ArticlePloS one2022
Risk factors for Fontan-associated hepatocellular carcinoma.
Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- A Meta-Analysis of Cumulative Incidence of Hepatocellular Carcinoma After the Fontan Operation.Digestive diseases and sciences · 2024Pooled it
- YAP1 induces hepatocellular carcinoma via DNA demethylation rather than by canonical driver gene mutations.Communications biology · 2026Article
- Impact of Respiratory Mechanics on Venous Return in Single Ventricle Physiology: A Clinical Imaging Study.JACC. Basic to translational science · 2026Article
- Functionally Single-Ventricle Complications After Fontan Palliation-A Narrative Review.Journal of clinical medicine · 2026Review
- Noninvasive risk stratification of liver nodule development in Fontan-associated liver disease using liver stiffness measurement.Hepatology international · 2026Article
- Article
- Hepatocellular carcinoma in Fontan-associated liver disease: Incidence, risk stratification, and surveillance implications.Hepatology communications · 2026Article
- Prognostic biomarkers in Fontan associated liver disease.Translational pediatrics · 2026Review
- Translating Fibrosis to Malignancy: Biomarkers and Therapeutic Opportunities in Liver Fibrosis and Hepatocellular Carcinoma.Medical sciences (Basel, Switzerland) · 2026Review
- Fontan-Associated Liver Disease (FALD) in the EUROFontan Experience. An Insight into European Awareness.Pediatric cardiology · 2026Observational
- Ultrasound Evaluation of Fontan-Associated Liver Disease: A State-of-the-Art Review.Diagnostics (Basel, Switzerland) · 2025Review
- Revisiting Hepatic Fibrosis Risk in Congenital Heart Disease: Insights from Non-Invasive Markers and Echocardiography.Children (Basel, Switzerland) · 2025Article
- The Cardiohepatic Axis in Heart Failure.JACC. Basic to translational science · 2025Review
- Article
- Impact of ursodeoxycholic acid treatment on Fontan-associated liver disease.Journal of gastroenterology · 2025Article
- Native liver T1 mapping on magnetic resonance imaging for an evaluation of congestive liver injury in children with congenital heart disease.The international journal of cardiovascular imaging · 2025Article
- Cancer mortality in children surviving congenital heart interventions: A study from the Pediatric Cardiac Care Consortium.Pediatric blood & cancer · 2024Article
- Article
- Fontan-associated liver disease: the importance of multidisciplinary teamwork in its management.Frontiers in medicine · 2024Review
- Challenges in Accurate Diagnosis of HCC in FALD: A Case Series.Pediatric cardiology · 2023Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThe incidence of hepatocellular carcinoma (HCC) in patients with Fontan-associated liver disease (i.e., FALD-HCC) has increased over time. However, the risk factors for HCC development remain unclear. Here, we compared the levels of non-invasive markers to the survival rate of FALD-HCC patients.
methodsFrom 2003 to 2021, 154 patients (66 men, 42.9%) developed liver disease after undergoing Fontan procedures. HCC was diagnosed in 15 (9.7%) (8 men, 53.3%) at a median age of 34 years (range, 21-45 years). We compared FALD-HCC and non-HCC cases; we generated marker level cutoffs using receiver operating characteristic curves. We sought to identify risk factors for HCC and mortality.
resultsThe incidence of HCC was 4.9% in FALD patients within 20 years after the Fontan procedure. Compared with non-HCC patients, FALD-HCC patients exhibited higher incidences of polysplenia and esophageal varices. At the time of HCC development, the hyaluronic acid (HA) level (p = 0.04) and the fibrosis-4 index (p = 0.02) were significantly higher in FALD-HCC patients than in non-HCC patients; the total bilirubin (T-BIL) level (p = 0.07) and the model for end-stage liver disease score [excluding the international normalized ratio (MELD-XI)] (p = 0.06) tended to be higher in FALD-HCC patients. Within approximately 20 years of the Fontan procedure, 10 patients died (survival rate, 96.9%). Kaplan-Meier curve analysis indicated that patients with T-BIL levels ≥ 2.2 mg/dL, HA levels ≥ 55.5 ng/mL, and MELD-XI scores ≥ 18.7 were at high risk of HCC, a generally poor prognosis, and both polysplenia and esophageal varices. Multivariate Cox regression analyses indicated that the complication of polysplenia [Hazard ratio (HR): 10.915] and a higher MELD-XI score (HR: 1.148, both p < 0.01) were independent risk factors for FALD-HCC.
conclusionsThe complication of polysplenia and a MELD-XI score may predict HCC development and mortality in FALD patients.
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