[Consequences of cholestasis from the pathologist's viewpoint].

The present review summarizes extrahepatic obstructive cholestasis and its hepatic morphological sequelae. The first part focuses on early and late changes visualized in liver biopsies. In the second part, pathogenic mechanisms involved in liver fibrosis are discussed. A third section deals with the morphological differentiation of liver atrophy occurring in obstruction and secondary biliary cirrhosis. Biliary obstruction induces a wide array of typical early and late changes of liver morphology. They comprise the visible accumulation of bile in hepatocytes and macrophages, liver cell damage (cholate stasis; apoptosis), alterations of cellular organelles, cytoskeleton and junctions, portal tract edema with cellular infiltrates, ductular reaction, bile infarcts, bile extravasation and, in the later stages, fibrosis and partial nodular change. The pathogenesis of septal fibrosis appears to involve, besides fibroblasts, myofibroblasts probably derived from the Ito cell system. Myofibroblasts seem to closely follow proliferating ductules which, therefore, have a crucial role in hepatic tissue remodeling. There are considerable structural similarities between liver atrophy occurring in biliary and/ or portal vein obstruction and secondary biliary cirrhosis. In both situations partial nodular change ensues, but with preserved vascular relations. In addition, both changes are partially reversible in the early stages of the disease. Irreversible late stages of atrophy and secondary biliary cirrhosis are, therefore, maximum alterations of a similar, dynamic process, involving part of the liver in the first case and the whole organ in the second, depending on the level of obstruction.