A study of some hepatic immunological markers, iron load and virus genotype in chronic hepatitis C.
OBJECTIVE
Host factors that may influence progression of hepatitis C infection to chronic hepatitis include T-cell responses and iron accumulation. We evaluated the hepatic expression of immunological markers relevant for a cytotoxic response in relation to viral and HFE genotype.


METHODS
Frozen liver biopsies were obtained at diagnosis from 28 HFE genotyped patients. Sections stained for CD8, MHC-I, beta(2)m, HFE and CD68 were analyzed blind by morphometry. Response to therapy was available in 12 cases.


RESULTS
A negative correlation was found between the number of CD8(+) cells and fibrosis. CD8(+) cells localized as clusters in portal tracts and sinusoids and were seen interacting with MHC-I positive lining cells. MHC-I and beta(2)m were expressed mainly in the endothelial and Kupffer cells. HFE was expressed in most, but not all, round and dendritic CD68(+) cells. Patients with virus genotype 3a had higher hepatic MHC-I and HFE expression, and a better-sustained response to IFN therapy than other patients.


CONCLUSIONS
In chronic hepatitis C virus infection MHC-I expression in the liver seems to relate to viral-genotype. In addition, the expression of MHC-I molecules by Kupffer cells places them as probable important players in the host response to HCV.
Cardoso
Elsa Maria
EM
Iron Genes and the Immune System, Institute for Molecular and Cell Biology, 4150-180 Porto, Portugal.
Duarte
Miguel Angelo
MA
Ribeiro
Eduarda
E
Rodrigues
Pedro
P
Hultcrantz
Rolf
R
Sampaio
Paula
P
Ehrlich
Rachel
R
Carvalho
João
J
Fraga
José
J
de Sousa
Maria
M
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D005838:Genotype; D000071020:Hemochromatosis Protein; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D007501:Iron / Q000378:metabolism*; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D016037:Single-Blind Method; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D015415:Biomarkers; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D007372:Interferons; D007501:Iron