Interaction between human hepatic stellate cells and hepatitis C virus

Primary infection with Hepatitis C virus (HCV) is usually benign but become s chronic in 50 to 70% of the patients with a high risk of cirrhosis and he patocarcinoma. In vivo, HCV replicates mainly in parenchymal cells; histolo gical data reveal that chronic hepatitis C is a progressive fibrotic diseas e. We, therefore, found it interesting to study the interaction between hum an hepatic stellate cells (HSC) and HCV in order to elucidate the physiopat hological mechanisms of this persistent infection. HSC were isolated by centrifugal elutriation from explants of normal liver obtained after surgery on benign or malignant liver tumors. The cells were incubated with the serum of a patient chronically infected with the HCV la genotype containing 10.106 Eq genomes/ml. After 4h adsorption at 37 degrees C, the presence of virus in the cell cultures was evaluated according to v iral RNA detection by RT-nested PCR and quantified with the b-DNA assay (Ch iron) at different times. The release of PDGF AB and TGF-beta in the supern atants was checked by commercially available kits (RD systems and Genzyme r espectively). Genomic viral RNA was continually detectable in the cell fraction more than 4 weeks after infection (j=29) by RT-nested PCR, but only intermittently i n the supernatants. Quantification with the b-DNA assay showed a low increa se in the amount of viral RNA present in the cell cultures during the secon d and third weeks of culture. Furthermore in the supernatant of HCV infecte d cells a decrease in the amount of PDGF AB as well as an increase in that of TGF-beta as compared to non infected cells could be found. These results suggest that HCV may persistently infect stellate cells induc ing functional modifications which could participate in the pathogenesis of the infection namely in the evolution towards chronicity.