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PBC: an infectious disease?
  1. G H HAYDON,
  2. J NEUBERGER
  1. Liver Unit, Queen Elizabeth Hospital
  2. Birmingham B15 2TH, UK
  1. Professor J Neuberger. Email:James.Neuberger{at}university-b.wmids.nhs.uk

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Primary biliary cirrhosis (PBC) is characterised by progressive destruction of the middle sized intrahepatic ducts, leading to liver failure and, in the absence of transplantation, death. While ursodeoxycholic acid may slow progression, there is as yet no curative therapy. As the pathogenesis of PBC is unknown, it is difficult to develop a logical therapeutic strategy. PBC has been considered an autoimmune disease although immunosuppressive therapy is relatively ineffective; here we discuss the possibility that there may be an infectious aetiology.

Autoimmune features of PBC

There are clear autoimmune aspects to PBC: there is a strong association with extrahepatic autoimmune diseases such as thyroid disease. Overlap syndromes between PBC and autoimmune hepatitis have been well documented1 ,2 although the response to immunosuppression is at best poor. One of the characteristic features of PBC is the association with disease specific autoantibodies: these include not only the antimitochondrial antibodies (AMA) but also antibodies to components of the nuclear pore complex (such as gp210). The antigens recognised by AMA have been identified (PDC-E2; OGDC-E2; E3BP; PDC-E1α; BCOADC-E2) and are located on the inner aspect of the mitochondrial membrane.3-7

AMA AND PBC

AMA may precede the clinical, biochemical, and histological features of PBC, suggesting that these antibodies may have a pathological role. However, these antigens are neither organ nor disease specific. Why the biliary epithelial cells are the main targets of disease may be explained by the observation that in PBC, but not other liver diseases and normal liver, biliary epithelial cells have E2 present on their plasma membrane. Several groups have attempted to generate animal models of PBC by immunising animals with antigens recognised by AMA: injections of tissue or recombinant mitochondrial antigens were given to murine and other animal models, generating AMA but no bile duct lesions.8 More recently, Joneset al have suggested that PBC-like …

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