Increase of liver stiffness and altered bile acid metabolism after triple CFTR modulator initiation in children and young adults with cystic fibrosis

Novel cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (elexacaftor/tezacaftor/ivacaftor—ETI) promise clinically significant and sustained improvements for patients with cystic fibrosis (CF). In this study, we investigated the impact of ETI therapy on liver stiffness and bile acid metabolism in a cohort of children and young adults with CF.

[1]  H. Mentzel,et al.  Ultrasound elastography in children — nice to have for scientific studies or arrived in clinical routine? , 2022, Molecular and Cellular Pediatrics.

[2]  M. Moustaki,et al.  Changes in share wave elastography after Lumacaftor/Ivacaftor treatment in children with cystic fibrosis. , 2022, Current Drug Safety.

[3]  A. Szwengiel,et al.  Serum bile acids in cystic fibrosis patients-glycodeoxycholic acid as a potential marker of liver disease. , 2021, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[4]  Etty Vider,et al.  A current review of the safety of cystic fibrosis transmembrane conductance regulator modulators , 2020, Journal of clinical pharmacy and therapeutics.

[5]  D. Burrin,et al.  Dysregulated FXR-FGF19 Signaling and Choline Metabolism is Associated with Gut Dysbiosis and Hyperplasia in a Novel Pig Model of Pediatric NASH. , 2020, American journal of physiology. Gastrointestinal and liver physiology.

[6]  C. Teneback,et al.  Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial , 2019, The Lancet.

[7]  L. Lands,et al.  Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. , 2019, The New England journal of medicine.

[8]  M. Toledano,et al.  The emerging burden of liver disease in cystic fibrosis patients: A UK nationwide study , 2019, PloS one.

[9]  R. Houwen,et al.  IVACAFTOR restores FGF19 regulated bile acid homeostasis in cystic fibrosis patients with an S1251N or a G551D gating mutation. , 2019, Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society.

[10]  P. Böelle,et al.  Cystic Fibrosis Liver Disease: Outcomes and Risk Factors in a Large Cohort of French Patients , 2018, Hepatology.

[11]  F. van Goor,et al.  VX‐445–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles , 2018, The New England journal of medicine.

[12]  A. Zolin,et al.  Cystic Fibrosis Mortality in Childhood. Data from European Cystic Fibrosis Society Patient Registry , 2018, International journal of environmental research and public health.

[13]  F. Woodley,et al.  Metabolomic responses to lumacaftor/ivacaftor in cystic fibrosis , 2018, Pediatric pulmonology.

[14]  D. Renz,et al.  ARFI-Elastographie der Leberbeteiligung bei Zystischer Fibrose , 2017, Monatsschrift Kinderheilkunde.

[15]  A. Carino,et al.  Insights on FXR selective modulation. Speculation on bile acid chemical space in the discovery of potent and selective agonists , 2016, Scientific Reports.

[16]  T. Fontanilla,et al.  Hepatic and Splenic Acoustic Radiation Force Impulse Shear Wave Velocity Elastography in Children with Liver Disease Associated with Cystic Fibrosis , 2015, BioMed research international.

[17]  S. Bota,et al.  How useful are ARFI elastography cut-off values proposed by meta-analysis for predicting the significant fibrosis and compensated liver cirrhosis? , 2015, Medical ultrasonography.

[18]  V. Keim,et al.  ARFI and transient elastography for characterization of cystic fibrosis related liver disease: first longitudinal follow-up data in adult patients. , 2013, Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society.

[19]  M. Friedrich-Rust,et al.  Non-invasive measurement of liver and pancreas fibrosis in patients with cystic fibrosis. , 2013, Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society.

[20]  G. Krombach,et al.  A pilot study of the characterization of hepatic tissue strain in children with cystic-fibrosis-associated liver disease (CFLD) by acoustic radiation force impulse imaging , 2013, Pediatric Radiology.

[21]  T. Berg,et al.  Non-Invasive Evaluation of Cystic Fibrosis Related Liver Disease in Adults with ARFI, Transient Elastography and Different Fibrosis Scores , 2012, PloS one.

[22]  M. Lupsor,et al.  Performance of Acoustic Radiation Force Impulse imaging for the staging of liver fibrosis: a pooled meta‐analysis , 2012, Journal of viral hepatitis.

[23]  Matthias Griese,et al.  A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. , 2011, The New England journal of medicine.

[24]  G. Gores,et al.  Hepatocyte death: a clear and present danger. , 2010, Physiological reviews.

[25]  F. Hofmann,et al.  Activation of CFTR by ASBT-mediated bile salt absorption. , 2005, American journal of physiology. Gastrointestinal and liver physiology.

[26]  A. Morabito,et al.  Liver disease in cystic fibrosis: A prospective study on incidence, risk factors, and outcome , 2002, Hepatology.

[27]  G. Davidson,et al.  Conjugated bile acids in serum and secretions in response to cholecystokinin/secretin stimulation in children with cystic fibrosis. , 1985, Gut.