Published online Dec 28, 2016. doi: 10.3748/wjg.v22.i48.10512
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
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.
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.