Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ticlopidine, an adenosine diphosphate receptor blocker, is widely used to prevent subacute stent thrombosis after percutaneous coronary intervention. Along with neutropenia and thrombotic thrombocytopenic purpura, cholestatic hepatitis is one of the most serious potential side-effects of ticlopidine therapy. Four patients with prolonged jaundice after ticlopidine therapy, including one fatal case, are presented. Alternative antithrombotic therapy for subsequent percutaneous coronary intervention is also described. Clopidogrel therapy was found to be safe and effective in two patients with a history of ticlopidine-related cholestatic hepatitis.
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PMID:Prolonged jaundice following percutaneous coronary intervention and ticlopidine therapy. 1186 96

In patients undergoing percutaneous coronary intervention and in those with acute coronary syndromes, clopidogrel plus aspirin is the first-line antiplatelet therapy for reducing cardiovascular events. Although clopidogrel is generally well tolerated, with rash, indigestion, vomiting, diarrhea, and bleeding being the most common adverse effects, rare but serious complications may occur. We describe a 78-year-old woman who underwent percutaneous coronary intervention with drug-eluting stents; clopidogrel and aspirin were started as antiplatelet therapy. Three weeks later, the patient developed mixed hepatocellular and cholestatic liver injury. Clopidogrel was discontinued, and her liver profile results began to improve. Her diagnostic work-up included screening for hepatitis, infectious mononucleosis, and rheumatologic diseases, as well as ultrasonography, magnetic resonance imaging, and endoscopic retrograde cholangiopancreaticography; all results were normal. On day 5 of hospitalization, because of the patient's risk for thrombosis secondary to the drug-eluting stents, clopidogrel was reintroduced; her liver enzyme levels increased. In the absence of any biliary obstruction or other obvious causes of hepatic injury, drug-induced hepatocellular injury and cholestatic jaundice were suspected, and clopidogrel was again discontinued. The patient's liver function tests gradually improved 3 days later and showed marked improvement at her 2-week follow-up visit after discharge. Use of the Maria and Victorino scale for diagnosis of drug-induced hepatotoxicity indicated a probable (score of 14) relationship between clopidogrel and mixed hepatocellular injury and cholestatic jaundice in this patient. Although routine liver function testing is not recommended in patients who receive clopidogrel, having a high index of clinical suspicion, drug rechallenge, and excluding other obvious causes are required to establish the diagnosis of a rare drug complication such as clopidogrel-induced hepatic injury.
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PMID:Clopidogrel-induced hepatocellular injury and cholestatic jaundice in an elderly patient: case report and review of the literature. 1939 67

Alpha-naphthylisothiocyanate (ANIT) causes cholestatic hepatitis characterized by intrahepatic bile duct epithelial cell injury and periportal hepatocellular necrosis. The progression of ANIT-induced hepatocyte injury is reported to involve extrahepatic cells including platelets. We showed recently that the procoagulant protein tissue factor (TF) is essential for ANIT-induced coagulation and contributes to ANIT-induced liver necrosis. Platelets have been shown to express TF and can contribute to coagulation cascade activation. To this end, we tested the hypothesis that platelet-dependent coagulation contributes to ANIT-induced liver injury. In ANIT (60 mg/kg)-treated mice, activation of the coagulation cascade occurred prior to a decrease of platelets in the blood. Immunostaining for glycoprotein IIb (CD41) revealed platelet accumulation along the borders of necrotic foci in livers of ANIT-treated mice. Antibody-mediated platelet depletion did not affect coagulation but markedly affected liver histopathology in ANIT-treated mice. Platelet depletion induced marked pooling of blood within necrotic lesions consistent with parenchymal-type peliosis as early as 24 h after ANIT treatment. In contrast, treatment with the P2Y(12) inhibitor clopidogrel significantly reduced ANIT-induced hepatocyte necrosis and serum alanine aminotransferase activity but did not exaggerate bleeding into necrotic foci. Clopidogrel also reduced hepatic neutrophil accumulation but did not affect induction of Intercellular adhesion molecule-1 or chemokine CxC motif ligand-1 messenger RNA expression in liver. The data indicate that ANIT-induced coagulation is platelet independent and that platelets contribute to ANIT-induced hepatocyte necrosis by promoting neutrophil accumulation. In contrast, severe thrombocytopenia induces parenchymal-type peliosis in the livers of ANIT-treated mice, a rare hepatic lesion associated with pooling of blood in the liver.
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PMID:Protective and damaging effects of platelets in acute cholestatic liver injury revealed by depletion and inhibition strategies. 2013 75

Clopidogrel is a thienopyridine-class antiplatelet drug commonly used in ischemic heart disease,cerebrovascular disease and peripheral artery disease.Liver toxicity due to this drug is very infrequent.We found 16 cases in the literature, and in only two of them liver biopsy was carried out. We report the case of a 78 year old patient with multiple conditions affected by severe toxic cholestatic hepatitis due to clopidogrel and the results of the liver biopsy performed. Hepatitis was resolved after discontinuing the drug.Based on the characteristics of this case and other previously published cases, we review the characteristics of toxic hepatitis due to clopidogrel and its diagnosis and treatment.
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PMID:[Cholestasic toxic hepatitis due to clopidogrel in a patient with multiple conditions]. 2712 14

Clopidogrel is a commonly prescribed antiplatelet agent that carries a rare risk of hepatotoxicity. We describe a case of severe clopidogrel-induced hepatitis with liver biopsy assessment. Prompt recognition and withdrawal of the offending agent are imperative to prevent progression and potentially fatal liver injury.
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PMID:Clopidogrel-Induced Severe Hepatitis: A Case Report and Literature Review. 2742 13