Effects of CFTR modulators on serum biomarkers of liver fibrosis in children with cystic fibrosis.

The cystic fibrosis (CF) transmembrane conductance regulator corrector/potentiator combinations lumacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor improve sweat chloride, pulmonary function, and nutrition. Yet it is unclear whether they may also impact the progression of liver fibrosis, which is a substantial source of morbidity and mortality for patients with CF. We conducted a retrospective, single-center analysis of children and adolescents with CF treated with lumacaftor/ivacaftor and/or elexacaftor/tezacaftor/ivacaftor therapy, focusing on alterations in liver function tests and fibrosis indices using previously-established thresholds that corresponded with increased liver elastography. In pairwise comparisons of before and during treatment timepoints, we found that those with CF-associated liver involvement experienced significant decreases in gamma-glutamyl transferase, aspartate aminotransferase-to-platelet index, and gamma-glutamyl transferase-to-platelet ratio while on lumacaftor/ivacaftor. These differences were not observed in patients treated with elexacaftor/tezacaftor/ivacaftor, nor were they observed in patients without underlying CF-associated liver disease. These results provide the first evidence that lumacaftor/ivacaftor may improve liver fibrosis in children and adolescents with CF and suggest it may be beneficial in the treatment of CF-associated liver disease.

Pediatric inflammatory bowel disease and imaging-related radiation: are we increasing the likelihood of malignancy?

BACKGROUND AND AIMS: Increasing use of diagnostic radiography has led to concern about the malignant potential of ionizing radiation. We aimed to quantify the cumulative effective dose (CED) from diagnostic medical imaging in children with inflammatory bowel disease (IBD) and to identify which children are at greatest risk for high amounts of image-related radiation exposure. PATIENTS AND METHODS: A retrospective chart review of pediatric IBD patients seen between January 1 and May 30, 2008 was conducted. The effective dose of radiation received from all of the radiology tests performed during the course of each patient's treatment was estimated using typical effective doses and our institution's computed tomography dose index. A CED ≥50 mSv was considered high. RESULTS: Complete records were available for 257 of 372 screened subjects. One hundred seventy-one had Crohn disease (CD) and 86 had ulcerative colitis (UC). The mean CED was 17.56 ± 15.91 mSv and was greater for children with CD than for those with UC (20.5 ± 17.5 vs 11.7 ± 9.9 mSv, P < 0.0001). Fifteen children (5.8%) had a CED ≥50 mSv, including 14 of 171 (8.2%) with CD and 1 of 86 (1.2%) with UC (P = 0.02). In children with CD, factors associated with high CED per multivariate analysis were any IBD-related surgery (odds ratio 42, 95% confidence interval 8-223, P < 0.0001) and platelet count (odds ratio 16, 95% confidence interval 1.5-175, P = 0.02). CONCLUSIONS: Although all doses of ionizing radiation have some malignancy-inducing potential, a small but important percentage of children with IBD are exposed to particularly high doses of ionizing radiation from diagnostic tests and procedures. Physicians caring for such patients must seek to limit radiation exposure whenever possible to lessen the lifetime risk of malignancy.