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.
Iron Genes and the Immune System, Institute for Molecular and Cell Biology, 4150-180 Porto, Portugal.
Elsa Maria
EM
Cardoso
Miguel Angelo
MA
Duarte
Eduarda
E
Ribeiro
Pedro
P
Rodrigues
Rolf
R
Hultcrantz
Paula
P
Sampaio
Rachel
R
Ehrlich
João
J
Carvalho
José
J
Fraga
Maria
M
de Sousa
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