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Eculizumab hepatotoxicity in pediatric aHUS

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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.

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Acknowledgements

The authors wish to thank Camille Bedrosian, MD, CMO, Alexion Pharmaceuticals, for helpful discussion of this manuscript.

Disclosures

CL is advisory board member of Alexion Pharmaceuticals and Achillon Pharmaceuticals. He has received travel and speaker stipends as well as unrestricted research funds from Alexion Pharmaceuticals.

Conflict of interest

The other authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Division of Nephrology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada

    Wesley Hayes, Sibylle Tschumi & Christoph Licht

  2. Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada

    Simon C. Ling

  3. Department of Paediatrics, University of Toronto, Toronto, ON, Canada

    Simon C. Ling & Christoph Licht

  4. Division of Nephrology, Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada

    Janusz Feber

  5. Division of Immunology, University of Heidelberg, Heidelberg, Germany

    Michael Kirschfink

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  1. Wesley Hayes
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  2. Sibylle Tschumi
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Correspondence to Christoph Licht.

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Hayes, W., Tschumi, S., Ling, S.C. et al. Eculizumab hepatotoxicity in pediatric aHUS. Pediatr Nephrol 30, 775–781 (2015). https://doi.org/10.1007/s00467-014-2990-5

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  • DOI: https://doi.org/10.1007/s00467-014-2990-5

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