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

Abstract

BackgroundHepatitis 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.MethodsA 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.ResultsA 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).ConclusionsSilymarin 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].

Silymarin improved diet-induced liver damage and insulin resistance by decreasing inflammation in mice

“…Silymarin has very strong antioxidant activity which can protect liver from both acute and chronic toxicity and injury (Gillessen et al 2014;Abdel-Moneim et al 2015;Luangchosiri et al 2015;Wu et al 2015). Also, silymarin can suppress various inflammatory responses by suppressing NF-jB pathway.…”

Is the Prophylactic Use of Hepatoprotectants Necessary in Anti-Tuberculosis Treatment?

“…After the records were screened according to the inclusion criteria, 6 articles [8,9,10,11,12,13] that involved 1,227 patients were included in this meta-analysis. The trial flowchart in our meta-analysis is shown in Figure 1.…”

“…In the experimental groups, patients received combinations of first-line anti-TB drugs including INH, RIF, PZA, ETB, and one kind of hepatoprotective drugs, while combinations of 4 kinds of anti-TB drugs and comparators were used in control groups. Two studies were conducted in China [9,11], 3 studies were conducted in Iran [8,12,13], and one study was conducted in Thailand [10]. The age of the participants ranged from 18 to 65 years in 2 included publications [9,12], older than 12 years in one study [11], older than 18 years in 2 studies [10,13], and more than 60 years old in one study [8].…”

“…Random sequence generation was adequate in 3 studies [10,11,12], and was not specifically described in the other 3 studies [8,9,13]. Allocation concealment was adequate in 2 studies [10,12] and unclear in 4 studies [8,9,11,13].…”

“…The antioxidant hepatoprotective drugs, including silymarin [9,10,11], garlic [12], N-acetylcysteine [8], and L -carnitine [13] have been found to prevent ATDH. However, other investigators have reported that hepatoprotective drugs may cause liver damage [14], and may be unsafe for TB patients [15].…”