More Cases of Hepatocellular Carcinoma after Fontan

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”

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

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Hepatocellular Carcinoma after the Fontan Procedure

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

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.