{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T10:49:51Z","timestamp":1792838991671,"version":"4.5.0"},"reference-count":82,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T00:00:00Z","timestamp":1643155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>In the last years the link between the presence of muscular alterations and hepatic encephalopathy (HE), both minimal and overt, has been deeply studied. The pathophysiological background supporting the relationship between muscle depletion, and HE is characterized by an imbalance between the capacity of muscle in ammonia metabolism and trafficking and the inability of the liver in removing ammonia through urea synthesis due to liver failure and\/or the presence of porto-systemic shunts. This review will focus on the clinical burden, the physio pathological mechanisms understanding the liver muscle axis and principles of management of muscular alterations in cirrhosis.<\/jats:p>","DOI":"10.3390\/jcm11030611","type":"journal-article","created":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T11:02:53Z","timestamp":1643194973000},"page":"611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Ammonia and the Muscle: An Emerging Point of View on Hepatic Encephalopathy"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6414-4404","authenticated-orcid":false,"given":"Simone","family":"Di Cola","sequence":"first","affiliation":[{"name":"Department of Translational and Precision Medicine, Centre for the Diagnosis and Treatment of Portal Hypertension, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7038-9539","authenticated-orcid":false,"given":"Silvia","family":"Nardelli","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Centre for the Diagnosis and Treatment of Portal Hypertension, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8596-2609","authenticated-orcid":false,"given":"Lorenzo","family":"Ridola","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Centre for the Diagnosis and Treatment of Portal Hypertension, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Gioia","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Centre for the Diagnosis and Treatment of Portal Hypertension, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliviero","family":"Riggio","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Centre for the Diagnosis and Treatment of Portal Hypertension, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3173-9767","authenticated-orcid":false,"given":"Manuela","family":"Merli","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Centre for the Diagnosis and Treatment of Portal Hypertension, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1002\/hep.27210","article-title":"Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver","volume":"60","author":"Vilstrup","year":"2014","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1097\/MCG.0000000000000826","article-title":"Early Hospital Readmissions and Mortality in Patients with Decompensated Cirrhosis Enrolled in a Large National Health Insurance Administrative Database","volume":"51","author":"Scaglione","year":"2017","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/ajg.2010.413","article-title":"Minimal Hepatic Encephalopathy Is Associated with Falls","volume":"106","author":"Roman","year":"2011","journal-title":"Am. J. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Nardelli, S., Gioia, S., Ridola, L., Carlin, M., Cioffi, A.D., Merli, M., Riggio, O., and Spagnoli, A. (2021). Risk of falls in patients with cirrhosis evaluated by timed up and go test: Does muscle or brain matter more?. Dig. Liver Dis., in press.","DOI":"10.1016\/j.dld.2021.06.019"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1053\/j.gastro.2009.08.003","article-title":"Hepatic Encephalopathy and Fitness to Drive","volume":"137","author":"Kircheis","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/j.cgh.2008.05.025","article-title":"Patients with Minimal Hepatic Encephalopathy Have Poor Insight into Their Driving Skills","volume":"6","author":"Bajaj","year":"2008","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.cgh.2015.11.007","article-title":"In patients with cirrhosis, driving simulator performance is associated with real-life driving","volume":"14","author":"Lauridsen","year":"2016","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_8","first-page":"151","article-title":"The burden of minimal hepatic encephalopathy: From diagnosis to therapeutic strategies","volume":"31","author":"Ridola","year":"2018","journal-title":"Ann. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1016\/j.cgh.2012.05.016","article-title":"In-Hospital Mortality and Economic Burden Associated with Hepatic Encephalopathy in the United States From 2005 to 2009","volume":"10","author":"Stepanova","year":"2012","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"37","DOI":"10.2147\/HMER.S87594","article-title":"Overt hepatic encephalopathy in Italy: Clinical outcomes and healthcare costs","volume":"7","author":"Roggeri","year":"2015","journal-title":"Hepatic Med. \u00c9vid. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.dld.2018.11.035","article-title":"Hepatic encephalopathy 2018: A clinical practice guideline by the Italian Association for the Study of the Liver (AISF)","volume":"51","author":"Montagnese","year":"2019","journal-title":"Dig. Liver Dis."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2019). EASL Clinical Practice Guidelines on nutrition in chronic liver disease 2019. J. Hepatol., 70, 172\u2013193.","DOI":"10.1016\/j.jhep.2018.06.024"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1146\/annurev.nutr.20.1.457","article-title":"Protein and amino acid metabolism during and after exercise and the effects of nutrition","volume":"20","author":"Rennie","year":"2000","journal-title":"Annu. Rev. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kim, G., Kang, S.H., Kim, M.Y., and Baik, S.K. (2017). Prognostic value of sarcopenia in patients with liver cirrhosis: A systematic review and meta-analysis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0186990"},{"key":"ref_15","first-page":"205","article-title":"Effect of sarcopenia on survival in patients with cirrhosis: A systematic review and meta-analysis","volume":"42","author":"Tantai","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1016\/j.dld.2019.09.004","article-title":"The additive value of sarcopenia, myosteatosis and hepatic encephalopathy in the predictivity of model for end-stage liver disease","volume":"51","author":"Lattanzi","year":"2019","journal-title":"Dig. Liver Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8061","DOI":"10.3748\/wjg.v20.i25.8061","article-title":"Clinical relevance of sarcopenia in patients with cirrhosis","volume":"20","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"270","DOI":"10.3350\/cmh.2019.0015","article-title":"Sarcopenia: Ammonia metabolism and hepatic encephalopathy","volume":"25","author":"Jindal","year":"2019","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_19","first-page":"E983","article-title":"Hyperammonemia-mediated autophagy in skeletal muscle contributes to sarcopenia of cirrhosis","volume":"303","author":"Qiu","year":"2012","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"G163","DOI":"10.1152\/ajpgi.00322.2015","article-title":"Hyperammonemia results in reduced muscle function independent of muscle mass","volume":"310","author":"McDaniel","year":"2016","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s13105-012-0150-6","article-title":"The dose-dependent effects of endotoxin on protein metabolism in two types of rat skeletal muscle","volume":"68","author":"Kovarik","year":"2012","journal-title":"J. Physiol. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1111\/liv.14160","article-title":"Prevalence and impact of sarcopenia in non-cirrhotic portal hypertension","volume":"39","author":"Lattanzi","year":"2019","journal-title":"Liver Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.jhep.2003.10.011","article-title":"Weight gain after transjugular intrahepatic portosystemic shunt is associated with improvement in body composition in malnourished patients with cirrhosis and hypermetabolism","volume":"40","author":"Plauth","year":"2004","journal-title":"J. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1111\/liv.14050","article-title":"The modification of quantity and quality of muscle mass improves the cognitive impairment after TIPS","volume":"39","author":"Gioia","year":"2019","journal-title":"Liver Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1093\/oxfordjournals.aje.a009520","article-title":"Epidemiology of Sarcopenia among the Elderly in New Mexico","volume":"147","author":"Baumgartner","year":"1998","journal-title":"Am. J. Epidemiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"482","DOI":"10.4093\/dmj.2020.0277","article-title":"Computed Tomography-Derived Myosteatosis and Metabolic Disorders","volume":"45","author":"Miljkovic","year":"2021","journal-title":"Diabetes Metab. J."},{"key":"ref_27","first-page":"126","article-title":"Sarcopenic obesity and myosteatosis are associated with higher mortality in patients with cirrhosis","volume":"7","author":"Angulo","year":"2015","journal-title":"J. Cachex-Sarcopenia Muscle"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1097\/MEG.0b013e32834aa4bb","article-title":"Protein energy malnutrition predicts complications in liver cirrhosis","volume":"23","author":"Huisman","year":"2011","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1002\/jcsm.12797","article-title":"Sarcopenia as a prognostic predictor of liver cirrhosis: A multicentre study in China","volume":"12","author":"Zeng","year":"2021","journal-title":"J. Cachex-Sarcopenia Muscle"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/S0168-8278(05)80599-9","article-title":"Prognostic variables in patients with cirrhosis and oesophageal varices without prior bleeding","volume":"21","author":"Bendtsen","year":"1994","journal-title":"J. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3132","DOI":"10.1016\/j.clnu.2020.01.021","article-title":"Sarcopenia associates with increased risk of hepatocellular carcinoma among male patients with cirrhosis","volume":"39","author":"Feng","year":"2020","journal-title":"Clin. Nutr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.cgh.2010.06.024","article-title":"Cirrhotic Patients Are at Risk for Health Care\u2013Associated Bacterial Infections","volume":"8","author":"Merli","year":"2010","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1111\/liv.13691","article-title":"A low muscle mass increases mortality in compensated cirrhotic patients with sepsis","volume":"38","author":"Lucidi","year":"2018","journal-title":"Liver Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1002\/hep.30692","article-title":"Muscle Alterations Are Associated With Minimal and Overt Hepatic Encephalopathy in Patients With Liver Cirrhosis","volume":"70","author":"Nardelli","year":"2019","journal-title":"Hepatology"},{"key":"ref_35","unstructured":"Child, C.G. (1964). Surgery and portal hypertension. The Liver and Portal Hypertension, Saunders. [3rd ed.]."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1002\/hep.510230516","article-title":"Does malnutrition affect survival in cirrhosis? PINC (Policentrica Italiana Nutrizione Cirrosi)","volume":"23","author":"Merli","year":"1996","journal-title":"Hepatology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1111\/j.1440-1746.2007.05222.x","article-title":"Malnutrition and hypermetabolism are not risk factors for the presence of hepatic encephalopathy: A cross-sectional study","volume":"23","author":"Weissenborn","year":"2008","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s12072-018-9875-9","article-title":"Myosteatosis and sarcopenia are associated with hepatic encephalopathy in patients with cirrhosis","volume":"12","author":"Bhanji","year":"2018","journal-title":"Hepatol. Int."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Miwa, T., Hanai, T., Nishimura, K., Maeda, T., Ogiso, Y., Imai, K., Suetsugu, A., Takai, K., Shiraki, M., and Shimizu, M. (2021). Handgrip strength stratifies the risk of covert and overt hepatic encephalopathy in patients with cirrhosis. J. Parenter. Enter. Nutr.","DOI":"10.1002\/jpen.2222"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s11011-012-9365-z","article-title":"Muscle depletion increases the risk of overt and minimal hepatic encephalopathy: Results of a prospective study","volume":"28","author":"Merli","year":"2012","journal-title":"Metab. Brain Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1002\/hep.510290619","article-title":"Clinical features and survival of cirrhotic patients with subclinical cognitive alterations detected by the number connection test and computerized psychometric tests","volume":"29","author":"Amodio","year":"1999","journal-title":"Hepatology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s11011-005-7919-z","article-title":"Attention, memory, and cognitive function in hepatic encephalopathy","volume":"20","author":"Weissenborn","year":"2005","journal-title":"Metab. Brain Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1001\/archneur.1996.00550080076015","article-title":"Neuropsychological Characterization and Detection of Subclinical Hepatic Encephalopathy","volume":"53","author":"McCrea","year":"1996","journal-title":"Arch. Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1023\/B:MEBR.0000043975.01841.de","article-title":"Characteristics of Minimal Hepatic Encephalopathy","volume":"19","author":"Amodio","year":"2004","journal-title":"Metab. Brain Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1111\/j.1478-3231.2007.01562.x","article-title":"Malnutrition and diabetes mellitus are related to hepatic encephalopathy in patients with liver cirrhosis","volume":"27","author":"Kalaitzakis","year":"2007","journal-title":"Liver Int."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1111\/hepr.12873","article-title":"Sarcopenia predicts minimal hepatic encephalopathy in patients with liver cirrhosis","volume":"47","author":"Hanai","year":"2017","journal-title":"Hepatol. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1002\/lt.24750","article-title":"A multicenter study to define sarcopenia in patients with end-stage liver disease","volume":"23","author":"Carey","year":"2017","journal-title":"Liver Transplant."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1093\/geronj\/38.6.673","article-title":"Age Changes in Body Composition Revealed by Computed Tomography","volume":"38","author":"Borkan","year":"1983","journal-title":"J. Gerontol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1126\/science.1082889","article-title":"Mitochondrial Dysfunction in the Elderly: Possible Role in Insulin Resistance","volume":"300","author":"Petersen","year":"2003","journal-title":"Science"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1159\/000182084","article-title":"Alterations in muscle attenuation following detraining and retraining in resistance-trained older adults","volume":"55","author":"Taaffe","year":"2009","journal-title":"Gerontology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1152\/jappl.2001.90.6.2157","article-title":"Attenuation of skeletal muscle and strength in the elderly: The Health ABC Study","volume":"90","author":"Goodpaster","year":"2001","journal-title":"J. Appl. Physiol. (1985)"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.cgh.2016.10.028","article-title":"Sarcopenia Is Risk Factor for Development of Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt Placement","volume":"15","author":"Nardelli","year":"2017","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1172\/JCI109322","article-title":"The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia","volume":"63","author":"Lockwood","year":"1979","journal-title":"J. Clin. Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1111\/hepr.12085","article-title":"Physical inactivity and insufficient dietary intake are associated with the frequency of sarcopenia in patients with compensated viral liver cirrhosis","volume":"43","author":"Hayashi","year":"2013","journal-title":"Hepatol. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1097\/MCO.0000000000000426","article-title":"Hyperammonemia and proteostasis in cirrhosis","volume":"21","author":"Dasarathy","year":"2018","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_56","first-page":"118","article-title":"Malabsorption and nutritional abnormalities in patients with liver cirrhosis","volume":"22","author":"Romiti","year":"1990","journal-title":"Ital. J. Gastroenterol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/j.jhep.2016.06.007","article-title":"Testosterone therapy increases muscle mass in men with cirrhosis and low testosterone: A randomised controlled trial","volume":"65","author":"Sinclair","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/j.1365-2265.1995.tb02040.x","article-title":"Hypothalamic-pituitary-testicular function in end-stage non-alcoholic liver disease before and after liver transplantation","volume":"43","author":"Handelsman","year":"1995","journal-title":"Clin. Endocrinol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1093\/ajcn\/nqz120","article-title":"Branched-chain amino acid and branched-chain ketoacid ingestion increases muscle protein synthesis rates in vivo in older adults: A double-blind, randomized trial","volume":"110","author":"Fuchs","year":"2019","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1530\/JOE-12-0260","article-title":"Myostatin inhibits myosatellite cell proliferation and consequently activates differentiation: Evidence for endocrine-regulated transcript processing","volume":"215","author":"Garikipati","year":"2012","journal-title":"J. Endocrinol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1097\/MCO.0b013e32834dd297","article-title":"Chronic low-grade inflammation and age-related sarcopenia","volume":"15","author":"Beyer","year":"2012","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.14218\/JCTH.2016.00069","article-title":"Hepatic Encephalopathy: An Update on the Pathophysiology and Therapeutic Options","volume":"5","author":"Elwir","year":"2017","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1053\/j.gastro.2009.06.020","article-title":"In the Zone: How a Hepatocyte Knows Where It Is","volume":"137","author":"Kaestner","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1023\/A:1020741226752","article-title":"Effect of portacaval anastomosis on glutamine synthetase protein and gene expression in brain, liver and skeletal muscle","volume":"14","author":"Desjardins","year":"1999","journal-title":"Metab. Brain Dis."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Anda, S., Zach, R., and Grallert, B. (2017). Activation of Gcn2 in response to different stresses. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0182143"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1002\/jcsm.12262","article-title":"Myostatin and beyond in cirrhosis: All roads lead to sarcopenia","volume":"8","author":"Dasarathy","year":"2017","journal-title":"Cachexia Sarcopenia Muscle"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1002\/jcsm.12212","article-title":"Elevated serum myostatin level is associated with worse survival in patients with liver cirrhosis","volume":"8","author":"Nishikawa","year":"2017","journal-title":"J. Cachex-Sarcopenia Muscle"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Rom\u00e1n, E., Garc\u00eda-Galcer\u00e1n, C., Torrades, T., Herrera, S., Mar\u00edn, A., Do\u00f1ate, M., Alvarado-Tapias, E., Malouf, J., N\u00e1cher, L., and Serra-Grima, R. (2016). Effects of an Exercise Programme on Functional Capacity, Body Composition and Risk of Falls in Patients with Cirrhosis: A Randomized Clinical Trial. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0151652"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.clinre.2017.09.005","article-title":"Physical exercise in cirrhotic patients: Towards prehabilitation on waiting list for liver transplantation. A systematic review and meta-analysis","volume":"42","author":"Brustia","year":"2018","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1007\/s00535-006-2002-z","article-title":"Long-term nutritional assessment and quality of life in patients with cirrhosis taking a late evening snack","volume":"42","author":"Okuda","year":"2007","journal-title":"J. Gastroenterol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0168-8278(97)80026-8","article-title":"Low doses of insulin-like growth factor-I improve nitrogen retention and food efficiency in rats with early cirrhosis","volume":"26","author":"Picardi","year":"1997","journal-title":"J. Hepatol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.jhep.2010.08.032","article-title":"Sarcopenia associated with portosystemic shunting is reversed by follistatin","volume":"54","author":"Dasarathy","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3125","DOI":"10.2527\/jas.2016-0532","article-title":"Inhibitors of myostatin as methods of enhancing muscle growth and development","volume":"94","author":"Chen","year":"2016","journal-title":"J. Anim. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2358","DOI":"10.1111\/liv.14938","article-title":"Serum testosterone levels and testosterone supplementation in cirrhosis: A systematic review","volume":"41","author":"Deng","year":"2021","journal-title":"Liver Int."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/S0168-8278(96)80249-2","article-title":"Hyperammonemia-induced depletion of glutamate and branched-chain amino acids in muscle and plasma","volume":"25","author":"Leweling","year":"1996","journal-title":"J. Hepatol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s00535-017-1370-x","article-title":"Supplementation with branched-chain amino acids ameliorates hypoalbuminemia, prevents sarcopenia, and reduces fat accumulation in the skeletal muscles of patients with liver cirrhosis","volume":"53","author":"Kitajima","year":"2017","journal-title":"J. Gastroenterol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/S1542-3565(05)00017-0","article-title":"Effects of Oral Branched-Chain Amino Acid Granules on Event-Free Survival in Patients With Liver Cirrhosis","volume":"3","author":"Muto","year":"2005","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Lattanzi, B., Bruni, A., Di Cola, S., Molfino, A., De Santis, A., Muscaritoli, M., and Merli, M. (2021). The Effects of 12-Week Beta-Hydroxy-Beta-Methylbutyrate Supplementation in Patients with Liver Cirrhosis: Results from a Randomized Controlled Single-Blind Pilot Study. Nutrients, 13.","DOI":"10.3390\/nu13072296"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1002\/hep.29107","article-title":"Ammonia lowering reverses sarcopenia of cirrhosis by restoring skeletal muscle proteostasis","volume":"65","author":"Kumar","year":"2017","journal-title":"Hepatology"},{"key":"ref_80","first-page":"3","article-title":"Treatment with L-ornithine L-aspartate (LOLA) infusion restores muscle protein synthesis responsiveness to feeding in patients with cirrhosis","volume":"30","author":"Reynolds","year":"1999","journal-title":"J. Hepatol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/8182195","article-title":"L-Ornithine L-Aspartate for the Treatment of Sarcopenia in Chronic Liver Disease: The Taming of a Vicious Cycle","volume":"2019","author":"Butterworth","year":"2019","journal-title":"Can. J. Gastroenterol. Hepatol."},{"key":"ref_82","first-page":"1044","article-title":"L-ornithine L-aspartate (LOLA) for the treatment of hepatic encephalopathy in cirrhosis: Evidence for novel hepatoprotective mechanisms","volume":"5","author":"Butterworth","year":"2018","journal-title":"J. Liver Clin."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/3\/611\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:07:56Z","timestamp":1760134076000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/3\/611"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,26]]},"references-count":82,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["jcm11030611"],"URL":"https:\/\/doi.org\/10.3390\/jcm11030611","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,26]]}}}