Liver damage and nonsteroidal anti-inflammatory drugs: case non-case study in the French Pharmacovigilance Database

This study investigates the relationship between exposure to non-steroidal anti-inflammatory drugs (NSAIDs) and liver injuries using the French Pharmacovigilance Database. We use the case/non-case methodology, where 'cases' were reports of the reactions of interest (liver injuries as recorded in the database according to the WHO-ART classification including cytolytic and cholestatic hepatitis, acute hepatitis, liver enzyme elevations). 'Non-cases' were all reports of reactions other than these being studied. Amineptine and acetaminophen were used as 'positive controls'. Among the 42,913 adverse drug reactions recorded in the database between January 1995 and December 1997, 5708 (13 per cent) were liver injuries. In comparison with other drugs in the database, liver injuries were inversely associated with exposure to NSAIDs, whatever the class of the drugs (OR 0.3 [0.3-0.4]). In contrast, liver injuries were significantly related to acetaminophen (OR 2.1 [1.9-2.3]), and amineptine (OR 14.0 [10.5-18.7]). Naproxen and diclofenac were associated with a higher frequency of liver injuries, respectively 15.7 per cent and 11.5 per cent. The risk associated with NSAIDs alone significantly decreased when the analysis was performed after exclusion of hepatotoxic drugs associated with NSAIDs (except for naproxen). The present results show the low frequency of liver damage associated with NSAIDs. The main factor appears to be concomitant exposure to other hepatotoxic drugs.