Characterization of CFTR mutations in people with cystic fibrosis and severe liver disease who are not eligible for CFTR modulators

• Published in: Journal of cystic fibrosis Vol. 22; no. 2; pp. 263 - 265
• Main Authors: Colombo, Carla, Ramm, Grant A, Lindblad, Anders, Corti, Fabiola, Porcaro, Luigi, Alghisi, Federico, Asherova, Irina, Evans, Helen, Kashirskaya, Nataliya, Kondratyeva, Elena, Lewindon, Peter J, de Monestrol, Isabelle, Oliver, Mark, Ooi, Chee Y., Padoan, Rita, Shankar, Sahana, Alicandro, Gianfranco
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2023
• Subjects: Aminophenols; Benzodioxoles - adverse effects; CFTR genotype; CFTR modulators; Cirrhosis; Cystic fibrosis; Cystic Fibrosis - drug therapy; Cystic Fibrosis - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Humans; Hypertension, Portal - etiology; Liver disease; Mutation; Portal hypertension; Pulmonary/Respiratory; Cirrhosis; Cystic fibrosis; CFTR genotype; CFTR modulators; Liver disease; Portal hypertension
• ISSN: 1569-1993; 1873-5010; 1873-5010
• DOI: 10.1016/j.jcf.2023.01.012

•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. 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. [Display omitted]