Disease Management

Clinical Immunotherapeutics

, Volume 5, Issue 6, pp 420-437

Primary Biliary Cirrhosis

Immunopathogenesis and Optimum Management
  • Leslie LillyAffiliated withHarvard Medical School and Harvard Digestive Diseases Center, Gastroenterology Division
  • , Carl L. BergAffiliated withHarvard Medical School and Harvard Digestive Diseases Center, Gastroenterology Division
  • , John L. GollanAffiliated withHarvard Medical School and Harvard Digestive Diseases Center, Gastroenterology Division

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Summary

Primary biliary cirrhosis is a well-characterised disorder of autoimmune origin whose exact pathogenesis remains poorly understood. Population studies have suggested an association with human leucocyte antigen (HLA)-DR8, and patients are universally positive for antimitochondrial antibodies; however, the clinical relevance of these observations is unclear. Other putative autoantigens have been proposed. Numerous abnormalities throughout the immune system as well as in complement pathways have been characterised, and major histocompatibility complex (MHC) expression on biliary epithelial cells is increased.

Consequently, drugs whose actions are primarily immunomodulatory have undergone testing in the therapy of primary biliary cirrhosis, but none have demonstrated particular promise. Ursodeoxycholic acid remains the therapy of choice, and it is believed to exert its beneficial effects by modifying bile salt pool content and kinetics, as well as possibly through immunological mechanisms. Improvement in biochemical and clinical parameters with ursodeoxycholic acid therapy is well recognised, and it also appears to improve hepatic histology and retard progression to transplantation or death. Antifibrotic therapy with colchicine has shown some promise in small studies; however, the results of larger clinical trials designed to examine its role in conjunction with ursodeoxycholic acid are not yet available.

Liver transplantation is the established treatment for end-stage primary biliary cirrhosis, and recurrent disease in the allograft has not been satisfactorily documented.