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Original Article| Volume 22, ISSUE 2, P256-262, March 2023

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Longitudinal effects of elexacaftor/tezacaftor/ivacaftor on liver tests at a large single adult cystic fibrosis centre

  • Daniel H Tewkesbury
    Affiliations
    Manchester University NHS Foundation Trust, Manchester, UK

    Division of Immunology, Immunity to Infection & Respiratory Medicine, University of Manchester, Manchester, UK
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  • Varinder Athwal
    Affiliations
    Manchester University NHS Foundation Trust, Manchester, UK

    Division of Diabetes, Endocrine and Gastroenterology, University of Manchester, Manchester, UK
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  • Rowland J Bright-Thomas
    Affiliations
    Manchester University NHS Foundation Trust, Manchester, UK

    Division of Immunology, Immunity to Infection & Respiratory Medicine, University of Manchester, Manchester, UK
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  • Andrew M Jones
    Affiliations
    Manchester University NHS Foundation Trust, Manchester, UK

    Division of Immunology, Immunity to Infection & Respiratory Medicine, University of Manchester, Manchester, UK
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  • Peter J Barry
    Correspondence
    Corresponding author at: Manchester Adult Cystic Fibrosis Centre, Wythenshawe Hospital, Southmoor Road, Manchester M23 9LT, UK.
    Affiliations
    Manchester University NHS Foundation Trust, Manchester, UK

    Division of Immunology, Immunity to Infection & Respiratory Medicine, University of Manchester, Manchester, UK
    Search for articles by this author
Published:January 19, 2023DOI:https://doi.org/10.1016/j.jcf.2023.01.007

      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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