title: Assessment of nonsteroidal anti-inflammatory drug-induced hepatotoxicity.
abstract: BACKGROUND
  Liver toxicity related to NSAIDs is of outstanding importance because of the wide use of these drugs. NSAIDs are responsible for roughly 10% of the total of cases of drug-induced hepatotoxicity. The assessment of NSAID-induced hepatotoxicity, presently based on clinical and analytical biomarkers, is critical for early diagnosis and immediate withdrawal of the causing drug.
  
  
  METHODS
  The review presents an overview of current knowledge of the assessments of NSAID-induced hepatotoxicity with emphasis on the causative drugs, the NSAID-specific mechanisms involved, and a summary of genetic and non-genetic risk factors. Additionally, the authors discuss genetic factors which show NSAID-specific risk, namely CYP2C, UGT2B7, GSTM1 and GSTT1, as well as HLA alleles. The paper includes a list of the NSAID 'usual suspects' that cause hepatotoxicity based on the integrated information of drug-induced hepatotoxicity databases.
  
  
  CONCLUSIONS
  The ultimate goal of this research is pre-prescription testing. Unfortunately, genetic testing, alone, is not sufficient to predict NSAID-induced hepatotoxicity. The development of genetic biomarkers capable of identifying at-risk individuals will not be complete until we develop the ability to fully characterize patients' phenomes and the phenome-genome interaction in patients with NSAID-induced hepatotoxicity. Additionally, a characterization of the metabolic profile of the causative drug in patients with NSAID-induced hepatotoxicity would add crucial information which is presently disregarded in most studies. The full development of robust biomarkers will require the combination of several disciplines including causal statistics, phenomics, genomics, transcriptomics and metabonomics.
authors.affiliation: Department of Pharmacology, Medical School University of Extremadura, Avda. de Elvas s/n, E-06071, Badajoz, Spain. jagundez@unex.es
authors.forename: José Ag
authors.initials: JA
authors.lastname: Agúndez
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Lucena
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.forename: Raúl J
authors.initials: RJ
authors.lastname: Andrade
authors.forename: Miguel
authors.initials: M
authors.lastname: Blanca
authors.forename: Pedro
authors.initials: P
authors.lastname: Ayuso
authors.forename: Elena
authors.initials: E
authors.lastname: García-Martín
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000493:pharmacokinetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D005819:Genetic Markers; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001189:Aryl Hydrocarbon Hydroxylases; D005819:Genetic Markers; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; C491474:UGT2B7 protein, human; C413545:glutathione S-transferase T1