[Ticlopidine-induced cholestasis]

We report a case of ticlopidine-induced cholestatic hepatitis.

An 82-year-old man suffered a myocardial infarction in February 1998. Because of persistent angina pectoris a coronary stent was implanted in May 1998. At this time medication with 1 x 250 mg ticlopidine was started in addition to the preexistent medication of aspirin 1 x 100 per day, metoprolol fumarate 1 x 95 mg per day and isosorbide dinitrate 1 x 100 mg per day. Three weeks after starting ticlopidine the patient complained of itching, and on day 28 painless jaundice developed. At this time, the serum activities of alkaline phosphatase (923 U/l), gamma-GT (823 U/l) and total bilirubin concentration (129 mumol/l) were markedly elevated, whereas the activities of the transaminases (AST 131 U/l, ALT 194 U/l) were slightly increased. An extra- or intrahepatic biliary obstruction was ruled out, and there were no signs of a toxic, infectious or immunological cause for the hepatic injury. Liver biopsy showed centro-acinar cholestasis. After drug discontinuation the itching stopped after 4 weeks and jaundice disappeared after 2 weeks. Eight months after the onset of symptoms, the activities of alkaline phosphatase (226 U/l) and gamma-GT (213 U/l) were still elevated but the patient was asymptomatic.

Ticlopidine-induced mild serum liver enzyme elevations have been observed in some studies (incidence 1-2%). The incidence of severe hepatitis has been estimated at 0.0013%. Only a few cases (in approximately 20 patients receiving ticlopidine) of a severe cholestatic pattern of injury have been reported. In all cases the jaundice resolved and serum liver enzyme concentrations normalised over a period of months. Characteristically, liver biopsies demonstrated centro-acinar cholestasis. Monitoring of serum liver enzyme concentrations is not recommended. When itching or jaundice occur in a patient taking ticlopidine, the possibility of toxic liver damage should be taken into account.