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New Algorithm for the Integration of Ultrasound Into Cystic Fibrosis Liver Disease Screening

Sellers, Zachary M.*; Lee, Lori W.; Barth, Richard A.; Milla, Carlos§

Journal of Pediatric Gastroenterology and Nutrition: October 2019 - Volume 69 - Issue 4 - p 404–410
doi: 10.1097/MPG.0000000000002412
Original Articles: Hepatology

Objectives: Liver nodularity occurs across the spectrum of cystic fibrosis liver disease (CFLD), from regenerative nodules to cirrhosis, and can occur without liver enzyme abnormalities. Our aims were to determine if incorporating abdominal ultrasound (US) with annual laboratory testing improves the detection of CFLD and establish CF-specific thresholds for liver screening labs.

Methods: CF patients at least 6 years old who were exocrine pancreatic-insufficient had an US with Doppler and shear wave elastography. Patients were divided into Normal, Echogenic, or Nodular groups, based on US findings. Results were compared with aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelets, AST to platelet ratio index (APRI), Fibrosis 4 (FIB-4), and gamma-glutamyl transferase (GGT) to platelet ratio (GPR). Receiver operator curve, sensitivity, specificity, positive predictive value, negative predictive value, and optimal cut-off with Youden Index were calculated.

Results: From 82 patients, incorporation of US identified more nodular livers than using labs alone. The Nodular group had significantly greater median AST (44), ALT (48), GGT (46), APRI (0.619), FIB-4 (0.286), GPR (1.431). Optimal cut-offs to detect liver nodularity in CF were AST >33, ALT >45, GGT >21, Platelets <230, APRI >0.367, FIB-4 >0.222, GPR >0.682. Using GGT, APRI, and GPR, we generated an algorithm to direct the use of US in CFLD screening.

Conclusions: Using modified serum lab thresholds, addition of liver fibrosis indices, and/or abdominal US can increase detection of liver nodularity in CF. A combination of GGT, GPR, and APRI can help direct which CF children should undergo US evaluation. These tools may improve earlier identification of fibrosis and/or cirrhosis in CF patients.

*Division of Pediatric Gastroenterology, Hepatology, and Nutrition

Department of Pediatrics

Division of Pediatric Radiology

§Division of Pediatric Pulmonary Medicine, Stanford University, Palo Alto, CA.

Address correspondence and reprint requests to Zachary M. Sellers, MD, PhD, Pediatric Gastroenterology, Hepatology, and Nutrition, Stanford University, 750 Welch Road, Suite 116, Palo Alto, CA 94304 (e-mail:

Received 9 July, 2018

Accepted 22 April, 2019

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This study was supported by funding provided by the Cystic Fibrosis Foundation (SELLER16L0 to Z.M.S.).

The authors report no conflicts of interest.

© 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,