title: Tacrolimus for primary treatment of steroid-resistant hepatic allograft rejection.
abstract: Twelve patients who experienced steroid-resistant rejection after primary liver transplantation while receiving cyclosporine-based therapy were converted to tacrolimus without receiving OKT3 or additional steroids. The indications for conversion were ongoing biopsy-confirmed rejection. All patients had received one course of high-dose intravenous steroids, which failed to reverse the rejection episode. No other antirejection therapy was given. Tacrolimus was initiated to reverse rejection and for maintenance therapy. The tacrolimus target level was 15-20 ng/ml (whole blood, IMX). All 12 patients had rapid reversal of the rejection episode and did not experience recurrent rejection (mean follow-up: 8.2 +/- 1.2 months). The mean bilirubin level dropped from 6.1 mg/dl at the initiation of tacrolimus therapy to 4.4 mg/dl by day 7 of therapy, 2.5 mg/dl by day 14, and 1.5 mg/dl by day 21 (P < 0.003). Serum glutamic pyruvic transaminase demonstrated a similar response. The serum creatinine level was unchanged at 1.5 mg/dl. No major adverse reactions were noted in this group of patients. Patient and graft survival rates were 100%. Four of the eight patients with a follow-up of >4 months are no longer receiving steroid therapy. Tacrolimus is effective as the primary therapy for the treatment of steroid-resistant rejection and provides a rapid and sustained biochemical response. Patients with mild to moderate rejection may be safely converted from cyclosporine to tacrolimus without an additional steroid bolus or OKT3 therapy. Early "preemptive" conversion to tacrolimus prior to the use of additional steroids or OKT3 may decrease overall rejection therapy requirements. This approach has promise for improved graft survival and fewer infectious and immunologic complications.
authors.affiliation: Department of Surgery, University of Chicago, Illinois 60637, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Millis
authors.forename: E S
authors.initials: ES
authors.lastname: Woodle
authors.forename: J B
authors.initials: JB
authors.lastname: Piper
authors.forename: D S
authors.initials: DS
authors.lastname: Bruce
authors.forename: K A
authors.initials: KA
authors.lastname: Newell
authors.forename: D S
authors.initials: DS
authors.lastname: Seaman
authors.forename: A L
authors.initials: AL
authors.lastname: Baker
authors.forename: J
authors.initials: J
authors.lastname: Hart
authors.forename: K
authors.initials: K
authors.lastname: Dasgupta
authors.forename: J R
authors.initials: JR
authors.lastname: Thistlethwaite
mesh_terms: D000328:Adult; D016572:Cyclosporine / Q000627:therapeutic use; D004351:Drug Resistance; D006084:Graft Rejection / Q000188:drug therapy; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008099:Liver / Q000276:immunology / Q000473:pathology; D016031:Liver Transplantation / Q000276:immunology*; D008775:Methylprednisolone / Q000627:therapeutic use; D016853:Muromonab-CD3 / Q000627:therapeutic use; D012189:Retrospective Studies; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D016572:Cyclosporine; D016559:Tacrolimus; D008775:Methylprednisolone