title: Preventive use of a hepatoprotectant against anti-tuberculosis drug-induced liver injury: A randomized controlled trial.
abstract: OBJECTIVE
  Hepatoprotectants are routinely prescribed in China to prevent anti-tuberculosis drug-induced liver injury (ATLI). However, their biological mechanisms have not yet been clearly demonstrated. This study aims to evaluate the preventive effects of Silybum marianum against drug-induced liver injury among tuberculosis patients and to provide clinical guidelines for tuberculosis management in China.
  
  
  METHODS
  A randomized controlled trial was performed in Jiangsu, China. Tuberculosis patients were randomly allocated to the experimental group (anti-tuberculosis therapy plus S. marianum capsule) or the control group (anti-tuberculosis therapy plus vitamin C tablet). The primary outcomes were the occurrence of probable and possible ATLI, the peak aspartate aminotransferase/alanine aminotransferase ratio and the maximum altered alkaline phosphatase or gamma-glutamyl transferase.
  
  
  RESULTS
  The final analysis comprised 183 cases in the experiment group and 187 cases in the control group. The risk of developing probable ATLI was not significantly different between the two groups. During the follow-up period, 43.72% of cases in the experiment group and 35.83% of cases in the control group were determined to have possible ATLI (relative risk = 1.23, 95% confidence interval: 0.94-1.54). When using a more strict definition of possible ATLI, the adjusted relative risk (95% confidence interval) was 1.76 (1.14-2.56). The risks of adverse drug reactions, prolonged treatment length, taking second-line tuberculosis drugs, and the clearance of tuberculosis bacteria were similar between the two groups.
  
  
  CONCLUSIONS
  No significant preventive effect of silymarin was found for either lowering the risk of liver injury or boosting the positive outcomes. Worse, we even found a potential risk of liver damage caused by the hepatoprotectant.
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.|Department of Social Medicine and Health Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Simin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Tuberculosis, The Third Hospital of Zhenjiang City, Zhenjiang, China.
authors.forename: Hongqiu
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Xianzhen
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Social Medicine and Health Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Social Medicine and Health Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Xianzhi
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Guisheng
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.|Department of Social Medicine and Health Education, School of Public Health, Nanjing Medical University, Nanjing, China.|The Innovation Center for Social Risk Governance in Health, Nanjing, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Wang
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000995:Antitubercular Agents / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000209:etiology* / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020944:Silybum marianum; D008517:Phytotherapy; D020011:Protective Agents / Q000008:administration & dosage* / Q000009:adverse effects; D012306:Risk; D012838:Silymarin / Q000008:administration & dosage* / Q000009:adverse effects; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D000995:Antitubercular Agents; D015415:Biomarkers; D020011:Protective Agents; D012838:Silymarin; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase
keywords: RCT; clinical trial; drug-induced liver injury; hepatoprotectant; tuberculosis