Defining therapeutic targets for liver fibrosis: Exploiting the biology of inflammation and repair

Liver fibrosis represents the generic wound healing response to chronic insults regardless of their mechanism. The causes of chronic liver injury and fibrosis have a wide geographic distribution and include chronic viral hepatitis, parasitic disease, inborn errors of metabolism, toxic damage (in world wide terms most commonly due to alcohol) and non alcoholic fatty liver disease. Liver disease is currently the 5th most common cause of death in the United Kingdom and unlike the other systemic diseases grouped in this rather depressing league table, its incidence is rising.Over the last 10 to 15 years our understanding of the pathogenesis of liver fibrosis and its dynamic nature has preceded a pace. This has been due to developments in technologies including the isolation of individual liver cell populations which has facilitated studies of their behaviour in tissue culture and in vivo. More recently there has been the development of appropriate animal models which are tractable and can be applied in gene knockout and transgenic mice.This review will highlight the development and understanding of liver fibrosis which have developed from the use of such complimentary animal and human model systems and describe how the greater understanding of this dynamic process is likely to inform the development of directed and effective antifibrotic approaches.