title: Clinical and histopathologic features of fluoroquinolone-induced liver injury.
abstract: OBJECTIVE
  Fluoroquinolone-induced liver injury is rare; no prospective studies of well-characterized case series have been published. We studied patients with fluoroquinolone-induced hepatotoxicity from the Drug-Induced Liver Injury Network (DILIN) to characterize injury patterns, outcomes, and associated features.
  
  
  METHODS
  We identified subjects with fluoroquinolone hepatotoxicity enrolled in the DILIN from September 2004 to January 2010. Demographic, clinical, and laboratory data were analyzed by descriptive statistical methods.
  
  
  RESULTS
  Of the 679 registrants in the DILIN prospective study, 12 had fluoroquinolone hepatotoxicity (6 ciprofloxacin, 4 moxifloxacin, 1 levofloxacin, and 1 gatifloxacin). Seven were women; median age was 57 years (range, 23-80 years), and median time from fluoroquinolone start to symptoms was only 4 days (range, 1-39 days). Nine patients developed symptoms on medication; 3 did so 2, 8, and 32 days after stopping the medication. Cases were equally distributed among hepatocellular injury (predominantly increased levels of alanine aminotransferase), cholestatic injury (predominantly increased levels of alkaline phosphatase), and both. Seven patients had immunoallergic features. Patients with mixed hepatocellular and cholestatic injury had mild disease without jaundice; all recovered. In contrast, 2 of 4 patients with hepatocellular injury and jaundice died, 1 of acute liver failure. One patient with cholestatic injury developed vanishing bile duct syndrome and required liver transplantation; another had a persistently increased serum level of alkaline phosphatase.
  
  
  CONCLUSIONS
  Fluoroquinolone liver injury is rapid in onset and often has immunoallergic features, indicating a hypersensitivity reaction. The pattern of injury can be hepatocellular, cholestatic, or mixed; mixed cases are the least severe. Acute and chronic liver failure can occur.
authors.affiliation: Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, USA.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Orman
authors.forename: Hari S
authors.initials: HS
authors.lastname: Conjeevaram
authors.forename: Raj
authors.initials: R
authors.lastname: Vuppalanchi
authors.forename: James W
authors.initials: JW
authors.lastname: Freston
authors.forename: James
authors.initials: J
authors.lastname: Rochon
authors.forename: David E
authors.initials: DE
authors.lastname: Kleiner
authors.forename: Paul H
authors.initials: PH
authors.lastname: Hayashi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D024841:Fluoroquinolones / Q000009:adverse effects*; D006651:Histocytochemistry; D006801:Humans; D006967:Hypersensitivity / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000473:pathology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase