Background:
In Fontan Associated Liver Disease (FALD), congestion of blood in the liver causes cirrhosis. This condition can cause death. Researchers want to understand what triggers this process and find new treatments for it.
Objective:
To understand how long-term congestion of blood in the liver causes liver scarring that eventually leads to cirrhosis.
Eligibility:
People aged 18 and older who are at risk of developing FALD from the Fontan procedure.
Design:
Participants will be screened with:
Medical history
Physical exam
Blood and urine tests
Liver ultrasound. This uses sound waves to take pictures of the body.
Participants will have an outpatient visit within 12 weeks after screening. Within 24 weeks later, they will have a 3-day hospital stay. About 2 weeks later, they will have a follow-up visit.
Visits will include repeats of the screening tests and:
Heart tests
Stool collection
Questionnaires
MRI of the liver. Participants will lie on a bed that slides in and out of the scanner. They will receive a contrast agent injected into a vein. While in the scanner, they will also have an MRCP to view the bile ducts and the pancreatic duct.
Fibroscan exam. This is an ultrasound that uses a special probe to look at the toughness of the liver.
Upper endoscopy. This uses a thin scope to look inside the upper digestive tract.
Liver biopsy. This will be taken through large vein in the neck or through the chest. Just before the biopsy, participants will have pressure measurements inside their liver. For this, a catheter will be inserted into a neck vein and guided into the liver.
Male and female subjects >= 18 years of age.
Past surgical history of Fontan procedure.
Prior enrollment in the Liver Diseases Branch protocol 91DK0214
Underwent cardiac catheterization or transjugular liver biopsy within ten years prior to the date of screening
Evidence of other forms of liver disease that typically result in cirrhosis.
Evidence of active Chronic Hepatitis B infection as defined by the presence of hepatitis B surface antigen (HBsAg) in serum and elevated HBV DNA (>10,000 IU/mL).
Hepatitis C as defined by the presence of hepatitis C RNA in serum.
Evidence of other liver disease such as primary sclerosing cholangitis, primary biliary cirrhosis, Wilson s disease, autoimmune hepatitis as defined by either liver histology or laboratory abnormalities.
male and female subjects \>=18 years of age who historically underwent Fontan procedure due to a severe CHD and thus are at risk for FALD by virtue of their altered physiology
Cohort
Prospective
Not listed
To generate understanding of how congestive hepatopathy drives the pathogenesis of cirrhosis in FALD
Identification of novel biomarkers correlating with disease progression markers in Fontan Associated Liver Disease Develop an understanding of the biological mechanisms and the genetic modifiers of the progression of Fontan Associated Liver Disease
Comparison of PAR-1 and PAR-2 receptor staining from liver tissue biopsies of Fontan patients and corelate their presence to the severity of the patients FALD
PAR-1 and PAR-2 immuno-staining in Fontan subjects liver tissue biopsies
Characterization of microbiome signatures in FALD
Characterization of microbiome signatures (taxonomic and functional), as well as identification of specific species
Evaluation of hepatic transcriptome in various stages of FALD
Identification of novel markers of fibrosis or the development of hepatic neoplasia from transcriptome analysis
Identification of genetic modifiers of FALD
Establishment of positive or negative correlation between candidate susceptible genes and disease phenotype
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