Hepatocellular carcinoma after Fontan surgery: A systematic review

Abstract

Aim: Fontan surgery is often the procedure of choice for patients with congenital single effective ventricle. In the long term, elevated systemic venous pressure and chronic ischemia following this procedure could lead to advanced chronic liver disease and there is also a risk of hepatocellular carcinoma (HCC). This review systematically summarizes the characteristics and outcomes of this rare condition. Methods: PubMed and Embase databases were searched from inception to January 2020 for studies reporting on HCC after Fontan surgery. The factors analyzed were clinical presentation, histology, imaging findings, treatments, and survival. Our primary analysis was based on biopsy-proven HCC. Results: The records selected were 26 observational studies (19 case reports/case series and seven cohort studies) including 65 biopsy-proven HCC. Age at the time of HCC diagnosis ranged from 12 to 52 years, and 62% of the patients were female. Only one case occurred earlier than 10 years after Fontan surgery. Twenty patients had no imaging or histological evidence of liver cirrhosis and 78.3% had elevated α-fetoprotein levels. Advanced stage was the most common at diagnosis. The most frequent treatments were transarterial chemoembolization (n = 18) and surgery (n = 12). One-year survival was 50% and only four patients (6.2%) were under liver imaging surveillance. We also analyzed 17 patients with non-biopsy-proven HCC. Conclusions: After Fontan surgery, HCC usually occurs at least 10 years later and can develop in the absence of cirrhosis. Biopsy is mandatory to confirm the diagnosis. Patients were diagnosed at a late stage and survival outcomes were poor, highlighting a need for liver surveillance.

Robust Effect of Hepatic Arterial Infusion Chemotherapy and Radiation Therapy on Hepatocellular Carcinoma Arising from Fontan-associated Liver Disease

“…In patients with FALD-HCC, liver transplantation and hepatectomy are generally very difficult due to a poor cardiac function and three to four times higher systemic venous pressure than in normal patients (9). Several reports have demonstrated that TACE was useful for the treatment of FALD-HCC, so we did consider performing TACE (2,4,9). In general, the presence of systemic-topulmonary venous shunt may cause unexpected embolism due to the embolic material used in TACE, as described in a previous case report of post-TACE cerebral infarction and retinal artery occlusion in a patient with FALD-HCC (13).…”

“…Owing to significant advances in paediatric cardiology, the number of long-term survivors without cyanosis has increased. In these patients, haemodynamic changes that occur during a prolonged lifespan often develop into pathological conditions, such as chronic heart failure and Fontan-associated liver disease (FALD), including liver cirrhosis (LC) and hepatocellular carcinoma (HCC) (2,3). In patients with FALD, hepatic congestion and systemic hypoxia caused by chronic heart failure and systemic-to-pulmonary shunt enhance hepatic fibrogenesis, which is one of the main risk factors for HCC (4).…”

“…However, these treatments are frequently ineffective in patients with FALD-HCC due to cardiac complications and congenital abnormalities. Since the treatment strategies for these patients are not well established and their prognosis is very limited (2,6), an effective treatment method is required.…”

Platelet count and abdominal dynamic CT are useful in predicting and screening for gastroesophageal varices after Fontan surgery

“…Depending on the time since surgery, patients who have undergone a Fontan procedure are at risk of developing gastrointestinal and liver complications, including advanced liver fibrosis, cirrhosis, hepatocellular carcinoma, portal hypertension, protein-losing gastroenteropathy, and GEVs [ 5 – 15 , 17 , 18 , 30 , 31 ]. As these complications significantly influence patients’ quality of life after the surgery, numerous efforts have been made to develop and establish non-invasive and accurate methods or parameters to screen for them [ 7 , 17 , 32 – 35 ].…”

From congestive hepatopathy to hepatocellular carcinoma, how can we improve patient management?

“…Currently, the prognosis of HCC-related to Fontan procedure is poor (1-year survival around 50%) and the management and surveillance of patients has to be improved. 85 , 94 Recently, the American Heart Association published new guidelines for the surveillance of the patients and a bi-annual screening for HCC should be proposed once the diagnosis of cardiac cirrhosis is established 21 ( Table 2 ).…”