Marilyn J Siegel1, A Jay Freeman2, Wen Ye3, Joseph J Palermo4, Jean P Molleston5, Shruti M Paranjape6, Janis Stoll7, Daniel H Leung8, Prakash Masand9, Boaz Karmazyn10, Roger Harned11, Simon C Ling12, Oscar M Navarro13, Wikrom Karnsakul14, Adina Alazraki15, Sarah Jane Schwarzenberg16, Frank Glen Seidel17, Alex Towbin18, Estella M Alonso19, Jennifer L Nicholas1, Karen F Murray20, Randolph K Otto21, Averell H Sherker22, John C Magee23, Michael R Narkewicz24. 1. Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO. 2. Division of Pediatric Gastroenterology, Hepatology and Nutrition, Emory University School of Medicine, Atlanta, GA. 3. Department of Biostatistics, University of Michigan Medical School, Ann Arbor, MI. 4. Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH. 5. Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN. 6. Division of Pediatric Pulmonology, John Hopkins School of Medicine, Baltimore, MD. 7. Division of Gastroenterology and Nutrition, Washington University School of Medicine, St Louis, MO. 8. Division of Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital, Houston, TX. 9. Division of Radiology, Texas Children's Hospital, Houston, TX. 10. Pediatric Radiology, Riley Hospital for Children, Indianapolis, IN. 11. Division of Pediatric Radiology, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, CO. 12. Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada. 13. Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada; Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, Ontario, Canada. 14. Division of Pediatric Gastroenterology, Hepatology and Nutrition, John Hopkins School of Medicine, Baltimore, MD. 15. Department of Radiology, Emory University School of Medicine and Children's Healthcare of Atlanta, Egleston, Atlanta, GA. 16. Pediatric Gastroenterology, University of Minnesota Masonic Children's Hospital, Minneapolis, MN. 17. Pediatric Radiology, Lucile Packard Children's Hospital, Stanford, CA. 18. Department of Radiology, Cincinnati Children's Hospital Medical Center and Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH. 19. Division of Pediatric Gastroenterology, Hepatology and Nutrition, Ann & Robert H. Lurie Children's Hospital, Chicago, IL. 20. Division of Gastroenterology and Hepatology, University of Washington and Seattle Children's Hospital, Seattle, WA. 21. Department of Radiology, Seattle Children's Hospital, Seattle, WA. 22. Liver Diseases Branch, NIDDK, NIH, Bethesda, MD. 23. Department of Surgery, University of Michigan Medical School, Ann Arbor, MI. 24. Digestive Health Institute, Children's Hospital Colorado and Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO. Electronic address: michael.narkewicz@childrenscolorado.org.
Abstract
OBJECTIVE: To assess if a heterogeneous pattern on research liver ultrasound examination can identify children at risk for advanced cystic fibrosis (CF) liver disease. STUDY DESIGN: Planned 4-year interim analysis of a 9-year multicenter, case-controlled cohort study (Prospective Study of Ultrasound to Predict Hepatic Cirrhosis in CF). Children with pancreatic insufficient CF aged 3-12 years without known cirrhosis, Burkholderia species infection, or short bowel syndrome underwent a screening research ultrasound examination. Participants with a heterogeneous liver ultrasound pattern were matched (by age, Pseudomonas infection status, and center) 1:2 with participants with a normal pattern. Clinical status and laboratory data were obtained annually and research ultrasound examinations biannually. The primary end point was the development of a nodular research ultrasound pattern, a surrogate for advanced CF liver disease. RESULTS: There were 722 participants who underwent screening research ultrasound examination, of which 65 were heterogeneous liver ultrasound pattern and 592 normal liver ultrasound pattern. The final cohort included 55 participants with a heterogeneous liver ultrasound pattern and 116 participants with a normal liver ultrasound pattern. All participants with at least 1 follow-up research ultrasound were included. There were no differences in age or sex between groups at entry. Alanine aminotransferase (42 ± 22 U/L vs 32 ± 19 U/L; P = .0033), gamma glutamyl transpeptidase (36 ± 34 U/L vs 15 ± 8 U/L; P < .001), and aspartate aminotransferase to platelet ratio index (0.7 ± 0.5 vs 0.4 ± 0.2; P < .0001) were higher in participants with a heterogeneous liver ultrasound pattern compared with participants with a normal liver ultrasound pattern. Participants with a heterogeneous liver ultrasound pattern had a 9.1-fold increased incidence (95% CI, 2.7-30.8; P = .0004) of nodular pattern vs a normal liver ultrasound pattern (23% in heterogeneous liver ultrasound pattern vs 2.6% in normal liver ultrasound pattern). CONCLUSIONS: Research liver ultrasound examinations can identify children with CF at increased risk for developing advanced CF liver disease.
OBJECTIVE: To assess if a heterogeneous pattern on research liver ultrasound examination can identify children at risk for advanced cystic fibrosis (CF) liver disease. STUDY DESIGN: Planned 4-year interim analysis of a 9-year multicenter, case-controlled cohort study (Prospective Study of Ultrasound to Predict Hepatic Cirrhosis in CF). Children with pancreatic insufficient CF aged 3-12 years without known cirrhosis, Burkholderia species infection, or short bowel syndrome underwent a screening research ultrasound examination. Participants with a heterogeneous liver ultrasound pattern were matched (by age, Pseudomonasinfection status, and center) 1:2 with participants with a normal pattern. Clinical status and laboratory data were obtained annually and research ultrasound examinations biannually. The primary end point was the development of a nodular research ultrasound pattern, a surrogate for advanced CF liver disease. RESULTS: There were 722 participants who underwent screening research ultrasound examination, of which 65 were heterogeneous liver ultrasound pattern and 592 normal liver ultrasound pattern. The final cohort included 55 participants with a heterogeneous liver ultrasound pattern and 116 participants with a normal liver ultrasound pattern. All participants with at least 1 follow-up research ultrasound were included. There were no differences in age or sex between groups at entry. Alanine aminotransferase (42 ± 22 U/L vs 32 ± 19 U/L; P = .0033), gamma glutamyl transpeptidase (36 ± 34 U/L vs 15 ± 8 U/L; P < .001), and aspartate aminotransferase to platelet ratio index (0.7 ± 0.5 vs 0.4 ± 0.2; P < .0001) were higher in participants with a heterogeneous liver ultrasound pattern compared with participants with a normal liver ultrasound pattern. Participants with a heterogeneous liver ultrasound pattern had a 9.1-fold increased incidence (95% CI, 2.7-30.8; P = .0004) of nodular pattern vs a normal liver ultrasound pattern (23% in heterogeneous liver ultrasound pattern vs 2.6% in normal liver ultrasound pattern). CONCLUSIONS: Research liver ultrasound examinations can identify children with CF at increased risk for developing advanced CF liver disease.
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Authors: Wen Ye; Daniel H Leung; Jean P Molleston; Simon C Ling; Karen F Murray; Jennifer L Nicholas; Suiyuan Huang; Boaz W Karmazyn; Roger K Harned; Prakash Masand; Adina L Alazraki; Oscar M Navarro; Randolph K Otto; Joseph J Palermo; Alexander J Towbin; Estella M Alonso; Wikrom W Karnsakul; Sarah Jane Schwarzenberg; Glenn F Seidel; Marilyn Siegel; John C Magee; Michael R Narkewicz; A Jay Freeman Journal: Hepatol Commun Date: 2021-05-13