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

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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
JournalAnnals of Internal Medicine
Volume84
Issue number2
StatePublished - 1976
Externally publishedYes

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Clinical Pathology
Isoniazid
hydrazine
Liver
Wounds and Injuries
Isonicotinic Acids
Acetylation
Hepatitis
Necrosis
Phenotype

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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. Annals of Internal Medicine, 84(2), 181-192.

Isoniazid liver injury : clinical spectrum, pathology, and probable pathogenesis. / Mitchell, J. R.; Zimmerman, H. J.; Ishak, K. G.; Thorgeirsson, U. P.; Timbrell, J. A.; Snodgrass, W. R.; Nelson, S. D.

In: Annals of Internal Medicine, Vol. 84, No. 2, 1976, p. 181-192.

Research output: Contribution to journalArticle

Mitchell, JR, Zimmerman, HJ, Ishak, KG, Thorgeirsson, UP, Timbrell, JA, Snodgrass, WR & Nelson, SD 1976, 'Isoniazid liver injury: clinical spectrum, pathology, and probable pathogenesis', Annals of Internal Medicine, vol. 84, no. 2, pp. 181-192.
Mitchell JR, Zimmerman HJ, Ishak KG, Thorgeirsson UP, Timbrell JA, Snodgrass WR et al. Isoniazid liver injury: clinical spectrum, pathology, and probable pathogenesis. Annals of Internal Medicine. 1976;84(2):181-192.
Mitchell, J. R. ; Zimmerman, H. J. ; Ishak, K. G. ; Thorgeirsson, U. P. ; Timbrell, J. A. ; Snodgrass, W. R. ; Nelson, S. D. / Isoniazid liver injury : clinical spectrum, pathology, and probable pathogenesis. In: Annals of Internal Medicine. 1976 ; Vol. 84, No. 2. pp. 181-192.
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