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Sorafenib plus DEB-TACE was technically feasible, but the combination did not improve TTP in a clinically meaningful manner compared with DEB-TACE alone.

Sarcopenia is associated with nonalcoholic fatty liver disease (NAFLD). This study investigated whether sarcopenia is associated with significant liver fibrosis in subjects with NAFLD. Data from the Korean National Health and Nutrition Examination Surveys 2008‐2011 database were analyzed. NALFD was defined by NAFLD liver fat score, comprehensive NAFLD score, or hepatic steatosis index. Degree of liver fibrosis was assessed by NAFLD fibrosis score (NFS), FIB‐4, and Forns index. Significant liver fibrosis was defined as FIB‐4 ≥2.67 and the highest quartile values of NFS and Forns index. Sarcopenia index (= total appendicular skeletal muscle mass [kg]/body mass index (kg/m2]) was calculated using dual‐energy X‐ray absorptiometry. Using the NAFLD liver fat score, NAFLD was identified in 2761 (28.5%) of 9676 subjects. Of subjects with NAFLD, sarcopenia was identified in 337 (12.2%). Sarcopenia was significantly associated with significant liver fibrosis assessed in fibrosis prediction models (all P < 0.05). In subgroups stratified according to body mass index and homeostasis model assessment of insulin resistance, a significant association between sarcopenia and significant liver fibrosis by NFS was consistently present (odds ratio = 1.76‐2.68 depending on the subgroup, all P < 0.05). Multivariate logistic regression analysis demonstrated an independent association between SI and significant liver fibrosis by NFS after adjusting for other confounders (odds ratio = 0.52‐0.67, all P < 0.01). Other NAFLD (comprehensive NAFLD score, hepatic steatosis index) and fibrosis prediction models (FIB‐4 and Forns index) produced similar results. Conclusion: Sarcopenia is associated with significant liver fibrosis in subjects with NAFLD, and the association is independent of obesity and insulin resistance. (Hepatology 2016;63:776–786)

Dietary protocols that increase serum levels of ketones, such as calorie restriction and the ketogenic diet, offer robust protection against a multitude of acute and chronic neurological diseases. The underlying mechanisms, however, remain unclear. Previous studies have suggested that the ketogenic diet may reduce free radical levels in the brain. Thus, one possibility is that ketones may mediate neuroprotection through antioxidant activity. In the present study, we examined the effects of the ketones β-hydroxybutyrate and acetoacetate on acutely dissociated rat neocortical neurons subjected to glutamate excitotoxicity using cellular electrophysiological and single-cell fluorescence imaging techniques. Further, we explored the effects of ketones on acutely isolated mitochondria exposed to high levels of calcium. A combination of β-hydroxybutyrate and acetoacetate (1 mM each) decreased neuronal death and prevented changes in neuronal membrane properties induced by 10 μM glutamate. Ketones also significantly decreased mitochondrial production of reactive oxygen species and the associated excitotoxic changes by increasing NADH oxidation in the mitochondrial respiratory chain, but did not affect levels of the endogenous antioxidant glutathione. In conclusion, we demonstrate that ketones reduce glutamate-induced free radical formation by increasing the NAD + /NADH ratio and enhancing mitochondrial respiration in neocortical neurons. This mechanism may, in part, contribute to the neuroprotective activity of ketones by restoring normal bioenergetic function in the face of oxidative stress. Keywordsglutamate; neurotoxicity; diet; mitochondria; oxidation; stress Address correspondence to: Jong M. Rho, MD., Neurology Research, NRC 4 th Fl., Barrow Neurological Institute and St. Joseph's Hospital & Medical Center, 350 W. Thomas Road, Phoenix, AZ 85013, Email: jong.rho@chw.edu. Section Editor: Molecular Neuroscience W. Sieghart, Brain Research Institute, University of Vienna, Division of Biochemistry and Molecular Biology, Spitalgasse 4, A-1090 Vienna, Austria Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Calorie restriction can decrease the risk of neurodegenerative disease and protect the brain against acute insults such as stroke (Mattson et al, 2002). Similarly, the ketogenic diet, a highfat, low-carbohydrate diet created to mimic the effects of calorie restriction, is an extremely efficacious treatment for medically intractable epilepsy Vining et al, 1998). Several metabolic changes occur during calorie restriction and the ketogenic diet, notably an increase in seru...