title: Review article: use of induction therapy in liver transplantation.
abstract: 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.
authors.affiliation: Nephrology, Dialysis and Organ Transplantation Service, CHU Rangueil, Toulouse, France. rostaing.l@chu-toulouse.fr
authors.forename: Lionel
authors.initials: L
authors.lastname: Rostaing
authors.forename: Faouzi
authors.initials: F
authors.lastname: Saliba
authors.forename: Yvon
authors.initials: Y
authors.lastname: Calmus
authors.forename: Sébastien
authors.initials: S
authors.lastname: Dharancy
authors.forename: Olivier
authors.initials: O
authors.lastname: Boillot
mesh_terms: D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000077552:Basiliximab; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016031:Liver Transplantation / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000074323:Alemtuzumab; D000077552:Basiliximab