FK506 CONVERSION FOR INTRACTABLE REJECTION OF THE LIVER ALLOGRAFT

Twenty-seven liver transplant recipients with intractable, biopsy-prov en, acute or chronic rejection (defined as vanishing bile duct syndrom e) were converted from cyclosporin to FK506. Successful conversion was achieved in 9 of 15 patients with acute rejection and in 6 of 12 pati ents with vanishing bile duct syndrome. A normal bilirubin was achieve d more quickly in those with acute rejection (within 1 month) than in those with chronic rejection (within 3 months). A preconversion total bilirubin of less than 12 mg/dl was considered significant with regard to a successful outcome (P = 0.002). Graft survival was 66.7% and pat ient survival 73% in the case of acute rejection, and 50% and 66.7%, r espectively, in the case of chronic rejection. Nephrotoxicity, neuroto xicity, and gastrointestinal side effects were the most serious compli cations of FK506 conversion. Six of ten patients had a drop in GFR tha t was 50% or greater after a minimum of 1 month of FK506 exposure. The mean maintenance dose of FK506 to maintain FK506 serum levels of 0.5- 1.5 ng/ml was 0.07 mg/kg per 12 h for adults (half the recommended dos e), compared to 0.15 mg/kg per 12 h for pediatric patients. This study demonstrates that FK506 can be used successfully to convert patients with intractable acute and chronic rejection. Careful adjustments of F K506 dosages and levels are required to minimize side effects.