Tag Archives: Fontan

Understanding Fontan-Associated Liver Disease (FALD)

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AJ Gumm, EB Rand. J Pediatr 2025; 277: 114389. Fontan-Associated Liver Disease

This review article provides a lot of useful advice regarding Fontan-Associated Liver Disease (FALD).

Key points:

  • FALD prevalence: “will be 70,000 by 2025, with the mean age of 23 years”
  • Early common manifestations are modest increases in AST and ALT. Elevation of bilirubin is a late finding. Mild elevation of INR is common in range of 1.4 to 1.8.
  • Ascites occurs in 2-17% of patients with FALD but can be due to other etiologies like PLE
  • Annual labs (HFP, GGT, CBC/d, PT/INR, AFP) recommended after 7 years post-Fontan
  • No special diet is recommended but it is worthwhile to avoid fatty liver disease
  • For varices, a TIPS procedure “may precipitate pulmonary hypertension resulting in cardiac failure.” ‘The safety of a nonselective beta-blocker to prevent a variceal bleed has not been established.” It is important to determine if there are cardiac options that could improve portal hypertension.
  • In patients with advanced liver disease, multidisciplinary teams are needed to determine if an isolated liver transplantation versus combined heart and liver transplantation (CHLT) is needed.
  • “If a patient requires a heart transplant, the presence of liver fibrosis or even cirrhosis alone is not an indication for liver transplantation, because cirrhosis has been reported to reverse after isolated heart transplantation in a single provocative case. However, if there is evidence of cirrhosis and liver decompensation, then a CHLT should be considered.”
  • Many hepatologists recommend trending elastography. Many recommend liver biopsy starting after 10 years status post Fontan

When to refer to hepatology:

  1. Concerning labs: high transaminases, GGT or bilirubin; low albumin (if liver-related), high INR (not due to warfarin), and high AFP
  2. Signs of portal hypertension (eg. splenomegaly, varies, reversal of flow on ultrasound)
  3. Liver masses
  4. More than 10 years post-Fontan. “100% of patients with Fontan circulation will develop liver disease in their lifetime”

My take: There is a lot that we do not know about FALD and management is complex due to coexistent abnormal cardiac physiology.

Related blog posts:

Success of Isolated Heart Transplantation in the Setting of Fontan-Associated Liver Disease & How COVID Vaccines Work

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A small retrospective analysis by my Emory colleagues (DS Rodriguez et al [Senior author R Romero]. J Pediatr 2021; 229: 78-85. Pretransplantation and Post-Transplantation Liver Disease Assessment in Adolescents Undergoing Isolated Heart Transplantation for Fontan Failure) examines outcomes of 9 patients with Fontan-associated liver disease (FALD) who underwent liver transplantation.

All of these patients underwent extensive evaluations. Key findings:

  • Central venous pressures and VAST scores decreased significantly post-transplantation
  • Fontan liver MRI score maximum was 10 pretransplantation and decreased significantly post-transplantation
  • Pretransplantation and post-transplantation liver biopsy scores did not differ in 4 paired biopsy specimens
  • Patients with FALD and MELD <15, MELD-XI <16 (MELD XI excludes INR), Fontan liver MRI score <10, and VAST (varices, ascites, splenomegaly, thrombocytopenia) score ≤2 can have successful short-term isolated heart transplantation outcomes

My take: This study provides reassurance that heart transplantation can proceed in patients with FALD, which is helpful as hepatic fibrosis is nearly universal in this population. After transplantation, surveillance is still needed for hepatic complications including hepatocellular carcinoma.

Related blog posts:

From Eric Topol’s Twitter Feed

Online Aspen Webinar (Part 9) -Liver Disease After Fontan, Acute on Chronic Liver Disease and Immunosuppression Withdrawal Strategies

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Below I’ve included a few more slides form recent Aspen Webinars

Fontan Associated Liver Disease  Greg Tiao

Related blog posts:

Acute on Chronic Liver Failure  Estella Alonso

Immunosuppression strategies ..and is withdrawal possible  Kathleen Campbell

More Cases of Hepatocellular Carcinoma after Fontan

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Several years ago, there were 4 cases of hepatocellular carcinoma (HCC) following Fontan procedure reported in the NEJM. (Reviewed in this blog: Hepatocellular carcinoma after Fontan Procedure).

Another recent report describes 3 patients who presented with HCC more than 10 years after Fontan procedure.  The age of these patients varied from 20 to 28 years. The authors use the term Fontan-Associated Liver Disease (FALD).  They note that FALD is strongly associated with the interval from the procedure, increasing in frequency with more time following surgery.  The risk of FALD is 4.4 times greater between years 11-15 years than in the first 10 years.

The authors recommend screening for HCC in patients 10 years after Fontan procedure. They suggest a baseline MRI followed by biannual ultrasounds and alpha-fetoprotein tests.

Related blog posts:

Warren Peak, Joshua Trree National Park

“When the Cause of Liver Disease Is the Heart”

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A recent review (S Ofei, C Gariepy. JPGN 2017; 64: 3-7) provides a good review of “congestive hepatopathy.”

Key points:

  • Overall, the liver receives 25% of cardiac output; though, 70% of blood flow to the liver is partially deoxygenated blood.  Cardiac disease can lead to liver disease due to hypoxic injury.
  • “Congestive hepatopathy (CH) results from chronic right heart dysfunction with decreased hepatic blood flow, arterial saturation, and increased central venous pressure.”  Ultimately, CH can lead to hepatic cirrhosis, termed ‘cardiac cirrhosis’ by the authors.
  • “Symptoms of CH are vague.” These symptoms could include abdominal pain nausea, and early satiety.
  • Treatment is uncertain.  “Guidelines and expert consensus..favor use of loop diuretics in patients with jaundice, hepatic congestion, and ascites.”
  • With regard to patients with Fontan-associated liver disease (FALD), “there is no consensus.” Patients should be treated for complications like varices, coagulopathy, and nutritional deficiencies.”  Some patients will need liver transplantation, though liver disease may be reversible with cardiac transplantation.  The article provides many references that provide more in-depth review of this topic.

My take: Overall, this article provides a succinct review of congestive hepatopathy.  There are many other cardiac conditions associated with liver dysfunction including heart disease associated with NAFLD, Alagille syndrome, and Kawasaki’s.

Cozumel

Cozumel

Related blog posts:

Hepatocellular Carcinoma after the Fontan Procedure

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Given the fact that chronic liver disease and cirrhosis can develop in patients after the Fontan procedure, it comes as little surprise that cases of hepatocellular carcinoma (HCC) are being reported as well (NEJM 2013; 368: 1756-57).

This letter to editor describes four patients ages 24 to 42 who developed HCC following a classic Fontan or a variation.  Three of the four had very elevated alpha-fetoprotein levels; the lowest of the four patients was 106 ng/mL.  The letter notes that cirrhosis “may develop…approximately 11 to 15 years after a Fontan procedure; an incidence of cancer of 1.5 to 5.0% per year” is estimated after development of cirrhosis based on previous studies.

The letter also describes difficulties with regard to potential screening and treatment.

Related blog entry/references:

Fontan and PLE

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In my practice, I am asked to give input on patients with Fontan procedure infrequently.  A few recent articles though are a good resource:

  • Nutr Clin Pract 2012; 27: 375-84
  • J Pediatr 2012;161:186-90

Both articles review the physiology and therapies available.  In essence, the Fontan operation establishes a passive connection between the systemic venous return and the pulmonary circulation.  When there are elevated inferior vena cava pressure, this can lead to hepatic dysfunction and protein-losing enteropathy.  The latter is related to engorged intestinal lymphatics, similar to that in congenital intestinal lymphangiectasia.  When lymphatic proteins leak, PLE only develops when the intestinal leak exceeds the patient’s ability to resynthesize lost proteins.

PLE presenting features: edema, diarrhea, bloating, pain, and pleural or pericardial effusions.  PLE places patient at risk for growth failure and associated problems. In more severe cases, hypocalcemia and infections due to lymphopenia can be present.

Potential treatments:

  • Agents that improve heart function -diuretics, pulmonary vasodilators (eg. sildenafil)
  • Corticosteroids including budesonide.  While improvement is common, hypoproteinemia returns after weaning of medication.  Systemic side effects occur even with budesonide.
  • Low molecular weight heparin.  Heparin likely helps by acting as a barrier to large molecules by improving the integrity of the basement membrane
  • Octreotide -has shown some effectiveness as an adjunct to other therapies in small studies
  • Albumin infusions
  • Diet: high protein (≥ 2 g/kg/day), low-fat (<25% of calories from fat), increase medium-chain triglycerides, & sodium-reduced
  • Surgical treatment (eg. atrial baffle fenestration) and cardiac transplantation

The second reference notes that many centers are delaying the Fontan procedure and accepting some degree of hypoxemia.  The problems with this approach include symptoms like headaches and decreased energy levels and the likelihood of developing pulmonary arteriovenous malformations.  Ultimately, the authors hypothesize that biomedical engineers may develop better solutions with miniaturized mechanical support devices to improve pulmonary blood flow.

Additional references:

  • Ann Thorac Surg 2010; 89: 837-42.  Budesonide for Fontan-associated PLE
  • Ann Thorac Surg 2011; 92: 1451-56.  Budesonide for Fontan-associated PLE
  • Congenit Heart Dis 2009; 4: 107-11.  Use of sildenafil for failing Fontan.