Hepatic injury associated with the use of nitrofurans: a clinicopathological study of 52 reported cases.
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)
Stricker
B H
BH
Netherlands Centre for Monitoring of Adverse Reactions to Drugs, Rijswijk.
Blok
A P
AP
Claas
F H
FH
Van Parys
G E
GE
Desmet
V J
VJ
D001706:Biopsy; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009336:Necrosis; D009426:Netherlands; D009581:Nitrofurans / Q000009:adverse effects*; D009582:Nitrofurantoin / Q000009:adverse effects / Q000031:analogs & derivatives; D013997:Time Factors
D006680:HLA Antigens; D009581:Nitrofurans; D009582:Nitrofurantoin; C002848:nifurtoinol