Hepatic iron overload in patients with chronic viral hepatitis: role of HFE gene mutations.
Mild to moderate hepatic iron overload is frequent in patients with chronic viral hepatitis (CH). We evaluated the role of hemochromatosis (HFE) gene mutations and other acquired factors in the development of iron overload in these patients. We studied 110 patients with chronic B or C viral hepatitis (31 women, 79 men), including 20 with cirrhosis, and 139 controls. Hepatic iron was evaluated by semiquantitative analysis in all the patients, and hepatic iron concentration (HIC) was determined in 97 of them (26 women, 71 men). C282Y and H63D mutations were sought in all the subjects by a polymerase chain reaction-restriction assay. The frequency of HFE genotypes and alleles did not differ in patients and controls. No relation was detected between hepatic iron stores and HFE gene mutations in women. In men, all C282Y heterozygotes had iron overload, and the H63D mutation was significantly more frequent in patients with more marked hepatic siderosis than in those with mild or no siderosis (P = .0039) and in controls (P = .0008). Heavy alcohol intake and hepatic cirrhosis were also associated with increased hepatic iron stores in the men. In the 71 men in whom HIC was measured, multiple regression analysis showed that this variable was related independently only to alcohol intake and HFE gene mutations. We suggest that in patients with CH, iron accumulates in the liver as the result of an interplay between genetic and acquired factors, and that increased liver iron stores may influence progression toward liver fibrosis.
Istituto di Scienze Biomediche, Università di Milano, Divisione di Medicina I, Ospedale S. Gerardo, Monza, Italy. Alberto.Piperno@unimi.it
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Piperno
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Vergani
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Malosio
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Parma
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Fossati
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Ricci
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Bovo
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Boari
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Mancia
D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D005260:Female; D005293:Ferritins / Q000097:blood; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006432:Hemochromatosis / Q000235:genetics; D000071020:Hemochromatosis Protein; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D008285:Major Histocompatibility Complex; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics; D012806:Siderosis / Q000150:complications / Q000378:metabolism*; D013054:Spectrophotometry, Atomic; D014168:Transferrin / Q000378:metabolism
C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin; D005293:Ferritins; D007501:Iron