title: Causality of Drugs Involved in Acute Liver Failure Leading to Transplantation: Results from the Study of Acute Liver Transplant (SALT).
abstract: BACKGROUND
  Several methods have been proposed to assess causality in drug-induced liver injury but none have been tested in the specific context of acute liver failure leading to transplantation (ALFT).
  
  
  OBJECTIVE
  We took advantage of the Study of Acute Liver Transplant (SALT), a European case-population study of ALFT, to test different causality scales.
  
  
  METHODS
  Causality was assessed by experts in SALT, a 7-country case-population study from 2005 to 2007 of adult otherwise unexplained ALFT, for all drugs found within 30 days prior to the date of initial symptoms of liver disease (index date), using information content, causality scales, and data circuit determined from a pilot study, Salome.
  
  
  RESULTS
  The consensus points from Salome were to provide full data on drugs including international non-proprietary name (INN) and doses except for non-steroidal anti-inflammatory drugs (NSAIDs) and to use the World Health Organization (WHO) causality scale. In SALT, among the 9,479 identified patients, 600 (6.3%) were cases of ALFT, of which 187 had been exposed to drugs within 30 days, without overdose. In 130 (69.5%) of these the causality score was possible, probable, or highly probable.
  
  
  CONCLUSIONS
  In ALFT cases, once other clinical causes have been excluded and drug exposure established within 30 days, the main discriminant characteristic for causality will be previous knowledge of possible hepatotoxicity.
authors.affiliation: Department of Pharmacology, University of Bordeaux, 33000 Bordeaux, France. sinemezgi.gulmez@u-bordeaux2.fr|INSERM CIC-P0005, 33000, Bordeaux, France. sinemezgi.gulmez@u-bordeaux2.fr.|INSERM CIC 0005 Pharmaco-épidémiologie, Service de Pharmacologie, Université Bordeaux Segalen, Bâtiment Le Tondu-Case 41, 146, Rue Léo Saignat, 33076, Bordeaux Cedex, France. sinemezgi.gulmez@u-bordeaux2.fr.
authors.forename: Sinem Ezgi
authors.initials: SE
authors.lastname: Gulmez
authors.affiliation: Department of Pharmacology, University of Bordeaux, 33000, Bordeaux, France. nicholas.moore@pharmaco.u-bordeaux2.fr.|INSERM CIC-P0005, 33000, Bordeaux, France. nicholas.moore@pharmaco.u-bordeaux2.fr.|INSERM CIC 0005 Pharmaco-épidémiologie, Service de Pharmacologie, Université Bordeaux Segalen, Bâtiment Le Tondu-Case 41, 146, Rue Léo Saignat, 33076, Bordeaux Cedex, France. nicholas.moore@pharmaco.u-bordeaux2.fr.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Moore
authors.affiliation: CHU Hôpital Saint-Eloi, INSERM1040-IRB, 34000, Montpellier, France.
authors.forename: Georges-Philippe
authors.initials: GP
authors.lastname: Pageaux
authors.affiliation: Department of Pharmacology, University of Bordeaux, 33000, Bordeaux, France.|INSERM CIC-P0005, 33000, Bordeaux, France.
authors.forename: Severine
authors.initials: S
authors.lastname: Lignot
authors.affiliation: Département d'Hépatogastroentérologie, Université Catholique de Louvain, Bruxelles, Belgium.
authors.forename: Yves
authors.initials: Y
authors.lastname: Horsmans
authors.affiliation: Department of Epidemiology, Erasmus Medical Centre, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Bruno
authors.initials: B
authors.lastname: Stricker
authors.affiliation: Hepatology Department, Beaujon Hospital, Clichy, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Bernuau
authors.affiliation: Department of Internal Medicine and Cardiology, Clinica San Gaudenzio, Novara, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Bissoli
authors.affiliation: Liver Transplantation Hepatobilliary Unit, Royal Free Hampstead NHS Trust, London, NW3-2QG, UK.
authors.forename: Douglas
authors.initials: D
authors.lastname: Thorburn
authors.affiliation: Pharmacologie médicale et clinique, CHU et Faculté de Médecine de Toulouse, INSERM 1027, 31000, Toulouse, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Montastruc
authors.affiliation: Department of Pharmacology, University of Bordeaux, 33000, Bordeaux, France.|INSERM CIC-P0005, 33000, Bordeaux, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Micon
authors.affiliation: Department of Pharmacology, University of Bordeaux, 33000, Bordeaux, France.|INSERM CIC-P0005, 33000, Bordeaux, France.
authors.forename: Fatima
authors.initials: F
authors.lastname: Hamoud
authors.affiliation: Department of Pharmacology, University of Bordeaux, 33000, Bordeaux, France.|INSERM CIC-P0005, 33000, Bordeaux, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Lassalle
authors.affiliation: Department of Pharmacology, University of Bordeaux, 33000, Bordeaux, France.|INSERM CIC-P0005, 33000, Bordeaux, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Jové
authors.affiliation: Department of Pharmacology, University of Bordeaux, 33000, Bordeaux, France.|INSERM CIC-P0005, 33000, Bordeaux, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Blin
authors.affiliation: CHU Hôpital Saint-Eloi, INSERM1040-IRB, 34000, Montpellier, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Larrey
mesh_terms: D015984:Causality; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology* / Q000209:etiology / Q000601:surgery; D005060:Europe / Q000453:epidemiology; D006801:Humans; D016031:Liver Transplantation / Q000706:statistics & numerical data*; D010865:Pilot Projects