CC chemokine receptor 5Δ32 polymorphism-a risk factor for ischemic-type biliary lesions following orthotopic liver transplantation

Abstract

Ischemic-type biliary lesions are a major complication following orthotopic liver transplantation. They occur in up to 26% of liver transplant recipients. Among other factors, unknown immunologic factors have always been assumed to be partly responsible for these lesions. CC-chemokines and their receptors play a key role in postoperative immunomodulation after liver transplantation. The non-function CC-chemokine receptor 5Δ32 polymorphism (CCR5Δ32) has been shown to lead to a lower rate of acute rejection after kidney transplantation; in liver transplantation the role of CCR5Δ32 is unclear. We investigated the influence of the CCR5Δ32 after liver transplantation with special regard to ischemic-type biliary lesions. The CC-chemokine receptor-5 (CCR5) of 146 recipients was analyzed by polymerase chain reaction to detect CCR5Δ32 in blood samples of patients after liver transplantation. One hundred twenty patients with wild-type CCR5 and 26 patients with CCR5Δ32 (1 homozygote, 25 heterozygote) were identified. Ischemic-type biliary lesions occurred in 14 of 120 patients with wild-type CCR5 and in 8 of 26 patients with CCR5Δ32 polymorphism (P = = 0.01). 5 year patient survival with CCR5Δ32 and CCR5 was 70% and 85%, respectively (P = .0067). Our results show that the CCR5Δ32 is a significant risk factor for the development of ischemic-type biliary lesions after liver transplantation and leads to a reduction in 5-year survival. In conclusion, the CCR5 status should be screened prospectively before liver transplantation. (Liver Transpl 2004;10:434–439.)