Histological evaluation of iron in liver biopsies: Relationship to HFE mutations

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 thi s study was to define the usefulness of the histological pattern of iron de position in determining the probability of an iron-loaded patient having HF E-related iron overload. METHODS: This study assessed liver biopsies containing stainable iron from 103 patients with various liver diseases; clinical information included hep atic iron concentration and HFE genotype (C282Y, H63D). The biopsies were e valuated using a reproducible histological scoring system for iron depositi on. Three separate components of histological iron deposition were recorded : 1) pattern (primarily hepatocellular with a zonal gradient, or reticuloen dothelial without an obvious zonal gradient), 2) pattern score to denote th e extent of iron within the acinus, and 3) quantitation grade of iron granu les 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 C282 Y mutation, indicating that this pattern alone cannot be used as a surrogat e marker for HH genotype. The predominantly reticuloendothelial pattern (no n-HH pattern) was observed in the remaining 31 patients, none of whom was c ompound heterozygous or homozygous for the C282Y mutation (negative predict ive value: 100%). Thus, the non-HH, reticuloendothelial pattern reliably pr edicts the absence of homozygosity for the C282Y mutation. CONCLUSIONS: The use of histological evaluation for iron deposition is simp le, assists in expanding information communicated from histopathologic obse rvations, and may be clinically useful in determining the necessity of furt her evaluation of HFE genotype in subjects with histological evidence of he patic iron overload. (C) 2000 by Am. Coll. of Gastroenterology).