Iron deposition and progression of disease in chronic hepatitis C. Role of interface hepatitis, portal inflammation, and HFE missense mutations.
Histologically detectable iron (HDI) and HFE mutations were searched for in liver biopsy specimens from 58 Italian patients with chronic hepatitis C, and morphologic features were compared to examine their reciprocal relation and their contribution to disease progression. HDI was evident in 48% of cases with features of nonhemochromatosis iron overload. Total, sinusoidal, and portal HDI increased with stage; grade was related to all iron scores because of the contribution of portal inflammation and interface hepatitis. HFE mutations were seen in 47% of patients with chronic hepatitis C and in 28% of control subjects; they were related to stage and the His63Asp mutation to portal HDI. On multivariate analysis, grade but not stage or HFE mutations was associated with HDI in all sites. Interface hepatitis with its sequelae (sinusoidal capillarization and microshunting) represents a major factor in iron deposition in chronic hepatitis C and justifies the features of HDI. HFE mutations are not responsible for HDI deposition but could favor the progression of virus-induced damage independently from interference with iron metabolism.
Pirisi
M
M
Department of Clinical and Experimental Pathology, University of Udine, Italy.
Scott
C A
CA
Avellini
C
C
Toniutto
P
P
Fabris
C
C
Soardo
G
G
Beltrami
C A
CA
Bartoli
E
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000032:analysis; D018450:Disease Progression; D005260:Female; D006680:HLA Antigens / Q000235:genetics*; D006432:Hemochromatosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000071020:Hemochromatosis Protein; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D020125:Mutation, Missense; D012150:Polymorphism, Restriction Fragment Length; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000914:Antibodies, Viral; C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D012367:RNA, Viral; D007501:Iron