**2.5 Fibrosis**

Hepatocellular carcinoma, fibrosis and its more severe form, hepatic cirrhosis represent a final common pathway of most chronic liver diseases, such as NAFLD and NASH. Fibrosis is caused by excessive secretion of extracellular matrix (ECM) that is not sufficiently balanced by degradation, leading to a net accumulation. In the models of toxic, biliary liver disease and NAFLD, hepatic stellate cells (HSC) are the primary source of ECM-producing fibroblasts [16]. Twenty genetically distinct types of fibrillary and non-fibrillar collagen, as well as non-collagenous glycoproteins-like elastin, laminin, and fibronectin, as well as glycosaminoglycanslike hyaluronan and proteoglycans, including aggrecan, fibromodulin, decorin, biglycan, glypicans, and syndecans, are all contained in the complex network of the ECM proteins. Together with increased amounts, the composition of the ECM proteins is also modified in fibrosis, leading to an increase in embryonic or woundhealing associated ECM and an increase in crosslinks that make the ECM more resistant to degradation, contributing to delay and incomplete reversibility of severe fibrosis. A more progressive pattern of liver damage may be caused by an inability to develop a ductular response, as seen in patients with denervated liver, who have undergone liver transplantation for NASH [16].

*Non-Alcoholic Fatty Liver Disease: Pathogenesis and the Significance of High-Density… DOI: http://dx.doi.org/10.5772/intechopen.108199*
