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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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 331×10 3/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

Bibliographical note

Funding Information:
Source of Funding: Supported by the Cystic Fibrosis Foundation (NARKEW17AB0 to M.N.) and the National Institutes of Health NIDDK U01 DK062453 to M.N. and NIDDK U24 DK062456 to Dr. John Magee and Dr Wen Ye.

Funding Information:
Conflicts of Interest: Dr. Molleston received grants from AbbVie, Albireo, Gilead, Mirum/Shire and the Cystic Fibrosis Foundation. Dr. Karnsakul received grants from Albireo, Cystic Fibrosis Foundation, and Gilead. Dr. Freeman receives grant support from the Cystic Fibrosis Foundation, NIH and Travere Therapeutics as well as a consults for AbbVie and Takeda. Dr. Murray received grants from Albireo, Cleveland Clinic, and Gilead. Dr. Leung received grants from AbbVie, Cystic Fibrosis Foundation, Gilead, Merck, and Mirum. Dr. Narkewicz received grants from Cystic Fibrosis Foundation, Gilead, AbbVie and consults for Vertex. Dr. Narkewicz's spouse owns stock in Becton Dickson and Co, Cerner, Johnson & Johnson, Laboratory Corp of America, Merck, PepsiCo, Proctor and Gamble, Stryker, United Health, and Zoetis. Dr. Schwarzenberg received grants from Gilead and the Cystic Fibrosis Foundation, and consults for Abbvie and UpToDate.

Publisher Copyright:
© 2022


  • 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

PubMed: MeSH publication types

  • Multicenter Study
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural


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