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

Academic Article

Abstract

  • 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) © 2014 by the American Association for the Study of Liver Diseases.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Metushi IG; Sanders C; Lee WM; Larson AM; Liou I; Davern T; Fix O; Schilsky M; McCashland T; Hay JE
  • Start Page

  • 1084
  • End Page

  • 1093
  • Volume

  • 59
  • Issue

  • 3