title: Liver transplant associated with paracetamol overdose: results from the seven-country SALT study.
abstract: OBJECTIVE
  Acute drug overdose, especially with paracetamol, may cause acute liver failure leading to registration for transplantation (ALFT). Population statistics and between-country differences for ALFT related to overdose have been poorly described. The aim of the present study was to evaluate overdose ALFT in the multi-country Study of Acute Liver Transplantation (SALT).
  
  
  METHODS
  All adult overdose-related ALFT, with or without suicidal intent, in France, Greece, Ireland, Italy, the Netherlands, Portugal and the UK between 2005 and 2007 were identified from liver transplant registries and hospital records. These were compared with whole-country and per capita use of paracetamol.
  
  
  RESULTS
  Six hundred cases of ALFT were identified in 52 of 57 eligible transplant centres, of which 114 involved overdose (72 intentional, 10 non-intentional, 32 uncertain). Overdose represented 20% of all-cause ALFT: Ireland 52%, UK 28%, France 18%, the Netherlands 8%, and Italy 1%. Overdose ALFT were mostly females (61%), mean age 33.6 ± 10.9 years. A total of 111 (97%) of the overdoses involved paracetamol. Event rates ranged from one ALFT for 20.7 tons of paracetamol in Ireland, to one for 1074 tons in Italy and one case in 60 million inhabitants over 3 years in Italy to one case in 286 000 inhabitants per year in Ireland. Per-country event rates for non-overdose ALFT exposed to paracetamol were between 2.5 and 4.0 per million treatment-years sold.
  
  
  CONCLUSIONS
  Paracetamol overdose was found to represent one-sixth of all-cause ALFT. There was a 50-fold difference in Europe in the rates of paracetamol overdose ALFT, and a 200-fold difference per million inhabitants.
authors.affiliation: CIC Bordeaux CIC1401 Pharmaco-épidémiologie, Université de Bordeaux, F-33076, Bordeaux, France.
authors.forename: Sinem Ezgi
authors.identifier: http://orcid.org/0000-0001-8815-9128
authors.initials: SE
authors.lastname: Gulmez
authors.affiliation: CHU St Eloi Hospital, Liver Unit, Montpellier, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Larrey
authors.affiliation: CHU St Eloi Hospital, Liver Unit, Montpellier, France.
authors.forename: Georges-Philippe
authors.initials: GP
authors.lastname: Pageaux
authors.affiliation: Beaujon Hospital, Liver Unit, Clichy, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Bernuau
authors.affiliation: Department of Internal Medicine, Clinica San Gaudenzio, Novara, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Bissoli
authors.affiliation: Department of Gastroenterology, Louvain Catholic University, Louvain, Belgium.
authors.forename: Yves
authors.initials: Y
authors.lastname: Horsmans
authors.affiliation: Liver Unit, Royal Free NHS Trust, London, UK.
authors.forename: Douglas
authors.initials: D
authors.lastname: Thorburn
authors.affiliation: Liver Unit, St Vincent's University Hospital and University College Dublin, Dublin, Ireland.
authors.forename: P Aiden
authors.initials: PA
authors.lastname: McCormick
authors.affiliation: Department of Epidemiology, Erasmus University, Rotterdam, Netherlands.
authors.forename: Bruno
authors.initials: B
authors.lastname: Stricker
authors.affiliation: IMS Health, Real World Evidence Solutions, France.
authors.forename: Massoud
authors.initials: M
authors.lastname: Toussi
authors.affiliation: CIC Bordeaux CIC1401 Pharmaco-épidémiologie, Université de Bordeaux, F-33076, Bordeaux, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Lignot-Maleyran
authors.affiliation: CIC Bordeaux CIC1401 Pharmaco-épidémiologie, Université de Bordeaux, F-33076, Bordeaux, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Micon
authors.affiliation: CIC Bordeaux CIC1401 Pharmaco-épidémiologie, Université de Bordeaux, F-33076, Bordeaux, France.
authors.forename: Fatima
authors.initials: F
authors.lastname: Hamoud
authors.affiliation: CIC Bordeaux CIC1401 Pharmaco-épidémiologie, Université de Bordeaux, F-33076, Bordeaux, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Lassalle
authors.affiliation: CIC Bordeaux CIC1401 Pharmaco-épidémiologie, Université de Bordeaux, F-33076, Bordeaux, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Jové
authors.affiliation: CIC Bordeaux CIC1401 Pharmaco-épidémiologie, Université de Bordeaux, F-33076, Bordeaux, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Blin
authors.affiliation: CIC Bordeaux CIC1401 Pharmaco-épidémiologie, Université de Bordeaux, F-33076, Bordeaux, France.
authors.forename: Nicholas
authors.identifier: http://orcid.org/0000-0003-1212-2817
authors.initials: N
authors.lastname: Moore
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000633:toxicity*; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology / Q000601:surgery*; D062787:Drug Overdose / Q000150:complications / Q000453:epidemiology / Q000601:surgery*; D005060:Europe; D005260:Female; D006801:Humans; D016031:Liver Transplantation / Q000706:statistics & numerical data*; D008297:Male
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen
keywords: DILI; acute liver failure; case-population study; liver transplantation; paracetamol overdose; pharmacoepidemiology; suicide