What is the cause of a hepatic adenoma, particularly in a pregnant patient?

Causes of Hepatic Adenoma in Pregnant Patients

Hepatic adenomas are primarily caused by oral contraceptive use, with genetic mutations (HNF1a, β-catenin, STAT3-related genes) and maternal cardiometabolic disorders (obesity, type 2 diabetes, hypertriglyceridemia, hypertension) as additional contributing factors. 1

Primary Etiologic Factors

Hormonal Contraceptive Use

• Oral contraceptive pills are the most established cause of hepatic adenomas, with a proven association between duration of use and adenoma development 2, 3
• The attributable risk is estimated at 3.3 cases per 100,000 users, increasing significantly after four or more years of use, especially with higher-dose formulations 2
• Longer duration of oral contraceptive use correlates with larger tumor size and higher rates of bleeding and rupture 3
• Benign hepatic adenomas are associated with oral contraceptive use, though the incidence remains rare in the United States 2

Genetic Mutations

The 2023 EASL guidelines identify three major genetic subtypes with distinct implications 1:

• HNF1a mutations (35% of cases): These patients face increased risk of gestational diabetes mellitus and require screening using local protocols during pregnancy 1
• β-catenin mutations (15% of cases): Exon 3 mutations carry higher malignant transformation risk compared to exons 7/8 mutations 1
• STAT3-related gene mutations (50% of cases): Result in reduced activation of STAT3 signaling 1

Cardiometabolic Disorders

• Maternal obesity, type 2 diabetes mellitus, hypertriglyceridemia, and hypertension are recognized contributing factors 1
• These conditions appear to create a metabolic environment conducive to adenoma development 1

Additional Risk Factors for Complications

Tumor-Specific Characteristics

• Tumor size is the most critical predictor of hemorrhage risk, with 32% hemorrhage rate in one large series of 261 cases 1
• Presence of β-catenin mutations on exons 7/8 increases hemorrhage risk 1
• Evidence of sonic hedgehog signaling activation correlates with bleeding complications 1

Behavioral Factors

• Alcohol consumption is identified as a risk factor for hemorrhage in existing adenomas 1

Clinical Pitfall to Avoid

Do not assume adenomas are solely hormone-driven: While oral contraceptives remain the primary cause, the genetic component (present in 100% of cases when all subtypes are considered) means that adenomas have a complex multifactorial etiology requiring genetic consideration for risk stratification 1. Women with HNF1a mutations need gestational diabetes screening, and those with β-catenin exon 3 mutations require closer surveillance for malignant transformation 1.