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1. Effect of lockdown on digestive system cancer care amongst older patients during the first wave of COVID-19: The CADIGCOVAGE multicentre cohort study

Author: Nathalie Ganne, François Hemery, Laurent Quero, Frédéric Prat, Thomas Aparicio, Nicola de Angelis, Gilles Galula, Richard Layese, Marc-Antoine Benderra, Atanas Pachev, Christophe Tournigand, Elena Paillaud, Florence Canouï-Poitrine, Hopital Saint-Louis [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), CHU Henri Mondor, Cooperator Multidisciplinary Oncology Group (GERCOR), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Département de Santé Publique [Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Service d'Oncologie médicale [CHU Tenon], CHU Tenon [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), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Gestionnaire, HAL Sorbonne Université 5
Subjects: Male, Paris, medicine.medical_specialty, Digestive cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, Digestive System Neoplasms, Health Services Accessibility, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Lockdown, Older patients, medicine, Humans, 030212 general & internal medicine, Pandemics, Aged, Retrospective Studies, Aged, 80 and over, Public health, Hepatology, SARS-CoV-2, business.industry, Mortality rate, Gastroenterology, COVID-19, Cancer, Emergency department, medicine.disease, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Communicable Disease Control, Cohort, Female, Observational study, business, Cohort study
Abstract: International audience; Background: The coronavirus disease 2019 (COVID-19) pandemic has had a dramatic impact on cancer diagnosis and treatment. Most patients newly diagnosed with digestive system cancer are aged 65 and over. Methods: We performed a retrospective, observational, multicentre cohort study based on prospectively collected electronic health records. All adults aged 65 or over and having been newly treated for a digestive system cancer between January 2018 until August 2020 were enroled. Results: Data on 7882 patients were analysed. The first COVID-19 lockdown period led to a 42.4% decrease in newly treated digestive system cancers, and the post-lockdown period was associated with a 17% decrease. The decrease in newly treated digestive system cancer did not differ as a function of age, sex, comorbidities, primary tumour site, and disease stage. The proportion of patients admitted to an emergency department increased during the lockdown period. We do not observe a higher 3-month mortality rate in 2020, relative to the corresponding calendar periods in 2018 and 2019. Conclusion: To avoid a decrease in newly treated cancers during future lockdown periods, access to healthcare will have to be modified. Although 3-month mortality did not increase in any of the patient subgroups, the 2020 cohort must be followed up for long-term mortality.
Published: 2022
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2. Non-invasive diagnosis and follow-up of portal hypertension

Author: Victor de Lédinghen, Thomas Sersté, Christophe Bureau, Marika Rudler, Dominique Thabut, Nathalie Ganne-Carrié, Delphine Weil, Charlotte Bouzbib, Laurent Castera, Christophe Cassinotto, Frédéric Oberti, M. Bourlière, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hépatologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Département radiologie diagnostique et interventionnelle Saint Eloi [CHRU Montpellier], Pôle Digestif [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Pierre, Service d’Hépato-Gastroentérologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), 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), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], 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), Hôpital Saint-Joseph [Marseille], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: medicine.medical_specialty, Cirrhosis, Portal venous pressure, [SDV]Life Sciences [q-bio], MESH: Elasticity Imaging Techniques, Chronic liver disease, Gastroenterology, Asymptomatic, MESH: Esophageal and Gastric Varices, Internal medicine, Medicine, In patient, MESH: Hypertension, Portal, MESH: Humans, Hepatology, medicine.diagnostic_test, business.industry, Non invasive, MESH: Follow-Up Studies, medicine.disease, Endoscopy, MESH: Endoscopy, Gastrointestinal, Portal hypertension, medicine.symptom, MESH: Liver Cirrhosis, business
Abstract: Compensated advanced chronic liver disease (cACLD) describes the spectrum of advanced fibrosis/cirrhosis in asymptomatic patients at risk of developing clinically significant portal hypertension (CSPH, defined by a hepatic venous pressure gradient (HVPG) 10 mmHg). Patients with cACLD are at high risk of liver-related morbidity and mortality. In patients at risk of chronic liver disease, cACLD is strongly suggested by a liver stiffness (LSM) value >15 kPa or clinical/biological/radiological signs of portal hypertension, and ruled out by LSM 150 G/L (favourable Baveno VI criteria) at the time of diagnosis. There is no non-invasive method alternative for oeso-gastroduodenal endoscopy in patients with unfavourable Baveno criteria (liver stiffness 20 kPa or platelet count 50 G/l). Platelet count and liver stiffness measurements must be performed once a year in patients with cACLD with favourable Baveno VI criteria at the time of diagnosis. A screening oeso-gastroduodenal endoscopy is recommended if Baveno VI criteria become unfavourable.
Published: 2022
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3. Health-related quality of life in locally advanced hepatocellular carcinoma treated by either radioembolisation or sorafenib (SARAH trial)

Author: Helena Pereira, Mohamed Bouattour, Marco D. Burgio, Eric Assenat, Jules Grégory, Jean-Pierre Bronowicki, Gilles Chatellier, Valérie Vilgrain, Elisabeth Delhom-Christol, Marjolène Fourcade, Boris Guiu, Alina Diana Ilonca, Julie Lonjon, Georges-Philippe Pageaux, Mohamed Abdel-Rehim, Wassim Allaham, Laurent Castera, Arnaud Dieudonné, Rachida Lebtahi, Maxime Ronot, Annie Sibert, Hélène Chor, Julie Devictor, Hélène Barraud, Christophe Bazin, Laetitia Imbert, Valérie Laurent, Elodie Mathias, Carine Chagneau-Derrode, Christelle Gallais, Rémy Perdrisot, Christine Silvain, Jean Pierre Tasu, Patrick Borentain, Bardia Farman, René Gerolami, Olivier Mundler, Jean-Francois Seitz, Vincent Vidal, Christophe Aubé, Francis Bouchet, Antoine Bouvier, Olivier Couturier, Frédéric Oberti, Laurent Vervueren, Isabelle Brenot-Rossi, Julien Darreon, Jean Luc Raoul, Anthony Sarran, Julia Chalaye, Charlotte Costentin, Emmanuel Itti, Hicham Kobeiter, Alain Luciani, Hélène Masset, René Adam, Maïté Lewin, Didier Samuel, Julien Edeline, Etienne Garin, Sophie Laffont, Yan Rolland, Isabelle Archambeaud, Thomas Carlier, Thomas Eugene, Eric Frampas, Christophe Cassinotto, Martine Guyot, Jean-Baptiste Hiriart, Bruno Lapuyade, Karine Tendero, Julien Vergniol, Philippe Bachellier, Julien Détour, Bernard Duclos, Michel Greget, Francois Habersetzer, Alessio Imperiale, Elise Enderlin, Philippe Merle, Agnès Rode, Julie Morvan, Eric Nguyen-Khac, Antoine Talbot, Thierry Yzet, Guillaume Baudin, Patrick Chevallier, Abakar Mahamat, Fabien Maurel, Thierry Piche, Micheline Razzouk, Patrick Hillon, Romaric Loffroy, Michel Toubeau, Julie Vincent, Jean-Marc Vrigneaud, Gabriele Barabino, Nadia Bouarioua, Muriel Cuilleron, Marie Ecochard, Nathalie Prevot-Bitot, Evelyne Rousset, Vincent Leroy, Ghislaine Reboulet, Julie Roux, Christian Sengel, Valérie Bourcier, Nathalie Ganne-Carrie, Olivier Seror, Sylvie Costo, Thông Dao, Cédric Desmonts, Jean-Pierre Pelage, Didier Defez, Jérôme Dumortier, Francesco Giammarile, Pierre-Jean Valette, Michela Bernardini, Nadia Ghazar, Olivier Pellerin, Julien Taieb, Pierre Weinmann, Alexandra Heurgue-Berlot, Claude Marcus, Daniele Sommacale, Maria-Angéla Castilla-Lièvre, Aurélie Forbes, Sophie Maitre, Lysiane Marthey, CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), 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 (UPC), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Equipe IFTIM [ImViA - EA7535], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Imagerie et Vision Artificielle [Dijon] (ImViA), and Université de Bourgogne (UB)-Université de Bourgogne (UB)
Subjects: Male, Sorafenib, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, Tare weight, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Locally advanced, Quality of life, Internal medicine, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Aged, Social functioning, Health related quality of life, business.industry, Liver Neoplasms, Middle Aged, medicine.disease, Embolization, Therapeutic, digestive system diseases, Confidence interval, Oncology, Hepatocellular carcinoma, Quality of Life, Female, business, medicine.drug
Abstract: Background The aim of this ancillary study of the SARAH trial is to compare health-related quality of life (HRQoL) in patients with locally advanced or inoperable hepatocellular carcinoma (HCC) treated with transarterial radioembolisation (TARE) or sorafenib. Methods This study included randomised patients who received either TARE or at least one dose of sorafenib with no major deviation in the protocol and who had at least one QoL follow-up assessment in addition to the baseline evaluation. QoL was assessed from the date of randomisation using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire, until disease progression or other reasons for stopping study participation. Data were analysed using linear mixed and time-dependent models. Results A total of 285 patients were included (122 and 163, in the TARE and sorafenib groups, respectively). Questionnaire completion rates were similar (77.5% versus 80.4%, in the TARE and sorafenib groups, respectively, p = 0.25). Longitudinal HRQoL analysis showed a significant treatment and time effects for fatigue and global health status, and significant treatment, time and treatment by time interaction effects for appetite loss, diarrhoea and social functioning. The median time to deterioration for the global health status was 3.9 months (95% confidence interval [CI] 3.7–4.3) versus 2.6 months (95% CI 2.0–3.0) in the TARE and sorafenib groups, respectively. Conclusions HRQoL was preserved longer with TARE than with sorafenib in locally advanced HCC. These data could be used to optimise management of patients with advanced or inoperable HCC.
Published: 2021
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4. Early liver transplantation for corticosteroid non-responders with acute severe autoimmune hepatitis: The SURFASA score

Author: Olivier Chazouillères, Florent Artru, Eleonora De Martin, Philippe Mathurin, Camille Besch, Christophe Duvoux, François Durand, Odile Goria, Hélène Fontaine, Hélène Agostini, Isabelle Ollivier-Hourmand, Noemi Reboux, Olivier Roux, Filomena Conti, Nathalie Ganne-Carrié, Didier Samuel, Georges-Philippe Pageaux, Philippe Ichai, Marilyne Debette-Gratien, Christine Silvain, Alexandra Heurgue, Jean-Marie Peron, Sylvie Radenne, Jérôme Dumortier, Audrey Coilly, Pauline Houssel-Debry, Sandrine Barge, Marc Bourlière, Pascal Potier, Jean-Charles Duclos-Vallée, Vincent Di Martino, Mylène Sebagh, and Victor de Ledinghen
Subjects: 0301 basic medicine, medicine.medical_specialty, Multivariate analysis, Hepatology, medicine.drug_class, Bilirubin, business.industry, medicine.medical_treatment, Odds ratio, Autoimmune hepatitis, Liver transplantation, medicine.disease, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, chemistry, Internal medicine, medicine, Corticosteroid, 030211 gastroenterology & hepatology, Prospective cohort study, business, Survival rate
Abstract: Background & Aims In acute severe autoimmune hepatitis (AS-AIH), the optimal timing for liver transplantation (LT) remains controversial. The objectives of this study were to determine early predictive factors for a non-response to corticosteroids and to propose a score to identify patients in whom LT is urgently indicated. Methods This was a retrospective, multicenter study (2009-2016). A diagnosis of AS-AIH was based on: i) Definite or probable AIH based on the simplified IAIHG score; ii) international normalized ratio (INR) ≥1.5 and/or bilirubin >200 μmol/L; iii) No previous history of AIH; iv) Histologically proven AIH. A treatment response was defined as LT-free survival at 90 days. The evolution of variables from corticosteroid initiation (day-D0) to D3 was estimated from: Δ%3 = (D3–D0)/D0. Results A total of 128 patients were included, with a median age of 52 (39–62) years; 72% were female. Overall survival reached 88%. One hundred and fifteen (90%) patients received corticosteroids, with a LT-free survival rate of 66% at 90 days. Under multivariate analysis, D0-INR (odds ratio [OR] 6.85; 95% CI 2.23–21.06; p Conclusion In patients with AS-AIH, INR at the introduction of corticosteroids and the evolution of INR and bilirubin are predictive of LT or death. Within 3 days of initiating corticosteroids, the SURFASA score can identify non-responders who require a referral for LT. This score needs to be validated in a prospective cohort. Lay summary The management of patients with acute severe autoimmune hepatitis is highly challenging, particularly regarding their early referral for liver transplantation. We found that international normalized ratio at the initiation of corticosteroid therapy and the evolution of international normalized ratio and bilirubin values after 3 days of therapy were highly predictive of liver transplantation or death. We are thus proposing a score that combines these variables and identifies patients in whom liver transplantation is urgently required.
Published: 2021
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5. 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
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6. Fragility index of positive phase II and III randomized clinical trials of treatments for hepatocellular carcinoma (2002-2022)

Author: Sabrina Sidali, Nanthara Sritharan, Claudia Campani, Jules Gregory, François Durand, Nathalie Ganne-Carrié, Maxime Ronot, Vincent Lévy, and Jean-Charles Nault
Subjects: Hepatology, Gastroenterology, Internal Medicine, Immunology and Allergy
Published: 2023
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7. Non-invasive diagnosis and follow-up of chronic infection with Hepatitis C Virus

Author: Stéphane Chevaliez, Sarah Shili-Masmoudi, Lucile Moga, Isaac Ruiz, Nathalie Ganne-Carrié, Albert Tran, M. Bourlière, Christophe Bureau, Victor de Lédinghen, Alain Luciani, Hôpital l'Archet, Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Henri Mondor, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Avicenne [AP-HP], Université Sorbonne Paris Nord, Hôpital Rangueil, CHU Toulouse [Toulouse], Hôpital Saint-Joseph [Marseille], 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Malbec, Odile
Subjects: Liver Cirrhosis, HBsAg, medicine.medical_specialty, Hepatitis C virus, [SDV]Life Sciences [q-bio], Hepacivirus, medicine.disease_cause, Gastroenterology, Virus, Fibrosis, Internal medicine, medicine, Humans, Hepatology, business.industry, Liver Diseases, virus diseases, Hepatitis C, Chronic, medicine.disease, Hepatitis C, digestive system diseases, [SDV] Life Sciences [q-bio], Chronic infection, Liver, HBeAg, Hepatocellular carcinoma, Elasticity Imaging Techniques, Portal hypertension, Persistent Infection, business, Follow-Up Studies
Abstract: Diagnosis of chronic hepatitis B virus (HBV) infection, initial staging of infection and monitoring of treated and untreated patients are mainly based on clinical, biological and imaging criteria allowing a complete non-invasive management for the majority of patients. Along to the conventional virological tools, rapid diagnostic tests and blotting paper tests for HBV DNA are validated alternatives. After diagnosis, the initial work-up should include HIV, HCV and HDV serologies, HBeAg status, and HBsAg and HBV DNA quantification. Assessment of severity (inflammation and fibrosis) is based on ALT serum levels and non-invasive evaluation of liver fibrosis by elastography or blood tests, which must be interpreted cautiously using specific cut-offs and taking into account ALT levels. Taken together, these parameters allow disease classification and treatment decision. Decision of hepatocellular carcinoma screening by ultra-sound every six months may be difficult in non-cirrhotic patients and the use of risk-scores such as PAGE-B is encouraged. Chronic HBV infection often has a dynamic and often unpredictable profile and regular monitoring is mandatory. In untreated patients, regular (3-12 months) follow-up should include ALT and HBV DNA serum levels. Periodical HBsAg quantification and non-invasive evaluation of liver fibrosis may refine disease outcome and prognosis. In treated patients, checking efficacy is mainly based on HBV DNA negativity. In patients with advanced fibrosis, evolution of liver stiffness can be useful for portal hypertension evaluation, but its improvement should not be considered to stop hepatocellular carcinoma screening. Finally, new parameters (HBV RNA, HBcrAg) are promising but their use is still restricted for research.
Published: 2022
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8. Non-invasive diagnosis and follow-up of rare genetic liver diseases

Author: Rodolphe Sobesky, Olivier Guillaud, Charlotte Bouzbib, Philippe Sogni, Aurélia Poujois, France Woimant, Jean Charles Duclos-Vallée, Marc Bourlière, Victor de Lédinghen, Nathalie Ganne-Carrié, Christophe Bureau, Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), National reference Centre for Wilson's Disease [Paris] (CRMR Wilson), Service de neurologie [Univ. Paris VII], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Hôpital Saint-Joseph [Marseille], 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), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Avicenne [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 Paris Cité (UPCité), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), École pratique des hautes études (EPHE), and Malbec, Odile
Subjects: medicine.medical_specialty, Cirrhosis, [SDV]Life Sciences [q-bio], Disease, Gastroenterology, Liver disease, Rare Diseases, Hepatolenticular Degeneration, Fibrosis, Internal medicine, alpha 1-Antitrypsin Deficiency, medicine, Humans, Hepatology, medicine.diagnostic_test, business.industry, Cystic fibrosis screening, Non invasive, medicine.disease, Molecular analysis, [SDV] Life Sciences [q-bio], Liver, Liver biopsy, business, Biomarkers, Copper, Follow-Up Studies
Abstract: International audience; Rare genetic liver diseases can result in multi-systemic damage, which may compromise the patient's prognosis. Wilson's disease and alpha-1 antitrypsin deficiency must be investigated in any patient with unexplained liver disease. Cystic fibrosis screening of new-borns is now implemented in most high-prevalence countries. The diagnosis of these diseases can be strongly suggested with specific non-invasive tests. Molecular analysis gene for these diseases is long and tedious but is recommended to confirm the diagnosis and help for the family screening. Liver biopsy is not systematic and is discussed when it helps diagnosis. Currently, for these three diseases, non-invasive fibrosis markers could identify patients with risk of cirrhosis and complications. Rare genetic liver diseases can result in multi-systemic damage, which may compromise the patient's prognosis. Wilson's disease, must be investigated in any patient with unexplained liver disease and/or unexplained neurological or neuropsychiatric disorders. The diagnosis is based on a combination of clinical, biological features, including copper balance. The exchangeable copper/total copper ratio is a new sensible and specific biological marker, useful for the diagnosis of the disease. Timely diagnosis and treatment will prevent serious complications from the disease. Neurological evaluation and familial screening are essential in patients with Wilson's disease.
Published: 2022
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9. Non-invasive diagnosis and follow-up of non-alcoholic fatty liver disease

Author: Sarra Smatti, Victor de Lédinghen, Bertrand Cariou, Maeva Guillaume, Charlotte Bouzbib, M. Bourlière, Nathalie Ganne-Carrié, Christophe Bureau, Raluca Pais, Adrien Lannes, Jérôme Boursier, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Clinique Pasteur [Toulouse], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Avicenne [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 Paris Cité (UPCité), Hôpital Saint-Joseph [Marseille], 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), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), École pratique des hautes études (EPHE), and Malbec, Odile
Subjects: Liver Cirrhosis, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Population, Disease, Asymptomatic, digestive system, Liver disease, Non-alcoholic Fatty Liver Disease, Internal medicine, Diabetes mellitus, medicine, Humans, education, education.field_of_study, Hepatology, medicine.diagnostic_test, business.industry, Fatty liver, Gastroenterology, nutritional and metabolic diseases, medicine.disease, digestive system diseases, [SDV] Life Sciences [q-bio], Liver, Liver biopsy, Elasticity Imaging Techniques, Metabolic syndrome, medicine.symptom, business, Follow-Up Studies
Abstract: International audience; NAFLD is a frequent disease that affects 25% of the worldwide population. There is no specific diagnostic test for NAFLD, and the diagnosis mainly relies on the elimination of the other causes of chronic liver diseases with liver biopsy kept for unsure diagnoses. Non-invasive tests are now available to assess NAFLD severity and therefore to help physicians decide on the patient management and follow-up. These non-invasive tests can also be used to define pathways that organize referrals from primary care and diabetology clinics to the liver specialist, with the ambition to improve the screening of asymptomatic patients with NAFLD and advanced liver disease. NAFLD being the liver expression of the metabolic syndrome, physicians need also take care to screen for diabetes and to evaluate the cardiovascular risk in those patients. These recommendations from the French Association for the Study of the Liver (AFEF) aim at providing guidance on the following questions: how to diagnose NAFLD; how non-invasive tests should be used to assess NAFLD severity; how to follow patients with NAFLD; when to perform liver biopsy in NAFLD; and how to decide referral to the liver specialist for a patient with NAFLD.
Published: 2022
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10. Non-invasive diagnosis and follow-up of primary biliary cholangitis

Author: Pascal Potier, Marie Decraecker, Florence Tanné, Christophe Bureau, Victor de Lédinghen, Nathalie Ganne-Carrié, Bertrand Hanslik, M. Bourlière, Alexandra Heurgue, Christophe Corpechot, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de référence des Maladies Vasculaires du Foie [Paris] (FILFOIE), Centre de référence pour les maladies biliaires inflammatoires et les hépatites auto-immunes [Paris] (CRMBIHAI), Health Care Provider of the European Reference Network onRare Liver Disorders (ERN-Liver), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Centre Hospitalier Régional d'Orléans (CHRO), Centre Montpellierain des maladies du foie et de l’appareil digestif [Montpellier] (C2MFAD), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Avicenne [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 Paris Cité (UPCité), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Saint-Joseph [Marseille], 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), Dupuis, Christine, and École pratique des hautes études (EPHE)
Subjects: medicine.medical_specialty, Cirrhosis, Hepatology, business.industry, Cholangitis, Liver Cirrhosis, Biliary, [SDV]Life Sciences [q-bio], Non invasive, Gastroenterology, Autoantibody, medicine.disease, Chronic inflammatory disease, PBC, [SDV] Life Sciences [q-bio], Bile Ducts, Intrahepatic, Liver stiffness, Internal medicine, Chronic cholestasis, medicine, Portal hypertension, Humans, business, Histological examination, Follow-Up Studies
Abstract: International audience; Non-invasive diagnosis and follow-up of primary biliary cholangitis Summary Primary biliary cholangitis (PBC) is a chronic inflammatory disease of the intrahepatic bile ducts [1]. It is characterised biologically by chronic cholestasis associated with the presence of specific autoantibodies, and histologically by lesions of nonsuppurative destructive cholangitis. If left untreated it can progress to cirrhosis, portal hypertension and liver failure. Diagnosis, staging and follow-up are largely based on non-or minimally-invasive assessment (blood tests, ultrasound, liver stiffness measurement). Histological examination of the liver and upper gastrointestinal endoscopy are sometimes necessary, but their indications remain limited. The purpose of this chapter is to provide the clinicians with what should be known about the non-invasive assessment of PBC and to provide specific recommendations for clinical practice.
Published: 2022
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11. ESM1 as a Marker of Macrotrabecular-Massive Hepatocellular Carcinoma

Author: Stefano Caruso, Valérie Paradis, Alexis Laurent, Marouane Boubaya, Nathalie Ganne-Carrié, Marianne Ziol, Valérie Vilgrain, Georges Philippe Pageaux, Cong Trung Nguyen, Hélène Regnault, Mohamed Bouattour, Boris Guiu, Giuliana Amaddeo, Léa Meunier, Christophe Aubé, Julien Calderaro, Jean-Charles Nault, Nathalie Barget, Olivier Seror, Jeanne Ramos, Justine Cohen, Alain Luciani, Frédéric Oberti, Sophie Michalak, Jean-Michel Pawlotsky, and Jessica Zucman-Rossi
Subjects: Male, Oncology, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, 03 medical and health sciences, 0302 clinical medicine, Antigen, Antigens, Neoplasm, Internal medicine, ESM1, Biopsy, Biomarkers, Tumor, Tumor Microenvironment, Carcinoma, Humans, Medicine, Carbonic Anhydrase IX, medicine.diagnostic_test, business.industry, Gene Expression Profiling, Liver Neoplasms, Middle Aged, Prognosis, medicine.disease, digestive system diseases, Subtyping, Neoplasm Proteins, 3. Good health, Gene expression profiling, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Immunohistochemistry, Female, Proteoglycans, 030211 gastroenterology & hepatology, business
Abstract: Purpose: Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) is a novel morphological subtype of HCC associated with early relapse after resection or percutaneous ablation, independently of classical clinical and radiological prognostic factors. The aim of the present study was to identify immunohistochemical markers of MTM-HCC, to ease its diagnosis and implementation into clinical practice. Experimental Design: To identify potential biomarkers of MTM-HCC, we first analyzed gene expression profiling data from The Cancer Genome Atlas study and further selected two candidate biomarkers. Performance of both biomarkers for diagnosis of MTM-HCC was further tested by immunohistochemistry in two independent series of 67 and 132 HCC biopsy samples. Results: Analysis of RNA sequencing data showed that MTM-HCC was characterized by a high expression of neoangiogenesis-related genes. Two candidate biomarkers, Endothelial-Specific Molecule 1 (ESM1) and Carbonic Anhydrase IX (CAIX), were selected. In the discovery series, sensitivity and specificity of ESM1 expression by stromal endothelial cells for the detection of MTM-HCC were 97% (28/29), and 92% (35/38), respectively. Sensitivity and specificity of CAIX were 48% (14/29) and 89% (34/38). In the validation set, sensitivity and specificity of ESM1 for the identification of MTM-HCC were 93% (14/15) and 91% (107/117), respectively. Interobserver agreement for ESM1 assessment was good in both series (Cohen Kappa 0.77 and 0.76). Conclusions: Using a molecular-driven selection of biomarkers, we identified ESM1 as a reliable microenvironment immunohistochemical marker of MTM-HCC. The results represent a step toward the implementation of HCC morpho-molecular subtyping into clinical practice.
Published: 2019
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12. Clinical Impact of Genomic Diversity From Early to Advanced Hepatocellular Carcinoma

Author: Stefano Caruso, Théo Z. Hirsch, Julien Calderaro, Pierre Nahon, Christophe Duvoux, Yoann Martin, Sandrine Faivre, Jean-Frédéric Blanc, Josep M. Llovet, Quentin Bayard, Nathalie Ganne-Carrié, Cécile Charpy, Alexis Laurent, Eric Letouzé, Marianne Ziol, Paulette Bioulac-Sage, Guillaume Morcrette, Sandra Rebouissou, Christiane Copie-Bergman, Laurence Chiche, Jessica Zucman-Rossi, Giuliana Amaddeo, Jean-Charles Nault, Olivier Seror, Gabrielle Couchy, and Sandrine Imbeaud
Subjects: Adult, Male, Oncology, medicine.medical_specialty, Carcinoma, Hepatocellular, Adolescent, ARID1A, Gene mutation, Young Adult, Internal medicine, Exome Sequencing, medicine, Carcinoma, Humans, Telomerase reverse transcriptase, Aged, Neoplasm Staging, Aged, 80 and over, Hepatology, business.industry, Liver Neoplasms, Genomics, Genetic Profile, Middle Aged, medicine.disease, BCLC Stage, Tumor progression, Hepatocellular carcinoma, Mutation, Female, Liver cancer, business
Abstract: To date, genomic analyses of hepatocellular carcinoma (HCC) have been limited to early stages obtained from liver resection. We aim to describe the genomic profiling of HCC from early to advanced stages. We analyzed 801 HCC from 720 patients (410 resections, 137 transplantations, 122 percutaneous ablations, and 52 noncurative) for 190 gene expressions and for 31 gene mutations. Forty-one advanced HCC and 156 whole exome of Barcelona Clinic Liver Cancer (BCLC) 0/A were analyzed by whole-exome sequencing. Genomic profiling was correlated with tumor stages, clinical features, and survival. Our cohort included patients classified in BCLC stage 0 (9.4%), A (59.5%), B (16.2%), and C (14.9%). Among the overall 801 HCC, the most frequently mutated genes were telomerase reverse transcriptase (TERT) (58.1%), catenin beta 1 (CTNNB1) (30.7%), tumor protein 53 (TP53; 18.7%), AT-rich interaction domain 1A (ARID1A) (13%), albumin (11.4%), apolipoprotein B (APOB) (9.4%), and AXIN1 (9.2%). Advanced-stage HCC (BCLC B/C) showed higher frequencies of splicing factor 3b subunit 1 (SF3B1) (P = 0.0003), TP53 (P = 0.0006), and RB Transcriptional Corepressor 1 mutations (P = 0.03). G1-G6 transcriptomic classification and the molecular prognostic 5-gene score showed different distributions according to the stage of the disease and the type of treatment with an enrichment of G3 (P < 0.0001), poor prognostic score (P < 0.0001), and increased proliferation and dedifferentiation at the transcriptomic level in advanced HCC. The 5-gene score predicted survival in patients treated by resection (P < 0.0001) and ablation (P = 0.01) and in advanced HCC (P = 0.04). Twenty-two percent of advanced HCC harbored potentially druggable genetic alterations, and MET amplification was associated with complete tumor response in patients with advanced HCC treated by a specific MET inhibitor. Conclusion: Genomic analysis across the different stages of HCC revealed the mechanisms of tumor progression and helped to identify biomarkers of response to targeted therapies.
Published: 2019
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13. Transient elastography predicts survival after radiofrequency ablation of hepatocellular carcinoma developing on cirrhosis

Author: Nathalie Ganne-Carrié, Lorraine Blaise, Véronique Grando, Marianne Ziol, Manon Allaire, Erwan Guyot, Olivier Sutter, Annie Mumana, Samia Rekik, Olivier Seror, Gisèle N'Kontchou, Pierre Nahon, and Jean-Charles Nault
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Milan criteria, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, Humans, Medicine, Aged, Aged, 80 and over, Radiofrequency Ablation, Univariate analysis, Hepatology, business.industry, Liver Neoplasms, Hazard ratio, Hepatitis C, Middle Aged, Prognosis, medicine.disease, Survival Rate, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Elasticity Imaging Techniques, Female, 030211 gastroenterology & hepatology, business, Transient elastography
Abstract: BACKGROUND AND AIM The prognostic value of transient elastography (TE) in cirrhotic patients with hepatocellular carcinoma (HCC) treated by percutaneous radiofrequency ablation (RFA) is currently unknown. METHOD(S) We included patients with histologically proven cirrhosis and with a first diagnosis of HCC inside Milan criteria treated by percutaneous RFA, and with TE available the year before treatment with 10 shots and interquartile range/median
Published: 2019
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14. Non-invasive diagnosis and follow-up of primary sclerosing cholangitis

Author: Pascal Potier, Victor de Lédinghen, Christophe Bureau, Jérôme Gournay, Nathalie Ganne-Carrié, Florence Tanne, Charlotte Bouzbib, M. Bourlière, Alexandra Heurgue, Eric Nguyen-Khac, Olivier Chazouillères, and Bertrand Hanslik
Subjects: medicine.medical_specialty, Colorectal cancer, Biliary cirrhosis, Cholangitis, Sclerosing, digestive system, Gastroenterology, Inflammatory bowel disease, Primary sclerosing cholangitis, Cholangiography, Cholestasis, Internal medicine, medicine, Humans, Cholangiopancreatography, Endoscopic Retrograde, Endoscopic retrograde cholangiopancreatography, Hepatology, medicine.diagnostic_test, business.industry, medicine.disease, Inflammatory Bowel Diseases, digestive system diseases, Bile Ducts, Intrahepatic, Bile Duct Neoplasms, Sample collection, business, Follow-Up Studies
Abstract: Primary sclerosing cholangitis (PSC) is a rare and chronic cholestatic liver disease of unknown cause commonly associated with inflammatory bowel disease (IBD) and characterized by progressive obliterative fibro-inflammation of the biliary tree. Although the natural course is highly variable, PSC is often progressive, leading to biliary cirrhosis and its complications. In addition, PSC is a condition harbouring broad neoplastic potential with increased susceptibility for the development of both biliary and colon cancer. As in other chronic liver diseases, non-invasive methods play a major role in the diagnosis and monitoring of PSC. MR cholangiography is the key exam for the diagnosis and has replaced diagnostic endoscopic retrograde cholangiopancreatography (ERCP). A strict and standardised protocol for carrying out MR cholangiography is recommended. Liver stiffness measured by FibroScan® correlates with the degree of liver fibrosis, has a prognostic value and should be repeated during follow-up. Invasive methods still play an important role, especially ERCP which is indicated for therapeutic purposes or for endo-biliary sample collection in suspected cholangiocarcinoma (following discussion in a multidisciplinary team meeting) and total colonoscopy which is recommended at the initial diagnosis of any PSC and annually in patients with IBD.
Published: 2021

15. Non-invasive diagnosis and follow-up of autoimmune hepatitis

Author: Charlotte Bouzbib, M. Bourlière, Alexandra Heurgue, Jérôme Gournay, Christophe Bureau, Sara Lemoinne, Bertrand Hanslik, Victor de Lédinghen, Nathalie Ganne-Carrié, Eric Nguyen-Khac, CHU Amiens-Picardie, 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), DESSAIVRE, Louise, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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], Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Montpellierain des maladies du foie et de l’appareil digestif [Montpellier] (C2MFAD), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre 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), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint-Joseph [Marseille], 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), Lemoinne, Sara, and École Pratique des Hautes Études (EPHE)
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Cholangitis, Sclerosing, Disease, Autoimmune hepatitis, Chronic liver disease, overlap syndrome, Gastroenterology, Primary sclerosing cholangitis, Biliary disease, Liver disease, immune system diseases, Internal medicine, medicine, Humans, Hepatology, autoimmune hepatitis, business.industry, Liver Cirrhosis, Biliary, Autoantibody, Overlap syndrome, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, [SDV] Life Sciences [q-bio], Hepatitis, Autoimmune, business, Follow-Up Studies
Abstract: International audience; Autoimmune hepatitis (AIH) is a liver disease characterised by necrotico-inflammatory lesions of hepatocytes, the presence of specific autoantibodies and response to corticosteroid treatment. AIH must be considered in any patient with acute or chronic liver disease. As there is no pathognomonic sign of AIH, the diagnosis is based on a combination of clinical, biological, immunological and histological findings, after excluding other causes of liver disease. The clinical and biological presentation of AIH is variable and AIH can be associated with an autoimmune biliary disease, primary biliary cholangitis or primary sclerosing cholangitis in an overlap syndrome. For these reasons, diagnosis of AIH can be challenging. Even if liver histology remains essential in the diagnosis of AIH, non-invasive tests can be used at different steps of the management of AIH: diagnosis of AIH, notably diagnosis of an overlap syndrome, assessment of severity of AIH, searching for extra-hepatic disease frequently associated to AIH, evaluation of response to therapy, decision of treatment withdrawal. This review aims to provide practical guidelines for the use of non-invasive tests for the diagnosis and the follow-up of AIH. (C) 2021 Published by Elsevier Masson SAS.
Published: 2021
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16. Cost-Utility Analysis of Transarterial Radioembolization With Yttrium-90 Resin Microspheres Compared With Sorafenib in Locally Advanced and Inoperable Hepatocellular Carcinoma

Author: Kevin Zarca, Maroua Mimouni, Helena Pereira, Gilles Chatellier, Valérie Vilgrain, Isabelle Durand-Zaleski, Eric Assenat, Elisabeth Delhom-Christol, Boris Guiu, Alina D. Ilonca, Julie Lonjon, Georges-Philippe Pageaux, Mohamed Abdel-Rehim, Wassim Al-laham, Mohamed Bouattour, Laurent Castera, Arnaud Dieudonné, Rachida Lebtahi, Maxime Ronot, Annie Sibert, Hélène Barraud, Christophe Bazin, Jean-Pierre Bronowicki, Valérie Laurent, Elodie Mathias, Carine Chagneau-Derrode, Rémy Perdrisot, Christine Silvain, Jean-Pierre Tasu, Patrick Borentain RenéGerolami, Olivier Mundler, Jean-Francois Seitz, Vincent Vidal, Christophe Aubé, Antoine Bouvier, Olivier Couturier, Frédéric Oberti, Laurent Vervueren, Isabelle Brenot-Rossi, Jean-Luc Raoul, Anthony Sar-ran, Julia Chalaye, Charlotte Costentin, Emmanuel Itti, Hicham Kobeiter, Alain Luciani, René Adam, Maïté Lewin, Didier Samuel, Julien Edeline, Etienne Garin, Yan Rolland, Isabelle Archambeaud, Thomas Eugene, Eric Frampas, Christophe Cassinotto, Martine Guyot, Jean-Baptiste Hiriart, Bruno Lapuyade, Julien Vergniol, Philippe Bachellier, Julien Detour, Bernard Duclos, Michel Greget, Francois Habersetzer, Alessio Imperiale, Philippe Merle, Agnès Rode, Julie Morvan, Eric Nguyen-Khac, Thierry Yzet, Guillaume Baudin, Patrick Chevallier, Abakar Mahamat, Thierry Piche, Micheline Razzouk, Patrick Hillon, Romaric Loffroy, Michel Toubeau, Julie Vincent, Gabriele Barabino, Nadia Bouarioua, Muriel Cuilleron, Marie Ecochard, Nathalie Prevot-Bitot, Vincent Leroy, Julie Roux, Christian Sengel, Valérie Bourcier, Nathalie Ganne- Carrie, Olivier Seror, Sylvie Costo, Thông Dao, Jean-Pierre Pelage, Jérôme Dumortier, Francesco Giammarile, Pierre-Jean Valette, Nadia Ghazzar, Olivier Pellerin, Julien Taieb, Pierre Weinmann, Alexandra Heurgue- Berlot, Claude Marcus, Daniele Sommacale, Maria-Angéla Castilla-Lièvre, Sophie Maitre, Lysiane Marthey, Direction de la Recherche Clinique et de l'Innovation [AP-HP] (DRCI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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), CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), 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), Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Département radiologie diagnostique et interventionnelle Saint Eloi [CHRU Montpellier], Pôle Digestif [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Equipe IFTIM [ImViA - EA7535], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Imagerie et Vision Artificielle [Dijon] (ImViA), Université de Bourgogne (UB)-Université de Bourgogne (UB), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and CHU Saint-Eloi-Université de Montpellier (UM)
Subjects: Sorafenib, Oncology, medicine.medical_specialty, Randomization, Carcinoma, Hepatocellular, Tare weight, Hepatocellular carcinoma, Cost-Benefit Analysis, [SDV.CAN]Life Sciences [q-bio]/Cancer, 02 engineering and technology, 030204 cardiovascular system & hematology, Transarterial Radioembolization, 03 medical and health sciences, 020210 optoelectronics & photonics, 0302 clinical medicine, Quality of life, Internal medicine, 0202 electrical engineering, electronic engineering, information engineering, medicine, Humans, Pharmacology (medical), Yttrium radioisotopes, Survival analysis, Pharmacology, Cost–utility analysis, business.industry, Liver Neoplasms, Cost-utility analysis, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, Microspheres, Quality of Life, business, medicine.drug
Abstract: International audience; Purpose: The SARAH (Sorafenib Versus Radioembolization in Advanced Hepatocellular Carcinoma) trial (ClinicalTrials.gov Identifier NCT01482442) did not show a significant survival benefit for patients treated with transarterial radioembolization (TARE) compared with continuous oral sorafenib. The improved toxicity profile of patients treated with TARE in the trial, however, could result in a quality of life benefit in economic evaluations. Our objective was to perform a cost-utility analysis of TARE versus sorafenib for locally advanced and inoperable hepatocellular carcinoma.Methods: This study used patient-level data of the SARAH trial regarding resource use, progression-free and overall survival, and quality of life for the within-trial period for the patients who received at least 1 dose of sorafenib or 1 treatment with TARE according to their randomization arm. Data were extrapolated by using a partitioned survival model that incorporated costs and health outcomes, measured in life-years and quality-adjusted life-years (QALYs).Findings: The use of TARE resulted in an average loss of 0.036 life-year and a gain of 0.006 QALY compared with sorafenib. The aerage cost for the TARE arm was €17,179 (95% CI, 9,926-24,280) higher than the sorafenib arm, for an incremental cost-effectiveness ratio of €3,153,086/QALY. The probabilistic sensitivity analysis revealed a 50% risk that the TARE strategy was dominated. TARE was consistently dominated by sorafenib or had an incremental cost-effectiveness ratio more than €450,000/QALY in all sensitivity analyses.Implications: This economic evaluation of SARAH found that using radioembolization with yttrium-90 microspheres for the treatment of hepatocellular carcinoma was not a cost-effective option at the usually accepted willingness-to-pay thresholds.
Published: 2021
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17. Nurse coordinator roles in the management of patients with hepatocellular carcinoma: A French national survey

Author: Ljiljana Jovic, Nathalie Ganne-Carrié, Jean-Baptiste Hazo, Espérie Burnet, Anne Leclercq, Julie Devictor, Mohamed Bouattour, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Hôpital Avicenne [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 Paris Cité (UPCité), and Gestionnaire, Hal Sorbonne Université
Subjects: medicine.medical_specialty, Carcinoma, Hepatocellular, Chronic liver disease, Patient pathway, Case management, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, MESH: Patient Care Team, Nursing, MESH: Liver Neoplasms, MESH: Nurse Administrators, Internal medicine, Surveys and Questionnaires, Health care, medicine, Humans, Nurse Administrators, Prospective Studies, MESH: Surveys and Questionnaires, Radiation treatment planning, MESH: Carcinoma, Hepatocellular, MESH: Cohort Studies, Nurse navigator, Patient Care Team, MESH: Humans, Hepatology, business.industry, Liver Neoplasms, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, University hospital, medicine.disease, MESH: Prospective Studies, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Nurse roles, MESH: France, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cohort, 030211 gastroenterology & hepatology, France, business, Liver cancer, Patient care pathway
Abstract: Hepatocellular carcinoma (HCC) mostly occurs in patients with chronic liver disease (CLD). HCC treatment may have a direct impact on CLD prognosis. HCC management can therefore become complex, involving multiple health care providers, such as oncologists, hepatologists, radiologists, and surgeons. In France, dedicated nurses have been involved in patient care pathways. Their impact is poorly documented. Purpose To determine the country-wide distribution of HCC nurse coordinators in French health care settings and to describe their roles and responsibilities. Patients and methods A survey using a multi-item questionnaire (including center characteristics, nurse coordinator characteristics, and quality indicators such as patient care pathway initiation timeline, scheduled length of hospital stay, diagnostic disclosure process) was conducted. All French liver cancer centers planning to participate in a prospective national cohort study for patients with HCC (CHIEF Cohort) were invited to take part in the survey. Bivariate analysis compared centers with a nurse coordinator to those without. Results Among the 42 of 72 centers that replied, 14 treated fewer than 75 HCC patients. Treatment mostly took place in hepatology units (34/42). Sixteen nurse coordinators were part of the health care team in 13 of the 42 centers. Among these 13 centers, 11 were university hospitals and 11 followed more than 75 patients per year. The median number of patients followed in these centers was 300 (min–max 44–600) in 2017. All nurse coordinators were involved in providing patient information and counseling. Other roles included treatment monitoring (13/16), care coordination (12/16), psychological support (12/16) and treatment planning (11/16). Thirteen nurse coordinators conducted diagnostic disclosure nurse consultations; seven conducted initial patient contact consultations; and six held outpatient nurse consultations, with wide heterogeneity between centers. The presence of a nurse coordinator was associated with completion of the full diagnostic disclosure process (p = 0.045). Conclusion In France, nurse coordinators for HCC patient pathway management are present mainly in university hepatology units with a caseload of more than 75 patients per year. All provide patient information and counseling but their roles in care coordination, patient support and holistic assessment are heterogeneous and not standardized.
Published: 2021
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18. The Use of Rifaximin in the Prevention of Overt Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt : A Randomized Controlled Trial

Author: Sébastien Dharancy, Isabelle Archambeaud, Aurélie Plessier, Agnès Sommet, Vanessa Rousseau, Louis d’Alteroche, Victor de Lédinghen, Frédéric Oberti, Nathalie Ganne-Carrié, Patrick Borentain, Nicolas Carbonell, Christophe Bureau, Jean-Pierre Vinel, Jean-Marie Peron, Dominique Thabut, Caroline Jezequel, CHU Toulouse [Toulouse], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Lille, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), grant PRHC 12 555 101 from the French Public Health Ministry, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Placebo, 01 natural sciences, Gastroenterology, Rifaximin, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Double-Blind Method, Gastrointestinal Agents, Randomized controlled trial, law, Internal medicine, Internal Medicine, Humans, Medicine, 030212 general & internal medicine, 0101 mathematics, Adverse effect, Hepatic encephalopathy, First episode, business.industry, 010102 general mathematics, Ascites, General Medicine, Middle Aged, medicine.disease, 3. Good health, chemistry, Hepatic Encephalopathy, Female, France, Portasystemic Shunt, Transjugular Intrahepatic, Gastrointestinal Hemorrhage, business, Transjugular intrahepatic portosystemic shunt
Abstract: International audience; BACKGROUND: The efficacy of rifaximin in the secondary prevention of overt hepatic encephalopathy (HE) is well documented, but its effectiveness in preventing a first episode in patients after transjugular intrahepatic portosystemic shunt (TIPS) has not been established. OBJECTIVE: To determine whether rifaximin prevents overt HE after TIPS compared with placebo. DESIGN: Randomized, double-blind, multicenter, placebo-controlled trial. (ClinicalTrials.gov: NCT02016196). PARTICIPANTS: 197 patients with cirrhosis undergoing TIPS for intractable ascites or prevention of variceal rebleeding. INTERVENTION: Patients were randomly assigned to receive rifaximin (600 mg twice daily) or placebo, beginning 14 days before TIPS and continuing for 168 days after the procedure. MEASUREMENTS: The primary efficacy end point was incidence of overt HE within 168 days after the TIPS procedure. RESULTS: An episode of overt HE occurred in 34% (95% CI, 25% to 44%) of patients in the rifaximin group (n = 93) and 53% (CI, 43% to 63%) in the placebo group (n = 93) during the postprocedure period (odds ratio, 0.48 [CI, 0.27 to 0.87]). Neither the incidence of adverse events nor transplant-free survival was significantly different between the 2 groups. LIMITATIONS: The study’s conclusion applies mainly to patients with alcoholic cirrhosis, who made up the study population. The potential benefit of rifaximin 6 months after TIPS and beyond remains to be investigated. CONCLUSION: In patients with cirrhosis treated with TIPS, rifaximin was well tolerated and reduced the risk for overt HE. Rifaximin should therefore be considered for prophylaxis of post-TIPS HE. PRIMARY FUNDING SOURCE: French Public Health Ministry.
Published: 2021
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19. Predictive Factors for Hepatocellular Carcinoma in Chronic Hepatitis B Using Structural Equation Modeling: A Prospective Cohort Study

Author: Jean-Pierre Bronowicki, Clovis Lusivika-Nzinga, Jean-Charles Duclos-Vallée, Ghassan Riachi, Anne Minello, Thomas Decaens, Louis d’Alteroche, Fabrice Carrat, Isabelle Portal, François Raffi, Fabien Zoulim, Sophie Metivier, Véronique Loustaud-Ratti, François Habersetzer, Jérôme Gournay, Olivier Chazouillères, Paul Calès, Victor de Ledinghen, Xavier Causse, Stanislas Pol, Céline Dorival, Isabelle Rosa, Dominique Larrey, Tarik Asselah, Marc Bourlière, Claire Geist, Nathanael Lapidus, Laurent Lam, Moana Gelu-Simeon, Laurent Alric, Vincent Leroy, Hélène Fontaine, Armand Abergel, Nathalie Ganne, Dominique Thabut, Philippe Mathurin, Albert Tran, Dominique Guyader, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint-Joseph [Marseille], Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre 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), Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, 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 de Paris (UP), Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, CRHU Nancy, Physiopathologie des Maladies Inflammatoires de l'Intestin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHI Créteil, Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Régional d'Orléans (CHRO), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'hépatologie [CHU Saint-Antoine], CHU Pointe-à-Pitre/Abymes [Guadeloupe], Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), CHU Toulouse [Toulouse], 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), CHU Rouen, Normandie Université (NU), Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), 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), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital de la Timone [CHU - APHM] (TIMONE), Immunité Innée - Innate Immunity, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], The ANRS CO22 HEPATHER cohort is sponsored and funded by INSERM‐ANRS and conducted in collaboration with Association Française pour l'étude du Foie (AFEF). The cohort received supports from ANR (Agence Nationale de la Recherche), DGS (Direction Générale de la Santé), MSD, Janssen, Gilead, Abbvie, BMS, and Roche., Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Pathologies biliaires, fibrose et cancer du foie [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université d'Angers (UA)-Université de Rennes (UR)-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 ), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], 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 Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: Male, Liver Cancer, medicine.medical_specialty, Hepatocarcinogenesis, Hepatitis B virus, Carcinoma, Hepatocellular, Epidemiology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Liver transplantation, Sciences du Vivant [q-bio]/Cancer, medicine.disease_cause, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Hepatitis B, Chronic, [SDV.CAN] Life Sciences [q-bio]/Cancer, Risk Factors, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, Aged, Hepatology, business.industry, Liver Neoplasms, Carcinoma, Hepatocellular, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cohort, 030211 gastroenterology & hepatology, Metabolic syndrome, business, Liver cancer
Abstract: International audience; BACKGROUND and AIMS: The factors predicting hepatocellular carcinoma (HCC) occurrence in chronic hepatitis B need to be precisely known to improve its detection. We identified pathways and individual predictive factors associated with HCC in the ANRS CO22 HEPATHER cohort. METHODS: The study analyzed HBV-infected patients recruited at 32 French expert hepatology centers from August 6, 2012, to December 31, 2015. We excluded patients with chronic HCV, HDV and a history of HCC, decompensated cirrhosis or liver transplantation. Structural equation models were developed to characterize the causal pathways leading to HCC occurrence. The association between clinical characteristics (age, gender, body-mass index, liver fibrosis, alcohol consumption, smoking status, diabetes, hypertension, dyslipidemia, alpha-fetoprotein, HBV DNA levels, antiviral therapy) and incident HCC was quantified. RESULTS: Among the 4,489 patients included, 33 patients reported incident HCC. The median follow-up was 45.2 months. Age (β = 0.18 by decade, 95% CI 0.14-0.23), male gender (β = 0.23, 95% CI 0.18-0.29), metabolic syndrome (β = 0.28, 95% CI 0.22-0.33), alcohol consumption (β = 0.09, 95% CI 0.05-0.14) and HBV DNA (β = 0.25, 95% CI 0.17-0.34) had a significant and direct effect on the occurrence of advanced liver fibrosis. Liver fibrosis (β = 0.71, 95% CI 0.55-0.87) predicted, in turn, the occurrence of HCC. CONCLUSIONS: Liver fibrosis mediates the effects of age, gender, alcohol, metabolic syndrome and HBV DNA on the occurrence of HCC. Elderly men with chronic hepatitis B, risky alcohol use, advanced liver fibrosis, metabolic syndrome and high HBV DNA levels should be monitored closely to detect the development of HCC.
Published: 2021
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20. Combination of Model for End-Stage Liver Disease and Lactate Predicts Death in Patients Treated With Salvage Transjugular Intrahepatic Portosystemic Shunt for Refractory Variceal Bleeding

Author: Charlotte Bouzbib, Olivier Sutter, Juan Carlos García-Pagán, Jean-Marie Péron, Vincent Le Pennec, Christophe Bureau, Nathalie Ganne-Carrié, Maxime Mallet, Dominique Thabut, Pol Olivas, Anna Baiges, Hélène Larrue, Thong Dao, Lucile Moga, Eric Trepo, Virginia Hernández-Gea, Aurélie Walter, Isabelle Ollivier-Hourmand, Marika Rudler, J.-C. Nault, Manon Allaire, and Marie Angèle Robic
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Organ Dysfunction Scores, medicine.medical_treatment, Esophageal and Gastric Varices, Gastroenterology, End Stage Liver Disease, Liver disease, Model for End-Stage Liver Disease, Predictive Value of Tests, Internal medicine, Hypertension, Portal, medicine, Humans, Lactic Acid, Survival rate, Salvage Therapy, Hepatology, business.industry, Middle Aged, medicine.disease, Prognosis, Survival Analysis, Exact test, Spain, Cohort, Portal hypertension, Female, France, Portasystemic Shunt, Transjugular Intrahepatic, business, Gastrointestinal Hemorrhage, Transjugular intrahepatic portosystemic shunt, Biomarkers
Abstract: BACKGROUND AND AIMS Data about the prognosis of salvage transjugular intrahepatic portosystemic shunt (TIPS) using covered stents for refractory variceal bleeding caused by portal hypertension are scarce. We aimed to assess survival and to identify predictors of mortality in these patients. APPROACH AND RESULTS One hundred sixty-four patients with cirrhosis from five centers treated with salvage TIPS between 2007 and 2017 were retrospectively divided into a derivation cohort (83 patients) and a validation cohort (81 patients). Comparisons were performed using the Mann-Whitney and Fischer's exact test. Six-week overall survival (OS) was correlated with variables on the day of the TIPS using Kaplan-Meier curves with log-rank test and univariate/multivariate analyses using the Cox model. Eighty-three patients were included in the derivation cohort (male, 78%; age, 55 years, alcohol-associated cirrhosis, 88%; Model for End-Stage Liver Disease [MELD], 19 [15-27]; arterial lactate, 3.7 mmol/L [2.0-8.3]). Six-week OS rate was 58%. At multivariate analysis, the MELD score (OR, 1.064; 95% CI, 1.005-1.126; P = 0.028) and arterial lactate (OR, 1.063; 95% CI, 1.013-1.114; P = 0.032) were associated with 6-week OS. Six-week OS rates were 100% in patients with arterial lactate ≤2.5 mmol/L and MELD score ≤ 15 and 5% in patients with lactate ≥12 mmol/L and/or MELD score ≥ 30. The 81 patients of the validation cohort had similar MELD and arterial lactate level but lower creatinine level (94 vs 106 µmol/L, P = 0.008); 6-week OS was 67%. Six-week OS rates were 86% in patients with arterial lactate ≤2.5 mmol/L and MELD score ≤ 15 and 10% for patients with lactate ≥12 mmol/L and/or MELD score ≥ 30. In the overall cohort, rebleeding rate was 15.8% at 6 weeks, and the acute-on-chronic liver failure grade (OR, 1.699; 95% CI, 1.056-1.663; P = 0.040) was independently associated with rebleeding. CONCLUSIONS After salvage TIPS, 6-week mortality remains high and can be predicted by MELD score and lactate. Survival rate at 6 weeks was >85% in patients with arterial lactate ≤2.5 mmol/L and MELD score ≤ 15, while mortality was >90% for lactate ≥12 mmol/L and/or MELD score ≥ 30.
Published: 2021

21. 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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22. Impact of cirrhosis aetiology on incidence and prognosis of hepatocellular carcinoma diagnosed during surveillance

Author: Nathalie Ganne-Carrié, Pierre Nahon, Cendrine Chaffaut, Gisèle N’Kontchou, Richard Layese, Etienne Audureau, Sylvie Chevret, Isabelle Archambeaud, Louis d’Alteroche, Frédéric Oberti, Dominique Roulot, Christophe Moreno, Alexandre Louvet, Thông Dao, Romain Moirand, Odile Goria, Eric Nguyen-Khac, Nicolas Carbonell, Jean-Charles Duclos-Vallée, Stanislas Pol, Victor de Ledinghen, Violaine Ozenne, Jean Henrion, Jean-Marie Péron, Albert Tran, Gabriel Perlemuter, Xavier Amiot, Jean-Pierre Zarski, Tarik Asselah, Dominique Guyader, Hélène Fontaine, Georges-Philippe Pageaux, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Jean-Pierre Bronowicki, Thomas Decaens, Ghassan Riachi, Paul Calès, Laurent Alric, Marc Bourlière, Philippe Mathurin, Sebastien Dharancy, Jean-Frédéric Blanc, Armand Abergel, Olivier Chazouillères, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Claire Wartelle, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Brigitte Bernard-Chabert, Sophie Hillaire, Vincent Di Martino, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Nord, 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), 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), Hôpital Henri Mondor, Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANRS CO12 CirVir group: Pierre Nahon1, Tarik Asselah2, Dominique Guyader3, Stanislas Pol4, Hélène Fontaine4, Georges-Philippe Pageaux5, Victor De Lédinghen6, Denis Ouzan7, Fabien Zoulim8, Dominique Roulot9, Albert Tran10, Jean-Pierre Bronowicki11, Thomas Decaens12, Ghassan Riachi13, Paul Calès14, Jean-Marie Péron15, Laurent Alric16, Marc Bourlière17, Philippe Mathurin18, Sebastien Dharancy18, Jean-Frédéric Blanc19, Armand Abergel20, Olivier Chazouillères21, Ariane Mallat22, Jean-Didier Grangé23, Pierre Attali24, Louis d’Alteroche25, Claire Wartelle26, Thông Dao27, Dominique Thabut28, Christophe Pilette29, Christine Silvain30, Christos Christidis31, Eric Nguyen-Khac32, Brigitte Bernard-Chabert 33, Sophie Hillaire34, Vincent Di Martino35. 1AP-HP, Hôpital Avicenne, Service d’Hépatologie, Bobigny, Université Sorbonne Paris Nord, Bobigny et INSERM U1138, Université de Paris, 2AP-HP, Hôpital Beaujon, Service d’Hépatologie, and University Paris Diderot, Sorbonne Paris Cité, CRI, UMR 1149, 3CHU Pontchaillou, Service d’Hépatologie, Rennes, 4AP-HP, Hôpital Cochin, Département d’Hépatologie et INSERM UMS20 et U1223, Institut Pasteur, Université Paris Descartes, Paris, 5Hôpital Saint Eloi, Service d’Hépatologie, Montpellier, 6Hôpital Haut-Lévêque, Service d’Hépatologie, Bordeaux, 7Institut Arnaud Tzanck, Service d’Hépatologie, St Laurent du Var, 8Hôpital Hôtel Dieu, Service d’Hépatologie, Lyon, 9AP-HP, Hôpital Avicenne, Service de Medeine Interne, Bobigny, 10CHU de Nice, Service d’Hépatologie, et INSERM U1065, Université de Nice-Sophia-Antipolis, Nice, 11Hôpital Brabois, Service d’Hépatologie, Vandoeuvre-les-Nancy, 12Hôpital Michallon, Service d’Hépatologie, Grenoble, 13Hôpital Charles-Nicolle, Service d’Hépatologie, Rouen, 14CHU d’Angers, Service d’Hépatologie, Angers, 15Hôpital Purpan, Service d’Hépatologie, Toulouse, 16CHU Toulouse, Service de Médecine Interne-Pôle Digestif UMR 152, Toulouse, 17Hôpital Saint Joseph, Service d’Hépatologie, Marseille, 18Hôpital Claude Huriez, Service d’Hépatologie, Lille, 19Hôpital St André, Service d’Hépatologie, Bordeaux, 20Hôpital Hôtel Dieu, Service d’Hépatologie, Clermont-Ferrand, 21AP-HP, Hôpital Saint-Antoine, Service d’Hépatologie, Paris, 22AP-HP, Hôpital Henri Mondor, Service d’Hépatologie, Créteil, 23AP-HP, Hôpital Tenon, Service d’Hépatologie, Paris, 24AP-HP, Hôpital Paul Brousse, Service d’Hépatologie, Villejuif, 25Hôpital Trousseau, Unité d’Hépatologie, CHRU de Tours, 26Hôpital d’Aix-En-Provence, Service d’Hépatologie, Aix-En-Provence, 27Hôpital de la Côte de Nacre, Service d’Hépatologie, Caen, 28AP-HP, Groupe Hospitalier de La Pitié-Salpêtrière, Service d’Hépatologie, Paris, 29CHU Le Mans, Service d’Hépatologie, Le Mans, 30CHU de Poitiers, Service d’Hépatologie, Poitiers, 31Institut Mutualiste Montsouris, Service d’Hépatologie, Paris, 32Hôpital Amiens Nord, Service d’Hépatologie, Amiens, 33Hôpital Robert Debré, Service d’Hépatologie, Reims, 34Hôpital Foch, Service d’Hépatologie, Suresnes, 35Hôpital Jean Minjoz, Service d’Hépatologie, Besançon. France., CIRRAL group: Nathalie Ganne-Carrié1, Cendrine Chaffaut2, Isabelle Archambeaud3, Louis d’Alteroche4, Frédéric Oberti5, Dominique Roulot6, Christophe Moreno7, Alexandre Louvet8, Thông Dao9, Romain Moirand10, Odile Goria11, Eric Nguyen-Khac12, Nicolas Carbonell13, Jean-Charles Duclos-Vallée14, Stanislas Pol15,16, Victor de Ledinghen17, Violaine Ozenne18, Jean Henrion19, Jean-Marie Péron20, Albert Tran21,22, Gabriel Perlemuter23, Xavier Amiot24, Jean-Pierre Zarski25, Sylvie Chevret2. 1AP-HP, Hôpital Avicenne, Service d’Hépatologie, Bobigny, Université Sorbonne Paris Nord, Bobigny et INSERM U1138, Université de Paris, 2SBIM, APHP, Hôpital Saint-Louis, Paris, Inserm, UMR-1153, ECSTRA Team, Paris, France, 3Liver, CHU, Nantes, France, 4Liver Unit, University Hospital, Tours, France, 5Liver Unit, University Hospital, Angers, France, 6AP-HP, Hôpital Avicenne, Service de Médecine Interne, Bobigny, Université Sorbonne Paris Nord, Bobigny, 7Liver unit, CUB Hôpital Erasme, Université Libre de Bruxelles, Belgium, 8Liver Unit, University Hospital, Lille, France, 9Liver Unit, University Hospital, Caen, France, 10Liver Unit, University Hospital, Rennes, France, 11Liver Unit, University Hospital, Rouen, France, 12Liver Unit, University Hospital, Amiens, France, 13 Liver Unit, APHP, CHU Saint-Antoine, Paris, France, 14Liver Unit, APHP, CHU Paul Brousse, Villejuif, France, 15Université Paris Descartes, APHP, Liver Unit, Hôpital Cochin, 16INSERM U1223, Institut Pasteur, Paris, France, 17Hepatology Unit, University Hospital, CHU Bordeaux, France, 18Liver Unit, APHP, CHU Lariboisière, Paris, France, 19Liver Unit, University Hospital, Haine Saint-Paul, Belgium, 20Liver Unit, Universitary Hospital Purpan, University Paul Sabatier III, Toulouse, 21Institut National de la Santé et de la Recherche Médicale (INSERM), U1065, Team 8, 'Hepatic Complications in Obesity', Nice, F-06204, Cedex 3, France, 22University Hospital of Nice, Digestive Centre, Nice, F-06202, Cedex 3, France, 23Liver Unit, University Hospital, Béclère, APHP, Clamart, France, 24Liver Unit, APHP, CHU Tenon, Paris, France, and 25Clinique d’hépato-gastroentérologie pôle Digidune CHU de Grenoble, France
Subjects: Alcoholic liver disease, medicine.medical_specialty, Cirrhosis, primary liver cancer, VIR, virus-related, ECOG Performance Status, [SDV.CAN]Life Sciences [q-bio]/Cancer, MIX, alcohol and virus-related, RC799-869, Gastroenterology, law.invention, Randomized controlled trial, law, Internal medicine, Internal Medicine, medicine, Immunology and Allergy, Hepatology, business.industry, Incidence (epidemiology), cirrhosis, competing risk analysis, US, abdominal ultrasound, Hazard ratio, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Diseases of the digestive system. Gastroenterology, medicine.disease, HR, hazard ratio, Hepatocellular carcinoma, ALC, alcohol-related, Etiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, HCC, hepatocellular carcinoma, Research Article, alcoholic liver disease
Abstract: Background & Aims In this study we aimed to analyse the impact of the aetiology of cirrhosis on the incidence, characteristics and prognosis of hepatocellular carcinoma (HCC) diagnosed during a surveillance program. Methods Individual data from a randomized trial and 2 prospective cohorts of patients with compensated histologically proven cirrhosis recruited between 2000 and 2016 were pooled. The influence of cirrhosis aetiology on survival after HCC detection was assessed using multivariable regression models. Results Among 3,533 patients (1,926 virus [VIR], 1,167 alcohol [ALC], 440 combined [MIX]), 431 were diagnosed with HCC after a median follow-up of 57.1 months. The 5-year HCC incidence was lowest in ALC (VIR 12.6%, ALC 9.1%, MIX 14.3%, p = 0.04). At the time of diagnosis, tumour burden and Child-Pugh score were comparable across aetiology groups, but early BCLC stages (0/A) were significantly less frequent in ALC (VIR 80%, ALC 37%, MIX 72%) as a result of worse ECOG performance status. However, similar access to first-line curative HCC treatment was reported across aetiology groups (p = 0.68). Median survival after HCC diagnosis was significantly reduced in ALC (VIR 39, ALC 21, MIX 34 months, p = 0.02). However, when adjusting for tumour size, ECOG and Child-Pugh score, the aetiology of the underlying cirrhosis no longer had a significant impact. Conclusion Compared to patients with virus-related cirrhosis, patients with alcohol-related compensated cirrhosis enrolled in a surveillance program have: i) the lowest 5-year HCC incidence; ii) worse overall prognosis, mostly driven by a poor general condition, despite similar access to first-line curative treatment. Lay summary It has been suggested that early detection of hepatocellular carcinoma (HCC) may be futile in patients with alcohol-related cirrhosis. By comparing outcomes in more than 3,000 patients with compensated cirrhosis included in surveillance programs, this study suggests that HCC surveillance enables early diagnosis in most patients with alcohol-related cirrhosis despite a higher competing risk of death in these patients. We also report similar access to first-line curative HCC treatment in these patients compared to those with viral cirrhosis, despite higher rates of comorbidities and impaired liver function. Following HCC detection, the later parameters were major drivers of death irrespective of the cause of cirrhosis. Registration CHC2000 (NCT00190385) and CIRRAL (NCT01213927) cohorts were registered at ClinicalTrials.gov and the full protocols are available at the following links (https://clinicaltrials.gov/ct2/show/NCT00190385) and https://clinicaltrials.gov/ct2/show/NCT01213927, respectively). The full CirVir protocol is available via the ANRS Web site (http://anrs.fr)., Graphical abstract, Highlights • Alcohol-related cirrhosis linked to the lowest incidence of HCC, the lowest overall survival and the highest incidence of decompensation. • Alcohol-related cirrhosis linked to fewer cases of early stage HCC, although tumour burden and Child-Pugh score were comparable across groups. • Patients with alcohol-related cirrhosis had worse survival after HCC diagnosis than those with virus-related cirrhosis. • The aetiology of cirrhosis had no impact on survival after HCC diagnosis following adjustment for other potential prognostic factors.
Published: 2021
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23. New insights into the pathophysiology and clinical care of rare primary liver cancers

Author: François Cauchy, Olivier Soubrane, Elia Gigante, Valérie Paradis, Nathalie Ganne-Carrié, Jean-Charles Nault, Maxime Ronot, 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 de Paris (UP), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpitaux Universitaires Paris Nord Val de Seine (HUPNVS), Hôpital Beaujon [AP-HP], 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), and CCSD, Accord Elsevier
Subjects: Pathology, Hepatocellular carcinoma, medicine.medical_treatment, liver imaging reporting and data system, Review, Liver transplantation, selective internal radiation therapy, WHO, 0302 clinical medicine, SIRT, HCC, cHCC-CCA, fluorescence in situ hybridisation, AFP, alpha-fetoprotein, HAS, hepatic angiosarcoma, Selective internal radiation therapy, Gastroenterology, Epithelial cell adhesion molecule, Mixed tumor, hepatic epithelioid haemangioendothelioma, 3. Good health, [SDV] Life Sciences [q-bio], EpCAM, epithelial cell adhesion molecule, HEH, hepatic epithelioid haemangioendothelioma, 030220 oncology & carcinogenesis, LI-RADS, 030211 gastroenterology & hepatology, cHCC-CCA, combined hepatocholangiocarcinoma, Fibrolamellar Carcinoma, IHC, immunohistochemistry, CK, cytokeratin, medicine.medical_specialty, FLC, fibrolamellar carcinoma, CCA, cholangiocarcinoma, APHE, AFP, CEUS, contrast-enhanced ultrasound, RT-PCR, Hepatic hemangioendothelioma, LI-RADS, liver imaging reporting and data system, World Health Organization, LT, liver transplantation, WHO, World Health Organization, 03 medical and health sciences, FISH, CA19-9, carbohydrate antigen 19-9, 5-FU, CCA, TACE, arterial phase hyperenhancement, HEH, HepPar1, RT-PCR, reverse transcription PCR, Fibrolamellar carcinoma, medicine.disease, chemistry, CLC, EpCAM, CEUS, CLC, cholangiolocellular carcinoma, cytokeratin, Hepatocholangiocarcinoma, IHC, [SDV]Life Sciences [q-bio], combined hepatocholangiocarcinoma, Hepatic angiosarcoma, chemistry.chemical_compound, reverse transcription PCR, LT, intrahepatic cholangiocarcinoma, 5-FU, 5-Fluorouracil, Immunology and Allergy, iCCA, intrahepatic cholangiocarcinoma, Intrahepatic Cholangiocarcinoma, liver transplantation, CA19-9, carbohydrate antigen 19-9, FISH, fluorescence in situ hybridisation, FLC, SIRT, selective internal radiation therapy, CK, immunohistochemistry, cholangiolocellular carcinoma, cholangiocarcinoma, epithelial cell adhesion molecule, 5-Fluorouracil, alpha-fetoprotein, Internal Medicine, medicine, HepPar1, hepatocyte specific antigen antibody, transarterial chemoembolisation, hepatocyte specific antigen antibody, iCCA, Hepatology, business.industry, TACE, transarterial chemoembolisation, HAS, APHE, arterial phase hyperenhancement, business, HCC, hepatocellular carcinoma, contrast-enhanced ultrasound
Abstract: International audience; Hepatocholangiocarcinoma, fibrolamellar carcinoma, hepatic haemangioendothelioma and hepatic angiosarcoma represent less than 5% of primary liver cancers. Fibrolamellar carcinoma and hepatic haemangioendothelioma are driven by unique somatic genetic alterations (DNAJB1-PRKCA and CAMTA1-WWTR1 fusions, respectively), while the pathogenesis of hepatocholangiocarcinoma remains more complex, as suggested by its histological diversity. Histology is the gold standard for diagnosis, which remains challenging even in an expert centre because of the low incidences of these liver cancers. Resection, when feasible, is the cornerstone of treatment, together with liver transplantation for hepatic haemangioendothelioma. The role of locoregional therapies and systemic treatments remains poorly studied. In this review, we aim to describe the recent advances in terms of diagnosis and clinical management of these rare primary liver cancers.
Published: 2021
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24. Impact of COVID-19 on the management of hepatocellular carcinoma in a high-prevalence area

Author: Olivier Seror, Daniele Sommacale, Alain Luciani, Nathalie Ganne-Carrié, Pierre Balladur, Violaine Ozenne, Manon Allaire, Ailton Sepulveda, François Cauchy, Clémence Hollande, Giuliana Amaddeo, Lorraine Blaise, Hélène Regnault, Marco Dioguardi Burgio, François Paye, Mohamed Bouattour, Chetana Lim, Pierre-Philippe Massault, Vincent Leroy, Anthony Dohan, Edouard Larrey, Stanislas Pol, Françoise Roudot-Thoraval, Raffaele Brustia, Sanaa El Mouhadi, Olivier Scatton, Marie Lequoy, Valérie Vilgrain, Jean-Charles Nault, CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Cirrhosis, Hepatocellular carcinoma, medicine.medical_treatment, TACE, Trans-arterial-chemo-embolization, Liver transplantation, law.invention, MTB, multi-disciplinary tumour board, MELD, Model for End stage Liver Disease, 0302 clinical medicine, Model for End-Stage Liver Disease, Interquartile range, law, Immunology and Allergy, OR, Odd Ratio, AP-HP, Assistance Publique-Hôpitaux de Paris, BCLC, Barcelona Clinic Liver Cancer, Gastroenterology, ICU, intensive care unit, Intensive care unit, 3. Good health, Management, 030220 oncology & carcinogenesis, 2019-nCoV, 030211 gastroenterology & hepatology, medicine.medical_specialty, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, LT, liver transplantation, Article, AFP, Alpha-fetoprotein, 03 medical and health sciences, IR, interventional radiology, Internal medicine, Internal Medicine, medicine, lcsh:RC799-869, IQR, interquartile range, Intention-to-treat analysis, Hepatology, AFEF, Societé Francaise d’Hépatologie, business.industry, COVID-19, SIRT, Selective internal radiation therapy, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Odds ratio, medicine.disease, PCR-RT, PCR real time, aOR, adjusted OR, CI, Confidence Interval, digestive system diseases, ITT, intention to treat, LR, liver resection, CT, computerized-tomography, EASL, European Association of Study of Liver, lcsh:Diseases of the digestive system. Gastroenterology, HCC, hepatocellular carcinoma, business
Abstract: Background Patients affected by HCC represent a vulnerable population during the COVID-19 pandemic and may suffer from the unusual allocation of healthcare resources. The aim of this study was to determine the impact of the COVID-19 pandemic on the management of HCC patients within six French referral centers of the metropolitan area of Paris. Materials and methods We performed a multicenter, retrospective, cross-sectional study on the management of patients affected by HCC during the first six weeks of COVID-19 pandemic (exposed), compared to the same period in 2019 (unexposed). Were included all patients discussed in multidisciplinary tumor meeting (MTB) and/or undergoing radiological or surgical programmed procedure during the study period, in a curative or palliative intent. Endpoints were the number of patients with a modification in the treatment strategy, or a delay in decision-to-treatment. Results After screening, n=670 patients were included (n=293 Exposed to COVID, n=377 Unexposed to COVID). A decrease of the numbers of patients with HCC presented in MTB in 2020 (p=0.034) and with a first diagnosis of HCC (n=104 Exposed to COVID, n=143 Unexposed to COVID, p=0.083) was find. Modification in the treatment strategy was observed in 13.1% of patients, with no differences between the two periods. Nevertheless 21.5% versus 9.5% of patients experienced a treatment delay longer than 1 month in 2020 compared to 2019 (p, Graphical abstract, Highlights • In COVID period, a decrease of the numbers of patients with hepatocellular carcinoma presented in Multidisciplinary Tumour Board and, in particular, with a first diagnosis of HCC was find. • Globally, modification in the treatment strategy was observed in 13.1% of patients, with no differences between the two periods but the main reason was significantly different in 2020 compared to 2019: COVID-19 in 2020 vs tumour progression in 2019. • More than 21% of patients experienced a treatment delay longer than 1 month in COVID period compared to 9.5% in 2019 , specially, in subgroup with active, recurrent HCC. The main reasons for the delay of treatment in 2020 was COVID-19 infection related • In 2020, 7.1% of patients had a diagnosis of an active COVID-19 infection and 4/21 (19.1%) died., During COVID pandemic era, less patients with hepatocellular carcinoma (HCC) have been presented in multidisciplinary tumor bord, specially with a first diagnosis of HCC
Published: 2021
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25. International French-speaking multicentre practice survey on hepatic hydrothorax (HH) : Results of the 'Hep Hep' study among 529 hepatogastroenterologist (HG) or pneumologist (PN) respondents

Author: Nathalie Ganne-Carrié, Eric Nguyen-Khac, Laure Elkrief, Isabelle Ollivier, Jean-Baptiste Nousbaum, Chantal Raherison, Marc Bourlière, Jean-François Cadranel, Véronique Loustaud-Ratti, Christophe Bureau, Xavier Causse, Manon Allaire, Jean-Marie Péron, Philippe Sogni, Bernard Maitre, Thong Dao, Bertrand Hanslik, Tristan Le Magoarou, Thierry Thevenot, Cadranel Jacques, Groupe Hospitalier Public du Sud de l'Oise [Creil] (GHPSO), Theranoscan [CHU Tenon] (GRC 4), CHU Tenon [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)-Sorbonne Université (SU), Service de Pneumologie = Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hépatologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), 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), CHU Toulouse [Toulouse], Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Soins Primaires, Santé Publique, Registre des cancers de Bretagne Occidentale (SPURBO), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Centre Hospitalier Régional d'Orléans (CHRO), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Saint-Joseph [Marseille], 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), 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), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Bordeaux population health (BPH), and 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)
Subjects: medicine.medical_specialty, Hepatic hydrothorax, business.industry, Internal medicine, [SDV]Life Sciences [q-bio], Medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021
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26. A simple clinical score to promote and enhance ferroportin disease screening

Author: Caroline de Kerguenec, Fabrice Laine, Séverine Cunat, Patricia Aguilar-Martinez, Xavier Causse, Lénaïck Détivaud, Bernard Drenou, Edouard Bardou-Jacquet, Gilles Pelletier, Olivier Loréal, Véronique Loustaud-Ratti, Houda Hamdi-Rozé, Yves Deugnier, Si Nafa Si Ahmed, Amandine Landemaine, Stéphane Durupt, Christophe Bureau, Martine Ropert, Nathalie Ganne-Carrié, Jeff Morcet, CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), CHU Toulouse [Toulouse], Hôpital Paul Brousse, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 de Paris (UP)-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), Hospices Civils de Lyon (HCL), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), None, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Jonchère, Laurent, and 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)
Subjects: Male, medicine.medical_specialty, Multivariate analysis, Iron Overload, [SDV]Life Sciences [q-bio], Iron, Ferroportin, Logistic regression, Likelihood ratios in diagnostic testing, genetic testing, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, Humans, Mass Screening, Cation Transport Proteins, 030304 developmental biology, Genetic testing, Aged, 0303 health sciences, Hepatology, biology, medicine.diagnostic_test, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Middle Aged, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Ferritin, [SDV] Life Sciences [q-bio], Logistic Models, diagnostic score, ROC Curve, Research Design, Cohort, biology.protein, 030211 gastroenterology & hepatology, Female, Hemochromatosis, Metabolic syndrome, business
Abstract: International audience; Background & aims - Ferroportin disease is a rare genetic iron overload disorder which may be underdiagnosed, with recent data suggesting it occurs at a higher prevalence than suspected. Costs and the lack of defined criteria to prompt genetic testing preclude large-scale molecular screening. Hence, we aimed to develop a readily available scoring system to promote and enhance ferroportin disease screening. Methods - Our derivation cohort included probands tested for ferroportin disease from 2008 to 2016 in our rare disease network. Data were prospectively recorded. Univariate and multivariate logistic regression were used to determine significant criteria, and odds ratios were used to build a weighted score. A cut-off value was defined using a ROC curve with a predefined aim of 90% sensitivity. An independent cohort was used for cross validation. Results - Our derivation cohort included 1,306 patients. Mean age was 55±14 years, ferritin 1,351±1,357 μg/L, and liver iron concentration (LIC) 166±77 μmol/g. Pathogenic variants (n = 32) were identified in 71 patients. In multivariate analysis: female sex, younger age, higher ferritin, higher LIC and the absence of hypertension or diabetes were significantly associated with the diagnosis of ferroportin disease (AUROC in whole derivation cohort 0.83 [0.78-0.88]). The weighted score was based on sex, age, the presence of hypertension or diabetes, ferritin level and LIC. An AUROC of 0.83 (0.77-0.88) was obtained in the derivation cohort without missing values. Using 9.5 as a cut-off, sensitivity was 93.6 (91.7-98.3) %, specificity 49.5 (45.5-53.6) %, positive likelihood ratio 1.8 (1.6-2.0) and negative likelihood ratio 0.17 (0.04-0.37). Conclusion - We describe a readily available score with simple criteria and good diagnostic performance that could be used to screen patients for ferroportin disease in routine clinical practice. Lay summary - Increased iron burden associated with metabolic syndrome is a very common condition. Ferroportin disease is a dominant genetic iron overload disorder whose prevalence is higher than initially thought. They can be difficult to distinguish from each other, but the limited availability of genetic testing and the lack of definitive guidelines prevent adequate screening. We herein describe a simple and definitive clinical score to help clinicians decide whether to perform genetic testing.
Published: 2020
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27. 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
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28. Sorafenib vs surgical resection for hepatocellular carcinoma with macrovascular invasion: A propensity score analysis

Author: Julien Calderaro, Ariane Mallat, Didier Samuel, Françoise Roudot-Thoraval, I. Bricault, Thomas Decaens, Christophe Duvoux, René Adam, Giuliana Amaddeo, Christian Letoublon, Alain Luciani, Alexis Laurent, Nathalie Ganne-Carrié, Charlotte Costentin, Eric Vibert, Jean-Charles Nault, Daniel Cherqui, Bernard Paule, CHU Henri Mondor, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire [Grenoble] (CHU), Université Paris 13 (UP13), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hématologie -Immunologie -Cibles thérapeutiques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de chirurgie digestive et de l'urgence, CHU Grenoble-Hôpital Michallon, Service de Neuroradiologie, Hôpital Henri Mondor, UMR INSERM U955, École nationale vétérinaire d'Alfort (ENVA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, 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), Hôpital Paul Brousse, Inserm U776 rythmes biologiques et Cancer, Rythmes Biologiques et Cancers, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Unité de Chronothérapie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Pôle Recherche Clinique-Santé Publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service d'hépatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Université Paris Descartes - Paris 5 (UPD5), Service d'hépato-gastroentérologie, Service de santé publique [Mondor], Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Grenoble Alpes (UGA), Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Paul-Brousse (Villejuif, Val-de-Marne), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri-Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Université Paris Descartes - Paris 5 (UPD5), and École nationale vétérinaire - Alfort (ENVA)
Subjects: Male, Niacinamide, Sorafenib, Surgical resection, medicine.medical_specialty, Carcinoma, Hepatocellular, Multivariate analysis, Bilirubin, [SDV]Life Sciences [q-bio], propensity analysis, Antineoplastic Agents, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Quality of life, Internal medicine, medicine, Humans, Propensity Score, Aged, Retrospective Studies, Hepatology, business.industry, Phenylurea Compounds, Mortality rate, Liver Neoplasms, surgical resection, hepatocellular carcinoma, Middle Aged, medicine.disease, 3. Good health, Surgery, Liver, chemistry, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Propensity score matching, macrovascular invasion, Female, 030211 gastroenterology & hepatology, France, business, medicine.drug
Abstract: Background and aim Sorafenib is the standard of care for patients with hepatocellular carcinoma (HCC) and macrovascular invasion (MVI), with limited survival. Retrospective surgical studies have reported prolonged survival in this situation. This study aimed to compare the overall survival of patients with HCC and MVI treated with surgical resection or sorafenib. Methods 143 patients with HCC and MVI but no extra-hepatic spread, treated with surgical resection (SR-patients; n=75) or sorafenib (SOR-patients; n=68) in four French centres between 1990 and 2013 were reviewed retrospectively. A propensity score analysis was performed to reduce bias. Results SR-patients were significantly younger and had a lower tumour burden than SOR-patients. Median overall survival (OS) rates were 10.1 months [95% CI: 4.1-16.1] in SR-patients and 12.9 months [95% CI: 7.9-17.9] in SOR-patients (p=0.959). The 90-day mortality rate was 16% (n=12) in SR-patients and 7.5% (n=5) in SOR-patients (p=0.196). SR-patients had a median disease-free survival of 4.60 months [95% CI: 3.3-5.9]. Under the propensity analysis, median OS was 12.0 months [95% CI: 5.5-18.5] in SR-patients versus 9.7 months [95% CI: 6.1-13.3] in SOR-patients (p = 0.682). Under multivariate analysis, extensive MVI (HR=1.956, p=0.024) and bilirubin >17 μmol/l (HR=1.738, p=0.011) were the two factors significantly associated with mortality. Conclusion Under a propensity score analysis, the overall survival of patients with HCC and MVI undergoing surgical resection was similar to that achieved with sorafenib. We were not able to identify a patient subgroup experiencing a surgery-related improvement in survival, and quality of life was not evaluable. This article is protected by copyright. All rights reserved.
Published: 2017
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29. The prevalence of esophageal varices needing treatment depends on gender, etiology and BMI

Author: Annalisa Berzigotti, Paul Calès, Federico Ravaioli, V. de Ledinghen, Nathalie Ganne-Carrié, Oana Farcau, S. Petta, C. Bureau, P. Nahon, Davide Festi, H. Stefanescu, and Arthur Berger
Subjects: medicine.medical_specialty, Esophageal varices, Hepatology, business.industry, Internal medicine, Gastroenterology, Etiology, Medicine, business, medicine.disease
Published: 2020
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30. Origin, HDV genotype and persistent viremia determine outcome and treatment response in patients with chronic hepatitis delta

Author: Isabelle Rosa, Fabien Zoulim, Vincent Thibault, Christophe Hézode, Victor de Ledinghen, Thierry Poynard, Xavier Causse, Sophie Hillaire, Hélène Fontaine, Richard Layese, Jérôme Gournay, Nathalie Ganne, Ghassan Riachi, Emmanuel Gordien, Eric Nguyen-Khac, Sophie Metivier, Olivier Chazouillères, Dominique Roulot, Roland Landman, Paul Calès, Dominique Salmon, Pierre Nahon, Cécile Goujard, Zahia Ben-Abdesselam, Ségolène Brichler, H. Labadie, Jean-François Cadranel, Caroline Lascoux-Combe, Véronique Loustaud-Ratti, Bruno Roche, P. Sellier, Corinne Castelnau, Frédéric Le Gal, Philippe Mathurin, Dominique Guyader, Julie Bottero, Françoise Roudot-Thoraval, Laurent Alric, François Habersetzer, Caroline Scholtes, Jean-Didier Grangé, Sylvie Naveau, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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 ), Hospices Civils de Lyon (HCL), Hôpital Paul Brousse, Hôpital Beaujon [AP-HP], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Jean Verdier [AP-HP], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pontchaillou [Rennes], Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Agence Nationale de Recherches sur le Sida et les Hépatites Virales, France REcherche Nord & sud Sida-HIV Hépatites, Université d'Angers (UA)-Université de Rennes (UR)-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 ), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Jonchère, Laurent
Subjects: Adult, Liver Cirrhosis, Male, 0301 basic medicine, medicine.medical_specialty, Carcinoma, Hepatocellular, Cirrhosis, Hepatitis D, Chronic, viruses, African origin, HDV persistent viremia, [SDV]Life Sciences [q-bio], Chronic liver disease, Severity of Illness Index, HDV genotype, 03 medical and health sciences, 0302 clinical medicine, Residence Characteristics, Internal medicine, medicine, Humans, Decompensation, Viremia, Retrospective Studies, Deltavir study, Liver infection, Hepatology, business.industry, Liver Neoplasms, virus diseases, Retrospective cohort study, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Viral Load, biochemical phenomena, metabolism, and nutrition, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Cohort, Female, 030211 gastroenterology & hepatology, France, Interferons, Hepatitis Delta Virus, Viral hepatitis, business, Viral load, Liver outcome
Abstract: International audience; Background & aims: HDV infection causes severe chronic liver disease in individuals infected with HBV. However, the factors associated with poor prognosis are largely unknown. Thus, we aimed to identify prognostic factors in patients with HDV infection.Methods: The French National Reference Centre for HDV performed a nationwide retrospective study on 1,112 HDV-infected patients, collecting epidemiological, clinical, virological and histological data from the initial referral to the last recorded follow-up.Results: The median age of our cohort was 36.5 (29.9-43.2) years and 68.6% of our cohort were male. Most patients whose birthplace was known were immigrants from sub-Saharan Africa (52.5%), southern and eastern Europe (21.3%), northern Africa and the Middle East (6.2%), Asia (5.9%) and South America (0.3%). Only 150 patients (13.8%) were French native. HDV load was positive in 659 of 748 tested patients (88.1%). HDV-1 was predominant (75.9%), followed by sub-Saharan genotypes: HDV-5 (17.6%), HDV-7 (2.9%), HDV-6 (1.8%) and HDV-8 (1.6%). At referral, 312 patients (28.2%) had cirrhosis, half having experienced at least 1 episode of hepatic decompensation. Cirrhosis was significantly less frequent in African than in European patients regardless of HDV genotype. At the end of follow-up (median 3.0 [0.8-7.2] years), 48.8% of the patients had developed cirrhosis, 24.2% had ≥1 episode(s) of decompensation and 9.2% had hepatocellular carcinoma. European HDV-1 and African HDV-5 patients were more at risk of developing cirrhosis. Persistent replicative HDV infection was associated with decompensation, hepatocellular carcinoma and death. African patients displayed better response to interferon therapy than non-African patients (46.4% vs. 29.1%, p
Published: 2020
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31. Optimizing curative management of hepatocellular carcinoma

Author: Pierre Nahon, Eric Vibert, Marianne Ziol, Olivier Seror, Jean-Charles Nault, and Nathalie Ganne-Carrié
Subjects: Oncology, medicine.medical_specialty, Percutaneous, Carcinoma, Hepatocellular, medicine.medical_treatment, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Internal medicine, Late Recurrence, medicine, Hepatectomy, Humans, Hepatology, business.industry, Liver Neoplasms, Distant relapse, medicine.disease, Ablation, Neoadjuvant Therapy, Molecular analysis, Treatment Outcome, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Neoplasm Recurrence, Local, business, Adjuvant
Abstract: The goal of curative management of hepatocellular carcinoma is to provide the best chance of remission. However, recurrence rates for both local and distant relapse are high. Patient subgroups at higher risk of these events can be identified based on histological patterns that are closely linked to specific molecular subtypes. Patient outcome has improved with more effective therapeutic strategies thanks to technological advances in surgical techniques and percutaneous ablation. The main goal of controlling the cause of liver disease is to decrease distant/late recurrence and prevent deterioration of hepatic function. Ongoing trials testing the combination of neoadjuvant and/or adjuvant regimens with these procedures as well as routine tumour molecular analysis may modify therapeutic algorithms for hepatocellular carcinoma in the future.
Published: 2019

32. Obesity survival paradox in cancer patients: Results from the Physical Frailty in older adult cancer patients (PF-EC) study

Author: Philippe Wind, Frédéric Pamoukdjian, Boris Duchemann, Laurent Zelek, Nathalie Ganne, Florence Canoui-Poitrine, Elena Paillaud, Georges Sebbane, Thomas Aparicio, Vincent Levy, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Gastro-entérologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Unité de recherche clinique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Hôpital Jean Verdier [AP-HP], UFR Santé, Médecine et Biologie Humaine (UFR SMBH), Université Sorbonne Paris Nord, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Paris 13 (UP13)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Réseau National Alimentation Cancer Recherche (réseau NACRe), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-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)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), CCSD, Accord Elsevier, Oncogeriatric Coordination Unit, Geriatric Department, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Hôpital avicenne, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Department of Gastroenterology, Department of Medical Oncology, Clinical Research Unit and Clinical Research Centre, Department of Surgery, Université Paris 13 (UP13), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Paris, Frail Elderly, 030209 endocrinology & metabolism, Comorbidity, Critical Care and Intensive Care Medicine, Metastasis, Body Mass Index, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Risk Factors, Internal medicine, Neoplasms, medicine, Humans, Obesity, Prospective Studies, Lung cancer, Aged, Cancer, 2. Zero hunger, Aged, 80 and over, 030109 nutrition & dietetics, Nutrition and Dietetics, Frailty, Obesity survival paradox, business.industry, Mortality rate, medicine.disease, Survival Analysis, Geriatric assessment, 3. Good health, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, C-Reactive Protein, Female, Older people, business, Body mass index, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Cohort study
Abstract: International audience; Background & aims: the obesity survival paradox is an emergent issue in oncology, but its existence remains unclear particularly in older cancer patients. We aimed to assess the obesity survival paradox in older cancer patients.Methods: all consecutive cancer outpatients 65 years and older referred for geriatric assessment (GA) before a decision on cancer treatment between November 2013 and September 2016 were enrolled in the PF-EC cohort study. The main outcome was 6-month mortality. A Cox univariate and multivariate proportional hazard regression models were performed with baseline GA, oncological variables (cancer site, extension and treatment modalities) and C-reactive protein (CRP). We assessed the prognostic value of body mass index categories (i.e. malnutrition = 30 kg/m(2)) in the whole study population and according to the metastatic status.Results: 433 patients with a mean age of 81.2 +/- 6.0 years were included, 51% were women, 44.3% had digestive cancers, 18% breast cancer and 14.5% lung cancer and 45% metastatic cancers. Eighty-eight of these patients (20.3%) were obese at baseline. Mortality rate was 17% during the 6-month follow-up period. After adjustment for sex, gait speed, Mini-Mental State Examination, cancer site and exclusive supportive care, obesity (compared to normal weight) was independently and negatively associated with 6-month mortality only in metastatic patients (aHR 0.17, 95% CI [0.03-0.92], P = 0.04).Conclusion: our study confirms the obesity survival paradox in older cancer patients only in the metastatic group. (C) 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.
Published: 2019
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33. Management of patients with pre-therapeutic advanced liver fibrosis following HCV eradication

Author: Nathalie Ganne-Carrié and Pierre Nahon
Subjects: APRI, AST-to-platelet ratio index, PHT, portal hypertension, medicine.medical_specialty, SVR, Cirrhosis, Hepatocellular carcinoma, Liver fibrosis, LSM, liver stiffness measurement, Population, DAAs, direct-acting antivirals, EHC, extrahepatic cancer, Early detection, Review, AST, aspartate aminotransferase, Virological response, ALT, alanine aminotransferase, MACEs, major adverse cardiovascular events, Internal Medicine, medicine, Immunology and Allergy, SVR, sustained virological response, FIB-4, fibrosis-4, lcsh:RC799-869, Portal hypertension, education, Intensive care medicine, education.field_of_study, AFP, alpha-fetoprotein, Hepatology, business.industry, Hazard ratio, Liver failure, Gastroenterology, medicine.disease, HR, hazard ratio, SMR, standardised mortality ratio, HCV, surveillance, lcsh:Diseases of the digestive system. Gastroenterology, HCC, hepatocellular carcinoma, business
Abstract: Summary: Patients with HCV-related bridging fibrosis or cirrhosis remain at risk of developing life-threatening complications even after achieving a sustained virological response. Although it is reduced, the risk of liver-related events in these patients justifies their inclusion in surveillance programmes dedicated to the early detection of hepatocellular carcinoma and the screening for portal hypertension. Biochemical parameters or non-invasive tests might indicate the potential progression of liver injury despite viral clearance. Specific attention must be focused on the management of comorbidities, while dedicated educational programmes must be encouraged to increase compliance and commitment to surveillance. Better knowledge of the long-term evolution of these patients, who now live longer, is essential to improve risk stratification and refine screening strategies in this growing population. Keywords: HCV, Hepatocellular carcinoma, Liver failure, Portal hypertension, surveillance, SVR
Published: 2019

34. Dynamic of systemic immunity and its impact on tumor recurrence after radiofrequency ablation of hepatocellular carcinoma

Author: Pierre Nahon, Lorraine Blaise, Olivier Seror, Philippe Rochigneux, Marianne Ziol, Françoise Mallet, Lucie Del Pozo, Gisèle N'Kontchou, Alejandro J. Garcia, Jean-Charles Nault, Nathalie Ganne-Carrié, Nathalie Barget, Daniel Olive, Véronique Grando-Lemaire, Valérie Bourcier, Anne-Sophie Chretien, Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: lcsh:Immunologic diseases. Allergy, medicine.medical_specialty, immune monitoring, Radiofrequency ablation, pdl1, [SDV]Life Sciences [q-bio], Hepatitis C virus, Immunology, Systemic immunity, medicine.disease_cause, Gastroenterology, lcsh:RC254-282, law.invention, 03 medical and health sciences, 0302 clinical medicine, Immune system, law, Internal medicine, medicine, Immunology and Allergy, dendritic cells, innate immunity, nk cells, 030304 developmental biology, Original Research, Hepatitis B virus, 0303 health sciences, Innate immune system, business.industry, Hematology, Acquired immune system, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Tumor recurrence, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cancer research, radiofrequency ablation, business, lcsh:RC581-607, CD8, 030215 immunology
Abstract: Background: Percutaneous radiofrequency ablation (RFA) is one of the main treatments of small hepatocellular carcinoma (HCC). However, it remains unclear whether this local treatment can induce systemic immune variations. Methods: We conducted a prospective study in a tertiary center including consecutive cirrhotic patients with unifocal HCC
Published: 2019
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35. A 17‐Beta‐Hydroxysteroid Dehydrogenase 13 Variant Protects From Hepatocellular Carcinoma Development in Alcoholic Liver Disease

Author: Jessica Zucman-Rossi, Jiecheng Yang, J.-C. Nault, Qian Cao, Marianne Ziol, Jean-Frédéric Blanc, Thierry Gustot, Alexis Laurent, Erwan Guyot, Pierre Nahon, Sandrine Imbeaud, Angela Sutton, Eric Letouzé, Paulette Bioulac-Sage, Christophe Moreno, Jacques Devière, Eric Trepo, Nathalie Ganne-Carrié, Quentin Bayard, J. Calderaro, School of Civil Engineering, Wuhan University [China], Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology [Brussels, Belgium], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Service d'Hépato-gastroentérologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Science and Technology Beijing [Beijing] (USTB), Université libre de Bruxelles (ULB), 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)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Genexpress, Génomique Fonctionnelle et Biologie Systémique pour la Santé, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Service de chirurgie digestive, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Jean Verdier [AP-HP], Zucman-Rossi, Jessica, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Alcoholic liver disease, Carcinoma, Hepatocellular, 17-Hydroxysteroid Dehydrogenases, Chronic liver disease, Gastroenterology, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Carcinoma, Humans, Liver Diseases, Alcoholic, ComputingMilieux_MISCELLANEOUS, Aged, Hepatology, business.industry, Liver Neoplasms, Case-control study, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Odds ratio, Middle Aged, medicine.disease, digestive system diseases, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, 030104 developmental biology, Hepatocellular carcinoma, Case-Control Studies, Cohort, 030211 gastroenterology & hepatology, Female, business
Abstract: Recently, a loss of function variant (rs72613567) in 17-beta-hydroxysteroid dehydrogenase 13 (HSD17B13) has been identified as protective of nonalcoholic (NAFLD) and alcoholic liver disease (ALD). However, the role of this single-nucleotide polymorphism (SNP) in the development of hepatocellular carcinoma (HCC) is currently unknown. A total of 3,315 European patients with HCC (n = 1,109) or without HCC, but with chronic liver disease (CLD; n = 2,206), from four centers were analyzed either by whole-exome sequencing (WES; exploratory cohort, 285 HCC) or genotyped for HSD17B13 rs72613567 (validation cohort, 824 HCC and all CLD). We included a control group of 33,337 healthy European individuals from the Exome Aggregation Consortium. We compared distribution of genotype using the chi-square test and logistic regression. In the exploratory cohort analyzed by WES, frequency of the TA allele of HSD17B13 rs72613567 was significantly decreased in HCC patients compared to healthy controls (P = 1.52 × 10-06 ). In the validation cohort, frequency of TA allele carriers was also decreased in patients with CLD and without HCC (39%) compared to healthy individuals (47%; P < 0.0001). The protective effect of the TA allele of HSD17B13 rs72613567 was identified in patients with ALD (odds ratio [OR] = 0.73; 95% confidence interval [CI], 0.65-0.82; P < 0.0001), NAFLD (OR = 0.64; 95% CI, 0.49-0.83; P = 0.0007), and hepatitis C (OR = 0.71; 95% CI, 0.60-0.85; P = 0.0002). In patients with ALD, the proportion of TA allele carriers with HCC was significantly lower (32%) than in CLD patients without HCC (40%), even after adjustment for age, sex, and fibrosis (OR = 0.64; 95% CI, 0.46-0.87; P = 0.005). Conclusion: The HSD17B13 rs72613567 loss of function variant is protective of HCC development in patients with ALD.
Published: 2019
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36. A novel spleen-dedicated stiffness measurement by FibroScan® improves the screening of high-risk oesophageal varices

Author: Federico Ravaioli, M. Rosselli, Giuseppe Mazzella, Mirella Fraquelli, Antonio Colecchia, Corina Rusu, Nathalie Ganne-Carrié, Giovanni Marasco, Paul Calès, Davide Festi, Horia Stefanescu, Victor de Ledinghen, Pietro Andreone, Stefanescu H., Marasco G., Cales P., Fraquelli M., Rosselli M., Ganne-Carrie N., de Ledinghen V., Ravaioli F., Colecchia A., Rusu C., Andreone P., Mazzella G., Festi D., Regional Institute of Gastroenterology and Hepatology [Cluj-Napoca], Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), II Gastroenterology Unit, Department of Medicine, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Physiopathologie du cancer du foie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, and Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO)
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Baveno VI criteria, liver stiffness measurement, portal hypertension, spleen stiffness measurement, Chronic liver disease, Esophageal and Gastric Varices, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Liver stiffness, Predictive Value of Tests, Internal medicine, medicine, Humans, Prospective Studies, ComputingMilieux_MISCELLANEOUS, Aged, Hepatology, medicine.diagnostic_test, business.industry, Platelet Count, Liver Diseases, Reproducibility of Results, Middle Aged, medicine.disease, 3. Good health, Endoscopy, Logistic Models, 030220 oncology & carcinogenesis, Multivariate Analysis, Portal hypertension, Elasticity Imaging Techniques, 030211 gastroenterology & hepatology, Female, business, Varices, Spleen
Abstract: Background & Aims Several non-invasive tests (NITs) have been developed to diagnose oesophageal varices (EV), including the recent Baveno VI criteria to rule out high-risk varices (HRV). Spleen stiffness measurement (SSM) with the standard FibroScan (R) (SSM@50Hz) has been evaluated. However, the EV grading could be underestimated because of a ceiling threshold (75 kPa) of the SSM@50Hz. The aims were to evaluate SSM by a novel spleen-dedicated FibroScan (R) (SSM@100Hz) for EV diagnosis compared with SSM@50Hz, other validated NITs and Baveno VI criteria. Methods This prospective multicentre study consecutively enrolled patients with chronic liver disease; blood data, endoscopy, liver stiffness measurement (LSM), SSM@50Hz and SSM@100Hz were collected. Results Two hundred and sixty patients met inclusion criteria. SSM@100Hz success rate was significantly higher than that of SSM@50Hz (92.5% vs 76.0%, P < .001). SSM@100Hz accuracy for the presence of EV (AUC = 0.728) and HRV (AUC = 0.756) was higher than in other NITs. SSM@100Hz AUC for large EV (0.782) was higher than SSM@50Hz (0.720, P = .027). AUC for HRV with SSM@100Hz (0.780) was higher than with LSM (0.615, P < .001). The spared endoscopy rate of Baveno VI criteria (8.1%) was significantly increased by the combination to SSM@50Hz (26.5%) or SSM@100Hz (38.9%, P < .001 vs others). The missed HRV rate was, respectively, 0% and 4.7% for combinations. Conclusions SSM@100Hz is a new performant non-invasive marker for EV and HRV providing a higher accuracy than SSM@50Hz and other NITs. The combination of Baveno VI criteria and SSM@100Hz significantly increased the spared endoscopy rate compared to Baveno VI criteria alone or combined with SSM@50Hz. Clinical trial number: NCT02180113.
Published: 2019
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37. Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment a prospective cohort study

Author: Albert Tran, Victor de Ledinghen, Armand Abergel, Céline Dorival, Olivier Chazouillères, Louis d’Alteroche, Isabelle Rosa, Didier Samuel, Moana Gelu-Simeon, Laurent Alric, Vincent Leroy, Jérôme Gournay, François Habersetzer, Dominique Guyader, Stanislas Pol, Véronique Loustaud-Ratti, Ghassan Riachi, Jean-Pierre Bronowicki, Hélène Fontaine, Anne Minello, Christophe Hézode, Philippe Mathurin, Claire Geist, Nathalie Ganne, Mélanie Simony, Dominique Thabut, François Raffi, Xavier Causse, Patrick Marcellin, Sophie Metivier, Paul Calès, Isabelle Portal, Marc Bourlière, Dominique Larrey, Fabien Zoulim, Fabrice Carrat, Alpha Diallo, Georges Haour, Tarik Asselah, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), ANRS France Recherche Nord & sud Sida-hiv hépatites, Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire de Nice (CHU Nice), Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), 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 Universitaire de Toulouse (CHU Toulouse), CHU Rouen, Normandie Université (NU), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Image Science for Interventional Techniques (ISIT), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Centre National de la Recherche Scientifique (CNRS), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional d'Orléans (CHRO), Service d'Hépato-gastro-entérologie [CHR Metz-Thionville], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Equipe EPICAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Intercommunal de Créteil (CHIC), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-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 ), Aix Marseille Université (AMU), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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 de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Toulouse [Toulouse], Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], CCSD, Accord Elsevier, Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Cirrhosis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Liver transplantation, Antiviral Agents, Gastroenterology, 03 medical and health sciences, Liver disease, Viewpoint, 0302 clinical medicine, Internal medicine, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Aged, Proportional Hazards Models, business.industry, Incidence, Liver Neoplasms, Hazard ratio, General Medicine, Hepatitis C, Hepatitis C, Chronic, Middle Aged, Hepatology, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Hepatocellular carcinoma, Female, France, business
Abstract: Although direct-acting antivirals have been used extensively to treat patients with chronic hepatitis C virus (HCV) infection, their clinical effectiveness has not been well reported. We compared the incidence of death, hepatocellular carcinoma, and decompensated cirrhosis between patients treated with direct-acting antivirals and those untreated, in the French ANRS CO22 Hepather cohort.We did a prospective study in adult patients with chronic HCV infection enrolled from 32 expert hepatology centres in France. We excluded patients with chronic hepatitis B, those with a history of decompensated cirrhosis, hepatocellular carcinoma, or liver transplantation, and patients who were treated with interferon-ribavirin with or without first-generation protease inhibitors. Co-primary study outcomes were incidence of all-cause mortality, hepatocellular carcinoma, and decompensated cirrhosis. The association between direct-acting antivirals and these outcomes was quantified using time-dependent Cox proportional hazards models. This study is registered with ClinicalTrials.gov, number NCT01953458.Between Aug 6, 2012, and Dec 31, 2015, 10 166 patients were eligible for the study. 9895 (97%) patients had available follow-up information and were included in analyses. Median follow-up was 33·4 months (IQR 24·0-40·7). Treatment with direct-acting antivirals was initiated during follow-up in 7344 patients, and 2551 patients remained untreated at the final follow-up visit. During follow-up, 218 patients died (129 treated, 89 untreated), 258 reported hepatocellular carcinoma (187 treated, 71 untreated), and 106 had decompensated cirrhosis (74 treated, 32 untreated). Exposure to direct-acting antivirals was associated with increased risk for hepatocellular carcinoma (unadjusted hazard ratio [HR] 2·77, 95% CI 2·07-3·71) and decompensated cirrhosis (3·83, 2·29-6·42). After adjustment for variables (age, sex, body-mass index, geographical origin, infection route, fibrosis score, HCV treatment-naive, HCV genotype, alcohol consumption, diabetes, arterial hypertension, biological variables, and model for end-stage liver disease score in patients with cirrhosis), exposure to direct-acting antivirals was associated with a decrease in all-cause mortality (adjusted HR 0·48, 95% CI 0·33-0·70) and hepatocellular carcinoma (0·66, 0·46-0·93), and was not associated with decompensated cirrhosis (1·14, 0·57-2·27).Treatment with direct-acting antivirals is associated with reduced risk for mortality and hepatocellular carcinoma and should be considered in all patients with chronic HCV infection.INSERM-ANRS (France Recherche NordSud Sida-HIV Hépatites), ANR (Agence Nationale de la Recherche), DGS (Direction Générale de la Santé), MSD, Janssen, Gilead, AbbVie, Bristol-Myers Squibb, and Roche.
Published: 2019
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38. Hepatocellular Carcinoma: the Impact of NAFLD

Author: Manon Allaire, Nathalie Ganne-Carrié, Jean-Charles Nault, Pierre Nahon, and Benoit Dupont
Subjects: medicine.medical_specialty, Cirrhosis, Hepatology, business.industry, Hepatitis B, medicine.disease, Gastroenterology, digestive system diseases, Transplantation, 03 medical and health sciences, Liver disease, 0302 clinical medicine, 030220 oncology & carcinogenesis, Virology, Hepatocellular carcinoma, Internal medicine, medicine, 030211 gastroenterology & hepatology, Steatohepatitis, Metabolic syndrome, business, neoplasms
Abstract: The burden of chronic liver diseases including hepatocellular carcinoma (HCC) due to non-alcoholic steatohepatitis (NASH) and metabolic syndrome (MS) is increasing worldwide. Moreover, MS and its components act as co-factors in HCC development in patients with other chronic liver diseases due to high alcohol intake or hepatitis B or C infection. Patients with NASH-related HCC are frequently older; their tumors are more frequently diagnosed in non-cirrhotic livers and at an advanced stage compared to HCC due to other etiologies. Patients with MS appear also to be at risk of post-operative complications after liver resection and transplantation. However, after adjustment for tumor burden and severity of the underlying liver disease, long-term outcomes appear to be similar for NASH-related HCC and HCC due to other etiologies. Research on preventive strategies, screening programs for patients with NASH without cirrhosis but at high risk of HCC development, and new therapeutic strategies are warranted in order to respond to this emerging menace.
Published: 2016
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39. Comparison of Trans-Arterial Chemoembolization and Bland Embolization for the Treatment of Hepatocellular Carcinoma: A Propensity Score Analysis

Author: Lorraine Blaise, Maxime Benhamou, Christian Sengel, Olivier Sutter, Julien Ghelfi, Yann Teyssier, Jean-Charles Nault, Nathalie Ganne-Carrié, Mélodie Abousalihac, Gaël S. Roth, Thomas Decaens, Olivier Seror, and Arnaud Seigneurin
Subjects: Cancer Research, medicine.medical_specialty, Cirrhosis, medicine.medical_treatment, survival, lcsh:RC254-282, Gastroenterology, Article, trans-arterial chemoembolization, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Embolization, bland embolization, intermediate stage, tumor response, business.industry, hepatocellular carcinoma, Odds ratio, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Oncology, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Propensity score matching, Bland Embolization, Lipiodol, 030211 gastroenterology & hepatology, business, medicine.drug
Abstract: Simple Summary In this study, efficacy and safety of embolization alone and trans-arterial chemoembolization were compared in 265 patients with intermediate stage hepatocellular carcinoma. Trans-arterial chemoembolization was associated with a significant increase of complete radiological response, but without significant impact on overall response, and survival outcomes after propensity score matching. Both techniques showed similar safety profiles. To this day, embolization alone and trans-arterial chemoembolization are two available options in the treatment of intermediate stage hepatocellular carcinoma. Abstract No definitive conclusion could be reached about the role of chemotherapy in adjunction of embolization in the treatment of hepatocellular carcinoma (HCC). We aim to compare radiological response, toxicity and long-term outcomes of patients with hepatocellular carcinoma (HCC) treated by trans-arterial bland embolization (TAE) versus trans-arterial chemoembolization (TACE). We retrospectively included 265 patients with HCC treated by a first session of TACE or TAE in two centers. Clinical and biological features were recorded before the treatment and radiological response was assessed after the first treatment using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Correlation between the treatment and overall, progression-free and transplantation-free survival was performed after adjustment using a propensity score matching: 86 patients were treated by bland embolization and 179 patients by TACE, including 44 patients with drug-eluting beads and 135 with lipiodol TACE, 89.8% of patients were male with a median age of 65 years old. Cirrhosis was present in 90.9% of patients with a Child Pugh score A in 84% of cases. After adjustment, no difference in the rate of AE, including liver failure, was observed between the two treatments. TACE was associated with a significant increase in complete radiological response (odds ratio (OR) = 8.5 (95% confidence interval (CI): 2.8–25.4)) but not in the overall response rate (OR = 2.2 (95% CI = 0.8–5.8)). No difference in terms of overall survival (p = 0.3905), progression-free survival (p = 0.4478) and transplantation-free survival (p = 0.9020) was observed between TACE and TAE. TACE was associated with a higher rate of complete radiological response but without any impact on overall radiological response, progression-free survival and overall survival compared to TAE.
Published: 2021
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40. Stratification of Hepatocellular Carcinoma Risk Following HCV Eradication or HBV Control

Author: Pierre Nahon, Nathalie Ganne-Carrié, and Erwan Vo Quang
Subjects: Oncology, medicine.medical_specialty, Cirrhosis, Population, viral hepatitis, lcsh:Medicine, Review, 03 medical and health sciences, antivirals, 0302 clinical medicine, Fibrosis, Internal medicine, medicine, education, risk scores, 030304 developmental biology, 0303 health sciences, education.field_of_study, business.industry, Incidence (epidemiology), lcsh:R, Cancer, hepatocellular carcinoma, General Medicine, medicine.disease, digestive system diseases, Hepatocellular carcinoma, surveillance, 030211 gastroenterology & hepatology, business, Liver cancer, Viral hepatitis
Abstract: Hepatocellular carcinoma (HCC) incidence has dramatically decreased in patients infected with HCV and HBV due to the widespread use of highly effective antiviral agents. Nevertheless, a substantial proportion of patients with advanced fibrosis or cirrhosis following HCV clearance of in case of HBV control whatever the stage of fibrosis remains at risk of liver cancer development. Cancer predictors in these virus-free patients include routine parameters estimating coexisting comorbidities, persisting liver inflammation or function impairment, and results of non-invasive tests which can be easily combined into HCC risk scoring systems. The latter enables stratification according to various liver cancer incidences and allocation of patients into low, intermediate or high HCC risk probability groups. All international guidelines endorse lifelong surveillance of these patients using semi-annual ultrasound, with known sensibility issues. Refining HCC prediction in this growing population ultimately will trigger personalized management using more effective surveillance tools such as contrast-enhanced imaging techniques or circulating biomarkers while taking into account cost-effectiveness parameters.
Published: 2021
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41. Prior surveillance and antiviral treatment improve the prognosis of HCC developed in HBV patients in the West

Author: Lorraine Blaise, Ségolène Brichler, Pierre Nahon, Weam El Hajj, Nathalie Ganne-Carrié, Véronique Grando, Daniela Fanica, Gisèle N'Kontchou, Kadiatou Diallo, Marianne Ziol, Jean-Charles Nault, Fatima Arbadi, and Manon Allaire
Subjects: Liver Cirrhosis, Hepatitis B virus, medicine.medical_specialty, Carcinoma, Hepatocellular, Cirrhosis, Antiviral Agents, Gastroenterology, Metastasis, 03 medical and health sciences, Hepatitis B, Chronic, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Retrospective Studies, Hepatology, business.industry, Liver Neoplasms, Hepatitis B, Prognosis, medicine.disease, Hepatitis D, digestive system diseases, HBeAg, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Coinfection, Etiology, 030211 gastroenterology & hepatology, business
Abstract: Summary Background In Western countries, hepatocellular carcinoma (HCC) in hepatitis B (HBV) patients without cirrhosis was poorly studied. The aim was to describe the characteristics and outcome of HBV-related HCC according to fibrosis stage. Method All patients with chronic HBV infection and HCC discussed in a multidisciplinary tumor board between 2007 and 2017 were retrospectively included. Results A total of 152 out of 2,038 HCC patients had underlying HBV infection. HBV viral load > 2000 IU/ml, positive HBeAg and Hepatitis D coinfection were observed in 41%, 13% and 13% of cases, respectively. HCC was uninodular in 53%, associated with portal thrombosis in 16% and/or metastasis in 9% of cases. 130 patients (86%) had cirrhosis. No difference regarding HCC risk factors and viral characteristics was observed according to fibrosis stage. 5-year survival was 48%(47% on cirrhosis versus 57% without cirrhosis, P = 0.26). At HCC diagnosis, 47% and 32% of cirrhotic and non-cirrhotic patients received an antiviral treatment (AVT), which was associated with less aggressive tumor and better survival (P = 0.005). In cirrhosis, screening was associated with a lower tumor burden and patients were more amenable to curative treatment with better outcome (P Conclusion HBV represents 8% of HCC etiologies without differences of viral characteristics according to fibrosis stage. AVT and surveillance were associated with less aggressive tumors, better access to curative treatment and outcome.
Published: 2021
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42. SAT-490-No Impact of Direct-Acting Antivirals on Recurrent Hepatocellular Carcinoma Tumour Growth in the ANRS CO22 Hepather Cohort

Author: Tarik Asselah, Pol Stanislas, Fabien Zoulim, Isabelle Rosa, A.V. Pichard, Hélène Fontaine, Olivier Chazouillères, Correas Jean Michel, Dominique Larrey, Marc Bourlière, Nathalie Ganne, Véronique Loustaud-Ratti, Jérôme Gournay, Philippe Mathurin, Vincent Leroy, Albert Tran, Jean-Pierre Bronowicki, Didier Samuel, Dorival Celine, Dominique Guyader, Paul Calès, Christophe Hézode, Metivier Sophie, Victor de Ledinghen, Fabrice Carrat, 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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hospices Civils de Lyon, Departement de Neurologie (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-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Lille, Épidémiologie clinique des maladies virales chroniques [iPLesp] (CLEPIVIR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Physiopathologie du système immunitaire (Inserm U1223), and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: Oncology, medicine.medical_specialty, Hepatology, business.industry, Internal medicine, [SDV]Life Sciences [q-bio], Cohort, Medicine, business, DIRECT ACTING ANTIVIRALS, Recurrent Hepatocellular Carcinoma
Abstract: International audience
Published: 2019
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43. Hepatocellular carcinoma in the setting of alcohol-related liver disease

Author: Pierre Nahon, Nathalie Ganne-Carrié, Génomique Fonctionnelle des Tumeurs Solides (U1162), and Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Male, Alcoholic liver disease, medicine.medical_specialty, Cirrhosis, Carcinoma, Hepatocellular, Carcinogenesis, [SDV]Life Sciences [q-bio], Context (language use), Chronic liver disease, Gastroenterology, Global Burden of Disease, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Prevalence, Humans, Liver Diseases, Alcoholic, Hepatology, Ethanol, business.industry, Incidence, Liver Neoplasms, medicine.disease, digestive system diseases, 3. Good health, 030104 developmental biology, Hepatocellular carcinoma, Toxicity, Etiology, 030211 gastroenterology & hepatology, Female, business
Abstract: Summary Alcohol-related liver disease is the most prevalent type of chronic liver disease worldwide, accounting for 30% of hepatocellular carcinoma (HCC) cases and HCC-specific deaths. Alcohol has been associated with an increased risk of several malignancies, this risk starting at doses as low as 10 g/1 unit/day. The carcinogenic process includes direct acetaldehyde toxicity through the formation of protein and DNA adducts, an increased production of reactive oxygen species, changes to lipid peroxidation and metabolism, inflammation and an impaired immune response and modifications to DNA methylation. A high annual incidence of HCC has been observed in large European cohorts of patients with alcoholic cirrhosis, reaching 2.9%, with numerous host factors modulating this risk (age, gender, liver failure, genetic polymorphisms affecting oncogenic pathways). Because of impaired surveillance and poor patient compliance, HCC is often detected late in patients with chronic liver disease of alcoholic aetiology. This delay in detection, which is frequently made in the context of advanced liver cirrhosis rather than in surveillance programmes, results in more advanced HCC that is less amenable to curative treatment. Consequently, patients with alcohol-related HCC generally have a worse prognosis than those with non-alcoholic HCC.
Published: 2018
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44. PNPLA3 and TM6SF2 variants as risk factors of hepatocellular carcinoma across various etiologies and severity of underlying liver diseases

Author: Sandrine Imbeaud, Paulette Bioulac-Sage, Jean-Charles Nault, Marianne Ziol, Eric Trepo, Philippe Amouyel, Alexis Laurent, Angela Sutton, Jean-Frédéric Blanc, Jessica Zucman-Rossi, Erwan Guyot, Thierry Gustot, Christophe Moreno, Jiecheng Yang, Qian Cao, Eric Letouzé, Nathalie Ganne-Carrié, Pierre Nahon, Jacques Devière, Julien Calderaro, and Stéphanie Debette
Subjects: Male, Cancer Research, medicine.medical_specialty, Alcoholic liver disease, Cirrhosis, Carcinoma, Hepatocellular, Single-nucleotide polymorphism, Chronic liver disease, Gastroenterology, Polymorphism, Single Nucleotide, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, Humans, Genetic Predisposition to Disease, Retrospective Studies, business.industry, Liver Diseases, Liver Neoplasms, Case-control study, Genetic Variation, Membrane Proteins, Hepatitis C, Lipase, Middle Aged, medicine.disease, digestive system diseases, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Female, business, Liver cancer, Genome-Wide Association Study
Abstract: Few single nucleotide polymorphisms (SNPs) have been reproducibly associated with hepatocellular carcinoma (HCC). Our aim was to test the association between nine SNPs and HCC occurrence. SNPs in genes linked to HCC (DEPDC5, GRIK1, KIF1B, STAT4, MICA, DLC1, DDX18) or to liver damage (PNPLA3-rs738409, TM6SF2-rs58542926) in GWAS were genotyped in discovery cohorts including 1,020 HCC, 2,021 controls with chronic liver disease and 2,484 healthy individuals and replication was performed in prospective cohorts of cirrhotic patients with alcoholic liver disease (ALD, n=249) and hepatitis C (n=268). In the discovery cohort, PNPLA3 and TM6SF2 SNPs were associated with HCC (OR=1.67 [CI95%:1.16-2.40], p=0.005; OR=1.45 [CI95%:1.08-1.94], p=0.01) after adjustment for fibrosis, age, gender and etiology. In contrast, STAT4-rs7574865 was associated with HCC only in HBV infected patients (p=0.03) and the other tested SNP were not linked with HCC risk. PNPLA3 and TM6SF2 variants were independently associated with HCC in patients with ALD (OR=3.91 [CI95%:2.52-6.06], p=1.14E-09; OR=1.79 [CI95%:1.25-2.56], p=0.001) but not with other etiologies. PNPLA3 SNP was also significantly associated with HCC developed on a non-fibrotic liver (OR=2.19 [CI95%:1.22-3.92], p=0.007). The association of PNPLA3 and TM6SF2 with HCC risk was confirmed in the prospective cohort with ALD. A genetic score including PNPLA3 and TM6SF2 minor alleles showed a progressive significant increased risk of HCC in ALD patients. In conclusion, PNPLA3-rs738409 and TM6SF2-rs58542926 are inherited risk variants of HCC development in patients with ALD in a dose dependent manner. The link between PNPLA3 and HCC on non-fibrotic liver suggests a direct role in liver carcinogenesis. This article is protected by copyright. All rights reserved.
Published: 2018

45. Virologic control and severity of liver disease determine survival after radiofrequency ablation of hepatocellular carcinoma on cirrhosis

Author: Samia Rekik, Valérie Bourcier, Véronique Grando, Marianne Ziol, Pierre Nahon, Gisèle N'Kontchou, Olivier Seror, Etienne Audureau, Erwan Guyot, Richard Layese, Jean-Charles Nault, Olivier Sutter, Annie Mumana, Manon Allaire, and Nathalie Ganne-Carrié
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Carcinoma, Hepatocellular, Radiofrequency ablation, Kaplan-Meier Estimate, Milan criteria, Gastroenterology, Severity of Illness Index, law.invention, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Esophageal varices, law, Internal medicine, medicine, Humans, Prospective Studies, Aged, Proportional Hazards Models, Retrospective Studies, Aged, 80 and over, Radiofrequency Ablation, Hepatology, business.industry, Proportional hazards model, Liver Neoplasms, Middle Aged, medicine.disease, digestive system diseases, Log-rank test, Treatment Outcome, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Female, Neoplasm Recurrence, Local, business
Abstract: Background We aimed to identify the main determinants of long-term overall survival (OS), including virologic control, and recurrence after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) on cirrhosis. Methods Cirrhotic patients treated by RFA for HCC within Milan criteria were included. Associations between patient features and events were estimated by the Kaplan–Meier method with the log rank test and using uni/multivariate Cox models. Results 389 cirrhotic patients (Child–Pugh A 86.6%, 473 tumors) were included. OS was 79.8%, 42.4% and 16%, and overall tumor recurrence 45%, 78% and 88% at 2, 5 and 10 years, respectively. In multivariate analysis, age, Child–Pugh, GGT, HCC near major vessels, esophageal varices, alkaline phosphatase and HBV predicted OS. Gender, ALT, AFP and alcohol intake were associated with tumor recurrence. Multinodular HCC (19.5%) was associated with risk of tumor recurrence outside Milan criteria. HBV patients had longer OS than other patients (P = 0.0059); negative HBV PCR at RFA was associated with decreased tumor recurrence (P = 0.0157). Using time-dependent analysis in HCV patients, a sustained virologic response was associated with increased OS (124.5 months) compared to other patients (49.2 months, P Conclusion Virologic response and severity of underlying liver disease were the main determinants of long-term OS after RFA for HCC developing on cirrhosis.
Published: 2018

46. SAT-021-How to use platelets and liver stiffness to rule out esophageal varices needing treatment?

Author: Annalisa Berzigotti, Horia Stefanescu, Oana Farcau, Davide Festi, Federico Ravaioli, Victor de Ledinghen, Nathalie Ganne-Carrié, Arthur Berger, Paul Calès, and Bureau christophe
Subjects: medicine.medical_specialty, Esophageal varices, Hepatology, Liver stiffness, business.industry, Internal medicine, medicine, Platelet, medicine.disease, business, Gastroenterology
Published: 2019
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47. Percutaneous Treatment of Localized Infiltrative Hepatocellular Carcinoma Developing on Cirrhosis

Author: Nicolas Sellier, Olivier Seror, Jean-Charles Nault, Valérie Bourcier, Véronique Grando, Marianne Ziol, Sandrine Barge, Gisèle N'Kontchou, Nathalie Ganne-Carrié, and Pierre Nahon
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Cirrhosis, Percutaneous, Radiofrequency ablation, Gastroenterology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, law, Internal medicine, medicine, Humans, Survival rate, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Liver Neoplasms, Hazard ratio, Hepatitis C, Middle Aged, Hepatitis B, Prognosis, medicine.disease, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Catheter Ablation, Female, 030211 gastroenterology & hepatology, Surgery, Radiology, business, Follow-Up Studies
Abstract: Infiltrating hepatocellular carcinoma (HCC) is characterized by a difficult diagnosis, dismal prognosis, and limited therapeutic options. We describe long-term results of percutaneous treatment of infiltrative HCC, i.e., multibipolar radiofrequency ablation (mbpRFA) and percutaneous intra-arterial ethanol injection (PIAEI). All cirrhotic patients with localized (up to two segments) infiltrating HCC treated by mbpRFA or PIAEI between 2002 and 2012 were included. Survival was analyzed using the Kaplan–Meier method, log-rank test, and Cox univariate followed by multivariate analyses. Fifty-one patients were considered eligible for mbpRFA (n = 20) or PIAEI (n = 31). Cirrhosis etiologies were alcohol (67 %), hepatitis C (33 %), hepatitis B (16 %), and/or NASH (16 %). HCC were multinodular in 31 % of cases, with a median main tumor size of 60 mm (range 30–200) and macrovascular invasion in 59 % of cases. The median serum level of alphafetoprotein was 125 ng/ml (range 2–215,000). Treatment-related adverse events occurred in 58 %, mainly postablation syndrome (31 %), and one death (2 %). Median overall survival was 18.3 months, with 63, 35, 20, and 12 % survival at 1, 2, 3, and 4 years, respectively. Baseline serum bilirubin >normal [hazard ratio (HR) 2.98; 95 % confidence interval (CI) 1.38–6.50; P = 0.0057] and tumor burden >70 mm (HR 1.02; 95 % CI 1.003–1.04; P = 0.0221) were associated with poorer overall survival. The radiological response using mRECIST criteria and an alphafetoprotein decrease 1 month post-procedure was associated with increased overall survival (P = 0.0002 and P = 0.024, respectively). Despite its overall poor prognosis, localized infiltrating HCC can be safely treated using percutaneous approaches, with potential survival benefits for these difficult-to-treat patients.
Published: 2016
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48. The effects of aminosalicylates or thiopurines on the risk of colorectal cancer in inflammatory bowel disease

Author: STEPHANE NANCEY, Francois MION, Nathalie Ganne-Carrié, ANTOINE CORTOT, Laurent Siproudhis, Bernard FLOURIE, ROBERT BENAMOUZIG, Isabelle Rosa, Jean-Ariel BRONSTEIN, Matthieu Allez, Frederic Gottrand, Guillaume Savoye, Gerard Thiefin, Xavier Roblin, Fabrice Carrat, Jean-Pierre Hugot, Bertrand Napoleon, Pierre DESREUMAUX, Laurent Peyrin-biroulet, Laurent Michaud, Christos CHRISTIDIS, Stéphane Nahon, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CESAME Study Group: Jean-Frédéric Colombel, Jacques Cosnes, Jean-Pierre Gendre, Marc Lémann, Xavier Hébuterne, Antoine Cortot, Yoram Bouhnik, David Laharie, Jean Louis Dupas, Bernard Flourié, Eric Lerebours, Laurent Beaugerie, Laurent Peyrin-Biroulet, Matthieu Allez, Bernard Messing, Guillaume Cadiot, Philippe Marteau, Jean-Claude Soulé, Jean-Marc Gornet, Michel Veyrac, Bernard Duclos, Philippe Beau, Arnaud Bourreille, Philippe Baumer, Franck Carbonnel, Denis Heresbach, Etienne-Henry Metman, Christian Florent, Antoine Blain, Jean-Luc Faucheron, Bruno Bonaz, Xavier Roblin, Pascal Potier, Christian Boehm, Thierry Kurtz, Hervé Lamouliatte, Isabelle Nion-Larmurier, Jean-Charles Delchier, Stanislas Chaussade, Anne Marie Weiss, Jean Pierre Cézard, Laurent Siproudhis, Stéphane Nahon, Daniel Sondag, Raymond Jian, Jean-Christophe Souquet, Pierre Bord, Benoit Coffin, Hélène D'almagne, Patrick Delasalle, Régis Fournier, Maryan Cavicchi, Marc-Henry Souffran, Luc Vandromme, Claire Guedon, Philippe Seksik, Christophe Michiels, Pascal Renard, Patrice Rogier, Sylvie Gouilloud, André Rotenberg, Guillaume Savoye, Alain Thevenin, Laurent Mallet, Franck Brazier, Francois Jean, Anne-Marie Justum, Jean-Paul Latrive, Jean-Luc Gerbal, Robert Pierrugues, Gérard Chardonnal, Laurence Picon, Nicole Reix, Nicolas Drouët D'aubigny, Hervé Uettwiller, Anne Courillon Mallet, Alain Palacci, Raoul-Jacques Bensaude, Pierre Bonniaud, Olivier Empinet, Andrée Nisard, Alain Rudelli, Bernard Tubiana, Philippe Capelle, Alain Dabadie, Daniel Evard, Pierre-Emile Julien, Magali Picon-Coste, Stéphane Schneider, Denis Goldfain, Jérôme Bellanger, Jean-Pierre Blondelot, Philippe Lamy, Sébastien Lemière, Jean Francois Mockly, Benoit Pellat, Gilles Gatineau-Sailliant, Bernard Nalet, Stéphane Nancey, Daniel Kusielewicz, Patrick Loison, Jean-Michel Popot, François Merite, Jean-Pol Roux, Pauline Afchain, Alain Blanquart, Laurent Heyries, Marc Reville, Dominique Viron, Frank Zerbib, Christophe Claviere, Didier Léostic, Philippe Pouderoux, Alain Moitry, Hervé Hagège, Jean-Pierre Hugot, Benoit Humeau, Jean-Marc Sabate, Emmanuel Lederman, Dominique Lescut, Fabrice Luneau, Bruno Mesnard, Lionel Smadja, Michel Steinberg, Marc Brun, Gilles Macaigne, Jean Luc Marchal, Stéphane Ollivier, Dominique Ouvry, Jean Paul Perche, Serge Rambaud, Robert Benamouzig, Jean Louis Cazenave, Jean-Charles Coffin, Martine Blazquez, Marion Lagneau, Bruno Person, Christian Wittersheim, Bertrand Napoleon, Israël Cemachovic, Franck Iglicki, Mehran Howaizi, Eric Leprince, Bruno Leurent, Thierry Morin, Riad Darsouni, Alain Attar, Philippe Baron, Anne Breton, Jean Marie Gillion, Jean-Marc Guemene, Claude Jouffre, Xavier Moreau, Pierre Claude, André Quinton, Vered Abitbol, Jean Michel Brichard, Benoit Desaint, Martin Bouygues, Philippe Chatrenet, Marcelo Salmeron, Jean Silvie, Bruno Waldner, Yves Emery, Armand Moraillon, Daniel Kunkel, Philippe Dubois, Patrick Faure, Christian L'Hirondel, Jean-Eric Labérenne, Pierre Moreau, Adelino Pereira, Genevieve Plihon, Thierry Wolff, Yann Ngo, Arnaud Boruchowicz, Béatrice Jost, Jean Pierre Gotlib, Odile Danne, Philippe Raoux, Marie-José Ramond-Bouhali, Andre Baetz, Bruno Veyres, Christian Chapoutot, Gérard Le Dréau, Jérôme Filippi, Jean Mudry, Philippe Kalt, Sophie Minault, Pierre-André Bounin, Tony Andréani, Jacky Charneau, Didier Reijasse, Jean-Louis Bolze, Jean Luc Thaunat, Christian Le Couteulx, Chantal Maurage, Robert Bader, Philippe Codjovi, Jean-Luc Migairou, Alain Morali, Philippe Rey, Bruno Richard Molard, Richard Petit, Stéphane Koch, Philippe Cassan, Jean-Paul Deschamps, Christine Meicler Caby, Jean-Jacques Meurisse, Philippe Prades, James Boulant, Michel Diacono, Jean-Marie Monsch, J-François Dupuy, Guy Bellaiche, Martine Guegan, Jean-Marc Comte, Jean-Michel Cayla, Francois Le Tallec, Franck Meurisse, Philippe Desurmont, Laurent Roget, Philippe Bouyssou, Bruno Le Gall, Francis Bloch, Loic Larvol, Monique Jullien, Jacques Moreau, Laurent Rebouissoux, Bruno Decroix, Nina Dib, Paul Dieterling, Frédéric Lenormand, Emmanuel Lagier, Philippe Fallourd, Serge Charpin, Hugues Bertrand, Gilles Bommelaer, Daniel Battistelli, Bernard Delon, Lionel Dentant, Etienne Dorval, Jérôme Dumortier, Eric Gaye-Bareyt, Yves Gerosa, Chantal Guez, Martine Mornet, Paul Benfredj, René Piperaud, Noel Stremsdoerfer, Eric Verdier, Alain Grinholtz, Georges Barjonet, Antoine See, Ramuntxo Arotçarena, Anne Baudet, Joel Broyer, Antoine Charachon, Hugues Blondon, Pascal Mouton, Hubert Claudez, Jacques Labat-Labourdette, Jacques Haëm, Patrick Estable, Patrick Levy, Alain Rosenbaum, Yvon Balavoine, Alain Blanchi, Pierre Coutarel, Nadege Delaperriere, Michel Dervichian, Francis Marois, Jacques Seroka, Laurent Michaud, Olivier Leroy, Emmanuel Meyran, Bernard Poilroux, Abdallah Tensaouti, Thierry Paupard, Dominique Agard, Sandrine Beaulieu, Kader Benfiguig, Patrice Capony, Jean Cottereau, Pierre Desreumaux, Jean-Michel Dramard, Mathieu Duché, Patrick Mamou, Isabelle Etienney, Gilles D'Abrigeon, Béatrice Godeberge, Gilbert Tucat, Jean Puech, Jean Roger, Marie-George Lapalus, Paul Bauret, Philippe Houcke, Béatrice Pornin, Bruno Champigneulle, Laurent Cuissard, Xavier-Richard David, Frédéric Lombard, Antoine Granveau, Jean-François Hamon, Olivier Ink, Fabienne Blondel, Alain Namias, Didier Pillon, Antoine Reignier, Gilles Tordjman, Christos Christidis, Simon Zirabe, Michel Audebert, Eric Bion, Claude Bourgeaux, Cécile Poupardin, Philippe Deplaix, Gérard Fratini, Thierry Garnier, Gerard Desseaux, Hervé Magois, Sylvain Lochum, Jean-Francois Vergier, Patrick Texereau, Christel Rat, Francoise Uzzan, Alain Vidal, Nadia Vinante, Bernard Watrin, Cécile Wurtz-Huckert, Bruno Barre, Dominique Chaslin Ferbus, Jean-François Contou, Dominique Coupier, Benoit David, Dany Gargot, Denis Huc, Remy Barraya, Roger Faroux, Jean-Luc Fourgeaud, Hubert Grimprel, Jean Auroux, Jean-François Rey, Jean Pierre Arnoux, Franck Lentini, Ludovic Tardy, Olivier Mouterde, Claire Spyckerelle, Bruno Vacherot, Alain Weissman, Michel Alpérine, Anne Le Sidaner, Pierre-Olivier Bonnet-Eymard, Jean Louis Colson, Daniel Pellet, Bernard Deltombe, André Edouard, Henri Maechel, Jean-Claude Jaillet, Julien Genes, Anne-Marie Leveque, Damien Lucidarme, Philippe Maignan, Nathalie Mallier Gehrke, Jérôme Sanchez, Frank Tusseau, Alban Casteur, Jacques Bottlaender, Denis Constantini, Thierry Coton, Philippe Even, Francois Druart, François Riot, Jean-Michel Gauchet, Geneviève Hecquet, Gerard Henry, Patrick Hochain, Jean Pierre Arpurt, Abdelkrim Medini, Michele Dartois-Hoguin, Henri Moindrot, Philippe Emery, Pierre Periac, Annie Prunier, Pascal Renkes, Christine Tawil-Longreen, Edmond Vincent, René-Louis Vitte, Christian Loeb, Alain Carwana, Didier Barbereau, Philippe Bohon, Céline Corrieri-Baizeau, Daniel Sahy, Philippe Derreveaux, Dominique David, François Desbazeille, Patrick Fontenelle, Jean Luc Slama, Yvon Le Mercier, Michel Certin, Jean Jacques Reig, Isabelle Rosa, Thierry Helbert, Patrick Tounian, Luc Turner, Valéry Perot, Luc Aillet, Arnaud Pauwels, Philippe Barré, Bernard Nury, Claude Cazalbou, Franck Devulder, Alain Durget, Jeanne Dubroca, Daniele Gaudy, Michel Greff, Christian Jacques, Jocelyne Lafarge, Gilles Kezachian, Ronan Le Gall, Alex Pariente, Tiphaine Pinault, Michaël Bismuth, Nathalie Boyer-Darrigrand, Philippe Bretagnolle, Stephane Carpentier, Franck Cholet, Christian Theodore, Rémi Combes, Francois Combet, Christophe Delanoe, Stéphanie De Montigny, Denis Soudan, Olivier Fourdan, Gilles Minier, Jeanne Languepin, Jean Roche, Jean-Louis Ginies, Olivier Nouel, Philippe Petitgars, Edith Robin, Romain Hamm, Jean François Roques, Sylvie Roussin-Bretagne, Agnès Sénéjoux, Sophie Muron, Nicolas Bardoux, Philippe Berthelemy, Patrick Madonia, Bertrand Carles, Catherine Reynier, Emmanuel Cuillerier, Innocenti Dadamessi, Jacques Danis, Bernard Debenes, Nathalie Dubuc-Rey, Gilles Lesur, Pauline Jouet, Catherine Lenaerts, Marc Garret, Alexandra Mineur, Bernard Chabry, Francois Pigot, Valérie Rossi, Ruth Tennenbaum, Julien Salloum, Maurice Hakim Slaoui, Stéphane Mathieu, Valérie Papapietro, Sheila Viola, Alexis Bezet, Claude Altman, Alain Audan, Jean Calabet, Claude Masliah, Laurent Fayemendy, Marc Duruy, Benoit Gauffeny, Ludovic Helie, Kamran Imani, Raoul Janin-Manificat, Jean-Paul Galmiche, Anne Kerlirzin, Laurent Bedenne, Christophe Locher, Gilles Michaudel, Gilles Missonnier, Michel Rinaldi-Dovio, Jean-Michel Rouillon, Stéphane Ecuer, Arnaud Patenotte, Jean Ariel Bronstein, Vincent Baty, Michel Bougnol, Pierre Bourbon, Philippe Cerbelaud, Annick Chavaillon, Franck Boiffin, Béatrice Dubern, Isabelle Duval De Laguierce, Fernand Greco, Florence Bouhot, Philippe Godeberge, Brigitte Grandmaison, Pascal Gros, Guy Targues, Jacques Corallo, Jean Boutin, Jacques Guillan, Jean Pierre Barbieux, Isabelle Loury Lariviere, Henri Le Genissel, Henri Leroi, Marc Bellaiche, Marie-Claire Elie-Legrand, Michel Dapoigny, Philippe Denoyel, Patrice Pienkowski, Philippe Pouche, Marc Michel Saurfelt, Jean Marie Thorel, Thierry Piche, Bruno Travers, Patrick Tuvignon, Marc Zalcberg, Guy Boulay, Christophe Zamora, Joelle Samama, Etienne Ricotie, Patrice De Fleury, Francois Maille, Jean Louis Mougenel, Olivier Gonot, Jean Philippe Menat, Mehdi Kaassis, Francoise Lang, Laurent Abramowitz, Nathalie Ganne, Olivier Pecriaux, Jacques-Arnaud Seyrig, Iradj Sobhani, Thierry Parmentier, Antoine Van Nieuwenhuyse, Francois-Xavier Weber, André Glibert, Catherine Bineau, Bernard Canet, Catherine Collin, Frederic Cordet, David David Parlier, Dominique Carre, Annie Peytier, Francine Fein, Jerome Barouk, Jacques Dewannieux, Johannes Hartwig, Jean-Louis Jouve, Bertrand Laplane, Gilles Lascar, Christophe Legrand, Pierre Le Marchand, Marie Pierre Liebaert, Michele Terdiman-Pire, Naceur Abdelli, Dominique Neveu, Philippe De La Lande, Patrick De Saint Louvent, Cécile Pelatan, Agnès Petit, Martial Richecoeur, Frederic Texier, Jean Brice Cazals, Bertrand Tissot, Christian Mourrut, Marie Doubremelle, Marc Foltz, Florence Gautier-Jubé, Jacques Martin, Elie Khouri, Thierry Lons, Martine Carlier-Bandu, Jean-Luc Monnin, Hervé Roche, Bernard Willemin, Xavier Houard, Abdelaziz Fatisse, Michèle Algard, Kamel Arab, Isabelle Borel, Cécile Lagarrigue, Ariane Chryssostalis, Dominique Boutroux, Jean-Pierre Dupuychaffray, Saïd Khaddari, François Mion, Thierry Puy-Montbrun, Jean-Philippe Girardet, Bruno Gury, Alain Landau, Monique Le Bihan, Sandrine Nieuviarts, Jean Ollivry, Philippe Le Bourgeois, Marie-Astrid Piquet, Michel-Pierre Escartin, Remi Systchenko, Franck Venezia, Michel Wantiez, Xavier Lesage, Elie Zrihen, Philippe Aygalenq, Barbara Dieumegard, Bernard Savarieau, Philippe Bulois, Stéphane Cattan, Jean-Lucien Diez, Olivier Fauchot, Eric Durous, Valérie Gazut, Christian Guilleminet, Jean-Marc Bories, Isabelle Joly Le Floch, Jean-Paul Vove, Stéphane Lelouch, Philippe Lévy, François Lhopital, Norma Marcato, Marianne Mozer-Bernardeau, Jean-Baptiste Nousbaum, Philippe Cattan, Alain Plane, Jean-Michel Raymond, Gilles Roseau, Gerald Rozental, Christian Boustière, Corinne Bonny, Mariepierre Cordier-Collet, Laurent Courat, Bernard Croguennec, Karine Delaunay-Tardy, Damien Labarriere, Edmond Geagea, Frédéric Gottrand, Eve Gelsi, Gerard Thiefin, Eric Wohlschies, Mathieu Miguet, Philippe Ponsot, Jean Suzanne, Yves Teste, Anne-Claire Dupont Gossart, Jean-Luc Baroni, Benabdallah Benchaa, Georges Blanc, Bernard Maroy, Philippe Bonjean, Catherine Brézault, Laure Bridoux-Henno, Claude Chayette, Dominique Auby, Robert Fiorucci, Georges Galindo, Gilles Hubert, Gilles Bonneau, Evelyne Marinier, Michele Pouteau, Afchine Alamdari, Bruno Delbende, Patrick Chamouard, Pascale D'Abravanel, Hélène Dall'Osto, Sophie Hervé, Jean Lefebvre, Damien Levoir, Philippe Lillo, Michel Rouch, Muriel Mathonnet, Mercédes De Lustrac, François-Jean Ramond, Bernard Roupret, Alain Soupison, Djamila Ait-Ouadda, Yves Barbaza, Brice Bayart, Thomas Bottini, Franck Cochet, Isabelle Goderel, Orélien Maury, Léa Mbonyingo, Vanessa Pourtau, Elise Rasoanarivo, Laure Romain-Huttin, Anne-Violaine Sallé, Jonathan Trang, Hakeem Admane, Elodie Drouet, 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), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Herrada, Anthony
Subjects: Adult, Male, medicine.medical_specialty, Colorectal cancer, Inflammatory bowel disease, Gastroenterology, Primary sclerosing cholangitis, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Pharmacology (medical), Prospective Studies, Prospective cohort study, Mesalamine, Aged, Retrospective Studies, Hepatology, business.industry, Anti-Inflammatory Agents, Non-Steroidal, Case-control study, Cancer, Retrospective cohort study, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Middle Aged, medicine.disease, Colitis, Inflammatory Bowel Diseases, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, 3. Good health, Aminosalicylic Acids, Treatment Outcome, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030220 oncology & carcinogenesis, Case-Control Studies, Cohort, Multivariate Analysis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030211 gastroenterology & hepatology, Female, business, Colorectal Neoplasms
Abstract: SummaryBackground Whether aminosalicylates or thiopurines reduce the risk of colorectal cancer (CRC) in inflammatory bowel (IBD) disease is controversial. Aim To assess simultaneously the chemopreventive effect of aminosalicylates or thiopurines in a case–control study nested in the CESAME observational cohort that enrolled consecutive patients with IBD between May 2004 and June 2005. Patients were followed up to December 2007. Methods Study population comprised 144 case patients who developed CRC from the diagnosis of IBD (65 and 79 cases diagnosed, respectively, before and from 2004, starting year of the prospective observational period of CESAME) and 286 controls matched for gender, age, IBD subtype and year of diagnosis, and cumulative extent of colitis. Exposure to aminosalicylates or thiopurines was defined by an exposure to the treatment during the year of the diagnosis of cancer. The propensity of receiving 5-ASA and thiopurines was quantified by a composite score taking into account patient and IBD characteristics. The role of aminosalicylates or thiopurines was assessed by multivariate analysis. Propensity scores and the history of primary sclerosing cholangitis were entered into the multivariate model for adjustment. Results By multivariate analysis adjusted for propensity, a significant protective effect of exposure to drugs during the year of cancer was found for aminosalicylates (OR = 0.587, 95% CI: 0.367–0.937, P = 0.0257), but not for thiopurines (OR = 0.762, 95% CI: 0.432–1.343, P = 0.3468). Conclusion In a case–control study nested in the CESAME cohort, a significant decrease in the risk of colorectal cancer in IBD was associated with exposure to aminosalicylates, not to thiopurines.
Published: 2017
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49. Eating patterns in patients with compensated cirrhosis: A case-control study

Author: Pierre Nahon, Nathalie Ganne-Carrié, Dominique Roulot, Léopold Fezeu, Séverine Brulé, Zahia Ben-Abdesselam, Chantal Julia, Camille Buscail, Carole Cagnot, Valérie Bourcier, Serge Hercberg, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Université Sorbonne Paris Cité (COMUE) (USPC), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Jean Verdier [AP-HP], Université Paris Nord (Paris 13), Agence Nationale de la Recherche (ANR), Institut National de la Santé et de la Recherche Médicale (INSERM), ANRS (France Recherche Nord and Sud Sida-HIV Hépatites), National Institute of Cancer (INCa, Institut National du Cancer), ARC foundation, ANRS, French Ministry of Health, Santé publique France Institute, Institut National de la Santé et de la Recherche Médicale, Institut National de la Recherche Agronomique, Conservatoire National des Arts et Métiers, Fondation pour la Recherche Médicale, Paris 13 University, Buscail, Camille, Ganne-Carrié, Nathalie, and Julia, Chantal
Subjects: 0301 basic medicine, Male, Alcoholic liver disease, Cirrhosis, Recommended Dietary Allowances, Gastroenterology, Eating, 0302 clinical medicine, Surveys and Questionnaires, Medicine, 2. Zero hunger, education.field_of_study, Nutrition and Dietetics, dietary intakes, Hepatitis B, Middle Aged, 3. Good health, liver cirrhosis, alcoholic cirrhosis, viral cirrhosis, nutritional status, Alimentation et Nutrition, Cohort, 030211 gastroenterology & hepatology, Female, lcsh:Nutrition. Foods and food supply, Nutritive Value, Adult, medicine.medical_specialty, Paris, Population, Médecine humaine et pathologie, lcsh:TX341-641, Article, 03 medical and health sciences, Internal medicine, Food and Nutrition, Humans, education, Life Style, Aged, 030109 nutrition & dietetics, business.industry, Case-control study, Feeding Behavior, medicine.disease, Cross-Sectional Studies, Nutrition Assessment, Case-Control Studies, Etiology, Human health and pathology, Observational study, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Food Science
Abstract: International audience; Background: There is growing evidence suggesting that maintaining an adequate nutritional status for patients with liver cirrhosis (LC) is relevant to prevent complications. The present study aimed to describe dietary behaviours of patients with compensated and non-complicated LC and comparing them with those of subjects from the general population. Methods: In this case-control study, patients were volunteers enrolled in the ALICIR (ALImentation et CIRrhose) study, an observational survey nested in two French prospective cohorts of patients with biopsy-proven compensated cirrhosis related either to excessive alcohol consumption (CIRRAL) or to hepatitis B or C virus infection (CirVir). Controls were selected from the NutriNet-Sante cohort. Dietary data were collected through a semi quantitative food frequency questionnaire. Dietary and nutritional data were compared using multi-adjusted paired Student's tests. Results: Between June 2014 and February 2016, 174 patients of CirVir (N = 97) or CIRRAL (N = 77) were matched with 348 controls from the NutriNet-Santé cohort, according to gender, age, BMI and educational level. Compared to controls, patients (mean ± SD) consumed more sodas (236.0 ± 29.8 mL vs. 83.0 ± 33.0 mL) and water (1787.6 ± 80.6 mL vs. 933.6 ± 85.3 mL), and lower amounts of salty snacks (4.2 ± 1.42 g vs. 9.0 ± 1.6 g) and alcoholic beverages (71.8 ± 23.4 g vs. 151.2 ± 25.9 g), with all p values < 0.0001. Dietary behaviours differed according to LC aetiology. Conclusions: Dietary behaviour of patients significantly differed from subjects from the general population.
Published: 2018
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50. Influence of Progenitor-Derived Regeneration Markers on Hepatitis C Virus-Related Cirrhosis Outcome (ANRS CO12 CirVir Cohort)

Author: Carole Cagnot, Marianne Ziol, Nathalie Ganne-Carrié, Fatiha Merabtene, Françoise Roudot-Thoraval, Richard Layese, Christophe Sattonnet, Pierre Bedossa, Valérie Bourcier, Pierre Nahon, Benoit Terris, Paulette Bioulac-Sage, Dominique Wendum, Nathalie Barget, Janick Selves, Emmanuel Sauce, Nathalie Sturm, Service d'Anatomie et cytologie pathologiques [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), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de santé publique [Mondor], Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (USPC), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Service d'Imagerie et de Cytométrie [CHU Saint-Antoine] (UMS LUMIC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), ANRS France Recherche Nord & sud Sida-hiv hépatites, Hôpital Beaujon [AP-HP], Service d'Anatomie et de cytologie pathologiques [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire [Grenoble] (CHU), Gestionnaire, Hal Sorbonne Université, Service d'Anatomie Pathologique [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Liver Cirrhosis, Male, Cirrhosis, Hepacivirus, medicine.disease_cause, Gastroenterology, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Prospective Studies, intermediate hepatobiliary cells, liver decompensation, medicine.diagnostic_test, Stem Cells, Hazard ratio, Biopsy, Needle, Epithelial cell adhesion molecule, hepatocellular carcinoma, Middle Aged, Epithelial Cell Adhesion Molecule, Prognosis, Hepatitis C, Immunohistochemistry, 3. Good health, Survival Rate, Hepatocellular carcinoma, Liver biopsy, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Keratins, 030211 gastroenterology & hepatology, Female, Adult, medicine.medical_specialty, Hepatitis C virus, Risk Assessment, 03 medical and health sciences, Internal medicine, medicine, Humans, Decompensation, Aged, Proportional Hazards Models, Hepatology, business.industry, Keratin7, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Liver Regeneration, 030104 developmental biology, chemistry, EpCAM, Multivariate Analysis, business, Biomarkers
Abstract: Progenitor-derived regeneration gives rise to the aberrant expression of biliary markers such as cytokeratin 7 (K7) and epithelial cell adhesion molecule (EpCAM) in hepatocytes. We aimed to describe the expression of these molecules in patients with compensated hepatitis C virus (HCV)-related cirrhosis and to investigate its potential influence on cirrhosis complications. Among patients with Child-Pugh A uncomplicated HCV-related cirrhosis enrolled in the prospective ANRS CO12 CirVir cohort, we selected individuals with a liver biopsy collected within 2 years before inclusion in the study. K7 and EpCAM immunostaining identified intermediate hepatobiliary cells. The influence of biliary marker expres-sion in hepatocytes on decompensation events and the occurrence of hepatocellular carcinoma (HCC) was studied using a multivariate Cox proportional hazards regression model. Among the 337 patients eligible for the study (men, 67%; median age, 52 years), 198 (58.8%) had biopsies with K7-positive hepatocytes including extensive staining in 40 (11.9%) and 203 had EpCAM-positive hepatocytes (60.6%). During follow-up (median, 54.2 months), 47 patients (14%) experienced a decompensation event, and HCC was diagnosed in 37 patients (11%). Extensive K7 staining was independently associated with the occurrence of a decompensation event (hazard ratio [HR], 3.00; 95% confidence interval [CI], 1.30-6.89; P = 0.010). EpCAM expression was independently associated with HCC occurrence (HR, 2.37; 95% CI, 1.07-5.23; P =0.033) along with age and a low prothrombin ratio. CONCLUSION Progenitor-derived regeneration depicted by K7 and EpCAM immunostaining of hepatocytes in liver biopsies of patients with compensated HCV-related cirrhosis marks a cirrhosis stage more prone to develop complications. (HEPATOLOGY 2018; 68:1534-1548).
Published: 2018
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