Utilizing ultrasound to identify children at greater risk of developing advanced cystic fibrosis liver disease
The 4-year interim results of a prospective, multi-center study suggest research-based ultrasound screening could be utilized to predict which children with cystic fibrosis are at greatest risk of developing advanced cystic fibrosis liver disease.
Researchers from the University of Colorado Anschutz Medical Campus (CO, USA) have released 4-year interim results of a prospective, case-controlled study of children with cystic fibrosis, suggesting a test for identifying those at greater risk of developing advanced cystic fibrosis liver disease.
The primary organs affected in individuals with cystic fibrosis are the lungs and pancreas, though it is not uncommon for the liver and other organs to be affected as well. Approximately 7–10% of individuals with the genetic condition develop advanced cystic fibrosis liver disease, which only affects individuals with cystic fibrosis, has no known cause and results from advanced liver scarring.
Senior study author Michael Narkewicz (University of Colorado School of Medicine and Children's Hospital Colorado; both CO, USA) commented: “As we develop new therapies for cystic fibrosis and for other liver diseases, it is critical that we better understand which patients with cystic fibrosis are at higher risk for cystic fibrosis liver disease.”
The planned 4-year interim results of the 9-year Prospective study of UltraSound to predict Hepatic cirrhosis in cystic fibrosis (PUSH) have been published in the Journal of Pediatrics. In the article, investigators detail their use of research-based ultrasound screening – with consensus grading by four radiologists – to determine the proportion of study participants with heterogeneous and normal liver patterns who developed nodular liver appearances, a hallmark of advanced cystic fibrosis liver disease.
The study cohort included 722 children, aged 3–12 years, with cystic fibrosis. Investigators matched – by age and participating center site – each individual presenting with heterogenous patterns on their livers at the start of the 4-year study with two study participants who had normal liver patterns. Researchers observed that, over the course of the study, those with such initial abnormal, heterogenous patterns had a 9.1-fold increased risk of developing nodular liver appearances and advanced cystic fibrosis liver disease, compared with study subjects with normal liver patterns.
Limitations of this study include the relatively short follow-up period and the lack of incorporation of histological correlation between nodular liver appearance and advanced cystic fibrosis liver disease development. Further, researchers did not incorporate other imaging technologies, such as elastography, which assesses liver stiffness – another parameter associated with the development of advanced cystic fibrosis liver disease.
Narkewicz stated: “This is the first large multi-center study of ways to predict which children with cystic fibrosis are at higher risk for advanced liver disease. The findings show that we have found an important way to project which patients might develop cystic fibrosis liver disease.”
“It also gives us clinical therapeutic targets for interventional therapies that could prevent the development of this liver disease,” Narkewicz concluded.
Siegel MJ, Freeman AJ, Ye W et al. Heterogeneous liver on research ultrasound identifies children with cystic fibrosis at high risk of advanced liver disease: interim results of a prospective observational case-controlled study. J. Pediatr. doi:10.1016/j.jpeds.2019.12.033 (2020) (Epub ahead of print);