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

Hepatology. May-Jun 1988;8(3):599-606. doi: 10.1002/hep.1840080327.


Fifty cases of nitrofurantoin-associated hepatic injury and two cases of nifurtoinol (hydroxymethylnitrofurantoin)-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.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Biopsy
  • HLA Antigens / analysis
  • Humans
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Necrosis
  • Netherlands
  • Nitrofurans / adverse effects*
  • Nitrofurantoin / adverse effects
  • Nitrofurantoin / analogs & derivatives
  • Time Factors


  • HLA Antigens
  • Nitrofurans
  • Nitrofurantoin
  • nifurtoinol