The pathobiology of biliary epithelia

Abstract

The morbidity and mortality from chronic biliary diseases (i.e., the cholangiopathies) remains substantial. End-stage liver disease from biliary causes of cirrhosis (e.g., primary biliary cirrhosis [PBC], and primary sclerosing cholangitis) account for approximately one third of patients referred for liver transplantation. A single-topic conference sponsored by the American Association for the Studies of Liver Diseases entitled "The Pathobiology of Biliary Epithelia" brought together investigators to review the status of the field of cholangiocyte pathobiology, identify new areas of interest, and propose future directions. This information was presented in 6 sessions: "Structural and Functional Characteristics of the Bile Duct System," "Biological Topics from Nonbiliary Epithelia," "Malignant Transformation of Cholangiocytes," "Cholangiocyte Proliferation and Death," "Transport Mechanisms in Bile Duct Epithelia," and "Pathobiology of Biliary Epithelia." In the 7 years since the first symposium on this topic, major advances have been made in our understanding of ductal bile formation, including, greater insight into the hormones, intracellular signaling mechanisms, and effector proteins responsible for bile secretion and absorption. More sophisticated imaging technologies have increased our understanding of the polarity of cholangiocytes, their embryology and ultrastructural anatomy, and in vivo human secretory responses to current medical therapy. Information on mediators of inflammation permeated many sessions, having potentially important roles in malignant transformation of cholangiocytes, cholangiocyte apoptosis, fluid and electrolyte transport, and have begun to be specifically characterized for certain biliary diseases, e.g., acquired immunodeficiency syndrome (AIDS) cholangiopathy and graft-versus-host disease (GVHD).