Lumacaftor-ivacaftor effects on cystic fibrosis-related liver involvement in adolescents with homozygous F508 del-CFTR

•The effects of lumacaftor-ivacaftor on CFTR associated liver disease remain unclear.•We investigated the effect of lumacaftor-ivacaftor in Cystic Fibrosis patients with liver involvement.•Gammaglutamyl transferase level improved significantly during 1 year follow up.•This was not correlated with an...

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Published in:Journal of cystic fibrosis 2022-03, Vol.21 (2), p.212-219
Main Authors: Drummond, David, Dana, Jérémy, Berteloot, Laureline, Schneider-Futschik, Elena K., Chedevergne, Frédérique, Bailly-Botuha, Céline, Nguyen-Khoa, Thao, Cornet, Mathieu, Le Bourgeois, Muriel, Debray, Dominique, Girard, Muriel, Sermet-Gaudelus, Isabelle
Format: Article
Language:English
Subjects:
Adolescent
Aminophenols - adverse effects
Aminopyridines
Benzodioxoles - adverse effects
Biomarkers
CFTR modulator
cirrhosis
Cystic Fibrosis - complications
Cystic Fibrosis - diagnosis
Cystic Fibrosis - drug therapy
Cystic Fibrosis Transmembrane Conductance Regulator - genetics
Cystic-fibrosis liver disease
Drug Combinations
hepatobiliary
Humans
Life Sciences
Liver - diagnostic imaging
liver enzymes
Mutation
pediatrics
Prospective Studies
Quinolones
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Summary:•The effects of lumacaftor-ivacaftor on CFTR associated liver disease remain unclear.•We investigated the effect of lumacaftor-ivacaftor in Cystic Fibrosis patients with liver involvement.•Gammaglutamyl transferase level improved significantly during 1 year follow up.•This was not correlated with any change in liver imaging.•These findings may suggest a potential benefit of CFTR modulators on CF liver disease. The effects of lumacaftor-ivacaftor on cystic fibrosis transmembrane conductance regulator (CFTR)-associated liver disease remain unclear. The objective of the study was to describe the effect of this treatment on features of liver involvement in a cystic fibrosis (CF) adolescent population homozygous for F508del. Clinical characteristics, liver blood tests, abdominal ultrasonography (US), and pancreas and liver proton density fat fraction (PDFF) by magnetic resonance imaging, were obtained at treatment initiation and at 12 months for all patients. Biomarkers of CFTR activity (sweat chloride test, nasal potential difference, and intestinal current measurement) were assessed at initiation and at 6 months therapy. Of the 37 patients who started ivacaftor/lumacaftor treatment, 28 were eligible for analysis. In this group, before treatment initiation, 4 patients were diagnosed with multinodular liver and portal hypertension, 19 with other forms of CF liver involvement, and 5 with no signs of liver involvement. During treatment, no hepatic adverse reactions were documented, and no patient developed liver failure. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gammaglutamyl transferase (GGT) decreased significantly following initiation of lumacaftor-ivacaftor, and remained so after 12 months treatment. This was not correlated with changes in clinical status, liver and pancreas US and PDFF, fecal elastase, or lumacaftor-ivacaftor serum levels. The most “responsive” patients demonstrated a significant increase in biomarkers of CFTR activity. These results may suggest a potential beneficial effect of CFTR modulators on CF liver disease and warrant further investigation in larger, prospective studies.
ISSN:1569-1993
1873-5010
DOI:10.1016/j.jcf.2021.07.018