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Case Report/Case Series |

Symptomatic Hepatocellular Liver Injury With Hyperbilirubinemia in Two Patients Treated With Rivaroxaban

Evangelia Liakoni, MD1; Alexandra E. Rätz Bravo, PhD1,2; Luigi Terracciano, MD3; Markus Heim, MD4; Stephan Krähenbühl, MD, PhD1
[+] Author Affiliations
1Department of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland
2Regional Pharmacovigilance Center, University Hospital Basel, Basel, Switzerland
3Institute of Pathology, University of Basel, Basel, Switzerland
4Department of Hepatology and Gastroenterology, University Hospital Basel, Basel, Switzerland
JAMA Intern Med. 2014;174(10):1683-1686. doi:10.1001/jamainternmed.2014.3912.
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Importance  Treatment with the new oral anticoagulant rivaroxaban can be associated with severe liver injury.

Observations  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 and Relevance  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.

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Figure 1.
Clinical Course of Patient 1

The patient was hospitalized on day 0, and rivaroxaban therapy was discontinued. A liver biopsy was obtained on day 3. On day 19, the patient had made a full clinical recovery. At this time, the activities of alkaline phosphatase and aspartate aminotransferase (not shown) had normalized, whereas the activity of alanine aminotransferase and the serum bilirubin concentration were still slightly elevated.

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Figure 2.
Liver Biopsy of Patient 1

A, At low magnification, the lobular architecture is preserved and a minimal lymphocytic inflammation of portal tracts and perivenular confluent bridging necrosis are detectable (hematoxylin-eosin, original magnification ×100). B, At higher magnification, perivenular confluent necrosis with cell dropout, mild mononuclear inflammation, and several macrophages containing ceroid pigment can be detected (hematoxylin-eosin, original magnification ×200).

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