Referral for Suspected Iron Overload with Hepatomegaly
Patients with suspected iron overload and hepatomegaly should be referred to hepatology/gastroenterology, as iron overload evaluation and management falls within the hepatology domain, and the liver is the primary target organ for iron deposition requiring specialist assessment. 1
Why Hepatology is the Appropriate Specialty
The European Association for the Study of the Liver (EASL) explicitly states that patients with evidence of significant, unexplained iron overload should be referred for assessment by a specialist in iron disorders, typically hepatologists or gastroenterologists. 1 The American Association for the Study of Liver Diseases similarly emphasizes that iron overload evaluation and management falls within the gastroenterology/hepatology domain. 1
The presence of hepatomegaly is particularly important because:
- The liver is the main target organ for iron deposition and overload, which are associated with significant liver morbidity and mortality 2
- Hepatomegaly in the context of suspected iron overload may indicate advanced disease requiring liver biopsy consideration 3
- C282Y homozygous patients with hepatomegaly should be offered liver biopsy to assess for cirrhosis 3
What the Hepatologist Will Do
Initial Diagnostic Workup
The specialist will pursue a systematic evaluation including:
- HFE genetic testing for C282Y and H63D mutations to evaluate for hereditary hemochromatosis 1, 4
- MRI with quantitative assessment of hepatic iron concentration to confirm and quantify iron overload 3, 1
- Evaluation for secondary causes of iron overload, including chronic liver diseases and hematologic disorders, if HFE testing is negative 1, 4
Assessment of Disease Severity
The hepatologist will determine if liver biopsy is needed based on:
- Serum ferritin >1000 μg/L 3
- Elevated liver enzymes (AST/ALT) 3
- Hepatomegaly on examination 3
- Age over 40 years in confirmed C282Y homozygotes 3
- Platelet count <200, which combined with ferritin >1000 μg/L and elevated transaminases predicts cirrhosis in 80% of C282Y homozygotes 5
Treatment Initiation
If true iron overload is confirmed, the hepatologist will initiate therapeutic phlebotomy:
- Weekly or biweekly removal of 500 mL blood until ferritin reaches 50-100 μg/L 1, 6
- Monitoring protocol includes checking hematocrit/hemoglobin before each phlebotomy and ferritin every 10-12 phlebotomies 1, 6
- Maintenance phlebotomy at less frequent intervals (typically 2-6 times per year) to maintain ferritin between 50-100 μg/L 6
Urgency of Referral
The referral should be made promptly but is not emergent unless the patient has signs of cardiac involvement, advanced liver disease, or symptoms of end-organ damage. 1 However, given the presence of hepatomegaly, which may indicate more advanced disease, the referral should not be delayed.
Critical Distinction: Not All Hyperferritinemia Requires Treatment
A key reason for specialist referral is to distinguish between:
- True iron overload (hemochromatosis, secondary iron accumulation) which requires phlebotomy 1
- Dysmetabolic hyperferritinemia and inflammatory hyperferritinemia which do not require iron removal 1, 7
The hepatologist has the expertise to make this distinction through appropriate testing, including MRI quantification of hepatic iron and assessment of transferrin saturation patterns. 3, 1
Common Pitfall to Avoid
Do not refer to hematology unless there is evidence of a primary hematologic disorder causing secondary iron overload (such as thalassemia, myelodysplastic syndrome, or other iron-loading anemias). 4, 2 The initial evaluation of iron overload with hepatomegaly belongs in hepatology, where liver-specific complications can be properly assessed and managed. 1