From the Guidelines
Ferritin levels should be the next serum test, in addition to hepatitis B (HBV) and C (HCV) testing, for a patient with mildly elevated transaminases to consider Alpha-1 antitrypsin (A1AT), antinuclear antibody (ANA), ceruloplasmin, protein electrophoresis, or ferritin levels.
Rationale
- The European Association for the Study of the Liver (EASL) recommends assessing serum iron parameters, including transferrin saturation and serum ferritin, as the first step in testing for haemochromatosis 1.
- Elevated ferritin and transferrin saturation are biochemical findings that indicate haemochromatosis with iron overload, and patients with abnormal liver blood tests should have these parameters determined as part of their workup 1.
- The EASL also recommends searching for common causes of hyperferritinemia, such as chronic alcohol consumption, inflammation, cell necrosis, tumors, and non-alcoholic fatty liver disease (NAFLD), before genetic tests are carried out 1.
- Mildly elevated serum ferritin is common in patients with NAFLD, but elevated serum ferritin and transferrin saturation in patients with suspected NAFLD should lead to testing for genetic hemochromatosis 1.
Key Points
- Ferritin is a marker of iron overload, but also an acute phase reactant, tumor marker, and indicator of increased angiogenesis 1.
- Transferrin saturation shows significant variability, which limits its usefulness, and blood samples for its measurement should be taken in the morning, but fasting does not improve diagnostic utility 1.
- Patients with a positive first-degree family history of haemochromatosis should be tested by HFE genotyping with appropriate genetic counseling 1.
From the Research
Evaluation of Mildly Elevated Transaminases
The initial evaluation of mildly elevated transaminases should include an assessment for metabolic syndrome and insulin resistance, as well as testing for hepatitis B and C 2, 3.
Next Serum Test to Consider
In addition to hepatitis B (HBV) and C (HCV) testing, the next serum test to consider for a patient with mildly elevated transaminases would be:
- Ferritin levels, as part of the initial evaluation to assess for hereditary hemochromatosis, a common cause of elevated transaminase levels 2, 3
- Other tests such as alpha-1 antitrypsin (A1AT), antinuclear antibody (ANA), ceruloplasmin, and protein electrophoresis may be considered if the initial evaluation is unremarkable and the elevation persists 2, 3, 4
Rationale for Test Selection
The selection of the next serum test is based on the prevalence of diseases that cause asymptomatic transaminase elevations, with a focus on common and serious liver diseases 2, 3.
- Ferritin levels are a key test in the initial evaluation, as hereditary hemochromatosis is a common cause of elevated transaminase levels 2, 3
- Alpha-1 antitrypsin deficiency is a rare cause of liver disease, and testing for A1AT may be considered if other causes are ruled out 5, 4
- Antinuclear antibody (ANA) testing may be considered if autoimmune hepatitis is suspected, although this is a less common cause of elevated transaminase levels 3, 4
- Ceruloplasmin and protein electrophoresis may be considered if Wilson's disease or other rare causes of liver disease are suspected 3, 4