Figure 1.

Model for the development of primary liver tumors. Several risk and etiologic factors can lead to development of primary tumors in the liver. HCV and HBV infection, heavy alcohol intake, exposure to aflatoxin, drugs, and others can lead to cycles of damage-cell death-regeneration in the liver. This, together with genome instability and changes in the microenvironment, can create a scenario where hepatocytes start to activate oncogenic and developmental pathways. Only those hepatocytes with mutations in cell cycle regulators will survive and divide, resulting in malignancy and metastases.