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.
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.
Authors: Jens Nürnberger; Thomas Philipp; Oliver Witzke; Anabelle Opazo Saez; Udo Vester; Hideo Andreas Baba; Andreas Kribben; Lothar Bernd Zimmerhackl; Andreas R Janecke; Mato Nagel; Michael Kirschfink Journal: N Engl J Med Date: 2009-01-29 Impact factor: 91.245
Authors: Marie-Agnès Dragon-Durey; Sidharth Kumar Sethi; Arvind Bagga; Caroline Blanc; Jacques Blouin; Bruno Ranchin; Jean-Luc André; Nobuaki Takagi; Hae Il Cheong; Pankaj Hari; Moglie Le Quintrec; Patrick Niaudet; Chantal Loirat; Wolf Herman Fridman; Véronique Frémeaux-Bacchi Journal: J Am Soc Nephrol Date: 2010-11-04 Impact factor: 10.121
Authors: June M McKoy; Cara Angelotta; Charles L Bennett; Martin S Tallman; Martha Wadleigh; Andrew M Evens; Timothy M Kuzel; Steve M Trifilio; Dennis W Raisch; Jonathan Kell; Daniel J DeAngelo; Francis J Giles Journal: Leuk Res Date: 2006-09-07 Impact factor: 3.156
Authors: Marlies H G Langenberg; Petronella O Witteveen; Nienke A G Lankheet; Jeanine Ml Roodhart; Hilde Rosing; Ingeborg J G M van den Heuvel; Jos H Beijnen; Emile E Voest Journal: Neoplasia Date: 2010-02 Impact factor: 5.715
Authors: Russell P Rother; Scott A Rollins; Christopher F Mojcik; Robert A Brodsky; Leonard Bell Journal: Nat Biotechnol Date: 2007-11 Impact factor: 54.908
Authors: Yohann Loriot; Gabriel Perlemuter; David Malka; Frédérique Penault-Llorca; Frédérique Penault-Lorca; Valérie Boige; Eric Deutsch; Christophe Massard; Jean Pierre Armand; Jean-Charles Soria Journal: Nat Clin Pract Oncol Date: 2008-03-18
Authors: T Trarbach; M Moehler; V Heinemann; C-H Köhne; M Przyborek; C Schulz; V Sneller; G Gallant; S Kanzler Journal: Br J Cancer Date: 2010-01-12 Impact factor: 7.640
Authors: C Wehling; O Amon; M Bommer; B Hoppe; K Kentouche; G Schalk; R Weimer; M Wiesener; B Hohenstein; B Tönshoff; R Büscher; H Fehrenbach; Ö-N Gök; M Kirschfink Journal: Clin Exp Immunol Date: 2016-11-25 Impact factor: 4.330
Authors: Raquel Medeiros de Souza; Bernardo Henrique Mendes Correa; Paulo Henrique Moreira Melo; Pedro Antunes Pousa; Tamires Sara Campos de Mendonça; Lucas Gustavo Castelar Rodrigues; Ana Cristina Simões E Silva Journal: Pediatr Nephrol Date: 2022-07-21 Impact factor: 3.651
Authors: Kioa L Wijnsma; Anne M Schijvens; John W A Rossen; A M D Mirjam Kooistra-Smid; Michiel F Schreuder; Nicole C A J van de Kar Journal: Pediatr Nephrol Date: 2017-03-25 Impact factor: 3.714