Heterogeneous Liver on Research Ultrasound Identifies Children with Cystic Fibrosis at High Risk of Advanced Liver Disease: Interim Results of a Prospective Observational Case-Controlled Study

CFLD Network

doi:10.1016/j.jpeds.2019.12.033

Heterogeneous Liver on Research Ultrasound Identifies Children with Cystic Fibrosis at High Risk of Advanced Liver Disease: Interim Results of a Prospective Observational Case-Controlled Study

CFLD Network

Pediatric Gastroenterology, Hepatology & Nutrition

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

OBJECTIVE: To assess if a heterogeneous pattern on research liver ultrasound examination can identify children at risk for advanced cystic fibrosis (CF) liver disease.

STUDY DESIGN: Planned 4-year interim analysis of a 9-year multicenter, case-controlled cohort study (Prospective Study of Ultrasound to Predict Hepatic Cirrhosis in CF). Children with pancreatic insufficient CF aged 3-12 years without known cirrhosis, Burkholderia species infection, or short bowel syndrome underwent a screening research ultrasound examination. Participants with a heterogeneous liver ultrasound pattern were matched (by age, Pseudomonas infection status, and center) 1:2 with participants with a normal pattern. Clinical status and laboratory data were obtained annually and research ultrasound examinations biannually. The primary end point was the development of a nodular research ultrasound pattern, a surrogate for advanced CF liver disease.

RESULTS: There were 722 participants who underwent screening research ultrasound examination, of which 65 were heterogeneous liver ultrasound pattern and 592 normal liver ultrasound pattern. The final cohort included 55 participants with a heterogeneous liver ultrasound pattern and 116 participants with a normal liver ultrasound pattern. All participants with at least 1 follow-up research ultrasound were included. There were no differences in age or sex between groups at entry. Alanine aminotransferase (42 ± 22 U/L vs 32 ± 19 U/L; P = .0033), gamma glutamyl transpeptidase (36 ± 34 U/L vs 15 ± 8 U/L; P < .001), and aspartate aminotransferase to platelet ratio index (0.7 ± 0.5 vs 0.4 ± 0.2; P < .0001) were higher in participants with a heterogeneous liver ultrasound pattern compared with participants with a normal liver ultrasound pattern. Participants with a heterogeneous liver ultrasound pattern had a 9.1-fold increased incidence (95% CI, 2.7-30.8; P = .0004) of nodular pattern vs a normal liver ultrasound pattern (23% in heterogeneous liver ultrasound pattern vs 2.6% in normal liver ultrasound pattern).

CONCLUSIONS: Research liver ultrasound examinations can identify children with CF at increased risk for developing advanced CF liver disease.

Original language	English (US)
Pages (from-to)	62-69.e4
Journal	Journal of Pediatrics
Volume	219
DOIs	https://doi.org/10.1016/j.jpeds.2019.12.033
State	Published - Apr 2020

Bibliographical note

Funding Information:
Funded by grants from the Cystic Fibrosis Foundation (NARKEW17AB0 [to M.N.]) and NIDDK ( U01 DK062453 [to M.N.] and U01 DK 062456 [to J.M.]). S.S. serves as a consultant for AbbVie. M.N. serves as a consultant for Vertex, has received research grants from Gilead , AbbVie , and has a family member with stock in AbbVie and Merck . The other authors declare no conflicts of interest. Original Article

Funding Information:
Funded by grants from the Cystic Fibrosis Foundation (NARKEW17AB0 [to M.N.]) and NIDDK (U01 DK062453 [to M.N.] and U01 DK 062456 [to J.M.]). S.S. serves as a consultant for AbbVie. M.N. serves as a consultant for Vertex, has received research grants from Gilead, AbbVie, and has a family member with stock in AbbVie and Merck. The other authors declare no conflicts of interest.

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

cirrhosis
cystic fibrosis liver disease
Cystic Fibrosis/complications
Prospective Studies
Risk Assessment
Humans
Child, Preschool
Male
Liver Diseases/diagnosis
Case-Control Studies
Ultrasonography
Female
Child
Liver/diagnostic imaging

PubMed: MeSH publication types

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

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10.1016/j.jpeds.2019.12.033

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@article{648f4711ec74480b9ebf36cf40bc332b,

title = "Heterogeneous Liver on Research Ultrasound Identifies Children with Cystic Fibrosis at High Risk of Advanced Liver Disease: Interim Results of a Prospective Observational Case-Controlled Study",

abstract = "OBJECTIVE: To assess if a heterogeneous pattern on research liver ultrasound examination can identify children at risk for advanced cystic fibrosis (CF) liver disease.STUDY DESIGN: Planned 4-year interim analysis of a 9-year multicenter, case-controlled cohort study (Prospective Study of Ultrasound to Predict Hepatic Cirrhosis in CF). Children with pancreatic insufficient CF aged 3-12 years without known cirrhosis, Burkholderia species infection, or short bowel syndrome underwent a screening research ultrasound examination. Participants with a heterogeneous liver ultrasound pattern were matched (by age, Pseudomonas infection status, and center) 1:2 with participants with a normal pattern. Clinical status and laboratory data were obtained annually and research ultrasound examinations biannually. The primary end point was the development of a nodular research ultrasound pattern, a surrogate for advanced CF liver disease.RESULTS: There were 722 participants who underwent screening research ultrasound examination, of which 65 were heterogeneous liver ultrasound pattern and 592 normal liver ultrasound pattern. The final cohort included 55 participants with a heterogeneous liver ultrasound pattern and 116 participants with a normal liver ultrasound pattern. All participants with at least 1 follow-up research ultrasound were included. There were no differences in age or sex between groups at entry. Alanine aminotransferase (42 ± 22 U/L vs 32 ± 19 U/L; P = .0033), gamma glutamyl transpeptidase (36 ± 34 U/L vs 15 ± 8 U/L; P < .001), and aspartate aminotransferase to platelet ratio index (0.7 ± 0.5 vs 0.4 ± 0.2; P < .0001) were higher in participants with a heterogeneous liver ultrasound pattern compared with participants with a normal liver ultrasound pattern. Participants with a heterogeneous liver ultrasound pattern had a 9.1-fold increased incidence (95% CI, 2.7-30.8; P = .0004) of nodular pattern vs a normal liver ultrasound pattern (23% in heterogeneous liver ultrasound pattern vs 2.6% in normal liver ultrasound pattern).CONCLUSIONS: Research liver ultrasound examinations can identify children with CF at increased risk for developing advanced CF liver disease.",

keywords = "cirrhosis, cystic fibrosis liver disease, Cystic Fibrosis/complications, Prospective Studies, Risk Assessment, Humans, Child, Preschool, Male, Liver Diseases/diagnosis, Case-Control Studies, Ultrasonography, Female, Child, Liver/diagnostic imaging",

author = "{CFLD Network} and Siegel, {Marilyn J.} and Freeman, {A. Jay} and Wen Ye and Palermo, {Joseph J.} and Molleston, {Jean P.} and Paranjape, {Shruti M.} and Janis Stoll and Leung, {Daniel H.} and Prakash Masand and Boaz Karmazyn and Roger Harned and Ling, {Simon C.} and Navarro, {Oscar M.} and Wikrom Karnsakul and Adina Alazraki and Schwarzenberg, {Sarah Jane} and Seidel, {Frank Glen} and Alex Towbin and Alonso, {Estella M.} and Nicholas, {Jennifer L.} and Murray, {Karen F.} and Otto, {Randolph K.} and Sherker, {Averell H.} and Magee, {John C.} and Narkewicz, {Michael R.}",

note = "Funding Information: Funded by grants from the Cystic Fibrosis Foundation (NARKEW17AB0 [to M.N.]) and NIDDK ( U01 DK062453 [to M.N.] and U01 DK 062456 [to J.M.]). S.S. serves as a consultant for AbbVie. M.N. serves as a consultant for Vertex, has received research grants from Gilead , AbbVie , and has a family member with stock in AbbVie and Merck . The other authors declare no conflicts of interest. Original Article Funding Information: Funded by grants from the Cystic Fibrosis Foundation (NARKEW17AB0 [to M.N.]) and NIDDK (U01 DK062453 [to M.N.] and U01 DK 062456 [to J.M.]). S.S. serves as a consultant for AbbVie. M.N. serves as a consultant for Vertex, has received research grants from Gilead, AbbVie, and has a family member with stock in AbbVie and Merck. The other authors declare no conflicts of interest. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2020",

month = apr,

doi = "10.1016/j.jpeds.2019.12.033",

language = "English (US)",

volume = "219",

pages = "62--69.e4",

journal = "Journal of Pediatrics",

issn = "0022-3476",

publisher = "Mosby Inc.",

}

TY - JOUR

T1 - Heterogeneous Liver on Research Ultrasound Identifies Children with Cystic Fibrosis at High Risk of Advanced Liver Disease

T2 - Interim Results of a Prospective Observational Case-Controlled Study

AU - CFLD Network

AU - Siegel, Marilyn J.

AU - Freeman, A. Jay

AU - Ye, Wen

AU - Palermo, Joseph J.

AU - Molleston, Jean P.

AU - Paranjape, Shruti M.

AU - Stoll, Janis

AU - Leung, Daniel H.

AU - Masand, Prakash

AU - Karmazyn, Boaz

AU - Harned, Roger

AU - Ling, Simon C.

AU - Navarro, Oscar M.

AU - Karnsakul, Wikrom

AU - Alazraki, Adina

AU - Schwarzenberg, Sarah Jane

AU - Seidel, Frank Glen

AU - Towbin, Alex

AU - Alonso, Estella M.

AU - Nicholas, Jennifer L.

AU - Murray, Karen F.

AU - Otto, Randolph K.

AU - Sherker, Averell H.

AU - Magee, John C.

AU - Narkewicz, Michael R.

N1 - Funding Information: Funded by grants from the Cystic Fibrosis Foundation (NARKEW17AB0 [to M.N.]) and NIDDK ( U01 DK062453 [to M.N.] and U01 DK 062456 [to J.M.]). S.S. serves as a consultant for AbbVie. M.N. serves as a consultant for Vertex, has received research grants from Gilead , AbbVie , and has a family member with stock in AbbVie and Merck . The other authors declare no conflicts of interest. Original Article Funding Information: Funded by grants from the Cystic Fibrosis Foundation (NARKEW17AB0 [to M.N.]) and NIDDK (U01 DK062453 [to M.N.] and U01 DK 062456 [to J.M.]). S.S. serves as a consultant for AbbVie. M.N. serves as a consultant for Vertex, has received research grants from Gilead, AbbVie, and has a family member with stock in AbbVie and Merck. The other authors declare no conflicts of interest. Publisher Copyright: © 2019 Elsevier Inc.

PY - 2020/4

Y1 - 2020/4

N2 - OBJECTIVE: To assess if a heterogeneous pattern on research liver ultrasound examination can identify children at risk for advanced cystic fibrosis (CF) liver disease.STUDY DESIGN: Planned 4-year interim analysis of a 9-year multicenter, case-controlled cohort study (Prospective Study of Ultrasound to Predict Hepatic Cirrhosis in CF). Children with pancreatic insufficient CF aged 3-12 years without known cirrhosis, Burkholderia species infection, or short bowel syndrome underwent a screening research ultrasound examination. Participants with a heterogeneous liver ultrasound pattern were matched (by age, Pseudomonas infection status, and center) 1:2 with participants with a normal pattern. Clinical status and laboratory data were obtained annually and research ultrasound examinations biannually. The primary end point was the development of a nodular research ultrasound pattern, a surrogate for advanced CF liver disease.RESULTS: There were 722 participants who underwent screening research ultrasound examination, of which 65 were heterogeneous liver ultrasound pattern and 592 normal liver ultrasound pattern. The final cohort included 55 participants with a heterogeneous liver ultrasound pattern and 116 participants with a normal liver ultrasound pattern. All participants with at least 1 follow-up research ultrasound were included. There were no differences in age or sex between groups at entry. Alanine aminotransferase (42 ± 22 U/L vs 32 ± 19 U/L; P = .0033), gamma glutamyl transpeptidase (36 ± 34 U/L vs 15 ± 8 U/L; P < .001), and aspartate aminotransferase to platelet ratio index (0.7 ± 0.5 vs 0.4 ± 0.2; P < .0001) were higher in participants with a heterogeneous liver ultrasound pattern compared with participants with a normal liver ultrasound pattern. Participants with a heterogeneous liver ultrasound pattern had a 9.1-fold increased incidence (95% CI, 2.7-30.8; P = .0004) of nodular pattern vs a normal liver ultrasound pattern (23% in heterogeneous liver ultrasound pattern vs 2.6% in normal liver ultrasound pattern).CONCLUSIONS: Research liver ultrasound examinations can identify children with CF at increased risk for developing advanced CF liver disease.

AB - OBJECTIVE: To assess if a heterogeneous pattern on research liver ultrasound examination can identify children at risk for advanced cystic fibrosis (CF) liver disease.STUDY DESIGN: Planned 4-year interim analysis of a 9-year multicenter, case-controlled cohort study (Prospective Study of Ultrasound to Predict Hepatic Cirrhosis in CF). Children with pancreatic insufficient CF aged 3-12 years without known cirrhosis, Burkholderia species infection, or short bowel syndrome underwent a screening research ultrasound examination. Participants with a heterogeneous liver ultrasound pattern were matched (by age, Pseudomonas infection status, and center) 1:2 with participants with a normal pattern. Clinical status and laboratory data were obtained annually and research ultrasound examinations biannually. The primary end point was the development of a nodular research ultrasound pattern, a surrogate for advanced CF liver disease.RESULTS: There were 722 participants who underwent screening research ultrasound examination, of which 65 were heterogeneous liver ultrasound pattern and 592 normal liver ultrasound pattern. The final cohort included 55 participants with a heterogeneous liver ultrasound pattern and 116 participants with a normal liver ultrasound pattern. All participants with at least 1 follow-up research ultrasound were included. There were no differences in age or sex between groups at entry. Alanine aminotransferase (42 ± 22 U/L vs 32 ± 19 U/L; P = .0033), gamma glutamyl transpeptidase (36 ± 34 U/L vs 15 ± 8 U/L; P < .001), and aspartate aminotransferase to platelet ratio index (0.7 ± 0.5 vs 0.4 ± 0.2; P < .0001) were higher in participants with a heterogeneous liver ultrasound pattern compared with participants with a normal liver ultrasound pattern. Participants with a heterogeneous liver ultrasound pattern had a 9.1-fold increased incidence (95% CI, 2.7-30.8; P = .0004) of nodular pattern vs a normal liver ultrasound pattern (23% in heterogeneous liver ultrasound pattern vs 2.6% in normal liver ultrasound pattern).CONCLUSIONS: Research liver ultrasound examinations can identify children with CF at increased risk for developing advanced CF liver disease.

KW - cirrhosis

KW - cystic fibrosis liver disease

KW - Cystic Fibrosis/complications

KW - Prospective Studies

KW - Risk Assessment

KW - Humans

KW - Child, Preschool

KW - Male

KW - Liver Diseases/diagnosis

KW - Case-Control Studies

KW - Ultrasonography

KW - Female

KW - Child

KW - Liver/diagnostic imaging

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UR - http://www.scopus.com/inward/citedby.url?scp=85081659573&partnerID=8YFLogxK

U2 - 10.1016/j.jpeds.2019.12.033

DO - 10.1016/j.jpeds.2019.12.033

M3 - Article

C2 - 32061406

AN - SCOPUS:85081659573

SN - 0022-3476

VL - 219

SP - 62-69.e4

JO - Journal of Pediatrics

JF - Journal of Pediatrics

ER -

Heterogeneous Liver on Research Ultrasound Identifies Children with Cystic Fibrosis at High Risk of Advanced Liver Disease: Interim Results of a Prospective Observational Case-Controlled Study

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

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