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1. Including Ratio of Platelets to Liver Stiffness Improves Accuracy of Screening for Esophageal Varices That Require Treatment

Author

Arthur Berger, Federico Ravaioli, Oana Farcau, Davide Festi, Horia Stefanescu, François Buisson, Pierre Nahon, Christophe Bureau, Nathalie Ganne-Carriè, Annalisa Berzigotti, Victor de Ledinghen, Salvatore Petta, Paul Calès, Sylvie Sacher Huvelin, Dominique Valla, Anne Olivier, Frédéric Oberti, Jérôme Boursier, Jean Paul Galmiche, Jean Pierre Vinel, Clotilde Duburque, Alain Attar, Isabelle Archambeaud, Robert Benamouzig, Marianne Gaudric, Dominique Luet, Patrice Couzigou, Lucie Planche, Emmanuel Coron, Jean-Baptiste Hiriart, Faiza Chermak, Maude Charbonnier, Patrick Marcellin, Dominique Guyader, Stanislas Pol, Hélène Fontaine, Dominique Larrey, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Jean-Pierre Zarski, Vincent Leroy, Ghassan Riachi, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Sebastien Dharancy, Jean-Frédéric Blanc, Armand Abergel, Lawrence Serfaty, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Yannick Bacq, Claire Wartelle, Thông Dao, Yves Benhamou, Christophe Pilette, Christine Silvain, Christos Christidis, Dominique Capron, Gérard Thiefin, Sophie Hillaire, Vincent Di Martino, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Regional Institute of Gastroenterology and Hepatology [Cluj-Napoca], Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 de Paris (UP), Université Paris 13 (UP13), Hôpital Cochin [AP-HP], Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Institutional support was provided by Programme hospitalier de recherche Clinique and agence nationale de recherches sur le sida et les hépatites virales, who had no other role in the present study., 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), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Berger A., Ravaioli F., Farcau O., Festi D., Stefanescu H., Buisson F., Nahon P., Bureau C., Ganne-Carrie N., Berzigotti A., de Ledinghen V., Petta S., Cales P., Huvelin S.S., Valla D., Olivier A., Oberti F., Boursier J., Galmiche J.P., Vinel J.P., Duburque C., Attar A., Archambeaud I., Benamouzig R., Gaudric M., Luet D., Couzigou P., Planche L., Coron E., Hiriart J.-B., Chermak F., Charbonnier M., Marcellin P., Guyader D., Pol S., Fontaine H., Larrey D., De Ledinghen V., Ouzan D., Zoulim F., Roulot D., Tran A., Bronowicki J.-P., Zarski J.-P., Leroy V., Riachi G., Peron J.-M., Alric L., Bourliere M., Mathurin P., Dharancy S., Blanc J.-F., Abergel A., Serfaty L., Mallat A., Grange J.-D., Attali P., Bacq Y., Wartelle C., Dao T., Benhamou Y., Pilette C., Silvain C., Christidis C., Capron D., Thiefin G., Hillaire S., and Di Martino V.

Subjects
Blood Platelets, Liver Cirrhosis, Noninvasive Diagnosis, medicine.medical_specialty, Cirrhosis, [SDV]Life Sciences [q-bio], Population, Esophageal and Gastric Varices, Chronic liver disease, Severity of Illness Index, Gastroenterology, End Stage Liver Disease, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Model for End-Stage Liver Disease, Esophageal varices, Internal medicine, Nonalcoholic fatty liver disease, medicine, Humans, education, Baveno VI Criteria, Retrospective Studies, education.field_of_study, Hepatology, business.industry, Retrospective cohort study, Portal Hypertension, medicine.disease, 3. Good health, MELD, 030220 oncology & carcinogenesis, Elasticity Imaging Techniques, 030211 gastroenterology & hepatology, business, Baveno VI Criteria, Blood Platelets, Cirrhosis, Elasticity Imaging Techniques, End Stage Liver Disease, Esophageal and Gastric Varices, Humans, Liver Cirrhosis, MELD, Noninvasive Diagnosis, Portal Hypertension, Retrospective Studies, Severity of Illness, Index
Abstract

International audience; Background & aims: Based on platelets and liver stiffness measurements, the Baveno VI criteria (B6C), the expanded B6C (EB6C), and the ANTICIPATE score can be used to rule out varices needing treatment (VNT) in patients with compensated chronic liver disease. We aimed to improve these tests by including data on the ratio of platelets to liver stiffness.Methods: In a retrospective analysis of data from 10 study populations, collected from 2004 through 2018, we randomly assigned data from 2368 patients with chronic liver disease of different etiologies to a derivation population (n = 1579; 15.1% with VNT, 50.2% with viral hepatitis, 28.9% with nonalcoholic fatty liver disease, 20.8% with alcohol-associated liver disease, with model for end-stage liver disease scores of 9.5 ± 3.0, and 93.0% with liver stiffness measurements ≥10 kPa) or a validation population (n = 789). Test results were compared with results from a sequential algorithm (VariScreen). VariScreen incorporated data on platelets or liver stiffness measurements and then the ratio of platelets to liver stiffness measurement, adjusted for etiology, patient sex, and international normalized ratio.Results: In the derivation population, endoscopies were spared for 23.9% of patients using the B6C (VNT missed in 2.9%), 24.3% of patients using the ANTICIPATE score (VNT missed in 4.6%), 34.5% of patients using VariScreen (VNT missed in 2.9%), and 41.9% of patients using the EB6C (VNT missed in 10.9%). Differences in spared endoscopy rates were significant (P ≤ .001), except for B6C vs ANTICIPATE and in missed VNT only for EB6C vs the others (P ≤ .009). VariScreen was the only safe test regardless of sex or etiology (missed VNT ≤5%). Moreover, VariScreen secured screening without missed VNT in patients with model for end-stage liver disease scores higher than 10. This overall strategy performed better than a selective strategy restricted to patients with compensated liver disease. Test performance and safety did not differ significantly among populations.Conclusions: In a retrospective study of data from 2368 patients with chronic liver disease, we found that the B6C are safe whereas the EB6C are unsafe, based on missed VNT. The VariScreen algorithm performed well in patients with chronic liver disease of any etiology or severity. It is the only test that safely rules out VNT and can be used in clinical practice.

Published
2021
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2. A predictive score of inadequate bowel preparation based on a self-administered questionnaire: PREPA-CO

Author

Aymeric Becq, Etienne Pateu, Nina Dib, Sandrine Bertrais, Adrien Lannes, Anne Olivier, Paul Calès, Carole Vitellius, Arthur Berger, Jérôme Boursier, Dominique Luet, François-Xavier Caroli-Bosc, Elodie Cesbron-Métivier, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre de recherche en éducation de Nantes (CREN), Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN)-Le Mans Université (UM), Service d'Endocrinologie, diabétologie et endocrinologie de la reproduction [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), Département d'hépatologie (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), École nationale supérieure d'architecture de Nantes (ENSA Nantes), Épidémiologie en Santé au Travail et Ergonomie (IRSET-ESTER), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Le Mans Université (UM)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), Service d'Endocrinologie, Diabétologie et d'Endocrinologie de la Reproduction [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université

Subjects
medicine.medical_specialty, Cirrhosis, Colon, [SDV]Life Sciences [q-bio], Colonoscopy, Boston Bowel Preparation Scale, Single Center, 03 medical and health sciences, 0302 clinical medicine, Bowel preparation, Predictive Value of Tests, Risk Factors, Diabetes mellitus, Internal medicine, Surveys and Questionnaires, Boston bowel preparation scale, Preoperative Care, medicine, Humans, Medical prescription, ComputingMilieux_MISCELLANEOUS, Framingham Risk Score, Hepatology, medicine.diagnostic_test, business.industry, Cathartics, Gastroenterology, medicine.disease, 3. Good health, Inadequate bowel preparation, Predictive model, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, business
Abstract

Introduction Inadequate bowel preparation before colonoscopy has a 20–30% rate and impedes on the quality of the procedure. The aim of this study was to develop a predictive score of inadequate bowel preparation, using a patient questionnaire on potential risk factors. Methods In this single center study, consecutive patients with colonoscopy indication were enrolled. The primary outcome was inadequate bowel preparation defined by Boston Bowel Preparation Scale (BBPS) score Results A total of 561 patients were included. Inadequate bowel preparation was seen in 25.0% of cases. Seven risk factors were selected into the prediction model of inadequate bowel preparation: diabetes or obesity, irregular physical activity, cirrhosis, use of antidepressants or neuroleptics, use of opiate medication, history of surgery and history of inadequate bowel preparation. The risk score, named PREPA-CO, had an AUROC of 0.621, adequately predicted bowel cleanliness in 68.3% of cases, with a specificity of 75.8% and a negative predictive value of 80.8%. Conclusion We developed a predictive score named “Prepa-Co”, allowing the identification of patients at high risk of inadequate bowel preparation. In clinical practice, this score could help tailor the prescription of the preparation to the patient.

Published
2020
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3. Large oesophageal varice screening by a sequential algorithm using a cirrhosis blood test and optionally capsule endoscopy

Author

Sylvie Sacher-Huvelin, Jérôme Boursier, Dominique Valla, Frédéric Oberti, Anne Olivier, Jean Paul Galmiche, Paul Calès, Christophe Bureau, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), CIC, Institut des Maladies de l'Appareil Digestif, University Hospital, Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Centre de recherche en éducation de Nantes (CREN), Le Mans Université (UM)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Department of Gastroenterology and Hepatology, Université de Nantes (UN), CIC 004, and Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, [SDV]Life Sciences [q-bio], Esophageal and Gastric Varices, Capsule Endoscopy, Proof of Concept Study, Gastroenterology, Decision Support Techniques, law.invention, 03 medical and health sciences, 0302 clinical medicine, Esophageal varices, Predictive Value of Tests, Capsule endoscopy, law, Internal medicine, Ascites, medicine, Humans, Blood test, Prospective Studies, endoscopy, Diagnostic Errors, Prospective cohort study, Aged, Hepatology, medicine.diagnostic_test, business.industry, portal hypertension, Reproducibility of Results, Middle Aged, liver fibrosis tests, medicine.disease, non‐invasive diagnosis, 3. Good health, Endoscopy, 030220 oncology & carcinogenesis, Screening, Elasticity Imaging Techniques, Portal hypertension, Female, 030211 gastroenterology & hepatology, oesophageal varice, medicine.symptom, business, Algorithms, Biomarkers
Abstract

International audience; BACKGROUND & AIMS: Large oesophageal varice (LEV) screening is recommended in cirrhosis. We performed a prospective study to improve non-invasive LEV screening.DESIGN: 287 patients with cirrhosis had upper gastrointestinal endoscopy (LEV reference), oesophageal capsule endoscopy (ECE), liver elastography and blood marker analyses. CirrhoMeter (cirrhosis blood test), the most accurate non-invasive LEV test, was segmented for cirrhosis (reference comparator) or LEV. VariScreen, a sequential and partially minimally invasive diagnostic algorithm, was developed by multivariate analysis. It uses CirrhoMeter first, then ECE if CirrhoMeter cannot rule LEV out or in, and finally endoscopy if CirrhoMeter+ECE combination remains uninformative.RESULTS: Diagnostic effectiveness rates for LEV were: cirrhosis-segmented CirrhoMeter: 14.6%, LEV-segmented CirrhoMeter: 34.6%, ECE: 60.6% and VariScreen: 66.4% (P≤.001 for overall or pair comparison). The respective missed LEV rates were: 2.8%, 5.6%, 8.3% and 5.6% (P=.789). Spared endoscopy rates were, respectively: 15.6%, 36.0%, 70.6% and 69%, (PCONCLUSION: VariScreen algorithm significantly reduced the missed LEV rate with ECE by 87%, ECE use by 38% and endoscopy requirement by 69%, and even 86% in compensated cirrhosis.

Published
2017
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4. ABHD11, a new diacylglycerol lipase involved in weight gain regulation

Author

Laurence Rocheteau-Beaujouan, Michel Didier, Charles Bettembourg, Sandrine Teixeira, Valérie Destelle, Sandrine Roche, Armelle Buzy, Joël Capdevielle, Johanna Escoubet, Aurélie Leroy, Margerie Clement, Christophe Cahours, Helene de Foucauld, Mireille Kenigsberg, Richard Legoux, Vincent Mikol, Murielle Derock, Cécile Orsini, Eric Perret, Willy Deshayes, Marie-Dominique Bock, Michaël Leguet, Mostafa Kabiri, Jean-Claude Guillemot, Antoine Berthemy, Florence Massey, Anne Olivier, Veeranagouda Yaligara, Pascal Gauthier, Marie-Agnès Chatoux, Pascale Chardenot, and Patrick Juvet

Subjects
0301 basic medicine, Diacylglycerol lipase, Physiology, Hydrolases, medicine.medical_treatment, Weight Gain, Biochemistry, Intestinal absorption, Feces, Gene Knockout Techniques, Mice, 0302 clinical medicine, Endocrinology, Mathematical and Statistical Techniques, Medicine and Health Sciences, Bile, Insulin, Lipases, Energy-Producing Organelles, Multidisciplinary, biology, Statistics, Serine hydrolase, Genomics, Endocannabinoid system, Lipids, Mitochondria, Body Fluids, Enzymes, Physical Sciences, MCF-7 Cells, Medicine, Signal transduction, Cellular Structures and Organelles, Anatomy, Transcriptome Analysis, Signal Transduction, Research Article, medicine.medical_specialty, Science, Bioenergetics, Research and Analysis Methods, Gene Expression Regulation, Enzymologic, 03 medical and health sciences, In vivo, Internal medicine, medicine, Genetics, Animals, Humans, Statistical Methods, Nutrition, Diabetic Endocrinology, Analysis of Variance, Gene Expression Profiling, Biology and Life Sciences, Proteins, Computational Biology, Cell Biology, Genome Analysis, In vitro, Hormones, Diet, 030104 developmental biology, biology.protein, Enzymology, Serine Proteases, 030217 neurology & neurosurgery, Mathematics
Abstract

Obesity epidemic continues to spread and obesity rates are increasing in the world. In addition to public health effort to reduce obesity, there is a need to better understand the underlying biology to enable more effective treatment and the discovery of new pharmacological agents. Abhydrolase domain-containing protein 11 (ABHD11) is a serine hydrolase enzyme, localized in mitochondria, that can synthesize the endocannabinoid 2-arachidonoyl glycerol (2AG) in vitro. In vivo preclinical studies demonstrated that knock-out ABHD11 mice have a similar 2AG level as WT mice and exhibit a lean metabolic phenotype. Such mice resist to weight gain in Diet Induced Obesity studies (DIO) and display normal biochemical plasma parameters. Metabolic and transcriptomic analyses on serum and tissues of ABHD11 KO mice from DIO studies show a modulation in bile salts associated with reduced fat intestinal absorption. These data suggest that modulating ABHD11 signaling pathway could be of therapeutic value for the treatment of metabolic disorders.

Published
2020

5. Structural Insights into the Forward and Reverse Enzymatic Reactions in Human Adenine Phosphoribosyltransferase

Author

Benoît Pinson, Irène Ceballos-Picot, Renaud Morales, Robert Barouki, Bertrand Daignan-Fornier, G.M. Pinon, Anne Olivier-Bandini, Françoise Chesney, Jessica Huyet, Franck Augé, Christelle Saint-Marc, Roland Lupoli, Abdul Rauf Siddiqi, Pierre Nioche, Mohammad Ozeir, Jean-Marc Remy, Jean-Francois Gibert, Marie-Claude Burgevin, Birkbeck College [University of London], Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sanofi Aventis R&D, Sanofi Aventis R&D [Chilly-Mazarin], Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), and Société Entomologique Antilles-Guyane (SEAG)

Subjects
0301 basic medicine, Models, Molecular, Protein Conformation, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Adenine phosphoribosyltransferase, Adenine Phosphoribosyltransferase, Biology, Crystallography, X-Ray, Biochemistry, Enzyme catalysis, Nucleobase, 03 medical and health sciences, Drug Discovery, Transferase, Humans, Purine metabolism, Molecular Biology, Nucleotide salvage, Pharmacology, chemistry.chemical_classification, 030102 biochemistry & molecular biology, Protein dynamics, Amino acid, 030104 developmental biology, chemistry, Biophysics, Molecular Medicine
Abstract

Summary Phosphoribosyltransferases catalyze the displacement of a PRPP α-1′-pyrophosphate to a nitrogen-containing nucleobase. How they control the balance of substrates/products binding and activities is poorly understood. Here, we investigated the human adenine phosphoribosyltransferase (hAPRT) that produces AMP in the purine salvage pathway. We show that a single oxygen atom from the Tyr105 side chain is responsible for selecting the active conformation of the 12 amino acid long catalytic loop. Using in vitro , cellular, and in crystallo approaches, we demonstrated that Tyr105 is key for the fine-tuning of the kinetic activity efficiencies of the forward and reverse reactions. Together, our results reveal an evolutionary pressure on the strictly conserved Tyr105 and on the dynamic motion of the flexible loop in phosphoribosyltransferases that is essential for purine biosynthesis in cells. These data also provide the framework for designing novel adenine derivatives that could modulate, through hAPRT, diseases-involved cellular pathways.

Published
2017
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6. An Unusual Cause of Abdominal Pain: Lupus Enteritis

Author

Johnny Sayegh, Jean-François Augusto, Julien Demiselle, Maud Cousin, and Anne Olivier

Subjects
030203 arthritis & rheumatology, medicine.medical_specialty, Abdominal pain, Lupus erythematosus, Systemic lupus erythematosus, business.industry, General Medicine, medicine.disease, Dermatology, Enteritis, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Prednisone, Edema, Ascites, Medicine, Abdomen, 030211 gastroenterology & hepatology, medicine.symptom, business, medicine.drug
Published
2016
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