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Frailty is classically associated with advanced age but is also an important predictor of clinical outcomes in comparatively young adults with cirrhosis. We examined the association of biological aging with frailty and post-transplant outcomes in a pilot of adults with cirrhosis undergoing liver transplantation (LT). Frailty was measured via the Liver Frailty Index (LFI). The primary epigenetic clock DNA methylation (DNAm) PhenoAge was calculated from banked peripheral blood mononuclear cells; we secondarily explored two first-generation clocks (Hannum; Horvath) and two additional second-generation clocks (GrimAge; GrimAge2). Twelve adults were included: seven frail (LFI ≥ 4.4, mean age 55 years) and five robust (LFI

RATIONALE & OBJECTIVE: Despite guidelines calling to improve physical activity in older adults, and evidence suggesting that prekidney transplant physical function is highly associated with posttransplant outcomes, only a small percentage of older patients treated with dialysis are engaged in structured exercise. We sought to elucidate barriers and facilitators of exercise among older adults treated with dialysis awaiting transplant and their care partners. STUDY DESIGN: Individual, in-depth, cognitive interviews were conducted separately for patients and care partners through secure web-conferencing. SETTING & PARTICIPANTS: Twenty-three patients (≥50 years of age, treated with dialysis from the University of San Francisco kidney transplantation clinic, with a short physical performance battery of ≤10) and their care partners. ANALYTICAL APPROACH: All audio interviews were transcribed verbatim. Three investigators independently coded data and performed qualitative thematic content. The interview guide was updated iteratively based on the Capability Opportunity Motivation Behavior model. RESULTS: Patients median age was 60 years (57 ± 63.5) and care partners median ages was 57 years (49.5 ± 65.5). Thirty-nine percent of patients and 78% of care partners were female, 39% of patients and 30% of care partners self-identified as African American, and 47% of dyads were spouse or partner relationships. Major themes for barriers to pretransplant exercise included lack of understanding of an appropriate regimen, physical impairments, dialysis schedules, and safety concerns. Major facilitators included having individualized or structured exercise programs, increasing social support for patients and care partners, and motivation to regain independence or functionality or to promote successful transplantation. LIMITATIONS: Participants geographically limited to Northern California. CONCLUSIONS: Although patients and care partners report numerous barriers to pretransplant exercise and activity, they also reported many facilitators. An individualized, structured, home-based exercise program could circumvent many of the reported barriers and allow older patients to improve pretransplant physical function.

ObjectiveTo evaluate associations between neighborhood income and burden of hospitalizations for children with short bowel syndrome (SBS).Study designWe used the Pediatric Health Information System (PHIS) database to evaluate associations between neighborhood income and hospital readmissions, readmissions for central line-associated bloodstream infections (CLABSI), and hospital length of stay (LOS) for patients

BackgroundWe aimed to characterize pain and analgesic use in a large contemporary cohort of patients with cirrhosis and to associate pain with unplanned health care utilization and clinical outcomes in this population.MethodsWe included all patients with cirrhosis seen in UCSF hepatology clinics from 2013 to 2020. Pain severity and location were determined using documented pain scores at the initial visit; "significant pain" was defined as moderate or severe using established cutoffs. Demographic, clinical, and medication data were abstracted from electronic medical records. Associations between significant pain and our primary outcome of 1-year unplanned health care utilization (ie, emergency department visit or hospitalization) and our secondary outcomes of mortality and liver transplantation were explored in multivariable models.ResultsAmong 5333 patients with cirrhosis, 32% had a nonzero pain score at their initial visit and 25% had significant (ie moderate/severe) pain. Sixty percent of patients with significant pain used ≥1 analgesic; 34% used opioids. Patients with cirrhosis with significant pain had similar Model for End-Stage Liver Disease-Sodium scores (14 vs. 13), but higher rates of decompensation (65% vs. 55%). The most common pain location was the abdomen (44%). Patients with abdominal pain, compared to pain in other locations, were more likely to have decompensation (72% vs. 56%). Significant pain was independently associated with unplanned health care utilization (adjusted odds ratio: 1.3, 95% CI: 1.1-1.5) and mortality (adjusted hazard ratio: 1.4, 95% CI: 1.2-1.6).ConclusionsPain among patients with cirrhosis is often not well-controlled despite analgesic use, and significant pain is associated with unplanned health care utilization and mortality in this population. Effectively identifying and treating pain are essential in reducing costs and improving quality of life and outcomes among patients with cirrhosis.

BackgroundAccording to the new AASLD Practice Guidance, all patients with primary sclerosing cholangitis (PSC) should be considered for participation in clinical trials. However, PSC's rarity has posed challenges to characterizing patient interest in trial participation and identifying predictors of patient willingness to participate in drug trials.MethodsPSC Partners Seeking a Cure developed the "Our Voices" survey to inform the development of the Externally-Led Patient-Focused Drug Development Forum, an FDA initiative to capture patient experiences and perspectives on drug development.ResultsOf 797 survey respondents from over 30 countries, 536 (67%) identified slowing disease progression as the most important outcome. Eighty-nine percent identified their hepatologist/gastroenterologist as someone they would approach for advice about trials. Although 61% reported being willing to participate in drug trials, only 26% had ever been asked to participate. Notable barriers to trial involvement included unknown long-term risks (71%), long travel times to the study center (32%), and a liver biopsy requirement (27%). On multivariable logistic regression, pruritus (OR 1.62, 95% CI: 1.09-2.40, p = 0.017) was positively associated with willingness to participate in disease-modifying therapy trials, while jaundice (OR 0.34, 95% CI: 0.19-0.61, p < 0.001) and inflammatory bowel disease (OR 0.64, 95% CI: 0.42-0.98, p = 0.038) were negatively associated. Pruritus (OR 2.25, 95% CI: 1.50-3.39, p < 0.001) was also independently associated with willingness to participate in symptom treatment trials.ConclusionsMost patients with PSC report interest in participating in clinical trials, but few have been asked to participate. Referral of patients with PSC by their hepatologist/gastroenterologist to clinical trials and patient education on trial participation are vital to closing the gap between trial interest and participation. Pruritus may serve as a key indicator of patient interest in trial participation.

BackgroundElectronic health record (EHR)-based clinical decision support is a scalable way to help standardize clinical care. Clinical decision support systems have not been extensively investigated in cirrhosis management. Human-centered design (HCD) is an approach that engages with potential users in intervention development. In this study, we applied HCD to design the features and interface for a clinical decision support system for cirrhosis management, called CirrhosisRx.MethodsWe conducted technical feasibility assessments to construct a visual blueprint that outlines the basic features of the interface. We then convened collaborative-design workshops with generalist and specialist clinicians. We elicited current workflows for cirrhosis management, assessed gaps in existing EHR systems, evaluated potential features, and refined the design prototype for CirrhosisRx. At the conclusion of each workshop, we analyzed recordings and transcripts.ResultsWorkshop feedback showed that the aggregation of relevant clinical data into 6 cirrhosis decompensation domains (defined as common inpatient clinical scenarios) was the most important feature. Automatic inference of clinical events from EHR data, such as gastrointestinal bleeding from hemoglobin changes, was not accepted due to accuracy concerns. Visualizations for risk stratification scores were deemed not necessary. Lastly, the HCD co-design workshops allowed us to identify the target user population (generalists).ConclusionsThis is one of the first applications of HCD to design the features and interface for an electronic intervention for cirrhosis management. The HCD process altered features, modified the design interface, and likely improved CirrhosisRx's overall usability. The finalized design for CirrhosisRx proceeded to development and production and will be tested for effectiveness in a pragmatic randomized controlled trial. This work provides a model for the creation of other EHR-based interventions in hepatology care.

Liver transplantation (LT) is a treatment for acute-on-chronic liver failure (ACLF), but high post-LT mortality has been reported. Existing post-LT models in ACLF have been limited. We developed an Expert-Augmented Machine Learning (EAML) model to predict post-LT outcomes. We identified ACLF patients who underwent LT in the University of California Health Data Warehouse. We applied the RuleFit machine learning (ML) algorithm to extract rules from decision trees and create intermediate models. We asked human experts to rate the rules generated by RuleFit and incorporated these ratings to generate final EAML models. We identified 1384 ACLF patients. For death at 1 year, areas under the receiver-operating characteristic curve were 0.707 (confidence interval [CI] 0.625-0.793) for EAML and 0.719 (CI 0.640-0.800) for RuleFit. For death at 90 days, areas under the receiver-operating characteristic curve were 0.678 (CI 0.581-0.776) for EAML and 0.707 (CI 0.615-0.800) for RuleFit. In pairwise comparisons, both EAML and RuleFit models outperformed cross-sectional models. Significant discrepancies between experts and ML occurred in rankings of biomarkers used in clinical practice. EAML may serve as a method for ML-guided hypothesis generation in further ACLF research.

BackgroundFrailty is a clinical state of increased vulnerability and is common in patients with cirrhosis. The liver frailty index (LFI) is a validated tool to evaluate frailty in cirrhosis, comprising of grip strength, chair stands, and balance tests. The chair-stand test is an easy to conduct frailty subcomponent that does not require specialized equipment and may be valuable to predict adverse clinical outcomes in cirrhosis. The objective of this study was to determine if the chair-stand test is an independent predictor of mortality and hospitalization in cirrhosis.MethodsA retrospective review of 787 patients with cirrhosis was conducted. Chair-stand times were collected at baseline in person and divided into three groups: 15 seconds (n = 221). Fine-Gray proportional hazards regression models were used to evaluate the association between chair-stand times and the outcomes of mortality and non-elective hospitalization.ResultsThe hazard of mortality (HR 3.21, 95% CI 2.16%-4.78%, p 15 seconds had increased all-cause mortality (HR 2.78, 95% CI 2.01%-3.83%, p 15 seconds is independently associated with mortality and non-elective hospitalizations. This test holds promise as a rapid prognostication tool in cirrhosis. Future work will include external validation and virtual assessment in this population.

RATIONALE & OBJECTIVE: In the Lifestyle Interventions and Independence for Elders (LIFE) trial, a structured exercise intervention slowed kidney function decline in sedentary older adults. Biomarkers of kidney health could distinguish potential mechanisms for this beneficial effect. STUDY DESIGN: Randomized controlled trial. SETTING & POPULATION: A total of 1,381 sedentary adults aged 70-89 years enrolled in the LIFE trial. INTERVENTION: Structured, 2-year, moderate-intensity exercise intervention versus health education. OUTCOMES: Physical activity was measured by step count. Primary outcomes were changes in 14 serum and urine biomarkers of kidney health collected at baseline, year 1, and year 2. We determined the effect of randomization on changes in kidney measures and then evaluated observational associations of achieved activity on each measure. RESULTS: Participants assigned to exercise walked on average 291 more steps per day than participants assigned to health education. The intervention was not significantly associated with changes in biomarkers of kidney health. In observational analyses, persons in the highest versus lowest quartile of activity (≥3,470 vs

PurposeTo evaluate recovery of platelet count after transjugular intrahepatic portosystemic shunt (TIPS) creation and patient factors predicting platelet recovery after TIPS creation.Materials and methodsAdults with cirrhosis who underwent TIPS creation at 9 U.S. hospitals from 2010 to 2015 were included in this retrospective analysis. Change in platelets from before TIPS to 4 months after TIPS creation was characterized. Logistic regression was used to assess factors associated with top quartile percentage platelet increase after TIPS. Subgroup analyses were performed among patients with a pre-TIPS platelet count of ≤50 ×109/L.ResultsA total of 601 patients were included. The median absolute change in platelets was 1 × 109/L (-26 × 109/L to 25 × 109/L). Patients with top quartile percent platelet increase experienced ≥32% platelet increase. In multivariable analysis, pre-TIPS platelet counts (odds ratio [OR], 0.97 per 109/L; 95% CI, 0.97-0.98), age (OR, 1.24 per 5 years; 95% CI, 1.10-1.39), and pre-TIPS model for end-stage liver disease (MELD) scores (OR, 1.06 per point; 95% CI, 1.02-1.09) were associated with top quartile (≥32%) platelet increase. Ninety-four (16%) patients had a platelet count of ≤50 × 109/L before TIPS. The median absolute platelet change was 14 × 109/L (2 × 109/L to 34 × 109/L). Fifty-four percent of patients in this subgroup were in the top quartile for platelet increase. In multivariable logistic regression, age (OR, 1.50 per 5 years; 95% CI, 1.11-2.02) was the only factor associated with top quartile platelet increase in this subgroup.ConclusionsTIPS creation did not result in significant platelet increase, except among patients with a platelet count of ≤50 × 109/L before TIPS. Lower pre-TIPS platelet counts, older age, and higher pre-TIPS MELD scores were associated with top quartile (≥32%) platelet increase in the entire cohort, whereas only older age was associated with this outcome in the patient subset with a pre-TIPS platelet count of ≤50 × 109/L.

The informal caregiver plays a critical role in supporting patients with various end-stage diseases throughout the solid organ transplantation journey. Caregiver responsibilities include assistance with activities of daily living, medication management, implementation of highly specialized treatments, transportation to appointments and treatments, and health care coordination and navigation. The demanding nature of these tasks has profound impacts across multiple domains of the caregiver's life: physical, psychological, financial, logistical, and social. Few interventions targeting caregiver burden have been empirically evaluated, with the majority focused on education or mindfulness-based stress reduction techniques. Further research is urgently needed to develop and evaluate interventions to improve caregiver burden and outcomes for the patient-caregiver dyad.

Sarcopenic obesity is associated with higher rates of morbidity and mortality than seen with either sarcopenia or obesity alone. We aimed to define sarcopenic visceral obesity (SVO) using CT-quantified skeletal muscle index and visceral-to-subcutaneous adipose tissue ratio and to examine its association with waitlist mortality in patients with cirrhosis. Included were 326 adults with cirrhosis awaiting liver transplantation in the ambulatory setting with available abdominal CT within 6 months from enrollment between February 2015 and January 2018. SVO was defined as patients with sarcopenia (skeletal muscle index

BACKGROUND & AIMS: Grades 3 to 4 hepatic encephalopathy (advanced HE), also termed brain failure, is an organ failure that defines acute-on-chronic liver failure. It is associated with poor outcomes in cirrhosis but cannot be predicted accurately. We aimed to determine the admission metabolomic biomarkers able to predict the development of advanced HE with subsequent validation. METHODS: Prospective inpatient cirrhosis cohorts (multicenter and 2-center validation) without brain failure underwent admission serum collection and inpatient follow-up evaluation. Serum metabolomics were analyzed to predict brain failure on random forest analysis and logistic regression. A separate validation cohort also was recruited. RESULTS: The multicenter cohort included 602 patients, of whom 144 developed brain failure (105 only brain failure) 3 days after admission. Unadjusted random forest analysis showed that higher admission microbially derived metabolites and lower isoleucine, thyroxine, and lysophospholipids were associated with brain failure development (area under the curve, 0.87 all; 0.90 brain failure only). Logistic regression area under the curve with only clinical variables significantly improved with metabolites (95% CI 0.65-0.75; P = .005). Four metabolites that significantly added to brain failure prediction were low thyroxine and maltose and high methyl-4-hydroxybenzoate sulfate and 3-4 dihydroxy butyrate. Thyroxine alone also significantly added to the model (P = .05). The validation cohort including 81 prospectively enrolled patients, of whom 11 developed brain failure. Admission hospital laboratory thyroxine levels predicted brain failure development despite controlling for clinical variables with high specificity. CONCLUSIONS: In a multicenter inpatient cohort, admission serum metabolites, including thyroxine, predicted advanced HE development independent of clinical factors. Admission low local laboratory thyroxine levels were validated as a predictor of advanced HE development in a separate cohort.

BACKGROUND: Personality traits influence clinical outcomes in chronic diseases, but their impact in cirrhosis is unknown. We studied the personality of patients with cirrhosis undergoing liver transplant (LT) evaluation and determined their correlation to clinical outcomes. METHODS: A multicenter prospective study of adult patients undergoing LT evaluation was performed from January 2018 to October 2019. The Big Five personality traits of conscientiousness, extraversion, openness, neuroticism, and agreeableness plus agency were assessed with the Midlife Development Inventory Personality Scale and compared with the general population. Frailty was assessed with the Liver Frailty Index. RESULTS: Two hundred sixty-three LT candidates were enrolled. Twenty-four percent had hepatitis C virus, 25% nonalcoholic steatohepatitis, and 25% ethyl alcohol (mean model for end-stage liver disease = 15.7). Compared with the general population, LT candidates had higher openness (3.1 versus 2.9; P < 0.001), extraversion (3.2 versus 3.1; P < 0.001), agreeableness (3.5 versus 3.4; P = 0.04), agency (2.9 versus 2.6; P < 0.001), neuroticism (2.2 versus 2.1; P = 0.001), and lower conscientiousness (3.3 versus 3.4; P = 0.007). Patients with higher conscientiousness were more likely to receive an LT (HR = 2.76; P = 0.003). CONCLUSIONS: Personality traits in LT candidates differ significantly from the general population, with higher conscientiousness associated with a higher likelihood of receiving a transplant.

GoalsWe sought to determine whether race/ethnicity is associated with hospitalization outcomes among patients admitted with acute cholangitis.BackgroundFew studies have evaluated the association between race and outcomes in patients with acute cholangitis.StudyWe analyzed United States hospitalizations from 2009 to 2018 using the Nationwide Inpatient Sample (NIS). We included patients 18 years old or above admitted with an ICD9/10 diagnosis of cholangitis. Race/ethnicity was categorized as White, Black, Hispanic, or Other. We used multivariable regression to determine the association between race/ethnicity and in-hospital outcomes of interest, including endoscopic retrograde cholangiopancreatography (ERCP), early ERCP (

Goals/backgroundPain is common among cirrhosis patients, particularly those hospitalized with acute illness. Managing pain in this population is challenging due to concern for adverse events and lack of guidelines for analgesic use. We sought to characterize analgesic use among inpatients with cirrhosis compared with matched noncirrhosis controls, as well as hospital-level variation in prescribing patterns.MethodsWe utilized the Vizient Clinical Database, which includes clinical and billing data from hospitalizations at >500 US academic medical centers. We identified cirrhosis patients hospitalized in 2017-2018, and a matched cohort of noncirrhosis patients. Types of analgesic given-acetaminophen (APAP), nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and adjuvants (eg, gabapentinoids, antidepressants) were defined from inpatient prescription records. Conditional logistic regression was used to associate cirrhosis diagnosis with analgesic use.ResultsOf 116,363 cirrhosis inpatients, 83% received at least 1 dose of an analgesic and 58% had regular inpatient analgesic use, rates that were clinically similar to noncirrhosis controls. Cirrhosis inpatients were half as likely to receive APAP (26% vs. 42%, P

Background and aimsNonselective beta-blockers (NSBB) protect patients with compensated cirrhosis; however, it is unclear if NSBB is associated with acute kidney injury (AKI) in patients with decompensated cirrhosis. We aimed to determine if the use of NSBB was associated with an increased risk of stage II AKI or greater and waitlist mortality (WLM) among patients with decompensated cirrhosis awaiting liver transplant stratified by cirrhosis severity.MethodsIncluded were 1816 outpatients listed for liver transplantation at UCSF from June 2012 to April 2022. Our primary outcome was stage 2 AKI (>200% increase in serum creatinine). Our secondary outcome was WLM (all-cause mortality). Our primary exposure was the use of any NSBB derived using natural language processing of clinical notes. Multivariable Cox proportional hazards models with time-dependent variables were used to determine the HR of NSBB use on stage 2 AKI and WLM, stratified by Child-Pugh Score.ResultsThe average age of the cohort was 58 years old, with 35% identifying as female. In multivariable time-dependent models, NSBB use was associated with 1.53 × (95 CI 1.19-1.97) the hazard of stage 2 AKI in the cohort overall and 1.80 × (95 CI 1.26-2.57) among those with Child C cirrhosis, respectively. Similarly, NSBB use was associated with 1.30 × (95 CI 1.07-1.59) and 1.45 × (95 CI 1.03-2.03) the hazard of WLM, overall and in Child C, respectively. NSBB use was not significantly associated with AKI nor WLM among those with Child A.ConclusionNSBB use is associated with Stage 2 AKI and WLM in patients awaiting liver transplantation and Child C cirrhosis. These data suggest cautious use of NSBBs in patients in this population.

BackgroundSymptom-focused trials are critically needed for patients with cirrhosis. However, this work would benefit from standard processes and validated measures.MethodsA writing group was formed among hepatologists, nurses, palliative care providers, pharmacists, and clinical trial experts focused on symptom management in patients with cirrhosis to define the key (1) components of trial design, (2) symptom targets, (3) measurement, and (4) outcomes for each target. From July 2022 to January 2023, panelists participated in an iterative process of developing and arriving at a consensus for each component. The goal was to provide consensus definitions that can be operationalized in future clinical trials, including for patients with cirrhosis.ResultsThe panel reached a consensus on key reporting features for clinical trials, along with considerations for study design. Nine key symptom targets (muscle cramps, pruritus, pain, fatigue, sexual dysfunction, sleep disorders, depression and anxiety, nausea/vomiting, and dyspnea/breathlessness) were identified. The panel selected instruments that can be considered for clinical trials based on psychometric validation and previous experience. The panel identified ongoing needs, including instrument validation, safety data, evidence about non-pharmacologic interventions, and comparative effectiveness studies.ConclusionThis expert panel identified key design, reporting, and measurement elements to standardize processes and measures in future symptom-focused clinical trials in the context of cirrhosis.

Cardiovascular disease is a leading complication after both liver and kidney transplantation. Factors associated with and rates of cardiovascular events (CVEs) after simultaneous liver-kidney transplant (SLKT) are unknown. This was a retrospective cohort study of adult SLKT recipients between 2002 and 2017 at six centers in six United Network for Organ Sharing regions in the US Multicenter SLKT Consortium. The primary outcome was a CVE defined as hospitalization due to acute coronary syndrome, arrhythmia, congestive heart failure, or other CV causes (stroke or peripheral vascular disease) within 1 year of SLKT. Among 515 SLKT subjects (mean age ± SD, 55.4 ± 10.6 years; 35.5% women; 68.1% White), 8.7% had a CVE within 1 year of SLKT. The prevalence of a CVE increased from 3.3% in 2002-2008 to 8.9% in 2009-2011 to 14.0% in 2012-2017 ( p  = 0.0005). SLKT recipients with a CVE were older (59.9 vs. 54.9 years, p

BackgroundWomen systematically experience lower rates of liver transplantation (LT) and higher rates of waitlist mortality than men. Self-rated health has been associated with patient outcomes in the global population. We, therefore, assessed gender differences in self-rated and clinician-rated health among LT candidates.MethodsAmbulatory LT candidates without hepatocellular carcinoma were enrolled from 2012 to 2018. Participants and their hepatologists were asked separately to rate the participant's overall general health on a 6-point scale (0="excellent" to 5="very poor"). Logistic regression was used to assess the associations between covariates and superior self-assessment, defined as 1 SD above the mean self-assessment score.ResultsOf 855 participants, the median (interquartile range) self-rated health score was 2 (1-3); 156 (18%) were categorized as superior self-rated health. The correlation between self-rated and clinician-rated health was positive (Spearman's rho 0.3, P

Since its release as a "research preview" in November 2022, ChatGPT, the conversational interface to the Generative Pretrained Transformer 3 large language model built by OpenAI, has garnered significant publicity for its ability to generate detailed responses to a variety of questions. ChatGPT and other large language models generate sentences and paragraphs in response to word patterns in training data that they have previously seen. By allowing users to communicate with an artificial intelligence model in a human-like way, however, ChatGPT has crossed the technological adoption barrier into the mainstream. Existing examples of ChatGPT use-cases, such as negotiating bills, debugging programing code, and writing essays, indicate that ChatGPT and similar models have the potential to have profound (and yet unknown) impacts on clinical research and practice in hepatology. In this special article, we discuss the general background and potential pitfalls of ChatGPT and associated technologies-and then we explore its uses in hepatology with specific examples.

Background and Aims The incidence and outcomes of breakthrough SARS-CoV-2 infections in vaccinated chronic liver disease (CLD) patients have not been well-characterized in non-veteran populations. We used the National COVID Cohort Collaborative (N3C), a dataset of 10.7 million patients, of whom 0.9 million have vaccination data, to describe outcomes in vaccinated CLD patients. Methods We identified all CLD patients with or without cirrhosis regardless of vaccination status who had SARS-CoV-2 testing in the N3C Data Enclave as of 1/15/2022. We used Poisson regression to estimate incidence rates of breakthrough infections and Cox survival analyses to associate vaccination status with all-cause mortality at 30 days among infected CLD patients. Results We isolated 278,457 total CLD patients: 43,079 (15%) vaccinated and 235,378 (85%) unvaccinated. Of the 43,079 vaccinated CLD patients, 32,838 (76%) were without cirrhosis and 10,441 (24%) were with cirrhosis. Estimated incidence rates for breakthrough infections were 5.6 and 5.1 per 1,000 person-months for 27,235 fully vaccinated CLD patients without cirrhosis and for 8,218 fully vaccinated CLD patients with cirrhosis, respectively. Of the 68,048 unvaccinated and 10,441 vaccinated CLD patients with cirrhosis in our cohort, 15% and 3.7%, respectively, developed SARS-CoV-2 infection. The combined 30-day all-cause rate of mechanical ventilation (without death) or death after SARS-CoV-2 infection for unvaccinated and vaccinated CLD patients with cirrhosis were 15.2% and 7.7%, respectively. Compared to unvaccinated patients with cirrhosis, full vaccination was associated with a 0.34-times adjusted hazard of death at 30 days. Conclusions In this N3C Data Enclave study, breakthrough infection rates were similar amongst CLD patients with and without cirrhosis. Full vaccination was associated with a 66% reduction in risk of all-cause mortality among CLD patients with cirrhosis after infection. These results provide an additional impetus for increasing vaccination uptake among patients with severe liver disease.

Cirrhosis is complicated by a high rate of nosocomial infections (NIs), which result in poor outcomes and are challenging to predict using clinical variables alone. Our aim was to determine predictors of NI using admission serum metabolomics and gut microbiota in inpatients with cirrhosis. In this multicenter inpatient cirrhosis study, serum was collected on admission for liquid chromatography-mass spectrometry metabolomics, and a subset provided stool for 16SrRNA analysis. Hospital course, including NI development and death, were analyzed. Metabolomic analysis using analysis of covariance (ANCOVA) (demographics, Model for End-Stage Liver Disease [MELD] admission score, white blood count [WBC], rifaximin, and infection status adjusted) and random forest analyses for NI development were performed. Additional values of serum metabolites over clinical variables toward NI were evaluated using logistic regression. Stool microbiota and metabolomic correlations were compared in patients with and without NI development. A total of 602 patients (231 infection admissions) were included; 101 (17%) developed NIs, which resulted in worse inpatient outcomes, including intensive care unit transfer, organ failure, and death. A total of 127 patients also gave stool samples, and 20 of these patients developed NIs. The most common NIs were spontaneous bacterial peritonitis followed by urinary tract infection, Clostridioides difficile, and pneumonia. A total of 247 metabolites were significantly altered on ANCOVA. Higher MELD scores (odds ratio, 1.05; p

The economic burden of chronic liver disease is rising; however, the financial impact of chronic liver disease on patients and families has been underexplored. We performed a scoping review to identify studies examining financial burden (patient/family health care expenditures), financial distress (material, behavioral, and psychological consequences of financial burden), and financial toxicity (adverse health outcomes of financial distress) experienced by patients with chronic liver disease and their families. We searched MEDLINE, Embase, Cochrane Library, and the Web of Science online databases for articles published since the introduction of the Model for End-Stage Liver Disease score for liver transplantation allocation in February 2002 until July 2021. Final searches were conducted between June and July 2021. Studies were included if they examined the prevalence or impact of financial burden or distress among patients with chronic liver disease and/or their caregivers. A total of 19 observational studies met inclusion criteria involving 24,549 patients and 276 caregivers across 5 countries. High rates of financial burden and distress were reported within the study populations, particularly among patients with hepatic encephalopathy, hepatocellular carcinoma, and liver transplantation recipients. Financial burden and distress were associated with increased pre- and posttransplantation health care utilization and poor health-related quality of life as well as caregiver burden, depression, and anxiety. None of the included studies evaluated interventions to alleviate financial burden and distress. Observational evidence supports the finding that financial burden and distress are underrecognized but highly prevalent among patients with chronic liver disease and their caregivers and are associated with poor health outcomes. There is a critical need for interventions to mitigate financial burden and distress and reduce financial toxicity in chronic liver disease care.

The burden of early hospitalization (within 6 months) following simultaneous liver-kidney transplant (SLKT) is not known. We examined risk factors associated with early hospitalization after SLKT and their impact on patient mortality conditional on 6-month survival. We used data from the US Multicenter SLKT Consortium cohort study of all adult SLKT recipients between 2002 and 2017 who were discharged alive following SLKT. We used Poisson regression to model rates of early hospitalizations after SLKT. Cox regression was used to identify risk factors associated with mortality conditional on survival at 6 months after SLKT. Median age (N = 549) was 57.7 years (interquartile range [IQR], 50.6-63.9) with 63% males and 76% Whites; 33% had hepatitis C virus, 20% had non-alcohol-associated fatty liver disease, 23% alcohol-associated liver disease, and 24% other etiologies. Median body mass index (BMI) and Model for End-Stage Liver Disease-sodium scores were 27.2 kg/m2 (IQR, 23.6-32.2 kg/m2 ) and 28 (IQR, 23-34), respectively. Two-thirds of the cohort had at least one hospitalization within the first 6 months of SLKT. Age, race, hospitalization at SLKT, diabetes mellitus, BMI, and discharge to subacute rehabilitation (SAR) facility after SLKT were independently associated with a high incidence rate ratio of early hospitalization. Number of hospitalizations within the first 6 months did not affect conditional survival. Early hospitalizations after SLKT were very common but did not affect conditional survival. Although most of the risk factors for early hospitalization were nonmodifiable, discharge to SAR after initial SLKT was associated with a significantly higher incidence rate of early hospitalization. Efforts and resources should be focused on identifying SLKT recipients at high risk for early hospitalization to optimize their predischarge care, discharge planning, and long-term follow-up.

Using in-depth interviews, we sought to characterize the everyday medical and social needs of pediatric liver transplant caregivers to inform the future design of solutions to improve care processes. Participants (parents/caregivers of pediatric liver transplant recipients) completed a survey (assessing socioeconomic status, economic hardship, health literacy, and social isolation). We then asked participants to undergo a 60-min virtual, semistructured qualitative interview to understand the everyday medical and social needs of the caregiver and their household. We intentionally oversampled caregivers who reported a social or economic hardship on the survey. Transcripts were analyzed using thematic analysis and organized around the Capability, Opportunity, Motivation-Behavior model. A total of 18 caregivers participated. Of the participants, 50% reported some form of financial strain, and about half had less than 4 years of college education. Caregivers had high motivation and capability in executing transplant-related tasks but identified several opportunities for improving care. Caregivers perceived the health system to lack capability in identifying and intervening on specific family social needs. Caregiver interviews revealed multiple areas in which family supports could be strengthened, including (1) managing indirect costs of prolonged hospitalizations (e.g., food, parking), (2) communicating with employers to support families' needs, (3) coordinating care across hospital departments, and (4) clarifying care team roles in helping families reduce both medical and social barriers. This study highlights the caregiver perspective on barriers and facilitators to posttransplant care. Future work should identify whether these themes are present across transplant centers. Caregiver perspectives should help inform future interventions aimed at improving long-term outcomes for children after liver transplantation.

The widespread move to online schooling during the COVID-19 crisis meant that parents played a significant role in educating their children. However, there is a paucity of research relating to parents' perceptions of online and remote learning designs. This study used multiple regression analyses and thematic analysis of parent survey responses during COVID-19 to examine which online tasks reduced parental stress and student difficulty, increased student autonomy and learning, and increased parental satisfaction. A key finding was that digital creativity tasks were related to lower levels of parental stress, lower student difficulty, greater student autonomy and greater parent satisfaction with school support. Parents also preferred more web-conferencing lessons and offline tactile activities, and less digital worksheets. These findings have implications for educator-parent collaboration and for remote learning broadly.

Equity is a core principle in both pediatrics and solid organ transplantation. Health inequities, specifically across race, socioeconomic position, or geography, reflect a moral failure. Ethical principles of prudential life span, maximin principle, and fair innings argue for allocation priority to children related to the number of life years gained, equal access to transplant, and equal opportunity for ideal posttransplant outcomes. Iterative policy changes have aimed to narrow these disparities to achieve pediatric transplant equity. These policy changes have focused on modifying pediatric priority for organ allocation to eliminate mortality on the pediatric transplant waiting list. Yet disparities remain in pediatric liver transplantation at all time points: from access to referral for transplantation, likelihood of living donor transplantation, use of exception narratives, waitlist mortality, and inequitable posttransplant outcomes. Black children are less likely to be petitioned for exception scores, have higher waitlist mortality, are less likely to be the recipient of a living donor transplant, and have worse posttransplant outcomes compared with White children. Children living in the most socioeconomically deprived neighborhoods have worse posttransplant outcomes. Children living farther from a transplant center have higher waitlist mortality. Herein we review the current knowledge of these racial and ethnic, socioeconomic, and geographic disparities for these children. To achieve equity, stakeholder engagement is required at all levels from providers and health delivery systems, learning networks, institutions, and society. Future initiatives must be swift, bold, and effective with the tripartite mission to inform policy changes, improve health care delivery, and optimize resource allocation to provide equitable transplant access, waitlist survival, and posttransplant outcomes for all children.

Background and aimsWe investigated the impact of the inclusion of kidney dysfunction type on the discrimination and calibration of the Model for End-Stage Liver Disease with sodium (MELD-Na-KT) score.Approach and resultsWe included all adults listed for ≥90 days without exception points from January 1, 2008, through December 31, 2018. We defined kidney dysfunction types as follows: acute kidney disease (AKD; an increase of ≥0.3 mg/dL or ≥50% in serum creatinine in the last 7 days or fewer than 72 days of hemodialysis), chronic kidney disease (CKD; an estimated glomerular filtration rate

IntroductionLoneliness, "a subjective feeling of being isolated", is a strong predictor of adverse health. We characterized loneliness in patients with end-stage liver disease (ESLD) awaiting liver transplantation (LT).MethodsWe surveyed loneliness in ambulatory ESLD adults awaiting LT at 7 U.S. sites using the validated UCLA Three-Item Loneliness Scale, May2020-Jan2021; "lonely"=total ≥5. Liver Frailty Index (LFI) assessed frailty; "frail"=LFI≥4.4. Logistic regression associated loneliness and co-variables.ResultsOf 454 participants, median MELDNa was 14 (IQR 10-19) and 26% met criteria for "lonely". Compared to those not lonely, those lonely were younger (57 v. 61y), more likely to be female (48% v. 31%) or frail (21 v. 11%), and less likely to be working (15% v. 26%) or in a committed partnership (52% v. 71%). After multivariable adjustment, frailty (OR=2.24, 95%CI=1.23-4.08), younger age (OR=1.19, 95%CI=1.07-1.34), female sex (OR=1.83, 95%CI=1.14-2.92), not working (OR=2.16, 95%CI=1.16-4.03), and not in a committed partnership (OR=2.07, 95%CI=1.29-3.32) remained significantly associated with higher odds of loneliness.ConclusionLoneliness is prevalent in adults awaiting LT, and independently associated with younger age, female sex and physical frailty. These data lay the foundation to investigate the extent to which loneliness impacts health outcomes in LT, as in the general population. Clinical Trial Registry Website: https://clinicaltrials.gov Trial Number: NCT03228290.

Background and aimsAccumulation of visceral adipose tissue is associated with hepatic inflammation and fibrosis, suggestive of its metabolic and inflammatory properties. We aimed to examine the histologic findings of visceral and subcutaneous adipose tissue and to associate these findings with clinical and radiologic characteristics in patients with cirrhosis.MethodsIncluded were 55 adults with cirrhosis who underwent liver transplantation from 3/2017-12/2018 and had an abdominal computed tomography (CT) scan within 6 months prior to transplant. Visceral-to-subcutaneous adipose tissue ratio (VSR) was calculated using visceral (VATI) and subcutaneous adipose tissue index (SATI) quantified by CT at the L3-vertebral level and normalized for height (cm2/m2). VAT (greater omentum), SAT (abdominal wall), and skeletal muscle (rectus abdominis) biopsies were collected at transplant.ResultsMajority of patients had VAT inflammation (71%); only one patient (2%) had SAT inflammation. Patients with VAT inflammation had similar median VATI (42 vs 41 cm2/m2), lower median SATI (64 vs 97 cm2/m2), and higher median VSR (0.63 vs 0.37, p = 0.002) than patients without inflammation. In univariable logistic regression, VSR was associated with VAT inflammation (OR 1.47, 95%CI 1.11-1.96); this association remained significant even after adjusting for age, sex, BMI, HCC, or MELD-Na on bivariable analyses.ConclusionIn patients with cirrhosis undergoing liver transplantation, histologic VAT inflammation was common, but SAT inflammation was not. Increased VSR was independently associated with VAT inflammation. Given the emerging data demonstrating the prognostic value of VSR, our findings support the value of CT-quantified VSR as a prognostic marker for adverse outcomes in the liver transplant setting.

Solid organ transplantation (SOT) is a life-saving procedure for people with end-stage organ failure. However, patients experience significant symptom burden, complex decision making, morbidity, and mortality during both pre- and post-transplant periods. Palliative care (PC) is well suited and historically underdelivered for the transplant population. This article, written by a team of transplant specialists (surgeons, cardiologists, nephrologists, hepatologists, and pulmonologists), PC clinicians, and an ethics specialist, shares 10 high-yield tips for PC clinicians to consider when caring for SOT patients.

ObjectiveTo characterize associations between living in primary care shortage areas and graft failure/death for children after liver transplantation.Study designThis was an observational study of all pediatric patients (aged

Background and aimsKidney dysfunction is associated with increased mortality among patients with cirrhosis. We investigated whether kidney dysfunction types [e.g., acute kidney injury (AKI), chronic kidney disease (CKD), and AKI on CKD] were differentially associated with inpatient mortality.MethodsWe utilized the nationwide inpatient sample, a nationally representative database, from 2007 to 2014. We included all hospitalizations with previously validated codes for cirrhosis or associated decompensated cirrhosis diagnoses. We defined kidney dysfunction types also from previously validated codes, and we grouped hospitalizations into the following diagnoses: normal, AKI, CKD, and AKI on CKD. Our primary outcome was inpatient mortality.ResultsThere were 1,293,779 hospitalizations with cirrhosis sampled in this study. Of these hospitalizations, 849,193 (66%) had normal kidney function, 176,418 (14%) had AKI, 157,600 (12%) had CKD, and 110,568 (9%) had AKI on CKD. We found that the proportion of hospitalizations with AKI, CKD, and AKI on CKD increased significantly throughout the study period (p

In this review article, we discuss the model for end-stage liver disease (MELD) score and its dual purpose in general and transplant hepatology. As the landscape of liver disease and transplantation has evolved considerably since the advent of the MELD score, we summarise emerging concepts, methodologies, and technologies that may improve mortality prognostication in the future. Finally, we explore how these novel concepts and technologies may be incorporated into clinical practice.

Racial/ethnic minorities experience higher rates of wait-list mortality and longer waiting times on the liver transplant wait list. We hypothesized that racial/ethnic minorities may encounter greater logistical barriers to maintaining "readiness" on the wait list, as reflected in offer nonacceptance. We identified all candidates who received an organ offer between 2009 and 2018 and investigated candidates who did not accept an organ offer using a free-text refusal reason associated with refusal code 801. We isolated patients who did not accept an organ offer due to "candidate-related logistical reasons" and evaluated their characteristics. We isolated 94,006 "no 801" patients and 677 "with 801 logistical" patients. Common reasons for offer decline among the 677 were 60% "unable to travel/distance," 22% "cannot be contacted," 13% "not ready/unspecified," and 5% "financial/insurance." Compared to "no 801," "with 801 logistical" patients were more likely to be Hispanic (19% vs. 15%, P

Acute kidney injury (AKI) and frailty are major drivers of outcomes among patients with cirrhosis. What is unknown is the impact of physical frailty on the development of AKI. We included adults with cirrhosis without hepatocellular carcinoma listed for liver transplantation at nine US centers (n = 1,033). Frailty was assessed using the Liver Frailty Index (LFI); "frail" was defined by LFI ≥ 4.2. Chronic kidney disease as a baseline estimated glomerular filtration rate