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.
Abstract
Background
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.
Methods
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.
Results
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.
Conclusions
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.
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Article info
Publication history
Published online: January 19, 2023
Accepted:
January 12,
2023
Received in revised form:
January 11,
2023
Received:
August 3,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
