title: Anti-tuberculosis drug-induced liver injury in Shanghai: validation of Hy's Law.
abstract: BACKGROUND
  The most reliable liver safety signal in a clinical trial is considered to be 'Hy's Law cases' defined as subjects experiencing hepatocellular injury and serum bilirubin elevations with no more likely cause than study drug. However, there is little published data to support the current biochemical criteria for Hy's Law cases or their use to estimate postmarketing risk of severe liver injury.
  
  
  OBJECTIVE
  The primary objective of this study was to identify and characterize Hy's Law cases in patients treated for tuberculosis (TB). A secondary objective was to identify patient risk factors for drug-induced liver injuries.
  
  
  METHODS
  We utilized eDISH (evaluation of Drug-Induced Serious Hepatoxicity) to retrospectively analyze data from 517 patients treated for activeTB, a regimen well known to be capable of causing severe hepatotoxicity.
  
  
  RESULTS
  We identified two Hy's Law cases, which is consistent with the treatment's known risk of liver failure. Despite monthly monitoring, neither Hy's Law case experienced a documented elevation in serum alanine aminotransferase exceeding 10 × upper limits of normal. Hepatoprotectant use and infection with chronic hepatitis B were associated with increased risk of liver injury.
  
  
  CONCLUSIONS
  Our observations support the current biochemical criteria for Hy's Law cases and their use to estimate postmarketing risk.
authors.affiliation: Shanghai Municipal Center for Disease Control and Prevention, 1380 Zhong Shan Road (W), Shanghai, 200336, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Shen
authors.forename: Zheng'an
authors.initials: Z
authors.lastname: Yuan
authors.forename: Jian
authors.initials: J
authors.lastname: Mei
authors.forename: Zurong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Juntao
authors.initials: J
authors.lastname: Guo
authors.forename: Zheyuan
authors.initials: Z
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Haihua
authors.initials: H
authors.lastname: Zhang
authors.forename: Jieping
authors.initials: J
authors.lastname: Pan
authors.forename: Wenming
authors.initials: W
authors.lastname: Huang
authors.forename: Huili
authors.initials: H
authors.lastname: Gong
authors.forename: Dong
authors.initials: D
authors.lastname: Yuan
authors.forename: Ping
authors.initials: P
authors.lastname: Xiao
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Shuai
authors.forename: Senlin
authors.initials: S
authors.lastname: Lin
authors.forename: Qichao
authors.initials: Q
authors.lastname: Pan
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.forename: Paul B
authors.initials: PB
authors.lastname: Watkins
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology* / Q000209:etiology / Q000503:physiopathology; D002681:China / Q000453:epidemiology; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011358:Product Surveillance, Postmarketing; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D000410:Alanine Transaminase