Heterogeneous liver on research ultrasound identifies children with cystic fibrosis at high risk of advanced liver disease.

Simon C Ling, Michael R Narkewicz, John C Magee, Randolph K Otto, Nicole Green, Jennifer L Nicholas, Estella M Alonso, Alex J Towbin, Sarah Jane Schwarzenberg, Adina Alazraki, Wikrom Karnsakul, Oscar M Navarro, Marilyn J Siegel, Roger Harned, Boaz Karmazyn, Prakash Masand, Janis Stoll, Joseph J Palermo, A Jay Freeman, Shruti M Paranjape, Wen Ye, Jean P Molleston, Daniel H Leung

Journal: Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 2023;22(4):745-755

PMID: 37032248

Abstract

BACKGROUND

This study examines whether heterogeneous (HTG) pattern on liver ultrasound (US) identifies children at risk for advanced cystic fibrosis liver disease (aCFLD).

METHODS

Prospective 6-year multicenter case-controlled cohort study. Children with pancreatic insufficient cystic fibrosis (CF) aged 3-12 years without known cirrhosis underwent screening US. Participants with HTG were matched (by age, Pseudomonas infection status and center) 1:2 with participants with normal (NL) US pattern. Clinical status and laboratory data were obtained annually and US bi-annually for 6 years. Primary endpoint was development of nodular (NOD) US pattern consistent with aCFLD.

RESULTS

722 participants underwent screening US, with 65 HTG and 592 NL. Final cohort included 55 HTG and 116 NL with ≥ 1 follow-up US. ALT, AST, GGTP, FIB-4, GPR and APRI were higher, and platelets were lower in HTG compared to NL. HTG had a 9.5-fold increased incidence (95% confidence interval [CI]:3.4, 26.7, p<0.0001, 32.7% vs 3.4%) of NOD versus NL. HTG had a sensitivity of 82% and specificity of 75% for subsequent NOD. Negative predictive value of a NL US for subsequent NOD was 96%. Multivariate logistic prediction model that included baseline US, age, and log(GPR) improved the C-index to 0.90 compared to only baseline US (C-index 0.78). Based on survival analysis, 50% of HTG develop NOD after 8 years.

CONCLUSIONS

Research US finding of HTG identifies children with CF with a 30-50% risk for aCFLD. A score based on US pattern, age and GPR may refine the identification of individuals at high risk for aCFLD.

CLINICAL TRIAL REGISTRATION

Prospective Study of Ultrasound to Predict Hepatic Cirrhosis in CF: NCT 01,144,507 (observational study, no consort checklist).

Copyright © 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Address: Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, USA.; Division of Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital, Department of Pediatrics, Baylor College of Medicine, Houston TX, USA.; Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN, USA.; Department of Biostatistics, University of Michigan Medical School, Ann Arbor, MI, USA.; Division of Pediatric Pulmonology, John Hopkins School of Medicine, Baltimore, MD, USA.; Division of Pediatric Gastroenterology, Hepatology and Nutrition, Emory University School of Medicine, Atlanta, GA, USA.; Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.; Division of Gastroenterology and Nutrition, Washington University School of Medicine, St Louis, MO, USA.; Division of Radiology, Texas Children's Hospital, Houston, TX, USA.; Pediatric Radiology, Riley Hospital for Children, Indianapolis, IN, USA.; Division of Pediatric Radiology, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, CO, USA.; Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.; Department of Medical Imaging, Department of Diagnostic Imaging, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.; Division of Pediatric Gastroenterology, Hepatology and Nutrition, John Hopkins School of Medicine, Baltimore, MD, USA.; Department of Radiology, Emory University School of Medicine and Children's Healthcare of Atlanta, Egleston, Atlanta, GA, USA.; Pediatric Gastroenterology, University of Minnesota Masonic Children's Hospital, Minneapolis, MN, USA.; Department of Radiology, Cincinnati Children's Hospital Medical Center and Department of Radiology, University of Cincinnati College of Medicine Cincinnati, OH, USA.; Division of Pediatric Gastroenterology, Hepatology and Nutrition, Ann & Robert H. Lurie Children's Hospital, Chicago, IL, USA.; Department of Radiology, Case Western Reserve School of Medicine, University Hospitals Rainbow Babies and Children's Hospital, Cleveland, OH, USA.; Division of Gastroenterology and Hepatology, University of Washington and Seattle Children's Hospital, Seattle, WA, USA.; Department of Radiology, Seattle Children's Hospital, Seattle, WA, USA.; Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.; Children's Hospital Colorado and Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Digestive Health Institute, University of Colorado School of Medicine, Aurora, CO, USA. Electronic address: [email protected].
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