Incidence and characteristics of antituberculosis drug-induced hepatotoxicity in children: a preliminary study
Abstract
Background Antituberculosis drugs show good efficacy but have adverse effects including hepatotoxicity.
Objective To find the incidence and characteristics of antituberculosis hepatotoxicity in children during the first 2 weeks of therapy.
Methods A cohort study was performed in Cipto Mangunkusumo, Persahabatan, and Tangerang Hospitals from August 2008 toMarch 2009. The diagnosis of tuberculosis (TB) based on TB scoring system. Laboratory tests were performed including transaminase enzymes, bilirubin, y-GT, albumin, ureum, and creatinine before and after 2 weeks of treatment. Patients were monitored during the first 2 weeks of therapy. Informed consent obtained from the parents.
Results Six of 81 subjects had hepatotoxicity reaction. Most of the patients were 1 to 5 years old (65%) and well nourished (50%). Extrapulmonary tuberculosis found in 67% of cases. Thirty-three percents of patients received four agents. Thirty-three percents of cases received 4 agents combined with other hepatotoxic drugs. Six subjects had hepatotoxicity (1 hepatitis, 2 mixed case, and 3 asymptomatic). Two of 50 children (4%) with pulmonary TB and 4 out of 31 ( 13%) children with extrapulmonary TB had hepatotoxicity reaction. Antituberculosis drug doses were similar between the hepatotoxicity group and control.
Conclusions Incidence of antituberculosis hepatotoxicity in the
first 2 weeks of therapy was 7%, consisted of hepatitis (1 cases), mixed (2 cases), and asymptomatic (3 cases). There was no difference in sex as well as in nutritional state distribution found in cases with hepatotoxicity.
References
2. Shakya R, Rao BS, Shrestha B. Incidence of hepatotoxicity due to antitubercular medicines and assessment of risk factors. Ann Pharmacother. 2004;38: 1074-9.
3. Navarro VJ, Senior JR. Drug-related hepatotoxicity. N Engl J Med. 2006;354:731-9.
4. Fernandez-Villar A, Sopena B, Fernandez-Villar J, VazquezGallardo R, Ulloa F, Leiro V, et al. The influence of risk factors on the severity of anti-tuberculosis drug-induced hepatotoxicity. Int J Tuberc Lung Dis. 2004;8: 1499-1505.
5. Ohkawa K, Hashiguchi M, Ohno K, Kiuchi C, Takahashi S, Kondo S, et al. Risk factors for antituberculosis chemotherapy-induced hepatotoxicity in Japanese pediatric subjects. Clin Pharmacal Ther. 2002;72:220-6.
6. Corrigan D, Paton J. Hepatic enzyme abnormalities in children on triple therapy for tuberculosis. Pediatr Pulmonol. 1999;27:37-42.
7. Durand F, Jebrak G, Pessayre D, Fournier M, Bernuau J. Hepatotoxicity of antitubercular treatments: rationale for monitoring liver status. Drug Saf. 1996; 15:394-405.
8. Thompson NP, Caplin ME, Hamilton MI, Gillespie SH, Clarke SW, Burroughs AK, et al. Antituberculosis medication and the liver: dangers and recommendations in management. Eur Respir J. 1995;8: 1384-8.
9. Chang KC, Leung CC, Yew WW, Tam CM. Standard anti-tuberculosis treatment and hepatotoxicity: do dosing schedules matter? Eur Respir ]. 2007;29:347-51.
10. Mahmood K, Hussain A, Jairamani KL, Talib A, Abbasi B, Salkeen S. Hepatotoxicity with antituberculosis drugs: the risks factors. Pak J Med Sci. 2007 ;23:33-8.
11. Schaberg T, Rebhan K, Lode H. Risk factors for side-effects of isoniazid, rifampin and pyrazinamide in subjects hospitalized for pulmonary tuberculosis. Eur Respir J. 1996;9:2026-30.
12. Ungo JR, Jones D, Ashkin D, Hollender ES, Bernstein D, Albanese AP, et al. Antituberculosis drug-induced hepatotoxicity. Am J Respir Crit Care Med. 1998; 157:1871-6.
13. Dossing, Wilcke JT, Askgaard DS, Nybo B. Liver injury during antituberculosis treatment: an 11-year study. [Abstract]. Tuber Lung Dis. 1996;77:335-40.
14. Black M, Mitchell JR, Zimmerman HJ, Ishak KG, Epler GR. Isoniazid-associated hepatitis in 114 patients. [Abstract]. Gastroenterol. 1975;69:289-302.
15. Pande JN, Singh SF, Khilnani GC, Khilnani S, Tandon RK. Risks factors for hepatotoxicity from antituberculosis drugs: a case-control study. Thorax. 1996;51: 132-6.
16. Singh J, Arora A, Garg PK, Thakur VS, Pande JN, Tandon RK. Antituberculosis treatment-induced hepatotoxicity: role of predictive factors. J Postgrad Med. 1995;71:359-62.
17. Smink F, Hoek v, Ringers J, Altena RV, Arend SM. Risk factors of acute hepatic failure during antituberculosis treatment: two cases and literature reviews. Neth J Med. 2006;64: 377-84.
18. Hwang SJ, Wu JC, Lee CN, Yen FS, Lu CL, Lin TP, et al. A prospective clinical study of isoniazid-rifampisinpyrazinamide-induc ed liver injury in area endemic for hepatitis B. [Abstract]. J Gastroenterol Hepatol. 1997; 12:87-91.
19. Madiyono B, Moeslichan S, Sastroasmoro S, Budiman I, Purwanto SH. Perkiraan besar sampel. In: Sastroasmoro S, Ismael S, editors. Dasar- dasar metodologi penelitian. 2nd ed. Jakarta: Sagung Seto, 2002; p. 259-286.
20. Oswari H. Penyakit hati akibat obat (PHAO) pada anak. Proceeding of znd Pediatric Gastroenterology National Congress; 2003 July 3-5; Bandung.
21. Oswari H. Kolestasis: atresia bilier dan sindrom hepatitis neonatal. In: Hadinegoro SR, Prawitasari T, Endyarni B, Kadim M, Sjakti HA, editors. Diagnosis dan tata laksana penyakit anak dengan gejala kuning. Proceeding of Continuing Medical Education, Department of Child Health,
University of Indonesia; 2007 Nov 12-13; Jakarta. Jakarta: Department of Child Health, University of Indonesia, 2007; p. 42-54.
22. Tsagaropoulou-stinga H, Mataki-emmanouilidou T, Karidakavalioti
S, Manios S. Hepatotoxic reactions in children with severe tuberculosis treated with isoniazid-rifampin. Pediatr Infect Dis. 1985;4:270-3.
23. O'Brien RJ, Long MW, Cross FS, Lyle MA, Snider DE. Hepatotoxicity from isoniazid and rifampin among children treated for tuberculosis. Pediatrics. 1983;72:491-9.
24. World Health Organization. Guidance for national tuberculosis programmes on the management of tuberculosis in children [homepage on internet]. c2006. Available from: http://www.who.int/child adolescent_ health/documents/htm _ tb 2006 3 71/en/index.html
25. Ramachandran P. Chemotherapy of tuberculosis meningitis with isoniazid plus rifampicin-interim findings in a trial in children. Indian] Tuberc. 1979;27:54-7.
26. Palusci VJ, O'Hare D, Lawrence RM. Hepatotoxicity and transaminase measurement during isoniazid chemoprophilaxis in children. Pediatr Infect Dis]. 1995; 14:144-8.
2 7. Steele MA, Burk RF, DesPrez RM. Toxic hepatitis with isoniazid and rifampin: a meta-analysis. Chest. 1991 ;99:465-71.
28. Rahajoe NN, Rahajoe N, Boediman I, Said M, Lazuardi S. The treatment of tuberculous meningitis in children with a combination of isoniazid, rifampisin and streptomycin-preliminary report. Tubercle. 1979;60:245-50.
29. Teleman MD, Chee CBE, Earnest A, Wang YT. Hepatotoxicity of tuberculosis chemotherapy under general programme conditions in Singapore. Int J Tuberc Lung Dis. 2002;8:699-705.
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Accepted 2016-09-12
Published 2009-12-31
