As a class, nonsteroidal anti-inflammatory drugs (NSAIDs) are a leading cause of drug-induced liver disease. For instance, in Denmark, NSAIDs accounted for approximately 9% (97 of 1100) of all drug-related liver injury reports between 1978 and 1987.<sup>20 Friis H., Andreasen P.B. Drug-induced hepatic injury: An analysis of 1,100 cases reported to the Danish Committee on Adverse Drug Reactions between 1978 and 1987 J Intern Med 1992 ;  232 : 133  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> The early history of NSAID-induced hepatic injury dates back more than 60 years.<sup>89 Zimmerman H.J.   Hepatotoxicity: The Adverse Effects of Drugs and Other Chemicals on the Liver New York: Appleton-Century-Crofts (1978). 

Cliccare qui per andare alla sezione Riferimenti</sup> Cinchophen was one of the earliest agents to be associated with hepatotoxicity. Its case fatality rate of nearly 50% forced its withdrawal from clinical use.<sup>54 Palmer W.L., Woodall P.S. Cinchophen—is there a safe method of administration? JAMA 1936 ;  107 : 760

Cliccare qui per andare alla sezione Riferimenti</sup> Numerous other NSAIDs have been developed or introduced into practice only to be abandoned during premarket or postmarket evaluation because of serious liver injury.<sup>42 Lewis J.H. Hepatic toxicity of nonsteroidal anti-inflammatory drugs Clin Pharm 1984 ;  3 : 128

Cliccare qui per andare alla sezione Riferimenti</sup> Examples of such agents include glafenine,<sup>78 Stricker B.H.C., Blok A.P., Bronkhorst F.B. Glafenine-associated hepatic injury: Analysis of 38 cases and review of the literature Liver 1986 ;  6 : 63

Cliccare qui per andare alla sezione Riferimenti</sup> an NSAID similar to cinchophen; ibufenac,<sup>14 Cuthbert M.F. Adverse reactions to nonsteroidal anti-inflammatory drugs Curr Med Res Opin 1974 ;  2 : 12

Cliccare qui per andare alla sezione Riferimenti</sup> a precursor of ibuprofen; fenclozic acid, an early arylalkanoic acid NSAID<sup>29 Hart F.D., Bain L.S., Huskisson E.C. , e al. Hepatic effects of fenclozic acid Ann Rheum Dis 1970 ;  29 : 684

Cliccare qui per andare alla sezione Riferimenti</sup> and fluproquazone, the precursor compound of quinazolone derivatives.<sup>46 Meythaler J.M., Varma R.R. Reye's syndrome in adults: Diagnostic considerations Arch Intern Med 1987 ;  147 : 61

Cliccare qui per andare alla sezione Riferimenti</sup> However, it was not until the withdrawal of benoxaprofen in 1982 because of reports of fatal jaundice in the United Kingdom that attention was intensively focused on the hepatotoxicity of NSAIDs as a group.<sup>46 Meythaler J.M., Varma R.R. Reye's syndrome in adults: Diagnostic considerations Arch Intern Med 1987 ;  147 : 61

Cliccare qui per andare alla sezione Riferimenti</sup> At that time, the Arthritis Advisory Committee of the Food and Drug Administration (FDA) concluded that hepatic injury should be considered a class characteristic of NSAIDs.<sup>55 Paulus H.E. FDA Arthritis Advisory Committee meeting Arthritis Rheum 1982 ;  25 : 1124

Cliccare qui per andare alla sezione Riferimenti</sup> However, this uniform characterization of hepatic injury obscures the many individual differences found within and among the different NSAID classes. The types and mechanisms of hepatic injury, as well as the hepatotoxic potential for different NSAID agents also can vary considerably. This article reviews the clinical-pathologic features of the hepatic injury associated with the currently available NSAIDs. Acetaminophen is not a true nonsteroidal anti-inflammatory drug and will not be discussed.