Highlights -ETI liver
- •ETI treatment led to a small increase in ALT, AST and bilirubin from 3 months.
- •Clinically significant increases above the normal range were rare.
- •Underlying liver disease was not associated with greater liver test abnormalities.
Elexacaftor/tezacaftor/ivacaftor (E/T/I) therapy has resulted in substantial improvements in health status for many with cystic fibrosis. Monitoring of liver tests is recommended due to observed rises in transaminases in trials and cases of hepatotoxicity. Comprehensive data in large populations of unselected individuals and those with established CF related liver disease (CFLD) is lacking.
Patients prescribed E/T/I at a large, adult centre had liver tests monitored at least 3 monthly for 12 months. Changes in individual liver tests were analysed and abnormalities were compared in those with and without CFLD.
255 of 267 eligible patients were included. Mild rises in median ALT, AST and bilirubin from baseline to 3 months (all p < 0.001) within normal limits were noted which were sustained. There were no differences in changes in liver tests between those with or without CFLD. There was a significant difference in alkaline phosphatase for those with raised levels at baseline versus those with normal baseline level (-18.5 vs +2.0 IU/L, p = 0.002). Clinically significant rises in ALT and AST occurred in 8 (3.1%) and 6 (2.4%) cases respectively, with derangements in 2 individuals attributed to therapy.
E/T/I leads to a mild, likely clinically insignificant increase in ALT, AST and bilirubin after 3 months which is sustained but does not appear to increase further in the vast majority. Underlying CFLD should not be a barrier to treatment. Although there was a reduction in ALP when elevated at baseline, this was not unique to those with pre-existing CFLD.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Journal of Cystic Fibrosis
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Cystic fibrosis.Lancet. 2016; 388: 2519-2531
- 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.Lancet. 2019; 394: 1940-1948
- Elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with a single Phe508del allele.N Engl J Med. 2019; 381: 1809-1819
- Triple therapy for cystic fibrosis phe508del-gating and -residual function genotypes.N Engl J Med. 2021; 385: 815-825
- Efficacy and safety of elexacaftor plus tezacaftor plus ivacaftor versus tezacaftor plus ivacaftor in people with cystic fibrosis homozygous for F508del-CFTR: a 24-week, multicentre, randomised, double-blind, active-controlled, phase 3b trial.Lancet Respir Med. 2022; 10: 267-277
- Delayed hepatic necrosis in a cystic fibrosis patient taking Elexacaftor/Tezacaftor/Ivacaftor (Kaftrio).Respir Med Case Rep. 2021; 34101553
- Acute liver failure in a patient with cystic fibrosis taking triple combination modulator.2021 ([cited 2022 20 May]; Available from:)
- Kaftrio, summary of product characteristics.2020 ([cited 2022 20 May]; Available from)
- Emerging clinical perspectives in cystic fibrosis liver disease.Curr Opin Pulm Med. 2021; 27: 593-599
- Review article: epidemiology, pathogenesis and management of liver disease in adults with cystic fibrosis.Aliment Pharmacol Ther. 2022; 55: 389-400
- Best practice guidance for the diagnosis and management of cystic fibrosis-associated liver disease.J Cyst Fibros. 2011; 10 (Suppl): S29-S36
- Pathophysiology of cystic fibrosis liver disease: a channelopathy leading to alterations in innate immunity and in microbiota.Cell Mol Gastroenterol Hepatol. 2019; 8: 197-207
- Pathophysiologic implications of innate immunity and autoinflammation in the biliary epithelium.Biochim Biophys Acta Mol Basis Dis. 2018; 1864 (Pt B): 1374-1379
- Cystic fibrosis-related liver disease: clinical presentations, diagnostic and monitoring approaches in the era of CFTR modulator therapies.J Hepatol. 2021;
- Effect of elexacaftor-tezacaftor-ivacaftor on body weight and metabolic parameters in adults with cystic fibrosis.J Cyst Fibros. 2022; 21: 265-271
- Assessment report.2020 ([cited 2022 14 March]; Available from:)https://www.ema.europa.eu/en/documents/assessment-report/kaftrio-epar-public-assessment-report_en.pdf
Published online: January 19, 2023
Accepted: January 12, 2023
Received in revised form: January 11, 2023
Received: August 3, 2022
Publication stageIn Press Corrected Proof
© 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.