{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:49:13Z","timestamp":1791830953248,"version":"4.3.4"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2018,4,11]],"date-time":"2018-04-11T00:00:00Z","timestamp":1523404800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Curr Gastroenterol Rep"],"published-print":{"date-parts":[[2018,5]]},"DOI":"10.1007\/s11894-018-0627-8","type":"journal-article","created":{"date-parts":[[2018,4,11]],"date-time":"2018-04-11T03:05:45Z","timestamp":1523415945000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Update on the Therapeutic Management of Hepatic Encephalopathy"],"prefix":"10.1007","volume":"20","author":[{"given":"Linda Skibsted","family":"Kornerup","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lise Lotte","family":"Gluud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Vilstrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gitte","family":"Dam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,4,11]]},"reference":[{"key":"627_CR1","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1002\/hep.27210","volume":"60","author":"H Vilstrup","year":"2014","unstructured":"\u2022\u2022 Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD, et al. 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. Hepatology. 2014;60:715\u201335. A thorough expert panel guideline for the diagnositics, classification, and treatment of HE including the grade of evidence available to support the recommendations.","journal-title":"Hepatology"},{"key":"627_CR2","doi-asserted-by":"publisher","first-page":"2718","DOI":"10.1111\/j.1572-0241.2001.04130.x","volume":"96","author":"M Romero-G\u00f3mez","year":"2001","unstructured":"Romero-G\u00f3mez M, Boza F, Garc\u00eda-Valdecasas MS, Garc\u00eda E, Aguilar-Reina J. Subclinical hepatic encephalopathy predicts the development of overt hepatic encephalopathy. Am J Gastroenterol. 2001;96:2718\u201323.","journal-title":"Am J Gastroenterol"},{"key":"627_CR3","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1136\/bmj.282.6260.263","volume":"282","author":"JB Saunders","year":"1981","unstructured":"Saunders JB, Walters JR, Davies AP, Paton A. A 20-year prospective study of cirrhosis. Br Med J (Clin Res Ed). 1981;282:263\u20136.","journal-title":"Br Med J (Clin Res Ed)"},{"key":"627_CR4","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1002\/hep.23500","volume":"51","author":"P Jepsen","year":"2010","unstructured":"Jepsen P, Ott P, Andersen PK, S\u00f8rensen HT, Vilstrup H. Clinical course of alcoholic liver cirrhosis: a Danish population-based cohort study. Hepatology. 2010;51:1675\u201382.","journal-title":"Hepatology"},{"key":"627_CR5","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1016\/S0168-8278(00)80243-3","volume":"32","author":"M Groeneweg","year":"2000","unstructured":"Groeneweg M, Moerland W, Quero JC, Hop WCJ, Krabbe PF, Schalm SW. Screening of subclinical hepatic encephalopathy. J Hepatol. 2000;32:748\u201353.","journal-title":"J Hepatol"},{"key":"627_CR6","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.jhep.2007.02.022","volume":"47","author":"P Sharma","year":"2007","unstructured":"Sharma P, Sharma BC, Puri V, Sarin SK. Critical flicker frequency: diagnostic tool for minimal hepatic encephalopathy. J Hepatol. 2007;47:67\u201373.","journal-title":"J Hepatol"},{"key":"627_CR7","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1002\/hep.23383","volume":"51","author":"TD Boyer","year":"2010","unstructured":"Boyer TD, Haskal ZJ. The role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension: update 2009. Hepatology. 2010;51:306.","journal-title":"Hepatology"},{"key":"627_CR8","doi-asserted-by":"publisher","first-page":"2738","DOI":"10.1111\/j.1572-0241.2008.02102.x","volume":"103","author":"O Riggio","year":"2008","unstructured":"Riggio O, Angeloni S, Salvatori FM, De Santis A, Cerini F, Farcomeni A, et al. Incidence, natural history, and risk factors of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt with polytetrafluoroethylene-covered stent grafts. Am J Gastroenterol. 2008;103:2738\u201346.","journal-title":"Am J Gastroenterol"},{"key":"627_CR9","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/j.jcrc.2009.01.008","volume":"24","author":"J Fichet","year":"2009","unstructured":"Fichet J, Mercier E, Gen\u00e9e O, Garot D, Legras A, Dequin PF, et al. Prognosis and 1-year mortality of intensive care unit patients with severe hepatic encephalopathy. J Crit Care. 2009;24:364\u201370.","journal-title":"J Crit Care"},{"key":"627_CR10","doi-asserted-by":"crossref","unstructured":"Bircher J, Haemmerli UP, Scollo-Lavizzari G, Hoffmann K (1971) Treatment of chronic portal-systemic encephalopathy with lactulose. Report of six patients and review of the literature. Am J Med 51:148\u201359.","DOI":"10.1016\/0002-9343(71)90233-6"},{"key":"627_CR11","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/0950-3528(92)90041-C","volume":"6","author":"K Weissenborn","year":"1992","unstructured":"Weissenborn K. Recent developments in the pathophysiology and treatment of hepatic encephalopathy. Baillieres Clin Gastroenterol. 1992;6:609\u201330.","journal-title":"Baillieres Clin Gastroenterol"},{"key":"627_CR12","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1002\/hep.28598","volume":"64","author":"LL Gluud","year":"2016","unstructured":"\u2022\u2022 Gluud LL, Vilstrup H, Morgan MY. Nonabsorbable disaccharides for hepatic encephalopathy: a systematic review and meta-analysis. Hepatology. 2016;64:908\u201322. This updated review and meta-analysis concludes that non-absorbable disacchaides have beneficial effects in treating and preventing HE. Additionally, non-absorbable disacchaides reduces serious liver-related morbidity and all-cause mortality.","journal-title":"Hepatology"},{"key":"627_CR13","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, Allawy A, Ten Have GAM, Thapaliya S, et al. Metabolic and molecular responses to leucine enriched branched chain amino acid supplementation in the skeletal muscle of alcoholic cirrhosis. Hepatology. 2015;61:2018\u201329.","journal-title":"Hepatology"},{"key":"627_CR14","doi-asserted-by":"publisher","unstructured":"\u2022 Gluud Lise L, Dam G, Les I, C\u00f3rdoba J, Marchesini G, Borre M, et al. Branched-chain amino acids for people with hepatic encephalopathy. Cochrane Database Syst Rev. 2015; \n                      https:\/\/doi.org\/10.1002\/14651858.CD001939.pub2\n                      \n                    . This updated Cochrane review concludes that branced-chain amino acids have a beneficial effect in treating HE. There was no effect on mortality.","DOI":"10.1002\/14651858.CD001939.pub2"},{"key":"627_CR15","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1023\/A:1020613314572","volume":"13","author":"C Rose","year":"1998","unstructured":"Rose C, Michalak A, Pannunzio P, Therrien G, Quack G, Kircheis G, et al. L-ornithine-L-aspartate in experimental portal-systemic encephalopathy: therapeutic efficacy and mechanism of action. Metab Brain Dis. 1998;13:147\u201357.","journal-title":"Metab Brain Dis"},{"key":"627_CR16","first-page":"1","volume":"0","author":"SS Sidhu","year":"2017","unstructured":"Sidhu SS, Sharma BC, Goyal O, Kishore H, Kaur N. L-ornithine L-aspartate in bouts of overt hepatic encephalopathy. Hepatology. 2017;0:1\u201311.","journal-title":"Hepatology"},{"key":"627_CR17","doi-asserted-by":"publisher","unstructured":"Goh ET, Stokes CS, Vilstrup H, Gluud LL, Morgan MY (2017). L-ornithine l-aspartate for hepatic encephalopathy: A systematic review with meta-analyses of randomised controlled trials. J Clin Exp Hepatol. 7 (Supplem(1):S65. \n                      https:\/\/doi.org\/10.1016\/j.jceh.2017.01.087","DOI":"10.1016\/j.jceh.2017.01.087"},{"key":"627_CR18","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1159\/000081994","volume":"51","author":"ML Zeneroli","year":"2005","unstructured":"Zeneroli ML, Avallone R, Corsi BL, Venturini I, Baraldi C, Baraldi M. Management of hepatic encephalopathy: role of rifaximin. Chemotherapy. 2005;51:90\u20135.","journal-title":"Chemotherapy"},{"key":"627_CR19","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1056\/NEJMoa0907893","volume":"362","author":"NM Bass","year":"2010","unstructured":"\u2022 Bass NM, Mullen KD, Sanyal A, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362:1071\u201381. This double-blind RCT studied the effect of rifaximin versus placebo over a 6-month period in 299 patients in remission from HE. Treatment with rifaximin significantly maintained HE remission and reduced HE-related hospitalization compared with placebo.","journal-title":"N Engl J Med"},{"key":"627_CR20","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1111\/apt.12803","volume":"40","author":"N Kimer","year":"2014","unstructured":"Kimer N, Krag A, M\u00f8ller S, Bendtsen F, Gluud LL. Systematic review with meta-analysis: the effects of rifaximin in hepatic encephalopathy. Aliment Pharmacol Ther. 2014;40:123\u201332.","journal-title":"Aliment Pharmacol Ther"},{"key":"627_CR21","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s11011-012-9372-0","volume":"28","author":"LL Gluud","year":"2013","unstructured":"Gluud LL, Dam G, Borre M, Les I, Cordoba J, Marchesini G, et al. Lactulose, rifaximin or branched chain amino acids for hepatic encephalopathy: what is the evidence? Metab Brain Dis. 2013;28:221\u20135.","journal-title":"Metab Brain Dis"},{"key":"627_CR22","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1007\/s11011-013-9383-5","volume":"28","author":"KR Patidar","year":"2013","unstructured":"Patidar KR, Bajaj JS. Antibiotics for the treatment of hepatic encephalopathy. Metab Brain Dis. 2013;28:307\u201312.","journal-title":"Metab Brain Dis"},{"key":"627_CR23","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/j.bbadis.2008.04.002","volume":"1782","author":"K Oettl","year":"2008","unstructured":"Oettl K, Stadlbauer V, Petter F, Greilberger J, Putz-Bankuti C, Hallstr\u00f6m S, et al. Oxidative damage of albumin in advanced liver disease. Biochim Biophys Acta Mol Basis Dis. 2008;1782:469\u201373.","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"627_CR24","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1002\/hep.22913","volume":"50","author":"R Jalan","year":"2009","unstructured":"Jalan R, Schnurr K, Mookerjee RP, Sen S, Cheshire L, Hodges S, et al. Alterations in the functional capacity of albumin in patients with decompensated cirrhosis is associated with increased mortality. Hepatology. 2009;50:555\u201364.","journal-title":"Hepatology"},{"key":"627_CR25","doi-asserted-by":"publisher","first-page":"1851","DOI":"10.1002\/hep.27322","volume":"60","author":"M Domenicali","year":"2014","unstructured":"Domenicali M, Baldassarre M, Giannone FA, Naldi M, Mastroroberto M, Biselli M, et al. Posttranscriptional changes of serum albumin: clinical and prognostic significance in hospitalized patients with cirrhosis. Hepatology. 2014;60:1851\u201360.","journal-title":"Hepatology"},{"key":"627_CR26","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/j.jhep.2014.09.005","volume":"62","author":"M Romero-G\u00f3mez","year":"2015","unstructured":"Romero-G\u00f3mez M, Montagnese S, Jalan R. Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure. J Hepatol. 2015;62:437\u201347.","journal-title":"J Hepatol"},{"key":"627_CR27","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1111\/jgh.13666","volume":"32","author":"BC Sharma","year":"2017","unstructured":"Sharma BC, Singh J, Srivastava S, Sangam A, Mantri AK, Trehanpati N, et al. Randomized controlled trial comparing lactulose plus albumin versus lactulose alone for treatment of hepatic encephalopathy. J Gastroenterol Hepatol. 2017;32:1234\u20139.","journal-title":"J Gastroenterol Hepatol"},{"key":"627_CR28","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1002\/hep.1840070403","volume":"7","author":"G Bakti","year":"1987","unstructured":"Bakti G, Fisch HU, Karlaganis G, Minder C, Bircher J. Mechanism of the excessive sedative response of cirrhotics to benzodiazepines: model experiments with triazolam. Hepatology. 1987;7:629\u201338.","journal-title":"Hepatology"},{"key":"627_CR29","first-page":"1","volume":"2017","author":"ET Goh","year":"2017","unstructured":"Goh ET, Andersen ML, Morgan MY, Gluud LL. Flumazenil versus placebo or no intervention for people with cirrhosis and hepatic encephalopathy. Cochrane Database Syst Rev. 2017;2017:1\u201378.","journal-title":"Cochrane Database Syst Rev"},{"key":"627_CR30","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1093\/ajcn\/69.6.1194","volume":"69","author":"MJ M\u00fcller","year":"1999","unstructured":"M\u00fcller MJ, B\u00f6ttcher J, Selberg O, Weselmann S, B\u00f6ker KHW, Schwarze M, et al. Hypermetabolism in clinically stable patients with liver cirrhosis. Am J Clin Nutr. 1999;69:1194\u2013201.","journal-title":"Am J Clin Nutr"},{"key":"627_CR31","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1093\/ajcn\/69.6.1066","volume":"69","author":"AJ McCullough","year":"1999","unstructured":"McCullough AJ, Raguso C. Effect of cirrhosis on energy expenditure. Am J Clin Nutr. 1999;69:1066\u20138.","journal-title":"Am J Clin Nutr"},{"key":"627_CR32","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.1172\/JCI111142","volume":"72","author":"P Paul","year":"1983","unstructured":"Paul P, Skutches CL, Boden G. Nature and quantity of fuels consumed in patients with alcoholic cirrhosis. J Clin Invest. 1983;72:1821\u201332.","journal-title":"J Clin Invest"},{"key":"627_CR33","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1002\/hep.1840070505","volume":"7","author":"UM Kabadi","year":"1987","unstructured":"Kabadi UM (1987) The association of hepatic glycogen depletion with hyperammonemia in cirrhosis. Hepatology. 7:821\u201324.","journal-title":"Hepatology."},{"key":"627_CR34","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1002\/hep.26370","volume":"58","author":"P Amodio","year":"2013","unstructured":"Amodio P, Bemeur C, Butterworth R, Cordoba J, Kato A, Montagnese S, et al. The nutritional management of hepatic encephalopathy in patients with cirrhosis: international society for hepatic encephalopathy and nitrogen metabolism consensus. Hepatology. 2013;58:325\u201336.","journal-title":"Hepatology"},{"key":"627_CR35","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1055\/s-0036-1571298","volume":"36","author":"RS Rahimi","year":"2016","unstructured":"Rahimi RS, Rockey DC (2016) Hepatic Encephalopathy: Pharmacological Therapies Targeting Ammonia. Semin Liver Dis 36:48\u201355.","journal-title":"Semin Liver Dis"},{"key":"627_CR36","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1080\/17425255.2017.1262843","volume":"13","author":"J Las Heras De","year":"2017","unstructured":"De Las Heras J, Ald\u00e1miz-Echevarr\u00eda L, Mart\u00ednez-Chantar ML, Delgado TC. An update on the use of benzoate, phenylacetate and phenylbutyrate ammonia scavengers for interrogating and modifying liver nitrogen metabolism and its implications in urea cycle disorders and liver disease. Expert Opin Drug Metab Toxicol. 2017;13:439\u201348.","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"627_CR37","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. L-ornithine phenylacetate (OP): a novel treatment for hyperammonemia and hepatic encephalopathy. Med Hypotheses. 2007;69:1064\u20139.","journal-title":"Med Hypotheses"},{"key":"627_CR38","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1002\/hep.29621","volume":"67","author":"RT Stravitz","year":"2018","unstructured":"Stravitz RT, Gottfried M, Durkalski V, et al. (2018) Safety, Tolerability, and Pharmacokinetics of L-Ornithine Phenylacetate in Patients with Acute Liver Injury\/Failure and Hyperammonemia. Hepatology. 67:1003\u201313.","journal-title":"Hepatology."},{"key":"627_CR39","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1177\/1756283X16658252","volume":"9","author":"M Ventura-Cots","year":"2016","unstructured":"Ventura-Cots M, Concepci\u00f3n M, Arranz JA, Sim\u00f3n-Talero M, Torrens M, Blanco-Grau A, et al. Impact of ornithine phenylacetate (OCR-002) in lowering plasma ammonia after upper gastrointestinal bleeding in cirrhotic patients. Ther Adv Gastroenterol. 2016;9:823\u201335.","journal-title":"Ther Adv Gastroenterol"},{"key":"627_CR40","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1097\/MCG.0b013e318299c789","volume":"47","author":"M Ventura-Cots","year":"2013","unstructured":"Ventura-Cots M, Arranz JA, Sim\u00f3n-Talero M, Torrens M, Blanco A, Riudor E, et al. Safety of ornithine phenylacetate in cirrhotic decompensated patients: an open-label, dose-escalating, single-cohort study. J Clin Gastroenterol. 2013;47:881\u20137.","journal-title":"J Clin Gastroenterol"},{"key":"627_CR41","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1002\/hep.26611","volume":"59","author":"DC Rockey","year":"2014","unstructured":"Rockey DC, Vierling JM, Mantry P, Ghabril M, Brown RS Jr, Alexeeva O, et al. Randomized, double-blind, controlled study of glycerol phenylbutyrate in hepatic encephalopathy. Hepatology. 2014;59:1073\u201383.","journal-title":"Hepatology"},{"key":"627_CR42","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1111\/fcp.12340","volume":"32","author":"N Weiss","year":"2018","unstructured":"Weiss N, Tripon S, Lodey M, et al (2018) Treating hepatic encephalopathy in cirrhotic patients admitted to ICU with sodium phenylbutyrate: a preliminary study. Fundam Clin Pharmacol 32:209\u201315.","journal-title":"Fundam Clin Pharmacol"},{"key":"627_CR43","first-page":"219","volume":"9","author":"ML Misel","year":"2013","unstructured":"Misel ML, Gish RG, Patton H, Mendler M. Sodium benzoate for treatment of hepatic encephalopathy. Gastroenterol Hepatol (N Y). 2013;9:219\u201327.","journal-title":"Gastroenterol Hepatol (N Y)"},{"key":"627_CR44","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1002\/hep.1840160123","volume":"16","author":"S Sushma","year":"1992","unstructured":"Sushma S, Dasarathy S, Tandon RK, Jain S, Gupta S, Bhist MS. Sodium benzoate in the treatment of acute hepatic encephalopathy: a double-blind randomized trial. Hepatology. 1992;16:138\u201344.","journal-title":"Hepatology"},{"key":"627_CR45","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, Tremblay M, Rose CF. AST-120 (spherical carbon adsorbent) lowers ammonia levels and attenuates brain edema in bile duct-ligated rats. Hepatology. 2011;53:1995\u20132002.","journal-title":"Hepatology"},{"key":"627_CR46","doi-asserted-by":"publisher","first-page":"S43","DOI":"10.1016\/S0168-8278(09)60107-0","volume":"50","author":"P Pockros","year":"2009","unstructured":"Pockros P, Hassanein T, Vierling J, Heuman D, Hillebrand D, Chojkier M, et al. Phase 2, multicenter, randomized study of Ast-120 (spherical carbon adsorbent) vs. lactulose in the treatment of low-grade hepatic encephalopathy (HE). J Hepatol. 2009;50:S43\u20134.","journal-title":"J Hepatol"},{"key":"627_CR47","doi-asserted-by":"publisher","first-page":"S84","DOI":"10.1016\/j.jhep.2012.08.005","volume":"58","author":"JS Bajaj","year":"2013","unstructured":"Bajaj JS, Sheikh MY, Chojkier M, et al. Ast-120 (spherical carbon adsorbent) in covert hepatic encephalopathy: results of the Astute trial. J Hepatol. 2013;58:S84.","journal-title":"J Hepatol"},{"key":"627_CR48","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/j.neuint.2006.02.002","volume":"49","author":"S Ahboucha","year":"2006","unstructured":"Ahboucha S, Pomier-Layrargues G, Mamer O, Butterworth RF. Increased levels of pregnenolone and its neuroactive metabolite allopregnanolone in autopsied brain tissue from cirrhotic patients who died in hepatic coma. Neurochem Int. 2006;49:372\u20138.","journal-title":"Neurochem Int"},{"key":"627_CR49","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1111\/j.1471-4159.2011.07244.x","volume":"117","author":"R Leke","year":"2011","unstructured":"Leke R, Bak LK, Iversen P, S\u00e3rensen M, Keiding S, Vilstrup H, et al. Synthesis of neurotransmitter GABA via the neuronal tricarboxylic acid cycle is elevated in rats with liver cirrhosis consistent with a high GABAergic tone in chronic hepatic encephalopathy. J Neurochem. 2011;117:824\u201332.","journal-title":"J Neurochem"},{"key":"627_CR50","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.jsbmb.2015.10.019","volume":"160","author":"M Johansson","year":"2016","unstructured":"Johansson M, Str\u00f6mberg J, Ragagnin G, Doverskog M, B\u00e4ckstr\u00f6m T. GABAA receptor modulating steroid antagonists (GAMSA) are functional in vivo. J Steroid Biochem Mol Biol. 2016;160:98\u2013105.","journal-title":"J Steroid Biochem Mol Biol"},{"key":"627_CR51","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1111\/j.1460-9568.2004.03610.x","volume":"20","author":"S Turkmen","year":"2004","unstructured":"Turkmen S, Lundgren P, Birzniece V, Zingmark E, Backstrom T, Johansson IM. 3\u03b2-20\u03b2-dihydroxy-5\u03b1-pregnane (UC1011) antagonism of the GABA potentiation and the learning impairment induced in rats by allopregnanolone. Eur J Neurosci. 2004;20:1604\u201312.","journal-title":"Eur J Neurosci"},{"key":"627_CR52","doi-asserted-by":"publisher","first-page":"G400","DOI":"10.1152\/ajpgi.00073.2015","volume":"309","author":"M Johansson","year":"2015","unstructured":"Johansson M, Agusti A, Llansola M, Montoliu C, Str\u00f6mberg J, Malinina E, et al. GR3027 antagonizes GABA A receptor-potentiating neurosteroids and restores spatial learning and motor coordination in rats with chronic hyperammonemia and hepatic encephalopathy. Am J Physiol Gastrointest Liver Physiol. 2015;309:G400\u20139.","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"627_CR53","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1002\/hep.24423","volume":"54","author":"Y Chen","year":"2011","unstructured":"Chen Y, Yang F, Lu H, Wang B, Chen Y, Lei D, et al. Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology. 2011;54:562\u201372.","journal-title":"Hepatology"},{"key":"627_CR54","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1016\/j.jhep.2013.12.019","volume":"60","author":"JS Bajaj","year":"2014","unstructured":"Bajaj JS, Heuman DM, Hylemon PB, Sanyal AJ, White MB, Monteith P, et al. Altered profile of human gut microbiome is associated with cirrhosis and its complications. J Hepatol. 2014;60:940\u20137.","journal-title":"J Hepatol"},{"key":"627_CR55","doi-asserted-by":"publisher","first-page":"1727","DOI":"10.1002\/hep.29306","volume":"66","author":"JS Bajaj","year":"2017","unstructured":"Bajaj JS, Kassam Z, Fagan A, Gavis EA, Liu E, Cox IJ, et al. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: a randomized clinical trial. Hepatology. 2017;66:1727\u201338.","journal-title":"Hepatology"},{"key":"627_CR56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2012\/480309","volume":"2012","author":"Z Poh","year":"2012","unstructured":"Poh Z, Chang PEJ. A current review of the diagnostic and treatment strategies of hepatic encephalopathy. Int J Hepatol. 2012;2012:1\u201310.","journal-title":"Int J Hepatol"},{"key":"627_CR57","doi-asserted-by":"crossref","unstructured":"McGee RG, Bakens A, Wiley K, Riordan SM, Webster AC (2011) Probiotics for patients with hepatic encephalopathy. Cochrane database Syst Rev CD008716.","DOI":"10.1002\/14651858.CD008716.pub2"},{"key":"627_CR58","doi-asserted-by":"publisher","first-page":"2448","DOI":"10.1002\/hep.26314","volume":"57","author":"W Laleman","year":"2013","unstructured":"Laleman W, Simon-Talero M, Maleux G, Perez M, Ameloot K, Soriano G, et al. Embolization of large spontaneous portosystemic shunts for refractory hepatic encephalopathy: a multicenter survey on safety and efficacy. Hepatology. 2013;57:2448\u201357.","journal-title":"Hepatology"},{"key":"627_CR59","first-page":"723","volume":"22","author":"AM Lynn","year":"2016","unstructured":"Lynn AM, Singh S, Congly S, Khemani D, Johnson DH, Wiesner RH, et al. Embolization of portosystemic shunts for treatment of medically-refractory hepatic encephalopathy. Liver Transplant Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc. 2016;22:723\u201331.","journal-title":"Liver Transplant Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc"},{"key":"627_CR60","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.cld.2011.12.004","volume":"16","author":"RT Frederick","year":"2012","unstructured":"Frederick RT. Extent of reversibility of hepatic encephalopathy following liver transplantation. Clin Liver Dis. 2012;16:147\u201358.","journal-title":"Clin Liver Dis"},{"key":"627_CR61","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s11011-010-9178-x","volume":"25","author":"DK Atluri","year":"2010","unstructured":"Atluri DK, Asgeri M, Mullen KD. Reversibility of hepatic encephalopathy after liver transplantation. Metab Brain Dis. 2010;25:111\u20133.","journal-title":"Metab Brain Dis"},{"key":"627_CR62","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1155\/2011\/832031","volume":"31","author":"R Garc\u00eda-Mart\u00ednez","year":"2011","unstructured":"Garc\u00eda-Mart\u00ednez R, Sim\u00f3n-Talero M, C\u00f3rdoba J. Prognostic assessment in patients with hepatic encephalopathy. Dis Markers. 2011;31:171\u20139.","journal-title":"Dis Markers"},{"key":"627_CR63","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1002\/lt.22197","volume":"17","author":"R Garcia-Martinez","year":"2011","unstructured":"Garcia-Martinez R, Rovira A, Alonso J, Jacas C, Sim\u00f3n-Talero M, Chavarria L, et al. Hepatic encephalopathy is associated with posttransplant cognitive function and brain volume. Liver Transpl. 2011;17:38\u201346.","journal-title":"Liver Transpl"}],"container-title":["Current Gastroenterology Reports"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s11894-018-0627-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11894-018-0627-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11894-018-0627-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T20:08:31Z","timestamp":1554926911000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s11894-018-0627-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,11]]},"references-count":63,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["627"],"URL":"https:\/\/doi.org\/10.1007\/s11894-018-0627-8","relation":{},"ISSN":["1522-8037","1534-312X"],"issn-type":[{"value":"1522-8037","type":"print"},{"value":"1534-312X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,11]]},"assertion":[{"value":"11 April 2018","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standard"}},{"value":"Linda Skibsted Kornerup, Hendrik Vilstrup, and Gitte Dam declare no conflict of interest.Lise Lotte Gluud reports personal fees from Norgine, Eli Lilly, Novo, and Alexion, grants from Alexion; and as an investigator in trial from Intercept, Abbvie, and Norgine.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"This article does not contain any studies with human or animal subjects performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human and Animal Rights and Informed Consent"}}],"article-number":"21"}}