{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T09:26:38Z","timestamp":1784366798557,"version":"3.55.0"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T00:00:00Z","timestamp":1737590400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T00:00:00Z","timestamp":1737590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Fonds de Recherche du Qu\u00e9bec - Sant\u00e9,Canada"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007827","name":"American College of Gastroenterology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007827","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000264","name":"Canadian Liver Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-130556"],"award-info":[{"award-number":["MOP-130556"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-130556"],"award-info":[{"award-number":["MOP-130556"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Metab Brain Dis"],"DOI":"10.1007\/s11011-024-01525-2","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T09:18:54Z","timestamp":1737623934000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Attenuating hyperammonemia preserves protein synthesis and muscle mass via restoration of perturbed metabolic pathways in bile duct-ligated rats"],"prefix":"10.1007","volume":"40","author":[{"given":"Cristina R.","family":"Bosoi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avinash","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana M.","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Welch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc-Andr\u00e9","family":"Cl\u00e9ment","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Tremblay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella A. M.","family":"Ten-Have","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marielle P. K. J.","family":"Engelen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"B\u00e9meur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaas E. P.","family":"Deutz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivasan","family":"Dasarathy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher F.","family":"Rose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,23]]},"reference":[{"key":"1525_CR1","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1111\/liv.13997","volume":"39","author":"L Aamann","year":"2019","unstructured":"Aamann L, Ochoa-Sanchez R, Oliveira M et al (2019) Progressive resistance training prevents loss of muscle mass and strength in bile duct-ligated rats. Liver Int 39:676\u2013683. https:\/\/doi.org\/10.1111\/liv.13997","journal-title":"Liver Int"},{"key":"1525_CR2","doi-asserted-by":"publisher","first-page":"e0384","DOI":"10.1097\/HC9.0000000000000384","volume":"8","author":"JS Bajaj","year":"2024","unstructured":"Bajaj JS, Fagan A, Gavis EA et al (2024) The RIVET RCT: Rifamycin SV MMX improves muscle mass, physical function, and ammonia in cirrhosis and minimal encephalopathy. Hepatol Commun 8:e0384. https:\/\/doi.org\/10.1097\/HC9.0000000000000384","journal-title":"Hepatol Commun"},{"key":"1525_CR3","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1007\/s12072-018-9875-9","volume":"12","author":"RA Bhanji","year":"2018","unstructured":"Bhanji RA, Moctezuma-Velazquez C, Duarte-Rojo A et al (2018) Myosteatosis and sarcopenia are associated with hepatic encephalopathy in patients with cirrhosis. Hepatol Int 12:377\u2013386. https:\/\/doi.org\/10.1007\/s12072-018-9875-9","journal-title":"Hepatol Int"},{"key":"1525_CR4","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/s11011-008-9112-7","volume":"24","author":"CR Bosoi","year":"2009","unstructured":"Bosoi CR, Rose CF (2009) Identifying the direct effects of ammonia on the brain. Metab Brain Dis 24:95\u2013102. https:\/\/doi.org\/10.1007\/s11011-008-9112-7","journal-title":"Metab Brain Dis"},{"key":"1525_CR5","doi-asserted-by":"publisher","first-page":"1995","DOI":"10.1002\/hep.24273","volume":"53","author":"CR Bosoi","year":"2011","unstructured":"Bosoi CR, Parent-Robitaille C, Anderson K et al (2011) AST-120 (spherical carbon adsorbent) lowers ammonia levels and attenuates brain edema in bile-duct ligated rats. Hepatology 53:1995\u20132002. https:\/\/doi.org\/10.1002\/hep.24273","journal-title":"Hepatology"},{"key":"1525_CR6","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1016\/j.freeradbiomed.2012.01.006","volume":"52","author":"CR Bosoi","year":"2012","unstructured":"Bosoi CR, Yang X, Huynh J et al (2012) Systemic oxidative stress is implicated in the pathogenesis of brain edema in rats with chronic liver failure. Free Radic Biol Med 52:1228\u20131235. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2012.01.006","journal-title":"Free Radic Biol Med"},{"key":"1525_CR7","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/j.jhep.2013.10.011","volume":"60","author":"CR Bosoi","year":"2014","unstructured":"Bosoi CR, Zwingmann C, Marin H et al (2014) Increased brain lactate is central to the development of brain edema in rats with chronic liver disease. J Hepatol 60:554\u2013560. https:\/\/doi.org\/10.1016\/j.jhep.2013.10.011","journal-title":"J Hepatol"},{"key":"1525_CR8","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1007\/s11011-016-9937-4","volume":"32","author":"CR Bosoi","year":"2017","unstructured":"Bosoi CR, Oliveira MM, Ochoa-Sanchez R et al (2017) The bile duct ligated rat: A relevant model to study muscle mass loss in cirrhosis. Metab Brain Dis 32:513\u2013518. https:\/\/doi.org\/10.1007\/s11011-016-9937-4","journal-title":"Metab Brain Dis"},{"key":"1525_CR9","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1111\/jnc.15290","volume":"157","author":"M-A Cl\u00e9ment","year":"2021","unstructured":"Cl\u00e9ment M-A, Bosoi CR, Oliveira MM et al (2021) Bile-duct ligation renders the brain susceptible to hypotension-induced neuronal degeneration: Implications of ammonia. J Neurochem 157:561\u2013573. https:\/\/doi.org\/10.1111\/jnc.15290","journal-title":"J Neurochem"},{"key":"1525_CR10","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1093\/ageing\/afy169","volume":"48","author":"AJ Cruz-Jentoft","year":"2019","unstructured":"Cruz-Jentoft AJ, Bahat G, Bauer J et al (2019) Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing 48:16\u201331. https:\/\/doi.org\/10.1093\/ageing\/afy169","journal-title":"Age Ageing"},{"key":"1525_CR11","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1097\/MOG.0000000000000261","volume":"32","author":"S Dasarathy","year":"2016","unstructured":"Dasarathy S (2016a) Etiology and management of muscle wasting in chronic liver disease. Curr Opin Gastroenterol 32:159\u2013165. https:\/\/doi.org\/10.1097\/MOG.0000000000000261","journal-title":"Curr Opin Gastroenterol"},{"key":"1525_CR12","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1097\/MOG.0000000000000261","volume":"32","author":"S Dasarathy","year":"2016","unstructured":"Dasarathy S (2016b) Cause and management of muscle wasting in chronic liver disease. Curr Opin Gastroenterol 32:159\u2013165. https:\/\/doi.org\/10.1097\/MOG.0000000000000261","journal-title":"Curr Opin Gastroenterol"},{"key":"1525_CR13","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1097\/mco.0000000000000426","volume":"21","author":"S Dasarathy","year":"2018","unstructured":"Dasarathy S, Hatzoglou M (2018) Hyperammonemia and proteostasis in cirrhosis. Curr Opin Clin Nutr Metab Care 21:30\u201336. https:\/\/doi.org\/10.1097\/mco.0000000000000426","journal-title":"Curr Opin Clin Nutr Metab Care"},{"key":"1525_CR14","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1016\/j.jhep.2016.07.040","volume":"65","author":"S Dasarathy","year":"2016","unstructured":"Dasarathy S, Merli M (2016) Sarcopenia from mechanism to diagnosis and treatment in liver disease. J Hepatol 65:1232\u20131244. https:\/\/doi.org\/10.1016\/j.jhep.2016.07.040","journal-title":"J Hepatol"},{"key":"1525_CR15","doi-asserted-by":"publisher","first-page":"G1124","DOI":"10.1152\/ajpgi.00202.2004","volume":"287","author":"S Dasarathy","year":"2004","unstructured":"Dasarathy S, Dodig M, Muc SM et al (2004a) Skeletal muscle atrophy is associated with an increased expression of myostatin and impaired satellite cell function in the portacaval anastamosis rat. Am J Physiol-Gastrointest Liver Physiol 287:G1124\u2013G1130. https:\/\/doi.org\/10.1152\/ajpgi.00202.2004","journal-title":"Am J Physiol-Gastrointest Liver Physiol"},{"key":"1525_CR16","doi-asserted-by":"publisher","first-page":"G1124","DOI":"10.1152\/ajpgi.00202.2004","volume":"287","author":"S Dasarathy","year":"2004","unstructured":"Dasarathy S, Dodig M, Muc SM et al (2004b) Skeletal muscle atrophy is associated with an increased expression of myostatin and impaired satellite cell function in the portacaval anastamosis rat. Am J Physiol Gastrointest Liver Physiol 287:G1124-1130. https:\/\/doi.org\/10.1152\/ajpgi.00202.2004","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"1525_CR17","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1016\/j.jhep.2010.08.032","volume":"54","author":"S Dasarathy","year":"2011","unstructured":"Dasarathy S, McCullough AJ, Muc S et al (2011) Sarcopenia associated with portosystemic shunting is reversed by follistatin. J Hepatol 54:915\u2013921. https:\/\/doi.org\/10.1016\/j.jhep.2010.08.032","journal-title":"J Hepatol"},{"key":"1525_CR18","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1007\/s11011-016-9938-3","volume":"32","author":"S Dasarathy","year":"2017","unstructured":"Dasarathy S, Mookerjee RP, Rackayova V et al (2017) Ammonia toxicity: from head to toe? Metab Brain Dis 32:529\u2013538. https:\/\/doi.org\/10.1007\/s11011-016-9938-3","journal-title":"Metab Brain Dis"},{"key":"1525_CR19","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1002\/hep.22897","volume":"50","author":"NA Davies","year":"2009","unstructured":"Davies NA, Wright G, Ytreb\u00f8 LM et al (2009) L-ornithine and phenylacetate synergistically produce sustained reduction in ammonia and brain water in cirrhotic rats. Hepatology 50:155\u2013164. https:\/\/doi.org\/10.1002\/hep.22897","journal-title":"Hepatology"},{"key":"1525_CR20","doi-asserted-by":"publisher","first-page":"7341","DOI":"10.1113\/JP272796","volume":"594","author":"G Davuluri","year":"2016","unstructured":"Davuluri G, Allawy A, Thapaliya S et al (2016a) Hyperammonaemia-induced skeletal muscle mitochondrial dysfunction results in cataplerosis and oxidative stress. J Physiol (Lond) 594:7341\u20137360. https:\/\/doi.org\/10.1113\/JP272796","journal-title":"J Physiol (Lond)"},{"key":"1525_CR21","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1016\/j.jhep.2016.06.004","volume":"65","author":"G Davuluri","year":"2016","unstructured":"Davuluri G, Krokowski D, Guan B-J et al (2016b) Metabolic adaptation of skeletal muscle to hyperammonemia drives the beneficial effects of L-leucine in cirrhosis. J Hepatol 65:929\u2013937. https:\/\/doi.org\/10.1016\/j.jhep.2016.06.004","journal-title":"J Hepatol"},{"key":"1525_CR22","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1023\/A:1020741226752","volume":"14","author":"P Desjardins","year":"1999","unstructured":"Desjardins P, Rao KV, Michalak A et al (1999) Effect of portacaval anastomosis on glutamine synthetase protein and gene expression in brain, liver and skeletal muscle. Metab Brain Dis 14:273\u2013280","journal-title":"Metab Brain Dis"},{"key":"1525_CR23","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1152\/japplphysiol.00736.2007","volume":"104","author":"HC Dreyer","year":"2008","unstructured":"Dreyer HC, Glynn EL, Lujan HL et al (2008) Chronic paraplegia-induced muscle atrophy downregulates the mTOR\/S6K1 signaling pathway. J Appl Physiol 104:27\u201333. https:\/\/doi.org\/10.1152\/japplphysiol.00736.2007","journal-title":"J Appl Physiol"},{"key":"1525_CR24","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.1007\/s10620-019-05576-9","volume":"64","author":"G Hirode","year":"2019","unstructured":"Hirode G, Vittinghoff E, Wong RJ (2019) Increasing Burden of Hepatic Encephalopathy Among Hospitalized Adults: An Analysis of the 2010\u20132014 National Inpatient Sample. Dig Dis Sci 64:1448\u20131457. https:\/\/doi.org\/10.1007\/s10620-019-05576-9","journal-title":"Dig Dis Sci"},{"key":"1525_CR25","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/978-981-13-1435-3_7","volume":"1088","author":"J Ilha","year":"2018","unstructured":"Ilha J, do Esp\u00edrito-Santo CC, de Freitas GR (2018) mTOR signaling pathway and protein synthesis: From training to aging and muscle autophagy. Adv Exp Med Biol 1088:139\u2013151. https:\/\/doi.org\/10.1007\/978-981-13-1435-3_7","journal-title":"Adv Exp Med Biol"},{"key":"1525_CR26","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1016\/j.mehy.2006.12.061","volume":"69","author":"R Jalan","year":"2007","unstructured":"Jalan R, Wright G, Davies NA, Hodges SJ (2007) L-Ornithine phenylacetate (OP): a novel treatment for hyperammonemia and hepatic encephalopathy. Med Hypotheses 69:1064\u20131069. https:\/\/doi.org\/10.1016\/j.mehy.2006.12.061","journal-title":"Med Hypotheses"},{"key":"1525_CR27","doi-asserted-by":"publisher","first-page":"10943","DOI":"10.1074\/jbc.M007758200","volume":"276","author":"Y-P Jiang","year":"2001","unstructured":"Jiang Y-P, Ballou LM, Lin RZ (2001) Rapamycin-insensitive Regulation of 4E-BP1 in Regenerating Rat Liver. J Biol Chem 276:10943\u201310951. https:\/\/doi.org\/10.1074\/jbc.M007758200","journal-title":"J Biol Chem"},{"key":"1525_CR28","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.jhep.2013.10.012","volume":"60","author":"M Jover-Cobos","year":"2014","unstructured":"Jover-Cobos M, Noiret L, Lee K et al (2014) Ornithine phenylacetate targets alterations in the expression and activity of glutamine synthase and glutaminase to reduce ammonia levels in bile duct ligated rats. J Hepatol 60:545\u2013553. https:\/\/doi.org\/10.1016\/j.jhep.2013.10.012","journal-title":"J Hepatol"},{"key":"1525_CR29","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1002\/jcsm.12095","volume":"8","author":"M Kalafateli","year":"2017","unstructured":"Kalafateli M, Mantzoukis K, Choi Yau Y et al (2017) Malnutrition and sarcopenia predict post-liver transplantation outcomes independently of the model for end-stage liver disease score. J Cachexia Sarcopenia Muscle 8:113\u2013121. https:\/\/doi.org\/10.1002\/jcsm.12095","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"1525_CR30","doi-asserted-by":"publisher","first-page":"238","DOI":"10.3746\/pnf.2015.20.4.238","volume":"20","author":"T Kokubo","year":"2015","unstructured":"Kokubo T, Maeda S, Tazumi K et al (2015) The Effect of L-Ornithine on the Phosphorylation of mTORC1 Downstream Targets in Rat Liver. Prev Nutr Food Sci 20:238\u2013245. https:\/\/doi.org\/10.3746\/pnf.2015.20.4.238","journal-title":"Prev Nutr Food Sci"},{"key":"1525_CR31","doi-asserted-by":"publisher","first-page":"G1024","DOI":"10.1152\/ajpgi.00244.2014","volume":"307","author":"RG Kristiansen","year":"2014","unstructured":"Kristiansen RG, Rose CF, Fuskev\u00e5g O-M et al (2014) L-Ornithine phenylacetate reduces ammonia in pigs with acute liver failure through phenylacetylglycine formation: a novel ammonia-lowering pathway. Am J Physiol Gastrointest Liver Physiol 307:G1024-1031. https:\/\/doi.org\/10.1152\/ajpgi.00244.2014","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"1525_CR32","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1002\/hep.29107","volume":"65","author":"A Kumar","year":"2017","unstructured":"Kumar A, Davuluri G, Silva RNE et al (2017) Ammonia lowering reverses sarcopenia of cirrhosis by restoring skeletal muscle proteostasis. Hepatology 65:2045\u20132058. https:\/\/doi.org\/10.1002\/hep.29107","journal-title":"Hepatology"},{"key":"1525_CR33","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/j.freeradbiomed.2019.09.031","volume":"145","author":"A Kumar","year":"2019","unstructured":"Kumar A, Davuluri G, Welch N et al (2019) Oxidative stress mediates ethanol-induced skeletal muscle mitochondrial dysfunction and dysregulated protein synthesis and autophagy. Free Radical Biol Med 145:284\u2013299. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2019.09.031","journal-title":"Free Radical Biol Med"},{"key":"1525_CR34","doi-asserted-by":"publisher","unstructured":"Kumar A, Welch N, Mishra S et al (2021) Metabolic reprogramming during hyperammonemia targets mitochondrial function and postmitotic senescence. JCI Insight 6. https:\/\/doi.org\/10.1172\/jci.insight.154089","DOI":"10.1172\/jci.insight.154089"},{"key":"1525_CR35","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.jceh.2018.04.007","volume":"9","author":"B Lattanzi","year":"2019","unstructured":"Lattanzi B, D\u2019Ambrosio D, Merli M (2019) Hepatic encephalopathy and sarcopenia: Two faces of the same metabolic alteration. J Clin Exp Hepatol 9:125\u2013130. https:\/\/doi.org\/10.1016\/j.jceh.2018.04.007","journal-title":"J Clin Exp Hepatol"},{"key":"1525_CR36","doi-asserted-by":"publisher","first-page":"913","DOI":"10.2147\/CIA.S149232","volume":"13","author":"I Liguori","year":"2018","unstructured":"Liguori I, Russo G, Aran L et al (2018) Sarcopenia: assessment of disease burden and strategies to improve outcomes. Clin Interv Aging 13:913\u2013927. https:\/\/doi.org\/10.2147\/CIA.S149232","journal-title":"Clin Interv Aging"},{"key":"1525_CR37","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1007\/s11011-012-9365-z","volume":"28","author":"M Merli","year":"2013","unstructured":"Merli M, Giusto M, Lucidi C et al (2013) Muscle depletion increases the risk of overt and minimal hepatic encephalopathy: results of a prospective study. Metab Brain Dis 28:281\u2013284. https:\/\/doi.org\/10.1007\/s11011-012-9365-z","journal-title":"Metab Brain Dis"},{"key":"1525_CR38","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s40265-018-1019-y","volume":"79","author":"S Montagnese","year":"2019","unstructured":"Montagnese S, Bajaj JS (2019) Impact of hepatic encephalopathy in cirrhosis on quality-of-life issues. Drugs 79:11\u201316. https:\/\/doi.org\/10.1007\/s40265-018-1019-y","journal-title":"Drugs"},{"key":"1525_CR39","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.cgh.2011.08.028","volume":"10","author":"AJ Montano-Loza","year":"2012","unstructured":"Montano-Loza AJ, Meza-Junco J, Prado CMM et al (2012) Muscle wasting is associated with mortality in patients with cirrhosis. Clin Gastroenterol Hepatol 10:166\u2013173. https:\/\/doi.org\/10.1016\/j.cgh.2011.08.028","journal-title":"Clin Gastroenterol Hepatol"},{"key":"1525_CR40","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1016\/j.cgh.2016.10.028","volume":"15","author":"S Nardelli","year":"2017","unstructured":"Nardelli S, Lattanzi B, Torrisi S et al (2017) Sarcopenia is risk factor for development of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt placement. Clin Gastroenterol Hepatol 15:934\u2013936. https:\/\/doi.org\/10.1016\/j.cgh.2016.10.028","journal-title":"Clin Gastroenterol Hepatol"},{"key":"1525_CR41","doi-asserted-by":"publisher","first-page":"5257","DOI":"10.3748\/wjg.v25.i35.5257","volume":"25","author":"S Nardelli","year":"2019","unstructured":"Nardelli S, Gioia S, Faccioli J et al (2019) Sarcopenia and cognitive impairment in liver cirrhosis: A viewpoint on the clinical impact of minimal hepatic encephalopathy. World J Gastroenterol 25:5257\u20135265. https:\/\/doi.org\/10.3748\/wjg.v25.i35.5257","journal-title":"World J Gastroenterol"},{"key":"1525_CR42","doi-asserted-by":"publisher","first-page":"411","DOI":"10.3138\/canlivj-2021-0042","volume":"5","author":"M Nguyen","year":"2022","unstructured":"Nguyen M, Mukaneza Y, Tremblay M et al (2022) Renal dysfunction independently predicts muscle mass loss in patients following liver transplantation. Can Liver J 5:411\u2013423. https:\/\/doi.org\/10.3138\/canlivj-2021-0042","journal-title":"Can Liver J"},{"key":"1525_CR43","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.jhep.2011.06.026","volume":"56","author":"M Oria","year":"2012","unstructured":"Oria M, Romero-Gim\u00e9nez J, Arranz JA et al (2012) Ornithine phenylacetate prevents disturbances of motor-evoked potentials induced by intestinal blood in rats with portacaval anastomosis. J Hepatol 56:109\u2013114. https:\/\/doi.org\/10.1016\/j.jhep.2011.06.026","journal-title":"J Hepatol"},{"key":"1525_CR44","doi-asserted-by":"publisher","first-page":"E983","DOI":"10.1152\/ajpendo.00183.2012","volume":"303","author":"J Qiu","year":"2012","unstructured":"Qiu J, Tsien C, Thapalaya S et al (2012) Hyperammonemia-mediated autophagy in skeletal muscle contributes to sarcopenia of cirrhosis. Am J Physiol Endocrinol Metab 303:E983-993. https:\/\/doi.org\/10.1152\/ajpendo.00183.2012","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"1525_CR45","doi-asserted-by":"publisher","first-page":"18162","DOI":"10.1073\/pnas.1317049110","volume":"110","author":"J Qiu","year":"2013","unstructured":"Qiu J, Thapaliya S, Runkana A et al (2013) Hyperammonemia in cirrhosis induces transcriptional regulation of myostatin by an NF-\u03baB-mediated mechanism. Proc Natl Acad Sci USA 110:18162\u201318167. https:\/\/doi.org\/10.1073\/pnas.1317049110","journal-title":"Proc Natl Acad Sci USA"},{"key":"1525_CR46","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1111\/liv.14680","volume":"41","author":"A Rabiee","year":"2021","unstructured":"Rabiee A, Ximenes RO, Nikayin S et al (2021) Factors associated with health-related quality of life in patients with cirrhosis: a systematic review. Liver Int 41:6\u201315. https:\/\/doi.org\/10.1111\/liv.14680","journal-title":"Liver Int"},{"key":"1525_CR47","doi-asserted-by":"publisher","first-page":"2626","DOI":"10.1016\/j.cgh.2020.10.019","volume":"19","author":"RS Rahimi","year":"2021","unstructured":"Rahimi RS, Safadi R, Thabut D et al (2021) Efficacy and safety of ornithine phenylacetate for treating overt hepatic encephalopathy in a randomized trial. Clin Gastroenterol Hepatol 19:2626-2635.e7. https:\/\/doi.org\/10.1016\/j.cgh.2020.10.019","journal-title":"Clin Gastroenterol Hepatol"},{"key":"1525_CR48","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1016\/j.jhep.2016.08.014","volume":"65","author":"K Rombouts","year":"2016","unstructured":"Rombouts K, B\u00e9meur C, Rose CF (2016) Targeting the muscle for the treatment and prevention of hepatic encephalopathy. J Hepatol 65:876\u2013878. https:\/\/doi.org\/10.1016\/j.jhep.2016.08.014","journal-title":"J Hepatol"},{"key":"1525_CR49","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1002\/hep.510300311","volume":"30","author":"C Rose","year":"1999","unstructured":"Rose C, Michalak A, Rao KV et al (1999) L-ornithine-L-aspartate lowers plasma and cerebrospinal fluid ammonia and prevents brain edema in rats with acute liver failure. Hepatology 30:636\u2013640. https:\/\/doi.org\/10.1002\/hep.510300311","journal-title":"Hepatology"},{"key":"1525_CR50","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1016\/j.jhep.2020.07.013","volume":"73","author":"CF Rose","year":"2020","unstructured":"Rose CF, Amodio P, Bajaj JS et al (2020) Hepatic encephalopathy: Novel insights into classification, pathophysiology and therapy. J Hepatol 73:1526\u20131547. https:\/\/doi.org\/10.1016\/j.jhep.2020.07.013","journal-title":"J Hepatol"},{"key":"1525_CR51","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1111\/cts.13257","volume":"15","author":"R Safadi","year":"2022","unstructured":"Safadi R, Rahimi RS, Thabut D et al (2022) Pharmacokinetics\/pharmacodynamics of L-ornithine phenylacetate in overt hepatic encephalopathy and the effect of plasma ammonia concentration reduction on clinical outcomes. Clin Transl Sci 15:1449\u20131459. https:\/\/doi.org\/10.1111\/cts.13257","journal-title":"Clin Transl Sci"},{"key":"1525_CR52","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1007\/s00424-016-1933-3","volume":"469","author":"K Sakuma","year":"2017","unstructured":"Sakuma K, Aoi W, Yamaguchi A (2017) Molecular mechanism of sarcopenia and cachexia: recent research advances. Pflugers Arch 469:573\u2013591. https:\/\/doi.org\/10.1007\/s00424-016-1933-3","journal-title":"Pflugers Arch"},{"key":"1525_CR53","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","volume":"168","author":"RA Saxton","year":"2017","unstructured":"Saxton RA, Sabatini DM (2017a) mTOR signaling in growth, metabolism, and disease. Cell 168:960\u2013976. https:\/\/doi.org\/10.1016\/j.cell.2017.02.004","journal-title":"Cell"},{"key":"1525_CR54","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1097\/meg.0000000000000529","volume":"28","author":"DL Shawcross","year":"2016","unstructured":"Shawcross DL, Dunk AA, Jalan R et al (2016) How to diagnose and manage hepatic encephalopathy: a consensus statement on roles and responsibilities beyond the liver specialist. Eur J Gastroenterol Hepatol 28:146\u2013152. https:\/\/doi.org\/10.1097\/meg.0000000000000529","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"1525_CR55","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1002\/lt.23495","volume":"18","author":"P Tandon","year":"2012","unstructured":"Tandon P, Ney M, Irwin I et al (2012) Severe muscle depletion in patients on the liver transplant wait list: its prevalence and independent prognostic value. Liver Transpl 18:1209\u20131216. https:\/\/doi.org\/10.1002\/lt.23495","journal-title":"Liver Transpl"},{"key":"1525_CR56","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/978-1-59745-157-4_4","volume-title":"Autophagosome and Phagosome","author":"I Tanida","year":"2008","unstructured":"Tanida I, Ueno T, Kominami E (2008) LC3 and Autophagy. In: Deretic V (ed) Autophagosome and Phagosome. Humana Press, Totowa, NJ, pp 77\u201388"},{"key":"1525_CR57","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1111\/jgh.12524","volume":"29","author":"C Tsien","year":"2014","unstructured":"Tsien C, Garber A, Narayanan A et al (2014) Post-liver transplantation sarcopenia in cirrhosis: a prospective evaluation. J Gastroenterol Hepatol 29:1250\u20131257. https:\/\/doi.org\/10.1111\/jgh.12524","journal-title":"J Gastroenterol Hepatol"},{"key":"1525_CR58","doi-asserted-by":"publisher","first-page":"2018","DOI":"10.1002\/hep.27717","volume":"61","author":"C Tsien","year":"2015","unstructured":"Tsien C, Davuluri G, Singh D et al (2015) Metabolic and molecular responses to leucine-enriched branched chain amino acid supplementation in the skeletal muscle of alcoholic cirrhosis. Hepatology 61:2018\u20132029. https:\/\/doi.org\/10.1002\/hep.27717","journal-title":"Hepatology"},{"key":"1525_CR59","doi-asserted-by":"publisher","first-page":"297","DOI":"10.3177\/jnsv.58.297","volume":"58","author":"K Tujioka","year":"2012","unstructured":"Tujioka K, Yamada T, Aoki M et al (2012) Dietary ornithine affects the tissue protein synthesis rate in young rats. J Nutr Sci Vitaminol 58:297\u2013302. https:\/\/doi.org\/10.3177\/jnsv.58.297","journal-title":"J Nutr Sci Vitaminol"},{"key":"1525_CR60","doi-asserted-by":"publisher","first-page":"E567","DOI":"10.1152\/ajpendo.90862.2008","volume":"296","author":"S Welle","year":"2009","unstructured":"Welle S, Burgess K, Mehta S (2009) Stimulation of skeletal muscle myofibrillar protein synthesis, p70 S6 kinase phosphorylation, and ribosomal protein S6 phosphorylation by inhibition of myostatin in mature mice. Am J Physiol Endocrinol Metab 296:E567\u2013E572. https:\/\/doi.org\/10.1152\/ajpendo.90862.2008","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"1525_CR61","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1007\/s11011-019-00427-y","volume":"34","author":"M Winterdahl","year":"2019","unstructured":"Winterdahl M, Abbas Z, Noer O et al (2019) Cerebral water content mapping in cirrhosis patients with and without manifest HE. Metab Brain Dis 34:1071\u20131076. https:\/\/doi.org\/10.1007\/s11011-019-00427-y","journal-title":"Metab Brain Dis"},{"key":"1525_CR62","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1002\/hep.22917","volume":"50","author":"LM Ytreb\u00f8","year":"2009","unstructured":"Ytreb\u00f8 LM, Kristiansen RG, Maehre H et al (2009) L-ornithine phenylacetate attenuates increased arterial and extracellular brain ammonia and prevents intracranial hypertension in pigs with acute liver failure. Hepatology 50:165\u2013174. https:\/\/doi.org\/10.1002\/hep.22917","journal-title":"Hepatology"}],"container-title":["Metabolic Brain Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11011-024-01525-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11011-024-01525-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11011-024-01525-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T05:54:48Z","timestamp":1740549288000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11011-024-01525-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,23]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["1525"],"URL":"https:\/\/doi.org\/10.1007\/s11011-024-01525-2","relation":{},"ISSN":["1573-7365"],"issn-type":[{"value":"1573-7365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,23]]},"assertion":[{"value":"17 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Christopher Rose has research collaborations in the last 12\u00a0months with, and is an advisor for Aza Technologies, Horizon Therapeutics, Lupin Pharma, Morphocell Technologies, Satellite Bioscience.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"110"}}