Characteristics and Survival Outcomes of Hepatocellular Carcinoma After the Fontan Operation

JACC Adv. 2025 Apr;4(4):101646. doi: 10.1016/j.jacadv.2025.101646. Epub 2025 Mar 12.

Abstract

Background: The Fontan operation is a surgical procedure to palliate single ventricle congenital heart disease. Hepatocellular carcinoma (HCC) is a rare complication of Fontan-associated liver disease (FALD).

Objectives: The authors aim to examine characteristics of individuals with Fontan circulation diagnosed with HCC and to describe tumor characteristics, treatment, and survival outcomes of these patients.

Methods: This was a multicenter retrospective case-control study of adults with Fontan circulation between 2005 and 2021. HCC cases were included based on histology or imaging-based diagnosis. Controls were randomly selected in a 3:1 ratio from the center in which the case was derived. Descriptive statistics were used to compare groups and Kaplan-Meier survival analysis was performed.

Results: There were 58 cases of HCC diagnosed at a median age of 31 (IQR: 26-38) years. Diagnosis was made at very early or early stage disease in 68%. Compared to controls, cases had higher prevalence of advanced FALD including varices, ascites, splenomegaly, and decreased platelets. Treatment with curative intent (combined heart-liver transplantation, resection, or ablation) was performed in 41%. Survival at 1 year was 78.9% and highest among those diagnosed at very early or early stage. Over half were undergoing active surveillance at diagnosis, which showed a nonsignificant trend toward higher survival (P = 0.088).

Conclusions: We describe the clinical characteristics, treatment, and survival in patients with FALD-HCC. Results suggest that adults with FALD-HCC diagnosed with early stage disease may have survival benefit. Our findings underscore the importance of HCC screening for early detection in individuals after the Fontan operation.

Keywords: Fontan operation; Fontan-associated liver disease; congenital heart disease; hepatocellular carcinoma; single ventricle.