Genetic, immunological and clinical risk factors for biliary strictures following liver transplantation.

Background Biliary strictures after liver transplantation ( LT) are a major cause of morbidity and reduced graft survival. Aims The purpose of this study was to investigate genetic, immunological and clinical risk factors for the occurrence of post- LT ischaemic type biliary lesions ( ITBLs) and biliary anastomotic strictures ( AS). Methods Clinical and laboratory data, chemokine receptor ( CCR) genotypes, chemotactic cytokines and anti-major-histocompatibility complex antibodies in serum were investigated in 162 LT patients. Results In the univariate analysis, older donor and recipient age, partial LT, high peak aspartate aminotransaminase ( AST) levels and CC chemokine receptor 5 delta32 loss-of-function mutation ( CCR5Δ32) were associated with ITBL, whereas LT for acute liver failure ( ALF), ABO-compatible non-identical LT, presence of donor-specific anti-human leucocyte antigen ( HLA) class II antibodies and fractalkine receptor ( CX3 CR1)-249 II allele were associated with AS. In the multivariate analysis, CCR5Δ32 was an independent risk factor for ITBL, whereas LT for ALF, ABO-compatible non-identical LT, and CX3 CR1-249 II allele remained predictive for AS. Serum levels of interferon-gamma and interleukin ( IL)-6 as well as IL-10 were significantly increased in patients with biliary strictures. Conclusion Specific chemokine receptor polymorphisms of the recipient are associated with development of post- LT biliary strictures. Altered cytokine profile may contribute to enhanced fibrotic tissue remodelling and biliary stricture formation. Screening of anti- HLA antibodies might be useful for early identification of at-risk patients who could benefit from closer surveillance and tailored immunosuppressive regimen. Our findings may have relevance for prediction and management of post- LT biliary strictures. [ABSTRACT FROM AUTHOR]