Large, single center investigation of the immunogenetic factors affecting liver transplantation

Background. Reports on the relevance of immunogenetic factors in liver tran splantation are often conflicting or inconclusive, We have, therefore, inve stigated a range of factors that may underlie liver graft survival. Methods. The influences of HLA, flow cytometric, and enhanced cytotoxic cro ssmatching and immunoglobulin (Ig)A levels on graft survival, and acute and chronic rejection were investigated for a single center involving 446 pati ents over 13 years. Results. The effect of HLA mismatching on graft survival was significant (P <10(-2)) and was reversed in recipients with autoimmune diseases (P<0.5x10( -2)), whereas the effect of HLA mismatches on the level of acute rejection was detrimental in all recipients. There was a significant effect of a posi tive cytotoxic crossmatch on 3-month (P<10(-5)) and 1-year (P<10(-4)) graft survival, and an additional effect of the flow cytometric crossmatch was s een for chronic rejection (P<10(-2)) and acute rejection (P<10(-2)). Recipi ents with HLA-A1,B8,DRB1*0301 had higher levels of acute rejection (P<0.5x1 0(-2)), and recipients who received an ABO compatible-nonidentical transpla nt have a significantly higher risk (P<10(-2)) of developing chronic reject ion. Finally, the beneficial effect of high serum IgA and, specifically, Ig A anti Fab, seen in renal transplants was not evident in liver transplants, and in fact the opposite may be true, at least for acute rejection (P<0.5x 10(-2)). Conclusions. By separating the recipients with autoimmune disease from othe r patients and by including acute and chronic rejection as outcome paramete rs, we have used the power of a large single-centre study to delineate the significance of some of the important immunogenetic factors involved in liv er transplantation.