A 48-year-old man presents with fatigue, arthralgia (MCP joints bilaterally), elevated liver enzymes (AST 85, ALT 92), serum ferritin 1850 µg/L, transferrin saturation 78%. Liver biopsy shows grade 3 hepatic iron deposition with periportal fibrosis. HFE gene testing reveals C282Y homozygosity. Regarding treatment with phlebotomy, what is the therapeutic target?

• A Serum ferritin <30 µg/L and transferrin saturation <15%
• B Serum ferritin 50–100 µg/L with normalization of transferrin saturation
• C Serum ferritin <500 µg/L is sufficient for symptomatic benefit
• D Serum ferritin <50 µg/L and transferrin saturation <30% ✓

Explanation

In hereditary hemochromatosis (HFE-related, C282Y homozygous), the therapeutic target for phlebotomy (venesection) is serum ferritin <50 µg/L (some guidelines suggest <50 µg/L as induction target) and transferrin saturation <30%. Initially, phlebotomy is performed weekly (450 mL removes ~200–250 mg iron) until target is reached (often 1–2 years). Maintenance phlebotomy is then done 3–4 times yearly to maintain ferritin 50–100 µg/L. The European Association for the Study of the Liver (EASL 2022) guidelines specify ferritin <50 µg/L during depletion phase. Liver fibrosis can regress with adequate iron depletion; cirrhosis is irreversible but prevents HCC progression.

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

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Written and medically reviewed by the StethoPrep medical team.