Primary biliary liver cirrhosis and overlap syndrome. Diagnosis and therapy

Abstract

Primary biliary cirrhosis represents a chronic cholestatic liver disease of unknown etiology. It primarily affects females, is associated with extrahepatic immune-mediated syndromes, shows an immunogenetic association with HLA DR8, and displays serum autoantibodies, which makes an autoimmune etiology likely. The diagnosis is reached in patients with elevated alkaline phosphatase, gamma glutamyl transferase and bilirubin levels who exhibit normal bile ducts upon ultrasound examination, and in whom specific antimitochondrial autoantibodies are detectable. Half of all PBC patients additionally show specific antinuclear autoantibodies. Immunosuppressive therapy is ineffective; steroids, transplant immunosuppressants, colchicine, d-penicillamine and methotrexate are of limited clinical benefit. Ursodeoxycholic acid has few side effects and leads to a biochemical response and a delay of disease progression in most cases. When ursodeoxycholic acid therapy is ineffective an overlap syndrome with autoimmune hepatitis can be present, which can respond to steroid treatment. The only curative option is liver transplantation which should be considered when bilirubin levels exceed 100 microM/l.