**6. Conclusion**

In summary, the CDE diet targets specifically hepatocytes and induce DR-containing elongated cells of an undifferentiated and migration-supporting phenotype expanding from portal tracts into the parenchyma. Myofibroblast activation and extracellular matrix deposition precedes this cell expansion, and a laminin-rich sheet sustains those DR while macrophages associate with invading DR. In the DDC model, accumulating protoporphyrin obstructs the hepatobiliary system leading to biliary damage and resulting in highly proliferative cells forming bile ductlike structures remaining restricted to portal mesenchyme, delineated by a thin layer of laminin and accompanied by dense portal inflammation. Moreover, cell-tracking experiments revealed that DR cells are able to generate a small number of functional hepatocytes after CDE but not after DDC exposure. Finally, the DR phenotype and signaling pathways involved in LPC differentiation in the CDE model mirrors the one observed in chronic HCV infection presenting signs of fibrosis and autoimmune hepatitis, while the DDC model could be used to study biliary injury such as PSC or PBC in humans. We believe that characterization of the most widely used dietary DR mouse models will help our understanding of the diversity of DR patterns observed in humans and will help the researchers to select the appropriate model in relation to the specific question addressed.
