Viruses, protozoans, bacteria and drugs as aetiological factors in primary sclerosing cholangitis

摘要

Both the aetiology and pathogenesis of primary sclerosing cholangitis (PSC) remain unknown. It is clear that, since inflammation and cytokines are involved in the generation of both small duct and fibrous ablative cholangitis, all forms of sclerosing cholangitis are associated with an immunopathogenesis, Associations with HLA haplotypes, the presence of autoantibodies such as pANCA, smooth muscle antibodies and antineutrophil antibodies, and the strong association with inflammatory bowel disease, particularly ulcerative colitis, appear to be consistent with a possible autoimmune pathogenesis1'2, However, the hypothesis that adult PSC is an autoimmune disease1'3 remains controversial. It is clear that non-immune factors such as infection with agents such as Cryptosporidium, toxic agents, ischaemia and neoplasia can also result in stricturing and dilation of the biliary tree4. The bacterial hypothesis was refined by Vierling5, who has pointed out that biliary epithelia, gut flora and bile all play active roles in both the innate and adaptive immune responses5 which may be responsible for sclerosing cholangitis lesions6, The hypothesis suggests that bacterial constituents in portal blood are the dominant stimuli which initiate the immunopathogenic process of peribiliary inflammation and cytokine-induced circumferential fibrosis in either the presence or absence of inflammatory bowel disease involving the colon.