Clopidogrel-Induced Hepatotoxicity: A Case Report

Abstract

Clopidogrel is an antiplatelet agent provided to patients undergoing percutaneous coronary intervention (PCI) to prevent stent thrombosis. It blocks P2Y12 receptors, thus inhibiting activation of GPIIb/IIIa receptor complex. Herein, we report a case of clopidogrel induced cholestatic hepatitis. Case Report A 75-year-old female status-post PCI with two drug eluting stents was started on clopidogrel 75mg daily. Six weeks later, she presented to clinic with nausea and the following labs: serum alanine aminotransferase (ALT) 469 U/L, aspartate aminotransferase (AST) 408 U/L, alkaline phosphatase (ALP) 335 U/L. Right upper quadrant ultrasound (RUQ US) showed gallstones but otherwise unremarkable. A week later she returned with emesis and TBILI of 3.2 mg/dL and lipase of 1248 U/L. MRCP was normal. She received 2 days of cephalosporins and underwent a cholecystectomy. Intra-operative cholangiogram revealed no choledocholithiasis. Six weeks post-procedure, she was jaundiced with TBILI of 11mg/d, ALP of 328U/L, AST of 79 U/L and ALT of 58 U/L. Hepatitis work-up including Hepatitis panel (A, B, C, E), ANA, Actin Antibody and Anti-Mitochondrial Antibody, HEV, CMV and histoplasma antigen, was negative. HIDA scan, repeat MRCP, blood and urine cultures were negative. Clopidogrel induced liver injury was suspected. It was replaced with ticagrelor. Liver enzymes continued to improve gradually and normalized at 24 weeks from discontinuation of clopidogrel. Discussion We report a rare case of clopidogrel induced severe cholestatic hepatitis. We used the Naranjo scale and Maria Victorino scale, in which our patient's scores were 7 and 14 respectively, indicating a probable drug induced hepatitis. Clopidogrel induced hepatotoxicity usually results in hepatocellular pattern of liver injury, though a few cases with mixed or cholestatic enzyme elevations have also been reported. The onset of symptoms with clopidogrel induced liver injury is usually within 2 to 24 weeks of starting clopidogrel, averaging 6 weeks as seen in our case, with fatigue and jaundice being the most common symptoms. The degree of hepatic injury from clopidogrel varies. In our literature review, we found one case of clopidogrel induced fulminant hepatitis that resulted in death. Hence, early recognition is crucial After identifying the potential cause, withdrawal of the offending agent is itself sufficient for recovery of liver function and normalization of liver enzymes in most cases.