Primary biliary cirrhosis: new therapeutic directions.

The immunologic mechanisms responsible for the development of primary biliary cirrhosis (PBC) remain poorly defined, although recent investigations have provided new clues as to the role of cellular membrane proteins such as the mitochondrial autoantigens and intercellular adhesion molecules. Additionally, new therapeutic agents have become available that markedly enhance the prospect for medical management of both hepatic and extrahepatic manifestations of PBC. Definitive therapy with ursodeoxycholic acid and/or methotrexate, and symptomatic relief of pruritus with rifampicin or metronidazole may become standard in the years ahead. The results of their use to date in the treatment of PBC are detailed in this review. Successful therapy of hepatic osteodystrophy associated with PBC has yet to be achieved, although early data suggest a role for ursodeoxycholic acid, estrogen, calcium, and vitamin D in the management of this debilitating problem. Orthotopic liver transplantation continues to be successful for the management of advanced disease (greater than 70% 5-year survival) and will remain an essential therapeutic tool until definitive medical therapy for PBC becomes available.