title: Biliary strictures after liver transplantation: role of interleukin 28B genotypes in cyclosporine treated.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Medical Sciences, Experimental and Clinical, Medical Liver Transplantation Section, Internal Medicine, University of Udine, Udine, Italy. Electronic address: pierluigi.toniutto@uniud.it.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Toniutto
authors.affiliation: Department of Medical Sciences, Experimental and Clinical, Medical Liver Transplantation Section, Internal Medicine, University of Udine, Udine, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Bitetto
authors.affiliation: Department of Medical Sciences, Experimental and Clinical, Medical Liver Transplantation Section, Internal Medicine, University of Udine, Udine, Italy.
authors.forename: Edmondo
authors.initials: E
authors.lastname: Falleti
authors.affiliation: Department of Surgery, Gastroenterology Unit, Azienda Ospedaliero-Universitaria, Udine, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Vadalà
authors.affiliation: Department of Medical Sciences, Experimental and Clinical, Medical Liver Transplantation Section, Internal Medicine, University of Udine, Udine, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Cmet
authors.affiliation: Department of Medical Sciences, Experimental and Clinical, Medical Liver Transplantation Section, Internal Medicine, University of Udine, Udine, Italy.
authors.forename: Annarosa
authors.initials: A
authors.lastname: Cussigh
authors.affiliation: Department of Surgery, Gastroenterology Unit, Azienda Ospedaliero-Universitaria, Udine, Italy.
authors.forename: Milutin
authors.initials: M
authors.lastname: Bulajic
authors.affiliation: Department of Surgery, Gastroenterology Unit, Azienda Ospedaliero-Universitaria, Udine, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zilli
authors.affiliation: Department of Medical Sciences, Experimental and Clinical, Medical Liver Transplantation Section, Internal Medicine, University of Udine, Udine, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Fabris
mesh_terms: D000328:Adult; D000368:Aged; D057868:Anastomotic Leak / Q000209:etiology; D002779:Cholestasis / Q000209:etiology*; D016572:Cyclosporine / Q000009:adverse effects*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D019694:Hepatitis B, Chronic / Q000150:complications / Q000601:surgery; D019698:Hepatitis C, Chronic / Q000150:complications / Q000601:surgery; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D016559:Tacrolimus / Q000009:adverse effects; D000095022:Interferon Lambda
chemical_list: D016572:Cyclosporine; D007166:Immunosuppressive Agents; D007372:Interferons; D007378:Interleukins; D016559:Tacrolimus; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: Biliary strictures; Calcineurin inhibitors; Interleukin 28B; Liver transplantation