title: Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland.
abstract: OBJECTIVE
  Little is known about the incidence of drug-induced liver injury (DILI) in the general population. We investigated the incidence and the quantitative risk of DILI in a population-based cohort.
  
  
  METHODS
  We performed a prospective study and collected data from 96 individuals diagnosed with DILI in Iceland from 2010 through 2011 (54 women; median age, 55 y). Liver injury was defined based on levels of alanine aminotransferase that were more than 3-fold the upper limit of normal and/or alkaline phosphatase levels more than 2-fold the upper limit of normal. Patients with acetaminophen toxicity were excluded. Drug history and clinical outcome were analyzed. Causality was assessed using the Roussel Uclaf Causality Assessment Method. The patients were registered in prescription databases for outpatients and inpatients.
  
  
  RESULTS
  The crude annual incidence rate of DILI was 19.1 (95% confidence interval [CI], 15.4-23.3) cases per 100,000 inhabitants. DILI was caused by a single prescription medication in 75% of cases, by dietary supplements in 16% of cases, and by multiple agents in 9% of cases. The most commonly implicated drugs were amoxicillin-clavulanate (21 of 96; 22%), diclofenac (6%), azathioprine (4%), infliximab (4%), and nitrofurantoin (4%). The median duration of therapy was 20 days (range, 8-77 days); 26 patients had jaundice (27%) and 22 patients were hospitalized (23%) for a median of 5 days (range, 2-8 days). Overall 35,252 patients received amoxicillin-clavulanate as outpatients, and DILI occurred in 1 of 2350 (43 of 100,000; 95% CI, 24-70). DILI also occurred in 1 of 9480 patients taking diclofenac (11 of 100,000; 95% CI, 4-24), 1 of 133 patients taking azathioprine (752 of 100,000; 95% CI, 205-1914), 1 of 148 patients taking infliximab (675 of 100,000; 95% CI, 184-718), and 1 of 1369 patients taking nitrofurantoin (73 of 100,000; 95% CI, 20-187).
  
  
  CONCLUSIONS
  In a population-based study in Iceland, the incidence of DILI was the highest reported to date. Amoxicillin-clavulanate was the most commonly implicated agent. The highest risk of hepatotoxicity was associated with azathioprine and infliximab, but the actual number of cases attributed to these agents was small.
authors: Department of Internal Medicine, Section of Gastroenterology and Hepatology, National University Hospital, Reykjavik, Iceland. einarsb@landspitali.is
authors: Einar S
authors: ES
authors: Björnsson
authors: Ottar M
authors: OM
authors: Bergmann
authors: Helgi K
authors: HK
authors: Björnsson
authors: Runar B
authors: RB
authors: Kvaran
authors: Sigurdur
authors: S
authors: Olafsson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology; D015331:Cohort Studies; D019587:Dietary Supplements / Q000009:adverse effects*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007055:Iceland / Q000453:epidemiology; D015994:Incidence; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016896:Treatment Outcome; D055815:Young Adult