Abstract
Background: Hepatitis is the most serious adverse effect of antitubercular therapy.[1] Silymarin is used as a protective agent in acute and chronic liver disorders[2]. We aimed to evaluate the hepatoprotective activity of silymarin in patients receiving antitubercular therapy.
Methods: After getting approval from the institutional human ethics committee and consent from the subjects, this randomized double-blinded placebo-controlled study was conducted. In this study, new cases of pulmonary tuberculosis were divided into two groups. Group 1 was assigned to receive silymarin and Group 2 received a placebo along with Category I antitubercular drugs. The outcome of interest were maximum liver enzymes at week 4 and 8 and the development of anti-TB DILI.
Results: A total of 83 out of 92 expected numbers of patients were enrolled. There were 13/42 (31%) and 30/41 (73.2%) patients who developed mild elevation of ALT as well as ALP in the silymarin and the placebo groups (p<0.001) respectively. The mean of ALT levels at week 8 in the silymarin and the placebo group was 29.83(12.7) IU/L and 49.21 (22.29) IU/L (p < 0.001). The mean of ALP levels at week 4 in the silymarin and the placebo group was 58.95(18.43) IU/L and 70.70 (30.40) IU/L (p = 0.03). The mean of AST levels at week 8 in the silymarin and the placebo group was 28.35(12.35) IU/L and 36.70 (14.41) IU/L (p = 0.007).
Conclusion: Silymarin had an effect on reducing ALT, AST, and ALP levels (P<0.001), No serious adverse events were reported. Silymarin is a good choice for the improvement of the liver biochemical profile. Larger clinical trials are required to confirm the result of our study.
Keywords: Tuberculosis, Drug-induced liver injury, Alanine transaminase, Aspartate transaminase, Alkaline phosphatase.
References
- Luangchosiri C, Thakkinstian A, Chitphuk S, Stitchantrakul W, Petraksa S, Sobhonslidsuk A. A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury. BMC Complement Altern Med [Internet]. 2015;15(1):1–7. Available from: http://dx.doi.org/10.1186/ s12906-015- 0861-7
- Asa B. Protective Effects of Silymarin in Isoniazid Induced Hepatotoxicity in Rabbits. Annals [Internet]. 2010;16(1):43–43. Available from: http://annalskemu.org/journal/index.php/annals/article/view/138
- Raviglione M, Sulis G. Tuberculosis 2015: Burden, challenges and strategy for control and elimination. Infect Dis Rep. 2016;8(2):33–7.
- Zumla A, George A, Sharma V, Herbert RHN, Oxley A, Oliver M. The WHO 2014 Global tuberculosis report-further to go. Lancet Glob Heal [Internet]. 2015;3(1):e10–2. Available from: http://dx.doi.org/10.1016/S2214-109X(14)70361-4
- Arbex MA, Varella M de CL, de Siqueira HR, de Mello FAF. Antituberculosis drugs: Drug interactions, adverse effects, and use in special situations. Part 2: Second-line drugs. J Bras Pneumol. 2010;36(5):641–56.
- Metushi I, Uetrecht J, Phillips E. Mechanism of isoniazid-induced hepatotoxicity: Then and now. Br J Clin Pharmacol. 2016;81(6):1030–6.
- Daftary A, Frick M, Amico KR, Wolf A, Metcalfe JZ, Isaakidis P, et al. HHS Public Access. Int J Tuberc Lung Dis. 2016;20(4): 430–4.
- Chiang CY, Van Deun A, Enarson DA. A poor drug-resistant tuberculosis programme is worse than no programme: Time for a change. Int J Tuberc Lung Dis. 2013;17 (6):714–8.
- Forget EJ, Menzies D. Adverse reactions to first-time antituberculosis drugs. Expert Opin Drug Saf. 2006;5(2):231–49.
- Kim EJ, Lee MY, Jeon YJ. Silymarin inhibits morphological changes in LPS-stimulated macrophages by blocking NF-κB pathway. Korean J Physiol Pharmacol. 2015;19 (3):211–8.
- Senousy BE, Belal SI, Draganov P V. Hepatotoxic effects of therapies for tuberculosis. Nat Rev Gastroenterol Hepatol [Internet]. 2010;7(10):543–56. Available from: http://dx.doi.org/10.1038/nrgastro.2010.134
- Baghaei P, Tabarsi P, Chitsaz E, Saleh M, Marjani M, Shemirani S, 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(1):17–22.
- Aithal GP, Watkins PB, Andrade RJ, Larrey D, Molokhia M, Takikawa H, et al. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther [Internet]. 2011;89(6):806–15. Available from: http://dx.doi.org/10.1038/ clpt.2011.58/nature06264
- Joint Tuberculosis Committee of the British Thoracic Society. Chemotherapy and management of tuberculosis in the United Kingdom: recommendations 1998. Joint Tuberculosis Committee of the British Thoracic Society. Thorax [Internet]. 1998;53(7):536–48. Available from: http://www.pubmedcentral.nih.gov/ articlerender. fcgi? artid=1745276&tool=pmcentrez&rendertype=abstract
- Migliori GB, Raviglione MC, Schaberg T, Davies PDO, Zellweger JP, Grzemska M, et al. Tuberculosis management in Europe. Eur Respir J. 1999;14(4):978–92.
- Singla R, Sharma SK, Mohan A, Makharia G, Sreenivas V, Jha B, et al. Evaluation of risk factors for antituberculosis treatment induced hepatotoxicity. Indian J Med Res. 2010;132(7):81–6.
- Lee CM, Lee SS, Lee JM, Cho HC, Kim WS, Kim HJ, et al. Early monitoring for detection of antituberculous drug-induced hepatotoxicity. Korean J Intern Med. 2016;31(1):65–72.
- Devarbhavi H, Dierkhising R, Kremers WK, Sandeep MS, Karanth D, Adarsh CK. Single-center experience with drug-induced liver injury from india: Causes, outcome, prognosis, and predictors of mortality. Am J Gastroenterol [Internet]. 2010;105(11):2396–404. Available from: http://dx.doi.org/10.1038/ajg.2010.287
- Oxlade O, Murray M. Tuberculosis and Poverty: Why Are the Poor at Greater Risk in India? PLoS One. 2012;7(11).
- Heo E, Kim DK, Oh SH, Lee JK, Park JH, Chung HS. Effect of prophylactic use of silymarin on anti-tuberculosis drugs induced hepatotoxicity. Tuberc Respir Dis (Seoul). 2017;80(3):265–9.
- Tao L, Qu X, Zhang Y, Song Y, Zhang SX. Prophylactic Therapy of Silymarin (Milk Thistle) on Antituberculosis Drug-Induced Liver Injury: A Meta-Analysis of Randomized Controlled Trials. Can J Gastroenterol Hepatol. 2019;2019.
Corresponding Author
Senthilkumar.E
Post Graduate, Department of Pharmacology, Dhanalakshmi Srinivasan Medical College, Perambalur
DOI: https://dx.doi.org/10.18535/jmscr/v8i10.19
