Opportunistic Screening for Hereditary Hemochromatosis With Unenhanced CT: Determination of an Optimal Liver Attenuation Threshold

The purpose of this study was to assess whether a specific liver attenuation threshold for unenhanced CT allows both sensitive opportunistic detection of unsuspected hereditary hemochromatosis and low overall screening test-positive rates.We used a standard ROI placement method on unenhanced CT studies of 3357 consecutive adults (mean age, 57.0 years) with no symptoms of liver disease who underwent colorectal screening. Hepatic attenuation (in HU) was measured to assess test-positive rates at various liver attenuation thresholds. To assess sensitivity, unenhanced hepatic CT attenuation was also measured in 12 patients with hereditary hemochromatosis (mean age, 48.3 years), who were homozygous for the HFE C282Y mutation. All scans were obtained at 120 kV. Serum ferritin levels were recorded for the hereditary hemochromatosis cohort.Mean liver attenuation ± SD among screened adults was 59.4 ± 12.7 HU, compared with 78.7 ± 13.1 HU (range, 59-105 HU) in the hereditary hemochromatosis cohort (p0.001). Screening test-positive rates were 30.6% (n = 1028) at 65 HU, 8.2% (n = 275) at 70 HU, 1.2% (n = 39) at 75 HU, and 0.2% (n = 7) at 80 HU. Corresponding sensitivities for hereditary hemochromatosis at these thresholds were 83.3% (10/12) at 65, 70, and 75 HU; and 50.0% (6/12) at 80 HU. Serum ferritin levels were elevated in all patients with hereditary hemochromatosis (mean, 1678 ng/mL; range, 477-3991 ng/mL).An unenhanced CT liver attenuation threshold of 75 HU was sensitive (83.3%) for hereditary hemochromatosis while maintaining an acceptably low screening test-positive rate (1.2%). An unexplained liver attenuation of 75 HU or more on unenhanced CT should trigger appropriate laboratory investigation for iron overload; early intervention with phlebotomy can limit or prevent organ damage in patients with hemochromatosis.