What is the treatment for hyperferritinemia?

Treatment of Hyperferritinemia

The treatment of hyperferritinemia should be directed at the underlying cause, with therapeutic phlebotomy being the first-line treatment for iron overload conditions such as hemochromatosis, while addressing the primary disease in secondary causes of hyperferritinemia. 1

Diagnostic Approach Before Treatment

Before initiating treatment, it's essential to determine the cause of hyperferritinemia:

• First, evaluate for common causes of hyperferritinemia without significant iron overload (>90% of outpatient cases): chronic alcohol consumption, inflammation (check CRP), cell necrosis (check AST, ALT, CK), tumors, non-alcoholic fatty liver disease (NAFLD), and metabolic syndrome 1

• Measure transferrin saturation alongside ferritin - if transferrin saturation is increased (>45% in females, >50% in males), consider hereditary hemochromatosis and perform genetic testing for HFE mutations (C282Y and H63D) 1

• If hyperferritinemia is very high (>7000-10,000 μg/L), consider hemophagocytic lymphohistiocytosis (HLH), especially when accompanied by other clinical features like fever, splenomegaly, and cytopenias 1

• Assess liver iron concentration using MRI (preferred non-invasive method) or liver biopsy (in selected cases) to confirm iron overload 2, 3

Treatment Based on Etiology

1. Hereditary Hemochromatosis (HFE-HC)

• Therapeutic phlebotomy is the mainstay of treatment - remove 500 mL of blood weekly or biweekly until target ferritin level is reached 1

• Check hemoglobin/hematocrit prior to each phlebotomy; allow it to fall by no more than 20% of prior level 1

• Monitor serum ferritin every 10-12 phlebotomies during initial treatment 1

• Target ferritin level: 50-100 μg/L 1

• After reaching target, continue maintenance phlebotomy at intervals to maintain ferritin between 50-100 μg/L 1

• If hemoglobin <12 g/dL, decrease frequency of phlebotomy; if <11 g/dL, discontinue phlebotomy and reassess 1

2. Secondary Iron Overload

• For transfusional iron overload or dyserythropoietic conditions where phlebotomy isn't feasible:
  • Iron chelation therapy with deferasirox (oral) or deferoxamine (parenteral) 1, 4
  • Monitor for adverse effects, particularly renal function, hepatic function, and GI symptoms 4
  • Deferasirox is contraindicated in patients with eGFR <40 mL/min/1.73m² 4

3. Inflammatory Conditions (including Adult-Onset Still's Disease)

• Treatment should target the underlying inflammatory condition rather than the hyperferritinemia itself 1
• Phlebotomy is not indicated when hyperferritinemia is due to inflammation without iron overload 5

4. Non-Alcoholic Fatty Liver Disease (NAFLD)

• In NAFLD with mild iron accumulation (dysmetabolic iron overload syndrome), lifestyle modifications are the primary treatment 5
• Phlebotomy may be considered in NAFLD with confirmed hepatic iron overload but is not recommended for hyperferritinemia due to inflammation alone 5

Dietary and Lifestyle Recommendations

• Dietary modifications should not substitute for appropriate iron removal therapy 1
• Avoid iron supplementation and iron-fortified foods 1
• Limit red meat consumption 1
• Avoid vitamin C supplements, especially before iron depletion, as they enhance iron absorption 1
• Restrict alcohol intake during iron depletion; patients with liver abnormalities should consume very little alcohol; those with cirrhosis should abstain completely 1
• Patients with hemochromatosis should avoid direct handling and consumption of raw shellfish due to risk of Vibrio vulnificus infection 1

Monitoring During Treatment

• During induction phase of phlebotomy: monitor ferritin monthly or after every 4th phlebotomy 1
• When ferritin decreases below 200 μg/L, check levels every 1-2 phlebotomy sessions 1
• During maintenance phase: monitor ferritin every 6 months 1
• Investigate unexpected changes in ferritin or transferrin saturation levels 1
• Consider monitoring folate and cobalamin levels in patients requiring numerous phlebotomies 1

Special Considerations

• Liver biopsy should be considered in C282Y homozygous patients with serum ferritin >1000 μg/L, elevated AST, hepatomegaly, or age >40 years 1
• In patients with end-stage liver disease due to hemochromatosis, liver transplantation may be necessary 1
• Family screening is recommended for siblings of patients with HFE-related hemochromatosis 1