What is the recommended management for a 3.7 cm liver lesion in a patient with hereditary hemochromatosis?

Management of a 3.7 cm Liver Lesion in Hereditary Hemochromatosis

This 3.7 cm liver lesion requires urgent evaluation for hepatocellular carcinoma (HCC) with dynamic imaging (CT or MRI) showing arterial hypervascularity, and if imaging is characteristic for HCC or AFP >200 ng/mL, you should proceed directly to treatment without biopsy. 1

Initial Diagnostic Approach

Imaging Evaluation

• Obtain dynamic contrast-enhanced CT or MRI immediately to assess the vascular profile of this lesion, specifically looking for arterial hypervascularity with washout in portal venous or delayed phases—the hallmark of HCC 1
• Lesions >2 cm with characteristic arterial hypervascularity on imaging are highly suspicious for HCC and warrant aggressive evaluation 1

Laboratory Assessment

• Check AFP level urgently: If AFP >200 ng/mL combined with imaging suggestive of HCC (arterial hypervascularity), the diagnosis of HCC is essentially confirmed and biopsy is not required 1
• Assess liver function tests, including aminotransferases, bilirubin, and albumin, though note that half of cirrhotic hemochromatosis patients have normal transaminases, so normal values do not exclude advanced disease 1
• Measure serum ferritin to assess iron burden and treatment adequacy 1

Determine Cirrhosis Status

• Establish whether cirrhosis is present, as this profoundly impacts prognosis and management 1
• If not previously documented, liver biopsy may be needed to stage fibrosis—but avoid biopsy of the lesion itself at this stage 1
• Cirrhosis in hemochromatosis patients carries significantly increased mortality, with HCC accounting for approximately 30% of all hemochromatosis-related deaths 1

When Biopsy is Indicated

Biopsy should only be performed if:

• Imaging appearances are atypical or non-diagnostic for HCC 1
• AFP is <200 ng/mL AND imaging does not show characteristic arterial hypervascularity 1

Critical caveat: Biopsy of lesions between 1-2 cm can be unreliable due to sampling error and difficulty distinguishing well-differentiated HCC from dysplastic nodules 1

Treatment Considerations Based on Findings

If HCC is Confirmed

• Proceed with HCC-specific treatment algorithms (resection, transplantation, ablation, or transarterial therapy depending on tumor burden, liver function, and patient candidacy) 1
• Continue lifelong HCC surveillance even after successful treatment, as the cancer risk persists despite iron depletion 1, 2

If Lesion is Benign (e.g., Focal Nodular Hyperplasia)

• FNH can occur with increased frequency in patients with vascular liver abnormalities, though this is more commonly described in hereditary hemorrhagic telangiectasia 1
• Do not biopsy or excise lesions consistent with FNH 1
• Characterize non-invasively using at least two imaging modalities 1

Concurrent Hemochromatosis Management

Phlebotomy Protocol

• Initiate or optimize therapeutic phlebotomy to achieve and maintain serum ferritin 50-100 µg/L 2
• Remove 500 mL weekly or biweekly during induction phase 1, 2
• Check hemoglobin before each session; do not allow >20% drop from baseline 2, 3
• Monitor ferritin every 10-12 phlebotomies 1, 2, 3

Critical Point About Cirrhosis

If cirrhosis is already established, phlebotomy will NOT reverse it, though it may prevent further progression and reduce HCC risk if initiated before cirrhosis develops 1, 2

Hepatic fibrosis may regress in approximately 30% of patients, but established cirrhosis is generally irreversible 2

Surveillance Strategy Going Forward

For Cirrhotic Patients

• Implement lifelong HCC surveillance with ultrasound every 6 months, regardless of iron depletion status 1
• Consider AFP measurement every 6 months, though ultrasound is the primary surveillance modality 1
• HCC risk remains elevated even after successful phlebotomy therapy 1, 2

For Non-Cirrhotic Patients

• HCC is exceedingly rare in non-cirrhotic hemochromatosis patients 1
• Routine HCC surveillance is not required if cirrhosis is definitively excluded 1

Common Pitfalls to Avoid

• Do not delay imaging: A 3.7 cm lesion in a hemochromatosis patient is HCC until proven otherwise 1
• Do not assume normal transaminases exclude cirrhosis: 50% of cirrhotic hemochromatosis patients have normal liver enzymes 1
• Do not biopsy if imaging and AFP are diagnostic: This only delays treatment and carries needle-tract seeding risk 1
• Do not stop HCC surveillance after iron depletion: Cancer risk persists lifelong in cirrhotic patients 1, 2