Primary biliary cirrhosis and other ductopenic diseases.

Several distinct conditions are characterized by a reduction in the number of small and medium-sized intrahepatic bile ducts. These diseases are associated with progressive cholestasis, which in turn leads to biliary fibrosis and ultimately cirrhosis. The best-characterized ductopenic condition in adulthood is primary biliary cirrhosis (PBC) for which there is now strong evidence of an autoimmune cause. The antigenic targets are epitopes on proteins of the 2-oxoacid dehydrogenase complex within mitochondria. Some of these proteins appear to be aberrantly expressed at the surface of cholangiocytes in PBC. The basis for the breakdown in tolerance remains uncertain, although there is recent evidence to indicate that apoptosis may play a key role at early stages in the pathogenesis of the disease. Related conditions include autoimmune overlap syndromes and AMA-negative PBC (autoimmune cholangitis). Primary sclerosing cholangitis is clinically and histologically distinct, although there is evidence that it also may have an immune-mediated cause. Ductopenia may also arise on the basis of drug-induced injury; the best example of this is progressive cholestasis complicating chlorpromazine therapy.