Benign Hepatic Nodules Mimicking Hepatocellular Carcinoma in the Setting of Fontan-associated Liver Disease: A Case Report

INTRODUCTION

Fontan procedure, which was originally introduced in 1971 by Fontan and Baudet,¹ is a palliative surgical operation for patients born with single ventricle congenital heart disease. This strategy redirects systemic venous blood flow directly to pulmonary circulation to minimize the oxygenated–deoxygenated blood mixture and alleviate the burden on a single ventricle,¹ which consequently results in elevated central venous pressure and diminished cardiac output.² These hemodynamic changes, also termed as Fontan physiology, cause end-organ damage throughout the body and thus present with some debilitating pathologies, such as peripheral venous insufficiency, plastic bronchitis, protein-losing enteropathy, and Fontan-associated liver disease (FALD).^3,4

We present a case of FALD in an adult with histopathologically proven benign nodules mimicking hepatocellular carcinoma (HCC) by imaging criteria. Arterially enhancing benign hepatic nodules with a washout appearance on both portal and more delayed venous phase images are rare, with very few scattered case reports throughout the English literature to date.⁵ Large-scale studies are needed to overcome the limitations of rare case reports.

CASE DESCRIPTION

A 37-year-old woman was referred to our ultrasonography (US) department with right upper quadrant pain. She had a history of pulmonary atresia with complex univentricular anatomy. She underwent five aortopulmonary shunt operations in early childhood, followed by classic Fontan operation at ten years of age (Fig. 1). She was on amiodarone and aspirin for atrial flutter. The blood test results on admission were unremarkable. Hepatitis B and C virus serologies were negative, and there was no history of alcohol abuse. She had not been under any hepatic surveillance and had not undergone any hepatic imaging previously. Physical examination revealed abdominal tenderness in epigastrium and right upper quadrant with palpation.

Grayscale and Doppler US examinations showed cirrhotic features, consistent with FALD. Additionally, several hypervascular liver lesions were found with a dominant lesion in segment 7 concerning HCC in the cirrhotic background (Fig. 2). However, serum alpha-fetoprotein level was within the normal range. Triphasic computed tomography (CT) of the liver was subsequently performed to further evaluate these findings on US. The lesion in question showed enhancement during the arterial phase, followed by washout during the portal and late venous phases (Fig. 3). Given the past medical history and radiological findings, US-guided biopsy was performed from the dominant lesion. The biopsy revealed sinusoidal dilatation and focal fibrosis without any features concerning malignancy. On follow-up examination, hepatic lesions showed size stability over 12 months, and thus benign etiology was favored. At the time of this case report, the patient is doing well on a routine follow-up program for FALD.

DISCUSSION

Fontan-associated liver disease refers to a spectrum of pathologies of the liver secondary to hemodynamic changes associated with Fontan physiology. Elevated central venous pressure and diminished cardiac output lead to hepatic venous congestion, ischemia, and eventually fibrosis.⁶ The histological features in the liver of patients with Fontan physiology are similar to those seen in congestive heart failure.⁷ Histological studies also show that almost half of the patients have developed advanced liver cirrhosis within 30 years after the Fontan procedure.⁸ In most of the patients with Fontan physiology, liver fibrosis is further complicated by hepatic nodules, some of which were proved to be HCC throughout the literature.^3–5,9–18 However, arterially enhancing benign hepatic nodules in this patient population may demonstrate washout on portal venous and/or more delayed phase images, as in our case.⁵ Hence, not all arterially enhancing nodules with a washout appearance on portal venous and/or more delayed phase images can be considered malignant. Although the underlying mechanism has not yet been elucidated clearly, these findings are postulated to be secondary to hemodynamic changes associated with Fontan physiology. Radiologists should consider histological confirmation before making the definitive diagnosis of HCC by imaging criteria.

CONCLUSION

Fontan-associated liver disease is an inevitable consequence of the Fontan procedure. In this patient population, arterially enhancing benign hepatic nodules with delayed washout pose a diagnostic challenge since these enhancement features overlap with HCC. Both radiologists and hepatologists should be aware of this benign complication not to misdiagnose these nodules as HCC. In FALD patients, all arterially enhancing hepatic nodules with delayed washout should be approached with caution, which may require follow-up imaging to document stability or biopsy if clinically indicated.

ETHICS COMMITTEE APPROVAL

The Institutional Review Board (IRB) approved this study.

INFORMED CONSENT

The requirement for the informed consent was waived since all the content herein has been fully deidentified.

FINANCIAL DISCLOSURE

This research received no direct funding. However, Dr Tirkes is supported by the National Cancer Institute and National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award numbers 1R01DK116963 and U01DK108323 (Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

NOTE

All the contents herein have been fully deidentified to protect the patient’s privacy.

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