Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2015; 21(41): 11815-11824
Published online Nov 7, 2015. doi: 10.3748/wjg.v21.i41.11815
Inflammation: A novel target of current therapies for hepatic encephalopathy in liver cirrhosis
Ming Luo, Jian-Yang Guo, Wu-Kui Cao
Ming Luo, Jian-Yang Guo, Department of Gastroenterology, Ningxia People’s Hospital, Yinchuan 750021, Ningxia Hui Autonomous Region, China
Wu-Kui Cao, Tianjin Liver Disease Institute, Tianjin Second People’s Hospital, Tianjin 300192, China
Author contributions: Cao WK designed the study and outlined the draft; Luo M wrote and organized the manuscript; and Guo JY searched the reference materials and contributed to the writing of the manuscript.
Conflict-of-interest statement: The authors have no conflicts of interest to declare in relation to this manuscript.
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:
Correspondence to: Wu-Kui Cao, PhD, Tianjin Liver Disease Institute, Tianjin Second People’s Hospital, No. 75 Sudi Road, Nankai District, Tianjin 300192, China.
Telephone: +86-22-27468102
Received: April 16, 2015
Peer-review started: April 18, 2015
First decision: May 18, 2015
Revised: June 19, 2015
Accepted: September 14, 2015
Article in press: September 14, 2015
Published online: November 7, 2015

Hepatic encephalopathy (HE) is a severe neuropsychiatric syndrome that most commonly occurs in decompensated liver cirrhosis and incorporates a spectrum of manifestations that ranges from mild cognitive impairment to coma. Although the etiology of HE is not completely understood, it is believed that multiple underlying mechanisms are involved in the pathogenesis of HE, and one of the main factors is thought to be ammonia; however, the ammonia hypothesis in the pathogenesis of HE is incomplete. Recently, it has been increasingly demonstrated that inflammation, including systemic inflammation, neuroinflammation and endotoxemia, acts in concert with ammonia in the pathogenesis of HE in cirrhotic patients. Meanwhile, a good number of studies have found that current therapies for HE, such as lactulose, rifaximin, probiotics and the molecular adsorbent recirculating system, could inhibit different types of inflammation, thereby improving the neuropsychiatric manifestations and preventing the progression of HE in cirrhotic patients. The anti-inflammatory effects of these current therapies provide a novel therapeutic approach for cirrhotic patients with HE. The purpose of this review is to describe the inflammatory mechanisms behind the etiology of HE in cirrhosis and discuss the current therapies that target the inflammatory pathogenesis of HE.

Keywords: Inflammation, Hepatic encephalopathy, Pathogenesis, Treatment

Core tip: Currently, inflammation appears to play a critical role in the pathogenesis of hepatic encephalopathy (HE) and is gradually being considered a critical therapeutic target for HE in patients with liver cirrhosis. Current therapies for HE, including lactulose, rifaximin, probiotics and the molecular adsorbent recirculating system, have been found to improve clinical manifestations and prevent the progression of HE by ameliorating inflammation in cirrhotic patients. This review will provide an overview of the inflammatory pathogenesis of HE, focusing on the recent findings on its therapeutic manipulation.