Liver pathology in genetic hemochromatosis: a review of 135 homozygous cases and their bioclinical correlations.
Liver pathology was assessed in 135 patients with well-defined genetic hemochromatosis ranging from mild disease to severe overload. Three lesions were clearly linked to iron-overload intensity--scarce sidero-necrosis, mild inflammation, and progressive fibrosis. Iron-free foci made of typical or dysplastic hepatocytes were found in 7.4% of the cases. An original grading allowed a reliable quantification of iron and the study of cellular and lobular distribution of iron, which permitted (a) the accurate identification of a decreasing iron gradient in hepatocytes from zone 1 to zone 3 in all cases, (b) the definition of a threshold hepatocytic/mesenchymal iron ratio related to the appearance of sidero-necrosis and to the development of fibrosis, and (c) demonstration that non-iron-related factors (mainly alcoholism) could shift iron from hepatocytes to sinusoidal cells without an increase in the total liver iron amount. This study provides a dynamic view of the iron overload process and suggests that sidero-necrosis and progressive sinusoidal iron overload play a role in the development of fibrosis in human genetic hemochromatosis.
Deugnier
Y M
YM
Clinique des Maladies du Foie, Inserm U49, Rennes, France.
Loréal
O
O
Turlin
B
B
Guyader
D
D
Jouanolle
H
H
Moirand
R
R
Jacquelinet
C
C
Brissot
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006432:Hemochromatosis / Q000235:genetics / Q000473:pathology*; D006720:Homozygote; D006801:Humans; D007501:Iron / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000473:pathology*; D008297:Male; D008875:Middle Aged
D007501:Iron