Detection of anti-isoniazid and anti-cytochrome P450 antibodies in patients with isoniazid-induced liver failure.


Journal Article

UNLABELLED: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.

Full Text

Cited Authors

  • Metushi, IG; Sanders, C; Acute Liver Study Group, ; Lee, WM; Uetrecht, J

Published Date

  • March 2014

Published In

Volume / Issue

  • 59 / 3

Start / End Page

  • 1084 - 1093

PubMed ID

  • 23775837

Pubmed Central ID

  • 23775837

Electronic International Standard Serial Number (EISSN)

  • 1527-3350

International Standard Serial Number (ISSN)

  • 0270-9139

Digital Object Identifier (DOI)

  • 10.1002/hep.26564


  • eng