Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets

• Published in: World journal of gastroenterology : WJG Vol. 22; no. 48; pp. 10512 - 10522
• Main Authors: Zhang, Chong-Yang, Yuan, Wei-Gang, He, Pei, Lei, Jia-Hui, Wang, Chun-Xu
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 28.12.2016
• Subjects: Acetyl-CoA C-Acetyltransferase - metabolism; Animals; CD4-Positive T-Lymphocytes - metabolism; Disease Progression; Fatty Liver, Alcoholic - complications; Hepatic Stellate Cells - drug effects; Hepatic Stellate Cells - pathology; Humans; Interleukins - metabolism; Intracellular Signaling Peptides and Proteins - metabolism; LIM Domain Proteins - metabolism; Liver Cirrhosis - drug therapy; Liver Cirrhosis - etiology; Liver Cirrhosis - pathology; Macrophages - metabolism; MicroRNAs - metabolism; Molecular Targeted Therapy - methods; Non-alcoholic Fatty Liver Disease - complications; Resveratrol; Review; Schistosomiasis - complications; Signal Transduction; Stilbenes - therapeutic use; T-Lymphocytes, Regulatory - metabolism; Triterpenes - therapeutic use; Ursodeoxycholic Acid - analogs & derivatives; Ursodeoxycholic Acid - therapeutic use; Ursolic Acid; Virus Diseases - complications; Pathology; Hepatic stellate cells; Treatment; Etiology; Liver cirrhosis; Fibrosis
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v22.i48.10512

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.