Liver Cirrhosis and/or Hepatocellular Carcinoma Occurring Late After the Fontan Procedure　― A Nationwide Survey in Japan ―

Abstract

Background: Fontan-associated liver disease (FALD) is an important late complication involving liver dysfunction, such as liver cirrhosis (LC) and hepatocellular carcinoma (HCC), in patients undergoing the Fontan procedure. However, the prevalence, clinical manifestation, and methods of diagnosis of FALD are still not well established. Methods and Results:This study comprised 2 nationwide surveys in Japan. First, the prevalence of LC and/or HCC in patients undergoing the Fontan procedure was determined. Second, clinical manifestations in patients with LC and/or HCC were analyzed, along with data from blood tests, echocardiography, and right heart catheterization. In the 1st survey, of the 2,700 patients who underwent the Fontan procedure, 31 were diagnosed with LC and/or HCC (1.15%), and 5 died due to liver diseases (mortality: 0.19%). In the 2nd survey, data were collected from 17 patients (12 with LC, 2 with HCC, and 3 with LC+HCC. Of these 17 patients, 5 died (mortality: 29.4%). The mean age at diagnosis of LC and HCC was 23 and 31 years, respectively. Computed tomography followed by ultrasound was most frequently used for diagnosis. Blood tests revealed low platelet counts, increased hemoglobin, aspartate aminotransferase, γ-guanosine triphosphate, and total bilirubin levels, and an elevated international normalized ratio of prothrombin time.Conclusions: LC and/or HCC in patients undergoing the Fontan procedure were not rare late complications and were associated with high mortality rates.

Liver disease secondary to congenital heart disease in children

“…The 11 patients who remained alive after this interval received chemoembolization (n = 5), surgical resection (n = 2), surgical resection and ablation (n = 1), oral chemotherapy (n = 1), ablation (n = 1) or sorafenib (n = 1). Although liver cirrhosis is often observed in children and adolescents after the Fontan operation [5,13,52,68,90], the occurrence of HCC is rare. However, the prognosis of children and adolescents with HCC after a Fontan operation is poor.…”

“…However, since the first report of HCC following Fontan palliation surgery was published in 2005 [5], the reported incidence of HCC in patients who have undergone Fontan palliation has increased [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. Fontan palliative surgery was introduced in 1968 for patients with congenital heart disease; this surgery separates the systemic and pulmonary circulations, producing a single-ventricle physiology [26].…”

Acute-onset abdominal pain in a woman in her 30s

“…Arterialised so-called Fontan nodules are a frequent finding in the Fontan population occurring in 26% of patients in one series and the underlying pathology is felt to be focal nodular hyperplasia3; however, these Fontan nodules are usually small measuring less that 3 cm and they do not demonstrate portal venous phase washout which is a feature of HCC. A Japanese nationwide survey found that of 2700 patients who had undergone the Fontan procedure, 1.15% developed cirrhosis and/or HCC 4. In the same survey, the mean age of diagnosis of cirrhosis was 23 and the mean age of diagnosis of HCC was 31.…”

Long Term Consequences of the Fontan Procedure and How to Manage Them

“…Given the increasing morbidity associated with liver disease, identifying it early and with less invasive assessment has become paramount. Imaging has been shown to accurately identify Arguably the most devastating liver-related complication after Fontan palliation is the development of hepatocellular carcinoma (HCC) [122]. Precise incidence late after Fontan palliation is unknown.…”

“…Precise incidence late after Fontan palliation is unknown. A recent nationwide study of all 2700 Fontan procedures in Japan demonstrated a prevalence of 1.15% [122]. Treatment for HCC can include resection, chemoembolization, or in advanced cases, liver transplant, which may need to be combined heart-liver transplant.…”