Current problems in primary biliary cirrhosis

Despite the many advances made in the field of PBC, the central questions of this enigmatic disease remain unanswered. The pathogenesis is uncertain and there is no effective therapy. Of the various aetiologies proposed for the disease none has really withstood the test of time: if the disease were truly auto-immune, it might be anticipated that there would be a clear-cut response to cortico-steroid therapy: although such treatment has a slight effect on improving liver chemistry, compared with other auto-immune diseases such as auto-immune chronic active hepatitis. Steroids are relatively ineffective. An infectious aetiology has been suggested but no organism has been reliably isolated or implicated in the disease. Attempts at treatment have been largely hindered by the long natural history and the uncertainty as to choosing appropriate endpoints for studies. Perhaps the most intriguing observation has been the association with the anti-mitochondrial antibodies. While the antigens have been identified, these are ubiquitous enzymes locate within the mitochondrion. How antibodies to such antigens are involved in the pathogenesis remains uncertain although our recent demonstrations that some antigens may be present on the surface of biliary epithelial cells may answer the question. However, further work may be required to confirm these findings and then to determine the reasons why there is such abnormal antigen expression in the disease.