A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury

BMC Complementary and Alternative Medicine

Abhasnee Sobhonslidsuk¹  Supanna Petraksa²  Wasana Stitchantrakul³  Sermsiri Chitphuk³  Ammarin Thakkinstian⁴  Chote Luangchosiri² 

[1] Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, 270 Praram 6 Road, Bangkok 10400, Thailand;Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand;Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand;Section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

关键词: Antioxidant;    Silymarin;    Tuberculosis;    Hepatotoxicity;    Drug-induced liver injury;   

Others  :  1232987
DOI  :  10.1186/s12906-015-0861-7

 received in 2015-04-29, accepted in 2015-09-15,  发布年份 2015

【 摘 要 】

Background

Hepatitis is a common adverse effect of antituberculosis drugs. Silymarin prevented drug-induced hepatoxicity in animals with anti-oxidative mechanisms but its effect in human has been unknown. We aimed to evaluate the efficacy of silymarin for preventing antituberculosis-drug induced liver injury (antiTB-DILI) in patients with tuberculosis.

Methods

A double-blind randomized placebo-controlled trial was performed. Tuberculosis patients were randomly allocated to receive placebo or silymarin. The outcomes of interests were antiTB-DILI and the maximum liver enzymes at week 4. Antioxidative enzymes (i.e., superoxide dismutase (SOD), glutathione and malondialdehyde assays) were assessed. The risks of antiTB-DILI between the two groups were compared. A number need to treat was estimated.

Results

A total of 55 out of 70 expected numbers of patients were enrolled. There were 1/27 (3.7 %) and 9/28 (32.1 %) patients who developed antiTB-DILI in the silymarin and the placebo groups. Risk reduction was 0.28 (0.10, 0.47), i.e., receiving silymarin was 28 % at lower risk for antiTB-DILI than placebo. This led to prevention of 28 patients from being antiTB-DILI among 100 treated patients. Median (IQR) of ALT levels at week 4 in the placebo and the silymarin group were 35.0 (15, 415) IU/L and 31.5 (20, 184) IU/L (p = 0.455). The decline of SOD level at week 4 in the silymarin group was less than the placebo group (p < 0.027).

Conclusions

Silymarin reduced the incidence of antiTB-DILI. The benefit of silymarin may be explained from superoxide dismutase restoration. Larger clinical trials are required to confirm the result of our small study [Clinicaltrials.Gov Identifier Nct01800487].

【 授权许可】

   
2015 Luangchosiri et al.

【 图 表 】

Fig. 1.

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