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Malnutrition is recognized as the most frequent complication in<jats:styled-content style=\"fixed-case\">ALD<\/jats:styled-content>, and despite the high clinical significance, there are no effective therapies to reverse malnutrition in<jats:styled-content style=\"fixed-case\">ALD<\/jats:styled-content>. Malnutrition is a relatively imprecise term, and sarcopenia or skeletal muscle loss, the major component of malnutrition, is primarily responsible for the adverse clinical consequences in patients with liver disease. It is, therefore, critical to define the specific abnormality (sarcopenia) rather than malnutrition in<jats:styled-content style=\"fixed-case\">ALD<\/jats:styled-content>, so that therapies targeting sarcopenia can be developed. Skeletal muscle mass is maintained by a balance between protein synthesis and proteolysis. Both direct effects of ethanol (EtOH) and its metabolites on the skeletal muscle and the consequences of liver disease result in disturbed proteostasis (protein homeostasis) and consequent sarcopenia. Once cirrhosis develops in patients with ALD, abstinence is unlikely to be effective in completely reversing sarcopenia, as other contributors including hyperammonemia, hormonal, and cytokine abnormalities aggravate sarcopenia and maintain a state of anabolic resistance initiated by EtOH. Cirrhosis is also a state of accelerated starvation, with increased gluconeogenesis that requires amino acid diversion from signaling and substrate functions. Novel therapeutic options are being recognized that are likely to supplant the current \u201cdeficiency replacement\u201d approach and instead focus on specific molecular perturbations, given the increasing availability of small molecules that can target specific signaling components. Myostatin antagonists, leucine supplementation, and mitochondrial protective agents are currently in various stages of evaluation in preclinical studies to prevent and reverse sarcopenia, in cirrhosis in general, and ALD, specifically. Translation of these data to human studies and clinical application requires priority for allocation of resources.<\/jats:p>","DOI":"10.1111\/acer.13425","type":"journal-article","created":{"date-parts":[[2017,5,29]],"date-time":"2017-05-29T16:12:41Z","timestamp":1496074361000},"page":"1419-1431","source":"Crossref","is-referenced-by-count":104,"title":["Sarcopenia in Alcoholic Liver Disease: Clinical and Molecular Advances"],"prefix":"10.1111","volume":"41","author":[{"given":"Jaividhya","family":"Dasarathy","sequence":"first","affiliation":[{"name":"Department of Family Medicine MetroHealth Medical Center Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur J.","family":"McCullough","sequence":"additional","affiliation":[{"name":"Department of Gastreoenterology, Hepatology and Pathobiology Cleveland Clinic Cleveland 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