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oai:repisalud.isciii.es:20.500.12105/170722024-01-15T18:17:19Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud author Robles-Díaz, Mercedes author Lucena, M Isabel author Kaplowitz, Neil author Stephens, Camilla author Medina-Cáliz, Inmaculada author González-Jiménez, Andrés author Ulzurrun, Eugenia author González, Ana F author Fernández, M Carmen author Romero-Gómez, Manuel author Jiménez-Pérez, Miguel author Bruguera, Miguel author Prieto, Martín author Bessone, Fernando author Hernández, Nelia author Arrese, Marco author Andrade, Raúl J authoraffiliation [Robles-Díaz, M; Lucena, MI; Stephens, C; Medina-Cáliz, I; González-Jiménez, A; Ulzurrun, E; González, AF; Andrade, RJ] Unidad de Gestión Clínica de Enfermedades Digestivas, Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Málaga, Spain. [Robles-Díaz, M; Lucena, MI; Stephens, C; Medina-Cáliz, I; Ulzurrun, E; Romero-Gómez, M; Bruguera, M; Prieto, M; Andrade, RJ] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain. [Kaplowitz, N] University of Southern California Research Center for Liver Diseases, Keck School of Medicine, Los Angeles, CA, United States. [Fernandez, MC] Servicio de Farmacia, Hospital de Torrecardenas, Almería, Spain. [ Romero-Gómez, M] Unidad de Gestión Clínica de Enfermedades Digestivas, Hospital Universitario de Valme, Sevilla, Spain. [Jiménez-Pérez, M] Unidad de Gestión Clínica de Enfermedades Digestivas, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario Carlos Haya, Málaga, Spain. [Bruguera, M] Instituto de Enfermedades Digestivas y Metabolismo, Hospital Clinic, Barcelona, Spain. [Prieto, M] Unidad de Gestión Clínica de Enfermedades Digestivas, Hospital la Fe, Valencia, Spain. [Bessone, F] Facultad de Ciencias Médicas, Servicio de Gastroenterología y Hepatología, Hospital Provincial del Centenario, Rosario, Argentina. [Hernández, N] Hospital de Clínicas Clínica de Gastroenterología, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay. 2024-01-15T18:17:19Z 2024-01-15T18:17:19Z 2014-07 0016-5085 http://hdl.handle.net/10668/1859 http://hdl.handle.net/20.500.12105/17072 24704526 10.1053/j.gastro.2014.03.050 1528-0012 Gastroenterology BACKGROUND & AIMS: Hy's Law, which states that hepatocellular drug-induced liver injury (DILI) with jaundice indicates a serious reaction, is used widely to determine risk for acute liver failure (ALF). We aimed to optimize the definition of Hy's Law and to develop a model for predicting ALF in patients with DILI. METHODS: We collected data from 771 patients with DILI (805 episodes) from the Spanish DILI registry, from April 1994 through August 2012. We analyzed data collected at DILI recognition and at the time of peak levels of alanine aminotransferase (ALT) and total bilirubin (TBL). RESULTS: Of the 771 patients with DILI, 32 developed ALF. Hepatocellular injury, female sex, high levels of TBL, and a high ratio of aspartate aminotransferase (AST):ALT were independent risk factors for ALF. We compared 3 ways to use Hy's Law to predict which patients would develop ALF; all included TBL greater than 2-fold the upper limit of normal (×ULN) and either ALT level greater than 3 × ULN, a ratio (R) value (ALT × ULN/alkaline phosphatase × ULN) of 5 or greater, or a new ratio (nR) value (ALT or AST, whichever produced the highest ×ULN/ alkaline phosphatase × ULN value) of 5 or greater. At recognition of DILI, the R- and nR-based models identified patients who developed ALF with 67% and 63% specificity, respectively, whereas use of only ALT level identified them with 44% specificity. However, the level of ALT and the nR model each identified patients who developed ALF with 90% sensitivity, whereas the R criteria identified them with 83% sensitivity. An equal number of patients who did and did not develop ALF had alkaline phosphatase levels greater than 2 × ULN. An algorithm based on AST level greater than 17.3 × ULN, TBL greater than 6.6 × ULN, and AST:ALT greater than 1.5 identified patients who developed ALF with 82% specificity and 80% sensitivity. CONCLUSIONS: When applied at DILI recognition, the nR criteria for Hy's Law provides the best balance of sensitivity and specificity whereas our new composite algorithm provides additional specificity in predicting the ultimate development of ALF. eng Idiosyncratic Hepatotoxicity Prognostic Risk Factor Prediction Progression Comorbilidad Enfermedad hepática inducida por drogas Ictericia Fallo hepático agudo Valor predictivo de las pruebas Factores de riesgo Sensibilidad y especificidad Factores sexuales Alanina transaminasa Algoritmos Bilirrubina Marcadores biológicos Niños Use of Hy's law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury. research article