DOI QR코드

DOI QR Code

Early monitoring for detection of antituberculous drug-induced hepatotoxicity

  • Lee, Chang Min (Department of Internal Medicine, Gyeongsang National University Hospital) ;
  • Lee, Sang Soo (Department of Internal Medicine, Gyeongsang National University Hospital) ;
  • Lee, Jeong Mi (Department of Internal Medicine, Gyeongsang National University Hospital) ;
  • Cho, Hyun Chin (Department of Internal Medicine, Gyeongsang National University Hospital) ;
  • Kim, Wan Soo (Department of Internal Medicine, Gyeongsang National University Hospital) ;
  • Kim, Hong Jun (Department of Internal Medicine, Gyeongsang National University Hospital) ;
  • Ha, Chang Yoon (Department of Internal Medicine, Gyeongsang National University Hospital) ;
  • Kim, Hyun Jin (Department of Internal Medicine, Gyeongsang National University Hospital) ;
  • Kim, Tae Hyo (Department of Internal Medicine, Gyeongsang National University Hospital) ;
  • Jung, Woon Tae (Department of Internal Medicine, Gyeongsang National University Hospital) ;
  • Lee, Ok Jae (Department of Internal Medicine, Gyeongsang National University Hospital)
  • Received : 2014.12.19
  • Accepted : 2015.05.11
  • Published : 2016.01.01

Abstract

Background/Aims: We investigated the time of onset of antituberculous drug-induced hepatotoxicity (ADIH) and related characteristics. Methods: Adult patients (n = 1,031) treated with first-line antituberculous drugs between February 2009 and January 2013 were enrolled. Results: Of the 1,031 patients, 108 patients (10.5%) developed ADIH a mean of $39.6{\pm}43.7$ days after treatment initiation. Twenty-eight patients (25.9%) developed ADIH within 7 days, 73 (67.6%) within 30 days, and the rest after 30 days. The ${\leq}30-day$ group was characterized by higher peak alanine aminotransferase (ALT) level and a high proportion of patients with maintenance of first-line antituberculous drugs compared to the > 30-day group. In subgroup analysis, the ${\leq}7-day$ group was characterized by higher baseline aspartate aminotransferase and ALT, high proportion of patients with maintenance of first-line antituberculous drugs, and high proportion of patients with extrapulmonary tuberculosis compared to patients with ADIH that developed beyond 7 days. In multivariate analysis, serum ALT > 40 IU/L (odds ratio [OR], 2.995; 95% confidence interval [CI], 1.580 to 5.680; p = 0.001) and presence of anti-hepatitis C virus (OR, 4.204; 95% CI, 1.822 to 9.700, p = 0.001) were independent risk factors for development of ADIH. Conclusions: Approximately 70% of the cases of ADIH occurred in the first month of antituberculous treatment, and were associated with continuation of the first-line drug regimen.

Keywords

References

  1. World Health Organization. Global tuberculosis report 2013 [Internet]. Geneva: World Health Organizaton, 2013 [cited 2015 Sep 10]. Available from: http://apps.who.int/iris/bitstream/10665/91355/1/9789241564656_eng.pdf.
  2. National Collaborating Centre for Chronic Conditions (UK); Centre for Clinical Practice at NICE (UK). Tuberculosis: clinical diagnosis and management of tuberculosis, and measures for its prevention and control. London: National Institute for Health and Clinical Excellence (NICE), 2011.
  3. Hovell MF, Sipan CL, Blumberg EJ, et al. Increasing Latino adolescents' adherence to treatment for latent tuberculosis infection: a controlled trial. Am J Public Health 2003;93:1871-1877. https://doi.org/10.2105/AJPH.93.11.1871
  4. Gangadharam PR. Isoniazid, rifampin, and hepatotoxicity. Am Rev Respir Dis 1986;133:963-965.
  5. Schaberg T, Rebhan K, Lode H. Risk factors for side-effects of isoniazid, rifampin and pyrazinamide in patients hospitalized for pulmonary tuberculosis. Eur Respir J 1996;9:2026-2030. https://doi.org/10.1183/09031936.96.09102026
  6. Yew WW, Leung CC. Antituberculosis drugs and hepatotoxicity. Respirology 2006;11:699-707. https://doi.org/10.1111/j.1440-1843.2006.00941.x
  7. Shang P, Xia Y, Liu F, et al. Incidence, clinical features and impact on anti-tuberculosis treatment of anti-tuberculosis drug induced liver injury (ATLI) in China. PLoS One 2011;6:e21836. https://doi.org/10.1371/journal.pone.0021836
  8. Sun HY, Chen YJ, Gau CS, Chang SC, Luh KT. A prospective study of hepatitis during antituberculous treatment in Taiwanese patients and a review of the literature. J Formos Med Assoc 2009;108:102-111. https://doi.org/10.1016/S0929-6646(09)60040-1
  9. Makhlouf HA, Helmy A, Fawzy E, El-Attar M, Rashed HA. A prospective study of antituberculous drug-induced hepatotoxicity in an area endemic for liver diseases. Hepatol Int 2008;2:353-360. https://doi.org/10.1007/s12072-008-9085-y
  10. Lorent N, Sebatunzi O, Mukeshimana G, Van den Ende J, Clerinx J. Incidence and risk factors of serious adverse events during antituberculous treatment in Rwanda: a prospective cohort study. PLoS One 2011;6:e19566. https://doi.org/10.1371/journal.pone.0019566
  11. Saukkonen JJ, Cohn DL, Jasmer RM, et al. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med 2006;174:935-952. https://doi.org/10.1164/rccm.200510-1666ST
  12. Ormerod LP, Skinner C, Wales J. Hepatotoxicity of antituberculosis drugs. Thorax 1996;51:111-113. https://doi.org/10.1136/thx.51.2.111
  13. Senaratne WV, Pinidiyapathirage MJ, Perera GA, Wick-remasinghe AR. Anti-tuberculosis drug inducd hepatitis - a Sri Lankan experience. Ceylon Med J 2006;51:9-14.
  14. Baghaei P, Tabarsi P, Chitsaz E, et al. Incidence, clinical and epidemiological risk factors, and outcome of drug-induced hepatitis due to antituberculous agents in new tuberculosis cases. Am J Ther 2010;17:17-22. https://doi.org/10.1097/MJT.0b013e31818f9eae
  15. Singanayagam A, Sridhar S, Dhariwal J, et al. A comparison between two strategies for monitoring hepatic function during antituberculous therapy. Am J Respir Crit Care Med 2012;185:653-659. https://doi.org/10.1164/rccm.201105-0850OC
  16. World Health Organization. Treatment of Tuberculosis: Guidelines. 4th ed. Geneva: World Health Organization, 2010.
  17. Yee D, Valiquette C, Pelletier M, Parisien I, Rocher I, Menzies D. Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis. Am J Respir Crit Care Med 2003;167:1472-1477. https://doi.org/10.1164/rccm.200206-626OC
  18. Agal S, Baijal R, Pramanik S, et al. Monitoring and management of antituberculosis drug induced hepatotoxicity. J Gastroenterol Hepatol 2005;20:1745-1752. https://doi.org/10.1111/j.1440-1746.2005.04048.x
  19. McNeill L, Allen M, Estrada C, Cook P. Pyrazinamide and rifampin vs isoniazid for the treatment of latent tuberculosis: improved completion rates but more hepatotoxicity. Chest 2003;123:102-106. https://doi.org/10.1378/chest.123.1.102
  20. Chang KC, Leung CC, Yew WW, Lau TY, Tam CM. Hepatotoxicity of pyrazinamide: cohort and case-control analyses. Am J Respir Crit Care Med 2008;177:1391-1396. https://doi.org/10.1164/rccm.200802-355OC
  21. Teleman MD, Chee CB, Earnest A, Wang YT. Hepatotoxicity of tuberculosis chemotherapy under general programme conditions in Singapore. Int J Tuberc Lung Dis 2002;6:699-705.
  22. Huang YS, Chern HD, Su WJ, et al. Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis. Hepatology 2003;37:924-930. https://doi.org/10.1053/jhep.2003.50144
  23. Gulbay BE, Gurkan OU, Yildiz OA, et al. Side effects due to primary antituberculosis drugs during the initial phase of therapy in 1149 hospitalized patients for tuberculosis. Respir Med 2006;100:1834-1842. https://doi.org/10.1016/j.rmed.2006.01.014
  24. Lomtadze N, Kupreishvili L, Salakaia A, et al. Hepatitis C virus co-infection increases the risk of anti-tuberculosis drug-induced hepatotoxicity among patients with pulmonary tuberculosis. PLoS One 2013;8:e83892. https://doi.org/10.1371/journal.pone.0083892
  25. Liu YM, Cheng YJ, Li YL, Liu CE, Hsu WH. Antituberculosis treatment and hepatotoxicity in patients with chronic viral hepatitis. Lung 2014;192:205-210. https://doi.org/10.1007/s00408-013-9535-8

Cited by

  1. Clinical features and outcomes of abdominal tuberculosis in southeastern Korea: 12 years of experience vol.18, pp.None, 2016, https://doi.org/10.1186/s12879-018-3635-2
  2. Management of adverse reactions to first-line tuberculosis antibiotics vol.18, pp.4, 2016, https://doi.org/10.1097/aci.0000000000000462
  3. Prophylactic Therapy of Silymarin (Milk Thistle) on Antituberculosis Drug-Induced Liver Injury: A Meta-Analysis of Randomized Controlled Trials vol.2019, pp.None, 2019, https://doi.org/10.1155/2019/3192351
  4. The clinical impact of drug-induced hepatotoxicity on anti-tuberculosis therapy: a case control study vol.20, pp.1, 2016, https://doi.org/10.1186/s12931-019-1256-y