Hyperlipidemia after liver transplantation: Natural history and treatment with the hydroxy-methylglutaryl-coenzyme A reductase inhibitor pravastatin

This study was designed to determine the frequency of hyperlipidemia after orthotopic liver transplantation and whether treatment with a hydroxy- methylglutaryl coenzyme A reductase inhibitor was safe and efficacious. Cholesterol levels were assessed in 45 consecutive adult liver transplants (mean ± SE). Four of 22 patients on cyclosporine (CsA) (18%) and three of 23 patients on FK506 (13%) had levels >225 mg/dl at 12 months (cholesterol levels for patients on CsA [total n=22]: pre-Tx = 140±11, 1 month = 183±36, 3 months = 221±12, 6 months = 211±11, 12 months = 202±14 [P<0.01 vs. pre- Tx]; FK506 [total n=23]: Pre-Tx = 151±13, 1 month = 187±22, 3 months = 188±10, 6 months = 184±13, 12 months = 164±9 [P=0.02 vs. CsA]). A separate cohort of patients with stable graft function, cholesterol >225 mg/dl, and two additional risk factors for coronary artery disease were started on pravastatin. Ninety-eight patients were enrolled. Sixteen patients (16%) discontinued the drug because of subjective complaints. No episodes of rhabdomyolysis or hepatotoxicity occurred (cholesterol levels for patients on CsA [total n=65]: pretreatment = 251±7, 6 months = 220±7 [P=0.01 vs. pretreatment], 12 months = 224±8 [P=0.01 vs. pretreatment]; FK506 [total n=17]: pretreatment = 251±17, 6 months = 219±17, 12 months = 208±17 [P=0.08 vs. pretreatment]). Natural killer cells isolated from normal volunteers (n=14) exhibited 27±9% specific lysis. Patients on FK506 or cyclosporine.based immunosuppression alone (n=11) exhibited 20±4% specific lysis. Standard immunosuppression plus pravastatin (n=10) decreased lysis to 0.2±10% (P<0.02 vs. controls and standard immunosuppression). We conclude: (1) posttransplant hyperlipidemia occurs less frequently in liver transplant patients than in renal or cardiac transplants; (2) pravastatin is safe and efficacious for cholesterol reduction in liver transplant patients; and (3) pravastatin coadministered with standard immunosuppression reduces natural killer cell-specific lysis in these recipients.