Non-invasive biomarkers of Fontan-associated liver disease

Juliet Emamaullee; Sara Khan; Carly Weaver; Cameron Goldbeck; George Yanni; Rohit Kohli; Yuri Genyk; Shengmei Zhou; Nick Shillingford; Patrick M. Sullivan; Cheryl Takao; Jon Detterich; Paul F. Kantor; John D. Cleveland; Cynthia Herrington; S. Ram Kumar; Vaughn Starnes; Sarah Badran; Neil D. Patel

JHEP Reports (Dec 2021)

Non-invasive biomarkers of Fontan-associated liver disease

Juliet Emamaullee,
Sara Khan,
Carly Weaver,
Cameron Goldbeck,
George Yanni,
Rohit Kohli,
Yuri Genyk,
Shengmei Zhou,
Nick Shillingford,
Patrick M. Sullivan,
Cheryl Takao,
Jon Detterich,
Paul F. Kantor,
John D. Cleveland,
Cynthia Herrington,
S. Ram Kumar,
Vaughn Starnes,
Sarah Badran,
Neil D. Patel

Affiliations

Juliet Emamaullee: Department of Surgery, University of Southern California, Los Angeles, CA, USA; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Liver Transplant Program, Children’s Hospital-Los Angeles, Los Angeles, CA, USA; Corresponding author. Address: 1510 San Pablo Street, Suite 412, Los Angeles, CA 90033, USA. Tel.: +1-323-442-5908; Fax: +1-323-442-6887
Sara Khan: Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Carly Weaver: Liver Transplant Program, Children’s Hospital-Los Angeles, Los Angeles, CA, USA
Cameron Goldbeck: Department of Surgery, University of Southern California, Los Angeles, CA, USA; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
George Yanni: Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Liver Transplant Program, Children’s Hospital-Los Angeles, Los Angeles, CA, USA
Rohit Kohli: Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Liver Transplant Program, Children’s Hospital-Los Angeles, Los Angeles, CA, USA
Yuri Genyk: Department of Surgery, University of Southern California, Los Angeles, CA, USA; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Liver Transplant Program, Children’s Hospital-Los Angeles, Los Angeles, CA, USA
Shengmei Zhou: Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Pathology, Children’s Hospital-Los Angeles, Los Angeles, CA, USA
Nick Shillingford: Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Pathology, Children’s Hospital-Los Angeles, Los Angeles, CA, USA
Patrick M. Sullivan: Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Heart Institute, Children’s Hospital-Los Angeles, Los Angeles, CA, USA
Cheryl Takao: Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Heart Institute, Children’s Hospital-Los Angeles, Los Angeles, CA, USA
Jon Detterich: Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Heart Institute, Children’s Hospital-Los Angeles, Los Angeles, CA, USA
Paul F. Kantor: Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Heart Institute, Children’s Hospital-Los Angeles, Los Angeles, CA, USA
John D. Cleveland: Department of Surgery, University of Southern California, Los Angeles, CA, USA; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Heart Institute, Children’s Hospital-Los Angeles, Los Angeles, CA, USA
Cynthia Herrington: Department of Surgery, University of Southern California, Los Angeles, CA, USA; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Heart Institute, Children’s Hospital-Los Angeles, Los Angeles, CA, USA
S. Ram Kumar: Department of Surgery, University of Southern California, Los Angeles, CA, USA; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Heart Institute, Children’s Hospital-Los Angeles, Los Angeles, CA, USA
Vaughn Starnes: Department of Surgery, University of Southern California, Los Angeles, CA, USA; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Heart Institute, Children’s Hospital-Los Angeles, Los Angeles, CA, USA
Sarah Badran: Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Heart Institute, Children’s Hospital-Los Angeles, Los Angeles, CA, USA
Neil D. Patel: Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Heart Institute, Children’s Hospital-Los Angeles, Los Angeles, CA, USA

Journal volume & issue: Vol. 3, no. 6
p. 100362

Abstract

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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/m2, 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.

Published in JHEP Reports

ISSN: 2589-5559 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the digestive system. Gastroenterology
Website: https://www.journals.elsevier.com/jhep-reports

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