title: Preventive use of hepatoprotectors yields limited efficacy on the liver toxicity of anti-tuberculosis agents in a large cohort of Chinese patients.
abstract: OBJECTIVE
  We aimed to explore the effectiveness of preventive usage of hepatoprotectors in patients with tuberculosis (TB) receiving anti-TB treatment.
  
  
  METHODS
  With stratified cluster sampling strategy, a prospective cohort with 4488 sputum smears positive pulmonary TB patients was established from 52 counties of four regions in China. During anti-TB treatment, prescriptions of hepatoprotectors were documented in detail, and liver enzymes were routinely monitored. Anti-TB drug-induced liver injury (ATLI) was assessed based on liver enzymes following the criteria of American Thoracic Society. The incidence of ATLI between the preventive usage group and reference group was compared by propensity score adjusted Cox proportional hazard analysis. Preexisting diseases, history of liver disease, hepatitis B surface antigen status, primary/re-treatment of TB, income per year, and liver enzymes before anti-TB treatment were included in the propensity score model.
  
  
  RESULTS
  After 6-9 months of follow-up and monitoring, 4304 patients sustained in our cohort. Two thousand seven hundred fifty-two (63.9%) patients preventively took hepatoprotectors with a median course of 183 days. Most frequently used drugs were Hu Gan Pian, silymarin, glucurone, and inosine. Two thousand one hundred forty-four (77.9%) patients took those drugs more than 6 months. Sixty-nine (2.4%) patients of preventive usage group and 37 (2.5%) of reference group experienced ATLI, respectively. Statistical significances were not found by propensity score analysis for the association between using hepatoprotectors (hazard ratio[HR] = 0.99, 95% confidence interval [CI]: 0.65-1.52), using hepatoprotectors in the whole course (HR = 0.94, 95% CI: 0.60-1.48), using Hu Gan Pians, silymarin, glucurone, and inosine with ATLI occurrence.
  
  
  CONCLUSIONS
  No preventive effect of hepatoprotectors was observed in patients receiving anti-TB treatment.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wu
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Xia
authors.forename: Xiaozhen
authors.initials: X
authors.lastname: Lv
authors.forename: Shaowen
authors.initials: S
authors.lastname: Tang
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Yang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Wang
authors.forename: Daiyu
authors.initials: D
authors.lastname: Hu
authors.forename: Feiying
authors.initials: F
authors.lastname: Liu
authors.forename: Yanli
authors.initials: Y
authors.lastname: Yuan
authors.forename: Dehua
authors.initials: D
authors.lastname: Tu
authors.forename: Feng
authors.initials: F
authors.lastname: Sun
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Siyan
authors.initials: S
authors.lastname: Zhan
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000209:etiology* / Q000517:prevention & control*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D020723:Glucuronic Acid / Q000008:administration & dosage; D006801:Humans; D007288:Inosine / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020011:Protective Agents / Q000008:administration & dosage*; D012838:Silymarin / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D020011:Protective Agents; D012838:Silymarin; D007288:Inosine; D020723:Glucuronic Acid
keywords: cohort; hepatoprotectors; liver injury; tuberculosis