The diversity of liver diseases among outpatient referrals for elevated serum ferritin

BACKGROUND: The aim of the present study was to examine the diversity of liver diseases in outpatients referred because of elevated serum ferritin. METHODS: A retrospective review was performed of outpatient referrals for serum ferritin elevations made to a tertiary care centre liver clinic between 1999 and 2005. Information regarding serum ferritin, transferrin saturation, liver biopsy, liver iron concentration and final diagnosis was extracted. Patients were stratified into two groups based on ferritin concentration: ferritin concentration 300 mu g/L to 1000 mu g/L, and ferritin concentration greater than 1000 mu g/L. RESULTS: A total of 482 charts were reviewed, of which 119 (25%) had ferritin concentrations greater than 1000 mu g/L. HFE-linked hemochromatosis, nonalcoholic steatohepatitis and alcohol-related liver disease were the top three diagnoses. HFE-linked hemochromatosis accounted for 28% to 42% of the diagnoses in all subgroups. The percentage of patients diagnosed with HFE-linked hemochromatosis was similar in the ferritin 300 mu g/L to 1000 mu g/L and the ferritin greater than 1000 mu g/L groups (P=0.067). Among patients with ferritin greater than 1000 mu g/L, 63% underwent a liver biopsy. Of those with all elevated liver iron concentration (greater than 35 mu mol/g dry weight), 71% had a transferrin saturation greater than 50% (88% of C282Y homozygotes and 43% of non-C282Y homozygotes). In non-C282Y homoygotes with an elevated serum ferritin concentration greater than 1000 mu g/L, 64% did not have iron overload on liver biopsy. CONCLUSION: HFE-linked hemochromatosis accounted for less than one-half of the diagnoses in an outpatient population referred for elevated ferritin, suggesting a need to search further for an alternate cause.