Early identification of children with cystic fibrosis (CF) at risk for severe liver disease (CFLD) would enable targeted study of preventative therapies. There is no gold standard test for CFLD. Ultrasonography (US) is used to identify CFLD, but with concerns for its diagnostic accuracy. We aim to determine if differences in standard blood tests, imaging variables and non-invasive liver fibrosis indices correlate with liver US patterns and thus provide supportive evidence that a heterogeneous US liver pattern reflects clinically relevant liver disease.
We studied baseline research abdominal US and bloodwork from 244 children with pancreatic insufficient CF, ages 3–12y, enrolled in a prospective study of the ability of US to predict CF cirrhosis (PUSH study). Children with a heterogeneous liver pattern on US (HTG, n = 62) were matched 1:2 in design with children with normal US (NL, n = 122). Analyses included children with nodular (NOD, n = 22) and homogeneous hyperechoic (HMG, n = 38) livers.
Univariate analysis showed significant differences between US groups for standard blood tests, spleen size, and non-invasive liver fibrosis indices. Multivariable models discriminated NOD vs. NL with excellent accuracy (AUROC 0.96). Models also distinguish HTG vs. NL (AUROC 0.76), NOD vs. HTG (0.78), and HMG vs NL (0.79).
Liver US patterns in children with CF correlate with platelet count, spleen size and indices of liver fibrosis. Multivariable models of these biomarkers have excellent discriminating ability for NL vs NOD, and good ability to distinguish other US patterns, suggesting that US patterns correlate with clinically relevant liver disease.
*The Hospital for Sick Children and Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
†University of Michigan, Ann Arbor, MI, United States
‡Baylor College of Medicine, Texas Children's Hospital, Houston, TX, United States
§Department of Diagnostic Imaging, The Hospital for Sick Children and Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada
||Washington University School of Medicine, St Louis, MO, United States
¶Johns Hopkins University School of Medicine, Baltimore, MD, United States
#Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, GA, United States
**University of Michigan Medical School, Ann Arbor, MI, United States
††Digestive Health Institute, Children's Hospital Colorado & University of Colorado School of Medicine, Aurora, CO, United States.
Address correspondence and reprint requests to Simon C. Ling, MBChB, The Hospital for Sick Children, Room 8418 Black Wing, 555 University Avenue, Toronto, Ontario M5G1X8, Canada (e-mail: firstname.lastname@example.org).
Received 16 November, 2018
Accepted 24 April, 2019
for the Cystic Fibrosis Liver Disease Research Network (CFLD-NET)
Grant support: The NIDDK (Grant Number U01 DK062456)
The Cystic Fibrosis Foundation (Grant Number NARKEW07A0)
SC Ling receives research support from Bristol Myers Squibb and Abbvie.
W Ye, no disclosures
DH Leung receives research support from Bristol Myers Squibb, Gilead, Abbvie, and Roche.
O Navarro, no disclosures
A Weymann, no disclosures
W Karnsakul receives research support from Gilead
AJ Freeman, no disclosures
J Magee, no disclosures
All authors were involved in study concept and design, acquisition of data, analysis and interpretation of results, drafting of the manuscript.
WY also performed the statistical analyses.
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