Role of iron load on fibrogenesis in chronic hepatitis C.
OBJECTIVE
In chronic viral hepatitis, an enhanced iron load is related to lower response to interferon. Furthermore, iron, through the production of oxygen radicals, may stimulate hepatocyte necrosis and the activation of cells responsible for synthesis and deposition of extracellular matrix. We investigated the relationship between iron load, evaluated by serum assays, and liver fibrogenesis in chronic active viral hepatitis.


METHODS
Serum iron, ferritin, transferrin saturation and serum markers of hepatic fibrogenesis (Laminin and the amino-terminal peptide of procollagen III-NPIIIP-) were assayed in 102 patients (47 females, 55 males, mean age 42.48 years) affected by chronic hepatitis C virus and in 81 healthy controls (47 males, 34 females). In hepatitis C virus patients (studied before alpha-interferon treatment) a semiquantitative score for portal inflammation, necrosis and fibrosis was applied to liver biopsy.


RESULTS
Serum indices of iron load were higher in hepatitis C virus patients than in controls, and were higher in cirrhotic than in chronic hepatitis cases. Ferritin and serum iron were positively correlated with NPIIIP and laminin; moreover cases with ferritin levels over the normal limit for sex and age had higher levels of NPIIIP and laminin than cases with normal or poor iron status.


CONCLUSIONS
Our data suggest that even a mild increase of iron load stimulates hepatic fibrogenesis, probably adding oxygen free radical injury to the damage of viral infection.
Casaril
M
M
Istituto di Patologia Medica, Policlinico Borgo Roma, Universita di Verona, Italy.
Stanzial
A M
AM
Tognella
P
P
Pantalena
M
M
Capra
F
F
Colombari
R
R
Corrocher
R
R
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D016009:Chi-Square Distribution; D005260:Female; D005293:Ferritins / Q000097:blood / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007501:Iron / Q000097:blood / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D016014:Linear Models; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011348:Procollagen N-Endopeptidase / Q000378:metabolism; D011994:Recombinant Proteins; D018709:Statistics, Nonparametric; D014168:Transferrin / Q000378:metabolism
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007797:Laminin; D011994:Recombinant Proteins; D014168:Transferrin; D005293:Ferritins; D007501:Iron; D011348:Procollagen N-Endopeptidase