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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.

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

Physical frailty and impaired cognition are common in patients with cirrhosis. Physical frailty can be assessed using performance-based tests, but the extent to which impaired cognition may impact performance is not well characterized. We assessed the relationship between impaired cognition and physical frailty in patients with cirrhosis. We enrolled 1,623 ambulatory adult patients with cirrhosis waiting for liver transplantation at 10 sites. Frailty was assessed with the liver frailty index (LFI; "frail," LFI ≥ 4.4). Cognition was assessed at the same visit with the number connection test (NCT); continuous "impaired cognition" was examined in primary analysis, with longer NCT (more seconds) indicating worse impaired cognition. For descriptive statistics, "impaired cognition" was NCT ≥ 45 seconds. Linear regression associated frailty and impaired cognition; competing risk regression estimated subhazard ratios (sHRs) of wait-list mortality (i.e., death/delisting for sickness). Median NCT was 41 seconds, and 42% had impaired cognition. Median LFI (4.2 vs. 3.8) and rates of frailty (38% vs. 20%) differed between those with and without impaired cognition. In adjusted analysis, every 10-second NCT increase associated with a 0.08-LFI increase (95% confidence interval [CI], 0.07-0.10). In univariable analysis, both frailty (sHR, 1.63; 95% CI, 1.43-1.87) and impaired cognition (sHR, 1.07; 95% CI, 1.04-1.10) associated with wait-list mortality. After adjustment, frailty but not impaired cognition remained significantly associated with wait-list mortality (sHR, 1.55; 95% CI, 1.33-1.79). Impaired cognition mediated 7.4% (95% CI, 2.0%-16.4%) of the total effect of frailty on 1-year wait-list mortality. Conclusion: Patients with cirrhosis with higher impaired cognition displayed higher rates of physical frailty, yet frailty independently associated with wait-list mortality while impaired cognition did not. Our data provide evidence for using the LFI to understand mortality risk in patients with cirrhosis, even when concurrent impaired cognition varies.

Background & aimsCirrhosis leads to malnutrition and muscle wasting that manifests as frailty, which may be influenced by cirrhosis aetiology. We aimed to characterize the relationship between frailty and cirrhosis aetiology.MethodsIncluded were adults with cirrhosis listed for liver transplantation (LT) at 10 US centrer who underwent ambulatory testing with the Liver Frailty Index (LFI; 'frail' = LFI ≥ 4.4). We used logistic regression to associate aetiologies and frailty, and competing risk regression (LT as the competing risk) to determine associations with waitlist mortality (death/delisting for sickness).ResultsOf 1,623 patients, rates of frailty differed by aetiology: 22% in chronic hepatitis C, 31% in alcohol-associated liver disease (ALD), 32% in non-alcoholic fatty liver disease (NAFLD), 21% in autoimmune/cholestatic and 31% in 'other' (P  .05 for each). No interaction between frailty and aetiology on the association with waitlist mortality was found (P > .05 for each interaction term).ConclusionsFrailty is more common in patients with ALD, NAFLD and 'other' aetiologies. However, frailty was associated with waitlist mortality independent of cirrhosis aetiology, supporting the applicability of frailty across all cirrhosis aetiologies.

Background and aimsFrailty, as measured by the Liver Frailty Index (LFI), is associated with liver transplant (LT) waitlist mortality. We sought to identify an optimal LFI cutoff that predicts waitlist mortality.Approach and resultsAdults with cirrhosis awaiting LT without hepatocellular carcinoma at nine LT centers in the United States with LFI assessments were included. Multivariable competing risk analysis assessed the relationship between LFI and waitlist mortality. We identified a single LFI cutoff by evaluating the fit of the competing risk models, searching for the cutoff that gave the best model fit (as judged by the pseudo-log-likelihood). We ascertained the area under the curve (AUC) in an analysis of waitlist mortality to find optimal cutoffs at 3, 6, or 12 months. We used the AUC to compare the discriminative ability of LFI+Model for End Stage Liver Disease-sodium (MELDNa) versus MELDNa alone in 3-month waitlist mortality prediction. Of 1,405 patients, 37 (3%), 82 (6%), and 135 (10%) experienced waitlist mortality at 3, 6, and 12 months, respectively. LFI was predictive of waitlist mortality across a broad LFI range: 3.7-5.2. We identified an optimal LFI cutoff of 4.4 (95% confidence interval [CI], 4.0-4.8) for 3-month mortality, 4.2 (95% CI, 4.1-4.4) for 6-month mortality, and 4.2 (95% CI, 4.1-4.4) for 12-month mortality. The AUC for prediction of 3-month mortality for MELDNa was 0.73; the addition of LFI to MELDNa improved the AUC to 0.79.ConclusionsLFI is predictive of waitlist mortality across a wide spectrum of LFI values. The optimal LFI cutoff for waitlist mortality was 4.4 at 3 months and 4.2 at 6 and 12 months. The discriminative performance of LFI+MELDNa was greater than MELDNa alone. Our data suggest that incorporating LFI with MELDNa can more accurately represent waitlist mortality in LT candidates.

Background & aimsTo date, studies evaluating the association between frailty and mortality in patients with cirrhosis have been limited to assessments of frailty at a single time point. We aimed to evaluate changes in frailty over time and their association with death/delisting in patients too sick for liver transplantation.MethodsAdults with cirrhosis, listed for liver transplantation at 8 US centers, underwent ambulatory longitudinal frailty testing using the liver frailty index (LFI). We used multilevel linear mixed-effects regression to model and predict changes in LFI (ΔLFI) per 3 months, based on age, gender, model for end-stage liver disease (MELD)-Na, ascites, and hepatic encephalopathy, categorizing patients by frailty trajectories. Competing risk regression evaluated the subhazard ratio (sHR) of baseline LFI and predicted ΔLFI on death/delisting, with transplantation as the competing risk.ResultsWe analyzed 2,851 visits from 1,093 outpatients with cirrhosis. Patients with severe worsening of frailty had worse baseline LFI and were more likely to have non-alcoholic fatty liver disease, diabetes, or dialysis-dependence. After a median follow-up of 11 months, 223 (20%) of the overall cohort died/were delisted because of sickness. The cumulative incidence of death/delisting increased by worsening ΔLFI group. In competing risk regression adjusted for baseline LFI, age, height, MELD-Na, and albumin, a 0.1 unit change in ΔLFI per 3 months was associated with a 2.04-fold increased risk of death/delisting (95% CI 1.35-3.09).ConclusionWorsening frailty was significantly associated with death/delisting independent of baseline frailty and MELD-Na. Notably, patients who experienced improvements in frailty had a lower risk of death/delisting. Our data support the longitudinal measurement of frailty, using the LFI, in patients with cirrhosis and lay the foundation for interventional work aimed at reversing frailty.Lay summaryFrailty, as measured at a single time point, is predictive of death in patients with cirrhosis, but whether changes in frailty over time are associated with death is unknown. In a study of over 1,000 patients with cirrhosis who underwent frailty testing, we demonstrate that worsening frailty is strongly linked with mortality, regardless of baseline frailty and liver disease severity. Notably, patients who experienced improvements in frailty over time had a lower risk of death/delisting. Our data support the longitudinal measurement of frailty in patients with cirrhosis and lay the foundation for interventional work aimed at reversing frailty.

Background & aimsFrailty is associated with mortality in patients with cirrhosis. We measured frailty using 3 simple tests and calculated Liver Frailty Index (LFI) scores for patients at multiple ambulatory centers. We investigated associations between LFI scores, ascites, and hepatic encephalopathy (HE) and mortality.MethodsAdults without hepatocellular carcinoma who were on the liver transplantation waitlist at 9 centers in the United States (N = 1044) were evaluated using the LFI; LFI scores of at least 4.5 indicated that patients were frail. We performed logistic regression analyses to assess associations between frailty and ascites or HE and competing risk regression analyses (with liver transplantation as the competing risk) to estimate sub-hazard ratios (sHRs) of waitlist mortality (death or removal from the waitlist).ResultsOf study subjects, 36% had ascites, 41% had HE, and 25% were frail. The odds of frailty were higher for patients with ascites (adjusted odd ratio 1.56, 95% confidence interval [CI] 1.15-2.14) or HE (odd ratio 2.45, 95% CI 1.80-3.33) than for those without these features. Larger proportions of frail patients with ascites (29%) or HE (30%) died while on the waitlist compared with patients who were not frail (17% of patients with ascites and 20% with HE). In univariable analysis, ascites (sHR 1.52, 95% CI 1.14-2.05), HE (sHR 1.84, 95% CI 1.38-2.45), and frailty (sHR 2.38, 95% CI 1.77-3.20) were associated with waitlist mortality. In adjusted models, only frailty remained significantly associated with waitlist mortality (sHR 1.82, 95% CI 1.31-2.52); ascites and HE were not.ConclusionsFrailty is a prevalent complication of cirrhosis that is observed more frequently in patients with ascites or HE and independently associated with waitlist mortality. LFI scores can be used to objectively quantify risk of death related to frailty-in excess of liver disease severity-in patients with cirrhosis.

Despite the rapidly increasing prevalence of obesity in the transplant population, the optimal management of obese liver transplant candidates remains undefined. Setting strict body mass index cutoffs for transplant candidacy remains controversial, with limited data to guide this practice. Body mass index is an imperfect measure of surgical risk in this population, partly due to volume overload and variable visceral adiposity. Weight loss before transplantation may be beneficial, but it remains important to avoid protein calorie malnutrition and sarcopenia. Intensive lifestyle modifications appear to be successful in achieving weight loss, though the durability of these interventions is not known. Pretransplant and intraoperative bariatric surgeries have been performed, but large randomized controlled trials are lacking. Traditional cardiovascular comorbidities are more prevalent in obese individuals and remain the basis for pretransplant cardiovascular evaluation and risk stratification. The recent US liver transplant experience demonstrates comparable patient and graft survival between obese and nonobese liver transplant recipients, but obesity presents important medical and surgical challenges during and after transplant. Specifically, obesity is associated with an increased incidence of wound infections, wound dehiscence, biliary complications and overall infection, and confers a higher risk of posttransplant obesity and metabolic syndrome-related complications. In this review, we examine current practices in the obese liver transplant population, offer recommendations based on the currently available data, and highlight areas where additional research is needed.

Background: Older adults have higher healthcare utilization after liver transplantation (LT), yet objective risk stratification tools in this population are lacking. We evaluated the Liver Frailty Index (LFI) as one potential tool. Methods: Ambulatory LT candidates ≥65 years without hepatocellular carcinoma (HCC) who underwent LT from 1/2012 to 6/2022 at 8 U.S. centers were included. Estimates of the difference in median using quantile regression were used to assess the adjusted association between LFI and hospitalized days within 90 days post‐LT. Results: Of 131 LT recipients, median (interquartile range [IQR]) (1st‐3rd quartiles) age was 68 years (66‐70); median pre‐LT MELD‐Na was 19 (15‐24). Median LFI was 4.1 (3.6‐4.7); 27% were frail (LFI≥4.5). Median hospitalized days within 90 days post‐LT was 11 (7‐20). Compared with non‐frail patients, frail patients were hospitalized for a median of 5 days longer post‐LT (95% CI.30‐9.7, p =.04). Each.5 unit increase in pre‐LT LFI was associated with an increase of 1.16 days (95%CI.42‐2.69, p =.02) in hospitalized days post‐LT. Conclusion: Among older adults undergoing LT, frailty was associated with more hospitalized days within 90 days after LT. The LFI can identify older adults who might benefit from pre‐LT or early post‐LT programs which may reduce post‐LT healthcare utilization, such as early rehabilitation or post‐hospital discharge programs. [ABSTRACT FROM AUTHOR]

Background: Patients with obesity have inferior outcomes after general surgery procedures, but studies evaluating post‐liver transplant (LT) outcomes have been limited by small sample sizes or lack of granularity of outcomes. We evaluated the relationship between obesity and post‐LT outcomes, including those observed in other populations to be obesity‐related. Methods: Included were 1357 LT recipients prospectively enrolled in the ambulatory pre‐LT setting at 8 U.S. centers. Recipient were categorized by body mass index (BMI, kg/m2): non‐obese (BMI < 30), class 1 obesity (BMI 30–<35), and classes 2–3 obesity (BMI ≥ 35). Post‐transplant complications were compared by BMI using Chi‐square and rank‐sum testing, logistic regression, Kaplan‐Meier curves, and Cox regression. Results: Classes 2–3 obesity was associated with higher adjusted odds than non‐obesity of venous thrombosis [adjusted odds ratio (aOR) 2.06, 95% CI 1.01–4.23, p =.047] and wound dehiscence (aOR 2.45, 95% CI 1.19–5.06, p =.02). Compared with non‐obese recipients, post‐LT hospital stay was significantly longer for recipients with classes 2–3 obesity [p =.01; median (Q1–Q3) 9 (6–14) vs. 8 (6–12) days) or class 1 obesity [p =.002; 9 (6–14) vs. 8 (6–11) days]. Likelihood of ICU readmission, infection, discharge to a non‐home facility, rejection, 30‐day readmission, and 1‐year readmission were similar across BMI categories (all p >.05). Conclusion: Compared to non‐obese recipients, obese recipients had similar post‐LT survival but longer hospital stay and higher likelihood of wound dehiscence and venous thrombosis. These findings underscore that obesity alone should not preclude LT, but recipients with obesity should be monitored for obesity‐related complications such as wound dehiscence and venous thrombosis. [ABSTRACT FROM AUTHOR]

Background: The etiology of acute liver failure (ALF) remains one of the most important factors in determining prognosis and predicting outcomes. In a significant proportion of ALF cases, however, the etiology remains unknown and is categorized as indeterminate ALF (IND‐ALF). In this study, we summarize findings from patients with IND‐ALF from 32 transplant centers across the United States, and we compare laboratory, prognostic, and outcome data for patients with IND‐ALF. Methods: Between 1998 and 2019, 3364 adult patients with ALF or acute liver injury (ALI) from 32 liver transplant centers were enrolled in the ALFSG registry. The primary clinical outcome of interest was 21‐day transplant‐free survival (TFS). Results: Of the 3364 patients enrolled in the ALFSG registry, 3.4 % (n = 114) were adjudicated as true indeterminate. On multivariate analysis, patients with a lower bilirubin, lower INR, lack of use of mechanical ventilation and no clinical features of coma at baseline had a higher odds ratio of transplant free survival. The number of deaths were similar between patients with true‐IND ALF versus patients with indeterminable ALF (29.8% vs. 27.2%), with almost half of the patients requiring liver transplant (42.1% vs. 45.7%). Conclusion: We illustrate the poor prognoses that true‐IND‐ALF and indeterminable ALF carry and the need for emergency liver transplantation in most cases. [ABSTRACT FROM AUTHOR]