Fontan-Associated Liver Disease: clinical and epidemiological impact on a large cohort in the UK, a multicenter retrospective study.

Background. Fontan-associated Liver Disease (FALD) arises from liver exposure to the hemodynamic changes associated with Fontan circulation. Improved surgical outcomes have led to a growing adult population of Fontan long-term survivors, characterised by chronic sequelae, primarily FALD. It is increasingly recognized that FALD begins in childhood; however, pediatric data are limited. Aim. This study aims to evaluate the prevalence of FALD in patients who underwent the Fontan procedure, and to investigate the impact of FALD on severity and survival outcomes. Methods.This retrospective multicenter cohort study was conducted across three pediatric hospitals in London, enrolling all patients who completed the Fontan sequence. Results. A total of 729 patients underwent the Fontan surgery between 1987 and 2024, at a median age of 3.9 years (IQR 3.2-4.8). Liver assessment was performed in 390 patients (53.5%), with a median follow-up of 12.8 years (IQR 9.4-18). The prevalence of altered LFTs or liver imaging was 10.9% at 0-5 years, 23.3% at 5.1-10 years, 63.7% at 10.1-15 years, 82.6% at 15.1-20 years, 91.0% at 20.1-25 years, and 100.0% at 25.1-40 years. Liver imaging, conducted in 276 patients (70.7%), was pathological in 227 patients (82.3%), including hepatomegaly (23.2%), caudate hypertrophy (17.8%), heterogeneous parenchyma (32.2%), coarse parenchyma (44.6%), FNH-like nodules (27.5%), cirrhotic appearance (40.9%), porto-systemic shunts (0.01%), and splenomegaly in (28.2%). The prevalence of hepatocellular carcinoma was 0.14%. A significant correlation was found between follow-up duration and worsening VAST and MELD-XI scores (p < 0.0005 and 0.0001). Age at Fontan correlated with MELD-XI score (p = 0.003). Cardiac isomerism and male gender were associated with higher MELD-XI scores (p = 0.004 and p = 0.036). Both the MELD-XI and VAST scores increased over time, with statistically significance from 10–15-year interval (p<0.001). Univariate Cox hazards regression analysis indicated that liver injury pre-Fontan was associated with increased mortality (HR 3.74, p = 0.041), alongside VAST (HR 2.93, p < 0.0005) and MELD-XI (HR 1.17, p = 0.015). Multivariable analysis confirmed the independent predictive value of VAST (HR 3.15, p < 0.0005) and MELD-XI (HR 1.21, p = 0.013) scores for mortality risk. ROC curve analysis identified a VAST score threshold of 1 (AUC 0.84) and a MELD-XI score cut-off of 10 (AUC 0.92) associated with increased mortality. Conclusions. FALD progressively leads to advanced liver disease in nearly all patients over time. The MELD-XI and VAST scores have been identified as independent predictors of mortality and disease severity.