Primary biliary cirrhosis: lessons learned from an organ-specific disease

Clin Exp Med. 2001 Dec;1(4):165-78. doi: 10.1007/s102380100000.

Abstract

Primary biliary cirrhosis is an autoimmune liver disease that predominantly affects women and is characterized by chronic progressive destruction of small intrahepatic bile ducts with portal inflammation and subsequent fibrosis. The serological hallmark is the presence of antimitochondrial antibodies, which are found in 95% of patients. These antibodies are directed against the 2-oxo-acid dehydrogenase complexes located on the inner membrane of mitochondria. Although the role of antimitochondrial antibodies in the pathogenesis 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 primary biliary cirrhosis, including the possible role of T-cell-mediated cytotoxicity and molecular mimicry. Primary biliary cirrhosis is usually diagnosed based on the triad of elevated alkaline phosphatase, antimitochondrial antibodies, and characteristic histological changes on liver biopsy. Biochemical liver abnormalities are consistent with the presence of cholestasis and include an elevation of both serum alkaline phosphatase and gamma-glutamyl transpeptidase, with or without elevation of aminotransferase levels. Ursodeoxycholic acid, 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 ursodeoxycholic acid still develop progressive disease and require transplantation; at present, liver transplantation is the only effective therapy for end-stage primary biliary cirrhosis.

Publication types

  • Review

MeSH terms

  • 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
  • Amino Acid Sequence
  • Autoantibodies / metabolism
  • Autoantigens / genetics
  • Autoantigens / metabolism
  • Bile Ducts, Intrahepatic / immunology
  • Female
  • Humans
  • Ketone Oxidoreductases / immunology
  • Liver Cirrhosis, Biliary / etiology*
  • Liver Cirrhosis, Biliary / immunology
  • Liver Cirrhosis, Biliary / pathology
  • Liver Cirrhosis, Biliary / therapy
  • Liver Transplantation
  • Male
  • Mitochondria / immunology
  • Models, Biological
  • Molecular Mimicry
  • Molecular Sequence Data
  • Multienzyme Complexes / immunology
  • T-Lymphocytes / immunology

Substances

  • Autoantibodies
  • Autoantigens
  • Multienzyme Complexes
  • Ketone Oxidoreductases
  • 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)