SILYMARIN FOR PREVENTION OF ANTI-TUBERCULOSIS DRUG-INDUCED LIVER INJURY: A META-ANALYSIS
CO Floro, AMM Fausto, MDS Velasco, JEL Camenforte, MA De Lusong Section of Gastroenterology, Department of Medicine, University of the Philippines – Philippine General Hospital
Significance: There is currently no drug that is proven to significantly prevent anti-tuberculosis drug-induced liver injury. Silymarin, a traditional herbal drug, has been used as a hepatoprotectant, and has been shown to prevent AT-DILI in animals. Recent treatment trials in humans, have conflicting results. The objective of this study is to evaluate the hepatoprotective effect of silymarin in preventing drug-induced liver injury in adult patients being treated with anti-tuberculosis drugs.
Methodology: A search of Medline, Cochrane Library, Science Direct, Biomed Central and EMBASE was performed for literature about silymarin and AT-DILI from inception to November 2016. Keywords used were ("Silymarin" OR "Silybin" OR "Milk Thistle) AND ("DILI" OR "Hepatotoxicity" OR "Liver injury") AND ("Tuberculosis" OR "TB" OR "Anti-Kochs"). Included were randomized controlled trials comparing silymarin to placebo in preventing the development of AT-DILI in adults diagnosed with tuberculosis. Excluded studies were: children, no serum aminotransferase and bilirubin levels, multi- interventions, reviews, case reports, and expert opinions. Statistical analysis was done using RevMan 5.3 software.
Results: The search revealed 1695 abstracts, and 3 papers were included, comprising of 494 patients, of which 244 and 250 patients took silymarin and placebo, respectively. The difference between silymarin and placebo groups in incidence of AT-DILI in adult patients with tuberculosis was not significant (RR=1.04; 95%CI=0.34-3.23; p=0.03). Results show significant heterogeneity, and attributed to differences in AT-DILI definitions, frequency and duration of monitoring, and small sample sizes.
Conclusion: While silymarin has an acceptable safety profile, available evidence from limited studies suggest that it exhibits no significant hepatoprotective effect against anti-Tuberculosis drug-related liver injury.
Keywords: Meta-analysis, silymarin, drug induced liver injury, tuberculosis