Raised serum ferritin

• raised serum ferritin (SF)
  • only 10% of cases of elevated SF are due to iron overload - chronic alcohol consumption, metabolic syndrome, obesity, diabetes, malignancy, infection and inflammatory conditions explain 90% of causes of elevated SF
    • there is a well-established link between elevated SF, metabolic syndrome and fatty liver
    • liver disease is a cause of elevated SF
      • damaged hepatocytes leak ferritin into the serum
        • in liver disease, SF can be considered as another type of liver function test (LFT)
          
          
  • assessment of raised serum ferritin
    • repeat serum ferritin (SF)
      • if repeat SF > 1000 µg/L then specialist referral
      • if less than 1000 µg/L then exclude hereditary haemochromatosis
        • transferrin (TIBC)
        • genetic testing should be carried out in patients with symptoms and serum iron parameters suggestive of haemochromatosis
        • if the diagnosis of haemochromatosis is still uncertain (after blood analysis and genetic testing) consider
          • magnetic resonance imaging provides a quantitative imaging technique for the detection of iron in the liver
          • liver biopsy is an alternative if facilities for MRI is not available concentration of iron deposits can be measured
    • as well as exclusion of hereditary haemochromatosis, investigation of elevated serum ferritin involves identifying alcohol consumption, metabolic syndrome, obesity, diabetes, liver disease, malignancy, infection or inflammation as causative factors
      • conditions such as malignancy, infection and inflammatory conditions may all cause elevated SF
        • normal screening tests for C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and antinuclear antibody (ANA) can help exclude the presence of these conditions
      • suggested investigations for liver disease include:
        • liver function tests (LFTs)
        • inflammatory markers, such as C-reactive protein, erythrocyte sedimentation rate or plasma viscosity
        • hepatitis B surface antigen (HBsAg)
        • hepatitis C virus antibody (HCV-Ab)
        • antinuclear antibodies (ANA)
        • antimitochondrial antibodies (AMA)
        • anti-smooth muscle antibodies (SMA)
        • alpha-1 antitrypsin (AAT)
        • copper
        • caeruloplasmin
        • screen for metabolic syndrome, obesity, diabetes
        • assess alcohol intake
        • liver ultrasound scan. Abdominal ultrasonography may demonstrate an echogenic liver suggesting alcohol- or non-alcohol-related fatty liver disease. In such cases non-invasive fibrosis assessment is indicated using transient elastography (Fibroscan®)
  • elevations of SF in the range 300-1000 µg/L are common, and often reflect the presence of the previously listed conditions such as diabetes, obesity or chronic alcohol consumption
    • mild elevations below 1000 µg/L are 'tolerable' and in the absence of hereditary haemochromatosis, the risk of hepatic iron overload is exceedingly low
      
      
  • referral criteria from primary care
    • specialist review is mandatory if SF exceeds 1000 µg/L due to the increased risk of fibrosis and cirrhosis above this threshold
      • referral to a gastroenterologist, haematologist or physician with an interest in iron overload is appropriate if serum ferritin is >1000 µg/L or
        • if the cause of elevated serum ferritin is still unclear
          

Reference:

1. Cullis J et al. Investigation and management of a raised serum ferritin. British Journal of Haematology. Volume181, Issue3. May 2018. Pages 331-340