바로가기메뉴

본문 바로가기 주메뉴 바로가기

Effect of Prophylactic Use of Silymarin on Anti-tuberculosis Drugs Induced Hepatotoxicity

Tuberculosis & Respiratory Diseases / Tuberculosis & Respiratory Diseases,
2017, v.80 no.3, pp.265-269






  • Downloaded
  • Viewed

Abstract

Background: The first line of anti-tuberculosis (TB) drugs are the most effective standard of drugs for TB. However, the use of these drugs is associated with hepatotoxicity. Silymarin has protective effects against hepatotoxicity of anti-TB drugs in animal models. This study aims to investigate the protective effect of silymarin on hepatotoxicity caused by antiTB drugs. Methods: This is a prospective, randomized, double-blind and placebo-controlled study. Patients were eligible if they were 20 years of age or order and started the first-line anti-tuberculosis drugs. Eligible patients were randomized for receiving silymarin or a placebo for the first 4 weeks. The primary outcome was the proportion of patients who showed elevated serum liver enzymes more than 3 times the upper normal limit (UNL) or total bilirubin (TBil) > 2× UNL within the first 8 weeks of anti-TB treatment. Results: We enrolled a total of 121 patients who silymarin or a placebo to start their anti-TB treatment, for the first 8 weeks. The proportions of elevated serum liver enzymes more than 3 times of UNL at week 2, week 4, and week 8 did not show any significant difference between the silymarin and placebo groups, at 0% versus 3.6% (p>0.999); 4.4% versus 3.6% (p>0.999); and 8.7% versus 10.8% (p=0.630), respectively. However, patients with TBil >2× ULN at week 8 were significantly low in the silymarin group (0% versus 8.7%, p=0.043). Conclusion: Our findings did not show silymarin had any significant preventive effect on the hepatotoxicity of anti-TB drugs.

keywords
Tuberculosis, Silymarin

Reference

1.

1. Saukkonen JJ, Cohn DL, Jasmer RM, Schenker S, Jereb JA, Nolan CM, et al. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med 2006;174:935-52.

2.

2. Sherif IO, Al-Gayyar MM. Antioxidant, anti-inflammatory and hepatoprotective effects of silymarin on hepatic dysfunction induced by sodium nitrite. Eur Cytokine Netw 2013;24:114-21.

3.

3. Karimi G, Vahabzadeh M, Lari P, Rashedinia M, Moshiri M. “Silymarin”, a promising pharmacological agent for treatment of diseases. Iran J Basic Med Sci 2011;14:308-17.

4.

4. Eminzade S, Uraz F, Izzettin FV. Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals. Nutr Metab (Lond) 2008;5:18.

5.

5. Jahan S, Khan M, Imran S, Sair M. The hepatoprotective role of Silymarin in isoniazid induced liver damage of rabbits. J Pak Med Assoc 2015;65:620-2.

6.

6. Liu Q, Garner P, Wang Y, Huang B, Smith H. Drugs and herbs given to prevent hepatotoxicity of tuberculosis therapy: systematic review of ingredients and evaluation studies. BMC Public Health 2008;8:365.

7.

7. Joint Committee for the Revision of Korean Guidelines for Tuberculosis; Korea Centers for Disease Control and Prevention. Korean guidelines for tuberculosis. 2nd ed. Seoul and Cheongwon: Joint Committee for the Revision of Korean Guidelines for Tuberculosis, Korea Centers for Disease Control and Prevention; 2014.

8.

8. Suk KT, Kim DJ, Kim CH, Park SH, Yoon JH, Kim YS, et al. A prospective nationwide study of drug-induced liver injury in Korea. Am J Gastroenterol 2012;107:1380-7.

9.

9. 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;167:1472-7.

10.

10. 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 2015;15:334.

11.

11. Agal S, Baijal R, Pramanik S, Patel N, Gupte P, Kamani P, et al. Monitoring and management of antituberculosis drug induced hepatotoxicity. J Gastroenterol Hepatol 2005;20:1745-52.

12.

12. Saukkonen JJ, Powell K, Jereb JA. Monitoring for tuberculosis drug hepatotoxicity: moving from opinion to evidence. Am J Respir Crit Care Med 2012;185:598-9.

13.

13. 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;31:65-72.

14.

14. Ramappa V, Aithal GP. Hepatotoxicity related to anti-tuberculosis drugs: mechanisms and management. J Clin Exp Hepatol 2013;3:37-49.

15.

15. Wu S, Xia Y, Lv X, Tang S, Yang Z, Zhang Y, et al. Preventive use of hepatoprotectors yields limited efficacy on the liver toxicity of anti-tuberculosis agents in a large cohort of Chinese patients. J Gastroenterol Hepatol 2015;30:540-5.

Tuberculosis & Respiratory Diseases