The Indian Journal of Pediatrics

, Volume 86, Issue 3, pp 211–213 | Cite as

Association between ATT and Hepatotoxicity: Food for Thought

  • Joseph L. MathewEmail author
Editorial Commentary

It is well known that anti tuberculosis therapy (ATT) is associated with the risk of hepatotoxicity in adults as well as children. This may range from mild asymptomatic elevations of liver enzymes to more serious hepatic injury including acute liver failure. In a series from Brazil, 10% of 81 liver transplants for acute liver failure (over a 10 y period) were related to ATT [1]. Among the ATT agents, Isoniazid is the most frequent culprit, followed by Rifampicin and Pyrazinamide. In fact, a unique experiment wherein patients with drug sensitive TB received rifampicin for 2 wk in doses as high as 20, 25, 30, or 35 mg/kg, (in addition to standard doses of other drugs) showed similar frequency of adverse events compared to the standard 10 mg/kg and only one episode of hepatotoxicity [2]. Investigations of alternate treatment regimens replacing isoniazid with moxifloxacin (in adults) showed higher incidence of hepatic injury, greater peak enzyme levels, and earlier onset of hepatotoxicity...



  1. 1.
    Martino RB, Abdala E, Villegas FC, D'Albuquerque LAC, Song ATW. Liver transplantation for acute liver failure due to antitubercular drugs – a single-center experience. Clinics (Sao Paulo). 2018;73:e344.Google Scholar
  2. 2.
    Boeree MJ, Diacon AH, Dawson R, et al. A dose-ranging trial to optimize the dose of rifampin in the treatment of tuberculosis. Am J Respir Crit Care Med. 2015;191:1058–65.CrossRefGoogle Scholar
  3. 3.
    Tweed CD, Wills GH, Crook AM, et al. Liver toxicity associated with tuberculosis chemotherapy in the REMoxTB study. BMC Med. 2018;16:46.Google Scholar
  4. 4.
    Abbara A, Chitty S, Roe JK, et al. Drug-induced liver injury from antituberculous treatment: a retrospective study from a large TB Centre in the UK. BMC Infect Dis. 2017;17:231.Google Scholar
  5. 5.
    Singla R, Sharma SK, Mohan A, et al. Evaluation of risk factors for antituberculosis treatment induced hepatotoxicity. Indian J Med Res. 2010;132:81–6.Google Scholar
  6. 6.
    Li Y, Zhu Y, Zhong Q, Zhang X, Shu M, Wan C. Serious adverse reactions from anti-tuberculosis drugs among 599 children hospitalized for tuberculosis. Pediatr Infect Dis J. 2017;36:720–5.Google Scholar
  7. 7.
    Aishatu G, Rasheedah I, Wahab J, Sheni M, Damilola O, Adeniyi O. Hepatotoxicity due to antituberculosis therapy among paediatric patients seen at the University of Ilorin Teaching Hospital, North Central Nigeria. Ethiop J Health Sci. 2017;27:115–20.Google Scholar
  8. 8.
    Leeb S, Buxbaum C, Fischler B. Elevated transaminases are common in children on prophylactic treatment for tuberculosis. Acta Paediatr. 2015;104:479–84.Google Scholar
  9. 9.
    World Health Organization. Guidance for National Tuberculosis Programmes on the Management of Tuberculosis in Children. Available at: Accessed 12th January 2019.
  10. 10.
    Jeong I, Park JS, Cho YJ, et al. Drug-induced hepatotoxicity of anti-tuberculosis drugs and their serum levels. J Korean Med Sci. 2015;30:167–72.CrossRefGoogle Scholar
  11. 11.
    Guaoua S, Ratbi I, El Bouazzi O, et al. NAT2 genotypes in Moroccan patients with hepatotoxicity due to antituberculosis drugs. Genet Test Mol Biomarkers. 2016;20:680–4.Google Scholar
  12. 12.
    Ben Fredj N, Gam R, Kerkni E, et al. Risk factors of isoniazid-induced hepatotoxicity in Tunisian tuberculosis patients. Pharmacogenomics J. 2017;17:372–7.CrossRefGoogle Scholar
  13. 13.
    Zazuli Z, Barliana MI, Mulyani UA,  et al. Polymorphism of PXR gene associated with the increased risk of drug-induced liver injury in Indonesian pulmonary tuberculosis patients. J Clin Pharm Ther. 2015;40:680–4.Google Scholar
  14. 14.
    Sharma SK, Jha BK, Sharma A, et al. Genetic polymorphisms of CYP2E1 and GSTM1 loci and susceptibility to anti-tuberculosis drug-induced hepatotoxicity. Int J Tuberc Lung Dis. 2014;18 : 588–93.Google Scholar
  15. 15.
    Indumathi CK, Sethuraman A, Jain S, Krishnamurthy S. Revised antituberculosis drug doses and hepatotoxicity in HIV negative children. Indian J Pediatr. 2018.
  16. 16.
    Wu S, Xia Y, Lv X, et al. Effect of scheduled monitoring of liver function during anti-tuberculosis treatment in a retrospective cohort in China. BMC Public Health. 2012;12:454.Google Scholar
  17. 17.

Copyright information

© Dr. K C Chaudhuri Foundation 2019

Authors and Affiliations

  1. 1.Department of PediatricsAdvanced Pediatrics Centre, PGIMERChandigarhIndia

Personalised recommendations