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1. Willingness to use a drug consumption room among people who use drugs in Lyon, France, a city with no open scene of drug use (the TRABOUL survey)

Author

Mathieu Chappuy, Philippe Lack, Baptiste David, Gilles Penavayre, Damien Thabourey, Maira Landulpho, Anthony Plasse, Christophe Icard, François Bailly, Faroudja Boutahra, Pierre Pradat, Marianne Maynard, Marie Jauffret-Roustide, Julia de Ternay, and Benjamin Rolland

Subjects
Drug consumption rooms, Harm reduction, People who use drugs, Opioids, France, Public aspects of medicine, RA1-1270
Abstract

Abstract Background Drug consumption rooms (DCRs) have been developed in cities with open drug scenes, with the aim to reduce drug-related harm. In Lyon, France's second-largest city, there is no distinct drug use area, which raised doubts regarding the need for a DCR. Methods We conducted a face-to-face survey of 264 people who use drugs (PWUDs), recruited in harm reduction or addiction treatment centers, in the streets or in squats. We assess their willingness to use a DCR, and we collected sociodemographic and medical features. Bivariable comparisons and analyses adjusted for sociodemographic parameters explored the association between willing to use a DCR and other variables, thus providing crude (ORs) and adjusted odds ratios (aORs) and 95% confidence intervals (95% CI). Results In total, 193 (73.1%) PWUDs accepted to participate (mean age 38.5 ± 9.3 years; 80.3% men). Among them, 64.2% declared willing to use a DCR. Being treatment-seeker (aOR 0.20, 95% CI [0.08–0.51]; p

Published
2023
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2. End-ischemic hypothermic oxygenated perfusion for extended criteria donors in liver transplantation: a multicenter, randomized controlled trial—HOPExt

Author

Pierre Pradat, Solene Pantel, Marianne Maynard, Laure Lalande, Sylvie Thevenon, Rene Adam, Marc-Antoine Allard, Fabien Robin, Michel Rayar, Emmanuel Boleslawski, Olivier Scatton, Mircea Chirica, François Faitot, Philippe Bachellier, Olivier Soubrane, Kayvan Mohkam, Jean-Yves Mabrut, and Mickaël Lesurtel

Subjects
Liver transplantation, Extended criteria donors, End-ischemic hypothermic oxygenated perfusion, Medicine (General), R5-920
Abstract

Abstract Background Given the scarce donor supply, an increasing number of so-called marginal or extended criteria donor (ECD) organs are used for liver transplantation. These ECD liver grafts are however known to be associated with a higher rate of early allograft dysfunction and primary non-function because of a greater vulnerability to ischemia–reperfusion injury. The end-ischemic hypothermic oxygenated machine perfusion (HOPE) technique may improve outcomes of liver transplantation with ECD grafts by decreasing reperfusion injury. Methods HOPExt trial is a comparative open-label, multicenter, national, prospective, randomized, controlled study, in two parallel groups, using static cold storage, the gold standard procedure, as control. The trial will enroll adult patients on the transplant waiting list for liver failure or liver cirrhosis and/or liver malignancy requiring liver transplantation and receiving an ECD liver graft from a brain-dead donor. In the experimental group, ECD liver grafts will first undergo a classical static cold (4 °C) storage followed by a hypothermic oxygenated perfusion (HOPE) for a period of 1 to 4 h. The control group will consist of the classic static cold storage which is the gold standard procedure in liver transplantation. The primary objective of this trial is to study the efficacy of HOPE used before transplantation of ECD liver grafts from brain-dead donors in reducing postoperative early allograft dysfunction within the first 7 postoperative days compared to simple cold static storage. Discussion We present in this protocol all study procedures in regard to the achievement of the HOPExt trial, to prevent biased analysis of trial outcomes and improve the transparency of the trial results. Enrollment of patients in the HOPExt trial has started on September 10, 2019, and is ongoing. Trial registration ClinicalTrials.gov NCT03929523. Registered on April 29, 2019, before the start of inclusion.

Published
2023
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3. Correction: End-ischemic hypothermic oxygenated perfusion for extended criteria donors in liver transplantation: a multicenter, randomized controlled trial—HOPExt

Author

Pierre Pradat, Solene Pantel, Marianne Maynard, Laure Lalande, Sylvie Thevenon, Rene Adam, Marc-Antoine Allard, Fabien Robin, Michel Rayar, Emmanuel Boleslawski, Olivier Scatton, Mircea Chirica, François Faitot, Philippe Bachellier, Olivier Soubrane, Kayvan Mohkam, Jean-Yves Mabrut, and Mickaël Lesurtel

Subjects
Medicine (General), R5-920
Published
2023
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4. Screening and care for alcohol use disorder in France: expectations, barriers and levers using a mixed-methods approach

Author

Marie Costa, Tangui Barré, Marion Coste, Issifou Yaya, Cyril Berenger, Marc Tanti, Christophe Cutarella, Marion Mora, Pierre Poloméni, Marianne Maynard, Danielle Teuma, Michaël Bazin, Gwenaelle Maradan, Perrine Roux, and Patrizia Maria Carrieri

Subjects
Alcohol use disorder, Access to care, Mixed-methods, Survey, Semi-structured interviews, Textual analysis, Public aspects of medicine, RA1-1270
Abstract

Abstract Background The widespread under-screening and under-treatment of alcohol use disorder (AUD) contributes to its health and socioeconomic burden. We conducted a mixed-methods (qualitative and qualitative) study in people with alcohol use disorder (PWAUD) to explore their expectations, as well as barriers and levers to AUD care. Methods Individuals with AUDIT > 15 (N = 179) were interviewed using computer-assisted interviews in several medical and non-medical sites (e.g., bars) (quantitative substudy). We also conducted semi-structured face-to-face interviews with 36 PWAUD (qualitative substudy). Using logistic regression, we explored factors associated with having previously received/sought care for AUD. Three major themes were identified in the qualitative textual analysis using a descending hierarchical classification. Results Not socializing with heavy drinkers (AOR [95%CI]:3.84[1.66–8.85]), regular smoking (9.72[3.91–24.15]) and feeling discriminated against (2.35[1.10–5.05]) were independent levers to having sought/received care for AUD, while being aged

Published
2020
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5. Economic Study of 2-Stage Exchange in Patients With Knee or Hip Prosthetic Joint Infection Managed in a Referral Center in France: Time to Use Innovative(s) Intervention(s) at the Time of Reimplantation to Reduce the Risk of Superinfection

Author

Hassan Serrier, Christell Julien, Cécile Batailler, Eugénie Mabrut, Corinne Brochier, Sylvie Thevenon, Marianne Maynard-Muet, Agnes Henry, Sébastien Lustig, Laure Huot, Tristan Ferry, and The Lyon BJI Study group

Subjects
prosthetic-joint infection, cost analysis, prevention, antibiotics, cement, healthcare system, Medicine (General), R5-920
Abstract

Objective: Chronic prosthetic joint infections (PJI) are serious complications in arthroplasty leading to prosthesis exchange and potential significant costs for health systems, especially if a subsequent new infection occurs. This study assessed the cost of chronic PJI managed with 2-stage exchange at the Lyon University Hospital, CRIOAc Lyon reference center, France. A threshold analysis was then undertaken to determine the reimbursement tariff of a hypothetical preventive device usable at the time of reimplantation, which possibly enables health insurance to save money according to the risk reduction of subsequent new infection. This analysis was also performed for a potential innovative device already available on the market, a dual antibiotic loaded bone cement used to fix cemented prosthesis that releases high concentrations of gentamicin and vancomycin locally (G+V cement).Method: Patients >18 years, admitted for a hip or knee chronic PJI managed with 2-stage exchange, between January 1, 2013, and December 31, 2015, were retrospectively identified. Following, resource consumption in relation to inpatient hospital stay, hospitalization at home, rehabilitation care, outpatient antibiotic treatments, imaging, laboratory analysis, and consultations were identified and collected from patient records and taken into account in the evaluation. Costs were assessed from the French health insurance perspective over the 2 years following prosthesis reimplantation.Results: The study included 116 patients (median age 67 y; 47% hip prosthesis). Mean cost of chronic PJI was estimated over the 2 years following prosthesis reimplantation at €21,324 for all patients, and at €51,697 and €15,745 for patients with (n = 18) and without (n = 98) a subsequent new infection after reimplantation, respectively. According to the threshold analysis the reimbursement tariff (i) should not exceed €2,820 for a device which can reduce the risk of a new infection by 50% and (ii) was between €2,988 and €3,984 if the G + V cement can reduce the risk of a new infection by 80% (this reduction risk is speculative and has to be confirmed by clinical trials).Conclusion: This study revealed that chronic PJI requiring a 2-stage revision is costly, with significant costs in relation to the reimplantation procedure (about 15 k€). However, following reimplantation the rate of subsequent new infection remained high, and the cost of reimplantation following a new infection is considerable, reaching 50k€ per patient. These first cost estimates of managing chronic PJI with 2-stage exchange in France underline the economic interest of preventing new infections.

Published
2021
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6. Impact on the Gut Microbiota of Intensive and Prolonged Antimicrobial Therapy in Patients With Bone and Joint Infection

Author

Benoît Levast, Nicolas Benech, Cyrielle Gasc, Cécile Batailler, Eric Senneville, Sébastien Lustig, Cécile Pouderoux, David Boutoille, Lilia Boucinha, Frederic-Antoine Dauchy, Valérie Zeller, Marianne Maynard, Charles Cazanave, Thanh-Thuy Le Thi, Jérôme Josse, Joël Doré, Frederic Laurent, and Tristan Ferry

Subjects
gut microbiota, antimicrobial therapy, antibiotics, bone and joint infection, dysbiosis, Medicine (General), R5-920
Abstract

There is a growing interest in the potentially deleterious impact of antibiotics on gut microbiota. Patients with bone and joint infection (BJI) require prolonged treatment that may impact significantly the gut microbiota. We collected samples from patients with BJI at baseline, end of antibiotics (EOT), and 2 weeks after antibiotic withdrawal (follow-up, FU) in a multicenter prospective cohort in France. Microbiota composition was determined by shotgun metagenomic sequencing. Fecal markers of gut permeability and inflammation as well as multi-drug-resistant bacteria (MDRB) and Clostridioides difficile carriage were assessed at each time point. Sixty-two patients were enrolled: 27 native BJI, 14 osteosynthesis-related BJI, and 21 prosthetic joint infections (PJI). At EOT, there was a significant loss of alpha-diversity that recovered at FU in patients with native BJI and PJI, but not in patients with osteosynthesis-related BJI. At EOT, we observed an increase of Proteobacteria and Bacteroidetes that partially recovered at FU. The principal component analysis (PCoA) of the Bray–Curtis distance showed a significant change of the gut microbiota at the end of treatment compared to baseline that only partially recover at FU. Microbiota composition at FU does not differ significantly at the genus level when comparing patients treated for 6 weeks vs. those treated for 12 weeks. The use of fluoroquinolones was not associated with a lower Shannon index at the end of treatment; however, the PCoA of the Bray–Curtis distance showed a significant change at EOT, compared to baseline, that fully recovered at FU. Levels of fecal neopterin were negatively correlated with the Shannon index along with the follow-up (r2 = 0.17; p < 0.0001). The PCoA analysis of the Bray–Curtis distance shows that patients with an elevated plasma level of C-reactive protein (≥5 mg/L) at EOT had a distinct gut microbial composition compared to others. MDRB and C. difficile acquisition at EOT and FU represented 20% (7/35) and 37.1% (13/35) of all MDRB/C. difficile-free patients at the beginning of the study, respectively. In patients with BJI, antibiotics altered the gut microbiota diversity and composition with only partial recovery, mucosal inflammation, and permeability and acquisition of MDRB carriage. Microbiome interventions should be explored in patients with BJI to address these issues.

Published
2021
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7. Longitudinal liver stiffness assessment in patients with chronic hepatitis C undergoing antiviral therapy.

Author

Stella M Martinez, Juliette Foucher, Jean-Marc Combis, Sophie Métivier, Maurizia Brunetto, Dominique Capron, Marc Bourlière, Jean-Pierre Bronowicki, Thong Dao, Marianne Maynard-Muet, Damien Lucidarme, Wassil Merrouche, Xavier Forns, and Victor de Lédinghen

Subjects
Medicine, Science
Abstract

BACKGROUND/AIMS: Liver stiffness (LS) measurement by means of transient elastography (TE) is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC). METHODS: TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. RESULTS: 323 treated (62.7%) and 192 untreated patients (37.3%) were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P

Published
2012
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8. Subclinical proximal tubulopathy in hepatitis B: The roles of nucleot(s)ide analogue treatment and the hepatitis B virus

Author

Thierry Poynard, Guillaume Lassailly, Juliette Foucher, Manh-Thông Dao, Xavier Duval, Isabelle Hourmand-Ollivier, Séverine Hommel, Vincent Di Martino, Pierre-Henri Bernard, Dominique Larrey, Nathalie Boyer, Anais Labrunie, Marc Bardou, Paul Carrier, Marilyne Debette-Gratien, Marie Essig, Eric Nguyen-Khac, Armand Abergel, Victor de Ledinghen, Véronique Loustaud-Ratti, Claire Vanlemmens, Nathalie Ganne-Carrié, Anne Gervais, Jean-Baptiste Hiriart, Fouchard-Hubert Isabelle, Christine Aurières, Pauline Pinet, Thierry Thevenot, Jérémie Jacques, Philippe Mathurin, Dominique Thabut, Christophe Renou, Daniel Cohen, Marianne Maynard, Valérie Canva, Julien Vergniol, Bertrand Hanslik, Anaïs Brayette, Sophie Alain, Matthieu Schnee, Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Pôle Universitaire d’Addictologie en Limousin, CH Esquirol [Limoges] (CH Esquirol), Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-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), Plate forme de bioinformatique et biostatistique (CEBIMER), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), 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), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 (GRAP), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Maladies infectieuses et tropicales [CHU Limoges], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hepatology, Hopital, Physiopathologie des Maladies Inflammatoires de l'Intestin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], Service d'Hépato-gastro-entérologie et oncologie digestive (CHU de Bordeaux), CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], 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), Paris School of Economics (PSE), Université Paris 1 Panthéon-Sorbonne (UP1)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-École des Ponts ParisTech (ENPC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Paris Jourdan Sciences Economiques (PJSE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), 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)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie (CIC-P803), Université de Bourgogne (UB)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Normandie Université (NU), Service d'Hépatologie [CHRU Besançon], Hôpital Haut-Lévêque [CHU Bordeaux], Hôpital Claude Huriez [Lille], CHU Lille, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Université Paris Cité (UPCité), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Service de gastroentérologie (CHD Vendee - Hopital Les Oudairies, La Roche Sur Yon), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Hôpital Saint-Éloi [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), 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), Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), Épidémiologie et recherches translationnelles sur les maladies rénales et cardiovasculaires (EPREC) (U1018 (Équipe 5)), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service Néphrologie/Dialyse [AP-HP Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], and Hôpital Charles Nicolle [Rouen]-CHU Rouen

Subjects
Hepatitis B virus, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Population, Renal function, medicine.disease_cause, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Nucleoside analogues, Internal medicine, medicine, Cumulative incidence, Renal insufficiency, education, education.field_of_study, Hepatology, business.industry, Proximal tubulopathy, Incidence (epidemiology), Hazard ratio, Entecavir, Hepatitis B, medicine.disease, 030220 oncology & carcinogenesis, Prospective Study, 030211 gastroenterology & hepatology, business, Biomarkers, medicine.drug
Abstract

International audience; BACKGROUND The recommended monitoring tools for evaluating nucleot(s)ide analogue renal toxicity, such as estimated glomerular filtration rate (eGFR) and phosphatemia, are late markers of proximal tubulopathy. Multiple early markers are available, but no consensus exists on their use. AIM To determine the 24 mo prevalence of subclinical proximal tubulopathy (SPT), as defined with early biomarkers, in treated vs untreated hepatitis B virus (HBV)-monoinfected patients. METHODS A prospective, non-randomized, multicenter study of HBV-monoinfected patients with a low number of renal comorbidities was conducted. The patients were separated into three groups: Naive, starting entecavir (ETV) treatment, or starting tenofovir disoproxil (TDF) treatment. Data on the early markers of SPT, the eGFR and phosphatemia, were collected quarterly. SPT was defined as a maximal tubular reabsorption of phosphate/eGFR below 0.8 mmoL/L and/or uric acid fractional excretion above 10%. The prevalence and cumulative incidence of SPT at month 24 (M24) were calculated. Quantitative data were analyzed using analyses of variance or Kruskal-Wallis tests, whereas chi-squared or Fisher's exact tests were used to analyze qualitative data. Multivariate analyses were used to adjust for any potential confounding factors. RESULTS Of the 196 patients analyzed, 138 (84 naive, 28 starting ETV, and 26 starting TDF) had no SPT at inclusion. At M24, the prevalence of SPT was not statistically different between naive and either treated group (21.1% vs 30.7%, P < 0.42 and 50.0% vs 30.7%, P = 0.32 for ETV and TDF, respectively); no patient had an eGFR lower than 50 mL/min/1.73 m(2) or phosphatemia less than 0.48 mmoL/L. In the multivariate analysis, no explanatory variables were identified after adjustment. The cumulative incidence of SPT over 24 mo (25.5%, 13.3%, and 52.9% in the naive, ETV, and TDF groups, respectively) tended to be higher in the TDF group vs the naive group (hazard ratio: 2.283, P = 0.05). SPT-free survival at M24 was 57.6%, 68.8%, and 23.5% for the naive, ETV, and TDF groups, respectively. The median survival time without SPT, evaluated only in the TDF group, was 5.9 mo. CONCLUSION The prevalence and incidence of SPT was higher in TDF-treated patients compared to naive patients. SPT in the naive population suggests that HBV can induce renal tubular toxicity.

Published
2020

9. The use of a thromboelastometry-based algorithm reduces the need for blood product transfusion during orthotopic liver transplantation

Author

Jean-Yves Mabrut, Diego Quattrone, Marianne Maynard, Nadia Steer, Mathieu Gazon, Aurélie Bonnet, Frédéric Aubrun, Pierre Pradat, and Nathalie Gilquin

Subjects
Male, medicine.medical_treatment, Blood Component Transfusion, Liver transplantation, Plasma, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, Interquartile range, Blood product, Coagulation testing, Humans, Medicine, Single-Blind Method, Prospective Studies, business.industry, 030208 emergency & critical care medicine, Middle Aged, Liver Transplantation, Thrombelastography, Thromboelastometry, Anesthesiology and Pain Medicine, Platelet transfusion, Female, France, Fresh frozen plasma, business, Algorithm, Algorithms, Tranexamic acid, medicine.drug
Abstract

BACKGROUND Orthotopic liver transplantation is associated with a risk of bleeding. Coagulation in cirrhotic patients is difficult to assess with standard coagulation tests because of rebalanced coagulation. This can be better assessed by thromboelastometry which can detect coagulation impairments more specifically in such patients. OBJECTIVES Our first objective was to compare the number of units of blood products transfused during liver transplantation when using an algorithm based on standard coagulation tests or a thromboelastometry-guided transfusion algorithm. DESIGN Randomised controlled trial. SETTING Single-centre tertiary care hospital in France, from December 2014 to August 2016. PARTICIPANTS A total of 81 adult patients undergoing orthotopic liver transplantation were studied. Patients were excluded if they had congenital coagulopathies. INTERVENTION Transfusion management during liver transplantation was guided either by a standard coagulation test algorithm or by a thromboelastometry-guided algorithm. Transfusion, treatments and postoperative outcomes were compared between groups. MAIN OUTCOME MEASURES Total number of transfused blood product units during the operative period (1 U is one pack of red blood cells (RBCs), fresh frozen plasma (FFP) or platelets). RESULTS Median [interquartile range] intra-operative transfusion requirement was reduced in the thromboelastometry group (3 [2 to 4] vs. 7 [4 to 10] U, P = 0.005). FFP and tranexamic acid were administered less frequently in the thromboelastometry group (respectively 15 vs. 46.3%, P = 0.002 and 27.5 vs. 58.5%, P = 0.005), whereas fibrinogen was more often infused in the thromboelastometry group (72.5 vs. 29.3%, P

Published
2019

10. Early hepatocellular carcinoma detection using magnetic resonance imaging is cost-effective in high-risk patients with cirrhosis

Author

Pierre Nahon, Marie Najean, Richard Layese, Kevin Zarca, Laeticia Blampain Segar, Carole Cagnot, Nathalie Ganne-Carrié, Gisèle N’Kontchou, Stanislas Pol, Cendrine Chaffaut, Fabrice Carrat, Maxime Ronot, Etienne Audureau, Isabelle Durand-Zaleski, Tarik Asselah, Dominique Guyader, Hélène Fontaine, Georges-Philippe Pageaux, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Thomas Decaensi, Ghassan Riachi, Paul Calès, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Sebastien Dharancy, Jean-Frédéric Blanc, Armand Abergel, Olivier Chazouillères, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Louis d’Alteroche, Claire Wartelle, Thông Dao, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Eric Nguyen-Khac, Brigitte Bernard-Chabert, Sophie Hillaire, Vincent Di Martino, Delphine Bonnet, Virginie Payssan-Sicart, Chloe Pomes, François Bailly, Marjolaine Beaudoin, Dominique Giboz, Kerstin Hartig-Lavie, Marianne Maynard, Eric Billaud, David Boutoille, Morane Cavellec, Marjorie Cheraud-Carpentier, Isabelle Hubert, Jaouad Benhida, Adrien Lannes, Françoise Lunel, Frédéric Oberti, Nathalie Boyer, Nathalie Giuily, Corinne Castelnau, Giovanna Scoazec, Aziza Chibah, Sylvie Keser, Karim Bonardi, Anaïs Vallet-Pichard, Philippe Sogni, Juliette Foucher, Jean-Baptiste Hiriart, Amy Wilson, Sarah Shili, Faiza Chermak, Christelle Ansaldi, Nisserine Ben Amara, Laëtitia Chouquet, Emilie De Luca, Valérie Oules, Rodolphe Anty, Eve Gelsi, Régine Truchi, Elena Luckina, Nadia Messaoudi, Joseph Moussali, Barbara De Dieuleveult, Damien Labarriere, Pascal Poter, Si Nafa Si Ahmed, Véronique Grando-Lemaire, Valérie Bourcier, Séverine Brulé, Thomas Stalhberger, Caroline Jezequel, Audrey Brener, Anne Laligant, Aline Rabot, Isabelle Renard, Thomas F. Baumert, Michel Dofföel, Catherine Mutter, Pauline Simo-Noumbissie, Esma Razi, Hélène Barraud, Mouni Bensenane, Abdelbasset Nani, Sarah Hassani-Nani, Marie-Albertine Bernard, Michael Bismuth, Ludovic Caillo, Stéphanie Faure, Marie Pierre Ripault, Christophe Bureau, Jean Marie Peron, Marie Angèle Robic, Léa Tarallo, Marine Faure, Bruno Froissart, Marie-Noelle Hilleret, Jean-Pierre Zarski, Odile Goria, Victorien Grard, Hélène Montialoux, Muriel François, Christian Ouedraogo, Christelle Pauleau, Anne Varault, Tony Andreani, Bénédicte Angoulevant, Azeline Chevance, Lawrence Serfaty, Teresa Antonini, Audrey Coilly, Jean-Charles Duclos Vallée, Mariagrazia Tateo, Corinne Bonny, Chanteranne Brigitte, Géraldine Lamblin, Léon Muti, Abdenour Babouri, Virginie Filipe, Camille Barrault, Laurent Costes, Hervé Hagège, Soraya Merbah, Paul Carrier, Maryline Debette-Gratien, Jérémie Jacques, Guillaume Lassailly, Florent Artu, Valérie Canva, Sébastien Dharancy, Alexandre Louvet, Marianne Latournerie, Marc Bardou, Thomas Mouillot, Yannick Bacq, Didier Barbereau, Charlotte Nicolas, Caroline Chevalier, Isabelle Archambeaud, Sarah Habes, Danièle Botta-Fridlund, Eric Saillard, Marie-Josée Lafrance, Patrice Cacoub, Patrizia Carrieri, Elisabeth Delarocque-Astagneau, Victor De Ledinghen, Céline Dorival, Jean Dubuisson, Chantal Housset, Dominique Larrey, Patrick Marcellin, Jean-Michel Pawlotsky, Ventzislava Petrov-Sanchez, Sophie Vaux, Linda Wittkop, Yazdan Yazdanpanah, Jessica Zucman-Rossi, Christophe Moreno, Romain Moirand, Nicolas Carbonell, Jean-Charles Duclos-Vallée, Victor de Ledinghen, Violaine Ozenne, Jean Henrion, Gabriel Perlemuter, Xavier Amiot, Sylvie Chevret, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Henri Mondor, Unité de recherche clinique en économie de la santé [Paris] (URC Eco), Délégation de la Recherche Clinique et de l’Innovation [Paris] (DRCI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANRS|Maladies infectieuses émergentes (ANRS|MIE), Université Sorbonne Paris Nord, Hôpital Cochin [AP-HP], Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-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)-Université Paris Cité (UPCité), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de santé publique [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), and Hôpital Beaujon [AP-HP]

Subjects
AMRI, abbreviated magnetic resonance imaging, NAFLD, non-alcoholic fatty liver disease, medicine.medical_specialty, Cirrhosis, Cost effectiveness, [SDV]Life Sciences [q-bio], Population, TACE, transarterial chemoembolization, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Gastroenterology, QALY, quality-adjusted life year, Internal medicine, Internal Medicine, LY, life years, Immunology and Allergy, Medicine, Early Hepatocellular Carcinoma, liver cancer risk, education, cost-effectiveness, RFA, radiofrequency ablation, education.field_of_study, AFP, alpha-fetoprotein, US, ultrasound, Hepatology, medicine.diagnostic_test, business.industry, cirrhosis, LYG, life years gained, Incidence (epidemiology), BCLC, Barcelona Clinic Liver Cancer, ICER, incremental cost-effectiveness ratio, Magnetic resonance imaging, medicine.disease, HR, hazard ratio, digestive system diseases, Hepatocellular carcinoma, SHR, subdistribution hazard ratio, surveillance, HCC, hepatocellular carcinoma, business, MRI, magnetic resonance imaging, Incremental cost-effectiveness ratio, Research Article, MRI
Abstract

Background & Aims Reinforced hepatocellular carcinoma (HCC) surveillance using magnetic resonance imaging (MRI) could increase early tumour detection but faces cost-effectiveness issues. In this study, we aimed to evaluate the cost-effectiveness of MRI for the detection of very early HCC (Barcelona Clinic Liver Cancer [BCLC] 0) in patients with an annual HCC risk >3%. Methods French patients with compensated cirrhosis included in 4 multicentre prospective cohorts were considered. A scoring system was constructed to identify patients with an annual risk >3%. Using a Markov model, the economic evaluation estimated the costs and life years (LYs) gained with MRI vs. ultrasound (US) monitoring over a 20-year period. The incremental cost-effectiveness ratio (ICER) was calculated by dividing the incremental costs by the incremental LYs. Results Among 2,513 patients with non-viral causes of cirrhosis (n = 840) and/or cured HCV (n = 1,489)/controlled HBV infection (n = 184), 206 cases of HCC were detected after a 37-month follow-up. When applied to training (n = 1,658) and validation (n = 855) sets, the construction of a scoring system identified 33.4% and 37.5% of patients with an annual HCC risk >3% (3-year C-Indexes 75 and 76, respectively). In patients with a 3% annual risk, the incremental LY gained with MRI was 0.4 for an additional cost of €6,134, resulting in an ICER of €15,447 per LY. Compared to US monitoring, MRI detected 5x more BCLC 0 HCC. The deterministic sensitivity analysis confirmed the impact of HCC incidence. At a willingness to pay of €50,000/LY, MRI screening had a 100% probability of being cost-effective. Conclusions In the era of HCV eradication/HBV control, patients with annual HCC risk >3% represent one-third of French patients with cirrhosis. MRI is cost-effective in this population and could favour early HCC detection. Lay summary The early identification of hepatocellular carcinoma in patients with cirrhosis is important to improve patient outcomes. Magnetic resonance imaging could increase early tumour detection but is more expensive and less accessible than ultrasound (the standard modality for surveillance). Herein, using a simple score, we identified a subgroup of patients with cirrhosis (accounting for >one-third), who were at increased risk of hepatocellular carcinoma and for whom the increased expense of magnetic resonance imaging would be justified by the potential improvement in outcomes., Graphical abstract, Highlights • HCC risk stratification in patients with cirrhosis aims at improving performance of cancer surveillance. • Using a simple scoring system, one-third of patients with cirrhosis with an annual HCC risk >3% can be easily identified. • Semi-annual surveillance using MRI in this population could enable the cost-effective detection of 5x more BCLC 0 HCCs.

Published
2022

11. Cannabis Use and Plasma Human Immunodeficiency Virus (HIV) RNA Levels in Patients Coinfected With HIV and Hepatitis C Virus Receiving Antiretroviral Therapy: Data From the ANRS CO13 HEPAVIH Cohort

Author

M Chalouni, D Vittecocq, C Rouzaud, C Gilbert, P Bellecave, H Stitou, Thoirain-Galvan, F Touam, C Debreux, D Croisier-Bertin, S Gillet, A de Monte, Patrick Miailhes, F Valour, M L Batard, Lionel Piroth, Joseph Koffi, Y Baazia, Dominique Salmon-Ceron, Morane Cavellec, Gilles Peytavin, B Spire, H Dutronc, C Partouche, Lawrence Serfaty, M Brollo, G Melica, P Catalan, Pascale Trimoulet, P Fischer, David Boutoille, A Mélard, M Mora, P Callard, C Tumiotto, Marianne Maynard, P Bertheau, L Lacaze-Buzy, M Nishimwe, T Pistone, S Fourati, F Roustant, Fabienne Marcellin, Chambrin, S Galim, J Haudebourg, L Traore, S Dominguez, Claudine Duvivier, Brodard, C Rivoisy, M Pauchard, H Laroche, C Katlama, C Allavena, Jean-Daniel Lelièvre, S Fafi-Kremer, K. Barange, S Anriamiandrisoa, D Lacoste, M Desvallees, Karine Lacombe, Marianne Ziol, P Duffau, M Baudoin, Laurent Alric, Y Lévy, Laurent Cotte, Athenaïs Gerber, Rio, P Fisher, C Deback, P Thilbaut, C Louisin, P Platterier, F. Boufassa, Jacques Izopet, S Tezkratt, Reliquet, Philippe Lack, Yazdan Yazdanpanah, Olivier Lortholary, C Pallier, Isabelle Poizot-Martin, S Caldato, Pierre-Marie Girard, A Joulie, P Tremeaux, F Bendjaballah, Julie Chas, François Bailly, J Krause, J Polo Devoto, N Hall, J F Paccalin, Eric Billaud, Yves Benhamou, E Bedel, D. Neau, Tangui Barré, S Gohier, A. Bicart-See, David Zucman, S. Radenne, A S Lascaux, S Ogoudjobi, M L Chaix, C Majerholc, D Malvy, B Marchou, S Reigadas, F Biron, Brigitte Autran, Amaury Martin, C Greib, J Lourenco, Félix Bonnet, E Blanchard, S Bouchez, J Selves, F Dauchy, C Viala, Tristan Ferry, M Partisani, F Marcellin, D. Zucman, D Lambert, Y Ousidhoum, F Z Makhoukhi, P Roux, I Faure, Firouzé Bani-Sadr, Vincent Di Beo, C Le Pendeven, C Protopopescu, M Hentzien, M Le Cam, C Pignon, M Mebarki, A-S Ritleg, M Vandenhende, Hélène Fontaine, Philippe Morlat, C Martins, Marc-Antoine Valantin, Iwaka-Bande, André Boibieux, S Castet-Lafarie, A. Naqvi, Patrice Cacoub, L. Wittkop, A Rodallec, H. Aumaitre, Melina Erica Santos, Dominique Wendum, Petrov-Sanchez, Linda Wittkop, L Berroukeche, I Kansau, D Beniken, Constance Delaugerre, E Farfour, Philippe Sogni, M Buisson, Majid Amiri, François Raffi, David Rey, A Salmon Rousseau, Patrick Mercié, L Le Guen, C Cazanave, Pascal Chavanet, M Santos, Conte, S Akel, P Mercié, E de Mautort, L Chalal, Avettand-Fenoel, Caroline Scholtes, J Zelie, S Nafissa, J F Viallard, D. Lebrasseur-Longuet, Di Beo, Y Nguyen, A Soria, J Adam, C Biron, B Terris, Sarah Maylin, M Favier, Jean-Michel Molina, T Lemboub, Giordanengo, I Kmiec, C. Solas, L Michel, F Charlotte, A.M. Roque, M Hessamfar, C Augustin-Normand, Cécile Goujard, J L Berger, S Breau, H Hue, Sicart-Payssan, J L Pellegrin, P Cervera, A Desclaux, R Bayoud, A. Simon, M Uzan, M Priester, C Cheneau, Caroline Lascoux-Combe, C Chesnel, S Abgrall, M Duong Van Huyen, N Bernard, D Garipuy, E Gardiennet, D Peyramond, D Bornarel, Michel Dupon, F Larroquette, O Zaegel, P Gantner, C Lions, A Waldner-Combernoux, P Miailhes, A Ivanova, Christian Chidiac, Fabien Zoulim, M Mole, R Ben Rayana, H Adle-Biassette, François Nicot, L Esterle, L Meyer, Martinez, F Ader, A Adda-Lievin, P Carrieri, A. Gervais, C Martell, S Mahy, E Lazzaro, P Sogni, T Barré, R Knight, M C Pertusa, J. Bottero, Patrizia Carrieri, T Perpoint, Olivier Bouchaud, D Costagliola, C Gatey, E. Rosenthal, Dominique Salmon, S Lepuil, L Dequae-Merchadou, E Teicher, S Parlier, C Bolliot, G Alexandre, Sophie Metivier, O Braik, M C Receveur, Corinne Brochier, C Hemon, R Usubillaga, François Boué, M Méchain, Camelia Protopopescu, A Ochoa, Catherine Tamalet, M J Ferro-Collados, M P Pietri, P Bioulac-Sage, M C Saint-Paul, T T Le-Thi, M Lefebvre, Paradis, Le Baut, Chloe Pomes, Y Quertainmont, C Bernard-Henry, C Amiel, Gilles Pialoux, R Fior, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Service des maladies infectieuses et tropicales [CH Lyon Sud - HCL] (Hôpital de la Croix-Rousse), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Service de médecine interne et maladies infectieuses [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, Service Maladies infectieuses et tropicales [AP-HP Hôpital Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Team MORPH3EUS (INSERM U1219 - UB - ISPED), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Interne [Hôpital Foch, Suresnes] (SMI), Hôpital Foch [Suresnes], Département d'hépatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunité Innée - Innate Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dupuis, Christine, INSERM U1197, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]

Subjects
Microbiology (medical), Hepatitis C virus, [SDV]Life Sciences [q-bio], Human immunodeficiency virus (HIV), 030508 substance abuse, HIV Infections, Hepacivirus, medicine.disease_cause, 03 medical and health sciences, Plasma, 0302 clinical medicine, medicine, Humans, In patient, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Cannabis, business.industry, Coinfection, HIV, Cannabis use, Hepatitis C, Chronic, Virology, Antiretroviral therapy, Hepatitis C, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, Cohort, RNA, 0305 other medical science, business
Abstract

International audience; No abstract available

Published
2020

12. Screening and care for alcohol use disorder in France : expectations, barriers and levers using a mixed-methods approach

Author

Danielle Teuma, Perrine Roux, Tangui Barré, Marc Tanti, Pierre Polomeni, Gwenaëlle Maradan, Cyril Berenger, Michaël Bazin, Issifou Yaya, Marie Costa, Marianne Maynard, Patrizia Carrieri, Marion Mora, Marion Coste, Christophe Cutarella, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Centre d'épidémiologie et de santé publique des armées [Marseille] (CESPA), Service de Santé des Armées, Clinique Saint Barnabé - Ramsay Santé [Marseille] (CSB-RS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpitaux du Bassin de Thau, Centre Hospitalier d'Allauch, Hôpitaux du Bassin de Thau (Sète), and Dupuis, Christine

Subjects
Adult, Male, medicine.medical_specialty, Family support, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Psychological intervention, 030508 substance abuse, Context (language use), Access to care, Alcohol use disorder, Semi-structured interviews, Health Services Accessibility, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, mental disorders, medicine, Humans, Mass Screening, Textual analysis, 030212 general & internal medicine, Psychiatry, Survey, Qualitative Research, media_common, Motivation, Mixed-methods, business.industry, Public health, Addiction, lcsh:Public aspects of medicine, Alcohol dependence, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, Middle Aged, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Alcoholism, Socioeconomic Factors, Female, France, Biostatistics, 0305 other medical science, business, Research Article
Abstract

BackgroundThe widespread under-screening and under-treatment of alcohol use disorder (AUD) contributes to its health and socioeconomic burden. We conducted a mixed-methods (qualitative and qualitative) study in people with alcohol use disorder (PWAUD) to explore their expectations, as well as barriers and levers to AUD care.MethodsIndividuals with AUDIT > 15 (N = 179) were interviewed using computer-assisted interviews in several medical and non-medical sites (e.g., bars) (quantitative substudy). We also conducted semi-structured face-to-face interviews with 36 PWAUD (qualitative substudy). Using logistic regression, we explored factors associated with having previously received/sought care for AUD. Three major themes were identified in the qualitative textual analysis using a descending hierarchical classification.ResultsNot socializing with heavy drinkers (AOR [95%CI]:3.84[1.66–8.85]), regular smoking (9.72[3.91–24.15]) and feeling discriminated against (2.35[1.10–5.05]) were independent levers to having sought/received care for AUD, while being aged ConclusionThese results underline the need for interventions targeting families and the social network to increase awareness about AUD and related care. Simplified and novel comprehensive care trajectories are urgently needed to reduce the clinical and public health burden of AUD.

Published
2020

13. Direct-acting antiviral therapy decreases hepatocellular carcinoma recurrence rate in cirrhotic patients with chronic hepatitis C

Author

Domitille Poinsot, Pierre Pradat, Victor Virlogeux, Samir Benmakhlouf, K. Hartig-Lavie, Fabien Zoulim, Caroline Scholtes, Jean-Yves Mabrut, Philippe Lack, Agnès Rode, Guillaume Ouziel, Christophe Combet, Christian Ducerf, Marie Ecochard, S. Radenne, A.-C. Uhres, Philippe Merle, Joseph Koffi, Fanny Lebossé, Massimo Levrero, François Bailly, Marianne Maynard, Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Service de Radiologie [Hôpital de la Croix-Rousse - HCL]

Subjects
Male, direct-acting antivirals, hepatitis c virus, hepatocellular carcinoma, recurrence, aged, aged, 80 and over, antiviral agents, carcinoma, hepatocellular, female, hepatitis c, chronic, humans, liver neoplasms, male, middle aged, retrospective studies, secondary prevention, Survival, diagnosis, analysis, Observation, medicine.disease_cause, Gastroenterology, Hepatitis, Cohort Studies, surgery, 0302 clinical medicine, Recurrence, Secondary Prevention, Prospective cohort study, Aged, 80 and over, Liver Neoplasms, Hazard ratio, Hepatitis C, Middle Aged, virology, 3. Good health, Liver, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Female, 030211 gastroenterology & hepatology, France, Infection, Radiology, medicine.medical_specialty, Carcinoma, Hepatocellular, Patients, Hepatitis C virus, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antiviral Agents, methods, Time, 03 medical and health sciences, Internal medicine, medicine, Carcinoma, Humans, Aged, Retrospective Studies, therapy, Hepatology, business.industry, Hepatitis C, Chronic, medicine.disease, Survival Analysis, digestive system diseases, Liver Transplantation, Transplantation, General Surgery, Immunology, pharmacology, business, transplantation
Abstract

Background and Aims Arrival of direct-acting antiviral agents against hepatitis C virus with high-sustained virological response rates and very few side effects has drastically changed the management of hepatitis C virus infection. The impact of direct-acting antiviral exposure on hepatocellular carcinoma recurrence after a first remission in patients with advanced fibrosis remains to be clarified. Methods 68 consecutive hepatitis C virus patients with a first hepatocellular carcinoma diagnosis and under remission, subsequently treated or not with a direct-acting antiviral combination, were included. Clinical, biological and virological data were collected at first hepatocellular carcinoma diagnosis, at remission and during the surveillance period. Results All patients were cirrhotic. Median age was 62 years and 76% of patients were male. Twenty-three patients (34%) were treated with direct-acting antivirals and 96% of them achieved sustained virological response. Median time between hepatocellular carcinoma remission and direct-acting antivirals initiation was 7.2 months (IQR: 3.6-13.5; range: 0.3-71.4) and median time between direct-acting antivirals start and hepatocellular carcinoma recurrence was 13.0 months (IQR: 9.2-19.6; range: 3.0-24.7). Recurrence rate was 1.7/100 person-months among treated patients vs 4.2/100 person-months among untreated patients (P=.008). In multivariate survival analysis, the hazard ratio for hepatocellular carcinoma recurrence after direct-acting antivirals exposure was 0.24 (95% confidence interval: 0.10–0.55; P

Published
2017

15. 2579. Impact on the Gut Microbiota of the Prolonged Antimicrobial Therapy in Patients with Bone and Joint Infection (BJI): Results From the OSIRIS Prospective Study in France

Author

Cécile Batailler, Benoît Levast, Marianne Maynard, Eric Senneville, Frédéric Laurent, Cécile Pouderoux, Lilia Boucihna, Frederic-Antoin Dauchy, Tristan Ferry, Valérie Zeller, David Boutoille, and Sébastien Lustig

Subjects
medicine.medical_specialty, biology, business.industry, Gut flora, biology.organism_classification, Antimicrobial, Abstracts, Infectious Diseases, Oncology, Internal medicine, Poster Abstracts, medicine, In patient, business, Prospective cohort study
Abstract

Background There is growing interest about the deleterious impact of antibiotics on loss of gut symbiosis, called dysbiosis. As patients with BJI require antibiotics usually during 6 to 12 weeks, it is of interest to determine whether dysbiosis is frequent in this population, and if it could potentially reversible or not. Methods Multicentric prospective cohort study in France (EudraCT 2016-003247-10) including patients with 3 categories of BJI: native, osteosynthesis-related and prosthetic joint infection (PJI). At the time of suspicion (V1), at the end of therapy (V2) and then 2 weeks after stopping therapy (V3), blood and fecal samples were collected. Extracted DNA from stool was sequenced using shotgun metagenomic sequencing based on illumina library and Iseq instrumentation. Data run through a dedicated pipeline in order to produce microbiome indexes such as Sympson or Shannon diversities indexes. Gut microbiome and inflammation markers were analyzed including fecal neopterin, a maker of gut inflammation. Results Concerning the 62 patients included (mean age, 60 years; mean duration of antibiotics, 66 days), 27 had native, 14 had osteosynthesis and 21 had PJI. The most frequently prescribed drug was a fluoroquinolone, followed by a third-generation cephalosporin and vancomycin. Stools from 42 of them were analyzed as per protocol. Overall, the mean Shannon richness index decreased from 0.904 at V1 to 0.845 at V2; the Bray-Curtis index underlined the difference in microbiome reconstitution at V3 in comparison with V1. We report significant microbiome loss of diversity at V2, that was reversible at V3 in patients with native BJI and osteosynthesis-related BJI, but not in patients with PJI (figure). Fecal neopterin increased between V1 and V2 (mean 221.6 and 698.1 pmol/g of feces, respectively) and then decreased at V3 (422.5 pmol/g), and could be a potential surrogate marker of gut dysbiosis. Of note, patients with abnormal CRP at the end of antibiotics had high neopterin values, that raises the hypothesis that abnormal CRP at the end of antibiotics could be in relation with gut dysbiosis rather than uncured BJI. Conclusion The impact of antibiotics on the gut microbiota of patients with BJI seems to be significant, especially in patients with PJI who could be candidate for fecal microbiota transplantation. Disclosures All authors: No reported disclosures.

Published
2019

16. Efficacy and safety of boceprevir-based triple therapy in HCV cirrhotic patients awaiting liver transplantation (ANRS HC29 BOCEPRETRANSPLANT)

Author

Amir Guidoum, Laurent Alric, Vincent Leroy, Si-Nafa Si-Ahmed, Didier Samuel, Jean-Charles Duclos-Vallée, Jean-Didier Grangé, Sébastien Dharancy, Lawrence Serfaty, Célia Wellems, Christophe Hézode, François Durand, Anne-Marie Taburet, François Bailly, Christelle Paul, Maria Patrizia Carrieri, Pierre Pradat, Cécile Bouix, Elina Teicher, Sophie Metivier, Antoine Vilotitch, Christophe Duvoux, Georges-Philippe Pageaux, Anne-Marie Roque-Afonso, Bruno Roche, Filomena Conti, Ventzislava Petrov-Sanchez, Rodolphe Anty, Hélène Fontaine, Frédérik Beaulieux, Michelle Sizorn, Louis d’Alteroche, Marianne Maynard, Valérie Canva, Danielle Botta-Fridlund, Pascal Lebray, Département d'hépatologie [CHU Cochin], Institut Pasteur [Paris]-CHU Cochin [AP-HP]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), 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 ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), ORS PACA, Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], CHU Trousseau [APHP]-Centre Hospitalier Régional Universitaire de Tours ( CHRU TOURS ), Service d'hépatologie [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Fédération Médico-Chirurgicale des Maladies de l'Appareil Digestif, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -CHU Saint-Eloi, Département d'hépato-gastroentérologie, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Service de Gastro-entérologie - Hépatologie [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre Hospitalier Universitaire de Nice ( CHU Nice ), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon, Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Hôpital Purpan [Toulouse], Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), ANRS, France REcherche Nord & sud Sida-hiv Hépatites (FRENSH), Unit for Basic and Clinical research on Viral Hepatitis, Centre hépato-biliaire ( CHB ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AP-HP Hôpital Paul Brousse, This work was funded and sponsored by ANRS (France REcherche Nord & sud Sida-HIV Hépatites [FRENSH]), Paris.Dr Fontaine reports personal fees from Gilead, Janssen, BMS, MSD, AbbVie, outside the submitted work.Dr Leroy reports advisory role for BMS, Gilead, AbbVie, and Janssen and personal fees from BMS, Gilead, AbbVie, and Janssen.Dr Alric reports personal fees from MSD, Janssen, Gilead, AbbVie, BMS, research grants from MSD, Janssen, Gilead, AbbVie, BMS, and non-financial support from MSD, Janssen, Gilead, AbbVie, BMS., The authors thank Audrey Kremer-Cochet, Laure Roguet, and Dr Alpha Diallo for their continued deep involvement in the study. They also thank members of the independent committee: Prof Eric Belissant (methodologist), Dr Michel Biour (pharmacologist), Dr Marc Bourlière (hepatologist), Dr Rodolphe Garraffo (pharmacologist), Prof Dominique Larrey (pharmacologist), Prof Philippe Mathurin (hepatologist), Prof Christophe Moréno (hepatologist). They also thank Merck Schering-Plough for supplying the boceprevir. Finally, the authors thank the patients and their families., Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), 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)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Grenoble-Université Grenoble Alpes (UGA), Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Claude Huriez [Lille], CHU Lille, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANRS France Recherche Nord & sud Sida-hiv hépatites, 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), Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'hépathologie - Hôpital Cochin [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Cochin [AP-HP], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale ( SESSTIM ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -ORS PACA-Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Nice, Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), 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), 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Université Grenoble Alpes (UGA)-CHU Grenoble, Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Paul Brousse-Université Paris-Sud - Paris 11 (UP11), Herrada, Anthony, CHU Trousseau [APHP], 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), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP]

Subjects
Liver Cirrhosis, Male, medicine.medical_treatment, Liver transplantation, Gastroenterology, chemistry.chemical_compound, Liver disease, 0302 clinical medicine, 030212 general & internal medicine, Liver Neoplasms, Hepatitis C, Middle Aged, 3. Good health, Treatment Outcome, Hepatocellular carcinoma, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, France, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Adolescent, Proline, Antiviral Agents, 03 medical and health sciences, Pharmacotherapy, Internal medicine, Boceprevir, Ribavirin, medicine, Humans, Adverse effect, Aged, Retrospective Studies, Hepatology, business.industry, Interferon-alpha, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Chronic, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Liver Transplantation, Surgery, chemistry, Quality of Life, business
Abstract

International audience; BACKGROUND AND AIMS:In this French multicentre, open-label study, we analyzed the efficacy, safety and patient-reported outcomes of a boceprevir-based triple therapy in HCV genotype 1 cirrhotic patients awaiting liver transplantation (LT).METHODS:Patients received PEG-IFN/ribavirin (RBV) for 48 weeks (W) and boceprevir from W4 to W48 or until LT.RESULTS:Fifty-one patients (80% males, median age: 56 years) were included. Fifty-seven percent had hepatocellular carcinoma and 43% end-stage liver disease. At enrolment, the median MELD score was 9 (range: 6-18); the Child-Pugh score was A in 65%, B in 35% and C in 2%. Therapy was discontinued because of severe adverse events (SAEs) in 39% of cases and virological inefficacy in 24%. 16% of patients had undetectable HCV RNA 24 weeks after the end of treatment (SVR24). LT was performed in 18 patients (35%). HCV RNA was undetectable in 16.6% at LT. Seven patients (14%) died and three deaths were attributed to treatment. SAEs (n=129) were observed in 84% of patients. Twenty-four percent of patients developed severe infections. Albumin

Published
2017

17. Boceprevir and telaprevir-based triple therapy for chronic hepatitis C: virological efficacy and impact on kidney function and model for end-stage liver disease score

Author

K. Hartig-Lavie, Fabien Zoulim, Pierre Pradat, G. Funingana, F. Gonçalves, Victor Virlogeux, Marianne Maynard, Majid Amiri, and François Bailly

Subjects
Adult, Male, medicine.medical_specialty, Cirrhosis, Drug-Related Side Effects and Adverse Reactions, Genotype, Proline, Hepatitis C virus, Kidney, Kidney Function Tests, medicine.disease_cause, Antiviral Agents, Severity of Illness Index, Gastroenterology, Telaprevir, End Stage Liver Disease, chemistry.chemical_compound, Liver disease, Model for End-Stage Liver Disease, Pegylated interferon, Virology, Internal medicine, Boceprevir, Ribavirin, medicine, Humans, Prospective Studies, Aged, Hepatology, business.industry, Interleukins, Interferon-alpha, virus diseases, Hepatitis C, Chronic, Middle Aged, Viral Load, medicine.disease, digestive system diseases, Treatment Outcome, Infectious Diseases, chemistry, Immunology, Female, Interferons, business, Oligopeptides, Glomerular Filtration Rate, medicine.drug
Abstract

Summary Triple therapy using telaprevir or boceprevir [hepatitis C virus (HCV)-NS3/NS4A protease inhibitors (PI)] in association with PEG-IFN/ribavirin has recently become the new standard of care (SOC) for treatment of HCV genotype 1 patients. Our objective was to assess the efficacy and tolerance of triple therapy in routine clinical practice. A total of 186 consecutive HCV patients initiating triple therapy were enrolled in a single centre study. Clinical, biological and virological data were collected at baseline and during follow-up as well as tolerance and side effect details. Among 186 HCV patients initiating triple therapy, 69% received telaprevir and 31% boceprevir. Sixty-one per cent of patients had cirrhosis. The overall extended rapid virological response (eRVR) rate and sustained virological response (SVR) rate were 57.0% and 59.7%, respectively. IL28B CC phenotype was associated with increased probability of achieving eRVR and SVR, whereas previous non-response was associated with low eRVR and SVR rates. The SVR rate increased from 30.8% in previously non-responders to 59.1% in partial non-responders and 75% in relapsers. SVR rate in naive patients was 62.5%. Glomerular filtration rate assessed by MDRD after 12 weeks of therapy was significantly reduced for both PI (P

Published
2014

18. Pretreatment Predictive Factors for Hepatitis C Therapy Outcome: Relevance of Anti-E1E2 Antibodies Compared to Ip-10 and Il28B Genotypes

Author

Pascale Berthillon, Isabelle Chemin, Pierre Pradat, Clémence Arnaud, Martina Spaziante, Gloria Taliani, Marie-Anne Petit, Christian Trepo, and Marianne Maynard

Subjects
Adult, Male, Genotype, Alpha interferon, Pilot Projects, Antiviral Agents, Polymorphism, Single Nucleotide, Antibodies, Polyethylene Glycols, chemistry.chemical_compound, Ribavirin, medicine, Humans, Pharmacology (medical), Pharmacology, Therapy Outcome, biology, business.industry, Interleukins, Interferon-alpha, Interleukin, Hepatitis C, Hepatitis C, Chronic, Viral Load, medicine.disease, Recombinant Proteins, Chemokine CXCL10, Treatment Outcome, Infectious Diseases, chemistry, Immunology, biology.protein, RNA, Viral, Drug Therapy, Combination, Female, Interferons, Antibody, Peptides, business, Viral load
Abstract

Background Unique serum anti-E1E2 antibodies were shown to be associated with spontaneous recovery or predictive of sustained virological response (SVR) in patients with chronic hepatitis C receiving pegylated interferon/ ribavirin (PEG-IFN/RBV) therapy. The objectives were to establish the relationship between pretreatment anti-E1E2 titres and HCV RNA kinetics during PEG-IFN/RBV therapy, and to examine whether the combined determination of interleukin (IL)28B rs12979860 and rs8099917, pretreatment inducible protein (IP)-10 levels and/or anti-E1E2 improved the prediction of SVR. Methods Sera from 26 treatment-naive consecutive HCV patients treated with PEG-IFN/RBV for 48 weeks were analysed. Serum anti-E1E2 titres and pretreatment IP-10 levels were measured by enzyme-linked immunosorbent assays. The IL28B variants were determined using genotyping real-time polymerase chain reaction method. Viral decline was measured at weeks (W) 4 and 12 and SVR assessed 6 months after the end of therapy. Results Baseline anti-E1E2 titres were correlated with HCV RNA decline at W4 and W12 and were highly predictive of SVR with 100% of patients negative for anti-E1E2 failing to achieve SVR. Receiver operating characteristic curve analyses indicate that the best prediction of SVR (AUC 0.990) was obtained with the combination of anti-E1E2 and IP-10 levels. Predictive values were better than those obtained with IP-10 alone or in combination with IL28B variants. Conclusions Pretreatment serum anti-E1E2 response predicts HCV RNA clearance kinetics and treatment outcome. The combination of anti-E1E2 and IP-10 significantly improved the prediction of treatment response. This warrants further investigation and validation on larger cohorts of patients in the context of new therapeutic strategies.

Published
2013

19. Evolution of glomerular filtration rate in HIV-infected, HIV-HBV-coinfected and HBV-infected patients receiving tenofovir disoproxil fumarate

Author

Corinne Brochier, Laurent Cotte, Pierre Pradat, Marianne Maynard, M.-A. Le Pogam, Patrick Miailhes, P. Trolliet, François Bailly, J.-B. Okon, and Fabien Zoulim

Subjects
Adult, Male, medicine.medical_specialty, Tenofovir, Organophosphonates, Human immunodeficiency virus (HIV), Renal function, HIV Infections, Disease, medicine.disease_cause, Antiviral Agents, Gastroenterology, Hepatitis B, Chronic, Risk Factors, Virology, Internal medicine, Hiv infected, medicine, Humans, Risk factor, Hepatology, Coinfection, business.industry, Adenine, virus diseases, Fibrosis stage, Middle Aged, medicine.disease, Infectious Diseases, Endocrinology, Female, Kidney Diseases, business, Glomerular Filtration Rate, medicine.drug, Kidney disease
Abstract

We aimed to compare the evolution of estimated glomerular filtration rate (eGFR) in HIV-, HIV-HBV- and HBV-infected patients treated with tenofovir disoproxil fumarate (TDF). Three groups of patients receiving TDF12 months were recruited: 194 HIV-infected patients, 85 HIV-HBV-coinfected patients and 50 HBV-infected patients. eGFR was estimated using the Modification of the Diet in Renal Disease (MDRD) equation. Multivariate regression models were constructed to estimate factors associated with eGFR decrease from baseline. A total of 329 patients were studied. Median follow-up was 2.7 years. Median eGFR decrease was -4.9 (-16.6 to +7.2) mL/min/1.73 m(2) . After multivariate stepwise regression analysis, age (P = 0.0002), non-African origin (P0.0001), baseline eGFR (P0.0001) and TDF duration (P = 0.02) were associated with eGFR decrease in the whole population, while hypertension, diabetes and type of infection were not. Age (P0.0001), non-African origin (P = 0.0004), baseline eGFR (P0.0001) and TDF duration (P = 0.007) remained associated with eGFR decline in HIV and HIV-HBV-infected patients, while other variables including HIV risk factor, CDC stage, CD4 and HIV-RNA levels were not. Age (P = 0.03), non-African origin (P = 0.004), baseline eGFR (P0.0001) and baseline HBV-DNA2000 IU/mL (P = 0.04) were associated with eGFR decline in HBV and HIV-HBV-infected patients, while other variables including HBV risk factor and fibrosis stage were not. Estimated glomerular filtration rate decline under TDF therapy appears mainly associated with older age, non-African origin, higher baseline eGFR and longer TDF administration but not with the type of viral infection. Regular follow-up of renal function, especially tubular function is recommended during TDF therapy.

Published
2013

20. Sofosbuvir plus daclatasvir with or without ribavirin for chronic hepatitis C infection: Impact of drug concentration on viral load decay

Author

Marie-Claude Gagnieu, Marianne Maynard, Pierre Pradat, François Bailly, Fabien Zoulim, Laure Choupeaux, Caroline Scholtes, Victor Virlogeux, Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), and Hôpital Edouard Herriot [CHU - HCL]

Subjects
Liver Cirrhosis, Male, Cirrhosis, Pyrrolidines, Sofosbuvir, analysis, Hepacivirus, Gastroenterology, Hepatitis, chemistry.chemical_compound, 0302 clinical medicine, 030212 general & internal medicine, biology, Imidazoles, Valine, Middle Aged, Viral Load, Hepatitis C, 3. Good health, virology, Treatment Outcome, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, France, Drug Monitoring, Infection, Viral load, medicine.drug, Glomerular Filtration Rate, medicine.medical_specialty, Daclatasvir, Patients, Genotype, Renal function, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antiviral Agents, methods, 03 medical and health sciences, Internal medicine, Ribavirin, medicine, Humans, Aged, Retrospective Studies, therapy, Hepatology, business.industry, Retrospective cohort study, Hepatitis C, Chronic, biology.organism_classification, medicine.disease, Virology, Kinetics, chemistry, Multivariate Analysis, Linear Models, Carbamates, pharmacology, business
Abstract

Background Sofosbuvir (SOF) plus daclatasvir (DCV) with or without ribavirin is one of the currently recommended treatment option for chronic hepatitis C. Aims Our objectives were to identify factors associated with SOF/DCV plasma concentrations [C] variations and to evaluate their impact on viral kinetics. Methods 130 consecutive HCV patients initiating SOF/DCV therapy with or without ribavirin were enrolled. Clinical, biological, virological and pharmacological data were collected at baseline, at week 4, 8, 12, and 24 of therapy and 12 weeks after the end of therapy. Results Mean age was 57 years, 68% of patients were males, 69% were infected by HCV genotype 1 and cirrhosis was observed in 76% of patients. Multivariate analysis showed that higher SOF [C] and DCV [C] during treatment were associated with eGFR impairment and absence of cirrhosis. We found a significant correlation between the magnitude of HCV viral load decrease from day 0 to week 4 and a higher SOF [C] at week 4 (p = 0.032) and a higher DCV [C] at week 8 (p = 0.013). Conclusions Pharmacological monitoring showed significant associations between elevated SOF or DCV [C] and absence of cirrhosis, decreased eGFR and viral load decrease during the first month of treatment.

Published
2016

21. Intensification with pegylated interferon during treatment with tenofovir in HIV-hepatitis B virus co-infected patients

Author

Karine Lacombe, Pierre-Marie Girard, Anders Boyd, Sarah Maylin, Lionel Piroth, Fanny Lebossé, Fabrice Carrat, Caroline Lascoux-Combe, Cécile Bouix, Patrick Miailhes, Nadia Mahjoub, Marianne Maynard-Muet, Constance Delaugerre, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], 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), Agroécologie [Dijon], Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Département d'infectiologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Services d'hépatologie, Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Maladies Infectieuses et Tropicales [CHU Saint Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de santé publique [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), Service des maladies infectieuses et tropicales [Lyon], This work was supported in part by the Institut de Médecine et d’Epidémiologie Appliquée and received additional grants from ANRS (Agence Nationale de Recherche sur le Sida et les Hépatites)., Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Institut Pierre Louis d'Epidémiologie et de Santé Publique ( iPLESP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hospices Civils de Lyon ( HCL ), Centre de Recherche en Cancérologie de Lyon ( 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 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, HBsAg, medicine.medical_specialty, Cirrhosis, Tenofovir, medicine.disease_cause, Antiviral Agents, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Gastroenterology, 03 medical and health sciences, Hepatitis B, Chronic, 0302 clinical medicine, Pegylated interferon, Virology, Internal medicine, medicine, Humans, Hepatitis B e Antigens, Longitudinal Studies, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Hepatitis B virus, Hepatology, business.industry, virus diseases, Middle Aged, Hepatitis B, medicine.disease, digestive system diseases, 3. Good health, Treatment Outcome, Infectious Diseases, HBeAg, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, 030211 gastroenterology & hepatology, Interferons, business, medicine.drug
Abstract

International audience; In hepatitis B “e” antigen (HBeAg) positive patients with hepatitis B virus (HBV) mono-infection, intensification of nucleos(t)ide analogue treatment with pegylated interferon (PegIFN) could help induce higher HBeAg seroclearance rates. Our aim was to determine the long-term effect of adding PegIFN to tenofovir (TDF)-containing antiretroviral therapy on seroclearance in HBeAg-positive patients co-infected with the human immunodeficiency virus (HIV) and HBV. In this prospective matched cohort study, 46 patients with 1-year PegIFN intensification during TDF-containing antiretroviral therapy (TDF+PegIFN) were matched 1:1 to controls undergoing TDF without PegIFN (TDF) using a time-dependent propensity score based on age, CD4+ count and liver cirrhosis status. Kinetics of HBeAg quantification (qHBeAg) and hepatitis B surface antigen quantification (qHBsAg) were estimated using mixed-effect linear regression and time to HBeAg seroclearance or HBsAg seroclearance was modelled using proportional hazards regression. At baseline, previous TDF exposure was a median 39.8 months (IQR=21.4–59.4) and median qHBeAg and qHBsAg levels were 6.9 PEIU/mL and 3.72 log10IU/mL, respectively (P>.5 between groups). Median follow-up was 33.4 months (IQR=19.0–36.3). During intensification, faster average declines of qHBeAg (−0.066 vs −0.027 PEIU/mL/month, P=.001) and qHBsAg (−0.049 vs −0.026 log10IU/mL/month, P=.09) were observed in patients undergoing TDF+PegIFN vs TDF, respectively. After intensification, qHBeAg and qHBsAg decline was no different between groups (P=.7 and P=.9, respectively). Overall, no differences were observed in HBeAg seroclearance (TDF+PegIFN=13.2 vs TDF=12.6/100 person·years, P=.5) or HBsAg seroclearance rates (TDF+PegIFN=1.8 vs TDF=1.3/100 person·years, P=.7). In conclusion, PegIFN intensification in HBeAg-positive co-infected patients did not lead to increased rates of HBeAg or HBsAg clearance, despite faster declines of antigen levels while on PegIFN.

Published
2016

22. Optimizing ribavirin dosage: A new challenge to improve treatment efficacy in genotype 1 hepatitis C patients

Author

Véronique Loustaud-Ratti, Marie-Claude Gagnieu, Christian Trepo, Marianne Maynard, Gérard Babany, Françoise Stanke-Labesque, and Pierre Marquet

Subjects
medicine.medical_specialty, Genotype, Anemia, Hepacivirus, Antiviral Agents, Gastroenterology, chemistry.chemical_compound, Text mining, Internal medicine, Ribavirin, Humans, Medicine, Dose-Response Relationship, Drug, biology, business.industry, General Medicine, Hepatitis C, Hepatitis C, Chronic, medicine.disease, biology.organism_classification, Treatment efficacy, chemistry, Drug Monitoring, business
Published
2009

23. Adefovir dipivoxil is effective for the treatment of cirrhotic patients with lamivudine failure

Author

François Bailly, Françoise Monchecourt, Christian Trepo, Fabien Zoulim, Parviz Parvaz, Jean-Pierre Zarski, Yves Benhamou, Aldo Trylesinski, Patrick Marcellin, Marianne Maynard, and Michel Beaugrand

Subjects
Adult, Liver Cirrhosis, Male, Hepatitis B virus, medicine.medical_specialty, Cirrhosis, Genotype, viruses, medicine.medical_treatment, Drug Resistance, Organophosphonates, Liver transplantation, medicine.disease_cause, Gastroenterology, Cohort Studies, Hepatitis B, Chronic, Internal medicine, medicine, Adefovir, Humans, Hepatitis B e Antigens, Aged, Retrospective Studies, Hepatology, business.industry, Adenine, virus diseases, Lamivudine, Alanine Transaminase, Middle Aged, Hepatitis B, medicine.disease, Surgery, HBeAg, Female, Liver function, business, medicine.drug
Abstract

Background/Aims: Data on the efficacy of adefovir dipivoxil (ADV) in elderly and cirrhotic patients with lamivudine-resistant (LAM-R) chronic hepatitis B are scarce. This retrospective cohort study evaluated the safety and efficacy of ADV in this specific patient population. Methods: Sixty-eight cirrhotic LAM-R patients, of whom 19 (27.9%) were elderly (≥65 years of age) and nine had severe disease (two post-orthotopic liver transplantation, four pre-orthotopic liver transplantation and three decompensated), with hepatitis B virus (HBV) infection received ADV. Virological and biochemical responses to the addition of ADV were analysed. Results: At inclusion, all patients were receiving LAM; ADV was added. 75.4% of patients received a combination of LAM and ADV throughout this study for a median treatment duration of 12.6 months; the remainder received ADV with an overlap with LAM treatment for a median duration of 7.9 months. At the end of follow-up, 41.2% of patients had undetectable HBV DNA (≤2000 copies/ml) with a median reduction of 3.4 log10 copies/ml. Time to reach undetectable HBV DNA was dependent on baseline alanine aminotransferase (ALT) levels and HBeAg status. Normalization of serum ALT levels was observed in 55.2% (32/58) of patients. In patients who were HBeAg positive at baseline, HBeAg loss and seroconversion occurred in 23% (9/39) and 10% (4/39) respectively. No resistance mutations and no significant side effects were observed during the study period. Conclusion: Adefovir dipivoxil provides effective and safe treatment in cirrhotic and elderly patients who failed LAM therapy.

Published
2009

24. Increased Ribavirin Bioavailability Associated With Telaprevir Use in Hepatitis C Patients Treated With PEGylated -Interferon/Ribavirin/Telaprevir Triple Therapy

Author

Majid Amiri, François Bailly, Marie-Claude Gagnieu, Patrick Miailhes, Mathilde Leclercq, Marianne Maynard, Victor Virlogeux, Fanny Lebossé, Fabien Zoulim, Pierre Pradat, and Giorgiana Hatu

Subjects
medicine.medical_specialty, Anemia, macromolecular substances, Antiviral Agents, Gastroenterology, Telaprevir, chemistry.chemical_compound, Pegylated interferon, Internal medicine, Ribavirin, medicine, In patient, Hepatology, business.industry, Brief Report, technology, industry, and agriculture, Hepatitis C, medicine.disease, Virology, Bioavailability, Infectious Diseases, chemistry, business, Glomerular Filtration Rate, medicine.drug
Abstract

Background: Anemia is more frequent in patients receiving telaprevir with PEGylated interferon/ribavirin (PEG-IFN/RBV) than in those receiving PEG-IFN/RBV alone. Objectives: The objective was to measure the impact of telaprevir on RBV bioavailability and to assess the concomitant renal function. Materials and Methods: Thirty-seven hepatitis C virus (HCV) patients non-responders to a previous course of PEG-IFN/RBV therapy and re-treated with triple therapy combining PEG-IFN/RBV and telaprevir were analyzed. RBV bioavailability was measured before the triple therapy initiation, during telaprevir treatment at week (W) 4 and W8, and after telaprevir cessation (post W16). The renal function was assessed by estimating the glomerular filtration rate (eGFR). Results: At W4, RBV bioavailability, expressed as mg/L/daily dose/kg body weight, was significantly increased (median increase = 0.06 mg/L/dose/kg; P < 0.001). In parallel, the renal function was impaired with a mean eGFR decrease of -6.8 mL/minutes/1.73 m² (P = 0.109). Between W4 and W8, RBV bioavailability continued to increase (P < 0.001) but subsequently decreased slightly after telaprevir discontinuation with a concomitant restoration of the renal function (eGFR increase of 6.34 mL/minutes/1.73 m²). Conclusions: Our results indicated a reversible increase in RBV bioavailability after telaprevir exposure, which might be linked to the impairment of the GFR. This also suggests a RBV-telaprevir pharmacological interaction, a possible source of severe anemia observed under triple therapy. These results suggest that RBV pharmacological monitoring may be clinically relevant, especially in the context of first-generation HCV protease inhibitor-based therapy.

Published
2015

25. Anti-E1E2 antibodies do predict response to triple therapy in treatment-experienced Hepatitis C Virus-cirrhosis cases

Author

Clémence Arnaud, Fabien Zoulim, Isabelle Chemin, Marianne Maynard, Marie-Anne Petit, Victor Virlogeux, Pascale Berthillon, Pierre Pradat, Christian Trepo, Isabelle Bordes, and François Bailly

Subjects
Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Hepatitis C virus, Population, Pilot Projects, medicine.disease_cause, Gastroenterology, Antiviral Agents, Antibodies, Telaprevir, chemistry.chemical_compound, Pegylated interferon, Predictive Value of Tests, Internal medicine, Boceprevir, Medicine, Humans, Protease inhibitor (pharmacology), education, Aged, education.field_of_study, Hepatology, business.industry, Ribavirin, Hepatitis C, Chronic, Middle Aged, medicine.disease, Treatment Outcome, chemistry, Immunology, Drug Therapy, Combination, Female, business, Peptides, medicine.drug
Abstract

Summary Background and aims We previously showed that pre-treatment serum anti-E1E2 predicted hepatitis C virus (HCV) RNA viral kinetics (VKs) and treatment outcome in patients with chronic hepatitis C receiving pegylated interferon/ribavirin (Peg-IFN/RBV) double therapy. Here, we determined whether baseline anti-E1E2 was correlated with the on-treatment VK and could predict virological outcome in treatment-experienced HCV-infected cirrhotic patients receiving protease inhibitor-based triple therapy. Methods Sera from 19 patients with HCV genotype 1 infection and compensated cirrhosis who failed to respond to a prior course of Peg-IFN/RBV were selected at time 0 before starting triple therapy with boceprevir or telaprevir. We assessed patients with sustained viral response 12 weeks after the end of triple therapy (SVR12) by analyzing VKs at weeks 4, 12, 24, 36, 48 (end of treatment) and 60. Results Patients baseline characteristics were similar to the well-defined CUPIC cohort (age, HCV subtype, baseline viremia, and treatment history). Among the 19 patients, 11 achieved an SVR12. Fifteen patients were positive for pre-treatment anti-E1E2 and all of them achieved SVR12. Moreover, anti-E1E2 and SVR12 correlated with prior response to IFN/RBV therapy (relapse, partial or null response). Conclusions Baseline anti-E1E2 could be considered as a new biomarker to predict SVR12 after triple therapy in this most difficult-to-treat population. These results warrant further validation on larger cohorts including patients receiving highly effective direct-acting antivirals to explore whether this test could help in better defining treatment duration for these very costly molecules.

Published
2014

26. The predictive value of core antigen testing for the management of hepatitis C patients receiving pegylated interferon/ribavirin treatment

Author

Hans L. Tillmann, Pascale Berthillon, J.I. Esteban, Pierre Pradat, Nicolas Voirin, M. Martinot, Christian Trepo, Michael P. Manns, Maria Buti, Gaston Picchio, Patrick Marcellin, Marianne Maynard, Johannes Wiegand, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Hepacivirus, Hepatitis C virus, Viremia, Interferon alpha-2, medicine.disease_cause, Antiviral Agents, Polyethylene Glycols, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Antigen, Predictive Value of Tests, Pegylated interferon, Interferon, Virology, Ribavirin, Humans, Medicine, 030304 developmental biology, 0303 health sciences, biology, business.industry, Viral Core Proteins, Interferon-alpha, Hepatitis C, biology.organism_classification, medicine.disease, Recombinant Proteins, 3. Good health, Treatment Outcome, Infectious Diseases, chemistry, RNA, Viral, Drug Therapy, Combination, 030211 gastroenterology & hepatology, Hepatitis C Antigens, business, medicine.drug
Abstract

A new quantitative marker of HCV viremia based on the detection of the core antigen of the virus has recently become commercially available in Europe. The usefulness of this test was examined for the management of patients treated with pegylated interferon/ribavirin. One hundred twenty-eight pegylated interferon/ribavirin treated patients were studied. Serum samples were available at baseline, week 4 and week 12 time-points, respectively. Core antigen was quantified using the trak-C assay (Ortho Clinical Diagnostics, Raritan, NJ). For all genotypes at week 4, the positive and negative predictive values of HCV core antigen were 81.4 and 92.9%, respectively, while at week 12 they were 67.9 and 100%, respectively. These predictive values varied substantially according to viral genotype. Among patients with a negative core antigen level (

Published
2004

27. Evolution of hepatitis B viral load and viral genome sequence during adefovir dipivoxil therapy

Author

Stanislas Pol, Bettina Werle, C. Trepo, Marianne Maynard, Fabien Zoulim, Patrick Marcellin, and K. Cinquin

Subjects
Hepatitis B virus, Genes, Viral, Hepatitis B virus DNA polymerase, Biopsy, viruses, Molecular Sequence Data, Organophosphonates, DNA-Directed DNA Polymerase, Biology, medicine.disease_cause, Antiviral Agents, Hepatitis B virus PRE beta, law.invention, Evolution, Molecular, Double-Blind Method, law, Virology, Drug Resistance, Viral, medicine, Adefovir, Humans, Amino Acid Sequence, Hepatitis B e Antigens, Hepatitis B Antibodies, Antigens, Viral, Polymerase chain reaction, Hepatitis B Surface Antigens, Hepatology, Adenine, virus diseases, Alanine Transaminase, RNA-Directed DNA Polymerase, Sequence Analysis, DNA, Viral Load, Hepatitis B, Molecular biology, digestive system diseases, Reverse transcriptase, Viral Breakthrough, Infectious Diseases, Liver, DNA, Viral, Mutation, Viral load, medicine.drug
Abstract

Phase II and III clinical trials of adefovir dipivoxil (ADV) for the treatment of chronic hepatitis B have shown that this hepadnavirus polymerase inhibitor is well tolerated and effectively suppresses hepatitis B virus (HBV) replication. We therefore analysed the evolution of viral load and the emergence of HBV polymerase mutants in a 22-patient subgroup from a phase III clinical trial of ADV for the treatment of HBeAg-positive chronic hepatitis B. HBV DNA serum titres were quantified using a real-time polymerase chain reaction (PCR) assay with molecular hybridization probes. Emergence of polymerase mutants was assessed by direct sequencing of the viral reverse transcriptase domain after PCR amplification of HBV DNA isolated from serum. Our results indicated that ADV therapy effectively suppressed HBV replication in these patients (median serum HBV decrease at week 48 of treatment = 4.3 log10 copies/mL). The initial drop of HBV DNA titres in serum at week 12 of ADV therapy seemed to be predictive of subsequent HBe seroconversion (P = 0.059). Neither viral breakthrough nor the selection of drug resistant mutants were observed during the study period. Our results showed that ADV administration for 48-72 weeks effectively suppresses HBV replication without the emergence of resistant viral mutants.

Published
2004

29. Perspectives on therapy of hepatitis B

Author

Fabien Zoulim, Christian Trepo, and Marianne Maynard

Subjects
Hepatitis B virus, HBsAg, Virus Replication, medicine.disease_cause, medicine, Adefovir, Animals, Humans, Hepatology, Nucleoside analogue, business.industry, Lamivudine, Drug Resistance, Microbial, Genetic Therapy, Hepatitis B, medicine.disease, Virology, digestive system diseases, Genetic Techniques, HBeAg, Hepatocellular carcinoma, Mutation, Immunology, Immunotherapy, business, medicine.drug
Abstract

Despite a high rate of viral clearance by immunocompetent adults, and the availability of efficient vaccines a large proportion of the world’s population (400 million) is chronically infected with hepatitis B virus (HBV). This is due to the fact that vertical transmission of HBV in neonates leads to a chronic infection in 90% of cases. The pathology is immune-mediated. The coexistence of repeated cycles of HBV replication and immune lysis of infected hepatocytes is associated with fibrosis, cirrhosis, and hepatocellular carcinoma. There are still 250 000 deaths each year resulting from hepatitis B. Current strategies for treating hepatitis B have focused on clearance of active HBV infection through suppression of viral replication. The efficacies of these treatments have been determined by monitoring the levels of HBV DNA in serum, serum alanine aminotransferase (ALT) levels, loss of viral antigens (HBeAg and HBsAg), seroconversion (antiHBe and anti-HBs), and ultimately by improvements in liver histology. Interferon-a (IFN-a) and the nucleoside analogs (lamivudine and adefovir) have proven their effectiveness by these clinical markers and are currently approved for treatment of chronic hepatitis B. Sustained virological response rate, however, ranges between 15 and 40% [1]. The actual rate of sustained response in non selected patients is supposed to be lower. Following the introduction of IFN acting mainly through immune potentiation, the development of new antivirals that inhibit the viral polymerase has provided new hope in the therapy of chronic hepatitis B. However, due to the slow kinetics of viral clearance, longterm treatment is mandatory and unfortunately, the spontaneous genetic heterogeneity of the virus prompted drug resistant mutants selected by the treatment. It is, therefore, similar to human immunodeficiency virus (HIV), critical to develop new antiviral strategies to better combat wild-type and mutant HBV infections.

Published
2003

30. Interferon-free direct-acting antiviral therapy decreases the rate of hepatocellular carcinoma recurrence in patients with chronic hepatitis C and advanced fibrosis

Author

Marie Ecochard, Philippe Merle, Caroline Scholtes, Jean-Yves Mabrut, A.-C. Uhres, G. Ouziel, S. Radenne, S. Benmakhlouf, Christian Ducerf, Agnès Rode, Marianne Maynard, Massimo Levrero, Christophe Combet, Pierre Pradat, P. Lack, Victor Virlogeux, Fanny Lebossé, François Bailly, K. Hartig-Lavie, Fabien Zoulim, J. Koffi, and D. Poinsot

Subjects
0301 basic medicine, medicine.medical_specialty, Hepatology, business.industry, Interferon free, Antiviral therapy, medicine.disease, Gastroenterology, Advanced fibrosis, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Chronic hepatitis, Internal medicine, Hepatocellular carcinoma, Immunology, medicine, 030211 gastroenterology & hepatology, In patient, business, Direct acting
Published
2017

31. Role of a 48-week pegylated interferon therapy in hepatitis B e antigen positive HIV-co-infected patients on cART including tenofovir: EMVIPEG study

Author

Stanislas Pol, Philippe Sogni, Lionel Piroth, Cécile Bouix, Marianne Maynard-Muet, Yoann Barthe, Patrice Cacoub, Caroline Lascoux-Combe, David Rey, Fabien Zoulim, Patrick Miailhes, Fabrice Carrat, and Fanny Lebossé

Subjects
Adult, Male, medicine.medical_specialty, HBsAg, Organophosphonates, HIV Infections, medicine.disease_cause, Emtricitabine, Gastroenterology, Antiviral Agents, Deoxycytidine, Polyethylene Glycols, Hepatitis B, Chronic, Pegylated interferon, Internal medicine, Antiretroviral Therapy, Highly Active, medicine, Humans, Hepatitis B e Antigens, Seroconversion, Tenofovir, Hepatitis B virus, Drug Carriers, Hepatology, business.industry, Coinfection, Adenine, virus diseases, Lamivudine, HIV, Interferon-alpha, Middle Aged, Viral Load, digestive system diseases, Recombinant Proteins, CD4 Lymphocyte Count, Treatment Outcome, HBeAg, Immunology, Female, business, Viral load, medicine.drug
Abstract

In hepatitis B e antigen (HBeAg) positive-HIV co-infected patients treated with combined antiretroviral therapy (cART), including tenofovir disoproxil fumarate (TDF), the rate of HBe seroconversion remains low. Whether adding pegylated interferon alfa (PegIFN) could increase the likelihood of HBeAg loss and HBe seroconversion has not been assessed.A 48-week PegIFN therapy was added to HBeAg positive-HIV co-infected patients on TDF and emtricitabine, or lamivudine for at least 6 months. The primary endpoint was HBV sustained response: HBe seroconversion with undetectable HBV DNA levels 24 weeks after completing PegIFN therapy (W72).Fifty-one patients (49 men, median age 46 years, range: 32-65), were included. Median duration of HIV, HBV infections and TDF therapy was 10.3 (0.6-22), 9.8 (0.5-16), and 3.3 (0.5-6.8)years, respectively. Median baseline CD4 count was 506 (175-1316)/mm(3). HIV viral load was50 copies/ml in 49 (96%) patients. Nine (18%) patients stopped PegIFN prematurely. Ten (20%) patients experienced HBeAg loss at W72 and four (8%) patients had a HBV sustained response. No HBs seroconversion was observed. Only patients with more than 350 CD4/mm(3) at baseline achieved HBe loss. HBeAg level10 PEIU/ml at W12 or a quantitative HBsAg decline0.5 log IU/ml at W24 had 100% and 84% negative predictive values for response, respectively.48-week PegIFN additional therapy to cART including TDF did not significantly increase the HBe seroconversion rate, despite an HBeAg loss in 20% of the patients. HBe and HBs kinetics may nevertheless be of help in tailoring and optimising this strategy.

Published
2014

32. Promoting older ethnic minorities health behaviors: Primary and secondary prevention considerations

Author

Marianne Maynard

Subjects
Self care management, Secondary prevention, medicine.medical_specialty, business.industry, Public health, Public Health, Environmental and Occupational Health, Ethnic group, Health psychology, Health promotion, Nursing, Health care, medicine, business, Health policy
Abstract

This article examines elderly ethnic minorities health care utilization patterns and health behaviors and their need for primary and secondary preventive care. Assessment issues are discussed along with ways to involve minority clients in identifying resources that could promote their own self care management. Suggestions are also made on ways health care practitioners can encourage minority clients to be active team players in our health care system.

Published
2013

33. Ribavirin in combination therapy for HCV chronic infection in HIV patients: How to win the war after winning the first battle?

Author

Marie-Claude Gagnieu, Claude Souvignet, Christian Trepo, and Marianne Maynard

Subjects
medicine.medical_specialty, Battle, Hepatology, Combination therapy, business.industry, media_common.quotation_subject, Ribavirin, Virology, chemistry.chemical_compound, Chronic infection, Spanish Civil War, chemistry, Internal medicine, Hiv patients, medicine, business, media_common
Published
2007

34. P0137 : Safety of boceprevir-based triple therapy in HCV cirrhotic patients awaiting liver transplantation. Analysis from a French multicenter, open-label study (ANRS HC29 bocepretransplant)

Author

Christophe Duvoux, Hélène Fontaine, G.-P. Pageaux, François Durand, C. Willems, Danielle Botta-Fridlund, Jean Charles Duclos-Vallée, Didier Samuel, Sophie Metivier, F. Beaulieux, Valérie Canva, Vincent Leroy, Fabio Conti, Pascal Lebray, C. Bouix, C. Paul, Rodolphe Anty, Louis d’Alteroche, Ventzislava Petrov-Sanchez, Pierre Pradat, Laurent Alric, and Marianne Maynard-Muet

Subjects
medicine.medical_specialty, chemistry.chemical_compound, Hepatology, Open label study, chemistry, business.industry, Internal medicine, medicine.medical_treatment, Boceprevir, medicine, Liver transplantation, business, Gastroenterology
Published
2015

35. Tenoxicam, a non-steroid anti-inflammatory drug, is unable to increase the response rate in patients with chronic hepatitis C treated by alpha interferon

Author

Frédéric Oberti, Solange Bresson-Hadni, Yannick Bacq, Armand Abergel, Maryline Baud, Jean-Marc Combis, François Bailly, Raphaëlle Barnoud, J.-J. Raabe, Vincent Leroy, Albert Tran, Anne Minello, Xavier Causse, Marianne Maynard-Muet, Jean-Pierre Zarski, Tariq Hicham, Suzanne Chousterman, Lynda Hamici, and Marie‐France St Marc Girardin

Subjects
Adult, Male, medicine.medical_specialty, Hepatitis C virus, Alpha interferon, Interferon alpha-2, medicine.disease_cause, Placebo, Gastroenterology, Piroxicam, Double-Blind Method, Tenoxicam, Internal medicine, 2',5'-Oligoadenylate Synthetase, medicine, Humans, Adverse effect, Interferon alfa, Hepatology, medicine.diagnostic_test, business.industry, Anti-Inflammatory Agents, Non-Steroidal, Interferon-alpha, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, Recombinant Proteins, Surgery, Liver biopsy, Drug Therapy, Combination, Female, business, medicine.drug
Abstract

The purpose of this study is to compare a combination of interferon (IFN)-alpha2a (Roferon) + Tenoxicam with IFN-alpha2a alone in the treatment of chronic hepatitis C. This prospective, randomized double-blind study included 149 patients, all of whom were diagnosed with active chronic hepatitis C but non-cirrhotic (ALT > or = 1.5 upper limit of normal, anti-hepatitis C virus (HCV) positive by enzyme-linked immunosorbant assay2 and RIBA3). The patients were randomized in two groups, as follows: G1 (n = 76): IFNalpha2a 3 million units times per week during 6 months + placebo; and G2 (n = 73): IFNalpha2a 3 million units three times per week + Tenoxicam (20 mg/day) during 6 months. Alanine aminotransferase (ALT) and HCV RNA were determined before and at months 6 and 12 of treatment. 2'5' oligoadenylate synthetase activity (2'5' AS) was dosed in mononuclear cells before and at 3-month treatment intervals in 28 patients. Liver biopsy was performed before and 6 months after the end of therapy. Parameters were similar before therapy for both groups. Biochemical and virological responses were similar for both groups at month 6 (49.3% vs. 42.9% and 43.3% vs. 38.3%, respectively) and month 12 (28.3% vs. 23.8% and 17.2% vs. 17.5%, respectively). HCV RNA level significantly decreased in both groups at month 6, with no difference whatever the therapy; however, the HCV RNA level returned to initial values at month 12 and was the only significant prognostic factor of a sustained response. No peak of 2'5' AS activity was observed during treatment in patients with dual therapy. A histological improvement was also noted in both groups without difference, regardless of therapy. The percentage of adverse events was identical for both groups. Paracetamol intake, assessed in 80 patients, was 49.1 g per 6 months in the G1 group and 22.5 g per 6 months in the G2 group (not significant). In conclusion, the non-steroid anti-inflammatory drug, Tenoxicam, does not increase IFNalpha efficacy in the treatment of chronic hepatitis C. This combination is well tolerated and partially lowers Paracetamol intake, but not preexisting alpha-IFN adverse events.

Published
1998

36. Life Satisfaction and Level of Activity of Male Elderly in Institutional and Community Settings

Author

Marianne Maynard, David H. Mise, and M. Jeanne Madigan

Subjects
Gerontology, business.industry, Human factors and ergonomics, Life satisfaction, Poison control, Human Males, medicine.disease, Health Professions (miscellaneous), Suicide prevention, Occupational safety and health, Scale (social sciences), Injury prevention, medicine, Medical emergency, Geriatrics and Gerontology, business
Abstract

This study examined the relationship between purposeful activity and life satisfaction of elderly males from five different living settings. Their participation in the study included the completion of a modified version of the Elders Interest Activity Scale, the Life Satisfaction Index-Z and a form eliciting basic demographic information. Findings revealed that subjects in the five environments had similar levels of life satisfaction; differences, however, were found in the present level of activity participation among the sample groups. Results indicated a significant positive but weak correlation between purposeful activity and life satisfaction.

Published
1996

37. Health and Well-Being Ratings of African American Adults with Sickle Cell Disease

Author

Marianne Maynard, Laura D. Martin, and Florence Neal-Smith

Subjects
Gerontology, Occupational therapy, Chronic condition, medicine.medical_specialty, business.industry, Self, MEDLINE, General Medicine, Disease, Occupational Therapy, Intervention (counseling), Scale (social sciences), Well-being, Medicine, business
Abstract

This paper examines Sickle Cell Disease (SCD), a chronic condition affecting predominantly individuals of African decent. The study describes the health and ratings of Adult African Americans with SCD using a Self-Evaluation of Life Function Scale. The majority of the respondents scored in the favorable range on the SELF scales suggesting good adaptation to their condition. Based on respondents comments more information and support would be beneficial, especially supportive counseling, occupational therapy intervention, and instruction to aid in self care management and job issues.

Published
1996

38. Assistive Device Use Among the Elderly

Author

Marianne Maynard, Leslie Houde, Amy Elsner Erickson, Janet Hawkins Watts, and Erin Wilson

Subjects
Gerontology, business.industry, Rehabilitation, Weak correlation, Occupational Therapy, Spouse, Activity limitation, Secondary analysis, National Health Interview Survey, Medicine, Geriatrics and Gerontology, Assistive device, business
Abstract

This study used data files from the National Health Interview Survey (NHIS), 1990: Assistive Devices Supplement sample of 117,042 adults from the 50 states and the District of Columbia. A subsample of 3,297 persons aged 65 years and older was selected on which to perform secondary analysis on the association of self-reported health status, activity limitation, total number of devices reported, and demographic variables. Twenty-three percent of persons aged 65 and older reported any assistive device. Black respondents reported more activity limitations than respondents from other races, but there was no relationship among race and total devices reported. Greater percentages of women than men have more activity limitations as well as report more than one device. Persons not living with a spouse reported more than one device. Reports of a higher total number of devices correlated with poorer health status and greater activity limitations. A weak correlation was found between higher total number of devices re...

Published
1996

39. A poxvirus vaccine is safe, induces T-cell responses, and decreases viral load in patients with chronic hepatitis C

Author

Christine Bain, Jean-Pierre Bronowicki, Jean Yves Bonnefoy, Géraldine Honnet, Jean Marc Limacher, François Habersetzer, Christian Trepo, Michel Doffoel, Marianne Maynard–Muet, Martine Baudin, Myew–Ling Toh, Thomas F. Baumert, Cyrille Feray, Vincent Leroy, Delphine Agathon, Geneviève Inchauspé, Jean-Pierre Zarski, Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, Immunothérapie des maladies infectieuses chroniques (IMIC), BIOMERIEUX-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Laboratoire d'Énergétique Moléculaire et Macroscopique, Combustion (EM2C), Université Paris Saclay (COmUE)-Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec, 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 des Maladies de l'Appareil Digestif, Université de Nantes (UN), Plate-forme de R&D - Puces à Cellules Transfectées (PCT), Cancéropôle du Grand-Est (CGE)-Centre Européen de Biologie et de Génomique Structurale (CEBGS), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Equipe 16, IFR Laennec (IL), Institut National de la Recherche Agronomique (INRA)-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)-Institut National de la Recherche Agronomique (INRA)-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)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), transgene, Transgene, Hôpital pasteur [Colmar], Scanella, Marie-Pierre, CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université Paris Saclay (COmUE), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Cancéropôle du Grand-Est (CGE)-Centre Européen de Biologie et de Génomique Structurale (CEBGS)-Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 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)-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)-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes (UGA)-CHU Grenoble, and 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 Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, MESH: Poxviridae, Modified vaccinia Ankara, T-Lymphocytes, Hepacivirus, Viral Nonstructural Proteins, Antibodies, Viral, medicine.disease_cause, MESH: Dose-Response Relationship, Drug, MESH: Genotype, chemistry.chemical_compound, 0302 clinical medicine, Interferon, MESH: Hepacivirus, 0303 health sciences, MESH: Middle Aged, Immunogenicity, Gastroenterology, Hepatitis C, Middle Aged, Viral Load, 3. Good health, MESH: Hepatitis C, Chronic, MESH: RNA, Viral, RNA, Viral, Female, 030211 gastroenterology & hepatology, MESH: Viral Load, Viral load, medicine.drug, Adult, Genotype, MESH: Interferon-gamma, Hepatitis C virus, [SDV.CAN]Life Sciences [q-bio]/Cancer, Interferon-gamma, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH: Viral Vaccines, medicine, Humans, Adverse effect, NS5B, 030304 developmental biology, MESH: Humans, Dose-Response Relationship, Drug, Hepatology, business.industry, Poxviridae, Viral Vaccines, MESH: Adult, Hepatitis C, Chronic, medicine.disease, MESH: Male, MESH: T-Lymphocytes, chemistry, Immunology, MESH: Viral Nonstructural Proteins, business, MESH: Female, MESH: Antibodies, Viral
Abstract

International audience; BACKGROUND & AIMS: Therapy for chronic hepatitis C (CHC) has limited efficacy, adverse effects, and high costs. Cohort and vaccine-based preclinical studies have indicated the importance of T-cell-based immunity in controlling viral infection. TG4040 is a recombinant poxvirus vaccine that expresses the hepatitis C virus (HCV) proteins NS3, NS4, and NS5B. We performed a phase I clinical trial to assess the safety, immunogenicity, and early antiviral efficacy of TG4040 in patients with CHC. METHODS: In an open-label, dose-escalating study, patients with mild CHC (genotype 1) were assigned to 3 groups of 3 patients each; they received subcutaneous injections of 10⁶, 10⁷, or 10⁸ plaque-forming units of TG4040 on study days 1, 8, and 15. Six additional patients were given the highest dose of vaccine (10⁸ plaque-forming units). Patients were followed for 6 months after the last injection. T-cell-based and antibody responses and levels of HCV RNA were measured. RESULTS: All 3 doses of TG4040 were well tolerated, without serious adverse events. Vaccine-induced HCV-specific cellular immune responses were observed in 5 of the 15 patients (33%). A transient decrease in circulating levels of HCV RNA, from -0.52 log₁₀ to -1.24 log₁₀, was observed in 8 patients; in 5 patients, the lowest level of HCV RNA was observed on day 37, after the first injection. The most pronounced decrease in viral load occurred in 2 patients, who also had marked vaccine-induced T-cell responses. CONCLUSIONS: In patients with CHC, the viral-vector-based vaccine TG4040 had a good safety profile, induced HCV-specific cellular immune responses, and reduced viral load. This vaccine should be investigated in further clinical studies, in combination with standard of care.

Published
2011

40. A randomized controlled trial of high-dose ursodesoxycholic acid for nonalcoholic steatohepatitis

Author

Marc Riviere, Victor de Ledinghen, Dominique Larrey, Marianne Maynard, Claire Wartelle-Bladou, Vlad Ratziu, Jean-Philippe Bastard, Christophe Renou, Lawrence Serfaty, Jean Spénard, Dominique Bonnefont-Rousselot, Frédéric Oberti, Philippe Mathurin, Philippe Sogni, 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), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Département d'hépato-gastroentérologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d'Hépato-gastroentérologie, Hôpital Huriez-Université de Lille, Hepatology, Hopital, Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hépato-gastro-enterologie, Hospices Civils de Lyon (HCL), Service d'hépatologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Service d'hépatologie [Saint-Antoine], 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)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Biochimie Métabolique [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), FRESGUN, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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 ), Laboratoire HIFIH, PRES Université Nantes Angers Le Mans ( UNAM ) -IFR132-UPRES 3859, Centre Hospitalier Universitaire d'Angers ( CHU Angers ), PRES Université Nantes Angers Le Mans ( UNAM ) -PRES Université Nantes Angers Le Mans ( UNAM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Hospices Civils de Lyon ( HCL ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -CHU Saint-Eloi, CHU Saint-Antoine [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP)-Université Pierre et Marie Curie - Paris 6 ( UPMC ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP]

Subjects
Blood Glucose, Male, Pathology, Cholagogues and Choleretics, Steatosis, MESH : Fatty Liver, MESH : Insulin, MESH : Cholagogues and Choleretics, MESH : Dose-Response Relationship, Drug, Aminotransferases, Gastroenterology, law.invention, MESH: Dose-Response Relationship, Drug, Liver disease, 0302 clinical medicine, Randomized controlled trial, law, Non-alcoholic Fatty Liver Disease, Nonalcoholic fatty liver disease, Insulin, MESH : Female, MESH : Hemoglobin A, Glycosylated, MESH: Cholagogues and Choleretics, MESH: Fatty Liver, MESH: Treatment Outcome, 0303 health sciences, education.field_of_study, MESH: Middle Aged, Ursodeoxycholic Acid, MESH: Follow-Up Studies, MESH : Adult, Middle Aged, Ursodeoxycholic acid, 3. Good health, MESH: Insulin Resistance, Treatment Outcome, Tolerability, MESH : Ursodeoxycholic Acid, MESH: Hemoglobin A, Glycosylated, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 030211 gastroenterology & hepatology, Female, Randomized clinical trials, MESH : Insulin Resistance, medicine.drug, Adult, medicine.medical_specialty, MESH : Male, Population, MESH : Treatment Outcome, MESH: Insulin, Placebo, 03 medical and health sciences, Internal medicine, Multicenter trial, medicine, Humans, MESH : Middle Aged, Nonalcoholic steatohepatitis, education, 030304 developmental biology, Glycated Hemoglobin, MESH: Humans, Hepatology, Dose-Response Relationship, Drug, business.industry, MESH : Humans, MESH : Follow-Up Studies, Insulin resistance, MESH: Adult, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH : Blood Glucose, medicine.disease, Fibrosis, MESH: Male, Fatty Liver, MESH: Blood Glucose, business, MESH: Ursodeoxycholic Acid, MESH: Female, Follow-Up Studies
Abstract

International audience; BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is a prevalent liver disease associated with increased morbidity and mortality. Ursodeoxycholic acid (UDCA) may have antioxidant, anti-inflammatory, and antifibrotic properties and may reduce liver injury in NASH. To date, no studies have assessed the efficacy and safety of high-dose UDCA (HD-UDCA) in patients with NASH. METHODS: We conducted a 12-month, randomized, double-blind, placebo-controlled multicenter trial to evaluate the efficacy and safety of HD-UDCA (28-35 mg/kg per day) in 126 patients with biopsy-proven NASH and elevated alanine aminotransferase (ALT) levels. The primary study end point was reduction in ALT levels from baseline in patients treated with HD-UDCA compared with placebo. Secondary study end points were the proportion of patients with ALT normalization, relative reduction in the scores of serum markers of fibrosis and hepatic inflammation, and safety and tolerability. RESULTS: HD-UDCA significantly reduced mean ALT levels -28.3% from baseline after 12 months compared with -1.6% with placebo (p

Published
2011

41. A Comparison of Female Professionals' Role Profiles With Occupational Adjustment and Life Satisfaction

Author

Marianne Maynard

Subjects
Organizational Behavior and Human Resource Management, Health personnel, Work (electrical), Female health, Applied psychology, Exploratory research, Life satisfaction, Role perception, Psychology, General Psychology, Applied Psychology, Work environment, Clinical psychology
Abstract

This exploratory study on 50 female health professionals examined the impact that multiple roles (work/family) had on occupational adjustment and life satisfaction. Results indicate some evidence that as the number of occupational roles increased, life satisfaction scores tended to decrease; however, as the number of family roles increased, scores on occupational adjustment and life satisfaction scales tended to increase.

Published
1993

42. ROM Dance Program Effects on Frail Elderly Women in an Adult Day-Care Center

Author

Marianne Maynard, Sheila Z. Selznick, and Margaret A. Valentine-Garzon

Subjects
Gerontology, medicine.medical_specialty, Activities of daily living, Dance, media_common.quotation_subject, Rehabilitation, Self-esteem, humanities, Occupational therapy treatment, Occupational Therapy, Day care center, Physical therapy, medicine, Frail elderly, Geriatrics and Gerontology, Range of motion, Psychology, media_common
Abstract

The purpose of this study was to determine if the Range of Motion (ROM) Dance Program, created by Harlowe and Yu (1984), when used as part of an occupational therapy treatment program, has an effect on chronically ill elderly patients' ROM, self-esteem, and participation in activities of daily living (ADL). Seventeen frail, elderly female individuals participated in this four-week study as either an experimental or control group member. Participants' age ranged from 64 to 85 and all had various impairments or conditions associated with aging. This research study compared the participant's pre-program scores to their post-program scores on ROM, self esteem, and ADL's participation. Analysis of the pre-program and initial post-program mean score variances failed to reveal any significant differences between experimental and control groups, in the ADL, self-esteem, or ROM variables. In addition, evaluation of one-month follow-up mean score variances also were not significantly different. These results appear...

Published
1993

43. Association of anti-E1E2 antibodies with spontaneous recovery or sustained viral response to therapy in patients infected with hepatitis C virus

Author

Pierre Pradat, Isabelle Bordes, Claude Vieux, Fabien Zoulim, Christian Trepo, Françoise Berby, Marianne Maynard, Pascale Berthillon, Ndiémé Ndongo, and Marie-Anne Petit

Subjects
medicine.drug_class, Hepatitis C virus, Hepacivirus, Immunoglobulins, medicine.disease_cause, Monoclonal antibody, Antibodies, Viral, Antiviral Agents, Virus, chemistry.chemical_compound, Epitopes, Pegylated interferon, Seroepidemiologic Studies, medicine, Humans, Longitudinal Studies, Hepatology, biology, business.industry, Ribavirin, Antibodies, Monoclonal, Reproducibility of Results, Hepatitis C, biology.organism_classification, medicine.disease, Virology, Antibodies, Anti-Idiotypic, Treatment Outcome, chemistry, Immunology, biology.protein, Antibody, business, Peptides, medicine.drug, Follow-Up Studies
Abstract

The monoclonal antibody (mAb) D32.10 recognizes a discontinuous epitope encompassing three regions E1 (amino acids 297-306), E2A (amino acids 480-494), and E2B (amino acids 613-621) juxtaposed on the surface of serum-derived hepatitis C virus (HCV) particles (HCVsp). The mAb D32.10 inhibits efficiently and specifically the binding of HCVsp to human hepatocytes. Therefore, we investigated the clinical relevance of anti-E1E2A,B response in the serum of patients infected with HCV. To this end, an enzyme-linked immunosorbent assay (ELISA) using synthetic E1-, E2A-, and E2B-derived peptides was used. The ELISA was validated in terms of sensitivity, specificity, and test efficiency. The detection of the anti-E1E2 D32.10 epitope-binding antibodies during natural HCV infection in more than 300 HCV-positive sera demonstrated significantly (P < 0.001) higher prevalence of these antibodies: (1) in patients who spontaneously cured HCV infection (46 of 52, 88.5%) showing high titers (70% ≥ 1/1000) compared to never-treated patients with chronic hepatitis C (7 of 50, 14%) who actively replicated the virus, and (2) in complete responders (20 of 52, 38.5%) who cleared virus following treatment and achieved a sustained viral response compared to nonresponders (4 of 40, 10%). Serum anti-E1E2 antibodies were monitored before, during, and after the current standard-of-care therapy (pegylated interferon plus ribavirin) in responder and nonresponder patients. Optimal cutoff values were assessed by receiver operating characteristic curve analysis. One month prior to therapy initiation, the threshold of 1131 (optical density × 1000) gave 100% and 86% positive and negative predictive values, respectively, for achieving or not achieving a sustained viral response. Conclusion: The anti-E1E2 D32.10 epitope-binding antibodies are associated with control of HCV infection and may represent a new relevant prognostic marker in serum. This unique D32.10 mAb may also have immunotherapeutic potential. (HEPATOLOGY 2010)

Published
2010

45. Prediction of sustained virological response by ribavirin plasma concentration at week 4 of therapy in hepatitis C virus genotype 1 patients

Author

Marie-Claude Gagnieu, Christian Trepo, Marianne Maynard, Pierre Pradat, and Claude Souvignet

Subjects
Adult, Male, Time Factors, Genotype, Hepatitis C virus, Hepacivirus, Interferon alpha-2, medicine.disease_cause, Antiviral Agents, Sensitivity and Specificity, Virus, Polyethylene Glycols, chemistry.chemical_compound, Flaviviridae, Plasma, Interferon, Predictive Value of Tests, Ribavirin, Medicine, Humans, Pharmacology (medical), Chromatography, High Pressure Liquid, Aged, Pharmacology, biology, business.industry, Standard treatment, virus diseases, Interferon-alpha, Middle Aged, biology.organism_classification, Virology, Hepatitis C, digestive system diseases, Recombinant Proteins, Infectious Diseases, Logistic Models, Treatment Outcome, chemistry, ROC Curve, Multivariate Analysis, Drug Therapy, Combination, Female, Viral disease, Drug Monitoring, business, medicine.drug
Abstract

Background Pegylated interferon/ribavirin combination is currently the standard treatment for chronic hepatitis C virus (HCV) infection. Body weight adjustment of ribavirin is crucial for response. However, previous studies found no relation between ingested dose and plasma concentration. The aim of this study was to define the ribavirin trough plasma concentration at week 4 (W4) associated with sustained virological response (SVR). Methods Thirty-one HCV genotype 1 patients (8 naive and 23 non-responders to a previous pegylated interferon/ribavirin therapy) were treated with pegylated interferon/ribavirin and assessed by HPLC for ribavirin plasma concentration at W4. Results Eleven patients (35%) achieved SVR, whereas 20 (65%) were non-responders. The median ribavirin plasma concentration at W4 (1.90 mg/l) varied from 1.62 mg/l in patients with subsequent non-response to 2.28 mg/l in sustained responders ( P=0.007). Receiver operating characteristic curve analysis indicated that the 2.01 mg/l threshold gave the best sensitivity and specificity (73% and 80%, respectively, area under the curve=0.80; P=0.007). Sixty-seven percent of patients with median ribavirin plasma concentration >2 mg/l achieved SVR versus only 16% below this level ( P=0.007). Multivariate regression analysis indicated that a ribavirin plasma concentration >2 mg/l at W4 was associated with SVR independent of gender, age, weight, baseline viral load and response to previous therapy. Conclusion These results, which remain to be confirmed in large clinical trials, highlight the potential relevance of ribavirin plasma level monitoring at an early stage of treatment. This monitoring could be of help in guiding antiviral therapy by offering dose adjustment in patients with ribavirin plasma level below the 2 mg/l threshold.

Published
2008

46. Take Charge Of Your Thoughts : Create Your Ideal Life

Author

Marianne Maynard and Marianne Maynard

Abstract

You are your thoughts -- you create your life. In author Marianne Maynard's powerful book, Take Charge of Your Thought--Create Your Ideal Life, you will learn how to take control of your life through examination of your highest ideals to achieve limitless success. Through an innovative step-by-step process, Maynard outlines how to focus your thoughts in order to enhance the quality of your life and accomplish your goals -- however grand they may seem to you. You'll learn how to become conscious of your thought process and how those processes have everything to do with where you are at this point in your life. The steps include using auto-suggestions and affirmations, believing in your dreams, and respecting your body as a temple by choosing a healthy physical and spiritual lifestyle. Incorporating the steps suggested in the book will enable you to express your highest ideals and live a prosperous and harmonious life Take the first step -- this book will become a personal and precious instrument guiding you to your own unique destiny.

Published
2010

47. Addressing Health Maintenance Needs of Minority Elders in a Senior Housing Unit

Author

Marianne Maynard

Subjects
Public housing, business.industry, Poison control, Health Professions (miscellaneous), Suicide prevention, Occupational safety and health, Unit (housing), Health promotion, Nursing, Injury prevention, Medicine, Health education, Geriatrics and Gerontology, business, Gerontology
Abstract

Extending the health education model to residential living apartments forseniors can provide a vital link in the continu- ity of care for the frail elderly. This paper describes a prevention model to promote health and reduce stress for residents rn a senior public housing unit. The assessment measurements, program con- tent and results are discussed alon with suggestions for conducting health promotion programs for el f ers.

Published
1990

48. Exploring Adult Day Care Participants' Responses to Psychosocial Stressors

Author

Otr, Marianne Maynard, and Faota

Subjects
Gerontology, Stress management, Stressor, Public Health, Environmental and Occupational Health, Day care, Stress level, Psychiatry and Mental health, Intervention (counseling), Psychosocial stress, Frail elderly, Psychology, Psychosocial, Applied Psychology, Clinical psychology
Abstract

To what degree is psychosocial stress present in the frail elderly and how effective are stress management procedures with this group? This quasi-experimental study explored this question with a group of 15 adult day care participants. Results showed that both experimental and control group participants scored in the low to moderate stress level range and that generally the 4 week intervention for the experimental group had limited effect on further reducing stress levels. Several demographic variables did show moderate to high correlations with health variable in the study. The paper describes measurements used, limitations and encourages further research in this area.

Published
1990

49. Amantadine triple therapy for non-responder hepatitis C patients. Clues for controversies (ANRS HC 03 BITRI)

Author

Marianne Maynard, Pierre Pradat, François Bailly, Frédéric Rozier, Chantal Nemoz, Si Nafa Si Ahmed, Patrice Adeleine, Christian Trépo, and and a French Multicenter Group

Subjects
Adult, Male, medicine.medical_specialty, Hepatitis C virus, Biopsy, Hepacivirus, Interferon alpha-2, Placebo, medicine.disease_cause, Gastroenterology, Antiviral Agents, Polyethylene Glycols, chemistry.chemical_compound, Double-Blind Method, Interferon, Pegylated interferon, Internal medicine, Ribavirin, medicine, Amantadine, Humans, Prospective Studies, Aged, Hepatology, business.industry, Interferon-alpha, Hepatitis C, Middle Aged, medicine.disease, Recombinant Proteins, Regimen, Treatment Outcome, chemistry, Immunology, RNA, Viral, Drug Therapy, Combination, Female, business, medicine.drug, Follow-Up Studies
Abstract

Background/Aims To determine whether addition of amantadine to pegylated interferon/ribavirin improved response rates among chronic hepatitis C patients, non-responders to interferon/ribavirin and study the dynamic of response. Methods In a double blind, multicenter, randomized trial, 200 non-responder patients received pegylated interferon 1.5μg/kg per week and ribavirin 800–1200mg/day, plus either amantadine 200mg/day or placebo for 48 weeks. Endpoints were virological responses, ALT normalization, and histological benefit overtime. Results Twenty percent of all patients achieved a sustained virological response (SVR). This rate was 8% higher in the triple therapy group (24%) compared with the double therapy group (16%) ( P =0.22). A better virological response rate at week 24 was observed in the triple regimen group (43 vs 29%; P =0.06), which was lost at week 48 suggesting viral escape. The biochemical response rate was also significantly higher with triple therapy at week 12 (63 vs 49%; P =0.05) and week 24 (64 vs 49%; P =0.03). Fibrosis stabilized or improved in 77% of all patients. Conclusions Re-treatment of interferon/ribavirin non-responder patients should be encouraged since a substantial proportion benefits from re-treatment with pegylated interferon/ribavirin ± amantadine. In triple therapy involving amantadine, a time wise response and an increased SVR rate in subgroups less prone to viral breakthrough suggest clues for existing controversies.

Published
2005

50. Sustained HBs seroconversion during lamivudine and adefovir dipivoxil combination therapy for lamivudine failure

Author

Christian Trepo, Philippe Chevallier, Muriel Lot, Parviz Parvaz, Marianne Maynard, Sandra Durantel, Fabien Zoulim, Michèle Chevallier, Department of Hepatogastroenterology, Hospices Civils de Lyon (HCL), Virology Laboratory, Virus des hépatites et pathologies associées, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathology Laboratory, Laboratoire Marcel Merieux, and Zoulim, Fabien

Subjects
Adult, Male, HBsAg, Organophosphonates, medicine.disease_cause, Polymerase Chain Reaction, viral persistence, Hepatitis B, Chronic, antivirals, medicine, Adefovir, Humans, Treatment Failure, Seroconversion, Hepatitis B virus, Hepatitis B Surface Antigens, drug resistance, Hepatology, Reverse-transcriptase inhibitor, biology, Adenine, virus diseases, Lamivudine, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, cccDNA, biology.organism_classification, Virology, digestive system diseases, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepadnaviridae, DNA, Viral, Drug Therapy, Combination, chronic hepatitis, hepatitis B virus, medicine.drug
Abstract

We describe the case of a patient with chronic hepatitis B who became resistant to lamivudine and was treated successfully with adefovir dipivoxil in addition to lamivudine. Lamivudine resistance was associated with the selection of a L180M+M204V polymerase mutant. After the addition of adefovir dipivoxil, serum HBV DNA levels dropped by more than 4log(10), which was followed by HBsAg clearance after 22 months of combination therapy. Moreover, anti-HBs antibody titers rose above 1000 mIU/mL after 32 months of the new treatment regimen. In parallel, HBV DNA declined below 100 copies/mL by a quantitative real time PCR assay. Analysis of intrahepatic viral DNA showed a significant decline of total HBV DNA and cccDNA which was accompanied by a decrease of the number of infected cells expressing viral antigens below the detection limit of immunostaining. In parallel, liver histology analysis showed an improvement in both the activity index and fibrosis score. This report suggests that in patients who previously failed lamivudine therapy, proactive antiviral treatment may lead to a beneficial virological and clinical effect.

Published
2005

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