Clinical Perspectives of Isoniazid-induced Liver Injury

Overview

Journal Liver Res

Date 2025 Feb 17

PMID 39959342

Authors

Saifei Lei

Ruizhi Gu

Xiaochao Ma

Affiliations

Soon will be listed here.

Abstract

Isoniazid (INH) is a synthetic anti-mycobacterial agent used to treat active or latent tuberculosis (TB). INH has been in clinical use for nearly 70 years and remains broadly utilized at the front line of anti-TB treatment. However, the potential for liver damage and even fulminant liver failure during INH-based TB treatment presents a major challenge for TB control programs worldwide. In this review, we discuss the hepatotoxic effects of INH and provide an overview of the mechanisms and their applications in prediction and prevention of INH hepatotoxicity in clinical practice.

Citing Articles

Drug-Induced Liver Injury-Pharmacological Spectrum Among Children.

Maris B, Grama A, Pop T Int J Mol Sci. 2025; 26(5).

PMID: 40076629 PMC: 11901067. DOI: 10.3390/ijms26052006.

References

Perez-Barriocanal F, VILLANUEVA G, Arteche E, Berenson M, Marin J . Protoporphyrin IX-induced impairment of biliary lipid secretion in the rat. Clin Sci (Lond). 1989; 77(5):473-8. DOI: 10.1042/cs0770473. View

Xiang Y, Ma L, Wu W, Liu W, Li Y, Zhu X . The incidence of liver injury in Uyghur patients treated for TB in Xinjiang Uyghur autonomous region, China, and its association with hepatic enzyme polymorphisms nat2, cyp2e1, gstm1 and gstt1. PLoS One. 2014; 9(1):e85905. PMC: 3900431. DOI: 10.1371/journal.pone.0085905. View

Chini E, Chini C, Espindola Netto J, de Oliveira G, van Schooten W . The Pharmacology of CD38/NADase: An Emerging Target in Cancer and Diseases of Aging. Trends Pharmacol Sci. 2018; 39(4):424-436. PMC: 5885288. DOI: 10.1016/j.tips.2018.02.001. View

Vilcheze C, Jacobs Jr W . The mechanism of isoniazid killing: clarity through the scope of genetics. Annu Rev Microbiol. 2007; 61:35-50. DOI: 10.1146/annurev.micro.61.111606.122346. View

Richards V, Chau B, White M, McQueen C . Hepatic gene expression and lipid homeostasis in C57BL/6 mice exposed to hydrazine or acetylhydrazine. Toxicol Sci. 2004; 82(1):318-32. DOI: 10.1093/toxsci/kfh232. View

Saukkonen J, Cohn D, Jasmer R, Schenker S, Jereb J, Nolan C . An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med. 2006; 174(8):935-52. DOI: 10.1164/rccm.200510-1666ST. View

Fountain F, Tolley E, Chrisman C, Self T . Isoniazid hepatotoxicity associated with treatment of latent tuberculosis infection: a 7-year evaluation from a public health tuberculosis clinic. Chest. 2005; 128(1):116-23. DOI: 10.1378/chest.128.1.116. View

Yamada S, Richardson K, Tang M, Halaschek-Wiener J, Cook V, Fitzgerald J . Genetic variation in carboxylesterase genes and susceptibility to isoniazid-induced hepatotoxicity. Pharmacogenomics J. 2010; 10(6):524-36. DOI: 10.1038/tpj.2010.5. View

Tafazoli S, Mashregi M, OBrien P . Role of hydrazine in isoniazid-induced hepatotoxicity in a hepatocyte inflammation model. Toxicol Appl Pharmacol. 2008; 229(1):94-101. DOI: 10.1016/j.taap.2008.01.002. View

10.

Wang P, Xie S, Hao Q, Zhang C, Jiang B . NAT2 polymorphisms and susceptibility to anti-tuberculosis drug-induced liver injury: a meta-analysis. Int J Tuberc Lung Dis. 2012; 16(5):589-95. DOI: 10.5588/ijtld.11.0377. View

11.

Kim S, Kim S, Yoon H, Shin D, Park S, Kim Y . TNF-α genetic polymorphism -308G/A and antituberculosis drug-induced hepatitis. Liver Int. 2011; 32(5):809-14. DOI: 10.1111/j.1478-3231.2011.02697.x. View

12.

Li F, Miao Y, Zhang L, Neuenswander S, Douglas J, Ma X . Metabolomic analysis reveals novel isoniazid metabolites and hydrazones in human urine. Drug Metab Pharmacokinet. 2011; 26(6):569-76. DOI: 10.2133/dmpk.DMPK-11-RG-055. View

13.

Hayashi P, Fontana R, Chalasani N, Stolz A, Talwalkar J, Navarro V . Under-reporting and Poor Adherence to Monitoring Guidelines for Severe Cases of Isoniazid Hepatotoxicity. Clin Gastroenterol Hepatol. 2015; 13(9):1676-82.e1. PMC: 4653068. DOI: 10.1016/j.cgh.2015.02.024. View

14.

. Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. International Union Against Tuberculosis Committee on Prophylaxis. Bull World Health Organ. 1982; 60(4):555-64. PMC: 2536088. View

15.

Kaplowitz N . Drug-induced liver injury. Clin Infect Dis. 2004; 38 Suppl 2:S44-8. DOI: 10.1086/381446. View

16.

Sachar M, Anderson K, Ma X . Protoporphyrin IX: the Good, the Bad, and the Ugly. J Pharmacol Exp Ther. 2015; 356(2):267-75. PMC: 4727154. DOI: 10.1124/jpet.115.228130. View

17.

Boelsterli U, Lim P . Mitochondrial abnormalities--a link to idiosyncratic drug hepatotoxicity?. Toxicol Appl Pharmacol. 2007; 220(1):92-107. DOI: 10.1016/j.taap.2006.12.013. View

18.

Warrington R, Tse K, Gorski B, Schwenk R, Sehon A . Evaluation of isoniazid-associated hepatitis by immunological tests. Clin Exp Immunol. 1978; 32(1):97-104. PMC: 1541309. View

19.

Attri S, Rana S, Vaiphei K, Sodhi C, Katyal R, Goel R . Isoniazid- and rifampicin-induced oxidative hepatic injury--protection by N-acetylcysteine. Hum Exp Toxicol. 2001; 19(9):517-22. DOI: 10.1191/096032700674230830. View

20.

Ohkura K, Fukino K, Shinohara Y, Hori H . N-acetyl transferase 2 polymorphisms associated with isoniazid pharmacodynamics: molecular features for ligand interaction. Anticancer Res. 2010; 30(8):3177-80. View