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Detection of anti-isoniazid and anti-cytochrome P450 antibodies in patients with isoniazid-induced liver failure.
- Source :
-
Hepatology (Baltimore, Md.) [Hepatology] 2014 Mar; Vol. 59 (3), pp. 1084-93. Date of Electronic Publication: 2014 Jan 27. - Publication Year :
- 2014
-
Abstract
- 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.<br />Conclusion: These data provide strong evidence that INH induces an immune response that causes INH-induced liver injury.<br /> (© 2014 by the American Association for the Study of Liver Diseases.)
- Subjects :
- Adult
Aged
Antibodies blood
Antitubercular Agents adverse effects
Antitubercular Agents immunology
Chemical and Drug Induced Liver Injury epidemiology
Cytochrome P-450 CYP2C9
Female
Humans
Isoniazid immunology
Liver Failure epidemiology
Liver Failure immunology
Male
Microsomes, Liver immunology
Middle Aged
Risk Factors
Seroepidemiologic Studies
Young Adult
Aryl Hydrocarbon Hydroxylases immunology
Autoantibodies blood
Chemical and Drug Induced Liver Injury immunology
Cytochrome P-450 CYP2E1 immunology
Cytochrome P-450 CYP3A immunology
Isoniazid adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1527-3350
- Volume :
- 59
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Hepatology (Baltimore, Md.)
- Publication Type :
- Academic Journal
- Accession number :
- 23775837
- Full Text :
- https://doi.org/10.1002/hep.26564