Early Diagnostic Paracentesis Improves Outcomes of Hospitalized Patients With Cirrhosis and Ascites: A Systematic Review and Meta-Analysis.

INTRODUCTION: Diagnostic paracentesis is recommended for patients with cirrhosis admitted to the hospital, but adherence is suboptimal with unclear impact on clinical outcomes. The aim of this meta-analysis was to assess the outcomes of early vs delayed diagnostic paracentesis among hospitalized patients with cirrhosis and ascites. METHODS: We searched multiple databases for studies comparing early vs delayed diagnostic paracentesis among hospitalized patients with cirrhosis and ascites. The pooled odds ratio (OR) and mean difference with confidence intervals (CIs) for proportional and continuous variables were calculated using the random-effects model. Early diagnostic paracentesis was defined as receiving diagnostic paracentesis within 12-24 hours of admission. The primary outcome was in-hospital mortality. Secondary outcomes were length of hospital stay, acute kidney injury, and 30-day readmission. RESULTS: Seven studies (n = 78,744) (n = 45,533 early vs n = 33,211 delayed diagnostic paracentesis) were included. Early diagnostic paracentesis was associated with lower in-hospital mortality (OR 0.61, 95% CI 0.46-0.82, P = 0.001), length of hospital stay (mean difference -4.85 days; 95% CI -6.45 to -3.20; P < 0.001), and acute kidney injury (OR 0.62, 95% CI 0.42-0.92, P = 0.02) compared with delayed diagnostic paracentesis, with similar 30-day readmission (OR 1.11, 95% CI 0.52-2.39, P = 0.79). Subgroup analysis revealed consistent results for in-hospital mortality whether early diagnostic paracentesis performed within 12 hours (OR 0.51, 95% CI 0.32-0.79, P = 0.003, I2 = 0%) or within 24 hours of admission (OR 0.67, 95% CI 0.45-0.98, P = 0.04, I2 = 82%). Notably, the mortality OR was numerically lower when diagnostic paracentesis was performed within 12 hours, and the results were precise and homogenous ( I2 = 0%). DISCUSSION: Findings from this meta-analysis suggest that early diagnostic paracentesis is associated with better patient outcomes. Early diagnostic paracentesis within 12 hours of admission may be associated with the greatest mortality benefit. Data from large-scale randomized trials are needed to validate our findings, especially if there is a greater mortality benefit for early diagnostic paracentesis within 12 hours.

Thirty-Day Readmissions Are Largely Not Preventable in Patients With Cirrhosis.

INTRODUCTION: Hospital readmissions are common in patients with cirrhosis, but there are few studies describing readmission preventability. We aimed to describe the incidence, causes, and risk factors for preventable readmission in this population. METHODS: We performed a prospective cohort study of patients with cirrhosis hospitalized at a single center between June 2014 and March 2020 and followed up for 30 days postdischarge. Demographic, clinical, and socioeconomic data, functional status, and quality of life were collected. Readmission preventability was independently and systematically adjudicated by 3 reviewers. Multinomial logistic regression was used to compare those with (i) preventable readmission, (ii) nonpreventable readmission/death, and (iii) no readmission. RESULTS: Of 654 patients, 246 (38%) were readmitted, and 29 (12%) were preventable readmissions. Reviewers agreed on preventability for 70% of readmissions. Twenty-two (including 2 with preventable readmission) died. The most common reasons for readmission were hepatic encephalopathy (22%), gastrointestinal bleeding (13%), acute kidney injury (13%), and ascites (6%), and these reasons were similar between preventable and nonpreventable readmissions. Preventable readmission was often related to paracentesis timeliness, diuretic adjustment monitoring, and hepatic encephalopathy treatment. Compared with nonreadmitted patients, preventable readmission was independently associated with racial and ethnic minoritized individuals (odds ratio [OR] 5.80; 95% CI, 1.96-17.13), nonmarried marital status (OR 2.88; 95% CI, 1.18-7.05), and admission in the prior 30 days (OR 3.45; 95% CI, 1.48-8.04). DISCUSSION: For patients with cirrhosis, readmission is common, but most are not preventable. Preventable readmissions are often related to ascites and hepatic encephalopathy and are associated with racial and ethnic minorities, nonmarried status, and prior admissions.

Health disparities in chronic liver disease.

The syndemic of hazardous alcohol consumption, opioid use, and obesity has led to important changes in liver disease epidemiology that have exacerbated health disparities. Health disparities occur when plausibly avoidable health differences are experienced by socially disadvantaged populations. Highlighting health disparities, their sources, and consequences in chronic liver disease is fundamental to improving liver health outcomes. There have been large increases in alcohol use disorder in women, racial and ethnic minorities, and those experiencing poverty in the context of poor access to alcohol treatment, leading to increasing rates of alcohol-associated liver diseases. Rising rates of NAFLD and associated fibrosis have been observed in Hispanic persons, women aged > 50, and individuals experiencing food insecurity. Access to viral hepatitis screening and linkage to treatment are suboptimal for racial and ethnic minorities and individuals who are uninsured or underinsured, resulting in greater liver-related mortality and later-stage diagnoses of HCC. Data from more diverse cohorts on autoimmune and cholestatic liver diseases are lacking, supporting the need to study the contemporary epidemiology of these disorders in greater detail. Herein, we review the existing literature on racial and ethnic, gender, and socioeconomic disparities in chronic liver diseases using a social determinants of health framework to better understand how social and structural factors cause health disparities and affect chronic liver disease outcomes. We also propose potential solutions to eliminate disparities, outlining health-policy, health-system, community, and individual solutions to promote equity and improve health outcomes.

PROMIS Profile-29 is a valid instrument with distinct advantages over legacy instruments for measuring the quality of life in chronic liver disease.

BACKGROUND AND AIMS: The Patient-Reported Outcomes Measurement Information System (PROMIS) is increasingly used to measure health-related quality of life, yet, it has not been well-studied in chronic liver disease (CLD). This study compares PROMIS Profile-29 to Short-Form Health Survey (SF-36) and Chronic Liver Disease Questionnaire (CLDQ) in patients with CLD. APPROACH AND RESULTS: In all, 204 adult outpatients with CLD completed PROMIS-29, CLDQ, SF-36 and usability questionnaires. Mean scores were compared between groups, the correlation between domain scores was assessed, and floor/ceiling effects were calculated. Etiologies of CLD were NAFLD (44%), hepatitis C (16%), and alcohol (16%). Fifty-three percent had cirrhosis and 33% were Child-Pugh B/C with a mean model for end-stage liver disease score of 12.0. In all 3 tools, the poorest scores were in physical function and fatigue. The presence of cirrhosis or complications was associated with worse scores in most PROMIS Profile-29 domains, indicating known group validity. Strong correlations ( r ≥ 0.7) were present between Profile-29 and SF-36 or CLDQ domains measuring similar concepts, indicating strong convergent validity. Profile-29 was completed faster than SF-36 and CLDQ (5.4 ± 3.0, 6.7 ± 3.3, 6.5 ± 5.2 min, p = 0.003) and rated equally on usability. All CLDQ and SF-36 domains reached the floor or ceiling, while none were noted for Profile-29. These floor/ceiling effects were magnified when assessed in those with and without cirrhosis, indicating the improved depth of measurement by Profile-29. CONCLUSIONS: Profile-29 is a valid, more efficient, well-received tool that provides an improved depth of measurement when compared to SF-36 and CLDQ and, therefore, an ideal tool to measure general health-related quality of life in CLD.

Clinical characteristics and prognosis of hospitalized patients with moderate alcohol-associated hepatitis.

BACKGROUND AND AIMS: Little is known about the clinical characteristics and prognosis of hospitalized patients with moderate alcohol-associated hepatitis (mAH) as compared to severe alcohol-associated hepatitis (sAH). Therefore, we aimed to describe the clinical characteristics and risk factors associated with mortality in hospitalized mAH patients. METHODS: Patients hospitalized with alcohol-associated hepatitis (AH) from 1 January 2010 to 31 December 2020 at a large US healthcare system [11 hospitals, one liver transplant centre] were retrospectively analysed for outcomes. Primary outcome was 90-day mortality. AH and mAH were defined according to NIAAA Alcoholic Hepatitis Consortia and Model for End-stage Liver Disease Score ≤ 20 respectively. Multivariable Cox regression analysis was performed to identify independent risk factors associated with 90-day mortality. RESULTS: 1504 AH patients were hospitalized during the study period, of whom 39% (n = 590) had mAH. Compared to sAH patients, mAH patients were older (50 vs. 48 years, p < 0.001) and less likely to have underlying cirrhosis (74% vs. 83%, p < 0.001). There were no differences between the two groups for median alcohol intake g/day (mAH 140.0 vs. sAH 112.0, p = 0.071). The cumulative proportion surviving at 90 days was 88% in mAH versus 62% in sAH (p < 0.001). On multivariable analysis, older age [HR 1.03 (95% CI 1.00-1.06), p = 0.020], corticosteroid use [HR 1.80 (95% CI 1.06-3.06), p = 0.030] and acute kidney injury (AKI) [HR 2.43 (95% CI 1.33-4.47), p = 0.004] were independently associated with 90-day mortality. CONCLUSIONS: mAH carries a 12% mortality rate at 90 days. Age, AKI and corticosteroid use were associated with an increased risk for 90-day mortality. Avoidance of corticosteroids and strategies to reduce the risk of AKI could improve outcomes in mAH patients.

Severe hepatic encephalopathy with mechanical ventilation may inform waitlist priority in acute liver failure: A UNOS database analysis.

BACKGROUND & AIMS: Patients with acute liver failure (ALF) awaiting liver transplantation (LT) may develop multiorgan failure, but organ failure does not impact waitlist prioritization. The aim of this study was to examine the impact of organ failure on waitlist mortality risk and post LT outcomes in patients with ALF. METHODS: We studied adults waitlisted for ALF in the United Network for Organ Sharing (UNOS) database (2002-2019). Organ failures were defined using a previously described Chronic Liver Failure modified sequential organ failure score assessment adapted to UNOS data. Regression analyses of the primary endpoints, 30-day waitlist mortality (Competing risk), and post-LT mortality (Cox-proportional hazards), were performed. Latent class analysis (LCA) was used to determine the organ failures most closely associated with 30-day waitlist mortality. RESULTS: About 3212 adults with ALF were waitlisted, for hepatotoxicity (41%), viral (12%) and unspecified (36%) etiologies. The median number of organ failures was three (interquartile range 1-3). Having ≥3 organ failures (vs. ≤2) was associated with a sub hazard ratio (HR) of 2.7 (95%CI 2.2-3.4)) and a HR of 1.5 (95%CI 1.1-2.5)) for waitlist and post-LT mortality, respectively. LCA identified neurologic and respiratory failure as most impactful on 30-day waitlist mortality. The odds ratios for both organ failures (vs. neither) were higher for mortality 4.5 (95% CI 3.4-5.9) and lower for delisting for spontaneous survival .5 (95%CI .4-.7) and LT .6 (95%CI .5-.7). CONCLUSION: Cumulative organ failure, especially neurologic and respiratory failure, significantly impacts waitlist and post-LT mortality in patients with ALF and may inform risk-prioritized allocation of organs.

Racial and ethnic disparities in psychosocial evaluation and liver transplant waitlisting.

Health disparities have been well-described in all stages of the liver transplantation (LT) process. Using data from psychosocial evaluations and the Stanford Integrated Psychosocial Assessment, our objective was to investigate potential racial and ethnic inequities in overall LT waitlisting and not waitlisting for medical or psychosocial reasons. In a cohort of 2271 candidates evaluated for LT from 2014 to 2021 and with 1-8 years of follow-up, no significant associations were noted between race/ethnicity and overall waitlisting and not waitlisting for medical reasons. However, compared with White race, Black race (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.07-2.56) and Hispanic/Latinx ethnicity (OR, 2.10; 95% CI, 1.16-3.78) were associated with not waitlisting for psychosocial reasons. After adjusting for sociodemographic variables, the relationship persisted in both populations: Black (OR, 1.95; 95% CI, 1.12-3.38) and Hispanic/Latinx (OR, 2.29; 95% CI, 1.08-4.86) (reference group, White). High-risk Stanford Integrated Psychosocial Assessment scores were more prevalent in Black and Hispanic/Latinx patients, likely reflecting upstream factors and structural racism. Health systems and LT centers should design programs to combat these disparities and improve equity in access to LT.

Measuring Medication Use, Obstacles, and Knowledge in Individuals With Cirrhosis.

BACKGROUND & AIMS: Although patient knowledge is modifiable, there are no widely accepted tools to measure patient understanding during cirrhosis care. We aimed to develop and validate "My Cirrhosis Coach" (MCC), a personalized, self-administered questionnaire to evaluate cirrhosis-related medication use, obstacles, and understanding. METHODS: Adults with cirrhosis were prospectively enrolled at 3 tertiary centers from July 2016 through July 2020. Psychometrics including confirmatory factor analysis was used to develop and validate a final questionnaire. Content validity was measured via the content validity index and expert performance. Discriminant validity was assessed by comparing scores between groups hypothesized to have varying performance. RESULTS: The MCC was tested in a diverse cohort (n = 713) with cirrhosis and its complications including ascites (45%) and hepatic encephalopathy (33%) with median Model for End-Stage Liver Disease-Sodium 10 (interquartile range, 9-15). A 6-factor model of the MCC fit the data well (root mean square error of approximation, 0.22; comparative fit index, 0.96; standardized root mean squared residual, 0.104; final domains: Medication Use & Accessibility, Medication Obstacles, Lactulose Use, Diuretic Use, Beta Blocker Use, and Dietary Sodium Use). The MCC had excellent content validity (content validity index, 81%-94%) and accuracy (91%-100%) ratings by experts. Mean domain scores ranged from 1.1 to 2.6 (range, 0-3; 3 indicating better performance). Those with a cirrhosis complication scored higher in the relevant medication domain (ie, diuretic use score in ascites). Compared with outpatients, inpatients scored higher in all knowledge domains except salt use and reported more medication obstacles. Scores differed by income, education level, and having an adult at home. CONCLUSIONS: In a large, diverse cohort, we validated the MCC, which can serve to standardize medication use and knowledge measurement in clinical practice and education-based studies in cirrhosis.

The prognostic impact of acute kidney injury recovery patterns in critically ill patients with cirrhosis.

BACKGROUND: The prognostic impact of acute kidney injury (AKI) recovery patterns in critically ill patients with cirrhosis is unknown. We aimed to compare mortality stratified by AKI recovery patterns and identify predictors of mortality in patients with cirrhosis and AKI admitted to the intensive care unit. MATERIALS AND METHODS: Patients with cirrhosis and AKI from 2016 to 2018 at 2 tertiary care intensive care units were analyzed (N=322). AKI recovery was defined by Acute Disease Quality Initiative consensus: return of serum creatinine <0.3 mg/dL of baseline within 7 days of AKI onset. Recovery patterns were categorized by Acute Disease Quality Initiative consensus: 0-2 days, 3-7 days, and no-recovery (persistence of AKI >7 d). Landmark competing risk univariable and multivariable models (liver transplant as competing risk) was used to compare 90-day mortality between AKI recovery groups and to determine independent predictors of mortality. RESULTS: Sixteen percent (N=50) and 27% (N=88) achieved AKI recovery within 0-2 and 3-7 days, respectively; 57% (N=184) had no-recovery. Acute on chronic liver failure was prevalent (83%) and patients with no-recovery were more likely to have grade 3 acute on chronic liver failure (N=95, 52%) compared to patients with AKI recovery [0-2: 16% (N=8); 3-7: 26% (N=23); p<0.001]. Patients with no-recovery had significantly higher probability of mortality [unadjusted-sub-HR (sHR): 3.55; 95% CI: 1.94-6.49; p<0.001] compared to patients with recovery within 0-2 days, while the probability was similar between 3-7 and 0-2 days (unadjusted-sub-HR: 1.71; 95% CI: 0.91-3.20; p=0.09). On multivariable analysis, AKI no-recovery (sub-HR: 2.07; 95% CI: 1.33-3.24; p=0.001), severe alcohol-associated hepatitis (sub-HR: 2.41; 95% CI: 1.20-4.83; p=0.01), and ascites (sub-HR: 1.60; 95% CI: 1.05-2.44; p=0.03) were independently associated with mortality. CONCLUSION: AKI no-recovery occurs in over half of critically ill patients with cirrhosis and AKI and is associated with worse survival. Interventions that facilitate AKI recovery may improve outcomes in this patient population.

High-quality diet, physical activity, and college education are associated with low risk of NAFLD among the US population.

BACKGROUND AND AIMS: The effects of diet quality (DQ), physical activity (PA), and socioeconomic status (SES) on the risk of NAFLD are unclear. We examined the association among DQ, PA, SES, and NAFLD risk. APPROACH AND RESULTS: This is a cross-sectional analysis of the National Health and Nutrition Examination Surveys, 2017-2018, which included 3589 participants with reliable information on vibration-controlled transient elastography (VCTE) measurements, 24-h dietary recalls, PA, and SES. DQ was assessed by the Healthy Eating Index (HEI)-2015. PA was determined by the Global Physical Activity Questionnaire. SES was assessed by the educational attainment and family poverty income ratio (PIR). Risk of NAFLD was considered by means of a composite outcome using VCTE measurements: non-NAFLD versus NAFLD without clinically significant fibrosis (CSF) versus NAFLD with CSF. The NAFLD risk was lower in physically active (≥600 metabolic equivalent of task [MET] min/week) versus inactive participants (<600 MET min/week) (OR: 0.71, p = 0.043). A high-quality diet (HQD) (HEI > 56.64) was associated with a lower risk of NAFLD (OR: 0.58, p < 0.01) compared with a non-HQD. The lowest NAFLD risk was observed in those physically active with HQD (OR: 0.43, p < 0.01). Body mass index and waist circumference significantly mediated the effect of DQ and PA on NAFLD risk. Education (college or above) (OR: 0.65, p = 0.034), but not PIR, was associated with a reduced NAFLD risk. HQD and increased PA partially mediated the effect of education on NAFLD risk. The total effect of education on NAFLD risk mediated by DQ was 29% and by PA was 8%. CONCLUSIONS: HQD, increased physical activity, and college education were associated with lower NAFLD risk in the US population.

Confusion assessment method accurately screens for hepatic encephalopathy and predicts short-term mortality in hospitalized patients with cirrhosis.

Hepatic encephalopathy (HE), a subtype of delirium, is common in cirrhosis and associated with poor outcomes. Yet, objective bedside screening tools for HE are lacking. We examined the relationship between an established screening tool for delirium, Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and short-term outcomes while comparing its performance with previously established measures of cognitive function such as West Haven criteria (WHC). Prospectively enrolled adults with cirrhosis who completed the CAM-ICU from 6/2014-6/2018 were followed for 90 days. Blinded provider-assigned West Haven Criteria (WHC) and other measures of cognitive function were collected. Logistic regression was used to test associations between CAM-ICU status and outcomes. Mortality prediction by CAM-ICU status was assessed using Area under the Receiver Operating Characteristics curves (AUROC). Of 469 participants, 11% were CAM-ICU( +), 55% were male and 94% were White. Most patients were Childs-Pugh class C (59%). CAM-ICU had excellent agreement with WHC (Kappa = 0.79). CAM-ICU( +) participants had similar demographic features to those CAM-ICU(-), but had higher MELD (25 vs. 19, p < 0.0001), were more often admitted to the ICU (28% vs. 7%, p < 0.0001), and were more likely to be admitted for HE and infection. CAM-ICU( +) participants had higher mortality (inpatient:37% vs. 3%, 30-day:51% vs. 11%, 90-day:63% vs. 23%, p < 0.001). CAM-ICU status predicted mortality with AUROC of 0.85, 0.82 and 0.77 for inpatient, 30-day and 90-day mortality, respectively. CAM-ICU easily screens for delirium/HE, has excellent agreement with WHC, and identifies a hospitalized cirrhosis cohort with high short-term mortality.

Development and Feasibility Testing of a Multilevel Intervention to Increase Hepatitis C Virus Screening Among Baby Boomers in Primary Care.

Chronic infection with hepatitis C virus (HCV) results in an increased risk of cirrhosis and hepatocellular carcinoma (HCC). Only 15% of baby boomers (born 1945-1965) have ever been screened. We aimed to develop a multilevel intervention to increase HCV screening for baby boomers in a primary care setting. This study included two phases: intervention development (phase 1) and feasibility testing (phase 2). In phase 1, we partnered with a Community Advisory Board and a Provider Advisory Board to develop a multilevel intervention to increase HCV screening to be delivered to both providers and patients in primary care. Phase 2 assessed intervention feasibility, acceptability, and usability by conducting Concurrent Think Aloud (CTA) interviews and surveys using previously validated scales with patients (n = 8) and providers (n = 7). Phase 1 results: The patient-level intervention included a mailed reminder letter and CDC pamphlet and a 7-min in-clinic educational video. The provider-level intervention included a 30-min educational session and monthly performance feedback e-mails. Phase 2 results: Qualitatively, both the patient and provider-level intervention were feasible, acceptable, and usable by the target audiences. Quantitatively, on a 1-4 scale, the range of patient-level scores was 3.00-4.00 and provider level was 3.50-4.00 for feasibility, acceptability, and usability. This intervention could improve HCV screening among a high-risk population and therefore reduce HCV-related morbidity and mortality. This project developed a feasible, acceptable, and usable multilevel intervention aimed at increasing HCV screening in primary care.

Acute kidney disease is common and associated with poor outcomes in patients with cirrhosis and acute kidney injury.

BACKGROUND & AIMS: Acute kidney disease (AKD) is the persistence of acute kidney injury (AKI) for up to 3 months, which is proposed to be the time-window where critical interventions can be initiated to alter downstream outcomes of AKI. In cirrhosis, AKD and its impact on outcomes have been scantly investigated. We aimed to define the incidence and outcomes associated with AKD in a nationwide US cohort of hospitalized patients with cirrhosis and AKI. METHODS: Hospitalized patients with cirrhosis and AKI in the Cerner-Health-Facts database from 1/2009-09/2017 (n = 6,250) were assessed for AKD and were followed-up for 180 days. AKI and AKD were defined based on KDIGO and ADQI AKD and renal recovery consensus criteria, respectively. The primary outcome measure was mortality, and the secondary outcome measure was de novo chronic kidney disease (CKD). Competing-risk multivariable models were used to determine the independent association of AKD with primary and secondary outcomes. RESULTS: AKD developed in 32% of our cohort. On multivariable competing-risk analysis adjusting for significant confounders, patients with AKD had higher risk of mortality at 90 (subdistribution hazard ratio [sHR] 1.37; 95% CI 1.14-1.66; p = 0.001) and 180 (sHR 1.37; 95% CI 1.14-1.64; p = 0.001) days. The incidence of de novo CKD was 37.5%: patients with AKD had higher rates of de novo CKD (64.0%) compared to patients without AKD (30.7%; p <0.001). After adjusting for confounders, AKD was independently associated with de novo CKD (sHR 2.52; 95% CI 2.01-3.15; p <0.001) on multivariable competing-risk analysis. CONCLUSIONS: AKD develops in 1 in 3 hospitalized patients with cirrhosis and AKI and it is associated with worse survival and de novo CKD. Interventions that target AKD may improve outcomes of patients with cirrhosis and AKI. LAY SUMMARY: In a nationwide US cohort of hospitalized patients with cirrhosis and acute kidney injury, acute kidney disease developed in 1 in 3 patients and was associated with worse survival and chronic kidney disease. Interventions that target acute kidney disease may improve outcomes of patients with cirrhosis and acute kidney injury.

Patient-Reported Outcome Measures Modestly Enhance Prediction of Readmission in Patients with Cirrhosis.

BACKGROUND & AIMS: Patients with cirrhosis have high rates of hospital readmission, but prediction models are suboptimal and have not included important patient-reported outcome measures (PROMs). In a large prospective cohort, we examined the impact of PROMs on prediction of 30-day readmissions. METHODS: We performed a prospective cohort study of adults with cirrhosis admitted to a tertiary center between June 2014 and March 2020. We collected clinical information, socioeconomic status, and PROMs addressing functional status and quality of life. We used hierarchical competing risk time-to-event analysis to examine the impact of PROMs on readmission prediction. RESULTS: A total of 654 patients were discharged alive, and 247 (38%) were readmitted within 30 days. Readmission was independently associated with cerebrovascular disease, ascites, prior hospital admission, admission via the emergency department, lower albumin, higher Model for End-Stage Liver Disease, discharge with public transportation, and impaired basic activities of daily living and quality-of-life activity domain. Reduced readmission was associated with cancer, admission for infection, children at home, and impaired emotional function. Compared with a model including only clinical variables, addition of functional status and quality-of-life variables improved the area under the receiver-operating characteristic curve from 0.72 to 0.73 and 0.75, with net reclassification indices of 0.22 and 0.18, respectively. Socioeconomic variables did not significantly improve prediction compared with clinical variables alone. Compared with a model using electronically available variables only, no models improved prediction when examined with integrated discrimination improvement. CONCLUSIONS: PROMs may marginally add to the prediction of 30-day readmissions for patients with cirrhosis. Poor social support and disability are associated with readmissions and may be high-yield targets for future interventions.

Eight-Fold Increase in Dietary Supplement-Related Liver Failure Leading to Transplant Waitlisting Over the Last Quarter Century in the United States.

We investigated the trends in listing and outcomes of drug-induced acute liver failure (DIALF) over the last quarter century in the United States using the United Network for Organ Sharing (UNOS) database. We examined waitlisted patients in the UNOS database between 1995 and 2020 with a diagnosis of DIALF and assessed trends in etiologies, demographic and clinical characteristics, and outcomes over 3 periods: 1995-2003, 2004-2012, and 2013-2020. Patients with DIALF and cirrhosis were classified as drug-induced acute-on-chronic liver failure. Implicated agents including acetaminophen (APAP) and herbal or dietary supplements (HDSs) were ascertained. There were 2146 individuals with DIALF during the study period. The observed demographic trends between the earliest and latest period included fewer pediatric patients (18.8% to 13.5%) but with an increasing number of males in non-APAP DIALF (31.8% to 41.4%) and increased racial diversity in APAP DIALF. Antimicrobials remained the most common non-APAP agents across all periods, but antiepileptics, propylthiouracil, and mushroom poisoning decreased, while HDSs markedly increased from 2.9% to 24.1% of all non-APAP DIALF patients. The overall 5-year post-liver transplantation (LT) patient survival improved significantly over the 3 periods (69.9% to 77.4% to 83.3%) and was evident for both APAP and non-APAP DIALF. Over the last quarter century, there has been an 8-fold increase in HDS-related liver failure necessitating waitlisting for liver transplantation in the United States. There are other important temporal trends during the study period, including improved survival following LT among both APAP and non-APAP DIALF patients.

Neighborhood poverty is associated with failure to be waitlisted and death during liver transplantation evaluation.

Liver transplantation (LT) is the final step in a complex care cascade. Little is known about how race, gender, rural versus urban residence, or neighborhood socioeconomic indicators impact a patient's likelihood of LT waitlisting or risk of death during LT evaluation. We performed a retrospective cohort study of adults referred for LT to the Indiana University Academic Medical Center from 2011 to 2018. Neighborhood socioeconomic status indicators were obtained by linking patients' addresses to their census tract defined in the 2017 American Community Survey. Descriptive statistics were used to describe completion of steps in the LT evaluation cascade. Multivariable analyses were performed to assess the factors associated with waitlisting and death during LT evaluation. There were 3454 patients referred for LT during the study period; 25.3% of those referred were waitlisted for LT. There was no difference seen in the proportion of patients from vulnerable populations who progressed to the steps of financial approval or evaluation start. There were differences in waitlisting by insurance type (22.6% of Medicaid vs. 34.3% of those who were privately insured; p < 0.01) and neighborhood poverty (quartile 1 29.6% vs. quartile 4 20.4%; p < 0.01). On multivariable analysis, neighborhood poverty was independently associated with waitlisting (odds ratio 0.56, 95% confidence interval [CI] 0.38-0.82) and death during LT evaluation (hazard ratio 1.49, 95% CI 1.09-2.09). Patients from high-poverty neighborhoods are at risk of failing to be waitlisted and death during LT evaluation.

Removal of medicaid restrictions were associated with increased hepatitis C virus treatment rates, but disparities persist.

Despite the release of a growing number of direct-acting antivirals and evolving policy landscape, many of those diagnosed with hepatitis C virus (HCV) have not received treatment. Those from vulnerable populations are at particular risk of being unable to access treatment, threatening World Health Organization (WHO) HCV elimination goals. The aim of this study was to understand the association between direct-acting antivirals approvals, HCV-related policy changes and access to HCV virus treatment in Indiana, and to explore access to treatment by race, birth cohort and insurance type. We performed a retrospective cohort study of adults with HCV from 05/2011-03/2021, using statewide electronic health data. Nine policy and treatment changes were defined a priori. A Lowess curve evaluated treatment trends over time. Monthly screening and treatment rates were examined. Multivariable logistic regression explored predictors of treatment. The population (N = 10,336) was 13.4% Black, 51.8% was born after 1965 and 44.7% was Medicaid recipients. Inflections in the Lowess curve defined four periods: (1) Interferon + DAA, (2) early direct-acting antivirals, (3) Medicaid expansion/optimization and (4) Medicaid restrictions (fibrosis/prescriber) removed. The largest increase in monthly treatment rates was during period 4, when Medicaid prescriber and fibrosis restrictions were removed (2.4 persons per month [PPM] in period 1 to 72.3 PPM in period 4, p < 0.001; 78.0% change in slope). Multivariable logistic regression analysis showed being born after 1965 (vs. before 1945; OR 0.69; 95% 0.49-0.98) and having Medicaid (vs. private insurance; OR 0.47; 95% CI 0.42-0.53), but not race was associated with lower odds of being treated. In conclusion, DAAs had limited impact on HCV treatment rates until Medicaid restrictions were removed. Additional policies may be needed to address HCV treatment-related age and insurance disparities.

Practice patterns and outcomes associated with intravenous albumin in patients with cirrhosis and acute kidney injury.

BACKGROUND & AIMS: Guidelines recommend albumin as the plasma-expander of choice for acute kidney injury (AKI) in cirrhosis. However, the impact of these recommendations on patient outcomes remains unclear. We aimed to determine the practice-patterns and outcomes associated with albumin use in a large, nationwide-US cohort of hospitalized cirrhotics with AKI. METHODS: A retrospective cohort study was performed in hospitalized cirrhotics with AKI using Cerner-Health-Facts database from January 2009 to March 2018. 6786 were included for analysis on albumin-practice-patterns, and 4126 had available outcomes data. Propensity-score-adjusted model was used to determine the association between albumin use, AKI-recovery and in-hospital survival. RESULTS: Median age was 61-years (60% male, 70% white), median serum-creatinine was 1.8 mg/dL and median Model for End-stage Liver Disease Sodium (MELD-Na) score was 24. Albumin was given to 35% of patients, of which 50% received albumin within 48-hours of AKI-onset, and 17% received appropriate weight-based dosing. Albumin was used more frequently in patients with advanced complications of cirrhosis, higher MELD-Na scores and patients admitted to urban-teaching hospitals. After propensity-matching and multivariable adjustment, albumin use was not associated with AKI-recovery (odds ratio [OR] 0.70, 95% confidence-interval [CI]: 0.59-1.07, P = .130) or in-hospital survival (OR 0.76 [95% CI: 0.46-1.25], P = .280), compared with crystalloids. Findings were unchanged in subgroup analyses of patients with varying cirrhosis complications and disease severity. CONCLUSIONS: USA hospitalized patients with cirrhosis and AKI frequently do not receive intravenous albumin, and albumin use was not associated with improved clinical outcomes. Prospective randomised trials are direly needed to evaluate the impact of albumin in cirrhotics with AKI.

Racial, Gender, and Socioeconomic Disparities in Liver Transplantation.

Liver transplantation (LT) is a life-saving therapy; therefore, equitable distribution of this scarce resource is of paramount importance. We searched contemporary literature on racial, gender, and socioeconomic disparities across the LT care cascade in referral, waitlist practices, allocation, and post-LT care. We subsequently identified gaps in the literature and future research priorities. Studies found that racial and ethnic minorities (Black and Hispanic patients) have lower rates of LT referral, more advanced liver disease and hepatocellular carcinoma at diagnosis, and are less likely to undergo living donor LT (LDLT). Gender-based disparities were observed in waitlist mortality and LT allocation. Women have lower LT rates after waitlisting, with size mismatch accounting for much of the disparity. Medicaid insurance has been associated with higher rates of chronic liver disease and poor waitlist outcomes. After LT, some studies found lower overall survival among Black compared with White recipients. Studies have also shown lower literacy and limited educational attainment were associated with increased posttransplant complications and lower use of digital technology. However, there are notable gaps in the literature on disparities in LT. Detailed population-based estimates of the advanced liver disease burden and LT referral and evaluation practices, including for LDLT, are lacking. Similarly, little is known about LT disparities worldwide. Evidence-based strategies to improve access to care and reduce disparities have not been comprehensively identified. Prospective registries and alternative "real-world" databases can provide more detailed information on disease burden and clinical practices. Modeling and simulation studies can identify ways to reduce gender disparities attributed to size or inaccurate estimation of renal function. Mixed-methods studies and clinical trials should be conducted to reduce care disparities across the transplant continuum.

Racial differences in primary sclerosing cholangitis mortality is associated with community socioeconomic status.

BACKGROUND AND AIMS: Natural history and outcomes data in PSC are mostly derived from cohorts where Blacks have been underrepresented. It is unknown if there are differences in mortality between Blacks and Whites with PSC. METHODS: PSC patients seen at our institution from June 1988 to Jan 2019 were identified by merging prospective ERCP hepatology-clinic databases and liver-transplant registry. Data on race, clinical events, and death was obtained through chart review. Data on community health were collected using indices from county health rankings. Cumulative incidence of death was calculated using liver transplant (LT) as a competing risk. RESULTS: Of 449 patients, 404 were White and 45 were Black. The median-duration of follow-up was 7 years (IQR:3, 13). Black patients were younger at presentation than White patients (36.3 vs 42.5 years., P = .013). Disease severity as indicated by Mayo Risk Score categories (low 27% vs 31%, intermediate 54% vs 49% and high 19% vs 19%, P = .690), comorbidity burden and frequency of cirrhosis (42% vs 35%, P = .411) were similar between Blacks and Whites. Cumulative incidence of liver-related death, with LT as a competing risk was significantly higher in Blacks compared to Whites (sHR 1.80, 95%CI 1.25, 2.61, P = .002). There was a significant interaction between race and community socioeconomic factors that attenuated the racial difference in mortality (sHR 1.01, 95%CI 0.99, 1.04, P = .345). CONCLUSIONS: Blacks with PSC present at a younger age with a similar disease severity as Whites but have higher liver related mortality that is mediated in part through community health.