Causes of hyperferritinaemia

We read the recent editorial on hyperferritinaemia ¹ with interest. The editorial discussed the aetiology of hyperferritinaemia in detail. Modest elevations in ferritin concentration (<1000 µg/L) are commonly encountered in routine clinical practice. Unexplained hyperferritinaemia can often lead to invasive and expensive diagnostic testing.

We undertook an audit of the causes of hyperferritinaemia. After seeking approval from the trust audit department, retrospective data collection was done during the period 1 December 1994–4 September 2011. All elevated ferritin results (>290 µg/L in women and >332 µg/L in men) were included. Patients with positive HFE mutations, inpatients, family studies or known family history of hereditary haemochromatosis were exclusion criteria. A detailed case-note evaluation was undertaken to assess the clinical course and follow-on investigations arranged to evaluate the causes of hyperferritinaemia. In a total of 541 patients identified in the specified period, application of exclusion criteria yielded 473 patients (men 350, women 123; median age 57 y, range 16–95 y). The median ferritin concentration was 587 µg/L (range 240–8250 µg/L). The median transferrin saturation was 46% (range 16.5113.6%). Causes of increased ferritin concentrations were ascribed to alcoholic liver disease (n = 210, 45%), non-alcoholic steatohepatosis (NASH) (n = 66, 14%), malignancy (n = 52, 11%), chronic liver disease (n = 25, 5%), chronic systemic disorders including chronic renal failure and congestive cardiac failure (n = 13, 3%), chronic inflammation (n = 9, 2%), haemosiderosis secondary to multiple transfusions (n = 5, 1%), ferrous sulphate supplementation (n = 4, 1.2%) and anorexia (n = 2, 0.4%). No major aetiology for elevated ferritin concentrations were found in 87 patients (18.4%).

Ferritin production and as a consequence plasma ferritin concentrations are increased in the absence of iron overload in certain liver diseases (including chronic viral hepatitis, alcoholic liver disease and NASH) and in chronic inflammatory disorders and malignancy. ^2–4 Our audit identified alcoholic liver disease as the most common cause of modest elevation in ferritin concentrations. NASH and malignancy were other significant aetiologies identified. Alcohol history and the presence of other liver diseases should be evaluated as the common causes for abnormal iron handling by the liver, before considering expensive (HFE mutation screening, magnetic resonance imaging liver) and invasive investigations (liver biopsy).