Association Between Polymorphisms in Cytokine Gene and Viral Infections in Renal and Liver Transplant Recipients: A Systematic Review

Purpose: Although transplantations are associated with an increased risk of post-transplantation infections, they greatly improve life expectancy and patients' quality of life. Cytokine genes play an important role in the success of transplants due to their immunological functions. A systematic review was conducted to evaluate cytokine gene polymorphisms and risk of cytomegalovirus (CMV), hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in kidney and liver transplant recipients. Methods: A systematic search was conducted using PubMed, EMBASE, Medline and Google Scholar from their inception until January 28, 2019 using appropriate key words. Review articles, case reports or series, studies conducted on non-human subjects and published in languages other than English were excluded. Data were abstracted using a standardized form. The quality of the studies included was assessed using "Risk of Bias Assessment tool for Non-randomized Studies (RoBANS)". Results: Thirty-one studies met our inclusion criteria; populations studied were diverse with a sample ranging from 20 to 1,671. Nineteen studies evaluated Interleukin (IL)-28B polymorphism, while six studies evaluated interferon lambda (IFN-lambda) gene polymorphisms and their impact on CMV, HCV, and HBV progression. Polymorphisms in IL-10 gene were investigated in six studies. Polymorphisms in IL-12B and IL-1B gene were associated with a higher risk of developing CMV infections while polymorphisms in IL-28B were associated with a lower incidence of CMV infection in renal transplant recipients. Similarly, polymorphisms in IL-28B were associated with higher liver dysfunction from HBV infection in liver transplant recipients. Studies included had low risk of bias. Conclusions: Cytokine gene polymorphisms IL-12B and IL-1B were found to be associated with an increased risk of infection in kidney transplants and IL-28B in liver transplant recipients. However, the small number and heterogeneity of studies limits the generalization of our results. Further research may lead to finding these associations in larger studies which perhaps improve the use of genetic testing and targeted antiviral therapy. This will further reduce the risk of viral infections associated with cytokine gene polymorphisms in post renal and liver transplant recipients.