title: Symptomatic hepatocellular liver injury with hyperbilirubinemia in two patients treated with rivaroxaban.
abstract: OBJECTIVE
  Treatment with the new oral anticoagulant rivaroxaban can be associated with severe liver injury.
  
  
  METHODS
  We report 2 patients with predominantly hepatocellular liver injury that had onset during treatment with rivaroxaban. Both were symptomatic, had massively elevated transaminase activity levels and hyperbilirubinemia, and fulfilled the criteria of Hy's law. Liver biopsy in 1 patient revealed centroacinar hepatocyte necrosis as the predominant finding. Both patients showed a rapid biochemical and clinical recovery after discontinuing rivaroxaban therapy. Between 2008 and 2013, 42 cases of liver injury possibly associated with rivaroxaban treatment have been reported to the Swiss Agency of Therapeutic Products (Swissmedic). Thirteen of these patients fulfilled the criteria of Hy's law.
  
  
  CONCLUSIONS
  Treatment with rivaroxaban can be associated with severe, symptomatic liver injury. Physicians should be aware of this adverse drug reaction. We propose rapid discontinuation of treatment with rivaroxaban in case of symptomatic liver injury and, taking into account its severity, avoiding reexposure.
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Liakoni
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland2Regional Pharmacovigilance Center, University Hospital Basel, Basel, Switzerland.
authors.forename: Alexandra E
authors.initials: AE
authors.lastname: Rätz Bravo
authors.affiliation: Institute of Pathology, University of Basel, Basel, Switzerland.
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.affiliation: Department of Hepatology and Gastroenterology, University Hospital Basel, Basel, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Heim
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Krähenbühl
mesh_terms: D000368:Aged; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects; D065427:Factor Xa Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005593:Fracture Fixation, Internal / Q000009:adverse effects; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D006932:Hyperbilirubinemia / Q000097:blood / Q000139:chemically induced*; D008099:Liver / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage / Q000009:adverse effects*; D009336:Necrosis / Q000139:chemically induced; D011322:Primary Prevention / Q000379:methods; D000069552:Rivaroxaban; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects*; D013978:Tibial Fractures / Q000601:surgery; D020246:Venous Thrombosis / Q000209:etiology / Q000517:prevention & control*
chemical_list: D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban