Hepatocellular Carcinoma After Fontan Operation

Abstract

H epatocellular carcinoma (HCC) is a recognized long-term complication following the Fontan operation, but the outcomes and risk factors for mortality have not been characterized in this population. 1,2 The purpose of this study was to: (1) describe the outcomes in patients with HCC diagnosis after Fontan pal-liation; and (2) identify risk factors for mortality in patients with HCC undergoing the Fontan operation. We identified all patients with Fontan palliation and a diagnosis of HCC from January 1, 1990, to December 31, 2016, from 9 adult congenital heart disease centers in North America and Europe. We compared the baseline characteristics of the survivors with the nonsurvivors by using the χ 2 test, Fisher exact test, 2-sided unpaired t test, or Mann-Whitney test, as appropriate. Study approval was obtained from the institutional review boards of the participating sites. Among a total of 2470 patients who had undergone the Fontan operation, there were 33 biopsy-proven cases (1.3%) of HCC. The median age (range) at the time of HCC diagnosis was 30 (12-52) years, median age at the time of Fontan operation was 5 (1-38) years, and the median duration from Fontan operation to HCC diagnosis was 22 (2-36) years. The most common type of Fontan connection was atriopulmonary in 17 (52%) patients with a systemic left ventricle in 26 (79%) patients. The mean tumor size was 51±8 mm, and 11 (33%) patients had metas-tasis at the time of HCC diagnosis, and cirrhosis was present in 17 (52%) patients at the time of HCC diagnosis. Among the 33 patients with HCC, 16 (49%) patients had symptoms at the time of diagnosis, including abdominal pain, jaundice, ascites, dyspnea, and fever. Twenty-six (79%) received at least 1 treatment for HCC, 7 (21%) received multiple forms of therapies, and 7 (21%) received hospice care. Treatments administered included: transarterial chemoembolization (n=10), surgical resec-tion (n=5), radiofrequency ablation (n=5), listing for heart-liver transplant (n=5, of which 1 patient received a transplant successfully), medical therapy with sorafenib (n=3), systemic chemotherapy (n=2), portosystemic shunt (n=2), and radiation therapy (n=1). Of the 33 patients, 18 (55%) died during a median follow-up of 26 (1-51) months. The causes of death were liver failure (n=5, 15%), metastatic disease with multiorgan failure (n=4, 12%), massive gastrointestinal bleeding (n=2, 6%), tumor rupture with hemoperitoneum (n=1, 3%), thromboembolic complication (n=1, 3%), and unknown cause (n=5, 15%). Survival (unadjusted) was 53% at 12 months and 37% at 24 months from the time of HCC diagnosis (Figure). In comparison with the patients that survived, those that died were more likely to have had symptoms at the time of diagnosis (20% versus 72%, P<0.001), larger tumor size (31±10 versus 72±11 mm, P=0.021), cardiac thrombus (0% versus 39%, P=0.01), and abnormal liver function tests (P<0.05). Alexander C. Egbe, MD, MPH et al