title: Eculizumab hepatotoxicity in pediatric aHUS.
abstract: BACKGROUND
  Eculizumab is a humanized anti-C5 antibody approved for the treatment of atypical hemolytic uremic syndrome (aHUS). Its use is increasing in children following reports of its safety and efficacy.
  
  
  METHODS
  We reviewed biochemical and clinical data related to possible drug-induced liver injury in 11 children treated with eculizumab for aHUS in a single center.
  
  
  RESULTS
  Elevated aminotransferases were observed in 7 children aged 6 to 11 years following eculizumab treatment for aHUS. Internationally accepted liver enzyme thresholds for drug-induced liver injury were exceeded in 5 cases. In all cases, liver injury was classified as mixed hepatocellular and cholestatic. Infectious and other causes were excluded in each case. One patient with no pre-existing liver disease developed tender hepatomegaly and liver enzyme derangement exceeding 20 times the upper limit of normal following initiation of eculizumab. Recurrent liver injury following re-challenge with eculizumab necessitated its discontinuation and transition to plasma therapy.
  
  
  CONCLUSIONS
  Hepatotoxicity in association with eculizumab is a potentially important yet previously unreported adverse event. We recommend monitoring liver enzymes in all patients receiving eculizumab. Further research is required to clarify the impact of this adverse event, to characterize the mechanism of potential hepatotoxicity, and to identify which patients are most at risk.
authors.affiliation: Division of Nephrology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
authors.forename: Wesley
authors.initials: W
authors.lastname: Hayes
authors.forename: Sibylle
authors.initials: S
authors.lastname: Tschumi
authors.forename: Simon C
authors.initials: SC
authors.lastname: Ling
authors.forename: Janusz
authors.initials: J
authors.lastname: Feber
authors.forename: Michael
authors.initials: M
authors.lastname: Kirschfink
authors.forename: Christoph
authors.initials: C
authors.lastname: Licht
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D065766:Atypical Hemolytic Uremic Syndrome / Q000188:drug therapy*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D008297:Male
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C481642:eculizumab