The first and second line of defense in canine liver regeneration. In liver sections proliferation is visualized by PCNA or Ki67 immunohistochemistry. K7 was used as a marker for hepatic progenitor cells. In healthy liver, both hepatocytes and HPCs are quiescent, indicated by a few hepatocytes that stain for PCNA and only a few K7 positive cells close to the portal area (indicated with arrow, asterisk indicates bile duct). After partial hepatectomy (PHx), liver regeneration occurs through hepatocyte proliferation (many PCNA positive hepatocytes indicated by arrows) but the HPC remains quiescent (few K7 positive cells). In chronic hepatitis the proliferative capacity of hepatocytes is exhausted indicated by a few Ki67 positive hepatocytes and a prominent ductular reaction (K7 positive, indicated by arrows) [6, 30].