Rejection episodes after liver transplantation during primary immunosuppression with FK506 or a cyclosporine-based regimen: a controlled, prospective, randomized trial.
As part of a European multicenter study to investigate the potency of FK506 in primary immunosuppression after liver transplantation, this comparison with our conventional cyclosporine-based quadruple regimen was carried out as a controlled, prospective, randomized trial. The 121 patients entering the study were randomly assigned to receive immunosuppressive regimens consisting either of FK506 and prednisolone (FK/n = 61) or of cyclosporine, prednisolone, azathioprine, and a 7-day course of rabbit antithymocyte globulin (CsA/n = 60). Rejection was suspected in the case of scant production of light bile or biochemical graft dysfunction, without evidence of vascular, biliary, or infectious complications. A liver biopsy for confirmation of the diagnosis was obtained each time. Initial therapy entailed a 3-d course of high-dose methyl-prednisolone. Steroid resistant rejections were treated with OKT3 monoclonal antibody or, in the group of primary CsA administration, conversion to FK506 as another treatment option. One-year patient (FK: 90.2%; CsA: 96.7%) and graft survival (FK: 88.5%; CsA: 91.7%) did not differ significantly. Overall, 41 patients (33.9%) experienced 50 acute, cellular rejection episodes (RE) [FK: 25 RE in 21 patients (34.4%); CsA: 25 RE in 20 patients (33.3%)]. The histological grading ranged from mild (FK: 14/25; CsA: 8/25) to moderate (FK: 9/25; CsA: 16/25) and severe (FK: 2/25; CsA: 1/25): not significantly different between the two groups. In the CsA-based group, three additional rejection episodes were classified as early chronic (n = 1) and chronic rejection (n = 2).(ABSTRACT TRUNCATED AT 250 WORDS)
Jonas
S
S
Klinik für Chirurgie, Klinikum Rudolf Virchow, Freie Universität Berlin, Germany.
Kling
N
N
Bechstein
W O
WO
Blumhardt
G
G
Lohmann
R
R
Lobeck
H
H
Neuhaus
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000009:adverse effects; D001379:Azathioprine / Q000008:administration & dosage / Q000009:adverse effects; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy*; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016030:Kidney Transplantation / Q000276:immunology*; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D011817:Rabbits; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011239:Prednisolone; D001379:Azathioprine; D016559:Tacrolimus