Recipient Interleukin-28B Rs12979860 C/T Polymorphism and Acute Cellular Rejection After Liver Transplantation: Role of the Calcineurin Inhibitor Used

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.