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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Metushi, Imir G. Sanders, Corron Lee, William M. Uetrecht, Jack
Description	Country affiliation: Canada Author Affiliation: Metushi IG ( Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.)
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. CONCLUSION: These data provide strong evidence that INH induces an immune response that causes INH-induced liver injury.
File Format	HTM / HTML
ISSN	02709139
e-ISSN	15273350
DOI	10.1002/hep.26564
Journal	Hepatology
Issue Number	3
Volume Number	59
Language	English
Publisher	Wiley
Publisher Date	2014-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Hepatology Aryl Hydrocarbon Hydroxylases Immunology Autoantibodies Blood Drug-induced Liver Injury Cytochrome P-450 Cyp2e1 Cytochrome P-450 Cyp3a Isoniazid Adverse Effects Antibodies Antitubercular Agents Epidemiology Cytochrome P-450 Cyp2c9 Liver Failure Microsomes, Liver Risk Factors Seroepidemiologic Studies Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Hepatology

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