Non-invasive biomarkers of fontan-associated liver disease

Abstract Background and 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 pediatric patients post-Fontan who underwent liver biopsy at a high volume, pediatric congenital heart disease center 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/uL for CHFS 0-2b, p=0.009), higher bilirubin (1.7±2.2 vs 0.9±0.7 mg/dL, p=0.0090, higher AST-to-Platelet Ratio Index and FIB-4 scores (APRI: 0.5±0.3 vs 0.4±0.1, p 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 prior to 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, noninvasive 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.