Long-term hepatic dysfunction is an increasingly recognized complication of corrective surgery for complex cyanotic congenital heart disease.1 We report four cases of hepatocellular carcinoma in patients with congenital heart disease with univentricular physiology that was palliated by means of the Fontan procedure (

Patient 1, a 32-year-old woman with a cirrhotic liver, was shown to have a 4-cm hepatocellular carcinoma on biopsy. She underwent transarterial chemoembolization and was put on the waiting list for combined heart and liver transplantation.

Patient 2, a 24-year-old man with portal-vein thrombosis, ascites, and innumerable bilobar hepatic nodules, was shown to have neither cirrhosis nor hepatocellular carcinoma on targeted biopsies. A third biopsy revealed well-differentiated hepatocellular carcinoma. He died from metastatic hepatocellular carcinoma.

Patient 3, a 33-year-old man with a dominant liver nodule, had findings on imaging that were characteristic of hepatocellular carcinoma. He was put on the waiting list for combined heart and liver transplantation and underwent radioembolization at another institution. He had massive gastrointestinal bleeding from a hepatic-artery pseudoaneurysm and subsequently died.

Patient 4, a 42-year-old woman with hepatitis C virus infection, advanced liver fibrosis, and two lesions characteristic of hepatocellular carcinoma, underwent successful chemoembolization after being put on the waiting list for combined heart and liver transplantation.

Patients with congenital heart disease who undergo the Fontan procedure may represent a novel group for screening for liver disease. Surveillance for hepatocellular carcinoma may be needed in such patients, especially if the alpha-fetoprotein level is elevated.2 Cirrhosis may develop in persons under the age of 25 years approximately 11 to 15 years after a Fontan procedure; an incidence of cancer of 1.5 to 5.0% per year is estimated on the basis of previous studies. Cirrhosis, a potential prerequisite for hepatocellular carcinoma, may develop because of repetitive mechanical stretch and compression (passive congestion) and tissue hypoxia (low cardiac output) related either to the circulation created by the Fontan procedure or to chronically elevated right atrial pressure.3 The interval for screening for liver disease is unknown.2

Diagnosing hepatocellular carcinoma in patients with congenital heart disease is difficult because hyperenhancing nodules are often present in such patients.4 In patients with cardiac failure and intrahepatic vascular shunts, the typical arterial enhancing pattern of hepatocellular carcinoma may not be obvious. Surgical resection of the carcinoma may be limited by portal hypertension. Local–regional therapy may be limited by the presence of cardiac pacemakers (radiofrequency ablation), extrahepatic shunts (radioembolization), and abnormal vasculature (chemoembolization). Liver transplantation is limited by cardiac function (hypoxemia, pulmonary hypertension, and elevated right atrial pressure). Combined heart and liver transplantation may be feasible, but experience in such cases is limited.5Since corrective surgery for patients with univentricular physiology has substantially reduced childhood mortality associated with complex cyanotic congenital heart disease, urgent attention and vigilance are needed to avoid a similar premature fate in early adulthood.

Source: NEJM