Search

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)., Competing Interests: Declaration of Competing Interest The authors disclosure the following Sarah Jane Schwarzenberg serves as a: consultant for AbbVie, Michael R Narkewicz serves as a consultant for Vertex, and has received research grants from Gilead, AbbVie and has a family member with stock in Merck. Jean Molleston has research funding from Abbvie, Albireo, Gillead, Shire. Daniel H. Leung has served as a consultant for Merck, Gilead and Vertex and has received research grants from Gilead, Abbvie and Mirum. A. Jay Freeman has done consulting work for AbbVie and Takeda and has received research support from Allergan and Travere Therapeutics. Wikrom Karnsakul has received grants from Albireo Pharma, Gilead, and Travere Therapeutics. Alexander J Towbin received author royalites from Elsevier, served as a consultant to Applied Radiology and received grant funding from the Cystic Fibrosis Foundation. Simon Ling has received research grants from Abbvie and Gilead. The remaining authors disclose no conflicts., (Copyright © 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2022. Published by Elsevier B.V.)