Interactions between human microbiome,liver diseases,and immunosuppression after liver transplant |
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Authors: | Milena Peruhova Monika Peshevska-Sekulovska Tsvetelina Velikova |
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Affiliation: | Milena Peruhova, Monika Peshevska-Sekulovska, Department of Gastroenterology, University Hospital Lozenetz, Sofia 1407, BulgariaMilena Peruhova, Tsvetelina Velikova, Medical Faculty, Sofia University St. Kliment Ohridski, Sofia 1407, BulgariaTsvetelina Velikova, Department of Clinical Immunology, University Hospital Lozenetz, Sofia 1407, Bulgaria |
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Abstract: | In liver transplant patients, solid tumors and post-transplant lymphoproliferative disorders have emerged as significant long-term mortality causes. In addition, it is assumed that de novo malignancy after liver transplantation (LT) is the second-leading cause of death after cardiovascular complications. Well-established risk factors for post-transplant lymphoproliferative disorders and solid tumors are calcineurin inhibitors, tacrolimus, and cyclosporine, the cornerstones of all immunosuppressive therapies used after LT. The loss of immunocompetence facilitated by the host immune system due to prolonged immunosuppressive therapy leads to cancer development, including LT patients. Furthermore, various mechanisms such as bacterial dysbiosis, activation through microbe-associated molecular patterns, leaky gut, and bacterial metabolites can drive cancer-promoting liver inflammation, fibrosis, and genotoxicity. Therefore, changes in human microbiota composition may contribute further to de novo carcinogenesis associated with the severe immunosuppression after LT. |
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Keywords: | Liver transplantation De novo malignancy Immunosuppressive therapy Calcineurin inhibitors Tacrolimus Cyclosporine Microbiome Carcinogenesis Immune tolerance |
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