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Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2020; 26(17): 1993-2011
Published online May 7, 2020. doi: 10.3748/wjg.v26.i17.1993
Metabolic inflammation as an instigator of fibrosis during non-alcoholic fatty liver disease
Angeliki Katsarou, Ioannis I Moustakas, Iryna Pyrina, Panagiotis Lembessis, Michael Koutsilieris, Antonios Chatzigeorgiou
Angeliki Katsarou, Ioannis I Moustakas, Panagiotis Lembessis, Michael Koutsilieris, Antonios Chatzigeorgiou, Department of Physiology, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
Angeliki Katsarou, 251 Hellenic Airforce General Hospital, Athens 11525, Greece
Iryna Pyrina, Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine Carl Gustav Carus of TU Dresden, Dresden 01307, Germany
Antonios Chatzigeorgiou, Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine Carl Gustav Carus of TU Dresden, Dresden 01307, Germany.
Author contributions: Katsarou A and Moustakas II wrote the manuscript; Lembessis P and Pyrina I contributed to the writing of the manuscript and designed the figure; Koutsilieris M and Chatzigeorgiou A designed, edited and wrote the manuscript.
Supported by the Deutsche Forschungsgemeinschaft, No. CH 1862/2-1 and No. CH 1862/3-1; the Hellenic Association for the Study of the Liver.
Conflict-of-interest statement: All the authors declare that they have no competing interests.
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 NonCommercial (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/
Corresponding author: Antonios Chatzigeorgiou, BSc, MD, PhD, Assistant Professor, Department of Physiology, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Athens 11527, Greece. achatzig@med.uoa.gr
Received: January 20, 2020
Peer-review started: January 20, 2020
First decision: April 4, 2020
Revised: April 9, 2020
Accepted: April 21, 2020
Article in press: April 21, 2020
Published online: May 7, 2020
Abstract

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive storage of fatty acids in the form of triglycerides in hepatocytes. It is most prevalent in western countries and includes a wide range of clinical and histopathological findings, namely from simple steatosis to steatohepatitis and fibrosis, which may lead to cirrhosis and hepatocellular cancer. The key event for the transition from steatosis to fibrosis is the activation of quiescent hepatic stellate cells (qHSC) and their differentiation to myofibroblasts. Pattern recognition receptors (PRRs), expressed by a plethora of immune cells, serve as essential components of the innate immune system whose function is to stimulate phagocytosis and mediate inflammation upon binding to them of various molecules released from damaged, apoptotic and necrotic cells. The activation of PRRs on hepatocytes, Kupffer cells, the resident macrophages of the liver, and other immune cells results in the production of proinflammatory cytokines and chemokines, as well as profibrotic factors in the liver microenvironment leading to qHSC activation and subsequent fibrogenesis. Thus, elucidation of the inflammatory pathways associated with the pathogenesis and progression of NAFLD may lead to a better understanding of its pathophysiology and new therapeutic approaches.

Keywords: Non-alcoholic fatty liver disease, Non-alcoholic steatohepatitis, Hepatic stellate cells, Inflammation, Liver fibrosis, Toll-like receptors, Nod-like receptors

Core tip: Non-alcoholic fatty liver disease (NAFLD) is a frequent disorder in western countries with a wide range of histopathological findings, varying from simple steatosis to fibrosis or even cirrhosis. Metabolic dysregulation, principally during obesity, triggers chronic inflammation in the liver, defined as steatohepatitis that favors the development of fibrosis and likely cirrhosis and hepatocellular cancer. In this review we summarize and discuss the current literature regarding the principal inflammatory pathways involved in the pathogenesis of NAFLD and progression to non-alcoholic steatohepatitis.