Emmanuel Gordien

MD, PhD
Head of Virology Unit
Assistance Publique – Hôpitaux... · Laboratoire de bactériologie, virologie - hygiène, Hôpital Avicenne

Publications

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    ABSTRACT: A French national quality control for serological and molecular diagnosis of hepatitis Delta virus (HDV) was organized. All participants detected total HDV antibodies; 8/14 failed to detect low titers of IgM; 6/11 laboratories failed to quantify and/or underestimated RNA viral load in several samples. These discrepancies are likely related to HDV molecular diversity.
    Journal of clinical microbiology 02/2014; · 4.16 Impact Factor
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    ABSTRACT: The prevalence of chronic hepatitis B and C was evaluated some twenty years ago among specific populations in Guadeloupe. The present study was designed to update these data and determine epidemiological features of chronic hepatitis B and C infections in the French Caribbean island of Guadeloupe. The present study was carried out at the Sainte Genevieve Health and Prevention Center (Guadeloupe), between May 2006 and July 2007. This is a medical center where patients can attend a free medical check-up paid for by the Social Security system. Data on hepatitis B (HBV) and C (HCV) status and epidemiological factors were collected for this study.A total of 2,200 patients were included in the study. The prevalence of HBV surface antigen was 1.41% (95% CI: 1.0-2.0), and 0.55% (95% CI: 0.28-0.96) for HCV. The vaccination rate against HBV was 42.0%. HBV transmission was associated with piercing (12.9%, p = 0.014) and familial exposure (6.4%, p < 0.001) and HCV transmission with gynecological surgery (50.0%, p = 0.01). The HBV profile was generally hepatitis B e antigen-negative (94.5%). No hepatitis delta was found. For HCV, genotype 1 was predominant (80%). This is the first study on the prevalence of HBV and HCV among a general clinic based population in Guadeloupe and the Caribbean islands. This study reveals that Guadeloupe is an area of low endemicity for HBV and low HCV prevalence. The reasons for these low prevalence rates are mainly related to the vaccination campaigns carried out during the past twenty years for HBV and the decrease of nosocomial transmission for HCV.
    BMC Research Notes 01/2014; 7(1):55.
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    ABSTRACT: Background Hepatitis delta virus (HDV) is a satellite of HBV and needs this latter's envelope for its morphogenesis and propagation. An estimated 5 to 20% of HBV-infected patients are also infected with HDV. No studies have ever been performed to determine the presence of HDV in follicular fluid (FF) and semen of HDV-infected patients. Objectives To investigate the presence of HDV markers in the FF or in the semen of two HDV-infected patients. Design Two unrelated HDV-infected patients, a woman and a man pursuing in vitro fertilization (IVF), participated in this study. FF was collected after analysis of oocyte retrieval. The supernatant of seminal plasma (SP) and the final pellet (FP) were fractionated from freshly ejaculated semen. Serological and molecular markers of HDV infection were searched for in these different samples. Results The woman was infected with an HDV-7 genotype strain and her HDV plasma viral load (VL) was 6 log copies/mL. HDV antibodies and RNA were also detected in the FF, however the RNA VL value there was lower by more than 4 log. The man was infected with an HDV-1 strain and his plasma VL was 6.7 log copies/mL. Total anti-HDV antibodies were positive in the serum, in the SP and in the FP, while IgM were detected only in the serum. However, HDV RNA was negative in the SP and in the FP. Conclusion HDV markers can be found in the follicular fluid or in the semen of infected patients.
    Journal of Clinical Virology. 01/2014;
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    ABSTRACT: In France, there are no consistent data estimating hepatitis delta virus (HDV) prevalence in the general population. To better characterize HDV/HBV infection and its trends over a 15-years period from 1997 to 2011, we used data retrieved from the National Epidemiological Donors database including viral and demographic characteristics of all French HBV infected blood donors. Of the 39,911,011 donations collected over the 15 year-study-period, 6214 (1.56 in 10(4) donations) were confirmed positive for HBV from which 72.3% were tested for HDV antibodies (Ab). HDV viral load was performed using a real-time PCR assay on positive HDV Ab samples and HDV genotype determined for each positive viremic sample. Among the 4492 HBV donations, 89 (1.98%) were HDV Ab positive. After being stable around 1.1% from 1997 to 2005, this rate has continuously increased to reach 6.5% in 2010, before declining to 0.85% in 2011. Of the 61 investigated HDV Ab positive individuals, 22.9% were viremic with a viral load ranging from 10(4) to 9.8×10(7)copiesmL(-1). Genotyping revealed 12 HDV-1, 1 HDV-6 and 1 HDV-7 in accordance with the geographical origin of individuals. Such a study gives unexpected features of HBV-HDV infection in the population of blood donors which is a priori, a healthy population. The increase of HDV prevalence mainly linked to migration of population from endemic countries, demonstrates that there is still no complete control of HBV infection and must encourage HBV vaccination campaigns and systematic screening for HDV in HBV-infected.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 12/2013; · 3.12 Impact Factor
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    ABSTRACT: The effect of tenofovir (TDF) alone or in combination with interferon on hepatitis D virus (HDV) replication is poorly characterized in patients infected with human immunodeficiency virus (HIV), hepatitis B virus (HBV) and HDV. We analyzed tri-infected patients undergoing treatment with either TDF alone (n=13) or including IFN at some point during TDF therapy (TDF+IFN, n=4). Linear mixed-effect models were used to estimate the mean change from baseline of HDV-RNA and hepatitis surface antigen (HBsAg) levels during treatment. Patients were followed for a median 31.6 (25-75%-tile: 15.0-47.4) months. In the TDF+IFN group, 3 initiated IFN-based therapy after a median 21.7 months (range=10.5-24.9) of lamivudine (LAM)+TDF, while the remaining patient had 46.8 months of prior LAM-exposure. Significant decreases in HDV-RNA were observed in both groups [TDF-alone: -0.380 log10 copies/ml per year (95%CI: -0.557, -0.202) vs TDF+IFN: -1.325 log10 copies/ml per year (95%CI: -1.931, -0.720)], while HDV-RNA decline overall was significantly faster in patients with TDF+IFN (p=0.002). Accordingly, two patients achieved HDV-RNA below the limit of quantification (LOQ: <1000 copies/mL) and one near LOQ (1450 copies/mL), all concomitantly treated with interferon. There were no significant changes in HBsAg levels for either group [TDF-alone: -0.008 log10 IU/ml per month (95%CI: -0.019, 0.004), TDF+IFN: -0.011 log10 IU/ml per year (95%CI: -0.037, 0.015)] and no significant difference in slope between treatment groups (p=0.8). Interferon-therapy might be more effective after extended previous anti-HBV antiviral exposure among tri-infected patients, however the long-term implications of these findings remain unknown.
    AIDS research and human retroviruses 08/2013; · 2.18 Impact Factor
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    ABSTRACT: Ten Hepatitis B virus (HBV) genotypes, as well as numerous subgenotypes, have been described in well-characterized ethnogeographical populations. Martinique has been at a crossroads between Africa, Europe, India and the Americas because of the slave trade (17(th) - 19(th) centuries), followed by an important immigration of Indian and West-African workers. In this study, we aimed to study molecular epidemiology of HBV infection in Martinique according to this unique settlement pattern. To that end blood samples from 86 consecutive HBV-infected patients from the main hospitals of the island, were retrospectively analyzed. Direct sequencing of PreS1 or Pre-C-C region or complete genome sequencing, followed by phylogenetic analyses were performed. HBV genotypes were: HBV/A1 (68.6%), HBV/A2 (10.5%), HBV/D, mainly HBV/D3 and HBV/D4 (8.1%); HBV/F (3.5%), and also HBV/E (2.3%), 2 strains isolated from 2 West-African patients. Moreover, 74% of the HBeAg-negative strains harbored classical Pre-C-C mutations, and most HBV/A1 strains also containing specific mutations. Finally, various patterns of deletion mutants in Pre-S and Pre-C-C regions were found. In conclusion our findings point to historical and migration-related issues in HBV-genotype distribution suggesting that HBV/A1, but not HBV/E, was imported from Africa during the slave trade, and further supporting the hypothesis that HBV/E has emerged recently in West-Africa (<150 years). Potential origins of "European" HBV/A2 and HBV/D3, "Amerindian" HBV/F, and HBV/D4 strains are also discussed. Such HBV genetic diversity, beyond its epidemiological interest, may have a clinical impact on the natural history of HBV infection in Martinique.
    Journal of General Virology 07/2013; · 3.13 Impact Factor
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    ABSTRACT: Mauritania is a highly endemic region for hepatitis B (HBV) and delta (HDV) viruses. No data are available on HDV's impact on the severity of liver disease in consecutive HBV-infected patients in Africa. This study evaluated the degree of liver fibrosis in a cohort of chronic HBV carriers. Three-hundred consecutive HBV-infected Mauritanian patients were checked for HDV infection via the detection of anti-HDV antibodies (Ab) and viral RNA. HBV- vs. HBV/HDV-infected patients were compared by physical examination, biological analyses, and the APRI (aspartate aminotransferase to platelet ratio index) and FibroMeter tests for determination of liver fibrosis. More than 30% of the patients had anti-HDVAb. Among these, 62.2% were HDV-RNA positive. Co-infected patients were older (>8-years) than HBV-mono-infected patients. They had more liver tests abnormalities and clinical or ultrasound signs of liver fibrosis. APRI and FibroMeter scores were also significantly increased in these patients. In multivariate analysis, beyond HDVAb, male gender and HBV-VL >3.7 logIU/mL were the only markers linked to significant liver fibrosis. In Mauritania, HDV co-infection worsens liver disease, both clinically and biologically, as confirmed by the APRI and FibroMeter tests. These tests may be useful for the management of delta hepatitis, which is a major health problem in Mauritania.
    The Journal of infection 06/2013; · 4.13 Impact Factor
  • Transfusion Clinique et Biologique 06/2013; 20(3):262–263. · 0.64 Impact Factor
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    Dataset: JCV2012 VHD
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    ABSTRACT: BACKGROUND & AIMS: Hepatitis Delta virus (HDV) infection causes fulminant hepatitis and increases the severity of chronic HBV infection, leading to cirrhosis, liver failure, or hepatocellular carcinoma. There are 8 HDV genotypes (1-8). We previously developed a TaqMan real-time reverse transcriptase (RT)-PCR method able to quantify viral load of all HDV genotypes (linear from 2 to 8 log(10) copies/mL). We compared its results with those from 3 commercial real-time RT-PCR assays: the Lightmix HDV kit (designed to quantify HDV-1), and the RoboGene and the DiaPro HDV-RNA quantification kits (designed to quantify all genotypes). METHODS: We selected RNA from 128 clinical samples of all HDV genotypes except HDV-4, with various HDV viral load values. We also analyzed 5 samples, collected over time, from each of 6 patients infected with strains of different genotypes. RESULTS: Quantification results from the commercial kits for HDV-1 from European or Asian samples were consistent with those from our method, however they underestimated (0.5 to 1 log(10) with Lightmix and DiaPro) and did not detect (1 and 4 samples with Lightmix and DiaPro respectively) HDV-1 African samples. Moreover, the commercial kits greatly underestimated HDV viral load of almost all non-genotype-1 strains (about 2-3 log(10)), and even did not detect HDV-7 or -8 RNA in several samples with high concentrations of virus. CONCLUSIONS: Commercial kits accurately quantify HDV-1 in samples from European and Asian patients. However, they can dramatically underestimate or fail to quantify HDV viral load from samples from African patients infected with strains of genotypes 1, and 5 to 8.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 01/2013; · 5.64 Impact Factor
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    ABSTRACT:   Hepatitis delta virus (HDV) coinfection or superinfection in hepatitis B virus (HBV)-infected patients results in a more aggressive liver disease, with more often fulminant forms and more rapid progression to cirrhosis and hepatocellular carcinoma. The mechanism(s) for this pejorative evolution remains unclear. To explore a specific HDV pathogenesis, we used a model of transient transfection of plasmids expressing the small (sHDAg or p24) or the large (LHDAg or p27) delta antigen in hepatocyte cell lines. We found that the production of reactive oxygen species was significantly higher in cells expressing p27. Consequently, p27 activated the signal transducer and activator of transcription-3 (STAT-3) and the nuclear factor kappa B (NF-κB) via the oxidative stress pathway. Moreover in the presence of antioxidants (PDTC, NAC) or calcium inhibitors (TMB-8, BAPTA-AM, Ruthenium Red), p27-induced activation of STAT-3 and NF-κB was dramatically reduced. Similarly, using a mutated form of p27, where the cysteine 211-isoprenylation residue was replaced by a serine, a significant reduction of STAT-3 and NF-κB activation was seen, suggesting the involvement of isoprenylation in this process. Additionally, we show that p27 is able to induce oxidative stress through activation of NADPH oxidase-4. These results provide insight into the mechanisms by which p27 can alter intracellular events relevant to HDV-related liver pathogenesis.
    Journal of Viral Hepatitis 10/2012; 19(10):744-53. · 3.08 Impact Factor
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    ABSTRACT: No recent data are available on hepatitis B virus (HBV) and hepatitis Delta virus (HDV) prevalence in Mauritania. One thousand twenty pregnant women and 946 patients visiting for routine checkups were screened for HBV and HDV infection. Demographic, epidemiological, ethnic, clinical, and biological data were recorded. HBV and HDV genotypes were determined by sequencing and phylogenetic analyses. In the pregnant women and patients cohorts, respectively, the prevalence of HBsAg (10.7% and 18.3%) and anti-HBcAb (66.3% and 76.5%) indicated high HBV endemicity. In pregnant women, exposure to HBV was significantly associated in multivariate analysis with education level, ethnicity, blood transfusion, and occupation. HDV antibodies (HDVAb) were found in 14.7% of pregnant women. In patients, HBsAg was found less frequently in females than in males. Again in multivariate analysis, exposure to HBV was significantly correlated with gender (males), and HDVAb positivity with age and gender. The HBV DNA viral load was >3 log IU/ml in only 10.1% of pregnant women and in 17.3% of patients. HDV-RNA was detectable in 21 (67.7%) of the 31 patients positive for HDVAb, and in 11 of the 16 pregnant women positive for HDVAb (68.8%). The most frequent HBV genotypes were: HBV/D, 53%; HBV/E, 35%; and HBV/A, 12%. Sub-genotyping revealed HBV/D1,/D7, and the recently described/D8. HDV genotypes were: HDV-1, 90.3% and HDV-5, 9.7%. This study confirms the high prevalence of HBV and HDV infections in Mauritania and demonstrates the high genetic diversity of HBV in this country.
    Journal of Medical Virology 08/2012; 84(8):1186-98. · 2.37 Impact Factor
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    ABSTRACT: In Mauritania, some authors have described a possible high prevalence of hepatitis delta virus (HDV) infection in the 1990s in studies of small-size samples. The aims of our study were to assess the prevalence of HDV in HBsAg positive blood donors in Mauritania, to identify the main risk factors for HDV transmission and to analyze genetic diversity of HDV strains. From October 2008 to December 2009, 11,100 consecutive blood donors were considered in this study. Among them, 1700 (15.3%) were HBsAg positive and 455 accepted to participate in this study. Demographic, epidemiological, ethnical, clinical and biological data were recorded. HDV screening, i.e., antibodies (HDVAb) and RNA (HDV-RNA) detection, was performed for all of them as well as HDV and HBV genotyping. Ninety/455 (19.78%) donors were HDVAb positive and HDV-RNA was detectable in 56 (62.2%) of them. HDV infection was significantly associated with older age, number of marriages, military profession, residence in the desert and a history of hospitalization. The HDV genotypes of the circulating strains were HDV-1 (89.3%) and HDV-5 (10.7%). HDV is highly endemic in Mauritanian blood donors indicating that a high number of them will develop chronic hepatitis, cirrhosis or hepatocellular carcinoma. Associated risk factors support nosocomial transmission of HDV. These data underline the need to reinforce HBV vaccination in newborns and in blood donors without HBV markers, together with screening for HDV in HBV-infected individuals.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 06/2012; 55(1):12-6. · 3.12 Impact Factor
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    ABSTRACT: jpHMM is a very accurate and widely used tool for recombination detection in genomic sequences of HIV-1. Here, we present an extension of jpHMM to analyze recombinations in viruses with circular genomes such as the hepatitis B virus (HBV). Sequence analysis of circular genomes is usually performed on linearized sequences using linear models. Since linear models are unable to model dependencies between nucleotides at the 5'- and 3'-end of a sequence, this can result in inaccurate predictions of recombination breakpoints and thus in incorrect classification of viruses with circular genomes. The proposed circular jpHMM takes into account the circularity of the genome and is not biased against recombination breakpoints close to the 5'- or 3'-end of the linearized version of the circular genome. It can be applied automatically to any query sequence without assuming a specific origin for the sequence coordinates. We apply the method to genomic sequences of HBV and visualize its output in a circular form. jpHMM is available online at http://jphmm.gobics.de for download and as a web server for HIV-1 and HBV sequences.
    Nucleic Acids Research 05/2012; 40(Web Server issue):W193-8. · 8.81 Impact Factor
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    ABSTRACT: Hepatitis delta virus (HDV) is a subviral pathogen of humans, a satellite of hepatitis B virus (HBV) that induces severe acute and chronic liver diseases. The genus Deltavirus consists of eight clades or genotypes, with HDV1 being ubiquitous and frequently characterized. In Turkey, HDV1 infection is highly endemic among HBsAg carriers, especially in the southeastern region. In this study, we analyzed 34 samples from patients who were chronically infected with HBV/HDV, originating from 22 cities of rural regions in the central and eastern parts of Turkey, in order to determine the levels of viral replication and genetic diversity. HDV RNA levels ranged between 3.02 and 8.75 Log copies/mL, and HBV DNA was detected in 25 samples (73.5%), with values ranging from 2.53 to 5.30 Log copies/mL. Analysis of nucleotides 900-1280 of HDV genomes (n = 34) and full-length (n = 17) sequences indicated that all of the strains belonged to genotype HDV1. However, a high genetic diversity was observed among the isolates, with a mean full-length dissimilarity score of 13.05%. HDV sequences clustered with sequences from Western Europe (n = 11), Eastern Europe and Asia (n = 19) or Africa (n = 4). HDV1 isolates related to strains of African origin had a serine residue instead of an alanine at position 202 of the large delta protein. HBV preS1 sequences obtained for 34 isolates indicated an HBV/D genotype in all cases. Taken together, our results indicate that in Turkey, where HBV-HDV dual infection is highly endemic, both viruses have high levels of replication, and HDV strains exhibit wide genetic diversity, which might reflect ancient evolution and/or successive outbreaks.
    Archives of Virology 01/2012; 157(4):647-59. · 2.03 Impact Factor
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    ABSTRACT: Liver steatosis is a main histopathological feature of Hepatitis C (HCV) infection because of genotype 3. Steatosis and/or mechanisms underlying steatogenesis can contribute to hepatocarcinogenesis. The aim of this retrospective study was to assess the impact of infection with HCV genotype 3 on hepatocellular carcinoma (HCC) occurrence in patients with ongoing HCV cirrhosis. Three hundred and fifty-three consecutive patients (193 men, mean age 58 ± 13 years), with histologically proven HCV cirrhosis and persistent viral replication prospectively followed and screened for HCC between 1994 and 2007. Log-rank test and Cox model were used to compare the actuarial incidence of HCC between genotype subgroups. The patients infected with a genotype 3 (n = 25) as compared with those infected with other genotypes (n = 328) had a lower prothrombin activity [78 (interquartile range 60-85) vs 84 (71-195) %, P = 0.03] and higher rate of alcohol abuse (48%vs 29%, P = 0.046). During a median follow-up of 5.54 years [2.9-8.6], 11/25 patients (44%) and 87/328 patients (26%) with a genotype 3 and non-3 genotype, respectively, develop a HCC. HCC incidences were significantly different among the genotype subgroups (P = 0.001). The 5-year occurrence rate of HCC was 34% (95% CI, 1.3-6.3) and 17% (95% CI, 5.7-9.2) in genotype 3 and non-3 genotype groups, respectively (P = 0.002). In multivariate analysis, infection with a genotype 3 was independently associated with an increased risk of HCC occurrence [hazard ratio 3.54 (95% CI, 1.84-6.81), P = 0.0002], even after adjustment for prothrombin activity and alcohol abuse [3.58 (1.80-7.13); P = 0.003]. For patients with HCV cirrhosis and ongoing infection, infection with genotype 3 is independently associated with an increased risk of HCC development.
    Journal of Viral Hepatitis 10/2011; 18(10):e516-22. · 3.08 Impact Factor
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    JAIDS Journal of Acquired Immune Deficiency Syndromes 07/2011; 57(3):e63-6. · 4.65 Impact Factor
  • Journal of Hepatology - J HEPATOL. 01/2011; 54.
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    ABSTRACT: Niger is a west African country that is highly endemic for hepatitis B virus (HBV) infection. The seroprevalence for HBV surface antigen (HBsAg) is about 20%; however, there are no reports on the molecular epidemiology of HBV strains spreading in Niger. In the present study, HBV isolates from the sera of 58 consecutive, asymptomatic, HBsAg-positive blood donors were characterized. Genotype affiliation was determined by amplification, sequencing and phylogenetic analysis of the preS1, polymerase/reverse transcriptase (RT/Pol) and precore (preC)/C regions. The first series of results revealed that different genomic fragments clustered with different genotypes on phylogenetic trees, suggesting recombination events. Twenty-four complete genomic sequences were obtained by amplification and sequencing of seven overlapping regions covering the whole genome, and were studied by extensive phylogenetic analysis. Among them, 20 (83.3%) were classified unequivocally as genotype E (HBV/E). The remaining four (16.7%) clustered on a distinct branch within HBV/D with strong bootstrap and posterior probability values. Complete molecular characterization of these four strains was achieved by the Simplot program, bootscanning analysis and cloning experiments, and enabled us to identify an HBV/D-E recombinant that formed a new HBV/D subgenotype spreading in Niger, tentatively named D8. Moreover, 20 new complete HBV/E nucleotide sequences were determined that exhibited higher genetic variability than is generally described in Africa. One was found to be a recombinant containing HBV/D sequences in the preS2 and RT/Pol regions. Taken together, these data suggest that, in Niger, genetic variability of HBV strains is still evolving, probably reflecting ancient endemic HBV infection.
    Journal of General Virology 02/2010; 91(Pt 6):1609-20. · 3.13 Impact Factor

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