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Mechanism of isoniazid-induced hepatotoxicity: then and now

Imir Metushi1, Jack Uetrecht2, Elizabeth Phillips3

  • 1Center for Advanced Laboratory Medicine, Department of Pathology, University of California San Diego, San Diego, CA, 92116, USA.

British Journal of Clinical Pharmacology
|January 17, 2016
PubMed

Insights

Isoniazid (INH) can cause liver injury through immune responses, not just metabolism. Two phenotypes exist: mild, resolving injury and severe cases with antibodies progressing to liver failure.

Area of Science:

  • Pharmacology
  • Immunology
  • Hepatology

Background:

  • Isoniazid (INH) is a crucial tuberculosis treatment but can cause drug-induced liver injury (DILI).
  • Previous theories suggested DILI was metabolic, not immune-mediated.
  • Recent evidence points to INH's direct bioactivation and potential immune involvement.

Purpose of the Study:

  • To explore the immune mechanisms underlying Isoniazid-induced liver injury (DILI).
  • To differentiate between phenotypes of INH-induced liver injury.
  • To investigate the role of anti-drug and anti-CYP P450 antibodies in severe DILI.

Main Methods:

  • Review of existing literature on Isoniazid DILI.
  • Analysis of proposed mechanisms of INH bioactivation.
  • Phenotypic classification of Isoniazid-induced liver injury cases.

Main Results:

  • Two distinct phenotypes of INH-induced liver injury have been identified.
  • Mild liver injury often resolves via immune tolerance.
  • Severe liver injury is linked to anti-drug/anti-CYP P450 antibodies and can lead to liver failure.

Conclusions:

  • Isoniazid-induced liver injury involves an immune response, challenging prior metabolic hypotheses.
  • The severity of INH-induced liver injury depends on the patient's immune reaction and antibody production.
  • Understanding these mechanisms is crucial for managing tuberculosis treatment and preventing liver failure.
Keywords:
biomarkerhepatotoxicityimmune mediatedreactive metabolitetolerance

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