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25 results on '"MESH: Liver Neoplasms"'

1. Patients Treated for HCV Infection and Listed for Liver Transplantation in a French Multicenter Study: What Happens at Five Years?

Author

Lucy Meunier, Mohamed Belkacemi, George Philippe Pageaux, Sylvie Radenne, Anaïs Vallet-Pichard, Pauline Houssel-Debry, Christophe Duvoux, Danielle Botta-Fridlund, Victor de Ledinghen, Filomena Conti, Rodolphe Anty, Vincent Di Martino, Marilyne Debette-Gratien, Vincent Leroy, Theophile Gerster, Pascal Lebray, Laurent Alric, Armand Abergel, Jérôme Dumortier, Camille Besch, Helene Montialoux, Didier Samuel, Jean-Charles Duclos-Vallée, Audrey Coilly, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Pontchaillou [Rennes], 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 ), Hôpital Paul Brousse, and Funding support came solely from institutional and/or departmental sources (institute: Montpellier University Hospital, 34000, France).

Subjects
MESH: Hepatitis C, MESH: Antiviral Agents, MESH: Liver Transplantation, MESH: Humans, liver transplantation, DAAs, MESH: Retrospective Studies, hepatocellular carcinoma, waiting list, MESH: Hepatitis C, Chronic, anti HCV therapy, decompensated cirrhosis, recurrence after liver transplantation, Infectious Diseases, MESH: Waiting Lists, MESH: Liver Neoplasms, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, MESH: Hepacivirus, MESH: Ascites, MESH: Liver Cirrhosis, MESH: Carcinoma, Hepatocellular
Abstract

International audience; Background: Direct-acting antiviral (DAA) agents for the treatment of hepatitis C virus (HCV) infection have been proven safe and effective in cirrhotic patients awaiting liver transplantation (LT). However, in the long term, data remain minimal regarding the clinical impact of viral eradication on patients listed for decompensated cirrhosis or hepatocellular carcinoma (HCC). We aimed to elucidate the clinical outcomes of patients regarding delisting and the evolution of HCC during the long-term follow-up. Methods: An observational, multicenter, retrospective analysis was carried out on prospectively collected data from HCV-positive patients treated with an interferon-free regimen while awaiting LT in 18 French hospitals. Results: A total of 179 patients were included in the study. The indication for LT was HCC in 104 (58.1%) patients and cirrhosis in 75 (41.9%) patients. The sustained virological response was 84.4% and the treatment was well tolerated. At five years, among 75 patients with cirrhosis treated for HCV, 19 (25.3%) were delisted following improvement after treatment. Predictive factors for delisting highlighted an absence of ascites, MELD score ≤ 15, and Child–Pugh score ≤ 7. No patients with refractory ascites were delisted. Among patients with HCC, 82 (78.9%) were transplanted. The drop-out rate was low (6.7%) and few recurrences of HCC after LT were observed. Conclusions: DAAs are safe and effective in patients awaiting LT for cirrhosis or HCC. A quarter of patients with cirrhosis can be delisted because of clinical improvement. Predictive factors for delisting, as a result of improvement, may assist prescribers, before initiating HCV infection therapy in the long-term perspective.

Published
2023

2. Non-invasive diagnosis and follow-up of chronic infection with hepatitis B virus

Author

Vincent Leroy, Stéphane Chevaliez, Marie Decraecker, Dominique Roulot, Jean Nana, Tarik Asselah, Xavier Causse, David Durantel, Vincent Thibaut, Nathalie Ganne-Carrié, Christophe Bureau, Victor de Lédinghen, Marc Bourlière, 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), 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], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Grenoble Alpes (UGA), CHU Grenoble, Hôpital Beaujon [AP-HP], Centre Hospitalier Régional d'Orléans (CHRO), 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), CHU Pontchaillou [Rennes], 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), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
MESH: Humans, Hepatology, MESH: Hepatitis B, Chronic, [SDV]Life Sciences [q-bio], Gastroenterology, MESH: Follow-Up Studies, ab, MESH: DNA, Viral, MESH: Hepatitis B Surface Antigens, MESH: Hepatitis B virus, MESH: RNA, MESH: Liver Neoplasms, MESH: Persistent Infection, MESH: Liver Cirrhosis, MESH: Carcinoma, Hepatocellular, MESH: Hepatitis B e Antigens
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 cutoffs 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

3. Small Steatotic HCC: A Radiological Variant Associated With Improved Outcome After Ablation

Author

Eric Assenat, Chloé Guillot, Margaux Hermida, Astrid Herrero, Christophe Cassinotto, Georges-Philippe Pageaux, Fabrizio Panaro, Ancelin Preel, Boris Guiu, Lauranne Piron, José Ursic-Bedoya, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Retiveau, Nolwenn

Subjects
Male, Percutaneous, Cirrhosis, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, medicine.medical_treatment, Gastroenterology, MESH: Magnetic Resonance Imaging, Liver disease, MESH: Liver Neoplasms, Neoplasm Metastasis, MESH: Carcinoma, Hepatocellular, MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, medicine.diagnostic_test, Liver Neoplasms, Hazard ratio, MESH: Follow-Up Studies, Middle Aged, Ablation, Magnetic Resonance Imaging, Treatment Outcome, Hepatocellular carcinoma, Catheter Ablation, Original Article, Female, MESH: Neoplasm Recurrence, Local, medicine.medical_specialty, Carcinoma, Hepatocellular, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Disease-Free Survival, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, Clinical significance, lcsh:RC799-869, Aged, Retrospective Studies, MESH: Humans, MESH: Catheter Ablation, Hepatology, business.industry, MESH: Retrospective Studies, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Magnetic resonance imaging, Original Articles, medicine.disease, MESH: Neoplasm Metastasis, MESH: Male, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, MESH: Disease-Free Survival, lcsh:Diseases of the digestive system. Gastroenterology, Neoplasm Recurrence, Local, business, MESH: Female, Follow-Up Studies
Abstract

Percutaneous thermal ablation is a validated treatment option for small hepatocellular carcinoma (HCC). Steatotic HCC can be reliably detected by magnetic resonance imaging. To determine the clinical relevance of this radiological variant, we included 235 patients (cirrhosis in 92.3%, classified Child‐Pugh A in 97%) from a prospective database on percutaneous thermal ablation for 100 ng/mL (P = 0.045), and multifocality (P = 0.015). During the follow‐up (median: 28.3 months), overall mortality (3.8% vs. 23.5%; P = 0.001) and HCC‐specific mortality (0.0% vs. 14.2%; P = 0.002) rates were lower in patients with steatotic HCC. Early (, Small steatotic HCC is reliably detected by MRI and is associated with slightly less advanced liver disease and a less aggressive tumor phenotype. PTA of such radiological HCC variant results in low rate of early recurrence and HCC‐related deaths, longer time‐to‐recurrence, longer recurrence‐free and overall survivals.

Published
2020

4. Software-based assessment of margin in hepatocellular carcinoma and liver metastases after percutaneous thermal ablation: a systematic review

Author

Minier, Chloé, Thèses d'exercice et mémoires - UFR de Médecine Montpellier-Nîmes, Université de Montpellier (UM), and Margaux Hermida

Subjects
Progression tumorale locale, Local tumor progression, MESH: Liver neoplasms, Volumetric assessment, Traitement d'image, Évaluation volumétrique, Marge d'ablation, MESH: Software, MESH: Techniques d'ablation, Image processing, MESH: Tumeurs du foie, MESH: Imagerie tridimensionnelle, MESH: Logiciel, MESH: Ablation techniques, MESH: Imaging, Three-dimensional, Ablation margin, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Purpose: to conduct a comprehensive review of clinical studies evaluating software or a new method for margin assessment after percutaneous thermoablation (PTA) of liver tumors.Materials and methods: three databases were used: Pubmed/MEDLINE, Embase and The Cochrane Library. Keywords were “software”, “ablation techniques”, “liver neoplasms”, "image processing”, “imaging, three-dimensional”, “volumetric assessment”, “ablation”, “ablative margin”, “local tumor progression”, “radiofrequency ablation”. Following criteria were: liver tumor treated by a thermoablation technique, at least 10 patients included, fusion of pre- and post-treatment CT, MRI or ConeBeam-CT images, post-ablation margin studies, description of technique used. After exhaustive extraction of data from articles, they were analyzed and grouped into tables in order to homogenize and synthesize data.Results: 678 articles were recorded. After applying exclusion criteria, 28 references were included. All studies were single-center, only 2 were prospective. Majority were feasibility (89.29%) or predictive (78.57%) studies. Four softwares were able to generate automatically margins. Time for use was inhomogeneously reported, ranged between 5–30 min (or more). Inter-operator reproducibility was high (k range: 0.686–1). Ascites, liver deformation, different position or undetectable tumor were major factor of error of coregistration. Margin was often the only significant risk factor for LTP. Visual assessment tended to overestimate assessment of margin. Mostly, LTP occurred at the location of thinnest margin or residual tumor.Conclusion: ablation margin is an independent risk factor for LTP. The therapeutic impact of margin assessment software should therefore be of major importance. The ideal ablation confirmation software would imply a fast and easy to use workflow, as automatic as possible, with high precision.; Objectif : réaliser une revue exhaustive des études cliniques évaluant un logiciel ou une nouvelle méthode d'évaluation des marges après thermoablation percutanée de tumeurs hépatiques.Matériels et méthodes : trois bases de données ont été utilisées : Pubmed/MEDLINE, Embase et The Cochrane Library. Les mots-clés étaient : « logiciel », « techniques d'ablation », « néoplasies hépatiques », « traitement d'image », « imagerie tridimensionnelle », « évaluation volumétrique », « ablation », « marge d’ablation », « progression tumorale locale », « ablation par radiofréquence ».Les critères d’inclusion étaient : tumeur hépatique traitée par thermoablation percutanée, dix ou plus patients inclus, fusion d’images CT, IRM ou ConeBeam-CT pré- et post-thermoablation, étude des marges d’ablation, description des étapes de fusion d’images et d’analyse. Après une extraction exhaustive des données des articles, celles-ci ont été analysées et regroupées au sein de tableaux.Résultats : 678 articles ont été recensés. Après application des critères d'exclusion, 28 références ont été incluses. Toutes étaient monocentriques, seulement 2 étaient prospectives. La majorité étaient des études de faisabilité (89,29 %) ou prédictives (78,57 %). Quatre logiciels étaient capables de générer automatiquement des marges. Le temps d'utilisation rapporté était hétérogène (rang : 5 - 30 minutes voire plus). La reproductibilité inter-opérateur était élevée (k rang : 0.686 – 1). L'ascite, la déformation du foie, une position différente ou une tumeur indétectable étaient les principaux facteurs d'erreur de fusion d’images. La marge était souvent le seul facteur de risque de progression tumorale locale (LTP). L'évaluation visuelle surestimait les marges. La plupart du temps, la LTP est survenue au niveau de la marge la plus fine ou de la tumeur résiduelle.Conclusion : la marge d'ablation est un facteur de risque indépendant de LTP. L'impact thérapeutique d'un logiciel d'évaluation des marges devrait donc être d'une importance majeure. Le logiciel idéal d'ablation-confirmation impliquerait un flux de travail rapide et facile à utiliser, aussi automatique que possible, avec une grande précision.

Published
2021

5. HCV Eradication in Primary or Secondary Prevention Optimizes Hepatocellular Carcinoma Curative Management

Author

Nahon, Pierre, Layese, Richard, Cagnot, Carole, Asselah, Tarik, Guyader, Dominique, Pol, Stanislas, Pageaux, Georges-Philippe, de Lédinghen, Victor, Ouzan, Denis, Zoulim, Fabien, Audureau, Etienne, Cirvir Group, Anrs Co12, 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), 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), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Hôpital Beaujon [AP-HP], 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), CHU Pontchaillou [Rennes], Hôpital Cochin [AP-HP], Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut Arnault Tzanck, Université de Lyon, Hospices Civils de Lyon (HCL), This study was sponsored by the ANRS (France REcherche Nord & sud Sida-hiv Hépatites: FRENSH). This work was also supported, in part, by a grant from AbbVie., ANRS CO12 CirVir group: Pierre Nahon, Tarik Asselah, 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, Paul Calès, 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, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Eric Nguyen-Khac, Brigitte Bernard-Chabert, Sophie Hillaire, Vincent Di Martino., 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), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Liver Cirrhosis, Male, 0301 basic medicine, Cancer Research, Multivariate analysis, Cirrhosis, Sustained Virologic Response, [SDV]Life Sciences [q-bio], MESH: Sustained Virologic Response, Hepacivirus, Gastroenterology, 0302 clinical medicine, MESH: Liver Neoplasms, Secondary Prevention, MESH: Hepacivirus, Prospective Studies, MESH: Incidence, MESH: Carcinoma, Hepatocellular, Secondary prevention, MESH: Aged, MESH: Middle Aged, MESH: Secondary Prevention, Incidence, Liver Neoplasms, MESH: Follow-Up Studies, Middle Aged, MESH: Hepatitis C, Chronic, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cohort, Female, MESH: Liver Cirrhosis, MESH: Neoplasm Recurrence, Local, MESH: Antiviral Agents, medicine.medical_specialty, Carcinoma, Hepatocellular, Antiviral Agents, Disease-Free Survival, 03 medical and health sciences, Internal medicine, medicine, Humans, Aged, MESH: Humans, business.industry, Hepatitis C, Chronic, medicine.disease, BCLC Stage, digestive system diseases, MESH: Male, MESH: Prospective Studies, Regimen, 030104 developmental biology, MESH: Disease-Free Survival, Liver function, Neoplasm Recurrence, Local, business, MESH: Female, Follow-Up Studies
Abstract

To assess the impact of HCV eradication on the outcomes of cirrhotic patients treated curatively for incidental hepatocellular carcinoma (HCC) detected during surveillance program. Data were collected on 1,323 French patients with compensated biopsy-proven HCV cirrhosis recruited in 35 centers (ANRS CO12 CirVir cohort). Sustained virologic responses (SVR) and the occurrence of HCC were recorded prospectively. During a median follow-up of 68.3 months, 218 patients developed HCC, 126 of whom underwent a curative procedure as first-line therapy (ablation = 95, resection = 31). The HCC BCLC stage was 0/A in 97.5% of patients; 74 (58.7%) never achieved SVR. During a median follow-up of 26.0 months after HCC treatment, 59 (46.8%) experienced HCC recurrence. SVR was not associated with a recurrence, whether considering final SVR status [HR = 0.77; 95% confidence interval (95% CI), 0.43–1.39; P = 0.39] or its time to achievement (prior to/after HCC occurrence; global P = 0.28). During the same timeframe, 46 patients with HCC (36.5%) died (liver failure: 41.9%, HCC progression: 37.2%, extrahepatic causes: 20.9%). Under multivariate analysis, SVR was associated with improved survival [HR = 0.21; 95% CI, 0.08–0.52; P = 0.001]. Survival benefit was explained by a lower incidence of liver decompensation and higher rates of sequential HCC re-treatment. Direct antiviral intake was not associated with a higher risk of HCC recurrence, but with improved survival (HR = 0.23; 95% CI, 0.06–0.83; P = 0.024). HCV eradication in primary or secondary prevention optimizes HCC management through preservation of liver function and improves survival, whatever the regimen. Prevention Relevance: Liver failure is a competing risk of death in patients with HCC eligible for curative procedures. HCV eradication does not decrease risk of HCC recurrence in the first two years, but enables sequential curative HCC treatments through preservation of liver function. Direct-acting antiviral agent intake is not associated with HCC recurrence and improves survival.

Published
2021

6. Letter: tenofovir may be superior to entecavir for treatment-naïve chronic hepatitis B patients-authors' reply

Author

Pol, Stanislas, Lusivika Nzinga, Clovis, Carrat, Fabrice, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 HAL-SU, Gestionnaire

Subjects
MESH: Antiviral Agents, MESH: Guanine, MESH: Hepatitis B virus, MESH: Humans, MESH: Tenofovir, MESH: Hepatitis B, Chronic, MESH: Liver Neoplasms, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Carcinoma, Hepatocellular
Abstract

International audience

Published
2021

7. 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

8. Editorial: similar risk of hepatocellular carcinoma in chronic hepatitis B patients treated with tenofovir or entecavir-new clues from Europe. Authors' reply

Author

Pol, Stanislas, Luzivika Nzinga, Clovis, Fontaine, Hélène, Carrat, Fabrice, Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Inserm-ANRS, ANR, DGS and MSD, Janssen, Gilead, Abbvie, BMS, Roche, HAL-SU, Gestionnaire, CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
MESH: Antiviral Agents, MESH: Guanine, MESH: Hepatitis B virus, MESH: Humans, MESH: Tenofovir, MESH: Hepatitis B, Chronic, MESH: Liver Neoplasms, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Europe, MESH: Carcinoma, Hepatocellular
Abstract

International audience

Published
2021

9. Similar 5-year HCC occurrence in Tenofovir- and Entecavir-treated HBV chronic infection in the French AFEF/ANRS CO22 Hepather cohort

Author

Pol, Stanislas, Bonnet, Delphine, Payssan-Sicart, Virginie, Pomes, Chloe, Bailly, François, Beaudoin, Marjolaine, Giboz, Dominique, Hartig-Lavie, Kerstin, Maynard, Marianne, Billaud, Eric, Boutoille, David, Cavellec, Morane, Chevalier, Caroline, Hubert, Isabelle, Goepfert, Pierre, Lannes, Adrien, Lunel, François, Boursier, Jérôme, Boyer, Nathalie, Giuily, Nathalie, Castelnau, Corinne, Scoazec, Giovanna, Chibah, Aziza, Keser, Sylvie, Bonardi, Karim, Vallet-Pichard, Anaïs, Sogni, Philippe, Foucher, Juliette, Hiriart, Jean-Baptiste, Legendre, Amandine, Chermak, Faiza, Irlès-Depé, Marie, Ahmed, Si Nafa Si, Ansaldi, Christelle, Amara, Nisserine Ben, Oules, Valérie, Dunette, Jacqueline, Anty, Rodolphe, Gelsi, Eve, Truchi, Régin, Luckina, Elena, Messaoudi, Nadia, Moussali, Joseph, Dieuleveult, Barbara De, Goin, Héloïse, Labarrière, Damien, Potier, Pascal, Grando-Lemaire, Véronique, Nahon, Pierre, Brulé, Séverin, Monard, Rym, Jezequel, Caroline, Brener, Audrey, Laligant, Anne, Rabot, Aline, Renard, Isabelle, Baumert, Thomas F, Dofföel, Michel, Mutter, Catherine, Simo-Noumbissie, Pauline, Razi, Esma, Barraud, Hélène, Bensenane, Mouni, Nani, Abdelbasset, Hassani-Nani, Sarah, Bernard, Marie-Albertine, Pageaux, Georges-Philippe, Bismuth, Michael, Caillo, Ludovic, Faure, Stéphani, Ripault, Marie Pierre, Bureau, Christophe, Launay, Sarah, Peron, Jean Marie, Robic, Marie Angèl, Tarallo, Lé, Faure, Marine, Froissart, Bruno, Hilleret, Marie-Noelle, Zarski, Jean-Pierre, Goria, Odile, Grard, Victorien, E Montialoux, Hélè, François, Muriel, Ouedraogo, Christian, Pauleau, Christelle, Varault, Anne, Andreani, Tony, E Angoulevant, Bénédic, Chevance, Azeline, Serfaty, Lawrence, Antonini, Teresa, Coilly, Audrey, Vallée, Jean-Charles Duclos, Tateo, Mariagrazia, Bonny, Corinne, Brigitte, Chanteranne, Lamblin, Géraldin, Muti, Léo, Babouri, Abdenour, Filipe, Virginie, Barrault, Camille, Costes, Laurent, Merbah, Soraya, Carrier, Paul, Debette-Gratien, Maryline, Jacques, Jérémie, Lassailly, Guillaume, Artu, Florent, Canva, Valérie, Dharancy, Sébastie, Louvet, Alexandre, Latournerie, Marianne, Bardou, Marc, Mouillot, Thomas, Bacq, Yannick, Barbereau, Didier, Nicolas, Charlotte, Archambeaud, Isabelle, Habes, Sarah, Botta-Fridlund, Danièl, Saillard, Eric, Lafrance, Marie-José, Nzinga, Clovis Luzivika, Dorival, Céline, Zoulim, Fabien, Cagnot, Carole, Decaens, Thomas, Thabut, Dominique, Asselah, Tarik, Mathurin, Philippe, Ganne, Nathalie, Samuel, Didier, Habersetzer, Françoi, Bronowicki, Jean-Pierre, Guyader, Dominique, Rosa, Isabelle, Leroy, Vincent, Chazouilleres, Olivier, Ledinghen, Victor De, Bourliere, Marc, Causse, Xavier, Cales, Paul, Metivier, Sophie, Loustaud-Ratti, Véroniqu, Abergel, Armand, Fontaine, Hélène, Carrat, Fabrice, 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), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)

Subjects
MESH: Antiviral Agents, MESH: Guanine, MESH: Hepatitis B virus, MESH: Humans, MESH: Tenofovir, MESH: Hepatitis B, Chronic, MESH: Liver Neoplasms, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Carcinoma, Hepatocellular, MESH: Prospective Studies, MESH: Treatment Outcome
Abstract

International audience; Background: Chronic hepatitis B virus (HBV) infection results in a high risk of cirrhosis and its complications, cirrhosis decompensation (DC), hepatocellular carcinoma (HCC), liver transplantation (LT), death or any of these outcomes (composite endpoint [CE]). Nucleos(t)ide analogues (NUCs) such as tenofovir or entecavir are associated with a reduction in these complications.Aim: To compare the impact of tenofovir and entecavir on these outcomes in patients treated for HBV infection and included in the prospective Hepather cohort.Methods: All patients with HBV infection who had received tenofovir or entecavir for more than 6 months at or after entry in the ANRS CO22 cohort were selected. Patients with HDV and HCV co-infection or prior liver event were excluded. Incidence rates of events were compared using inverse probability of treatment weighting (IPW).Results: The cohort included 1800 patients (986 tenofovir and 814 entecavir). Median follow-up was 4.2 years. The incidences of HCC, DC, LT, ACD, LRD and CE were not different between tenofovir- (1.8 (0.9; 3.2), 0.6 (0.2; 1.6), 0.2 (0.0; 0.8), 1.7 (0.8; 3.0), 0.8 (0.2, 1.8) and 4.1 (3.0; 5.4) per 1000 person-years) and entecavir-treated patients (1.6 (0.7; 3.0), 0.7 (0.2; 1.8), 0.2 (0.0; 1.0), 3.0 (1.7, 4.8), 0.5 (0.1; 1.5) and 5.0 (3.3; 7.2)) per 1000 person-years, respectively.Conclusion: The risk of liver-related events or death was not different between tenofovir- and entecavir-treated patients in this large prospective cohort of predominantly non-cirrhotic French patients.Trial registration number: NCT019553458.

Published
2021

10. International Multicenter Validation of GES Score for HCC Risk Stratification in Chronic Hepatitis C Patients

Author

MA Hashim, Nabiel Mikhail, Gamal Shiha, M Hassan, Mohammed Eslam, S.K. Sarin, Kentaro Matsuura, Manish Kumar, L Ni, AM Ahumada, Shigeru Mikami, Reham Soliman, SA Lopez, J Zou, Hidenori Toyoda, Suri, Haruki Uojima, Atsushi Hiraoka, Hiroshi Abe, Akito Nozaki, PK Jalal, Kunihiko Tsuji, Masanori Atsukawa, K Takaguchi, Anu Osinusi, Fabrice Carrat, Imam Waked, Toru Ishikawa, Tomohiro Watanabe, Ganne-Carrié Nathalie, R Bañares, Nasser Mousa, J Azzi, Mansoura University [Egypt], 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), 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), Hôpitaux Paris Seine-Saint-Denis [Bobigny], Kitasato University, Yokohama National University, Kagawa University [Japan], Ehime University [Matsuyama, Japon], Nippon Medical School [Tokyo, Japon], Nagoya City University [Nagoya, Japan], St. Marianna University School of Medicine [Kanagawa, Japan], Gilead Sciences, Inc. [Foster City, CA, USA], Institute of Liver and Biliary Sciences [New Delhi], Baylor College of Medicine (BCM), Baylor University, Hospital General Universitario 'Gregorio Marañón' [Madrid], Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Westmead Hospital [Sydney], The University of Sydney, and HAL-SU, Gestionnaire

Subjects
MESH: Antiviral Agents, History, medicine.medical_specialty, Carcinoma, Hepatocellular, Polymers and Plastics, Hepatitis C virus, AFP, HCV genotypes, Hepacivirus, MESH: Risk Assessment, medicine.disease_cause, Antiviral Agents, Risk Assessment, Industrial and Manufacturing Engineering, law.invention, Chronic hepatitis, Randomized controlled trial, MESH: Liver Neoplasms, MESH: Risk Factors, Risk Factors, law, Virology, Internal medicine, Humans, Medicine, MESH: Hepacivirus, Business and International Management, MESH: Carcinoma, Hepatocellular, HCC risk scores, Survival analysis, Retrospective Studies, MESH: Humans, Hepatology, business.industry, Liver Neoplasms, MESH: Retrospective Studies, Hepatitis C, Chronic, medicine.disease, MESH: Hepatitis C, Chronic, CHC, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Hepatocellular carcinoma, Risk stratification, Cohort, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

Background and Aims: We have recently demonstrated the ability of a simple predictive model (GES) score to determine the risk of hepatocellular carcinoma (HCC) after using direct-acting antivirals. However, our results were restricted to Egyptian patients with hepatitis C virus (HCV) genotype 4. Therefore, we studied a large, independent cohort of multiethnic populations through our international collaborative activity. Methods: Depending on their GES scores, patients are stratified into low risk (≤ 6/12.5), intermediate risk (> 6–7.5/12.5), and high risk (> 7.5/12.5) for HCC. A total of 12038 patients with chronic HCV were analyzed in this study, of whom 11202 were recruited from 54 centers in France, Japan, India, the U.S., and Spain, and the remaining 836 were selected from the Gilead-sponsored randomized controlled trial conducted across the U.S., Europe, Canada, and Australia. Descriptive statistics and survival analysis were performed using Kaplan–Meier and log-rank tests. The performance of the GES score was evaluated using Harrell’s C-index (HCI). Results : The GES score proved successful at stratifying all patients into 3 risk groups, namely low-risk, intermediate-risk, and high-risk. It also displayed significant predictive value for HCC development in all participants (P < 0 .0001), with HCI ranging from 0.55 to 0.76 among all cohorts after adjusting for HCV genotypes and patient ethnicities. Conclusion: The GES score can be used to stratify HCV patients into 3 categories of risk for HCC, namely low-risk, intermediate-risk, and high-risk, irrespective of their ethnicities or HCV genotypes. This international multicenter validation may allow the use of GES score in individualized HCC risk-based surveillance programs. Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: The protocol was approved by the Institutional Research Board of each participating center, as per local regulations

Published
2021

11. Changing trends in hepatocellular carcinoma management: Results from a nationwide database in the last decade

Author

Erika Nogue, Fabrizio Panaro, Christophe Cassinotto, Boris Guiu, Nicolas Molinari, Mathieu Morell, Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Montpelliérain Alexander Grothendieck (IMAG), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and CCSD, Accord Elsevier

Subjects
0301 basic medicine, Male, Cancer Research, Percutaneous, Epidemiology, Hepatocellular carcinoma, [SDV]Life Sciences [q-bio], MESH: Aged, 80 and over, 0302 clinical medicine, MESH: Liver Neoplasms, MESH: Carcinoma, Hepatocellular, MESH: Aged, Aged, 80 and over, MESH: Middle Aged, medicine.diagnostic_test, Incidence (epidemiology), Selective internal radiation therapy, Liver Neoplasms, Disease Management, Interventional radiology, MESH: Follow-Up Studies, MESH: Hepatectomy, Middle Aged, Prognosis, [SDV] Life Sciences [q-bio], Survival Rate, Oncology, MESH: Young Adult, 030220 oncology & carcinogenesis, Radiological weapon, Catheter Ablation, Female, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, MESH: Survival Rate, Adolescent, Thermal ablation, MESH: Disease Management, MESH: Prognosis, MESH: Chemoembolization, Therapeutic, 03 medical and health sciences, Young Adult, medicine, Hepatectomy, Humans, Chemoembolization, Therapeutic, Aged, Retrospective Studies, MESH: Adolescent, MESH: Humans, MESH: Catheter Ablation, business.industry, General surgery, MESH: Adult, MESH: Retrospective Studies, medicine.disease, MESH: Male, 030104 developmental biology, Liver cirrhosis, Surgery, business, MESH: Female, Follow-Up Studies
Abstract

International audience; Objective: The therapeutic strategies for hepatocellular carcinoma (HCC) have greatly expanded in recent years. However, the actual usage of each of these treatments in clinical routine remains unknown. Here, we analysed the distribution and changes of the main surgical and radiological therapeutic procedures nationwide during the last decade.Methods: Retrospectively, analysis of the data on all >18-year-old patients with a diagnosis of HCC identified in the French Program for the Medicalization of Information Systems database that contains all discharge summaries from all French hospitals. The number and percentage of the therapeutic procedures performed from January 2010 to December 2019 were extracted.Results: A total of 68,416 therapeutic procedures were performed in 34,000 HCC patients. Whereas HCC incidence remained stable, the annual number of procedures frankly increased over the decade (from 4267 to 8042). Trans-arterial chemoembolization was the most frequently performed technical procedure, with a double-digit annual growth from 2010 (n = 1932) to 2015 (n = 4085), before stabilization from 2016. Selective internal radiation therapy displayed the highest increase in the decade (+475%). Among curative treatments, the annual number of percutaneous tumour ablations more than doubled in 10 years, till representing 64% of curative treatments in cirrhotic patients in 2019. Surgical tumour resections showed a 1.5-fold increase in 10 years, due to the great increase in minimally invasive approaches, whereas the proportion of open resection progressively decreased.Conclusion: Minimally invasive procedures have gained major importance in HCC management during the last decade. Percutaneous thermal ablation has emerged as the first curative treatment performed for patients with HCC.Trial registration: ClinicalTrials.gov NCT04163627.

Published
2020

12. Study protocol of the HYPER-LIV01 trial: a multicenter phase II, prospective and randomized study comparing simultaneous portal and hepatic vein embolization to portal vein embolization for hypertrophy of the future liver remnant before major hepatectomy for colo-rectal liver metastases

Author

François Quenet, Christian Sengel, Lauranne Piron, Anthony Dohan, Patrick Chevallier, Emilie Lermite, Chloé Guillot, Boris Guiu, Laurent Vervueren, Agnès Rode, Antoine Bouvier, Jean-Baptiste Pinaquy, Christophe Laurent, Emmanuel Deshayes, Bruno Lapuyade, Salvy-Córdoba, Nathalie, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut du Cancer de Montpellier (ICM), 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), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Bordeaux [Bordeaux], CHU d'Angers [Département Urgences], PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Radiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Radiologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), and Centre Hospitalier Universitaire [Grenoble] (CHU)

Subjects
Male, Cancer Research, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, medicine.medical_treatment, MESH: Hepatomegaly, Phases of clinical research, 030218 nuclear medicine & medical imaging, Muscle hypertrophy, law.invention, Study Protocol, Liver metastases, 0302 clinical medicine, Portal vein embolization, Postoperative Complications, Randomized controlled trial, law, Surgical oncology, MESH: Liver Neoplasms, MESH: Postoperative Complications, Medicine, Multicenter Studies as Topic, Embolization, Prospective Studies, MESH: Treatment Outcome, Randomized Controlled Trials as Topic, MESH: Middle Aged, Portal Vein, Liver Neoplasms, MESH: Follow-Up Studies, MESH: Hepatectomy, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Embolization, Therapeutic, medicine.anatomical_structure, Treatment Outcome, Oncology, Colo-rectal cancer, Liver, 030220 oncology & carcinogenesis, MESH: Liver Regeneration, Female, Colorectal Neoplasms, MESH: Clinical Trials, Phase II as Topic, Hepatomegaly, MESH: Preoperative Care, Venous deprivation, Adult, medicine.medical_specialty, Major hepatectomy, Urology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, lcsh:RC254-282, 03 medical and health sciences, Clinical Trials, Phase II as Topic, [SDV.CAN] Life Sciences [q-bio]/Cancer, Preoperative Care, Genetics, Hepatectomy, Humans, Vein, MESH: Liver Failure, MESH: Humans, business.industry, MESH: Adult, MESH: Portal Vein, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Prospective Studies, MESH: Male, Liver Regeneration, MESH: Embolization, Therapeutic, MESH: Randomized Controlled Trials as Topic, Tumor progression, MESH: Multicenter Studies as Topic, Liver function, business, MESH: Female, MESH: Colorectal Neoplasms, Liver Failure, MESH: Liver, Follow-Up Studies
Abstract

Background In patients undergoing major liver resection, portal vein embolization (PVE) has been widely used to induce hypertrophy of the non-embolized liver in order to prevent post-hepatectomy liver failure. PVE is a safe and effective procedure, but does not always lead to sufficient hypertrophy of the future liver remnant (FLR). Hepatic vein(s) embolization has been proposed to improve FLR regeneration when insufficient after PVE. The sequential right hepatic vein embolization (HVE) after right PVE demonstrated an incremental effect on the FLR but it implies two different procedures with no time gain as compared to PVE alone. We have developed the so-called liver venous deprivation (LVD), a combination of PVE and HVE during the same intervention, to optimize the phase of liver preparation before surgery. The main objective of this randomized phase II trial is to compare the percentage of change in FLR volume at 3 weeks after LVD or PVE. Methods Patients eligible to this multicenter prospective randomized phase II study are subjects aged from 18 years old suffering from colo-rectal liver metastases considered as resectable and with non-cirrhotic liver parenchyma. The primary objective is the percentage of change in FLR volume at 3 weeks after LVD or PVE using MRI or CT-Scan. Secondary objectives are assessment of tolerance, post-operative morbidity and mortality, post-hepatectomy liver failure, rate of non-respectability due to insufficient FLR or tumor progression, per-operative difficulties, blood loss, R0 resection rate, post-operative liver volume and overall survival. Objectives of translational research studies are evaluation of pre- and post-operative liver function and determination of biomarkers predictive of liver hypertrophy. Sixty-four patients will be included (randomization ratio 1:1) to detect a difference of 12% at 21 days in FLR volumes between PVE and LVD. Discussion Adding HVE to PVE during the same procedure is an innovative and promising approach that may lead to a rapid and major increase in volume and function of the FLR, thereby increasing the rate of resectable patients and limiting the risk of patient’s drop-out. Trial registration This study was registered on clinicaltrials.gov on 15th February 2019 (NCT03841305).

Published
2020

13. Intra-arterial idarubicin_lipiodol without embolization can provide prolonged complete response in hepatocellular carcinoma: A case report

Author

Sophie Gehin, Mathieu Boulin, Pauline Pistre, Boris Guiu, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), 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 EPICAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), and 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

Subjects
Male, Hepatocellular carcinoma, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, medicine.medical_treatment, Gastroenterology, Ethiodized Oil, 0302 clinical medicine, MESH: Infusions, Intra-Arterial, MESH: Liver Neoplasms, Pharmacology (medical), Embolization, MESH: Carcinoma, Hepatocellular, Complete response, MESH: Treatment Outcome, MESH: Aged, Standard treatment, Liver Neoplasms, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 3. Good health, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Lipiodol, 030211 gastroenterology & hepatology, medicine.drug, medicine.medical_specialty, Intra-arterial therapy, Carcinoma, Hepatocellular, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, MESH: Ethiodized Oil, Internal medicine, medicine, Humans, Infusions, Intra-Arterial, Idarubicin, Contraindication, Aged, MESH: Humans, business.industry, MESH: Idarubicin, medicine.disease, digestive system diseases, MESH: Male, Regimen, MESH: Antineoplastic Agents, business
Abstract

International audience; Hepatocellular carcinoma is the fourth leading cause of cancer death. For unresectable intermediate-stage hepatocellular carcinoma, the standard treatment is transarterial chemoembolization. To date, the overall survival at three years remains low, and there is currently no consensus about the best anticancer agent and optimal treatment regimen. We report the case of a hepatocellular carcinoma patient with a vascular contraindication to embolization who achieved a complete response after four intra-arterial infusions of idarubicin emulsified with lipiodol. The patient maintained his response over a three-year period without any hepatocellular carcinoma treatment, demonstrating the major role of the anticancer agent in the efficacy of transarterial therapies for intermediate-stage hepatocellular carcinoma.

Published
2020

14. Risk factors of de novo malignancies after liver transplantation: a French national study on 11004 adult patients

Author

Christophe Duvoux, Mario Altieri, Nassim Kamar, Jean Gugenheim, Sébastien Dharancy, Filomena Conti, Armand Abergel, Olivier Sérée, Georges-Philippe Pageaux, Ephrem Salamé, Jean Hardwigsen, Karim Boudjema, Pascal Lebray, Philippe Segol, Camille Besch, Vincent Leroy, Didier Samuel, Guy Launoy, Claire Vanlemmens, Sylvie Radenne, Maryline Debette-Gratien, Olivier Chazouillères, Xavier Blaizot, Martine Neau-Cransac, Claire Francoz, Marianne Latournerie, Jérôme Dumortier, Audrey Coilly, Pauline Houssel-Debry, François Durand, Olivier Boillot, Faouzi Saliba, Thierry Lobbedez, CCSD, Accord Elsevier, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), 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)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), 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), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, CHU Pontchaillou [Rennes], Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Centre de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Hôpital Henri Mondor, Ecole Polytechnice Universitaire de Nice (EPU Nice -Polytech'Nice-Sophia), 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)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Néphrologie - Immunologie Clinique [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-PRES Université de Toulouse, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), 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 [Grenoble] (CHU), CHU Bordeaux [Bordeaux], 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), Hospices Civils de Lyon (HCL), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), and CHU Strasbourg

Subjects
Oncology, Adult, Male, medicine.medical_specialty, MESH: Liver Transplantation, Liver tumor, medicine.medical_treatment, Liver transplantation, Malignancy, Primary sclerosing cholangitis, 03 medical and health sciences, Liver disease, 0302 clinical medicine, MESH: Liver Neoplasms, MESH: Risk Factors, Risk Factors, Internal medicine, medicine, Humans, MESH: Incidence, Lung cancer, Retrospective Studies, MESH: Humans, Hepatology, business.industry, Incidence, Liver Neoplasms, Gastroenterology, Retrospective cohort study, MESH: Adult, MESH: Retrospective Studies, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Competing risk, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Male, Liver Transplantation, 030220 oncology & carcinogenesis, Population study, 030211 gastroenterology & hepatology, business, Liver transplantationde novomalignancies
Abstract

International audience; Background: After liver transplantation (LT),de novo malignancies are one of the leading causes of late mortality. The aim of the present retrospective study was to identify the risk factors of de novo malignancies in a large cohort of LT recipients in France, using Fine and Gray competing risks regression analysis.Methods: The study population consisted in 11004 adults transplanted between 2000 and 2013, who had no history of pre-transplant malignancy, except primary liver tumor. A Cox model adapted to the identification of prognostic factors (competitive risks) was used.Results: From the entire cohort, one (or more)de novo malignancy was reported in 1480 L T recipients (13.45%). The probability to develop a de novo malignancy after LT was 2.07% at 1 year, 13.30% at 5 years, and 28.01% at 10 years. Of the known reported malignancies, the most common malignancies were hematological malignancy (22.36%), non-melanoma skin cancer (19.53%) and lung cancer (12.36%). According to Fine and Gray competing risks regression multivariate analysis, were significant risk factors for post-LT de novo malignancy: recipient age (Subdistribution Hazard Ratio (SHR) = 1.03 95%CI 1.03-1.04), male gender (SHR = 1.45 95%CI 1.27-1.67), non-living donor (SHR = 1.67 95%CI 1.14-2.38), a first LT (SHR = 1.35 95%CI 1.09-1.69) and the type of initial liver disease (alcohol-related liver disease (SHR = 1.63 95%CI 1.22-2.17), primary sclerosing cholangitis (SHR = 1.98 95%CI 1.34-2.91), and primary liver tumor (SHR = 1.88 95%CI 1.41-2.54)). Initial immunosuppressive regimen had no significant impact.Conclusion: The present study confirms that LT recipient characteristics are associated with the risk ofde novo malignancy and this underlines the need for personalized screening in order to improve survival.

Published
2020

15. mTOR Inhibition Is Most Beneficial After Liver Transplantation for Hepatocellular Carcinoma in Patients With Active Tumors

Author

Antonio Daniele Pinna, Natalie Filmann, Lionel Rostaing, Jens Brockmann, Michael Heise, Andreas A. Schnitzbauer, Simone I. Strasser, Giorgio Rossi, Silvio Nadalin, Jean Gugenheim, Tom M. Ganten, Umberto Cillo, Norman M. Kneteman, Koert P. de Jong, André Roy, Víctor Sánchez Turrión, Thomas Becker, Christoph Duvoux, Markus Rentsch, Jürgen Klempnauer, Utz Settmacher, George Philippe Pageaux, Christian Klein, Roberto Troisi, Edward K. Geissler, Darius F. Mirza, Gunnar Söderdahl, Peter Neuhaus, Jan Lerut, Hans J. Schlitt, Patrizia Burra, Vincenzo Mazzaferro, Johann Pratschke, T. Scholz, Neville V. Jamieson, Wolf O. Bechstein, James Powel, Thomas Soliman, Heikki Mäkisalo, Magnus Rizell, René Adam, Bart van Hoek, Michele Colledan, Itxarone Bilbao, Philippe Bachellier, Olivier Chazoullières, Sherrie Bhoori, Jaques Pirenne, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, Schnitzbauer, A, Filmann, N, Adam, R, Bachellier, P, Bechstein, W, Becker, T, Bhoori, S, Bilbao, I, Brockmann, J, Burra, P, Chazoullieres, O, Cillo, U, Colledan, M, Duvoux, C, Ganten, T, Gugenheim, J, Heise, M, van Hoek, B, Jamieson, N, de Jong, K, Klein, C, Klempnauer, J, Kneteman, N, Lerut, J, Makisalo, H, Mazzaferro, V, Mirza, D, Nadalin, S, Neuhaus, P, Pageaux, G, Pinna, A, Pirenne, J, Pratschke, J, Powel, J, Rentsch, M, Rizell, M, Rossi, G, Rostaing, L, Roy, A, Scholz, T, Settmacher, U, Soliman, T, Strasser, S, Soderdahl, G, Troisi, R, Turrion, V, Schlitt, H, Geissler, E, Universitätsklinikum Frankfurt, Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, Les Hôpitaux Universitaires de Strasbourg (HUS), University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, IRCCS Istituto Nazionale dei Tumori [Milano], Vall d'Hebron University Hospital [Barcelona], Universitätsklinikum Münster, Universita degli Studi di Padova, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Azienda Ospedaliera di Padova, Azienda Ospedaliera Ospedale Papa Giovanni XXIII [Bergamo, Italy], 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), UniversitätsKlinikum Heidelberg, Centre Hospitalier Universitaire de Nice (CHU Nice), Leiden University Medical Center (LUMC), Cambridge University Hospitals - NHS (CUH), University of Cambridge [UK] (CAM), Addenbrooke's Hospital, Cambridge University NHS Trust, University Medical Center Groningen [Groningen] (UMCG), University of Groningen [Groningen], Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Medizinische Hochschule Hannover (MHH), University of Alberta, Université Catholique de Louvain = Catholic University of Louvain (UCL), Helsinki University Hospital, University Hospitals Birmingham [Birmingham, Royaume-Uni], Queens Elizabeth Hospital [Birmingham], Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Policlinico S. Orsola-malpighi, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO)-Servizio sanitario regionale Emilia-Romagna, UZLeuven, Royal Infirmary of Edinburgh, Ludwig-Maximilians-Universität München (LMU), Sahlgrenska University Hospital [Gothenburg], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, CHU Grenoble, Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Uppsala University Hospital, Universitätsklinikum Jena [Jena], Medizinische Universität Wien = Medical University of Vienna, Royal Prince Alfred Hospital, Karolinska University Hospital [Stockholm], Ghent University Hospital, Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain], University Hospital Regensburg, Fraunhofer Institute for Toxicology and Experimental Medicine (Fraunhofer ITEM), Fraunhofer (Fraunhofer-Gesellschaft), Publica, Schnitzbauer, A. A., Filmann, N., Adam, R., Bachellier, P., Bechstein, W. O., Becker, T., Bhoori, S., Bilbao, I., Brockmann, J., Burra, P., Chazoullieres, O., Cillo, U., Colledan, M., Duvoux, C., Ganten, T. M., Gugenheim, J., Heise, M., van Hoek, B., Jamieson, N., de Jong, K. P., Klein, C. G., Klempnauer, J., Kneteman, N., Lerut, J., Makisalo, H., Mazzaferro, V., Mirza, D. F., Nadalin, S., Neuhaus, P., Pageaux, G. -P., Pinna, A. D., Pirenne, J., Pratschke, J., Powel, J., Rentsch, M., Rizell, M., Rossi, G., Rostaing, L., Roy, A., Scholz, T., Settmacher, U., Soliman, T., Strasser, S., Soderdahl, G., Troisi, R., Turrion, V. S., Schlitt, H. J., Geissler, E. K., Università degli Studi di Padova = University of Padua (Unipd), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Herrada, Anthony, Groningen Institute for Organ Transplantation (GIOT), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
Male, Oncology, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, medicine.medical_treatment, Medizin, Liver transplantation, MESH: Intention to Treat Analysis, mTOR-inhibition, 0302 clinical medicine, MESH: Liver Neoplasms, Clinical endpoint, MESH: Carcinoma, Hepatocellular, Milan criteria, MESH: Aged, MESH: Middle Aged, Liver Neoplasms, Hazard ratio, Middle Aged, Intention to Treat Analysis, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, multivariate COX regression, Female, 030211 gastroenterology & hepatology, MESH: Immunosuppressive Agents, MESH: Neoplasm Recurrence, Local, Immunosuppressive Agents, medicine.drug, medicine.medical_specialty, MESH: Liver Transplantation, Carcinoma, Hepatocellular, MESH: Survival Rate, AFP, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 03 medical and health sciences, Internal medicine, medicine, Carcinoma, Humans, Survival rate, Aged, Sirolimus, MESH: Humans, business.industry, medicine.disease, digestive system diseases, MESH: Male, Liver Transplantation, Surgery, MESH: Sirolimus, Neoplasm Recurrence, Local, business, MESH: Female
Abstract

OBJECTIVE: The aim of this study was to evaluate the survival benefit of sirolimus in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) (exploratory analysis of the SiLVER-trial). SUMMARY AND BACKGROUND DATA: Patients receiving LT) for HCC are at a high risk for tumor recurrence. Calcineurin inhibitors have shown evidence to promote cancer growth, whereas mammalian target of rapamycin (mTOR) inhibitors like sirolimus have anticancer effects. In the SiLVER-trial (Clinicaltrials.gov: NCT00355862), the effect of sirolimus on the recurrence of HCC after LT was investigated in a prospective randomized trial. Although the primary endpoint of improved disease-free survival (DFS) with sirolimus was not met, outcomes were improved for patients in the sirolimus-treatment arm in the first 3 to 5 years. To learn more about the key variables, a multivariate analysis was performed on the SiLVER-trial data. PATIENTS AND METHODS: Data from 508 patients of the intention-to-treat analysis were included in exploratory univariate and multivariate models for overall survival (OS), DFS and a competing risk analysis for HCC recurrence. RESULTS: Sirolimus use for ≥3 months after LT for HCC independently reduced the hazard for death in the multivariate analysis [hazard ratio (HR): 0.7 (95% confidence interval, CI: 0.52-0.96, P = 0.02). Most strikingly, patients with an alpha-fetoprotein (AFP) ≥10 ng/mL and having used sirolimus for ≥3 months, benefited most with regard to OS, DFS, and HCC-recurrence (HR: 0.49-0.59, P = 0.0079-0.0245). CONCLUSIONS: mTOR-inhibitor treatment with sirolimus for ≥3 months improves outcomes in LT for HCC, especially in patients with AFP-evidence of higher tumor activity, advocating particularly for mTOR inhibitor use in this subgroup of patients. CLINICAL TRIAL REGISTRATION: EudraCT: 2005-005362-36 CLINICALTRIALS.GOV:: NCT00355862. ispartof: ANNALS OF SURGERY vol:272 issue:5 pages:855-862 ispartof: location:United States status: published

Published
2020

16. Increased recurrence rates of hepatocellular carcinoma after DAA therapy in a hepatitis C-infected Egyptian cohort: A comparative analysis

Author

Shimaa Afify, Mohamed Salaheldin, Ahmad Sweedy, Naglaa Youssef, Arnaud Fontanet, A. El Tahan, Kévin Jean, G. Esmat, Mohamed Eltabbakh, Anna L. Funk, M. El Kassas, Yusuke Shimakawa, Helwan University [Caire], Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Université Ain Shams, Laboratoire Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Cairo University, National Hepatology and Tropical Medicine Research Institute [Cairo], Institut Carnot Pasteur Maladie Infectieuse ANR-11-CARN-017-01, The authors declare no personal conflict of interests. Anna Funk is part of the Pasteur‐Paris University (PPU) International PhD Program and has received funding from the Institut Carnot Pasteur Maladie Infectieuse (ANR 11‐CARN 017‐01). This work benefited from the kind contribution of Alice Zuccaire., Institut Pasteur [Paris] (IP)-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)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and 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)

Subjects
Male, Oncology, Rate ratio, MESH: Egypt, 0302 clinical medicine, MESH: Liver Neoplasms, Recurrence, Prospective Studies, hepatitis c, MESH: Carcinoma, Hepatocellular, Prospective cohort study, education.field_of_study, MESH: Middle Aged, Liver Neoplasms, hepatocellular carcinoma, Hepatitis C, Middle Aged, MESH: Hepatitis C, Chronic, 3. Good health, Infectious Diseases, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cohort, symbols, Egypt, Female, 030211 gastroenterology & hepatology, Liver cancer, medicine.medical_specialty, Carcinoma, Hepatocellular, Population, 03 medical and health sciences, symbols.namesake, Virology, Internal medicine, medicine, Humans, Poisson regression, education, MESH: Humans, Hepatology, business.industry, DAAs, Hepatitis C, Chronic, medicine.disease, MESH: Male, MESH: Prospective Studies, digestive system diseases, MESH: Recurrence, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female
Abstract

International audience; In Egypt, hepatocellular carcinoma (HCC) is the most common form of cancer and direct-acting antivirals (DAA) are administered on a large scale to patients with chronic HCV infection to reduce the risk. In this unique setting, we aimed to determine the association of DAA exposure with early-phase HCC recurrence in patients with a history of HCV-related liver cancer. This was a prospective cohort study of an HCV-infected population from one Egyptian specialized HCC management centre starting from the time of successful HCC intervention. The incidence rates of HCC recurrence between DAA-exposed and nonexposed patients were compared, starting from date of HCC complete radiological response and censoring after 2 years. DAA exposure was treated as time varying. Two Poisson regressions models were used to control for potential differences in the exposed and nonexposed group; multivariable adjustment and balancing using inverse probability of treatment weighting (IPTW). We included 116 patients: 53 treated with DAAs and 63 not treated with DAAs. There was 37.7% and 25.4% recurrence in each group after a median of 16.0 and 23.0 months of follow-up, respectively. Poisson regression using IPTW demonstrated an association between DAAs and HCC recurrence with an incidence rate ratio of 3.83 (95% CI: 2.02-7.25), which was similar in the multivariable-adjusted model and various sensitivity analyses. These results add important evidence towards the possible role of DAAs in HCC recurrence and stress the need for further mechanistic studies and clinical trials to accurately confirm this role and to identify patient characteristics that may be associated with this event.

Published
2018

17. [Prevention of liver fibrosis and liver cancer linked to hepatitis B virus in Africa: the Prolifica study]

Author

Cohen, Damien, Shimakawa, Yusuke, Ndow, Gibril, Sow, Amina, Tamba, Saydiba, Njie, Ramou, Lo, Gora, Ghosh, Sumantra, Toure-Kane, Coumba, Ka, Mourtalla, Mboup, Souleymane, Okeke, Edith, Toure, Souleymane, Diop, Madoky, D'Alessandro, Umberto, Taylor-Robinson, Simon, Mendy, Maimuna, Zoulim, Fabien, Thursz, Mark R, Lemoine, Maud, Chemin, Isabelle, 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), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-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)-Institut Pasteur [Paris] (IP)-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), Imperial College London, Medical Research Council Unit The Gambia (MRC), Hôpital Aristide-Le-Dantec, University of Jos [Nigeria], Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Shimakawa, Yusuke, Wellcome Trust, British Liver Trust, and Medical Research Council

Subjects
Liver Cirrhosis, PRACTICE GUIDELINES MANAGEMENT, MESH: Poverty, Research & Experimental Medicine, DIAGNOSIS, VALIDATION, Health Services Accessibility, MESH: Liver Neoplasms, HEPATOCELLULAR-CARCINOMA, General & Internal Medicine, INFECTION, Humans, MESH: Africa South of the Sahara, Poverty, Africa South of the Sahara, RISK, MESH: Health Services Accessibility, Science & Technology, MESH: Humans, Hepatitis B Surface Antigens, MESH: Hepatitis B, Health Policy, Liver Neoplasms, GAMBIA, DNA, Hepatitis B, digestive system diseases, MESH: Hepatitis B Surface Antigens, Medicine, Research & Experimental, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Health Policy, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, VIRAL-HEPATITIS, MESH: Liver Cirrhosis, Life Sciences & Biomedicine
Abstract

International audience; Despite the existence of an effective vaccine, HBV infects 257 million people worldwide and is the cause of the majority of HCC. With an annual mortality rate of 887 000 patients in 2015, this cancer is the second deadliest. Low-income countries such as ones in sub-Saharan Africa are the most at risk due to the limited access to healthcare. To overcome this and born from an international research collaboration within an EU project, the Prolifica study aimed at evaluating a screen-and-treat program to prevent HBV complications, and more particularly HCC. Based on communities, facilities and hospitals HBsAg+ detection, the study lasted from 2011 to 2016. From the "cost effectiveness" feasibility of such a program to the development of simple scores for antiviral treatment, Prolifica uncovered data of crucial importance in a region with low HBV infection awareness, transmissions modes and prevention means which could have impacts on public health policies.

Published
2019

18. Prévention de la fibrose et du cancer du foie liés au virus de l’hépatite B en Afrique

Author

Cohen, Damien, Shimakawa, Yusuke, Ndow, Gibril, Sow, Amina, Tamba, Saydiba, Njie, Ramou, Lo, Gora, Ghosh, Sumantra, Touré-Kane, Coumba, Ka, Mourtalla, Mboup, Souleymane, Okeke, Edith, Toure, Souleymane, Diop, Madoky, D'Alessandro, Umberto, Taylor-Robinson, Simon, Mendy, Maimuna, Zoulim, Fabien, Thursz, Mark, Lemoine, Maud, Chemin, Isabelle, 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), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Imperial College London, Medical Research Council Unit The Gambia (MRC), Hôpital Aristide-Le-Dantec, University of Jos [Nigeria], Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), 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 Pasteur [Paris] (IP)-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)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and 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)

Subjects
MESH: Health Services Accessibility, MESH: Humans, MESH: Hepatitis B, MESH: Liver Neoplasms, MESH: Poverty, MESH: Health Policy, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Africa South of the Sahara, MESH: Liver Cirrhosis, digestive system diseases, MESH: Hepatitis B Surface Antigens
Abstract

International audience; Despite the existence of an effective vaccine, HBV infects 257 million people worldwide and is the cause of the majority of HCC. With an annual mortality rate of 887 000 patients in 2015, this cancer is the second deadliest. Low-income countries such as ones in sub-Saharan Africa are the most at risk due to the limited access to healthcare. To overcome this and born from an international research collaboration within an EU project, the Prolifica study aimed at evaluating a screen-and-treat program to prevent HBV complications, and more particularly HCC. Based on communities, facilities and hospitals HBsAg+ detection, the study lasted from 2011 to 2016. From the "cost effectiveness" feasibility of such a program to the development of simple scores for antiviral treatment, Prolifica uncovered data of crucial importance in a region with low HBV infection awareness, transmissions modes and prevention means which could have impacts on public health policies.

Published
2019

19. Control of progression towards liver fibrosis and hepatocellular carcinoma by SOCS3 polymorphisms in chronic HCV-infected patients

Author

Pascal Pineau, Hanane Salih Alj, Imane Zaidane, Rachid Saile, Fatima Zahra Jadid, Soumaya Benjelloun, Hajar Chihab, Sanaa Tazi, Sayeh Ezzikouri, Agnès Marchio, Raouia Elfihry, Wafaa Badre, Kamal Marhoum El Filali, Mohammed Tahiri, Institut Pasteur du Maroc, Réseau International des Instituts Pasteur (RIIP), Université Hassan II [Casablanca] (UH2MC), CHU Ibn Rochd [Casablanca], Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), MARCHIO, Agnes, and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Liver Cirrhosis, Male, 0301 basic medicine, Oncology, Cirrhosis, Genetic Linkage, Hepacivirus, medicine.disease_cause, Linkage Disequilibrium, MESH: Genotype, Liver disease, Gene Frequency, MESH: Liver Neoplasms, MESH: Hepacivirus, SOCS3, MESH: Carcinoma, Hepatocellular, MESH: Polymorphism, Single Nucleotide, Liver Neoplasms, MESH: Genetic Predisposition to Disease, Viral Load, MESH: Case-Control Studies, MESH: Gene Expression Regulation, 3. Good health, HCV infection, MESH: Hepatitis C, Chronic, Infectious Diseases, Real-time polymerase chain reaction, MESH: Linkage Disequilibrium, MESH: Suppressor of Cytokine Signaling 3 Protein, Hepatocellular carcinoma, Disease Progression, Female, MESH: Disease Progression, MESH: Liver Cirrhosis, MESH: Viral Load, Microbiology (medical), medicine.medical_specialty, Carcinoma, Hepatocellular, Genotype, Hepatitis C virus, MESH: Genetic Linkage, Single-nucleotide polymorphism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Polymorphism, Single Nucleotide, Microbiology, 03 medical and health sciences, Insulin resistance, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, MESH: Polymorphism, Genetic, Genetics, medicine, MESH: Gene Frequency, Humans, Genetic Predisposition to Disease, Polymorphism, Molecular Biology, Alleles, Ecology, Evolution, Behavior and Systematics, Polymorphism, Genetic, MESH: Humans, MESH: Alleles, mRNA expression, Hepatitis C, Chronic, medicine.disease, MESH: Male, 030104 developmental biology, Gene Expression Regulation, Suppressor of Cytokine Signaling 3 Protein, Case-Control Studies, MESH: Biomarkers, MESH: Female, Biomarkers
Abstract

Chronic Hepatitis C is one of the most important risk factors of liver cirrhosis and hepatocellular carcinoma. Before reaching these ultimate steps, insulin resistance triggered by hepatitis C virus infection is known to participate in the progression of liver disease. The present study aims to investigate the influence of two functional polymorphisms on SOCS3 mRNA expression and on the outcomes of CHC progression in a North African context.In this case-control study, 601 Moroccan subjects composed of 200 healthy controls, 101 resolvers and 300 patients with persistent HCV infection including 95 mild chronic hepatitis, 131 Advanced Liver Diseases and 74 HCC were enrolled. They were genotyped for the 4874 A/G (rs4969170) and A + 930- G (rs4969168) SOCS3 variants using TaqMan SNPs assays. SOCS3 mRNA expression was assessed using Real Time PCR technique.Logistic regression analysis showed that variation at rs4969168 was associated with spontaneous clearance of HCV (P 0.05). In addition, minor allele frequencies were significantly higher in AdLD patients when compared to the mCHC group both for rs4969168 (P = 7.0 E-04) and rs4969170 (P = 4.0 E-05). A significant association between haplotype and liver disease progression was also found. Moreover, SOCS3 mRNA was significantly more expressed in peripheral leukocytes from patients with HCC than in those from mCHC. Finally, rs4969170 was significantly associated with LDL-lipoprotein (P = 0.04), total cholesterol (P = 5.0 E-04), and higher fasting glucose levels (P = 0.005) in patients with persistent HCV infection.Our results underline the importance of the functional SOCS3 polymorphisms in the modulation of CHC progression and suggest their contribution to HCC development by affecting its mRNA expression and perturbing key metabolic parameters.

Published
2018

20. Assessment of the targeting specificity of a fluorescent albumin conceived as a preclinical agent of the liver function

Author

Michel Bessodes, Pascal Houzé, Johanne Seguin, Katia Lemdani, Nathalie Mignet, Rabah Gahoual, Daniel Scherman, Hugo Salmon, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Unité de pharmacologie chimique et génétique et d'imagerie (UPCGI - UMR 8151 / UMR_S 1022 ), Centre de recherche de Vitry-Alfortville, Rhone Poulenc SA, Laboratoire de Neurochimie, Hospices Civils de Lyon (HCL), Mignet, Nathalie, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Université Paris sciences et lettres (PSL), Service de biochimie métabolique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP), Paris Sciences et Lettres (PSL), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], and PSL Research University (PSL)

Subjects
0301 basic medicine, [SDV]Life Sciences [q-bio], Contrast Media, Lactose, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [SPI.MAT]Engineering Sciences [physics]/Materials, chemistry.chemical_compound, Mice, MESH: Liver Neoplasms, [CHIM] Chemical Sciences, General Materials Science, Tissue Distribution, MESH: Animals, Mice, Inbred BALB C, medicine.diagnostic_test, Liver Neoplasms, Optical Imaging, [CHIM.MATE]Chemical Sciences/Material chemistry, Carbocyanines, Human serum albumin, Fluorescence, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Biochemistry, Liver, Hepatocyte, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Female, MESH: Carbocyanines, medicine.drug, MESH: Cell Line, Tumor, MESH: Mice, Inbred BALB C, MESH: Serum Albumin, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, Flow cytometry, 03 medical and health sciences, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Cell Line, Tumor, MESH: Contrast Media, medicine, MESH: Transplantation, Homologous, Animals, Humans, Transplantation, Homologous, [CHIM]Chemical Sciences, MESH: Lactose, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], MESH: Tissue Distribution, MESH: Mice, Serum Albumin, MESH: Optical Imaging, MESH: Humans, Albumin, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 030104 developmental biology, chemistry, Liver function, MESH: Female, MESH: Liver
Abstract

International audience; In the context of increasing liver diseases, no contrast agent is currently available in Europe and the United States to directly assess the liver function. Only neolactosylated human serum albumin is being clinically used in Asia. In order to perform preclinical studies in the context of liver diseases, we conceived a fluorescent lactosylated albumin for the quantification of liver functional cells (l-Cyal). Precise characterization was achieved in order to determine the amounts of lactose and Cyanine 5 (Cy5) coupled to the albumin. In addition, potential aggregation was characterized by asymmetrical flow field-flow fractionation hyphenated to multi-angle light scattering (AF4-MALS). The optimal functionalized albumin exhibited a mass greater than 87 kDa which corresponds to the addition of 34 lactose moieties per protein and 1-2 Cy5 labels. Also, no significant formation of aggregates could be identified due to the modification of the native albumin. In healthy mice, the accumulation of l-Cyal in the liver and its selectivity for hepatocyte cells were shown by optical imaging and flow cytometry. Administration of l-Cyal to mice bearing liver metastases showed a reduced signal in the liver related to a decrease in the number of hepatocytes. The l-Cyal bioimaging contrast agent could be particularly useful for assessing the state of liver related diseases.

Published
2018

21. Droplet digital PCR detects high rate of TP53 R249S mutants in cell-free DNA of middle African patients with hepatocellular carcinoma

Author

Aubin Béré, Pascal Pineau, Paul Jean Adrien Atangana, Dominique Noah Noah, Claudine Bekondi, Narcisse-Patrice Komas, Marie Amougou Atsama, Agnès Marchio, Richard Njouom, Serge-Magloire Camengo-Police, Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur de Bangui, Hôpital Central de Yaoundé, Hôpital de l'Amitié [Bangui], This work was supported by Institut Pasteur International Network (Action Concertée Inter-Pasteurienne No17-2010, and Grant Dedonder), by the direction of Research Applications and Relations with the Industry (VALO Express), and by the French Ligue Nationale contre le Cancer (Equipe labélisée d’Anne Dejean)., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and MARCHIO, Agnes

Subjects
0301 basic medicine, Male, Aflatoxin B1, MESH: Mutation Rate, Hepatocellular carcinoma, Gene Expression, medicine.disease_cause, Gastroenterology, Polymerase Chain Reaction, Cell-free DNA, 0302 clinical medicine, MESH: Aged, 80 and over, Mutation Rate, MESH: Liver Neoplasms, Digital polymerase chain reaction, Cameroon, MESH: Tumor Suppressor Protein p53, MESH: Carcinoma, Hepatocellular, Aged, 80 and over, MESH: Aged, education.field_of_study, Hematology, MESH: Middle Aged, Liver Neoplasms, MESH: Aflatoxin B1, General Medicine, Middle Aged, Viral Load, MESH: Case-Control Studies, 3. Good health, Central African Republic, MESH: Hepatitis B virus, Cell-free fetal DNA, Droplet digital PCR, MESH: Central African Republic, 030220 oncology & carcinogenesis, Female, alpha-Fetoproteins, Liver cancer, MESH: Viral Load, Cell-Free Nucleic Acids, Adult, medicine.medical_specialty, Hepatitis B virus, Carcinoma, Hepatocellular, MESH: Gene Expression, Adolescent, MESH: Hepatitis B, Chronic, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Malignancy, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Hepatitis B, Chronic, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, education, Aged, MESH: Adolescent, Hepatitis B Surface Antigens, MESH: Humans, business.industry, MESH: Adult, MESH: Polymerase Chain Reaction, MESH: Cameroon, medicine.disease, MESH: Male, MESH: DNA, Viral, MESH: Hepatitis B Surface Antigens, 030104 developmental biology, TP53 mutants, Case-Control Studies, DNA, Viral, MESH: Cell-Free Nucleic Acids, MESH: alpha-Fetoproteins, Tumor Suppressor Protein p53, business, MESH: Female
Abstract

International audience; Hepatocellular carcinoma (HCC) is still a major killing malignancy in sub-Saharan Africa. Lifelong intoxication with aflatoxin B1 is considered as one of the primary causes of this situation. The role of aflatoxin in HCC from a given population is commonly estimated through the prevalence of R249S mutation of TP53, a hallmark for previous exposure to the mycotoxin. However, the role of AFB1 is barely known in large part of Africa. We conducted a survey on circulating cell-free DNA from 149 patients with HCC and 213 control subjects with and without liver diseases from Cameroon and Central African Republic using droplet digital PCR technique. We observed a mutation prevalence of 24.8% (n = 37/149) in patients with tumor and 5.6% (n = 12/213) in controls (P = 2.2E-07). Patients with mutations usually displayed significantly increased circulating alpha-fetoprotein (AFP) values, high hepatitis B virus (HBV) DNA loads as well as worsened values of blood cells count. Interestingly, the fraction of droplets positive for R249S was significantly larger in patients with liver cancer (15.3 ± 3.7%) than in controls (0.5 ± 0.3%, P = 7.1E-04). Our survey indicates that AFB1 is instrumental for HCC development in Middle Africa and that droplet digital PCR might be used in the region both to diagnose HCC and to conduct public health surveys on populations at risk of chronic aflatoxin intoxication.

Published
2018

22. Is there an oncological interest in the combination of CRS/HIPEC for peritoneal carcinomatosis of HCC? Results of a multicenter international study

Author

Vadim Gushchin, M. Teo, Frédéric Dumont, David L. Morris, Jean-Jacques Tuech, Guillaume Passot, Lilian Schwarz, R. Kianmanesh, J. Abba, M. De Simone, Antonio Sommariva, D. Kecmanovic, Jan Franko, D. Delroeux, Rami Younan, S.S. Zaveri, Catherine Arvieux, G. Ferron, Olivier Glehen, Mao-Chih Hsieh, Marc Pocard, Frédéric Marchal, P.K. Pande, Gérard Lorimier, Beate Rau, M.-C. Hsieh, Cécile Brigand, F. Rajan, Seung Hyuk Baik, S. Carrère, P. Meeus, F. Guyon, N. Pirro, Y. Liu, P. Ortega-Deballon, Edward A. Levine, P. Piso, Dario Baratti, F. Zinzindohoue, E. Thibaudeau, A. Sardi, Diane Goéré, J.-M. Bereder, A.A.K. Tentes, R. Lo Dico, Mohammad Alyami, J. Porcheron, O. Sgarbura, S. Mehta, L. Gonzalez-Bayon, Aditi Bhatt, M.P. Holtzman, Pascale Mariani, Wim Ceelen, S.A. Ahrendt, K. Abboud, O. Facy, E. Orsenigo, David L. Bartlett, Paul H. Sugarbaker, P. Cachin, N. Bakrin, Laurent Villeneuve, R.P. Edwards, B. Paquette, J.F. Pingpank, P. Rat, K. Lehmann, Y. Yonemura, S. O'Dwyer, P. Peyrat, John Spiliotis, D. Bouzard, Sanket Mehta, K.W. Lee, I. H. J. T. de Hingh, François Quenet, L. Sideris, S. Msika, Roman Yarema, Eduardo Hiroshi Akaishi, Clarisse Eveno, H.J. Zeh, Pierre Dubé, Eun Jung Park, Vahan Kepenekian, Département de chirurgie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Institut Gustave Roussy (IGR), Département de chirurgie, CRLCC Val d'Aurelle - Paul Lamarque, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), and Hospices Civils de Lyon (HCL)

Subjects
Male, MESH: Combined Modality Therapy, Colorectal cancer, Hepatocellular carcinoma, 0302 clinical medicine, MESH: Liver Neoplasms, Pseudomyxoma peritonei, MESH: Peritoneal Neoplasms, Cytoreductive surgery, MESH: Carcinoma, Hepatocellular, Peritoneal Neoplasms, MESH: Treatment Outcome, MESH: Aged, Univariate analysis, MESH: Middle Aged, Standard treatment, Liver Neoplasms, General Medicine, Cytoreduction Surgical Procedures, Middle Aged, Prognosis, Combined Modality Therapy, 3. Good health, Survival Rate, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Hyperthermic intraperitoneal chemotherapy, Female, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, MESH: Survival Rate, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Prognosis, 03 medical and health sciences, medicine, Humans, MESH: Cytoreduction Surgical Procedures, MESH: Hyperthermia, Induced, Aged, Retrospective Studies, MESH: Adolescent, MESH: Humans, HIPEC, business.industry, MESH: Adult, MESH: Retrospective Studies, Hyperthermia, Induced, medicine.disease, MESH: Male, Surgery, Peritoneal Cancer Index, Ovarian cancer, business, MESH: Female, Peritoneal carcinomatosis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Introduction Peritoneal metastasis (PM) of hepatocellular carcinoma (HCC) without distant spread are rare. The related prognosis is poor without standard treatment available. The role of cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is poorly documented. Methods An international multicentric cohort was constituted by retrospective analysis of 21 patients undergoing CRS/HIPEC for PM of HCC between 1992 and 2016 from 10 reference centers of PSOGI. Data on clinical features, treatment strategies, and survival outcomes were analyzed. Results The median time interval from the diagnosis of PM to the procedure was 4.5 months. The median peritoneal cancer index was 14. Sixteen patients had complete cytoreduction (CCR0-1). Ten patients had grades 3 to 4 complications. The median duration of follow-up was 52.2 months. The median OS was 46.7 months. The projected 3y-OS and 5y-OS were 88.9 and 49.4% respectively. The median OS for patients with CCR0-1 resection was not reached whereas it was 5.9 months for those with CCR2-3 resection after CRS (p = 0.0005). The median RFS was 26.3 months and projected RFS at 3 years of 36.5 months Three prognostic factors were associated with improved RFS in the univariate analysis: preoperative chemotherapy (p = 0.0156), PCI >15 (p = 0.009), Number of chemotherapy agents used for HIPEC (p = 0.005). Conclusion CRS/HIPEC is a safe and effective approach in selected patients with PM of HCC. CRS/HIPEC gives the patient a chance for a good relapse free and overall survival and should be considered as an option.

Published
2018

23. TP53INP1 Downregulation Activates a p73-Dependent DUSP10/ERK Signaling Pathway to Promote Metastasis of Hepatocellular Carcinoma

Author

Ng, Kai-Yu, Chan, Lok-Hei, Chai, Stella, Tong, Man, Guan, Xin-Yuan, Lee, Nikki, Yuan, Yunfei, Xie, Dan, Lee, Terence, Dusetti, Nelson, Carrier, Alice, Ma, Stephanie, Ma, Man, Yuan, Xin-Yuan, Ma, Nelson, Ma, Alice, City University of Hong Kong [Hong Kong] (CUHK), State key Laboratory for Liver Research, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University [Hong Kong] (POLYU), 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, 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), and Sun Yat-sen University Cancer Center (SYSUCC)

Subjects
0301 basic medicine, MAPK/ERK pathway, Oncology, MESH: Signal Transduction, Cancer Research, Lung Neoplasms, [SDV]Life Sciences [q-bio], MESH: Heat-Shock Proteins, Metastasis, Mice, 0302 clinical medicine, MESH: Liver Neoplasms, Tumor Cells, Cultured, MESH: Animals, Neoplasm Metastasis, MESH: Carcinoma, Hepatocellular, MESH: Mitogen-Activated Protein Kinase Phosphatases, Heat-Shock Proteins, Mitogen-Activated Protein Kinase 1, Mice, Inbred BALB C, Mitogen-Activated Protein Kinase 3, MESH: Protein Array Analysis, Liver Neoplasms, Prognosis, 3. Good health, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, MESH: Dual-Specificity Phosphatases, Dual-Specificity Phosphatases, MESH: Tumor Protein p73, Signal transduction, MESH: Mitogen-Activated Protein Kinase 3, Signal Transduction, MESH: Mitogen-Activated Protein Kinase 1, medicine.medical_specialty, MESH: Xenograft Model Antitumor Assays, Carcinoma, Hepatocellular, Protein Array Analysis, MESH: Mice, Inbred BALB C, Mice, Nude, MESH: Carrier Proteins, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MESH: Prognosis, 03 medical and health sciences, MESH: Gene Expression Profiling, Downregulation and upregulation, Internal medicine, Carcinoma, medicine, MESH: Mice, Nude, Animals, Humans, MESH: Tumor Cells, Cultured, neoplasms, MESH: Mice, MESH: Humans, Gene Expression Profiling, Cancer, Tumor Protein p73, medicine.disease, Xenograft Model Antitumor Assays, MESH: Neoplasm Metastasis, digestive system diseases, MESH: Lung Neoplasms, Gene expression profiling, 030104 developmental biology, Cancer research, Mitogen-Activated Protein Kinase Phosphatases, Carrier Proteins
Abstract

Identifying critical factors involved in the metastatic progression of hepatocellular carcinoma (HCC) may offer important therapeutic opportunities. Here, we report that the proapoptotic stress response factor TP53INP1 is often selectively downregulated in advanced stage IV and metastatic human HCC tumors. Mechanistic investigations revealed that TP53INP1 downregulation in early-stage HCC cells promoted metastasis via DUSP10 phosphatase-mediated activation of the ERK pathway. The DUSP10 promoter included putative binding sites for p73 directly implicated in modulation by TP53INP1. Overall, our findings show how TP53INP1 plays a critical role in limiting the progression of early-stage HCC, with implications for developing new therapeutic strategies to attack metastatic HCC. Cancer Res; 77(17); 4602–12. ©2017 AACR.

Published
2017

24. TP53 R72P polymorphism modulates DNA methylation in hepatocellular carcinoma

Author

Soumaya Benjelloun, Pascal Pineau, Henda Triki, Anne Dejean, Khadija Rebbani, Abdellah Essaid El Feydi, Agnès Marchio, Olfa Bahri, Mostafa Kandil, Rajaa Afifi, Sayeh Ezzikouri, Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur du Maroc, Réseau International des Instituts Pasteur (RIIP), Department of Medicine C, Ibn-Sina University Hospital, Rabat, Université Chouaib Doukkali (UCD), Laboratoire de Virologie Clinique, Référence Régional OMS pour la Poliomyélite et la Rougeole - Laboratory of Clinical Virology, WHO Regional Reference Laboratory on Poliomyelitis and Measles, Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Pasteur Tunis, Institut

Subjects
Male, Cancer Research, [SDV]Life Sciences [q-bio], MESH: Africa, Northern, MESH: Genotype, 0302 clinical medicine, MESH: DNA Methylation, Africa, Northern, MESH: Liver Neoplasms, Chromosome instability, Genotype, TP53, MESH: Carcinoma, Hepatocellular, Genetics, MESH: Aged, 0303 health sciences, education.field_of_study, DNA methylation, MESH: Middle Aged, MESH: Codon, MESH: Polymorphism, Single Nucleotide, Liver Neoplasms, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Oncology, 030220 oncology & carcinogenesis, Molecular Medicine, Female, Liver cancer, Adult, Carcinoma, Hepatocellular, Population, Biology, Polymorphism, Single Nucleotide, Cell Line, 03 medical and health sciences, Germline mutation, Genetic predisposition, medicine, Humans, Epigenetics, Polymorphism, Codon, education, Aged, 030304 developmental biology, MESH: Humans, Research, MESH: Adult, Hepatocellular Carcinoma, medicine.disease, MESH: Male, MESH: Cell Line, Cancer research, MESH: Female
Abstract

Background Hepatocellular carcinoma (HCC) is characterized by widespread epidemiological and molecular heterogeneity. Previous work showed that in the western part of North Africa, a region of low incidence of HCC, mutations are scarce for this tumor type. As epigenetic changes are considered possible surrogates to mutations in human cancers, we decided, thus, to characterize DNA methylation in HCC from North-African patients. Methods A set of 11 loci was investigated in a series of 45 tumor specimens using methylation-specific and combined-bisulfite restriction assay PCR. Results obtained on clinical samples were subsequently validated in liver cancer cell lines. Results DNA methylation at tumor suppressor loci is significantly higher in samples displaying chromosome instability. More importantly, DNA methylation was significantly higher in Arg/Arg when compared to Pro/Pro genotype carriers at codon 72 rs1042522 of TP53 (65% vs 20% methylated loci, p = 0.0006), a polymorphism already known to affect somatic mutation rate in human carcinomas. In vitro experiments in cell lines indicated that enzymes controlling DNA methylation were differentially regulated by codon 72 Arg or Pro isoforms of p53. Furthermore, the Arg72-carrying version of p53 was shown to re-methylate DNA more rapidly than the pro-harboring isoform. Finally, Pro-carrying cell lines were shown to be significantly more resistant to decitabine treatment (two-fold, p = 0.005). Conclusions Our data suggest that Arg72Pro polymorphism in a WT p53 context may act as a primary driver of epigenetic changes in HCC. It suggests, in addition, that rs1042522 genotype may predict sensitivity to epigenetic-targeted therapy. This model of liver tumorigenesis that associates low penetrance genetic predisposition to epigenetic changes emerges from a region of low HCC incidence and it may, therefore, apply essentially to population living in similar areas. Surveys on populations submitted to highly mutagenic conditions as perinatally-acquired chronic hepatitis B or aflatoxin B1 exposure remained to be conducted to validate our observations as a general model. Electronic supplementary material The online version of this article (doi:10.1186/s12943-015-0340-2) contains supplementary material, which is available to authorized users.

Published
2015

25. Towards an HBV cure: state-of-the-art and unresolved questions-report of the ANRS workshop on HBV cure

Author

William S. Mason, François-Loïc Cosset, Raymond F. Schinazi, Helene Strick-Marchand, Michael Kann, Françoise Barré-Sinoussi, Monsef Benkirane, Julie Lucifora, Marie Michel, Fabien Zoulim, Karine Lacombe, Camille Sureau, Brigitte Autran, Mirjam B. Zeisel, Jürgen Beck, Jean François Delfraissy, Fabrice Carrat, David Durantel, Massimo Levrero, Percy A. Knolle, Christian Trepo, Jia-Horng Kao, Maladies Virales et Hépatiques, inserm U1110, 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), Fox Chase Cancer Center, Institut National de la Transfusion Sanguine [Paris] (INTS), University Hospital Freiburg, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Pathogenèse des Virus de l'Hépatite B (PVHB), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunité Innée - Innate Immunity, Hospices Civils de Lyon (HCL), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Emory University [Atlanta, GA], Régulation des Infections Rétrovirales, Institut Pasteur [Paris] (IP), France REcherche Nord & sud Sida-hiv Hépatites (FRENSH), Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France Université de Strasbourg, Strasbourg, France., Centre de Recherche en Cancérologie de Lyon (CRCL), Centre Léon Bérard [Lyon] - Université Claude Bernard Lyon 1 (UCBL) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Fox Chase Cancer Center, Philadelphia, USA, INTS, Laboratoire de Virologie Moléculaire, Paris, France, Department of Internal Medicine 2/Molecular Biology, University Hospital Freiburg, Freiburg, Germany, Center for Life Nanosciences (CNLS)-IIT/Sapienza, Rome, Italy Laboratory of Gene Expression, Department of Internal Medicine (DMISM), Sapienza University of Rome, Italy., Université de Bordeaux, Microbiologie fondamentale et Pathogénicité, UMR 5234, Bordeaux, France CNRS, Microbiologie fondamentale et Pathogénicité, UMR 5234, Bordeaux, France CHU de Bordeaux, Bordeaux, France, Technische Universität München, Institut für Molekulare Immunologie, München, Germany, IGH Institut de Génétique Humaine UPR 1142 CNRS, Montpellier France, Institut Pasteur [Paris] - Institut National de la Santé et de la Recherche Médicale (INSERM), Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC) - IFR113 - Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure - Lyon (ENS Lyon) - Université Claude Bernard Lyon 1 (UCBL) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Immunité Innée, Université de Lyon (UCBL), Lyon, France Department of Hepatology, Croix-Rousse Hospital, Hospices Civils de Lyon, Lyon, France, Department of Internal Medicine, Department of Medical Research, Graduate Institute of Clinical Medicine, and Hepatitis Research Center, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan, Université Pierre et Marie Curie - Paris 6 (UPMC) - Institut National de la Santé et de la Recherche Médicale (INSERM), Center for AIDS Research, Emory University School of Medicine and Veterans Affairs Medical Center, Atlanta, Georgia, USA, Institut Pasteur [Paris], ANRS (France Recherche Nord & Sud Sida-HIV Hépatites), Paris, France, Service d'Immunologie [CHU Pitié-Salpétrière], 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 International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Naiglin, Laurence, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Equipee 16, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Institut Pasteur [Paris]-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)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
Liver Cirrhosis, surface-antigen, [SDV]Life Sciences [q-bio], hepatocellular-carcinoma, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH: Global Health, Global Health, in-vivo, MESH: Liver Neoplasms, Medicine, Viral suppression, MESH: Incidence, immune-responses, MESH: Carcinoma, Hepatocellular, ComputingMilieux_MISCELLANEOUS, Incidence, molecular determinants, Liver Neoplasms, Gastroenterology, virus diseases, ddc, 3. Good health, [SDV] Life Sciences [q-bio], Vaccination, MESH: Hepatitis B virus, humanized mice, hepatitis-b-virus, epigenetic regulation, cell-function, viral entry, Disease Progression, MESH: Disease Progression, MESH: Liver Cirrhosis, Viral hepatitis, MESH: Antiviral Agents, Hepatitis B virus, medicine.medical_specialty, Carcinoma, Hepatocellular, MESH: Hepatitis B, Chronic, Antiviral Agents, Hepatitis B, Chronic, Acquired immunodeficiency syndrome (AIDS), Humans, Intensive care medicine, MESH: Humans, business.industry, medicine.disease, digestive system diseases, MESH: DNA, Viral, DNA, Viral, Immunology, business, Viral persistence
Abstract

Affiliations ECOFECT; International audience; HBV infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Although HBV infection can be efficiently prevented by vaccination, and treatments are available, to date there is no reliable cure for the >240 million individuals that are chronically infected worldwide. Current treatments can only achieve viral suppression, and lifelong therapy is needed in the majority of infected persons. In the framework of the French National Agency for Research on AIDS and Viral Hepatitis 'HBV Cure' programme, a scientific workshop was held in Paris in June 2014 to define the state-of-the-art and unanswered questions regarding HBV pathobiology, and to develop a concerted strategy towards an HBV cure. This review summarises our current understanding of HBV host-interactions leading to viral persistence, as well as the roadblocks to be overcome to ultimately address unmet medical needs in the treatment of chronic HBV infection.

Published
2015

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