Liver injury from cyclosporine A (original) (raw)

Abstract

To assess the incidence of cyclosporine A-induced hepatotoxicity, we retrospectively analyzed liver biochemical test results in 59 patients with endogenous uveitis who received cyclosporine A. All patients had normal liver tests before treatment and had at least six determinations during a 6- to 36-month course of therapy with cyclosporine A at a dose of 2–10 mg/kg/day. Thirty-four (58%) patients developed at least one abnormality of liver tests, and 19 (32%) had a prolonged pattern of abnormalities. The usual abnormalities consisted of a mild, transient increase in alkaline phosphatase levels occasionally accompanied by slight elevations in serum bilirubin and aminotransferase activities. Peak alkaline phosphatase levels ranged from 125 to 243 units/liter and persisted for seven days to 48 months. Thus, biochemical evidence of mild cholestatic liver injury was common in patients receiving cyclosporine A. These abnormalities are usually self-limited and asymptomatic but may cause diagnostic difficulty if a preexisting liver disease is present.

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References

  1. Busuttil RW, Goldstein LI, Danovitch GM, Ament ME, Memsic LBF: Liver transplantation today. Ann Intern Med 104:377–389, 1986
    Google Scholar
  2. Scharschmidt BF: Human liver transplantation: Analysis of data on 540 patients from four centers. Hepatology 4:95S-101S, 1984
    Google Scholar
  3. Klintmalm GBG, Iwatsuki S, Starzl TE: Cyclosporin A hepatotoxicity in 66 renal allograft recipients. Transplantation 32:488–489, 1981
    Google Scholar
  4. Atkinson K, Biggs J, Dodds A, Concannon A: Cyclosporin-associated hepatotoxicity after allogeneic marrow transplantation in man: Differentiation from other causes of post transplant liver disease. Transplant Proc 15:s2761–2767, 1983
    Google Scholar
  5. McKenzie FN, Moses GC, Henderson AR: Routine “cardiac” and “hepatic” serum enzyme profiles in cardiac transplant patients treated with cyclosporine A: Operative and postoperative findings. Clin Chem 31:822–825, 1985
    Google Scholar
  6. Laupacis A, Keown PA, Ulan RA, Sinclair NR, Stiller CR: Hyperbilirubinemia and cyclosporin A levels. Lancet 2:1426–1427, 1981
    Google Scholar
  7. Schade RR, Guglielmi A, Van Thiel DH, Thompson ME, Warty V, Griffith B, Sanghvi A, Bahnson H, Hardesty R: Cholestasis in heart transplant recipients treated with cyclosporine. Transplant Proc 15:2757–2760, 1983
    Google Scholar
  8. Loertscher R, Wenk M, Harder F, Brunner F, Follath F, Thiel G: Hyperbilirubinemia and cyclosporin A levels in renal transplant patients. Lancet 2:635–636, 1981
    Google Scholar
  9. Lorber I, Van Buren CT, Flechner SM, Williams C, Kahan BD: Hepatobiliary and pancreatic complications of cyclosporine therapy in 466 renal transplant recipients. Transplantation 43:35–40, 1987
    Google Scholar
  10. Kahan BD, Flechner SM, Lorber MI, Golden D, Conley S, Van Buren CT: Complications of cyclosporine-prednisone immunosuppression in 402 renal allograft recipients exclusively followed at a single center from one to five years. Transplantation 43:197–204, 1987
    Google Scholar
  11. Ferguson RM, Rynasiewicz JJ, Sutherland DER, Simmons RL, Najarian JS: Cyclosporin A in renal transplantation: A prospective randomized trial. Surgery 92:175–182, 1982
    Google Scholar
  12. Palestine A, Nussenblatt R, Chan CC: Side effects of systemic cyclosporine in patients not undergoing transplantation. Am J Med 77:652–656, 1984
    Google Scholar
  13. Stone BG, Udani M, Sanghvi A, Warty V, Plocki K, Dedetti CD, Van Thiel DH: Cyclosporin A-induced cholestasis. The mechanism in a rat model. Gastroenterology 93:344–351, 1987
    Google Scholar
  14. Rotolo FS, Branum GD, Bowers BA, Meyers WC: Effect of cyclosporine on bile secretion in rats. Am J Surg 151:35–40, 1986
    Google Scholar
  15. Nicchitta CV, Kamoun M, Williamson JR: Cyclosporin augments receptor-mediated cellular Ca fluxes in isolated hepatocytes. J Biol Chem 260:13613–13618, 1985
    Google Scholar
  16. Stacey NH, Kotecka B: Inhibition of taurocholate and ouabain transport in isolated rat hepatocytes by cyclosporin A. Gastroenterology 95:780–786, 1988
    Google Scholar

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Authors and Affiliations

  1. Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, USA
    Chris Kassianides MD, Robert Nussenblatt MD, Alan G. Palestine MD, Susan D. Mellow RN & Jay H. Hoofnagle MD
  2. Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland
    Chris Kassianides MD, Robert Nussenblatt MD, Alan G. Palestine MD, Susan D. Mellow RN & Jay H. Hoofnagle MD

Authors

  1. Chris Kassianides MD
  2. Robert Nussenblatt MD
  3. Alan G. Palestine MD
  4. Susan D. Mellow RN
  5. Jay H. Hoofnagle MD

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Kassianides, C., Nussenblatt, R., Palestine, A.G. et al. Liver injury from cyclosporine A.Digest Dis Sci 35, 693–697 (1990). https://doi.org/10.1007/BF01540169

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