What is the treatment for hepatic iron overload?

Treatment of Hepatic Iron Overload

Therapeutic phlebotomy is the first-line treatment for hepatic iron overload, with a target ferritin level of 50-100 μg/L for both initial and maintenance therapy. 1

Treatment Algorithm Based on Etiology

Primary Iron Overload (Hereditary Hemochromatosis)

1. Initial Treatment Phase:

   • Weekly phlebotomy (removal of 500 mL blood) as tolerated 1
   • Check hematocrit/hemoglobin prior to each phlebotomy
   • Allow hematocrit/hemoglobin to fall by no more than 20% of prior level
   • Check serum ferritin level every 10-12 phlebotomies
   • Continue until serum ferritin reaches 50-100 μg/L

2. Maintenance Phase:

   • Regular phlebotomy at intervals to maintain serum ferritin between 50-100 μg/L 1
   • Typically requires 3-4 phlebotomies per year

3. Important Precautions:

   • Avoid vitamin C supplements (can increase iron absorption)
   • Avoid iron supplements
   • Avoid raw shellfish (risk of Vibrio vulnificus infection) 1

Secondary Iron Overload

Treatment varies based on underlying cause:

1. Secondary Iron Overload with Anemia/Ineffective Erythropoiesis:

   • Iron chelation therapy is the treatment of choice 1
   • Options include:
     • Deferoxamine (Desferal): 40 mg/kg/day via subcutaneous infusion for 8-12 hours, 5-7 nights weekly
     • Deferasirox (Exjade): Oral administration (note: carries black box warnings for renal failure, hepatic failure, and GI hemorrhage) 2
   • Target: Reduce hepatic iron concentration (HIC) to <15,000 μg/g dry weight 1
   • Monitor therapy with:
     • Serum ferritin (less reliable than in hemochromatosis)
     • Consider follow-up liver biopsy to assess iron removal 1
     • 24-hour urinary iron excretion monitoring

2. Secondary Iron Overload with Normal Erythropoiesis:

   • Phlebotomy using similar regimen as for hemochromatosis 1
   • Examples where phlebotomy is beneficial:
     • Porphyria cutanea tarda (PCT)
     • Non-alcoholic fatty liver disease (NAFLD) - improves insulin resistance and ALT levels 1

3. Special Considerations:

   • Chronic hepatitis C: Phlebotomy not recommended for mild iron overload (HIC <2500 μg/g dry weight) 1
   • Alcoholic liver disease: No published evidence supporting phlebotomy benefit 1
   • Post-hematopoietic stem cell transplantation: Phlebotomy recommended to prevent progression of liver fibrosis 3

Advanced Disease Management

• Advanced cirrhosis is not reversed with iron removal 1
• Decompensated liver disease may require orthotopic liver transplantation (OLT) 1
• Iron depletion before OLT is critical to reduce perioperative complications 1

Monitoring and Follow-up

• Regular monitoring of serum ferritin levels
• For primary hemochromatosis: Ferritin reliably reflects iron burden during therapy 1
• For secondary iron overload: Ferritin may be misleading; consider:
  • Repeat liver biopsy 1
  • MRI techniques for non-invasive iron quantification

Clinical Outcomes

• Phlebotomy improves liver function tests, with significant decreases in ALT levels 4
• Iron depletion can prevent progression of liver fibrosis 5
• Initial serum ferritin strongly correlates with number of phlebotomies needed to reach target 4
• Excessive iron accumulation is an important predictor of liver failure, making iron removal a critical therapeutic target 5

Common Pitfalls and Caveats

• Vitamin C supplements should be strictly avoided as they increase iron absorption 1
• Patient compliance with long-term phlebotomy can be challenging; providing an estimated endpoint may improve adherence 4
• In patients with beta thalassemia post-transplant, HSCT alone cannot reduce liver iron overload and liver fibrosis may progress without specific iron-reduction therapy 3
• Iron overload can induce hepatic ferroptosis and insulin resistance, which may be improved with iron chelation 6