Potential conflict of interest: Nothing to report.
Detection of anti-isoniazid and anti–cytochrome P450 antibodies in patients with isoniazid-induced liver failure
Article first published online: 27 JAN 2014
© 2014 by the American Association for the Study of Liver Diseases
Volume 59, Issue 3, pages 1084–1093, March 2014
How to Cite
Metushi, I. G., Sanders, C., The Acute Liver Study Group, Lee, W. M. and Uetrecht, J. (2014), Detection of anti-isoniazid and anti–cytochrome P450 antibodies in patients with isoniazid-induced liver failure. Hepatology, 59: 1084–1093. doi: 10.1002/hep.26564
This work is supported by grants from the Canadian Institutes of Health Research (CIHR). J.U. holds the Canadian chair in Adverse Drug Reactions. I.G.M. is a trainee of the Drug Safety and Effectiveness Cross Disciplinary Training Program, which is funded by the CIHR. The Acute Liver Failure Study Group is supported by the National Institutes of Health Research Grant to UT Southwestern Medical Center, Dallas, TX (U-01-DK58369-014).
See Editorial on Page 746
- Issue published online: 25 FEB 2014
- Article first published online: 27 JAN 2014
- Accepted manuscript online: 14 JUN 2013 09:44AM EST
- Manuscript Accepted: 29 MAY 2013
- Manuscript Revised: 6 MAY 2013
- Manuscript Received: 10 FEB 2013
Isoniazid (INH)-induced hepatotoxicity remains one of the most common causes of drug-induced idiosyncratic liver injury and liver failure. This form of liver injury is not believed to be immune-mediated because it is not usually associated with fever or rash, does not recur more rapidly on rechallenge, and previous studies have failed to identify anti-INH antibodies (Abs). In this study, we found Abs present in sera of 15 of 19 cases of INH-induced liver failure. Anti-INH Abs were present in 8 sera; 11 had anti–cytochrome P450 (CYP)2E1 Abs, 14 had Abs against CYP2E1 modified by INH, 14 had anti-CYP3A4 antibodies, and 10 had anti-CYP2C9 Abs. INH was found to form covalent adducts with CYP2E1, CYP3A4, and CYP2C9. None of these Abs were detected in sera from INH-treated controls without significant liver injury. The presence of a range of antidrug and autoAbs has been observed in other drug-induced liver injury that is presumed to be immune mediated. Conclusion: These data provide strong evidence that INH induces an immune response that causes INH-induced liver injury. (Hepatology 2014;59:1084–1093)