title: Phenotypic characterization of idiosyncratic drug-induced liver injury: the influence of age and sex.
abstract: Increased age and female sex are suggested risk factors for drug-induced hepatotoxicity (DILI). We studied the influence of these variables on the propensity to develop DILI, as well as its clinical expression and outcome. All cases of DILI submitted to the Spanish Registry between April 1994 and August 2007 were analyzed. Six hundred three DILI cases (310 men; mean age, 54 years) showed a similar sex distribution, reaching two peaks in the 40- to 49-year-old and 60- to 69-year-old age groups. No cases were recorded in the 20- to 29-year-old group. Patients aged > or =60 years accounted for 46% of the cases, with a male predominance (158 males, 118 females; P= 0.009), as opposed to younger patients. Older age was independently associated with cholestatic type of injury (odds ratio for an age interval for 1 year: 1.024 [95% confidence interval: 1.010-1.038]; male/female ratio, 1:2; P = 0.001) and younger age with hepatocellular damage (odds ratio: 0.983 [95% confidence interval: 0.972-0.994]; female/male ratio, 1:2; P = 0.002). In the mixed group, no age effect was evident. Outcome with fulminant liver failure/liver transplantation was more frequently encountered in women (P < 0.01). conclusion: Neither older age nor female sex are predisposing factors to overall DILI. However, older age is a determinant for cholestatic damage with a male predominance, whereas younger age is associated with cytolytic damage and a female overrepresentation. Women distinctly exhibit the worst outcome. Knowledge of these phenotypic associations could guide differential diagnosis and attribution of causality in DILI.
authors.affiliation: Clincal Pharmacology Service, School of Medicine, University Hospital Virgen de la Victoria, Málaga, Spain. lucena@uma.es
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Lucena
authors.forename: Raúl J
authors.initials: RJ
authors.lastname: Andrade
authors.forename: Neil
authors.initials: N
authors.lastname: Kaplowitz
authors.forename: Miren
authors.initials: M
authors.lastname: García-Cortes
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Fernández
authors.forename: Manuel
authors.initials: M
authors.lastname: Romero-Gomez
authors.forename: Miguel
authors.initials: M
authors.lastname: Bruguera
authors.forename: Hacibe
authors.initials: H
authors.lastname: Hallal
authors.forename: Mercedes
authors.initials: M
authors.lastname: Robles-Diaz
authors.forename: Jose F
authors.initials: JF
authors.lastname: Rodriguez-González
authors.forename: Jose Maria
authors.initials: JM
authors.lastname: Navarro
authors.forename: Javier
authors.initials: J
authors.lastname: Salmeron
authors.forename: Pedro
authors.initials: P
authors.lastname: Martinez-Odriozola
authors.forename: Ramón
authors.initials: R
authors.lastname: Pérez-Alvarez
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Borraz
authors.forename: Ramón
authors.initials: R
authors.lastname: Hidalgo
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology* / Q000235:genetics*; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017678:Sex Distribution; D012737:Sex Factors; D055815:Young Adult