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      Newly Developed Sarcopenia as a Prognostic Factor for Survival in Patients who Underwent Liver Transplantation

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          Abstract

          Introduction

          The relationship between a perioperative change in sarcopenic status and clinical outcome of liver transplantation (LT) is unknown. We investigated whether post-LT sarcopenia and changes in sarcopenic status were associated with the survival of patients.

          Method

          This retrospective study was based on a cohort of 145 patients from a single transplant center who during a mean of 1 year after LT underwent computed tomography imaging evaluation. The cross-sectional area of the psoas muscle of LT patients was compared with that of age- and sex-matched healthy individuals. The Cox proportional hazards regression model was used to determine whether post-LT sarcopenia and changes in sarcopenic status affect post-LT survival.

          Results

          The mean age at LT of the 116 male and 29 female patients was 50.2 ± 7.9 years; the mean follow-up duration was 51.6 ± 32.9 months. All pre-LT patients with sarcopenia still had sarcopenia 1 year after LT; 14 (15%) patients had newly developed sarcopenia. The mean survival duration was 91.8 ± 4.2 months for non-sarcopenic patients and 80.0 ± 5.2 months for sarcopenic patients (log-rank test, p = 0.069). In subgroup analysis, newly developed sarcopenia was an independent negative predictor for post-LT survival (hazard ratio: 10.53, 95% confidence interval: 1.37–80.93, p = 0.024).

          Conclusion

          Sarcopenia in LT recipients did not improve in any of the previously sarcopenic patients and newly developed within 1 year in others. Newly developed sarcopenia was associated with increased mortality. Newly developed sarcopenia can be used to stratify patients with regard to the risk of post-LT mortality.

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          Most cited references19

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          Malnutrition in cirrhosis: contribution and consequences of sarcopenia on metabolic and clinical responses.

          Malnutrition is the most common, reversible complication of cirrhosis that adversely affects survival, response to other complications, and quality of life. Sarcopenia, or loss of skeletal muscle mass, and loss of adipose tissue and altered substrate use as a source of energy are the 2 major components of malnutrition in cirrhosis. Current therapies include high protein supplementation especially as a late evening snack. Exercise protocols have the potential of aggravating hyperammonemia and portal hypertension. Recent advances in understanding the molecular regulation of muscle mass has helped identify potential novel therapeutic targets including myostatin antagonists, and mTOR resistance. Copyright © 2012 Elsevier Inc. All rights reserved.
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            Sarcopenia is a prognostic factor in living donor liver transplantation.

            The aims of this study were to investigate sarcopenia as a novel predictor of mortality and sepsis after living donor liver transplantation (LDLT) and to evaluate the effects of early enteral nutrition on patients with sarcopenia. Two hundred four patients undergoing preoperative computed tomography within the month before LDLT were retrospectively evaluated. The lengths of the major and minor axes of the psoas muscle were simply measured at the caudal end of the third lumbar vertebra, and the area of the psoas muscle was calculated. A psoas muscle area lower than the 5th percentile for healthy donors of each sex was defined as sarcopenia. Ninety-six of the 204 patients (47.1%), including 58.3% (60/103) of the male patients and 35.6% (36/101) of the female patients, were diagnosed with sarcopenia. Sarcopenia was independently and significantly associated with overall survival: there was an approximately 2-fold higher risk of death for patients with sarcopenia versus patients without sarcopenia (hazard ratio = 2.06, P = 0.047). Sarcopenia was an independent predictor of postoperative sepsis (hazard ratio = 5.31, P = 0.009). Other independent predictors were a younger recipient age (P < 0.001) and a higher body mass index (P = 0.02). Early enteral nutrition within the first 48 hours after LDLT was performed for 24.2% in 2003-2007 and for 100% in 2008-2011, and the incidence of postoperative sepsis for patients with sarcopenia (n = 96) was 28.2% (11/39) in 2003-2007 and 10.5% (6/57) in 2008-2011 (P = 0.03). In conclusion, sarcopenia is an independent predictor of mortality and sepsis after LDLT. The incidence of postoperative sepsis was reduced even in patients with sarcopenia after the routine application of early enteral nutrition.
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              Glucocorticoid-induced skeletal muscle atrophy is associated with upregulation of myostatin gene expression.

              The mechanisms by which excessive glucocorticoids cause muscular atrophy remain unclear. We previously demonstrated that dexamethasone increases the expression of myostatin, a negative regulator of skeletal muscle mass, in vitro. In the present study, we tested the hypothesis that dexamethasone-induced muscle loss is associated with increased myostatin expression in vivo. Daily administration (60, 600, 1,200 micro g/kg body wt) of dexamethasone for 5 days resulted in rapid, dose-dependent loss of body weight (-4.0, -13.4, -17.2%, respectively, P < 0.05 for each comparison), and muscle atrophy (6.3, 15.0, 16.6% below controls, respectively). These changes were associated with dose-dependent, marked induction of intramuscular myostatin mRNA (66.3, 450, 527.6% increase above controls, P < 0.05 for each comparison) and protein expression (0.0, 260.5, 318.4% increase above controls, P < 0.05). We found that the effect of dexamethasone on body weight and muscle loss and upregulation of intramuscular myostatin expression was time dependent. When dexamethasone treatment (600 micro g. kg-1. day-1) was extended from 5 to 10 days, the rate of body weight loss was markedly reduced to approximately 2% within this extended period. The concentrations of intramuscular myosin heavy chain type II in dexamethasone-treated rats were significantly lower (-43% after 5-day treatment, -14% after 10-day treatment) than their respective corresponding controls. The intramuscular myostatin concentration in rats treated with dexamethasone for 10 days returned to basal level. Concurrent treatment with RU-486 blocked dexamethasone-induced myostatin expression and significantly attenuated body loss and muscle atrophy. We propose that dexamethasone-induced muscle loss is mediated, at least in part, by the upregulation of myostatin expression through a glucocorticoid receptor-mediated pathway.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                30 November 2015
                2015
                : 10
                : 11
                : e0143966
                Affiliations
                [1 ]Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Republic of Korea
                [2 ]Department of Surgery, Ajou University School of Medicine, Suwon, Republic of Korea
                [3 ]Office of Biostatistics, Ajou University School of Medicine, Suwon, Republic of Korea
                [4 ]Department of Diagnostic Radiology, Ajou University School of Medicine, Suwon, Republic of Korea
                University of Modena & Reggio Emilia, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JYJ HJW SJH. Performed the experiments: JYJ HJW SYO WX JHL SJH. Analyzed the data: JYJ HJW JDL HJK DJK KWL SJH. Contributed reagents/materials/analysis tools: WX JHL HJK DJK KWL SJH. Wrote the paper: JYJ HJW SYO JDL.

                Article
                PONE-D-15-17600
                10.1371/journal.pone.0143966
                4664264
                26619224
                ed45a0c1-793d-4d1f-bd65-00009f28f4f9
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 25 April 2015
                : 11 November 2015
                Page count
                Figures: 5, Tables: 3, Pages: 14
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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