Effects of elexacaftor/tezacaftor/ivacaftor on liver fibrosis markers in adults with cystic fibrosis

J Cyst Fibros. 2024 Mar;23(2):349-353. doi: 10.1016/j.jcf.2023.09.006. Epub 2023 Sep 19.

Abstract

Background: There are limited studies to date on the effects of elexacaftor/tezacaftor/ivacaftor (E/T/I) on markers of liver fibrosis in adults with cystic fibrosis (CF). This study aims to analyse changes in makers of liver fibrosis before and after initiation of E/T/I in CF adults.

Methods: Outcome measures of liver fibrosis, including liver stiffness measurement (LSM) using FibroScan, AST-to-platelet-ratio index (APRI) and gamma-GT-to-platelet-ratio (GPR) were available in 74 CF adults following initiation of E/T/I. This was compared to historical data collected in 2018 prior to UK availability of E/T/I.

Results: The median duration of E/T/I therapy at the time liver fibrosis markers were repeated was 21 (IQR: 17-25) months. There was an increase in APRI from historical measurement to follow-up but no change in LSM or GPR. There were no differences in change in fibrosis markers according to CF liver disease (CFLD) status, although those with a raised LSM at baseline (>6.8 kPa) (n = 14) had a significant reduction in LSM from historical measurement to follow-up versus those with a normal historical value (-3.3 kPa vs 0.25 kPa, p < 0.01).

Conclusions: Apart from APRI, we found no changes in liver fibrosis outcomes after initiation of E/T/I in adults with CF. Those with a historical diagnosis of CFLD had no significant worsening or improvement of liver fibrosis markers. We did observe a reduction in LSM in those with liver nodularity, with an initial highest result suggesting a potential positive treatment effect of E/T/I in this category of those with severe CFLD.

Keywords: CFTR modulator therapy; Cystic fibrosis liver disease; Liver fibrosis.

MeSH terms

  • Adult
  • Aminophenols* / therapeutic use
  • Benzodioxoles* / therapeutic use
  • Biomarkers* / blood
  • Chloride Channel Agonists / therapeutic use
  • Cystic Fibrosis* / complications
  • Cystic Fibrosis* / drug therapy
  • Drug Combinations
  • Female
  • Humans
  • Indoles* / therapeutic use
  • Liver Cirrhosis* / diagnosis
  • Liver Cirrhosis* / drug therapy
  • Liver Cirrhosis* / etiology
  • Male
  • Pyrazoles* / therapeutic use
  • Pyridines* / therapeutic use
  • Pyrroles / therapeutic use
  • Pyrrolidines / therapeutic use
  • Quinolines / therapeutic use
  • Quinolones* / therapeutic use

Substances

  • elexacaftor
  • tezacaftor
  • ivacaftor