Characteristics and Survival Outcomes of Hepatocellular Carcinoma After the Fontan Operation

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.

Graphical abstract

Figure 1

Flow Diagram for BCLC Staging, Treatment, and Recurrence at Last Follow-Up for the Cohort of Patients With HCC After Fontan Palliation BCLC staging was available for 56 patients.

Figure 2

Kaplan-Meier Survival Analysis Grouped by BCLC Stage at Diagnosis Excluding Two Patients for Which There Were Missing Data (N = 56) Number at risk table and log-rank P value are shown.

Figure 3

Kaplan-Meier Survival Analysis Excluding One Patient Diagnosed at Autopsy (n = 57) Stratified by Treatment: Curative Therapy (Resection, Liver Transplantation, and Ablation) vs Other Liver-Directed Therapy (TACE), TARE, External Radiotherapy), Systemic Therapy, and Symptomatic/Palliative Therapy Number at risk table and log-rank P value are shown.

Figure 4

Kaplan-Meier Survival Analysis Excluding One Patient Diagnosed at Autopsy (N = 57) by Active HCC Surveillance Status Active surveillance was defined as ultrasound or cross-sectional imaging 3 to 12 months before diagnosis. Number at risk table and log rank P value are shown.

Central Illustration

18 North American Adult Congenital Heart Disease Centers Contributed 58 Cases of HCC and 172 Controls of Adults With Fontan Circulation Clinical, laboratory, and imaging differences were found including higher prevalence of atriopulmonary Fontan and prior Fontan revision, greater burden of cardiac comorbidities, and evidence of worse FALD in HCC cases 1-year survival of Fontan HCC cases was 79%. ACHD = adult congenital heart disease; BCLC = Barcelona Clinic Liver Cancer Stage.