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      Association Between Liver Transplant Wait-list Mortality and Frailty Based on Body Mass Index

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          Abstract

          Among liver transplant candidates, does the association of frailty and increased risk of wait-list mortality differ by body mass index? In this cohort study, the prevalence of frailty among nonobese candidates and those with class 1 obesity and class 2 or greater obesity was similar. Frailty was associated with a 2-fold higher risk of mortality in nonobese candidates and those with class 1 obesity, and a 3-fold higher risk of mortality in candidates with class 2 or greater obesity. Frailty assessment at transplant evaluation may aid in identification of patients at higher risk of death, mainly obese patients for whom the clinician’s visual evaluation may be less reliable to assess muscle mass and nutritional status. Among liver transplant candidates, obesity and frailty are associated with increased risk of death while they are on the wait-list. However, use of body mass index (BMI) may not detect candidates at a higher risk of death owing to the fact that ascites and muscle wasting are seen across transplant candidates of all BMI measurements. To evaluate whether the association between wait-list mortality and frailty varied by BMI of liver transplant candidates. A prospective cohort study was conducted at 9 liver transplant centers in the United States from March 1, 2012, to May 1, 2018, among 1108 adult liver transplant candidates without hepatocellular carcinoma. At outpatient evaluation, the Liver Frailty Index score was calculated (grip strength, chair stands, and balance), with frailty defined as a Liver Frailty Index score of 4.5 or more. Candidates’ BMI was categorized as nonobese (18.5-29.9), class 1 obesity (30.0-34.9), and class 2 or greater obesity (≥35.0). The risk of wait-list mortality was quantified using competing risks regression by candidate frailty, adjusting for age, sex, race/ethnicity, Model for End-stage Liver Disease Sodium score, cause of liver disease, and ascites, including an interaction with candidate BMI. Of 1108 liver transplant candidates (474 women and 634 men; mean [SD] age, 55 [10] years), 290 (26.2%) were frail; 170 of 670 nonobese candidates (25.4%), 64 of 246 candidates with class 1 obesity (26.0%), and 56 of 192 candidates with class 2 or greater obesity (29.2%) were frail ( P  = .57). Frail nonobese candidates and frail candidates with class 1 obesity had a higher risk of wait-list mortality compared with their nonfrail counterparts (nonobese candidates: adjusted subhazard ratio, 1.54; 95% CI, 1.02-2.33; P  = .04; and candidates with class 1 obesity: adjusted subhazard ratio, 1.72; 95% CI, 0.99-2.99; P  = .06; P  = .75 for interaction). However, frail candidates with class 2 or greater obesity had a 3.19-fold higher adjusted risk of wait-list mortality compared with nonfrail candidates with class 2 or greater obesity (95% CI, 1.75-5.82; P  < .001; P  = .047 for interaction). This study’s finding suggest that among nonobese liver transplant candidates and candidates with class 1 obesity, frailty was associated with a 2-fold higher risk of wait-list mortality. However, the mortality risk associated with frailty differed for candidates with class 2 or greater obesity, with frail candidates having a more than 3-fold higher risk of wait-list mortality compared with nonfrail patients. Frailty assessments may help to identify vulnerable patients, particularly those with a BMI of 35.0 or more, in whom a clinician’s visual evaluation may be less reliable to assess muscle mass and nutritional status. This cohort study evaluates whether the association between wait-list mortality and frailty varies by body mass index of liver transplant candidates.

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          Sarcopenic obesity and myosteatosis are associated with higher mortality in patients with cirrhosis

          Abstract Background and aims Obesity is frequently associated with cirrhosis, and cirrhotic patients may develop simultaneous loss of skeletal muscle and gain of adipose tissue, culminating in the condition of sarcopenic obesity. Additionally, muscle depletion is characterized by both a reduction in muscle size and increased proportion of muscular fat, termed myosteatosis. In this study, we aimed to establish the frequency and clinical significance of sarcopenia, sarcopenic obesity and myosteatosis in cirrhotic patients. Methods We analysed 678 patients with cirrhosis. Sarcopenia, sarcopenic obesity and myosteatosis were analysed by CT scan using the third lumbar vertebrae skeletal muscle and attenuation indexes, using previously validated gender‐and body mass index‐specific cutoffs. Results Patients were predominately men (n = 457, 67%), and cirrhosis aetiology was hepatitis C virus in 269 patients (40%), alcohol in 153 (23%), non‐alcoholic steatohepatitis/cryptogenic in 96 (14%), autoimmune liver disease in 55 (8%), hepatitis B virus in 43 (6%), and others in 5 patients (1%). Sarcopenia was present in 292 (43%), 135 had sarcopenic obesity (20%) and 353 had myosteatosis (52%). Patients with sarcopenia (22 ± 3 vs. 95 ± 22 months, P < 0.001), sarcopenic obesity (22 ± 3 vs. 95 ± 22 months, P < 0.001), and myosteatosis (28 ± 5 vs. 95 ± 22 months, P < 0.001) had worse median survival than patients without muscular abnormalities. By multivariate Cox regression analysis, both sarcopenia [hazard ratio (HR) 2.00, 95% confidence interval (CI) 1.44–2.77, P < 0.001], and myosteatosis (HR 1.42, 95% CI 1.02–1.07, P = 0.04) were associated with mortality. Conclusions Sarcopenia, sarcopenic obesity and myosteatosis are often present in patients with cirrhosis, and sarcopenia and myosteatosis are independently associated with a higher long‐term mortality in cirrhosis.
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            Frailty predicts waitlist mortality in liver transplant candidates.

            We aimed to determine whether frailty, a validated geriatric construct of increased vulnerability to physiologic stressors, predicts mortality in liver transplant candidates. Consecutive adult outpatients listed for liver transplant with laboratory Model for End-Stage Liver Disease (MELD) ≥ 12 at a single center (97% recruitment rate) underwent four frailty assessments: Fried Frailty, Short Physical Performance Battery (SPPB), Activities of Daily Living (ADL) and Instrumental ADL (IADL) scales. Competing risks models associated frailty with waitlist mortality (death/delisting for being too sick for liver transplant). Two hundred ninety-four listed liver transplant patients with MELD ≥ 12, median age 60 years and MELD 15 were followed for 12 months. By Fried Frailty score ≥3, 17% were frail; 11/51 (22%) of the frail versus 25/243 (10%) of the not frail died/were delisted (p = 0.03). Each 1-unit increase in the Fried Frailty score was associated with a 45% (95% confidence interval, 4-202) increased risk of waitlist mortality adjusted for MELD. Similarly, the adjusted risk of waitlist mortality associated with each 1-unit decrease (i.e. increasing frailty) in the Short Physical Performance Battery (hazard ratio 1.19, 95% confidence interval 1.07-1.32). Frailty is prevalent in liver transplant candidates. It strongly predicts waitlist mortality, even after adjustment for liver disease severity demonstrating the applicability and importance of the frailty construct in this population.
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              Body weight is a strong predictor of postural stability.

              Proper balance control is a key aspect of acitivities of daily living. The aim of this study was to determine the contribution of body weight to predict balance stability. The balance stability of 59 male subjects with BMI ranging from 17.4 to 63.8kg/m(2) was assessed using a force platform. The subjects were tested with and without vision. A stepwise multiple regression analysis was used to determine the independent effect of body weight, age, body height and foot length on balance stability (i.e., mean speed of the center of foot pressure). With vision, the stepwise multiple regression revealed that body weight accounted for 52% of the variance of balance stability. The addition of age contributed a further 3% to explain balance control. Without vision, body weight accounted for 54% of the variance and the addition of age and body height added a further 8% and 1% to explain the total variance, respectively. The final model explained 63% of the variance. A decrease in balance stability is strongly correlated to an increase in body weight. This suggests that body weight may be an important risk factor for falling. Future studies should examine more closely the combined effect of aging and obesity on falling and injuries and the impact of obesity on the diverse range of activities of daily living.
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                Author and article information

                Journal
                JAMA Surgery
                JAMA Surg
                American Medical Association (AMA)
                2168-6254
                September 11 2019
                Affiliations
                [1 ]Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
                [2 ]Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland
                [3 ]Center for Liver Disease and Transplantation, Columbia University Medical Center, New York, New York
                [4 ]Department of Hepatology, Baylor University Medical Center, Dallas, Texas
                [5 ]Department of Medicine, Duke University School of Medicine, Durham, North Carolina
                [6 ]Center for Liver Diseases, Thomas A. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
                [7 ]Division of Gastroenterology and Hepatology, Loma Linda University Health, Loma Linda, California
                [8 ]Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
                [9 ]Division of Gastroenterology and Hepatology, University of Arkansas Medical School, Little Rock
                [10 ]Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
                [11 ]Division of Hepatology, Dallas Veterans Administration Medical Center, Dallas, Texas
                [12 ]Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
                [13 ]Department of Medicine, University of California, San Francisco
                Article
                10.1001/jamasurg.2019.2845
                6739734
                31509169
                2af5f9db-c827-4567-8e0f-d7cee08f0b0f
                © 2019
                History

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