title: Recipient interleukin-28B Rs12979860 C/T polymorphism and acute cellular rejection after liver transplantation: role of the calcineurin inhibitor used.
abstract: BACKGROUND
  Interleukin-28 (IL-28B) rs12979860 C/T polymorphism is known to predict the outcome of antiviral therapy in hepatitis C. In addition to its interferon-like and antiviral functions, IL-28B possesses the ability to modulate CD8 T cells function. This study aimed to investigate whether recipient IL-28B polymorphism may have a role in predicting the occurrence of acute cellular rejection (ACR) after liver transplantation (LT).
  
  
  METHODS
  Two hundred fifty-one consecutive LT recipients were enrolled. All the patients underwent per protocol liver biopsies at 1, 3, and 12 months after LT. ACR episodes in the first post-LT year were recorded and graded according to the Banff score.
  
  
  RESULTS
  At least one moderate to severe (Banff score ≥ 5) ACR episode was reported in 75 patients (29.9%). ACR was associated with IL-28B polymorphism: C/C=21/102 (20.6%), C/T=43/126 (34.1%), and T/T=11/23 (47.8%) (P=0.003). At logistic regression analysis, IL-28B polymorphism was found to be a predictor of ACR (P=0.012) together with cytomegalovirus reactivation (P=0.023). The association between IL-28B polymorphism and ACR occurrence was evident in tacrolimus but not in cyclosporine-treated patients. ACR episodes occurred more frequently from hepatitis C virus (HCV) negatives carrying the IL-28B C/C genotype (17.8%) to HCV negatives carrying at least one T allele or HCV positives carrying at least one C allele (33.3%) to HCV positives carrying the T/T genotype (50.0%, P=0.002).
  
  
  CONCLUSIONS
  HCV etiology in association with the carriage of IL-28B T/T genotype predicted the highest frequency of ACR. Recipient's IL-28B genotyping could be a useful tool in individualizing immunosuppressive therapy according to the risk of ACR occurrence.
authors.affiliation: Department of Experimental and Clinical Medicine, Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Bitetto
authors.forename: Carlo
authors.initials: C
authors.lastname: Fabris
authors.forename: Edmondo
authors.initials: E
authors.lastname: Falleti
authors.forename: Ezio
authors.initials: E
authors.lastname: Fornasiere
authors.forename: Claudio
authors.initials: C
authors.lastname: Avellini
authors.forename: Sara
authors.initials: S
authors.lastname: Cmet
authors.forename: Annarosa
authors.initials: A
authors.lastname: Cussigh
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Fontanini
authors.forename: Mario
authors.initials: M
authors.lastname: Pirisi
authors.forename: Stefano Ginanni
authors.initials: SG
authors.lastname: Corradini
authors.forename: Manuela
authors.initials: M
authors.lastname: Merli
authors.forename: Antonio
authors.initials: A
authors.lastname: Molinaro
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Toniutto
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000209:etiology / Q000235:genetics*; D006526:Hepatitis C / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008103:Liver Cirrhosis / Q000209:etiology; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D000095022:Interferon Lambda
chemical_list: D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda