Background: Fibrotest (FT) and Actitest (AT) are biochemical markers of fibrosis and activity for use as a non-invasive alternative to liver biopsy in patients with chronic hepatitis C virus. The aim of this study was to perform a validation study the discordances between FT and AT(FT/AT) and liver biopsy in patients with chronic hepatitis C in Japan. Methods: 117 serum samples of chronic hepatitis C patients sended at -80°C at the Biochemistry Department of Pitié Salpetrière Hospital were analysed between july and august 2007. FT/AT components were assessed on thawed sera for 110 patients. 96 from 110 patients had liver biopsy at the moment of serum analysis. Liver biopsy fibrosis and activity scores were assessed by a pathologist in Japan according to METAVIR scoring system. For each individual test-FT/AT the following statistical analysis were performed Result: FT observed AUROC for the diagnosis of advanced fibrosis was 0.81 and after adjustment according to the prevalence of different stages of fibrosis the AUROC was 0.89. This difference could be explained by the non-homogenous distribution of different stages of fibrosis (low prevalence of extremes stages of fibrosis -F0 and F4-and high prevalence of adjacent intermediate stages -F1 and F2). The observed AUROC of FT for the diagnosis of precirrhosis and cirrhosis was 0.86 and the observed AUROC of AT for the diagnosis of moderate to severe activity was 0.74 . Conclusion: These results are similar to those observed in all independent validations worldwide. Background: Accurate monitoring of HCV-RNA level throughout anti-HCV therapy is key factor for predicting sustained virological response (SVR). Real-time detection polymerase chain reaction (RTD-PCR) based methods are sensitive, have wide dynamic range of quantification and carryover contamination caused by classical PCR. Aim: To compare RTD-PCR based assays; Cobas Ampliprep/Cobas TaqMan (CAP/CTM) and recently developed Abbott RealTime HCV for HCV RNA quantification and measurements differences by 2 assays in different genotypes. Methods: In total, 253 serum samples were used including, 135, 39, 24, 15, and 40 with genotypes 1b, 2a, 2b, 3a and 4 respectively were tested quantatively for HCV-RNA by CAP/CTM and Abott RealTime. Results: Good correlation between two assays as overall (r=0.96) with correlation coefficient (R) in genotypes 1b, 2a, 2b, 3a ranged between 0.99 to 0.98 and least in genotype 4 (r=0.78). Mean differences between CAP/CTM and Abott RealTime was significnat in genotypes 1b and 4. Significantly HCV-RNA genotype 4 underestimation by CAP/CTM (4.3+0.9 log IU/ml) than Abbott RealTime (4.8+0.9 log IU/ml; P=0.01). In genotype 1b, significantly higher HCV-RNA measurement by CAP/CTM (5.7+1.7log IU/ml) than Abbott RealTime (5.0+1.4log IU/ml, P=0.001). Two HCV genotype 4 samples showed measurement differences (CAP/CTM minus Abbott RealTime) of -3.75 and -1.68 log IU/ml. Studying genotype 4 sequences within 5 UTR , target for CAP/CTM RT-PCR amplification, revealed nucleotide polymorphisms at positions A107, A165, T203, A205, and A243. Conclusion: Different measurement efficiency by commonly used CAP/CTM in different genotypes compared to Abbott RealTime. 6 New York, New York, USA, 7 Vertex Pharmaceuticals, 8 Cambridge, MA, USA, 9 Duke Clinical Research Institute , 10 Duke University, Durham, NC, USA Background: PROVE1 is a placebo-controlled study of 250 subjects with genotype 1 chronic hepatitis C randomized to 48 weeks of peginterferon-alfa-2a 180 ug/week (P) plus ribavirin 1000-1200 mg/d (R) (PR48, n=75), or 3 regimens of 750 mg q8h telaprevir (TVR) with PR: TVR/PR for 12wks followed by PR for 0wks (T12/PR12, n=17), 12wks (T12/PR24, n=79) or 36wks (T12/PR48, n=79). The impact of African American race (AA) and bridging fibrosis on sustained virologic response (SVR) was examined. Methods: Subjects with cirrhosis were excluded from study. Fibrosis was categorized as mild/minimal, portal, or bridging from biopsy within 2 years. ITT analysis was performed. Results: Overall, SVR was achieved by 41% of subjects in the PR48 group, 35% in T12/PR12 group, 61% in T12/PR24 group, and 68% in T12/PR48 group. Subgroup analyses indicated SVR was improved with TVR/PR (TVR/PR arms pooled) vs PR48 alone in AA subjects (44% (8/18) vs 11% (1/9)), and in subjects with bridging fibrosis (69% (22/32) vs. 26% (5/19)). Adverse events leading to discontinuations were more frequent in the TVR/PR groups (21% vs. 10%). Rashes, gastrointestinal events and anemia were more common in the T/PR arms, and rashes were more frequently severe (7% vs 1%). Conclusions: TVR-based treatment for 24 or 48 weeks was associated with an increase in SVR rates compared to PR48. Subgroups with impaired response to standard Peg-IFN/RBV therapy appeared to benefit from the addition of telaprevir. Adverse events leading to discontinuation were more frequent in TVR-based regimens. Background and aims: Induction of Type I IFNs is a core issue in antiviral responses and must be tightly controlled. The protein kinase TBK1 is critically involved in virus-triggered type I IFN signaling. In previous studies, an alternatively spliced isoform of TBK1, termed TBK1s, was identified to be induced in both human and mouse cells. Bound to RIG-1, it is able to disrupt the interaction between RIG-I and VISA. This study was designed to observe the expression of TBK1s in HCV-infected patients. Methods: Total RNA was extracted from samples of peripheral blood mononuclear cells obtained from 11 HCV patients, 9 HCV patients treated with IFN-/ribavirin and 9 healthy controls, and subjected to real -time PCR using the primer-probe sets for human Tbk1s, Tbk1 and IFN-genes. Results: The TBK1s expression was significantly elevated in HCV-infected patients, while treatment of HCV-infected patients with IFN-/ribavirin resulted in down-regulation of TBK1s to the normal level. Conclusions: The study strongly supports the idea that expression of TBK1s is correlated with HCV infection, and indicates that TBK1s may play an important role in the regulation of HCV infection.This work was supported by NSFC(30571643, 30672380, 30700702 Background: Infringement of iron metabolism is one of fibrosis progressing factors during diffuse liver diseases. The interrelation between the syndrome of iron overload (SIO) and SVR achievement is studied during chronic HCV infection treatment. Methods: 68 patients with chronic HCV infection (genotyping: 1-34; 1+3-5; 3-22; 2-6; 4-2) are investigated. SIO criteria: iron increase-more than 37 mkMol/l, ferritin -more than 200 mkMol/l, percent of transferriny saturation with iron (%Tf) -more than 50%. Results: SIO revealed in 10 patients (14.7%): 5 patients -1 genotype (2 assotiative with a diabetes) and 5 patients-genotype 3 (3 -in combination with liver steatosis and obesity). Venipuncture series were done up to getting ferritin referential parameter values before therapy beginning. RVR: SIO -5 patients, normal metabolism -48; EVR: 6 and 54, SVR: 4 and 54 relatively. 5 nonresponding patients (SIO) had steatosis and diabetes, hereditary hemochromatosis (C282Y/H63D) is verified in 1 case. Increase of ferritini values and %Tf during therapy and positive HLA-A3 and HLA-B7 is registered in nonresponding patients. Conclusions: SIO in HLA-A3, HLA-B7 and C282Y/H63D positive patients is independent predictor of nonresponse during peginterferon alpha-2a (40 kd)" ribavirin treatment.