A Fresh Look at the Mechanism of Isoniazid-Induced Hepatotoxicity

Isoniazid (INH)-induced hepatotoxicity remains a significant clinical problem, and the current mechanistic hypothesis is incomplete; it is simply referred to as metabolic idiosyncrasy, 1 which is believed to involve cytotoxicity caused by bioactivation of acetylhydrazine, 2 a metabolite of INH. However, this hypothesis is based on animal studies, involving characteristics that are very different from those that pertain to hepatotoxicity in humans, such as delayed onset. This issue therefore deserves a fresh look.