Gilles Duverlie

Université de Picardie Jules Verne, Amiens, Picardie, France

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Publications (110)513.03 Total impact

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    ABSTRACT: Genetic recombination is now a well-established feature of the hepatitis C virus (HCV) variability and evolution, with the recent identification of circulating recombinant forms. In Amiens University Hospital Centre (France), a discrepancy of genotyping results was observed for 9 samples, between their 5' untranslated region assigned to genotype 1b and their NS5B region assigned to genotype 1a, suggesting the existence of a recombinant strain. In the present study, clinical and phylogenetic analyses of these isolates were conducted and a putative relationship with previously identified HCV 1b/1a recombinants was investigated. The results revealed that all 9 strains displayed a breakpoint within the beginning of the core protein, were closely related between each others and with the H23 strain identified in Uruguay (Moreno, 2009). Then, the clinical characteristics of the 9 unlinked individuals infected with this 1b/1a genotype were analysed. This is the first report on the circulation, in a French population, of a HCV recombinant strain 1b/1a. The identification of this genotype in other patients and in other geographical zones would allow to further investigate its prevalence in the population and to better understand its molecular epidemiology.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 10/2015; DOI:10.1016/j.meegid.2015.09.030 · 3.02 Impact Factor
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    ABSTRACT: With the growing importance of BKV, effective and efficient screening for BKV replication in plasma and urine samples is very important to monitor renal transplant and hematopoietic stem cell transplant recipients, who are at increased risk of BKV-associated diseases. However, recent assays proposed by many manufacturers have not been tested and the available tests have not been standardized. The aim of the present study was to evaluate and compare the performance of 3 commercially available kits, R-gene®, GeneProof® and RealStar®, according to various genotypes in plasma and urine specimens and to determine the correlation with a reference laboratory. A qualitatively excellent global agreement (96.8%) was obtained. RealStar® PCR tended to give better sensitivity especially for subtype Ib1 samples. Comparison of 30 plasma samples and 53 urine samples showed a good agreement between the three assays with Spearman's Rho correlation coefficient between 0.92 and 0.98 (p< 0.001). Moreover, a perfect correlation was obtained for comparison of the assays on the Acrometrix® BKV panel (p< 0.001 for all). According to Bland–Altman analysis, more than 95% (240/249) of samples comparisons were situated in the range “mean ± 2SD”. The greatest variability between assays was observed for 10.2% subtype Ib2 samples having a difference of more than 1 log 10 copies/mL. In conclusion, this study demonstrated the reliable and comparable performances of R-gene®, GeneProof® and RealStar® real-time PCR systems for BKV quantification in urine and plasma samples. All three real-time PCR assays are appropriate for screening of BKV replication in patients.
    Journal of clinical microbiology 10/2015; DOI:10.1128/JCM.02116-15 · 3.99 Impact Factor
  • Cyril Page · Gilles Duverlie · Henri Sevestre · Rachel Desailloud
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    ABSTRACT: Erythrovirus B19 (EVB19) has been incriminated, over recent years, in the onset and/or pathogenesis of many diseases, especially autoimmune thyroid diseases. This review of the literature (published over the last 40 years using Pubmed and Science Direct search engines) was designed to define the role of EVB19, particularly in autoimmune thyroid diseases.Two cases of subacute thyroiditis, one case of Graves' disease (associated with type 1 diabetes and rheumatoid arthritis), and one case of Hashimoto's thyroiditis following acute EVB19 infection were reported. A retrospective case–control study in a pediatric population demonstrated the role of EVB19 in Hashimoto's thyroiditis. Four retrospective studies of pathology slides (including PCR, immunohistochemistry or in situ hybridization) and a prospective case–control study on pathology slides demonstrated the presence of EVB19 in thyroid tissue of patients with benign multinodular goiter, Graves' disease, autoimmune thyroiditis (including Hashimoto's thyroiditis), and thyroid cancer. EVB19 can be demonstrated in the thyroid gland in a wide range of diseases. Although acute EVB19 infection could theoretically trigger autoimmune thyroid disease, there is currently no evidence that EVB19 plays a specific role in the pathophysiology of autoimmune thyroid diseases. J. Med. Virol. © 2014 Wiley Periodicals, Inc.
    Journal of Medical Virology 09/2015; 87(1). DOI:10.1002/jmv.23963 · 2.35 Impact Factor
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    ABSTRACT: Importance: HCV glycoproteins E1 and E2 play an essential role in virus entry into liver cells as well as in virion morphogenesis. In infected cells, these two proteins form a complex in which E2 interacts with cellular receptors, whereas the function of E1 remains poorly understood. However, recent structural data suggest that E1 could be the protein responsible for the fusion process between viral and cellular membranes. Here, we investigated the oligomeric state of HCV envelope glycoproteins. We demonstrate that E1 forms functional trimers after virion assembly and that in addition to the requirement of E2, a determinant for this oligomerization is present in a conserved GxxxG motif located within E1 transmembrane domain. Taken together, these results indicate that a rearrangement of E1E2 heterodimer complexes likely occurs during the assembly of HCV particles to yield a trimeric form of E1E2 heterodimer. Gaining structural information on this trimer will be helpful for the design of an anti-HCV vaccine.
    Journal of Virology 08/2015; DOI:10.1128/JVI.00991-15 · 4.44 Impact Factor
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    ABSTRACT: Despite the validation of direct acting antivirals for hepatitis C treatment, discovery of new compounds with different modes of action may still be of importance for the treatment of special patient populations. We recently identified a natural molecule, epigallocatechin-3-gallate (EGCG) as an inhibitor of hepatitis C virus (HCV) targeting the viral particle. The aim of this work was to discover new natural compounds with higher anti-HCV activity than EGCG and determine their mode of action. Eight natural molecules with structure similarity to EGCG were selected. HCV JFH1 in cell culture and HCV pseudoparticle systems were used to determine antiviral activity and mechanism of action of the compounds. We identified delphinidin, a polyphenol belonging to the anthocyanidin family, as a new inhibitor of HCV entry. Delphinidin inhibits HCV entry, in a pan-genotypic manner, by acting directly on the viral particle and impairing its attachment to the cell surface. Importantly, it is also active against HCV in primary human hepatocytes with no apparent cytotoxicity and in combination with interferon and boceprevir in cell culture. Different approaches showed that neither aggregation nor destruction of the particle occurred. Cryo-transmission electron microscopy observations of HCV pseudoparticles treated with delphinidin or EGCG showed a bulge on particles that was not observed in control conditions. In conclusion, EGCG and delphinidin inhibit HCV entry by a new mechanism, i.e. alteration of the viral particle structure that impairs its attachment to the cell surface. In this article, we identify a new inhibitor of hepatitis C virus (HCV) infection, delphinidin, which prevents HCV entry. This natural compound, a plant pigment responsible for the blue-purple color of flowers and berries, belongs to the flavonoid family, like the catechin EGCG, the major component present in green tea extract, which is also an inhibitor of HCV entry. We studied the mode of action of these two compounds against HCV and demonstrated that they both act directly on the virus, inducing a bulging of the viral envelope. This deformation might be responsible for the inhibition of the virus attachment to the cell surface. The discovery of such anti-HCV inhibitors with an unusual mode of action is important to better characterize the mechanism of HCV entry into hepatocyte and to help developing a new class of anti-HCV entry inhibitors. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Journal of Virology 07/2015; 89(19). DOI:10.1128/JVI.01473-15 · 4.44 Impact Factor
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    ABSTRACT: In our study, we characterized the effect of monensin, an ionophore that is known to raise the intracellular pH, on the hepatitis C virus (HCV) life cycle. We showed that monensin inhibits HCV entry in a pangenotypic and dose-dependent manner. Monensin induces an alkalization of intracellular organelles, leading to an inhibition of the fusion step between viral and cellular membranes. Interestingly, we demonstrated that HCV cell-to-cell transmission is dependent on the vesicular pH. Using the selective pressure of monensin, we selected a monensin-resistant virus which has evolved to use a new entry route that is partially pH and clathrin independent. Characterization of this mutant led to the identification of two mutations in envelope proteins, the Y297H mutation in E1 and the I399T mutation in hypervariable region 1 (HVR1) of E2, which confer resistance to monensin and thus allow HCV to use a pH-independent entry route. Interestingly, the I399T mutation introduces an N-glycosylation site within HVR1 and increases the density of virions and their sensitivity to neutralization with anti-apolipoprotein E (anti-ApoE) antibodies, suggesting that this mutation likely induces conformational changes in HVR1 that in turn modulate the association with ApoE. Strikingly, the I399T mutation dramatically reduces HCV cell-to-cell spread. In summary, we identified a mutation in HVR1 that overcomes the vesicular pH dependence, modifies the biophysical properties of particles, and drastically reduces cellto- cell transmission, indicating that the regulation by HVR1 of particle association with ApoE might control the pH dependence of cell-free and cell-to-cell transmission. Thus, HVR1 and ApoE are critical regulators of HCV propagation.
    Journal of Virology 06/2015; 89(16). DOI:10.1128/JVI.00192-15 · 4.44 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate tropism prediction performances of three algorithms [geno2pheno false-positive rate 10% (G2P10), position-specific scoring matrix (PSSM) and a combination of the 11/25 and net charge rules] and to investigate the viral and host factors potentially involved in the X4 or R5 prediction in human immunodeficiency virus-1 (HIV-1) patients. Viral tropism was determined in 179 HIV-1-infected patients eligible for CCR5 antagonist therapy. HIV-1 RNA or DNA was extracted and amplified for env gp120 sequencing. In parallel, demographic, viral, immunological and clinical determinants were analyzed. According to the G2P10 algorithm, 48 patients harbored X4 or X4R5 virus. The tropism prediction was concordant for 87.7 and 88.2% of samples when comparing G2P10 with PSSM or with a combination of the 11/25 and net charge rules, respectively. X4 prediction was significantly associated with more than 35 amino acids in the V3 domain (p < 0.0001) and loss of an N-linked glycosylation site (p < 0.0001). Of the factors studied, only the nadir CD4 T-cell count was significantly associated with X4 tropism (p = 0.01). We determined that the X4 virus detection is closely linked to the nadir CD4 T-cell count below 100 cells/mm(3) that must be taken into account when considering a CCR5 antagonist therapy switch. © 2015 S. Karger AG, Basel.
    Intervirology 05/2015; 58(3):155-159. DOI:10.1159/000398798 · 1.68 Impact Factor
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    ABSTRACT: The pre-therapeutic presence of protease inhibitor (PI) resistance-associated variants (RAVs) has not been shown to be predictive of triple-therapy outcome in treatment-naïve patients. However, they may influence the outcome in patients with less effective Pegylated Interferon (IFN)-ribavirin (RBV) backbones. Using HCV population sequence analysis, we retrospectively investigated the prevalence of baseline NS3 RAVs in a multicenter cohort of poor IFN-RBV responders (i.e. prior null-responders or patients with a viral load decrease of <1 logUI/ml during the pegIFN/RBV lead-in phase). The impact of the presence of these RAVs on triple-therapy outcome was studied. Among 282 patients, the prevalence of baseline RAVs ranged from 5.7% [3.3%-9.0%] to 22.0% [17.3%-27.3%] according to the algorithm used. Among mutations conferring a >3-fold shift in IC50 for telaprevir or boceprevir, T54S was the most frequently detected mutation (3.9%), followed by A156T, R155K (0.7%), V36M and V55A (0.35%). Mutations were more frequently found in patients infected with genotype 1a (7.5-23.6%) than 1b (3.3-19.8%) (p=0.03). No other socio-demographic or viro-clinical characteristic was significantly associated with a higher prevalence of RAVs. No obvious effect of baseline RAVs was observed on viral load. In this cohort of poor responders to IFN-RBV, no link was found with the sustained virological response to triple-therapy, whatever the algorithm used for the detection of mutations. Based on cross-study comparison, baseline RAVs are not more frequent in poor IFN-RBV responders than in treatment-naïve patients and, even in these difficult-to-treat patients, this study demonstrates no impact on treatment outcome, arguing against resistance analysis prior to treatment. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Journal of clinical microbiology 04/2015; 53(7). DOI:10.1128/JCM.03633-14 · 3.99 Impact Factor
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    ABSTRACT: Hepatitis C virus (HCV) chronic infection is a major cause of hepatocellular carcinoma. Sorafenib is the only medical treatment that has been approved for the treatment of this cancer. It is a multikinase inhibitor with anti-tumor activity against a wide variety of cancers. Sorafenib blocks angiogenesis and tumor cell proliferation through inhibition of kinases, such as VEGFR2, PDGFR, or the serine/threonine kinases RAF. Previous studies have reported an anti-HCV effect of sorafenib in vitro, but various mechanisms of action have been described. The aim of this study was to clarify the action of sorafenib on the complete HCV infectious cycle. In order to examine the action of sorafenib on all steps of the HCV infectious cycle, we used a combination of validated cell culture models, based on the HuH-7 reference cell line and primary human hepatocytes. We found that sorafenib blocks HCV infection by altering the viral entry step and the production of viral particles. Moreover, we observed that treatment with sorafenib lead to a modification of Claudin-1 expression and localization, which could partly be responsible for the anti-HCV effect. Collectively, our findings confirm the anti-HCV effect of sorafenib in vitro, while highlighting the complexity of the action of sorafenib on the HCV infectious cycle. Copyright © 2015. Published by Elsevier B.V.
    Antiviral research 03/2015; 24. DOI:10.1016/j.antiviral.2015.03.012 · 3.94 Impact Factor
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    ABSTRACT: It is generally accepted that thyroid follicle cells are at least semi-permissive for erythrovirus B19 (EVB19). Thus, various laboratory techniques have been successfully used to detect EVB19 in the thyroid gland, including polymerase chain reaction (PCR), immunohistochemistry, and in situ hybridization. However, the detection of EVB19 within the thyroid gland is problematic, and none of the detection protocols in the literature have been unequivocally validated. This multidisciplinary study in which 32 thyroidectomy subjects undergoing thyroidectomy in a French University hospital were prospectively recruited was performed over a period of 3 years. Prior to surgery, all the subjects were assayed for blood levels of anti-EVB19 antibodies and (using a quantitative PCR [qPCR] assay) EVB19 itself. A qPCR assay for EVB19 and an immunohistochemical assay (based on polyclonal anti-VP2 antibodies) were performed on the thyroidectomy samples. None of the subjects had an acute EVB19 infection. A viral load was detected in two serum samples and six thyroid biopsies. Three subjects had both a positive immunohistochemical assay and a positive qPCR assay for the thyroid tissue. It is noteworthy that the thyroid immunohistochemical and qPCR assays were negative in the two patients with detectable serum loads of EVB19. In conclusion, EVB19 can be detected in thyroid follicle cells by using immunohistochemical and qPCR assays. Ideally, patients should be tested with both PCR and immunohistochemical assays, in order to unequivocally confirm or rule out the presence of EVB19 in the thyroid gland. The present protocol must now be validated in larger series - notably with respect to its reliability and in order to determine qPCR positivity thresholds for application in future large-scale studies. J. Med. Virol. 00: 1-6, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Journal of Medical Virology 03/2015; 87(6). DOI:10.1002/jmv.24147 · 2.35 Impact Factor
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    ABSTRACT: Multilayered blood safety programs reduce the risk of transfusion-transmitted diseases; however, there remains a risk of window period transmission of screened viruses and transmission of unscreened and emerging viruses from asymptomatic donors. To reduce this risk, a riboflavin-and-UV-light-based pathogen reduction process was evaluated against eight viral agents. Riboflavin and UV light was evaluated against the following eight viral agents: encephalomyocarditis virus (EMC), hepatitis A virus (HAV), hepatitis C virus (HCV), influenza A (FLUAV), La Crosse virus (LACV), pseudorabies virus (PRV), sindbis virus (SINV), and vesicular stomatitis virus (VSV). Before treatment, a sample was removed to determine the product's initial viral load. After treatment the product's viral load was reevaluated and the log reduction was calculated. Virus reduction after treatment with riboflavin and UV light is equivalent in platelet (PLT) and plasma units, as demonstrated by a 3.2-log reduction of EMC in plasma, PLTs, and PLT additive solution containing 35% plasma. Additionally, the following viral reductions values were observed: HAV 1.8 log, HCV at least 4.1 log, FLUAV at least 5.0 log, LACV at least 3.5 log, PRV 2.5 log, SINV 3.2 log, and VSV at least 6.3 log. The results observed in this study suggest that treating PLT and plasma products with a riboflavin-and-UV-light-based pathogen reduction process could potentially eliminate window period transmission of screened viruses and greatly reduce the risk of transfusion transmission of unscreened viruses. © 2015 AABB.
    Transfusion 03/2015; 55(7). DOI:10.1111/trf.13030 · 3.23 Impact Factor
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    ABSTRACT: 1) Objectives The SUPPLIVER project aims at developing a liver supply system based on cell encapsulation in alginate beads. 2) Material and methods After hepatic cells and alginate were mixed, beads were produced by an extrusion method that made the droplets fall in a gelation bath. Abioreactor was designed to host the beads under a fluidized bed perfusion regimen. The biological components were inserted in a complete and safe extracorporeal circuit based on a therapeutic plasmapheresis device. In vitro trials were performed to assess biological functions and both ex vivo and preliminary in vivo studies focused on the system's safety. 3) Results The encapsulation and fluidization processes were validated, showing the maintenance of hepatic functions once spheroids of hepatocytes were formed before encapsulation. The whole extracorporeal circuit was built, including all the monitoring processes for priming and treatment. The first preclinical trials were successful on a sheep model. 4) Conclusion The multidisciplinary consortium succeeded in demonstrating the feasibility of the proposed integrated approach, from cell collection to extra-corporeal circuit functions. It led to a promising combined advanced therapies medicinal product, that still needs to be challenged in a large model of hepatic failure.
    IRBM 02/2015; 36(2). DOI:10.1016/j.irbm.2015.01.010 · 0.52 Impact Factor
  • Etienne Brochot · Sandra Bodeau · Gilles Duverlie
    Therapeutic Drug Monitoring 12/2014; Publish Ahead of Print(4). DOI:10.1097/FTD.0000000000000161 · 2.38 Impact Factor
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    ABSTRACT: Anemia is a well-known RBV-related event in HCV therapy which is exacerbated by the addition of telaprevir and boceprevir. This retrospective study evaluated and compared ribavirin exposure and parameters able to influence hemoglobin decrease in a large population of patients treated with dual or triple therapy. Patients on triple therapy had higher ribavirin concentrations at week 12 of treatment (3460 ng/mL vs 1843 ng/mL; p< 0.0001). An association was also observed between week 12 eGFR and ribavirin concentration only for patients on triple therapy (p= 0.002).The proportion of patients with a > 20 ml/min/1.73m2 decrease in eGFR at week 12 was higher among patients on triple therapy: 32%, 14% and 5% for boceprevir, telaprevir and dual therapy, respectively (p= 0.025 and 0.026). No correlation was observed between boceprevir and telaprevir concentrations and hemoglobin or eGFR decrease. Exacerbation of anemia in patients on triple therapy is related to higher ribavirin concentrations. We provide an explanation for this increase in plasma RBV concentration. Triple therapy with PEG-IFN, RBV and telaprevir or boceprevir will remain the only HCV treatment option for many patients. Our data show that the RBV dose can be decreased while maintaining adequate plasma concentrations and reducing anemia. This article is protected by copyright. All rights reserved
    The Journal of Clinical Pharmacology 12/2014; 55(5). DOI:10.1002/jcph.454 · 2.48 Impact Factor
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    ABSTRACT: Objective: Sofosbuvir and simeprevir in combination with standard therapy are now available for the treatment of patients chronically infected with hepatitis C virus (HCV) genotype 1. With boceprevir and telaprevir, four treatment options are, therefore, now available to clinicians. Phase 3 studies conducted with simeprevir and sofosbuvir compared sustained virological response (SVR) data with those obtained with standard combination therapy and did not include a control arm. It is important to quantify the contribution of these molecules compared to the first direct antiviral agents available. Material and methods: For HCV genotype 1 patients, we performed a literature review and compared all SVR data from phase 3 randomized placebo-controlled trials conducted with these four molecules according to virological characteristics (genotype, viral load) and patient characteristics (IL28B polymorphism, stage of fibrosis). Results: Simeprevir and sofosbuvir provide a net gain in terms of SVR compared to boceprevir and telaprevir except in the case of telaprevir for treatment-naïve HCV genotype 1b patients. Sofosbuvir achieves higher SVR rates than simeprevir except for treatment-naïve IL28B CC patients and naïve HCV genotype 1b patient. Further, simeprevir moderately improve SVR rates compared to telaprevir in treatment-naïve patients with F3-F4 fibrosis and with HCV genotype 1a infection. Conclusion: Sofosbuvir and simeprevir greatly improve the virological response rate compared to first-generation protease inhibitors. All of these data may help in guiding the physician's treatment decisions, based on financial constraints and patient characteristics. These data can be easily updated with future treatment and demonstrate the contribution of new treatment regimens to achieve optimal SVR rates.
    Scandinavian Journal of Gastroenterology 11/2014; 50(4). DOI:10.3109/00365521.2014.978364 · 2.36 Impact Factor
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    ABSTRACT: Core plays a critical role during HCV assembly, not only as a structural component of the virion, but also as a regulator of the formation of assembly sites. In this study, we observed that core is expressed later than other HCV proteins in a single viral cycle assay, resulting in a relative increase of core expression during a late step of the viral life cycle. This delayed core expression results from an increase of core half-life, indicating that core is initially degraded and is stabilized at a late step of the HCV life cycle. A stabilization-mediated delayed kinetics of core expression was also observed using heterologous expression systems. Core stabilization did not depend on its interaction with non-structural proteins or lipid droplets but was correlated to its expression levels and its oligomerization status. Therefore in the course of a HCV infection, core stabilization likely occurs when the prior amplification of the viral genome during an initial replication step allows core to be synthesized at higher levels as a stable protein during the assembly step of the viral life cycle.
    Journal of General Virology 10/2014; 96(Pt_2). DOI:10.1099/vir.0.070433-0 · 3.18 Impact Factor
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    ABSTRACT: Cell microencapsulation in alginate hydrogel has shown interesting applications in regenerative medicine and the biomedical field through implantation of encapsulated tissue or for bioartificial organ development. Although alginate solution is known to have low antiviral activity, the same property regarding alginate gel has not yet been studied. The aim of this work is to investigate the potential protective effect of alginate encapsulation against hepatitis C virus (HCV) infection for a hepatic cell line (HuH-7) normally permissive to the virus. Our results showed that alginate hydrogel protects HuH-7 cells against HCV when the supernatant was loaded with HCV. In addition, alginate hydrogel blocked HCV particle release out of the beads when the HuH-7 cells were previously infected and encapsulated. There was evidence of interaction between the molecules of alginate hydrogel and HCV, which was dose- and incubation time-dependent. The protective efficiency of alginate hydrogel towards HCV infection was confirmed against a variety of viruses, whether or not they were enveloped. This promising interaction between an alginate matrix and viruses, whose chemical mechanisms are discussed, is of great interest for further medical therapeutic applications based on tissue engineering.
    PLoS ONE 10/2014; 9(10):e109969. DOI:10.1371/journal.pone.0109969 · 3.23 Impact Factor
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    ABSTRACT: Le taux d’échec de la culture d’hépatocytes primaires humains (HPH) par absence d’adhésion cellulaire après dissociation reste encore élevé. Ceci pourrait s’expliquer par le contexte pathologique (foie d’hépatopathie chronique) et thérapeutique (embolisation portale, chimiothérapie d’induction, radiofréquence) du donneur, altérant la qualité du parenchyme et favorisant la survenue de complications postopératoires. Entre décembre 2011 et mars 2014, nous avons étudié pour 51 patients, la relation entre l’adhésion (plating) des cellules isolées à partir des pièces d’hépatectomies à J1 et les suites postopératoires. Nos résultats montrents qu'il existe une corrélation entre l’échec de la culture d’HPH (absence de plating) et la survenue de complications majeures Clavien III à V (OR = 4,9 IC95 % [0,045–0,88] p = 0,024). Ces complications (27 %) sont dominées par la fistule biliaire (18 %), l’insuffisance hépatocellulaire (6 %) et le décès (4 %). Il n’y a pas de corrélation entre le plating et la chimiothérapie d’induction, la stéatose ou la fibrose hépatique (p = 0,98 ; p = 0,4 et p = 0,19). Une viabilité cellulaire ≥ 50 % après dissociation à J0 semble être un facteur de bon pronostic de plating (p = 0,08). Cette donnée permettrait au chirurgien de disposer d’un nouveau moyen d’appréhender le foie non tumoral et de prédire les suites postopératoires dès J1. Ces résultats préliminaires devront être confirmés sur une cohorte plus importante de patients.
    116e Congrès Françaisde Chirurgie, Paris; 10/2014
  • Virginie Morel · Gilles Duverlie · Etienne Brochot
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    ABSTRACT: Background Simeprevir (Olysio®), a second-wave protease inhibitor recently approved for the treatment of chronic hepatitis C, is not indicated in patients with genotype 1a strain harboring the Q80K protease mutation. Phase 2 and 3 studies on this molecule mainly focused on North American patients and the prevalence of Q80K is particularly high in the USA (around 50%). The prevalence of this mutation in other parts of the world is currently unknown. Objectives The purpose of our study was to perform a detection of this mutation in a single PCR technique and to study the prevalence of this Q80K mutation in a non-U.S. population. We can thus estimate the proportion of HCV positive patients who can be treated with simeprevir. Study design We conducted a meta-analysis of response rates in the presence or absence of this mutation in randomized trials and then describe a simple and reliable method to detect this mutation. We also examined bilirubin levels in our cohort of 95 HCV genotype 1a patients. Results Ten patients (10.5%) had a Q80K mutation and 12 patients exhibited bilirubin levels above the upper limit of normal at baseline. In our cohort, 21 patients (22%) were therefore ineligible for treatment with simeprevir. The prevalence of this mutation seems to be much lower in European patients. Conclusion In conclusion, before considering treatment with simeprevir, physicians must be able to screen for the Q80K mutation.
    Journal of Clinical Virology 09/2014; 61(1). DOI:10.1016/j.jcv.2014.06.023 · 3.02 Impact Factor
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    ABSTRACT: Simeprevir (TMC435, Olysio™), a second-generation hepatitis C virus (HCV) protease inhibitor, has been recently approved for the treatment of genotype 1 chronic hepatitis C in combination with pegylated interferon and ribavirin. This molecule has very different characteristics from first-generation protease inhibitors. Results from trials show that simeprevir is highly effective and safe, with few adverse events. We discuss the specific features of this new treatment option for HCV infection, in terms of in vitro data, pharmacological data, and clinical trials. We also discuss the impact of Q80K polymorphism at baseline. Studies evaluating interferon-free regimens with simeprevir are ongoing. Future combinations of two or more direct-acting antiviral agents, targeting different viral enzymes and with synergistic antiviral effects, will be approved, allowing treatment of pan-genotypic HCV with optimized sustained virologic responses. Simeprevir will undoubtedly be part of future treatment strategies.
    Pharmacogenomics and Personalized Medicine 08/2014; 7:241-9. DOI:10.2147/PGPM.S52715

Publication Stats

2k Citations
513.03 Total Impact Points


  • 2010–2015
    • Université de Picardie Jules Verne
      Amiens, Picardie, France
  • 1998–2015
    • Institut Universitaire de France
      Lutetia Parisorum, Île-de-France, France
  • 2013
    • Centre Hospitalier Universitaire de Dijon
      • Hepato-Gastroenterology Service
      Dijon, Bourgogne, France
  • 2011
    • Université Libre de Bruxelles
      • Faculty of Medicine
      Bruxelles, Brussels Capital, Belgium
  • 2006–2011
    • Centre Hospitalier Universitaire de Limoges
      Limages, Limousin, France
    • Centre Hospitalier Universitaire d'Amiens
      • Laboratoire de Virologie
      Amiens, Picardie, France
  • 2003–2010
    • Institut Pasteur de Lille
      Lille, Nord-Pas-de-Calais, France
  • 2007
    • University of Birmingham
      • Institute for Biomedical Research
      Birmingham, England, United Kingdom
    • Institut National de la Transfusion Sanguine, Paris
      Lutetia Parisorum, Île-de-France, France
  • 2002–2007
    • Institut de Biologie de Lille
      Lille, Nord-Pas-de-Calais, France
  • 2005
    • Centre Hospitalier Universitaire de Tours
      Tours, Centre, France
  • 2001
    • CUNY Graduate Center
      New York, New York, United States
  • 2000
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
  • 1997
    • Universitair Ziekenhuis Ghent
      Gand, Flanders, Belgium