The Spectrum of Nimesulide-Induced-Hepatotoxicity. An Overview
Maria Virginia Reggiardo,
Nimesulide is the unique molecule of the sulphonanilides class of non-steroidal antiinflammatory drugs [NSAIDs]: Nimesulide has analgesic, anti-pyretic, potent anti-inflammatory activities and very good gastro-intestinal [GI] tolerability. Therapeutic action is multifactorial, including cyclooxigenase-2 (COX-2) inhibition, scavenging of free radicals and inhibition of various pathways of inflammation. Nimesulide is oxidatively metabolised via liver cytochromes P450. Several unproven hepatotoxicy-predisposing-factors thought to be present in rheumatologic patients have been linked to a higher incidence of hepatic reactions in this sub-population. However, the molecular mechanism underlying hepatotoxicy remains to be elucidated. Nimesulide has been associated over two decades with reports of severe liver damage. The clinical presentation of nimesulide-related-hepatoxicity includes, malaise, pruritus, a wide range of ALT/AST elevation, and an average 4 fold elevation of alkaline phosphatase and GGT. Liver biopsy shows a predominance of hepatocellular involvement, less frequently cholestatic and mixed patterns. Both, the hepatitis pattern and the mixed-type combining cholestatic jaundice, might evolve into fulminant hepatic failure. However, the incidence of nimesulide-inducedhepatotoxicity is not homogeneous across the medical literature. Indeed, most of the countries find it to be comparable to that of other NSAIDs, while a significant higher hepatotoxicity is suggested by reports from Finland, Ireland and Argentina. Our series in Argentina comprising 43 cases is worrisome particularly because it evidences a significant proportion of severe forms. In the present work we analyze the epidemilogical characteristics of nimesulide-induced-hepatotoxicity and we describe the clinical and histologic spectrum of nimesulide-associated-liver damage based on the comparison of our series of 43 cases and worldwide published observations in the pertinent medical literature.
Keywords: Cholestasis, drug-induced liver injury, fulminant hepatic failure, hepatitis, hepatotoxicity, Nimesulide, analgesic, anti-pyretic, potent anti-inflammatory, cyclooxigenase-2 (COX-2), alkaline phosphatase, biopsy, homogeneous, anti-pyretic effects, cholestatic jaundice, cyclooxygenase, cytochromes P-450, cimetidine, warfarin, acenocoumarol, hypoglycemics agents, digoxin, furosemide, nitric oxide synthase, transplant hepatologysts, paracetamol, diclofenac, oxidative-phosphorilation, pharmacovigilance chronologic criteria, microsteatosis, Non-steroidal antiinflammatory drugs, Drugs Induced Liver Injury, Gastro-Intestinal, Years-old, Cyclooxigenase-2, European Medicines Evaluation Agency, Prostaglandin E2, Platelet-activating factor, Liver Function Tests, Hepatic Venous Pressure Gradient, Orthotopic Liver Transplantation
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