TY - JOUR
T1 - Long-term follow-up and liver outcomes in children with cystic fibrosis and nodular liver on ultrasound in a multi-center study
AU - CFLD Research Network
AU - Leung, Daniel H.
AU - Ye, Wen
AU - Schwarzenberg, Sarah J.
AU - Freeman, A. Jay
AU - Palermo, Joseph J.
AU - Weymann, Alexander
AU - Alonso, Estella M.
AU - Karnsakul, Wikrom W.
AU - Murray, Karen F.
AU - Stoll, Janis M.
AU - Huang, Suiyuan
AU - Karmazyn, Boaz
AU - Masand, Prakash
AU - Magee, John C.
AU - Alazraki, Adina L.
AU - Towbin, Alexander J.
AU - Nicholas, Jennifer L.
AU - Green, Nicole
AU - Otto, Randolph K.
AU - Siegel, Marilyn J.
AU - Ling, Simon C.
AU - Navarro, Oscar M.
AU - Harned, Roger K.
AU - Narkewicz, Michael R.
AU - Molleston, Jean P.
N1 - 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
PY - 2023/3
Y1 - 2023/3
N2 - 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.
AB - 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.
KW - ALT, alanine aminotransferase
KW - APRI, aspartate aminotransferase to platelet ratio index
KW - AST, aminotransferase
KW - CAP, continuous attenuation parameter
KW - CFRD, cystic-fibrosis-related diabetes
KW - CFTR, cystic fibrosis transmembrane regulator
KW - Cirrhosis
KW - Cystic fibrosis liver disease
KW - FEV1, forced expiratory volume in one second
KW - FIB4, fibrosis index based on four factors
KW - FVC, forced vital capacity
KW - GGT, gamma-glutamyl transferase
KW - IGT, impaired glucose tolerance
KW - INR, international normalized ratio
KW - LSM, liver stiffness measurement
KW - NL, normal
KW - NOD, nodular
KW - PELD, pediatric end-stage liver disease
KW - PUSH, prediction by ultrasound of the risk of hepatic cirrhosis
KW - US, ultrasound
KW - Ultrasound
KW - VCTE, vibration controlled transient elastography
KW - WBC, white blood cell count
KW - abbreviations: CF, cystic fibrosis
UR - http://www.scopus.com/inward/record.url?scp=85136123189&partnerID=8YFLogxK
U2 - 10.1016/j.jcf.2022.07.017
DO - 10.1016/j.jcf.2022.07.017
M3 - Article
C2 - 35985930
AN - SCOPUS:85136123189
SN - 1569-1993
VL - 22
SP - 248
EP - 255
JO - Journal of Cystic Fibrosis
JF - Journal of Cystic Fibrosis
IS - 2
ER -