Robles-Díaz, MercedesLucena, M IsabelKaplowitz, NeilStephens, CamillaMedina-Cáliz, InmaculadaGonzález-Jiménez, AndrésUlzurrun, EugeniaGonzález, Ana FFernández, M CarmenRomero-Gómez, ManuelJiménez-Pérez, MiguelBruguera, MiguelPrieto, MartínBessone, FernandoHernández, NeliaArrese, MarcoAndrade, Raúl J2015-03-262015-03-262014-07Robles-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.e50016-5085http://hdl.handle.net/10668/1859Journal Article;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.enIdiosyncratic HepatotoxicityPrognostic Risk FactorPredictionProgressionComorbilidadEnfermedad hepática inducida por drogasIctericiaFallo hepático agudoValor predictivo de las pruebasFactores de riesgoSensibilidad y especificidadFactores sexualesAlanina transaminasaAlgoritmosBilirrubinaMarcadores biológicosNiñosMedical Subject Headings::Named Groups::Persons::Age Groups::AdultMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Aged::Aged, 80 and overMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Nitrogenous Group Transferases::Transaminases::Alanine TransaminaseMedical Subject Headings::Information Science::Information Science::Computing Methodologies::AlgorithmsMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Phosphoric Monoester Hydrolases::Alkaline PhosphataseMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Nitrogenous Group Transferases::Transaminases::Aspartate AminotransferasesMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Azoles::Pyrroles::Tetrapyrroles::Bile Pigments::BilirubinMedical Subject Headings::Chemicals and Drugs::Biological Factors::Biological MarkersMedical Subject Headings::Named Groups::Persons::Age Groups::ChildMedical Subject Headings::Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort StudiesMedical Subject Headings::Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::ComorbidityMedical Subject Headings::Diseases::Digestive System Diseases::Liver Diseases::Drug-Induced Liver InjuryMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Hyperbilirubinemia::JaundiceMedical Subject Headings::Diseases::Digestive System Diseases::Liver Diseases::Hepatic Insufficiency::Liver Failure::Liver Failure, AcuteMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, StatisticalMedical Subject Headings::Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Research Design::Sensitivity and Specificity::Predictive Value of TestsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective StudiesMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk FactorsMedical Subject Headings::Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Sensitivity and SpecificityMedical Subject Headings::Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Sex FactorsMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Young AdultMedical Subject Headings::Named Groups::Persons::Age Groups::Adolescentresearch article24704526open access10.1053/j.gastro.2014.03.0501528-0012