title: Genetic, immunological and clinical risk factors for biliary strictures following liver transplantation.
abstract: BACKGROUND
  Biliary strictures after liver transplantation (LT) are a major cause of morbidity and reduced graft survival.
  
  
  OBJECTIVE
  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 (CX3CR1)-249II 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 CX3CR1-249II 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology, University Hospital Essen, Essen, Germany.
authors.forename: Speranta
authors.initials: S
authors.lastname: Iacob
authors.forename: Vito R
authors.initials: VR
authors.lastname: Cicinnati
authors.forename: Alexander
authors.initials: A
authors.lastname: Dechêne
authors.forename: Monika
authors.initials: M
authors.lastname: Lindemann
authors.forename: Falko M
authors.initials: FM
authors.lastname: Heinemann
authors.forename: Vera
authors.initials: V
authors.lastname: Rebmann
authors.forename: Stanislav
authors.initials: S
authors.lastname: Ferencik
authors.forename: Georgios C
authors.initials: GC
authors.lastname: Sotiropoulos
authors.forename: Irinel
authors.initials: I
authors.lastname: Popescu
authors.forename: Peter A
authors.initials: PA
authors.lastname: Horn
authors.forename: Guido
authors.initials: G
authors.lastname: Gerken
authors.forename: Andreas
authors.initials: A
authors.lastname: Paul
authors.forename: Susanne
authors.initials: S
authors.lastname: Beckebaum
mesh_terms: D000328:Adult; D000368:Aged; D000714:Anastomosis, Surgical / Q000009:adverse effects / Q000706:statistics & numerical data; D000073883:CX3C Chemokine Receptor 1; D002779:Cholestasis / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D003430:Cross-Sectional Studies; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D007511:Ischemia / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D016031:Liver Transplantation / Q000009:adverse effects* / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D011183:Postoperative Complications / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D011237:Predictive Value of Tests; D054390:Receptors, CCR2 / Q000235:genetics / Q000276:immunology; D019713:Receptors, CCR5 / Q000235:genetics* / Q000276:immunology; D019707:Receptors, Chemokine / Q000235:genetics* / Q000276:immunology; D012307:Risk Factors
chemical_list: C515334:CCR2 protein, human; C584933:CCR5 protein, human; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D058851:GPI-Linked Proteins; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D036341:Intercellular Signaling Peptides and Proteins; C099187:MHC class I-related chain A; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; C423230:ULBP2 protein, human