Safety of in vivo gene therapy in children: mechanisms and management of liver injury
Jeyaraj, Rebecca Brown, Li-An K Jagadisan, Barath Muntoni, Francesco Baruteau, Julien Gupte, Girish Breuer, Judith Gissen, Paul Oo, Ye H Dhawan, Anil
Jeyaraj, Rebecca
Brown, Li-An K
Jagadisan, Barath
Muntoni, Francesco
Baruteau, Julien
Gupte, Girish
Breuer, Judith
Gissen, Paul
Oo, Ye H
Dhawan, Anil
Abstract
Gene therapies based on recombinant adeno-associated viruses (rAAVs) are radically changing the disease course of several inherited disorders with historically few treatment options. Increasing use of these therapies has revealed multiple immune-mediated adverse effects. Liver injury following systemic delivery of rAAV gene therapy is now well documented, ranging from asymptomatic liver enzyme elevations to rare cases of fatal liver failure. Most cases of severe or fatal liver failure have been reported in patients with neuromuscular disorders, who receive high systemic rAAV doses compared with patients receiving liver-targeted therapies. This Review summarises the principles of modern gene therapy and important adverse effects. We discuss mechanisms of liver injury and current uncertainties, focusing on the T cell-mediated immune response that is thought to underlie the development of severe hepatocellular injury. Finally, we describe the clinical management of liver injury in paediatric patients, recognising the scarce evidence to inform decisions about immunosuppression, and consider strategies to help address this risk.
MIDER Authors
Date
2026-02-09
Type
Article
Subject
Paediatrics, Liver, Genetic therapy
Collections
Citation
Jeyaraj R, Brown LK, Jagadisan B, Muntoni F, Baruteau J, Gupte G, Breuer J, Gissen P, Oo YH, Dhawan A. Safety of in vivo gene therapy in children: mechanisms and management of liver injury. Lancet Child Adolesc Health. 2026 Feb 9:S2352-4642(25)00380-3. doi: 10.1016/S2352-4642(25)00380-3. Epub ahead of print.
Journal / Source Title
The Lancet Child & adolescent health
DOI
10.1016/S2352-4642(25)00380-3
PMID
41679325
Publisher
Elsevier Ltd
Publisher’s URL
https://www.sciencedirect.com/journal/the-lancet-child-and-adolescent-health