Fontan Associated Liver Disease

Study Overview
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Brief Summary
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Fontan-associated liver disease (FALD), including the development of cardiac cirrhosis and liver neoplasms (benign and malignant), occurs in a majority of patients with congenital heart disease palliated with the Fontan operation. However, the specific phenotype (fibrosis only, fibrosis + lesions, etc.) of disease and severity/timing of onset are variable. Chronic passive congestion of the liver due to the absence of a functional sub-pulmonary ventricle and resultant chronic central venous hypertension is suspected to be one of the chief drivers of FALD and recent work has demonstrated that ultrasound shear wave elastography can be used to noninvasively detect and measure the degree of liver congestion. Chronic passive congestion of the liver may also be a predictor of other Fontan-related complications, such as protein losing enteropathy, plastic bronchitis, and intractable ascites.

Official Title
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Can Ultrasound Liver Stiffness Pre-Fontan, Post-Fontan, or Change Over Time Predict Onset and Severity of Fontan-Related Complications, Including Fontan-Associated Liver Disease

Conditions
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Fontans

Intervention / Treatment
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* Diagnostic Test: Liver Stiffness Ultrasound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Single ventricle physiology congenital heart disease undergoing Fontan operation; ≤5 years of age at the time of stage 3 Fontan operation; Ability to return for follow-up imaging. Exclusion Criteria: Inability to undergo ultrasound imaging. Non-English speaking patients, as breath-hold is required for US shear wave elastography in older children due to excursion of the liver with breathing.

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Liver Stiffness Ultrasound|Research imaging will include liver assessments of stiffness (ultrasound shear wave elastography), tissue attenuation (if available), and blood flow (gray-scale and Doppler imaging).|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre/Post Fontan Liver Stiffness Changes | to determine if there are differences between patients with regard to liver stiffness (hepatic congestion) pre- and post-Fontan operation or with regard to change in liver stiffness over time. This information will be used to drive future hypothesis-driven research related to predicting Fontan-related outcomes based on measured liver stiffness. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlate liver stiffness measurements with clinical outcomes at 3-, 5-, and 10-years post stage 3 Fontan operation | Time to anatomic Fontan pathway obstruction or physiologically high resistance, need for Fontan pathway intervention, need for cardiac transplant evaluation or actual transplantation, and need for mechanical cardiac support evaluation or actual implementation (e.g., ventricular assist device) Lymphatic abnormalities (e.g., protein losing enteropathy, plastic bronchitis, intractable ascites) FALD i. MRI outcomes (e.g., increased liver stiffness [do US and MRI measures of liver stiffness correlate?], portal hypertension, development of focal liver lesions) ii. Liver laboratory assessments (e.g., ALT, AST, bilirubin, alkaline phosphatase, GGT) iii. PELD score iv. VAST score v. Need for liver transplant evaluation or actual transplantation d. Available biopsy (liver and cardiac) data e. Available cardiac catheterization data f. Available cardiac echocardiography and/or cardiac MRI data | 10 years |