Immunosuppression minimization vs. complete drug withdrawal in liver transplantation

Abstract

Despite the increase in long-term survival, liver transplant recipients still exhibit higher morbidity and mortality than the general population. This is in part attributed to the lifelong administration of immunosuppression and its associated side effects. Several studies reported in the last decades have evaluated the impact of immunosuppression minimization in liver transplant recipients, but results have been inconsistent due to the heterogeneity of study designs and insufficient sample sizes. On the other hand, complete immunosuppression withdrawal has proven to be feasible in approximately 20% of carefully selected liver transplant recipients, especially in older patients and those with longer duration after transplantation. The long-term risks and clinical benefits of this strategy, however, also need to be clarified. As a consequence, and despite the general perception that a large proportion of liver recipients are over-immunosuppressed, it is currently not possible to derive evidence-based guidelines on how to manage long-term immunosuppression to improve clinical outcomes. Large clinical trials of drug minimization and/or withdrawal focused on clinically-relevant long-term outcomes are required. Development of personalized medicine tools and a deeper understanding of the pathogenesis of idiopathic inflammatory graft lesions will be pre-requisites to achieve these goals.

Keywords: ATG; CNI; HCV; IS; Immunosuppression minimization; Immunosuppression withdrawal; Liver transplantation; MMF; RCT; RISET; US; United States; anti-thymocyte globulin; calcineurin inhibitor; hepatitis C virus; immunosuppression; mTOR; mammalian target of rapamycin; mofetil mycophenolate; randomized clinical trial; reprogramming the immune system for the establishment of tolerance.