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

Liver Int. 2012 Sep;32(8):1253-61. doi: 10.1111/j.1478-3231.2012.02810.x. Epub 2012 May 2.


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 (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.

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.

MeSH terms

  • Adult
  • Aged
  • Anastomosis, Surgical / adverse effects
  • Anastomosis, Surgical / statistics & numerical data
  • CX3C Chemokine Receptor 1
  • Cholestasis / epidemiology*
  • Cholestasis / genetics
  • Cholestasis / immunology
  • Cross-Sectional Studies
  • Female
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / immunology
  • Graft Survival / genetics
  • Graft Survival / immunology
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / immunology
  • Ischemia / epidemiology*
  • Ischemia / genetics
  • Ischemia / immunology
  • Liver Transplantation / adverse effects*
  • Liver Transplantation / statistics & numerical data
  • Male
  • Middle Aged
  • Morbidity
  • Postoperative Complications / epidemiology*
  • Postoperative Complications / genetics
  • Postoperative Complications / immunology
  • Predictive Value of Tests
  • Receptors, CCR2 / genetics
  • Receptors, CCR2 / immunology
  • Receptors, CCR5 / genetics*
  • Receptors, CCR5 / immunology
  • Receptors, Chemokine / genetics*
  • Receptors, Chemokine / immunology
  • Risk Factors


  • CCR2 protein, human
  • CCR5 protein, human
  • CX3C Chemokine Receptor 1
  • CX3CR1 protein, human
  • GPI-Linked Proteins
  • HLA Antigens
  • Histocompatibility Antigens Class I
  • Intercellular Signaling Peptides and Proteins
  • MHC class I-related chain A
  • Receptors, CCR2
  • Receptors, CCR5
  • Receptors, Chemokine
  • ULBP2 protein, human