Editorial
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 14, 2016; 22(42): 9251-9256
Published online Nov 14, 2016. doi: 10.3748/wjg.v22.i42.9251
Hepatic encephalopathy: Ever closer to its big bang
Pablo A Souto, Ariel R Marcotegui, Lisandro Orbea, Juan Skerl, Juan Carlos Perazzo
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
Author contributions: Souto PA, Marcotegui AR, Orbea L and Skerl J contributed equally to this work, designed and performed the research and analyzed the data; Perazzo JC wrote the editorial article.
Conflict-of-interest statement: The authors declare that they don´t have any conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Juan Carlos Perazzo, MD, Professor, Department of Pathology, Head of the Hepatic Encephalopathy and Portal Hypertension Research Group, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Uriburu 950 5th floor Ciudad, Buenos Aires 1053, Argentina. perazzopat@gmail.com
Telephone: +54-11-52852738
Received: July 1, 2016
Peer-review started: July 1, 2016
First decision: August 8, 2016
Revised: September 9, 2016
Accepted: October 19, 2016
Article in press: October 31, 2016
Published online: November 14, 2016
Processing time: 134 Days and 10.7 Hours
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.

Keywords: Ammonia; Skeletal muscle; Minimal hepatic encephalopathy; Hyperammonemia

Core tip: This work is a contribution to the current knowledge of hepatic encephalopathy (HE) and shows new important data about aspect less studied, as ammonia effect inducing morphological ultrastructural damage in skeletal muscle and gut. These alterations were observed in a Minimal HE model without liver damage, which suggests that the damage caused by ammonia may occur before liver failure.