title: Early steroid withdrawal after liver transplantation: the Canadian tacrolimus versus microemulsion cyclosporin A trial: 1-year follow-up.
abstract: Corticosteroid therapy contributes significant toxicity to liver transplantation. The safety and efficacy of early steroid withdrawal were determined in patients treated with either tacrolimus or microemulsion cyclosporin A (micro-CsA). The primary outcome was the proportion of patients who were steroid-free 1 year posttransplantation. From the seven Canadian adult liver transplant centers, 143 patients were randomly allocated oral treatment with either tacrolimus (n = 71) or micro-CsA (n = 72), together with corticosteroids and azathioprine. Eligibility criteria for steroid withdrawal included freedom from acute rejection for a minimum of 3 months, and prednisone </=0.15 mg/kg/d. In eligible patients, the daily steroid dose was reduced by 2.5 mg each month until complete discontinuation was achieved. At 1 year after transplantation, 75% of the tacrolimus patients and 63% of the micro-CsA patients were steroid-free (P =.20). Of all of the patients who became eligible for steroid withdrawal, steroid discontinuation was achieved in over 80%. One-year patient survival was 97% with tacrolimus and 89% with micro-CsA (P =.052). Graft survival was 97% and 86%, respectively (P =.017). The overall incidence of acute rejection during the first year was 35% with tacrolimus and 43% with micro-CsA (P =.26). There was no difference in survival, acute rejection, or rate of steroid withdrawal when adjusting for hepatitis C. All acute rejection episodes experienced during steroid withdrawal were steroid-responsive. Steroid-resistant rejection occurred in 5.6% of the tacrolimus and 9.7% of the micro-CsA patients. One patient, in the micro-CsA group, experienced refractory rejection. Chronic rejection was not observed in either group. The toxicity profiles were similar. Postoperative serum creatinine levels were similar, and dialysis was required in less than 10% of patients in each group. Infectious complications were similar in both groups. Neurotoxicity was a serious adverse event in 13% and 10% of patients receiving tacrolimus and micro-CsA, respectively. Early steroid withdrawal is safe and effective after liver transplantation using either tacrolimus plus azathioprine or micro-CsA plus azathioprine immunoprophylaxis.
authors.affiliation: University of Toronto, Canada. paul.greig@uhn.on.ca
authors.forename: Paul
authors.initials: P
authors.lastname: Greig
authors.forename: Leslie
authors.initials: L
authors.lastname: Lilly
authors.forename: Charles
authors.initials: C
authors.lastname: Scudamore
authors.forename: Siegfried
authors.initials: S
authors.lastname: Erb
authors.forename: Eric
authors.initials: E
authors.lastname: Yoshida
authors.forename: Norman
authors.initials: N
authors.lastname: Kneteman
authors.forename: Vince
authors.initials: V
authors.lastname: Bain
authors.forename: Cameron
authors.initials: C
authors.lastname: Ghent
authors.forename: Paul
authors.initials: P
authors.lastname: Marotta
authors.forename: David
authors.initials: D
authors.lastname: Grant
authors.forename: William
authors.initials: W
authors.lastname: Wall
authors.forename: Jean
authors.initials: J
authors.lastname: Tchervenkov
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Barkun
authors.forename: Andre
authors.initials: A
authors.lastname: Roy
authors.forename: Denis
authors.initials: D
authors.lastname: Marleau
authors.forename: Vivian
authors.initials: V
authors.lastname: McAlister
authors.forename: Kevork
authors.initials: K
authors.lastname: Peltekian
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002170:Canada; D002648:Child; D002908:Chronic Disease; D016572:Cyclosporine / Q000008:administration & dosage*; D004655:Emulsions; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy / Q000401:mortality; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage*
chemical_list: D000305:Adrenal Cortex Hormones; D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus