Intrahepatic iron variation may greatly affect the hepatic iron index

The quantitative hepatic iron index is considered the gold standard for the diagnosis of primary hemochromatosis. While intrahepatic variability in the amount of stainable iron in histologic sections of liver is well known, the quantitative variability has not been addressed. Eight native livers removed at transplantation for cirrhosis associated with hepatitis C were studied. Iron-stained sections from multiple different areas of each liver were examined, and small areas were graded for iron content on a scale of 0 to 4. The fragments of liver corresponding to these were then cut out of the corresponding section of the paraffin block and sent for iron quantitation. We found that marked quantitative heterogeneity in iron content (>260%) can exist in a given liver, leading, in two cases, to false positive results for the diagnosis of hemochromatosis. In addition, it was found that quantitative iron content did indeed linearly correlate with histologic grading. Thus, intrahepatic variation in iron content in a given liver is yet another reason to interpret the hepatic iron index with caution.