Apoptosis: a mechanism of acute and chronic liver injury

Apoptosis represents the physiological way to eliminate excessive cells during embryogenesis and tissue remodelling. Under these conditions, apoptosis occurs in a controlled environment where dying cells are promptly removed by phagocytosis and replaced by new cells generated by mitosis. Apoptosis, however, is also an essential feature of a wide variety of acute and chronic diseases, including liver diseases. Imbalance between cell proliferation and death always leads to loss of tissue homeostasis and onset of various diseases. Excessive apoptosis has, indeed, been identified in acute and chronic viral hepatitis, alcoholic and non-alcoholic hepatitis, cholestatic liver disease, Wilson's disease, and graft versus host disease (GVHD). Sustained apoptosis has also been linked with the development of hepatic fibrosis. In contrast, insufficient apoptosis has been associated with development and progression of tumours of the liver and the biliary tree. Thus identification of target molecules involved in apoptosis may offer new options for pharmacological and/or gene mediated therapies for patients with liver diseases (fig 5).