Mechanisms and Strategies for Tolerance in Liver Transplantation

Although there has been improvement in immunosuppressive therapy in preventing acute rejection following liver transplantation, there is less progress in reducing morbidity and mortality related to immunosuppression. In particular, the use of the current maintenance agents is associated with high rates of chronic kidney disease and metabolic and neoplastic complications. The search for improved treatment algorithms includes trial and error dose minimization or even complete withdrawal; most of which have been attempted with variable success rates. These strategies would be potentially more successful if more were known about long-term immune adaptive mechanisms that occur in response to transplantation. In addition, biomarkers signifying immunoregulation or tolerance, which could more clearly define the capability of withdrawing therapy, are needed to apply a more specific approach to patient management. This review will provide an overview of the mechanisms of liver transplant tolerance and the current and future strategies for immunosuppression withdrawal.