77 results on '"Alexandra Ducancelle"'
Search Results
2. Analysis of hepatic fibrosis markers in the serum of chronic hepatitis B patients according to basal core promoter/precore mutants
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Caroline Lefeuvre, Marine Roux, Simon Blanchard, Hélène Le Guillou-Guillemette, Jérôme Boursier, Françoise Lunel-Fabiani, Pascale Jeannin, Adeline Pivert, and Alexandra Ducancelle
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Medicine ,Science - Abstract
Abstract The A1762T/G1764A double mutant in the basal core promoter (BCP) region of the hepatitis B virus (HBV) is associated with severe hepatic lesions while the G1899A mutation with the double mutant is associated with a significant reduction in the risk of severe fibrosis. This study aims to measure a number of markers in the serum of patients with chronic HBV infection and to assess relationships between these markers and BCP/precore mutants with consideration of the stage of fibrosis. The serum levels of resistin, TGF-β1, MMP-1, TIMP-1, collagen IA1 and PDGF-BB, which are markers that are known to be involved in the process of hepatic fibrosis, were assayed. The serum levels of PDGF-BB and TIMP-1, and the mutation profile were independently associated with advanced fibrosis. A higher level of TIMP-1 was associated with advanced fibrosis regardless of the mutation status, and a higher level of PDGF-BB was associated with nonsevere fibrosis in patients infected with viruses harboring the A1762T/G1764A or A1762T/G1764A/G1899A mutations. Our results suggest an impact of the A1762T/G1764A mutant on the biological pathway related to TGF-β1 and PDGF-BB. In vitro studies are needed to understand the impact of these mutants on the serum secretion of markers involved in fibrosis severity.
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- 2022
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3. Acute hepatitis B in pregnancy with surprisingly rapid clearance of serum HBs antigen associated with a favourable outcome
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Steven Roger, Julien Fontana, Alexandra Ducancelle, Hélène Le Guillou-Guillemette, Clémence M Canivet, and Caroline Lefeuvre
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Hepatitis B virus ,Pregnancy ,HBsAg loss ,Precore mutation ,Infectious and parasitic diseases ,RC109-216 - Abstract
Acute hepatitis B (AHB) is usually asymptomatic, but it can progress to chronic hepatitis B (HB) defined by HB surface antigen (HBsAg) persisting beyond 6 months. Nevertheless, the delay of HBsAg seroclearance is not well-defined. During pregnancy, the immune system of the pregnant women is altered and delayed HBsAg loss can be observed, leading to chronic infection. Here, we present an uncommon case of AHB in a pregnant woman in whom rapid HBsAg seroclearance (52 days after AHB) was associated with a favourable outcome (no injury to liver). This patient received tenofovir disoproxil fumarate promptly after diagnosis. The case raises questions about the use of antiviral treatment in AHB. This is generally not recommended in AHB, but it would be potentially useful in pregnant women to reduce the risk of chronic HB infection and could also prevent the transmission of the maternal precore mutation, thus reducing the significant risk of fulminant hepatitis in the infant. This case also highlights the impact of the hepatitis B virus (HBV) genotype and precore/core mutations on the clinical course of the disease.
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- 2022
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4. Study Protocol: Randomised Controlled Trial Assessing the Efficacy of Strategies Involving Self-Sampling in Cervical Cancer Screening
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Caroline Lefeuvre, Hélène De Pauw, Anne-Sophie Le Duc Banaszuk, Adeline Pivert, Alexandra Ducancelle, Franck Rexand-Galais, and Marc Arbyn
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cervical cancer ,screening coverage ,under-screened women ,urinary self-sampling ,vaginal self-sampling ,cancer screening test ,Public aspects of medicine ,RA1-1270 - Abstract
Objectives: The cervical cancer screening coverage remains moderate (60%) in France. The aim of the study is to evaluate the efficacy of two experimental invitation strategies (offer of urine or vaginal self-sampling kits) to reach under-screened populations and compare them with the current invitation strategy in rural departments (low medical density and low participation rate) in France.Methods: The study is a randomised controlled trial with three arms: a control arm (conventional invitation letter) and two experimental arms (mailing of a urine or vaginal self-sampling kit). The target population includes women aged 30–65 years, who had no screening test recorded since more than 4 years and who did not respond to an invitation letter within 12 months before. The primary outcome measure is the participation rate in each arm. A team of psychologists will also investigate attitudes and experiences by semi-structured/focus-group interviews with voluntary CapU4 participants and with health professionals.Result and conclusion: CapU4 will identify effective strategies to reach women not responding to current screening invitations and will generate information about acceptance of self-sampling among women and health professionals.
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- 2022
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5. Age-Related Expression of IFN-λ1 Versus IFN-I and Beta-Defensins in the Nasopharynx of SARS-CoV-2-Infected Individuals
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Charly Gilbert, Caroline Lefeuvre, Laurence Preisser, Adeline Pivert, Raffaella Soleti, Simon Blanchard, Yves Delneste, Alexandra Ducancelle, Dominique Couez, and Pascale Jeannin
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IFN - interferon ,defensin ,nasopharyngeal mucosa ,SARS – CoV – 2 ,COVID - 19 ,ageing ,Immunologic diseases. Allergy ,RC581-607 - Abstract
SARS-CoV-2 coronavirus infection induces heterogeneous symptoms, ranging from asymptomatic to lethal forms. Severe forms usually occur in the elderly and/or individuals with comorbidities. Children generally remain asymptomatic to primary infection, suggesting that they may have an effective local innate immune response. IFN-I and -III have non-redundant protective roles against SARS-CoV-2, although sometimes damaging the host. The expression and role of anti-viral peptides during SARS-CoV-2 infection have thus far been little studied. We aimed to identify the innate immune molecules present at the SARS-CoV-2 entry point. We analyzed the mRNA levels of type I (IFN-α and -β) and type III (IFN-λ1-3) interferons and selected antiviral peptides (i.e., β-defensins 1-3, α-defensins [HNP1-3, HD5] pentraxin-3, surfactant protein D, the cathelicidin LL-37 and interleukin-26) in nasopharyngeal swabs from 226 individuals of various ages, either infected with SARS-CoV-2 (symptomatic or asymptomatic) or negative for the virus. We observed that infection induced selective upregulation of IFN-λ1 expression in pediatric subjects (≤15 years), whereas IFN-α, IFN-β, IFN-λ2/λ3, and β-defensin 1-3 expression was unaffected. Conversely, infection triggered upregulation of IFN-α, IFN-β, IFN-λ2/λ3, and β-defensin 1-3 mRNA expression in adults (15-65 years) and the elderly (≥ 65 years), but without modulation of IFN-λ1. The expression of these innate molecules was not associated with gender or symptoms. Expression of the interferon-stimulated genes IFITM1 and IFITM3 was upregulated in SARS-CoV-2-positive subjects and reached similar levels in the three age groups. Finally, age-related differences in nasopharyngeal innate immunity were also observed in SARS-CoV-2-negative subjects. This study shows that the expression patterns of IFN-I/-III and certain anti-viral molecules in the nasopharyngeal mucosa of SARS-CoV-2-infected subjects differ with age and suggests that susceptibility to SARS-CoV-2 may be related to intrinsic differences in the nature of mucosal anti-viral innate immunity.
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- 2021
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6. A Pleiotropic Role of the Hepatitis B Virus Core Protein in Hepatocarcinogenesis
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Caroline Lefeuvre, Hélène Le Guillou-Guillemette, and Alexandra Ducancelle
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hepatitis B virus ,hepatitis B virus core protein ,hepatocellular carcinoma ,hepatocarcinogenesis ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Chronic hepatitis B virus (HBV) infection is one of the most common factors associated with hepatocellular carcinoma (HCC), which is the sixth most prevalent cancer among all cancers worldwide. However, the pathogenesis of HBV-mediated hepatocarcinogenesis is unclear. Evidence currently available suggests that the HBV core protein (HBc) plays a potential role in the development of HCC, such as the HBV X protein. The core protein, which is the structural component of the viral nucleocapsid, contributes to almost every stage of the HBV life cycle and occupies diverse roles in HBV replication and pathogenesis. Recent studies have shown that HBc was able to disrupt various pathways involved in liver carcinogenesis: the signaling pathways implicated in migration and proliferation of hepatoma cells, apoptosis pathways, and cell metabolic pathways inducing the development of HCC; and the immune system, through the expression and production of proinflammatory cytokines. In addition, HBc can modulate normal functions of hepatocytes through disrupting human host gene expression by binding to promoter regions. This HBV protein also promotes HCC metastasis through epigenetic alterations, such as micro-RNA. This review focuses on the molecular pathogenesis of the HBc protein in HBV-induced HCC.
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- 2021
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7. Publisher Correction: A first experience of transduction for differentiated HepaRG cells using lentiviral technology
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Adeline Pivert, Caroline Lefeuvre, Cong-Tri Tran, Claude Baillou, David Durantel, Hélène Le Guillou-Guillemette, François M. Lemoine, Françoise Lunel-Fabiani, and Alexandra Ducancelle
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Medicine ,Science - Published
- 2021
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8. Natural non-homologous recombination led to the emergence of a duplicated V3-NS5A region in HCV-1b strains associated with hepatocellular carcinoma.
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Hélène Le Guillou-Guillemette, Adeline Pivert, Elise Bouthry, Cécile Henquell, Odile Petsaris, Alexandra Ducancelle, Pascal Veillon, Sophie Vallet, Sophie Alain, Vincent Thibault, Florence Abravanel, Arielle A Rosenberg, Elisabeth André-Garnier, Jean-Baptiste Bour, Yazid Baazia, Pascale Trimoulet, Patrice André, Catherine Gaudy-Graffin, Dominique Bettinger, Sylvie Larrat, Anne Signori-Schmuck, Hénia Saoudin, Bruno Pozzetto, Gisèle Lagathu, Sophie Minjolle-Cha, Françoise Stoll-Keller, Jean-Michel Pawlotsky, Jacques Izopet, Christopher Payan, Françoise Lunel-Fabiani, and Christophe Lemaire
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Medicine ,Science - Abstract
BACKGROUND:The emergence of new strains in RNA viruses is mainly due to mutations or intra and inter-genotype homologous recombination. Non-homologous recombinations may be deleterious and are rarely detected. In previous studies, we identified HCV-1b strains bearing two tandemly repeated V3 regions in the NS5A gene without ORF disruption. This polymorphism may be associated with an unfavorable course of liver disease and possibly involved in liver carcinogenesis. Here we aimed at characterizing the origin of these mutant strains and identifying the evolutionary mechanism on which the V3 duplication relies. METHODS:Direct sequencing of the entire NS5A and E1 genes was performed on 27 mutant strains. Quasispecies analyses in consecutive samples were also performed by cloning and sequencing the NS5A gene for all mutant and wild strains. We analyzed the mutant and wild-type sequence polymorphisms using Bayesian methods to infer the evolutionary history of and the molecular mechanism leading to the duplication-like event. RESULTS:Quasispecies were entirely composed of exclusively mutant or wild-type strains respectively. Mutant quasispecies were found to have been present since contamination and had persisted for at least 10 years. This V3 duplication-like event appears to have resulted from non-homologous recombination between HCV-1b wild-type strains around 100 years ago. The association between increased liver disease severity and these HCV-1b mutants may explain their persistence in chronically infected patients. CONCLUSIONS:These results emphasize the possible consequences of non-homologous recombination in the emergence and severity of new viral diseases.
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- 2017
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9. Successful Treatment Using Simeprevir, Sofosbuvir and Rituximab of a Severe Form of Hepatitis C Virus-related Mixed Cryoglobulinemia with Cardiac Involvement
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Rafael Mahieu, Christian Lavigne, Geoffrey Urbanski, Isabelle Fouchard Hubert, Alexandra Ducancelle, and Françoise Lunel-Fabiani
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Mixed cryoglobulinemia ,hepatitis C virus ,sofosbuvir ,simeprevir ,Medicine - Abstract
Numerous extrahepatic manifestations have been reported in hepatitis C virus (HCV) infection, particularly mixed cryoglobulinemia (MC). MC generally responds to clearance of HCV under pegylated-interferon plus ribavirin treatment. New direct-acting antiviral agents have been licensed for HCV under different combinations but have not been studied in severe forms of MC. Here, we present a case report describing a life-threatening form of MC with multivisceral involvement, which was successfully treated with concomitant rituximab, sofosbuvir and simeprevir. In light of the rapid clinical remission associated with sustained virological response and the excellent side-effect profile, this treatment should be considered as a first-line therapy in severe forms of MC.
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- 2015
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10. High endemicity and low molecular diversity of hepatitis B virus infections in pregnant women in a rural district of North Cameroon.
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Alexandra Ducancelle, Pierre Abgueguen, Jacques Birguel, Wael Mansour, Adeline Pivert, Hélène Le Guillou-Guillemette, Jean-Jacques Sobnangou, Amélie Rameau, Jean-Marie Huraux, and Françoise Lunel-Fabiani
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Medicine ,Science - Abstract
BACKGROUND: A program, supported by the GEMHEP (Groupe d'étude Moléculaire des Hépatites), was established in 2007 in the sanitary district of Tokombéré, to prevent perinatal transmission of hepatitis B virus (HBV). It comprises screening for HBV surface antigen (HBsAg) in all pregnant women and vaccinating the newborn if tests are positive. METHODS/PRINCIPAL FINDINGS: 1276 women were enrolled in the study after providing informed consent. Demographic data and blood samples were available for 1267 of the enrolled patients. HBsAg was determined locally using a rapid test (Vikia HBsAg, Biomerieux). Tests for HBV and HDV virological markers (HBeAg, anti-HDV antibodies (Ab), HBV-DNA, HDV-RNA, HBV and HDV genotypes) were performed on the confirmed HBsAg-positive samples in the virology unit of the Angers University Hospital (France). HBsAg was found in 259 of the 1267 pregnant women (20.4%) between January 2009 and April 2010, of whom 59 were HBeAg-positive (22.7%) with high levels of HBV-DNA. Anti-HDV Ab were found in 19 (7.3%) of the HBsAg-positive women. The prevalence rates of HBsAg and HDV were not age-dependent whereas HBeAg carriers were statistically younger than non carriers. Basal core promoter (BCP) and precore (PC) mutations and genotypes were determined by sequencing. Of 120 amplified sequences, 119 belonged to HBV genotype E (HBV/E) and the 9 HDV strains belonged to HDV clade 1. In the PC region, 83/228 patients (36.4%) harbored a G1896A mutant or mixed phenotype virus. In the BCP region, the double mutation A1762T/G1764A and the G1757A substitution were detected respectively in 26/228 patients (11.4%) and 189/228 patients (82.8%). CONCLUSIONS: Our results confirm the high prevalence and low molecular diversity of HBV in Far Northern Cameroon; more than 20% of the infected women were highly viremic, suggesting a high rate of HBV perinatal transmission and supporting the WHO recommendation to vaccinate at birth against hepatitis B.
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- 2013
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11. Comparison of performance between three SARS‐CoV‐2 molecular assays (Aptima™, Laboratory Developed Test‐Fusion, and R‐GENE®) with special attention to turnaround time, a key point in laboratory management
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Caroline Lefeuvre, Adeline Pivert, Emilie Przyrowski, Elise Bouthry, Estelle Darviot, Rafaël Mahieu, Françoise Lunel‐Fabiani, Alexandra Ducancelle, and Hélène Le Guillou‐Guillemette
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COVID-19 Testing ,Infectious Diseases ,SARS-CoV-2 ,Virology ,COVID-19 ,Humans ,Sensitivity and Specificity - Abstract
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the importance of rapid diagnostic testing to identify individuals with SARS-CoV-2 infections and to limit the spread of the virus. Many molecular assays have become commercially available to cope with this surging demand for timely diagnosis of COVID-19 cases, but identifying individuals requires accurate diagnostic tools. We compared the performance of three molecular SARS-CoV-2 assays: Aptima™ SARS-CoV-2 assay running on the Panther system (Hologic), an in-house assay (Laboratory Developed Test, LDT) running on the Fusion module of the Panther Fusion system (LDT-Fusion; Hologic), and the R-GENE® SARS-CoV-2 assay (bioMérieux). In addition, we also evaluated the turnaround time. This parameter is crucial to managing the SARS-CoV-2 diagnosis and represents a key point in the quality management at the laboratory. Aptima™ and LDT-Fusion assays exhibited an excellent positive percent agreement (PPA) (100.0%), while the R-GENE® assay showed a slightly decreased PPA (98.2%). The Hologic assays have a higher throughput with less hands-on time than the R-GENE® assays (24-25 vs. 71 min). Both Hologic assays are used on a fully automated random-access testing system with on-demand testing capabilities that avoid run series, unlike the R-GENE® assay. Automated random-access testing systems should be preferred during periods of high SARS-CoV-2 prevalence.
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- 2022
12. What is the true place of the SARS‐CoV‐2 rapid point‐of‐care antigen test in the hospital setting? Lessons learned from real life
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Steven Roger, Caroline Lefeuvre, Adeline Pivert, Alexandra Ducancelle, Dominique Savary, Élise Bouthry, and Hélène Le Guillou‐Guillemette
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Adult ,Aged, 80 and over ,Male ,Time Factors ,Adolescent ,SARS-CoV-2 ,COVID-19 ,Middle Aged ,Sensitivity and Specificity ,Hospitals ,COVID-19 Serological Testing ,Young Adult ,Infectious Diseases ,Point-of-Care Testing ,COVID-19 Nucleic Acid Testing ,Virology ,Humans ,Female ,Antigens, Viral ,Aged - Abstract
To assist in the clinical management of patients and to support infection control, we tested the use of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) point-of-care antigen test (AgPOC) for unplanned hospitalization, coupled with a nucleic acid amplification test (NAAT) using specimens collected at the same time upon arrival. The aim of this study was to assess the performance of the AgPOC in this specific use compared to NAAT for SARS-CoV-2 diagnosis, in the context of the low prevalence of infection. For 5 months (between two peaks in France of the SARS-CoV-2 pandemic), all patients admitted who undertook the AgPOC/NAAT paired tests were included in the study. AgPOC performances were determined considering the clinical status and the delay of symptoms onset. NAAT and AgPOC results were available for 4425 subjects. AgPOC results showed a homogeneous specificity (97%) but a low sensitivity at 45.8%. Considering the national guidelines, sensitivity dropped to 32.5% in cases of symptomatic patients with symptoms older than 5 days or more. This study shows the poor performance of AgPOC for entry screening of patients in hospitals. AgPOC may represent a useful tool in the hospital setting only if the use is restricted to patients with consistent symptoms less than 4 days old.
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- 2021
13. [Basic core promoter and precore mutations of hepatitis B virus]
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Alexandra, Ducancelle, Adeline, Pivert, and Françoise, Lunel-Fabiani
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Since hepatitis B virus (HBV) replication involves an error-prone reverse transcription step, the rate of nucleotide changes during replication is higher than that found in other DNA viruses. As a result, HBV has a "quasispecies" distribution in infected individuals. Such selection processes to allow the emergence of variant viruses, such as precore (PC) and basal core promoter (BCP) mutants. The dominant PC variant is a point mutation of G to A at nucleotide 1896 (G1896A) that produces a premature stop codon, which terminates translation of the precore protein, resulting in the lack of HBe-antigen synthesis. BCP variants at nucleotides 1762 (A1762T) and 1764 (G1764A) likewise impair the production of HBeAg but at the transcriptional rather than the translational level. The impact of mutations in the precore and basal core promoter regions of the HBV virus on the course of chronic liver disease is not well established.
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- 2022
14. From national HBV and HDV screenings to vaccination and treatment in healthcare workers: The Mauritanian pilot study
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Hélène Le Guillou-Guillemette, Kader Abdel, Ahmed El Bara, Adeline Pivert, Françoise Lunel-Fabiani, Pascal Veillon, Alexandra Ducancelle, Mohamed Abdallahi Bollahi, Cindy Ng Wing Sang, SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), and Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH)
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Hepatitis B virus ,medicine.medical_specialty ,HBsAg ,Health Personnel ,[SDV]Life Sciences [q-bio] ,viruses ,030231 tropical medicine ,Pilot Projects ,Hbv vaccination ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Health care ,medicine ,Humans ,Seroprevalence ,Hcv prevalence ,Prospective Studies ,030212 general & internal medicine ,Hepatitis B Antibodies ,ComputingMilieux_MISCELLANEOUS ,Hepatitis B Surface Antigens ,General Veterinary ,General Immunology and Microbiology ,business.industry ,Vaccination ,Mauritania ,Public Health, Environmental and Occupational Health ,virus diseases ,Hepatitis B ,medicine.disease ,digestive system diseases ,3. Good health ,Infectious Diseases ,HBeAg ,Molecular Medicine ,business - Abstract
Objectives Hepatitis B and D infections are highly endemic in Mauritania, with prevalences ranging from 10 to 20%. With the present prospective transversal pilot study, we aimed to evaluate the prevalences of HBV, HCV, and HDV infections in healthcare workers (HCWs), and offer treatment or vaccination as required. Methods At inclusion, each HCW was screened for anti-HBc Ab (followed by HBsAg assay when positive). Additional biological analyses were performed for HBsAg + cases. Depending on the results, HBV vaccination or anti-viral treatment was offered. Results A total of 3,857 HCWs were included, of whom 1,363 tested negative for anti-HBc Ab and received full vaccination. Of the 2,494 HCWs who were positive for anti-HBc Ab, 1,246 were positive for anti-HBs Ab and 418 were positive for HBsAg. Three HCWs were positive for HBeAg; 66 and 18 had HBV DNA levels respectively > 2,000 and > 20,000 IU/mL; and 48 were positive for anti-HDV Ab among whom 10 were positive for HDV RNA. HCV prevalence was 0.5%. Only seven HCWs fulfilled the criteria for treatment and five of them were treated. Conclusion Few HCWs in Mauritania are immunised against HBV. The prevalences of anti-HBc Ab and HBsAg observed in this work were similar to those observed in our earlier works, whereas prevalence of active HDV infection was less high. HBV and HDV infections are a serious health concern in Mauritania. New recommendations developed in accordance with WHO guidelines should include mandatory HBV screening and immunisation for HCWs.
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- 2021
15. Residual risk of mother-to-child transmission of hepatitis B virus infection despite timely birth-dose vaccination in Cameroon (ANRS 12303): a single-centre, longitudinal observational study
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Yusuke Shimakawa, Pascal Veillon, Jacques Birguel, Adeline Pivert, Virginie Sauvage, Hélène Le Guillou-Guillemette, Steven Roger, Richard Njouom, Alexandra Ducancelle, Pierre Amta, Jean Marie Huraux, Jean-Pierre Adoukara, Françoise Lunel-Fabiani, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Hôpital de Tokombéré, Institut National de la Transfusion Sanguine [Paris] (INTS), Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), This study was funded by Agence nationale de recherches sur le sida et les hépatites virales (ANRS)., Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM), Service de Virologie [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
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Hepatitis B virus ,Hepatitis B Surface Antigens ,Vaccination ,virus diseases ,General Medicine ,Hepatitis B ,Antiviral Agents ,Infectious Disease Transmission, Vertical ,digestive system diseases ,Pregnancy ,DNA, Viral ,Humans ,Female ,Hepatitis B Vaccines ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Cameroon ,Vaccines, Combined ,Pregnancy Complications, Infectious - Abstract
International audience; BackgroundIn sub-Saharan Africa, administration of hepatitis B virus (HBV) birth-dose vaccines remains suboptimal. Evidence is scarce on whether African countries should focus on increasing vaccine coverage or developing strategies incorporating additional measures, such as peripartum antiviral prophylaxis to pregnant women at high risk. To better inform decision makers, we estimated the residual risk of mother-to-child transmission despite HBV birth-dose vaccine in Cameroon.MethodsWe did a single-centre, longitudinal observational study. Pregnant women were systematically screened for HBV surface antigen (HBsAg) at Tokombéré District Hospital (Tokombéré district, Cameroon). Children born to HBsAg-positive mothers in 2009–16 who received the HBV birth-dose vaccine and three subsequent doses of pentavalent vaccine at 6, 10, and 14 weeks were followed up prospectively in 2015–17. In children, capillary blood was obtained for HBsAg rapid test and dried blood spots to quantify HBV DNA concentrations. Venous blood was also collected from HBsAg-positive children. Mother-to-child transmission was confirmed by whole-genome sequencing.FindingsBetween Jan 31, 2009, and Dec 31, 2016, 22 243 (66·8%) of 33 309 pregnant women accepted antenatal HBV screening, of whom 3901 (17·5%) were HBsAg positive. 2004 (51·4%) of 3901 children who were born to HBsAg-positive mothers received the HBV birth-dose vaccine, of whom 1800 (89·8%) also completed the three-dose pentavalent vaccine. In total, the current analysis included 607 children who had a follow-up serosurvey. The prevalence of HBsAg was 5·6% in children who received the birth-dose vaccine in less than 24 h, 7·0% in those who received it 24–47 h after birth, and 16·7% in those who received it 48–96 h after birth (ptrend=0·083). 35 (89·7%) of 39 infected children were born to mothers positive for HBV e antigen with high HBV DNA of 5·3 log10 IU/mL or more. Whole-genome sequencing of HBV in infected mother-child pairs confirmed high identity proportions of 99·97–100%.InterpretationWe documented a substantial risk of mother-to-child transmission despite timely administration of the HBV birth-dose vaccine within 24 h after birth. To reach WHO's elimination targets, peripartum antiviral prophylaxis might be required in parts of Africa, in addition to increasing coverage of the HBV birth-dose vaccine.
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- 2022
16. Humoral response to a third injection of BNT162b2 vaccine in patients on maintenance haemodialysis
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Marine Dekervel, Marine Asfar, Sophie Blanchi, Virginie Besson, Anne-Sophie Garnier, Giorgina Barbara Piccoli, Lise-Marie Pouteau, Jean-François Augusto, Massimo Torreggiani, Chloé Mellaza, Alexandra Ducancelle, Jean-Paul Imiela, Amaury Dujardin, Nicolas Henry, Axelle Paquin, Adaptation et diversité en milieu marin (AD2M), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Le Mans (CH Le Mans), Centre Hospitalier de Laval (CH Laval), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Néphrologie-Dialyse-Transplantation [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), and Université d'Angers (UA)
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medicine.medical_specialty ,SARS-Cov-2 ,[SDV]Life Sciences [q-bio] ,Population ,030204 cardiovascular system & hematology ,immunogenicity ,Immunoglobulin G ,Serology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Seroconversion ,education ,AcademicSubjects/MED00340 ,030203 arthritis & rheumatology ,Transplantation ,education.field_of_study ,BNT162b2 vaccine ,biology ,business.industry ,Immunogenicity ,COVID-19 ,3. Good health ,Vaccination ,haemodialysis ,Nephrology ,Cohort ,biology.protein ,Original Article ,Antibody ,business - Abstract
Background Humoral response against sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after two doses of BNT162b2 (Pfizer-BioNTech) has been proven to be less intense in maintenance dialysis patients as compared with healthy subjects, leading the French authorities to recommend a third injection in this population. Here we investigated the response to the third injection in two cohorts of haemodialysis (HD) patients. Methods Data from two prospective observational cohorts were collected. In the first (‘systematic’) cohort, patients from two HD centres (n = 66) received a third injection of BNT162b2, regardless of the response after two injections. In the second (‘conditional’) cohort, the injection was only prescribed to patients (n = 34) with no or low response to the previous two doses. In both cohorts, the third dose was injected 1–2 months after the second dose. Serology was performed after the second and third doses to assess anti-Spike immunoglobulin G (S IgG) antibody titre. Results In the systematic cohort, anti-S IgG was found in 83.3 and 92.4% of patients after the second and third doses of BNT162b2, respectively. In this cohort, 6/11 (54.5%) and 20/21 (95.2%) patients switched from non-responder to low responder and from low responder to high responder, respectively. In low and high responders to two doses, 50/55 (90.9%) at least doubled their anti-S IgG titre. Similar trends were observed in the conditional cohort. Conclusions In maintenance HD patients, humoral response against SARS-CoV-2 was boosted after a third dose of BNT162b2, allowing seroconversion in more than half of non-responders. These data may support an intensified vaccination protocol with a third dose of BNT162b2 in dialysis patients., Graphical Abstract Graphical Abstract
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- 2021
17. Serological diagnosis of secondary syphilis in a Rituximab‐treated patient: an emerging diagnostic challenge?
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Anne Croue, N Dupin, C Le Clec'h, H. Le Guillou-Guillemette, M Letzelter, Caroline Lefeuvre, Philippe Grange, Alexandra Ducancelle, N Benhaddou, and Pierre Abgueguen
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Treated patient ,medicine.medical_specialty ,business.industry ,MEDLINE ,Dermatology ,Secondary syphilis ,medicine.disease ,Syphilis Serodiagnosis ,Serology ,Infectious Diseases ,Humans ,Medicine ,Syphilis ,Rituximab ,business ,medicine.drug - Published
- 2021
18. Age-Related Expression of IFN-lambda1 Versus IFN-I and Beta-Defensins in the Nasopharynx of SARS-CoV-2-Infected Individuals
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Charly Gilbert, Caroline Lefeuvre, Laurence Preisser, Adeline Pivert, Raffaella Soleti, Simon Blanchard, Yves Delneste, Alexandra Ducancelle, Dominique Couez, Pascale Jeannin, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), institutional grants from the French National Institute of Health and Medical Research (INSERM) and the University of Angers.- grant from CSL Behring, Blanchard, Simon, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), and Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes (UN)-Université d'Angers (UA)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes (UN)-Université d'Angers (UA)
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COVID - 19 ,COVID -19 ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Immunology ,nasopharyngeal mucosa ,SARS -CoV -2 ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,medicine.disease_cause ,Asymptomatic ,IFN - interferon ,[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity ,Virus ,Cathelicidin ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Immunology and Allergy ,Defensin ,[SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity ,030304 developmental biology ,Coronavirus ,0303 health sciences ,Innate immune system ,business.industry ,Surfactant protein D ,RC581-607 ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences ,3. Good health ,Beta defensin ,ageing ,SARS – CoV – 2 ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,mucosal immunity ,medicine.symptom ,Immunologic diseases. Allergy ,business ,030217 neurology & neurosurgery ,defensin ,IFN -interferon - Abstract
SARS-CoV-2 coronavirus infection induces heterogeneous symptoms, ranging from asymptomatic to lethal forms. Severe forms usually occur in the elderly and/or individuals with comorbidities. Children generally remain asymptomatic to primary infection, suggesting that they may have an effective local innate immune response. IFN-I and -III have non-redundant protective roles against SARS-CoV-2, although sometimes damaging the host. The expression and role of anti-viral peptides during SARS-CoV-2 infection have thus far been little studied. We aimed to identify the innate immune molecules present at the SARS-CoV-2 entry point. We analyzed the mRNA levels of type I (IFN-α and -β) and type III (IFN-λ1-3) interferons and selected antiviral peptides (i.e., β-defensins 1-3, α-defensins [HNP1-3, HD5] pentraxin-3, surfactant protein D, the cathelicidin LL-37 and interleukin-26) in nasopharyngeal swabs from 226 individuals of various ages, either infected with SARS-CoV-2 (symptomatic or asymptomatic) or negative for the virus. We observed that infection induced selective upregulation of IFN-λ1 expression in pediatric subjects (≤15 years), whereas IFN-α, IFN-β, IFN-λ2/λ3, and β-defensin 1-3 expression was unaffected. Conversely, infection triggered upregulation of IFN-α, IFN-β, IFN-λ2/λ3, and β-defensin 1-3 mRNA expression in adults (15-65 years) and the elderly (≥ 65 years), but without modulation of IFN-λ1. The expression of these innate molecules was not associated with gender or symptoms. Expression of the interferon-stimulated genes IFITM1 and IFITM3 was upregulated in SARS-CoV-2-positive subjects and reached similar levels in the three age groups. Finally, age-related differences in nasopharyngeal innate immunity were also observed in SARS-CoV-2-negative subjects. This study shows that the expression patterns of IFN-I/-III and certain anti-viral molecules in the nasopharyngeal mucosa of SARS-CoV-2-infected subjects differ with age and suggests that susceptibility to SARS-CoV-2 may be related to intrinsic differences in the nature of mucosal anti-viral innate immunity.
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- 2021
19. Utility of hyposmia and hypogeusia for the diagnosis of COVID-19
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Sami Rehaiem, Jeanne Brochon, V. Rabier, Joël Jenvrin, Paul Le Turnier, Vincent Thibault, Anne Maillard, François Raffi, Pierre Abgueguen, Matthieu Revest, Vincent Dubée, Hélène Cormier, Faouzi Souala, Pauline Comacle, Cécile Paillé, Marie Chauveau, Benjamin Gaborit, Pierre Tattevin, Marine de la Chapelle, Rafael Mahieu, Charles Declerck, Mélanie Poinot, David Boutoille, Cédric Arvieux, Valérie Delbos, Marion Baldeyrou, Jean Marc Chapplain, Alexandra Ducancelle, Colin Deschanvres, Charlotte Pronier, François Bénézit, Yves Marie Vandamme, Solène Patrat-Delon, Maeva Lefebvre, Raphaël Lecomte, Charlotte Biron, CHU Pontchaillou [Rennes], and Centre hospitalier universitaire de Nantes (CHU Nantes)
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2019-20 coronavirus outbreak ,Pediatrics ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,[SDV]Life Sciences [q-bio] ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Pneumonia, Viral ,MEDLINE ,03 medical and health sciences ,Betacoronavirus ,Olfaction Disorders ,0302 clinical medicine ,Hyposmia ,Surveys and Questionnaires ,Pandemic ,Medicine ,Humans ,030212 general & internal medicine ,Pandemics ,ComputingMilieux_MISCELLANEOUS ,Retrospective Studies ,Internet ,business.industry ,SARS-CoV-2 ,Hypogeusia ,COVID-19 ,3. Good health ,Infectious Diseases ,France ,medicine.symptom ,business ,Ageusia ,Coronavirus Infections ,030217 neurology & neurosurgery - Abstract
International audience; [No abstract available]
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- 2020
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20. A Highly Prevalent Polymorphism in the Core Region Impairs Quantification of Hepatitis B Virus (HBV) by the cobas TaqMan HBV Assay
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Syria Laperche, Alexandra Ducancelle, Pierre Cappy, Annabelle Servant-Delmas, Laure Boizeau, Stéphane Chevaliez, Vincent Thibault, Institut National de la Transfusion Sanguine [Paris] (INTS), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
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0301 basic medicine ,Microbiology (medical) ,diagnosis ,Cobas taqman ,[SDV]Life Sciences [q-bio] ,030106 microbiology ,underquantification ,viral surveillance ,Biology ,medicine.disease_cause ,Plasma viral load ,03 medical and health sciences ,Blood donations ,chemistry.chemical_compound ,0302 clinical medicine ,Virology ,Genotype ,medicine ,Hepatitis B virus HBV ,Humans ,Genetic variability ,plasma viral load ,Hepatitis B virus ,Viral Load ,3. Good health ,Europe ,chemistry ,DNA, Viral ,030211 gastroenterology & hepatology ,France ,hepatitis B virus ,DNA - Abstract
International audience; The high genetic variability of hepatitis B virus (HBV) can impair DNA quantification. Here, we investigate a major underquantification of HBV by the cobas TaqMan HBV assay (CTM; Roche). In France, between 2005 and 2017, HBV DNA was detected in 3,102 blood donations by use of the CTM (95% limit of detection [LOD], 4.8 IU/ml). HBV strains were sequenced in the S region (LOD, ∼30 IU/ml). Concordant (n = 120) and discordant (n = 45) samples were identified according to the agreement between the plasma viral load (pVL) determined by the CTM and sequencing; all samples were also quantified using the RealTime HBV assay (RTH; Abbott). The viral signature, cloning, and mutagenesis were used to characterize the polymorphism responsible for CTM misquantification. A CTM-RTH discordance (>1 log IU/ml) was found in 14/45 samples that had low pVLs and were successfully genotyped (pVL genoS). PreC/C clones of concordant (C1, C2) and discordant (D1, D2) strains were used to challenge the CTM. Strains D1 and D2 were highly underquantified (42- and 368-fold). In clones, mutating the region corresponding to the CTM reverse primer from a discordant sequence to a concordant sequence restored the levels of quantification to 24% (D1→C1) and 59% (D2→C1) of theoretical levels, while mutating the sequence of a concordant strain to that of a discordant strain led to 78-fold (C1→D1) and 146-fold (C1→D2) decreases in quantification. Moreover, mutating positions 1961 and 1962 was enough to induce a 5-fold underquantification. We conclude that the CTM underestimates pVLs for HBV strains with mutations in the reverse primer target. Specifically, the polymorphism at nucleotides 1961 and 1962 is naturally present in 4.79 and 4.22% of genotype A and D strains, which are highly frequent in Europe, leading to a 5-fold decrease in quantification. Quantification using the new-generation Roche C4800 assay is not affected by this polymorphism.
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- 2020
21. Urinary HPV DNA testing as a tool for cervical cancer screening in women who are reluctant to have a Pap smear in France
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Pascal Veillon, Anne-Sophie Le Duc-Banaszuk, Alexandra Ducancelle, Adeline Pivert, Hélène Le Guillou-Guillemette, Caroline Lefeuvre, Françoise Lunel-Fabiani, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), and Centre régional de coordination des dépistages des cancers-Pays de la Loire
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Adult ,0301 basic medicine ,Microbiology (medical) ,medicine.medical_specialty ,Urinary system ,[SDV]Life Sciences [q-bio] ,030106 microbiology ,Uterine Cervical Neoplasms ,Urine ,Cervical cancer screening ,Sensitivity and Specificity ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Genotype ,Biopsy ,medicine ,Humans ,030212 general & internal medicine ,Papillomaviridae ,Early Detection of Cancer ,ComputingMilieux_MISCELLANEOUS ,Aged ,Medical attention ,Vaginal Smears ,Colposcopy ,medicine.diagnostic_test ,Obstetrics ,business.industry ,Papillomavirus Infections ,virus diseases ,Middle Aged ,female genital diseases and pregnancy complications ,3. Good health ,Hpv testing ,Infectious Diseases ,DNA, Viral ,Female ,France ,business ,Papanicolaou Test - Abstract
Summary Objectives In France, cervical cancer screening is based on human papillomavirus (HPV) testing on cervical samples (women aged 30-65) and cytological examination of Pap smears (25-29), but screening coverage is unsatisfactory. The CapU3 study aimed to propose urinary HPV testing on 13,535 women aged 35 to 65 who had not had a Pap smear since 2010. Methods High-risk HPV (HR-HPV) detection was performed using a real-time PCR (Anyplex II HPV 28 Detection, Seegene®). Women with HR-HPV positive results were encouraged to have a cervical smear as soon as possible to detect the presence of cervical lesions. Results The participation rate was 15.4%. Out of the 1,915 analyzed specimens, 1,711 and 190 were negative and positive, respectively, for at least 1 HR-HPV genotype. HR-HPV genotypes other than HPV-16 or HPV-18 were mostly detected as HPV-53 (23.7%) and HPV-68 (14.2%). A satisfactory gynecological follow-up was observed for HPV-positive women (92.1%). 23 abnormal smears were observed and eight high-grade cytological lesions after colposcopy and biopsy were diagnosed. Conclusions As home HPV urinary testing is non-invasive and does not require medical attention, this method may be an alternative for women who are reluctant to have a Pap smear and thus extend screening coverage.
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- 2020
22. Assessment of SARS-CoV-2 serological tests for the diagnosis of COVID-19 through the evaluation of three immunoassays: Two automated immunoassays (Euroimmun and Abbott) and one rapid lateral flow immunoassay (NG Biotech)
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Françoise Lunel-Fabiani, Achille Kouatchet, Vincent Dubée, Alexandra Ducancelle, Thomas Nicol, Hélène Le Guillou-Guillemette, Orianne Serri, Adeline Pivert, Françoise Joubaud, Caroline Lefeuvre, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre Hospitalier Universitaire d'Angers (CHU Angers), and PRES Université Nantes Angers Le Mans (UNAM)
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0301 basic medicine ,Male ,2019-20 coronavirus outbreak ,Time Factors ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,[SDV]Life Sciences [q-bio] ,Performance ,030106 microbiology ,Pneumonia, Viral ,Antibodies, Viral ,Sensitivity and Specificity ,Article ,Serology ,03 medical and health sciences ,Betacoronavirus ,0302 clinical medicine ,COVID-19 Testing ,Lateral flow immunoassay ,Virology ,Clinical information ,Medicine ,Humans ,Serologic Tests ,030212 general & internal medicine ,Pandemics ,ComputingMilieux_MISCELLANEOUS ,Aged ,Retrospective Studies ,Automation, Laboratory ,Immunoassay ,business.industry ,Clinical Laboratory Techniques ,SARS-CoV-2 ,COVID-19 ,Middle Aged ,3. Good health ,Immunoglobulin A ,Infectious Diseases ,Negative response ,Immunoglobulin G ,Immunology ,Female ,business ,Coronavirus Infections ,Automated immunoassays - Abstract
Highlights • For IgG detection >14 days after symptoms onset was 100.0 % for all assays. • Specificity for IgG was greater than 98 % for CLIA and LFIA compared to ELISA. • LFIA (NG-Test®) is reliable and accurate to diagnose SARS-CoV-2 infection. • Best agreement was observed between CLIA and LFIA assays (97 %; k = 0.936)., Background The emergence of new SARS-CoV-2 has promoted the development of new serological tests that could be complementary to RT-PCR. Nevertheless, the assessment of clinical performances of available tests is urgently required as their use has just been initiated for diagnose. Objectives The aim of this study was to assess the performance of three immunoassays for the detection of SARS-CoV-2 antibodies. Methods Two automated immunoassays (Abbott SARS-CoV-2 CLIA IgG and Euroimmun Anti-SARS-CoV-2 ELISA IgG/IgA assays) and one lateral flow immunoassay (LFIA NG-Test® IgG-IgM COVID-19) were tested. 293 specimens were analyzed from patients with a positive RT-PCR response, from patients with symptoms consistent with COVID-19 but exhibiting a negative response to the RT-PCR detection test, and from control group specimens. Days since symptoms onset were collected from clinical information sheet associated with respiratory tract samples. Results Overall sensitivity for IgG was equivalent (around 80 %) for CLIA, ELISA and LFIA. Sensitivity for IgG detection, >14 days after onset of symptoms, was 100.0 % for all assays. Overall specificity for IgG was greater for CLIA and LFIA (more than 98 %) compared to ELISA (95.8 %). Specificity was significantly different between IgA ELISA (78.9 %) and IgM LFIA (95.8 %) (p 14 days after onset of symptoms for all immunoassays. Specificity was also excellent for IgG CLIA and IgG LFIA. Our study shows that NG-Test® is reliable and accurate for routine use in clinical laboratories.
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- 2020
23. Practical approach to method verification in plasma and validation in cerebrospinal fluid under accreditation using a flexible scope in molecular virology: setting up the HIV, HBV and HCV Aptima™ Quant Dx assays
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Françoise Lunel-Fabiani, Cong T. Tran, Alexandra Ducancelle, Hélène Le Guillou-Guillemette, Adeline Pivert, Caroline Lefeuvre, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), and Université d'Angers (UA)
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0301 basic medicine ,Hepatitis B virus ,Coefficient of variation ,[SDV]Life Sciences [q-bio] ,030106 microbiology ,Clinical Biochemistry ,Human immunodeficiency virus (HIV) ,Hepacivirus ,medicine.disease_cause ,Real-Time Polymerase Chain Reaction ,Turnaround time ,03 medical and health sciences ,Time frame ,medicine ,Humans ,Mathematics ,Blood-Borne Infections ,Scope (project management) ,Biochemistry (medical) ,Reproducibility of Results ,General Medicine ,Repeatability ,Viral Load ,3. Good health ,Internal quality ,030104 developmental biology ,Molecular Diagnostic Techniques ,pol Gene Products, Human Immunodeficiency Virus ,HIV-1 ,RNA, Viral ,Reagent Kits, Diagnostic ,Viral load ,Biomedical engineering - Abstract
BackgroundOur laboratory obtained the ISO 15189 accreditation for the plasmatic HIV-1, HBV and HCV viral load (VL) using the m2000 RealTime™ system, which was recently changed for the platform Panther®. Here, we discuss a strategy for performing method validation/verification very quickly.MethodsWe performed the mandatory (repeatability, internal quality assessment [IQA], measurement uncertainty [MU]) and optional technical verifications for CE/IVD assays using the flexible scope range A. We also performed the mandatory assays for the validation of HIV-1 VL in the cerebrospinal fluid (CSF) using the flexible scope range B. The change was checked by following up on the turnaround time (TAT).ResultsThe coefficient of variation (CV%) for repeatability and IQA complied with the limit of 0.25 log. The MU results ranged from 0.04 to 0.25 log copies or IU/mL. The comparisons of methods showed excellent correlations (R2 = 0.96 for the three parameters) but a delayed centrifugation on HCV VL showed variations of up to 2 log IU/mL. An excellent linearity for HIV-1 in the CSF was obtained from 1.5 to 5 log copies/mL with R2 = 0.99. The TAT increased (84%–98%) in routine usage.ConclusionsThe three Aptima assays are well suited for routine laboratory use and can be integrated within less than 2 weeks in accordance with flexible scope range A. Our data allows us to confidently perform HIV-1 VL in CSF following flexible scope range B. Finally, we provide an organizational guide for flexible scope management in molecular virology within a short time frame.
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- 2020
24. Publisher Correction: A first experience of transduction for differentiated HepaRG cells using lentiviral technology
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Hélène Le Guillou-Guillemette, Alexandra Ducancelle, Cong-Tri Tran, David Durantel, Caroline Lefeuvre, Claude Baillou, Françoise Lunel-Fabiani, François M. Lemoine, and Adeline Pivert
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Multidisciplinary ,Science ,Genetic Vectors ,Lentivirus ,Cell Culture Techniques ,Gene Expression ,Biology ,Flow Cytometry ,Publisher Correction ,Cell Line ,Cell biology ,Mice ,Transduction (genetics) ,Genes, Reporter ,Transduction, Genetic ,Hepatocytes ,Animals ,Medicine ,Transgenes ,Genetic Engineering - Abstract
Currently, there is a lack of systems for studying the role of hepatitis B viral proteins, such as HBeAg and HBcAg, on liver injury. It is necessary to develop an original tool in order to clarify the role of these viral proteins in hepatic stellate cell activation, and to understand the molecular mechanisms of liver injury. HepaRG are the most reliable hepatocyte-like cells for studying liver functions or disorders. In this paper, we demonstrate that the transduction of differentiated HepaRG (dHepaRG) cells can be performed successfully using lentiviral particles. The production of a functional Green Fluorescent Protein (GFP) assessed by Fluorescence Activated Cell Sorting and fluorescence microscopy is up to 16% of GFP positive cells using a multiplicity of infection (MOI) of 2.4. We demonstrate that this technology can allow the stable expression of GFP during the long lifecycle of the cell (up to four weeks after the cell's passage). With this innovative tool, we aim to express viral proteins such as HBeAg or HBcAg in dHepaRG cells. The preliminary results of this work shows that HBeAg can be efficiently produced in dHepaRG cells and that increased MOI allows a better production of this protein. Our future objective will be to study the role of HBc and HBe proteins on the induction of hepatic fibrosis.
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- 2021
25. Human papillomavirus does not play a role in the Barrett esophagus: a French cohort
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Sandrine Bertrais, M. Le Rhun, Françoise Lunel-Fabiani, Nina Dib, Adeline Pivert, Dominique Luet, E. Cesbron-Metivier, Emmanuel Coron, C. Couffon, Sophie Michalak, Charlène Brochard, André Ricard, Alexandra Ducancelle, F.-X. Caroli Bosc, M. Bodin, Nicolas Musquer, CHU Pontchaillou [Rennes], Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Neuropathies du système nerveux entérique et pathologies digestives, implication des cellules gliales entériques, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
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Male ,medicine.medical_specialty ,Biopsy ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Real-Time Polymerase Chain Reaction ,Gastroenterology ,Virus ,Barrett's esophagus ,Barrett Esophagus ,03 medical and health sciences ,Esophagus ,0302 clinical medicine ,Internal medicine ,Prevalence ,medicine ,Humans ,Prospective Studies ,Human papillomavirus ,human papillomavirus ,HPV DNA ,Papillomaviridae ,Aged ,Hyperplasia ,business.industry ,Papillomavirus Infections ,HPV infection ,General Medicine ,[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,Middle Aged ,medicine.disease ,humanities ,3. Good health ,medicine.anatomical_structure ,Dysplasia ,Case-Control Studies ,030220 oncology & carcinogenesis ,Cohort ,Etiology ,Female ,030211 gastroenterology & hepatology ,France ,business ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition - Abstract
International audience; The role of human papillomavirus (HPV) in Barrett's esophagus (BE) has been examined but remains unclear. The purpose of the study is to dispute the connection between HPV and BE in a prospective case-control study. Biopsies were performed above and inside the Barrett's segment for BE patients and in the distal third of the esophagus for control patients for histological interpretation and for virological analysis. Biopsies for virological analysis were placed in a virus transport medium and immediately frozen in liquid nitrogen. Virological analysis involved real-time PCR using the SyBr® green protocol with modified SPF10 general primers. A total of 180 patients (119 control and 61 BE, respectively) were included. In BE patients, 31, 18, and 12 patients had, respectively, no dysplasia, low-grade dysplasia, and high grade dysplasia. Overall, nine were found to be HPV positive: five were control patients and four BE patients. HPV positive status was not associated with BE. No factors were associated with HPV, in particular the degree of BE dysplasia. HPV infection appears unlikely to be significant in the etiology of BE compared with control patients. (ClinicalTrials.gov, Number NCT02549053).
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- 2017
26. A first experience of transduction for differentiated HepaRG cells using lentiviral technology
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Françoise Lunel-Fabiani, Caroline Lefeuvre, Hélène Le Guillou-Guillemette, Claude Baillou, Adeline Pivert, Alexandra Ducancelle, François M. Lemoine, David Durantel, Cong-Tri Tran, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Dieu-Nosjean, Marie-Caroline, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Gestionnaire, Hal Sorbonne Université
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[SDV]Life Sciences [q-bio] ,viruses ,lcsh:Medicine ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,Biology ,Article ,Green fluorescent protein ,Flow cytometry ,03 medical and health sciences ,Transduction (genetics) ,0302 clinical medicine ,Multiplicity of infection ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,medicine ,[SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,lcsh:Science ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,medicine.diagnostic_test ,lcsh:R ,virus diseases ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Hepatitis B ,Hepatic stellate cell activation ,[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,digestive system diseases ,3. Good health ,Cell biology ,[SDV] Life Sciences [q-bio] ,HBcAg ,HBeAg ,Cell culture ,030220 oncology & carcinogenesis ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,lcsh:Q ,Microbiology techniques - Abstract
Currently, there is a lack of systems for studying the role of hepatitis B viral proteins, such as HBeAg and HBcAg, on liver injury. It is necessary to develop an original tool in order to clarify the role of these viral proteins in hepatic stellate cell activation, and to understand the molecular mechanisms of liver injury. HepaRG are the most reliable hepatocyte-like cells for studying liver functions or disorders. In this paper, we demonstrate that the transduction of differentiated HepaRG (dHepaRG) cells can be performed successfully using lentiviral particles. The production of a functional Green Fluorescent Protein (GFP) assessed by Fluorescence Activated Cell Sorting and fluorescence microscopy is up to 16% of GFP positive cells using a multiplicity of infection (MOI) of 2.4. We demonstrate that this technology can allow the stable expression of GFP during the long lifecycle of the cell (up to four weeks after the cell’s passage). With this innovative tool, we aim to express viral proteins such as HBeAg or HBcAg in dHepaRG cells. The preliminary results of this work shows that HBeAg can be efficiently produced in dHepaRG cells and that increased MOI allows a better production of this protein. Our future objective will be to study the role of HBc and HBe proteins on the induction of hepatic fibrosis.
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- 2019
27. Different precore/core mutations of hepatitis B interact with, limit, or favor liver fibrosis severity
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Pascal Veillon, Evelyne Schvoerer, Joël Gozlan, Hélène Le Guillou-Guillemette, Sylvie Larrat, Françoise Lunel-Fabiani, Adeline Pivert, Vincent Mackiewicz, Véronique Brodard, Véronique Loustaud-Ratti, Vincent Thibault, Emmanuel Gordien, Sophie Alain, Alexandra Ducancelle, Jérôme Boursier, Sandrine Castelain, Sandrine Bertrais, Marianne Coste-Burel, Bénédicte Roquebert, Paul Calès, Sarah Maylin, Stéphane Chevaliez, and Viorica Balan
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Hepatitis B virus ,medicine.medical_specialty ,HBsAg ,Mutation ,Hepatology ,business.industry ,Gastroenterology ,Hepatitis B ,medicine.disease ,medicine.disease_cause ,Virology ,3. Good health ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Fibrosis ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,030211 gastroenterology & hepatology ,Hepatic fibrosis ,business ,Viral hepatitis - Abstract
BACKGROUND AND AIM The impact of basal core promoter (BCP) and precore (PC) mutants of the hepatitis B virus (HBV) on liver disease severity remains controversial. The aim of the present study was to screen BCP and PC mutations in 252 HBV surface antigen (HBsAg) positive carriers in France and to assess relationships between these mutations and severe fibrosis. METHODS Direct sequencing of the precore/core gene was used to detect A1762T/G1764A and G1757A mutations in the BCP and G1896A and G1899A mutations in the PC region. RESULTS The prevalences of A1762T/G1764A, G1757A, G1896A, and G1899A mutations were 34.1%, 38.7%, 54.9%, and 29.3% (P
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- 2016
28. Zona : risques et prévention sous immuno-modulateurs
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Cong Tri Tran, Charles Masson, Françoise Lunel-Fabiani, and Alexandra Ducancelle
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030203 arthritis & rheumatology ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,030212 general & internal medicine - Abstract
Resume Le zona est une infection potentiellement grave ou invalidante, notamment chez des patients presentant une immunodepression due a une pathologie ou un traitement. Les traitements immuno-modulateurs peuvent etre associes a une augmentation du risque infectieux. Certains facteurs de risque sont bien reconnus, comme l’âge avance et la prise de corticoides. Pour les medications comme le methotrexate, le tofacitinib, les anti-TNF alpha (infliximab, adalimumab, etanercept, certolizumab, golimumab), l’abatacept, le tocilizumab, le rituximab, les donnees sont plus divergentes. Neanmoins, les patients sous biomedicaments sont plus a risque de developper un zona, en raison de la pathologie justifiant ce traitement ou du fait du traitement lui-meme. Un vaccin contre le zona a montre son efficacite et sa securite d’emploi chez les patients immunocompetents. Il n’est pas cependant recommande actuellement chez les patients immunodeprimes, en particulier les personnes sous biomedicaments, du fait du manque d’etude sur le rapport benefice/risque de ce vaccin vivant attenue. Pourtant, des etudes recentes montrent des resultats encourageants sur l’efficacite et la securite du vaccin utilise chez des patients immunodeprimes ou sous biomedicaments, laissant suggerer une possible utilisation future. D’autres voies alternatives sont egalement a l’essai, et permettraient de proteger cette population du risque de zona et de ses complications. Une reflexion nouvelle dans le choix ou le non-choix de la realisation de la vaccination contre le zona – qui ?, Quand ?, Comment ? Avec quelle repetition ? – est devenue necessaire selon les maladies systemiques chroniques, les periodes de la vie, le statut virologique varicelle-zona, les differentes et successives therapeutiques.
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- 2016
29. Sequence Variation in Amplification Target Genes and Standards Influences Interlaboratory Comparison of BK Virus DNA Load Measurement
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Pilar Domingo-Calap, Bruno MOULIN, Valerie Giordanengo, Seiamak Bahram, Véronique Avettand-Fenoel, Sébastien Hantz, Samira Fafi-Kremer, Jerome LeGoff, ALEXANDRA DUCANCELLE, Bruno POZZETTO, Sophie Caillard, ERIC SOULIER, Peggy Perrin, Sylvie Pillet, Morgane Solis, Astrid VABRET, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), French BKV Study Group, Laboratoire de Virologie [Hôpitaux universitaires de Strasbourg], Immunorhumathologie moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM), Virulence bactérienne précoce, Université de Strasbourg (EA7290), Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, Service de Néphrologie et Transplantation, Interaction virus-hôte et maladies du foie, Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Virulence Bactérienne Précoce : fonctions cellulaires et contrôle de l'infection aigüe et subaigüe, Université de Strasbourg (UNISTRA), Centre National de la Recherche Scientifique (CNRS)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), and BRICHEUX, Genevieve
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Microbiology (medical) ,Laboratory Proficiency Testing ,viruses ,030230 surgery ,Biology ,medicine.disease_cause ,[SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology ,Sensitivity and Specificity ,Sciences du Vivant [q-bio]/Médecine humaine et pathologie ,isolation & purification ,03 medical and health sciences ,0302 clinical medicine ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Virology ,Genetic variation ,Genotype ,medicine ,Humans ,Sequence variation ,methods ,standards ,Gene ,[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Genetics ,Sciences du Vivant [q-bio]/Ingénierie biomédicale ,Polyomavirus Infections ,0303 health sciences ,diagnosis ,virology ,030306 microbiology ,genetics ,Genetic Variation ,virus diseases ,Viral Load ,[SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology ,DNA extraction ,Hospitals ,3. Good health ,BK virus ,BK Virus ,DNA, Viral ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,France ,Primer (molecular biology) ,Viral load - Abstract
International guidelines define a BK virus (BKV) load of ≥4 log 10 copies/ml as presumptive of BKV-associated nephropathy (BKVN) and a cutoff for therapeutic intervention. To investigate whether BKV DNA loads (BKVL) are comparable between laboratories, 2 panels of 15 and 8 clinical specimens (urine, whole blood, and plasma) harboring different BKV genotypes were distributed to 20 and 27 French hospital centers in 2013 and 2014, respectively. Although 68% of the reported results fell within the acceptable range of the expected result ±0.5 log 10 , the interlaboratory variation ranged from 1.32 to 5.55 log 10 . Polymorphisms specific to BKV genotypes II and IV, namely, the number and position of mutations in amplification target genes and/or deletion in standards, arose as major sources of interlaboratory disagreements. The diversity of DNA purification methods also contributed to the interlaboratory variability, in particular for urine samples. Our data strongly suggest that (i) commercial external quality controls for BKVL assessment should include all major BKV genotypes to allow a correct evaluation of BKV assays, and (ii) the BKV sequence of commercial standards should be provided to users to verify the absence of mismatches with the primers and probes of their BKV assays. Finally, the optimization of primer and probe design and standardization of DNA extraction methods may substantially decrease interlaboratory variability and allow interinstitutional studies to define a universal cutoff for presumptive BKVN and, ultimately, ensure adequate patient care.
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- 2015
30. Evaluation of the Aptima™ HBV Quant Dx assay for semi-quantitative HBV viral load from dried blood spots
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Caroline Lefeuvre, Hélène Le Guillou-Guillemette, Steven Roger, Alexandra Ducancelle, Marine Grison, Adeline Pivert, Françoise Lunel-Fabiani, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), and Université d'Angers (UA)
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0301 basic medicine ,Hepatitis B virus ,[SDV]Life Sciences [q-bio] ,030106 microbiology ,medicine.disease_cause ,Sensitivity and Specificity ,Plasma ,03 medical and health sciences ,0302 clinical medicine ,Virology ,medicine ,Humans ,030212 general & internal medicine ,Dried blood ,ComputingMilieux_MISCELLANEOUS ,Whole blood ,Hepatitis ,Detection limit ,Spots ,business.industry ,Viral Load ,medicine.disease ,3. Good health ,Infectious Diseases ,Dried Blood Spot Testing ,business ,Viral load ,Semi quantitative - Abstract
Background The detection and quantification of hepatitis B virus (HBV) DNA from dried blood spots (DBS) is a major tool for chronic hepatitis B management in resource-limited settings. This strategy fits in perfectly with the hepatitis control plan promoted by the World Health Organization. However, few commercial methods are validated for viral load (VL) measurement on DBS. Objectives Our objective was to evaluate the performance of the HBV VL measurement of the Aptima™ HBV Quant Dx assay on DBS compared to plasma samples on the Panther® platform (Hologic). Study design 266 whole blood samples for routine measurement were included. Five spots of 75 μL of whole blood were loaded onto a card before centrifugation and plasma settling. Results 149 samples were quantifiable and 117 were not detected. We achieved excellent linearity (r² = 0.994) over a wide range of measurements suitable for clinical practice, and a 95 % lower limit of detection (LLOD-95 %) at 2.65 log10 IU/mL (445 IU/mL). A good performance of this assay was observed for samples with HBV VL > LLOD-95 % and 100 % of samples were detected if HBV VL was above 2.95 log10 IU/mL. The correlation between the two matrices for quantitative VLs was good (r² = 0.978) with a very low bias (-0.002 log10 IU/mL). Conclusion The Aptima™ assay can properly detect and quantify HBV DNA in DBS, providing a satisfactory use in clinical monitoring and therapeutic decisions. DBS represents an excellent alternative to plasma, especially in resource-limited countries, while maintaining the performance and advantages of an automated technique.
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- 2020
31. Fatal Myopericarditis Following an Influenza A (H3N2) Infection
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Caroline Lefeuvre, Françoise Lunel-Fabiani, Antonio Monteiro-Rodrigues, Alexandra Ducancelle, Stéphane Triau, Hélène Le Guillou-Guillemette, François Templier, Cong Tri Tran, Vincent Enouf, Sylvie Behillil, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université Bretagne Loire (UBL), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Génomique virale et vaccination, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
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0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Myocarditis ,Adolescent ,Fulminant ,[SDV]Life Sciences [q-bio] ,Orthomyxoviridae ,medicine.disease_cause ,Pericardial effusion ,Pericardial Effusion ,03 medical and health sciences ,Lethargy ,Fatal Outcome ,Cardiac tamponade ,Influenza, Human ,medicine ,Influenza A virus ,Humans ,Phylogeny ,biology ,Sequence Analysis, RNA ,business.industry ,Influenza A Virus, H3N2 Subtype ,Articles ,General Medicine ,medicine.disease ,biology.organism_classification ,030112 virology ,Heart Arrest ,3. Good health ,Cardiac Tamponade ,RNA ,Female ,business ,Sequence Analysis ,Myopericarditis - Abstract
Patient: Female, 14 Final Diagnosis: Myopericarditis Symptoms: Cardiac tamponade • dyspnea • pericardial effusion • tachycardia Medication: — Clinical Procedure: Cardiopulmonary resuscitation Specialty: Infectious Diseases Objective: Unusual clinical course Background: Influenza viruses induce uncomplicated infections in most cases in individuals with no known predisposing factors. Acute febrile illness is generally limited to upper respiratory symptoms and several constitutional symptoms, including headache, lethargy, and myalgia. However, influenza A virus is a cause of severe morbidity and mortality worldwide. Some patients are at risk for serious and fatal complications. Cardiac involvement is a well-known condition, but, clinically apparent influenza myocarditis is not common. Few reports exist regarding recurrent fulminant influenza myocarditis. Case Report: We report here a fatal case of heart failure following myocarditis in a 14-year-old female who had seasonal flu symptoms but was otherwise healthy. H3N2 influenza virus infection was detected by molecular analyses of throat and nasal swabs, suggesting damage to myocardial cells caused directly by the virus. Conclusions: Pericardial effusion myopericarditis may occur during influenza virus infection in young individuals, even those with no known predisposing factors. Physicians need to be aware that acute myopericarditis can be a fatal complication of recent influenza virus infection in all patients with instable hemodynamics. Early diagnosis and treatment could reduce, in some cases, the risk of severe cardiac events. However, this sudden and fatal outcome was difficult to predict in a healthy young female with no known risk factors.
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- 2018
32. Natural non-homologous recombination led to the emergence of a duplicated V3-NS5A region in HCV-1b strains associated with hepatocellular carcinoma
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Françoise Stoll-Keller, Henia Saoudin, Arielle A. Rosenberg, Dominique Bettinger, Pascal Veillon, Odile Petsaris, Cécile Henquell, Bruno Pozzetto, Catherine Gaudy-Graffin, Jean-Baptiste Bour, Sophie Minjolle-Cha, Jacques Izopet, Christopher Payan, E. Bouthry, Alexandra Ducancelle, Adeline Pivert, Hélène Le Guillou-Guillemette, Gisèle Lagathu, Sylvie Larrat, P. André, Anne Signori-Schmuck, Sophie Vallet, Françoise Lunel-Fabiani, Jean-Michel Pawlotsky, Yazid Baazia, Elisabeth André-Garnier, Christophe Lemaire, Florence Abravanel, Pascale Trimoulet, Sophie Alain, Vincent Thibault, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Clermont-Ferrand, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Service de Bactériologie, Virologie, Hygiène [CHU Limoges], CHU Limoges, Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), CHU Pontchaillou [Rennes], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Virologie de l'hépatite C (EA 4474), Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Hôtel-Dieu de Nantes, Laboratoire de sérologie-virologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de bactériologie-Virologie-Hygiène [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet - Saint-Étienne (UJM), Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de Recherche en Horticulture et Semences (IRHS), Université d'Angers (UA)-Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Université Grenoble Alpes (UGA), Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Université Jean Monnet [Saint-Étienne] (UJM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA)-Université d'Angers (UA), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Université de Tours-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de la Santé et de la Recherche Médicale (INSERM), and AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA)-Université d'Angers (UA)
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RNA viruses ,0301 basic medicine ,Mutant ,lcsh:Medicine ,Hepacivirus ,Viral Nonstructural Proteins ,Biochemistry ,Cohort Studies ,Database and Informatics Methods ,Viral Envelope Proteins ,Gene Duplication ,Gene duplication ,Evolutionary Emergence ,lcsh:Science ,Homologous Recombination ,Pathology and laboratory medicine ,Phylogeny ,Data Management ,Recombination, Genetic ,Genetics ,Multidisciplinary ,Hepatitis C virus ,Liver Neoplasms ,Phylogenetic Analysis ,Medical microbiology ,Hepatitis C ,3. Good health ,Nucleic acids ,Phylogenetics ,Viruses ,Host-Pathogen Interactions ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Pathogens ,Sequence Analysis ,Recombination ,Research Article ,Computer and Information Sciences ,Evolutionary Processes ,Carcinoma, Hepatocellular ,DNA recombination ,Bioinformatics ,030106 microbiology ,Viral quasispecies ,Biology ,Research and Analysis Methods ,Microbiology ,Viral Evolution ,Evolution, Molecular ,03 medical and health sciences ,Virology ,Humans ,Evolutionary Systematics ,Gene ,DNA sequence analysis ,Taxonomy ,Medicine and health sciences ,Cloning ,Evolutionary Biology ,Polymorphism, Genetic ,Biology and life sciences ,Flaviviruses ,lcsh:R ,Organisms ,Viral pathogens ,RNA ,Bayes Theorem ,DNA ,Hepatitis viruses ,Organismal Evolution ,Microbial pathogens ,030104 developmental biology ,Genetic Loci ,Microbial Evolution ,Mutation ,lcsh:Q ,Homologous recombination ,Sequence Alignment - Abstract
International audience; Background: The emergence of new strains in RNA viruses is mainly due to mutations or intra and inter-genotype homologous recombination. Non-homologous recombinations may be deleterious and are rarely detected. In previous studies, we identified HCV-1b strains bearing two tandemly repeated V3 regions in the NS5A gene without ORF disruption. This polymorphism may be associated with an unfavorable course of liver disease and possibly involved in liver carcinogenesis. Here we aimed at characterizing the origin of these mutant strains and identifying the evolutionary mechanism on which the V3 duplication relies.Methods: Direct sequencing of the entire NS5A and E1 genes was performed on 27 mutant strains. Quasispecies analyses in consecutive samples were also performed by cloning and sequencing the NS5A gene for all mutant and wild strains. We analyzed the mutant and wild-type sequence polymorphisms using Bayesian methods to infer the evolutionary history of and the molecular mechanism leading to the duplication-like event.Results: Quasispecies were entirely composed of exclusively mutant or wild-type strains respectively. Mutant quasispecies were found to have been present since contamination and had persisted for at least 10 years. This V3 duplication-like event appears to have resulted from non-homologous recombination between HCV-1b wild-type strains around 100 years ago. The association between increased liver disease severity and these HCV-1b mutants may explain their persistence in chronically infected patients.Conclusions: These results emphasize the possible consequences of non-homologous recombination in the emergence and severity of new viral diseases.
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- 2017
33. Herpes zoster: Risk and prevention during immunomodulating therapy
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Alexandra Ducancelle, Françoise Lunel-Fabiani, Charles Masson, Cong Tri Tran, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), and Université Paris 13 (UP13)
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Male ,medicine.medical_specialty ,Herpes Zoster Vaccine ,viruses ,[SDV]Life Sciences [q-bio] ,Population ,Disease ,medicine.disease_cause ,Herpes Zoster ,Risk Assessment ,Immunomodulation ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Tocilizumab ,Rheumatology ,Internal medicine ,Rheumatic Diseases ,medicine ,Adalimumab ,Humans ,030212 general & internal medicine ,education ,030203 arthritis & rheumatology ,education.field_of_study ,Biological Products ,business.industry ,Biotherapy ,Abatacept ,Vaccination ,Varicella zoster virus ,virus diseases ,Infliximab ,3. Good health ,Treatment Outcome ,chemistry ,Immunology ,Immunomodulators ,Varicella-zoster virus ,Female ,Immunization ,business ,medicine.drug ,Follow-Up Studies - Abstract
International audience; Herpes zoster can be serious or incapacitating, particularly in patients whose immune system is compromised by a disease or treatment. Immunomodulating drugs can increase the risk of infection. Well-established risk factors include advanced age and glucocorticoid therapy. The data are somewhat conflicting for medications such as methotrexate, tofacitinib, TNFα antagonists (infliximab, adalimumab, etanercept, certolizumab, and golimumab), abatacept, tocilizumab, and rituximab. Nevertheless, the risk of herpes zoster is increased in patients taking biological agents, because of the underlying diseases and/or effects of the drugs. A live attenuated herpes zoster vaccine has been proven effective and safe in immunocompetent individuals. At present, however, it is not recommended for patients with immunodeficiencies, including those taking biological drugs, as no studies have assessed its risk/benefit ratio in this population. This situation may change in the near future, as recent data support the effectiveness and safety of the herpes zoster vaccine in patients who take biotherapies or have other causes of immunodeficiency. Alternative approaches designed to protect these patients from herpes zoster and its complications are also under evaluation. There is a need to define the indications of the herpes zoster vaccine in terms of the target population, timing, modalities, and frequency, according to the underlying chronic systemic disease, age group, varicella-zoster virus status, and exposure to therapeutic agents.
- Published
- 2017
34. A Single Test Combining Blood Markers and Elastography is More Accurate Than Other Fibrosis Tests in the Main Causes of Chronic Liver Diseases
- Author
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Dominique Salmon, Paul Calès, Victor de Ledinghen, Brigitte Le Bail, Alexandra Ducancelle, Julien Vergniol, Jean-Pierre Zarski, Vincent Leroy, Eric Nguyen Khac, Nathalie Sturm, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépato-gastroentérologie [CHU Grenoble Alpes], Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Département d'anatomie et cythologie pathologique, CHU Grenoble-Hôpital Michallon, Laboratoire d'anatomie pathologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Département d'hépato-gastroentérologie, CHU Grenoble-Université Grenoble Alpes (UGA), Service d'Hépato-gastroentérologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Service Maladies infectieuses et tropicales [AP-HP Hôpital Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Centre d'investigation de la fibrose hépatique [CHU de Bordeaux] (Hôpital Haut-Lévêque ), Hôpital Haut-Lévêque [CHU de Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), and Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble
- Subjects
Adult ,Liver Cirrhosis ,Male ,Pathology ,medicine.medical_specialty ,[SDV]Life Sciences [q-bio] ,Disease ,Severity of Illness Index ,End Stage Liver Disease ,03 medical and health sciences ,0302 clinical medicine ,Fibrosis ,Severity of illness ,Medicine ,Blood test ,Humans ,Aspartate Aminotransferases ,Prospective Studies ,Stage (cooking) ,Prospective cohort study ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Platelet Count ,Liver Diseases ,Fatty liver ,Gastroenterology ,Middle Aged ,medicine.disease ,3. Good health ,Liver ,ROC Curve ,030220 oncology & carcinogenesis ,Elasticity Imaging Techniques ,030211 gastroenterology & hepatology ,Female ,Elastography ,business ,Biomarkers - Abstract
International audience; BACKGROUND AND GOAL: International guidelines suggest combining a blood test and liver stiffness measurement (LSM) to stage liver fibrosis in chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). Therefore, we compared the accuracies of these tests between the main etiologies of chronic liver diseases.STUDY: Overall, 1968 patients were included in 5 etiologies: CHC: 698, chronic hepatitis B: 152, human immunodeficiency virus/CHC: 628, NAFLD: 225, and alcoholic liver disease (ALD): 265. Sixteen tests [13 blood tests, LSM (Fibroscan), 2 combined: FibroMeters] were evaluated. References were Metavir staging and CHC etiology. Accuracy was evaluated mainly with the Obuchowski index (OI) and accessorily with area under the receiver operating characteristics (F≥2, F≥3, cirrhosis).RESULTS: OIs in CHC were: FibroMeters: 0.812, FibroMeters: 0.785 to 0.797, Fibrotest: 0.762, CirrhoMeters: 0.756 to 0.771, LSM: 0.754, Hepascore: 0.752, FibroMeter: 0.750, aspartate aminotransferase platelet ratio index: 0.742, Fib-4: 0.741. In other etiologies, most tests had nonsignificant changes in OIs. In NAFLD, CHC-specific tests were more accurate than NAFLD-specific tests. The combined FibroMeters had significantly higher accuracy than their 2 constitutive tests (FibroMeters and LSM) in at least 1 diagnostic target in all etiologies, except in ALD where LSM had the highest OI, and in 3 diagnostic targets (OIs and 2 area under the receiver operating characteristics) in CHC and NAFLD.CONCLUSIONS: Some tests developed in CHC outperformed other tests in their specific etiologies. Tests combining blood markers and LSM outperformed single tests, validating recent guidelines and extending them to main etiologies. Noninvasive fibrosis evaluation can thus be simplified in the main etiologies by using a unique test: either LSM alone, especially in ALD, or preferably combined to blood markers.
- Published
- 2017
35. Maladies systémiques et biomédicaments : comprendre, apprécier et prévenir le risque de réactivation d’hépatite B
- Author
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Françoise Lunel-Fabiani, Charles Masson, and Alexandra Ducancelle
- Subjects
Rheumatology - Abstract
Resume Les reactivations d’infections par le virus de l’hepatite B (VHB) sont connues chez les porteurs chroniques de l’antigene (Ag) HBs et representent une complication classique des traitements immunosuppresseurs. Elles ont ete decrites egalement chez des patients ayant ete en contact avec le VHB. Depuis l’utilisation de plus en plus frequente des biotherapies (anti-TNF-α, rituximab, abatacept, tocilizumab) dans les maladies systemiques, de nombreuses publications ont fait etat du risque de reactivation de l’hepatite B. Les societes savantes concernees ont emis des recommandations visant a prevenir ces reactivations. Il s’agit principalement du depistage des marqueurs d’infection chronique (AgHBs) ou ancienne (Ac anti-HBc) par le VHB, avant l’instauration de ces traitements, d’une vaccination des sujets n’ayant pas de marqueurs et de propositions de suivis rapproches et ou de traitements antiviraux delivres avant la mise sous-immunosuppresseurs ou lors des reactivations. Dans cette mise au point, nous tentons de clarifier les mecanismes physiopathologiques des reactivations d’hepatite B sous-biotherapie, en particulier dans les infections B occultes, chez les patients ayant des marqueurs d’infection ancienne par le VHB, chez qui persiste, dans les noyaux des hepatocytes, de l’ADN du VHB sous une forme de resistance (ADNccc). Les risques sont apprecies en fonction du statut du patient vis-a-vis du VHB, des differentes molecules utilisees et selon les donnees de la litterature. Enfin, nous discutons les differentes recommandations et modalites de vaccination, de traitement preemptif et de prise en charge des patients, en fonction du risque et des circonstances de survenue de ces reactivations.
- Published
- 2014
36. Correlation between the promoter basal core and precore mutations and HBsAg quantification in French blood donors infected with hepatitis B virus
- Author
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A. Servant-Delmas, Adeline Pivert, Syria Laperche, Alexandra Ducancelle, Françoise Lunel-Fabiani, and H. Le Guillou-Guillemette
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Hepatitis B virus ,0303 health sciences ,HBsAg ,virus diseases ,Biology ,Hepatitis B ,medicine.disease_cause ,medicine.disease ,Virology ,digestive system diseases ,Virus ,3. Good health ,03 medical and health sciences ,Titer ,0302 clinical medicine ,Infectious Diseases ,HBeAg ,Genotype ,medicine ,030211 gastroenterology & hepatology ,Viral load ,030304 developmental biology - Abstract
Hepatitis B virus (HBV) basal core promoter (BCP) and precore (PC) mutations, HBV viral load and HBV surface antigen (HBsAg) quantitation were screened to assess correlations between these HBV markers in asymptomatic chronic hepatitis B carriers in France. From January 2006 to July 2007, 200 sera were collected from patients who were discovered to be HBsAg-positive when they volunteered to give blood. Direct sequencing of precore/core gene was used to detect A1762T/G1764A mutations in the BCP and G1896A in the PC region. HBV viral load and HBsAg were quantified with two commercials assays. The prevalence of the BCP and PC mixed/mutants were 37% and 60% respectively (P = 0.0001). HBV DNA level and HBsAg titer were significantly lower in subjects harboring the mixed/mutant PC virus compared to those infected by the wild phenotype. No significant difference was observed in HBV viral loads of blood donors infected by wild or mixed/mutant BCP viruses. Mutant or mixed PC virus was associated with male gender, HBeAb-positive status and HBV/D and HBV/E genotypes. BCP mutations were associated with age, and both HBV/A-HBV/E genotypes.The genetic properties of HBV in this cohort showed that most of the blood donors had a negative HBeAg serological status and harbored the PC mutant phenotype in combination with low levels of both HBV DNA and HBsAg. As the study was conducted in healthy subjects who could be considered as asmptomatic carriers, these results suggest a possible protective effect of the G1896A mutation against severe liver lesions. J. Med. Virol. 87:529–535, 2015. © 2014 Wiley Periodicals, Inc.
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- 2014
37. Severe viral hepatitis in a patient with chronic lymphocytic leukemia (CLL) complicated with autoimmune hemolytic anemia (AIHA), treated with steroids
- Author
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Mathilde Hunault-Berger, Frédéric Oberti, Marie-Christine Rousselet, Caroline Eymerit-Morin, Aline Tanguy-Schmidt, Corentin Orvain, Alexandra Ducancelle, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Bernardo, Elizabeth, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), and Université d'Angers (UA)
- Subjects
Hepatitis, Viral, Human ,[SDV]Life Sciences [q-bio] ,Biopsy ,Chronic lymphocytic leukemia ,viral hepatitis ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Autopsy ,Disease ,autoimmune hemolytic anemia (AIAH) ,03 medical and health sciences ,Fatal Outcome ,0302 clinical medicine ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,hemic and lymphatic diseases ,Virology ,chronic lymphocytic leukemia (CLL) ,medicine ,Humans ,Aged ,Disseminated intravascular coagulation ,Hepatitis ,business.industry ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,3. Good health ,Infectious Diseases ,Liver ,030220 oncology & carcinogenesis ,Immunology ,Female ,Steroids ,Anemia, Hemolytic, Autoimmune ,Autoimmune hemolytic anemia ,business ,Viral hepatitis ,Esophagitis ,Immunosuppressive Agents ,030215 immunology - Abstract
International audience; Infectious complications are a major cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL) due to impaired immunity secondary to the disease itself and to the immunosuppressive therapies administered to these patients. We report a 78-year-old woman with CLL who was treated with steroids for autoimmune hemolytic anemia (AIHA). A few weeks later, she was admitted for severe acute hepatitis with disseminated intravascular coagulation (DIC). Despite the symptomatic treatment of DIC, standard reanimation and probabilistic antibiotics, the patient died within 24h with severe hepatic failure. Autopsy was in favor of a disseminated viral infection with esophageal, hepatic and pulmonary cytopathologic lesions with acidophilic intranuclear inclusions suggestive of herpes virus, even though HSV 1 and 2, CMV and HHV6 PCRs were negative. This case of severe viral hepatitis with esophagitis occurring three weeks after the introduction of high-dose steroid treatment for AIHA in a CLL patient calls for anti-herpetic prophylaxis in such patients, immunodepressed by their diseases and the treatment they receive.
- Published
- 2015
38. Prognostic durability of liver fibrosis tests and improvement in predictive performance for mortality by combining tests
- Author
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Alexandra Ducancelle, Frédéric Oberti, Isabelle Fouchard-Hubert, Paul Calès, Valérie Moal, Sandrine Bertrais, Jérôme Boursier, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), and PRES Université Nantes Angers Le Mans (UNAM)
- Subjects
0301 basic medicine ,Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Multivariate analysis ,Time Factors ,Adolescent ,[SDV]Life Sciences [q-bio] ,Chronic liver disease ,Gastroenterology ,Risk Assessment ,03 medical and health sciences ,Liver disease ,Young Adult ,0302 clinical medicine ,Liver Function Tests ,Fibrosis ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Aspartate Aminotransferases ,Young adult ,Hepatology ,medicine.diagnostic_test ,business.industry ,Platelet Count ,Middle Aged ,medicine.disease ,Prognosis ,Confidence interval ,3. Good health ,Surgery ,030104 developmental biology ,Predictive value of tests ,Chronic Disease ,Multivariate Analysis ,030211 gastroenterology & hepatology ,Female ,business ,Liver function tests ,Biomarkers ,Follow-Up Studies - Abstract
International audience; BACKGROUND AND AIM: There is currently no recommended time interval between noninvasive fibrosis measurements for monitoring chronic liver diseases. We determined how long a single liver fibrosis evaluation may accurately predict mortality, and assessed whether combining tests improves prognostic performance.METHODS: We included 1559 patients with chronic liver disease and available baseline liver stiffness measurement (LSM) by Fibroscan, aspartate aminotransferase to platelet ratio index (APRI), FIB-4, Hepascore, and FibroMeterV2G .RESULTS: Median follow-up was 2.8 years during which 262 (16.8%) patients died, with 115 liver-related deaths. All fibrosis tests were able to predict mortality, although APRI (and FIB-4 for liver-related mortality) showed lower overall discriminative ability than the other tests (differences in Harrell's C-index: P < 0.050). According to time-dependent AUROCs, the time period with optimal predictive performance was 2-3 years in patients with no/mild fibrosis, 1 year in patients with significant fibrosis, and
- Published
- 2016
39. Does Epoetin Beta Still Have a Place in Peginterferon Alpha-2a Plus Ribavirin Treatment Strategies for Chronic Hepatitis C?
- Author
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Manh Thông Dao, Nicolas Picard, Patrick Saulnier, Véronique Loustaud-Ratti, Dominique Larrey, Pascal Veillon, Françoise Lunel-Fabiani, Alexandra Ducancelle, Louis d’Alteroche, Nathalie Boyer-Darrigand, Hélène Le Guillou-Guillemette, Isabelle Fouchard-Hubert, Centre Hospitalier Universitaire d'Angers ( CHU Angers ), PRES Université Nantes Angers Le Mans ( UNAM ), Laboratoire HIFIH, Université d'Angers ( UA ), Micro et nanomédecines biomimétiques ( MINT ), Université d'Angers ( UA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Bretagne Loire ( UBL ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Micro et Nanomédecines Biomimétiques (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL), Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Univ Angers, Okina
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Male ,0301 basic medicine ,Simple noninvasive index ,Sustained virology response ,Gene Expression ,Hepacivirus ,Pharmacology ,medicine.disease_cause ,Gastroenterology ,Polyethylene Glycols ,chemistry.chemical_compound ,0302 clinical medicine ,Recurrence ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Pegylated interferon ,Significant fibrosis ,Pyrophosphatases ,Epoetin beta ,HCV-Infected Patients ,virus diseases ,Alanine Transaminase ,Anemia ,Middle Aged ,Viral Load ,Recombinant Proteins ,3. Good health ,Treatment Outcome ,Interferon alpha ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,RNA, Viral ,Drug Therapy, Combination ,Female ,030211 gastroenterology & hepatology ,ITPA ,[SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy ,Growth factors ,Viral load ,medicine.drug ,Adult ,medicine.medical_specialty ,Genotype ,Hepatitis C virus ,Immunology ,Alpha interferon ,Antiviral Agents ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Virology ,Internal medicine ,Ribavirin ,medicine ,Humans ,Double blind ,Aspartate Aminotransferases ,Combination therapy ,Erythropoietin ,[ SDV ] Life Sciences [q-bio] ,business.industry ,Interleukins ,Virus genotype-1 patients ,Interferon-alpha ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,[SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy ,Cell Biology ,Hepatitis C, Chronic ,[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,digestive system diseases ,030104 developmental biology ,chemistry ,Antiviral treatment ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Interferons ,business - Abstract
International audience; To investigate the impact of epoetin beta (EPO) on sustained virological response (SVR) in hepatitis C virus (HCV)-infected patients treated with peginterferon-ribavirin (RBV). Controlled, randomized, pragmatic multicenter study to assess 2 strategies, ie, the use (EPO group) or nonuse (control group) of EPO in terms of achieving SVR in treatment-naive, genotype non-2/non-3 HCV-infected patients receiving a 48-week treatment regimen of pegylated interferon alpha-2a (peg-IFN) plus RBV (randomization 2:1). The single-nucleotide polymorphisms of interferon lambda 3 (IFNL3) (rs12979860 and rs8099917), interferon lambda 4 (IFNL4) (ss469415590), and inosine triphosphatase (ITPA) (rs1127354 and rs7270101) were determined retrospectively. Two hundred twenty-seven patients were included in the study. In the global population (n = 227), the overall SVR rate was 52% (118/227). Nonresponse and relapse occurred in respectively 46/227 (20.3%) and 42/227 (18.5%) patients. In the intention-to-treat analysis, 55.5% of patients with anemia (n = 164) had a SVR, specifically 57.4% in the EPO group versus 52.4% in the control group, but the difference was not statistically significant. In the anemic population, independent factors associated with SVR were IFNL3 and IFNL4 polymorphisms, pretreatment HCV RNA level, iron level, and aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio. EPO has little impact on SVR in patients treated with peg-IFN+RBV and should be recommended only for patients with severe anemia.
- Published
- 2016
40. Hypogammaglobulinemia and risk of severe infection in kidney transplant recipients
- Author
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Virginie Langs, Agnès Duveau, Myriam Ammi, Jean-François Subra, R. Legall, Jean Picquet, Thibaut Culty, Alexandra Ducancelle, Alain Chevailler, Cyril Sargentini, Jean-François Augusto, Julien Demiselle, Anne-Sophie Garnier, Johnny Sayegh, Caroline Poli, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Néphrologie-Dialyse-Transplantation [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), PRES Université Nantes Angers Le Mans (UNAM), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA), Réanimation Médicale, Université d'Angers - Faculté de médecine (UA UFR Médecine), Laboratoire d'Immunologie et d'Allergologie, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Department of Kidney Transplantation CHU Angers, and PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre Hospitalier Universitaire d'Angers (CHU Angers)
- Subjects
Graft Rejection ,Male ,Time Factors ,[SDV]Life Sciences [q-bio] ,030232 urology & nephrology ,030230 surgery ,Gastroenterology ,Kidney transplant ,Hypogammaglobulinemia ,0302 clinical medicine ,Postoperative Complications ,Agammaglobulinemia ,Risk Factors ,Odds Ratio ,Prevalence ,Prospective cohort study ,biology ,Hazard ratio ,Age Factors ,Bacterial Infections ,Middle Aged ,3. Good health ,Infectious Diseases ,Virus Diseases ,Cohort ,Female ,Antibody ,Immunosuppressive Agents ,Adult ,medicine.medical_specialty ,Adolescent ,03 medical and health sciences ,Young Adult ,Internal medicine ,medicine ,Humans ,In patient ,Aged ,Proportional Hazards Models ,Retrospective Studies ,severe infection ,Immunosuppression Therapy ,Transplantation ,business.industry ,Odds ratio ,medicine.disease ,Kidney Transplantation ,Transplant Recipients ,Immunoglobulin G ,Immunology ,biology.protein ,Risk factor ,business ,immunoglobulin ,Follow-Up Studies - Abstract
Background Recent data have outlined a link between hypogammaglobulinemia (HGG) and infection risk and suggested that HGG correction may decrease post-transplant infections. Methods We analyzed the risk factors of HGG and the relationship between HGG and the risk of severe infection in a cohort of 318 kidney transplant recipients (KTR) who were transplanted between 2003 and 2013. Immunoglobulin (Ig) concentration was measured prospectively at day 15 (D15), month 6 (M6), month 12 (M12), and month 24 (M24) post transplant. Results The prevalence of IgG HGG was 56% and 36.8% at D15 and M6 respectively. Age was the sole identified risk factors for D15 IgG HGG (odds ratio [OR] 1.02, P = 0.019). Risk factors for M6 IgG HGG were the presence of D15 IgG HGG (OR 6.41, P
- Published
- 2016
41. Successful Treatment Using Simeprevir, Sofosbuvir and Rituximab of a Severe Form of Hepatitis C Virus-related Mixed Cryoglobulinemia with Cardiac Involvement
- Author
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Geoffrey Urbanski, Françoise Lunel-Fabiani, Rafael Mahieu, Christian Lavigne, I. Hubert, and Alexandra Ducancelle
- Subjects
Simeprevir ,hepatitis C virus ,Sofosbuvir ,business.industry ,Ribavirin ,Hepatitis C virus ,simeprevir ,lcsh:R ,Mixed cryoglobulinemia ,lcsh:Medicine ,medicine.disease_cause ,Virology ,sofosbuvir ,Simeprevir + sofosbuvir ,chemistry.chemical_compound ,chemistry ,Concomitant ,Internal Medicine ,medicine ,Rituximab ,business ,medicine.drug - Abstract
Numerous extrahepatic manifestations have been reported in hepatitis C virus (HCV) infection, particularly mixed cryoglobulinemia (MC). MC generally responds to clearance of HCV under pegylated-interferon plus ribavirin treatment. New direct-acting antiviral agents have been licensed for HCV under different combinations but have not been studied in severe forms of MC. Here, we present a case report describing a life-threatening form of MC with multivisceral involvement, which was successfully treated with concomitant rituximab, sofosbuvir and simeprevir. In light of the rapid clinical remission associated with sustained virological response and the excellent side-effect profile, this treatment should be considered as a first-line therapy in severe forms of MC.
- Published
- 2015
42. Venous thrombosis in immunocompetent patients with acute cytomegalovirus infection: a complication that may be underestimated
- Author
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Valérie Delbos, S. Jomaa, Pierre Abgueguen, Serge Fanello, Eric Pichard, Alexandra Ducancelle, Service des maladies infectieuses et tropicales [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service des Maladies Infectieuses et Tropicales [Hôpital Charles Nicolle, Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and CHU d'Angers
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Adult ,Male ,Human cytomegalovirus ,Microbiology (medical) ,medicine.medical_specialty ,Complications ,[SDV]Life Sciences [q-bio] ,Congenital cytomegalovirus infection ,Cytomegalovirus ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Betaherpesvirinae ,Internal medicine ,medicine ,Humans ,cytomegalovirus infection ,030212 general & internal medicine ,Aged ,Retrospective Studies ,Aged, 80 and over ,0303 health sciences ,biology ,030306 microbiology ,business.industry ,virus diseases ,General Medicine ,immunocompetent patient ,Middle Aged ,medicine.disease ,biology.organism_classification ,Thrombosis ,3. Good health ,Pulmonary embolism ,Surgery ,Venous thrombosis ,Infectious Diseases ,Immunoglobulin M ,Immunoglobulin G ,Cytomegalovirus Infections ,Female ,venous thrombosis ,Pulmonary Embolism ,business ,Complication ,Immunocompetence ,Meningitis - Abstract
International audience; In the present study, we retrospectively studied clinical and laboratory findings associated with cytomegalovirus (CMV) infection in immunocompetent patients. We focused on severe CMV infection. Among 38 patients, five had a severe form of infection: one had meningitis, one had symptomatic thrombocytopenia and three had venous thromboses with pulmonary embolism, a rarely described complication. CMV-induced thrombosis has been reported in immunocompromised patients such as transplant recipients and patients with AIDS. Recent case reports have also described thrombotic phenomena in immunocompetent patients with CMV infection. Our study suggests that venous thrombosis during acute CMV infection is an underestimated complication.
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- 2010
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43. Development and validation of a non-radioactive DNA polymerase assay for studying cytomegalovirus resistance to foscarnet
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Alexandra Ducancelle, Marie-Christine Mazeron, Marie-José Sanson-Le Pors, Françoise Petit, Sophie Alain, Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Université de Limoges (UNILIM), Biologie moléculaire et cellulaire des microorganismes (EA3175), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)
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Foscarnet ,Human cytomegalovirus ,DNA polymerase ,Cytomegalovirus ,MESH: Catalytic Domain ,DNA-Directed DNA Polymerase ,chemistry.chemical_compound ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Catalytic Domain ,MESH: Colorimetry ,MESH: DNA-Directed DNA Polymerase ,Polymerase ,MESH: Inhibitory Concentration 50 ,0303 health sciences ,MESH: Drug Resistance, Viral ,biology ,virus diseases ,3. Good health ,MESH: Reproducibility of Results ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Colorimetry ,MESH: Foscarnet ,medicine.drug ,MESH: Antiviral Agents ,MESH: Cytomegalovirus ,MESH: Mutation ,Antiviral Agents ,Sensitivity and Specificity ,Inhibitory Concentration 50 ,Viral Proteins ,03 medical and health sciences ,Virology ,Drug Resistance, Viral ,medicine ,Gene ,030304 developmental biology ,030306 microbiology ,MESH: Digoxigenin ,Mutagenesis ,Reproducibility of Results ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,MESH: Viral Proteins ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Molecular biology ,MESH: Sensitivity and Specificity ,chemistry ,Foscarnet Sodium ,Mutation ,biology.protein ,Digoxigenin ,DNA - Abstract
International audience; Phenotypic characterisation of the human cytomegalovirus (HCMV) pUL54 DNA polymerase is a useful tool for testing for mutations in the UL54 gene thought to render HCMV resistant to foscarnet. In this study, an in-house non-isotopic method for assessing polymerase enzymatic activity in the presence and absence of foscarnet was developed and its utility for HCMV polymerase phenotyping evaluated. Polymerase activity was assessed by monitoring the incorporation of digoxigenin-labelled nucleotides into the growing DNA chain and foscarnet concentrations inhibiting enzymatic activity by 50% were determined. HCMV DNA polymerases were synthesised in vitro by expression of UL54 under the control of the T7 promoter. Mutations of interest were introduced into the wild-type UL54 gene by site-directed mutagenesis. Mutated polymerases and polymerases from HCMV reference strains were studied. The activity of polymerases containing mutations known to confer resistance to foscarnet (V715M, T700A and N495K) was inhibited by concentrations of foscarnet eight to 14 times higher than those required to inhibit wild-type polymerases. Our in-house non-radioactive phenotypic assay was sensitive and reproducible. It is also easy to perform and could provide a convenient method for characterising mutations conferring resistance to foscarnet in HCMV.
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- 2007
44. Home-based urinary HPV DNA testing in women who do not attend cervical cancer screening clinics
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Justine Reiser, Anne Sophie Le Duc-Banaszuk, Alexandra Ducancelle, Françoise Lunel-Fabiani, Hélène Le Guillou-Guillemette, Adeline Pivert, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), and PRES Université Nantes Angers Le Mans (UNAM)
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Microbiology (medical) ,Adult ,medicine.medical_specialty ,Urinary system ,[SDV]Life Sciences [q-bio] ,HR HPV ,cervical cancer screening ,Urine ,Cervical cancer screening ,Sensitivity and Specificity ,Human Papillomavirus DNA Tests ,Specimen Handling ,03 medical and health sciences ,0302 clinical medicine ,Abnormal PAP Smear ,Pregnancy ,medicine ,Humans ,Mass Screening ,030212 general & internal medicine ,Papillomaviridae ,Early Detection of Cancer ,Aged ,Colposcopy ,Gynecology ,Pap smears ,030219 obstetrics & reproductive medicine ,medicine.diagnostic_test ,Obstetrics ,business.industry ,high-risk human Papillomavirus ,Papillomavirus Infections ,Middle Aged ,Uterine Cervical Dysplasia ,Home based ,HPV DNA detection ,3. Good health ,Self Care ,Hpv testing ,Infectious Diseases ,DNA, Viral ,self-sampling for HPV testing ,Patient Compliance ,Female ,France ,business ,Papanicolaou Test - Abstract
International audience; In France, cervical cancer screening is currently based on cytological examination of a Pap smear for women aged 25 to 65, but screening coverage is unsatisfactory. Previous studies have shown that self-sampling for human papillomavirus (HPV) testing increases rates of compliance. With this purpose in mind, we performed the CapU study to evaluate the acceptance of a urinary HPV test. Letters proposing a new cervical cancer screening method using at-home urine self-sampling were sent to 5000 women aged 40-65 years who had not had a Pap smear over the past three years. The participating patients had to send their urine samples to the Angers Hospital Virology Laboratory for analysis using real-time PCR. Of the 771 samples received, 687 were analyzed. High-risk HPV were detected in 29 women. In follow-up, 28 women with positive urinary HPV results had a Pap smear or colposcopy done. The cytological results showed nine abnormal Pap smears, among which histology studies confirmed three cases of cervical intraepithelial neoplasia grade III lesions. Our study shows that urinary HPV testing may be pertinent to women who do not have cervical Pap smears done and lead to the diagnosis of high-grade cervical lesions.
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- 2015
45. Identification of a duplicated V3 domain in NS5A associated with cirrhosis and hepatocellular carcinoma in HCV-1b patients
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Elisabeth André-Garnier, J. B. Bour, Jacques Izopet, Christophe Lemaire, S. Vallet, Adeline Pivert, Arielle R. Rosenberg, Pascale Trimoulet, Christopher Payan, E. Bouthry, Pascal Veillon, Sophie Alain, Dominique Bettinger, P. André, Alexandra Ducancelle, Catherine Gaudy-Graffin, Jean-Michel Pawlotsky, Françoise Stoll-Keller, Odile Petsaris, Cécile Henquell, Yazid Baazia, Bruno Pozzetto, Françoise Lunel-Fabiani, Florence Abravanel, Henia Saoudin, V. Thibault, Anne Signori-Schmuck, Sandrine Bertrais, Gisèle Lagathu, H. Le Guillou-Guillemette, Sylvie Larrat, S. Minjolle-Cha, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA), CHU Limoges, Service de virologie [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Clermont-Ferrand, Hôtel-Dieu de Nantes, Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Avicenne, Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Laboratoire de Bactériologie de l'Hôpital de la Croix-Rousse, Hospices Civils de Lyon (HCL), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Centre National de la Recherche Scientifique (CNRS)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Université Joseph Fourier - Grenoble 1 (UJF), Biologie structurale des interactions entre virus et cellule hôte (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CHU Pontchaillou [Rennes], Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor, The authors thank A. Lefebvre, E. Muel, Y. Desille, I. Renard, A. Plages, A. Rodallec and W. Merrouche for their assistance in clinical data recording.Funding: This study was funded by the ANRS (Agence de Nationale de Recherche sur le VIH et les hépatites, appel d’offre Mars 2006)., PRES Université Nantes Angers Le Mans [UNAM], Interactions cellulaires et applications thérapeutiques (ICAT), Université d'Angers (UA) - CHU Angers - CRLCC Paul Papin - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Service de virologie, Université Pierre et Marie Curie - Paris 6 (UPMC) - Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Pitié-Salpêtrière [APHP], Centre de Physiopathologie Toulouse Purpan, Université Paul Sabatier - Toulouse 3 (UPS) - IFR30 - IFR150 - Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Cochin [APHP], Université européenne de Bretagne (UEB) - Université de Bretagne Occidentale (UBO) - IFR148 ScInBioS, Centre Hospitalier Universitaire de Dijon (CHU Dijon), CHU Bordeaux [Bordeaux] - Groupe hospitalier Pellegrin, Hospices Civils de Lyon, Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH), Institut National de la Santé et de la Recherche Médicale (INSERM) - Université François Rabelais - Tours - CHRU Tours, CHU Besançon, Université de Franche-Comté (UFC), Laboratoire de biologie structurale des interactions entre virus et cellule hôte, Université Joseph Fourier - Grenoble 1 (UJF) - Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg - Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Henri Mondor [Créteil], and Jonchère, Laurent
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Adult ,Liver Cirrhosis ,Male ,hepatitis C virus ,Cirrhosis ,Carcinoma, Hepatocellular ,Hepatitis C virus ,[SDV]Life Sciences [q-bio] ,Viral quasispecies ,Hepacivirus ,Biology ,Viral Nonstructural Proteins ,medicine.disease_cause ,NS5A ,Liver disease ,Virology ,Gene Duplication ,Gene duplication ,medicine ,Prevalence ,Humans ,Aged ,Hepatitis ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Sequence Analysis, RNA ,cirrhosis ,Liver Neoplasms ,Hepatitis C ,hepatocellular carcinoma ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,digestive system diseases ,3. Good health ,Protein Structure, Tertiary ,[SDV] Life Sciences [q-bio] ,Mutagenesis, Insertional ,Infectious Diseases ,Cross-Sectional Studies ,Hepatocellular carcinoma ,RNA, Viral ,Female ,V3 domain ,France ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; Background The NS5A protein of the hepatitis C virus has been shown to be involved in the development of hepatocellular carcinoma. Objectives In a French multicenter study, we investigated the clinical and epidemiological features of a new HCV genotype 1b strain bearing a wide insertion into the V3 domain. Study Design We studied NS5A gene sequences in 821 French patients infected with genotype 1b HCV. Results We identified an uncharacterized V3 insertion without ORF disruption in 3.05% of the HCV sequences. The insertion comprised 31 amino-acids for the majority of patients; 3 patients had 27 amino-acids insertions and 1 had a 12 amino-acids insertion. Sequence identity between the 31 amino-acids insertions and the V3 domain ranged from 48 to 96% with E-values above 4e-5, thus illustrating sequence homology and a partial gene duplication event that to our knowledge has never been reported in HCV. Moreover we showed the presence of the duplication at the time of infection and its persistence at least during 12 years in the entire quasispecies. No association was found with extrahepatic diseases. Conversely, patients with cirrhosis were two times more likely to have HCV with this genetic characteristic (p=0.04). Moreover, its prevalence increased with liver disease severity (from 3.0% in patients without cirrhosis to 9.4% in patients with both cirrhosis and HCC, p for trend=0.045). Conclusions We identified a duplicated V3 domain in the HCV-1b NS5A protein for the first time. The duplication may be associated with unfavorable evolution of liver disease including a possible involvement in liver carcinogenesis
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- 2015
46. Développement d'un test colorimétrique pour tester la sensibilité de l'ADN polymérase du cytomégalovirus humain au foscarnet
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M.-J. Sanson-Le Pors, S. Alain, Alexandra Ducancelle, Françoise Petit, Marie-Christine Mazeron, Anne-Marie Fillet, and C. Scieux
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Foscarnet ,Human cytomegalovirus ,Mutation ,biology ,DNA polymerase ,Mutagenesis ,virus diseases ,General Medicine ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,medicine.disease_cause ,Virology ,chemistry.chemical_compound ,chemistry ,Foscarnet Sodium ,medicine ,biology.protein ,DNA ,Polymerase ,medicine.drug - Abstract
We described a colorimetric method to determine the biochemical phenotype of wild-type and mutated cytomegalovirus (HCMV) DNA polymerases by measuring the incorporation of digoxigenin-labelled nucleotides into the growing DNA chain. Mutations V715M and E756K, which are known to confer foscarnet-resistance, were used as controls. Mutation N495K and a combination of changes K415R and S291P, both observed in foscarnet-resistant isolates, were studied. The mutations were introduced by site-directed mutagenesis into wild-type gene UL54 cloned in an expression vector and then polymerases were synthesised by using a commercially available coupled transcription-translation system. The polymerase activity was measured with and without foscarnet. The activity of polymerases containing the V715M or E756K mutations was inhibited by foscarnet at concentrations 70- and 30-fold higher than that of wild-type polymerase, respectively. Change N495K and combination of K415R and S291P, induced a five- and ten-fold decrease in susceptibility to foscarnet, respectively. The results of this non-radioactive assay were consistent with those obtained with the conventional radioactive assay. Therefore, this novel phenotypic method could be useful for the characterisation of mutations that confer HCMV resistance to foscarnet.
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- 2005
47. A Novel Mutation in the Ul54 Gene of Human Cytomegalovirus Isolates that Confers Resistance to Foscarnet
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Marie-José Sanson-Le Pors, Françoise Petit, Sophie Alain, Gaël Champier, Marie-Christine Mazeron, Alexandra Ducancelle, Bucek, Ingrid, Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université de Limoges (UNILIM), Biologie moléculaire et cellulaire des microorganismes (EA3175), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7)
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Foscarnet ,Human cytomegalovirus ,viruses ,Cytomegalovirus ,DNA-Directed DNA Polymerase ,Drug resistance ,Recombinant virus ,chemistry.chemical_compound ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,MESH: DNA-Directed DNA Polymerase ,Pharmacology (medical) ,Recombination, Genetic ,[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,MESH: Microbial Sensitivity Tests ,MESH: Drug Resistance, Viral ,virus diseases ,Infectious Diseases ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Cytomegalovirus Infections ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,MESH: Recombination, Genetic ,MESH: Foscarnet ,Cidofovir ,medicine.drug ,MESH: Antiviral Agents ,Ganciclovir ,MESH: Cytomegalovirus ,MESH: Mutation ,Microbial Sensitivity Tests ,Biology ,Antiviral Agents ,Virus ,Viral Proteins ,Drug Resistance, Viral ,medicine ,Humans ,Pharmacology ,MESH: Humans ,MESH: Cytomegalovirus Infections ,Fibroblasts ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,MESH: Viral Proteins ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Virology ,chemistry ,MESH: Fibroblasts ,Foscarnet Sodium ,Mutation ,[SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology - Abstract
International audience; Foscarnet is currently licensed for the treatment of human cytomegalovirus (HCMV) infection. Mutations proven to confer resistance to foscarnet have mostly been mapped to regions II, III and VI of the HCMV UL54-encoded DNA polymerase. We previously showed that sequential foscarnet-resistant HCMV isolates recovered from a patient with lymphoma had change N495K in region delta-C of the DNA polymerase. To evaluate the impact of change N495K on HCMV sensitivity to foscarnet, a recombinant HCMV strain carrying the mutation was produced by homologous recombination. The recombinant virus showed a 3.4-fold increase in foscarnet resistance, and remained sensitive to ganciclovir and cidofovir. In addition, the recombinant strain showed a reduction of infectious virus yield compared with its parent strain. Change N495K should be added to the list of mutations conferring resistance to foscarnet and be taken into account in the genotypic diagnosis of antiviral resistance.
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- 2005
48. Comparison of sequential cytomegalovirus isolates in a patient with lymphoma and failing antiviral therapy
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Marie-Christine Mazeron, Jean-Claude Brouet, Catherine Scieux, Marie-José Sanson-Le Pors, Alexandra Ducancelle, Stéphanie Belloc, Françoise Petit, Sophie Alain, and Marion Malphettes
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Foscarnet ,Ganciclovir ,Human cytomegalovirus ,Mutation, Missense ,Organophosphonates ,Cytomegalovirus ,Biology ,Lymphoma, T-Cell ,Antiviral Agents ,Virus ,Evolution, Molecular ,Cytosine ,chemistry.chemical_compound ,Organophosphorus Compounds ,Betaherpesvirinae ,Virology ,Drug Resistance, Viral ,Genotype ,medicine ,Humans ,Genotyping ,Aged ,Molecular Epidemiology ,virus diseases ,Sequence Analysis, DNA ,medicine.disease ,biology.organism_classification ,Infectious Diseases ,chemistry ,Cytomegalovirus Infections ,DNA, Viral ,Female ,Cidofovir ,Polymorphism, Restriction Fragment Length ,medicine.drug - Abstract
Background: Long-term anti-cytomegalovirus (CMV) treatments in immunocompromised patients are hampered by resistance to antiviral drugs. Longitudinal changes in the resistance genotype may depend on changes in selective pressure and the complexity of CMV isolates. Objective: To evaluate longitudinal changes in the CMV resistance genotype and phenotype along with strain-specific variability in a patient with non-Hodgkin’s lymphoma in whom successive anti-CMV treatments failed. Study design: The resistance phenotype and genotype of seven CMV isolates collected from one patient during a 2-year follow-up period were retrospectively analysed. In parallel, we used glycoprotein B (gB) genotyping, and a - and UL10 - 13 -sequence analysis to study CMV interstrain variability. Results: The patient was infected by at least three CMV strains plus variants of the parental strains. Resistance to ganciclovir, cidofovir and foscarnet was successively detected during the follow-up period. UL97 protein kinase changes responsible for resistance to ganciclovir were initially detected at residues 591 and 592, and then at position 594. Decreased sensitivity to foscarnet coincided with the appearance of amino acid substitution N495K in DNA polymerase, whereas cross-resistance to ganciclovir and cidofovir was due to the L501I substitution. Conclusions: The CMV isolates obtained from our patient were complex mixtures of strains. Changes in resistance genotypes depended on resistance selective pressure and were not linked to interstrain variation.
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- 2004
49. Diagnostic de l'infection à CMV chez les patients immunodéprimés
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Sophie Alain, Alexandra Ducancelle, and Marie-Christine Mazeron
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Gynecology ,medicine.medical_specialty ,business.industry ,medicine ,Congenital cytomegalovirus infection ,medicine.disease ,business ,Virus load ,Analytical Chemistry - Abstract
Resume Le cytomegalovirus (CMV) est responsable d'infections graves qui mettent en jeu le pronostic fonctionnel ou vital chez les patients immunodeprimes, receveurs d'allogreffe et sujets infectes par le VIH. Un traitement anticipe (preemptif) peut etre institue chez les patients a haut risque de developper ces complications severes de l'infection. La mesure de la charge virale systemique est un outil indispensable pour predire la survenue de la maladie a CMV. Les seuils de charge virale systemique a partir desquels le traitement anticipe est recommande dependent du type d'immunodepression, du type de greffe et de la nature du traitement immunosuppresseur. Le diagnostic des localisations viscerales de la maladie s'appuie sur la recherche du virus dans l'organe atteint et peut s'aider de la mesure de la charge virale systemique. Il faut differencier les excretions virales liees a des reactivations locales asymptomatiques, tres frequentes chez les malades immunodeprimes, de la maladie productive responsable des symptomes cliniques. C'est pourquoi, la confrontation des donnees cliniques, anatomo-pathologiques et virologiques est indispensable.
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- 2002
50. Interest of Human Papillomavirus DNA quantification and genotyping in paired cervical and urine samples to detect cervical lesions
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G. Agius, Françoise Lunel, L. Catala, M. A. De Brux, Pascal Veillon, E. Postec, A. Beby-Defaux, H. Le Guillou-Guillemette, F. Charles-Pétillon, Christopher Payan, Sébastien Hantz, P. Descamps, Sophie Alain, F. Labrousse, Alexandra Ducancelle, M. C. Legrand, H. Caly, Adeline Pivert, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de Bactériologie, Virologie, Hygiène [CHU Limoges], CHU Limoges, Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges, Laboratoire de Microélectronique et de Physique des Semiconducteurs (LaMIPS), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-NXP Semiconductors [France], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Laboratoire de cristallographie et sciences des matériaux (CRISMAT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-NXP Semiconductors [France]-Presto Engineering Europe, and Hôpital Dupuytren [CHU Limoges]
- Subjects
Pathology ,[SDV]Life Sciences [q-bio] ,Uterine Cervical Neoplasms ,Urine ,Cervix Uteri ,Gastroenterology ,Human Papillomavirus DNA Tests ,0302 clinical medicine ,Pregnancy ,Genotype ,Prevalence ,Longitudinal Studies ,Prospective Studies ,Papillomaviridae ,Cervical cancer ,0303 health sciences ,Obstetrics and Gynecology ,virus diseases ,General Medicine ,Urine test ,Middle Aged ,Viral Load ,female genital diseases and pregnancy complications ,3. Good health ,Real-time polymerase chain reaction ,030220 oncology & carcinogenesis ,Female ,France ,Viral load ,Adult ,medicine.medical_specialty ,Human papillomavirus ,Adolescent ,Concordance ,Context (language use) ,Real-Time Polymerase Chain Reaction ,Sensitivity and Specificity ,03 medical and health sciences ,Internal medicine ,Quantification ,medicine ,Humans ,Genotyping ,Aged ,Vaginal Smears ,030306 microbiology ,business.industry ,Papillomavirus Infections ,HPV genotyping ,medicine.disease ,DNA, Viral ,business - Abstract
International audience; BackgroundCervical cancer is caused by persistent infection with high-risk human papillomavirus (HR-HPV). Conventional human papillomavirus (HPV) testing requires cervical sampling. However, vaginal and urine self-sampling methods are more acceptable for patients and result in increased participation when they are available in screening programs. In this context, we have developed a non-invasive screening method via the detection of HPV DNA in urine samples.PurposeTo compare HPV viral loads and genotypes in paired cervical and urine samples, and to assess correlation between virological and cytological results in women seeking gynecological consultation.MethodsPaired urine and cervical specimens were collected and analyzed from 230 of 245 women participating in the previously described prospective PapU study. HPV DNA detection and quantification were performed using a real-time PCR method with short fragment PCR primers. Genotyping was carried out using the INNO-LiPA HPV genotyping assay.ResultsThe prevalence of HPV in the 230 paired urine and cervical smear samples was 42 and 49%, respectively. Overall agreement for HPV positivity and negativity between the paired samples was 90% (κ=0.80). High HPV viral load in both cervical and urine samples was associated with cytological abnormalities. HPV-positive women were mostly infected with HR-HPV types. The agreement between high- and low-risk HPV (LR-HPV) detection in both samples was 97% (κ=0.95 for HR-HPV and κ=0.97 for LR-HPV).ConclusionsHigh concordance rates for HPV-DNA quantification and high/low-risk HPV genotyping in paired urine/cervical samples suggest that urinary HPV DNA testing could be useful for cervical lesion screening.
- Published
- 2014
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