What is Hereditary Hemochromatosis (HH)?

From the Guidelines

Hemochromatosis should be managed with regular phlebotomy to reduce iron levels, with treatment targets of ferritin <50 µg/L during the induction phase and <100 µg/L during the maintenance phase, as recommended by the European Association for the Study of the Liver 1. The primary goal of treatment is to prevent complications such as cirrhosis, hepatocellular carcinoma, diabetes, arthropathy, and other end-organ damage. Key aspects of management include:

• Regular phlebotomy to reduce iron levels, with initial weekly sessions removing about 500 ml of blood until ferritin levels drop below 50 ng/mL and transferrin saturation falls below 50% 1
• Maintenance therapy involving 2-4 phlebotomies per year to keep ferritin levels <100 µg/L
• Iron chelation therapy with medications like deferasirox or deferoxamine for those who cannot tolerate phlebotomy
• Avoidance of iron supplements, vitamin C supplements with meals, and limited alcohol consumption
• Regular monitoring of iron studies (ferritin, transferrin saturation) every 3-6 months
• Family screening due to the genetic nature of the disorder, usually caused by mutations in the HFE gene Early diagnosis and treatment are crucial, as hemochromatosis is often asymptomatic until significant organ damage has occurred. The diagnosis of hemochromatosis can be made based on serum iron parameters, including transferrin saturation and ferritin levels, as well as the presence of hepatic iron overload on MRI or liver biopsy in patients with other HFE genotypes 1. It is essential to assess the stage of liver fibrosis and other end-organ damage at diagnosis, as this determines disease management, and patients with advanced fibrosis should be included in a screening program for hepatocellular carcinoma 1.

From the Research

Definition and Causes of Hemochromatosis

• Hemochromatosis is defined as systemic iron overload of genetic origin, caused by a reduction in the concentration of the iron regulatory hormone hepcidin, or a reduction in hepcidin-ferroportin binding 2.
• The most common form of haemochromatosis is due to homozygous mutations (specifically, the C282Y mutation) in HFE, which encodes hereditary haemochromatosis protein 2.
• Non-HFE forms of haemochromatosis due to mutations in HAMP, HJV or TFR2 are much rarer 2.

Diagnosis and Treatment of Hemochromatosis

• Diagnosis is noninvasive and includes clinical examination, assessment of plasma iron parameters, imaging and genetic testing 2.
• The mainstay therapy is phlebotomy, although iron chelation can be used in some patients 2.
• Erythrocytapheresis is a new therapeutic modality that can remove up to three times more red blood cells per single procedure and could thus have a clinical and economic benefit 3.
• A randomized trial showed that erythrocytapheresis is highly effective treatment to reduce iron overload and from a societal perspective might potentially also be a cost-saving therapy 3.

Clinical Manifestations and Complications of Hemochromatosis

• The deposition of excess iron into parenchymal cells leads to cellular dysfunction and the clinical manifestations of the disease, including liver, pancreas, joints, heart, skin, and pituitary gland involvement 4.
• Individuals with hereditary hemochromatosis have an increased risk of hepatocellular carcinoma and colorectal and breast cancers 4.
• Phlebotomy is the mainstay of treatment and can help improve heart function, reduce abnormal skin pigmentation, and lessen the risk of liver complications 4.

Comparison of Phlebotomy and Erythrocytapheresis

• A study compared the effect of erythrocytapheresis on the course of iron parameters, with special focus on serum hepcidin, and found that decreases in serum ferritin over time were similar for both treatments but more pronounced using erythrocytapheresis when expressed per treatment procedure 5.
• Another study found that erythrocytapheresis leads to a more pronounced decrease in serum ferritin per treatment procedure, without a larger decrease in serum hepcidin, which may be clinically relevant and may prevent an increase in intestinal iron uptake and an ensuing vicious circle of more frequent treatment procedures 5.