Sex, ethnicity, and slow acetylator profile are the major causes of hepatotoxicity induced by antituberculosis drugs
Article first published online: 22 JAN 2013
© 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd
Journal of Gastroenterology and Hepatology
Volume 28, Issue 2, pages 323–328, February 2013
How to Cite
Chamorro, J. G., Castagnino, J. P., Musella, R. M., Nogueras, M., Aranda, F. M., Frías, A., Visca, M., Aidar, O., Perés, S. and de Larrañaga, G. F. (2013), Sex, ethnicity, and slow acetylator profile are the major causes of hepatotoxicity induced by antituberculosis drugs. Journal of Gastroenterology and Hepatology, 28: 323–328. doi: 10.1111/jgh.12069
- Issue published online: 22 JAN 2013
- Article first published online: 22 JAN 2013
- Accepted manuscript online: 28 NOV 2012 07:28AM EST
- Manuscript Accepted: 4 OCT 2012
- National Ministry of Health
- arylamine N-acetyltransferase 2;
- cytochrome P450 2E1;
- drug toxicity;
Background and Aim
Treatment with antituberculosis (TB) drugs produces liver damage in a large proportion of patients. Isoniazid, an antibacterial drug, is primarily responsible for this hepatotoxicity. Several polymorphisms of the N-acetyltransferase 2 (NAT-2) and cytochrome P450 2E1 enzymes, which are involved in the metabolism of isoniazid, may be directly associated with the development of hepatotoxicity. This study was designed to analyze the association between the NAT-2 and CYP2E1 polymorphisms with the development of anti-TB drug-induced hepatotoxicity (ATDH).
One hundred and seventy-five TB patients who had been treated with anti-TB drugs were studied. The allelic and genotypic frequency distributions of the NAT-2 and CYP2E1 enzymes were studied using polymerase chain reaction–restriction fragment length polymorphisms methodology. A binary logistic regression analysis was used to compare the results between TB patients with and without the development of hepatotoxicity.
Having a slow acetylator status (odds ratio [OR] = 2.615; confidence interval [CI] = 1.264–5.411; P = 0.01), being female (OR = 2.734; CI = 1.325–5.639, P = 0.006), and having Bolivian ethnicity (OR = 2.711; CI = 1.307–6.625, P = 0.007) were found to be independent predictor variables for ATDH.
This study showed that a patient's NAT-2 acetylator status, gender, and ethnic origin may be regarded as important risk factors for developing hepatotoxicity. Contrary to expectations, the CYP2E1 c1/c2 polymorphism did not show a significant association with hepatotoxicity in this study. Given the increases in TB cases and ATDH incidence levels, as well as the associated hospitalization costs, it may also be helpful to know patients’ acetylator status prior to or at the beginning of the TB treatment regimen.