report, almost all patients had some evidence of liver abnormality 20 years following the Fontan procedure, with a third having regenerative nodules and 6% established cirrhosis As reported elsewhere, there was little correlation between liver abnormalities and clinical status.166 Other factors may also contribute to liver disease in the Fontan population, including hypoxemic damage occurring during episodes of low cardiac output Hepatitis C infection should be considered in older patients who had cardiac surgery prior to screening for the virus, as should alcohol-related liver damage The clinical characteristics of Fontan-associated liver disease remain to be clearly defined, but, as more patients survive into adulthood, it is becoming apparent that the disease is similar to other forms of liver disease with variable degrees of fibrosis and cirrhosis Mild abnormalities of liver enzymes, especially γ-glutamyl transferase, are common, as is a minor elevation in the indirect bilirubin Excepting for a mild elevation in the prothrombin time, indices of synthetic function such as albumin are usually normal unless there is advanced cirrhosis (or PLE).167 Ultrasound of the liver frequently demonstrates heterogeneous echotexture and arterialized nodules.168 These nodules are striking but appear to be benign and may be an attempt to increase blood flow to the liver by increasing arterial supply.161 MRI or ultrasound elastography of the liver demonstrates increased liver stiffness.169–174 Although this finding is likely a combined result of congestion and fibrosis, one small study has shown that liver and splenic stiffness on elastography was strongly correlated with the degree of biopsyproven fibrosis.172 Perhaps the most feared consequence of advanced liver disease in the Fontan circulation is the development of hepatocellular carcinoma.175–179 What once seemed isolated to rare case reports has become more common as more patients survive well into adulthood Unfortunately, the detection of hepatocellular carcinoma may be challenging, particularly on a background of abnormal hepatic parenchyma.180 Screening tests such as serum α-fetoprotein may be helpful but are not sensitive or specific enough to reliably diagnose each case Regular abdominal ultrasound to detect nodular growth may be helpful Contrast computed tomography (CT) or MRI, both the gold standard for diagnosis of hepatocellular carcinoma in other settings, may be less reliable in the Fontan circulation The tumor is supplied from the hepatic arterial circulation, whereas the normal liver receives most of its blood supply from the portal vein These tests detect early contrast enhancement in the tumor and later enhancement in the surrounding tissue Elevated systemic venous pressure in the Fontan circulation may interfere with this relationship.181 In addition to the development of hepatocellular carcinoma, progression of cirrhosis and its complications may herald the failure of the Fontan circulation Portal hypertension is not uncommon, with splenomegaly seen in 20% of patients at a median of 10 years after the Fontan operation Venous collaterals from the liver or esophageal varices are seen in more than half of those with functional limitation.182 Abdominal ascites may be cardiac in origin but can also be associated with liver cirrhosis In this setting, the development of ascites is a poor prognostic sign As intraabdominal fluid increases, a vicious cycle ensues with increased abdominal pressure leading to increased venous hypertension and an even more pronounced decrease in cardiac output Ascites is often relatively resistant to diuretic treatment and, while not reported in the literature, some patients have been managed with repeated peritoneal taps to drain abdominal fluid in the hope of maintaining a functional Fontan circulation either as a palliative procedure or while awaiting heart or heart and liver transplantation Liver disease is a frequent, serious and progressive entity following the Fontan operation, but screening algorithms and management are less well defined Serial monitoring with liver biopsy is not practical and may be impacted by the heterogeneity of the hepatic manifestations For now, regular surveillance with abdominal ultrasound and elastography, as well as serial measurements of serum α-fetoprotein, may be the best option, particularly in those patients more than 10 years out from the Fontan procedure Multiple societies, interest groups, and individuals are working on follow-up protocols for all organ systems, particularly the liver.183,184 Continued work toward the development of medical and surgical strategies to lower venous pressure and improve cardiac output may slow the progression of liver disease The Fontan operation has helped to save or prolong many lives, but more work is needed to help manage the complications that result from this unique circulation Lymphatic Insufficiency The physiology created by the Fontan operation results in both obligate central venous hypertension and persistent low cardiac output.185Although these physiologic abnormalities may be well tolerated, at least for a few decades, there is a subset of patients in whom severe complications may occur much earlier Plastic bronchitis and PLE are both feared complications of the Fontan circulation, and both may lead to significant morbidity and mortality.155,186 In recent years, a great deal has been learned about the role of the lymphatic system in the pathophysiology of plastic bronchitis and PLE.187–189 The lymphatic system, the scavenger of the circulatory system, is responsible for retrieving interstitial fluid and returning it to the central circulation via the connection of the thoracic duct to the innominate vein For patients with Fontan physiology, there is obligate lymphatic hypertension that results from the transmission of the elevation in CVP (Fig 73.20) The lymphatic system is further inundated by the increase in lymphatic fluid production that results from increased intravascular and intrahepatic hydrostatic pressure associated with heart failure.190 Although MRI imaging demonstrates universal dilation of the lymphatics in patients with Fontan physiology, there appear to be some patients in whom the lymphatic hypertension and dilation lead to lymphatic insufficiency, often with severe consequences FIG 73.20 Elevated central venous pressure results in increased lymphatic production and elevated intralymphatic pressure leading to lymphatic insufficiency Plastic Bronchitis Plastic bronchitis is characterized by the development of abnormal lymphatic vessels in the peribronchial region These abnormal vessels form tiny fistulous connections to the airways, allowing for a slow but insidious leakage of lymphatic fluid The fluid itself dissipates over time with respiration, leaving