Proton cerebral magnetic resonance spectroscopy and neuropsychometric abnormalities in patients with chronic hepatitis C infection

General session 1 GWll MOSQUITO

1 CELLS BIND AND REPLICATE HEPATITIS C VIRUS

R. Germi’. J.M. Crance*. D. Garin*. J. Guimet’. M.A. Thtlu3. A. Jouans, J.I? Zarski3. E. Drouet’ ‘Univ. J. Fourier, Grenoble, France. 2CRSSA E. Pardt, Grenoble, France. 3Hosp. A. Michallon, Grenoble, France.

Hepatitis C virus (HCV), a Flaviviridae virus, is mainly transmitted by parenteral route, but 20 % of infections present no identifiable risk factor. Several works showed HCV replication in lymphocyte and hepatocyte human cell lines as in Vero cells, but HCV replication was low and without virus adaptation. The aim of our work was to select cell lines able to replicate HCV in culture. Virus adsorption and replication were studied by inoculating mosquito Aedes pseuabscutellaris AP61 cells and control mammalian Vero cells with GR416 HCVpositive plasma (genotype lb, 0.5~10~ copies/ml). The viral genome was detected by RT-PCR method (primers and 32P probe in SUTR). Successive virus passages in cells were provided. The putative CD81 HCV receptor was detected by flow cytometry assay. AP61 and Vero cells were able to bind HCV. The virus RNA was detected 28 days post-infection in four virus passages, evidencing HCV replication and production infectious virus. Vero cells and not AP61 cells were found to express CD81. We selected an original HCV replication system, able to keep the virus in culture during several virus passages. HCV, like other Flaviviridae, binds on and replicates in CD81negative mosquito cells suggesting that this cells might express their own HCV receptor compatible with the phylogenetic evolution of Flaviviridae. Such a functional receptor, present in vivo might allow the hypothesis of HCV arthropod-mediated transmission.

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( PR(YTON CEREBRAL MAGNETIC RESONANCE SPECTROSCOPY AND NEUROPSYCHOMETRIC ABNORMALITIES IN PATIENTS WITH CHRONIC HEPATITIS C INFECTION D.M. Forton’, N. Haraarden2. H.C. Thomas’. SD. Tavlor-Robinson’ ‘Hepatology Section, Imperial College School of Medicine, St Marys Hospital, London, UK. ‘CDR Ltd, Reading, UK. Patients with chronic hepatitis C (HCV) score lower on quality of life scales compared to normals and patients with chronic hepatitis B (HBV). We examine the hypothesis that a direct cerebral effect of HCV underlies this. Computerlsed oeuropsychometric testing (CDR) of 19 patients with histologically mild HCV hepatitis was performed. The mean scores and (SD) are shown compared to agematched control (MC) data (n=171-250).

I Simde

I

R&m

HCV MC

Tim&m 278(45) 255(35) pco.04

I Gwice Resetion

Time/m 460(44) 431(46) pco.02

I Did

Vi&mce sp%dh 431(41) 405(38) FO.02

I Stxtial

GdinS Memmyhm 1088(232) 864(260) p
I SD&l w. I word hiemOrY Sensitivity 0.71 0.82 ns

Recognitio n speedh 898(191) 851(170)

t-test l-l.9 In vivo cerebral ‘A MR spectroscopy. Spectra were acquired from VOX&

positioned in the basal ganglia (BG), white matter (WM) and occipital grey matter (GM) using a l.ST spectroscopy system in 3 patient groups; 1) 27 patients with biopsy proven mild HCV infection (mean age 44.7,46% male, mean liver necroiuflammatory score 3.3118, mean liver fibrosis score 1.6/6). 33% had a history of previous intravenous drug abuse (lVDA+ve.) at least 6 months prior to the study. 2) 11 HBeAg+ve patients with HBV infection without cirrhosis, none IVDA+ve. 3) 20 healthy volunteers (mean age 42.0, 50% male), none IVDA+ve. A significant elevation in BG Choline/Cmatine was seen in the HCV group compared to the other groups [median Cho/Cr and (SD): HCV 1.12(0.15); HBV 0.96(0.15)**; Vols. 1.05(0.13)*. **p
I