How to manage a patient with haemochromatosis, elevated ferritin (iron storage protein) levels, early cirrhosis on liver ultrasound, and negative genetic testing for hereditary haemochromatosis (HH)?

From the Guidelines

Therapeutic phlebotomy should be initiated immediately to reduce iron overload, with a target serum ferritin level of 50-100 μg/L, as recommended by the most recent guidelines 1. The patient's elevated ferritin level of 700 μg/L and early cirrhosis on liver ultrasound indicate significant iron overload, which requires prompt treatment to prevent further organ damage. The negative genetic testing for hereditary hemochromatosis (HH) suggests that the patient may have a non-HFE form of hemochromatosis or another underlying condition contributing to iron overload. Key aspects of management include:

• Therapeutic phlebotomy: initially performed weekly to remove 500ml of blood (approximately 200-250mg of iron) until ferritin levels decrease to 50-100 μg/L, as recommended by the EASL clinical practice guidelines on haemochromatosis 1.
• Maintenance phlebotomy: continue every 2-4 months with regular monitoring of ferritin levels to maintain the target range of 50-100 μg/L, as suggested by the guidelines 1.
• Dietary modifications: limiting alcohol consumption, avoiding iron supplements and vitamin C with meals, and reducing consumption of red meat, as recommended by the guidelines 1.
• Investigation of secondary causes: including alcohol use disorder, metabolic syndrome, viral hepatitis, and other liver diseases, as suggested by the guidelines 1.
• Regular monitoring: ferritin levels checked every 3 months during initial treatment and liver function tests performed biannually, as recommended by the guidelines 1.
• Hepatocellular carcinoma screening: ultrasound every 6 months due to cirrhosis, as recommended by the guidelines 1.
• Screening for complications: diabetes (annual HbA1c), cardiac involvement (echocardiogram), and hypogonadism (hormone levels), as suggested by the guidelines 1. The patient's treatment plan should be individualized based on their specific needs and response to therapy, with regular monitoring and adjustments as necessary, as recommended by the guidelines 1.

From the Research

Management of Haemochromatosis

• The patient has haemochromatosis with elevated ferritin levels (700), early cirrhosis on liver ultrasound, and negative genetic testing for hereditary haemochromatosis (HH) 2, 3.
• The first-line therapy for haemochromatosis involves regular and life-long phlebotomy to remove iron from the blood, which improves the prognosis and may prevent the development of end-stage liver disease such as cirrhosis and hepatocellular carcinoma 2.
• Phlebotomy therapy has been shown to improve hepatic fibrosis in patients with haemochromatosis 3.

Diagnostic Considerations

• Diagnosis of haemochromatosis is initially suspected by increased serum levels of ferritin, a non-specific parameter also elevated in inflammatory diseases that must be excluded to be on the safer diagnostic side 2.
• A serum ferritin level less than 1000 microg/L was predictive of absence of cirrhosis 4.
• Genetic testing for haemochromatosis, including HFE testing for the two main mutations (p.Cys282Tyr and p.His63Asp), should be performed in all patients with primary iron overload and unexplained increased transferrin saturation and/or serum ferritin values 5.

Monitoring and Treatment

• Patients with haemochromatosis should be monitored for iron deficiency due to excessive therapeutic phlebotomy, which can lead to symptoms and signs of iron deficiency 6.
• Symptomatic iron deficiency in haemochromatosis patients may be treated safely with a brief course of ferrous sulfate 6.
• The frequency of phlebotomies should be adjusted based on parameters of body iron status to prevent iron deficiency 6.