BACKGROUND: The success of orthotopic liver transplantation (OLT) has been limited by the adverse effects of immunosuppression. The purpose of this study was to determine the safety and feasibility of withdrawing immunosuppression in OLT recipients to achieve tolerance. METHODS: Eighteen adult OLT recipients in our steroid-free protocol without rejection were selected for this protocol. All patients chosen for this trial were on tacrolimus monotherapy with normal liver function tests (LFTs). Tacrolimus was weaned as long as LFTs remained stable. Weaning was halted for elevations of liver enzymes and tacrolimus was increased to the last dosage at which the patients had normal LFTs. Rejection was treated by increasing tacrolimus to levels of 10-15 ng/ml. Mycophenolate mofetil (MMF) or sirolimus was added if there was severe rejection by biopsy. Steroids were used if there was no improvement. RESULTS: One patient has been weaned off immunosuppression. Three additional patients were weaned completely off but had tacrolimus resumed because of mild elevations in LFTs. Eleven of 18 (61%) patients had rejection. Two patients required steroid therapy and one required rabbit antithymocyte globulin in addition to MMF and steroids. One of the patients with rejection developed diabetes and one patient had renal failure, which subsequently resolved. One patient died following a stroke. CONCLUSIONS: Clinical tolerance can be achieved in a minority of patients, even when being maintained on minimum immunosuppression. The potential benefit of achieving tolerance must be weighed against the risks of rejection therapy in patients doing well on low-dose immunosuppression.
BACKGROUND: The success of orthotopic liver transplantation (OLT) has been limited by the adverse effects of immunosuppression. The purpose of this study was to determine the safety and feasibility of withdrawing immunosuppression in OLT recipients to achieve tolerance. METHODS: Eighteen adult OLT recipients in our steroid-free protocol without rejection were selected for this protocol. All patients chosen for this trial were on tacrolimus monotherapy with normal liver function tests (LFTs). Tacrolimus was weaned as long as LFTs remained stable. Weaning was halted for elevations of liver enzymes and tacrolimus was increased to the last dosage at which the patients had normal LFTs. Rejection was treated by increasing tacrolimus to levels of 10-15 ng/ml. Mycophenolate mofetil (MMF) or sirolimus was added if there was severe rejection by biopsy. Steroids were used if there was no improvement. RESULTS: One patient has been weaned off immunosuppression. Three additional patients were weaned completely off but had tacrolimus resumed because of mild elevations in LFTs. Eleven of 18 (61%) patients had rejection. Two patients required steroid therapy and one required rabbit antithymocyte globulin in addition to MMF and steroids. One of the patients with rejection developed diabetes and one patient had renal failure, which subsequently resolved. One patient died following a stroke. CONCLUSIONS: Clinical tolerance can be achieved in a minority of patients, even when being maintained on minimum immunosuppression. The potential benefit of achieving tolerance must be weighed against the risks of rejection therapy in patients doing well on low-dose immunosuppression.
Authors: Marc Martínez-Llordella; Juan José Lozano; Isabel Puig-Pey; Giuseppe Orlando; Giuseppe Tisone; Jan Lerut; Carlos Benítez; Jose Antonio Pons; Pascual Parrilla; Pablo Ramírez; Miquel Bruguera; Antoni Rimola; Alberto Sánchez-Fueyo Journal: J Clin Invest Date: 2008-08 Impact factor: 14.808
Authors: Marcus N Scherer; Bernhard Banas; Kiriaki Mantouvalou; Andreas Schnitzbauer; Aiman Obed; Bernhard K Krämer; Hans J Schlitt Journal: Langenbecks Arch Surg Date: 2007-04-21 Impact factor: 3.445
Authors: D Vrochides; M Hassanain; P Metrakos; J Tchervenkov; J Barkun; P Chaudhury; M Cantarovich; S Paraskevas Journal: Hippokratia Date: 2012-01 Impact factor: 0.471