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World J Gastroenterol. Jun 14, 2017; 23(22): 3954-3963
Published online Jun 14, 2017. doi: 10.3748/wjg.v23.i22.3954
Role of non-steroidal anti-inflammatory drugs on intestinal permeability and nonalcoholic fatty liver disease
Erika Utzeri, Paolo Usai
Erika Utzeri, Paolo Usai, Department of Medical Sciences, University of Cagliari, 09124 Cagliari, Italy
Author contributions: Usai P substantially contributed to the conception and design of the review; Utzeri E contributed to the acquisition of data and drafting the article.
Conflict-of-interest statement: Utzeri E and Usai P declare no conflict of interest related to this publication.
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: Paolo Usai, Associate Professor, Department of Medical Sciences, University of Cagliari, Via Università, 40, 09124 Cagliari, Italy.
Telephone: +39-70-51096138 Fax: +39-70-51096138
Received: October 26, 2016
Peer-review started: October 28, 2016
First decision: December 19, 2016
Revised: January 19, 2017
Accepted: February 7, 2017
Article in press: February 7, 2017
Published online: June 14, 2017

The use of non-steroidal anti-inflammatory drugs (NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of digestive system complications in the course of their use. Recent data suggests that the complications of the lower gastro-intestinal tract may be as frequent and severe as those of the upper tract. NSAIDs enteropathy is due to enterohepatic recycling of the drugs resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites. Thus leading to so-called topical effects, which, in turn, lead to an impairment of the intestinal barrier. This process determines bacterial translocation and toxic substances of intestinal origin in the portal circulation, leading to an endotoxaemia. This condition could determine a liver inflammatory response and might promote the development of non-alcoholic steatohepatitis, mostly in patients with risk factors such as obesity, metabolic syndrome and a high fat diet, which may induce a small intestinal bacterial overgrowth and dysbiosis. This alteration of gut microbiota may contribute to nonalcoholic fatty liver disease and its related disorders in two ways: firstly causing a malfunction of the tight junctions that play a critical role in the increase of intestinal permeability, and then secondly leading to the development of insulin resistance, body weight gain, lipogenesis, fibrogenesis and hepatic oxidative stress.

Keywords: Non-steroidal anti-inflammatory drugs, Intestinal barrier, Intestinal permeability, Non-steroidal anti-inflammatory drugs - enteropathy, Nonalcoholic fatty liver disease, Nonalcoholic steatohepatitis, Microbiota, Metabolic syndrome, Proton pump inhibitors, Endotoxaemia

Core tip: Among the gastro-intestinal effects, in non-steroidal anti-inflammatory drugs (NSAIDs) users, those of the lower tract seem to be rising. NSAIDs enteropathy is due to the enterohepatic recycling of drugs, resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites, leading to so called topical effects. The impairment of the intestinal barrier represents the initial damage of NSAIDs enteropathy that leads to the translocation of bacteria and toxic substances of intestinal origin in the portal circulation, promoting an endotoxaemia. This condition, mostly in patients with risk factors for nonalcoholic fatty liver diseas, such as obesity and metabolic syndrome, might lead to liver inflammatory response that could promote the development of nonalcoholic steatohepatitis.