PRIMARY BILIARY CIRRHOSIS: Clinical and Associated Autoimmune Features and Natural History

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Primary biliary cirrhosis (PBC) is an autoimmune cholestatic liver disease in which the biliary epithelial cells lining the small intrahepatic bile ducts are the target for immune mediated damage. Although ranking far below hepatitis viruses and alcohol-related liver diseases, PBC is an important cause of chronic liver disease worldwide, and in the western world it represents one of the most common indications for liver transplantation. Furthermore, in affected patients, the symptoms typical of the condition often have a significant effect on quality of life and patients respond poorly to treatment. In addition, PBC provides an important model for the study of autoimmunity in humans. The identification of the major autoantigens, together with the availability of liver tissue from different stages of the disease process means that aspects of the immunopathogenesis of the condition can be accurately studied, with potentially important implications for our understanding of both PBC in particular and autoimmunity in general. Current concepts of disease pathogenesis and increasing knowledge of the clinical course of the disease have allowed us to propose a model for the natural history of PBC from initial breakdown of self tolerance to the complications of decompensated stage IV disease when patient prognosis is significantly affected unless transplantation is performed (Fig. 1). This article discusses the stages in the natural history of PBC with reference to this model.

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CAUSATION

The most widely accepted hypothesis is that PBC arises in a susceptible individual as a result of exposure to one or more environmental factors. Ninety percent of affected individuals are women,11, 41, 90 but the age and severity of disease at the time of diagnosis are similar in men and women.62 This apparent increase in PBC susceptibility in women mirrors a similar trend in other autoimmune diseases. Associated autoimmune diseases, especially sicca syndrome, are more common in women,62 but as

NATURAL HISTORY

Since the earliest definitive descriptions of PBC, our perception of the condition has changed from being a rare disease with a poor prognosis presenting with jaundice and symptoms of liver failure,89 to being a more common condition often presenting without symptoms following detection through screening with a significantly better prognosis.41, 66 To a considerable extent these changes result from earlier diagnosis leading to a change in our perception of the spectrum of disease. This spectrum

Fatigue

Profound fatigue, which can often adversely affect patient quality of life is an often underdiagnosed symptom of PBC. In an unpublished survey by the United Kingdom-PBC support group (personal communication, 1997) fatigue was voted the worst of all symptoms associated with the disease. Early case series reported fatigue as a symptom in only a small proportion of patients. A demographic study in Ontario, Canada, in which patients reported their own symptoms by questionnaire, reported fatigue to

COMPLICATIONS OF PRIMARY BILIARY CIRRHOSIS

The complications of PBC can be subdivided into metabolic sequelae and complications of cirrhosis.

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    Address reprint requests to Margaret F. Bassendine, FRCP, Centre for Liver Research, School of Clinical Medical Sciences, 4th Floor, William Leech Building, The Medical School, Framlington Place, Newcastle upon Tyne, NE2 4HH, United Kingdom, [email protected]

    *

    Centre for Liver Research, The Medical School, University of Newcastle upon Tyne, New Castle upon Tyne, United Kingdom

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