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To describe the virological profile of HCV in HBV/HCV co-infection, we investigated the variability of HVR-1 and NS5A domains, which may be involved in viral persistence and replication efficiency. We studied 95 patients: 37 with serological markers of HBV/HCV co-infection, 33 with single HBV and 25 with single HCV infection. HVR-1 complexity and NS5A gene variability were respectively explored by means of PCR-SSCP and direct sequencing. Serum HBV genomes were detected in all coinfected patients: 19 also had circulating HCV particles (group BC-I), whereas HCV were undetectable in the other 18 (group BC-II). Group BC-I was characterised by a significantly lower HBV replication capacity, that reflects the replicative dominance of HCV, although the dominant virus had the same degree of variability as the HCV in single infection. HBV viral load was higher in group BC-II, but not significantly different from that observed in the single infection. Our data indicate an alternation in replicative dominance in co-infection: HBV can suppress HCV replication to undetectable levels, whereas HCV may reduce but does not abrogate the replication capacity of HBV. Furthermore, in the cases of HCV dominance, circulating HBV genomes did not have a significant effect on the viral heterogeneity of HCV.

Background/Aims : Experimental studies have demonstrated that the wild-type PKR-NS5A strain of hepatitis C virus (HCV) may have oncogenic potential through the binding and functional repression of PKR protein kinase. To assess whether the NS5A-PKR-binding domain may be involved in HCV-related liver carcinogenesis, its sequence was analyzed in the sera of 85 patients with hepatocellular carcinoma (HCC) and in 51 patients with chronic active hepatitis (CAH). In 13 HCC cases sequence analysis was also performed in tumor and nontumor liver tissues. Methods : The nucleotide sequences of the PKR-binding domain were inferred by direct sequencing of the amplified HCV products and deduced amino acids were compared with the sequence of HCV-J. Results : A wild-type or single mutated strain which retains PKR-binding activity was found in 88% of HCC and 69% of CAH cases ( P =0.0096). All but three HCC cases showed no divergences in amino acid changes between serum and liver tissues. The wild-type strains were equally distributed between the HCC with or without cirrhosis. Conclusions : The prevalence of the wild-type NS5A-PKR strain is significantly higher in HCC than in CAH. These data suggest that inhibition of PKR activity by HCV might represent a potential mechanism of HCV-related carcinogenesis.

Background: Chronic hepatitis C virus (HCV) infection has occasionally been associated with diseases of the central nervous system, thus suggesting that the virus has a direct effect on cerebral function. Objective: To investigate the presence and heterogeneity of HCV populations in the cerebrospinal fluid (CSF), plasma and peripheral blood mononuclear cells (PBMC) of HIV-infected and anti-HCV-positive patients. Methods: Reverse transcriptase-polymerase chain reaction was used to detect HCV RNA in 21 paired CSF/plasma samples and 20 PBMC samples from HIV/HCV-positive patients. HCV was genotyped by means of a hybridization assay, and its compartmental heterogeneity was analysed by cloning the related amplicons. Results: All of the plasma samples, 14 out of 20 PBMC samples and five out of 21 CSF samples were positive for HCV RNA. Of the five patients with HCV-positive CSF, two had the same genotype in the plasma/CSF/PBMC samples, two had a different genotype in the CSF from that in plasma and PBMC, and one had the same genotype in paired CSF/plasma samples. An analysis of the HCV permutations showed that two patients seemingly infected with the same genotype in different compartments harbored mixed infection in the CSF but not in the plasma and PBMC samples. Conclusions: These findings of different HCV genetic diversification in different compartments suggest that CSF is an independent site of viral replication and persistence.