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Use of Hy's Law and a New Composite Algorithm to Predict Acute Liver Failure in Patients With Drug-Induced Liver Injury

Robles–Diaz, Mercedes, Lucena, M. Isabel, Kaplowitz, Neil, Stephens, Camilla, Medina–Cáliz, Inmaculada, González–Jimenez, Andres, Ulzurrun, Eugenia, Gonzalez, Ana F., Fernandez, M. Carmen, Romero–Gómez, Manuel, Jimenez–Perez, Miguel, Bruguera, Miguel, Prieto, Martín, Bessone, Fernando, Hernandez, Nelia, Arrese, Marco, Andrade, Raúl J.·2014·Gastroenterology
DOI 10.1053/j.gastro.2014.03.050
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Abstract

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% sensitivit…

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Crossref · 10.1053/j.gastro.2014.03.050

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  • In 2014, Robles-Diaz et al. found that, at the time of diagnosis, using either AST or ALT, whichever was higher/ULN divided by ALP/ULN, defining this as new R ratio (nR), resulted in better sensitivity and specificity for predicting liver failure.

    “In 2014, Robles-Diaz et al.. found that, at the time of diagnosis, using either AST or ALT, whichever was higher/ULN divided by ALP/ ULN, defining this as new R ratio (nR), resulted in better sensitivity and specificity for predicting liver failure [30].”

    From DILI Differences and Similarities between the US and Europe (2026) · cites this paper as [30]

  • An algorithm developed by the Spanish DILI Registry to identify patients at higher risk of ALF at DILI recognition showed 82% specificity and 80% sensitivity.

    “An algorithm developed by the Spanish DILI Registry to identify patients at higher risk of ALF at DILI recognition showed 82% specificity and 80% sensitivity.79”

    From Nomenclature, diagnosis and management of drug-induced autoimmune-like hepatitis (DI-ALH): An expert opinion meeting report (2023) · cites this paper as [79]

Citations

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Research works printed but not linked: 28

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Metadata

Authors
Robles–Diaz, M., Lucena, M. I., Kaplowitz, N., Stephens, C., Medina–Cáliz, I., González–Jimenez, A., Ulzurrun, E., Gonzalez, A. F., Fernandez, M. C., Romero–Gómez, M., Jimenez–Perez, M., Bruguera, M., Prieto, M., Bessone, F., Hernandez, N., Arrese, M., & Andrade, R. J.
Venue
Gastroenterology
Publisher
Elsevier BV
Published
2014-07
Volume
147
Issue
1
Pages
109-118.e5
ISSN
0016-5085
DOI
10.1053/j.gastro.2014.03.050
Cited by
301
References
2
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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