Hepatic injury associated with the use of nitrofurans: A clinicopathological study of 52 reported cases

Abstract

Fifty cases of nitrofurantoin‐associated hepatic injury and two cases of nifurtoinol (hydroxymethylnitro‐furantoin)‐associated hepatic injury reported to the Netherlands Centre for Monitoring of Adverse Reactions to Drugs were analyzed in detail. In 38 cases, a causal relationship was considered likely [i.e., “highly probable” (n = 4), “probable” (n = 23) or “possible” (n = 11)]. In 25 cases, hepatic injury was of the acute type whereas 13 cases presented a chronic type of reaction. Both types were more common in the elderly. Eighty per cent of the acute reactions appeared within the first 6 weeks of treatment and were sometimes accompanied by fever (28%), rash (12%) and eosinophilia (16%). Biochemically, the pattern was mainly hepatocellular (32%), whereas mixed cholestatic‐hepatocellular (4%) and cholestatic (4%) patterns were uncommon. Although mild to moderate liver enzyme elevations (60%) were common, these were primarily symptomatic. The reaction was fatal in one “acute” and one “chronic” case. In the chronic cases, nuclear (82%) and smooth muscle (73%) antibodies and LE cells (50%) were frequently present. HLA typing showed no increase of the HLA B8 or HLA DRw3 haplotype. HLA DR2 (56%) and HLA DRw6 (56%) were more frequent than in controls (both 29%), but this was not statistically significant. Histology showed mainly necrosis, varying from spotty to massive, in the acute cases and a pattern consistent with chronic active hepatitis in the chronic cases. The incidence of symptomatic nitrofurantoin‐induced hepatic injury in The Netherlands may be estimated at approximately 1:3,000 to 5,000 (0.020 to 0.035%). The mechanism of nitrofurantoin‐induced hepatic injury seems to be immunoallergic. Copyright © 1988 American Association for the Study of Liver Diseases