Training/Practice
Contemporary Issues in Cardiology Practice
Fontan-Associated Liver Disease: Evidence for Early Surveillance of Liver Health in Pediatric Fontan Patients

https://doi.org/10.1016/j.cjca.2018.11.019Get rights and content

Abstract

The growing awareness of Fontan-associated liver disease (FALD) in adults with Fontan physiology has provided the impetus to better understand the natural history of FALD and develop a reliable noninvasive method to diagnose and monitor liver health in this population. Biochemical and imaging tests have been investigated to determine their association with liver pathology. The congestive hepatopathy that develops after the Fontan procedure has made interpreting these tests challenging. We have reviewed and summarized the current understanding and ongoing challenges with respect noninvasive measures of liver health in Fontan patients including biochemical tests, elastography, hepatic ultrasound, cross-sectional imaging, and hemodynamics and how they relate to liver pathology. It has been demonstrated from biopsy data that liver disease is universal and progressive in Fontan patients. Traditional biochemical tests, elastography, and imaging methods are often abnormal in Fontan patients but do not reliably indicate significant liver pathology. Although a reliable means for surveillance of FALD remains elusive, this continues to be an active area of investigation, with promising recent developments. Therapeutic options for FALD are limited, with cardiac transplant as the only option that can stabilize FALD pathology and improve symptomatology. Given the limited therapeutic options and the prevalence of liver disease in Fontan patients, there is a compelling case for early routine surveillance of liver health and promotion of global liver health.

Résumé

La sensibilisation grandissante à la maladie du foie associée à l’intervention de Fontan (FALD) chez les adultes ayant subi une telle intervention a donné l’impulsion nécessaire pour tenter de mieux comprendre l’histoire naturelle de la FALD et d’élaborer une méthode non invasive fiable de diagnostic et de surveillance de la santé hépatique dans cette population. Les tests biochimiques et les méthodes d’imagerie dont on dispose ont été analysés afin d’évaluer l’association entre leurs résultats et la pathologie hépatique. L’hépatopathie congestive qui apparaît après l’intervention de Fontan rend plus difficile l’interprétation des résultats de ces tests. Nous avons effectué une recension et une synthèse des connaissances actuelles et des difficultés persistantes relatives aux méthodes non invasives d’évaluation de la santé du foie chez les patients ayant subi une intervention de Fontan, y compris les épreuves biochimiques, l’élastographie, l’échographie du foie, l’imagerie transversale et l’hémodynamique, et à leur association avec la pathologie hépatique. Les données issues de biopsies ont démontré que chez les patients ayant subi une intervention de Fontan, la maladie du foie est universelle et progressive. Les épreuves biochimiques classiques, l’élastographie et les méthodes d’imagerie produisent souvent des résultats anormaux dans cette population de patients, mais ne donnent aucune indication fiable d’une pathologie hépatique importante. Même s’il reste toujours à trouver un moyen de surveillance fiable de la FALD, ce domaine de recherche n’en demeure pas moins actif et a connu récemment des développements prometteurs. Les options de traitement de la FALD sont rares, et la transplantation cardiaque est le seul moyen de stabiliser cette pathologie et d’en atténuer les symptômes. L’éventail restreint d’options thérapeutiques et la prévalence de la maladie hépatique chez les patients ayant subi une intervention de Fontan mettent en relief l’importance de la surveillance précoce et systématique et de la promotion globale de la santé hépatique.

Section snippets

Pathology

The liver pathology in FALD is thought to be initiated with distension of hepatic sinusoids, causing chronic congestion, inflammation, and sinusoidal fibrosis. This can progress to include centrilobular fibrosis, bridging fibrosis, and portal fibrosis due to portal hypertension. This continues to progress to cirrhosis, at which point liver dysfunction becomes more clinically apparent. The complications of liver failure and risk of hepatocellular carcinoma are significant morbidities at this

Elastography

Liver biopsy is the gold standard for the diagnosis of liver fibrosis and cirrhosis. To minimize the need for this invasive procedure, liver elastography has been validated as a noninvasive technique for the assessment of liver fibrosis and cirrhosis in primary hepatic disease. This technology has been applied in the Fontan population with the intention to use it for diagnosis and surveillance of FALD. Three modalities of elastography have been studied in FALD. Transient elastography (TE) and

Biochemical Tests

Most biochemical tests of liver health in Fontan patients have not been demonstrated to be reliable indicators of pathology. Although often abnormal in Fontan patients, transaminitis and impaired synthetic function have not demonstrated a reliable association with other measures of liver health that include elastography, hemodynamic measurements, or liver fibrosis. Alpha-fetoprotein (AFP) is used as a specific marker for hepatocellular carcinoma (HCC) and would complement ultrasound imaging for

Imaging

The significance of most imaging abnormalities with respect to the severity of FALD remains unclear. Cross-sectional imaging with computed tomography (CT) and magnetic resonance imaging (MRI) often reveals abnormalities in Fontan patients. CT and MRI in Fontan patients often demonstrate abnormalities such as zonal enhancement and reticular changes that are typically associated with liver congestion and fibrosis in other disease processes. Less commonly, hypervascular nodules are found, which

Transplant

The growing knowledge of FALD has led to questions regarding the role of concurrent liver transplantation in those with a failing Fontan who are listed for cardiac transplant. Hepatic failure is typically cited as a reason for combined heart and liver transplant (CHLT) as opposed to an isolated heart transplant (IHT). This concept is being challenged with reports showing positive outcomes following IHT in Fontan patients with FALD. Investigations following IHT in patients with FALD have

Conclusion

FALD is ubiquitous and progressive, but an evidence-based protocol for surveillance has not been established. Laboratory investigations are largely unhelpful in guiding management. Nearly all results of investigations of liver health—including biochemical markers, ultrasound, cross-sectional imaging, and elastography—will be abnormal in Fontan patients. The clinical significance and appropriate action to take upon discovery of mild abnormalities in individual tests is unclear. Patients with

Disclosures

The authors have no conflicts of interest to disclose.

References (5)

There are more references available in the full text version of this article.

Cited by (13)

  • Prenatal Diagnosis and Management of Single-Ventricle Heart Disease

    2022, Canadian Journal of Cardiology
    Citation Excerpt :

    Although the excessive load on the single-ventricle heart is gradually lifted throughout these stages and the saturations gradually improve, the Fontan circulation has its challenges. Systemic venous congestion may occur, manifesting as plastic bronchitis in the lungs, protein-losing enteropathy in the intestines,50 congestive hepatopathy with fibrosis (Fontan-associated liver disease),51,52 or kidney disease53 among others. Cardiac suture lines, among other factors, may lead to arrhythmias, and the single ventricle may decompensate with valve regurgitation and systolic and/or diastolic function, leading to heart failure.

  • Hepatic and Renal Consequences of Single-Ventricle Physiology Palliated With the Fontan Operation

    2022, Canadian Journal of Cardiology
    Citation Excerpt :

    Fontan-associated liver disease (FALD) results from the systemic venous connections that are created in the Fontan procedure to separate the venous and arterial circulations in the absence of a pulmonary ventricle. This alters the hemodynamics of venous return, causing chronic liver congestion that can progress to fibrosis and cirrhosis.3,4 The result of having the superior vena cava (SVC) and IVC connect directly to the pulmonary arteries without an intervening pulmonary ventricle elevates the central venous pressure (CVP) that is transmitted to the efferent hepatic circulation.

View all citing articles on Scopus

See page 219 for disclosure information.

View full text