PRIMARY SCLEROSING CHOLANGITIS SHOULD NOT BE GROUPED WITH AUTOIMMUNE LIVER DISEASES

PRIMARY SCLEROSING CHOLANGITIS SHOULD NOT BE GROUPED WITH AUTOIMMUNE LIVER DISEASES.
Trevor J Doran, Andrew Geczy & Geoff McCaughan. Tissue Typing, ARCBS-NSW and Aust National Liver Transplant Unit, Sydney NSW, Australia

We challenge the generally held view that Primary Sclerosing Cholangitis (PSC) should be grouped with autoimmune Chronic Active Hepatitis (a-CAH) and Primary Biliary Cirrhosis (PBC) as the autoimmune group of primary diseases leading to liver transplantation.
The aetiology of PSC is unknown. Furthermore, there is considerable diversity within patients. For example some, but not all, have reduced clearance of circulating immune complexes, some have antibodies to perinuclear antigens (pANCA), some have associated ulcerative colitis (or other inflammatory bowel disease) and some have circulating antibodies to bile duct (and colon) epithelial cells.
Various reports on the significance of the HLA system claim that either HLA-B8, DRB1*0301 (DR3 or DR17) or DRB3*0101 (DRw52a) or combinations of these are increased in PSC. There are also reports that either DRB1*1501 or DRB1*1301 is increased while DRB1*0401 may be associated with rapid disease progression. Alternatively, there are reports that none of these antigens is associated with PSC.
We have used the incidence of the HLA type A1,B8,DRB1*0301 to compare PSC with a-CAH and PBC. In both a-CAH (n=26) and PBC (n=45) the frequency of this haplotype was raised (p<10-2) over the normal population. However, in our PSC recipients (n=36) the frequency of this haplotype is the same as that seen in recipients with non-autoimmune diseases and is less than the frequency in either a-CAH or PBC (p<10-2). Furthermore, the effect of HLA matching in a-CAH and PBC shows a reduced 1-year graft survival whereas HLA matching in PSC and non-autoimmune diseases shows enhanced graft survival (p<0.5x10-2). Therefore, while PSC does show autoimmune characteristics, we have shown that, based on clinical variability, the differing HLA profile and the effect of HLA matching, PSC (or perhaps a subgroup of PSC recipients) can clearly not be classified with a-CAH and PBC as the autoimmune liver diseases. This has important ramifications in terms of liver transplant outcome analyses.