- Anne M Larson, MD, FACP, AGAF
Anne M Larson, MD, FACP, AGAF
- Director, Swedish Liver Center
- Medical Director of Liver Transplantation
- Amy L Graziani, PharmD
Amy L Graziani, PharmD
- Associate Professor in Pharmacy, Adjunct Faculty
- University of Pennsylvania School of Medicine and University of the Sciences, Philadelphia, PA
Isoniazid (INH, isonicotinylhydrazide) is a synthetic antibiotic that is bactericidal against replicating Mycobacterium tuberculosis. The drug acts by inhibiting the oxygen-dependent steps in the synthesis of mycolic acid, a component of the mycobacterial cell wall. INH has been associated with two syndromes of hepatotoxicity: mild INH hepatotoxicity and INH hepatitis.
The pathophysiology and prevention of INH hepatotoxicity will be reviewed here. The clinical use of INH is discussed separately. (See "Treatment of latent tuberculosis infection in HIV-negative adults" and "Treatment of pulmonary tuberculosis in HIV-negative patients".)
MILD INH HEPATOTOXICITY
Mild, nonspecific hepatic injury occurs in up to 20 percent of patients taking isoniazid (INH, isonicotinylhydrazide). This is typically subclinical and evidenced only by mildly elevated serum aminotransferases (usually <100 IU/L) [1-3]. Liver biopsy in such patients usually demonstrates minor focal hepatocellular damage . Adults are more likely to be affected than children; men and women appear to be equally vulnerable. There is no relationship to race or the rate of hepatic acetylation of the drug.
The prognosis for mild INH hepatotoxicity is excellent, with an overall mortality rate of only 0.001 percent . Virtually all cases are self-limited; INH therapy can be continued with careful clinical and laboratory monitoring.
INH hepatitis is a less common but more serious liver injury syndrome than mild isoniazid (INH, isonicotinylhydrazide) hepatotoxicity; it is typically symptomatic and may be fatal [5,6]. The features are generally indistinguishable from viral hepatitis [5,7-11].
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- MILD INH HEPATOTOXICITY
- INH HEPATITIS
- Prevalence and risk factors
- Clinical manifestations
- - During treatment of latent TB infection
- Normal baseline liver function
- Abnormal baseline liver function
- - During treatment of TB disease
- Normal baseline liver function
- Abnormal baseline liver function
- MECHANISM OF HEPATOTOXICITY
- INFORMATION FOR PATIENTS