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1. Practical management of patients on Janus kinase inhibitor (JAKi) therapy: Practical fact sheets drawn up by the Rheumatism and Inflammation Club (CRI), a group endorsed by the French Society for Rheumatology (SFR)

Author: Claire Daïen, Anne Tournadre, Victor de Lédinghen, Thao Pham, Marie-Elise Truchetet, Clément Prati, Thierry Lequerré, Christophe Richez, Gaetane Nocturne, Jean Sibilia, Benoit Le Goff, Raphaèle Seror, Jacques Morel, Valérie Pourcher, Philippe Goupille, Estibaliz Lazaro, Divi Cornec, Rhumatologie Bordeaux (SERVICE DE RHUMATOLOGIE), CHU Bordeaux [Bordeaux], Service de Rhumatologie [CHU de Montpellier], CHU Montpellier, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Haut-Lévêque [CHU de Bordeaux], Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Le Kremlin-Bicêtre (Rheumatology Department), Department of Rheumatology, Département d'hépatologie et de gastroentérologie [CHU Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], Service de rhumatologie [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Rhumatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Rhumatologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service de Rhumatologie [CHU Sainte Marguerite], Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], and Michel, Geneviève
Subjects: medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Rheumatic Diseases, Internal medicine, Humans, Janus Kinase Inhibitors, Medicine, Societies, Medical, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Janus kinase inhibitor, Inflammation, 030203 arthritis & rheumatology, 0303 health sciences, business.industry, Disease Management, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Antirheumatic Agents, [SDV.IMM]Life Sciences [q-bio]/Immunology, Club, business, Rheumatism
Abstract: International audience
Published: 2019
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2. Implementation of infliximab standardized doses after pharmacokinetic modelization in a cohort of patients with Crohn’s disease

Author: Aude Berroneau, S Djabarouti, F Xuereb, Florian Poullenot, Lucie Sauvaget, Julien Ollivier, D Breilh, David Laharie, Pauline Rivière, Frank Zerbib, Département d'hépatologie et de gastroentérologie [CHU Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Bibliothèque Sainte-Geneviève (BSG), Université Sorbonne Nouvelle - Paris 3, Université de Bordeaux (UB), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Département de pharmacocinétique et pharmacologie clinique, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CCSD, Accord Elsevier, and Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Crohn’s disease, medicine.medical_specialty, medicine.medical_treatment, Dose banding, Pharmacokinetic, Monte-Carlo simulation, Drug Costs, Modelling, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, Pharmacokinetics, Crohn Disease, Gastrointestinal Agents, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cost Savings, Internal medicine, Article CLINIQUE, Medicine, Humans, Drug Dosage Calculations, Prospective Studies, Prospective cohort study, Infusions, Intravenous, Retrospective Studies, Crohn's disease, Chemotherapy, Hepatology, Dose-Response Relationship, Drug, business.industry, Significant difference, Gastroenterology, medicine.disease, Infliximab, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Hospitalization, 030220 oncology & carcinogenesis, Cohort, 030211 gastroenterology & hepatology, Female, France, business, Monte Carlo Method, medicine.drug
Abstract: International audience; BACKGROUND:According to infliximab (IFX) license in Crohn's disease (CD), infusion doses are based on patient's body-weight. Dose banding providing standardized doses (SD) has been implemented in parenteral chemotherapy in order to optimize aseptic unit capacity and reduce drug expenditure, duration of hospital stay and costs without decreasing efficacy.MATERIAL AND METHOD:The first part was a single-center retrospective analysis of consecutive CD patients receiving IFX maintenance therapy to determine standardized doses covering more than 50% of infusions. The second part was a prospective cohort study assessing the impact of SD compared to body-weight doses (BWD) on admission duration and costs.RESULTS:Six IFX SD covering more than 90% of infusion doses were implemented for dose banding. According to the Monte-Carlo simulation, there was no significant difference between IFX SD and BWD maintenance regimens. When assessed prospectively in 116 patients (75 patients treated with SD and 41 with BWD) corresponding to 128 infusions, hospitalization duration was shortened by 70 min per patient (p
Published: 2019
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3. Resection of small bowel adenocarcinoma metastases: Results of the ARCAD-NADEGE cohort study

Author: Cedric Lecaille, Mohamad Chehimi, Romain Coriat, Marc Pocard, Thomas Aparicio, Sylvain Manfredi, David Tougeron, Eric Terrebonne, Isabelle Baumgaertner, Aziz Zaanan, Jean-Louis Legoux, Jean-Baptiste Bachet, Olivier Bouché, Anne-Laure Villing, Pauline Afchain, Jean-Marc Gornet, Robert Benamouzig, Johan Gagnière, Corinne Sarda, Jean-Luc Faucheron, Pierre Rompteaux, J. Forestier, Nathalie Bonichon-Lamichhane, Thierry Lecomte, Service de Gastro-entérologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service de Chirurgie Digestive et Hépatobiliaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service d'Hépato-Gastro-Entérologie [Hôpital Saint-Louis, AP-HP], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Gastro-entérologie et hépatologie [Hôpital Cochin], [AP-HP], Hôpital Cochin [AP-HP], Service de gastro-entérologie [Henri Mondor AP-HP, Créteil], Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Oncologie 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), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Clinique Tivoli Ducos [Bordeaux], CHU Robert Debré [Reims], Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Polyclinique Bordeaux Nord Aquitaine, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Saint-Quentin, Hôpital d'Auxerre, Partenaires INRAE, Hopital de castres, Service Hépato-gastro-entérologie et oncologie digestive [CHR Orléans], Centre Hospitalier Régional d'Orléans (CHRO), A.R.C.A.D. (Aide et Recherche en CAncerologie Digestive) fundation [NA2009], Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Service Chirurgie Disgestive, Centre Hospitalier Universitaire Estaing, Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), AP HP, Departement Oncologie, Centre Hospitalier Universitaire Henri Mondor, Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Cooperator Multidisciplinary Oncology Group (GERCOR), Service de Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université de Reims Champagne-Ardenne (URCA), Unité de Chirurgie Colorectale, CHU Grenoble-Hôpital Michallon, Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Pontchaillou, Service d'Hépato-Gastroentérologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Département d'hépatologie et de gastroentérologie [CHU Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], Université de Picardie Jules Verne (UPJV), Regional Hospital of Orleans, Centre de Recherche en Nutrition Humaine, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), CHU Trousseau [APHP], Service d'Oncologie Médicale [CHU Saint-Antoine], and CHU Saint-Antoine [AP-HP]
Subjects: Male, Lymphovascular invasion, [SDV]Life Sciences [q-bio], Gastroenterology, Metastasis, 0302 clinical medicine, Duodenal Neoplasms, Positron Emission Tomography Computed Tomography, Clinical endpoint, Prospective Studies, Neoplasm Metastasis, Digestive System Surgical Procedures, Aged, 80 and over, Univariate analysis, Small bowel adenocarcinoma, General Medicine, Middle Aged, Prognosis, Magnetic Resonance Imaging, Primary tumor, 3. Good health, Survival Rate, medicine.anatomical_structure, Oncology, Metastases resection, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, France, Cohort study, medicine.drug, Adult, Ampulla of Vater, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Adenocarcinoma, Disease-Free Survival, 03 medical and health sciences, Internal medicine, medicine, Humans, Aged, Neoplasm Staging, Lung, business.industry, medicine.disease, Oxaliplatin, Adjuvant chemotherapy, Hepatic metastases, Surgery, business, Follow-Up Studies
Abstract: Introduction Data are lacking with regard to curative resection of metastasis from small bowel adenocarcinoma (SBA). This study evaluated outcomes and prognostic factors in patients with curatively resected metastatic SBA. Methods A series of 34 patients undergoing resection of metastatic SBA from January 2009 to November 2014 at French centers were included into this cohort study. The primary endpoint was overall survival (OS). Secondary endpoints were recurrence-free survival (RFS) and prognostic factors. Univariate analyses were performed to determine prognostic risk factors. Results The sites of SBA metastases were peritoneal (29.4%), liver (26.5%), lymph nodes (11.8%), lung (2.9%), multiple (14.7%), and other (14.7%). Thirty (88.2%) patients received adjuvant or perioperative chemotherapy, mainly was oxaliplatin-based (76.5%). The median OS was 28.6 months and RFS was 18.7 months. Fourteen (41.2%) patients survived for more than 36 months. In univariate analysis, poor differentiation (P = 0.006), invaded margins (P = 0.003), and lymphatic invasion in the primary tumor (P = 0.039) were associated with decreased OS. Conclusion Overall survival of patients after resection of metastatic SBA remains poor, but long-term survivors are observed. Resection of metastatic SBA should be consider if patients are expected to be operated on with curative intent and have moderately or well-differentiated tumors.
Published: 2019
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4. Value of Contrast-Enhanced Ultrasound Quantification Criteria for Identifying Patients not Responding to Bevacizumab-Based Therapy for Colorectal Liver Metastases

Author: Jean-Yves Douillard, Olivier Bouché, Olivier Capitain, Aurore Bleuzen, François Tranquart, Thierry Lecomte, Philippe Manzoni, Jean-Philippe Spano, Claude Marcus, Christophe Aubé, Paul-Armand Dujardin, Aurélie Ferru, Jean-Pierre Tasu, Hervé Trillaud, Julie Léger, Catherine Labbe-Devilliers, Sylvain Manfredi, Eric Terrebonne, Denis Smith, Christophe Borg, Olivier Lucidarme, Advice-US Consulting, Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Reims Champagne-Ardenne (URCA), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de radiologie [CHRU Besancon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Département d'hépatologie et de gastroentérologie [CHU Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Saint-André, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service d'Oncologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Radiologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de Radiologie (POITIERS - Radio), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Radiologie (TOURS - Radio), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Université de Tours (UT)
Subjects: medicine.medical_specialty, Bevacizumab, Colorectal cancer, medicine.medical_treatment, Urology, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030218 nuclear medicine & medical imaging, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Vascularity, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Prospective cohort study, Chemotherapy, business.industry, Liver Neoplasms, Area under the curve, medicine.disease, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, medicine.symptom, Colorectal Neoplasms, business, medicine.drug, Contrast-enhanced ultrasound
Abstract: To evaluate changes in tumor vascularization parameters based on contrast-enhanced ultrasound (CEUS) quantification criteria of at least one visible liver metastasis as an early predictor of non-response to chemotherapy, including bevacizumab for colorectal cancer (CRC) liver metastases. This multicenter prospective study included patients who received first-line bevacizumab-based chemotherapy. Tumor enhancement measured using CEUS within one liver metastasis and in relation to the surrounding healthy liver was quantified within 8 days before the first infusion of bevacizumab (E0), 24 hours after the end of the first infusion of bevacizumab (E1), in the 24 hours before the 2nd and 3 rd infusion of bevacizumab on day 15 (E2) and day 30 (E3), respectively, and after 2 months of treatment (E4). Endpoints were tumor response using RECIST criteria at 2 months, progression-free survival (PFS) and overall survival (OS). Among the 137 patients included in this study, 109 were analyzed. Only CEUS parameters calculated in relation to healthy liver were significant. High wash-in and wash-out rates at baseline were significantly associated with a better tumor response. Increases over time E2-E0 and E3-E0 for peak enhancement were significantly associated with shorter progression-free survival. Increases over time E2-E0 and E3-E0 for peak enhancement and wash-in area under the curve were significantly associated with a shorter overall survival. This large study demonstrated that early dynamic changes in the vascularity of liver metastases evaluated by quantified CEUS are associated with outcome in patients receiving first-line bevacizumab-based treatment for metastatic CRC.ZIEL: Bewertung der Veränderungen der Tumorvaskularisations-Parameter anhand der Quantifizierungskriterien des kontrastverstärkten Ultraschalls (CEUS) bei mindestens einer sichtbaren Lebermetastase als früher prädiktiver Marker für ein Nicht-Ansprechen auf die Chemotherapie mit Bevacizumab bei Lebermetastasen des kolorektalen Karzinoms (CRC). Diese multizentrische, prospektive Studie umfasste Patienten, die eine Chemotherapie mit Bevacizumab als Mittel der ersten Wahl erhalten hatten. Die mittels CEUS gemessene Kontrastverstärkung des Tumors innerhalb einer Lebermetastase und in Relation zur umgebenden gesunden Leber wurde innerhalb von 8 Tagen vor der ersten Infusion von Bevacizumab (E0), 24 Stunden nach Ende der ersten Bevacizumab-Infusion (E1), 24 Stunden vor der 2. und 3. Bevacizumab-Infusion an Tag 15 (E2) bzw. Tag 30 (E3) sowie nach 2 Monaten Behandlung (E4) quantifiziert. Endpunkte waren das Ansprechen des Tumors mittels RECIST-Kriterien nach 2 Monaten, das progressionsfreie Überleben (PFS) und die Gesamtüberlebenszeit (OS). Von den 137 in dieser Studie eingeschlossenen Patienten wurden 109 analysiert. Nur diejenigen CEUS-Parameter, die relativ zur gesunden Leber berechnet wurden, waren signifikant. Bei Behandlungsbeginn waren hohe Wash-in und Wash-out Raten signifikant mit einem besseren Ansprechens des Tumors assoziiert. Die Anstiege über die Zeit von E2-E0 und E3-E0 für das Peak-Enhancement waren signifikant mit einem kürzeren progressionsfreien Überleben assoziiert. Die Anstiege über die Zeit von E2-E0 und E3-E0 für das Peak-Enhancement und der „area-under the curve“ des Wash-in zeigten einen signifikanten Zusammenhang mit einer geringeren Gesamtüberlebenszeit. Diese große Studie zeigte einen Zusammenhang zwischen den frühen dynamischen Veränderungen der Vaskularisierung von Lebermetastasen mittels quantifizierter CEUS und dem Erfolg einer Bevacizumab-basierten First-Line-Therapie bei Patienten mit metastasierendem CRC.
Published: 2018
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5. Retreatment With Sofosbuvir Plus Grazoprevir/Elbasvir Plus Ribavirin of Patients With Hepatitis C Virus Genotype 1 or 4 Who Previously Failed an NS5A- or NS3-Containing Regimen: The ANRS HC34 REVENGE Study

Author: Caroline Jezequel, Laurent Alric, Didier Samuel, Sophie Metivier, Stanislas Pol, Christophe Hézode, Christelle Tual, Severine Gibowski, Dominique Larrey, Jean-Michel Pawlotsky, Claire Laforest, Albert Tran, Eric Bellissant, Aurelie Pailhe, Victor de Ledinghen, Marc Bourlière, Alain Renault, Fabien Zoulim, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-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), IMRB - VHC/'Viruses-Hepatology-Cancers' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris], CHU Pontchaillou [Rennes], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Toulouse [Toulouse], Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Hôpital Paul Brousse, 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-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANRS France Recherche Nord & sud Sida-hiv hépatites, Hôpital Saint-Joseph [Marseille], Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-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 Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Centre de Recherche Translationnelle ( CRT ), Pharmacochimie et Pharmacologie Pour le Développement ( PHARMA-DEV ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique ( CNRS ), CHU Saint-Eloi-Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), CHU Purpan, Centre méditérannéen de médecine moléculaire ( C3M ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Translationnelle (CRT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Inserm, UMR-1053, Université de Bordeaux, Bordeaux, F-33076, France, Département d'hépatologie et de gastroentérologie [CHU Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Cyclopropanes, Male, Sofosbuvir, Sustained Virologic Response, Hepacivirus, medicine.disease_cause, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, grazoprevir/elbasvir, Prospective Studies, Treatment Failure, Sulfonamides, Imidazoles, virus diseases, Hepatitis C, Middle Aged, 3. Good health, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious Diseases, Grazoprevir, Retreatment, RNA, Viral, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.drug, Microbiology (medical), Elbasvir, medicine.medical_specialty, Genotype, Hepatitis C virus, Antiviral Agents, sofosbuvir, 03 medical and health sciences, Internal medicine, Quinoxalines, Ribavirin, medicine, Humans, NS5A, Aged, Benzofurans, DAA, business.industry, [ SDV.SP.PHARMA ] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Chronic, medicine.disease, Virology, Amides, digestive system diseases, Regimen, 030104 developmental biology, chemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Carbamates, hepatitis C, business, RAS
Abstract: International audience; Background: Failure to achieve sustained virological response (SVR) with hepatitis C virus (HCV) direct-acting antiviral (DAA)–based regimens is commonly associated with emergence of resistance-associated substitutions (RASs). Retreatment of patients who failed prior DAAs remains challenging. The aim of this prospective and randomized study was to evaluate the efficacy (primary endpoint: SVR 12 weeks after end of treatment [SVR12]) and safety of sofosbuvir + grazoprevir/elbasvir + ribavirin for 16 or 24 weeks in patients who had failed to achieve SVR on previous NS5A- or NS3-based therapy and with evidence of RASs at failure.Methods: Patients were chronically infected with HCV genotype 1 or 4. Most of them had advanced fibrosis or compensated cirrhosis (liver stiffness 5.8–48.8 kPa).Results: All patients achieved HCV RNA below the lower limit of quantification (either target detected [unquantifiable] or target not detected) during treatment. SVR12 was achieved by 25 of 26 patients. The only patient who did not reach SVR was a patient who died, but HCV RNA was negative at this time (5 weeks after stopping treatment). No patient discontinued treatment because of adverse events or virological failure. Globally, treatment was well tolerated.Conclusions: Our findings support the concept of retreating with sofosbuvir + grazoprevir/elbasvir + ribavirin, for 16 weeks, genotype 1 or 4 DAA-experienced patients with proven NS5A or NS3 RASs.
Published: 2018
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6. Common variants in glucuronidation enzymes and membrane transporters as potential risk factors for colorectal cancer: a case control study

Author: Sabrina Falkowski, Jean-Baptiste Woillard, Deborah Postil, Denis Smith, Rosine Guimbaud, Claire Thalamas, Pierre Marquet, Nicolas Picard, Koukeb Rouguieg-Malki, Nicole Tubiana-Mathieu, Antoine Pariente, Eric Terrebonne, Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), 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), Centre d'Investigation Clinique de Limoges (CIC1435), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'hépatologie et de gastroentérologie [CHU Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Unité de Pharmaco-épidémiologie [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Université de Bordeaux Ségalen [Bordeaux 2], Département d'Oncologie [CHU Bordeaux] (Cancérologie/Oncologie/Digestive), GH Sud Haut-Lévêque [CHU Hôpitaux de Bordeaux] (Centre médico chirurgical Magellan)-Hôpital Saint-André [CHU de Bordeaux], Département d'Oncologie Digestive [CHU Toulouse], CHU Toulouse [Toulouse], Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pharmacologie, toxicologie et pharmacovigilance [CHU Limoges], This work was funded by the Ligue Nationale contre le Cancer, the Regional Health Agency of Limousin and the Limoges University Hospital. The funders had no involvement in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript., BMC, BMC, Hôpital Haut-Lévêque - CHU de Bordeaux (Centre médico chirurgical Magellan)-Hôpital Saint-André [CHU de Bordeaux], Département Oncologie médicale digestive [CHU Toulouse], Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse]
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Genotype, Biomarkers, Tumor, Genetics, medicine, Humans, Genetic Predisposition to Disease, Glucuronosyltransferase, Aged, OATP, Haplotype, Case-control study, Membrane Transport Proteins, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Colorectal cancer, Multidrug Resistance-Associated Protein 2, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Pharmacogenetics, Case-Control Studies, 030220 oncology & carcinogenesis, biology.protein, Efflux transporters, Population study, Female, Efflux, Colorectal Neoplasms, SLCO1B1, UGT, Follow-Up Studies, Research Article
Abstract: Background Associations between polymorphisms of UDP-glucuronosyltransferases (UGTs) or efflux transporters (e.g., P-glycoprotein and MRP2) and different types of cancer have been described, whereas the role of influx transporters (e.g. OATP1B1 and OATP2B1) has been seldom explored. The GenColon study investigated potential associations between variant alleles of UGTs, efflux and influx transporters and CRC. Methods Three hundred CRC cases were matched with 300 controls for age, sex and enrolment site. Fifteen SNPs in UGT1A6–9, UGT2B7, ABCB1, ABCC2, SLCO1B1 and SLCO2B1 genes were characterized using Taqman® PCR. Using multivariate conditional logistic regression, we investigated the relationships between CRC and “environmental” risk factors (physical activity, housing and working areas, consumption of red meat, tobacco, alcohol); genetic polymorphisms, in the study population and in the subgroups with “environmental” risk factors. Results No significant association was observed for the analyzed SNPs (or haplotypes). However, an increased CRC risk was found in carriers of the UGT1A8 rs1042597-G variant allele (additive risk OR = 3.39[1.29–8.89], p = 0.02951) in the subgroup of meat-consumers (n = 84), and in carriers of the ABCB1 rs1045642-T (exon26) variant allele (additive risk; OR = 1.89[1.10–3.39], p = 0.0257) in the “never alcohol consumption subgroup” (n = 125). In addition, as previously reported, the following CRC risk factors were identified: absence of physical activity (OR = 6.35[3.70–10.9], p 30 years (3.37[1.63–6.96], p = 0.0010). Conclusions Variant genotypes of influx transporters (OATP1B1 and 2B1) were not associated with CRC. This study confirmed the influence of lifestyle factors, but not the previously reported detrimental effect of SNPs in intestinal UGTs or efflux transporters, except for a UGT1A8 variant in subjects consuming meat and the exon 26 SNP of ABCB1 in the never alcohol consumption subgroup. Trial registration Registered in Direction Générale de la Santé the 1st July 2008 under the number DGS2008–0144. Electronic supplementary material The online version of this article (10.1186/s12885-017-3728-0) contains supplementary material, which is available to authorized users.
Published: 2017
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7. Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection

Author: Marc, Bourlière, Stuart C, Gordon, Steven L, Flamm, Curtis L, Cooper, Alnoor, Ramji, Myron, Tong, Natarajan, Ravendhran, John M, Vierling, Tram T, Tran, Stephen, Pianko, Meena B, Bansal, Victor, de Lédinghen, Robert H, Hyland, Luisa M, Stamm, Hadas, Dvory-Sobol, Evguenia, Svarovskaia, Jie, Zhang, K C, Huang, G Mani, Subramanian, Diana M, Brainard, John G, McHutchison, Elizabeth C, Verna, Peter, Buggisch, Charles S, Landis, Ziad H, Younes, Michael P, Curry, Simone I, Strasser, Eugene R, Schiff, K Rajender, Reddy, Michael P, Manns, Kris V, Kowdley, Stefan, Zeuzem, Shyamasundaran, Kottilil, Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Henry Ford Health System, Feinberg School of Medicine, Northwestern University [Evanston], Baylor College of Medicine (BCM), Baylor University, Monash Medical Centre [Clayton, Australia], Département d'hépatologie et de gastroentérologie [CHU Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Gilead Sciences, Inc. [Foster City, CA, USA], Institute for Interdisciplinary Medicine Hamburg, University of Washington [Seattle], Gastro One, Miami University [Ohio] (MU), Pennsylvania State University (Penn State), Penn State System, Dept. of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School [Hannover] (MHH), Virginia Mason Medical Center, Saarland University [Saarbrücken], POLARIS-1 Investigators, and POLARIS-4 Investigators
Subjects: Cyclopropanes, Liver Cirrhosis, Male, 0301 basic medicine, Aminoisobutyric Acids, Sofosbuvir, Hepacivirus, Viral Nonstructural Proteins, medicine.disease_cause, Gastroenterology, 0302 clinical medicine, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, Sulfonamides, virus diseases, General Medicine, Hepatitis C, Middle Aged, Pibrentasvir, 3. Good health, Drug Combinations, Female, 030211 gastroenterology & hepatology, medicine.drug, Adult, medicine.medical_specialty, Macrocyclic Compounds, Genotype, Proline, Lactams, Macrocyclic, Voxilaprevir, Hepatitis C virus, Antiviral Agents, Heterocyclic Compounds, 4 or More Rings, Sofosbuvir/velpatasvir, 03 medical and health sciences, Leucine, Quinoxalines, Internal medicine, Drug Resistance, Viral, medicine, Humans, Protease Inhibitors, Aged, business.industry, Glecaprevir, medicine.disease, Virology, digestive system diseases, Regimen, 030104 developmental biology, Carbamates, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Patients who are chronically infected with hepatitis C virus (HCV) and who do not have a sustained virologic response after treatment with regimens containing direct-acting antiviral agents (DAAs) have limited retreatment options.We conducted two phase 3 trials involving patients who had been previously treated with a DAA-containing regimen. In POLARIS-1, patients with HCV genotype 1 infection who had previously received a regimen containing an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive either the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the protease inhibitor voxilaprevir (150 patients) or matching placebo (150 patients) once daily for 12 weeks. Patients who were infected with HCV of other genotypes (114 patients) were enrolled in the sofosbuvir-velpatasvir-voxilaprevir group. In POLARIS-4, patients with HCV genotype 1, 2, or 3 infection who had previously received a DAA regimen but not an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir-voxilaprevir (163 patients) or sofosbuvir-velpatasvir (151 patients) for 12 weeks. An additional 19 patients with HCV genotype 4 infection were enrolled in the sofosbuvir-velpatasvir-voxilaprevir group.In the three active-treatment groups, 46% of the patients had compensated cirrhosis. In POLARIS-1, the rate of sustained virologic response was 96% with sofosbuvir-velpatasvir-voxilaprevir, as compared with 0% with placebo. In POLARIS-4, the rate of response was 98% with sofosbuvir-velpatasvir-voxilaprevir and 90% with sofosbuvir-velpatasvir. The most common adverse events were headache, fatigue, diarrhea, and nausea. In the active-treatment groups in both trials, the percentage of patients who discontinued treatment owing to adverse events was 1% or lower.Sofosbuvir-velpatasvir-voxilaprevir taken for 12 weeks provided high rates of sustained virologic response among patients across HCV genotypes in whom treatment with a DAA regimen had previously failed. (Funded by Gilead Sciences; POLARIS-1 and POLARIS-4 ClinicalTrials.gov numbers, NCT02607735 and NCT02639247 .).
Published: 2017
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8. Quantification of portal–bridging fibrosis area more accurately reflects fibrosis stage and liver stiffness than whole fibrosis or perisinusoidal fibrosis areas in chronic hepatitis C

Author: Jean-Pierre Zarski, Jérôme Boursier, Victor de Lédinghen, Brigitte Le Bail, Jeremy Sandrini, Paul Calès, Marie-Christine Rousselet, Julien Chaigneau, Nathalie Sturm, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Département d'anatomie et cythologie pathologique, CHU Grenoble-Hôpital Michallon, Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, 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), Laboratoire d'anatomie pathologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Département d'hépatologie et de gastroentérologie [CHU Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], BaRITOn - Bordeaux Research in Translational Oncology, and Université de Bordeaux Ségalen [Bordeaux 2]
Subjects: Adult, Liver Cirrhosis, Male, Pathology, medicine.medical_specialty, Cirrhosis, [SDV]Life Sciences [q-bio], Gastroenterology, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, image analysis, Fibrosis, Internal medicine, medicine, Humans, automated segmentation, Stage (cooking), liver biopsy, medicine.diagnostic_test, business.industry, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, 3. Good health, Fatty Liver, Fibroscan, Liver, 030220 oncology & carcinogenesis, Portal fibrosis, Liver biopsy, Disease Progression, Elasticity Imaging Techniques, Female, 030211 gastroenterology & hepatology, Elastography, Steatosis, business, Algorithms, morphometry
Abstract: International audience; Morphometry provides an objective evaluation of fibrosis in liver diseases. We developed an image analysis algorithm using automated thresholding and segmentation to separately quantify the areas and the fractal dimensions of portal–bridging fibrosis and perisinusoidal fibrosis in chronic hepatitis C liver biopsies. We studied 427 digitized liver biopsies and compared the automated measures of the different fibrosis compartments with (1) the Metavir F (fibrosis) and A (activity) histological scores, (2) the digitally assessed area of steatosis, and (3) the liver stiffness measured by elastography (Fibroscan). The perisinusoidal fibrosis area was higher than that of portal fibrosis in stages ≤F2; it reached its highest value in F2 stage and stabilized thereafter. The F3 stage was characterized by equal proportions of portal–bridging and perisinusoidal fibrosis, whereas portal–bridging area was predominant in cirrhosis. Measurement of portal–bridging fibrosis showed highly significantly different values between contiguous F stages; the ratio of portal–bridging fibrosis/perisinusoidal fibrosis displayed less overlap between Metavir stages than did the whole fibrosis area values. Fractal dimension showed that portal–bridging fibrosis tended to display a homogeneous surface-like spatial organization, whereas perisinusoidal fibrosis appeared more heterogeneous according to stage and curvilinear. The portal–bridging fibrosis area was low in cases with low Metavir activity and little steatosis, and became predominant with increasing activity and steatosis. Using stepwise multiple linear regression analysis, the liver stiffness was independently correlated to the portal–bridging fibrosis area (first step, P
Published: 2014
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9. Efficacy of adalimumab in patients with Crohn's disease and symptomatic small bowel stricture: a multicentre, prospective, observational cohort (CREOLE) study

Author: David Laharie, Gilles Bommelaer, Carmen Stefanescu, Silvio Danese, Jacques Moreau, Matthieu Allez, Stéphane Nancey, Romain Altwegg, Anne Bourrier, Jean-Yves Mary, Xavier Roblin, Vered Abitbol, Laurence Picon, Yoram Bouhnik, Guillaume Savoye, Xavier Hébuterne, Laurent Peyrin-Biroulet, Guillaume Bouguen, Edouard Louis, Franck Carbonnel, Magaly Zappa, Maria Nachury, Hedia Brixi, Mathurin Fumery, Arnaud Bourreille, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon, Service d'hépato-gastro-entérologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Département d'hépatologie et de gastroentérologie, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service de gastro-entérologie et nutrition clinique, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Service de Gastro-entérologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Service des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille], Fédération Hospitalière de France-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Claude Huriez [Lille], Service d'hépato-gastro-entérologie et cancérologie digestive [CHU de Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'hépato-gastro-entérologie, cancérologie digestive et assistance nutritionnelle [CHU de Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Hépato-Gastro-Onco-Entérologie [CHRU de Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Gastro-entérologie et Nutrition[Rangueil], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Service d'Hépato-Gastroentérologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Autophagie infections immunité – Autophagy Infection Immunity, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Hépato-gastro-entérologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service des Maladies de l'Appareil Digestif, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Département d'Hépato-Gastroentérologie, Hôtel-Dieu-CHU Clermont-Ferrand-Université de Clermont-Ferrand, Gastroenterology, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed)-Humanitas University [Milan] (Hunimed), Université de Liège, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Fédération Hospitalière de France-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'Hépato-Gastroentérologie [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), OUERTANI, jeannette, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service des Maladies de l'Appareil Digestif [CHU Rennes], CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Bouhnik, Y, Carbonnel, F, Laharie, D, Stefanescu, C, Hebuterne, X, Abitbol, V, Nachury, M, Brixi, H, Bourreille, A, Picon, L, Bourrier, A, Allez, M, Peyrin-Biroulet, L, Moreau, J, Savoye, G, Fumery, M, Nancey, S, Roblin, X, Altwegg, R, Bouguen, G, Bommelaer, G, Danese, S, Louis, E, Mary, Jy, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), CHU Lille-CHU Lille, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS 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)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, medicine.medical_treatment, CROHN'S DISEASE, Disease, 03 medical and health sciences, 0302 clinical medicine, Clinical endpoint, Adalimumab, Medicine, IBD CLINICAL, Crohn's disease, business.industry, Inflammatory Bowel Disease, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Bowel resection, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Surgery, 030220 oncology & carcinogenesis, Cohort, ABDOMINAL MRI, 030211 gastroenterology & hepatology, Observational study, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, business, Cohort study, medicine.drug
Abstract: ObjectiveThe efficacy of anti-tumour necrosis factors (anti-TNFs) in patients with Crohn's disease (CD) and symptomatic small bowel stricture (SSBS) is controversial. The aim of this study was to estimate the efficacy of adalimumab in these patients and to identify the factors predicting success.DesignWe performed a multicentre, prospective, observational cohort study in patients with CD and SSBS. The included patients underwent magnetic resonance enterography at baseline and subsequently received adalimumab. The primary endpoint was success at week 24, defined as adalimumab continuation without prohibited treatment (corticosteroids after the eight week following inclusion, other anti-TNFs), endoscopic dilation or bowel resection. The baseline factors independently associated with success were identified using a logistic regression model, leading to a simple prognostic score. Secondary endpoints were prolonged success after week 24 (still on adalimumab, without dilation nor surgery) and time to bowel resection in the whole cohort.ResultsFrom January 2010 to December 2011, 105 patients were screened and 97 were included. At week 24, 62/97 (64%) patients had achieved success. The prognostic score defined a good prognosis group with 43/49 successes, an intermediate prognosis group with 17/28 successes and a poor prognosis group with 1/16 successes. After a median follow-up time of 3.8 years, 45.7%±6.6% (proportion±SE) of patients who were in success at week 24 (ie, 29% of the whole cohort) were still in prolonged success at 4 years. Among the whole cohort, 50.7%±5.3% of patients did not undergo bowel resection 4 years after inclusion.ConclusionsA successful response to adalimumab was observed in about two-thirds of CD patients with SSBS and was prolonged in nearly half of them till the end of follow-up. More than half of the patients were free of surgery 4 years after treatment initiation.Clinical Trial registration numberNCT01183403; Results.
Published: 2017
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10. Risk of Incident Cancer in Inflammatory Bowel Disease Patients Starting Anti-TNF Therapy While Having Recent Malignancy

Author: Poullenot, Florian, Seksik, Philippe, Beaugerie, Laurent, Amiot, Aurélien, Nachury, Maria, Abitbol, Vered, Stefanescu, Carmen, Reenaers, Catherine, Fumery, Mathurin, Pelletier, Anne-Laure, Nancey, Stéphane, Peyrin-Biroulet, Laurent, Bourreille, Arnaud, Hébuterne, Xavier, Brixi, Hedia, Savoye, Guillaume, Lourenço, Nelson, Altwegg, Romain, Buisson, Anthony, Cazelles-Boudier, Christine, Racine, Antoine, Vergniol, Julien, Laharie, David, Getaid, Groupe d'Etude Thérapeutique Des Affections, CHU Bordeaux [Bordeaux], Université Pierre et Marie Curie - Paris 6 (UPMC), Microorganismes et physiopathologie intestinale (ERL INSERM U1157 - CNRS UMR 7203), Laboratoire des biomolécules (LBM UMR 7203), Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Paris Descartes - Paris 5 (UPD5), Service de Gastro-entérologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Liège, Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Université de Picardie Jules Verne (UPJV), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Archet 2 [Nice] (CHU), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Hopital Saint-Louis [AP-HP] (AP-HP), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA), Centre Hospitalier de la Côte Basque (CHCB), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Hôpital Haut-Lévêque [CHU Bordeaux], Université de Bordeaux (UB), Groupe d’Étude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID), Abbvie, MSD, Biocodex, Ferring, Covidien, Takeda, Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Gastroentérologie et nutrition [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 International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Le CHCB, Centre Hospitalier de la Côte Basque, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Département d'hépatologie et de gastroentérologie [CHU Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Hôpital Beaujon, Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Service de Hépato-gastro-entérologie et cancérologie digestive [APHP Bichat Claude Bernard], Service d'hépato-gastroentérologie, 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), Infection bactérienne, inflammation, et carcinogenèse digestive, Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-gastroentérologie [HU Robert Debré, Reims], Hôpital universitaire Robert Debré [Reims], Service d'Hépato-Gastroentérologie [Rouen], Institute for Research and Innovation in Biomedicine (IRIB), Service d'hépato-gastro-entérologie [Hôpital Saint-Louis, APHP], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hépato-gastro-entérologie, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Department of Hepato-Gastroenterology, University Hospital Estaing of Clermont-Ferrand, Université d'Auvergne (Clermont Ferrand 1) (UdA), Hôpital de Bayonne [Bayonne], Service d'Hépato-gastro-entérologie [APHP Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, and GETAID
Subjects: Male, Anti-Inflammatory Agents, Inflammatory bowel disease, Gastroenterology, 0302 clinical medicine, Crohn Disease, Neoplasms, Immunology and Allergy, Young adult, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, education.field_of_study, Incidence (epidemiology), Incidence, Neoplasms, Second Primary, Middle Aged, 3. Good health, Survival Rate, risk of incident cancer, 030220 oncology & carcinogenesis, Cohort, 030211 gastroenterology & hepatology, Female, previous cancer, Adult, medicine.medical_specialty, Adolescent, Population, Malignancy, Disease-Free Survival, 03 medical and health sciences, Young Adult, inflammatory bowel disease, Internal medicine, medicine, Humans, education, Survival rate, Aged, business.industry, Tumor Necrosis Factor-alpha, Adalimumab, Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, anti-TNF, medicine.disease, Infliximab, Colitis, Ulcerative, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract: International audience; Background:Patients with inflammatory bowel disease (IBD) and history of malignancy within the last 5 years are usually contraindicated for receiving anti-tumor necrosis factor (anti-TNF) agents. The aim of this study is to assess survival without incident cancer in a cohort of IBD patients exposed to anti-TNF while having previous malignancy within past 5 years.Methods:Data from IBD patients with previous malignancy diagnosed within the last 5 years before starting an anti-TNF agent were collected through a Groupe d'Etude Therapeutiques des Affections Inflammatoires du tube Digestif multicenter survey. Inclusion date corresponded to the first anti-TNF administration after cancer diagnosis.Results:Twenty centers identified 79 cases of IBD patients with previous malignancy diagnosed 17 months (median; range: 1-65) before inclusion. The most frequent cancer locations were breast (n = 17) and skin (n = 15). After a median follow-up of 21 (range: 1-119) months, 15 (19%) patients developed incident cancer (8 recurrent and 7 new cancers), including 5 basal-cell carcinomas. Survival without incident cancer was 96%, 86%, and 66% at 1, 2, and 5 years, respectively. Crude incidence rate of cancer was 84.5 (95% CI, 83.1-85.8) per 1000 patient-years.Conclusions:In a population of refractory IBD patients with recent malignancy, anti-TNF could be used taking into account a mild risk of incident cancer. Pending prospective and larger studies, a case-by-case joint decision taken with the oncologist is recommended for managing these patients in daily practice.
Published: 2016
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11. Improved fibrosis staging by elastometry and blood test in chronic hepatitis C

Author: Calès, Paul, Boursier, Jérôme, Ducancelle, Alexandra, Oberti, Frédéric, Hubert, Isabelle, Hunault, Gilles, De Ledinghen, Victor, Zarski, Jean-Pierre, Salmon, Dominique, Lunel, Françoise, Bronowicki, J.P., Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Service d'Hépato-gastroentérologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Laboratoire de virologie [CHU Angers], Département d'hépatologie et de gastroentérologie [CHU Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], BaRITOn - Bordeaux Research in Translational Oncology, Université de Bordeaux Ségalen [Bordeaux 2], Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, 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 de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)
Subjects: Adult, Liver Cirrhosis, Male, fibroscan, medicine.medical_specialty, Cirrhosis, FIBROMETER, diagnosis, Biopsy, [SDV]Life Sciences [q-bio], Population, blood test, Severity of Illness Index, Gastroenterology, Chronic hepatitis, Predictive Value of Tests, Fibrosis, Internal medicine, Humans, Medicine, Blood test, Prospective Studies, education, liver biopsy, liver fibrosis, education.field_of_study, reliability, Hepatology, medicine.diagnostic_test, business.industry, cirrhosis, Reproducibility of Results, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, 3. Good health, Liver, Liver biopsy, Elasticity Imaging Techniques, Female, diagnostic accuracy, hepatitis C, business, Biomarkers
Abstract: International audience; AIMS:Our main objective was to improve non-invasive fibrosis staging accuracy by resolving the limits of previous methods via new test combinations. Our secondary objectives were to improve staging precision, by developing a detailed fibrosis classification, and reliability (personalized accuracy) determination.METHODS:All patients (729) included in the derivation population had chronic hepatitis C, liver biopsy, 6 blood tests and Fibroscan. Validation populations included 1584 patients.RESULTS:The most accurate combination was provided by using most markers of FibroMeter and Fibroscan results targeted for significant fibrosis, i.e. 'E-FibroMeter'. Its classification accuracy (91.7%) and precision (assessed by F difference with Metavir: 0.62 ± 0.57) were better than those of FibroMeter (84.1%, P < 0.001; 0.72 ± 0.57, P < 0.001), Fibroscan (88.2%, P = 0.011; 0.68 ± 0.57, P = 0.020), and a previous CSF-SF classification of FibroMeter + Fibroscan (86.7%, P < 0.001; 0.65 ± 0.57, P = 0.044). The accuracy for fibrosis absence (F0) was increased, e.g. from 16.0% with Fibroscan to 75.0% with E-FibroMeter (P < 0.001). Cirrhosis sensitivity was improved, e.g. E-FibroMeter: 92.7% vs. Fibroscan: 83.3%, P = 0.004. The combination improved reliability by deleting unreliable results (accuracy
Published: 2014
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12. Triple therapy in treatment-experienced patients with HCV-cirrhosis in a multicentre cohort of the French Early Access Programme (ANRS CO20-CUPIC) – NCT01514890

Author: Stanislas Pol, Thierry Poynard, Isabelle Rosa, Armand Abergel, Valérie Canva, Lawrence Serfaty, Véronique Loustaud-Ratti, Jean-Pierre Zarski, Cyrille Feray, Xavier Causse, Patrick Hillon, J.-J. Raabe, Fabien Zoulim, Christophe Hézode, Pierre Attali, Dominique Guyader, Hélène Fontaine, Pierre-Henri Bernard, Patrice Cacoub, Laurent Alric, Didier Samuel, Dominique Larrey, Céline Dorival, Albert Tran, Ventzislava Petrov-Sanchez, Marc Bourlière, Ghassan Riachi, Jean-Michel Pawlotsky, Patrick Marcellin, Fabrice Carrat, Véronique Grando-Lemaire, Sophie Metivier, Damien Lucidarme, Vincent Di Martino, Victor de Lédinghen, Thong Dao, Jean-Pierre Bronowicki, Yoann Barthe, 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 Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins (DS3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche en biothérapie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), 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-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-gastroentérologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'hépatologie et de gastroentérologie [CHU Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pathologies biliaires, fibrose et cancer du foie, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépato-gastro-entérologie, Assistance Publique - Hôpitaux de Marseille (APHM), 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-gastro-entérologie [CHR Metz-Thionville], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Service d'hépatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), 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), Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), CHU Saint-Antoine [AP-HP], Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Image Science for Interventional Techniques (ISIT), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Centre National de la Recherche Scientifique (CNRS), Service d’Hépato-Gastro-Entérologie [Orléans], Centre Hospitalier Régional d'Orléans (CHRO), Service d'Hépatologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Foie, métabolismes et cancer, 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 ), Groupe Hospitalier de l'Institut Catholique Lillois, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service Hépato-gastroentérologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Immunologie - Immunopathologie - Immunothérapie (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHI Créteil, Service d'Hépato-gastro-entérologie [APHP Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Recherches fondamentales, cliniques et thérapeutiques sur les hépatites virales, ANRS France Recherche Nord & sud Sida-hiv hépatites, Service de bactériologie, virologie, hygiène [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Hôpital Charles Nicolle [Rouen]-CHU Rouen, CHU Toulouse [Toulouse], Service d'hépatologie [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-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), 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 ), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Service de santé publique [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), 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, Service d'Hépato-Gastroentérologie [Purpan-Toulouse], Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépatologie [Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Jean Verdier [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Pathologies biliaires, fibrose et cancer du foie (Inserm UMR_S 938), CHU Saint-Antoine [APHP]-Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'Hépato-Gastroentérologie [Rouen], Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'Hépato-Gastroentérologie [CHRU Clermont-Ferrand], Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont Université-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Centre Hospitalier Régional d'Orléans (CHR), Service d'Hépatologie, Hôpital Jean Minjoz, Centre Hospitalier Universitaire de Besançon, Université de Franche Comté, Hôpital Jean Minjoz, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], and Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Liver Cirrhosis, Male, Cirrhosis, Blood transfusion, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Chronic hepatitis C, Gastroenterology, Telaprevir, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Pegylated interferon, Medicine, Prospective Studies, Aged, 80 and over, Boceprevir, Middle Aged, Viral Load, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Cohort, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, France, Safety, Oligopeptides, medicine.drug, Adult, medicine.medical_specialty, Serine Proteinase Inhibitors, Proline, Antiviral Agents, 03 medical and health sciences, Internal medicine, Ribavirin, Humans, Adverse effect, Aged, Hepatology, business.industry, Interferon-alpha, Hepatitis C, Chronic, medicine.disease, Surgery, Treatment, chemistry, business
Abstract: International audience; Background & AimsIn phase III trials, the safety profile of triple therapy (pegylated interferon/ribavirin with boceprevir or telaprevir) seems to be similar in HCV treatment-experienced cirrhotic and non-cirrhotic patients, but few cirrhotics were included. We report the week 16 safety and efficacy analysis in a cohort of compensated cirrhotics treated in the French Early Access Programme.Methods674 genotype 1 patients, prospectively included, received 48 weeks of triple therapy. The analysis is restricted to 497 patients reaching week 16.ResultsA high incidence of serious adverse events (40.0%), and of death and severe complications (severe infection or hepatic decompensation) (6.4%), and a difficult management of anaemia (erythropoietin and transfusion use in 50.7% and 12.1%) were observed. Independent predictors of anaemia
Published: 2013
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13. Determination of reliability criteria for liver stiffness evaluation by transient elastography

Author: Brigitte Le-Bail, Sandrine Bertrais, Marie-Christine Rousselet, Jérôme Boursier, Paul Calès, Isabelle Fouchard-Hubert, Victor de Ledinghen, Jean-Pierre Zarski, Frédéric Oberti, Yves Gallois, Nathalie Sturm, Service d'Hépato-gastroentérologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Département d'hépatologie et de gastroentérologie [CHU Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Département de Pathologie Cellulaire et Tissulaire [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service d'Hépato-gastroentérologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Remodelage osseux et biomatériaux, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), the Multicentric Group from ANRS/HC/EP23 FIBROSTAR Studies, Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Groupe d'Études Remodelage Osseux et bioMatériaux (GEROM)
Subjects: Adult, Liver Cirrhosis, Male, Pathology, medicine.medical_specialty, Multivariate analysis, Biopsy, Large population, Chronic liver disease, Severity of Illness Index, 03 medical and health sciences, Hepatitis B, Chronic, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Predictive Value of Tests, Liver stiffness, Interquartile range, Humans, Medicine, Reliability (statistics), ComputingMilieux_MISCELLANEOUS, Hepatology, medicine.diagnostic_test, business.industry, Reproducibility of Results, Hepatitis C, Chronic, Middle Aged, medicine.disease, 3. Good health, Fatty Liver, Liver, 030220 oncology & carcinogenesis, Liver biopsy, Elasticity Imaging Techniques, Female, 030211 gastroenterology & hepatology, Radiology, business, Transient elastography, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Liver stiffness evaluation (LSE) is usually considered as reliable when it fulfills all the following criteria: ≥10 valid measurements, ≥60% success rate, and interquartile range / median ratio (IQR/M) ≤0.30. However, such reliable LSE have never been shown to be more accurate than unreliable LSE. Thus, we aimed to evaluate the relevance of the usual definition for LSE reliability, and to improve reliability by using diagnostic accuracy as a primary outcome in a large population. 1,165 patients with chronic liver disease from 19 French centers were included. All patients had liver biopsy and LSE. 75.7% of LSE were reliable according to the usual definition. However, these reliable LSE were not significantly more accurate than unreliable LSE with, respectively: 85.8% versus 81.5% well-classified patients for the diagnosis of cirrhosis (P = 0.082). In multivariate analyses with different diagnostic targets, LSE median and IQR/M were independent predictors of fibrosis staging, with no significant influence of ≥10 valid measurements or LSE success rate. These two reliability criteria determined three LSE groups: "very reliable" (IQR/M ≤0.10), "reliable" (0.10IQR/M ≤0.30, or IQR/M0.30 with LSE median7.1 kPa), and "poorly reliable" (IQR/M0.30 with LSE median ≥7.1 kPa). The rates of well-classified patients for the diagnosis of cirrhosis were, respectively: 90.4%, 85.8%, and 69.5% (P10(-3) ). According to these new reliability criteria, 9.1% of LSE were poorly reliable (versus 24.3% unreliable LSE with the usual definition, P10(-3) ), 74.3% were reliable, and 16.6% were very reliable.The usual definition for LSE reliability is not relevant. LSE reliability depends on IQR/M according to liver stiffness median level, defining thus three reliability categories: very reliable, reliable, and poorly reliable LSE. (HEPATOLOGY 2013).
Published: 2013
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14. Letter: mucosal healing in ulcerative colitis - higher relevance than in Crohn's disease? Authors' reply

Author: Jérôme Filippi, Xavier Roblin, Stéphane Nancey, David Laharie, Laurent Peyrin-Biroulet, UL, NGERE, Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Département d'hépatologie et de gastroentérologie [CHU Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'Hépato-gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Nice, 03 medical and health sciences, 0302 clinical medicine, Gastrointestinal Agents, medicine, Humans, Pharmacology (medical), Intestinal Mucosa, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, computer.programming_language, Wound Healing, 0303 health sciences, Crohn's disease, Hepatology, business.industry, Gastroenterology, Antibodies, Monoclonal, medicine.disease, University hospital, Ulcerative colitis, 3. Good health, [SDV] Life Sciences [q-bio], Mucosal healing, Family medicine, Colitis, Ulcerative, Female, 030211 gastroenterology & hepatology, business, computer
Abstract: *Service d’H epato-gastroent erologie, CHU de Bordeaux, Pessac, France. Department of Gastroenterology and Clinical Nutrition, Faculty of Medicine, University Hospital of Nice, University of Nice Sophia Antipolis, Nice, France. Department of Hepato-Gastroenterology, University Hospital of Saint-Etienne, Saint-Etienne, France. Department of Gastroenterology, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre-B enite, France. Inserm U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy-Brabois, Vandoeuvre-l es-Nancy, France. E-mail: david.laharie@chu-bordeaux.fr
Published: 2013
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15. High-Dose Pegylated Interferon-α and Ribavirin in Nonresponder Hepatitis C Patients and Relationship With IL-28B Genotype (SYREN Trial)

Author: Chevaliez, Stéphane, Hézode, Christophe, Soulier, Alexandre, Costes, Bruno, Bouvier-Alias, Magali, Rouanet, Stéphanie, Foucher, Juliette, Bronowicki, Jean-Pierre, Tran, Albert, Rosa, Isabelle, Mathurin, Philippe, Alric, Laurent, Leroy, Vincent, Couzigou, Patrice, Mallat, Ariane, Charaf-Eddine, Mariem, Babany, Gérard, Pawlotsky, Jean-Michel, Centre National de Référence Virus des hépatites B, C et Delta, Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Biochimie [Mondor], Produits Roche, Roche, Département d'hépatologie et de gastroentérologie, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Pôle Digestif, Hôpital Archet 2 [Nice] (CHU), Service d'hépato-gastro-entérologie, CHI Créteil, Service d'Hépato-gastroentérologie, Hôpital Huriez-Université de Lille, Service de médecine interne et maladies digestives, CHU Toulouse [Toulouse], Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, This study is investigator-initiated. It has been funded by Roche France, which provided the study drugs, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service Médecine Interne et immunologie clinique [CHU Toulouse], Pôle Maladies de l'appareil digestif [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Hepatitis C virus, nonresponder, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, IL28B genotype, high-dose pegylated IFN-α
Abstract: International audience; BACKGROUND & AIMS: In patients with chronic hepatitis C who failed to respond to standard therapy, high-dose pegylated interferon (IFN)-α and/or ribavirin could induce a stronger antiviral response and prevent treatment failure and HCV resistance when combined with direct-acting antivirals. The influence of genetic determinants in this context remains unknown. METHODS: Eighty-three patients infected with HCV genotype 1 who were nonresponsive to standard therapy received pegylated IFN-α2a (360 μg once per week or 180 μg twice per week) with ribavirin (1.0-1.2 or 1.2-1.6 g/d) for up to 72 weeks. Virological responses were assessed at different time points, and the influence of the IL-28B genotype was studied. RESULTS: At weeks 12 and 24, respectively, 47 (56.6%) and 50 (60.2%) patients achieved a ≥2-Log(10) decrease of HCV RNA levels; 8 (9.6%) and 21 (25.3%) patients had undetectable HCV RNA after 12 and 24 weeks of treatment, respectively. Patients with a CT IL-28B genotype responded significantly better and earlier than those with a TT genotype. In multivariate analysis, the IL-28B genotype was an independent predictor of the virological responses at weeks 4, 12, and 24. CONCLUSIONS: High-dose pegylated IFN-α with standard or high doses of ribavirin induces a potent antiviral response in a substantial number of patients who did not respond to standard therapy. The IL-28B genotype is an independent predictor of the antiviral response. High-dose pegylated IFN-α in combination with ribavirin and protease inhibitors appears as an attractive option for future study in this population.
Published: 2011
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16. High-Dose Pegylated Interferon-α and Ribavirin in Nonresponder Hepatitis C Patients and Relationship With IL-28B Genotype (SYREN Trial).: High-Dose peg-IFN and Ribavirin and IL28B in HCV nonresponders

Author: Laurent Alric, Vincent Leroy, Bruno Costes, Magali Bouvier–Alias, Patrice Couzigou, Mariem Charaf–Eddine, Stéphanie Rouanet, Jean-Pierre Bronowicki, Stéphane Chevaliez, Jean-Michel Pawlotsky, Isabelle Rosa, Christophe Hézode, Philippe Mathurin, Juliette Foucher, Alexandre Soulier, Gérard Babany, Albert Tran, Ariane Mallat, Centre National de Référence Virus des hépatites B, C et Delta, Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Biochimie [Mondor], Produits Roche, Roche, Département d'hépatologie et de gastroentérologie, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Pôle Digestif, Hôpital Archet 2 [Nice] (CHU), Service d'hépato-gastro-entérologie, CHI Créteil, Service d'Hépato-gastroentérologie, Hôpital Huriez-Université de Lille, Service de médecine interne et maladies digestives, CHU Toulouse [Toulouse], Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, This study is investigator-initiated. It has been funded by Roche France, which provided the study drugs, and Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Male, Time Factors, Hepacivirus, medicine.disease_cause, Gastroenterology, Polyethylene Glycols, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Interferon, Pegylated interferon, nonresponder, Genotype, Odds Ratio, Medicine, 0303 health sciences, education.field_of_study, Hepatitis C virus, Hepatitis C, Middle Aged, Viral Load, Recombinant Proteins, 3. Good health, Phenotype, Treatment Outcome, RNA, Viral, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, high-dose pegylated IFN-α, medicine.drug, Adult, medicine.medical_specialty, Population, Context (language use), IL28B genotype, Interferon alpha-2, Antiviral Agents, Risk Assessment, 03 medical and health sciences, Internal medicine, Drug Resistance, Viral, Ribavirin, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, education, Aged, 030304 developmental biology, Chi-Square Distribution, Hepatology, business.industry, Interleukins, Interferon-alpha, Hepatitis C, Chronic, medicine.disease, Logistic Models, chemistry, Immunology, Linear Models, Interferons, business
Abstract: International audience; BACKGROUND & AIMS: In patients with chronic hepatitis C who failed to respond to standard therapy, high-dose pegylated interferon (IFN)-α and/or ribavirin could induce a stronger antiviral response and prevent treatment failure and HCV resistance when combined with direct-acting antivirals. The influence of genetic determinants in this context remains unknown. METHODS: Eighty-three patients infected with HCV genotype 1 who were nonresponsive to standard therapy received pegylated IFN-α2a (360 μg once per week or 180 μg twice per week) with ribavirin (1.0-1.2 or 1.2-1.6 g/d) for up to 72 weeks. Virological responses were assessed at different time points, and the influence of the IL-28B genotype was studied. RESULTS: At weeks 12 and 24, respectively, 47 (56.6%) and 50 (60.2%) patients achieved a ≥2-Log(10) decrease of HCV RNA levels; 8 (9.6%) and 21 (25.3%) patients had undetectable HCV RNA after 12 and 24 weeks of treatment, respectively. Patients with a CT IL-28B genotype responded significantly better and earlier than those with a TT genotype. In multivariate analysis, the IL-28B genotype was an independent predictor of the virological responses at weeks 4, 12, and 24. CONCLUSIONS: High-dose pegylated IFN-α with standard or high doses of ribavirin induces a potent antiviral response in a substantial number of patients who did not respond to standard therapy. The IL-28B genotype is an independent predictor of the antiviral response. High-dose pegylated IFN-α in combination with ribavirin and protease inhibitors appears as an attractive option for future study in this population.
Published: 2011
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17. INFLUENCE OF HCV GENOTYPE 1 SUBTYPES ON THE VIRUS RESPONSE TO PEG INTERFERON ALPHA-2a PLUS RIBAVIRIN THERAPY

Author: Sophie Thebault, Etienne Chatelut, Jean-Louis Payen, Christophe Renou, Laurent Alric, Jean-Jacques Meurisse, Jacques Izopet, Yves Imbert, Daniel Garipuy, Florence Nicot, Thierry Morin, B. Castan, Karine Sauné, Stéphane Sire, Jean-Marc Combis, Bruno Guérin, Karl Barange, Hervé Desmorat, Jean-Michel Dramard, S. Metivier, Jean-Marie Peron, Pierre Barel, Virology Laboratory, Hospital, Département d'hépatologie et de gastroentérologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Gastroenterology, Toulouse University hospital, Val d'Ariège Hospital, Ambroise Paré Cinic, General Medicine, Internal Medicine, Ducuing Hospital, Polyclinique du Parc, Hepato-gastro-enterology, Bigorre Hospital, Hepatology, Hopital, Laboratory of Virology, EA3035, Institut Claudius Regaud, VIROLOGIE, and CHU Toulouse [Toulouse]
Subjects: Adult, Male, Genotype, Hepacivirus, Hepatitis C virus, HIV Infections, medicine.disease_cause, Antiviral Agents, Polyethylene Glycols, 03 medical and health sciences, chemistry.chemical_compound, Flaviviridae, 0302 clinical medicine, Pegylated interferon, Virology, Ribavirin, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, 030304 developmental biology, Aged, 0303 health sciences, biology, business.industry, Interferon-alpha, virus diseases, Hepatitis C, Hepatitis C, Chronic, Middle Aged, Viral Load, biology.organism_classification, medicine.disease, Recombinant Proteins, digestive system diseases, 3. Good health, Infectious Diseases, Treatment Outcome, chemistry, Drug Therapy, Combination, Female, Viral disease, business, medicine.drug
Abstract: International audience; New factors that influence the viral response in HCV non-genotype 2/3 patients must be identified in order to optimize anti-HCV treatment. This multicenter prospective study evaluates the influence of HCV variability and pharmacological parameters on the virological response of these patients to pegylated interferon α2a (peg-IFN-α2a: 180 µg/week) and ribavirin (800-1200 mg/day) for 48 weeks. HCV subtypes were identified by sequencing the NS5B region. Serum ribavirin and peg-IFN-α2a concentrations were measured at weeks 4 and 12. The 115 patients (67 men; median age=49, range [31-76]) included 64 who had never been treated and 27 co-infected with HIV. The mean baseline HCV RNA was 6.30 ± 0.06 log IU/mL and the HCV genotypes were: G1 (n=93) with 1a (n=37) and 1b (n=50), G4 (n=20) and G5 (n=2). Most patients (79/108; 73%) had an early virological response. Independent predictors of an early virological response were interferon naive patients (OR=2.98 [1.15; 7.72]) and ribavirin of > 2,200 ng/mL at week 12 (OR=3.41 [1.31; 8.90]). Forty of 104 patients (38%) had a sustained virological response. The only independent predictors of a sustained virological response were subtype 1b (OR=6.82 [1.7; 26.8]), and HCV RNA 2,200 ng/mL was associated with an early virological response and patients infected with HCV subtype 1b had a better chance of a sustained virological response than did those infected with subtype 1a.
Published: 2011
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18. A New Combination of Blood Test and Fibroscan for Accurate Non-Invasive Diagnosis of Liver Fibrosis Stages in Chronic Hepatitis C

Author: Sandrine Bertrais, Frédéric Oberti, Paul Calès, Nathalie Sturm, Isabelle Fouchard-Hubert, Victor de Ledinghen, Marie-Christine Rousselet, Jérôme Boursier, Juliette Foucher, Jean-Pierre Zarski, Vincent Leroy, Yves Gallois, Nina Dib, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Département d'hépato-gastroentérologie, CHU Grenoble-Université Grenoble Alpes (UGA), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Institut Albert Bonniot - Ontogénèse et oncogénèse moléculaires, CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Albert Bonniot, Département d'hépatologie et de gastroentérologie, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Yahoo! Research [Barcelona], Université Grenoble Alpes (UGA)-CHU Grenoble, and Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Liver fibrosis, [SDV]Life Sciences [q-bio], Gastroenterology, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Chronic hepatitis, Internal medicine, Severity of illness, Biopsy, medicine, Blood test, Humans, Prospective Studies, Prospective cohort study, Hematologic Tests, Hepatology, medicine.diagnostic_test, business.industry, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, 3. Good health, Logistic Models, 030220 oncology & carcinogenesis, Elasticity Imaging Techniques, 030211 gastroenterology & hepatology, Female, Hepatic fibrosis, business
Abstract: International audience; OBJECTIVES: Precise evaluation of the level of liver fibrosis is recommended in patients with chronic hepatitis C (CHC). Blood fibrosis tests and Fibroscan are now widely used for the non-invasive diagnosis of liver fibrosis. Detailed fibrosis stage classifications have been developed to provide an estimation of the liver fibrosis stage from the results of these non-invasive tests. Our aim was to develop a new and more accurate fibrosis stage classification by using new scores combining non-invasive fibrosis tests.METHODS: In all, 729 patients with CHC (exploratory set: 349; validation set: 380) had liver biopsy for Metavir fibrosis (F) staging, and 6 fibrosis tests: Fibroscan, Fibrotest, FibroMeter, Hepascore, FIB-4, APRI. RESULTS: Exploratory set: Fibroscan and FibroMeter were the independent predictors of different diagnostic targets of liver fibrosis. New fibrosis indexes combining FibroMeter and Fibroscan were thus developed for the diagnosis of clinically significant fibrosis (CSF-index) or severe fibrosis (SF-index). The association of CSF- and SF-indexes provided a new fibrosis stage classification (CSF/SF classification): F0/1, F1/2, F2±1, F2/3, F3±1, F4. Validation set: CSF/SF classification had a high diagnostic accuracy (85.8% well-classified patients), significantly higher than the diagnostic accuracies of FibroMeter (69.7%, P
Published: 2011
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19. TRANSIENT ELASTOGRAPHY AND BIOMARKERS FOR LIVER FIBROSIS ASSESSMENT AND FOLLOW-UP OF INACTIVE HEPATITIS B CARRIERS

Author: Castera, Laurent, Bernard, Pierre-Henri, LeBail, Brigitte, Foucher, Juliette, Trimoulet, Pascale, Merrouche, Wassil, Couzigou, Patrice, De Ledinghen, Victor, Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de Biochimie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Département d'hépatologie et de gastroentérologie, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], and CHU Bordeaux [Bordeaux]
Subjects: Medicine
Abstract: International audience; ABSTRACT Aim To evaluate longitudinally transient elastography (TE) and biomarkers for liver fibrosis assessment and follow-up of hepatitis B virus (HBV) inactive carriers. Methods Three hundred and twenty-nine consecutive HBeAg-negative HBV patients (201 inactive carriers) who underwent TE, Fibrotest® and APRI the same day were studied. Results TE (median 4.8 vs. 6.8 kPa, p7.2 kPa) confirmed during follow-up in two with significant fibrosis (F2 and F3) on liver biopsy. Conclusions Non invasive tools, particularly transient elastography, could be useful, in addition to HBV DNA and transaminase levels, for follow-up of HBV inactive carriers as well as better selection of patients who require a liver biopsy.
Published: 2010
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20. Danoprevir, an HCV NS3/4A protease inhibitor, improves insulin sensitivity in patients with genotype 1 chronic hepatitis C

Author: Michel Vidaud, Rami Moucari, Stefan Zeuzem, Yves Benhamou, Dominique Guyader, Bill Bradford, Patrice Couzigou, Nicole Forestier, Hélène Voitot, Patrick Marcellin, Scott D. Seiwert, Dominique Larrey, Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Johann Wolfgang Goethe University Medical Center, Microenvironnement et remodelage, Centre Hospitalier Universitaire [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 )-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 ), Département d'hépatologie et de gastroentérologie, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Biochimie et Génétique Moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), InterMune Laboratory, Brisbane, California, USA., 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 )-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 ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon
Subjects: Cyclopropanes, Male, medicine.medical_treatment, MESH: Sulfonamides, Hepacivirus, Isoindoles, Viral Nonstructural Proteins, medicine.disease_cause, Gastroenterology, MESH: Genotype, chemistry.chemical_compound, 0302 clinical medicine, MESH: Hepacivirus, Sulfonamides, 0303 health sciences, MESH: Middle Aged, MESH: Protease Inhibitors, Danoprevir, virus diseases, Hepatitis C, Middle Aged, Viral Load, 3. Good health, MESH: Hepatitis C, Chronic, MESH: Insulin Resistance, MESH: RNA, Viral, RNA, Viral, Female, 030211 gastroenterology & hepatology, MESH: Viral Load, Viral load, Adult, MESH: Antiviral Agents, medicine.medical_specialty, Genotype, Lactams, Proline, Lactams, Macrocyclic, Hepatitis C virus, Antiviral Agents, 03 medical and health sciences, Insulin resistance, Internal medicine, medicine, Humans, Protease Inhibitors, Protease inhibitor (pharmacology), 030304 developmental biology, MESH: Humans, MESH: Lactams, business.industry, Ribavirin, Insulin, MESH: Adult, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Chronic, medicine.disease, MESH: Male, chemistry, Immunology, MESH: Viral Nonstructural Proteins, Insulin Resistance, business, MESH: Female
Abstract: International audience; BACKGROUND/AIM: Insulin resistance (IR) is a major predictor of treatment failure in patients with hepatitis C virus (HCV) infection treated with peginterferon/ribavirin. The aim of this study was to evaluate the short-term effect of an HCV protease inhibitor monotherapy on IR in parallel with an antiviral effect. PATIENTS/METHODS: In a phase 1b placebo-controlled study, four cohorts of treatment-naïve patients with genotype 1 HCV received danoprevir (ITMN-191/RG7227), a protease inhibitor, or placebo (8/2 patients in each cohort respectively) in a gelatin capsule every 12 h (100, 200 mg) or 8 h (100, 200 mg) for 14 days. A fifth cohort including prior non-responders to peginterferon/ribavirin was similarly randomised to receive placebo or 300 mg danoprevir every 12 h. IR was assessed with the homeostasis model (HOMA-IR) at baseline and days 7, 14 and 15. RESULTS: Serum HCV-RNA and HOMA-IR correlated significantly (Spearman rho=0.379, p
Published: 2010
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21. Réduction des risques infectieux Chez les usagers de drogues

Author: Bello, Pierre-Yves, Ben Lakhdar, Christian, Carrieri, Maria Patrizia, Costes, Jean-Michel, Couzigou, Patrice, Dubois-Arber, Françoise, Guichard, Anne, Jauffret-Roustide, Marie, Le Naour, Gwenola, Lucidarme, Damien, Michel, Laurent, Polomeni, Pierre, Rémy, André-Jean, Simmat-Durand, Laurence, Institut de Veille Sanitaire (INVS), UMR CNRS 8179, Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Observatoire Français des Drogues et des Toxicomanies, OFDT, Département d'hépatologie et de gastroentérologie, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Université de Lausanne (UNIL), Institut National de Prévention et d'Education pour la Santé (INPES), CERMES3 - Centre de recherche Médecine, sciences, santé, santé mentale, société (CERMES3 - UMR 8211 / U988 / UM 7), École des hautes études en sciences sociales (EHESS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Triangle : action, discours, pensée politique et économique (TRIANGLE), Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Lettres et Sciences Humaines (ENS LSH)-Sciences Po Lyon - Institut d'études politiques de Lyon (IEP Lyon), Université de Lyon-Université de Lyon-Université Lumière - Lyon 2 (UL2), Service d'hépato-gastro-entérologie, Groupe Hospitalier de l'Institut Catholique Lillois, Troubles du comportement alimentaire de l'adolescent (UMR_S 669), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Centre de traitement des addictions, Centre Hospitalier Emile Roux [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'addictologie [Bondy], Hôpital Jean Verdier [AP-HP], Service de hépato-gastro-entérologie - cancérologie digestive [CH de Perpignan], Centre Hospitalier Saint Jean de Perpignan, Institut national de la santé et de la recherche médicale(INSERM), Duchange, Nathalie, Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lausanne = University of Lausanne (UNIL), Université Lumière - Lyon 2 (UL2)-Sciences Po Lyon - Institut d'études politiques de Lyon (IEP Lyon), Université de Lyon-Université de Lyon-Ecole Normale Supérieure Lettres et Sciences Humaines (ENS LSH)-Centre National de la Recherche Scientifique (CNRS), and Université Paris-Sud - Paris 11 (UP11)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: drogues, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, risques infectieux, Réduction des risques, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, usages
Abstract: La réduction des risques infectieux chez les usagers de drogues est un objectif de santé publique compte tenu de la prévalence élevée du VIH et du VHC constatée dans ces populations.Dès les années 1985-90, les nombreuses actions engagées par des associations et des professionnels de santé dans plusieurs pays dont la France ont abouti progressivement à des politiques publiques de réduction des risques. Elles ont permis le développement de dispositifs tels que les programmes d’échanges de seringues et les traitements de substitution aux opiacés.Un des enjeux de la réduction des risques est de s’adapter aux évolutions des pratiques et contextes de consommation de drogues ainsi qu’aux profils de consommateurs.À la demande du ministère de la Santé et des Sports, l’Inserm a coordonné une expertise collective pluridisciplinaire qui propose un bilan des connaissances sur l’évolution des usages de drogues et les dommages associés, sur les programmes de réduction des risques infectieux et leur impact à partir des données internationales. Une attention particulière a été portée à la situation des femmes et des détenus.
Published: 2010

22. Improved diagnostic accuracy of blood tests for severe fibrosis and cirrhosis in chronic hepatitis C

Author: Philippe Halfon, Frédéric Oberti, Nathalie Sturm, Marie Christine Rousselet, Jérôme Boursier, Yannick Bacq, Juliette Foucher, Vincent Leroy, Victor de Ledinghen, Anne de Muret, Marc Bourlière, Paul Calès, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Service de gastro-entérologie [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire alphabio, Yahoo! Research [Barcelona], Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Service d'Anatomopathologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service d'Hépato-gastroentérologie, Assistance Publique - Hôpitaux de Marseille (APHM), Institut Albert Bonniot - Ontogénèse et oncogénèse moléculaires, CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Albert Bonniot, Département d'hépatologie et de gastroentérologie, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], and CHU Bordeaux [Bordeaux]
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, FIBROMETER, [SDV]Life Sciences [q-bio], Diagnostic accuracy, Gastroenterology, Sensitivity and Specificity, 03 medical and health sciences, 0302 clinical medicine, Reference Values, Internal medicine, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Hepatology, medicine.diagnostic_test, Receiver operating characteristic, FibroTest, business.industry, Biopsy, Needle, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, 3. Good health, Liver, 030220 oncology & carcinogenesis, Liver biopsy, 030211 gastroenterology & hepatology, Female, Hepatic fibrosis, business, Biomarkers
Abstract: OBJECTIVE Blood tests are usually designed to identify significant fibrosis. We evaluated their diagnostic accuracy, and how to increase it, for the clinically important targets of severe fibrosis and cirrhosis. METHODS The accuracy for severe fibrosis or cirrhosis of four blood tests was evaluated based on Metavir staging in 1056 patients with chronic hepatitis C recruited in five independent hospitals. RESULTS Using original scores, an original diagnostic target (significant fibrosis) and best diagnostic cutoff, the correct classification rates in severe fibrosis and cirrhosis stages were, respectively: FibroMeter: 90.1, 100%, Fibrotest: 78.2, 95.1%, Hepascore: 73.8, 94.9%, aspartate aminotransferase to platelet ratio index (APRI): 71.4, 88.0% (P
Published: 2008
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23. Liver fibrosis staging with contrast-enhanced ultrasonography: prospective multicenter study compared with METAVIR scoring

Author: M. Morichaut-Beauchant, J. B. Galtier, P. Couzigou, L. Castéra, C. Prevost, Pierre Ingrand, S. Sironneau, J. Roumy, J. Drouillard, F. Machet, P. Foucher, J. F. Blanc, Yannick Bacq, L. D’Alteroche, H. Trillaud, P. H. Bernard, F. Tranquard, Jean-Pierre Tasu, Jérôme Lebigot, Hervé Laumonier, C. Chaigneau, F. Staub, Frédéric Oberti, Christophe Aubé, Pierre Levillain, V. de Ledinghen, C. Tournoux-Facon, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie physico-chimique (IBPC (FR_550)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Fibrose hépatique et cancer du foie, Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Innovation pour les Technologies des Energies Nouvelles et les nanomatériaux (LITEN), Institut National de L'Energie Solaire (INES), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Département d'hépatologie et de gastroentérologie, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département d'hépatologie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre National de la Recherche Scientifique (CNRS), Service de gastro-entérologie [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Liver Cirrhosis, Male, Biopsy, [SDV]Life Sciences [q-bio], Contrast Media, Gastroenterology, 030218 nuclear medicine & medical imaging, Computer-Assisted, 0302 clinical medicine, Fibrosis, 80 and over, Phospholipids, Neuroradiology, Ultrasonography, Aged, 80 and over, Observer Variation, medicine.diagnostic_test, Ultrasound, Interventional radiology, General Medicine, Middle Aged, 3. Good health, medicine.anatomical_structure, Liver biopsy, 030220 oncology & carcinogenesis, Microbubbles, 030211 gastroenterology & hepatology, Female, Radiology, France, Algorithms, Adult, medicine.medical_specialty, Sulfur Hexafluoride, Sensitivity and Specificity, Young Adult, 03 medical and health sciences, Internal medicine, Image Interpretation, Computer-Assisted, medicine, Humans, Radiology, Nuclear Medicine and imaging, Vein, Image Interpretation, Aged, business.industry, Reproducibility of Results, medicine.disease, Image Enhancement, business
Abstract: International audience; We prospectively assessed contrast-enhanced sonography for evaluating the degree of liver fibrosis as diagnosed via biopsy in 99 patients. The transit time of microbubbles between the portal and hepatic veins was calculated from the difference between the arrival time of the microbubbles in each vein. Liver biopsy was obtained for each patient within 6 months of the contrast-enhanced sonography. Histological fibrosis was categorized into two classes: (1) no or moderate fibrosis (F0, F1, and F2 according to the METAVIR staging) or (2) severe fibrosis (F3 and F4). At a cutoff of 13 s for the transit time, the diagnosis of severe fibrosis was made with a specificity of 78.57%, a sensitivity of 78.95%, a positive predictive value of 78.33%, a negative predictive value of 83.33%, and a performance accuracy of 78.79%. Therefore, contrast-enhanced ultrasound can help with differentiation between moderate and severe fibrosis.
Published: 2009
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24. [Risk of transmission of hepatitis C through endoscopy of the digestive tract].

Author: Ouzan D
Subjects: Cross Infection prevention & control, Cross Infection transmission, Cross Infection virology, Disinfection, Endoscopes adverse effects, Gastroscopes, Hepacivirus, Hepatitis C virology, Humans, Risk Factors, Endoscopes virology, Gastroscopy adverse effects, Hepatitis C transmission
Abstract: NOSOCOMIAL TRANSMISSION: Increasingly implicated in HCV infection in patients with no patent risk factors, nosocomial transmission has been demonstrated between patients hospitalized in the same ward and from health carers to patients. The risk of HCV transmission by medical instruments could only be quantified with a prospective study of examined patients. There is a theoretical risk for all endoscopic examinations whatever organ explored. Instrumental manipulations have been found as the only risk factor in blood donors. VALUE OF FORMER DISINFECTION GUIDELINES: Disinfection protocols for endoscopes have been found to eliminate 3 viruses (HCV, HBV, HIV). The endoscope-related risk could be due to minimal bleeding provoked by biopsies (risk factors independent of HCV infection) via the operator channel. THREE REPORTED CASES OF HVC INFECTION: One case of HVC infection following retrograde cholangiography and two after coloscopy have been reported. In all three cases disinfection was found to be insufficient. Recently, an official statement by the French health authorities indicates that a 20-min gluteraldehyde bath is necessary for optimal efficacy. Instruments susceptible to cause bleeding must be sterilized. The sterilization process must be tracable. The anesthesia-related risk appears to be due to use of multidose bottles or reuse of syringes. SAFE ENDOSCOPY: Disinfection procedures must be rigorously applied. One new perspective is the culture of titratable virus models. Several arguments show that well-conducted disinfection of endoscopes and medical instruments can eliminate all risk of viral transmission, including HCV.
Published: 1999

25. [What are the precautions to be taken in hepatitis C?].

Author: Ouzan D
Subjects: Disease Transmission, Infectious prevention & control, Hepatitis C prevention & control, Humans, Risk Factors, Hepatitis C transmission
Published: 1997

26. [Appearance of hepatitis C virus replication and increase of aminotransferase activity after corticoid treatment of presumed autoimmune hepatitis. 2 cases].

Author: Béchade D, Oui B, Mayet F, Trouette H, Schouler L, Jouglen J, Raymond JM, and Couzigou P
Subjects: Aged, Autoimmune Diseases diagnosis, Autoimmune Diseases drug therapy, Diagnosis, Differential, Female, Hepatitis diagnosis, Hepatitis drug therapy, Hepatitis C diagnosis, Hepatitis C virology, Humans, Middle Aged, Virus Replication, Glucocorticoids adverse effects, Hepacivirus physiology, Hepatitis C enzymology, Prednisolone adverse effects, Transaminases blood
Abstract: Autoimmune-related and hepatitis C virus-related chronic hepatitis are sometimes difficult to differentiate. We report two cases of chronic hepatitis with high levels of serum anti-smooth muscle antibodies, positive hepatitis C virus serology, and negative serum RNA, which were first treated with corticotherapy. Both patients responded with marked increases in aminotransferase levels, and positive RNA. The first case may have been type 1 autoimmune hepatitis with hepatitis C virus infection, and the second chronic hepatitis C with positive serum auto-antibodies. The increase in viral antigen expression on the surface of the hepatocytes following corticosteroid treatment may have favoured a direct cytopathogenic effect of hepatitis C virus.
Published: 1996

27. [Risk of transmission of hepatitis C virus by digestive endoscopy].

Author: Rey JF, Halfon P, Feryn JM, Khiri H, Masseyeff MF, and Ouzan D
Subjects: Disinfection methods, Hepacivirus genetics, Hepatitis C genetics, Hepatitis C transmission, Humans, RNA, Viral analysis, Risk Factors, Endoscopy, Digestive System adverse effects, Hepatitis C etiology
Abstract: Objective: In 30 to 50% of cases, the route of transmission of virus C remains unknown. The aim of this study was to investigate the effectiveness of manual cleaning and disinfection procedures after endoscopic examinations in highly infected patients., Methods: In 39 patients with chronic hepatitis C and a high level of replication, a gastroscopy with biopsy was performed with a fully submersible endoscope. Cleaning and disinfection were carried out with the following protocol: cleaning with detergent solution (Sekulyse), rinsing, 3 to 5 min immersion into a glutaraldehyde disinfectant solution (Sekucid) and final rinsing. One hundred mL of sterile water was flushed through the biopsy channel immediately after removal of the endoscope (T1), after cleaning (T2), and after final disinfection (T3). These 100 mL were collected in aliquots for viral and bacterial screening. Virus C particles were searched for in the effluent of the biopsy channel using two methods of polymerase chain reaction., Results: Virus C particles were found in 2 of 39 patients in T1 aliquots collected before washing. Routine cleaning with a detergent eliminated all viral particles, as tests were negative at T2 and T3. The usual bacteria (Pseudomonas, Streptococcus, Neisseria...) were detected at T1 and had disappeared after total disinfection at T3., Conclusion: Virus C hepatitis could be transmitted during endoscopic examination, but cleaning and disinfection procedures effectively eliminated all viral particles.
Published: 1995

28. [Necrotizing amebic colitis].

Author: Béchade D, Beyssac R, Raymond JM, de Mascarel A, Masson B, and Amouretti M
Subjects: Adult, Colectomy, Dysentery, Amebic surgery, Female, Humans, Necrosis, Time Factors, Dysentery, Amebic pathology
Abstract: We report a case of necrotizing amebic colitis in a 43 year-old patient, 10 years after a stay in Senegal, successfully treated by right hemicolectomy. Entamoeba histolytica were found in colon necrosis and amoebiasis serology was positive, leading to the diagnosis. The epidemiologic, physiopathologic, clinical and therapeutic features of this exceptional affection are described. A few cases have been previously reported in non endemic areas where pre-operative diagnosis is rarely made. In endemic areas, a conservative treatment by ileostomy and colonic lavage seems to reduce the death rate.
Published: 1994

29. [Treatment of chronic hepatitis caused by hepatitis B virus].

Author: Ouzan D
Subjects: Hepatitis B drug therapy, Humans, Interferons therapeutic use, Vidarabine therapeutic use, Vidarabine Phosphate therapeutic use, Hepatitis B therapy
Published: 1990

30. [Alcoholics, hepato-gastroenterologists and psychotherapists].

Author: Béraud C and Fleury B
Subjects: Alcoholism psychology, Humans, Liver Diseases, Alcoholic psychology, Physician-Patient Relations, Alcoholism therapy, Gastroenterology, Liver Diseases, Alcoholic therapy, Psychotherapy
Published: 1987

31. [Alcohol dehydrogenase and aldehyde dehydrogenase isoenzymes: role in metabolism and hepatic toxicity of alcohol].

Author: Fleury B, Nalpas B, Couzigou P, Iron A, and Poupon RE
Subjects: Animals, Chemical Phenomena, Chemistry, Ethanol metabolism, Humans, Alcohol Dehydrogenase physiology, Aldehyde Dehydrogenase physiology, Ethanol adverse effects, Isoenzymes physiology, Liver metabolism, Liver Diseases, Alcoholic chemically induced
Published: 1988

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31 results on '"Département d'hépatologie et de gastroentérologie"'

1. Practical management of patients on Janus kinase inhibitor (JAKi) therapy: Practical fact sheets drawn up by the Rheumatism and Inflammation Club (CRI), a group endorsed by the French Society for Rheumatology (SFR)

2. Implementation of infliximab standardized doses after pharmacokinetic modelization in a cohort of patients with Crohn’s disease

3. Resection of small bowel adenocarcinoma metastases: Results of the ARCAD-NADEGE cohort study

4. Value of Contrast-Enhanced Ultrasound Quantification Criteria for Identifying Patients not Responding to Bevacizumab-Based Therapy for Colorectal Liver Metastases

5. Retreatment With Sofosbuvir Plus Grazoprevir/Elbasvir Plus Ribavirin of Patients With Hepatitis C Virus Genotype 1 or 4 Who Previously Failed an NS5A- or NS3-Containing Regimen: The ANRS HC34 REVENGE Study

6. Common variants in glucuronidation enzymes and membrane transporters as potential risk factors for colorectal cancer: a case control study

7. Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection

8. Quantification of portal–bridging fibrosis area more accurately reflects fibrosis stage and liver stiffness than whole fibrosis or perisinusoidal fibrosis areas in chronic hepatitis C

9. Efficacy of adalimumab in patients with Crohn's disease and symptomatic small bowel stricture: a multicentre, prospective, observational cohort (CREOLE) study

10. Risk of Incident Cancer in Inflammatory Bowel Disease Patients Starting Anti-TNF Therapy While Having Recent Malignancy

11. Improved fibrosis staging by elastometry and blood test in chronic hepatitis C

12. Triple therapy in treatment-experienced patients with HCV-cirrhosis in a multicentre cohort of the French Early Access Programme (ANRS CO20-CUPIC) – NCT01514890

13. Determination of reliability criteria for liver stiffness evaluation by transient elastography

14. Letter: mucosal healing in ulcerative colitis - higher relevance than in Crohn's disease? Authors' reply

15. High-Dose Pegylated Interferon-α and Ribavirin in Nonresponder Hepatitis C Patients and Relationship With IL-28B Genotype (SYREN Trial)

16. High-Dose Pegylated Interferon-α and Ribavirin in Nonresponder Hepatitis C Patients and Relationship With IL-28B Genotype (SYREN Trial).: High-Dose peg-IFN and Ribavirin and IL28B in HCV nonresponders

17. INFLUENCE OF HCV GENOTYPE 1 SUBTYPES ON THE VIRUS RESPONSE TO PEG INTERFERON ALPHA-2a PLUS RIBAVIRIN THERAPY

18. A New Combination of Blood Test and Fibroscan for Accurate Non-Invasive Diagnosis of Liver Fibrosis Stages in Chronic Hepatitis C

19. TRANSIENT ELASTOGRAPHY AND BIOMARKERS FOR LIVER FIBROSIS ASSESSMENT AND FOLLOW-UP OF INACTIVE HEPATITIS B CARRIERS

20. Danoprevir, an HCV NS3/4A protease inhibitor, improves insulin sensitivity in patients with genotype 1 chronic hepatitis C

21. Réduction des risques infectieux Chez les usagers de drogues

22. Improved diagnostic accuracy of blood tests for severe fibrosis and cirrhosis in chronic hepatitis C

23. Liver fibrosis staging with contrast-enhanced ultrasonography: prospective multicenter study compared with METAVIR scoring

24. [Risk of transmission of hepatitis C through endoscopy of the digestive tract].

25. [What are the precautions to be taken in hepatitis C?].

26. [Appearance of hepatitis C virus replication and increase of aminotransferase activity after corticoid treatment of presumed autoimmune hepatitis. 2 cases].

27. [Risk of transmission of hepatitis C virus by digestive endoscopy].

28. [Necrotizing amebic colitis].

29. [Treatment of chronic hepatitis caused by hepatitis B virus].

30. [Alcoholics, hepato-gastroenterologists and psychotherapists].

31. [Alcohol dehydrogenase and aldehyde dehydrogenase isoenzymes: role in metabolism and hepatic toxicity of alcohol].

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31 results on '"Département d'hépatologie et de gastroentérologie"'

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