Baseline Ultrasound and Clinical Correlates in Children with Cystic Fibrosis

Abstract

Objective To investigate the relationship between abdominal ultrasound (US) findings and demographic, historical and clinical features in children with CF. Study design Children age 3-12 years with CF without known cirrhosis, were enrolled in a prospective, multi-center study of US to predict hepatic fibrosis. Consensus US patterns were assigned by 3 radiologists as normal, heterogeneous, homogeneous, or cirrhosis. Data were derived from direct collection and U.S. or Toronto CF registries. Chi-square or ANOVA were used to compare variables among US groups and between normal and abnormal. Logistic regression was used to study risk factors for having abnormal US. Results Findings in 719 subjects were normal (n=590, 82.1%), heterogeneous (64, 8.9%), homogeneous (41, 5.7%), and cirrhosis (24, 3.3%). Cirrhosis (p=0.0004), homogeneous (p<0.0001) and heterogeneous (p=0.03) were older than normal. More males were heterogeneous (p=0.001). More heterogeneous (15.0%, p=0.009) and cirrhosis (25.0%, p=0.005) had CF-related diabetes or impaired glucose tolerance versus normal (5.4%). Early infection with Pseudomonas aeruginosa (<2 years old) was associated with a lower risk (OR 0.42, p=0.0007) of abnormal. Ursodeoxycholic acid use (OR 3.69, p <0.0001) and CF-related diabetes (OR 2.21, p=0.019) were associated with increased risk of abnormal. Conclusions Unsuspected cirrhosis is seen in 3.3% of young patients with CF, heterogeneous in 8.9%. abnormal US is associated with CF-related diabetes, and early P aeruginosa is associated with normal US. Prospective assessment of these risk factors may identify potential interventional targets.

The CF gastrointestinal microbiome: Structure and clinical impact

“…There is also a suggestion that early antibiotic treatments may have more global effects on health in CF. In a large prospective study of children with CF who underwent screening liver ultrasounds, early (≤2 years of age) Pseudomonas infection, which usually results in more antibiotic exposure, was protective for the findings of an abnormal ultrasound . This finding provides further evidence that early alterations of the GI microbiota may have long‐term impacts distant from the intestinal tract.…”

Diagnosing cystic fibrosis-related diabetes: current methods and challenges

“…Leung et al looked at 719 CF subjects and nearly 20% had liver disease on ultrasound, which was then sub-classified as heterogeneous, homogenous or cirrhotic. Patients with heterogeneous or cirrhotic disease on ultrasound were more likely to have CFRD or impaired glucose tolerance than the cohort with normal livers on ultrasound [49]. These findings may be a result of more severe genotypes causing liver disease, also causing CFRD.…”

“…The prevalence of CFRD is higher in those with CF liver disease [48] including those with ultrasound abnormalities [49]. Leung et al looked at 719 CF subjects and nearly 20% had liver disease on ultrasound, which was then sub-classified as heterogeneous, homogenous or cirrhotic.…”

Data that empower: The success and promise of CF patient registries

“…Extensive baseline data are already available and study participants can potentially be followed by either dataset alone. Examples from the US include enhancing registry data with detailed genetic and biomarker information to investigate associations between genotypes and phenotypes; understanding the role of environmental and genetic effects on lung function; combining imaging data with registry data to understand early stage liver disease; obtaining information from people with CF and their families regarding early acquisition of P. aeruginosa ; and providing baseline data for a study of optimal length of IV treatment for adults with pulmonary exacerbations…”