title: Drug-induced liver injury: results from the hospital-based Berlin Case-Control Surveillance Study.
abstract: OBJECTIVE
  Drug-induced liver injury (DILI) is often responsible for acute liver failure, drug withdrawal, boxed warnings or drug non-approval. Therefore, we conducted a case-control study to determine the hepatotoxic risk of a wide range of drugs.
  
  
  METHODS
  The Berlin Case-Control Surveillance Study FAKOS included all 51 Berlin hospitals in a hospital network. Between 2002 and 2011, 198 patients with acute idiopathic hepatitis, 377 inpatient controls and 708 outpatient controls were ascertained. Case patients were thoroughly validated using anamnestic, clinical, laboratory and histological data. Drug exposure was obtained in a face-to-face interview. A possible drug aetiology was assessed in individual patients by applying the updated Council for International Organizations of Medical Sciences (CIOMS) scale. Drug risks were further quantified [odds ratios (OR) with 95% confidence intervals (CI)] in a case-control design with unconditional logistic regression analysis. Drug intake in the last 28 days before index date was considered for the analysis.
  
  
  RESULTS
  The study corroborated hepatotoxic risks for a number of drugs, including phenprocoumon (OR 3.3, 95% CI 1.5, 6.7), amiodarone (OR 5.5, 95% CI 1.3, 21.2), clozapine (OR 34.6, 95% CI 2.8, 824.9) and flupirtine (OR 40.2, 95% CI 5.5, 856.9). Increased risks were also suggested for less commonly reported substances such as angiotensin II receptor blockers, atypical antipsychotics and for biperiden, a drug never before reported to be hepatotoxic.
  
  
  CONCLUSIONS
  Our study identified a large number of drugs as possible causes of hepatotoxicity. The observed risk for seldom reported substances highlights the need for further post-authorization safety studies not exclusively focusing on drugs already labelled as potentially hepatotoxic.
authors.affiliation: Department of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.
authors.forename: Antonios
authors.initials: A
authors.lastname: Douros
authors.affiliation: Department of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bronder
authors.affiliation: Institute for Social Medicine, Epidemiology and Health Economy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Andersohn
authors.affiliation: Department of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Klimpel
authors.affiliation: Department of Surgery, Maria-Heimsuchung Caritas Klinik Pankow, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Thomae
authors.affiliation: Department of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Giselle
authors.initials: G
authors.lastname: Sarganas
authors.affiliation: Department of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Reinhold
authors.initials: R
authors.lastname: Kreutz
authors.affiliation: Department of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.
authors.forename: Edeltraut
authors.initials: E
authors.lastname: Garbe
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001604:Berlin; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D016009:Chi-Square Distribution; D005260:Female; D006761:Hospitals; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D017114:Liver Failure, Acute / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis; D008111:Liver Function Tests; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: D015415:Biomarkers; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin
keywords: drug safety; hepatotoxicity; pharmacovigilance