Review
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2016; 22(48): 10512-10522
Published online Dec 28, 2016. doi: 10.3748/wjg.v22.i48.10512
Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets
Chong-Yang Zhang, Wei-Gang Yuan, Pei He, Jia-Hui Lei, Chun-Xu Wang
Chong-Yang Zhang, Jia-Hui Lei, Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Wei-Gang Yuan, Chun-Xu Wang, Department of Anthropotomy, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Pei He, Department of Obstetrics and Gynecology, Wuhan NO.1 Hospital Affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Author contributions: Zhang CY and Yuan WG contributed equally to this work; Zhang CY and Yuan WG wrote the paper; He P and Lei JH created the schematics; Wang CX provided technical support.
Supported by the National Natural Science Foundation of China, No. 81300251.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Chun-Xu Wang, Department of Anthropotomy, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Jie-fang Road, Wuhan 430030, Hubei Province, China. wangchunxu12345@126.com
Telephone: +86-133-17146583 Fax: +86-27-83692617
Received: August 25, 2016
Peer-review started: August 26, 2016
First decision: September 29, 2016
Revised: October 12, 2016
Accepted: November 15, 2016
Article in press: November 16, 2016
Published online: December 28, 2016
Processing time: 123 Days and 0.3 Hours
Abstract

Liver fibrosis is a reversible wound-healing process aimed at maintaining organ integrity, and presents as the critical pre-stage of liver cirrhosis, which will eventually progress to hepatocellular carcinoma in the absence of liver transplantation. Fibrosis generally results from chronic hepatic injury caused by various factors, mainly viral infection, schistosomiasis, and alcoholism; however, the exact pathological mechanisms are still unknown. Although numerous drugs have been shown to have antifibrotic activity in vitro and in animal models, none of these drugs have been shown to be efficacious in the clinic. Importantly, hepatic stellate cells (HSCs) play a key role in the initiation, progression, and regression of liver fibrosis by secreting fibrogenic factors that encourage portal fibrocytes, fibroblasts, and bone marrow-derived myofibroblasts to produce collagen and thereby propagate fibrosis. These cells are subject to intricate cross-talk with adjacent cells, resulting in scarring and subsequent liver damage. Thus, an understanding of the molecular mechanisms of liver fibrosis and their relationships with HSCs is essential for the discovery of new therapeutic targets. This comprehensive review outlines the role of HSCs in liver fibrosis and details novel strategies to suppress HSC activity, thereby providing new insights into potential treatments for liver fibrosis.

Keywords: Liver cirrhosis; Fibrosis; Hepatic stellate cells; Etiology; Pathology; Treatment

Core tip: This review discusses the molecular mechanisms of liver fibrosis with respect to hepatic stellate cells (HSCs). In particular, we describe the functional significance of HSCs with respect to major events triggering fibrosis and novel therapeutic strategies to suppress the activity of activated HSCs.