Silymarin Compared With N-Acetylcysteine to Protect the Liver During Tuberculosis Drug Treatment

Trial details

Who runs it

Assiut University

Trial code

NCT07875322

Record updated

21 October 2026

Original description

Worldwide, tuberculosis (TB) infection caused by Mycobacterium Tuberculosis, remains one of the top 10 deadly diseases having a significant socioeconomic burden in the world, especially in developing countries. According to global estimates, the latest global TB report indicates that in 2022, roughly 1.3 million individuals died from TB.Read full original descriptionShow less

Silymarin Versus N-Acetylcysteine as Protective Effect Against Anti-tuberculosis Drugs Induced Liver Injury: Randomized Comparative Study

Worldwide, tuberculosis (TB) infection caused by Mycobacterium Tuberculosis, remains one of the top 10 deadly diseases having a significant socioeconomic burden in the world, especially in developing countries. According to global estimates, the latest global TB report indicates that in 2022, roughly 1.3 million individuals died from TB.

The WHO estimated the TB incidence in Egypt in 2019 is 12,000 per 100,000 population. Although Between 1990 and 2019, TB incidence in Egypt declined from 35 to 12 per 100,000 population, while TB mortality declined from 3.5 to 0.43 per 100,000 population. This burden is still a matter of concern, particularly in light of the fact that 66% of TB cases occur among the socially and economically productive age groups of 15-54 years.

TB is a preventable and curable disease, bout 85% of people who develop TB disease can be successfully treated. Anti-tuberculosis chemotherapy is the primary treatment for tuberculosis with first-line drugs, including isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E), are commonly used. The WHO recommends (2HRZE/4HR regimen) as a treatment option.

However, Anti-tuberculosis Chemotherapy has serious problems such as disease relapse, the emergence of resistance to drugs and drug-induced liver injury which is a major toxicity of anti-TB treatment.

Among the patients receiving the combination treatment, ATDILI is the most prevalent within the first two months of treatment, which occurs in 4.8% to as high as 36% of patients. Half of ATDILI occurs within 2 weeks of treatment initiation.

Several studies have been conducted in animal models to show the beneficial hepatoprotective effect of some drugs and herbal medicine to prevent and reduce hepatotoxicity from antituberculosis drugs, from these drugs (silymarin and N-acetylcysteine).

It has been proposed that hepatoprotective actions of silymarin may result from the scavenging of free radicals and inhibition of lipid peroxidation, leading to faster recovery after injury.

N-acetylcysteine (NAC) is an antioxidant which exerts its hepato-protective effect by replenishing glutathione stores and enhancing the cellular antioxidant defense mechanism. NAC has been previously studied and used for many years in the treatment of paracetamol-induced hepatotoxicity, with good evidence of efficacy and safety, also was found to be beneficial in non-paracetamol induced acute liver failure. It was demonstrated that the mortality was reduced to 28% using NAC compared to 53% using a placebo.

both silymarin and N-acetylcysteine have been investigated as hepatoprotective agents, but there are relatively few direct head-to-head comparisons in patients receiving anti-TB therapy. Despite the results of animal studies showing the protective effect of silymarin against ATDILI, RCT addressing this issue are limited with inconclusive results. Unfortunately, there are no comprehensive scientific reports on NAC hepato-protective effect on ATDILI.

As there is a lack of randomized controlled trials from Egypt comparing silymarin or N-acetylcysteine for the prevention of Anti-tuberculosis drug-induced liver injury, highlighting the need for locally generated evidence.

Therefore, this study is designed to evaluate the preventive effect of silymarin against the development of ATDH in new TB cases on a standard anti TB drug regimen, also evaluating the effects of NAC on TB treatment.

Inclusion: New cases of TB aged ≥18 years old who received a standard anti-TB regimen for active or latent pulmonary/extrapulmonary TB infection. (isoniazid 5 mg/kg, rifampin 10 mg/kg, ethambutol 15 mg/kg and pyrazinamide 25 mg/kg for first 2 months followed by 4 months of isoniazid 5 mg/kg and rifampin 10 mg/kg).

Exclusion: Discontinuation of drug due to other adverse effects except hepatotoxicity; HIV-positive patients. Patients with advanced liver disease; Patients receiving concomitant hepatotoxic medications/substances (e.g., sodium valproate, methotrexate, any sulfonamide, regular-dose acetaminophen, and alcohol), systemic corticosteroids, antioxidants (e.g. vitamins E and C); Patients refused to be included in the study; Pregnant/lactating women.

ClinicalTrials.gov NCT07875322