Published in:
01-01-2014 | Original Research Article
Anti-Tuberculosis Drug-Induced Liver Injury in Shanghai: Validation of Hy’s Law
Published in: Drug Safety | Issue 1/2014
Login to get accessAbstract
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.