Fontan-Associated Liver Disease (FALD) in the EUROFontan Experience. An Insight into European Awareness
Anna Gozzi, Luca Vedovelli, Emma Bergonzoni, Irene Cao, Emanuela Angeli, Rossana Zanoni, Roberta Biffanti, Gianfranco Butera, Konstantinos Dimopoulos, Alvaro Gonzalez Rocafort, Mark G. Hazekamp, Andrzej Kansky, Marien Lenoir, Thomas Martens, Giovanni Meliota, Bart Meyns, Matej Nosáľ, Carlo Pace Napoleone, Friso M. Rijnberg, Eva Sames Dolzer, Giuseppe Scrascia, Ugo Vairo, Joeri Van Puyvelde, Giovanni Di Salvo, Claudia Montanaro, Massimo A. Padalino
Abstract
Fontan-Associated Liver Disease (FALD) is a dramatically emerging problem even if not precisely defined in term of debated diagnosis and surveillance protocols. We analyze FALD prevalence, clinical impact and implications in a European cohort of patients. It's a retrospective observational multicenter study including Fontan patients operated between 1990 and 2022. Anatomical, clinical, surgical and liver-related data were collected, defining FALD as a spectrum of time-related structural-functional liver modifications due to congestive hepatopathy (from mild liver fibrosis to liver cirrhosis and hepatocellular carcinoma) diagnosed through multiparametric evaluations. 14 centers routinely conducted liver assessment after Fontan completion. Out of 2141 patients, 343 (16%) were diagnosed with FALD (M/F = 198/145; median age 18 years, IQR 15-26) with a median follow-up time of 14 years (IQR 9-20) from Fontan surgery. Among these, there were 19 (5.5%) deaths, 5 (26.3%) of whom related to advanced liver disease/cancer. FALD showed no significant association with gender (p = 0.4, adjusted p-value = 0.5), dominant ventricular morphology (p = 0.060, adjusted p-value = 0.086) nor surgery type (p = 0.3, adjusted p-value = 0.4). Significant association emerged between FALD and fenestration absence (p < 0.001, adjusted p-value < 0.001), systemic ventricular (p < 0.001, adjusted p-value < 0.001) and atrio-ventricular valve (p < 0.001) dysfunction, III-IV NYHA classes (p < 0.001, adjusted p-value < 0.001), tachyarrhythmias (p < 0.001) and liver stiffness ≥ 22 kPa on transient elastography (p < 0.001, adjusted p-value < 0.001). The analysis demonstrated no significant association between FALD and abnormal liver function tests (p = 0.2), heart transplantation (p = 0.6, adjusted p-value = 0.6), worse survival (p = 0.38). This study shows significant mortality related to FALD, which is also associated to clinical signs of failing Fontan circulation, stressing the pressing need of universally shared diagnostic criteria and surveillance protocols, to prevent and/or early-identify FALD and its more lethal complications.