Isoniazid liver injury: clinical spectrum, pathology, and probable pathogenesis

J. R. Mitchell, H. J. Zimmerman, K. G. Ishak, U. P. Thorgeirsson, J. A. Timbrell, W. R. Snodgrass, S. D. Nelson

Research output: Contribution to journalReview article

362 Scopus citations

Abstract

The clinical spectrum of isoniazid induced liver injury seems to be clinically, biochemically, and histologically indistinguishable from viral hepatitis, except that the injury occurs primarily in persons older than 35 yr. A possible relation between susceptibility of patients to isoniazid liver injury and rapid metabolism (acetylation) of the drug has been found. Examination of isoniazid metabolites showed that patients with rapid acetylator phenotype hydrolyze much more isoniazid to isonicotinic acid and the free hydrazine moiety than do slow acetylators. The hydrazine moiety liberated from isoniazid is primarily acetylhydrazine, and studies in animals show this metabolite to be converted to a potent acylating agent that produces liver necrosis. It seems likely that formation of chemically reactive metabolites is also the biochemical event initiating isoniazid liver injury in man. Recognition of the seriousness of isoniazid hepatic injury, not readily accepted at first, has led to revisions in the uses of isoniazid prophylaxis.

Original languageEnglish (US)
Pages (from-to)181-192
Number of pages12
JournalUnknown Journal
Volume84
Issue number2
DOIs
StatePublished - Jan 1 1976

ASJC Scopus subject areas

  • Internal Medicine

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    Mitchell, J. R., Zimmerman, H. J., Ishak, K. G., Thorgeirsson, U. P., Timbrell, J. A., Snodgrass, W. R., & Nelson, S. D. (1976). Isoniazid liver injury: clinical spectrum, pathology, and probable pathogenesis. Unknown Journal, 84(2), 181-192. https://doi.org/10.7326/0003-4819-84-2-181