title: Age-related differences in reporting of drug-associated liver injury: data-mining of WHO Safety Report Database.
abstract: OBJECTIVE
  Age-differences in the frequency and manifestations of drug-induced liver injury are not fully characterized. Data-mining analyses were performed to assess the impact of age on liver event reporting frequency with different phenotypes and agents.
  
  
  METHODS
  236 drugs associated with hepatotoxicity were evaluated using the Empirical Bayes Geometric Mean (EBGM) of the relative reporting ratio with 90% confidence interval (EB05 and EB95) calculated for the age groups: 0-17, 18-64, and⩾65years (or elderly), for overall, serious (acute liver failure), hepatocellular, and cholestatic liver injury, using the WHO Safety Report Database.
  
  
  RESULTS
  Overall, cases of age 0-17, 18-64, and 65years or older comprised 6%, 62%, and 32% of liver event reports. Acute liver failure and hepatocellular injury were more frequently reported among children compared to adults and the elderly while reports with cholestatic injury were more frequent among the elderly (p<0.00001). A potential to cause mitochondrial dysfunction was more prevalent among the drugs with increased pediatric reporting frequency while high lipophilicity and biliary excretion were more common among the drugs associated with higher reporting frequency in the elderly.
  
  
  CONCLUSIONS
  Age-specific phenotypes and potential drug properties associated with age-specific hepatotoxicity were identified in reported liver events; further analyses are warranted.
authors.affiliation: Division of Gastroenterology, Duke University Medical Center, Durham, NC, United States; Durham Veterans Administration Medical Center, Durham, NC, United States. Electronic address: Christine.M.Hunt@earthlink.net.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Hunt
authors.affiliation: Global Clinical Safety and Pharmacovigilance, GlaxoSmithKline, Research Triangle Park, NC, United States.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Yuen
authors.affiliation: Worldwide Epidemiology, GlaxoSmithKline, Stockley Park, UK.
authors.forename: Heide A
authors.initials: HA
authors.lastname: Stirnadel-Farrant
authors.affiliation: Division of Gastroenterology, University of Arkansas for Medical Sciences, Little Rock, AR, United States; Division of Gastroenterology, Central Arkansas Veterans Healthcare System, Little Rock, AR, United States.
authors.forename: Ayako
authors.initials: A
authors.lastname: Suzuki
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D057225:Data Mining; D016208:Databases, Factual; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008099:Liver / Q000187:drug effects; D008875:Middle Aged; D014944:World Health Organization; D055815:Young Adult
keywords: Acute liver failure; Aging; Cholestatic injury; Data-mining; Drug-induced liver injury; Hepatotoxicity; Lipophilicity; Mitochondrial dysfunction; Pediatric