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Eculizumab hepatotoxicity in pediatric aHUS
Wesley Hayes1, Sibylle Tschumi, Simon C Ling
1Division of Nephrology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
Eculizumab treatment for atypical hemolytic uremic syndrome (aHUS) may cause liver injury in children. Monitoring liver enzymes is recommended to detect this potential adverse event.
Area of Science:
- Pediatric Nephrology
- Hepatology
- Pharmacovigilance
Background:
- Eculizumab, a C5 inhibitor, is increasingly used in children for atypical hemolytic uremic syndrome (aHUS).
- Previous reports focused on eculizumab's safety and efficacy in aHUS, with limited data on potential hepatotoxicity.
Purpose of the Study:
- To investigate the incidence and characteristics of drug-induced liver injury (DILI) in children treated with eculizumab for aHUS.
- To identify potential risk factors and clinical presentations of eculizumab-associated hepatotoxicity.
Main Methods:
- Retrospective review of biochemical and clinical data of 11 children with aHUS treated with eculizumab.
- Assessment of liver enzymes and exclusion of other causes of liver injury.
Main Results:
- Elevated aminotransferases were observed in 7 of 11 children (63.6%), with 5 exceeding DILI thresholds.
- Liver injury was mixed hepatocellular and cholestatic in all affected patients.
- One patient experienced severe hepatotoxicity and recurrent injury upon re-challenge, leading to treatment discontinuation.
Conclusions:
- Hepatotoxicity is a previously unreported adverse event associated with eculizumab treatment in children with aHUS.
- Monitoring of liver enzymes is crucial for early detection of eculizumab-induced liver injury.
- Further research is needed to elucidate the mechanism and identify at-risk populations.
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