Sarcopenia is associated with increased wait-list mortality, but a standard definition is lacking. In this retrospective study, we sought to determine the optimal definition of sarcopenia in end-stage liver disease (ESLD) patients awaiting liver transplantation (LT). Included were 396 patients newly listed for LT in 2012 at 5 North American transplant centers. All computed tomography scans were read by 2 individuals with interobserver correlation of 98%. Using image analysis software, the total cross-sectional area (cm2) of abdominal skeletal muscle at the third lumbar vertebra was measured. The skeletal muscle index (SMI), which normalizes muscle area to patient height, was then calculated. The primary outcome was wait-list mortality, defined as death on the waiting list or removal from the waiting list for reasons of clinical deterioration. Sex-specific potential cutoff values to define sarcopenia were determined with a grid search guided by log-rank test statistics. Optimal search methods identified potential cutoffs to detect survival differences between groups. The overall median SMI was 47.6 cm2/m2: 50.0 in men and 42.0 in women. At a median of 8.8 months follow-up, mortality was 25% in men and 36% in women. Patients who died had lower SMI than those who survived (45.6 versus 48.5 cm2/m2; P < 0.001), and SMI was associated with wait-list mortality (hazard ratio, 0.95; P < 0.001). Optimal search method yielded SMI cutoffs of 50 cm2/m2 for men and 39 cm2/m2 for women; these cutoff values best combined statistical significance with a sufficient number of events to detect survival differences between groups. In conclusion, we recommend that an SMI < 50 cm2/m2 for men and < 39 cm2/m2 for women be used to define sarcopenia in patients with ESLD awaiting LT.

BackgroundSarcopenia, characterized by low muscle mass, associates with mortality in patients with cirrhosis. Skeletal muscle area in a single computed tomography image at the level of the third lumbar vertebrate (L3) is a valid representative of whole body muscle mass. Controversy remains regarding applicability of psoas muscle to identify patients at greater risk of mortality. We aimed to determine psoas muscle index (PMI) association with skeletal muscle index (SMI) and to evaluate the capacity of PMI to predict liver transplant waitlist mortality.MethodsWe evaluated listed adult patients with cirrhosis from 2012 to 2013 at four North American liver transplant centres. From L3 computed tomography images within 3 months of listing, we determined SMI and PMI expressed by cm2/m2. Low SMI was defined as SMI <39 cm2/m2 in women and <50 cm2/m2 in men as published by us earlier. Cut‐offs for PMI to predict mortality were established using a receiver‐operating characteristic analysis. Mortality predictors were determined using competing‐risk analysis with reported results as subdistribution hazard ratios (sHRs).ResultsOf 353 waitlist candidates, 68% were men, mean age 56 ± 9 years, and Model for End‐stage Liver Disease of 16 ± 8 points. Low SMI was present more frequently in men than women (51 vs. 36%, P = 0.02). Moderately strong correlation between SMI and PMI was observed (r > 0.7, P < 0.001). Low PMI (males < 5.1 cm2/m2; females < 4.3 cm2/m2) yielded poor and moderate concordance with low SMI in men and women, respectively (Kappa coefficient 0.31 and 0.63). SMI (39 ± 9 vs. 43 ± 7 cm2/m2; P = 0.009) and PMI (4.4 ± 1.3 vs. 5.2 ± 1.1 cm2/m2; P = 0.001) were lower in women who died and/or were delisted (compared with non‐deceased patients) whereas men who died and/or were delisted had only lower SMI (47 ± 7 vs. 51 ± 9 cm2/m2; P = 0.003), but not PMI compared with non‐deceased patients. In women, both SMI (sHR 0.94, P = 0.048) and PMI (sHR 0.58, P = 0.002) were predictors of mortality, while in men, SMI was significant (sHR 0.95, P = 0.001) and PMI showed a trend to be (sHR 0.85, P = 0.09) associated with mortality. Overall, 104 patients (29%) were misclassified between SMI and PMI categories. Using PMI cut‐offs, 66% and 28% of low SMI men and women, who have a higher risk of mortality, were incorrectly classified as low risk.ConclusionsSkeletal muscle index is a more complete and robust measurement than PMI, especially in men with cirrhosis. Low PMI identifies an incomplete subset of patients at increased risk of mortality indicated by low SMI. Given the poor performance of PMI, SMI should not be substituted by PMI.

The Liver Frailty Index (LFI), composed of 3 performance‐based tests (grip strength, chair stands, and balance), is a tool specifically developed in patients with cirrhosis to objectively measure physical function, a critical determinant of health outcomes. We aimed to (1) determine the range of LFI scores in adults with chronic liver disease but without cirrhosis, (2) determine the range of LFI scores in adults without known liver disease, and (3) evaluate reproducibility of the LFI in adults with cirrhosis listed for liver transplantation. Intraclass correlation coefficient (ICC) assessed interrater reliability of the LFI. Included were 91 adults with chronic liver disease, 109 adults without known liver disease, and 166 adults with cirrhosis with median Model for End‐Stage Liver Disease–sodium of 16. Median (interquartile range) LFI was 3.6 (3.1‐4.1) in adults with cirrhosis, 3.1 (2.5‐3.7) in adults with chronic liver disease but not cirrhosis, and 2.7 (2.2‐3.2) in adults without liver disease (P < 0.001). Using established LFI cutoffs for robust, prefrail, and frail categories, adults with cirrhosis or chronic liver disease were less likely to be robust (29% versus 53% versus 77%) and more likely to be prefrail (57% versus 42% versus 22%) or frail (14% versus 5% versus 1%) when compared with adults without liver disease (P < 0.001). The LFI had excellent reliability with ICC of 0.93 (95% confidence interval, 0.91‐0.95). In conclusion, the LFI has external validity in noncirrhotic populations and is highly reproducible among different raters. This objective assessment tool can be implemented in outpatient clinical practice or research to operationalize the concept of physical frailty.

Background Sarcopenia and functional impairment are common and lethal extra-hepatic manifestations of cirrhosis. We aimed to determine the association between computed-tomography (CT)-based measures of muscle mass and quality (sarcopenia) and performance-based measures of muscle function. Methods Adults listed for liver transplant underwent testing of muscle function [grip strength, Short Physical Performance Battery (SPPB)] within 3 months of abdominal CT. Muscle mass (cm2/m2) =total cross-sectional area of psoas, paraspinal, and abdominal wall muscles at L3 on CT, normalized for height. Muscle quality=mean Hounsfield units (HU) for total skeletal muscle area at L3. Results Among 292 candidates, median grip strength was 31kg, SPPB score was 11, muscle mass was 49cm2/m2, and muscle quality was 35HU. Grip strength weakly correlated with muscle mass (ρ=0.26, p<0.001) and quality (ρ=0.27; p<0.001) in men, and muscle quality (ρ=0.23, p=0.02), but not muscle mass, in women. SPPB correlated weakly with muscle quality in men (ρ=0.38; p<0.001) and women (ρ=0.25; p=0.02), however did not correlate with muscle mass in men or women. After adjustment for gender, MELD-Na, hepatocellular carcinoma, and BMI, grip strength (HR 0.74, 95%CI 0.59–0.92, p=0.008), SPPB (HR 0.89, 95%CI 0.82–0.97, p=0.01), and muscle quality (HR 0.77, 95%CI 0.63–0.95, p=0.02) were associated with wait-list mortality, but muscle mass was not (HR 0.91, 95%CI 0.75–1.11, p=0.35). Conclusions Performance-based tests of muscle function are only modestly associated with CT-based muscle measures. Given that they predict wait-list mortality and can be conducted quickly and economically, tests of muscle function may have greater clinical utility than CT-based measures of sarcopenia.

The emerging epidemic of older cirrhotics has led to a sharp increase in the number of ≥65 year olds considering liver transplantation (LT). However, clinicians lack objective measures to risk stratify older patients. We aimed to determine whether the Short Physical Performance Battery (SPPB), a well-validated geriatric measure of physical function, has greater prognostic value in older versus younger LT candidates. Adult outpatients listed for LT with laboratory MELD ≥12 underwent physical function testing using the SPPB, consisting of gait speed, chair stands, and balance. Patients were categorized by age (“younger”= <65 years; “older”= ≥65 years) and SPPB (“impaired”= ≤9; “robust”= >9). Competing risks models associated age and SPPB with wait-list death/delisting. Of 463 LT candidates, 21% were ≥65 years; 18% died/delisted. Older patients had slower gait (1.1 vs.1.3m/sec; p<0.001), a trend of slower chair stands (12.8 vs.11.8sec; p=0.06), and a smaller proportion able to complete all balance tests (65 vs.78%; p=0.01); SPPB was lower in older vs. younger patients (10 vs.11; p=0.01). When compared to younger robust patients as a reference group, younger impaired patients (HR 1.77; p=0.03) and older impaired patients (HR 2.70; p=0.003) had significantly higher risk of wait-list mortality, but there was no difference in risk for older robust patients (HR 1.38; p=0.35) [test of equality p=0.01]. After adjustment for MELD-Na, only older impaired patients had an increased risk of wait-list mortality compared to younger robust patients (HR 2.36; p=0.01) [test of equality p=0.05]. In conclusion, functional impairment, as assessed by the SPPB, predicts death/delisting for LT candidates ≥ 65 years independent of MELD-Na. Further research into activity-based interventions to reduce adverse transplant outcomes in this population is warranted.

Background: Patients with end-stage liver disease (ESLD) awaiting liver transplantation (LT) are seriously ill and experience fluctuating periods of clinical decompensation. Discussion of a patient's advance care planning (ACP) wishes early in their dynamic disease course is critical to providing value-aligned care while awaiting LT. We aimed to evaluate current ACP documentation and assess readiness to engage in ACP in this population. Methods:We conducted a retrospective study of adults undergoing LT evaluation from 1/17-6/17 and assessed characteristics associated with documentation using logistic regression. We then administered a survey to LT candidates from 3/18-5/18 to determine self-reported readiness to engage in ACP (range 1=not at all ready to 5=very ready).Results: Among 170 LT candidates, median [interquartile range (IQR)] age was 58 (53-65), 65% were men, MELDNa was 15 (11-21), and Child Pugh A/B/C were 33/38/29%. Nine percent reported completing ACP prior to LT evaluation, but 0% had legal ACP forms or end-of-life wishes documented in the medical record. A durable power of attorney (DPOA) was discussed with 10%. In univariable analysis, white race (OR 4.16, p=0.03) and female sex (OR 3.06, p=0.04) were associated with ACP documentation, but Child Pugh score and MELDNa were not. Of the 41 Terms of use and reuse: academic research for non-commercial purposes, see here for full terms. https://www.springer.com/aamterms-v1

OBJECTIVES: Frailty is prevalent in patients with cirrhosis and is hypothesized to result in part from sarcopenia, but the precise contribution of sarcopenia to frailty in this population is poorly understood. METHODS: Included were patients with cirrhosis from 2011 to 2014 who had an ambulatory frailty assessment and abdominal computed tomography scan within 3 months. Logistic regression assessed the associations between frailty (=Liver Frailty Index ≥4.5), and sarcopenia (=skeletal muscle index of <39 cm2/m2 for women and <50 cm2/m2 for men). RESULTS: Two hundred ninety-one participants were included: 33% were female. The median (interquartile range) Liver Frailty Index was 3.7 (3.3–4.2); 19% were frail. The median (interquartile range) skeletal muscle index was 49 cm2/m2 (31–69); 36% had sarcopenia. Among the 54 frail participants, 48% had sarcopenia. In univariable logistic regression, sarcopenia was associated with a 1.86× increased odds of being frail (95% confidence interval [CI], 1.02–3.38). After adjusting for sex, etiology, hepatocellular carcinoma, MELDNa, ascites, encephalopathy, and hypertension, sarcopenia was associated with a 2.38× increased odds of being frail (95% CI, 1.17–4.85). After stratifying by sex and adjusting for MELDNa, sarcopenia among males was associated with a significantly increased odds of frailty (odds ratio 2.81, 95% CI, 1.19–6.67), whereas sarcopenia among females was not (odds ratio 1.38; 95% CI, 0.45–4.25). DISCUSSION: In patients with cirrhosis, sarcopenia was associated with a nearly 2-fold increased odds of being frail. Two-thirds of frail men displayed sarcopenia compared with only one-quarter of frail women. Contributors to the frail phenotype may differ by sex and support the need for sex-specific strategies to reduce frailty in this population.

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