CLOPIDOGREL-INDUCED LIVER INJURY

F Batwa MD, E Lamoureaux MD, G Friedman MD

The Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Quebec

The thienopyridine derivatives ticlopidine and clopidogrel are specific and potent inhibitors of platelets aggregation that are metabolized in the liver into active substances. Several studies showed that clopidogrel is superior to aspirin in patients with ischemic risk and clopidogrel was subsequently approved in many countries for secondary prevention of myocardial infarction and ischemic stroke in patients with symptomatic atherosclerotic vascular disease. Because the occurrence of severe adverse events has been associated with ticlopidine therapy, clopidogrel has replaced ticlopidine in clinical practice. Several case reports have associated ticlopidine with the development of serious medical problems including severe liver injury and hepatitis, but since its introduction into clinical practice only one case has associated clopidogrel with the development of such a potentially lethal complication.
We report an 84-year-old woman who presented with clinical and laboratory signs of acute mixed hepatocellular-cholestatic hepatitis. Symptoms have appeared 8 weeks after she was started on clopidogrel 75 mg/day as an adjunctive therapy to aspirin to prevent further transient ischemic attacks. Infectious etiologies were excluded by serology and autoantibodies were negative. There was no history of alcohol abuse and no history of toxic exposure. Further workup showed no evidence of hemochromatosis or other metabolic liver disease. Endoscopic retrograde cholangiopancreatography did not reveal any biliary tract disease. Liver biopsy confirmed the finding of drug related hepatotoxicity and the drug was discontinued. Complete resolution of symptoms and biochemical profile occurred over several weeks. After excluding all possible causes of acute hepatitis, we think that clopidogrel was the cause of this patient's hepatitis Despite clopidogrel's usual good tolerability, physicians should be aware of potential severe hepatitis to occur with this drug.