title: Hepatic encephalopathy: Ever closer to its big bang.
abstract: Hepatic encephalopathy (HE) is a neuropsychiatric disorder that commonly complicates the course of patients with liver disease. Despite the fact that the syndrome was probably first recognized hundreds of years ago, the exact pathogenesis still remains unclear. Minimal hepatic encephalopathy (MHE) is the earliest form of HE and is estimated to affect more that 75% of patients with liver cirrhosis. It is characterized by cognitive impairment predominantly attention, reactiveness and integrative function with very subtle clinical manifestations. The development of MHE is associated with worsen in driving skills, daily activities and the increase of overall mortality. Skeletal muscle has the ability to shift from ammonia producer to ammonia detoxifying organ. Due to its large size, becomes the main ammonia detoxifying organ in case of chronic liver failure and muscular glutamine-synthase becomes important due to the failing liver and brain metabolic activity. Gut is the major glutamine consumer and ammonia producer organ in the body. Hepatocellular dysfunction due to liver disease, results in an impaired clearance of ammonium and in its inter-organ trafficking. Intestinal bacteria, can also represent an extra source of ammonia production and in cirrhosis, small intestinal bacterial overgrowth and symbiosis can be observed. In the study of HE, to get close to MHE is to get closer to its big bang; and from here, to travel less transited roads such as skeletal muscle and intestine, is to go even closer. The aim of this editorial is to expose this road for further and deeper work.
authors.affiliation: Pablo A Souto, Ariel R Marcotegui, Lisandro Orbea, Juan Skerl, Juan Carlos Perazzo, Department of Pathology, Laboratory of Hyperammonemia and Hepatic Encephalopathy, Center of Applied and Experimental Pathology, Faculty of Medicine, University of Buenos Aires, Buenos Aires 1053, Argentina.
authors.forename: Pablo A
authors.initials: PA
authors.lastname: Souto
authors.affiliation: Pablo A Souto, Ariel R Marcotegui, Lisandro Orbea, Juan Skerl, Juan Carlos Perazzo, Department of Pathology, Laboratory of Hyperammonemia and Hepatic Encephalopathy, Center of Applied and Experimental Pathology, Faculty of Medicine, University of Buenos Aires, Buenos Aires 1053, Argentina.
authors.forename: Ariel R
authors.initials: AR
authors.lastname: Marcotegui
authors.affiliation: Pablo A Souto, Ariel R Marcotegui, Lisandro Orbea, Juan Skerl, Juan Carlos Perazzo, Department of Pathology, Laboratory of Hyperammonemia and Hepatic Encephalopathy, Center of Applied and Experimental Pathology, Faculty of Medicine, University of Buenos Aires, Buenos Aires 1053, Argentina.
authors.forename: Lisandro
authors.initials: L
authors.lastname: Orbea
authors.affiliation: Pablo A Souto, Ariel R Marcotegui, Lisandro Orbea, Juan Skerl, Juan Carlos Perazzo, Department of Pathology, Laboratory of Hyperammonemia and Hepatic Encephalopathy, Center of Applied and Experimental Pathology, Faculty of Medicine, University of Buenos Aires, Buenos Aires 1053, Argentina.
authors.forename: Juan
authors.initials: J
authors.lastname: Skerl
authors.affiliation: Pablo A Souto, Ariel R Marcotegui, Lisandro Orbea, Juan Skerl, Juan Carlos Perazzo, Department of Pathology, Laboratory of Hyperammonemia and Hepatic Encephalopathy, Center of Applied and Experimental Pathology, Faculty of Medicine, University of Buenos Aires, Buenos Aires 1053, Argentina.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Perazzo
mesh_terms: D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D018450:Disease Progression; D006501:Hepatic Encephalopathy / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000648:ultrastructure; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D011379:Prognosis
chemical_list: D000641:Ammonia
keywords: Ammonia; Hyperammonemia; Minimal hepatic encephalopathy; Skeletal muscle