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.
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.
Authors: Jussi J Saukkonen; David L Cohn; Robert M Jasmer; Steven Schenker; John A Jereb; Charles M Nolan; Charles A Peloquin; Fred M Gordin; David Nunes; Dorothy B Strader; John Bernardo; Raman Venkataramanan; Timothy R Sterling Journal: Am J Respir Crit Care Med Date: 2006-10-15 Impact factor: 21.405
Authors: Raúl J Andrade; M Isabel Lucena; Neil Kaplowitz; Beatriz García-Muņoz; Yolanda Borraz; Ketevan Pachkoria; Miren García-Cortés; M Carmen Fernández; Gloria Pelaez; Luis Rodrigo; José A Durán; Joan Costa; Ramón Planas; Anabel Barriocanal; Carlos Guarner; Manuel Romero-Gomez; Teresa Muņoz-Yagüe; Javier Salmerón; Ramón Hidalgo Journal: Hepatology Date: 2006-12 Impact factor: 17.425
Authors: J C Wu; S D Lee; P F Yeh; C Y Chan; Y J Wang; Y S Huang; Y T Tsai; P Y Lee; L P Ting; K J Lo Journal: Gastroenterology Date: 1990-02 Impact factor: 22.682