What is the treatment for Hemochromatosis (iron overload)?

Treatment of Hemochromatosis (Iron Overload)

Phlebotomy is the first-line treatment for hemochromatosis and should be initiated immediately in all patients with documented iron overload to prevent irreversible organ damage and reduce mortality. 1, 2

Primary Treatment: Therapeutic Phlebotomy

Induction Phase

• Remove 450-500 mL of blood (one unit) weekly or biweekly until iron stores are depleted 2, 3
• Monitor hemoglobin/hematocrit before each session and avoid reducing hemoglobin by more than 20% from baseline 2, 3
• Check serum ferritin every 10-12 phlebotomies to track progress 3
• Continue until serum ferritin reaches 50-100 μg/L, which indicates adequate iron depletion 2, 3

The evidence supporting phlebotomy is compelling: adequately phlebotomized patients demonstrate 93% survival at 5 years compared to only 48% in inadequately treated patients, with 10-year survival of 78% versus 32% 1. This dramatic mortality benefit underscores the critical importance of aggressive initial treatment.

Maintenance Phase

• Continue periodic phlebotomy for life to maintain serum ferritin between 50-100 μg/L 2
• Frequency varies by individual iron reaccumulation rate: typically 3-4 times yearly for men and 1-2 times yearly for women 3
• Monitor serum ferritin, hemoglobin, and hematocrit regularly 3

Clinical Improvements with Phlebotomy

Phlebotomy reverses multiple manifestations when initiated early 1, 2:

• Fatigue and malaise improve
• Elevated transaminases normalize 1
• Skin pigmentation resolves 1
• Fibrosis improves in 15-69% of non-cirrhotic patients depending on initial severity 1
• Esophageal varices may improve or resolve even in cirrhotic patients 1

Critical caveat: Survival approaches normal population levels only when treatment begins before development of cirrhosis or diabetes 1, 4. Once cirrhosis develops, hepatocellular carcinoma risk persists despite adequate iron removal, accounting for approximately 30% of hemochromatosis-related deaths 4, 2.

Alternative Treatment: Iron Chelation Therapy

Iron chelation is reserved for patients who cannot tolerate phlebotomy or when phlebotomy is not feasible 1

• Deferoxamine (parenteral) is the treatment of choice for secondary iron overload with ineffective erythropoiesis 1
• Deferasirox is the most studied oral chelator but is not approved for hemochromatosis by the European Medicines Agency and should not be used in advanced liver disease 2
• Chelation is primarily indicated for transfusion-dependent anemias where phlebotomy would worsen anemia 1, 5

Dietary and Lifestyle Modifications

Strict dietary restrictions are essential adjuncts to phlebotomy 2, 3:

Avoid Completely

• Iron supplements and iron-fortified foods 2
• Vitamin C supplements, especially before iron depletion, as they enhance iron absorption 2, 3
• Raw or undercooked shellfish due to Vibrio vulnificus infection risk in iron-overloaded patients 2

Limit Significantly

• Red meat from mammals; choose lean white poultry meat instead (maximum 200 g weekly) 6
• Alcohol consumption, which increases iron absorption and accelerates liver damage 3

Recommended

• Varied vegetarian, semi-vegetarian, or flexitarian diet 6
• At least 600 g vegetables and fruits daily 6
• Protein-rich legumes and pulses 6
• Fish 2-4 times weekly (350-500 g total) 6
• Green or black tea, coffee with meals to reduce iron absorption 6

Monitoring and Surveillance

During Treatment

• Hemoglobin/hematocrit before each phlebotomy 2, 3
• Serum ferritin every 10-12 phlebotomies during induction 3
• Regular monitoring of ferritin, hemoglobin, and hematocrit during maintenance 3

Long-Term Surveillance

All patients with cirrhosis require lifelong hepatocellular carcinoma (HCC) screening even after successful iron depletion 1, 4, 2. HCC risk does not decrease with phlebotomy in cirrhotic patients 1. While optimal surveillance methods and intervals are not definitively established for hemochromatosis, recommendations follow protocols for other cirrhotic conditions 1.

Critical Pitfalls to Avoid

• Delayed diagnosis leads to irreversible organ damage, particularly cardiac and hepatic 4, 7
• Do not wait for symptoms to initiate treatment—iron-overload cardiomyopathy is reversible only if treated before overt heart failure develops 7
• Avoid excessive phlebotomy that could cause anemia and worsen fatigue 3
• Do not discontinue maintenance therapy—lifelong treatment is mandatory as iron reaccumulates 2
• Remember that ferritin is an acute phase reactant; inflammatory conditions may falsely elevate levels 3

Emerging Therapies

Rusfertide, a hepcidin mimetic, showed promise in a 2023 phase 2 trial, with 94% of patients achieving phlebotomy independence during 24 weeks of treatment 8. However, this remains investigational and phlebotomy remains the established standard of care 1, 2.