There is a clear association between mutation-specific CFTR modulator therapies (CFTRmt) and adverse liver effects. Their use in patients with moderate-severe pre-existing liver disease is not recommended. Liver function tests (LFTs) should be evaluated 3 monthly for the first year and then annually (MHRA, 2022, SmPCs).

We reviewed the effect of CFTRmt on LFTs and liver ultrasound in our paediatric cohort between 2013 and 2022. 

A single-centre retrospective observational study was conducted in a tertiary Paediatric CF centre. We evaluated LFTs and liver ultrasound, before and after commencing CFTRmt treatment. 81 patients, 6 to 19 years old, were analysed, with 41 males and 40 females.

16% patients had new derangement of LFTs after starting. In 5%, ALT and AST were both greater than twice the upper limit of normal (ULN), and in only 2.5% ALT and/or AST were greater than 5 times ULN. 22% had abnormal baseline scans; of these, 3 deteriorated after commencing CFTRmt. 14% had normal baseline scans but deteriorated. 65% patients had normal scans after commencing treatment. No patients had cirrhosis. 

2 patients, both with normal baseline investigations, paused treatment after starting due to abnormal liver tests. ALT was > 5 times ULN, AST > 3 times ULN and liver ultrasounds were abnormal. Both re-started and currently continue on Kaftrio. Both had SARS-CoV-2 around the time of derangement.

Our results reflect reduced rates and severity of deranged LFTs after starting a CFTRmt compared to other studies (Milla et al., 2017, Am J Respir Crit Care Med), with no results >8 ULN. Overall, our real-world data has shown CFTRmt are safe to use in most patients, with appropriate monitoring.