Summary
Phenytoin has been associated with acute hepatotoxicity. Chronic liver enzyme abnormalities associated with phenytoin have been attributed to enzyme induction. There have been no reports of phenytoin-induced chronic hepatitis. We describe an asymptomatic 52-year-old woman who received phenytoin sodium for 11 years and was found to have elevated serum aminotransferases. Assays for hepatitis A, B, and C were negative. Liver biopsy was performed and showed chronic persistent hepatitis. This documentation of phenytoin-induced chronic persistent hepatitis was proven by histology and its etiology confirmed by drug withdrawal and by rechallenge. Although uncommon, this entity is important to recognize in the differential diagnosis of asymptomatic chronic hepatic enzyme dysfunction.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aiges HW, Daum F, Olson M, Kahn E, Teichberg S: The effects of phenobarbital and diphenylhydantoin on liver function and morphology. J Pediatr 97:22–26, 1980
Andreasen PB, Lyngbye J, Trolle E: Abnormalities in liver function tests during long-term diphenylhydantoin therapy in epileptic outpatients. Acta Med Scand 194:261–264, 1973
Mullick FG, Ishak KG: Hepatic injury associated with diphenylhydantoin therapy: A clinicopathologic study of 20 cases. Am J Clin Pathol 74:442–452, 1980
Campbell CB, McGuffie C, Weedon AP, Powell LW: Cholastatic liver disease associated with diphenylhydantoin therapy: Possible pathogenic importance of altered bile salt metabolism. Dig Dis 22:255–262, 1977
Spechler SJ, Sperber H, Doos WG, Koff, RS: Cholestasis and toxic epidermal neurolysis associated with phenytoin sodium ingestion. The role of bile duct injury. Ann Intern Med 95:455–456, 1981
Taylor JW, Stein MN, Murphy MJ, Mitros FA: Cholestatic liver dysfunction after long-term phenytoin therapy. Arch Neurol 41:500, 1984
Dhar GJ, Pierach CA, Ahmed PN, Howard RB: Diphenylhydantoin-induced hepatic necrosis. Postgrad Med 56:128–134, 1974
Spielberg P, Gordon GB, Blake DA, Goldstein DA, Franklin Herlong H: Predisposition to phenytoin hepatoxicity assessed in vitro. N Engl J Med 305:722–727, 1981
Doecke CJ, Veronese ME, Pond SM, Miners JO, Birkett DJ, Sanson LN, McManus ME: Relationship between phenytoin and tolbutamide hydroxylations in human liver microsomes. Br J Clin Pharmacol 31:125–130, 1991
Veronese ME, MacKenzie PI, Doecke CJ, McManus ME, Miners JD, Birkett DJ: Tolbutamide and phenytoin hydroxylations by cDNA-expressed human liver cytochrome P4502C9. Biochem Biophys Res Commun 175:1112–1118, 1991
Leeder JS, Riley RJ, Cook VA, Spielberg SP: Human anticytochrome P450 antibodies in aromatic anticonvulant-induced hypersensitivity reactions. J Pharmacol Exper Ther 1992 (in press)
Rivera Velasco JR, Rodrigo Salz LR, Perez Alvarezy R, Gonzalez Gonzalez M: Chronic active hepatitis from diphenylhydantoin. Med Clin 87:214, 1986
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Roy, A.K., Mahoney, H.C. & Levine, R.A. Phenytoin-induced chronic hepatitis. Digest Dis Sci 38, 740–743 (1993). https://doi.org/10.1007/BF01316808
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01316808