Association Between Transient Elastography and Controlled Attenuated Parameter and Liver Ultrasound in Children With Cystic Fibrosis

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

doi:10.1002/hep4.1719

Association Between Transient Elastography and Controlled Attenuated Parameter and Liver Ultrasound in Children With Cystic Fibrosis

Hepatol Commun. 2021 May 13;5(8):1362-1372. doi: 10.1002/hep4.1719. eCollection 2021 Aug.

Authors

Wen Ye¹, Daniel H Leung², Jean P Molleston³, Simon C Ling⁴, Karen F Murray⁵, Jennifer L Nicholas⁶, Suiyuan Huang¹, Boaz W Karmazyn⁷, Roger K Harned⁸, Prakash Masand⁹, Adina L Alazraki¹⁰, Oscar M Navarro^{11

12}, Randolph K Otto¹³, Joseph J Palermo^{14

15}, Alexander J Towbin^{16

17}, Estella M Alonso¹⁸, Wikrom W Karnsakul¹⁹, Sarah Jane Schwarzenberg²⁰, Glenn F Seidel²¹, Marilyn Siegel⁶, John C Magee²², Michael R Narkewicz²³, A Jay Freeman²⁴

Affiliations

¹ Department of BiostatisticsUniversity of Michigan School of Public HealthAnn ArborMIUSA.
² Division of Gastroenterology, Hepatology and NutritionDepartment of PediatricsTexas Children's HospitalBaylor College of MedicineHoustonTXUSA.
³ Pediatric Gastroenterology, Hepatology and NutritionRiley Hospital for Children at IU HealthIndiana University School of MedicineIndianapolisINUSA.
⁴ The Hospital for Sick ChildrenDepartment of PediatricsUniversity of TorontoTorontoONCanada.
⁵ Division of Gastroenterology and HepatologyUniversity of Washington and Seattle Children's HospitalSeattleWAUSA.
⁶ Mallinckrodt Institute of RadiologyWashington University School of MedicineSt. LouisMOUSA.
⁷ Pediatric RadiologyRiley Hospital for Children at IU HealthIndiana University School of MedicineIndianapolisINUSA.
⁸ Division of Pediatric RadiologyChildren's Hospital Colorado and University of Colorado School of MedicineAuroraCOUSA.
⁹ Division of RadiologyTexas Children's HospitalHoustonTXUSA.
¹⁰ Department of RadiologyEmory University School of Medicine and Children's Healthcare of AtlantaAtlantaGAUSA.
¹¹ Department of Medical ImagingUniversity of TorontoTorontoONCanada.
¹² Department of Diagnostic ImagingThe Hospital for Sick ChildrenTorontoONCanada.
¹³ Department of RadiologyUniversity of Washington and Seattle Children's HospitalSeattleWAUSA.
¹⁴ Division of Pediatric Gastroenterology, Hepatology and NutritionCincinnati Children's Hospital Medical CenterCincinnatiOHUSA.
¹⁵ Department of PediatricsUniversity of Cincinnati College of MedicineCincinnatiOHUSA.
¹⁶ Department of RadiologyCincinnati Children's Hospital Medical CenterCincinnatiOHUSA.
¹⁷ Department of RadiologyUniversity of Cincinnati College of MedicineCincinnatiOHUSA.
¹⁸ Division of Pediatric Gastroenterology, Hepatology and NutritionAnn & Robert H. Lurie Children's HospitalChicagoILUSA.
¹⁹ Division of Pediatric Gastroenterology, Hepatology and NutritionJohn Hopkins School of MedicineBaltimoreMDUSA.
²⁰ Pediatric GastroenterologyUniversity of Minnesota Masonic Children's HospitalMinneapolisMNUSA.
²¹ Pediatric RadiologyLucile Packard Children's HospitalPalo AltoCAUSA.
²² Department of SurgeryUniversity of Michigan Medical SchoolAnn ArborMIUSA.
²³ Digestive Health InstituteChildren's Hospital Colorado and Section of Pediatric Gastroenterology, Hepatology and NutritionDepartment of PediatricsUniversity of Colorado School of MedicineAuroraCOUSA.
²⁴ Division of Pediatric Gastroenterology, Hepatology and NutritionEmory University School of Medicine/Children's Healthcare of AtlantaAtlantaGAUSA.

Abstract

Methods to identify children with cystic fibrosis (CF) at risk for development of advanced liver disease are lacking. We aim to determine the association between liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) with research ultrasound (US) patterns and conventional hepatic markers as a potential means to follow liver disease progression in children with CF. ELASTIC (Longitudinal Assessment of Transient Elastography in CF) is a nested cohort of 141 patients, ages 7-21, enrolled in the Prediction by US of Risk of Hepatic Cirrhosis in CF (PUSH) Study. We studied the association between LSM with research-grade US patterns (normal [NL], heterogeneous [HTG], homogeneous [HMG], or nodular [NOD]) and conventional hepatic markers. In a subgroup (n = 79), the association between controlled attenuation parameter (CAP) and US pattern was explored. Among 133 subjects undergoing VCTE, NOD participants (n = 26) had a significantly higher median (interquartile range) LSM of 9.1 kPa (6.3, 15.8) versus NL (n = 72, 5.1 kPa [4.2, 7.0]; P < 0.0001), HMG (n = 17, 5.9 kPa [5.2, 7.8]; P = 0.0013), and HTG (n = 18, 6.1 kPa [4.7, 7.0]; P = 0.0008) participants. HMG participants (n = 14) had a significantly higher mean CAP (SD) (270.5 dB/m [61.1]) compared with NL (n = 40, 218.8 dB/m [46.5]; P = 0.0027), HTG (n = 10, 218.1 dB/m [60.7]; P = 0.044), and NOD (n = 15, 222.7 dB/m [56.4]; P = 0.041) participants. LSM had a negative correlation with platelet count (r_s = $-$ 0.28, P = 0.0071) and positive correlation with aspartate aminotransferase-to-platelet ratio index (r_s = 0.38, P = 0.0002), Fibrosis-4 index (r_s = 0.36, P = 0.0007), gamma-glutamyltransferase (GGT; r_s = 0.35, P = 0.0017), GGT-to-platelet ratio (r_s = 0.35, P = 0.003), and US spleen size z-score (r_s = 0.27, P = 0.0073). Conclusion: VCTE is associated with US patterns and conventional markers in patients with liver disease with CF.

Abstract

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