A study of some hepatic immunological markers, iron load and virus genotype in chronic hepatitis C

J Hepatol. 2004 Aug;41(2):319-26. doi: 10.1016/j.jhep.2004.04.027.

Abstract

Background/aims: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use
  • Biomarkers / metabolism*
  • Endothelial Cells / metabolism
  • Female
  • Genotype
  • Hemochromatosis Protein
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / metabolism*
  • Hepatitis C, Chronic / virology*
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Interferons / therapeutic use
  • Iron / metabolism*
  • Kupffer Cells / metabolism
  • Liver / metabolism*
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Mutation
  • Single-Blind Method
  • Treatment Outcome
  • Viral Load

Substances

  • Antiviral Agents
  • Biomarkers
  • HFE protein, human
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • Interferons
  • Iron