There are at present a number of concepts of the pathogenesis of cirrhosis, the most widely held of which is that cirrhosis develops as degeneration, nodular regeneration, and fibrosis occur in sequence.1-4 According to this view, a variety of etiologic factors damage liver cells, many of which die while others regenerate. Foci of nodular regeneration are thought to occur in this way, compressing the stroma that formerly surrounded necrotic cells, giving rise to fibrous bands.
In studies of rat and human liver in various stages of cirrhosis I have found a different sequence of events in the development of the cirrhotic process. Using tritiated thymidine (H3-thymidine) and autoradiography to detect proliferating cells, the earliest change giving rise to fibrosis was proliferation of cells of blood vessels and lymphatics. From these studies, the pathogenesis of nutritional cirrhosis is suggested to be as follows. Swelling of liver and Kupffer
MACDONALD RA. Pathogenesis of Nutritional Cirrhosis. Arch Intern Med. 1962;110(4):424-434. doi:10.1001/archinte.1962.03620220016004