chapter  Chapter 28
19 Pages

Primary Biliary Cirrhosis Bench to Bedside

WithShinji Shimoda, Akiyoshi Nishio, Hiromi Ishibashi, M. Eric Gershwin

Primary biliary cirrhosis (PBC) is an autoimmune liver disease that predominantly affects women and characterized by chronic progressive destruction of small intrahepatic bile ducts with portal inflammation and subsequent fibrosis. The serologic hallmark of PBC is the presence of antimitochondrial antibodies (AMA), which are found in 95% of patients with PBC. The AMA are directed against the 2-oxo-acid dehydrogenase complexes located on the inner membrane of mitochondria. Although the role of AMA in the pathogenesis of PBC is unknown, the presence of antibodies has allowed detailed immunological definition of the antigenic epitopes, the autoantibodies and the T-cell response. Theories have been proposed regarding the mechanism of immune-mediated bile duct damage in PBC, including the possible role of T-cell-mediated cytotoxicity and molecular mimicry. PBC is usually diagnosed based on the triad of elevated alkaline phosphatase, AMA, and characteristic histological changes on liver biopsy. Biochemical liver abnormalities tests are consistent with the presence of cholestasis and reveal an elevation of both serum alkaline phosphatase and γ-glutamyl transpeptidase, with or without elevation of aminotransferase levels. Ursodeoxycholic acid (UDCA), a dihydroxy bile acid, appears to be the only effective therapy in preventing or delaying the need for liver transplantation. However, a number of patients receiving UDCA still develop progressive disease and require transplantation; at present, liver transplantation is the only effective therapy for end-stage PBC.