INTRODUCTION: 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.
OBJECTIVES: 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.