Eculizumab hepatotoxicity in pediatric aHUS.
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BORIS DOI
Date of Publication
2015
Publication Type
Article
Division/Institute
Contributor
Hayes, Wesley | |
Ling, Simon C | |
Feber, Janusz | |
Kirschfink, Michael | |
Licht, Christoph |
Subject(s)
Series
Pediatric nephrology
ISSN or ISBN (if monograph)
0931-041X
Publisher
Springer
Language
English
Publisher DOI
PubMed ID
25416628
Description
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.
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.
File(s)
| File | File Type | Format | Size | License | Publisher/Copright statement | Content | |
|---|---|---|---|---|---|---|---|
| Eculizumab hepatoxicity in pediatric aHUS PepNeph 2014.pdf | text | Adobe PDF | 256.19 KB | published |