A 42-year-old asymptomatic man is screened after his brother was diagnosed with hereditary hemochromatosis (HFE C282Y homozygous). His serum ferritin is 420 ng/mL (normal <300) and transferrin saturation is 58%. HFE genetic testing shows C282Y homozygosity. Liver function tests are normal. Which is the most appropriate next step?

• A Proceed directly to liver biopsy to quantify hepatic iron
• B MRI liver for iron quantification, then start phlebotomy if hepatic iron is elevated
• C Initiate weekly therapeutic phlebotomy ✓
• D No treatment; reassess ferritin annually as he is unlikely to develop iron overload

Explanation

In a B282Y homozygote with elevated ferritin and transferrin saturation (>45 percent in men), iron overload is confirmed and therapeutic phlebotomy should be initiated without requiring liver biopsy. Biopsy is reserved for suspected advanced fibrosis (ferritin >1000 ng/mL or elevated LFTs). Annual monitoring alone is inappropriate when iron overload is already present. MRI can quantify liver iron but is not mandatory before starting phlebotomy in clear-cut cases.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.