title: 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.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Chote
authors.initials: C
authors.lastname: Luangchosiri
authors.affiliation: Section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Ammarin
authors.initials: A
authors.lastname: Thakkinstian
authors.affiliation: Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Sermsiri
authors.initials: S
authors.lastname: Chitphuk
authors.affiliation: Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Wasana
authors.initials: W
authors.lastname: Stitchantrakul
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Supanna
authors.initials: S
authors.lastname: Petraksa
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. Abhasnee.sob@mahidol.ac.th.|Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, 270 Praram 6 Road, Bangkok, 10400, Thailand. Abhasnee.sob@mahidol.ac.th.
authors.forename: Abhasnee
authors.initials: A
authors.lastname: Sobhonslidsuk
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000995:Antitubercular Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008875:Middle Aged; D020011:Protective Agents / Q000627:therapeutic use*; D012838:Silymarin / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D020011:Protective Agents; D012838:Silymarin; D008315:Malondialdehyde; D013482:Superoxide Dismutase