CF liver disease; CFTR modulator; ELX/TEZ/IVA; SERPINA1; Z allele; children; cystic fibrosis; drug-induced liver injury; Pediatrics, Perinatology and Child Health
Abstract :
[en] 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.
Disciplines :
Pediatrics
Author, co-author :
Kinuani, Rachel ; Pediatric Pulmonology and Cystic Fibrosis Unit, Department Women-Mother-Child, Service of Pediatrics, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland ; Department of Pediatrics, Divisions of Pediatrics Pulmonology, University Hospital Liège, Liège, Belgium
Ezri, Jessica; Pediatric Gastro-Enterology Unit, Department Women-Mother-Child, Service of Pediatrics, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
Kernen, Yann; General Pediatric Private Practice, Yverdon-les-Bains, Switzerland
Rochat, Isabelle; Pediatric Pulmonology and Cystic Fibrosis Unit, Department Women-Mother-Child, Service of Pediatrics, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
Blanchon, Sylvain; Pediatric Pulmonology and Cystic Fibrosis Unit, Department Women-Mother-Child, Service of Pediatrics, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
Language :
English
Title :
Case Report: When cystic fibrosis, elexacaftor/tezacaftor/ivacaftor therapy, and alpha1 antitrypsin deficiency get together.
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