Objective: Hepatic iron overload is observed in many forms of chronic liver disease. Hereditary hemochromatosis (HH) results in hepatic iron overload and is associated with 2 missense mutations in the HFE gene. The aim of this study was to define the usefulness of the histological pattern of iron deposition in determining the probability of an iron-loaded patient having HFE-related iron overload.
Methods: This study assessed liver biopsies containing stainable iron from 103 patients with various liver diseases; clinical information included hepatic iron concentration and HFE genotype (C282Y, H63D). The biopsies were evaluated using a reproducible histological scoring system for iron deposition. Three separate components of histological iron deposition were recorded: 1) pattern (primarily hepatocellular with a zonal gradient, or reticuloendothelial without an obvious zonal gradient), 2) pattern score to denote the extent of iron within the acinus, and 3) quantitation grade of iron granules within affected hepatocytes.
Results: The predominantly hepatocellular pattern (HH pattern) was observed in 72 biopsies of which only 42 were from patients homozygous for the C282Y mutation, indicating that this pattern alone cannot be used as a surrogate marker for HH genotype. The predominantly reticuloendothelial pattern (non-HH pattern) was observed in the remaining 31 patients, none of whom was compound heterozygous or homozygous for the C282Y mutation (negative predictive value: 100%). Thus, the non-HH, reticuloendothelial pattern reliably predicts the absence of homozygosity for the C282Y mutation.
Conclusions: The use of histological evaluation for iron deposition is simple, assists in expanding information communicated from histopathologic observations, and may be clinically useful in determining the necessity of further evaluation of HFE genotype in subjects with histological evidence of hepatic iron overload.