What are liver adenomas?

Liver Adenomas: Definition, Characteristics, and Management

Liver adenomas are rare benign liver tumors that require monitoring due to their potential for hemorrhage and malignant transformation. They occur predominantly in reproductive-aged women and are associated with estrogen exposure 1.

Pathophysiology and Characteristics

Liver adenomas (hepatocellular adenomas or HCAs) have distinct pathological features:

• They are composed of thin-walled capillaries perfused by arterial pressure
• They lack portal venous supply and are fed solely by arterial vessels
• They typically have missing or incomplete tumor capsules
• They contain peliotic sinusoids and no scar tissue, predisposing them to intralesional hemorrhage 1

On imaging, liver adenomas may appear:

• Hyper-echoic, hypo-echoic, or iso-echoic with heterogeneity on B-mode ultrasound
• With rapid large enhancement in arterial phase on contrast-enhanced ultrasound (CEUS)
• With centripetal filling pattern (periphery toward center) during arterial phase 1

Genetic Classification

HCAs have been classified into four subtypes based on molecular and pathological features:

1. HNF1α-mutated HCA (35%) - Associated with increased risk of gestational diabetes
2. β-catenin-mutated HCA (15%) - Highest risk of hemorrhage and malignant transformation
3. Inflammatory HCA - Related to STAT3 activation
4. Unclassified HCA 1, 2

Risk Factors

The primary risk factors for liver adenomas include:

• Female sex (female:male ratio up to 5:1)
• Oral contraceptive use (estrogen exposure)
• Obesity, type 2 diabetes, hypertriglyceridemia, and hypertension
• Alcohol consumption
• Glycogen storage disease type I 1, 3

Clinical Significance and Complications

Liver adenomas require monitoring due to two main complications:

1. Hemorrhage risk (25-30% of cases) - Risk factors include:

   • Tumor size (especially >5 cm)
   • β-catenin mutation
   • Activation of sonic hedgehog signaling
   • Alcohol consumption 1

2. Malignant transformation risk (approximately 10%) - Risk factors include:

   • Rapid increase in size or number
   • β-catenin mutation (especially exon 3)
   • Male sex 1, 4

Management Approach

Management depends on tumor size, location, and patient factors:

For adenomas <5 cm:

• Regular ultrasound monitoring
• No specific intervention required unless growth occurs
• During pregnancy: ultrasound monitoring each trimester 1

For adenomas ≥5 cm:

• Consider resection or bland embolization due to higher risk of hemorrhage
• Women planning pregnancy should have treatment prior to conception 1

For adenomas with concerning features:

• Percutaneous ethanol injections, radiofrequency ablation, or partial liver resection for adenomas showing:
  • Increase in size or number
  • Evidence of bleeding
  • Concerning features for malignant transformation 1

Monitoring Recommendations

For patients with liver adenomas:

• Hepatic profile (liver function tests) every 6 months
• Abdominal ultrasound every 12-24 months for smaller lesions
• CT/MRI with contrast every 6-12 months once adenomas are detected or for larger lesions
• Close monitoring during pregnancy with ultrasound each trimester 1

Important Caveats

• α-Fetoprotein and CEA levels are often normal even with malignant transformation
• No reliable biomarker exists for adenoma-to-HCC transformation; clinical vigilance is essential
• Sudden increase in size, number, or vascularity of adenomas should raise concern for malignant transformation 1
• MRI with hepato-specific contrast agents is considered superior for detecting and subtyping HCAs 2

Liver adenomas differ from other benign liver tumors like focal nodular hyperplasia (FNH) and hemangiomas, which generally have more benign clinical courses and rarely require intervention 1.