Fig. 2

Schematic representation of the events involved in the progression of liver injury. (1) Chronic tissue damage significantly impairs the regenerative capacity of the liver. Therefore, activation of secondary proliferation pathways characterized by proliferation of hepatocyte progenitor cells (HPCs) occurs. These cells are the source of hepatocyte, cholangiocytes, and drainage tubule regeneration. The proliferation of HPCs is accompanied by a ductular reaction (DR) that leads to the recruitment of macrophages (KCs) and stellate cells, resulting in persistent inflammation (2). Persistent inflammation, stellate cell activation, and epithelial abnormalities may lead to fibrosis (3). Extensive liver fibrosis can block the blood flow through the liver, promoting cirrhosis evolution (4). Cirrhosis can be defined as the final stage of fibrosis and is associated with significant changes in liver architecture that predispose to malignant liver tumors (HCC) (5). As shown in the figure (red arrow), approximatively about 20% of cases of HCC may develop in a non-cirrhotic liver, suggesting multiple mechanisms of hepatocarcinogenesis