From the Guidelines
Elevated iron levels in the blood, known as iron overload or hemochromatosis, can occur due to several causes, with hereditary hemochromatosis being the most common cause, as stated in the EASL clinical practice guidelines on haemochromatosis 1. The causes of elevated iron levels can be categorized into genetic and acquired factors. Genetic factors include hereditary hemochromatosis, which is an autosomal recessive disorder that increases iron absorption from food. Acquired factors include:
- Multiple blood transfusions, which directly add iron to the bloodstream
- Certain types of anemia, such as thalassemia
- Chronic liver diseases, such as alcoholic liver disease and hepatitis C
- Excessive iron supplementation or consumption
- Rare conditions like African iron overload, which is caused by dietary iron overload from consuming food or beverages prepared in iron cookware
- Certain medications that contain iron
According to the EASL clinical practice guidelines on haemochromatosis 1, the diagnosis of hemochromatosis should not be based on C282Y homozygosity alone, but requires evidence of increased iron stores. The guidelines also recommend that patients with increased liver iron evident on liver biopsy or MRI should be clinically assessed and biochemically tested for haemochromatosis.
The clinical manifestations of hemochromatosis are dependent on disease stage and are determined by the degree of iron overload and the severity of organ damage, as stated in the EASL clinical practice guidelines on haemochromatosis 1. Common symptoms of hemochromatosis include fatigue, joint pain, abdominal pain, and skin darkening. Treatment typically involves regular blood removal (phlebotomy) to reduce iron levels, along with addressing the underlying cause when possible.
In patients with non-alcoholic fatty liver disease (NAFLD), high ferritin levels are common, and iron depletion may improve insulin resistance, as stated in the EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease 1. Hepatic iron accumulation is associated with insulin resistance, and iron depletion improves insulin resistance.
In patients with chronic kidney disease, the distinction between absolute and functional iron deficiency is crucial to understanding what constitutes adequate transferrin saturation and serum ferritin levels, as stated in the NKF-K/DOQI clinical practice guidelines for anemia of chronic kidney disease 1. A TSAT of < 20% and serum ferritin levels < 100 ng/mL are indicative of absolute iron deficiency.
From the Research
Causes of Elevated Iron Levels
Elevated iron levels can be caused by various factors, including:
- Genetic disorders such as hereditary hemochromatosis, which is characterized by an inappropriate increase in intestinal iron absorption due to reduced expression of the iron regulatory protein, hepcidin 2
- Iron overload, which can be caused by altered hepcidin levels 3
- Increased intestinal iron uptake, which can be caused by lowering of hepcidin as a result of intensive bloodletting 4
Risk Factors for Elevated Iron Levels
Certain risk factors can contribute to the development of elevated iron levels, including:
- Obesity, which can compound the risk of liver injury in people with hereditary (HFE) haemochromatosis 2
- Alcohol consumption, which can also increase the risk of liver injury in people with hereditary (HFE) haemochromatosis 2
Diagnosis and Treatment of Elevated Iron Levels
Elevated iron levels can be diagnosed through laboratory testing for serum ferritin and transferrin saturation, and genetic testing for the HFE mutation can be performed in patients with elevated iron indices and a suspicion for hemochromatosis or liver disease 3. Treatment for elevated iron levels typically involves phlebotomy, which is a relatively safe and efficacious therapy when offered before cirrhosis develops 5. Alternative treatments, such as erythrocytapheresis, may also be effective in reducing iron overload and improving transferrin saturation levels 6, 4