Incidence, outcomes, and risk factors of antituberculosis drugs induced liver injury in Thailand: A retrospective cohort study

Main Article Content

Pattaraporn Akkahadsee https://orcid.org/0009-0002-4105-8850
Sirot Jantharaksa https://orcid.org/0009-0007-2919-0409
Ratree Sawangjit https://orcid.org/0000-0002-6868-4336
Panumart Phumart https://orcid.org/0000-0002-6868-4336

Keywords

tuberculosis, drug-induced liver injury, hepatotoxicity, risk factors

Abstract

Background: Tuberculosis (TB) is a persistent health concern in numerous regions, including Thailand. The adverse effects of tuberculosis (TB) treatments, particularly liver injuries, can complicate treatment protocols, thereby increasing the likelihood of treatment discontinuation and the risk of subsequent drug resistance. Objective: This study was conducted to investigate the incidence, predisposing factors, and treatment outcomes associated with antituberculosis drugs induced liver injury (ATDILI) in Northeastern Thailand. Methods: A retrospective analysis was conducted at Mahasarakham Hospital in 2019. Patient data were retrieved from hospital records and databases. Inclusion criteria included receiving a first-time TB diagnosis, starting a standard TB regimen, and having normal liver function. To compare baseline characteristics between ATDILI patients and controls, Chi-square tests and T-tests were used. Bivariate and multivariable regression analyses were conducted to identify factors associated with drug-induced hepatitis. Results: 346 of 602 TB patients (57.5%) were enrolled. The study found an incidence of ATDILI at 14.45% (50 cases), which is notably higher than the Thai average of 4.8%. Risk factors were identified as malnutrition (adjusted OR=6.71, 95%CI 3.11:14.45), concurrent diseases (adjusted OR=2.42, 95%CI 1.20:4.89), and alcohol consumption (adjusted OR=4.24, 95%CI 1.45:12.38). In terms of therapeutic outcomes, only 18 patients were cured (36.0%). The probability of hepatotoxic events was addressed during the initial treatment phase, emphasizing the critical need for rigorous liver function monitoring during the first month of TB therapy. The ATDILI group had a mortality rate of 16%, which was higher than the national TB-related average of 8.2%. Conclusion: The marked presence of ATDILI in the cohort under study accentuates the immediate need for enhanced clinical monitoring, especially among susceptible groups. It is imperative to implement strategies aimed at early detection, prompt intervention, and holistic management of ATDILI, complemented by endeavors to boost cure rates for the affected population.

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References

1. World Health Organization. Global tuberculosis report. 2022:68.
2. World Health Organization. Guidelines for treatment of drug-susceptible tuberculosis and patient care, 2017 update. 2017.
3. Bureau of Tuberculosis DoDC, Ministry of Public Health. National Tuberculosis control Programme Guidelines, Thailand, 2018. Aksorn grarphic and desgn. 2018:120.
4. Saukkonen JJ, Cohn DL, Jasmer RM, et al. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med. 2006;174(8):935-52. https://doi.org/10.1164/rccm.200510-1666ST
5. Døssing M, Wilcke JT, Askgaard DS, et al. Liver injury during antituberculosis treatment: an 11-year study. Tuber Lung Dis. 1996;77(4):335-40. https://doi.org/10.1016/s0962-8479(96)90098-2
6. Sharma SK, Singla R, Sarda P, et al. Safety of 3 different reintroduction regimens of antituberculosis drugs after development of antituberculosis treatment-induced hepatotoxicity. Clin Infect Dis. 2010;50(6):833-9. https://doi.org/10.1086/650576
7. Shakya R, Rao BS, Shrestha B. Incidence of hepatotoxicity due to antitubercular medicines and assessment of risk factors. Ann Pharmacother. 2004;38(6):1074-9. https://doi.org/10.1345/aph.1D525
8. Kaona FA, Tuba M, Siziya S, et al. An assessment of factors contributing to treatment adherence and knowledge of TB transmission among patients on TB treatment. BMC Public Health. 2004;4:68. Epub 20041229. https://doi.org/10.1186/1471- 2458-4-68
9. Zierski M, Bek E. Side-effects of drug regimens used in short-course chemotherapy for pulmonary tuberculosis. A controlled clinical study. Tubercle. 1980;61(1):41-9. https://doi.org/10.1016/0041-3879(80)90060-4
10. Krittiyanunt S, Sakulbamrungsil R, Wongwiwatthananukit S, et al. Risk Factors of Antituberculosis Drugs-Induced Hepatotoxicity in Thai Patients. Thai J Pharm Sci. 2002;26(3-4):121-8.
11. Singh J, Arora A, Garg PK, et al. Antituberculosis treatment-induced hepatotoxicity: role of predictive factors. Postgrad Med J. 1995;71(836):359-62. https://doi.org/10.1136/pgmj.71.836.359
12. Mahmoud Anees K. Hepatotoxicity of antituberculous drugs: incidence, severity and risk factors. 2007.
13. Wondwossen A, Waqtola C, Gemeda A. Incidence of antituberculosis-drug-induced hepatotoxicity and associated risk factors among tuberculosis patients in Dawro Zone, South Ethiopia: A cohort study. Int J Mycobacteriol. 2016;5(1):14-20. Epub 20151030. https://doi.org/10.1016/j.ijmyco.2015.10.002
14. Mo P, Zhu Q, Teter C, Yang et al. Prevalence, drug-induced hepatotoxicity, and mortality among patients multi-infected with HIV, tuberculosis, and hepatitis virus. Int J Infect Dis. 2014;28:95-100. Epub 20140909. https://doi.org/10.1016/j.ijid.2014.06.020
15. Chen R, Wang J, Tang S, et al. Association of polymorphisms in drug transporter genes (SLCO1B1 and SLC10A1) and antituberculosis drug-induced hepatotoxicity in a Chinese cohort. Tuberculosis (Edinb). 2015;95(1):68-74. Epub 20141127. https:// doi.org/10.1016/j.tube.2014.11.004
16. Wu S, Wang YJ, Tang X, et al. Genetic Polymorphisms of Glutathione S-Transferase P1 (GSTP1) and the Incidence of Anti- Tuberculosis Drug-Induced Hepatotoxicity. PLoS One. 2016;11(6):e0157478. Epub 20160609. https://doi.org/10.1371/journal. pone.0157478
17. Mohamed Noor NF, Salleh MZ, Mohd Zim MA, et al. NAT2 polymorphism and clinical factors that increase antituberculosis drug-induced hepatotoxicity. Pharmacogenomics. 2022;23(9):531-41. Epub 20220526. https://doi.org/10.2217/pgs-2022- 0022
18. Lee SW, Chung LS, Huang HH, et al. NAT2 and CYP2E1 polymorphisms and susceptibility to first-line anti-tuberculosis druginduced hepatitis. Int J Tuberc Lung Dis. 2010;14(5):622-6.
19. Phumart P. Incidence and Risk factor of Antituberculous drugs induced hepatitis in Thailand: Prince of Sonkla University; 2009.
20. Babalık A, Arda H, Bakırcı N, et al. Management of and risk factors related to hepatotoxicity during tuberculosis treatment. Tuberk Toraks. 2012;60(2):136-44.
21. Bouazzi OE, Hammi S, Bourkadi JE, et al. First line anti-tuberculosis induced hepatotoxicity: incidence and risk factors. Pan Afr Med J. 2016;25:167. Epub 20161116. https://doi.org/10.11604/pamj.2016.25.167.10060
22. Molla Y, Wubetu M, Dessie B. Anti-Tuberculosis Drug Induced Hepatotoxicity and Associated Factors among Tuberculosis Patients at Selected Hospitals, Ethiopia. Hepat Med. 2021;13:1-8. Epub 20210128. https://doi.org/10.2147/hmer.S290542
23. Gezahegn LK, Argaw E, Assefa B, et al. Magnitude, outcome, and associated factors of anti-tuberculosis drug-induced hepatitis among tuberculosis patients in a tertiary hospital in North Ethiopia: A cross-sectional study. PLoS One. 2020;15(11):e0241346. Epub 20201110. https://doi.org/10.1371/journal.pone.0241346
24. Wang N, Chen X, Hao Z, et al. Incidence and Temporal Trend of Antituberculosis Drug-Induced Liver Injury: A Systematic Review and Meta-Analysis. J Trop Med. 2022;2022:8266878. Epub 20221004. https://doi.org/10.1155/2022/8266878
25. Morasert T, Ruengchaisiwawaith T. Prevalence and Risk Factors Associated with First-Line Anti-Tuberculosis Induced Hepatotoxicity in Suratthani Hospital, Thailand. J Med Assoc Thai. 2021;104(2):233-9.
26. Hosmer DW, Lemeshow S. Applied Logistic Regression2002.
27. Lima Mde F, Melo HR. Hepatotoxicity induced by antituberculosis drugs among patients coinfected with HIV and tuberculosis. Cad Saude Publica. 2012;28(4):698-708. https://doi.org/10.1590/s0102-311x2012000400009
28. Tahaoğlu K, Ataç G, Sevim T, et al. The management of anti-tuberculosis drug-induced hepatotoxicity. Int J Tuberc Lung Dis. 2001;5(1):65-9.
29. Ormerod LP, Horsfield N. Frequency and type of reactions to antituberculosis drugs: observations in routine treatment. Tuber Lung Dis. 1996;77(1):37-42. https://doi.org/10.1016/s0962-8479(96)90073-8
30. Thongraung W, Sittidach M, Khwansuwan P, et al. Evaluation of the physicians’ approach to the diagnosis and treatment of patients with antituberculosis drug-induced hepatotoxicity. J Eval Clin Pract. 2012;18(6):1119-25. Epub 20110622. https://doi. org/10.1111/j.1365-2753.2011.01706.x
31. Li X, Gao P, Niu J. Metabolic Comorbidities and Risk of Development and Severity of Drug-Induced Liver Injury. Biomed Res Int. 2019;2019:8764093. Epub 20190818. https://doi.org/10.1155/2019/8764093
32. Warmelink I, ten Hacken NH, van der Werf TS, et al. Weight loss during tuberculosis treatment is an important risk factor for drug-induced hepatotoxicity. Br J Nutr. 2011;105(3):400-8. Epub 20100928. https://doi.org/10.1017/s0007114510003636

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