title: Liver injury from nonsteroidal anti-inflammatory drugs in the United States.
abstract: OBJECTIVE
  Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used and have been associated with hepatotoxicity. Studies of liver injury from NSAIDs have been retrospective and prospective data are lacking. The aim was to report the features and outcomes of the subjects with severe drug-induced liver injury from NSAIDS.
  
  
  METHODS
  The U.S. Drug Induced Liver Injury Network is a prospective registry of idiosyncratic drug hepatotoxicity. All patients are evaluated in a standard fashion and followed up for at least 6 months.
  
  
  RESULTS
  Of 1221 Drug Induced Liver Injury Network cases that were adjudicated, 30 cases were attributed to eight different NSAIDs. The mean age was 52 years old, 24 (80%) were women, and 21 (70%) were Caucasian. The mean latency was 67 days. Common signs and symptoms at presentation were nausea (73%), jaundice (67%) and dark urine (67%). Mean peak serum aspartate aminotransferase, alanine aminotransferase, total bilirubin and alkaline phosphatase were 898 U/L, 1060 U/L, 12.2 mg/dl and 326 U/L. The most common pattern of injury was hepatocellular (70%) and autoantibodies were detected in 33% of cases. Diclofenac, was the most frequently implicated NSAID (16/30 cases), and characterized by hepatocellular injury. Seventeen cases resulted in hospitalization or prolongation of hospitalization and one patient died from complications of Stevens-Johnson syndrome because of diclofenac.
  
  
  CONCLUSIONS
  Hepatocellular injury is the most common pattern seen with NSAID hepatotoxicity, and diclofenac is the most frequently implicated agent. Given the number of NSAID alternatives, diclofenac should be reserved for patients who fail other NSAIDs and a high level of suspicion for hepatotoxicity should be maintained.
authors.affiliation: Division of Hepatology, Carolinas Medical Center, Charlotte, NC, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Schmeltzer
authors.affiliation: Duke Clinical Research Institute, Duke University, Durham, NC, USA.
authors.forename: Andrzej S
authors.initials: AS
authors.lastname: Kosinski
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Kleiner
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Jay H
authors.initials: JH
authors.lastname: Hoofnagle
authors.affiliation: Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, CA, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Stolz
authors.affiliation: Department of Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fontana
authors.affiliation: Division of Hepatology, Carolinas Medical Center, Charlotte, NC, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Russo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality / Q000628:therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D011446:Prospective Studies; D012042:Registries; D012307:Risk Factors; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal
keywords: diclofenac; hepatotoxicity; medication; nonsteroidal