title: Risk of acute liver injury associated with use of antibiotics. Comparative cohort and nested case-control studies using two primary care databases in Europe.
abstract: OBJECTIVE
  To assess the impact of varying study designs, exposure and outcome definitions on the risk of acute liver injury (ALI) associated with antibiotic use.
  
  
  METHODS
  The source population comprised of patients registered in two primary care databases, in the UK and in Spain. We identified a cohort consisting of new users of antibiotics during the study period (2004-2009) and non-users during the study period or in the previous year. Cases with ALI were identified within this cohort and classified as definite or probable, based on recorded medical information. The relative risk (RR) of ALI associated with antibiotic use was computed using Poisson regression. For the nested case-control analyses, up to five controls were matched to each case by age, sex, date and practice (in CPRD) and odds ratios (OR) were computed with conditional logistic regression.
  
  
  RESULTS
  The age, sex and year adjusted RRs of definite ALI in the current antibiotic use periods was 10.04 (95% CI: 6.97-14.47) in CPRD and 5.76 (95% CI: 3.46-9.59) in BIFAP. In the case-control analyses adjusting for life-style, comorbidities and use of medications, the OR of ALI for current users of antibiotics was and 5.7 (95% CI: 3.46-9.36) in CPRD and 2.6 (95% CI: 1.26-5.37) in BIFAP.
  
  
  CONCLUSIONS
  Guided by a common protocol, both cohort and case-control study designs found an increased risk of ALI associated with the use of antibiotics in both databases, independent of the exposure and case definitions used. However, the magnitude of the risk was higher in CPRD compared to BIFAP.
authors.affiliation: London School of Hygiene and Tropical Medicine, Faculty of Epidemiology and Population Health, London, UK.|Amgen Limited, London, UK.
authors.forename: Ruth
authors.identifier: http://orcid.org/0000-0001-8934-347X
authors.initials: R
authors.lastname: Brauer
authors.affiliation: London School of Hygiene and Tropical Medicine, Faculty of Epidemiology and Population Health, London, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Douglas
authors.affiliation: Fundación Centro Español de Investigación Farmacoepidemiológica (CEIFE), Madrid, Spain.
authors.forename: Luis Alberto
authors.initials: LA
authors.lastname: Garcia Rodriguez
authors.affiliation: Amgen Limited, London, UK.
authors.forename: Gerald
authors.initials: G
authors.lastname: Downey
authors.affiliation: Agencia Española de Medicamentos y Productos Sanitarios (AEMPS), Medicines for Human Use Department, Division of Pharmacoepidemiology and Pharmacovigilance, Madrid, Spain.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Huerta
authors.affiliation: Clinical Pharmacology Unit, University Hospital Príncipe de Asturias, Department of Biomedical Sciences, University of Alcala, Alcalá de Henares, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: de Abajo
authors.affiliation: Epidemiology, Pfizer Ltd, Tadworth, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bate
authors.affiliation: Amgen Limited, London, UK.
authors.forename: Maurille
authors.initials: M
authors.lastname: Feudjo Tepie
authors.affiliation: Utrecht University, Faculty of Science, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht, The Netherlands.
authors.forename: Mark C H
authors.identifier: http://orcid.org/0000-0002-5764-5788
authors.initials: MC
authors.lastname: de Groot
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Raymond
authors.initials: R
authors.lastname: Schlienger
authors.affiliation: Epidemiology, Pfizer Research and Development, New York, NY, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Reynolds
authors.affiliation: London School of Hygiene and Tropical Medicine, Faculty of Epidemiology and Population Health, London, UK.
authors.forename: Liam
authors.initials: L
authors.lastname: Smeeth
authors.affiliation: Utrecht University, Faculty of Science, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht, The Netherlands.
authors.forename: Olaf
authors.initials: O
authors.lastname: Klungel
authors.affiliation: Fundación Centro Español de Investigación Farmacoepidemiológica (CEIFE), Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ruigómez
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D015331:Cohort Studies; D016208:Databases, Factual; D005060:Europe; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011320:Primary Health Care / Q000706:statistics & numerical data*; D012307:Risk Factors
chemical_list: D000900:Anti-Bacterial Agents
keywords: BIFAP; CPRD; acute liver injury, antibiotics; case-control study; incidence rate; pharmacoepidemiology; primary care databases