Fontan-Associated Liver Disease (FALD) in the EUROFontan Experience. An Insight into European Awareness

Anna Gozzi¹, Luca Vedovelli², Emma Bergonzoni³, Irene Cao³, Emanuela Angeli⁴, Rossana Zanoni⁴, Roberta Biffanti⁵, Gianfranco Butera⁶, Kostantinos Dimopoulos⁷, Alvaro Gonzalez Rocafort⁸, Mark G Hazekamp⁹, Andrzej Kansky¹⁰, Marien Lenoir¹¹, Thomas Martens¹², Giovanni Meliota¹³, Bart Meyns¹⁴, Matej Nosal¹⁵, Carlo Pace Napoleone¹⁶, Friso M Rijnberg⁹, Eva Sames Dolzer¹⁷, Giuseppe Scrascia¹⁸, Ugo Vairo¹³, Joeri Van Puyvelde¹⁴, Giovanni Di Salvo⁵, Claudia Montanaro⁷, Massimo A Padalino¹⁹

Affiliations

¹ Pediatrics Unit, San Bortolo Hospital, Vicenza, Italy.
² Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padova, Padua, Italy.
³ Pediatric and Congenital Cardiac Surgery, Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padova, Padua, Italy.
⁴ Pediatric Cardiac Surgery and Adult Congenital Heart Disease Program, Department of CardioThoracic and Vascular Medicine, IRCCS, Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy.
⁵ Pediatric Cardiology Unit, Department of Woman and Child's Health, University of Padova, Padua, Italy.
⁶ Department of Cardiac Surgery, Cardiology and Heart Lung Transplant, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
⁷ Adult Congenital Heart Centre and Centre for Pulmonary Hypertension, Royal Brompton Hospital, Royal Brompton & Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London, UK National Heart and Lung Institute, Imperial College London, London, UK.
⁸ Servicio de Cirugía Cardiaca Infantil y Cardiopatías Congénitas del Adulto, Alianza Estratégica Hospital Universitario La Paz-Hospital Universitario Ramón y Cajal, Madrid, Spain.
⁹ Leiden University Medical Center (LUMC), Leiden, Netherlands.
¹⁰ Congenital Cardiac Surgery, Medical University of Warsaw, Warsaw, Poland.
¹¹ Department of Congenital Heart Surgery, La Timone Children Hospital, Marseille, France.
¹² Department of Cardiac Surgery, University Hospital of Ghent, Ghent, Belgium.
¹³ Department of Pediatric Sciences, Pediatric Cardiology, Giovanni XXIII Pediatric Hospital, Bari, Italy.
¹⁴ Department of Cardiac Surgery, University Hospitals Leuven, Louvain, Belgium.
¹⁵ National Institute of Cardio-Vascular Diseases, Childrens Heart Center, Bratislava, Slovakia.
¹⁶ Pediatric Cardiac Surgery Department, Regina Margherita Children's Hospital, Turin, Italy.
¹⁷ Division of Pediatric and Congenital Heart Surgery, Kepler University Hospital, Linz, Austria.
¹⁸ Department of Pediatric Sciences, Pediatric Cardiac Surgery Unit, Giovanni XXIII Pediatric Hospital, Bari, Italy.
¹⁹ Pediatric and Congenital Cardiac Surgery, Department of Precision and Regenerative Medicine and Jonian Area, University of Bari Aldo Moro, Bari, Italy. massimo.padalino@uniba.it.

PMID: 40080110
DOI: 10.1007/s00246-025-03781-0

Fontan-Associated Liver Disease (FALD) in the EUROFontan Experience. An Insight into European Awareness

Anna Gozzi et al. Pediatr Cardiol. 2025.

. 2025 Mar 13.

doi: 10.1007/s00246-025-03781-0. Online ahead of print.

Authors

Affiliations

¹ Pediatrics Unit, San Bortolo Hospital, Vicenza, Italy.
² Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padova, Padua, Italy.
³ Pediatric and Congenital Cardiac Surgery, Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padova, Padua, Italy.
⁴ Pediatric Cardiac Surgery and Adult Congenital Heart Disease Program, Department of CardioThoracic and Vascular Medicine, IRCCS, Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy.
⁵ Pediatric Cardiology Unit, Department of Woman and Child's Health, University of Padova, Padua, Italy.
⁶ Department of Cardiac Surgery, Cardiology and Heart Lung Transplant, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
⁷ Adult Congenital Heart Centre and Centre for Pulmonary Hypertension, Royal Brompton Hospital, Royal Brompton & Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London, UK National Heart and Lung Institute, Imperial College London, London, UK.
⁸ Servicio de Cirugía Cardiaca Infantil y Cardiopatías Congénitas del Adulto, Alianza Estratégica Hospital Universitario La Paz-Hospital Universitario Ramón y Cajal, Madrid, Spain.
⁹ Leiden University Medical Center (LUMC), Leiden, Netherlands.
¹⁰ Congenital Cardiac Surgery, Medical University of Warsaw, Warsaw, Poland.
¹¹ Department of Congenital Heart Surgery, La Timone Children Hospital, Marseille, France.
¹² Department of Cardiac Surgery, University Hospital of Ghent, Ghent, Belgium.
¹³ Department of Pediatric Sciences, Pediatric Cardiology, Giovanni XXIII Pediatric Hospital, Bari, Italy.
¹⁴ Department of Cardiac Surgery, University Hospitals Leuven, Louvain, Belgium.
¹⁵ National Institute of Cardio-Vascular Diseases, Childrens Heart Center, Bratislava, Slovakia.
¹⁶ Pediatric Cardiac Surgery Department, Regina Margherita Children's Hospital, Turin, Italy.
¹⁷ Division of Pediatric and Congenital Heart Surgery, Kepler University Hospital, Linz, Austria.
¹⁸ Department of Pediatric Sciences, Pediatric Cardiac Surgery Unit, Giovanni XXIII Pediatric Hospital, Bari, Italy.
¹⁹ Pediatric and Congenital Cardiac Surgery, Department of Precision and Regenerative Medicine and Jonian Area, University of Bari Aldo Moro, Bari, Italy. massimo.padalino@uniba.it.

PMID: 40080110
DOI: 10.1007/s00246-025-03781-0

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.

Keywords: Congestive hepatopathy; FALD; Follow-up; Fontan; Fontan-associated liver disease.

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Conflict of interest statement

Declarations. Conflicts of interest: The authors declare that the research was conducted in the absence of any commercial or finance relationships perceived as conflicts of interest.

References

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Fontan-Associated Liver Disease (FALD) in the EUROFontan Experience. An Insight into European Awareness

Affiliations

Fontan-Associated Liver Disease (FALD) in the EUROFontan Experience. An Insight into European Awareness

Authors

Affiliations

Abstract

Conflict of interest statement

References

LinkOut - more resources

Full Text Sources