Author(s): Cardoso, Elsa M. ; Duarte, Miguel A. ; Ribeiro, Eduarda ; Rodrigues, Pedro ; Hultcrantz, Rolf ; Sampaio, Paula ; Ehrlich, Rachel ; Carvalho, João ; Fraga, José ; de Sousa, Maria
Date: 2016
Persistent ID: http://hdl.handle.net/10314/3507
Origin: Repositório Institucional do Instituto Politécnico da Guarda
Subject(s): HFE; MHC-I; IFN; Hepatitis C virus; Liver
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.
We thank Dr Graça Porto for critical review of the manuscript. This study was supported by the EU QLG1-CT-1999-00665 project, the Calouste Gulbenkian Foundation/FCT Project on Hemochromatosis (Portugal) and the INNOVA Foundation/APBRF (USA).
