title: Clinical and histologic features of azithromycin-induced liver injury.
abstract: OBJECTIVE
  Rare cases of azithromycin-induced hepatotoxicity have been reported, with variable clinical and histologic features. We characterized clinical features and outcomes of azithromycin-induced liver injury.
  
  
  METHODS
  We identified patients with azithromycin-induced liver injury from the Drug-Induced Liver Injury Network Prospective Study who had causality scores of definite, highly likely, or probable. Demographic, clinical, and laboratory data and 6-month outcomes were examined.
  
  
  RESULTS
  Eighteen patients (72% female; mean age, 37 y) had causality scores of definite (n = 1), highly likely (n = 9), or probable (n = 8). Common presenting symptoms were jaundice, abdominal pain, nausea, and/or pruritus. For 16 patients, abnormal results from liver tests were first detected 14 days after azithromycin cessation (range, 9-20 d). The median duration of azithromycin treatment was 4 days (range, 2-7 d). The pattern of injury was hepatocellular in 10 patients, cholestatic in 6 patients, and mixed in 2 patients. The mean peak level of alanine aminotransferase was 2127 IU/L, of alkaline phosphatase was 481 IU/L, and of total bilirubin was 9.2 mg/dL. Liver histology showed ductopenia and veno-occlusive changes in a few patients. Two individuals had severe hypersensitivity cutaneous reactions. After 6 months, 8 patients had recovered, 4 patients had chronic injury, 1 patient died, and 1 patient underwent liver transplantation (outcomes were unavailable for 4 patients). Two of the patients who died or underwent liver transplantation had underlying chronic liver disease.
  
  
  CONCLUSIONS
  Azithromycin-induced liver injury occurs within 1 to 3 weeks after azithromycin initiation and predominantly is hepatocellular in nature. Although most patients recover fully, severe cutaneous reactions, chronic injury, and serious complications leading to death or liver transplantation can occur (ClinicalTrials.gov identifier, NCT00345930).
authors.affiliation: Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Martinez
authors.affiliation: Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Raj
authors.initials: R
authors.lastname: Vuppalanchi
authors.affiliation: Department of Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fontana
authors.affiliation: Department of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Andrew
authors.initials: A
authors.lastname: Stolz
authors.affiliation: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: David E
authors.initials: DE
authors.lastname: Kleiner
authors.affiliation: Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Hayashi
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Jiezhun
authors.initials: J
authors.lastname: Gu
authors.affiliation: Liver Disease Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jay H
authors.initials: JH
authors.lastname: Hoofnagle
authors.affiliation: Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address: nchalasa@iupui.edu.
authors.forename: Naga
authors.initials: N
authors.lastname: Chalasani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D017963:Azithromycin / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007223:Infant; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016019:Survival Analysis; D013997:Time Factors; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin
keywords: Antibiotic; DILI; Liver Toxicity; Macrolide
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