title: Hyperlipidemia after liver transplantation: natural history and treatment with the hydroxy-methylglutaryl-coenzyme A reductase inhibitor pravastatin.
abstract: 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.
authors.affiliation: Dumont-UCLA Transplant Center, UCLA School of Medicine, Los Angeles, California, USA.
authors.forename: D K
authors.initials: DK
authors.lastname: Imagawa
authors.forename: S
authors.initials: S
authors.lastname: Dawson
authors.forename: C D
authors.initials: CD
authors.lastname: Holt
authors.forename: P S
authors.initials: PS
authors.lastname: Kirk
authors.forename: F M
authors.initials: FM
authors.lastname: Kaldas
authors.forename: C R
authors.initials: CR
authors.lastname: Shackleton
authors.forename: P
authors.initials: P
authors.lastname: Seu
authors.forename: S M
authors.initials: SM
authors.lastname: Rudich
authors.forename: M M
authors.initials: MM
authors.lastname: Kinkhabwala
authors.forename: P
authors.initials: P
authors.lastname: Martin
authors.forename: L I
authors.initials: LI
authors.lastname: Goldstein
authors.forename: N G
authors.initials: NG
authors.lastname: Murray
authors.forename: P I
authors.initials: PI
authors.lastname: Terasaki
authors.forename: R W
authors.initials: RW
authors.lastname: Busuttil
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy* / Q000209:etiology*; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008055:Lipids / Q000097:blood; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000627:therapeutic use*; D011446:Prospective Studies
chemical_list: D000924:Anticholesteremic Agents; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007376:Interleukin-2; D008055:Lipids; D002784:Cholesterol; D017035:Pravastatin