Hepatic Encephalopathy in Our Genes?
Authors: Jan Albrecht
Journal: Annals of Internal Medicine (2010)

Editorials7 September 2010Hepatic Encephalopathy in Our Genes?Jan Albrecht, PhDJan Albrecht, PhDFrom Polish Academy of Sciences, 02-106 Warsaw, Poland.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-153-5-201009070-00008 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Hepatic encephalopathy is a complex disorder characterized by gradual impairment of the ability to perform mental tasks and to react to external stimuli. It can eventually evolve to coma. Hepatic encephalopathy results from inefficient clearance of toxins, mainly ammonia, from the blood (1). Cirrhosis is the major cause of chronic liver dysfunction and affects 1 million Europeans (2) and 5.5 million Americans (3). In Europe, cirrhosis accounts for 13.7 per 100 000 deaths—only slightly below the rate for pneumonia (15.5 per 100 000 deaths) but higher than that for diabetes (13.4 per 100 000 deaths) or car accidents (9.1 per 100 000 deaths) (2).... References1. Albrecht J, Jones EA. Hepatic encephalopathy: molecular mechanisms underlying the clinical syndrome. J Neurol Sci. 1999;170:138-46. [PMID: 10617392] CrossrefMedlineGoogle Scholar2. Eurostat. Accessed at ec.europa.eu/health/ph_information/dissemination/echi/echi_en.htm on 26 July 2010. Google Scholar3. Leevy CB, Phillips JA. Hospitalizations during the use of rifaximin versus lactulose for the treatment of hepatic encephalopathy. Dig Dis Sci. 2007;52:737-41. [PMID: 17245628] CrossrefMedlineGoogle Scholar4. Quero JC, Schalm SW. Subclinical hepatic encephalopathy. Semin Liver Dis. 1996;16:321-8. [PMID: 8989817] CrossrefMedlineGoogle Scholar5. Hartmann IJ, Groeneweg M, Quero JC, Beijeman SJ, de Man RA, Hop WC, et al. The prognostic significance of subclinical hepatic encephalopathy. Am J Gastroenterol. 2000;95:2029-34. [PMID: 10950053] CrossrefMedlineGoogle Scholar6. Romero-Gómez M, Boza F, García-Valdecasas MS, García E, Aguilar-Reina J. Subclinical hepatic encephalopathy predicts the development of overt hepatic encephalopathy. Am J Gastroenterol. 2001;96:2718-23. [PMID: 11569701] CrossrefMedlineGoogle Scholar7. Romero-Gómez M, Jover M, Del Campo JA, Royo JL, Hoyas E, Galán JJ, et al. Variations in the promoter region of the glutaminase gene and the development of hepatic encephalopathy in patients with cirrhosis. A cohort study. Ann Intern Med. 2010;153:281-8. LinkGoogle Scholar8. Als-Nielsen B, Gluud LL, Gluud C. Non-absorbable disaccharides for hepatic encephalopathy: systematic review of randomised trials. BMJ. 2004;328:1046. [PMID: 15054035] CrossrefMedlineGoogle Scholar9. Romero-Gómez M, Grande L, Camacho I, Benitez S, Irles JA, Castro M. Altered response to oral glutamine challenge as prognostic factor for overt episodes in patients with minimal hepatic encephalopathy. J Hepatol. 2002;37:781-7. [PMID: 12445419] CrossrefMedlineGoogle Scholar10. Romero-Gómez M, Grande L, Camacho I. Prognostic value of altered oral glutamine challenge in patients with minimal hepatic encephalopathy. Hepatology. 2004;39:939-43. [PMID: 15057897] CrossrefMedlineGoogle Scholar11. Romero-Gómez M, Ramos-Guerrero R, Grande L, de Terán LC, Corpas R, Camacho I, et al. Intestinal glutaminase activity is increased in liver cirrhosis and correlates with minimal hepatic encephalopathy. J Hepatol. 2004;41:49-54. [PMID: 15246207] CrossrefMedlineGoogle Scholar12. Olde Damink SW, Jalan R, Deutz NE, Redhead DN, Dejong CH, Hynd P, et al. The kidney plays a major role in the hyperammonemia seen after simulated or actual GI bleeding in patients with cirrhosis. Hepatology. 2003;37:1277-85. [PMID: 12774005] CrossrefMedlineGoogle Scholar13. Elgadi KM, Meguid RA, Qian M, Souba WW, Abcouwer SF. Cloning and analysis of unique human glutaminase isoforms generated by tissue-specific alternative splicing. Physiol Genomics. 1999;1:51-62. [PMID: 11015561] CrossrefMedlineGoogle Scholar14. Aledo JC, Gómez-Fabre PM, Olalla L, Márquez J. Identification of two human glutaminase loci and tissue-specific expression of the two related genes. Mamm Genome. 2000;11:1107-10. [PMID: 11130979] CrossrefMedlineGoogle Scholar15. Albrecht J, Norenberg MD. Glutamine: a Trojan horse in ammonia neurotoxicity. Hepatology. 2006;44:788-94. [PMID: 17006913] CrossrefMedlineGoogle Scholar16. Bak LK, Schousboe A, Waagepetersen HS. The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer. J Neurochem. 2006;98:641-53. [PMID: 16787421] CrossrefMedlineGoogle Scholar17. Cauli O, Rodrigo R, Llansola M, Montoliu C, Monfort P, Piedrafita B, et al. Glutamatergic and gabaergic neurotransmission and neuronal circuits in hepatic encephalopathy. Metab Brain Dis. 2009;24:69-80. [PMID: 19085094] CrossrefMedlineGoogle Scholar18. Shawcross DL, Davies , Williams R, Jalan R. Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis. J Hepatol. 2004;40:247-54. [PMID: 14739095] CrossrefMedlineGoogle Scholar19. Rama Rao KV, Reddy PV, Tong X, Norenberg MD. Brain edema in acute liver failure: inhibition by L-histidine. Am J Pathol. 2010;176:1400-8. [PMID: 20075201] CrossrefMedlineGoogle Scholar20. Stravitz RT, Lee WM, Kramer AH, Kramer DJ, Hynan L, Blei AT. Therapeutic hypothermia for acute liver failure: toward a randomized, controlled trial in patients with advanced hepatic encephalopathy. Neurocrit Care. 2008;9:90-6. [PMID: 18389180] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Polish Academy of Sciences, 02-106 Warsaw, Poland.Disclosures: None disclosed. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M10-1566.Corresponding Author: Jan Albrecht, PhD, Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego Street 5, 02-106 Warsaw, Poland; e-mail, [email protected]pan.pl. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoVariations in the Promoter Region of the Glutaminase Gene and the Development of Hepatic Encephalopathy in Patients With Cirrhosis Manuel Romero-Gómez , María Jover , José A. Del Campo , José L. Royo , Elena Hoyas , José J. Galán , Carmina Montoliu , Eugenia Baccaro , Mónica Guevara , Juan Córdoba , Germán Soriano , José M. Navarro , Carmen Martínez-Sierra , Lourdes Grande , Antonio Galindo , Emilia Mira , Santos Mañes , and Agustín Ruiz Metrics Cited ByImpact of depressive symptoms and hepatic encephalopathy on health-related quality of life in cirrhotic hepatitis C patientsCovert and Overt Hepatic Encephalopathy: Current Options for Diagnosis and TreatmentHepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failureUseful Tests for Hepatic Encephalopathy in Clinical PracticeAlterations of Blood Brain Barrier Function in Hyperammonemia: An OverviewAssessment and Usefulness of Clinical Scales for Semiquantification of Overt Hepatic Encephalopathy 7 September 2010Volume 153, Issue 5Page: 335-336KeywordsAmino acidsAmmoniaBloodBrainBrain diseasesCirrhosisGlutamineLiverNeurotransmittersRisk management ePublished: 7 September 2010 Issue Published: 7 September 2010 CopyrightCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...