CC chemokine receptor 5delta32 polymorphism-a risk factor for ischemic-type biliary lesions following orthotopic liver transplantation

Liver Transpl. 2004 Mar;10(3):434-9. doi: 10.1002/lt.20095.

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 5delta32 polymorphism (CCR5delta32) has been shown to lead to a lower rate of acute rejection after kidney transplantation; in liver transplantation the role of CCR5delta32 is unclear. We investigated the influence of the CCR5delta32 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 CCR5delta32 in blood samples of patients after liver transplantation. One hundred twenty patients with wild-type CCR5 and 26 patients with CCR5delta32 (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 CCR5delta32 polymorphism (P = = 0.01). 5 year patient survival with CCR5delta32 and CCR5 was 70% and 85%, respectively (P =.0067). Our results show that the CCR5delta32 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.

MeSH terms

  • Adult
  • Bile Ducts, Intrahepatic / blood supply*
  • Bile Ducts, Intrahepatic / immunology
  • Biliary Tract Diseases / genetics*
  • Biliary Tract Diseases / immunology
  • Humans
  • Ischemia / genetics
  • Ischemia / immunology*
  • Liver Transplantation / adverse effects*
  • Liver Transplantation / immunology
  • Middle Aged
  • Polymorphism, Genetic
  • Receptors, CCR5 / blood
  • Receptors, CCR5 / genetics*
  • Receptors, CCR5 / immunology
  • Retrospective Studies
  • Risk Factors
  • Treatment Outcome

Substances

  • Receptors, CCR5