Mechanism of isoniazid-induced hepatotoxicity: then and now

British Journal of Clinical Pharmacology
I G MetushiElizabeth Phillips

Abstract

Isoniazid (INH) remains a mainstay for the treatment of tuberculosis despite the fact that it can cause liver failure. Previous mechanistic hypotheses have classified this type of drug-induced liver injury (DILI) as 'metabolic idiosyncrasy' which was thought not to involve an immune response and was mainly due to the bioactivation of the acetylhydrazine metabolite. However, more recent studies support an alternative hypothesis, specifically, that INH itself is directly bioactivated to a reactive metabolite, which in some patients leads to an immune response and liver injury. Furthermore, there appear to be two phenotypes of INH-induced liver injury. Most cases involve mild liver injury, which resolves with immune tolerance, while other cases appear to have a more severe phenotype that is associated with the production of anti-drug/anti-CYP P450 antibodies and can progress to liver failure.

References

Feb 1, 1976·Annals of Internal Medicine·J R MitchellS D Nelson
Sep 1, 1992·Annals of the Rheumatic Diseases·M Salazar-PáramoI García-De La Torre
Feb 1, 1991·Chest·M A SteeleR M DesPrez
Nov 1, 1985·Clinical Pharmacology and Therapeutics·B H LauterburgJ R Mitchell
Jul 1, 1973·Annals of Internal Medicine·W C Maddrey, J K Boitnott
Nov 1, 1973·Annals of Internal Medicine·T L BadgerW R Starke
Mar 27, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yi-Shin HuangShou-Dong Lee
Oct 3, 2002·American Journal of Respiratory and Critical Care Medicine·Surendra K SharmaNarinder K Mehra
Apr 2, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yi-Shin HuangShou-Dong Lee
Apr 5, 2005·Toxicologic Pathology·Paul B Watkins
Aug 2, 2006·Annual Review of Pharmacology and Toxicology·Jack Uetrecht
Apr 10, 2008·Liver International : Official Journal of the International Association for the Study of the Liver·Virginia LeiroArturo González-Quintela
Jun 3, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Shintaro NakayamaOsamu Okazaki
Jul 20, 2010·Nature Genetics·Jonathan B SingerCharles A Paulding
Dec 1, 2010·Cytokine & Growth Factor Reviews·Robert SabatJens Geginat
Jan 5, 2011·Clinical & Developmental Immunology·Linda HammerichFrank Tacke
Mar 18, 2011·Clinical Pharmacology and Therapeutics·I G MetushiJ P Uetrecht
Sep 20, 2011·The Journal of Allergy and Clinical Immunology·Tai-Ming KoShuen-Iu Hung
Dec 14, 2011·Liver International : Official Journal of the International Association for the Study of the Liver·Sang-Heon KimYoung-Koo Jee
Jun 19, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Imir G MetushiJack Uetrecht
Oct 24, 2013·Molecular and Cellular Biochemistry·Imir G Metushi, Jack Uetrecht
Dec 7, 2013·Journal of Immunotoxicology·Imir G Metushi, Jack Uetrecht
Mar 7, 2014·Journal of the Chinese Medical Association : JCMA·Yi-Shin Huang
Mar 14, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Imir G MetushiJack Uetrecht
May 3, 2014·Chemical Research in Toxicology·Imir G MetushiJack Uetrecht
May 23, 2014·Toxicological Sciences : an Official Journal of the Society of Toxicology·Rachel J ChurchAlison H Harrill
Jun 10, 2014·Proceedings of the National Academy of Sciences of the United States of America·Douglas G MackAndrew P Fontenot
Oct 7, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Imir G MetushiJack Uetrecht
Nov 12, 2014·Annual Review of Medicine·Rebecca PavlosElizabeth Phillips
Dec 10, 2014·Chemical Research in Toxicology·Xiaoli MengB Kevin Park
Mar 11, 2015·Gastroenterology·Naga ChalasaniUNKNOWN United States Drug Induced Liver Injury Network
Aug 9, 2015·The Journal of Allergy and Clinical Immunology·Katie D WhiteElizabeth J Phillips

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Citations

Aug 18, 2016·Drug Metabolism Reviews·Jinping GanDonglu Zhang
Oct 25, 2016·Chemical Research in Toxicology·Tiffany Cho, Jack Uetrecht
Mar 28, 2017·British Journal of Clinical Pharmacology·Sarah L GaronElizabeth J Phillips
Mar 16, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Christine M HuntArie Regev
Jun 16, 2017·Gene Regulation and Systems Biology·Lisl Km ShodaBrett A Howell
Dec 19, 2016·Advances in Pharmacological Sciences·Zanelle BekkerJan B Du Plessis
Dec 5, 2018·Journal of Biomaterials Applications·Gangquan ChenChao Zhang
Mar 4, 2020·Acta Pharmacologica Sinica·Tai RaoDong-Sheng Ou-Yang
Aug 14, 2019·Frontiers in Pharmacology·Jack Uetrecht
Nov 23, 2018·Current Pharmacology Reports·Yifan BaoXiao-Bo Zhong
Feb 23, 2020·Frontiers in Pharmacology·Siyu FuTaoyou Zhou
Sep 15, 2020·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Yuli L HsiehAmber Kunkel
Aug 28, 2020·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Muhammed Shiraz MoosaKaren Cohen
May 12, 2019·Tuberculosis·Emily R ErwinRosemarie C Rosell
Nov 13, 2020·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Yuli L HsiehAmber Kunkel
May 1, 2021·International Journal of Molecular Sciences·Alessio GerussiPietro Invernizzi
Feb 25, 2017·Microbiology Spectrum·G Shelton McMullan, James H Lewis
Jul 25, 2021·International Journal of Environmental Research and Public Health·Makhliyo AbdusalomovaAbduvohid Sodikov
Jun 23, 2021·Journal of Clinical Pharmacology·Yong-Soon ChoUNKNOWN Center for Personalized Precision Medicine of Tuberculosis
Feb 23, 2021·Canadian Journal of Physiology and Pharmacology·Sukumaran SanjayZachariah Bobby
Sep 10, 2019·Journal of Medicinal Chemistry·Amit S Kalgutkar
Sep 28, 2017·Chemical Research in Toxicology·Chaitanya K JaladankiPrasad V Bharatam
Sep 18, 2021·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Joseph William ClintonJames H Lewis

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