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Rossi-Tamisier M.,Center Hospitalo University Timone | Gerolami R.,Center Hospitalo University Conception | Colson P.,Center Hospitalo University Timone | Colson P.,Aix - Marseille University
Journal of Clinical Virology | Year: 2013

Background: Hepatitis E virus (HEV) is an emerging clinical threat in Europe among kidney and liver-transplant recipients. The incidence and prevalence of HEV infection in this special population are poorly known. False-negative results have been observed for anti-HEV IgG detection in severely immunocompromized persons. Moreover, large discrepancies have been reported between rates of anti-HEV IgG detection in blood donors and hepatitis E cases. Objectives: To compare anti-HEV IgG and IgM prevalence using two different commercial microplate enzyme-immuno assays (MEIAs) (Adaltis and Wantai) in 64 kidney-/liver-transplant recipients. Study design: Serum samples tested in our routine clinical practice over the 12/2009-12/2011 period with Adaltis MEIAs were retrospectively tested using Wantai MEIAs. IgG-positive sera were further tested by an immunoblot while those found IgM-positive were further tested with an immunochromatography rapid test and for the presence of HEV RNA. Results: Positive results on anti-HEV IgG testing were obtained for seven (10.9%) compared to 20 (31.3%) serum samples with Adaltis and Wantai assays, respectively (p= 0.005). Then, 6/7 (86%) of the serum samples positive with Adaltis and 16/20 (80%) of those positive with Wantai were positive with the immunoblot. One patient with chronic HEV infection was IgG-negative with both MEIAs. Regarding anti-HEV IgM, Adaltis and Wantai assays were concordant for 97% of the serum samples, prevalence being 8% with both MEIAs. Conclusions: The accuracy of currently available commercial or in-house anti-HEV IgG MEIAs should be tested comparatively on a panel of serum samples collected from solid organ-transplant recipients, including some who experienced PCR-documented HEV infection. © 2012 Elsevier B.V. Source

Colson P.,Center Hospitalo University Timone | Colson P.,Aix - Marseille University | Gayet S.,Center Hospitalo University Sainte Marguerite | Gerolami R.,Center Hospitalo University Conception
Antiviral Therapy | Year: 2011

HCV displays considerable levels of nucleotide and amino acid diversity. Recently, the relevance of natural polymorphisms in worldwide isolates has been addressed in view of future protease inhibitor (PI)-based treatments; geno-type-and subtype-specific natural polymorphisms within HCV NS3 protease were identified at amino acid sites associated either with resistance to PIs or with compensatory mutations. Here, we describe a case of chronic infection with HCV of genotype 3 subtype h (HCV-3h), formerly only described from three patients originating from Somalia, and we provide the first NS3 protease sequence for such strains. NS3 protease sequences of HCV-3h recovered in the present study harbour specific amino acid residues not encountered in other reference HCV genotypes and sub-types at nine of the 181 NS3 protease positions; none of these amino acids are known to confer resistance to PIs. Of note, 5′ untranslated region sequence-based genotyping classifies them into genotype 1. ©2011 International Medical Press. Source

Kaba M.,Aix - Marseille University | Kaba M.,Center Hospitalo University Timone | Moal V.,Aix - Marseille University | Gerolami R.,Center Hospitalo University Conception | And 2 more authors.
Intervirology | Year: 2013

Mammalian hepatitis E virus (HEV), the etiological agent of hepatitis E in humans, is a recently discovered infectious agent. It was identified for the first time in 1983 using electron microscopy on a faecal specimen of a person infected with non-A, non-B enterically-transmitted hepatitis. Based on retrospective and prospective studies, HEV was long described as one of the leading causes of acute viral hepatitis in tropical and subtropical countries, whereas in developed countries hepatitis E was considered an imported disease from HEV hyperendemic countries. Data from studies conducted during the past decade have greatly shifted our knowledge on the epidemiology and clinical spectrum of HEV. Recently, it has been shown that contrary to previous beliefs, hepatitis E is also an endemic disease in several developed countries, particularly in Japan and in Europe, as evidenced by reports of high anti-HEV immunoglobulin G prevalence in healthy individuals and an increasing number of non-travel-related acute hepatitis E cases. Moreover, a porcine reservoir and growing evidence of zoonotic transmission have been reported in these countries. This review summarizes the current knowledge on the epidemiology and prevention of transmission of mammalian HEV. Copyright © 2013 S. Karger AG, Basel. Source

Mezouar S.,Aix - Marseille University | Mege D.,Aix - Marseille University | Darbousset R.,Aix - Marseille University | Farge D.,Service de Medecine Interne et Pathologie Vasculaire | And 5 more authors.
Seminars in Oncology | Year: 2014

Platelet-derived microparticles (PMPs) represent the most abundant microparticle (MP) subtype. Their presence reflects platelet activity, physiopathology, and the thrombotic state of cancer patients. The quantity and composition of PMPs strictly depends on the way MPs were generated. Because platelets play a key role in cancer progression, as well as formation of metastasis, PMPs also may be important in the proliferation of cancer cells, cancer cell interactions, metastatic progression, angiogenesis, and inflammation. Alternatively, the concentration of circulating PMPs may differ according to the stage of a cancer and thus potentially could be used as a biomarker. Here we review the mechanisms underlying the generation and composition of PMPs and the clinical and experimental studies describing the involvement of PMPs in cancer and the Trousseau syndrome. Lastly, we focus on their clinical relevance, as well as their potential application as biomarkers in cancer. © 2014 Elsevier Inc. Source

Mezouar S.,Aix - Marseille University | Darbousset R.,Aix - Marseille University | Dignat-George F.,Aix - Marseille University | Dignat-George F.,Center Hospitalo University Conception | And 2 more authors.
International Journal of Cancer | Year: 2015

Venous thromboembolism constitutes one of the main causes of death during the progression of a cancer. We previously demonstrated that tissue factor (TF)-bearing cancer cell-derived microparticles accumulate at the site of injury in mice developing a pancreatic cancer. The presence of these microparticles at the site of thrombosis correlates with the size of the platelet-rich thrombus. The objective of this study was to determine the involvement of TF expressed by cancer cell-derived microparticles on thrombosis associated with cancer. We observed that pancreatic cancer cell derived microparticles expressed TF, its inhibitor tissue factor pathway inhibitor (TFPI) as well as the integrins αvβ1 and αvβ3. In mice bearing a tumor under-expressing TF, a significant decrease in circulating TF activity associated with an increase bleeding time and a 100-fold diminished fibrin generation and platelet accumulation at the site of injury were observed. This was mainly due to the interaction of circulating cancer cell-derived microparticles expressing TFPI with activated platelets and fibrinogen. In an ectopic model of cancer, treatment of mice with Clopidogrel, an anti-platelet drug, decreased the size of the tumors and restored hemostasis by preventing the accumulation of cancer cell-derived microparticles at the site of thrombosis. In a syngeneic orthotopic model of pancreatic cancer Clopidogrel also significantly inhibited the development of metastases. Together, these results indicate that an anti-platelet strategy may efficiently treat thrombosis associated with cancer and reduce the progression of pancreatic cancer in mice. What's new? Tissue factor (TF) plays a key role in coagulation and is capable of activating inflammatory and angiogenic responses, potentially facilitating the progression of cancer. As a result, anticoagulant or antiplatelet drugs could be effective means of prevention for tumor progression and metastasis. Here, pancreatic cancer cell-derived microparticles were found to express TF and its inhibitor TFPI. The microparticles interacted with platelets, with effects on bleeding and platelet accumulation, in mice. In cancer mouse models, treatment with the antiplatelet drug clopidogrel restored hemostasis, resulted in decreased tumor size, and prevented the development of metastases. © 2014 UICC. Source

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