Long-term follow-up and liver outcomes in children with cystic fibrosis and nodular liver on ultrasound in a multi-center study

CFLD Research Network

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3 Scopus citations


Background: Nodular liver (NOD) in cystic fibrosis (CF) suggests advanced CF liver disease (aCFLD); little is known about progression of liver disease (LD) after detection of sonographic NOD. Methods: Clinical, laboratory, and ultrasound (US) data from Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in CFLD Study participants with NOD at screening or follow-up were compared with normal (NL). Linear mixed effects models were used for risk factors for LD progression and Kaplan-Meier estimator for time-to-event. Results: 54 children with NOD (22 screening, 32 follow-up) and 112 NL were evaluated. Baseline (BL) and trajectory of forced expiratory volume, forced vital capacity, height/BMI z-scores were similar in NOD vs NL. Platelets were lower in NOD at BL (250 vs 331×103/microL; p < 0.001) and decreased by 8600/year vs 2500 in NL. Mean AST to Platelet Ratio Index (1.1 vs 0.4; p < 0.001), Fibrosis-4 Index (0.4 vs 0.2, p < 0.001), and spleen size z-score (SSZ) [1.5 vs 0.02; p < 0.001] were higher in NOD at BL; SSZ increased by 0.5 unit/year in NOD vs 0.1 unit/year in NL. Median liver stiffness (LSM) by transient elastography was higher in NOD (8.2 kPa, IQR 6–11.8) vs NL (5.3, 4.2–7, p < 0.0001). Over 6.3 years follow-up (1.3–10.3), 6 NOD had esophageal varices (cumulative incidence in 10 years: 20%; 95% CI: 0.0%, 40.0%), 2 had variceal bleeding, and 2 underwent liver transplantation; none had ascites or hepatic encephalopathy. No NL experienced liver-related events. Conclusions: NOD developed clinically evident portal hypertension faster than NL without worse growth or lung disease.

Original languageEnglish (US)
Pages (from-to)248-255
Number of pages8
JournalJournal of Cystic Fibrosis
Issue number2
StatePublished - Mar 2023


  • ALT, alanine aminotransferase
  • APRI, aspartate aminotransferase to platelet ratio index
  • AST, aminotransferase
  • CAP, continuous attenuation parameter
  • CFRD, cystic-fibrosis-related diabetes
  • CFTR, cystic fibrosis transmembrane regulator
  • Cirrhosis
  • Cystic fibrosis liver disease
  • FEV1, forced expiratory volume in one second
  • FIB4, fibrosis index based on four factors
  • FVC, forced vital capacity
  • GGT, gamma-glutamyl transferase
  • IGT, impaired glucose tolerance
  • INR, international normalized ratio
  • LSM, liver stiffness measurement
  • NL, normal
  • NOD, nodular
  • PELD, pediatric end-stage liver disease
  • PUSH, prediction by ultrasound of the risk of hepatic cirrhosis
  • US, ultrasound
  • Ultrasound
  • VCTE, vibration controlled transient elastography
  • WBC, white blood cell count
  • abbreviations: CF, cystic fibrosis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Pediatrics, Perinatology, and Child Health


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