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

Abstract

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].

• Authors: Chote Luangchosiri, Ammarin Thakkinstian, Sermsiri Chitphuk, Wasana Stitchantrakul, Supanna Petraksa, Abhasnee Sobhonslidsuk
• Journal: BMC complementary and alternative medicine (BMC Complement Altern Med) Vol. 15 Pg. 334 (Sep 23 2015) ISSN: 1472-6882 [Electronic] England
• PMID: 26400476 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antitubercular Agents
• Protective Agents
• Silymarin
• Malondialdehyde
• Superoxide Dismutase

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Animals
• Antitubercular Agents (adverse effects)
• Chemical and Drug Induced Liver Injury (drug therapy)
• Double-Blind Method
• Female
• Humans
• Male
• Malondialdehyde (metabolism)
• Middle Aged
• Protective Agents (therapeutic use)
• Silymarin (therapeutic use)
• Superoxide Dismutase (metabolism)
• Young Adult