Immunosuppression minimization and withdrawal in liver transplantation: The "holy grail"?

Abstract

Liver transplantation typically necessitates the use of life long immunosuppressive drugs, to suppress the immune system and minimize the risk of rejection. Prolonged use of immunosuppressive drugs can, however, lead to various side effects, including an increased risk of infections, renal dysfunction, and several metabolic complications. To address this, transplant professionals work to tailor immunosuppression to the patient needs, with the ultimate goal of minimizing drug doses.The "holy grail" of immunosuppression following liver transplantation has been its complete withdrawal. Over the past decade, researchers have juggled with immunosuppression minimization in recipients of liver grafts, but the results were disparate due to the diversity in study designs and limited sample size. Nevertheless, immunosuppression withdrawal has been observed possible in approximately 20 % of strictly selected recipients, particularly in extremes of age and when performed over a prolonged period. The predominant stumbling-block was the occurrence of rejection during the process of immunosuppression withdrawal. Currently, there is a lack of scientific evidence for selecting patients in whom immunosuppressant minimization would be possible without risk of allograft rejection and on the precise methods of immunosuppression withdrawal.The development of clinical tools for personalized medication adjustments and a broader comprehension of the pathogenesis of late graft rejection are essential for this. This article centers on the physiological mechanisms of immune tolerance, strategies for minimizing and withdrawing immunosuppression after liver transplantation, and the biomarkers indicative of sustained tolerance in liver transplantation.