Clinical Outcomes of Fontan-Associated Hepatocellular Carcinoma: a Single-Center Retrospective Study

Fontan-associated liver disease (FALD) is a long-term complication after Fontan surgery, and the development of hepatocellular carcinoma (HCC) in relatively young patients has become a major clinical concern. This study aimed to clarify the diagnostic triggers, clinicopathological characteristics, treatment strategies, and outcomes of FALD-HCC.

We retrospectively reviewed 297 patients with FALD who visited our department between 2003 and 2025. Among them, 28 patients (9.4%) developed HCC. Diagnostic triggers, tumor characteristics, initial treatment modalities, and clinical courses were analyzed.

HCC developed at a median age of 32.6 years, with an interval of 26.1 years after Fontan surgery. Diagnosis was triggered by tumor marker elevation, including alpha-fetoprotein and/or des-gamma-carboxy prothrombin, in 46.4% of patients, routine surveillance imaging in 35.7%, and symptom-driven imaging in 17.9%. Most patients had a single tumor, frequently located in the peripheral liver. At diagnosis, 71.5% were classified as stage I or II disease. Histological evaluation, available in selected cases, revealed variable tumor differentiation and advanced fibrosis in noncancerous liver tissue. Initial treatments included hepatic resection, transcatheter arterial chemoembolization, stereotactic body radiotherapy, proton beam therapy, systemic therapy, or palliative care alone in patients with advanced liver failure. Three-year survival rates were favorable, reaching 100% in patients treated with hepatic resection or stereotactic body radiotherapy.

When FALD-HCC was detected at an early stage through surveillance, a broad range of treatment options, including locoregional therapies, could be applied and were associated with favorable clinical outcomes. Although selection bias limits direct comparison, treatment of FALD-HCC should be considered.