Hepatic fibrogenesis: from within and outwith.
Liver disease is now the fifth commonest cause of death in the United Kingdom and the incidence is increasing. Chronic injury to the liver typically due to toxic insult, viral infection, immunological or metabolic diseases usually results in a stereotypical response with both parenchymal regeneration and wound healing. Chronic hepatic injury results in liver fibrosis with eventual progression to cirrhosis and end stage liver disease. At this point the majority of the clinical complications arise such as portal hypertension and the development of liver cancer. If the causative disease can be effectively treated the liver can regenerate and at the least partial resolution of liver fibrosis may occur. Unfortunately, unless the primary disease can be eradicated there are no specific anti-fibrotic treatments in routine clinical use. This highlights the urgent need to both increase our understanding of the mechanisms of hepatic fibrogenesis and to develop novel therapies to arrest or reverse the fibrotic process. This article initially outlines the main cellular pathway of fibrogenesis within the liver-the activation of the quiescent hepatic stellate cell into an activated myofibroblast phenotype, resulting in the production of fibrillar collagen. We will then discuss newly emerging sources of scar forming cells during hepatic injury together with the role of hepatic macrophages which have a regulatory function in both the formation and resolution of liver fibrosis.
Henderson
Neil C
NC
The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. Neil.Henderson@ed.ac.uk
Forbes
Stuart J
SJ
D000818:Animals; D018450:Disease Progression; D024022:Fibrillar Collagens / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D055166:Hepatic Stellate Cells / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology*; D008264:Macrophages / Q000378:metabolism*; D010641:Phenotype; D006113:United Kingdom / Q000453:epidemiology
D024022:Fibrillar Collagens