Hepatic adenoma (HA) is a rare, non-cancerous growth that develops in the liver parenchyma. These tumors originate from hepatocytes, the liver’s primary cell type. The true prevalence is difficult to determine because many adenomas are small and asymptomatic, but they are most often found in women of childbearing age. Although benign, HAs carry two risks that require careful management. First, they are highly vascular, increasing the danger of spontaneous rupture and severe internal bleeding. Second, a small risk exists for the adenoma to transform into a malignant liver cancer, known as hepatocellular carcinoma.
Primary Causes and Risk Factors
The development of hepatic adenoma is strongly linked to hormonal influences, specifically high levels of exogenous sex steroids. Estrogen promotes the proliferation of hepatocytes, and adenoma cells often possess estrogen receptors, making them sensitive to these hormones. This explains the association between hepatic adenomas and the use of estrogen-containing oral contraceptive medications. The risk rises with the duration of use and the dosage of estrogen, though modern, lower-dose pills have reduced the overall incidence.
The use of anabolic or androgenic steroids is also a known risk factor, particularly in men. Other hormonal states, such as pregnancy, can cause existing adenomas to grow due to naturally elevated hormone levels. Beyond external hormonal factors, intrinsic genetic changes within the liver cells can drive tumor formation, leading to distinct molecular subtypes.
The HNF1-alpha-inactivated subtype accounts for approximately 35 to 40% of cases. This subtype results from a mutation that removes the control of the Hepatocyte Nuclear Factor 1 Alpha protein. This loss of function disrupts normal hepatocyte differentiation and metabolic balance, leading to the unchecked multiplication of liver cells and tumor growth.
Another significant subtype is the beta-catenin-activated adenoma, representing about 15 to 20% of cases. This group is considered the highest risk for malignant transformation. A mutation in the CTNNB1 gene causes the beta-catenin protein to become overactive, constitutively activating the Wnt/beta-catenin signaling pathway. This constant activation promotes abnormal gene expression and rapid cell proliferation.
Recognizing Symptoms and Diagnostic Process
Many hepatic adenomas are discovered incidentally when a patient undergoes abdominal imaging for an unrelated health concern. Up to half of all adenomas are asymptomatic, especially when they are small. When symptoms occur, they are often vague, including a dull ache or mild pain in the upper right quadrant of the abdomen, or a feeling of abdominal fullness. The most concerning symptoms are sudden, severe pain in the upper abdomen accompanied by signs of shock, which indicate a life-threatening rupture and hemorrhage.
Because symptoms are non-specific, specialized imaging is necessary for a definitive diagnosis and to differentiate the adenoma from other liver masses. A multi-phase contrast-enhanced Magnetic Resonance Imaging (MRI) scan is the preferred tool, providing detailed information about the tumor’s internal structure and blood supply. The patterns of how the mass takes up and releases the injected contrast agent help classify the lesion and suggest the molecular subtype. Computed Tomography (CT) scans may also be used to assess the size and location of the tumor.
While a tissue biopsy is the most definitive way to confirm a diagnosis, it is often avoided due to the risk of causing bleeding from the vascular tumor. Biopsy is typically reserved for cases where imaging results are ambiguous or when the appearance suggests a high-risk beta-catenin-activated subtype requiring immediate surgical planning. The combination of patient history, imaging results, and molecular classification guides subsequent management decisions.
Treatment and Long-Term Management
The initial step in managing a hepatic adenoma is the immediate discontinuation of any associated hormonal agents, such as oral contraceptives or anabolic steroids. Removing the hormonal stimulus often causes the adenoma to shrink over 6 to 12 months, which can resolve the condition for smaller lesions. Following this cessation, repeat imaging is necessary to monitor the tumor’s size and stability.
For women with asymptomatic adenomas measuring 5 centimeters or less, the primary strategy is watchful waiting and active surveillance. This involves regular follow-up imaging, typically with a contrast-enhanced MRI, every six months for the first two years and then annually thereafter. If the tumor remains stable and the patient is no longer exposed to hormonal factors, the risk of complications is lowered.
Surgical resection is generally recommended for adenomas larger than 5 centimeters due to the increased risk of rupture and malignant transformation. Surgery is also advised for any adenoma that causes symptoms, shows evidence of rapid growth during surveillance, or is classified as the high-risk beta-catenin-activated subtype, regardless of size. For men, surgical removal is often recommended for all adenomas, even small ones, because tumors in males carry a higher intrinsic risk of becoming cancerous.
In the event of a complication such as rupture and hemorrhage, immediate intervention is required to stabilize the patient. This may involve emergency surgery to stop the bleeding and remove the adenoma, or a less invasive procedure called transarterial embolization (TAE). TAE involves injecting particles into the blood vessel supplying the tumor to block the blood flow, which controls the hemorrhage and reduces tumor size.