RT Journal Article
T1 Use of Hy's law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury.
A1 Robles-Díaz, Mercedes
A1 Lucena, M Isabel
A1 Kaplowitz, Neil
A1 Stephens, Camilla
A1 Medina-Cáliz, Inmaculada
A1 González-Jiménez, Andrés
A1 Ulzurrun, Eugenia
A1 González, Ana F
A1 Fernández, M Carmen
A1 Romero-Gómez, Manuel
A1 Jiménez-Pérez, Miguel
A1 Bruguera, Miguel
A1 Prieto, Martín
A1 Bessone, Fernando
A1 Hernández, Nelia
A1 Arrese, Marco
A1 Andrade, Raúl J
K1 Idiosyncratic Hepatotoxicity
K1 Prognostic Risk Factor
K1 Prediction
K1 Progression
K1 Comorbilidad
K1 Enfermedad hepática inducida por drogas
K1 Ictericia
K1 Fallo hepático agudo
K1 Valor predictivo de las pruebas
K1 Factores de riesgo
K1 Sensibilidad y especificidad
K1 Factores sexuales
K1 Alanina transaminasa
K1 Algoritmos
K1 Bilirrubina
K1 Marcadores biológicos
K1 Niños
AB BACKGROUND & AIMSHy'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.METHODSWe 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).RESULTSOf 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.CONCLUSIONSWhen 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.
PB WB Saunders
SN 0016-5085
YR 2014
FD 2014-07
LK http://hdl.handle.net/10668/1859
UL http://hdl.handle.net/10668/1859
LA en
LA en
NO Robles-Diaz M, Lucena MI, Kaplowitz N, Stephens C, Medina-Cáliz I, González-Jimenez A, et al. Use of Hy's law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury. Gastroenterology. 2014                         ; 147(1):109-118.e5
NO Journal Article;
DS RISalud
RD Apr 10, 2025