Recipient HLA-DR3, tumour necrosis factor-α promoter allele-2 (tumour necrosis factor-2) and cytomegalovirus infection are inter-related risk factors for chronic rejection of liver grafts

Background/Aims: The tumour necrosis factor (TNF)-2 promoter allele, which elicits elevated expression of TNF-α, is in linkage disequilibrium with the extended haplotype HLA-A1-B8-DR3-DQ2. TNF-2 and HLA-DR3 have been implicated in renal and cardiac graft rejection and loss. Cytomegalovirus (CMV) infection has been associated with chronic allograft rejection. We examined the relationship between HLA-DR3, promoter allele TNF-2 and cytomegalovirus in relation to chronic rejection following liver transplantation. Methods: (i) Retrospective analysis of HLA-DR3 was performed in 307 liver transplant recipients and 283 donors. (ii) Prospective analysis of TNF-α promoter allele status, HLA-DR3 status and cytomegalovirus infection was assessed in 123 recipients. Results: (i) Retrospective analysis. Recipient HLA-DR3 (relative risk 1.9; 95% C.I. 1.01–3.58) was a risk factor for chronic rejection. (ii) Prospective analysis. Recipient HLA-DR3 was a risk factor for chronic rejection (relative risk 3.41; 95% C.I. 1.66–7.03) which was elevated further by superimposed CMV infection (relative risk 5.01; 95% C.I. 2–12.55). Recipient TNF-2 was associated with chronic rejection (relative risk 2.29; 95% C.I. 0.9–5.83) through linkage to HLA-DR3. Conclusions: Recipient HLA-DR3, TNF-2 status and CMV infection were inter-related risk factors for chronic rejection of liver grafts.