Methods to determine hepatic iron content
- Maria Isabel Fiel, MD, FAASLD
Maria Isabel Fiel, MD, FAASLD
- Professor of Pathology
- Icahn School of Medicine at Mount Sinai
Hereditary hemochromatosis, hematopoietic stem cell transplantation, myelodysplastic syndrome, chronic liver disease, dialysis, and blood transfusions for sickle cell disease and thalassemia can all cause iron to accumulate in the liver [1,2]. Iron overload is not just limited to the liver, but can also accumulate in other organs, particularly the heart and endocrine organs, resulting in end-organ damage and dysfunction . Hemosiderosis is a commonly used term for iron accumulation in tissues from any cause. (See "Approach to the patient with suspected iron overload".)
Excess oxygen radicals and injury from tissue peroxidation are the main reasons why iron overload causes tissue damage [1,4]. Reducing the degree of iron overload is therefore paramount for most of these diseases to achieve successful treatment. Assessment of total body iron stores can be used to tailor titration of chelation therapy or phlebotomy in an attempt to reduce iron overload and its attendant complications . Phlebotomy has been shown to slow the progression to cirrhosis in hereditary hemochromatosis, and it also reduces the risk of developing hepatocellular carcinoma . The complications of fibrosis and cirrhosis developing in patients increase when there is significant iron overload, which is defined as hepatic iron concentration (HIC) greater than three times the upper limit of normal (greater than 90 micromol/g dry weight). Liver fibrosis may be reversible with phlebotomy therapy .
In the past, the diagnosis for hereditary hemochromatosis was based on results of liver biopsy specimens and hepatic iron content and distribution . Since the discovery of the HFE gene mutation (substitution by tyrosine for cysteine at amino acid 282; C282Y) and two other genetic mutations (aspartate for histidine [H63D] and cysteine for serine [S65C]), the diagnosis of hereditary hemochromatosis has become more straightforward . Tests for the HFE gene are performed when serum ferritin and transferrin saturation are elevated. However, a small number of individuals with hereditary hemochromatosis may be missed with these genetic tests . Additionally, phenotypic penetrance in hereditary hemochromatosis is variable with regard to the degree of iron overload and the risk of liver disease, fibrosis, and cirrhosis . As a result, a positive genetic test does not ensure that iron overload had developed. (See "Clinical manifestations and diagnosis of hereditary hemochromatosis", section on 'Making the diagnosis of HH'.)
Determination of the HIC is the most definitive proof of iron overload. It can be used to estimate the total iron burden and the approximate amount of phlebotomy required for a patient with iron overload [1,9-11]. The HIC can also detect mild iron overload, which may be missed with less sensitive modalities . An elevated serum ferritin level alone is often not adequate for estimating total iron burden, particularly if coexisting inflammation is present. The hepatic iron index is calculated based on the HIC and in the past was used to make a diagnosis of hereditary hemochromatosis; however, most patients can now be diagnosed by genetic testing .
This topic will review the tests that can be done to determine hepatic iron content, with a focus on the HIC. The approach to a patient with suspected iron overload and the diagnosis of hereditary hemochromatosis are discussed separately. (See "Approach to the patient with suspected iron overload" and "Clinical manifestations and diagnosis of hereditary hemochromatosis".)
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