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

David K. Imagawa, Sherfield Dawson, Curtis D. Holt, Pamela S. Kirk, Fady M. Kaldas, Christopher R. Shackleton, Philip Seu, Steve M. Rudich, Milan Kinkhabwala, Paul Martin, Leonard I. Goldstein, Natalie G B Murray, Paul I. Terasaki, Ronald W. Busuttil

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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.

Original languageEnglish (US)
Pages (from-to)934-942
Number of pages9
JournalTransplantation
Volume62
Issue number7
DOIs
StatePublished - Oct 15 1996
Externally publishedYes

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Pravastatin
Coenzyme A
Hyperlipidemias
Natural History
Liver Transplantation
Oxidoreductases
Immunosuppression
Tacrolimus
Cholesterol
Transplants
Therapeutics
Natural Killer Cells
Cyclosporine
Liver
Rhabdomyolysis
Coronary Artery Disease
Healthy Volunteers
Kidney

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Hyperlipidemia after liver transplantation : Natural history and treatment with the hydroxy-methylglutaryl-coenzyme A reductase inhibitor pravastatin. / Imagawa, David K.; Dawson, Sherfield; Holt, Curtis D.; Kirk, Pamela S.; Kaldas, Fady M.; Shackleton, Christopher R.; Seu, Philip; Rudich, Steve M.; Kinkhabwala, Milan; Martin, Paul; Goldstein, Leonard I.; Murray, Natalie G B; Terasaki, Paul I.; Busuttil, Ronald W.

In: Transplantation, Vol. 62, No. 7, 15.10.1996, p. 934-942.

Research output: Contribution to journalArticle

Imagawa, DK, Dawson, S, Holt, CD, Kirk, PS, Kaldas, FM, Shackleton, CR, Seu, P, Rudich, SM, Kinkhabwala, M, Martin, P, Goldstein, LI, Murray, NGB, Terasaki, PI & Busuttil, RW 1996, 'Hyperlipidemia after liver transplantation: Natural history and treatment with the hydroxy-methylglutaryl-coenzyme A reductase inhibitor pravastatin', Transplantation, vol. 62, no. 7, pp. 934-942. https://doi.org/10.1097/00007890-199610150-00011
Imagawa, David K. ; Dawson, Sherfield ; Holt, Curtis D. ; Kirk, Pamela S. ; Kaldas, Fady M. ; Shackleton, Christopher R. ; Seu, Philip ; Rudich, Steve M. ; Kinkhabwala, Milan ; Martin, Paul ; Goldstein, Leonard I. ; Murray, Natalie G B ; Terasaki, Paul I. ; Busuttil, Ronald W. / Hyperlipidemia after liver transplantation : Natural history and treatment with the hydroxy-methylglutaryl-coenzyme A reductase inhibitor pravastatin. In: Transplantation. 1996 ; Vol. 62, No. 7. pp. 934-942.
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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.",
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T1 - Hyperlipidemia after liver transplantation

T2 - Natural history and treatment with the hydroxy-methylglutaryl-coenzyme A reductase inhibitor pravastatin

AU - Imagawa, David K.

AU - Dawson, Sherfield

AU - Holt, Curtis D.

AU - Kirk, Pamela S.

AU - Kaldas, Fady M.

AU - Shackleton, Christopher R.

AU - Seu, Philip

AU - Rudich, Steve M.

AU - Kinkhabwala, Milan

AU - Martin, Paul

AU - Goldstein, Leonard I.

AU - Murray, Natalie G B

AU - Terasaki, Paul I.

AU - Busuttil, Ronald W.

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N2 - 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.

AB - 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.

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