Healing of focal injury in the rat liver.

The healing process of focal hepatic injury produced by thrusting a liquid nitrogen-cooled or fire-heated needle in rat liver was investigated by light and electron microscopy and autoradiography. Twenty-four hours after the injury, necrotic areas were sharply demarcated from the surrounding normal hepatic tissue, and their margin was infiltrated with monocytes, macrophages, neutrophils, and platelets. Following the inflammatory infiltration, Ito cells, cholangiolar cells, and capillary endothelial cells proliferated in the peripheral areas of the necrosis. In accordance with the proliferation of Ito cells, collagen fibers markedly increased. Autoradiography demonstrated that cells proliferating in necrotic areas were predominantly Ito cells, and that hepatocytes adjacent to the damaged sites showed DNA synthesis. Necrotic and fibrotic areas were gradually decreased in size; and by 2 weeks, damaged sites were restored to almost normal histologic appearance, occasional scars remaining. The results of this study indicate that small focal hepatic injury is repaired locally by a mechanism resembling that of wound healing, and that Ito cells play an important role in that process.