Review article: use of induction therapy in liver transplantation

Induction therapy is used relatively infrequently in liver transplantation, but developments in induction regimens and strategies for their use are prompting a re-examination of its benefits. Rabbit antithymocyte globulin (rATG) induces protracted, dose-dependent lymphocytopenia with preferential reconstitution of regulatory T-lymphocytes. Non-depleting interleukin-2 receptor antagonists (IL-2RA) act selectively on activated T-lymphocytes with a shorter duration of effect. IL-2RA induction with delayed and reduced calcineurin inhibitor (CNI) exposure appears to preserve efficacy, while more aggressive CNI minimisation has been attempted successfully using rATG. Steroid-free tacrolimus monotherapy with rATG or IL-2RA induction is effective if adequate tacrolimus exposure is maintained. Early concerns that addition of induction to a conventional maintenance regimen could lead to accelerated progression of hepatitis C disease, or to an increased risk of hepatocellular cancer recurrence, now appear unfounded using modern regimens. Similarly, with routine use of systemic prophylaxis, recent prospective and retrospective data have not shown a higher rate of infections overall, or cytomegalovirus infection specifically, using rATG or IL-2RA induction. Historical evidence that lymphocyte-depleting agents increased the risk of non-Hodgkin lymphoma has not been confirmed for rATG. Wider use of induction in liver transplantation is now merited, using individualized strategies to support reduced CNI exposure or steroid-free immunosuppression.