Although clinical trials report a risk of derangement of liver function tests in paediatric patients with cystic fibrosis (CF) the risk appears to be low, a new Irish study is reporting.
In a paper published in the February 2021 edition of the Irish Medical Journal (IMJ), researchers noted that the most common CF transmembrane conductance regulator (CFTR) variant was F508del, and in Ireland 55 per cent of patients were F508del homozygous.
They also stated that the combination of lumacaftor (a CFTR corrector) and ivacaftor (a CFTR potentiator) was licensed for the treatment of patients with CF who are homozygous for the F508del mutation to patients 12 years and older in 2017, and to patients aged 6-11 years in early 2018.
Serious adverse reactions related to elevated liver transaminase levels were reported in clinical trials, however.
Consequently, it was recommended that serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin were monitored prior to initiating the drug; every three months for the first year of treatment, and then annually.
Writing in the IMJ, Paluck et al said they wanted to assess in clinical practice, whether F508del homozygous paediatric CF patients had a derangement of LFTs while on lumacaftor/ivacaftor therapy.
During the trial, a retrospective chart review audit in a single CF centre was used.
Thirty-nine (43%) patients out of 91 CF clinic patients met criteria to start treatment.
Results showed a statistically significant decrease in ALT, ALP, GGT and total bilirubin levels, and no change in AST levels during the first three months of treatment.
In two patients (5%) AST levels rose to greater than three times the upper limit of normal during treatment, however these levels then decreased with continued use.
A similar trend of improved LFTs was seen in a subgroup of patients with pre-existing liver disease (6/15.4% of patients). No patients died or experienced hepatic encephalopathy.
“Our results were unexpected and encouraging,” the researchers concluded.
“They suggest that, although the clinical trials raised a concern that commencing a child on this new CFTR modulator therapy came with a significant risk of derangement of LFTs, the risk appears to be low, and therapy may actually help improve LFTs.”
IMJ; Vol 114, No. 2, P259.