Focal nodular hyperplasia: A comprehensive review with a particular focus on pathogenesis and complications

Focal nodular hyperplasia (FNH) is a benign hepatic tumor most commonly detected incidentally during imaging. Typically affecting women of reproductive age, FNH is characterized by a well-circumscribed lesion with proliferating hepatocytes and a distinctive central stellate fibrous scar. This review aims to discuss the pathophysiology, rare complications, and management strategies associated with FNH.

FNH accounts for approximately 8% of all primary liver lesions and around 25% of benign liver tumors. It is the second most common benign liver lesion after hepatic hemangioma. The prevalence of FNH is estimated to be between 0.9% and 3%, with a higher incidence in females, particularly those aged 20 to 50 years. Most FNH lesions are solitary, but about 20-30% of cases involve multiple lesions. FNH is also associated with other vascular anomalies such as hemangiomas in 23% of cases and adenomas in 3.6% of cases.

The exact cause of FNH is not fully understood. Previously, exogenous hormones, particularly oral contraceptive pills (OCPs), were thought to be implicated due to higher prevalence in women using OCPs. However, this association has not been definitively proven. Estrogens, particularly estradiol, have proangiogenic effects, promoting vascular endothelial growth factor (VEGF) production and endothelial proliferation, which may contribute to FNH development.

Recent theories suggest FNH results from a hyperplastic reaction to vascular anomalies such as dystrophic arteries, arteriovenous shunts, or congenital vascular malformations. These anomalies cause altered oxygenation and oxidative stress, triggering hepatocyte hypertrophy and stellate cell activation, leading to scar formation. Genetic studies have shown alterations in the expression of angiopoietin genes (ANGPT1 and ANGPT2), which regulate vessel maturation. An increased ANGPT1/ANGPT2 ratio has been observed, where ANGPT1 promotes vessel formation and ANGPT2 acts as an antagonist. This dysregulation, along with VEGF, may play a role in the formation of dystrophic vessels characteristic of FNH.

Most patients with FNH are asymptomatic, with lesions often discovered incidentally during imaging, surgery, or autopsy. When symptomatic, patients may experience vague abdominal pain, early satiety, and dyspepsia, especially if the lesion is large or exerts pressure on adjacent structures. Rarely, FNH presents as a palpable abdominal mass.

Diagnosis of FNH typically involves imaging techniques such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI). Liver enzyme tests and alpha-fetoprotein levels are generally normal and not useful for diagnosis. Imaging may reveal typical features like a central scar, although these features are not always present, making differentiation from malignant lesions like hepatocellular carcinoma (HCC) challenging. In ambiguous cases, a biopsy may be necessary.

Complications from FNH are rare but can include pain, rupture, and compression of nearby structures such as the hepatic vein, stomach, or biliary system. There have been reported cases of acute cholecystitis associated with FNH, although the causal relationship is unclear. In one instance, a 10-year-old girl with epigastric pain and acute cholecystitis was found to have a 6-7 cm FNH lesion, managed conservatively with antibiotics.

Another case involved a 23-year-old female with nausea, vomiting, and abdominal pain caused by a large FNH compressing the stomach, leading to gastric outlet obstruction. Surgical resection of the lesion resolved the symptoms, and histopathological examination confirmed the diagnosis of FNH.

Management of FNH is typically conservative, as these lesions are benign and often asymptomatic. Surgical resection, radiofrequency ablation, or arterial embolization are reserved for cases with significant symptoms, such as unexplained pain, or when the lesion is large or growing, posing a risk of complications. Routine follow-up with imaging is recommended to monitor for changes in lesion size or characteristics.

FNH is a benign liver tumor with a generally favorable prognosis. Understanding its pathogenesis, which involves vascular anomalies and genetic factors, helps in managing this condition effectively. While complications are rare, appropriate management and monitoring are essential to address any potential issues and ensure patient well-being.

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https://www.xiahepublishing.com/2310-8819/JCTH-2023-00265

The study was recently published in the Journal of Clinical and Translational Hepatology.

The Journal of Clinical and Translational Hepatology(JCTH) is owned by the Second Affiliated Hospital of Chongqing Medical University and published by XIA & HE Publishing Inc. JCTH publishes high quality, peer reviewed studies in the translational and clinical human health sciences of liver diseases. JCTH has established high standards for publication of original research, which are characterized by a study’s novelty, quality, and ethical conduct in the scientific process as well as in the communication of the research findings. Each issue includes articles by leading authorities on topics in hepatology that are germane to the most current challenges in the field. Special features include reports on the latest advances in drug development and technology that are relevant to liver diseases. Regular features of JCTH also include editorials, correspondences and invited commentaries on rapidly progressing areas in hepatology. All articles published by JCTH, both solicited and unsolicited, must pass our rigorous peer review process.

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