The Spectrum of Nimesulide-Induced-Hepatotoxicity. An Overview

Fernando Bessone1,*, Luis Colombato2, Eduardo Fassio3, Maria Virginia Reggiardo1,Julio Vorobioff1 and Hugo Tanno1
1Hepatology Department, University of Rosario School of Medicine-Rosario-Argentina; 2Gastroenterology Department,
British Hospital-Buenos Aires-Argentina; 3Hepatology Department-Hospital Alejandro Posadas- Buenos Aires-
Argentina
Abstract: 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.

 


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