Case Report: When cystic fibrosis, elexacaftor/tezacaftor/ivacaftor therapy, and alpha1 antitrypsin deficiency get together.
Details
Serval ID
serval:BIB_E1BEAED053D6
Type
Article: article from journal or magazin.
Publication sub-type
Case report (case report): feedback on an observation with a short commentary.
Collection
Publications
Institution
Title
Case Report: When cystic fibrosis, elexacaftor/tezacaftor/ivacaftor therapy, and alpha1 antitrypsin deficiency get together.
Journal
Frontiers in pediatrics
ISSN
2296-2360 (Print)
ISSN-L
2296-2360
Publication state
Published
Issued date
2024
Peer-reviewed
Oui
Volume
12
Pages
1378744
Language
english
Notes
Publication types: Case Reports
Publication Status: epublish
Publication Status: epublish
Abstract
In the last 10 years, the care of patients with cystic fibrosis (CF) has been revolutionized with the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs, with a major impact on symptoms and life expectancy, especially considering the newest and highly effective elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) therapy. Conversely, adverse effects are relatively frequent, with some being life-threatening, such as severe hepatitis. Clinical trials on children starting CFTR modulators have reported transaminase elevations >3× upper limit of the norm in 10%-20% of patients, whereas real-life studies have reported discontinuation rates three times higher than those observed in phase 3 trials. We report the case of a 10-year-old boy with CF who developed severe acute hepatitis 2 weeks after starting ELX/TEZ/IVA therapy. An extensive screening for potential causes led to the identification of heterozygous alpha1-antitrypsin (AAT) deficiency with genotype MZ. The Z allele of SERPINA1 gene, encoding AAT, is known as a risk factor for CF liver disease. We hypothesized that it may act as a risk factor for drug-induced liver injury from CFTR modulators, notably ELX/TEZ/IVA. Therefore, checking AAT before starting CFTR modulator therapy can be suggested, in particular for children with previous, even transient, liver disease.
Keywords
CF liver disease, CFTR modulator, Elx/tez/iva, Serpina1, Z allele, children, cystic fibrosis, drug-induced liver injury, ELX/TEZ/IVA, SERPINA1
Pubmed
Web of science
Open Access
Yes
Create date
29/04/2024 9:01
Last modification date
02/05/2024 6:21