Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jun 27, 2019; 11(6): 489-512
Published online Jun 27, 2019. doi: 10.4254/wjh.v11.i6.489
Dietary approach and gut microbiota modulation for chronic hepatic encephalopathy in cirrhosis
Daniela Campion, Ilaria Giovo, Paola Ponzo, Giorgio M Saracco, Federico Balzola, Carlo Alessandria
Daniela Campion, Ilaria Giovo, Paola Ponzo, Giorgio M Saracco, Federico Balzola, Carlo Alessandria, Division of Gastroenterology and Hepatology, Città della Salute e della Scienza di Torino Hospital, University of Turin, 10126 Turin, Italy
Author contributions: Campion D, Giovo I, Ponzo P and Alessandria C drafted and edited the manuscript; Saracco GM and Balzola F supervised the editing of the manuscript.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
Open-Access: This article is an open-access article that 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:
Corresponding author: Carlo Alessandria, MD, Doctor, Division of Gastroenterology and Hepatology, Città della Salute e della Scienza di Torino Hospital, University of Turin, Bramante 88, 10126 Turin, Italy.
Telephone: +39-011-6335561 Fax: +39-011-6335714
Received: March 15, 2019
Peer-review started: March 15, 2019
First decision: April 22, 2019
Revised: May 15, 2019
Accepted: May 20, 2019
Article in press: May 21, 2019
Published online: June 27, 2019

Hepatic encephalopathy (HE) is a common and serious neuropsychiatric complication of cirrhosis, acute liver failure, and porto-systemic shunting. HE largely contributes to the morbidity of patients with liver disease, severely affecting the quality of life of both patients and their relatives and being associated with poor prognosis. Its presentation is largely variable, manifesting with a broad spectrum of cognitive abnormalities ranging from subtle cognitive impairment to coma. The pathogenesis of HE is complex and has historically been linked with hyperammonemia. However, in the last years, it has become evident that the interplay of multiple actors, such as intestinal dysbiosis, gut hyperpermeability, and neuroinflammation, is of crucial importance in its genesis. Therefore, HE can be considered a result of a dysregulated gut-liver-brain axis function, where cognitive impairment can be reversed or prevented by the beneficial effects induced by “gut-centric” therapies, such as non-absorbable disaccharides, non-absorbable antibiotics, probiotics, prebiotics, and fecal microbiota transplantation. In this context dietary modifications, by modulating the intestinal milieu, can also provide significant benefit to cirrhotic patients with HE. This review will provide a comprehensive insight into the mechanisms responsible for gut-liver-brain axis dysregulation leading to HE in cirrhosis. Furthermore, it will explore the currently available therapies and the most promising future treatments for the management of patients with HE, with a special focus on the dietary approach.

Keywords: Cirrhosis, Hepatic encephalopathy, Diet therapy, Gut microbiota, Leaky gut, Hyperammonemia, Prebiotics, Probiotics, Gluten-casein free diet, Gut microbiota transplantation

Core tip: Hepatic encephalopathy (HE) is a serious complication of cirrhosis resulting from a multifactorial impairment of gut-liver-brain axis functioning. Multiple interrelated factors (e.g., intestinal hyperpermeability, dysbiosis, hyperammonemia, inflammation) cooperate in its development. “Gut-centric” therapies, including non-absorbable disaccharides, antibiotics, prebiotics, probiotics, and fecal microbiota transplantation have been successfully employed to manage HE: pertinent current knowledge will be reviewed. Furthermore, the utility of dietary modifications in this context is increasingly recognized, thus opening a new promising research path. This review sheds light on dietary therapeutic strategies for HE, exploring how they can target the mechanisms underlying gut-liver-brain axis dysregulation.