Prognostic biomarkers in Fontan associated liver disease

Fontan相关肝病的预后生物标志物

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Abstract

Fontan-associated liver disease (FALD) is a universal consequence of the Fontan circulation and a growing cause of morbidity. Clinical outcome stratification is difficult because conventional tests lack sensitivity. In this review, we aim to discuss current prognostic tools for FALD. Histology remains the reference standard, capturing the characteristic pericentral and bridging "reverse lobulation" pattern of fibrosis. However, the invasive nature of liver biopsy and susceptibility to sampling bias limit its use. Magnetic resonance elastography (MRE) provides whole-organ stiffness assessment with concurrent evaluation of splenomegaly and varices, yet stiffness thresholds are not standardized and may overestimate fibrosis in the setting of hepatic congestion. Serum and composite indices [e.g., aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 (FIB-4) index, Model for End-Stage Liver Disease excluding international normalized ratio (MELD-XI)] provide some limited prognostic information in FALD; however, there is a need for disease-specific models. Emerging work integrates imaging and laboratory data to build risk calculators such as the FALD and Fontan Liver Risk Score (FonLiver). Multicenter pediatric validation and outcome-based calibration remain major gaps. Future progress requires prospective, multicenter pediatric studies with harmonized imaging protocols and novel biomarkers. Such integration is essential to move FALD prognostication from descriptive observation toward predictive and ultimately preventative care, optimizing timing of intervention and associated transplant decisions for individuals living with Fontan circulation.

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