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

Author: Arthur Berger, Federico Ravaioli, Oana Farcau, Davide Festi, Horia Stefanescu, François Buisson, Pierre Nahon, Christophe Bureau, Nathalie Ganne-Carriè, Annalisa Berzigotti, Victor de Ledinghen, Salvatore Petta, Paul Calès, Sylvie Sacher Huvelin, Dominique Valla, Anne Olivier, Frédéric Oberti, Jérôme Boursier, Jean Paul Galmiche, Jean Pierre Vinel, Clotilde Duburque, Alain Attar, Isabelle Archambeaud, Robert Benamouzig, Marianne Gaudric, Dominique Luet, Patrice Couzigou, Lucie Planche, Emmanuel Coron, Jean-Baptiste Hiriart, Faiza Chermak, Maude Charbonnier, Patrick Marcellin, Dominique Guyader, Stanislas Pol, Hélène Fontaine, Dominique Larrey, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Jean-Pierre Zarski, Vincent Leroy, Ghassan Riachi, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Sebastien Dharancy, Jean-Frédéric Blanc, Armand Abergel, Lawrence Serfaty, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Yannick Bacq, Claire Wartelle, Thông Dao, Yves Benhamou, Christophe Pilette, Christine Silvain, Christos Christidis, Dominique Capron, Gérard Thiefin, Sophie Hillaire, Vincent Di Martino, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Regional Institute of Gastroenterology and Hepatology [Cluj-Napoca], Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université Paris 13 (UP13), Hôpital Cochin [AP-HP], Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Institutional support was provided by Programme hospitalier de recherche Clinique and agence nationale de recherches sur le sida et les hépatites virales, who had no other role in the present study., École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Berger A., Ravaioli F., Farcau O., Festi D., Stefanescu H., Buisson F., Nahon P., Bureau C., Ganne-Carrie N., Berzigotti A., de Ledinghen V., Petta S., Cales P., Huvelin S.S., Valla D., Olivier A., Oberti F., Boursier J., Galmiche J.P., Vinel J.P., Duburque C., Attar A., Archambeaud I., Benamouzig R., Gaudric M., Luet D., Couzigou P., Planche L., Coron E., Hiriart J.-B., Chermak F., Charbonnier M., Marcellin P., Guyader D., Pol S., Fontaine H., Larrey D., De Ledinghen V., Ouzan D., Zoulim F., Roulot D., Tran A., Bronowicki J.-P., Zarski J.-P., Leroy V., Riachi G., Peron J.-M., Alric L., Bourliere M., Mathurin P., Dharancy S., Blanc J.-F., Abergel A., Serfaty L., Mallat A., Grange J.-D., Attali P., Bacq Y., Wartelle C., Dao T., Benhamou Y., Pilette C., Silvain C., Christidis C., Capron D., Thiefin G., Hillaire S., and Di Martino V.
Subjects: Blood Platelets, Liver Cirrhosis, Noninvasive Diagnosis, medicine.medical_specialty, Cirrhosis, [SDV]Life Sciences [q-bio], Population, Esophageal and Gastric Varices, Chronic liver disease, Severity of Illness Index, Gastroenterology, End Stage Liver Disease, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Model for End-Stage Liver Disease, Esophageal varices, Internal medicine, Nonalcoholic fatty liver disease, medicine, Humans, education, Baveno VI Criteria, Retrospective Studies, education.field_of_study, Hepatology, business.industry, Retrospective cohort study, Portal Hypertension, medicine.disease, 3. Good health, MELD, 030220 oncology & carcinogenesis, Elasticity Imaging Techniques, 030211 gastroenterology & hepatology, business, Baveno VI Criteria, Blood Platelets, Cirrhosis, Elasticity Imaging Techniques, End Stage Liver Disease, Esophageal and Gastric Varices, Humans, Liver Cirrhosis, MELD, Noninvasive Diagnosis, Portal Hypertension, Retrospective Studies, Severity of Illness, Index
Abstract: International audience; Background & aims: Based on platelets and liver stiffness measurements, the Baveno VI criteria (B6C), the expanded B6C (EB6C), and the ANTICIPATE score can be used to rule out varices needing treatment (VNT) in patients with compensated chronic liver disease. We aimed to improve these tests by including data on the ratio of platelets to liver stiffness.Methods: In a retrospective analysis of data from 10 study populations, collected from 2004 through 2018, we randomly assigned data from 2368 patients with chronic liver disease of different etiologies to a derivation population (n = 1579; 15.1% with VNT, 50.2% with viral hepatitis, 28.9% with nonalcoholic fatty liver disease, 20.8% with alcohol-associated liver disease, with model for end-stage liver disease scores of 9.5 ± 3.0, and 93.0% with liver stiffness measurements ≥10 kPa) or a validation population (n = 789). Test results were compared with results from a sequential algorithm (VariScreen). VariScreen incorporated data on platelets or liver stiffness measurements and then the ratio of platelets to liver stiffness measurement, adjusted for etiology, patient sex, and international normalized ratio.Results: In the derivation population, endoscopies were spared for 23.9% of patients using the B6C (VNT missed in 2.9%), 24.3% of patients using the ANTICIPATE score (VNT missed in 4.6%), 34.5% of patients using VariScreen (VNT missed in 2.9%), and 41.9% of patients using the EB6C (VNT missed in 10.9%). Differences in spared endoscopy rates were significant (P ≤ .001), except for B6C vs ANTICIPATE and in missed VNT only for EB6C vs the others (P ≤ .009). VariScreen was the only safe test regardless of sex or etiology (missed VNT ≤5%). Moreover, VariScreen secured screening without missed VNT in patients with model for end-stage liver disease scores higher than 10. This overall strategy performed better than a selective strategy restricted to patients with compensated liver disease. Test performance and safety did not differ significantly among populations.Conclusions: In a retrospective study of data from 2368 patients with chronic liver disease, we found that the B6C are safe whereas the EB6C are unsafe, based on missed VNT. The VariScreen algorithm performed well in patients with chronic liver disease of any etiology or severity. It is the only test that safely rules out VNT and can be used in clinical practice.
Published: 2021
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2. Impact of cirrhosis aetiology on incidence and prognosis of hepatocellular carcinoma diagnosed during surveillance

Author: Nathalie Ganne-Carrié, Pierre Nahon, Cendrine Chaffaut, Gisèle N’Kontchou, Richard Layese, Etienne Audureau, Sylvie Chevret, Isabelle Archambeaud, Louis d’Alteroche, Frédéric Oberti, Dominique Roulot, Christophe Moreno, Alexandre Louvet, Thông Dao, Romain Moirand, Odile Goria, Eric Nguyen-Khac, Nicolas Carbonell, Jean-Charles Duclos-Vallée, Stanislas Pol, Victor de Ledinghen, Violaine Ozenne, Jean Henrion, Jean-Marie Péron, Albert Tran, Gabriel Perlemuter, Xavier Amiot, Jean-Pierre Zarski, Tarik Asselah, Dominique Guyader, Hélène Fontaine, Georges-Philippe Pageaux, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Jean-Pierre Bronowicki, Thomas Decaens, Ghassan Riachi, Paul Calès, Laurent Alric, Marc Bourlière, Philippe Mathurin, Sebastien Dharancy, Jean-Frédéric Blanc, Armand Abergel, Olivier Chazouillères, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Claire Wartelle, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Brigitte Bernard-Chabert, Sophie Hillaire, Vincent Di Martino, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Nord, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Hôpital Henri Mondor, Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANRS CO12 CirVir group: Pierre Nahon1, Tarik Asselah2, Dominique Guyader3, Stanislas Pol4, Hélène Fontaine4, Georges-Philippe Pageaux5, Victor De Lédinghen6, Denis Ouzan7, Fabien Zoulim8, Dominique Roulot9, Albert Tran10, Jean-Pierre Bronowicki11, Thomas Decaens12, Ghassan Riachi13, Paul Calès14, Jean-Marie Péron15, Laurent Alric16, Marc Bourlière17, Philippe Mathurin18, Sebastien Dharancy18, Jean-Frédéric Blanc19, Armand Abergel20, Olivier Chazouillères21, Ariane Mallat22, Jean-Didier Grangé23, Pierre Attali24, Louis d’Alteroche25, Claire Wartelle26, Thông Dao27, Dominique Thabut28, Christophe Pilette29, Christine Silvain30, Christos Christidis31, Eric Nguyen-Khac32, Brigitte Bernard-Chabert 33, Sophie Hillaire34, Vincent Di Martino35. 1AP-HP, Hôpital Avicenne, Service d’Hépatologie, Bobigny, Université Sorbonne Paris Nord, Bobigny et INSERM U1138, Université de Paris, 2AP-HP, Hôpital Beaujon, Service d’Hépatologie, and University Paris Diderot, Sorbonne Paris Cité, CRI, UMR 1149, 3CHU Pontchaillou, Service d’Hépatologie, Rennes, 4AP-HP, Hôpital Cochin, Département d’Hépatologie et INSERM UMS20 et U1223, Institut Pasteur, Université Paris Descartes, Paris, 5Hôpital Saint Eloi, Service d’Hépatologie, Montpellier, 6Hôpital Haut-Lévêque, Service d’Hépatologie, Bordeaux, 7Institut Arnaud Tzanck, Service d’Hépatologie, St Laurent du Var, 8Hôpital Hôtel Dieu, Service d’Hépatologie, Lyon, 9AP-HP, Hôpital Avicenne, Service de Medeine Interne, Bobigny, 10CHU de Nice, Service d’Hépatologie, et INSERM U1065, Université de Nice-Sophia-Antipolis, Nice, 11Hôpital Brabois, Service d’Hépatologie, Vandoeuvre-les-Nancy, 12Hôpital Michallon, Service d’Hépatologie, Grenoble, 13Hôpital Charles-Nicolle, Service d’Hépatologie, Rouen, 14CHU d’Angers, Service d’Hépatologie, Angers, 15Hôpital Purpan, Service d’Hépatologie, Toulouse, 16CHU Toulouse, Service de Médecine Interne-Pôle Digestif UMR 152, Toulouse, 17Hôpital Saint Joseph, Service d’Hépatologie, Marseille, 18Hôpital Claude Huriez, Service d’Hépatologie, Lille, 19Hôpital St André, Service d’Hépatologie, Bordeaux, 20Hôpital Hôtel Dieu, Service d’Hépatologie, Clermont-Ferrand, 21AP-HP, Hôpital Saint-Antoine, Service d’Hépatologie, Paris, 22AP-HP, Hôpital Henri Mondor, Service d’Hépatologie, Créteil, 23AP-HP, Hôpital Tenon, Service d’Hépatologie, Paris, 24AP-HP, Hôpital Paul Brousse, Service d’Hépatologie, Villejuif, 25Hôpital Trousseau, Unité d’Hépatologie, CHRU de Tours, 26Hôpital d’Aix-En-Provence, Service d’Hépatologie, Aix-En-Provence, 27Hôpital de la Côte de Nacre, Service d’Hépatologie, Caen, 28AP-HP, Groupe Hospitalier de La Pitié-Salpêtrière, Service d’Hépatologie, Paris, 29CHU Le Mans, Service d’Hépatologie, Le Mans, 30CHU de Poitiers, Service d’Hépatologie, Poitiers, 31Institut Mutualiste Montsouris, Service d’Hépatologie, Paris, 32Hôpital Amiens Nord, Service d’Hépatologie, Amiens, 33Hôpital Robert Debré, Service d’Hépatologie, Reims, 34Hôpital Foch, Service d’Hépatologie, Suresnes, 35Hôpital Jean Minjoz, Service d’Hépatologie, Besançon. France., CIRRAL group: Nathalie Ganne-Carrié1, Cendrine Chaffaut2, Isabelle Archambeaud3, Louis d’Alteroche4, Frédéric Oberti5, Dominique Roulot6, Christophe Moreno7, Alexandre Louvet8, Thông Dao9, Romain Moirand10, Odile Goria11, Eric Nguyen-Khac12, Nicolas Carbonell13, Jean-Charles Duclos-Vallée14, Stanislas Pol15,16, Victor de Ledinghen17, Violaine Ozenne18, Jean Henrion19, Jean-Marie Péron20, Albert Tran21,22, Gabriel Perlemuter23, Xavier Amiot24, Jean-Pierre Zarski25, Sylvie Chevret2. 1AP-HP, Hôpital Avicenne, Service d’Hépatologie, Bobigny, Université Sorbonne Paris Nord, Bobigny et INSERM U1138, Université de Paris, 2SBIM, APHP, Hôpital Saint-Louis, Paris, Inserm, UMR-1153, ECSTRA Team, Paris, France, 3Liver, CHU, Nantes, France, 4Liver Unit, University Hospital, Tours, France, 5Liver Unit, University Hospital, Angers, France, 6AP-HP, Hôpital Avicenne, Service de Médecine Interne, Bobigny, Université Sorbonne Paris Nord, Bobigny, 7Liver unit, CUB Hôpital Erasme, Université Libre de Bruxelles, Belgium, 8Liver Unit, University Hospital, Lille, France, 9Liver Unit, University Hospital, Caen, France, 10Liver Unit, University Hospital, Rennes, France, 11Liver Unit, University Hospital, Rouen, France, 12Liver Unit, University Hospital, Amiens, France, 13 Liver Unit, APHP, CHU Saint-Antoine, Paris, France, 14Liver Unit, APHP, CHU Paul Brousse, Villejuif, France, 15Université Paris Descartes, APHP, Liver Unit, Hôpital Cochin, 16INSERM U1223, Institut Pasteur, Paris, France, 17Hepatology Unit, University Hospital, CHU Bordeaux, France, 18Liver Unit, APHP, CHU Lariboisière, Paris, France, 19Liver Unit, University Hospital, Haine Saint-Paul, Belgium, 20Liver Unit, Universitary Hospital Purpan, University Paul Sabatier III, Toulouse, 21Institut National de la Santé et de la Recherche Médicale (INSERM), U1065, Team 8, 'Hepatic Complications in Obesity', Nice, F-06204, Cedex 3, France, 22University Hospital of Nice, Digestive Centre, Nice, F-06202, Cedex 3, France, 23Liver Unit, University Hospital, Béclère, APHP, Clamart, France, 24Liver Unit, APHP, CHU Tenon, Paris, France, and 25Clinique d’hépato-gastroentérologie pôle Digidune CHU de Grenoble, France
Subjects: Alcoholic liver disease, medicine.medical_specialty, Cirrhosis, primary liver cancer, VIR, virus-related, ECOG Performance Status, [SDV.CAN]Life Sciences [q-bio]/Cancer, MIX, alcohol and virus-related, RC799-869, Gastroenterology, law.invention, Randomized controlled trial, law, Internal medicine, Internal Medicine, medicine, Immunology and Allergy, Hepatology, business.industry, Incidence (epidemiology), cirrhosis, competing risk analysis, US, abdominal ultrasound, Hazard ratio, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Diseases of the digestive system. Gastroenterology, medicine.disease, HR, hazard ratio, Hepatocellular carcinoma, ALC, alcohol-related, Etiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, HCC, hepatocellular carcinoma, Research Article, alcoholic liver disease
Abstract: Background & Aims In this study we aimed to analyse the impact of the aetiology of cirrhosis on the incidence, characteristics and prognosis of hepatocellular carcinoma (HCC) diagnosed during a surveillance program. Methods Individual data from a randomized trial and 2 prospective cohorts of patients with compensated histologically proven cirrhosis recruited between 2000 and 2016 were pooled. The influence of cirrhosis aetiology on survival after HCC detection was assessed using multivariable regression models. Results Among 3,533 patients (1,926 virus [VIR], 1,167 alcohol [ALC], 440 combined [MIX]), 431 were diagnosed with HCC after a median follow-up of 57.1 months. The 5-year HCC incidence was lowest in ALC (VIR 12.6%, ALC 9.1%, MIX 14.3%, p = 0.04). At the time of diagnosis, tumour burden and Child-Pugh score were comparable across aetiology groups, but early BCLC stages (0/A) were significantly less frequent in ALC (VIR 80%, ALC 37%, MIX 72%) as a result of worse ECOG performance status. However, similar access to first-line curative HCC treatment was reported across aetiology groups (p = 0.68). Median survival after HCC diagnosis was significantly reduced in ALC (VIR 39, ALC 21, MIX 34 months, p = 0.02). However, when adjusting for tumour size, ECOG and Child-Pugh score, the aetiology of the underlying cirrhosis no longer had a significant impact. Conclusion Compared to patients with virus-related cirrhosis, patients with alcohol-related compensated cirrhosis enrolled in a surveillance program have: i) the lowest 5-year HCC incidence; ii) worse overall prognosis, mostly driven by a poor general condition, despite similar access to first-line curative treatment. Lay summary It has been suggested that early detection of hepatocellular carcinoma (HCC) may be futile in patients with alcohol-related cirrhosis. By comparing outcomes in more than 3,000 patients with compensated cirrhosis included in surveillance programs, this study suggests that HCC surveillance enables early diagnosis in most patients with alcohol-related cirrhosis despite a higher competing risk of death in these patients. We also report similar access to first-line curative HCC treatment in these patients compared to those with viral cirrhosis, despite higher rates of comorbidities and impaired liver function. Following HCC detection, the later parameters were major drivers of death irrespective of the cause of cirrhosis. Registration CHC2000 (NCT00190385) and CIRRAL (NCT01213927) cohorts were registered at ClinicalTrials.gov and the full protocols are available at the following links (https://clinicaltrials.gov/ct2/show/NCT00190385) and https://clinicaltrials.gov/ct2/show/NCT01213927, respectively). The full CirVir protocol is available via the ANRS Web site (http://anrs.fr)., Graphical abstract, Highlights • Alcohol-related cirrhosis linked to the lowest incidence of HCC, the lowest overall survival and the highest incidence of decompensation. • Alcohol-related cirrhosis linked to fewer cases of early stage HCC, although tumour burden and Child-Pugh score were comparable across groups. • Patients with alcohol-related cirrhosis had worse survival after HCC diagnosis than those with virus-related cirrhosis. • The aetiology of cirrhosis had no impact on survival after HCC diagnosis following adjustment for other potential prognostic factors.
Published: 2021
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3. Early hepatocellular carcinoma detection using magnetic resonance imaging is cost-effective in high-risk patients with cirrhosis

Author: Pierre Nahon, Marie Najean, Richard Layese, Kevin Zarca, Laeticia Blampain Segar, Carole Cagnot, Nathalie Ganne-Carrié, Gisèle N’Kontchou, Stanislas Pol, Cendrine Chaffaut, Fabrice Carrat, Maxime Ronot, Etienne Audureau, Isabelle Durand-Zaleski, Tarik Asselah, Dominique Guyader, Hélène Fontaine, Georges-Philippe Pageaux, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Thomas Decaensi, Ghassan Riachi, Paul Calès, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Sebastien Dharancy, Jean-Frédéric Blanc, Armand Abergel, Olivier Chazouillères, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Louis d’Alteroche, Claire Wartelle, Thông Dao, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Eric Nguyen-Khac, Brigitte Bernard-Chabert, Sophie Hillaire, Vincent Di Martino, Delphine Bonnet, Virginie Payssan-Sicart, Chloe Pomes, François Bailly, Marjolaine Beaudoin, Dominique Giboz, Kerstin Hartig-Lavie, Marianne Maynard, Eric Billaud, David Boutoille, Morane Cavellec, Marjorie Cheraud-Carpentier, Isabelle Hubert, Jaouad Benhida, Adrien Lannes, Françoise Lunel, Frédéric Oberti, Nathalie Boyer, Nathalie Giuily, Corinne Castelnau, Giovanna Scoazec, Aziza Chibah, Sylvie Keser, Karim Bonardi, Anaïs Vallet-Pichard, Philippe Sogni, Juliette Foucher, Jean-Baptiste Hiriart, Amy Wilson, Sarah Shili, Faiza Chermak, Christelle Ansaldi, Nisserine Ben Amara, Laëtitia Chouquet, Emilie De Luca, Valérie Oules, Rodolphe Anty, Eve Gelsi, Régine Truchi, Elena Luckina, Nadia Messaoudi, Joseph Moussali, Barbara De Dieuleveult, Damien Labarriere, Pascal Poter, Si Nafa Si Ahmed, Véronique Grando-Lemaire, Valérie Bourcier, Séverine Brulé, Thomas Stalhberger, Caroline Jezequel, Audrey Brener, Anne Laligant, Aline Rabot, Isabelle Renard, Thomas F. Baumert, Michel Dofföel, Catherine Mutter, Pauline Simo-Noumbissie, Esma Razi, Hélène Barraud, Mouni Bensenane, Abdelbasset Nani, Sarah Hassani-Nani, Marie-Albertine Bernard, Michael Bismuth, Ludovic Caillo, Stéphanie Faure, Marie Pierre Ripault, Christophe Bureau, Jean Marie Peron, Marie Angèle Robic, Léa Tarallo, Marine Faure, Bruno Froissart, Marie-Noelle Hilleret, Jean-Pierre Zarski, Odile Goria, Victorien Grard, Hélène Montialoux, Muriel François, Christian Ouedraogo, Christelle Pauleau, Anne Varault, Tony Andreani, Bénédicte Angoulevant, Azeline Chevance, Lawrence Serfaty, Teresa Antonini, Audrey Coilly, Jean-Charles Duclos Vallée, Mariagrazia Tateo, Corinne Bonny, Chanteranne Brigitte, Géraldine Lamblin, Léon Muti, Abdenour Babouri, Virginie Filipe, Camille Barrault, Laurent Costes, Hervé Hagège, Soraya Merbah, Paul Carrier, Maryline Debette-Gratien, Jérémie Jacques, Guillaume Lassailly, Florent Artu, Valérie Canva, Sébastien Dharancy, Alexandre Louvet, Marianne Latournerie, Marc Bardou, Thomas Mouillot, Yannick Bacq, Didier Barbereau, Charlotte Nicolas, Caroline Chevalier, Isabelle Archambeaud, Sarah Habes, Danièle Botta-Fridlund, Eric Saillard, Marie-Josée Lafrance, Patrice Cacoub, Patrizia Carrieri, Elisabeth Delarocque-Astagneau, Victor De Ledinghen, Céline Dorival, Jean Dubuisson, Chantal Housset, Dominique Larrey, Patrick Marcellin, Jean-Michel Pawlotsky, Ventzislava Petrov-Sanchez, Sophie Vaux, Linda Wittkop, Yazdan Yazdanpanah, Jessica Zucman-Rossi, Christophe Moreno, Romain Moirand, Nicolas Carbonell, Jean-Charles Duclos-Vallée, Victor de Ledinghen, Violaine Ozenne, Jean Henrion, Gabriel Perlemuter, Xavier Amiot, Sylvie Chevret, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Henri Mondor, Unité de recherche clinique en économie de la santé [Paris] (URC Eco), Délégation de la Recherche Clinique et de l’Innovation [Paris] (DRCI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANRS|Maladies infectieuses émergentes (ANRS|MIE), Université Sorbonne Paris Nord, Hôpital Cochin [AP-HP], Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de santé publique [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Hôpital Beaujon [AP-HP]
Subjects: AMRI, abbreviated magnetic resonance imaging, NAFLD, non-alcoholic fatty liver disease, medicine.medical_specialty, Cirrhosis, Cost effectiveness, [SDV]Life Sciences [q-bio], Population, TACE, transarterial chemoembolization, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Gastroenterology, QALY, quality-adjusted life year, Internal medicine, Internal Medicine, LY, life years, Immunology and Allergy, Medicine, Early Hepatocellular Carcinoma, liver cancer risk, education, cost-effectiveness, RFA, radiofrequency ablation, education.field_of_study, AFP, alpha-fetoprotein, US, ultrasound, Hepatology, medicine.diagnostic_test, business.industry, cirrhosis, LYG, life years gained, Incidence (epidemiology), BCLC, Barcelona Clinic Liver Cancer, ICER, incremental cost-effectiveness ratio, Magnetic resonance imaging, medicine.disease, HR, hazard ratio, digestive system diseases, Hepatocellular carcinoma, SHR, subdistribution hazard ratio, surveillance, HCC, hepatocellular carcinoma, business, MRI, magnetic resonance imaging, Incremental cost-effectiveness ratio, Research Article, MRI
Abstract: Background & Aims Reinforced hepatocellular carcinoma (HCC) surveillance using magnetic resonance imaging (MRI) could increase early tumour detection but faces cost-effectiveness issues. In this study, we aimed to evaluate the cost-effectiveness of MRI for the detection of very early HCC (Barcelona Clinic Liver Cancer [BCLC] 0) in patients with an annual HCC risk >3%. Methods French patients with compensated cirrhosis included in 4 multicentre prospective cohorts were considered. A scoring system was constructed to identify patients with an annual risk >3%. Using a Markov model, the economic evaluation estimated the costs and life years (LYs) gained with MRI vs. ultrasound (US) monitoring over a 20-year period. The incremental cost-effectiveness ratio (ICER) was calculated by dividing the incremental costs by the incremental LYs. Results Among 2,513 patients with non-viral causes of cirrhosis (n = 840) and/or cured HCV (n = 1,489)/controlled HBV infection (n = 184), 206 cases of HCC were detected after a 37-month follow-up. When applied to training (n = 1,658) and validation (n = 855) sets, the construction of a scoring system identified 33.4% and 37.5% of patients with an annual HCC risk >3% (3-year C-Indexes 75 and 76, respectively). In patients with a 3% annual risk, the incremental LY gained with MRI was 0.4 for an additional cost of €6,134, resulting in an ICER of €15,447 per LY. Compared to US monitoring, MRI detected 5x more BCLC 0 HCC. The deterministic sensitivity analysis confirmed the impact of HCC incidence. At a willingness to pay of €50,000/LY, MRI screening had a 100% probability of being cost-effective. Conclusions In the era of HCV eradication/HBV control, patients with annual HCC risk >3% represent one-third of French patients with cirrhosis. MRI is cost-effective in this population and could favour early HCC detection. Lay summary The early identification of hepatocellular carcinoma in patients with cirrhosis is important to improve patient outcomes. Magnetic resonance imaging could increase early tumour detection but is more expensive and less accessible than ultrasound (the standard modality for surveillance). Herein, using a simple score, we identified a subgroup of patients with cirrhosis (accounting for >one-third), who were at increased risk of hepatocellular carcinoma and for whom the increased expense of magnetic resonance imaging would be justified by the potential improvement in outcomes., Graphical abstract, Highlights • HCC risk stratification in patients with cirrhosis aims at improving performance of cancer surveillance. • Using a simple scoring system, one-third of patients with cirrhosis with an annual HCC risk >3% can be easily identified. • Semi-annual surveillance using MRI in this population could enable the cost-effective detection of 5x more BCLC 0 HCCs.
Published: 2022
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4. Extrahepatic cancers are the leading cause of death in patients achieving hepatitis B virus control or hepatitis C virus eradication

Author: Thong Dao, Pierre Nahon, Christos Christidis, Jean-Pierre Zarski, Pierre Attali, Valérie Bourcier, Ghassan Riachi, Victor de Ledinghen, Laurent Alric, Dominique Thabut, Claire Wartelle, Eric Nguyen-Khac, Patrick Marcellin, Carole Cagnot, Dominique Roulot, Christophe Pilette, Armand Abergel, Fabien Zoulim, Vincent Di Martino, Eric Letouzé, Richard Layese, Jean-Pierre Bronowicki, Jean-Frédéric Blanc, Christine Silvain, Ariane Mallat, Stanislas Pol, Denis Ouzan, Jean-Didier Grangé, Angela Sutton, Jean-Marie Péron, Brigitte Bernard-Chabert, Dominique Larrey, Albert Tran, David Zucman, Marc Bourlière, Etienne Audureau, Lawrence Serfaty, Manon Allaire, Paul Calès, Yannick Bacq, Dominique Guyader, Philippe Mathurin, Françoise Roudot-Thoraval, Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), 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), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ANRS France Recherche Nord & sud Sida-hiv hépatites, Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Université Paris Descartes - Paris 5 (UPD5), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut Arnault Tzanck, Hospices Civils de Lyon (HCL), Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département d'hépato-gastroentérologie, CHU Grenoble-Université Grenoble Alpes (UGA), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Hôpital Claude Huriez [Lille], CHU Lille, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Tenon [AP-HP], Onxeo S.A., Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier d'Aix en Provence [Aix-en-Provence] (CHIAP ), CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Le Mans (CH Le Mans), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hellenic Open University [Patras], Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 (GRAP), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Foch [Suresnes], Service d'Hépatologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANRS (France Recherche Nord & sud Sida‐HIV Hépatites‐FRENCH)HECAM (Hepatocellular Carcinoma Multi‐Technological) Consortium, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], CHU Saint-Eloi, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre d'investigation de la fibrose hépatique [CHU de Bordeaux] (Hôpital Haut-Lévêque ), Hôpital Haut-Lévêque [CHU de Bordeaux], Université Nice Sophia Antipolis (... - 2019) (UNS), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), SIGMA Clermont, Hépatologie Gastro-Entérologie, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service d'hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UMR INSERM U955, École nationale vétérinaire d'Alfort (ENVA), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépato-gastroentérologie [CHU Amiens-Picardie], Service de Médecine Interne [Hôpital Foch, Suresnes] (SMI), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes (UGA)-CHU Grenoble, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], CHU Trousseau [APHP], and Univ Angers, Okina
Subjects: Liver Cirrhosis, Male, Cirrhosis, Databases, Factual, [SDV]Life Sciences [q-bio], medicine.disease_cause, Gastroenterology, Cohort Studies, 0302 clinical medicine, Neoplasms, Prospective Studies, education.field_of_study, Hepatocellular / virology, Liver Neoplasms, Liver Neoplasms / epidemiology, Hepatitis C, Middle Aged, Hepatitis B, Prognosis, 3. Good health, 030220 oncology & carcinogenesis, Disease Progression, Female, Liver Cirrhosis / epidemiology, 030211 gastroenterology & hepatology, France, Databases Factual, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Hepatitis C virus, Antiviral Agents / therapeutic use, Population, Liver Neoplasms / pathology, Chronic / complications, Antiviral Agents, Risk Assessment, Article, Liver Cirrhosis / virology, 03 medical and health sciences, Hepatitis B, Chronic, Liver Cirrhosis / physiopathology, Internal medicine, medicine, Humans, education, Aged, Hepatitis B virus, Chronic / drug therapy, Neoplasms / pathology, Hepatology, business.industry, Carcinoma, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Chronic, medicine.disease, Chronic / pathology, Survival Analysis, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatocellular / epidemiology, Liver Neoplasms / virology, Neoplasms / virology Prognosis, Carcinom, Standardized mortality ratio, Hepatocellular / pathology, Male Middle Aged Neoplasms / mortality, business
Abstract: Comment in Does cirrhosis associated with well controlled viral hepatitis confer a risk for extrahepatic cancer? Yang JD, Gores GJ. Hepatology. 2018 Oct;68(4):1217-1219. doi: 10.1002/hep.30063. Epub 2018 Jul 10.; International audience; Data on extrahepatic cancers (EHCs) in compensated viral cirrhosis are limited. The objective of the prospective multicenter Agence Nationale de Recherche sur le SIDA et les Hépatites virales CO12 CirVir cohort was to assess the occurrence of all clinical events in patients with compensated viral cirrhosis, including all types of cancer. Patients with the following inclusion criteria were enrolled in 35 French centers: (1) biopsy-proven hepatitis B virus (HBV) or hepatitis C virus (HCV) cirrhosis, (2) Child-Pugh A, or (3) absence of previous liver complications including primary liver cancer (PLC). Patients were followed up prospectively every 6 months. The standardized mortality ratio (SMR) was calculated according to age and gender using 5-year periods. The impact of sustained viral response (SVR) in HCV patients and maintained viral suppression in HBV patients were assessed using time-dependent analysis. A total of 1,671 patients were enrolled between 2006 and 2012 (median age, 54.9 years; men, 67.3%; HCV, 1,323; HBV, 317; HCV-HBV, 31). Metabolic features and excessive alcohol and tobacco consumption were recorded in 15.2%, 36.4%, and 56.4% of cases, respectively. After a median follow-up of 59.7 months, 227 PLCs were diagnosed (5-year cumulative incidence [CumI] 13.4%) and 93 patients developed EHC (14 patients with lymphoid or related tissue cancer and 79 with solid tissue cancer; 5-year EHC CumI, 5.9%). Compared to the general French population, patients were younger at cancer diagnosis, with significantly higher risk of EHC in HCV patients (SMR, 1.31; 95 confidence interval [CI], 1.04-1.64; P = 0.017) and after SVR (SMR = 1.57; 95% CI, 1.08-2.22; P = 0.013). EHC was the fourth leading cause of death in the whole cohort and the first in patients with viral control/eradication.CONCLUSION: Compared to the general French population, HCV cirrhosis is associated with a higher risk of EHC and the first cause of death in patients with viral cirrhosis who achieve virological control/eradication. (Hepatology 2018).
Published: 2018
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5. Prognostic value of viral eradication for major adverse cardiovascular events in hepatitis C cirrhotic patients

Author: Patrice Cacoub, Pierre Nahon, Richard Layese, Lorraine Blaise, Anne Claire Desbois, Valérie Bourcier, Carole Cagnot, Patrick Marcellin, Dominique Guyader, Stanislas Pol, Dominique Larrey, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Jean-Pierre Zarski, Ghassan Riachi, Paul Calès, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, 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, Dominique Capron, Gérard Thiefin, David Zucman, Vincent Di Martino, Corinne Isnard Bagnis, Marianne Ziol, Angela Sutton, Eric Letouze, Françoise Roudot-Thoraval, Etienne Audureau, Hélène Fontaine, Vincent Leroy, Sebastien Dharancy, Yves Benhamou, Sophie Hillaire, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunologie - Immunopathologie - Immunothérapie (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Pôle Recherche Clinique-Santé Publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Université Sorbonne Paris Nord - UFR des Sciences de la communication (USPN UP13 UFR SC), Université Sorbonne Paris Nord, Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), 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), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut Arnault Tzanck, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Avicenne [AP-HP], Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Département d'hépato-gastroentérologie, CHU Grenoble-Université Grenoble Alpes (UGA), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Saint-André, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, CHU Saint-Antoine [AP-HP], 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), CHU Tenon [AP-HP], Hôpital Paul Brousse, Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier d'Aix en Provence [Aix-en-Provence] (CHIAP ), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Le Mans (CH Le Mans), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Mutualiste de Montsouris (IMM), Institut mutualiste Monsouris (IMM), Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Foch [Suresnes], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), ANRS CO12 CirVir group : Pierre Nahon, Patrick Marcellin, Dominique Guyader, Stanislas Pol, Hélène Fontaine, Dominique Larrey, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Jean-Pierre Zarski, Vincent Leroy, Ghassan Riachi, 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, Yves Benhamou, Christophe Pilette, Christine Silvain, Christos Christidis, Dominique Capron, Gérard Thiefin, Sophie Hillaire, Vincent Di Martino, Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Service de Gastro-entérologie - Hépatologie [Purpan], CHU Toulouse [Toulouse], Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], CHU Trousseau [APHP], Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Service de Néphrologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Universités, Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], ANRS France Recherche Nord & sud Sida-hiv hépatites, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du système immunitaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Cochin [AP-HP], CHU Saint-Eloi, Centre d'investigation de la fibrose hépatique [CHU de Bordeaux] (Hôpital Haut-Lévêque ), Hôpital Haut-Lévêque [CHU de Bordeaux], Service de Gastro-entérologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Hôpital Purpan [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 6602, Institut Pascal, Université Clermont Auvergne (UCA), Centre National de la Recherche Scientifique (CNRS), SIGMA Clermont, Hépatologie Gastro-Entérologie, Centre Hospitalier Universitaire Estaing, Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Service d'hépatologie [Saint-Antoine], Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], 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), UMR INSERM U955, École nationale vétérinaire d'Alfort (ENVA), CHU Tenon [APHP], Onxeo S.A., CHU Trousseau [APHP]-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Hellenic Open University [Patras], Service d'Hépatogastroentérologie, CHU Amiens-Picardie, Service de Médecine Interne [Hôpital Foch, Suresnes] (SMI), Service d'Hépatologie, Hôpital Jean Minjoz, Centre Hospitalier Universitaire de Besançon, Université de Franche Comté, Hôpital Jean Minjoz, Service d'Explorations Fonctionnelles Neurologie [CHU Pitié-Salpêtrière], Université Sorbonne Paris Cité (USPC), Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13), Equipe labellisée Ligue Contre le Cancer [Saint-Denis], Université Paris 13 (UP13)-PRES Sorbonne Paris Cité, Service d'hépatologie [CHU Pontchaillou], Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de pathologie [Hôpital Haut Lévêque], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Service d'Hépatologie [Hôtel-Dieu], Hôpital Hôtel-Dieu [Paris], Service d'Hépatologie [Avicenne], Service d'Hépatologie [Nancy], Département d'hépatologie (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD), Service d'hépatologie [CHU Saint-Antoine], Service d'Hépatologie, Hôpital Henri Mondor, AP-HP, Créteil, France., Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Service de néphrologie [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupe Hospitalier Universitaire Paris Seine-Saint-Denis (GHUPSSD), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Sigma CLERMONT (Sigma CLERMONT)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-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)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes (UGA)-CHU Grenoble, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP]
Subjects: Male, Liver Cirrhosis, Survival rate, Cirrhosis, Biopsy, [SDV]Life Sciences [q-bio], Kaplan-Meier Estimate, Gastroenterology, Severity of Illness Index, Cohort Studies, 0302 clinical medicine, Liver Function Tests, Prevalence, Needle, 030212 general & internal medicine, Myocardial infarction, Chronic, medicine.diagnostic_test, Biopsy, Needle, Hepatitis C, Middle Aged, Prognosis, Immunohistochemistry, 3. Good health, Cardiovascular Diseases, Predictive value of tests, 030211 gastroenterology & hepatology, Female, France, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Antiviral Agents, Risk Assessment, 03 medical and health sciences, Age Distribution, Predictive Value of Tests, Internal medicine, medicine, Humans, cardiovascular diseases, Sex Distribution, Aged, Proportional Hazards Models, Retrospective Studies, business.industry, Hepatitis C, Chronic, medicine.disease, Heart failure, business, Liver function tests, Mace
Abstract: International audience; BACKGROUND: The objective was to examine the role of a sustained virological response (SVR) on major adverse cardiovascular events (MACEs) in patients with compensated hepatitis C virus (HCV) cirrhosis.METHODS: Patients with the following criteria were enrolled in 35 French centers: (1) biopsy-proven HCV cirrhosis; (2) Child-Pugh A; (3) positive viremia; and (4) no prior liver complication, and then prospectively followed. All patients received HCV treatment after inclusion. MACEs included stroke, myocardial infarction, ischemic heart disease, heart failure, peripheral arterial disease, cardiac arrest, and cardiovascular death. SVR, defined as negative viremia 12 weeks posttreatment, was considered as a time-dependent covariate, and its effect on MACE occurrence was assessed. The median follow up was 57.5 months, ending in December 2015.RESULTS: Sixty-two of 878 (7.1%) patients presented a total of 79 MACEs. The main predictive baseline factors of MACEs were Asian ethnic origin, history of MACEs, arterial hypertension, diabetes mellitus, current smoking, low serum albumin level, high total bilirubin level, and low platelet count. In multivariate analysis, SVR was associated with a decreased risk of MACEs (hazard ratio=0.35, 95% CI 0.09-0.97, P=.044), whereas Asian ethnic origin, arterial hypertension, smoking, and low serum albumin level remained predictive of MACE occurrence. The 5-year survival rate was 60.1% versus 87.5% in patients who did versus those who did not present a MACE (PCONCLUSIONS: In patients with compensated HCV-related cirrhosis, Asian ethnic origin, arterial hypertension, smoking, and low serum albumin are independent predictive factors of cardiovascular events, whereas an SVR is associated with a decreased rate of cardiovascular events.
Published: 2018
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6. Sorafenib vs surgical resection for hepatocellular carcinoma with macrovascular invasion: A propensity score analysis

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

Author: Andrea Mulliri, Alexis Laurent, Arnaud Alves, Ariane Mallat, Benjamin Menahem, Charlotte Costentin, Christophe Duvoux, Jean Lubrano, and Guy Launoy
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, medicine.medical_treatment, Liver transplantation, Milan criteria, Gastroenterology, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Liver Function Tests, Internal medicine, Carcinoma, Hepatectomy, Humans, Medicine, Survival rate, Survival analysis, Transplantation, Hepatology, medicine.diagnostic_test, business.industry, Liver Neoplasms, Odds ratio, medicine.disease, Survival Analysis, Intention to Treat Analysis, Liver Transplantation, Survival Rate, Treatment Outcome, Liver, Research Design, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Female, 030211 gastroenterology & hepatology, Surgery, Neoplasm Recurrence, Local, business, Liver function tests
Abstract: This meta-analysis compared the effects of liver transplantation (LT) and liver resection (LR) on overall survival (OS) and disease-free survival (DFS) in patients with hepatocellular carcinoma (HCC) small transplantable HCC or within Milan criteria. Articles comparing LR with LT for HCC, based on Milan criteria or small size, published up to June 2015 were selected, and a meta-analysis was performed. No randomized controlled trial has been published to date comparing survival outcomes in patients with HCC who underwent LR and LT. Nine studies were identified, including 570 patients who underwent LR and 861 who underwent LT. For HCC within the Milan criteria, the 1-year OS rates following LR and LT were 84.5% (473/560) and 84.4% (710/841), respectively (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.71-1.33; P = 0.8), and the 5-year OS rates were 47.9% (273/570) and 59.3% (509/858), respectively (OR, 0.60; 95% CI, 0.35-1.02; P = 0.06). One-year DFS rates were similar (OR, 1.00; 95% CI, 0.39-2.61; P = 1.00), whereas the 3-year DFS rate was significantly lower in the LR group (54.4%, 210/386) than in the LT group (74.2%, 317/427; OR, 0.24; 95% CI, 0.07-0.80; P = 0.02), and the 5-year DFS rate was significantly lower for LR than LT (OR, 0.18; 95% CI, 0.06-0.53; P
Published: 2017
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8. Sofosbuvir-Daclatasvir-Simeprevir Plus Ribavirin in Direct-Acting Antiviral–Experienced Patients With Hepatitis C

Author: Giovanna Scoazec, Isaac Ruiz, Alexandre Soulier, Ariane Mallat, Anne Varaut, Murielle François, Françoise Roudot-Thoraval, Christophe Hézode, Slim Fourati, Stéphane Chevaliez, and Jean-Michel Pawlotsky
Subjects: 0301 basic medicine, Microbiology (medical), Simeprevir, medicine.medical_specialty, Daclatasvir, Sofosbuvir, business.industry, Ribavirin, 030106 microbiology, Hepatitis C, medicine.disease, Gastroenterology, Virological response, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Infectious Diseases, chemistry, Internal medicine, medicine, 030211 gastroenterology & hepatology, Adverse effect, business, Direct acting, medicine.drug
Abstract: We assessed the broadly used, off-label combination of sofosbuvir, daclatasvir, simeprevir, and ribavirin in direct-acting antiviral-experienced patients, as recommended in current guidelines despite scarce data. After 24 weeks' treatment, sustained virological response 12 weeks after the end of treatment was achieved in 6 patients (60%). Two cirrhotic patients relapsed and 2 discontinued treatment due to serious adverse events.
Published: 2017
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9. Intrahepatic immune changes after hepatitis c virus eradication by direct-acting antiviral therapy

Author: Fouad Lafdil, Christophe Hézode, Pascale Maillé, Hélène Regnault, Alain Luciani, Ariane Mallat, Alexis Laurent, Aurélie Rodrigues, Camilia Machou, Giuliana Amaddeo, Sébastien Mulé, Cong Trung Nguyen, Jean-Michel Pawlotsky, and Julien Calderaro
Subjects: Liver Cirrhosis, Male, Myxovirus Resistance Proteins, medicine.medical_specialty, Cirrhosis, Carcinoma, Hepatocellular, Sustained Virologic Response, Carcinogenesis, Hepatitis C virus, Cell, Hepacivirus, medicine.disease_cause, Gastroenterology, Antiviral Agents, 03 medical and health sciences, 0302 clinical medicine, Immune system, Immunity, Internal medicine, Tumor Microenvironment, Medicine, Humans, Ubiquitins, Adaptor Proteins, Signal Transducing, Aged, Aged, 80 and over, Hepatology, business.industry, Gene Expression Profiling, Liver Neoplasms, RNA-Binding Proteins, HCCS, Hepatitis C, Chronic, Middle Aged, medicine.disease, Immunohistochemistry, digestive system diseases, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cytokines, RNA, Viral, 030211 gastroenterology & hepatology, Female, business
Abstract: Background & aims The recent approval of direct acting anti-virals (DAA) has dramatically changed the landscape of hepatitis C virus (HCV) therapy. Whether viral clearance could promote liver carcinogenesis is debated. It has been hypothesized that changes in intrahepatic immune surveillance following viral cure could favour tumour growth. This study aimed at characterizing the intrahepatic immune changes induced by HCV cure following DAA therapy. Methods Patients with compensated cirrhosis who underwent surgical resection for hepatocellular carcinoma (HCC) after sustained virological response (SVR) to DAA therapy were included. A control group of untreated HCV-infected patients with compensated cirrhosis was selected. RNA was extracted from tumoral and non-tumoral tissues and analysed using the Nanostring Immuno-Oncology-360 panel. Immune cells were quantified by immunohistochemistry. Results Twenty patients were included: 10 patients with a DAA-induced SVR and 10 untreated controls. All of them had a de novo BCLC 0/A HCC. Non-tumoral tissue profiling showed down-regulation of interferon-related genes (including MX1, ISG15 and IFIT1) after DAA therapy. No other differences in immune profiles/immune cell densities were identified between the two groups. The intra-tumoral immune profiles of HCCs that occurred after DAA therapy were not qualitatively or quantitatively different from those of tumours occurring in untreated patients. Conclusion In conclusion, removal of HCV infection after DAA-based therapy results only in a down-regulation of interferon-stimulated genes in non-tumoral tissues from patients with cirrhosis who develop HCC. These minor changes in the liver immune microenvironment are unlikely to favour HCC occurrence or recurrence after DAA-induced SVR.
Published: 2019

10. Validation of Baveno VI Criteria for Screening and Surveillance of Esophageal Varices in Patients With Compensated Cirrhosis and a Sustained Response to Antiviral Therapy

Author: Dominique Thabut, Christophe Bureau, Richard Layese, Valérie Bourcier, Maryam Hammouche, Carole Cagnot, Patrick Marcellin, Dominique Guyader, Stanislas Pol, Dominique Larrey, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Jean-Pierre Zarski, Odile Goria, Paul Calès, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Jean-Frédéric Blanc, Armand Abergel, Lawrence Serfaty, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Yannick Bacq, Claire Wartelle-Bladou, Thông Dao, Christophe Pilette, Christine Silvain, Christos Christidis, Dominique Capron, Brigitte Bernard-Chabert, Sophie Hillaire, Vincent Di Martino, Angela Sutton, Etienne Audureau, Françoise Roudot-Thoraval, Pierre Nahon, Hélène Fontaine, Vincent Leroy, Ghassan Riachi, Sebastien Dharancy, Claire Wartelle, Gérard Thiefin, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Toulouse [Toulouse], Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANRS France Recherche Nord & sud Sida-hiv hépatites, Hôpital Beaujon [AP-HP], CHU Pontchaillou [Rennes], Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Avicenne [AP-HP], Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Michallon, Hôpital Charles Nicolle [Rouen], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Saint-Joseph [Marseille], Hôpital Claude Huriez [Lille], CHU Lille, Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU Saint-Antoine [AP-HP], INSERM U64 [AP-HP Hôpital Tenon], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Tenon [AP-HP], Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], CHU Trousseau [APHP], Centre Hospitalier d'Aix en Provence [Aix-en-Provence] (CHIAP ), 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), Centre Hospitalier Le Mans (CH Le Mans), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Mutualiste de Montsouris (IMM), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Hôpital Robert Debré Paris, Hôpital Robert Debré, Hôpital Foch [Suresnes], Hôpital JeanMinjoz, Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Liver Cirrhosis, Male, 0301 basic medicine, Cirrhosis, Sustained Virologic Response, MESH: Sustained Virologic Response, MESH: Elasticity Imaging Techniques, medicine.disease_cause, Gastroenterology, Endoscopy, Gastrointestinal, 0302 clinical medicine, Esophageal varices, MESH: Practice Guidelines as Topic, Interquartile range, Mass Screening, MESH: Middle Aged, medicine.diagnostic_test, Portal Hypertension, Middle Aged, MESH: Endoscopy, Gastrointestinal, MESH: Hepatitis C, Chronic, Survival Rate, Population Surveillance, Hepatocellular carcinoma, Practice Guidelines as Topic, Disease Progression, Elasticity Imaging Techniques, Female, 030211 gastroenterology & hepatology, MESH: Disease Progression, Variceal Bleeding, MESH: Liver Cirrhosis, MESH: Antiviral Agents, medicine.medical_specialty, MESH: Survival Rate, MESH: Hepatitis B, Chronic, Hepatitis C virus, Esophageal and Gastric Varices, Antiviral Agents, MESH: Population Surveillance, 03 medical and health sciences, Elastometry, MESH: Esophageal and Gastric Varices, Hepatitis B, Chronic, Esophagus, Internal medicine, Hypertension, Portal, medicine, Humans, MESH: Mass Screening, MESH: Platelet Count, Hepatitis B virus, Prothrombin time, MESH: Hypertension, Portal, MESH: Humans, Hepatology, Platelet Count, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Chronic, medicine.disease, digestive system diseases, MESH: Male, 030104 developmental biology, business, Varices, MESH: Female
Abstract: International audience; Background & aims: Management of patients with cirrhosis includes endoscopic screening and surveillance to detect esophageal varices (EV) and prevent bleeding. However, the Baveno VI guidelines recommend avoiding endoscopies for patients with liver stiffness measurements below 20 kPa and platelet counts above 150,000 (favorable Baveno VI status) and endoscopic assessment of patients with higher levels of liver stiffness and platelet counts (unfavorable Baveno VI status). We aimed to validate the Baveno VI guidelines, evaluating outcomes of patients in the ANRS-CO12 CirVir cohort with compensated cirrhosis associated with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, with or without a sustained response to antiviral therapy.Methods: We performed an ancillary study using data from 891 patients in the ANRS CO12 CirVir cohort, treated at 35 centers in France, with HCV or HBV infection and biopsy-proven cirrhosis, Child-Pugh A scores, no previous complications, and no hepatocellular carcinoma who underwent an endoscopic procedure and had interpretable liver stiffness measurements and platelet counts. Progression of portal hypertension (PHT) was defined as the onset of varices needing treatment (VNT) or PHT-related bleeding. An sustained response to antiviral therapy was defined as undetectable level of HCV RNA by polymerase chain reaction assay (
Published: 2019
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11. Impact of hepatobiliary phase liver MRI versus Contrast-Enhanced Ultrasound after an inconclusive extracellular gadolinium-based contrast-enhanced MRI for the diagnosis of benign hepatocellular tumors

Author: Laurence Baranes, Frederic Pigneur, Elie Serge Zafrani, Julien Calderaro, Charlotte Costentin, Daniel Azoulay, Vincent Roche, Lambros Tselikas, Alain Rahmouni, Marion Roux, Alexis Laurent, Edouard Herin, Alain Luciani, and Ariane Mallat
Subjects: Adenoma, Adult, Male, medicine.medical_specialty, Urology, Gadolinium, Contrast Media, chemistry.chemical_element, Sensitivity and Specificity, 030218 nuclear medicine & medical imaging, Lesion, 03 medical and health sciences, Meglumine, 0302 clinical medicine, Internal medicine, Biopsy, Organometallic Compounds, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Retrospective Studies, Ultrasonography, Radiological and Ultrasound Technology, medicine.diagnostic_test, business.industry, Liver Neoplasms, Ultrasound, Gastroenterology, Focal nodular hyperplasia, Middle Aged, Hepatocellular adenoma, Hepatology, medicine.disease, Magnetic Resonance Imaging, chemistry, Focal Nodular Hyperplasia, Female, 030211 gastroenterology & hepatology, Radiology, medicine.symptom, business, Contrast-enhanced ultrasound
Abstract: To compare the added values of hepatobiliary phase (HBP) MRI and contrast-enhanced ultrasound (CEUS) in addition to inconclusive extracellular gadolinium-based contrast-enhanced MRI (CE-MRI) to characterize benign hepatocellular tumors (BHT). Eighty-three BHT-46 focal nodular hyperplasia (FNH) and 37 hepatocellular adenomas (HCA)-with inconclusive CE-MRI in 54 patients (43 women and 11 men, mean age 42 years old ± 14.8) were retrospectively analyzed. All patients underwent both HBP-MRI and CEUS. Two radiologists independently reviewed 2 sets of images, SET-1: CE-MRI and HBP-MRI; SET-2: CE-MRI and CEUS, and classified lesions as “definite FNH,” “possible FNH,” or “definitely not FNH.” Sensitivity (Se) and specificity (Spe) were compared between the two sets; subgroup analyses according to the lesion’s size were performed. Regardless of lesion size, the respective Se and Spe of both datasets were not statistically different (95.7 and 100% vs. 76.1 and 94.6% for set-1 and -2 respectively; p = 0.18). For lesions larger than 35 mm, although both sets had similar specificity (100%), sensitivity was higher for SET-1 (100% vs. 40%); p = 0.04. Tumor classifications using SET-1 and SET-2 could have changed patient management in 35/54 (64.8%) and 33/54 (61.1%) of all patients, respectively. HBP-MRI or CEUS should be performed after an inconclusive CE-MRI. Both can change patient management by avoiding unnecessary biopsy or surveillance. The use of HBP-MRI should be advocated over CEUS in larger (>35 mm) lesions.
Published: 2016
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12. Retreatment with sofosbuvir and simeprevir of patients with hepatitis C virus genotype 1 or 4 who previously failed a daclatasvir‐containing regimen

Author: Magali Bouvier-Alias, Ariane Mallat, Isaac Ruiz, Françoise Roudot-Thoraval, Alexandre Soulier, Stéphane Chevaliez, Jean-Michel Pawlotsky, Giovanna Scoazec, Anne Varaut, Cyrille Feray, and Christophe Hézode
Subjects: Male, 0301 basic medicine, Simeprevir, medicine.medical_specialty, Pyrrolidines, Daclatasvir, Sustained Virologic Response, Sofosbuvir, Hepatitis C virus, Pilot Projects, medicine.disease_cause, Antiviral Agents, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pegylated interferon, Internal medicine, medicine, Humans, Treatment Failure, NS5A, Hepatology, business.industry, Ribavirin, Imidazoles, Valine, Hepatitis C, Chronic, Middle Aged, Surgery, 030104 developmental biology, chemistry, Asunaprevir, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, Carbamates, business, medicine.drug
Abstract: UNLABELLED Failure to achieve sustained virological response (SVR) with hepatitis C virus (HCV) direct-acting antiviral-based regimens is commonly associated with emergence of resistance-associated variants (RAVs). To avoid cross-resistance, recent guidelines recommend that patients who have failed on nonstructural protein 5A (NS5A) inhibitors should be retreated with sofosbuvir (SOF; NS5B inhibitor) combined with simeprevir (SIM; protease inhibitor [PI]); however, supporting evidence is lacking. This "real-world" study comprised patients who had failed to achieve SVR on previous NS5A-based therapy with daclatasvir (DCV) plus pegylated interferon (Peg-IFN) and ribavirin (RBV), with (n = 3) or without (n = 13) asunaprevir (ASV; PI). All 16 patients were retreated for 12 weeks with SOF plus SIM, without RBV. Antiviral efficacy was evaluated using the primary endpoint of SVR12 (SVR 12 weeks post-treatment); on-treatment response was also assessed. Patients (N = 16; 13 male; mean age: 54 years [range, 43-73]) were chronically infected with HCV genotype (GT) 1 (1a, n = 11; 1b, n = 3) or 4 (n = 2); they had advanced fibrosis or compensated cirrhosis (FibroScan, 9.6-70 kPa; cirrhosis, n = 9); median baseline HCV-RNA level was 1.38 × 10(6) IU/mL. No patient discontinued treatment because of adverse events or virological failure. All patients achieved HCV RNA below lower limit of quantification (
Published: 2016
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13. Incidence of Hepatocellular Carcinoma After Direct Antiviral Therapy for HCV in Patients With Cirrhosis Included in Surveillance Programs

Author: Pierre Nahon, Richard Layese, Valérie Bourcier, Carole Cagnot, Patrick Marcellin, Dominique Guyader, Stanislas Pol, Dominique Larrey, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Jean-Pierre Zarski, Ghassan Riachi, Paul Calès, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, 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, David Zucman, Vincent Di Martino, Angela Sutton, Françoise Roudot-Thoraval, Etienne Audureau, Hélène Fontaine, Vincent Leroy, Sebastien Dharancy, Sophie Hillaire, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANRS France Recherche Nord & sud Sida-hiv hépatites, Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Université Paris Descartes - Paris 5 (UPD5), 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), Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut Arnault Tzanck, Hospices Civils de Lyon (HCL), Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département d'hépato-gastroentérologie, CHU Grenoble-Université Grenoble Alpes (UGA), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Hôpital Claude Huriez [Lille], CHU Lille, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Tenon [AP-HP], Onxeo S.A., Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier d'Aix en Provence [Aix-en-Provence] (CHIAP ), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Le Mans (CH Le Mans), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hellenic Open University [Patras], Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Foch [Suresnes], Service d'Hépatologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANRS, Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Nicolle [Rouen]-CHU Rouen, CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [APHP], Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], CHU Saint-Eloi, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre d'investigation de la fibrose hépatique [CHU de Bordeaux] (Hôpital Haut-Lévêque ), Hôpital Haut-Lévêque [CHU de Bordeaux], Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes (UGA)-CHU Grenoble, Hôpital Purpan [Toulouse], Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Service de médecine interne et maladies digestives [CHU Toulouse], SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), SIGMA Clermont, Hépatologie Gastro-Entérologie, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service d'hépatologie [CHU Saint-Antoine], UMR INSERM U955, École nationale vétérinaire d'Alfort (ENVA), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépato-gastroentérologie [CHU Amiens-Picardie], Service de Médecine Interne [Hôpital Foch, Suresnes] (SMI), Univ Angers, Okina, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP]
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Cirrhosis, [SDV]Life Sciences [q-bio], Gastroenterology, Antiviral Agents, Telaprevir, 03 medical and health sciences, 0302 clinical medicine, Liver neoplasms, Internal medicine, medicine, Humans, Aged, Proportional Hazards Models, Retrospective Studies, Hepatology, business.industry, Incidence, Carcinoma, Retrospective cohort study, Hepatocellular, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Middle Aged, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, 3. Good health, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cohort, 030211 gastroenterology & hepatology, Female, Liver function, Interferons, business, Liver cancer, medicine.drug
Abstract: International audience; Background & aims - Retrospective studies have found an unexpectedly high incidence of hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV)-associated cirrhosis who received direct-acting antiviral (DAA) agents. We analyzed data from the ANRS CO12 CirVir cohort to compare the incidence of HCC in patients with cirrhosis who received DAA therapy vs patients treated with interferon (IFN). Methods - Data were collected from 1270 patients with compensated biopsy-proven HCV-associated cirrhosis recruited from 2006 through 2012 at 35 centers in France. For descriptive purpose, patients were classified as follows: patients who received DAA treatment (DAA group, n = 336), patients who achieved a sustained virologic response (SVR) following an IFN-based regimen (SVR-IFN group, n = 495), or patients who never received DAA treatment and never had an SVR following IFN therapy (non-SVR group, n = 439). The patients were included in HCC surveillance programs based on ultrasound examination every 6 months, and clinical and biological data were recorded. To account for confounding by indication due to differences in patient characteristics at treatment initiation, we constructed a time-dependent Cox regression model weighted by the inverse probability of treatment and censoring (IPTCW) to assess the treatment effects of DAA on time until HCC. Results - Compared with patients in the SVR-IFN group, patients in the DAA group were older, higher proportions had diabetes or portal hypertension, and liver function was more severely impaired. The crude 3-year cumulative incidences of HCC were 5.9% in the DAA group, 3.1% in the SVR-IFN group, and 12.7% in the non-SVR group (overall P < .001; unadjusted hazard ratio [HR] for HCC 2.03; 95% confidence interval [CI] 1.07-3.84; P = .030 for the DAA group vs the SVR-IFN group). HCC characteristics were similar among groups. Among patients with HCC, the DAA group received less-frequent HCC screening than the other 2 groups (P = .002). After Cox analyses weighted by the IPTCW, we found no statistically significant increase in risk of HCC associated with DAA use (HR 0.89; 95% CI 0.46-1.73; P = .73). Conclusions - Analysis of data from the ANRS CO12 CirVir cohort reveals that the apparent increase in HCC incidence observed in patients with cirrhosis treated with DAAs compared with patients who achieved SVR following an IFN therapy can be explained by patient characteristics (age, diabetes, reduced liver function) and lower screening intensity.
Published: 2018
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14. Compliance With Hepatocellular Carcinoma Surveillance Guidelines Associated With Increased Lead-Time Adjusted Survival of Patients With Compensated Viral Cirrhosis: A Multi-Center Cohort Study

Author: Charlotte E. Costentin, Richard Layese, Valérie Bourcier, Carole Cagnot, Patrick Marcellin, Dominique Guyader, Stanislas Pol, Dominique Larrey, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Jean-Pierre Zarski, Ghassan Riachi, Paul Calès, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, 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, David Zucman, Vincent Di Martino, Angela Sutton, Eric Letouzé, Sandrine Imbeaud, Jessica Zucman-Rossi, Etienne Audureau, Françoise Roudot-Thoraval, Pierre Nahon, Hélène Fontaine, Vincent Leroy, Sebastien Dharancy, Dominique Capron, Gérard Thiefin, Sophie Hillaire, CHU Henri Mondor, Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ANRS France Recherche Nord & sud Sida-hiv hépatites, Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Université Paris Descartes - Paris 5 (UPD5), 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), Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], CHU Saint-Eloi-Université de Montpellier (UM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut Arnault Tzanck, Hospices Civils de Lyon (HCL), Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département d'hépato-gastroentérologie, CHU Grenoble-Université Grenoble Alpes (UGA), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), CHU Toulouse [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Hôpital Claude Huriez [Lille], CHU Lille, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], UMR INSERM U955, École nationale vétérinaire - Alfort (ENVA), Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Tenon [AP-HP], Onxeo S.A., Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], CHU Trousseau [APHP], Centre Hospitalier d'Aix en Provence [Aix-en-Provence] (CHIAP ), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Le Mans (CH Le Mans), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hellenic Open University [Patras], Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Foch [Suresnes], Service d'Hépatologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Université Paris 13 (UP13), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor [Créteil], Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], CHU Saint-Eloi, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre d'investigation de la fibrose hépatique [CHU de Bordeaux] (Hôpital Haut-Lévêque ), Hôpital Haut-Lévêque [CHU de Bordeaux], Université Nice Sophia Antipolis (... - 2019) (UNS), Hôpital Purpan [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), SIGMA Clermont, Hépatologie Gastro-Entérologie, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service d'hépatologie [CHU Saint-Antoine], Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), École nationale vétérinaire d'Alfort (ENVA), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépato-gastroentérologie [CHU Amiens-Picardie], Service de Médecine Interne [Hôpital Foch, Suresnes] (SMI), Labex Immuno-oncology, Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes (UGA)-CHU Grenoble, Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP]
Subjects: Male, Liver Cirrhosis, medicine.medical_specialty, Carcinoma, Hepatocellular, [SDV]Life Sciences [q-bio], Hepacivirus, Kaplan-Meier Estimate, Antiviral Agents, 03 medical and health sciences, 0302 clinical medicine, Liver neoplasms, Internal medicine, Medicine, Humans, Prospective Studies, Prospective cohort study, Early Detection of Cancer, Aged, Hepatology, business.industry, Hazard ratio, Carcinoma, Gastroenterology, Hepatocellular, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Hepatitis B, Middle Aged, medicine.disease, 3. Good health, Transplantation, Liver, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Practice Guidelines as Topic, Multivariate Analysis, 030211 gastroenterology & hepatology, Female, Guideline Adherence, France, business, Liver cancer, Viral hepatitis, hepatitis B virus, Follow-Up Studies
Abstract: International audience; Background & aims - Semi-annual surveillance for hepatocellular carcinoma (HCC) is recommended for patients with cirrhosis. We aimed to determine how compliance with HCC surveillance guidelines affects survival times of patients with hepatitis C virus- or hepatitis B virus-associated compensated cirrhosis who developed HCC. Methods - We collected data from the prospective ANRS CO12 CirVir study, from March 2006 through June 2012, on 1671 patients with biopsy-proven viral cirrhosis and no previous liver complications who were undergoing surveillance for HCC at 35 centers in France. Only 216 patients who developed HCC during the follow-up period were included in the analysis. Patients were considered to be compliant with surveillance guidelines if the time between their last surveillance image evaluation and diagnosis of HCC were fewer than 7 months and noncompliant if this time was 7 months or longer. Results - HCC was detected in 216 patients, at a median follow-up time of 59.7 months. Of these patients, 140 (80.5%) were Barcelona Clinic Liver Cancer stage 0/A, 135 (69.9%) received first-line curative treatment (15 underwent transplantation, 29 underwent resection, 89 received percutaneous ablation, and 2 received resection and percutaneous ablation), and 129 (60.0%) were compliant with surveillance guidelines. Seventy-nine of the patients with HCC died; 49 deaths were associated with tumor progression. After lead-time adjustment, overall survival (OS) time was longer in patients compliant with surveillance guidelines (median OS time, 53.2 months) than noncompliant patients (median OS time, 25.4 months) (P = .0107); this difference remained significant even when we changed lead time assumptions. In multivariate analysis adjusted for a propensity score, compliance with HCC surveillance guidelines was associated with low tumor burden, allocation of curative treatment, and increased OS time compared with noncompliance (hazard ratio for OS, 2.19; 95% confidence interval, 1.16-4.14; P = .0150). Conclusions - In an analysis of data from the ANRS CO12 CirVir cohort, we associated compliance with HCC surveillance guidelines (fewer than 7 months between image evaluations) with early diagnosis, allocation of curative treatment, and longer adjusted OS of patients with hepatitis C virus- or hepatitis B virus-associated compensated cirrhosis and a diagnosis of HCC.
Published: 2018
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15. Visceral fat area predicts survival in patients with advanced hepatocellular carcinoma treated with tyrosine kinase inhibitors

Author: Charlotte Costentin, Alexis Laurent, Jean-Charles Nault, Sandrine Katsahian, Ariane Mallat, Lambros Tselikas, Frederic Pigneur, Guoqing Diao, Alain Luciani, Thomas Decaens, Christophe Duvoux, and Anaïs Charles Nelson
Subjects: Male, Niacinamide, Sorafenib, Sarcopenia, medicine.medical_specialty, Pathology, Carcinoma, Hepatocellular, medicine.drug_class, Intra-Abdominal Fat, Gastroenterology, Tyrosine-kinase inhibitor, Internal medicine, medicine, Humans, Protein Kinase Inhibitors, Aged, Retrospective Studies, Alanine, Predictive marker, Hepatology, Triazines, business.industry, Phenylurea Compounds, Liver Neoplasms, Retrospective cohort study, Middle Aged, Prognosis, medicine.disease, Survival Rate, Hepatocellular carcinoma, Multivariate Analysis, Lean body mass, Female, Hand-Foot Syndrome, France, alpha-Fetoproteins, Tomography, X-Ray Computed, business, Progressive disease, medicine.drug
Abstract: Background Anthropometric measurements have been linked to resistance to anti-angiogenic treatment and survival. Methods Patients with advanced hepatocellular carcinoma treated with sorafenib or brivanib in 2008–2011 were included in this retrospective study. Anthropometric measurements were assessed using computed tomography and were correlated with drug toxicity, radiological response, and overall survival. Results 52 patients were included, Barcelona Clinic Liver Classification B (38%) and C (62%), with a mean value of α-fetoprotein of 29,554 ± 85,654 ng/mL, with a median overall survival of 10.5 months. Sarcopenia was associated with a greater rate of hand–foot syndrome ( P = 0.049). Modified Response Evaluation Criteria In Solid Tumours (mRECIST) and Choi criteria were significantly associated with survival, but RECIST criteria were not. An absence of hand–foot syndrome and high-visceral fat area were associated with progressive disease as assessed by RECIST and mRECIST criteria. In multivariate analyses, high visceral fat area (HR = 3.6; P = 0.002), low lean body mass (HR = 2.4; P = 0.015), and presence of hand–foot syndrome (HR = 1.8; P = 0.004) were significantly associated with overall survival. In time-dependent multivariate analyses; only high visceral fat area was associated with survival. Conclusion Visceral fat area is associated with survival and seems to be a predictive marker for primary resistance to tyrosine kinase inhibitors in patients with advanced hepatocellular carcinoma.
Published: 2015
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16. Differentiating focal nodular hyperplasia from hepatocellular adenoma: Is hepatobiliary phase MRI (HBP-MRI) using linear gadolinium chelates always useful?

Author: Laurence Baranes, Lambros Tselikas, Frederic Pigneur, Anaïs Charles-Nelson, Marion Roux, Alexis Laurent, Alain Luciani, Charlotte Costentin, Daniel Azoulay, Julien Calderaro, Sandrine Kastahian, Thomas Decaens, Ariane Mallat, M. Chiaradia, and Alain Rahmouni
Subjects: Adult, Male, Gd bopta, medicine.medical_specialty, Urology, Gadolinium, chemistry.chemical_element, Contrast Media, Sensitivity and Specificity, 030218 nuclear medicine & medical imaging, Adenoma, Liver Cell, Diagnosis, Differential, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Text mining, Meglumine, Internal medicine, Organometallic Compounds, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Aged, Retrospective Studies, Observer Variation, Radiological and Ultrasound Technology, business.industry, Liver Neoplasms, Gastroenterology, Focal nodular hyperplasia, Reproducibility of Results, Hepatocellular adenoma, Hepatology, Middle Aged, medicine.disease, Image Enhancement, Magnetic Resonance Imaging, chemistry, Liver, Focal Nodular Hyperplasia, 030220 oncology & carcinogenesis, Hepatobiliary phase, Female, Radiology, business
Abstract: To assess the value of Hepatobiliary phase MRI (HPB-MRI) to differentiate FNH and HCA, and evaluate its impact on diagnostic accuracy, diagnostic confidence, inter-observer variability, and patient clinical management.Forty-nine patients referred for Gd-BOPTA-enhanced MRI were retrospectively included in this IRB-approved study, with a total of 119 lesions-90 FNH and 29 HCA. Two observers separately assessed in 2 distinct randomized reading sessions the performance of MRI with (HBP-MRI) or without (conventional MRI) the use of HBP images. Each lesion was ranked with a 5-point scale (from 1 Typical FNH to 5 Certainly not a FNH). Sensitivity, specificity, overall accuracy, and inter-observer agreement for the differentiation of FNH from HCA were calculated and compared between conventional and HBP-MRI.Both sensitivity (respective values of 38.9% and 97.8%), overall accuracy (respective values of 53.8% and 98.3%), and inter-observer agreement (respective values of Kappa 0.56 and 0.88) were significantly higher using HBP-MRI than with conventional MRI, with unchanged specificity (100%). The sensitivity of conventional MRI for the diagnosis of FNH was significantly lower in lesions ≤ 3 cm (20% vs. 88%). Overall, HBP could have changed lesion management in 59/119 cases (49.5%), including 53 FNH and 6 HCA with no impact in 60/119 lesions (50.5%) including all 35 lesions classified as scores 1 and 2 for the diagnosis of FNH.The clinical impact of HBP-MRI is mostly important for smaller than 3-cm FNH, and more limited in larger FNH lesions as well as for HCA diagnosis for which conventional MRI is already accurate. The use of extracellular contrast agents upfront could limit the required use of linear HBP contrast agents for benign hepatocellular lesion characterization. On HBP, all FNH appeared hypointense compared to adjacent liver while close to 97% of HCA appeared hypointense.
Published: 2017

17. Eradication of Hepatitis C Virus Infection in Patients With Cirrhosis Reduces Risk of Liver and Non-Liver Complications

Author: Pierre Nahon, Valérie Bourcier, Richard Layese, Etienne Audureau, Carole Cagnot, Patrick Marcellin, Dominique Guyader, 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, Sébastien Dharancy, Jean-Frédéric Blanc, Armand Abergel, Lawrence Serfaty, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Yannick Bacq, Claire Wartelle, Thông Dao, Yves Benhamou, Christophe Pilette, Christine Silvain, Christos Christidis, Dominique Capron, Brigitte Bernard-Chabert, David Zucman, Vincent Di Martino, Vincent Thibaut, Dominique Salmon, Marianne Ziol, Angela Sutton, Stanislas Pol, Françoise Roudot-Thoraval, Gérard Thiefin, Sophie Hillaire, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Cochin [AP-HP], Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), 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), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Arnault Tzanck, Hospices Civils de Lyon (HCL), Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département d'hépato-gastroentérologie, CHU Grenoble-Université Grenoble Alpes (UGA), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), ScaLable Information Discovery and Exploitation [Grenoble] (SLIDE), Laboratoire d'Informatique de Grenoble (LIG ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), CHU Toulouse [Toulouse], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Hôpital Saint-Joseph [Marseille], Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Saint-André, Hôpital Hôtel-Dieu de Clermont-Ferrand, CHU Clermont-Ferrand, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Service d'hépato-gastro-entérologie [APHP Henri Mondor], CHU Tenon [AP-HP], Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Service de gastro-entérologie [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre Hospitalier d'Aix en Provence [Aix-en-Provence] (CHIAP ), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Mobilités : Vieillissement, Pathologie, Santé (COMETE), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Le Mans (CH Le Mans), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Mutualiste de Montsouris (IMM), CHU Amiens-Picardie, Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Foch [Suresnes], Service d'hépatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Pontchaillou [Rennes], Université Paris Descartes - Paris 5 (UPD5), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Service Maladies infectieuses et tropicales [AP-HP Hôpital Cochin], Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépatologie médicale [CHU Cochin], Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de santé publique [Mondor], Service d'Hépato-gastroentérologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Hôpital Henri Mondor, Assistance Publique - Hôpitaux de Paris (AP-HP), Department of hepatology, CHU Saint-Eloi, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre de Recherche sur le Cancer de Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Hôpital Purpan [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Service d'hépato-gastro-entérologie, Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital Huriez-Université de Lille, Hôpital Claude Hurriez, Inserm, UMR-1053, Université de Bordeaux, Bordeaux, F-33076, France, Centre hospitalier universitaire de Bordeaux, Department of Hepatology, Hôpital Saint-André, Bordeaux, F-33076, France, Service d'Hépato-Gastro-Entérologie, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Hopital d'Aix en Provence, Service d'Hépatogastroentérologie, Service de Médecine Interne (Med Int - Hôpital Foch), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), FHDH-ANRS CO4, Service d'anatomie pathologique, Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Jean Verdier, Génomique Fonctionnelle des Tumeurs Solides ( U1162 ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Beaujon, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Cochin [AP-HP], Université Montpellier 1 ( UM1 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Centre méditérannéen de médecine moléculaire ( C3M ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Université de Lorraine ( UL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), ScaLable Information Discovery and Exploitation [Saint Martin d’Hères] ( SLIDE ), Laboratoire d'Informatique de Grenoble ( LIG ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National Polytechnique de Grenoble ( INPG ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National Polytechnique de Grenoble ( INPG ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Service d'Hépato-Gastroentérologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques ( HIFIH ), Université d'Angers ( UA ), Hepato-gastro-enterology, Toulouse University hospital, Institut de Recherche en Santé Digestive - IRSD [Purpan, Toulouse], Institut National de la Recherche Agronomique ( INRA ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse ( ENVT ), Institut National Polytechnique de Toulouse ( INPT ) -Institut National Polytechnique de Toulouse ( INPT ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Assistance Publique - Hôpitaux de Marseille ( APHM ), CHU Saint-Antoine [APHP], 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse, Service de gastro-entérologie, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Service d'Hépato-Gastro-Enterologie et Nutrition [Caen], Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -CHU Caen, Mobilités : Vieillissement, Pathologie, Santé ( COMETE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Caen Normandie ( UNICAEN ), Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Service de Médecine Interne ( Med Int - Hôpital Foch ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Université Paris Descartes - Paris 5 ( UPD5 ), CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Hôpital Jean Verdier AP-HP Bondy, Hôpital Jean Verdier, Laboratoire de Recherche Vasculaire Translationnelle ( LVTS ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Charles Nicolle [Rouen], CHU Rouen, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), CHU Trousseau [APHP], Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes (UGA)-CHU Grenoble, Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)
Subjects: 0301 basic medicine, Liver Cirrhosis, Male, Cirrhosis, Sustained Virologic Response, Direct Antivirals, Gastroenterology, Body Mass Index, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Prospective Studies, Prospective cohort study, Metabolic Syndrome, education.field_of_study, Incidence, Hazard ratio, Liver Neoplasms, virus diseases, Hepatitis C, Bacterial Infections, gamma-Glutamyltransferase, Middle Aged, Prognosis, 3. Good health, ANRS CirVir, Cardiovascular Diseases, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Female, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, France, medicine.medical_specialty, Carcinoma, Hepatocellular, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Lower risk, Antiviral Agents, 03 medical and health sciences, Spontaneous bacterial peritonitis, Internal medicine, medicine, Diabetes Mellitus, Humans, Aspartate Aminotransferases, education, Aged, Dyslipidemias, Hepatology, business.industry, Platelet Count, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, digestive system diseases, Surgery, 030104 developmental biology, Prothrombin Time, business, HCV Clearance, Follow-Up Studies
Abstract: International audience; BACKGROUND & AIMS: We performed a prospective study to investigate the effects of a sustained viral response (SVR) on outcomes of patients with hepatitis C virus (HCV) infection and compensated cirrhosis. METHODS: We collected data from 1323 patients included in the prospective Agence Nationale pour la Recherche sur le SIDA et les hépatites virales (ANRS) viral cirrhosis (CirVir) cohort, recruited from 35 clinical centers in France from 2006 through 2012. All patients had HCV infection and biopsy-proven cirrhosis, were Child-Pugh class A, and had no prior liver complications. All patients received anti-HCV treatment before or after inclusion (with interferon then with direct antiviral agents) and underwent an ultrasound examination every 6 months, as well as endoscopic evaluations. SVR was considered as a time-dependent covariate; its effect on outcome was assessed by the Cox proportional hazard regression method. We used a propensity score to minimize confounding by indication of treatment and capacity to achieve SVR. RESULTS: After a median follow-up period of 58.2 months, 668 patients (50.5%) achieved SVR. SVR was associated with a decreased incidence of hepatocellular carcinoma (hazard ratio [HR] compared with patients without an SVR, 0.29; 95% confidence interval [CI], 0.19-0.43; P < .001) and hepatic decompensation (HR, 0.26; 95% CI, 0.17-0.39; P < .001). Patients with SVRs also had a lower risk of cardiovascular events (HR, 0.42; 95% CI, 0.25-0.69; P = .001) and bacterial infections (HR, 0.44; 95% CI, 0.29-0.68; P < .001). Metabolic features were associated with a higher risk of hepatocellular carcinoma in patients with SVRs, but not in patients with viremia. SVR affected overall mortality (HR, 0.27 compared with patients without SVR; 95% CI, 0.18-0.42; P < .001) and death from liver-related and non-liver-related causes. Similar results were obtained in a propensity score-matched population. CONCLUSIONS: We confirmed a reduction in critical events, liver-related or not, in a prospective study of patients with HCV infection and compensated cirrhosis included in the CirVir cohort who achieved an SVR. We found an SVR to reduce overall mortality and risk of death from liver-related and non-liver-related causes. A longer follow-up evaluation is required to accurately describe and assess specific risk factors for complications in this population.
Published: 2017
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18. Cannabinoid receptor 2 counteracts interleukin-17-induced immune and fibrogenic responses in mouse liver

Author: Alexandra Bizy, Fouad Lafdil, Nabila Hamdaoui, Elie-Serge Zafrani, Adrien Guillot, Keve Zoltani, Rachid Souktani, Ariane Mallat, and Sophie Lotersztajn
Subjects: medicine.medical_specialty, Hepatology, biology, medicine.medical_treatment, Interleukin, Proinflammatory cytokine, Endocrinology, Cytokine, Internal medicine, medicine, biology.protein, Cannabinoid receptor type 2, STAT protein, lipids (amino acids, peptides, and proteins), Cannabinoid, Receptor, STAT5
Abstract: Interleukin (IL)-17 is a proinflammatory and fibrogenic cytokine mainly produced by T-helper (Th)17 lymphocytes, together with the hepatoprotective and antifibrogenic cytokine, IL-22. Cannabinoid receptor 2 (CB2) is predominantly expressed in immune cells and displays anti-inflammatory and antifibrogenic effects. In the present study, we further investigated the mechanism underlying antifibrogenic properties of CB2 receptor and explored its effect on the profibrogenic properties of IL-17. After bile duct ligation (BDL), the hepatic expression of Th17 markers and IL-17 production were enhanced in CB2−/− mice, as compared to wild-type (WT) counterparts, and correlated with increased fibrosis in these animals. In contrast, IL-22-induced expression was similar in both animal groups. Inhibition of Th17 differentiation by digoxin lowered Th17 marker gene expression and IL-17 production and strongly reduced liver fibrosis in CB2−/− BDL mice. In vitro, differentiation of CD4+ naive T cells into Th17 lymphocytes was decreased by the CB2 agonist, JWH-133, and was associated with reduced Th17 marker messenger RNA expression and IL-17 production, without modification of IL-22 release. The inhibitory effect of JWH-133 on IL-17 production relied on signal transducer and activator of transcription (STAT)5 phosphorylation. Indeed, STAT5 phosphorylation and translocation into the nucleus was enhanced in JWH133-treated Th17 lymphocytes, and the addition of a STAT5 inhibitor reversed the inhibitory effect of the CB2 agonist on IL-17 production, without affecting IL-22 levels. Finally, in vitro studies also demonstrated that CB2 receptor activation in macrophages and hepatic myofibroblasts blunts IL-17-induced proinflammatory gene expression. Conclusion: These data demonstrate that CB2 receptor activation decreases liver fibrosis by selectively reducing IL-17 production by Th17 lymphocytes via a STAT5-dependent pathway, and by blunting the proinflammatory effects of IL-17 on its target cells, while preserving IL-22 production. (Hepatology 2014;58:296–306)
Published: 2013
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19. Nomogram for individualized prediction of hepatocellular carcinoma occurrence in hepatitis C virus cirrhosis (ANRS CO12 CirVir)

Author: Denis Ouzan, Yves Benhamou, Ariane Mallat, Jean-Claude Trinchet, Yannick Bacq, Brigitte Bernard-Chabert, Carole Cagnot, Armand Abergel, Jean-Frédéric Blanc, Victor de Ledinghen, Claire Wartelle, Richard Layese, Christophe Pilette, Vincent Di Martino, Jean-Pierre Bronowicki, Stanislas Pol, Dominique Capron, Nathalie Ganne-Carrié, Philippe Mathurin, Christine Silvain, Marc Bourlière, Ghassan Riachi, Fabien Zoulim, Dominique Guyader, Laurent Alric, Valérie Bourcier, Jean-Didier Grangé, David Zucman, Paul Calès, Albert Tran, Dominique Roulot, Patrick Marcellin, Jean-Pierre Zarski, Françoise Roudot-Thoraval, Thong Dao, Pierre Nahon, Christos Christidis, Lawrence Serfaty, Jean-Marie Péron, Dominique Larrey, Pierre Attali, Génomique Fonctionnelle des Tumeurs Solides ( U1162 ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Jean Verdier, Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), France REcherche Nord & sud Sida-hiv Hépatites (FRENSH), Service d'hépatologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Service des maladies du foie, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Centre Hospitalier Universitaire de Rennes, Foie, métabolismes et cancer, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'hépatologie médicale [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Institut Pasteur [Paris], CHU Saint-Eloi, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut Arnaud Tzanck, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Hôpital Avicenne, CHU Nice, Centre méditérannéen de médecine moléculaire ( C3M ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Hôpital Michallon, Hôpital Charles Nicolle [Rouen], Interactions cellulaires et applications thérapeutiques ( ICAT ), Université d'Angers ( UA ) -CHU Angers-CRLCC Paul Papin-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Pharmacochimie et Pharmacologie Pour le Développement ( PHARMA-DEV ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique ( CNRS ), Service d'Hépato-gastroentérologie, Assistance Publique - Hôpitaux de Marseille ( APHM ), Hôpital Claude Huriez, Hôpital Saint-André, CHU Estaing [Clermont-Ferrand], Service d'hépatologie [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], CHU Henri Mondor, CHU Tenon [APHP], Hôpital Paul Brousse, CHU Trousseau [Tours], CHRU Tours, Hôpital Général Aix en Provence, CHU Caen, CHU Pitié-Salpêtrière [APHP], CHU Le MAns, Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Institut Mutualiste de Montsouris ( IMM ), Centre hospitalier universitaire d'Amiens ( CHU Amiens-Picardie ), CHU Amiens-Picardie, AP-HP Hôpital universitaire Robert-Debré [Paris], Hôpital Foch [Suresnes], Hôpital Jean Minjoz, This study was sponsored by the ANRS (France REcherche Nord & Sud Sida-hiv Hépatites: FRENSH). The funding sponsor had no role in the design or conducting of the study: collection, management, analysis, interpretation of data, nor preparation, review, or approval of the manuscript, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Hôpital Beaujon [AP-HP], CHU Pontchaillou [Rennes], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris] (IP), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Arnault Tzanck, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Hôpital Avicenne [AP-HP], Centre Hospitalier Universitaire de Nice (CHU Nice), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, CHU Rouen, Normandie Université (NU)-Normandie Université (NU), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Hôpital Saint-Joseph [Marseille], Hôpital Claude Huriez [Lille], CHU Lille, CHU Clermont-Ferrand, Service d'hépatologie [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Henri Mondor [Créteil], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier d'Aix en Provence [Aix-en-Provence] (CHIAP ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Le Mans (CH Le Mans), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Mutualiste de Montsouris (IMM), Jonchère, Laurent, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Sorbonne Université (SU)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT)
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, education, education.field_of_study, Framingham Risk Score, Hepatology, business.industry, Hazard ratio, Liver Neoplasms, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Hepatitis C, Nomogram, Hepatitis C, Chronic, Middle Aged, medicine.disease, Confidence interval, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Surgery, Nomograms, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, business
Abstract: International audience; Unlabelled - The aim of this work was to develop an individualized score for predicting hepatocellular carcinoma (HCC) in patients with hepatitis C (HCV)-compensated cirrhosis. Among 1,323 patients with HCV cirrhosis enrolled in the French prospective ANRS CO12 CirVir cohort, 720 and 360 were randomly assigned to training and validation sets, respectively. Cox's multivariate model was used to predict HCC, after which a nomogram was computed to assess individualized risk. During follow-up (median, 51.0 months), 103 and 39 patients developed HCC in the training and validation sets, respectively. Five variables were independently associated with occurrence of HCC: age > 50 years (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.16; 3.25; P = 0.012); past excessive alcohol intake (HR, 1.55; 95% CI, 1.02; 2.36; P = 0.041); low platelet count (
Published: 2016
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20. Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis: A randomized trial comparing 3- and 6-month periodicities

Author: Valérie Bourcier, Sylvie Chevret, Jean-Pierre Bronowicki, Jean-Pierre Vinel, Isabelle Ollivier, Valérie Vilgrain, Cendrine Chaffaut, Sophie Hillaire, Philippe Mathurin, Paul Calès, Jean-Claude Trinchet, Ariane Mallat, Michel Beaugrand, Dominique Roulot, Françoise Degos, Gisèle N'Kontchou, Hélène Fontaine, Jean Henrion, Service d'hépato-gastroentérologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Jean Verdier [AP-HP], Université Paris Nord (Paris 13), Service d'hépatologie, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital de Jolimont, Hopital de Jolimont, Service d'hépatologie médicale [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Foch [Suresnes], Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Gastro-entérologie - Hépatologie [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service d'Hépato-gastroentérologie, Hôpital Huriez-Université de Lille, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'imagerie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Biostatistique et épidemiologie clinique, UFR Santé, Médecine et Biologie Humaine (UFR SMBH), Université Sorbonne Paris Nord, Service d’Hépatologie [Hôpital Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Université Paris 13 (UP13), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Beaujon, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP]
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Cirrhosis, [SDV]Life Sciences [q-bio], medicine.disease_cause, Gastroenterology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Belgium, Randomized controlled trial, law, Internal medicine, Carcinoma, Humans, Medicine, Cumulative incidence, Early Detection of Cancer, Ultrasonography, Hepatitis B virus, Hepatology, business.industry, Incidence, Incidence (epidemiology), Liver Neoplasms, Middle Aged, medicine.disease, 3. Good health, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Female, 030211 gastroenterology & hepatology, France, alpha-Fetoproteins, Radiology, business, Follow-Up Studies
Abstract: International audience; Detection of small hepatocellular carcinoma (HCC) eligible for curative treatment is increased by surveillance, but its optimal periodicity is still debated. Thus, this randomized trial compared two ultrasonographic (US) periodicities: 3 months versus 6 months. A multicenter randomized trial was conducted in France and Belgium (43 sites). Patients with histologically proven compensated cirrhosis were randomized into two groups: US every 6 months (Gr6M) or 3 months (Gr3M). For each focal lesion detected, diagnostic procedures were performed according to European Association for the Study of the Liver guidelines. Cumulative incidence of events was estimated, then compared using Gray's test. The prevalence of HCC ≤30 mm in diameter was the main endpoint. A sample size of 1,200 patients was required. A total of 1,278 patients were randomized (Gr3M, n = 640; Gr6M, n = 638; alcohol 39.2%, hepatitis C virus 44.1%, hepatitis B virus 12.5%). At least one focal lesion was detected in 358 patients (28%) but HCC was confirmed in only 123 (9.6%) (uninodular 58.5%, ≤30 mm in diameter 74%). Focal-lesion incidence was not different between Gr3M and Gr6M groups (2-year estimates, 20.4% versus 13.2%, P = 0.067) but incidence of lesions ≤10 mm was increased (41% in Gr3M versus 28% in Gr6M, P = 0.002). No difference in either HCC incidence (P = 0.13) or in prevalence of tumors ≤30 mm in diameter (79% versus 70%, P = 0.30) was observed between the randomized groups. Conclusion: US surveillance, performed every 3 months, detects more small focal lesions than US every 6 months, but does not improve detection of small HCC, probably because of limitations in recall procedures. (HEPATOLOGY 2011;)
Published: 2011
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21. Impact of tumour differentiation to select patients before liver transplantation for hepatocellular carcinoma

Author: Claire Vanlemmens, Ariane Mallat, Pierre-Henri Bernard, Christophe Duvoux, Olivier Boillot, François Durand, Karim Boudjema, Georges Philippe Pageaux, Yvon Calmus, Jean Hardwigsen, Philippe Wolf, Christian Ducerf, Olivier Chazouillères, Thomas Decaens, Françoise Roudot-Thoraval, Jean Gugenheim, M.N. Hilleret, René Adam, Daniel Cherqui, Sébastien Dharancy, and Hanaa Badran
Subjects: medicine.medical_specialty, Hepatology, Receiver operating characteristic, business.industry, Proportional hazards model, medicine.medical_treatment, Retrospective cohort study, Milan criteria, Liver transplantation, Gastroenterology, Surgery, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Predictive value of tests, Cohort, Medicine, 030211 gastroenterology & hepatology, business, Prospective cohort study
Abstract: AIM: To generate a new score with improved accuracy compared with Milan criteria to select patients. PATIENTS: The training cohort comprised 373 patients transplanted for hepatocellular carcinoma (HCC) between 1988 and 1998 (cohort 1). An algorithm was derived from the analysis of patient data by the proportional hazard Cox regression model. The area under the receiver operating characteristic (AUROC) was used to determine a cut-off value. The validation cohort comprised 140 patients transplanted between 1999 and 2001 (cohort 2). RESULTS: Multivariate analysis identified three predictors of 5-year tumour-free survival: tumour differentiation (P=0.02), diameter (P
Published: 2011
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22. Endocannabinoids in the pathophysiology of obesity – The liver

Author: Sophie Lotersztajn and Ariane Mallat
Subjects: Liver injury, medicine.medical_specialty, Fatty liver, Adipose tissue, Disease, Biology, medicine.disease, Bioinformatics, Endocannabinoid system, Liver disease, Endocrinology, Insulin resistance, Fibrosis, Internal medicine, Drug Discovery, medicine, Molecular Medicine, lipids (amino acids, peptides, and proteins)
Abstract: With the increasing prevalence of obesity and co-morbidities, non-alcoholic fatty liver disease (NAFLD) has become the most common cause of liver disease in Western countries. Clinical and experimental studies have identified CB1 and CB2 receptors as potential novel therapeutic targets in the management of NAFLD. CB2 receptors in the adipose tissue probably participate in the pathogenesis of obesity-associated insulin resistance and non-alcoholic fatty liver disease. However, hepatic CB2 receptors display beneficial effects in various aspects of liver disease, including liver injury, regeneration and fibrosis. Hence, additional preclinical studies are warranted to define the contribution of adipose tissue versus liver CB2 receptors during chronic liver diseases. Although the development of CB1 antagonists has recently been suspended due to an alarming rate of mood disorders, preliminary preclinical data obtained with peripheral CB1 antagonists give real hopes in the development of active CB1 molecules devoid of central adverse effects.
Published: 2010
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23. Daily Cannabis Use: A Novel Risk Factor of Steatosis Severity in Patients With Chronic Hepatitis C

Author: Jean–Michel Pawlostky, Ariane Mallat, Charlotte Costentin, Christophe Hézode, Elie Serge Zafrani, Fatiha Medkour, Francoise Roudot Thoraval, Ali Hessami, Magali Bouvier–Alias, and Sophie Lotersztajn
Subjects: Adult, Male, medicine.medical_specialty, Genotype, medicine.medical_treatment, Marijuana Smoking, Hepacivirus, Severity of Illness Index, Gastroenterology, Body Mass Index, Predictive Value of Tests, Risk Factors, Internal medicine, Severity of illness, medicine, Humans, Risk factor, Cannabis smoking, Hepatology, biology, business.industry, Hepatitis C, Odds ratio, Hepatitis C, Chronic, Middle Aged, Viral Load, medicine.disease, biology.organism_classification, Surgery, Fatty Liver, Logistic Models, Liver, Multivariate Analysis, RNA, Viral, Female, Cannabis, Steatosis, business, Body mass index
Abstract: Steatosis is highly prevalent in patients with chronic hepatitis C (CHC) and has been reported to increase fibrosis and reduce the rate of viral eradication. Two recent studies indicate that endocannabinoids promote experimental steatosis via activation of hepatic CB1 receptors. We therefore investigated the impact of cannabis smoking on steatosis severity during CHC.A total of 315 consecutive patients with untreated CHC undergoing liver biopsy were included. Detailed histories of recent cannabis, alcohol, and tobacco use were recorded. Steatosis, activity, and fibrosis stage were assessed by 2 pathologists according to METAVIR. Marked steatosis was defined as/=30%. Patients were categorized as cannabis nonusers (63.5%), occasional cannabis smokers (12.4%), or daily cannabis smokers (24.1%).Multivariate analysis identified 6 predictors of marked steatosis: daily cannabis use (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.01-4.5]), activity grade/=A2 (OR, 2.1; 95% CI, 1.0-4.3), genotype 3 (OR, 5.4; 95% CI, 2.6-11.3), hyperglycemia or diabetes (OR, 5.1; 95% CI, 1.8-15.0), body mass index27 kg/m(2) (OR, 2.1; 95% CI, 1.0-4.3), and serum HCV RNA load (OR, 1.7; 95% CI, 1.0-2.9). Upon adjustment of HCV genotype (3 vs non-3) or alcohol intake (30 g/day vs/=30 g/day), marked steatosis was more frequent in daily cannabis users compared with occasional users and nonusers (P = .03 and P = .008, respectively).Our results identify daily cannabis smoking as a novel independent predictor of steatosis severity during CHC and strongly argue for a steatogenic role of the cannabinoid system. Cannabis use should be discouraged in patients with CHC.
Published: 2008
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24. Complications and competing risks of death in compensated viral cirrhosis (ANRS CO12 CirVir prospective cohort)

Author: Yannick Bacq, Victor de Ledinghen, Gérard Thiéfin, Claire Wartelle, Marc Bourlière, Sylvie Chevret, Lawrence Serfaty, Christophe Pilette, Jean-Pierre Zarski, S. Allam, Denis Ouzan, Dominique Guyader, Yves Benhamou, Jean-Didier Grangé, Cendrine Chaffaut, Jean-Marie Péron, Dominique Larrey, Ariane Mallat, Dominique Roulot, Fabien Zoulim, Dominique Capron, Odile Goria, Catherine Buffet, Vincent Di Martino, Jean-Pierre Bronowicki, Armand Abergel, Christine Silvain, Sophie Hillaire, Mohand Ait Ahmed, Pierre Nahon, Stanislas Pol, Christos Christidis, Valérie Bourcier, Jean-Claude Trinchet, Thong Dao, Jean-Frédéric Blanc, Laurent Alric, Albert Tran, Paul Calès, Philippe Mathurin, Patrick Marcellin, Service d'Hépato-gastroentérologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), 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), Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hépatologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Cellules souches normales et cancéreuses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut Arnaud Tzanck, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Service de Gastro-entérologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Département digestif, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département d'hépato-gastroentérologie, CHU Grenoble-Université Grenoble Alpes (UGA), CHU Rouen, Normandie Université (NU), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Service d'hépato-gastro-entérologie, Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital Huriez-Université de Lille, Inserm, UMR-1053, Université de Bordeaux, Bordeaux, F-33076, France, Centre hospitalier universitaire de Bordeaux, Department of Hepatology, Hôpital Saint-André, Bordeaux, F-33076, France, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service d'hépatologie [Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC), 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), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de gastro-entérologie [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hopital d'Aix en Provence, Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Mobilités : Attention, Orientation et Chronobiologie (COMETE), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Le Mans (CH Le Mans), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Hépatogastroentérologie, CHU Amiens-Picardie, Institut Mutualiste de Montsouris (IMM), Hôpital Foch [Suresnes], Hôpital JeanMinjoz, Service d'hépato-gastroentérologie, Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistique et épidemiologie clinique, Agence Nationale de Recherches sur le Sida et les Hepatites Virales, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes (UGA)-CHU Grenoble, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Jean Verdier, Centre de recherche sur l'Inflammation ( CRI ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -CHU Saint-Eloi, Université Montpellier 1 ( UM1 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hospices Civils de Lyon ( HCL ), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, CHU Nice, Centre méditérannéen de médecine moléculaire ( C3M ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques ( HIFIH ), Université d'Angers ( UA ), Hepato-gastro-enterology, Toulouse University hospital, Pharmacochimie et Pharmacologie Pour le Développement ( PHARMA-DEV ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique ( CNRS ), Assistance Publique - Hôpitaux de Marseille ( APHM ), Centre Hospitalier Universitaire Estaing, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Service de gastro-entérologie, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Service d'Hépato-Gastro-Enterologie et Nutrition [Caen], Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -CHU Caen, Mobilités : Attention, Orientation et Chronobiologie ( COMETE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Assistance publique - Hôpitaux de Paris (AP-HP), Centre de recherche biomédicale Bichat-Beaujon ( CRB3 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Jean Verdier [AP-HP], Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département d'hépatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), 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), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépatologie et de Gastroentérologie [Lyon], Université Nice Sophia Antipolis (1965 - 2019) (UNS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Saint-André, Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [APHP], Institut mutualiste Monsouris (IMM), CHU Saint-Eloi-Université de Montpellier (UM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Service d'hépatologie [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Service d'Hépato-gastro-entérologie [CHU Saint-Antoine]
Subjects: Liver Cirrhosis, Male, Cirrhosis, [SDV]Life Sciences [q-bio], Hepatocellular / physiopathology, Liver Neoplasms / mortality, medicine.disease_cause, Gastroenterology, Cohort Studies, Liver disease, Cause of Death, Liver Cirrhosis / complications, Longitudinal Studies, Prospective Studies, Prospective cohort study, Liver Failure / mortality, Hepatocellular / virology, Liver Neoplasms, Hepatitis C / complications, Middle Aged, Hepatitis B, Hepatitis C, 3. Good health, Hepatocellular carcinoma, Disease Progression, Female, France, Liver cancer, Hepatitis C / pathology, Hepatitis B / pathology, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Liver Neoplasms / pathology, Milan criteria, Risk Assessment, Liver Cirrhosis / virology, Predictive Value of Tests, Internal medicine, Liver Failure / pathology, medicine, Humans, Decompensation, Hepatitis B / complications, Proportional Hazards Models, Hepatitis B virus, Liver Failure / virology, Analysis of Variance, Hepatology, [ SDV ] Life Sciences [q-bio], business.industry, Carcinoma, medicine.disease, Survival Analysis, digestive system diseases, Liver Neoplasms / virology, Liver Cirrhosis / mortality, Multivariate Analysis, Hepatocellular / mortality, business, Liver Failure
Abstract: International audience; Various critical events, liver related or not, occur in patients with compensated cirrhosis, but their respective burden remains to be prospectively assessed. The aim of this prospective cohort study involving 35 French centers was to capture the whole spectrum of complications occurring in compensated viral cirrhosis (VC) using competing risks analyses. Inclusion criteria were: histologically proven cirrhosis resulting from hepatitis C virus (HCV) or hepatitis B virus (HBV); Child-Pugh A; and no previous hepatic complications. The cohort was considered as a multistate disease model, cumulative incidences (CumIs) of events were estimated in a competing risks framework. A total of 1,654 patients were enrolled from 2006 to 2012 (HCV, 1,308; HBV, 315; HCV-HBV, 31). During a median follow-up of 34 months, at least one liver nodule was detected in 271 patients, confirmed as hepatocellular carcinoma (HCC) in 128 (4-year cumI: 10.5%) and cholangiocarcinoma in 3. HCC incidence was higher in HCV (4-year cumI: 11.4% vs. 7.4%; P = 0.05). HCC fulfilled Milan criteria in 79.3%, leading to curative treatment in 70.4%. Liver decompensation occurred more frequently in HCV patients (4-year cumI: 10.8% vs. 3.6%; P = 0.0004). Virological eradication/control was achieved in 34.1% of HCV and 88.6% of HBV patients and was associated with a marked decrease in HCC, decompensation, and bacterial infection incidences. Survival was shorter in HCV patients (4-year cumI: 91.6% vs. 97.2%; P = 0.0002). Death (n = 102; missing data: 6) was attributed to liver disease in 48 (47%; liver cancer: n = 18; miscellaneous, n = 30) and extrahepatic causes in 48 (47%; bacterial infection: n = 13; extrahepatic cancers: n = 10; cardiovascular events: n = 5; miscellaneous, n = 20). CONCLUSION: After 3 years of follow-up, extrahepatic events still explained half of deaths in patients with compensated VC. A strong decrease in complications was linked to virological eradication/control. (Hepatology 2015;62:737-750)
Published: 2015
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25. Targeting cannabinoid receptors in hepatocellular carcinoma?

Author: Sophie Lotersztajn and Ariane Mallat
Subjects: 0301 basic medicine, Sorafenib, medicine.medical_specialty, Cannabinoid receptor, medicine.medical_treatment, Gastroenterology, Anandamide, Biology, Endocannabinoid system, Monoacylglycerol lipase, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, Endocrinology, chemistry, Fatty acid amide hydrolase, Internal medicine, medicine, Cancer research, lipids (amino acids, peptides, and proteins), Cannabinoid, Receptor, medicine.drug
Abstract: Hepatocellular carcinoma (HCC) represents a major health problem, accounting for 90% of primary liver cancer and the second cause of cancer-related death worldwide.1 The tumour predominantly occurs in cirrhotic livers following exposure to various risk factors, including hepatitis B and C virus infection, excessive alcohol intake and metabolic syndrome. The majority of patients are diagnosed at intermediate or advanced stages and are ineligible for curative treatment. Several mechanisms contribute to the initiation and progression of HCC, including chronic inflammation, DNA damage, epigenetic modifications, senescence, telomerase reactivation, chromosomal instability, neo-angiogenesis. However, despite advances in the comprehension of HCC biology, sorafenib remains the single drug approved for HCC treatment with a marginal improvement of overall survival in patients. Endocannabinoids comprise a family of lipidic ligands for two canonical ubiquitous cannabinoid receptors, CB1 and CB2, among which anandamide, a CB1 ligand catabolised by fatty acid amide hydrolase (FAAH), and 2-arachydonoylglycerol, a CB1/CB2 ligand degraded by monoacylglycerol lipase (MAGL), are best characterised.2 Both compounds also interact with non-cannabinoid receptors, transient receptor potential (TRP) channels or G protein-coupled receptor 55. The endocannabinoid system (ECS) has been identified as a pivotal regulator …
Published: 2016
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26. Sphingosine 1-Phosphate Triggers Both Apoptotic and Survival Signals for Human Hepatic Myofibroblasts

Author: Julien Davaille, Liying Li, Sophie Lotersztajn, and Ariane Mallat
Subjects: MAPK/ERK pathway, Ceramide, medicine.medical_specialty, Time Factors, Cell Survival, Apoptosis, Biology, Pertussis toxin, Models, Biological, Biochemistry, Phosphates, chemistry.chemical_compound, Sphingosine, Internal medicine, medicine, Humans, Sphingosine-1-phosphate, Receptor, Molecular Biology, Protein kinase B, Cells, Cultured, PI3K/AKT/mTOR pathway, Cell Death, organic chemicals, Cell Biology, Fibroblasts, Kinetics, Endocrinology, Liver, chemistry, Cancer research, lipids (amino acids, peptides, and proteins), Lysophospholipids
Abstract: Hepatic myofibroblasts (hMFs) are central in the development of liver fibrosis during chronic liver diseases, and their removal by apoptosis contributes to the resolution of liver fibrosis. We previously identified Edg receptors for sphingosine 1-phosphate (S1P) in human hMFs. Here, we investigated the effects of S1P on hMF apoptosis. S1P reduced viability of serum-deprived hMFs by an apoptotic process that was unrelated to the conversion of S1P into sphingosine and ceramide. The apoptotic effects of S1P were receptor-independent because dihydro-S1P, an Edg agonist, had no effect. S1P also stimulated a receptor-dependent survival pathway, revealed by enhanced activation of caspase-3 by S1P in the presence of pertussis toxin. Cell survival relied on two pertussis toxin-sensitive events, activation of ERK and activation of phosphatidylinositol 3-kinase (PI3K)/Akt by S1P. Both pathways were also activated by dihydro-S1P. Blunting either ERK or PI3K enhanced caspase-3 stimulation by S1P, and simultaneous inhibition of both pathways resulted in additive effects on caspase-3 activation. In conclusion, S1P induces apoptosis of human hMFs via a receptor-independent mechanism and stimulates a survival pathway following activation of Edg receptors. The survival pathway arises from the sequential activation of G(i)/G(o) proteins and independent stimulations of ERK and PI3K/Akt. Therefore, blocking Edg receptors may sensitize hepatic myofibroblasts to apoptosis by S1P.
Published: 2002
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27. Effects of noradrenalin and albumin in patients with type I hepatorenal syndrome: A pilot study

Author: Françoise Roudot-Thoraval, Daniel Dhumeaux, David Zanditenas, Jean-Luc Monin, Ariane Mallat, Christophe Hézode, Anthony Chauvat, and Christophe Duvoux
Subjects: medicine.medical_specialty, Mean arterial pressure, Creatinine, Aldosterone, Hepatology, business.industry, Albumin, Furosemide, Renal function, medicine.disease, chemistry.chemical_compound, Endocrinology, Hepatorenal syndrome, Pharmacokinetics, chemistry, Internal medicine, medicine, business, medicine.drug
Abstract: Treatment of hepatorenal syndromes (HRSs) is currently based on vasopressin analogs. The aim of this pilot study was to evaluate the efficacy and safety of noradrenalin (NA) in the treatment of type 1 HRS. Between 1998 and 2000, 12 consecutive patients with type 1 HRS (7 men, 5 women; mean age, 54 +/- 11 years; mean Child-Pugh score, 11.3 +/- 1.7) were treated with intravenous NA (0.5-3 mg/h), in combination with intravenous albumin and furosemide. NA was given for 10 +/- 3 days, at a mean dose of 0.8 +/- 0.3 mg/h. Reversal of HRS was observed in 10 of 12 patients (83%; 95% confidence interval, 52%-98%) after a median of 7 days (range, 5-10 days). Serum creatinine levels fell from 358 +/- 161 to 145 +/- 78 micromol/L (P
Published: 2002
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28. Increased Nitric Oxide Output from Alveolar Origin during Liver Cirrhosis versus Bronchial Source during Asthma

Author: Alain Harf, Ariane Mallat, Christophe Delclaux, Bruno Mahut, Daniel Cherqui, Christophe Delacourt, Sylva Laoud, Françoise Zerah-Lancner, and Christophe Duvoux
Subjects: Adult, Liver Cirrhosis, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pathology, Cirrhosis, Bronchi, Nitric Oxide, Critical Care and Intensive Care Medicine, Gastroenterology, Nitric oxide, chemistry.chemical_compound, Internal medicine, medicine, Humans, Expiration, Asthma, Bronchus, business.industry, Respiration, Respiratory disease, Middle Aged, medicine.disease, Pulmonary Alveoli, medicine.anatomical_structure, ROC Curve, chemistry, Female, Pulmonary alveolus, business
Abstract: The aim of this study was to assess the usefulness of nitric oxide (NO) output measurement at multiple expiratory flow rates during diseases characterized by increased exhaled NO (FE(NO)) that could come from alveolar (liver cirrhosis) or bronchial (asthma) sources. It has been proposed that NO output measurements expressed as a function of expiratory flow allow alveolar NO concentration (FA(NO)) and maximal bronchial NO output (Qbr,max (NO)) to be computed. In 36 healthy nonsmoking subjects, we found that maximal bronchial NO output (37 +/- 3 nl/min) was correlated with the height of the subjects (p = 0.02). Alveolar NO concentration was 5.1 +/- 0.3 (SEM) ppb, which represented 31 +/- 2% and 61 +/- 3% of FE(NO) at 50 and 200 ml/s expiratory flow rate, respectively. Nonsmoking subjects with asthma (n = 28) were characterized by an increase in Qbr,max (NO) (133 +/- 14 nl/min) as compared with healthy nonsmoking subjects (p0.0001). FE(NO)50, FE(NO)200, and Qbr,max (NO) were equally efficient in differentiating subjects with asthma from healthy subjects. Patients with liver cirrhosis (n = 26, 14 smokers and 12 nonsmokers) had an increased FA(NO) compared with healthy subjects (cirrhosis: 8.3 +/- 0.9 ppb, healthy nonsmokers [n = 36] and smokers [n = 20], n = 56: 4.7 +/- 0.3 ppb, p0.05), which was correlated with the alveolar-arterial oxygen difference (p = 0.007). FA(NO) and FE(NO)200, but not FE(NO)50 values, allowed patients with liver cirrhosis to be differentiated from healthy subjects. These results suggest that a two-compartment model for NO output allows the increase in FE(NO) from alveolar sources to be differentiated from the increase from bronchial sources.
Published: 2002
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29. The liver X receptor in hepatic stellate cells: A novel antifibrogenic target?

Author: Sophie Lotersztajn and Ariane Mallat
Subjects: medicine.medical_specialty, Hepatology, Cell, Inflammation, Lipid metabolism, Biology, medicine.disease, Article, medicine.anatomical_structure, Endocrinology, Nuclear receptor, Fibrosis, Internal medicine, Lipogenesis, medicine, Hepatic stellate cell, Cancer research, medicine.symptom, Liver X receptor
Abstract: Background & Aims: Liver X receptors (LXRs) are lipid- activated nuclear receptors with important roles in cholesterol trans- port, lipogenesis, and anti-inflammatory signaling. Hepatic stellate cells activate during chronic liver injury and mediate the fibrotic response. These cells are also major repositories for lipids, but the role of lipid metabolism during stellate cell activation remains unclear. We investigated the role of LXR signaling stellate cell activa- tion and susceptibility to fibrotic liver disease. Methods: Immortalized and primary stellate cells purified from mice were treated with highly specific LXR ligands. Carbon tetrachloride and methionine/choline deficiency were used as chronic liver injury models. Reciprocal bone marrow transplants were performed to test the importance of hematopoietically derived cells to the fibrotic response. Results: LXR ligands suppressed markers of fibrosis and stellate cell activation in primary mouse stellate cells. Lxrab(� /� ) stellate cells produce increased levels of inflammatory mediators, and conditioned media from Lxrab(� /� ) cells increases the fibrogenic program of wild-type cells. Furthermore, Lxrab(� /� ) stellate cells exhibit altered lipid morphology and increased expression of fibrogenic genes, sug- gesting they are primed for activation. In vivo, Lxrab(� /� ) mice have marked susceptibility to fibrosis in two injury models. Bone marrow transplants point to altered stellate cell function, rather than hema- topoietic cell inflammation, as the primary basis for the Lxrab(� /� ) phenotype. Conclusions: These results reveal an unexpected role for LXR signal- ing and lipid metabolism in the modulation of hepatic stellate cell function.
Published: 2011
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30. Cigarette smoke exposure: A novel cofactor of NAFLD progression?

Author: Ariane Mallat and Sophie Lotersztajn
Subjects: medicine.medical_specialty, Cirrhosis, Mice, Transgenic, Disease, Gastroenterology, Mice, Primary biliary cirrhosis, Fibrosis, Internal medicine, medicine, Animals, Humans, Sidestream smoke, Apolipoproteins B, Hepatology, business.industry, Lipogenesis, Adenylate Kinase, Smoking, Fatty liver, medicine.disease, Dietary Fats, Fatty Liver, Disease Models, Animal, Hepatocellular carcinoma, Disease Progression, Tobacco Smoke Pollution, Metabolic syndrome, Sterol Regulatory Element Binding Protein 1, business
Abstract: Cigarette smoke exposure, whether passive or active, carries a high disease burden worldwide [1]. In a recent comprehensive assessment of the mortality attributable to modifiable risk factors in the US adult population, tobacco use was held responsible for 467,000 deaths (approximately one out of five) in 2005 [2]. Despite the large body of evidence documenting the pluriorgan morbidity of tobacco, reports investigating the impact of cigarette smoking on pathogenesis of liver injury have long remained scant. Initial evidence arose from two retrospective studies suggesting that cigarette smoking may increase prevalence and/or severity of alcoholic [3] and HBV-related cirrhosis [4]. Accordingly, two recent studies in patients with primary biliary cirrhosis identified tobacco use as an independent predictor of advanced fibrosis at presentation [5,6]. In contrast, in patients with chronic hepatitis C, the impact of tobacco use on fibrosis progression remains controversial [7,8] and available data would suggest that cigarette smoking may aggravate necroinflammation, thereby contributing to accelerated fibrogenesis [7–10]. Finally, in line with the carcinogenic properties of tobacco in several organs, a number of studies indicate that cigarette smoking is associated with an increased incidence of hepatocellular carcinoma in cirrhotic patients [11–14]. Non-alcoholic fatty liver disease (NAFLD), the hepatic hallmark of the metabolic syndrome, is a worrisome
Published: 2009
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31. Biological Effects of C-type Natriuretic Peptide in Human Myofibroblastic Hepatic Stellate Cells

Author: Catherine Pavoine, Jeanne Tran Van Nhieu, Ariane Mallat, Jiangchuan Tao, Cyrille Gallois, Sophie Lotersztajn, Souâd Belmadani, and Pierre-François Méry
Subjects: Liver Cirrhosis, medicine.medical_specialty, MAP Kinase Kinase 4, Liver cytology, medicine.drug_class, Mitogen-activated protein kinase kinase, Biology, Biochemistry, Internal medicine, Adipocytes, medicine, Natriuretic peptide, Humans, Receptor, Cyclic GMP, Protein Kinase Inhibitors, Molecular Biology, Cells, Cultured, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase Kinases, Mitogen-Activated Protein Kinase 3, Voltage-dependent calcium channel, Kinase, JNK Mitogen-Activated Protein Kinases, Thrombin, Natriuretic Peptide, C-Type, DNA, Cell Biology, Transcription Factor AP-1, Endocrinology, Liver, Guanylate Cyclase, Calcium-Calmodulin-Dependent Protein Kinases, Hepatic stellate cell, Calcium, Mitogen-Activated Protein Kinases, Receptors, Atrial Natriuretic Factor, cGMP-dependent protein kinase
Abstract: During chronic liver diseases, hepatic stellate cells (HSC) acquire a myofibroblastic phenotype, proliferate, and synthetize fibrosis components. Myofibroblastic HSC (mHSC) also participate to the regulation of intrahepatic blood flow, because of their contractile properties. Here, we examined whether human mHSC express natriuretic peptide receptors (NPR). Only NPR-B mRNA was identified, which was functional as demonstrated in binding studies and by increased cGMP levels in response to C-type natriuretic peptide (CNP). CNP inhibited mHSC proliferation, an effect blocked by the protein kinase G inhibitor 8-(4 chlorophenylthio)-cGMP and by the NPR antagonist HS-142-1 and reproduced by analogs of cGMP. Growth inhibition was associated with a reduction of extracellular signal-regulated kinase and c-Jun N-terminal kinase and with a blockade of AP-1 DNA binding. CNP and cGMP analogs also blunted mHSC contraction elicited by thrombin, by suppressing calcium influx. The relaxing properties of CNP were mediated by a blockade of store-operated calcium channels, as demonstrated using a calcium-free/calcium readdition protocol. These results constitute the first evidence for a hepatic effect of CNP and identify mHSC as a target cell. Activation of NPR-B by CNP in human mHSC leads to inhibition of both growth and contraction. These data suggest that during chronic liver diseases, CNP may counteract both liver fibrogenesis and associated portal hypertension.
Published: 1999
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32. [Untitled]

Author: Martine Blazquez, Elie Serge Zafrani, Ariane Mallat, Bernard Campillo, Jean-Claude Bognel, and Jean-Philippe Richardet
Subjects: Long lasting, medicine.medical_specialty, Amoxicillin/clavulanic acid, Physiology, business.industry, Gastroenterology, Amoxicillin, medicine.disease, Ductopenia, Transplant surgery, Cholestasis, Internal medicine, Clavulanic acid, medicine, Acide clavulanique, business, medicine.drug
Published: 1999
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33. Le système endocannabinoïde, une nouvelle cible pour le traitement de la fibrose hépatique

Author: Fatima Teixeira-Clerc, Ariane Mallat, Boris Julien, Christophe Hézode, Sophie Lotersztajn, Pascale Grenard, J. Tran Van Nhieu, and Vanessa Deveaux
Subjects: medicine.medical_specialty, Cannabis smoking, Cannabinoid receptor, medicine.medical_treatment, General Medicine, Hepatitis C, Biology, Pharmacology, medicine.disease, Endocannabinoid system, Endocrinology, nervous system, Rimonabant, Internal medicine, medicine, Cannabinoid receptor type 2, lipids (amino acids, peptides, and proteins), Cannabinoid, Hepatic fibrosis, medicine.drug
Abstract: The cannabinoid system comprises specific G protein-coupled receptors (CB1 and CB2), exogenous (marijuana-derived cannabinoids) and endogenous (endocannabinoids) ligands, and a machinery dedicated to endocannabinoid synthesis and degradation. Studies over two decades have extensively documented the crucial role of the cannabinoid system in the regulation of a variety of pathophysiological conditions. However, its role in liver pathology has only been recently unravelled, probably given the low expression of CB1 and CB2 in the normal liver. We have recently demonstrated that CB1 and CB2 receptors display opposite effects in the regulation of liver fibrogenesis during chronic liver injury. Indeed, both receptors are up-regulated in the liver of cirrhotic patients, and expressed in liver fibrogenic cells. Moreover, CB1 receptors are profibrogenic and accordingly, the CB1 antagonist rimonabant reduces fibrosis progression in three experimental models. In keeping with these results, daily cannabis smoking is a risk factor for fibrosis progression in patients with chronic hepatitis C. In contrast, CB2 display antifibrogenic effects, by a mechanism involving reduction of liver fibrogenic cell accumulation. These results may offer new perspectives for the treatment of liver fibrosis, combining CB2 agonist and CB1 antagonist therapy.
Published: 2008
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34. P0843 : On-treatment viral kinetics do not predict SVR in patients with advanced liver disease receiving sofosbuvir in combination with daclatasvir or simeprevir for 12 weeks

Author: Christophe Hézode, Cyrille Feray, M. Francois, Isaac Ruiz, Magali Bouvier-Alias, Stéphane Chevaliez, Jean-Michel Pawlotsky, Ariane Mallat, and G. Scoazec
Subjects: Simeprevir, medicine.medical_specialty, Daclatasvir, Hepatology, Sofosbuvir, business.industry, medicine.disease, Viral kinetics, Gastroenterology, Liver disease, Internal medicine, medicine, In patient, business, medicine.drug
Published: 2015
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35. Platelet-derived Growth Factor-BB and Thrombin Generate Positive and Negative Signals for Human Hepatic Stellate Cell Proliferation

Author: Philippe Mavier, Anne-Marie Preaux, Aida Habib, Jacques Maclouf, Cyrille Gallois, Ariane Mallat, Sophie Lotersztajn, and Jiangchuan Tao
Subjects: MAPK/ERK pathway, Hepatic stellate cell proliferation, medicine.medical_specialty, biology, Growth factor, medicine.medical_treatment, Cell Biology, Biochemistry, Cell biology, Endocrinology, Thrombin, Internal medicine, Second messenger system, medicine, biology.protein, Hepatic stellate cell, Receptor, Molecular Biology, Platelet-derived growth factor receptor, medicine.drug
Abstract: Proliferation of myofibroblastic hepatic stellate cells (HSC) in response to growth factors is essential for the development of liver fibrosis. We have reported that prostaglandins (PG) and cyclic AMP (cAMP) inhibit growth of human HSC. This PG/cAMP pathway transduces the endothelin (ET) B-mediated antiproliferative effect of endothelin-1 (ET-1) and up-regulates ETB receptors. Here, we show that platelet-derived growth factor (PDGF)-BB and thrombin, although mitogenic, generate growth inhibitory PGE2 in myofibroblastic human HSC. The two peptides elicit early PGE2 and cAMP synthesis, and also promote delayed induction of cyclooxygenase (COX)-2. Both early and delayed production of PGE2 counteract the mitogenic effect of PDGF-BB and thrombin because: (i) pretreatment with the COX inhibitor ibuprofen markedly enhances the mitogenic effect of both peptides; (ii) blocking early synthesis of PGE2 greatly enhances extracellular signal-regulated kinase (ERK) activation by both growth factors; (iii) enhancement of DNA synthesis by ibuprofen is only lost when the inhibitor is added after COX-2 induction has occurred. Finally, PDGF-BB and thrombin raise ETB receptors through the PG pathway. Thus, ibuprofen blunts growth factor-induced increase in ETB receptors. Up-regulation of the growth inhibitory ETB receptors by both mitogens may enhance the antiproliferative effect of ET-1 and thereby establish a negative feedback of their mitogenic effect. Our results shed light on novel growth inhibitory signals evoked by two mitogenic growth factors expressed during liver injury.
Published: 1998
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36. Role of NF-κB in the Antiproliferative Effect of Endothelin-1 and Tumor Necrosis Factor-α in Human Hepatic Stellate Cells

Author: Stéphanie Moulin, Aida Habib, Ariane Mallat, Sophie Lotersztajn, Jacques Maclouf, Cyrille Gallois, and Jiangchuan Tao
Subjects: medicine.medical_specialty, P50, biology, Stimulation, NF-κB, Cell Biology, Biochemistry, Endothelin 1, chemistry.chemical_compound, Endocrinology, chemistry, Internal medicine, Hepatic stellate cell, medicine, Cancer research, biology.protein, Tumor necrosis factor alpha, Cyclooxygenase, Molecular Biology, Sodium salicylate
Abstract: During chronic liver diseases, hepatic stellate cells (HSC) acquire an activated myofibroblast-like phenotype and proliferate and synthesize fibrosis components. Endothelin-1 (ET-1), which inhibited the growth of human myofibroblastic HSC, increased the formation of two NF-κB DNA binding complexes; this effect was also observed with tumor necrosis factor-α (TNF-α). The complexes were identified as the p50/p50 and p50/p65 NF-κB dimers. Activation of NF-κB was associated with the degradation of the inhibitory protein IκB-α; no IκB-β was detected. Activation of NF-κB and degradation of IκB-α were prevented by the NF-κB inhibitors sodium salicylate and MG-132. In addition to cyclooxygenase-1 (COX-1), COX-2 is also constitutively expressed in human HSC, and the use of dexamethasone and of SC-58125, a selective COX-2 inhibitor, revealed that COX-2 accounts for basal COX activity. Moreover, COX-2 mRNA and protein were up-regulated by ET-1 and TNF-α, whereas COX-1 was unaffected. Induction of COX-2 and stimulation of COX activity by ET-1 and TNF-α were prevented by sodium salicylate and MG-132, suggesting that activation of NF-κB by either factor is needed for stimulation of COX-2. Finally, SC-58125 and dexamethasone reduced the growth inhibitory effect of ET-1 and TNF-α, indicating that activation of COX-2 is required for inhibition of HSC proliferation. Taken together, our results suggest that NF-κB, by inducing COX-2 expression, may play an important role in the negative regulation of human myofibroblastic HSC proliferation.
Published: 1998
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37. Hepatic Stellate Cells and Intrahepatic Modulation of Portal Pressure

Author: Ariane Mallat
Subjects: medicine.medical_specialty, Pathology, Portal venous pressure, Endothelin I, Vasodilation, Nitric Oxide, Biological effect, Internal medicine, Hypertension, Portal, medicine, Animals, Humans, Cells, Cultured, Carbon Monoxide, Endothelin-1, business.industry, Spider Cell, Gastroenterology, medicine.disease, Portal Pressure, Endocrinology, Liver, Vasoconstriction, Hepatic stellate cell, Portal hypertension, medicine.symptom, business, Blood Flow Velocity
Published: 1998
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38. Growth inhibitory properties of endothelin-1 in activated human hepatic stellate cells: a cyclic adenosine monophosphate-mediated pathway. Inhibition of both extracellular signal-regulated kinase and c-Jun kinase and upregulation of endothelin B receptors

Author: C Serradeil-Le Gal, V Iourgenko, Ariane Mallat, D A Brenner, Philippe Mavier, Laura Fouassier, Danielle Raufaste, Sophie Lotersztajn, Daniel Dhumeaux, Anne-Marie Preaux, C Bradham, Cyrille Gallois, and Jacques Maclouf
Subjects: medicine.medical_specialty, Ibuprofen, Viper Venoms, Biology, Adenylyl cyclase, chemistry.chemical_compound, Genes, jun, Internal medicine, Adipocytes, Cyclic AMP, medicine, Humans, Cyclic adenosine monophosphate, RNA, Messenger, Receptor, Cells, Cultured, Binding Sites, Forskolin, Endothelin-1, Receptors, Endothelin, Colforsin, General Medicine, Epoprostenol, Receptor, Endothelin B, Endothelin 1, Up-Regulation, Cell biology, Endocrinology, Liver, chemistry, Prostaglandins, cardiovascular system, Hepatic stellate cell, cAMP-dependent pathway, Endothelin receptor, Protein Kinases, Cell Division, Adenylyl Cyclases, Research Article
Abstract: During chronic liver diseases, hepatic stellate cells (HSC) acquire an activated myofibroblast-like phenotype, proliferate, and synthetize fibrosis components. We have shown that endothelin-1 (ET-1) inhibits the proliferation of activated human HSC via endothelin B (ETB) receptors. We now investigate the transduction pathway involved in the growth inhibitory effect of ET-1 in activated HSC. Endothelin-1 and the ETB receptor agonist, sarafotoxin-S6C, increased synthesis of PGI2 and PGE2, leading to elevation of cAMP. The cyclooxygenase inhibitor ibuprofen and the adenylyl cyclase inhibitor SQ22536 both blunted the growth inhibitory effect of ET-1. Analysis of early steps associated with growth inhibition indicated that: (a) similar to ET-1, forskolin decreased c-jun mRNA induction without affecting c-fos and krox 24 mRNA expression; (b) ET-1, sarafotoxin-S6C, as well as forskolin, reduced activation of both c-Jun kinase and extracellular signal-regulated kinase. Finally, forskolin, PGI2, and PGE2 raised by fivefold the number of ET binding sites after 6 h, and increased the proportion of ETB receptors from 50% in control cells to 80% in treated cells. In conclusion, ET-1 inhibits proliferation of activated HSC via ETB receptors, through a prostaglandin/cAMP pathway that leads to inhibition of both extracellular signal-regulated kinase and c-Jun kinase activities. Upregulation of ETB receptors by prostaglandin/cAMP raises the possibility of a positive feedback loop that would amplify the growth inhibitory response. These results suggest that ET-1 and agents that increase cAMP might be of interest to limit proliferation of activated HSC during chronic liver diseases.
Published: 1996
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39. Multiple hepatic functions of endothelin-1: physiopathological relevance

Author: Sophie Lotersztajn and Ariane Mallat
Subjects: Liver Cirrhosis, medicine.medical_specialty, Portal venous pressure, Molecular Sequence Data, Biology, Liver disease, Cholestasis, Internal medicine, medicine, Bile, Humans, Amino Acid Sequence, Receptor, Endothelin-1, Hepatology, Receptors, Endothelin, medicine.disease, Endothelin 1, Peptide Fragments, Endocrinology, Liver, Portal hypertension, Liver function, Endothelin receptor, Glycogen, Liver Circulation
Abstract: N I 1988, Y~agisawa et ai. isolated a potent vasoconstricting peptide from the supematant of bovine endotheiial ceils, and named it endotbeiin1 (ET1) (1). Besides vasoregulatory effects in numerous vascular beds, ET-i and related peptides, ET-2 and ET-3, were soon shown to elicit a wide variety of biological effects, such as hormone secretion, positive ino~opism, bronchocons~ction, etc. (24). It was initially shown that the liver is a target tissue for endotheiins by demonstrating that the peptides increase portal pressure and activate giycogenoiysis (5,6). Subsequently, a flurry of papers have investigated vasocontractile effects of ET-i in the normal liver (79), while evidence has accumulated to show that the peptide may play a role in the pa~ogenesis of circulatory disorders observed during liver diseases, such as portal hypertension or ischemia/reperfusion injury (10-15). At the same time, the identification of several non-vascular hepatic effects of the peptide raised the question of their role in other facets of liver disease such as cholestasis or liver fibrogenesis (5,6,1621). This review will focus on these various aspects, after a brief overview of the general properties of endothelin peptides.
Published: 1996
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40. Fibroblast growth factor 2 and transforming growth factor β1 interactions in human liver myofibroblasts

Author: Ariane Mallat, Sylvie Blazejewski, Philippe Mavier, Daniel Dhumeaux, Anne-Marie Preaux, and Jean Rosenbaum
Subjects: medicine.medical_specialty, Platelet-derived growth factor, chemistry.chemical_compound, Transforming Growth Factor beta, Internal medicine, medicine, Humans, Growth factor receptor inhibitor, RNA, Messenger, Platelet-Derived Growth Factor, Analysis of Variance, Hepatology, biology, Gastroenterology, Fibroblast growth factor receptor 4, Fibroblasts, Fibroblast growth factor receptor 3, FGF1, Receptors, Fibroblast Growth Factor, Fibronectins, Cell biology, Endocrinology, Liver, chemistry, Fibroblast growth factor receptor, biology.protein, Fibroblast Growth Factor 2, Cell Division, Platelet-derived growth factor receptor, Transforming growth factor
Abstract: Background & Aims: During liver fibrogenesis, myofibroblastic liver cells proliferate and synthesize components of fibrosis. Fibroblast growth factor 2 (FGF-2) is expressed in vivo in myofibroblastic liver cells (MFLCs) during fibrogenesis, and exogenous FGF-2 is mitogenic for MFLCs. The aim of this study was to study the expression and role of endogenous FGF-2 in cultured human MFLCs. Methods: FGF-2 and FGF-2 receptors were studied using immunoblotting. All RNA studies used ribonuclease protection. Growth of MFLCs was studied using [ 3 H]thymidine incorporation and direct cell counting. Results: MFLCs expressed FGF-2 and its receptors FGF receptor 1 and FGF receptor 2. An antibody to FGF-2 blocked the mitogenic effect of transforming growth factor β1 (TGF-β1) for MFLCs but not TGF-β1-induced increase in cellular fibronectin messenger RNA (mRNA). TGF-β1 increased levels of FGF-2 and FGF receptor mRNAs in MFLCs. We have previously shown that TGF-β1 also increased platelet-derived growth factor (PDGF) A chain mRNA in these cells and that anti-PDGF antibody blunted the mitogenic effect of TGF-β1. The present results show that anti-FGF-2 and anti-PDGF-AA are not additive and that FGF-2 and PDGF-AA are not sequentially induced by TGF-β1. Conclusions: FGF-2 mediates the mitogenic but not the profibrogenic effect of TGF-β1 for human MFLCs, and autocrine FGF-2 and PDGF-A interact in the mediation of the mitogenic effect of TGF-β1.
Published: 1995
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41. Liver transplantation for hepatocellular carcinoma: a model including α-fetoprotein improves the performance of Milan criteria

Author: Christophe, Duvoux, Françoise, Roudot-Thoraval, Thomas, Decaens, Fabienne, Pessione, Hanaa, Badran, Tullio, Piardi, Claire, Francoz, Philippe, Compagnon, Claire, Vanlemmens, Jérome, Dumortier, Sébastien, Dharancy, Jean, Gugenheim, Pierre-Henri, Bernard, René, Adam, Sylvie, Radenne, Fabrice, Muscari, Filomena, Conti, Jean, Hardwigsen, Georges-Philippe, Pageaux, Olivier, Chazouillères, Ephrem, Salame, Marie-Noelle, Hilleret, Pascal, Lebray, Armand, Abergel, Marilyne, Debette-Gratien, Michael D, Kluger, Ariane, Mallat, Daniel, Azoulay, Daniel, Cherqui, Stephane, Bouvier, Le Corre, Morgane, 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), Pôle Recherche Clinique-Santé Publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Pôle évaluation - biostatistique, Agence de la biomédecine [Saint-Denis la Plaine], Service de Transplantation, Hôpital de Hautepierre [Strasbourg], Service d'hépatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), service d'Hépato-gastro-entérologie, Hospices Civiles de Lyon-Hôpital Edouard Heriault, Hôpital Claude Hurriez, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Chirurgie Générale et Digestive [Rangueil], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'hépatologie [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Chirurgie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de Chirurgie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Etaing, Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, CHU Saint-Antoine [AP-HP], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Service d'hépatologie [Saint-Antoine], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, medicine.medical_treatment, 030230 surgery, Liver transplantation, Gastroenterology, MESH: Proportional Hazards Models, 0302 clinical medicine, MESH: Practice Guidelines as Topic, MESH: Liver Neoplasms, Medicine, MESH: Carcinoma, Hepatocellular, MESH: Middle Aged, Liver Neoplasms, Middle Aged, MESH: Predictive Value of Tests, Hepatocellular carcinoma, Predictive value of tests, Area Under Curve, Practice Guidelines as Topic, 030211 gastroenterology & hepatology, Female, alpha-Fetoproteins, MESH: Neoplasm Recurrence, Local, Adult, medicine.medical_specialty, MESH: Liver Transplantation, Carcinoma, Hepatocellular, AFP, Milan criteria, MESH: Multivariate Analysis, Decision Support Techniques, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, Carcinoma, Humans, Neoplasm Invasiveness, MESH: Patient Selection, Proportional Hazards Models, MESH: Humans, Hepatology, Receiver operating characteristic, business.industry, Proportional hazards model, Patient Selection, MESH: Decision Support Techniques, MESH: Adult, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatocellular Carcinoma, MESH: Neoplasm Invasiveness, medicine.disease, Confidence interval, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Male, Surgery, Liver Transplantation, Multivariate Analysis, MESH: Area Under Curve, MESH: alpha-Fetoproteins, Neoplasm Recurrence, Local, business, MESH: Female
Abstract: International audience; BACKGROUND & AIMS: The aim of this study was to generate an improved prognostic model for predicting recurrence in liver transplant candidates with hepatocellular carcinoma (HCC). METHODS: Predictors of recurrence were tested by a Cox model analysis in a training cohort of 537 patients transplanted for HCC. A prognostic score was developed and validated in a national cohort of 435 patients followed up prospectively. RESULTS: α-Fetoprotein (AFP) independently predicted tumor recurrence and correlated with vascular invasion and differentiation. At a Cox score threshold of 0.7 (area under the receiver operating characteristic curve, 0.701; 95% confidence interval, 0.63-0.76; accuracy, 75.8%), a model combining log(10) AFP, tumor size, and number was highly predictive of tumor recurrence and death. By using a simplified version of the model, with untransformed AFP values, a cut-off value of 2 was identified. In the validation cohort, a score greater than 2 predicted a marked increase in 5-year risk of recurrence (50.6% ± 10.2% vs 8.8% ± 1.7%; P < .001) and decreased survival (47.5% ± 8.1% vs 67.8% ± 3.4%; P = .002) as compared with others. Among patients exceeding Milan criteria, a score of 2 or lower identified a subgroup of patients with AFP levels less than 100 ng/mL with a low 5-year risk of recurrence (14.4% ± 5.3% vs 47.6% ± 11.1%; P = .006). Among patients within Milan criteria, a score greater than 2 identified a subgroup of patients with AFP levels greater than 1000 ng/mL at high risk of recurrence (37.1% ± 8.9% vs 13.3% ± 2.0%; P < .001). Net reclassification improvement showed that predictability of the AFP model was superior to Milan criteria. CONCLUSIONS: Prediction of tumor recurrence is improved significantly by a model that incorporates AFP. We propose the adoption of new selection criteria for HCC transplant candidates, taking into account AFP.
Published: 2012
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42. Inhibition of gastric alcohol dehydrogenase activity by histamine H2- receptor antagonists has no influence on the pharmacokinetics of ethanol after a moderate dose

Author: C Dutreuil, Daniel Dhumeaux, J C Delchier, Ariane Mallat, G Simonneau, Françoise Roudot-Thoraval, L E Blanc, J F Bergmann, and H Trout
Subjects: Adult, Male, medicine.medical_specialty, Administration, Oral, Pharmacology, Ranitidine, First pass effect, chemistry.chemical_compound, Histamine H2 receptor, Internal medicine, medicine, Gastric mucosa, Humans, Pharmacology (medical), Cimetidine, Alcohol dehydrogenase, Analysis of Variance, Ethanol, biology, Chemistry, Alcohol Dehydrogenase, Famotidine, Endocrinology, medicine.anatomical_structure, Histamine H2 Antagonists, Gastric Mucosa, biology.protein, Histamine, Research Article, medicine.drug
Abstract: Ethanol undergoes gastric first pass metabolism by alcohol dehydrogenase (ADH). We have shown that cimetidine and famotidine both cause competitive inhibition of human gastric ADH in vitro. However, in a randomized 4-way cross-over study in 12 healthy subjects a 7-day course of treatment with cimetidine (800 mg day-1), ranitidine (300 mg day-1) or famotidine (40 mg day-1), did not modify the pharmacokinetics of ethanol given as a post-prandial 0.3 g kg-1 dose. We conclude that gastric mucosal concentrations of histamine H2-receptor blockers achieved after oral dosing are probably too low to cause significant inhibition of gastric ADH in vivo.
Published: 1994
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43. Non-invasive assessment of liver graft fibrosis by transient elastography after liver transplantation

Author: Elie-Serge Zafrani, Fatiha Medkour, Catherine Douvin, Françoise Roudot-Thoraval, Jeanne Tran Van Nhieu, Daniel Cherqui, Christophe Duvoux, Calina Atanasiu, Camille Barrault, Ariane Mallat, and Michael D. Kluger
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, medicine.medical_treatment, Liver transplantation, Gastroenterology, Postoperative Complications, Fibrosis, Interquartile range, Internal medicine, Biopsy, medicine, Humans, Prospective Studies, Hepatology, medicine.diagnostic_test, business.industry, Reproducibility of Results, Middle Aged, medicine.disease, Liver Transplantation, Transplantation, Liver biopsy, Hepatocellular carcinoma, Elasticity Imaging Techniques, Female, Radiology, business, Transient elastography
Abstract: Liver stiffness measurement (LSM) by transient elastography (TE) (FibroScan) is a validated method of quantifying liver fibrosis in non-transplanted patients with hepatitis C virus (HCV). It could be useful in follow-up after liver transplantation (LT). The aim of this study was to assess the diagnostic accuracy of LSM in evaluating liver fibrosis after LT in patients with and without recurrent HCV.Forty-three patients (mean age 57.6 ± 9.9 years), 28 (65.1%) HCV-positive patients and 15 (34.9%) HCV-negative patients underwent gold standard liver biopsy and TE 55.8 ± 4.9 months after transplantation. Liver fibrosis was scored on biopsy specimens according to METAVIR (F0-F4). Accuracy of TE and optimal stiffness cut-off values for fibrosis staging were determined by a receiver-operating characteristics (ROC) curve analysis.Median stiffness values were significantly different for METAVIR score less than 2 (5.8 kPa) vs. METAVIR score greater to equal to 2 (9.6 kPa) (P0.001). The area under the ROC curve was 0.83 for METAVIR score greater to equal to 2 (95%CI: 0.71-0.95). The optimal stiffness cut-off value was 7 kPa for METAVIR scores greater to equal to 2. The results were similar whether the patients had recurrent HCV infection or not.These results indicate that transient elastography accurately identifies LT recipients with significant fibrosis, irrespective of HCV status. It is a promising non-invasive tool to assess graft fibrosis progression after LT in patients with HCV recurrence, as well as for screening of late graft fibrosis of other etiologies. Transient elastography could reduce the use of invasive protocol biopsies.
Published: 2011

44. Phase II study of sirolimus in treatment-naive patients with advanced hepatocellular carcinoma

Author: Emmanuel Itti, Christophe Duvoux, Anne Hulin, Françoise Roudot-Thoraval, Elie Serge Zafrani, Alexis Laurent, Alain Luciani, Thomas Decaens, and Ariane Mallat
Subjects: Adult, Liver Cirrhosis, Male, Mucositis, medicine.medical_specialty, Cirrhosis, Carcinoma, Hepatocellular, Phases of clinical research, Kaplan-Meier Estimate, Infections, Gastroenterology, Multimodal Imaging, Therapy naive, Pharmacokinetics, Internal medicine, Acne Vulgaris, medicine, Clinical endpoint, Humans, Fatigue, Aged, Sirolimus, Hepatology, business.industry, TOR Serine-Threonine Kinases, Liver Neoplasms, Middle Aged, medicine.disease, Surgery, Epistaxis, Treatment Outcome, Hepatocellular carcinoma, Positron-Emission Tomography, Toxicity, Disease Progression, Female, business, Tomography, X-Ray Computed, Immunosuppressive Agents, medicine.drug
Abstract: Background Rapalogs are emerging as promising targeted anticancer drugs. Activation of the PI3K/Akt/mTOR pathway has been observed in 15–50% of hepatocellular carcinomas. Methods In this phase II study, patients with advanced hepatocellular carcinoma and underlying cirrhosis received sirolimus (20 mg/week for 1 month then 30 mg/week). Tumour response was assessed every 8 weeks. The primary endpoint was the objective tumour response rate according to the Response Evaluation Criteria in Solid Tumours criteria. Secondary endpoints included the objective response according to the modified Response Evaluation Criteria in Solid Tumours criteria, safety, and pharmacokinetic parameters. Results Twenty-five patients received sirolimus for a median of 20.6 weeks. Two patients had an objective response (8%, 95CI: 0.98–26.03), including one complete response, and 8 patients had stable disease. There were 2 cases of grade 5 toxicity (infections) and 5 cases of grade 3 toxicity. The main grade 1/2 toxicity was mild transient fatigue (76%). Median time to radiological progression and overall survival were 15.3 weeks (range: 8.2–173.9) and 26.4 weeks (range: 8.2–173.9) respectively. Use of the modified Response Evaluation Criteria in Solid Tumours criteria did not identify any further responders. Conclusion These data suggest that first-line sirolimus shows antitumoural efficacy in advanced hepatocellular carcinoma. Larger trials with Child A patients are needed.
Published: 2011

45. Liver stiffness diminishes with antiviral response in chronic hepatitis C

Author: Magali Bouvier-Alias, Laurent Castera, Christophe Hézode, Isabelle Rosa, Françoise Roudot-Thoraval, Ariane Mallat, Dominique Roulot, Vincent Leroy, Jean-Michel Pawlotsky, Service d'hépato-gastro-entérologie [APHP Henri Mondor], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hépatologie, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre National de Référence Virus des hépatites B, C et Delta, Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hépato-gastro-entérologie, CHI Créteil, Service de Gastro-entérologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'hépato-gastroentérologie, and CHU Grenoble-Université Grenoble Alpes (UGA)
Subjects: medicine.medical_specialty, Cirrhosis, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Pharmacology (medical), [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Prospective cohort study, Hepatology, business.industry, Ribavirin, Odds ratio, Hepatitis C, medicine.disease, 3. Good health, Surgery, chemistry, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Hepatic fibrosis, Transient elastography, Off Treatment, business
Abstract: Aliment Pharmacol Ther 2011; 34: 656–663 Summary Background Transient elastography measures liver stiffness, which correlates with the hepatic fibrosis stage and has excellent accuracy for the diagnosis of cirrhosis in patients with chronic hepatitis C. Aim To assess prospectively the kinetics of liver stiffness in treated patients with chronic hepatitis C and compare them with the viral kinetics on treatment and with the final outcome of therapy. Methods 91 patients with chronic hepatitis C with significant fibrosis (>7.0 kPa) at baseline were included. They received therapy with pegylated interferon-α and ribavirin. The kinetics of liver stiffness were characterized during therapy and thereafter by means of Fibroscan, and compared with the virological responses at weeks 4, 12, 24, end of treatment and 12 and 24 weeks after. Results A significant liver stiffness decrease was observed during therapy, which continued after treatment only in patients who achieved a sustained virological response. In this group, the median intra-patient decrease relative to baseline at the end of follow-up was −3.4 kPa, vs−1.8 kPa in the patients who did not achieve an SVR. Similar dynamics were observed in cirrhotic and non-cirrhotic patients. In multivariate analysis, only the SVR was associated with long-term improvement of liver stiffness (odds ratio: 3.10; 95% confidence interval: 1.20–8.02, P = 0.019). Conclusions In patients with advanced fibrosis at the start of therapy, liver stiffness is significantly reduced during treatment, but improvement continues off treatment only in patients who achieve a sustained virological response. Liver stiffness assessment earlier than 6 months after the end of therapy does not appear to be clinically meaningful.
Published: 2011
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46. High-Dose Pegylated Interferon-α and Ribavirin in Nonresponder Hepatitis C Patients and Relationship With IL-28B Genotype (SYREN Trial).: High-Dose peg-IFN and Ribavirin and IL28B in HCV nonresponders

Author: Laurent Alric, Vincent Leroy, Bruno Costes, Magali Bouvier–Alias, Patrice Couzigou, Mariem Charaf–Eddine, Stéphanie Rouanet, Jean-Pierre Bronowicki, Stéphane Chevaliez, Jean-Michel Pawlotsky, Isabelle Rosa, Christophe Hézode, Philippe Mathurin, Juliette Foucher, Alexandre Soulier, Gérard Babany, Albert Tran, Ariane Mallat, Centre National de Référence Virus des hépatites B, C et Delta, Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Biochimie [Mondor], Produits Roche, Roche, Département d'hépatologie et de gastroentérologie, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Pôle Digestif, Hôpital Archet 2 [Nice] (CHU), Service d'hépato-gastro-entérologie, CHI Créteil, Service d'Hépato-gastroentérologie, Hôpital Huriez-Université de Lille, Service de médecine interne et maladies digestives, CHU Toulouse [Toulouse], Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, This study is investigator-initiated. It has been funded by Roche France, which provided the study drugs, and Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Male, Time Factors, Hepacivirus, medicine.disease_cause, Gastroenterology, Polyethylene Glycols, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Interferon, Pegylated interferon, nonresponder, Genotype, Odds Ratio, Medicine, 0303 health sciences, education.field_of_study, Hepatitis C virus, Hepatitis C, Middle Aged, Viral Load, Recombinant Proteins, 3. Good health, Phenotype, Treatment Outcome, RNA, Viral, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, high-dose pegylated IFN-α, medicine.drug, Adult, medicine.medical_specialty, Population, Context (language use), IL28B genotype, Interferon alpha-2, Antiviral Agents, Risk Assessment, 03 medical and health sciences, Internal medicine, Drug Resistance, Viral, Ribavirin, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, education, Aged, 030304 developmental biology, Chi-Square Distribution, Hepatology, business.industry, Interleukins, Interferon-alpha, Hepatitis C, Chronic, medicine.disease, Logistic Models, chemistry, Immunology, Linear Models, Interferons, business
Abstract: International audience; BACKGROUND & AIMS: In patients with chronic hepatitis C who failed to respond to standard therapy, high-dose pegylated interferon (IFN)-α and/or ribavirin could induce a stronger antiviral response and prevent treatment failure and HCV resistance when combined with direct-acting antivirals. The influence of genetic determinants in this context remains unknown. METHODS: Eighty-three patients infected with HCV genotype 1 who were nonresponsive to standard therapy received pegylated IFN-α2a (360 μg once per week or 180 μg twice per week) with ribavirin (1.0-1.2 or 1.2-1.6 g/d) for up to 72 weeks. Virological responses were assessed at different time points, and the influence of the IL-28B genotype was studied. RESULTS: At weeks 12 and 24, respectively, 47 (56.6%) and 50 (60.2%) patients achieved a ≥2-Log(10) decrease of HCV RNA levels; 8 (9.6%) and 21 (25.3%) patients had undetectable HCV RNA after 12 and 24 weeks of treatment, respectively. Patients with a CT IL-28B genotype responded significantly better and earlier than those with a TT genotype. In multivariate analysis, the IL-28B genotype was an independent predictor of the virological responses at weeks 4, 12, and 24. CONCLUSIONS: High-dose pegylated IFN-α with standard or high doses of ribavirin induces a potent antiviral response in a substantial number of patients who did not respond to standard therapy. The IL-28B genotype is an independent predictor of the antiviral response. High-dose pegylated IFN-α in combination with ribavirin and protease inhibitors appears as an attractive option for future study in this population.
Published: 2011
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47. Mitogenic effect of transforming growth factor-β1 on human ito cells in culture: Evidence for mediation by endogenous platelet-derived growth factor

Author: Daniel Dhumeau, M D Jean Rosenbaum, Philippe Mavier, Ariane Mallat, Daniel Cherqui, Nadine Martin, Frédéric Charlotte, Anne-Marie Preaux, and Khin Maung Win
Subjects: medicine.medical_specialty, Platelet-derived growth factor, Hepatology, Cell growth, Liver cytology, Growth factor, medicine.medical_treatment, Biology, digestive system, Cell biology, chemistry.chemical_compound, Endocrinology, chemistry, Cell culture, Internal medicine, medicine, Hepatic stellate cell, Autocrine signalling, Transforming growth factor
Abstract: We assessed the effect of transforming growth factor-beta 1 on the proliferation of human Ito cells. Ito cells in their myofibroblastlike phenotype were grown from explants of human liver and were characterized with electron microscopy and positive immunostaining for desmin and smooth muscle alpha-actin. Transforming growth factor-beta 1 was mitogenic for human Ito cells whatever the culture conditions, although it was, as previously described, inhibitory of growth for rat Ito cells. The mitogenic effect of transforming growth factor-beta 1 was likely due to induction of autocrine platelet-derived growth factor chain secretion by Ito cells themselves because (a) the mitogenic effect of transforming growth factor-beta 1 was blocked by specific platelet-derived growth factor antibodies, (b) transforming growth factor-beta 1 increased platelet-derived growth factor-A chain messenger RNA expression and platelet-derived growth factor-AA secretion by human Ito cells and (c) human Ito cells expressed the alpha-type platelet-derived growth factor-A receptor messenger RNA. Exogenous platelet-derived growth factor-AA was also mitogenic for human Ito cells, mimicking the effect of transforming growth factor-beta 1. Our data suggest that results obtained with rat Ito cells must be extrapolated with caution to human ones. The mitogenic effect of transforming growth factor-beta 1 on human Ito cells probably has pathophysiological relevance because transforming growth factor-beta 1 has been demonstrated in vivo at sites of active liver fibrogenesis.
Published: 1993
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48. Beneficial paracrine effects of cannabinoid receptor 2 on liver injury and regeneration

Author: Alexandre Louvet, Thierry Tordjmann, Andreas Zimmer, Sylvie Manin, Marie-Pierre Belot, Vanessa Deveaux, Marie-Noële Chobert, Sophie Lotersztajn, Thomas Cadoudal, Fatima Teixeira-Clerc, Ariane Mallat, 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), Department of Molecular Psychiatry, Rheinische Friedrich-Wilhelms-Universität Bonn, Signalisation calcique et interactions cellulaires dans le foie, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), This work was supported by the INSERM, the Université Paris-Est, and by grants (to S.L) of the Agence Nationale de la Recherche and Fondation pour la Recherche Médicale, Guellaen, Georges, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10
Subjects: medicine.medical_treatment, Apoptosis, Receptor, Cannabinoid, CB2, chemistry.chemical_compound, Liver disease, Mice, 0302 clinical medicine, Carbon Tetrachloride, Cells, Cultured, Liver injury, Mice, Knockout, 0303 health sciences, Alanine Transaminase, Liver regeneration, 3. Good health, medicine.anatomical_structure, Hepatocyte, Matrix Metalloproteinase 2, 030211 gastroenterology & hepatology, lipids (amino acids, peptides, and proteins), Chemical and Drug Induced Liver Injury, medicine.medical_specialty, Biology, Nitric oxide, 03 medical and health sciences, Internal medicine, Proliferating Cell Nuclear Antigen, Paracrine Communication, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, Hepatectomy, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Aspartate Aminotransferases, 030304 developmental biology, Hepatology, Cannabinoids, Interleukin-6, Tumor Necrosis Factor-alpha, Regeneration (biology), medicine.disease, Liver Regeneration, Mice, Inbred C57BL, Disease Models, Animal, Endocrinology, chemistry, Alanine transaminase, biology.protein, Hepatocytes
Abstract: International audience; The cannabinoid receptor 2 (CB2) plays a pleiotropic role in innate immunity and is a crucial mediator of liver disease. In this study, we investigated the impact of CB2 receptors on the regenerative process associated with liver injury. Following acute hepatitis induced by carbon tetrachloride (CCl(4)), CB2 was induced in the nonparenchymal cell fraction and remained undetectable in hepatocytes. Administration of CCl(4) to CB2(-/-) mice accelerated liver injury, as shown by increased alanine/aspartate aminotransferase levels and hepatocyte apoptosis, and delayed liver regeneration, as reflected by a retarded induction of hepatocyte proliferating cell nuclear antigen expression; proliferating cell nuclear antigen induction was also delayed in CB2(-/-) mice undergoing partial hepatectomy. Conversely, following treatment with the CB2 agonist JWH-133, CCl(4)-treated WT mice displayed reduced liver injury and accelerated liver regeneration. The CCl(4)-treated CB2(-/-) mice showed a decrease in inducible nitric oxide synthase and tumor necrosis factor-alpha expression, and administration of the nitric oxide donor moldomine (SIN-1) to these animals reduced hepatocyte apoptosis, without affecting liver regeneration. Impaired liver regeneration was consecutive to an interleukin-6 (IL-6)-mediated decrease in matrix metalloproteinase 2 (MMP-2) activity. Indeed, CCl(4)-treated CB2(-/-) mice displayed lower levels of hepatic IL-6 messenger RNA and increased MMP-2 activity. Administration of IL-6 to these mice decreased MMP-2 activity and improved liver regeneration, without affecting hepatocyte apoptosis. Accordingly, administration of the MMP inhibitor CTTHWGFTLC to CCl(4)-treated CB2(-/-) mice improved liver regeneration. Finally, in vitro studies demonstrated that incubation of hepatic myofibroblasts with JWH-133 increased tumor necrosis factor-alpha and IL-6 and decreased MMP-2 expressions. CONCLUSION: CB2 receptors reduce liver injury and promote liver regeneration following acute insult, via distinct paracrine mechanisms involving hepatic myofibroblasts. These results suggest that CB2 agonists display potent hepatoprotective properties, in addition to their antifibrogenic effects.
Published: 2010
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49. Endocannabinoids and their role in fatty liver disease

Author: Ariane Mallat and Sophie Lotersztajn
Subjects: Liver Cirrhosis, medicine.medical_specialty, Cannabinoid receptor, Adipose tissue, Pharmacology, Insulin resistance, Piperidines, Internal medicine, Cannabinoid Receptor Modulators, Hypertension, Portal, medicine, Animals, Humans, Receptor, Receptors, Cannabinoid, Cannabinoid Receptor Antagonists, Cannabinoid Receptor Agonists, Inflammation, business.industry, musculoskeletal, neural, and ocular physiology, Fatty liver, Gastroenterology, General Medicine, medicine.disease, Endocannabinoid system, Fatty Liver, Endocrinology, nervous system, Lipogenesis, Pyrazoles, lipids (amino acids, peptides, and proteins), Steatosis, Insulin Resistance, Rimonabant, business, Endocannabinoids
Abstract: The endocannabinoid system comprises receptors, CB1 and CB2, their endogenous lipidic ligands and machinery dedicated to endocannabinoid synthesis and degradation. An overactive endocannabinoid system appears to contribute to the pathogenesis of several diseases, including liver diseases. With the increasing incidence of non-alcoholic fatty liver disease (NAFLD) in parallel with the obesity epidemic, the development of effective therapies is gaining considerable interest. Several recent experimental lines of evidence identify CB receptors as potential novel therapeutic targets in the management of NAFLD. Endogenous activation of peripheral CB1 receptors is a key mediator of insulin resistance and enhances liver lipogenesis in experimental models of NAFLD. Moreover, we have shown that adipose tissue CB2 receptors are markedly upregulated and promote fat inflammation, thereby contributing to insulin resistance and liver steatosis. Data from our group also indicate that tonic activation of CB1 receptors is responsible for progression of liver fibrosis, whereas CB2 receptors display anti-fibrogenic properties. The clinical relevance of these findings is supported by studies in patients with chronic hepatitis C indicating that daily cannabis use is an independent predictor of both fibrosis and steatosis severity. Moreover, preliminary data derived from clinical trials strongly suggest that selective CB1 antagonism improves insulin resistance and reduces liver fat. Tempering these promises, the first generation of CB1 antagonists raised concern due to an alarming rate of mood disorders and the development program of these molecules was suspended. Current research efforts are therefore focused on developing formulations of CB1 antagonists that do not enter the central nervous system, and preliminary experimental data obtained with such molecules are encouraging.
Published: 2010

50. Association of caffeine intake and histological features of chronic hepatitis C

Author: Elie-Serge Zafrani, Ariane Mallat, Fatiha Medkour, Françoise Roudot-Thoraval, Christophe Hézode, Charlotte Costentin, and Jean-Michel Pawlotsky
Subjects: Adult, Male, medicine.medical_specialty, Chronic liver disease, Gastroenterology, Coffee, chemistry.chemical_compound, Interquartile range, Internal medicine, Caffeine, Surveys and Questionnaires, Epidemiology, medicine, Humans, Hepatology, biology, medicine.diagnostic_test, business.industry, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, biology.organism_classification, Surgery, chemistry, Liver, Liver biopsy, Multivariate Analysis, Female, Cannabis, business, Body mass index
Abstract: The severity of chronic hepatitis C (CHC) is modulated by host and environmental factors. Several reports suggest that caffeine intake exerts hepatoprotective effects in patients with chronic liver disease. The aim of this study was to evaluate the impact of caffeine consumption on activity grade and fibrosis stage in patients with CHC.A total of 238 treatment-naïve patients with histologically-proven CHC were included in the study. Demographic, epidemiological, environmental, virological, and metabolic data were collected, including daily consumption of alcohol, cannabis, tobacco, and caffeine during the six months preceding liver biopsy. Daily caffeine consumption was estimated as the sum of mean intakes of caffeinated coffee, tea, and caffeine-containing sodas. Histological activity grade and fibrosis stage were scored according to Metavir. Patients (154 men, 84 women, mean age: 45±11 years) were categorized according to caffeine consumption quartiles: group 1 (225 mg/day, n=59), group 2 (225-407 mg/day, n=57), group 3 (408-678 mg/day, n=62), and group 4 (678 mg/day, n=60).There was a significant inverse relationship between activity grade and daily caffeine consumption: activity gradeA2 was present in 78%, 61%, 52%, and 48% of patients in group 1, 2, 3, and 4, respectively (p0.001). By multivariate analysis, daily caffeine consumption greater than 408 mg/day was associated with a lesser risk of activity gradeA2 (OR=0.32 (0.12-0.85). Caffeine intake showed no relation with fibrosis stage.Caffeine consumption greater than 408 mg/day (3 cups or more) is associated with reduced histological activity in patients with CHC. These findings support potential hepatoprotective properties of caffeine in chronic liver diseases.
Published: 2010

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