Molecular mechanisms of hepatic fibrosis in non-alcoholic steatohepatitis

Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease in Western countries. The more severe form of this condition, non-alcoholic steatohepatitis (NASH), may progress to cirrhosis and its complications. Fibrosis and cirrhosis are the final outcomes of all chronic liver diseases; however, some morphological and biological differences distinguish fibrosis due to NASH from the forms secondary to other causes of liver damage. Fibrosis due to NASH develops primarily in the pericentral areas, surrounding groups of hepatocytes and thickening the space of Disse. This pericellular fibrosis eventually forms septa isolating regenerating nodules. The main cell type responsible for extracellular matrix deposition is represented by hepatic stellate cells that undergo activation in conditions of liver injury enabling them to participate in the liver wound healing process. Although the profibrogenic mechanisms operating in NASH are partly in common with those observed in other chronic liver diseases, the altered pattern of circulating adipokines, oxidative stress generation and the hormonal profile associated with the metabolic syndrome might have a specific role for the induction of fibrogenesis in this condition. In this paper, we review recent developments regarding the basic mechanisms of NASH and the involvement of hepatic stellate cells in this disease.