631 Augmentation of PPAR-alpha expression induced by hepatitis C virus core protein

HEPATOLOGY, Vol. 34, No. 4, Suppl. 1, 2003

AASLD ABSTRACTS

cirrhosis, however, there is impairment in hepatocyte proliferation. Our data suggest that hepatocyte proliferation is not a useful method for screening patients for HCC.

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Disclosures: Furq aan A h m e d - No relationships to disclose P. Wilfredo Canchis - No relationships to disclose Luis Chiriboga - No relationships to disclose Jennifer Davila - No relationships to disclose Brian R Edlin - No relationships to disclose M . Isabel Fiel - No relationships to disclose Ira M Jacobson - No relationships to disclose Sang Kim - No relationships to disclose Lydia Petrovic - No relationships to disclose Andrew H Talal - No relationships to disclose Alex Teixeira - No relationships to disclose Herman Yee - No relationships to disclose 631

AUGMENTATION OF PPAR-ALPHA EXPRESSION INDUCED BY HEPATITIS C VIRUS CORE PROTEIN. Romy Zemel, Felsenstein

Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Petach-Tikva, Israel; Nir Barak, Rabin Medical Center, Petah-Tikva, Israel; Larisa Bachmatove, FelsensteinMedical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Petach-Tikva, Israel; Rafit Droll, Molecular Hepatology Lab., FelsensteinMedical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Petach-Tikva, Israel; Yawn Rotman, Ran Tur-Kaspa, Rabin Medical Center, Petah-Tikva, Israel Persistent infection with hepatitis C virus (HCV) might lead to hepatocellular carcinoma (HCC). The mechanism by which HCV contribute to carcinogenic potential is poorly understood. Nevertheless the HCV core encoded protein was suggested to be involved in the tumorigenic process. The aim of our work was to study the effect of HCV core on the peroxisomal pathways of lipid oxidation. Since PPAR-c~is a transcription factor that governs peroxisomal pathways of lipid oxidation and ultimately produc~on of reactive oxygen species, we analyzed the effect of HCV core protein on PPAR-c~ expression. The expression level of PPAR-c~ mRNA was quantLfied in hepatoma cell lines, H3B and HepG2 stably expressing HCV core protein using real time RT -PCIL The expression level of PPAR-c~ protein was determined using western blot analysis. Lipid peroxidation products were evaluated as thiobarbitoiric acid-reactive substances (TBARS). To evaluate the effect of HCV core protein on peroxisom proliferation the level of catalase, a peroxisomal marker, in the core expressing cell lines was determined by western blot analysis. Our findings demonstrate elevation of PPAR-c~in HCV core expressing hepatoma cell lines both at the levels of mRNA and protein. TBARS levels were significantly lower in the core expressing cells, while catalase levels were unimpaired. Treatment of cells with Wy 14643, (a PPAR-c~agonist), resulted in the elevation of PPAR-cY,similar to the effect obtained by HCV core. Moreover, treatment of HCV core expressing cells with Wy 14643 resulted in a significant elevation of PPAR-cY, compare to the effect obtained by core or by Wy 14643 alone. The elevation of PPAR-c~ expression with the reduction of TBARS levels in response to HCV core may indicate a change in hepatocyte oxidation. In conclusion, our preliminary results suggest the involvement of HCV core protein in increasing oxidative stress causing a disproportionate augmentation of PPAR-cY,altering hep atocyte oxidation without changing levels of catalase a H202 -degrading enzyme. Disclosures: Larisa Bachmatove - No relationships to disclose Nir Barak - No relationships to disclose Rafit Drori - No relationships to disclose Yaron Rotman - No relationships to disclose Ran Tur-Kaspa - No relationships to disclose Romy Zemel - No relationships to disclose

465A

632 HEPATITIS C VIRUS INFECTION IN A JUVENILE PRISON: HIGH PREVALENCE OF HCV AMONG IMMIGRANTS FROM THE FORMER SOVIET UNION TO GERMANY.

Manuela F Meyer, Heiner Wedemeyer, Medizinische Hochschule, Hannover, Germany; Johannes Dreesman, Niedersiichsisches Landesgesundheitsamt, Hannover, Germany; Michael P Manns, Medizinische Hochschule, Hannover, Germany; Arrnin Baillot, Niedersiichsisches Landesgesundheitsamt, Hannover, Germany; Marc Lehmann, Jugendanstalt Hameln, Hameln, Germany Introduction: A high prevalence of hepatitis C virus infection of up to 80 % has been reported for prison communities in the US and in Europe. However, for young inmates there are no data available on the prevalence and course of viral hepatitis. We here report data of a prospective study performed in the largest German prison for young men (age 16-247. In the year 2002, all 1176 new incoming prisoners were asked to participate in the study and >95% gave informed consent. All individuals were tested for antibodies against HIV, HAV, HBV and HCV as well as for HCV-RNA. 62% of prisoners were born in Germany, while 11.7% had migrated to Germany from countries of the former Soviet Union (£SU) after 1989. Each prisoner who tested positive for anti-HCV or HCV-RNA (n-97; 8.7% of samples tested) was then asked for informed consent to fi~her evaluation of medical history and diagnostic procedures which was denied by 8 individuals. Of the remaining 89 individuals, i.v. drug abuse was self-reported by 84 (94%7. Results: Anti-HCV antibodies in the absence of HCV viremia were detected in 19 individuals (21%7. In the 70 HCV viremic patients, ALT was >5 times upper limit of normal (ULN), between 1.5 and 5 times ULN and <1.5 times ULN in 11 (16%7, 32 (46%) and 27 (39%) individuals, respectively. The clinical severity of liver disease was rather mild, none of the individuals had a Child Pugh score of B or C and AST/ALT ratio was <1 in all but two of the viremic patients. Interestingly, 5 individuals (6%) tested positive for HCV-RNA without being positive for anti-HCV antibodies. Four of them cleared HCV during follow-up without clinical signs of acute hepatitis and without developing antiHCV antibodies. Hepatitis C markers were significantly more prevalent among immigrants from the former Soviet Union than among German inmates (30% vs. 6%, respectively; p<0.0001). Of the 89 inmates tested positive for anti-HCV or HCV-RNA, 43 were German and 40 were from the fSU. HIV coinfection was found in 5 individuals, all of t h e m were German (p-0.03). In contrast, HBsAg was detected in 5 fSU immigrants only and anti-HBc antibodies were also more prevalent among fSU immigrants (24/40 vs. 7/43, p<0.0001). Similarly, anti-HAV antibodies were less frequently detected in Germans (21/40 vs. 4/43, p<0.0001). HCV genotype distribution (genotype 1 59% vs. 46%7, ALT, bilirubin, prothrombin time and all other biochemical parameters tested did no differ among the two groups. Conclusions: (I) Acute HCV infection may be cleared in absence of anti-HCV antibodies more often than previously thought. (II) Although the overall prevalence of hepatitis C among young prison inmates in Germany is low, the subgroup of immigrants from the former Soviet Union tests positive in about one third for hepatitis C markers. More than 10% of those suffer from active HBV coinfection and 60% are anti-HBc-positive. Taking the increasing migration from the East to the West in Europe into account, the epidemiology of viral hepatitis in Europe will change and prevention and information programs are urgently needed. Disclosures: Armin Baillot - No relationships to disclose Johannes Dreesman - No relationships to disclose Marc Lehmann - No relationships to disclose Michael P Manns - No relationships to disclose Manuela F Meyer - No relationships to disclose Heiner Wedemeyer - No relationships to disclose