A comprehensive evaluation of emergency department utilization by patients with cirrhosis.

BACKGROUND: Emergency Department (ED) based care is required for cirrhosis management, yet the burden of cirrhosis-related ED healthcare utilization (HCU) is understudied. We aimed to describe ED utilization within a statewide health system and compare the outcomes of high ED use (HEDU) versus non-HEDU in individuals with cirrhosis. METHODS: We retrospectively reviewed charts of adults with cirrhosis who presented to any of 16 EDs within the Indiana University Health system in 2021. Patient characteristics, features of the initial ED visit, subsequent 90-day healthcare use, and 360-day outcomes were collected. Multivariable logistic regression models were used to identify predictors HEDU status which was defined as ≥2 ED visits within 90 days after the index ED visit. RESULTS: There were 2124 eligible patients (mean age 61.3 years, 53% male, and 91% White). Major etiologies of cirrhosis were alcohol (38%), MASH (27%), and viral hepatitis (21%). Cirrhosis was newly diagnosed in the ED visit for 18.4%. Most common reasons for ED visits were abdominal pain (21%), shortness of breath (19%), and ascites/volume overload (16%). Of the initial ED visits 20% (n=424) were potentially avoidable. The overall 90-day mortality was 16%. Within 90 days, there were 366 HEDU (20%). Notable variables independently associated with HEDU were MELD-Na (aOR=1.044, 95% CI 1.005-1.085), prior ED encounter (aOR=1.520, 95% CI 1.136-2.034), and avoidable initial ED visit (aOR=1.938, 95% CI 1.014-3.703). CONCLUSIONS: Abdominal pain, shortness of breath, and ascites/fluid overload are the common presenting reasons for ED visits for patients with cirrhosis. Patients with cirrhosis presenting to the ED experience a 90-day mortality rate of 16%, and among those who initially visited the ED, 20% were HEDU. We identified several variables independently associated with HEDU. Our observations pave the way for developing interventions to optimize the care of patients with cirrhosis presenting to the ED and to lower repeated ED visits.

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. This meta-analysis aimed 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 (MD) with confidence intervals (CI) 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 (LOS), acute kidney injury (AKI), 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), LOS (MD -4.85 days; 95% CI -6.45, -3.20; P<0.001), and AKI (OR 0.62, 95% CI 0.42-0.92, P=0.02) compared to 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%). CONCLUSIONS: 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.

Plasma exchange for acute and acute-on-chronic liver failure: A systematic review and meta-analysis.

Plasma exchange (PE) is a promising therapeutic option in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). However, the impact of PE on patient survival in these syndromes is unclear. We aimed to systematically investigate the use of PE in patients with ALF and ACLF compared with standard medical therapy (SMT). We searched PubMed/Embase/Cochrane databases to include all studies comparing PE versus SMT for patients ≥ 18 years of age with ALF and ACLF. Pooled risk ratios (RR) with corresponding 95% CIs were calculated by the Mantel-Haenszel method within a random-effect model. The primary outcome was 30-day survival for ACLF and ALF. Secondary outcomes were overall and 90-day survival for ALF and ACLF, respectively. Five studies, including 343 ALF patients (n = 174 PE vs. n = 169 SMT), and 20 studies, including 5,705 ACLF patients (n = 2,856 PE vs. n = 2,849 SMT), were analyzed. Compared with SMT, PE was significantly associated with higher 30-day (RR 1.41, 95% CI 1.06-1.87, p = 0.02) and overall (RR 1.35, 95% CI 1.12-1.63, p = 0.002) survival in ALF patients. In ACLF, PE was also significantly associated with higher 30-day (RR 1.36, 95% CI 1.22-1.52, p < 0.001) and 90-day (RR 1.21, 95% CI 1.10-1.34, p < 0.001) survival. On subgroup analysis of randomized controlled trials, results remained unchanged in ALF, but no differences in survival were found between PE and SMT in ACLF. In conclusion, PE is associated with improved survival in ALF and could improve survival in ACLF. PE may be considered in managing ALF and ACLF patients who are not liver transplant (LT) candidates or as a bridge to LT in otherwise eligible patients. Further randomized controlled trials are needed to confirm the survival benefit of PE in ACLF.

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.

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.

Patient-reported outcomes in HCC: A scoping review by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.

BACKGROUND AND AIMS: HCC is a leading cause of mortality in patients with advanced liver disease and is associated with significant morbidity. Despite multiple available curative and palliative treatments, there is a lack of systematic evaluation of patient-reported outcomes (PROs) in HCC. APPROACH AND RESULTS: The American Association for the Study of Liver Diseases Practice Metrics Committee conducted a scoping review of PROs in HCC from 1990 to 2021 to (1) synthesize the evidence on PROs in HCC and (2) provide recommendations on incorporating PROs into clinical practice and quality improvement efforts. A total of 63 studies met inclusion criteria investigating factors associated with PROs, the relationship between PROs and survival, and associations between HCC therapy and PROs. Studies recruited heterogeneous populations, and most were cross-sectional. Poor PROs were associated with worse prognosis after adjusting for clinical factors and with more advanced disease stage, although some studies showed better PROs in patients with HCC compared to those with cirrhosis. Locoregional and systemic therapies were generally associated with a high symptom burden; however, some studies showed lower symptom burden for transarterial radiotherapy and radiation therapy. Qualitative studies identified additional symptoms not routinely assessed with structured questionnaires. Gaps in the literature include lack of integration of PROs into clinical care to guide HCC treatment decisions, unknown impact of HCC on caregivers, and the effect of palliative or supportive care quality of life and health outcomes. CONCLUSION: Evidence supports assessment of PROs in HCC; however, clinical implementation and the impact of PRO measurement on quality of care and longitudinal outcomes need future investigation.

Quality measures in HCC care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.

The burden of HCC is substantial. To address gaps in HCC care, the American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) aimed to develop a standard set of process-based measures and patient-reported outcomes (PROs) along the HCC care continuum. We identified candidate process and outcomes measures for HCC care based on structured literature review. A 13-member panel with content expertise across the HCC care continuum evaluated candidate measures on importance and performance gap using a modified Delphi approach (two rounds of rating) to define the final set of measures. Candidate PROs based on a structured scoping review were ranked by 74 patients with HCC across 7 diverse institutions. Out of 135 measures, 29 measures made the final set. These covered surveillance (6 measures), diagnosis (6 measures), staging (2 measures), treatment (10 measures), and outcomes (5 measures). Examples included the use of ultrasound (± alpha-fetoprotein [AFP]) every 6 months, need for surveillance in high-risk populations, diagnostic testing for patients with a new AFP elevation, multidisciplinary liver tumor board (MLTB) review of Liver Imaging-Reporting and Data System 4 lesions, standard evaluation at diagnosis, treatment recommendations based on Barcelona Clinic Liver Cancer staging, MLTB discussion of treatment options, appropriate referral for evaluation of liver transplantation candidacy, and role of palliative therapy. PROs include those related to pain, anxiety, fear of treatment, and uncertainty about the best individual treatment and the future. The AASLD PMC has developed a set of explicit quality measures in HCC care to help bridge the gap between guideline recommendations and measurable processes and outcomes. Measurement and subsequent implementation of these metrics could be a central step in the improvement of patient care and outcomes in this high-risk population.

The kidney releases a nonpolymerizing form of uromodulin in the urine and circulation that retains the external hydrophobic patch domain.

Uromodulin [Tamm-Horsfall protein (THP)] is a glycoprotein uniquely produced in the kidney. It is released by cells of the thick ascending limbs apically in the urine and basolaterally in the renal interstitium and systemic circulation. Processing of mature urinary THP, which polymerizes into supramolecular filaments, requires cleavage of an external hydrophobic patch (EHP) at the COOH-terminus. However, THP in the circulation is not polymerized, and it remains unclear if nonaggregated forms of THP exist natively in the urine. We propose that an alternative processing path, which retains the EHP domain, can lead to a nonpolymerizing form of THP. We generated an antibody that specifically recognizes THP with retained EHP (THP + EHP) and established its presence in the urine in a nonpolymerized native state. Proteomic characterization of urinary THP + EHP revealed its COOH-terminus ending at F617. In the human kidney, THP + EHP was detected in thick ascending limb cells and less strongly in the renal parenchyma. Using immunoprecipitation followed by proteomic sequencing and immunoblot analysis, we then demonstrated that serum THP has also retained EHP. In a small cohort of patients at risk for acute kidney injury, admission urinary THP + EHP was significantly lower in patients who subsequently developed acute kidney injury during hospitalization. Our findings uncover novel insights into uromodulin biology by establishing the presence of an alternative path for cellular processing, which could explain the release of nonpolymerizing THP in the circulation. Larger studies are needed to establish the utility of urinary THP + EHP as a sensitive biomarker of kidney health and susceptibility to injury.NEW & NOTEWORTHY In this work, we discovered and characterized a novel form of uromodulin that does not polymerize because it retains an external hydrophobic patch at the COOH-terminus. These findings establish an alternative form of cellular processing of this protein and elucidate new aspects of its biology. We also provide evidence suggesting that measuring urinary nonpolymerizing uromodulin could be a promising assay to assess the risk of acute kidney injury.

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.

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.

CAD-LT score effectively predicts risk of significant coronary artery disease in liver transplant candidates.

BACKGROUND & AIMS: Patients with cirrhosis and significant coronary artery disease (CAD) are at risk of peri-liver transplantation (LT) cardiac events. The coronary artery disease in liver transplantation (CAD-LT) score and algorithm aim to predict the risk of significant CAD in LT candidates and guide pre-LT cardiac evaluation. METHODS: Patients who underwent pre-LT evaluation at Indiana University (2010-2019) were studied retrospectively. Stress echocardiography (SE) and cardiac catheterization (CATH) reports were reviewed. CATH was performed for predefined CAD risk factors, irrespective of normal SE. Significant CAD was defined as CAD requiring percutaneous or surgical intervention. A multivariate regression model was constructed to assess risk factors. Receiver-operating curve analysis was used to compute a point-based risk score and a stratified testing algorithm. RESULTS: A total of 1,771 pre-LT patients underwent cardiac evaluation, including results from 1,634 SE and 1,266 CATH assessments. Risk-adjusted predictors of significant CAD at CATH were older age (adjusted odds ratio 1.05; 95% CI 1.03-1.08), male sex (1.69; 1.16-2.50), diabetes (1.57; 1.12-2.22), hypertension (1.61; 1.14-2.28), tobacco use (pack years) (1.01; 1.00-1.02), family history of CAD (1.63; 1.16-2.28), and personal history of CAD (6.55; 4.33-9.90). The CAD-LT score stratified significant CAD risk as low (≤2%), intermediate (3% to 9%), and high (≥10%). Among patients who underwent CATH, a risk-based testing algorithm (low: no testing; intermediate: non-invasive testing vs. CATH; high: CATH) would have identified 97% of all significant CAD and potentially avoided unnecessary testing (669 SE [57%] and 561 CATH [44%]). CONCLUSIONS: The CAD-LT score and algorithm (available at www.cad-lt.com) effectively stratify pre-LT risk for significant CAD. This may guide more targeted testing of candidates with fewer tests and faster time to waitlist. LAY SUMMARY: The coronary artery disease in liver transplantation (CAD-LT) score and algorithm effectively stratify patients based on their risk of significant coronary artery disease. The CAD-LT algorithm can be used to guide a more targeted cardiac evaluation prior to liver transplantation.

Pre-Liver Transplant Cardiac Catheterization Is Associated With Low Rate of Myocardial Infarction and Cardiac Mortality.

BACKGROUND AND AIMS: A study at Indiana University demonstrated a reduction in myocardial infarction (MI) incidence with increased frequency of cardiac catheterization (CATH) in liver transplant (LT) candidates. A strict protocol for performing CATH based upon predefined risk factors, rather than noninvasive testing alone, was applied to a subgroup (2009-2010) from that study. CATH was followed by percutaneous coronary intervention (PCI) in cases of significant coronary artery disease (CAD; ≥50% stenosis). The current study applies this screening protocol to a larger cohort (2010-2016) to assess post-LT clinical outcomes. APPROACH AND RESULTS: Among 811 LT patients, 766 underwent stress testing (94%) and 559 underwent CATH (69%), of whom 10% had CAD requiring PCI. The sensitivity of stress echocardiography in detecting significant CAD was 37%. Predictors of PCI included increasing age, male gender, and personal history of CAD (P < 0.05 for all). Compared to patients who had no CATH, patients who underwent CATH had higher mortality (P = 0.07), and the hazard rates (HR) for mortality increased with CAD severity (normal CATH, HR, 1.35; 95% confidence interval [CI], 0.79-2.33; P = 0.298; nonobstructive CAD, HR, 1.53; 95% CI, 0.84-2.77; P = 0.161; and significant CAD, HR, 1.96; 95% CI, 0.93-4.15; P = 0.080). Post-LT outcomes were compared to the 2009-2010 subgroup from the previous study and showed similar 1-year overall mortality (8% and 6%, P = 0.48), 1-year MI incidence (<1% and <1%, P = 0.8), and MI deaths as a portion of all deaths (3% and 9%, P = 0.35). CONCLUSIONS: Stress echocardiography alone is not reliable in screening LT patients for CAD. Aggressive CAD screening with CATH is associated with low rate of MI and cardiac mortality and validates the previously published protocol when extrapolated over a larger sample and longer follow-up period.

Admission Factor V Predicts Transplant-Free Survival in Acute Liver Failure.

BACKGROUND AND AIMS: Traditional laboratory markers are insensitive in distinguishing between patients with acute liver failure (ALF) who will require urgent liver transplantation (LT) from those who will recover spontaneously, particularly within 24 h of presentation. Coagulation factor-V (FV) may improve the accuracy of outcome prediction in ALF due to its predominant synthesis in the liver and short half-life in plasma. METHODS: Patients enrolled in the ALF Study Group Registry from a single site had FV determined within 24 h of presentation (Derivation-Cohort). Area under the receiver operating characteristic curves (AUROC) dichotomized by ALF etiology [acetaminophen (APAP) or non-APAP] were constructed to evaluate the diagnostic performance of FV for transplant-free-survival (TFS). Multivariate logistic regression modeling was performed using FV and other clinical variables to predict TFS. Accuracy of FV and multivariable model were performed in a Validation-Cohort from a different site. RESULTS: 90-patients (56% with APAP) were included in the Derivation-Cohort. Median FV was significantly higher in TFS versus those who died/LT (31% vs. 15%, respectively; p = 0.001). When dichotomized by etiology, AUROC for FV was 0.77 for APAP (cutoff, sensitivity, specificity 10.5%, 79%, 69%, respectively) and 0.77 for non-APAP (22%, 85%, 67%, respectively). When the optimal cutoffs for FV in the Derivation-Cohort were applied to the Validation-Cohort (N = 51; 59% with APAP), AUROC for FV was 0.75 for APAP (sensitivity/specificity 81/44) and 0.95 for non-APAP (sensitivity/specificity 90/73). In multivariate analyses, AUROC for FV model was 0.86 in the Derivation-Cohort and 0.90 in the Validation-Cohort. CONCLUSION: Admission FV may improve selection of patients who are likely to improve without LT.

Changing epidemiology and outcomes of acute kidney injury in hospitalized patients with cirrhosis - a US population-based study.

BACKGROUND & AIMS: Acute kidney injury (AKI) is a significant clinical event in cirrhosis yet contemporary population-based studies on the impact of AKI on hospitalized cirrhotics are lacking. We aimed to characterize longitudinal trends in incidence, healthcare burden and outcomes of hospitalized cirrhotics with and without AKI using a nationally representative dataset. METHODS: Using the 2004-2016 National Inpatient Sample (NIS), admissions for cirrhosis with and without AKI were identified using ICD-9 and ICD-10 codes. Regression analysis was used to analyze the trends in hospitalizations, costs, length of stay and inpatient mortality. Descriptive statistics, simple and multivariable logistic regression were used to assess associations between individual characteristics, comorbidities, and cirrhosis complications with AKI and death. RESULTS: In over 3.6 million admissions for cirrhosis, 22% had AKI. AKI admissions were more costly (median $13,127 [IQR $7,367-$24,891] vs. $8,079 [IQR $4,956-$13,693]) and longer (median 6 [IQR 3-11] days vs. 4 [IQR 2-7] days). Over time, AKI prevalence doubled from 15% in 2004 to 30% in 2016. CKD was independently and strongly associated with AKI (adjusted odds ratio 3.75; 95% CI 3.72-3.77). Importantly, AKI admissions were 3.75 times more likely to result in death (adjusted odds ratio 3.75; 95% CI 3.71-3.79) and presence of AKI increased risk of mortality in key subgroups of cirrhosis, such as those with infections and portal hypertension-related complications. CONCLUSIONS: The prevalence of AKI is significantly increased among hospitalized cirrhotics. AKI substantially increases the healthcare burden associated with cirrhosis. Despite advances in cirrhosis care, a significant gap remains in outcomes between cirrhotics with and without AKI, suggesting that AKI continues to represent a major clinical challenge. LAY SUMMARY: Sudden damage to the kidneys is becoming more common in people who are hospitalized and have cirrhosis. Despite advances in cirrhosis care, those with damage to the kidneys remain at higher risk of dying.

Hospital-Acquired Versus Community-Acquired Acute Kidney Injury in Patients With Cirrhosis: A Prospective Study.

INTRODUCTION: In patients with cirrhosis, differences between acute kidney injury (AKI) at the time of hospital admission (community-acquired) and AKI occurring during hospitalization (hospital-acquired) have not been explored. We aimed to compare patients with hospital-acquired AKI (H-AKI) and community-acquired AKI (C-AKI) in a large, prospective study. METHODS: Hospitalized patients with cirrhosis were enrolled (N = 519) and were followed for 90 days after discharge for mortality. The primary outcome was mortality within 90 days; secondary outcomes were the development of de novo chronic kidney disease (CKD)/progression of CKD after 90 days. Cox proportional hazards and logistic regressions were used to determine the independent association of either AKI for primary and secondary outcomes, respectively. RESULTS: H-AKI occurred in 10%, and C-AKI occurred in 25%. In multivariable Cox models adjusting for significant confounders, only patients with C-AKI had a higher risk for mortality adjusting for model for end-stage liver disease-Na: (hazard ratio 1.64, 95% confidence interval [CI] 1.04-2.57, P = 0.033) and adjusting for acute on chronic liver failure: (hazard ratio 2.44, 95% CI 1.63-3.65, P < 0.001). In univariable analysis, community-acquired-AKI, but not hospital-acquired-AKI, was associated with de novo CKD/progression of CKD (odds ratio 2.13, 95% CI 1.09-4.14, P = 0.027), but in multivariable analysis, C-AKI was not independently associated with de novo CKD/progression of CKD. However, when AKI was dichotomized by stage, C-AKI stage 3 was independently associated with de novo CKD/progression of CKD (odds ratio 4.79, 95% CI 1.11-20.57, P = 0.035). DISCUSSION: Compared with H-AKI, C-AKI is associated with increased mortality and de novo CKD/progression of CKD in patients with cirrhosis. Patients with C-AKI may benefit from frequent monitoring after discharge to improve outcomes.

Associations Between Mean Arterial Pressure and Poor ICU Outcomes in Critically Ill Patients With Cirrhosis: Is 65 The Sweet Spot?

OBJECTIVES: Mean arterial pressure is critically important in patients with cirrhosis in the ICU, however, there is limited data to guide therapies and targets. DESIGN: Retrospective observational study. SETTING: Tertiary care ICU. PATIENTS: Two hundred and seventy-three critically ill patients with cirrhosis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We performed a comprehensive time-weighted mean arterial pressure analysis (time-weighted-average-mean arterial pressure and cumulative-time-below various mean arterial pressure-thresholds) during the first 24-hours after ICU admission (median: 25 mean arterial pressure measurements per-patient). Time-weighted-average-mean arterial pressure captures both the severity and duration of hypotension below a mean arterial pressure threshold and cumulative-time-below is the total time spent below a mean arterial pressure threshold. Individual univariable and multivariable logistic regression models were assessed for each time-weighted-average-mean arterial pressure and cumulative-time-below mean arterial pressure threshold (55, 60, 65, 70, and 75 mm Hg) for ICU-mortality. Time-weighted-average-mean arterial pressure: for 1 mm Hg decrease in mean arterial pressure below 75, 70, 65, 60, and 55 mm Hg, the odds for ICU-mortality were 14%, 18%, 26%, 41%, and 74%, respectively (p < 0.01, all thresholds). The association between time-weighted-average-mean arterial pressure and ICU-mortality for each threshold remained significant after adjusting for model for end-stage liver disease-sodium score, mechanical ventilation, vasopressor use, renal replacement therapy, grade 3/4 hepatic encephalopathy, WBC count, and albumin. Cumulative-time-below: odds for ICU-mortality were 4%, 6%, 10%, 12%, and 12% for each-hour spent below 75, 70, 65, 60, and 55 mm Hg, respectively. In the adjusted models, significant associations only remained for mean arterial pressure less than 65 mm Hg (odds ratio, 1.07; 95% CI, 1.00-1.14; p = 0.05) and < 60 mm Hg (odds ratio, 1.10; 95% CI, 1.01-1.18; p = 0.04). CONCLUSIONS: These data suggest that maintaining a mean arterial pressure of greater than 65 mm Hg may be a reasonable target in patients with cirrhosis admitted to the ICU. However, further prospective randomized trials are needed to determine the optimal mean arterial pressure-targets in this patient population.

Postoperative Atrial Fibrillation and Flutter in Liver Transplantation: An Important Predictor of Early and Late Morbidity and Mortality.

Postoperative atrial fibrillation/flutter (POAF) is the most common perioperative arrhythmia and may be particularly problematic after liver transplantation (LT). This study is a single-center retrospective analysis of POAF to determine its incidence following LT, to identify risk factors, to assess its impact on clinical outcomes, and to summarize management strategies. The records of all patients who underwent LT between 2010 and 2018 were reviewed. Extracted data included pre-LT demographics and cardiac evaluation, in-hospital post-LT cardiac events, early and late complications, and survival. Among 1011 patients, the incidence of post-LT POAF was 10%. Using binary logistic regression, pre-LT history of atrial fibrillation was the strongest predictor of POAF (odds ratio [OR], 6.72; 95% confidence interval [CI], 2.00-22.57; P < 0.001), followed by history of coronary artery disease (CAD; OR, 2.52; 95% CI, 1.10-5.81; P = 0.03). Cardiac stress testing abnormality and CAD on cardiac catheterization were also associated with higher risk. Median time to POAF onset after LT was 3 days with 72% of cases resolving within 48 hours. POAF patients had greater hospital length of stay, death during the LT admission, and 90-day and 1-year mortality. POAF was an independent risk factor for post-LT mortality (OR, 2.0; 95% CI, 1.3-3.0; P < 0.01). Amiodarone was administered to 73% of POAF patients with no evidence of increased serum alanine aminotransferase levels. POAF occurred in 10% of post-LT patients with early onset and rapid resolution in most affected patients. POAF patients, however, had significant morbidity and mortality, suggesting that POAF is an important marker for worse early and late post-LT outcomes.