Liver fibrosis - mouse models and relevance in human liver diseases

Liver fibrosis, the excessive accumulation of extracellular matrix (ECM) in the liver, develops as a long-term consequence of chronic liver injury, and significantly contributes to the mortal complications of chronic liver disease. Different cell types contribute to the hepatic wound healing response. Hepatic stellate cells (HSC) are the main fibrogenic cell in the liver. Upon liver injury, HSCs transdifferentiate into myofibroblasts and contribute to ECM deposition in the liver. Small animal models have provided insight into the activation process of HSCs and the complex interplay of the different cell types involved in liver fibrogenesis. Animal models not only allow one to identify relevant profibrogenic pathways, but also to test the contribution of these pathways to liver disease in preclinical settings. In this review, mouse models of toxic, cholestatic, apoptotic, acoholic, viral and metabolic liver fibrosis will be discussed, with a particular emphasis on the underlying pathophysiology, relevance to human liver disease and drug development.