Review
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2020; 26(16): 1861-1878
Published online Apr 28, 2020. doi: 10.3748/wjg.v26.i16.1861
Macrophages in metabolic associated fatty liver disease
Jawaher Alharthi, Olivier Latchoumanin, Jacob George, Mohammed Eslam
Jawaher Alharthi, Olivier Latchoumanin, Jacob George, Mohammed Eslam, Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney 2145, NSW, Australia
Author contributions: Alharthi J, Latchoumanin O, George J and Eslam M contributed to conceptualization and the writing of the manuscript and all authors approved the submission of the final version of the manuscript.
Conflict-of-interest statement: The authors declare no competing interests for this manuscript.
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: Mohammed Eslam, MD, PhD, Associate Professor, Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, 176 Hawkesbury Rd, Sydney 2145, NSW, Australia. mohammed.eslam@sydney.edu.au
Received: December 23, 2019
Peer-review started: December 23, 2019
First decision: February 18, 2020
Revised: March 10, 2020
Accepted: April 17, 2020
Article in press: April 17, 2020
Published online: April 28, 2020
Abstract

Metabolic associated fatty liver disease (MAFLD), formerly named non-alcoholic fatty liver disease is the most common liver disorder in many countries. The inflammatory subtype termed steatohepatitis is a driver of disease progression to cirrhosis, hepatocellular carcinoma, liver transplantation, and death, but also to extrahepatic complications including cardiovascular disease, diabetes and chronic kidney disease. The plasticity of macrophages in response to various environmental cues and the fact that they can orchestrate cross talk between different cellular players during disease development and progression render them an ideal target for drug development. This report reviews recent advances in our understanding of macrophage biology during the entire spectrum of MAFLD including steatosis, inflammation, fibrosis, and hepatocellular carcinoma, as well as for the extra-hepatic manifestations of MAFLD. We discuss the underlying molecular mechanisms of macrophage activation and polarization as well as cross talk with other cell types such as hepatocytes, hepatic stellate cells, and adipose tissue. We conclude with a discussion on the potential translational implications and challenges for macrophage based therapeutics for MAFLD.

Keywords: Metabolic associated fatty liver disease, Macrophages, Inflammation, Fibrosis, Hepatic stellate cells

Core tip: In this work, we review the recent advances in our understanding of macrophage biology during the entire spectrum of metabolic associated fatty liver disease (MAFLD) including steatosis, inflammation, fibrosis, and hepatocellular carcinoma, as well as for the extra-hepatic manifestations of MAFLD. We discuss the underlying molecular mechanisms of macrophage activation and polarization as well as cross talk with other cell types such as hepatocytes, hepatic stellate cells and adipose tissue. We conclude with a discussion on the potential translational implications and challenges for macrophage based therapeutics for MAFLD.