Highlights
- •Among 171 patients with severe CFLD, 19 (11.1%) were not eligible for CFTR modulators.
- •All ineligible patients carried at least one mutation leading to complete loss of CFTR function.
- •There remains an unmet therapy need for ineligible patients with CFLD.
Abstract
Cystic-fibrosis-related liver disease (CFLD) is a variable phenotype of CF. The severe
CFLD variant with cirrhosis or portal hypertension has a poor prognosis and life expectancy.
CFTR modulator therapies are now available for people with CF and eligibility for
such treatment is based on their CFTR genotype. We evaluated the genetic eligibility
for elexacaftor, tezacaftor, ivacaftor (ETI), and ivacaftor (IVA) monotherapy in a
previously reported CF cohort of 1591 people with CF of whom 171 with severe CFLD.
Based on their CFTR mutations, 13% (N=184/1420) of subjects without CFLD and 11% (N=19/171)
of those with severe CFLD are not eligible for either ETI or IVA therapy.
The non-eligible patients without CFLD or with severe CFLD can currently not take
advantage of the potential benefits of these new treatments. Although this study cannot
provide any data regarding the effect of ETI or IVA on the progression of severe CFLD,
the consequences for ineligibility of patients with extreme liver phenotype may be
even more significant because of their poorer disease risk profile.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: February 02, 2023
Accepted:
January 23,
2023
Received in revised form:
January 12,
2023
Received:
June 28,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.
