Aetiopathogenesis of primary sclerosing cholangitis.

The aetiology and pathogenesis of PSC have not yet been clearly defined. The hypothesis that PSC is an immune mediated disease is supported by associations with HLA haplotypes, the presence of autoantibodies, increased levels of total serum immunoglobulins and the association with other autoimmune diseases. PSC does not, however, have many of the characteristics of classical autoimmunity, particularly the usual female preponderance of disease and lack of a good response to immunosuppression. Non-immune mechanisms such as bacterial infection, ischaemia and toxicity are also clearly important in the development of the disease and these factors may trigger peribiliary inflammation and cytokine-induced hepatic fibrosis. PSC may be triggered in genetically susceptible individuals by toxic or infectious agents gaining access to the liver via a diseased and permeable colon.