Biliary strictures after liver transplantation: role of interleukin 28B genotypes in cyclosporine treated

Int J Surg. 2014 Oct;12(10):1082-7. doi: 10.1016/j.ijsu.2014.09.004. Epub 2014 Sep 16.

Abstract

Introduction: The role of Interleukin 28B (IL-28B) genetic polymorphisms in influencing the occurrence of biliary complications after liver transplantation has never been evaluated. This study aimed to investigate whether IL-28B rs12979860C/T polymorphisms associate with the occurrence of biliary complications after liver transplantation and if these complications may influence survival.

Methods: One hundred seventy one recipients (133 males) who underwent liver transplantation were recruited. To confirm the mechanical etiology of cholestasis, endoscopic cholangio pancreatography, percutaneous and/or trans-Kehr cholangiography or cholangio magnetic resonance were performed. Two main clinical pictures were identified: biliary strictures and biliary leakage. Immunosuppressive therapy was based on cyclosporine (N = 54) or tacrolimus (N = 117), in association with steroids during the first month after operation. IL-28B rs12979860C/T genotypes were detected by means of polymerase chain reaction.

Results: Forty patients (23.4%) presented anastomotic strictures, 7 (4.1%) non-anastomotic strictures, 10 (5.8%) leakage, 8 (4.7%) leakage plus anastomotic strictures. IL-28B rs12979860C/C genotype in association with cyclosporin was found to be an independent predictor of anastomotic strictures occurrence (p = 0.008). A significant difference in 5 years survival was observed between patients with viral etiology of liver disease experiencing either anastomotic or non-anastomotic strictures (16/23) and the remaining patients (104/112, p = 0.001).

Conclusions: In recipients carrying rs12979860 IL-28B C/C genotype the use of cyclosporine seems to contribute to enhance the probability of developing biliary complications which in hepatitis B and C positives appear to reduce patient survival. If confirmed in larger studies the use of cyclosporine in these patients could be revised.

Keywords: Biliary strictures; Calcineurin inhibitors; Interleukin 28B; Liver transplantation.

MeSH terms

  • Adult
  • Aged
  • Anastomotic Leak / etiology
  • Cholestasis / etiology*
  • Cyclosporine / adverse effects*
  • Female
  • Genetic Variation
  • Genotype*
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / surgery
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / surgery
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Interferons
  • Interleukins / genetics*
  • Liver Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Tacrolimus / adverse effects

Substances

  • interferon-lambda, human
  • Immunosuppressive Agents
  • Interleukins
  • Cyclosporine
  • Interferons
  • Tacrolimus