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Non-invasive biomarkers of Fontan-associated liver disease

BACKGROUND & AIMS: Fontan-associated liver disease (FALD) has emerged as an important morbidity following surgical palliation of single ventricle congenital heart disease. In this study, non-invasive biomarkers that may be associated with severity of FALD were explored. METHODS: A retrospective...

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Autores principales: Emamaullee, Juliet, Khan, Sara, Weaver, Carly, Goldbeck, Cameron, Yanni, George, Kohli, Rohit, Genyk, Yuri, Zhou, Shengmei, Shillingford, Nick, Sullivan, Patrick M., Takao, Cheryl, Detterich, Jon, Kantor, Paul F., Cleveland, John D., Herrington, Cynthia, Ram Kumar, S., Starnes, Vaughn, Badran, Sarah, Patel, Neil D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517550/
https://www.ncbi.nlm.nih.gov/pubmed/34693238
http://dx.doi.org/10.1016/j.jhepr.2021.100362
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author Emamaullee, Juliet
Khan, Sara
Weaver, Carly
Goldbeck, Cameron
Yanni, George
Kohli, Rohit
Genyk, Yuri
Zhou, Shengmei
Shillingford, Nick
Sullivan, Patrick M.
Takao, Cheryl
Detterich, Jon
Kantor, Paul F.
Cleveland, John D.
Herrington, Cynthia
Ram Kumar, S.
Starnes, Vaughn
Badran, Sarah
Patel, Neil D.
author_facet Emamaullee, Juliet
Khan, Sara
Weaver, Carly
Goldbeck, Cameron
Yanni, George
Kohli, Rohit
Genyk, Yuri
Zhou, Shengmei
Shillingford, Nick
Sullivan, Patrick M.
Takao, Cheryl
Detterich, Jon
Kantor, Paul F.
Cleveland, John D.
Herrington, Cynthia
Ram Kumar, S.
Starnes, Vaughn
Badran, Sarah
Patel, Neil D.
author_sort Emamaullee, Juliet
collection PubMed
description BACKGROUND & AIMS: Fontan-associated liver disease (FALD) has emerged as an important morbidity following surgical palliation of single ventricle congenital heart disease. In this study, non-invasive biomarkers that may be associated with severity of FALD were explored. METHODS: A retrospective cohort of paediatric patients post-Fontan who underwent liver biopsy at a high volume at a paediatric congenital heart disease centre was reviewed. RESULTS: Among 106 patients, 66% were male and 69% were Hispanic. The mean age was 14.4 ± 3.5 years, and biopsy was performed 10.8 ± 3.6 years post-Fontan. The mean BMI was 20.8 ± 5 kg/m(2), with 27.4% meeting obesity criteria. Bridging fibrosis was observed in 35% of patients, and 10.4% of all patients had superimposed steatosis. Bridging fibrosis was associated with lower platelet counts (168.3 ± 58.4 vs. 203.9 ± 65.8 K/μl for congestive hepatic fibrosis score [CHFS] 0–2b, p = 0.009), higher bilirubin (1.7 ± 2.2 vs. 0.9 ± 0.7 mg/dl, p = 0.0090), higher aspartate aminotransferase-to-platelet ratio index [APRI] and fibrosis-4 [FIB-4] scores (APRI: 0.5 ± 0.3 vs. 0.4 ± 0.1, p <0.01 [AUC: 0.69] and FIB-4: 0.6 ± 0.4 vs. 0.4 ± 0.2, p <0.01 [AUC: 0.69]), and worse overall survival (median 2 years follow-up post-biopsy, p = 0.027). Regression modelling of temporal changes in platelet counts before and after biopsy correlated with fibrosis severity (p = 0.005). CONCLUSIONS: In this large, relatively homogeneous adolescent population in terms of age, ethnicity, and Fontan duration, bridging fibrosis was observed in 35% of patients within the first decade post-Fontan. Bridging fibrosis was associated with worse survival. Changes in platelet counts, even years before biopsy, and APRI/FIB-4 scores had modest discriminatory power in identifying patients with advanced fibrosis. Steatosis may represent an additional risk factor for disease progression in obese patients. Further prospective studies are necessary to develop strategies to screen for FALD in the adolescent population. LAY SUMMARY: In this study, the prevalence of Fontan-associated liver disease (FALD) in the young adult population and clinical variables that may be predictive of fibrosis severity or adverse outcomes were explored. Several lab-based, non-invasive markers of bridging fibrosis in FALD were identified, suggesting that these values may be followed as a prognostic biomarker for FALD progression in the adolescent population.
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spelling pubmed-85175502021-10-21 Non-invasive biomarkers of Fontan-associated liver disease Emamaullee, Juliet Khan, Sara Weaver, Carly Goldbeck, Cameron Yanni, George Kohli, Rohit Genyk, Yuri Zhou, Shengmei Shillingford, Nick Sullivan, Patrick M. Takao, Cheryl Detterich, Jon Kantor, Paul F. Cleveland, John D. Herrington, Cynthia Ram Kumar, S. Starnes, Vaughn Badran, Sarah Patel, Neil D. JHEP Rep Research Article BACKGROUND & AIMS: Fontan-associated liver disease (FALD) has emerged as an important morbidity following surgical palliation of single ventricle congenital heart disease. In this study, non-invasive biomarkers that may be associated with severity of FALD were explored. METHODS: A retrospective cohort of paediatric patients post-Fontan who underwent liver biopsy at a high volume at a paediatric congenital heart disease centre was reviewed. RESULTS: Among 106 patients, 66% were male and 69% were Hispanic. The mean age was 14.4 ± 3.5 years, and biopsy was performed 10.8 ± 3.6 years post-Fontan. The mean BMI was 20.8 ± 5 kg/m(2), with 27.4% meeting obesity criteria. Bridging fibrosis was observed in 35% of patients, and 10.4% of all patients had superimposed steatosis. Bridging fibrosis was associated with lower platelet counts (168.3 ± 58.4 vs. 203.9 ± 65.8 K/μl for congestive hepatic fibrosis score [CHFS] 0–2b, p = 0.009), higher bilirubin (1.7 ± 2.2 vs. 0.9 ± 0.7 mg/dl, p = 0.0090), higher aspartate aminotransferase-to-platelet ratio index [APRI] and fibrosis-4 [FIB-4] scores (APRI: 0.5 ± 0.3 vs. 0.4 ± 0.1, p <0.01 [AUC: 0.69] and FIB-4: 0.6 ± 0.4 vs. 0.4 ± 0.2, p <0.01 [AUC: 0.69]), and worse overall survival (median 2 years follow-up post-biopsy, p = 0.027). Regression modelling of temporal changes in platelet counts before and after biopsy correlated with fibrosis severity (p = 0.005). CONCLUSIONS: In this large, relatively homogeneous adolescent population in terms of age, ethnicity, and Fontan duration, bridging fibrosis was observed in 35% of patients within the first decade post-Fontan. Bridging fibrosis was associated with worse survival. Changes in platelet counts, even years before biopsy, and APRI/FIB-4 scores had modest discriminatory power in identifying patients with advanced fibrosis. Steatosis may represent an additional risk factor for disease progression in obese patients. Further prospective studies are necessary to develop strategies to screen for FALD in the adolescent population. LAY SUMMARY: In this study, the prevalence of Fontan-associated liver disease (FALD) in the young adult population and clinical variables that may be predictive of fibrosis severity or adverse outcomes were explored. Several lab-based, non-invasive markers of bridging fibrosis in FALD were identified, suggesting that these values may be followed as a prognostic biomarker for FALD progression in the adolescent population. Elsevier 2021-09-14 /pmc/articles/PMC8517550/ /pubmed/34693238 http://dx.doi.org/10.1016/j.jhepr.2021.100362 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Emamaullee, Juliet
Khan, Sara
Weaver, Carly
Goldbeck, Cameron
Yanni, George
Kohli, Rohit
Genyk, Yuri
Zhou, Shengmei
Shillingford, Nick
Sullivan, Patrick M.
Takao, Cheryl
Detterich, Jon
Kantor, Paul F.
Cleveland, John D.
Herrington, Cynthia
Ram Kumar, S.
Starnes, Vaughn
Badran, Sarah
Patel, Neil D.
Non-invasive biomarkers of Fontan-associated liver disease
title Non-invasive biomarkers of Fontan-associated liver disease
title_full Non-invasive biomarkers of Fontan-associated liver disease
title_fullStr Non-invasive biomarkers of Fontan-associated liver disease
title_full_unstemmed Non-invasive biomarkers of Fontan-associated liver disease
title_short Non-invasive biomarkers of Fontan-associated liver disease
title_sort non-invasive biomarkers of fontan-associated liver disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517550/
https://www.ncbi.nlm.nih.gov/pubmed/34693238
http://dx.doi.org/10.1016/j.jhepr.2021.100362
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