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P08 Precision medicines in practice: the connection between CFTR modulators and deranged liver enzymes
  1. Chloe Ireland,
  2. Octavio Aragon Cuevas,
  3. Alice McCloskey
  1. Liverpool John Moores University


Background and Aim For most of the 83 years since acknowledging cystic fibrosis (CF) as a separate disease entity, treatment has primarily focused on symptomatic relief.1 Following the discovery of the CFTR gene, efforts have been made to produce therapies to target the underlying dysfunctions caused by CFTR mutations.2 Moderate transaminase elevations are commonly observed in CF patients. Severe transaminase elevations have been observed in patients taking CFTR modulators in clinical trials with the initial STRIVE trial revealing that treatment discontinuation was commonly due to an increase in hepatic enzymes.3 Consequently, liver function test (LFTs) monitoring is recommended for all patients before commencing therapy, every three months for the first year and annually thereafter. This audit aims to assess the compliance of LFT monitoring in clinical practice for paediatric patients initiated on CFTR modulators, evaluate the incidence of liver-related adverse effects, and examine trends between the CFTR modulator used and the clinical significance of LFT derangements, and determine if there are any sex-related correlations.

Methods Patient data, including date and age on treatment initiation, gender, LFT results at baseline (AST, ALT, ALP, GGT and total bilirubin), first derangement since initiation and monitoring frequency were extracted from the clinical system Meditech®, pseudonymised and analysed. There were 91 records of patients being treated with a CFTR modulator. Some patients were on more than one CFTR modulator as treatment can be switched if eligible. For the purpose of the audit after consultation with the local CF clinical team, a two-month deviation outside of the recommended monitoring frequency was considered non-compliant. LFT derangements were classified as clinically significant if the result was higher than 3 times the upper limit of normal (ULN).

Results Our study found that most patients (50/91 – 54.9%) on CFTR modulators in the tertiary centre did not have their LFTs monitored following the recommended guidelines. A statistically significant increase in LFT abnormalities from pre- to post- intervention with a CFTR modulator was observed (p=0.015). Kaftrio®/Kalydeco® (3/20 – 15%) and Orkambi® (1/29 – 3.4%) were the only CFTR modulators that led to patients developing clinically significant derangements (>3x ULN). Additionally, a greater proportion of females (24/51 – 47.1%) than males (15/40 – 37.5%) had abnormal LFTs within the tertiary centre contrary to previous epidemiological studies where males have been documented to have a greater risk of abnormal LFTs. However, the strength of this association was negligible (φ =0.096, p=0.360).

Conclusion In conclusion, the tertiary centre’s compliance with LFT monitoring guidelines for patients initiated on CFTR modulators was substandard. Most records of treatment initiation occurred during COVID-19, which impacted monitoring as many hospitals suspended routine clinical work to limit the spread of the infection in high-risk groups. Time constraints limited the audit during the data extraction period; therefore, results should be interpreted cautiously. In the absence of the COVID-19 pandemic a re-audit process should include patient lifestyle data and consider other medication regimens that could potentially alter LFTs. Introducing a blood clerk would enable the CF unit to monitor LFT changes more efficiently.


  1. Guimbellot J, Taylor-Cousar JL. Combination CFTR modulator therapy in children and adults with cystic fibrosis. The Lancet Respiratory Medicine 2021;9:677–679.

  2. Lopes-Pacheco M. CFTR Modulators: The Changing Face of Cystic Fibrosis in the Era of Precision Medicine. Frontiers of Pharmacology 2020;10:1662.

  3. Gavioli EM, Guardado N, Haniff F, et al. A current review of the safety of cystic fibrosis transmembrane conductance regulator modulators. Journal of Clinical Pharmacy and Therapeutics 2021;46:286–294.

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