, EMBASE, Web of Science, and The Cochrane Library databases for peer-reviewed journal articles comparing use of liver transplant in ALD to no-transplant. Two reviewers independently conducted screening, full text review, and data extraction according to the PRISMA guidelines. We report the quality of the evidence according to the GRADE criteria. RESULTS: We analyzed data from 10 studies. Of 1332 participants, 34.2% (456/1332) had undergone liver transplantation, while 65.8% (876/1332) had not. While random effects meta-analysis suggested transplant in comparison to no-transplant had an association of reduced mortality that did not reach statistical significance, relative risk (RR) = 0.51 (0.25-1.05), but not relapse risk, RR = 0.52 (0.18-1.53), significant heterogeneity limited these findings. When restricted to prospective data, transplant compared to no-transplant significantly reduced mortality, RR = 0.25 (0.13-0.46, P < 0.01), and relapse, RR = 0.25 (0.14-0.45, P < 0.01), with insignificant heterogeneity but persistent small-study effects. The overall quality of the evidence was Very Low. Heterogeneity analysis suggested that AUD assessment and treatment was often not reported while ALD, relapse assessment and rate, and data collection were institutionally rather than standardly defined. CONCLUSION: Systematic review of liver transplantation for ALD suggests reduced mortality and relapse in heterogeneous, institution-specific populations with inherent bias. To understand efficacy of transplanting ALD, our research approach must change.

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.