Author: "Pascal Lebray" / Topic: internal medicine - Searchworks@Jio Institute Digital Library Search Results

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1. LCR1 and LCR2, two multi‐analyte blood tests to assess liver cancer risk in patients without or with cirrhosis

Author: Thierry Poynard, Luminita Bonyhay, Vincent Thibault, Chantal Housset, Olivier Lucidarme, Françoise Imbert-Bismut, An Ngo, Dominique Thabut, Eric Savier, Daniel Eyraud, Laetitia Fartoux, Marika Rudler, F. Drane, Pascal Lebray, Yen Ngo, Mona Munteanu, Olivier Scatton, Olivier Deckmyn, Raluca Pais, Marc Antoine Valantin, Olivier Rosmorduc, Joseph Moussalli, Valentina Peta, Frédéric Charlotte, Vlad Ratziu, Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], 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: medicine.medical_specialty, Cirrhosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Chronic liver disease, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Blood test, Pharmacology (medical), 030212 general & internal medicine, Hepatology, medicine.diagnostic_test, Proportional hazards model, business.industry, Cancer, Retrospective cohort study, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, 3. Good health, Lcr1 and Lcr2 Blood Tests for Hepatoma Screening, 030211 gastroenterology & hepatology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Original Article, Liver cancer, business, Cohort study
Abstract: International audience; BACKGROUND: No blood test has been shown to be effective in the prediction of primary liver cancer in patients without cirrhosis.AIM: To construct and internally validate two sequential tests for early prediction of liver cancer. These tests enable an algorithm which could improve the performance of the standard surveillance protocol recommended (imaging with or without AFP), limited to patients with cirrhosis.METHODS: We performed a retrospective analysis in prospectively collected specimens from an ongoing cohort. We designed an early sensitive high-risk test (LCR1) that combined (using Cox model) hepatoprotective proteins (apolipoproteinA1, haptoglobin) with known risk factors (gender, age, gammaglutamyltranspeptidase), and a marker of fibrosis (alpha2-macroglobulin). To increase the specificity, we then combined (LCR2) these components with alpha-fetoprotein.RESULTS: A total of 9892 patients, 85.9% without cirrhosis, were followed up for 5.9 years [IQR: 4.3-9.4]. LCR1 and LCR2 time-dependent AUROCs were not different in construction and validation randomised subsets. Among 2027 patients with high-LCR1 then high-LCR2, 167 cancers (113 with cirrhosis, 54 without cirrhosis) were detected, that is 12 patients needed to screen one cancer. The negative predictive value was 99.5% (95% CI 99.0-99.7) in the 2026 not screened patients (11 cancers without cirrhosis) higher than the standard surveillance, which detected 113 cancers in 755 patients screened, that is seven patients needed to screen one cancer, but with a lower negative predictive value 98.0% (97.5-98.5; Z = 4.3; P < 0.001) in 3298 not screened patients (42 cancers without cirrhosis).CONCLUSIONS: In patients with chronic liver disease the LCR1 and LCR2 tests identify those with a high risk of liver cancer, including in those without cirrhosis. NCT01927133.
Published: 2018
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2. Reply to: 'Combined heart-liver transplantation for congestive hepatopathy with bridging fibrosis: Is it warranted?'

Author: Manon Allaire, Jean François Cadranel, Anna Sessa, and Pascal Lebray
Subjects: medicine.medical_specialty, Hepatology, business.industry, medicine.medical_treatment, Gastroenterology, RC799-869, 030230 surgery, Liver transplantation, Diseases of the digestive system. Gastroenterology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Congestive hepatopathy, Fibrosis, Internal medicine, Internal Medicine, medicine, Immunology and Allergy, 030211 gastroenterology & hepatology, business, Letter to the Editor, Bridging fibrosis
Published: 2021

3. 2020 position statement and recommendations of the European Liver and Intestine Transplantation Association (ELITA): management of hepatitis B virus-related infection before and after liver transplantation

Author: Fabien Zoulim, Silvia Martini, Mario Angelico, Pascal Lebray, Christophe Duvoux, Mario Rizzetto, Riccardo Volpes, Frederik Nevens, Paolo Cortesi, Audrey Coilly, Constantino Fondevila, Cyrille Feray, Didier Samuel, Maria Buti, Wojciech G. Polak, James Fung, François Durand, Marina Berenguer, Luca S. Belli, Duvoux, C, Belli, L, Fung, J, Angelico, M, Buti, M, Coilly, A, Cortesi, P, Durand, F, Feray, C, Fondevila, C, Lebray, P, Martini, S, Nevens, F, Polak, W, Rizzetto, M, Volpes, R, Zoulim, F, Samuel, D, and Berenguer, M
Subjects: medicine.medical_specialty, HBsAg, Hepatitis B virus, Carcinoma, Hepatocellular, medicine.medical_treatment, hepatitis B virus-related infection, liver transplant, position statement, epatitis B immunoglobulin (HBIG), nucleos(t)ides analogues (NA), Immunoglobulins, Liver transplantation, medicine.disease_cause, Antiviral Agents, Recurrence, Internal medicine, Carcinoma, medicine, Humans, Pharmacology (medical), Intestine transplantation, Hepatology, business.industry, Gold standard, Liver Neoplasms, Gastroenterology, virus diseases, medicine.disease, Hepatitis B, digestive system diseases, Liver Transplantation, Clinical trial, Regimen, Treatment Outcome, Neoplasm Recurrence, Local, business
Abstract: Background: Prophylaxis of HBV recurrence is critical after liver transplantation in HBV patients. Despite new prophylactic schemes, most European LT centres persist on a conservative approach combining hepatitis B immunoglobulin (HBIG) and nucleos(t)ides analogues (NA). Aim: This setting prompted the European Liver Intestine Transplantation Association (ELITA) to look for a consensus on the prevention of HBV recurrence. Methods: Based on a 4-round Delphi process, ELITA investigated 16 research questions and established 50 recommendations. Results: Prophylaxis should be driven according to 3 simplified risk groups: Low and high virological risk patients, with undetectable and detectable HBV DNA pre-LT, respectively, and special populations (HDV, HCC, poorly adherent patients). In low-risk patients, short-term (4weeks) combination of third-generation NA+ HBIG, or third generation NA monotherapy can be considered as prophylactic options. In high-risk patients, HBIG can be discontinued once HBV DNA undetectable. Combined therapy for 1year is advised. HBV-HCC patients should be treated according to their virological risk. In HDV/HBV patients, indefinite dual prophylaxis remains the gold standard. Full withdrawal of HBV prophylaxis following or not HBV vaccination should only be attempted in the setting of clinical trials. Organs from HBsAg+ve donors may be considered after assessment of risks, benefits, and patient consent. They should not be used if HDV is present. In poorly adherent patients, dual long-term prophylaxis is recommended. Budget impact analysis should be taken into account to drive prophylactic regimen. Conclusions: These ELITA recommendations should stimulate a more rational and homogeneous approach to HBV prophylaxis across LT programs.
Published: 2021

4. From congestive hepatopathy to hepatocellular carcinoma, how can we improve patient management?

Author: Pascal Lebray, Anna Sessa, Manon Allaire, Alberto Tiritilli, Mourad Medmoun, Pierre Iaria, Jean-François Cadranel, HAL-SU, Gestionnaire, University of Naples Federico II = Università degli studi di Napoli Federico II, 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 de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Groupe Hospitalier Public du Sud de l'Oise [Creil] (GHPSO), University of Naples Federico II, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: NAFLD, non-alcoholic fatty liver disease, medicine.medical_specialty, Cirrhosis, Heart disease, ACE, angiotensin-converting enzyme, medicine.medical_treatment, INR, international normalised ratio, Review, 030204 cardiovascular system & hematology, MELD, model for end-stage liver disease, Fontan procedure, 03 medical and health sciences, Liver disease, Combined heart and liver transplant, 0302 clinical medicine, Model for End-Stage Liver Disease, ALT, alanine aminotransferase, Internal medicine, Internal Medicine, Immunology and Allergy, Medicine, NFS, NAFLD fibrosis score, Gamma-glutamyltransferase, BNP, B-type natriuretic peptide, FALD, Fontan-associated liver disease, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, AFP, α-fetoprotein, ALP, alkaline phosphatase, Hepatology, biology, GGT, gamma-glutamyltransferase, business.industry, AST, aspartate amino transferase, Congestive hepatopathy, Fontan-associated liver disease, Gastroenterology, medicine.disease, 3. Good health, Heart failure, biology.protein, Cardiology, 030211 gastroenterology & hepatology, HCC, hepatocellular carcinoma, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, FIB-4, Fibrosis-4 index
Abstract: International audience; Heart failure and liver disease often coexist because of systemic disorders and diseases that affect both organs as well as complex cardio-hepatic interactions. Heart failure can cause acute or chronic liver injury due to ischaemia and passive venous congestion, respectively. Congestive hepatopathy is frequently observed in patients with congenital heart disease and after the Fontan procedure, but also in older patients with chronic heart failure. As congestive hepatopathy can evolve into cirrhosis and hepatocellular carcinoma, screening for liver injury should be performed in patients with chronic cardiac diseases and after Fontan surgery. Fibrosis starts in the centro-lobular zone and will extend progressively to the portal area. Chronic liver injury can be reversible if heart function improves. However, in the case of terminal heart failure, uncontrolled by medical resources or by assistive device support, the combination of heart and liver transplants must be discussed in patients with chronic advanced liver fibrosis. In this review of the literature, we will focus on congestive hepatopathy and its complications, such as liver fibrosis and hepatocellular carcinoma, with the aim of improving the management and surveillance of patients experiencing these complications.
Published: 2021
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5. 'De novo' cholangiocarcinoma 20 years after liver transplantation for primary sclerosing cholangitis: Lifelong screening needed!

Author: Pascal Lebray, Frédéric Charlotte, Jean-Christophe Vaillant, Pauline Bourdeleau, Manon Allaire, and Edouard Larrey
Subjects: medicine.medical_specialty, Poor prognosis, Hepatology, business.industry, Internal medicine, medicine.medical_treatment, Gastroenterology, medicine, Liver transplantation, medicine.disease, business, Primary sclerosing cholangitis
Abstract: We report a rare and very late case of de novo cholangiocarcinoma in a patient transplanted for primary sclerosing cholangitis. An exhaustive analysis of the literature and of our case highlight the very poor prognosis of this type of tumor due to the delay in diagnosis and the potential value of a six-monthly MRI surveillance as soon as cholangitis recurs, but also in the presence of chronic digestive inflammation, whatever the mechanism.
Published: 2022
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6. Risk factors of de novo malignancies after liver transplantation: a French national study on 11004 adult patients

Author: Christophe Duvoux, Mario Altieri, Nassim Kamar, Jean Gugenheim, Sébastien Dharancy, Filomena Conti, Armand Abergel, Olivier Sérée, Georges-Philippe Pageaux, Ephrem Salamé, Jean Hardwigsen, Karim Boudjema, Pascal Lebray, Philippe Segol, Camille Besch, Vincent Leroy, Didier Samuel, Guy Launoy, Claire Vanlemmens, Sylvie Radenne, Maryline Debette-Gratien, Olivier Chazouillères, Xavier Blaizot, Martine Neau-Cransac, Claire Francoz, Marianne Latournerie, Jérôme Dumortier, Audrey Coilly, Pauline Houssel-Debry, François Durand, Olivier Boillot, Faouzi Saliba, Thierry Lobbedez, CCSD, Accord Elsevier, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, CHU Pontchaillou [Rennes], Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Centre de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Henri Mondor, Ecole Polytechnice Universitaire de Nice (EPU Nice -Polytech'Nice-Sophia), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Néphrologie - Immunologie Clinique [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-PRES Université de Toulouse, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hospices Civils de Lyon (HCL), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), and CHU Strasbourg
Subjects: Oncology, Adult, Male, medicine.medical_specialty, MESH: Liver Transplantation, Liver tumor, medicine.medical_treatment, Liver transplantation, Malignancy, Primary sclerosing cholangitis, 03 medical and health sciences, Liver disease, 0302 clinical medicine, MESH: Liver Neoplasms, MESH: Risk Factors, Risk Factors, Internal medicine, medicine, Humans, MESH: Incidence, Lung cancer, Retrospective Studies, MESH: Humans, Hepatology, business.industry, Incidence, Liver Neoplasms, Gastroenterology, Retrospective cohort study, MESH: Adult, MESH: Retrospective Studies, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Competing risk, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Male, Liver Transplantation, 030220 oncology & carcinogenesis, Population study, 030211 gastroenterology & hepatology, business, Liver transplantationde novomalignancies
Abstract: International audience; Background: After liver transplantation (LT),de novo malignancies are one of the leading causes of late mortality. The aim of the present retrospective study was to identify the risk factors of de novo malignancies in a large cohort of LT recipients in France, using Fine and Gray competing risks regression analysis.Methods: The study population consisted in 11004 adults transplanted between 2000 and 2013, who had no history of pre-transplant malignancy, except primary liver tumor. A Cox model adapted to the identification of prognostic factors (competitive risks) was used.Results: From the entire cohort, one (or more)de novo malignancy was reported in 1480 L T recipients (13.45%). The probability to develop a de novo malignancy after LT was 2.07% at 1 year, 13.30% at 5 years, and 28.01% at 10 years. Of the known reported malignancies, the most common malignancies were hematological malignancy (22.36%), non-melanoma skin cancer (19.53%) and lung cancer (12.36%). According to Fine and Gray competing risks regression multivariate analysis, were significant risk factors for post-LT de novo malignancy: recipient age (Subdistribution Hazard Ratio (SHR) = 1.03 95%CI 1.03-1.04), male gender (SHR = 1.45 95%CI 1.27-1.67), non-living donor (SHR = 1.67 95%CI 1.14-2.38), a first LT (SHR = 1.35 95%CI 1.09-1.69) and the type of initial liver disease (alcohol-related liver disease (SHR = 1.63 95%CI 1.22-2.17), primary sclerosing cholangitis (SHR = 1.98 95%CI 1.34-2.91), and primary liver tumor (SHR = 1.88 95%CI 1.41-2.54)). Initial immunosuppressive regimen had no significant impact.Conclusion: The present study confirms that LT recipient characteristics are associated with the risk ofde novo malignancy and this underlines the need for personalized screening in order to improve survival.
Published: 2020
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7. Long-term prognostic value of the FibroTest in patients with non-alcoholic fatty liver disease, compared to chronic hepatitis C, B, and alcoholic liver disease

Author: Valentina Peta, Marika Rudler, Thierry Poynard, An Ngo, Chantal Housset, Frédéric Charlotte, Françoise Imbert-Bismut, Pascal Lebray, Mona Munteanu, Vlad Ratziu, Vincent Thibault, Olivier Lucidarme, Dominique Thabut, Yen Ngo, Joseph Moussalli, Raluca Pais, Olivier Deckmyn, Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP]
Subjects: Adult, Male, Alcoholic liver disease, medicine.medical_specialty, Time Factors, [SDV]Life Sciences [q-bio], Population, Gastroenterology, Cohort Studies, 03 medical and health sciences, Hepatitis B, Chronic, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Internal medicine, medicine, Humans, Pharmacology (medical), Prospective Studies, education, Prospective cohort study, Liver Diseases, Alcoholic, Survival analysis, education.field_of_study, Hepatology, FibroTest, business.industry, Fatty liver, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Hepatitis C, Chronic, Middle Aged, Hepatitis B, Prognosis, medicine.disease, Survival Analysis, 3. Good health, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, France, business, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract: International audience; Background: Although the FibroTest has been validated as a biomarker to determine the stage of fibrosis in non‐alcoholic fatty liver disease (NAFLD) with results similar to those in chronic hepatitis C (CHC), B (CHB), and alcoholic liver disease (ALD), it has not yet been confirmed for the prediction of liver‐related death. Aim: To validate the 10‐year prognostic value of FibroTest in NAFLD for the prediction of liver‐ related death. Method: Patients in the prospective FibroFrance cohort who underwent a FibroTest between 1997 and 2012 were pre‐included. Mortality status was obtained from physicians, hospitals or the national register. Survival analyses were based on univariate (Kaplan‐Meier, log rank, AUROC) and multivariate Cox risk ratio taking into account age, sex and response to anti‐viral treatment as covariates. The comparator was the performance of the FibroTest in CHC, the most validated population. Results: 7082 patients were included; 1079, 3449, 2051, and 503 with NAFLD, CHC, CHB, and ALD, respectively. Median (range) follow‐up was 6.0 years (0.1‐19.3). Ten year survival (95% CI) without liver‐related death in patients with NAFLD was 0.956 (0.940‐0.971; 38 events) and 0.832 (0.818‐0.847; 226 events; P = 0.004)in CHC. The prognostic value (AUROC / Cox risk ratio) of FibroTest in patients with NAFLD was 0.941 (0.905‐0.978)/1638 (342‐7839) and even higher than in patients with CHC 0.875 (0.849‐0.901; P = 01)/2657 (993‐6586). Conclusions: The FibroTest has a high prognostic value in NAFLD for the prediction of liver‐related death. (ClinicalTrials.gov number, NCT01927133).
Published: 2018
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8. 12 Weeks of a Ribavirin‐Free Sofosbuvir and Nonstructural Protein 5A Inhibitor Regimen Is Enough to Treat Recurrence of Hepatitis C After Liver Transplantation

Author: Audrey Coilly, Carole Cagnot, Pascal Lebray, Stéphane Chevaliez, Alpha Diallo, Victor de Lédinghen, Jean-Charles Duclos-Vallée, Danielle Botta-Fridlund, Claire Francoz, Camille Besch, Nassim Kamar, Christine Silvain, P. Perré, Albert Tran, Jérôme Dumortier, François Habersetzer, Claire Fougerou-Leurent, Aurelie Veislinger, Valérie Canva, Vincent Di Martino, Georges-Philippe Pageaux, Filomena Conti, Caroline Jezequel, Christophe Duvoux, Armando Abergel, Christophe Moreno, Sylvie Radenne, Maryline Debette-Gratien, H. Montialoux, Emilie Rossignol, Vincent Leroy, Louis d’Alteroche, and Pauline Houssel-Debry
Subjects: Liver Cirrhosis, Male, Sofosbuvir, medicine.medical_treatment, Viral Nonstructural Proteins, 030230 surgery, Liver transplantation, medicine.disease_cause, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Belgium, Recurrence, Prospective Studies, 10. No inequality, education.field_of_study, Graft Survival, virus diseases, Hepatitis C, Middle Aged, Sciences bio-médicales et agricoles, Prognosis, 3. Good health, Treatment Outcome, Disease Progression, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, France, Viral load, medicine.drug, Adult, medicine.medical_specialty, Hepatitis C virus, Population, Drug Administration Schedule, 03 medical and health sciences, Internal medicine, Ribavirin, medicine, Humans, education, Aged, Dose-Response Relationship, Drug, Hepatology, business.industry, Hepatitis C, Chronic, medicine.disease, digestive system diseases, Liver Transplantation, Regimen, chemistry, business
Abstract: Sofosbuvir (SOF) combined with nonstructural protein 5A (NS5A) inhibitors has demonstrated its efficacy in treating a recurrence of hepatitis C virus (HCV) after liver transplantation (LT). However, the duration of treatment and need for ribavirin (RBV) remain unclear in this population. Our aim was to determine whether LT recipients could be treated with an SOF + NS5A inhibitor-based regimen without RBV for 12 weeks post-LT. Between October 2013 and December 2015, 699 LT recipients experiencing an HCV recurrence were enrolled in the multicenter ANRS CO23 CUPILT cohort. We selected patients receiving SOF and NS5A inhibitor ± RBV and followed for at least 12 weeks after treatment discontinuation. The primary efficacy endpoint was a sustained virological response 12 weeks after the end of treatment (SVR12). Among these 699 patients, 512 fulfilled the inclusion criteria. Their main characteristics were: 70.1% genotype 1, 18.2% genotype 3, 21.1% cirrhosis, and 34.4% previously treated patients. We identified four groups of patients according to their treatment and duration: SOF + NS5A without RBV for 12 (156 patients) or 24 (239 patients) weeks; SOF + NS5A + RBV for 12 (47 patients) or 24 (70 patients) weeks. SVR12 values reached 94.9%, 97.9%, 95.7%, and 92.9%, respectively (P = 0.14). Only 20 patients experienced a treatment failure. Under multivariate analysis, factors such as fibrosis stage, previous treatment, HCV genotype, and baseline HCV viral load did not influence SVR12 rates in the four groups (P = 0.21). Hematological adverse events (AEs) were more common in the RBV group: anemia (P < 0.0001) and blood transfusion (P = 0.0001). Conclusion: SOF + NS5A inhibitors without RBV for 12 weeks constituted reliable therapy for recurrent HCV post-LT with an excellent SVR12 whatever the fibrosis stage, HCV genotype, and previous HCV treatment. (Hepatology 2018; 00:000-000)., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2018
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9. NAFLD and liver transplantation: Current burden and expected challenges

Author: Olivier Scatton, Filomena Conti, Raluca Pais, Thomas M. Runge, Yvon Calmus, Thierry Poynard, Vlad Ratziu, A. Sidney Barritt, and Pascal Lebray
Subjects: 0301 basic medicine, medicine.medical_specialty, Carcinoma, Hepatocellular, medicine.medical_treatment, Disease, Liver transplantation, Chronic liver disease, Gastroenterology, Article, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Risk Factors, Internal medicine, Humans, Medicine, Intensive care medicine, Hepatology, business.industry, Liver Neoplasms, Fatty liver, nutritional and metabolic diseases, medicine.disease, digestive system diseases, Liver Transplantation, Europe, 030104 developmental biology, Diabetes Mellitus, Type 2, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Metabolic syndrome, Steatohepatitis, business
Abstract: Because of global epidemics of obesity and type 2 diabetes, the prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing both in Europe and the United States, becoming one of the most frequent causes of chronic liver disease and predictably, one of the leading causes of liver transplantation both for end-stage liver disease and hepatocellular carcinoma. For most transplant teams around the world this will raise many challenges in terms of pre- and post-transplant management. Here we review the multifaceted impact of NAFLD on liver transplantation and will discuss: (1) NAFLD as a frequent cause of cryptogenic cirrhosis, end-stage chronic liver disease, and hepatocellular carcinoma; (2) prevalence of NAFLD as an indication for liver transplantation both in Europe and the United States; (3) the impact of NAFLD on the donor pool; (4) the access of NAFLD patients to liver transplantation and their management on the waiting list in regard to metabolic, renal and vascular comorbidities; (5) the prevalence and consequences of post-transplant metabolic syndrome, recurrent and de novo NAFLD; (6) the alternative management and therapeutic options to improve the long-term outcomes with particular emphasis on the correction and control of metabolic comorbidities.
Published: 2016
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10. Sofosbuvir‐based treatment of hepatitis C with severe fibrosis (METAVIR F3/F4) after liver transplantation

Author: A. Rohel, Christophe Moreno, Jean-Charles Duclos-Vallée, Sylvie Radenne, Camille Besch, Armand Abergel, Nassim Kamar, Albert Tran, Georges-Philippe Pageaux, Pascal Lebray, Pauline Houssel-Debry, Valérie Canva, Claire Francoz, Danielle Botta-Fridlund, Jérôme Dumortier, Alpha Diallo, Vincent Leroy, Christophe Duvoux, Louis d’Alteroche, Claire Fougerou-Leurent, Audrey Coilly, Vincent Di Martino, Didier Samuel, Filomena Conti, Victor de Lédinghen, and Emilie Rossignol
Subjects: Compassionate Use Trials, Liver Cirrhosis, Male, Pyrrolidines, Cirrhosis, Sofosbuvir, medicine.medical_treatment, Hepacivirus, 030230 surgery, Liver transplantation, medicine.disease_cause, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Belgium, Recurrence, Prospective Studies, Imidazoles, Valine, Hepatitis C, Middle Aged, 3. Good health, Treatment Outcome, Female, 030211 gastroenterology & hepatology, France, Immunosuppressive Agents, medicine.drug, Reoperation, medicine.medical_specialty, Daclatasvir, Genotype, Hepatitis C virus, Antiviral Agents, 03 medical and health sciences, Internal medicine, Ribavirin, medicine, Humans, Protease Inhibitors, Aged, Transplantation, Hepatology, business.industry, medicine.disease, Liver Transplantation, chemistry, Immunology, Surgery, Carbamates, business
Abstract: Recurrence of hepatitis C virus (HCV) after liver transplantation (LT) can rapidly lead to liver graft cirrhosis and, therefore, graft failure and retransplantation or death. The aim of the present study was to assess efficacy and tolerance of sofosbuvir (SOF)–based regimens for the treatment of HCV recurrence in patients with severe fibrosis after LT. The Compassionate Use of Protease Inhibitors in Viral C Liver Transplantation (CULPIT) study is a prospective multicenter cohort including patients with HCV recurrence following LT treated with second generation direct antivirals. The present study focused on patients included between October 2013 and November 2014 and diagnosed with HCV recurrence and liver graft extensive fibrosis (METAVIR F3/F4). A SOF-based regimen was administered to 125 patients fulfilling inclusion criteria. The median delay from LT was 95.9 ± 69.6 months. The characteristics of patients were as follows: mean age, 59.4 ± 9.0 years; 78.4% male; infected by HCV genotype 1: 78.2%, mean HCV RNA: 6.1 ± 1.0 log10 IU/mL. Eighty patients had failed previous post-LT antiviral therapy (64.0%) including triple therapy with first generation protease inhibitors in 19 (15.2%) patients. The main combination regimen was SOF/daclatasvir (73.6%). Ribavirin was used in 60 patients. Sustained virological response 12 weeks after treatment was 92.8% (on an intention-to-treat basis); 7 patients with virological failure were observed. Serious adverse events occurred in 25.6% of the patients during antiviral treatment. During antiviral treatment and follow-up, 3 patients were retransplanted and 4 patients died. In conclusion, SOF-based antiviral treatment shows very promising results in patients with HCV recurrence and severe fibrosis after LT. Liver Transplantation 22 1367–1378 2016 AASLD. © 2016 by the American Association for the Study of Liver Diseases
Published: 2016
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11. Longterm Risk of Solid Organ De Novo Malignancies After Liver Transplantation: A French National Study on 11,226 Patients

Author: Guy Launoy, Pascal Lebray, Olivier Chazouillères, Claire Francoz, Thierry Lobbedez, Sylvie Radenne, Nassim Kamar, Maryline Debette-Gratien, Sébastien Dharancy, Marie-Lorraine Woehl-Jaegle, Dominique Debray, Olivier Sérée, Jean Gugenheim, Marianne Latournerie, Vincent Leroy, Martine Neau-Cransac, Pauline Houssel-Debry, Jean Hardwigsen, Mario Altieri, Faouzi Saliba, Geraldine Hery, Olivier Boillot, Alessandra Mazzola, Rémy De Mil, Filomena Conti, Claire Vanlemmens, Georges-Philippe Pageaux, Elodie Guillaume, Philip Robinson, Emmanuel Jacquemin, Christophe Duvoux, François Durand, Ephrem Salamé, Philippe Segol, Didier Samuel, Jérôme Dumortier, Armand Abergel, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hospices Civils de Lyon (HCL), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Edouard Herriot [CHU - HCL], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pathologies biliaires, fibrose et cancer du foie [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pédiatrie multidisciplinaire [Hôpital de la Timone Enfants - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Henri Mondor [Créteil], Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Universitaire Pontchaillou, Intéractions cellulaires et physiopathologie hépathique (Orsay, Essonne) UMRS 1174 (ICPH ), Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, Equipe EPICAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), 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]), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Pôle des Pathologies Digestives Hépatiques et Transplantation [Hôpital Hautepierre-Strasbourg], Hôpital de Hautepierre [Strasbourg], Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), CHU Henri Mondor, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), CHU Saint-Eloi, Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Paul Brousse-Université Paris-Sud - Paris 11 (UP11), 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), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER
Subjects: Adult, Male, Alcoholic liver disease, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030230 surgery, Liver transplantation, Gastroenterology, Risk Assessment, Liver transplantation (LT), End Stage Liver Disease, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Risk Factors, Internal medicine, Neoplasms, medicine, Humans, education, Liver Diseases, Alcoholic, Transplantation, education.field_of_study, Hepatology, business.industry, Incidence (epidemiology), Incidence, Absolute risk reduction, Middle Aged, medicine.disease, Confidence interval, 3. Good health, Liver Transplantation, Standardized mortality ratio, Treatment Outcome, 030211 gastroenterology & hepatology, Surgery, Female, France, Risk assessment, business, Follow-Up Studies
Abstract: IF 3.756; International audience; De novo malignancies are one of the major late complications and causes of death after liver transplantation (LT). Using extensive data from the French national Agence de la Biomédecine database, the present study aimed to quantify the risk of solid organ de novo malignancies (excluding nonmelanoma skin cancers) after LT. The incidence of de novo malignancies among all LT patients between 1993 and 2012 was compared with that of the French population, standardized on age, sex, and calendar period (standardized incidence ratio; SIR). Among the 11,226 LT patients included in the study, 1200 de novo malignancies were diagnosed (10.7%). The risk of death was approximately 2 times higher in patients with de novo malignancy (48.8% versus 24.3%). The SIR for all de novo solid organ malignancies was 2.20 (95% confidence interval [CI], 2.08‐2.33). The risk was higher in men (SIR = 2.23; 95% CI, 2.09‐2.38) and in patients transplanted for alcoholic liver disease (ALD; SIR = 2.89; 95% CI, 2.68‐3.11). The cancers with the highest excess risk were laryngeal (SIR = 7.57; 95% CI, 5.97‐9.48), esophageal (SIR = 4.76; 95% CI, 3.56‐6.24), lung (SIR = 2.56; 95% CI, 2.21‐2.95), and lip‐mouth‐pharynx (SIR = 2.20; 95% CI, 1.72‐2.77). In conclusion, LT recipients have an increased risk of de novo solid organ malignancies, and this is strongly related to ALD as a primary indication for LT.
Published: 2018
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12. Combined heart and liver transplantation: State of knowledge and outlooks

Author: Shaida Varnous and Pascal Lebray
Subjects: Heart Defects, Congenital, Liver Cirrhosis, medicine.medical_specialty, Cirrhosis, Carcinoma, Hepatocellular, medicine.medical_treatment, Biopsy, Liver transplantation, Chronic liver disease, Gastroenterology, Contraindications, Procedure, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Liver Function Tests, Risk Factors, Internal medicine, Preoperative Care, medicine, Humans, Heart transplantation, Heart Failure, Amyloid Neuropathies, Familial, Hepatology, medicine.diagnostic_test, business.industry, Liver Neoplasms, Age Factors, Ascites, medicine.disease, Prognosis, Liver Transplantation, Transplantation, Liver, 030220 oncology & carcinogenesis, Liver biopsy, Heart Transplantation, 030211 gastroenterology & hepatology, Liver function, business, Liver Failure
Abstract: Various types of liver impairment have been described in patients with end-stage heart failure who are awaiting heart transplantation. The liver impairment may be severe, characterized by a high model for end-stage liver disease (MELD) Score and/or the presence of ascites, both of which are associated with a high risk of failure after single heart transplantation. A liver function assessment is therefore necessary before registration on the heart transplant list, moreover in case of long-developing heart failure, such as with congenital heart disease or in the presence of risk factors for chronic liver disease including excessive alcohol consumption, metabolic syndrome or chronic viral hepatitis B or C. In these instances, screening for cirrhosis with liver biopsy and for hepatocellular carcinoma through imaging must be systematic and when present, the indication for combined heart-liver transplantation must be considered. Its benefits, however, in case of liver failure with a high MELD score or multi-organ failure remains to be demonstrated. An exception in which the liver shows no morphological or functional alteration is with familial amyloid neuropathy, during which moderate to severe heart failure implies surgical treatment consisting of a liver or even heart-liver transplantation. These must be done early and are mainly contraindicated according to the level of neurological damage.
Published: 2018

13. Evolution of platelet functions in cirrhotic patients undergoing liver transplantation: A prospective exploration over a month

Author: Sébastien Bertil, Corinne Vezinet, Pascale Gaussem, Louis Puybasset, Jean Szymezak, Christilla Bachelot-Loza, Yann Loncar, Jean-Christophe Vaillant, Benjamin Granger, David M. Smadja, Ludovic Suner, Dominique Helley, Pascal Lebray, Ovidiu Gostian, Axelle Dupont, and Daniel Eyraud
Subjects: Liver Cirrhosis, Male, P-selectin, Platelet Aggregation, Physiology, medicine.medical_treatment, lcsh:Medicine, Liver transplantation, Cardiovascular Medicine, Pathology and Laboratory Medicine, Gastroenterology, Vascular Medicine, 0302 clinical medicine, Animal Cells, Medicine and Health Sciences, Platelet, Prospective Studies, Prospective cohort study, lcsh:Science, Multidisciplinary, Liver Diseases, Liver Neoplasms, Hematology, Middle Aged, Thrombosis, Body Fluids, P-Selectin, Blood, Cirrhosis, Liver, Cardiovascular Diseases, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Female, Anatomy, Cellular Types, Research Article, Platelets, Blood Platelets, medicine.medical_specialty, Carcinoma, Hepatocellular, Platelet Function Tests, CD40 Ligand, Surgical and Invasive Medical Procedures, Hemorrhage, Gastroenterology and Hepatology, Blood Plasma, 03 medical and health sciences, Digestive System Procedures, Signs and Symptoms, Diagnostic Medicine, Internal medicine, medicine, Humans, Platelet activation, Blood Coagulation, Transplantation, Blood Cells, Coagulation Disorders, business.industry, Platelet Count, lcsh:R, Biology and Life Sciences, Cell Biology, Organ Transplantation, medicine.disease, Platelet Activation, Liver Transplantation, Concomitant, lcsh:Q, business
Abstract: This prospective observational study was designed to analyze platelet functions across time in 50 patients scheduled for liver transplantation (LT) secondary to decompensated cirrhosis or hepatocellular carcinoma. Platelet functions were assessed before LT (pre-LT), one week (D7) and 1 month (D28) after LT. Platelet count significantly increased from pre-LT time to day 28 as well as circulating CD34+hematopoietic stem cells. To avoid any influence of platelet count on assays, platelet function was evaluated on platelet-rich-plasma adjusted to pre-LT platelet count. Although platelet secretion potential did not differ between time-points, as evaluated by the expression of CD62P upon strong activation, platelet aggregation in response to various agonists significantly increased along time, however with no concomitant increase of circulating markers of platelet activation: platelet microvesicles, platelet-leukocyte complexes, soluble CD40L and soluble CD62P. In the multivariate analysis, hepatic function was associated with platelet count and function. A lower platelet aggregation recovery was correlated with Child C score. History of thrombosis or bleeding was associated with respective higher or lower values of platelet aggregation. This longitudinal analysis of platelet functions in LT patients showed an improvement of platelet functions along time together with platelet count increase, with no evidence of platelet hyperactivation at any time-point.
Published: 2018

14. Daclatasvir plus sofosbuvir, with or without ribavirin, for hepatitis C virus genotype 3 in a French early access programme

Author: Hélène Fontaine, Victor de Ledinghen, Eric Nguyen-Khac, Pascal Lebray, Fabien Zoulim, Jean-Pierre Bronowicki, Christophe Hézode, Raoudha Akremi, Yue Zhao, Larysa Fedchuk, Yacia Bennai, Marc Bourlière, Isabelle Hubert-Fouchard, Louis d’Alteroche, Anne Filipovics, Vincent Di Martino, Christine Silvain, Dominique Larrey, Dominique Guyader, Isabelle Rosa, Danielle Botta-Fridlund, Vincent Leroy, Nathalie Boyer, 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), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Service d'hépatologie, 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), 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, 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), Institut Pasteur [Paris], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Département d'hépato-gastroentérologie, Université Grenoble Alpes (UGA)-CHU Grenoble, Hôpital Saint-Joseph [Marseille], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Pontchaillou [Rennes], CHI Créteil, CHU Amiens-Picardie, Bristol-Myers Squibb Company, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), This was a compassionate use programme authorized by a regulatory authority. No financial support was provided by BMS., Herrada, Anthony, 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 Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Pasteur [Paris] (IP), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Grenoble-Université Grenoble Alpes (UGA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Liver Cirrhosis, Male, Cirrhosis, Pyrrolidines, Sofosbuvir, Sustained Virologic Response, Viral Hepatitis, MESH: Sustained Virologic Response, Hepacivirus, medicine.disease_cause, Gastroenterology, Cohort Studies, MESH: Genotype, chemistry.chemical_compound, Liver disease, 0302 clinical medicine, Recurrence, MESH: Hepacivirus, 030212 general & internal medicine, MESH: Cohort Studies, MESH: Aged, education.field_of_study, MESH: Middle Aged, Imidazoles, Valine, Hepatitis C, Middle Aged, real‐world data, 3. Good health, MESH: Hepatitis C, Chronic, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, France, MESH: Liver Cirrhosis, MESH: Imidazoles, medicine.drug, Adult, MESH: Antiviral Agents, medicine.medical_specialty, MESH: Liver Transplantation, Daclatasvir, Genotype, Hepatitis C virus, Population, compassionate use, Antiviral Agents, sofosbuvir, 03 medical and health sciences, MESH: Ribavirin, Internal medicine, Ribavirin, medicine, Humans, genotype 3, daclatasvir, education, Aged, MESH: Humans, Hepatology, real-world data, business.industry, MESH: Sofosbuvir, MESH: Adult, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Chronic, medicine.disease, Virology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Male, Liver Transplantation, MESH: Recurrence, MESH: France, MESH: Drug Therapy, Combination, chemistry, Carbamates, hepatitis C, business, MESH: Female
Abstract: International audience; BACKGROUND & AIMS:Optimally effective treatment for hepatitis C virus genotype 3 (GT3) is urgently needed, particularly in advanced liver disease. Daclatasvir plus sofosbuvir was efficacious in phase 3 studies. Real-world data for daclatasvir+sofosbuvir in advanced GT3 infection are presented from the French Temporary Authorisation for Use programme, which allowed patients in need without other treatment options access to daclatasvir ahead of its market authorization.METHODS:Patients with F3/F4 fibrosis and/or extrahepatic hepatitis C virus manifestations, post-liver transplant hepatitis C virus recurrence and/or indication for liver/kidney transplant, were treated with daclatasvir+sofosbuvir (60+400 mg daily) for a recommended duration of 24 weeks. Addition of ribavirin and/or shorter treatment was at physician's discretion. The primary efficacy analysis was sustained virological response at post-treatment week 12 (SVR12; modified intention-to-treat). Safety was assessed by spontaneous adverse event reporting.RESULTS:The efficacy population comprised 333 patients, mostly cirrhotic (77%, of whom 18% were decompensated) and treatment experienced (72%). After 24 weeks of daclatasvir+sofosbuvir, SVR12 was 89% (174/196) overall (95% CI 83.6-92.5%), 98% (43/44) without cirrhosis (95% CI 88.2-99.6%) and 86% (129/150) with any degree of cirrhosis (95% CI 79.5-90.7%), without SVR12 increase in those who received additional ribavirin for 24 weeks (SVR12 82% [50/61; 95% CI 70.5-89.6%]). Among 516 GT3-infected patients with safety data, 5 discontinued for adverse events and 11 died.CONCLUSIONS:Daclatasvir+sofosbuvir achieved high SVR12 rates and was well tolerated in this large real-world cohort of GT3-infected patients with advanced liver disease, without benefit of ribavirin in those treated 24 weeks.
Published: 2017
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15. Peak hyperammonemia and atypical acute liver failure: The eruption of an urea cycle disorder during hyperemesis gravidarum

Author: Nicolas Weiss, Damien Galanaud, Marc Dommergues, Jacques Bernuau, Pascal Lebray, Chris Ottolenghi, Filomena Conti, Fanny Mochel, Dominique Thabut, Marika Rudler, Jean-Paul Bonnefont, and Sophie Demeret
Subjects: medicine.medical_specialty, Hepatology, Urea cycle disorder, business.industry, medicine.medical_treatment, Hyperammonemia, Liver transplantation, Ornithine, medicine.disease, Gastroenterology, 03 medical and health sciences, Hyperemesis gravidarum, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, chemistry, Inborn error of metabolism, Urea cycle, Internal medicine, medicine, 030211 gastroenterology & hepatology, business, 030217 neurology & neurosurgery, Ornithine transcarbamylase deficiency
Abstract: Summary Inborn urea cycle disorders are under-recognised metabolic causes of hyperammonemia in adults. A 28-year-old primigravida, seven weeks pregnant, affected by hyperemesis gravidarum developed acute liver injury (ALI) and then acute liver failure (ALF) in less than 48 h. Because the patient developed atypical features, especially mildly elevated aminotransferases contrasting with very high blood ammonia levels (281 μmol/L), concomitant with normal serum creatinine, an inborn error of metabolism was suspected. We performed emergency metabolic analyses, stopped all protein intake and started with intravenous (i.v.) high caloric intake, nitrogen scavenger drugs and haemodialysis. The neurological and hepatic status of the patient quickly improved together with normalisation of her ammonemia levels. High plasma glutamine and urinary orotic acid, alongside low plasma arginine, citrulline and ornithine were suggestive of an ornithine transcarbamylase deficiency, later confirmed by molecular analyses. Foetal sex was female, as determined by foetal DNA analysis in maternal blood, and foetal development was unremarkable throughout the pregnancy. Delivery was induced at 39 weeks with a close monitoring of ammonemia levels and i.v. perfusion of carbohydrates and lipids during labour and immediately post-partum to avoid hypercatabolism. Delivery was uneventful and the patient delivered a healthy female baby. Urea cycle disorders should be contemplated in non-jaundiced patients with ALI or ALF, severe hyperammonemia and normal serum creatinine regardless of serum aminotransferase levels. The prompt recognition of this rare condition and the rapid initiation of adequate metabolic therapy are mandatory to prevent irreversible neurological sequelae and to avoid liver transplantation.
Published: 2017

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

Author: Amir Guidoum, Laurent Alric, Vincent Leroy, Si-Nafa Si-Ahmed, Didier Samuel, Jean-Charles Duclos-Vallée, Jean-Didier Grangé, Sébastien Dharancy, Lawrence Serfaty, Célia Wellems, Christophe Hézode, François Durand, Anne-Marie Taburet, François Bailly, Christelle Paul, Maria Patrizia Carrieri, Pierre Pradat, Cécile Bouix, Elina Teicher, Sophie Metivier, Antoine Vilotitch, Christophe Duvoux, Georges-Philippe Pageaux, Anne-Marie Roque-Afonso, Bruno Roche, Filomena Conti, Ventzislava Petrov-Sanchez, Rodolphe Anty, Hélène Fontaine, Frédérik Beaulieux, Michelle Sizorn, Louis d’Alteroche, Marianne Maynard, Valérie Canva, Danielle Botta-Fridlund, Pascal Lebray, Département d'hépatologie [CHU Cochin], Institut Pasteur [Paris]-CHU Cochin [AP-HP]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale ( SESSTIM - U912 INSERM - Aix Marseille Univ - IRD ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), ORS PACA, Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], CHU Trousseau [APHP]-Centre Hospitalier Régional Universitaire de Tours ( CHRU TOURS ), Service d'hépatologie [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Fédération Médico-Chirurgicale des Maladies de l'Appareil Digestif, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -CHU Saint-Eloi, Département d'hépato-gastroentérologie, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Service de Gastro-entérologie - Hépatologie [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre Hospitalier Universitaire de Nice ( CHU Nice ), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon, Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Hôpital Purpan [Toulouse], Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), ANRS, France REcherche Nord & sud Sida-hiv Hépatites (FRENSH), Unit for Basic and Clinical research on Viral Hepatitis, Centre hépato-biliaire ( CHB ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AP-HP Hôpital Paul Brousse, This work was funded and sponsored by ANRS (France REcherche Nord & sud Sida-HIV Hépatites [FRENSH]), Paris.Dr Fontaine reports personal fees from Gilead, Janssen, BMS, MSD, AbbVie, outside the submitted work.Dr Leroy reports advisory role for BMS, Gilead, AbbVie, and Janssen and personal fees from BMS, Gilead, AbbVie, and Janssen.Dr Alric reports personal fees from MSD, Janssen, Gilead, AbbVie, BMS, research grants from MSD, Janssen, Gilead, AbbVie, BMS, and non-financial support from MSD, Janssen, Gilead, AbbVie, BMS., The authors thank Audrey Kremer-Cochet, Laure Roguet, and Dr Alpha Diallo for their continued deep involvement in the study. They also thank members of the independent committee: Prof Eric Belissant (methodologist), Dr Michel Biour (pharmacologist), Dr Marc Bourlière (hepatologist), Dr Rodolphe Garraffo (pharmacologist), Prof Dominique Larrey (pharmacologist), Prof Philippe Mathurin (hepatologist), Prof Christophe Moréno (hepatologist). They also thank Merck Schering-Plough for supplying the boceprevir. Finally, the authors thank the patients and their families., Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Grenoble-Université Grenoble Alpes (UGA), Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Claude Huriez [Lille], CHU Lille, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANRS France Recherche Nord & sud Sida-hiv hépatites, Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'hépathologie - Hôpital Cochin [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Cochin [AP-HP], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale ( SESSTIM ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -ORS PACA-Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Nice, Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Université Grenoble Alpes (UGA)-CHU Grenoble, Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Paul Brousse-Université Paris-Sud - Paris 11 (UP11), Herrada, Anthony, CHU Trousseau [APHP], Service d'hépatologie [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP]
Subjects: Liver Cirrhosis, Male, medicine.medical_treatment, Liver transplantation, Gastroenterology, chemistry.chemical_compound, Liver disease, 0302 clinical medicine, 030212 general & internal medicine, Liver Neoplasms, Hepatitis C, Middle Aged, 3. Good health, Treatment Outcome, Hepatocellular carcinoma, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, France, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Adolescent, Proline, Antiviral Agents, 03 medical and health sciences, Pharmacotherapy, Internal medicine, Boceprevir, Ribavirin, medicine, Humans, Adverse effect, Aged, Retrospective Studies, Hepatology, business.industry, Interferon-alpha, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Chronic, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Liver Transplantation, Surgery, chemistry, Quality of Life, business
Abstract: International audience; BACKGROUND AND AIMS:In this French multicentre, open-label study, we analyzed the efficacy, safety and patient-reported outcomes of a boceprevir-based triple therapy in HCV genotype 1 cirrhotic patients awaiting liver transplantation (LT).METHODS:Patients received PEG-IFN/ribavirin (RBV) for 48 weeks (W) and boceprevir from W4 to W48 or until LT.RESULTS:Fifty-one patients (80% males, median age: 56 years) were included. Fifty-seven percent had hepatocellular carcinoma and 43% end-stage liver disease. At enrolment, the median MELD score was 9 (range: 6-18); the Child-Pugh score was A in 65%, B in 35% and C in 2%. Therapy was discontinued because of severe adverse events (SAEs) in 39% of cases and virological inefficacy in 24%. 16% of patients had undetectable HCV RNA 24 weeks after the end of treatment (SVR24). LT was performed in 18 patients (35%). HCV RNA was undetectable in 16.6% at LT. Seven patients (14%) died and three deaths were attributed to treatment. SAEs (n=129) were observed in 84% of patients. Twenty-four percent of patients developed severe infections. Albumin
Published: 2017
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17. Staging chronic hepatitis B into seven categories, defining inactive carriers and assessing treatment impact using a fibrosis biomarker (FibroTest®) and elastography (FibroScan®)

Author: Olivier Deckmyn, Hugo Perazzo, Marika Rudler, Thierry Poynard, Mona Munteanu, J. Vergniol, Vincent Thibault, Dominique Thabut, Yen Ngo, Vlad Ratziu, Victor de Lédinghen, Juliette Foucher, Wassil Merrouche, and Pascal Lebray
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Cirrhosis, Esophageal and Gastric Varices, Gastroenterology, Cohort Studies, Hepatitis B, Chronic, Internal medicine, medicine, Humans, Prospective Studies, Hepatology, FibroTest, business.industry, Incidence (epidemiology), Liver Neoplasms, Viral Load, Hepatitis B, medicine.disease, HBeAg, Hepatocellular carcinoma, Carrier State, Disease Progression, Elasticity Imaging Techniques, Female, business, Transient elastography, Varices, Biomarkers
Abstract: Background & Aims The first aim was to extend the validation of FibroTest® (FT) and transient elastography (TE) as markers of occurrence of cirrhosis without complications (F4.1), oesophageal varices (F4.2), and severe complications (F4.3) in patients with chronic hepatitis B (CHB). The second aim was to validate a previous definition of an inactive carrier based on normal FT and ActiTest® (normal-FT-AT). The third aim was to assess the long-term dynamics of fibrosis in patients with sustained virological response. Methods The 10-year updated individual data of 1434 patients were pooled from two prospective cohorts. Results Of the 1312 patients without a history of complications, varices had occurred after 10years in 14 patients (F4.2, incidence of 1.7%, 95% CI [0.6–2.8]), and severe complications in 25 (F4.3 3.7% [1.8–5.7]), including hepatocellular carcinoma (HCC) in 21 (3.7% [1.5–5.8]). Using Cox-multivariate analysis adjusted for treatment, viral load, HBeAg status and ALT, FT, and TE were predictive of liver complications (n=37; AUROC=0.83 [0.71–0.90]; p p Normal FT-AT better identified patients with lower fibrosis progression than the ALT-based standard: 3/163 (1.8%) vs. 16/181 (8.8%; p =0.004) in the Paris cohort, and 5/195 (2.6%) vs. 15/228 (6.6%; p =0.05) in the Bordeaux cohort. Of the 582 responders, 23 had complications (incidence 6.2% [3.2–9.1]) including 19 HCC (5.8% [2.6–9.0]) and 10 with varices (2.6% [0.8–4.4]). Of the 138 responders with advanced fibrosis, only 31% (15–47%) had fibrosis regression. Conclusions FibroTest® and TE identified three categories of cirrhosis with increasing morbidity. Normal FibroTest® and ActiTest® were better able to identify inactive hepatitis B carriers than the standard definition. Despite virological response, the overall incidence of cirrhosis increased, with a remaining 5.8% risk of HCC.
Published: 2014
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18. Variability in definitions of transaminase upper limit of the normal impacts the APRI performance as a biomarker of fibrosis in patients with chronic hepatitis C: 'APRI c’est fini ?'

Author: Raluca Pais, Joseph Moussalli, Hugo Perazzo, Mona Munteanu, Vlad Ratziu, Pascal Lebray, Dominique Thabut, Thierry Poynard, Françoise Imbert-Bismut, Yen Ngo, Yves Benhamou, Denis Monneret, and Victor de Ledhingen
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Pathology, Cirrhosis, Gastroenterology, Transaminase, Reference Values, Fibrosis, Internal medicine, Biopsy, medicine, Humans, Blood test, Aspartate Aminotransferases, Retrospective Studies, Hepatology, medicine.diagnostic_test, Platelet Count, FibroTest, business.industry, Hepatitis C, Chronic, Middle Aged, medicine.disease, Biomarker (medicine), Female, business, Body mass index, Biomarkers
Abstract: The aspartate aminotransferase platelet ratio index (APRI) is a validated, non-patented blood test for diagnosing fibrosis or cirrhosis in patients with chronic hepatitis C. We assess the impact of two limitations, the variability of the upper limit of normal for aspartate aminotransferase (AST-ULN) and the risk of overestimating fibrosis stage due to necroinflammatory activity.The variability of AST-ULN was assessed by an overview of the literature and an assessment of AST-ULN in 2 control populations 7521 healthy volunteers and 393 blood donors. We assessed the impact of AST-ULN variability on APRI performance for estimating fibrosis prevalence and on the Obuchowski measure using individual data of 1651 patients with APRI, FibroTest and biopsy.The overview, and the analysis of the control populations found that ULN-AST ranged from 26 to 49 IU/L according to gender, body mass index and serum cholesterol. When this AST-ULN variability was applied to the chronic hepatitis group, the prevalence of advanced fibrosis and cirrhosis as presumed by APRI varied (P0.001) from 34.7% to 68.5%, and from 11.4% to 32.3%, respectively. This spectrum effect induced variability in APRI performance, which could be similar 0.862 (if AST-ULN=26 IU/L) or lower 0.820 (AST-ULN≥30IU/L) than the stable FibroTest performance (0.867; P=0.35 and P0.0001 respectively). When applied to 18 acute hepatitis C patients, the rate of false positives of APRI varied from 0% to 61% due to AST-ULN.The AST-ULN variability is high highly associated with the variability of metabolic risk factors between the different control groups. This variability induces a spectrum effect, which could cause misleading interpretations of APRI performance for the staging of fibrosis, comparisons of APRI with other non-invasive tests, and estimates of false positive rate.
Published: 2014
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19. Staging chronic hepatitis C in seven categories using fibrosis biomarker (FibroTest™) and transient elastography (FibroScan®)

Author: Wassil Merrouche, Eugene R. Schiff, Massimo Colombo, Mona Munteanu, Yen Ngo, Olivier Deckmyn, Thierry Poynard, Marika Rudler, Clifford A. Brass, V. Ratziu, Janice K. Albrecht, Juliette Foucher, Victor de Lédinghen, Dominique Thabut, Pascal Lebray, J. Vergniol, and Vincent Thibault
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Cirrhosis, Esophageal and Gastric Varices, Gastroenterology, Cohort Studies, Esophageal varices, Internal medicine, medicine, Hepatic Insufficiency, Humans, Decompensation, Prospective Studies, Hepatology, FibroTest, business.industry, Liver Neoplasms, Hepatitis C, Chronic, Middle Aged, Jaundice, Prognosis, medicine.disease, Hepatocellular carcinoma, Disease Progression, Elasticity Imaging Techniques, Female, medicine.symptom, Transient elastography, business, Varices
Abstract: FibroTest™ (FT) and Transient Elastography (TE) have been validated as non-invasive markers of METAVIR fibrosis stages from F0 to F4 using biopsy, and as prognostic markers of liver related mortality in patients with chronic hepatitis C. The aim was to extend the validation of FT and TE as markers of critical steps defined by occurrence of cirrhosis without complications (F4.1), esophageal varices (F4.2), and severe complications (F4.3): primary liver cancer, variceal bleeding, or decompensation (ascites, encephalopathy, or jaundice).The updated individual data of 3927 patients (1046 cirrhotics) without complications at baseline were pooled from three prospective cohorts called "EPIC", "Paris", and "Bordeaux" cohorts.At 5 years, among 501 patients without varices at baseline (F4.1) varices occurred in 19 patients [F4.2 incidence of 4.0% (95% CI 2.2-5.8)]. The predictive performance (AUROC) of FT was 0.77 (0.66-0.84; p0.001). At 10 years severe complications occurred in 203 patients, [F4.3 incidence of 13.4% (9.6-17.1)], including primary liver cancer in 84 patients [6.4% (3.5-9.3)]. FT was predictive (Cox adjusted on treatment) of severe complications [AUROC 0.79 (76-82); p0.0001], including primary liver cancer [AUROC 0.84 (80-87); p0.0001]. Similarly TE was predictive of severe complications [AUROC 0.77 (72-81); p0.0001], including primary liver cancer [AUROC 0.86 (81-90); p0.0001].FibroTest™ and TE increase were associated with the occurrence of all severe complications including hepatocellular carcinoma, hepatic insufficiency, and variceal bleeding. FibroTest™ increase was also associated with the occurrence of esophageal varices.
Published: 2014
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20. Ribavirin for Chronic Hepatitis E Virus Infection in Transplant Recipients

Author: Florence Abravanel, Sophie Hillaire, Louis d’Alteroche, Vincent Mallet, Jacques Izopet, Lionel Rostaing, Audrey Coilly, Anne-Marie Roque-Afonso, Sébastien Dharancy, Maryvonne Hourmant, Michael Bismuth, Nassim Kamar, Anne Minello, Jérôme Dumortier, Lionel Couzi, Matthias Büchler, Pascal Lebray, Valérie Garrigue, Stanislas Pol, Simona Tripon, and Sylvie Radenne
Subjects: Adult, Male, medicine.medical_specialty, Side effect, Anemia, viruses, Viremia, Virus Replication, medicine.disease_cause, Antiviral Agents, Gastroenterology, Drug Administration Schedule, Organ transplantation, chemistry.chemical_compound, Hepatitis E virus, Internal medicine, Ribavirin, Humans, Medicine, Aged, Retrospective Studies, business.industry, virus diseases, Retrospective cohort study, Organ Transplantation, General Medicine, Middle Aged, Viral Load, medicine.disease, digestive system diseases, Hepatitis E, chemistry, Chronic Disease, Immunology, Female, business, Viral load
Abstract: Background There is no established therapy for hepatitis E virus (HEV) infection. The aim of this retrospective, multicenter case series was to assess the effects of ribavirin as monotherapy for solid-organ transplant recipients with prolonged HEV viremia. Methods We examined the records of 59 patients who had received a solid-organ transplant (37 kidney-transplant recipients, 10 liver-transplant recipients, 5 heart-transplant recipients, 5 kidney and pancreas-transplant recipients, and 2 lung-transplant recipients). Ribavirin therapy was initiated a median of 9 months (range, 1 to 82) after the diagnosis of HEV infection at a median dose of 600 mg per day (range, 29 to 1200), which was equivalent to 8.1 mg per kilogram of body weight per day (range, 0.6 to 16.3). Patients received ribavirin for a median of 3 months (range, 1 to 18); 66% of the patients received ribavirin for 3 months or less. Results All the patients had HEV viremia when ribavirin was initiated (all 54 in whom genotyping was performed had HEV genotype 3). At the end of therapy, HEV clearance was observed in 95% of the patients. A recurrence of HEV replication occurred in 10 patients after ribavirin was stopped. A sustained virologic response, defined as an undetectable serum HEV RNA level at least 6 months after cessation of ribavirin therapy, occurred in 46 of the 59 patients (78%). A sustained virologic response was also observed in 4 patients who had a recurrence and were re-treated for a longer period. A higher lymphocyte count when ribavirin therapy was initiated was associated with a greater likelihood of a sustained virologic response. Anemia was the main identified side effect and required a reduction in ribavirin dose in 29% of the patients, the use of erythropoietin in 54%, and blood transfusions in 12%. Conclusions This retrospective, multicenter study showed that ribavirin as monotherapy may be effective in the treatment of chronic HEV infection; a 3-month course seemed to be an appropriate duration of therapy for most patients.
Published: 2014
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21. Long term prognostic value of the FibroTest in patients with non-alcoholic-fatty-liver disease (NAFLD), compared to chronic hepatitis C (CHC), B (CHB), and alcoholic liver disease (ALD)

Author: Mona Munteanu, Marika Rudler, F. Drane, Pascal Lebray, Hugo Perazzo, Raluca Pais, V. Ratziu, Yen Ngo, J. Massard, Marc-Antoine Valantin, Thierry Poynard, Francoise Imbert Bismut, Joseph Moussalli, Frédéric Charlotte, Dominique Thabut, Olivier Deckmyn, Chantal Housset, L. Olivier, Laurent Hannoun, and Vincent Thibault
Subjects: medicine.medical_specialty, Alcoholic liver disease, Hepatology, FibroTest, business.industry, Fatty liver, Non alcoholic, Disease, medicine.disease, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Chronic hepatitis, 030220 oncology & carcinogenesis, Internal medicine, medicine, 030211 gastroenterology & hepatology, In patient, business, Value (mathematics)
Published: 2018
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22. Slow regression of liver fibrosis presumed by repeated biomarkers after virological cure in patients with chronic hepatitis C

Author: Vincent Thibault, Helmi M'Kada, Olivier Deckmyn, Marc Antoine Valantin, Thierry Poynard, Pascal Lebray, Joseph Moussalli, Mona Munteanu, Yen Ngo, Vlad Ratziu, Yves Benhamou, Francoise Imbert Bismut, Frédéric Charlotte, Dominique Thabut, Christine Katlama, and Marika Rudler
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, HIV Infections, Kaplan-Meier Estimate, Disease, Antiviral Agents, Gastroenterology, Cohort Studies, Fibrosis, Internal medicine, Biopsy, medicine, Humans, Prospective Studies, Prospective cohort study, Hepatology, medicine.diagnostic_test, Coinfection, FibroTest, business.industry, Hepatitis C, Chronic, Middle Aged, medicine.disease, Regression, Disease Progression, Elasticity Imaging Techniques, Biomarker (medicine), Female, business, Follow-Up Studies
Abstract: Chronic hepatitis C is both a virologic and fibrotic disease and complications can occur in patients with sustained virologic response (SVR) with residual fibrosis. Due to the limitations of repeated biopsies, no studies have assessed the dynamic of fibrosis before and after treatment. Using biopsy as reference, FibroTest™ has been validated as a biomarker of fibrosis progression and regression, with similar prognostic values. The aim was to estimate the impact of SVR on the dynamic of fibrosis presumed by FibroTest™.In a prospective cohort, the main end point was the 10-year regression rate of fibrosis, defined as a minimum 0.20 decrease in FibroTest™, equivalent to one METAVIR stage.A total of 933 patients with both repeated FibroTest™ and transient elastography were included. At 10 years, among the 415 patients with baseline advanced fibrosis, 49% (95% CI 33-64%) of the 108 SVR had a regression, which was greater than in the 219 non-responders [23% (14-33%; p0.001 vs. SVR)] and not lower than in the 88 non-treated [45% (10-80%; p = 0.39 vs. SVR)] patients. In all 171 SVR, cirrhosis regressed in 24/43 patients, but 15 new cirrhosis cases occurred out of 128 patients, that is only a net reduction of 5.3% [(24-15) = 9/171); (2.4-9.8%)]. Four cases of primary liver cancer occurred in SVR [4.6% (0-9.8)], and 13 in non-responders [5.6% (1.5-9.8); p = 0.07].In patients with chronic hepatitis C, and as presumed by FibroTest™, virological cure was associated with slow regression of fibrosis 10years later, a disappointing 5% decrease in cirrhosis cases, and a remaining 5% risk of primary liver cancer.
Published: 2013
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23. Telaprevir Activity in Treatment-Naive Patients Infected Hepatitis C Virus Genotype 4: A Randomized Trial

Author: Gaston Picchio, Sandra De Meyer, Vlad Ratziu, Pascal Lebray, Donghan Luo, Katrien De Backer, Yves Benhamou, Anne Ghys, Maria Beumont, and Joseph Moussalli
Subjects: medicine.medical_specialty, Combination therapy, business.industry, Hepatitis C virus, Ribavirin, Pharmacology, Placebo, medicine.disease_cause, Gastroenterology, Telaprevir, chemistry.chemical_compound, Infectious Diseases, chemistry, Pegylated interferon, Internal medicine, medicine, Immunology and Allergy, Adverse effect, business, medicine.drug, Peginterferon alfa-2a
Abstract: Background. This partially blinded, randomized, phase 2a C210 study evaluated the antiviral activity of telaprevir-based regimens in treatment-naive patients with chronic hepatitis C virus (HCV) genotype 4 infection. Methods. Twenty-four patients received telaprevir 750 mg every 8 hours for 15 days (T; n = 8), telaprevir in combination with pegylated interferon alfa-2a and ribavirin (Peg-IFN/RBV) for 15 days (TPR; n = 8), or Peg-IFN/ RBV plus placebo for 15 days (PR; n = 8), followed by Peg-IFN/RBV for 46 or 48 weeks. The primary objective was to assess the effect of telaprevir on HCV RNA levels. Results. HCV RNA levels decreased slightly with T and PR; TPR produced substantial, rapid declines. On day 15, median reductions in the HCV RNA load from baseline were −0.77, −4.32, and −1.58 log10 IU/mL for T, TPR, and PR, respectively, and 0 patients in the T group, 1 in the TPR group, and 0 in the PR group had undetectable HCV RNA. Five of 8 patients who received telaprevir monotherapy had viral breakthrough within 15 days of treatment. Adverse event incidence was similar across treatments and comparable with the incidences from previous clinical trials. One patient (in T group) had a serious adverse event (considered unrelated to telaprevir) that led to treatment discontinuation. Conclusions. Telaprevir with Peg-IFN/RBV had greater activity than Peg-IFN/RBV treatment or telaprevir monotherapy against HCV genotype 4. Telaprevir was generally safe and well tolerated. Further investigation of telaprevir combination therapy in patients with HCV genotype 4 infection is warranted. Clinical Trials Registration. NCT00580801.
Published: 2013
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24. Should we keep using Ribavirin to Treat Hepatitis C Recurrence after Liver Transplantation? Results from the CO23 ANRS Cupilt Study

Author: Jean Charles Duclos-Vallée, F. Durand, Valérie Canva, V. Di Martino, Abou Diallo, G.-P. Pageaux, S. Radenne, Claire Fougerou-Leurent, Emilie Rossignol, Aurelie Veislinger, Pauline Houssel-Debry, Rodolphe Anty, H. Danjou, Vincent Leroy, Christophe Duvoux, L. D’Alteroche, C. Silvain, Audrey Coilly, V. de Ledinghen, Camille Besch, Caroline Jezequel, Maryline Debette-Gratien, A. Rohel, François Habersetzer, Nassim Kamar, H. Montialoux, Jérôme Dumortier, Armando Abergel, Christophe Moreno, Fabio Conti, Pascal Lebray, Danielle Botta-Fridlund, P. Perré, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Service d'Hépatologie, Hôpital Henri Mondor, AP-HP, Créteil, France., Hôpital Henri Mondor, Hôpital Paul Brousse, Département d'hépatologie, Hospices Civils de Lyon (HCL), 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 de Besançon (CHRU Besançon), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Services de Maladies de l'Appareil Digestif, Hôpital Claude Huriez, Centre Hospitalier Universitaire de Lille, Lille, France, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille, CHU Pitié-Salpêtrière [AP-HP], Service d'hépato-gastroentérologie, Hôpital de la Conception, AP-HM, Marseille, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, Service de Transplantation, Centre Hospitalier Universitaire de Strasbourg, Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg ), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Unité de la recherche fondamentale et clinique sur l' hépatite virale, France Recherche Nord & Sud Asdi-VIH Hépatites, Agence Nationale de Recherche sur le Sida, Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, Hepatology, business.industry, medicine.medical_treatment, Ribavirin, [SDV]Life Sciences [q-bio], Hepatitis C, 030230 surgery, Liver transplantation, medicine.disease, Gastroenterology, 3. Good health, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, Internal medicine, Medicine, 030211 gastroenterology & hepatology, business
Abstract: International audience; EASL International Liver Congress, APR 13-17, 2016, Barcelona, SPAIN
Published: 2016
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25. Peptic ulcer bleeding in patients with or without cirrhosis: different diseases but the same prognosis?

Author: Pascal Lebray, Dominique Thabut, Marika Rudler, H. Benosman, J. Massard, G. Rousseau, Thierry Poynard, and L. Deforges
Subjects: medicine.medical_specialty, education.field_of_study, Cirrhosis, Hepatology, business.industry, Population, Gastroenterology, medicine.disease, Pathophysiology, Internal medicine, medicine, Etiology, Portal hypertension, Pharmacology (medical), In patient, Prospective cohort study, business, education
Abstract: Summary Background Physiopathology and prognosis of peptic ulcer bleeding (PUB) have never been described in cirrhotic patients. Aim To assess risk factors and outcome of PUB in two groups of patients with PUB with or without cirrhosis. Methods We included prospectively all patients with PUB referred to our ICU of Hepatology and Gastroenterology between January 2008 and March 2011. All patients were treated according to international recommendations. Diagnosis of cirrhosis was based on clinical, biological and morphological exams. Aetiologies, characteristics and outcomes of PUB were compared in cirrhotic vs. noncirrhotic patients. Results A total of 203 patients with PUB were included prospectively. Twenty-nine patients had cirrhosis (group Cirr+), and 174 patients had no cirrhosis (group Cirr−). Demographic data were similar between the two groups except for age and alcohol consumption. Aetiology of cirrhosis was alcohol in 97% of cirrhotic patients. Characteristics of PUB were not different between the two groups. Ninety-three per cent of patients with cirrhosis had endoscopic portal hypertension. Aetiology of PUB was different between the group Cirr+ and Cirr− (Helicobacter pylori = 10.3% vs. 48.8%, P
Published: 2012
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26. FibroTest® and Fibroscan® performances revisited in patients with chronic hepatitis C. Impact of the spectrum effect and the applicability rate

Author: Thierry Poynard, Victor de Ledinghen, Jean-Pierre Zarski, Carol Stanciu, Mona Munteanu, Julien Vergniol, Julie France, Anca Trifan, Joseph Moussalli, Pascal Lebray, Dominique Thabut, and Vlad Ratziu
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Pathology, Cirrhosis, Population, Gastroenterology, Chronic hepatitis, Internal medicine, medicine, Humans, In patient, Prospective Studies, Prospective cohort study, education, education.field_of_study, Hepatology, business.industry, FibroTest, Significant difference, Reproducibility of Results, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, Elasticity Imaging Techniques, Female, business
Abstract: Two widely used biomarkers of fibrosis, FibroTest and liver stiffness measurement (LSM), have been mostly validated in patients with chronic hepatitis C (CHC) using the standard area under the ROC curve (sAUROC) which is not the most appropriate method due to the risk of fibrosis spectrum effect. Furthermore the performance of these biomarkers have not been assessed in "intention to diagnose" which takes into account the failures and non-reliable results.The aim was to compare the accuracy of FibroTest and LSM for the diagnosis of fibrosis using sAUROC, the pairwise comparison of fibrosis stages by Obuchowski measure (wAUROC), and these AUROCs reassessed after taking into account the applicability rates.One thousand two hundred and eighty-nine patients with CHC and 604 healthy volunteers were analyzed. The performances of biomarkers assessed were compared in a patients-only group (P1: n=1289), in a population combining both patients and healthy volunteers (P2: n=1893) and in a simulated population (P3: n=1893) with the prevalence of stages observed in a reference population, to demonstrate the impact of spectrum effect. Applicability rates were estimated prospectively in 24,872 consecutive FibroTest and in 13,669 consecutive LSM examinations.Using wAUROC, the conclusions of studies with reliable results in P1 were different than in those of P2 and in P3. There was a lower performance of FibroTest versus LSM in P1 (0.864 [0.855-0.873] vs. 0.883 [0.874-0.892]; P=0.002) which was not found in P2 (0.893 [0.887-0.900] vs. 0.894 [0.887-0.901]; P=0.86) and in P3 (0.899 [0.893-0.905] vs 0.902 [0.895-0.909]; P=0.60). Using the sAUROC, in P1, P2 and P3, there was no significant difference between FibroTest and LSM performance for advanced fibrosis and a lower performance of FibroTest versus LSM for cirrhosis. In intention to diagnose, using wAUROCs performances were higher for FibroTest vs. LSM in P1 (0.857 [0.848-0.866] vs. 0.814 [0.807-0.821]; P0.0001) and P2 (0.885 [0.879-0.892] vs. 0.743 [0.737-0.749]; P0.0001), without difference in P3 (0.891 [0.885-0.897] vs. 0.894 [0.887-0.901]; P=0.90). Using sAUROC, the significant differences in favor of FibroTest vs LSM persisted also for the diagnosis of advanced fibrosis, both in P1 and P2 (P0.0001) and for the diagnosis of cirrhosis in P1 (P0.001).When the spectrum effects and applicability rates were taken into account, LSM had lower performance results than FibroTest for the diagnosis of fibrosis stages.
Published: 2011
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27. HIV-1 or hepatitis C chronic infection in serodiscordant infertile couples has no impact on infertility treatment outcome

Author: Ouriel Rosenblum, Roland Tubiana, Manuela Bonmarchand, Anne-Geneviève Marcelin, Pascal Lebray, Christine Katlama, Danielle Vauthier-Brouzes, Nadia Prisant, Vincent Thibault, Catherine Poirot, Jean Louis Golmard, and Gilles Lefebvre
Subjects: Adult, Male, Infertility, medicine.medical_specialty, Pregnancy Rate, Treatment outcome, Clinical pregnancy, Human immunodeficiency virus (HIV), HIV Infections, Fertilization in Vitro, medicine.disease_cause, Viral infection, Pregnancy, Internal medicine, medicine, Humans, Sperm Injections, Intracytoplasmic, Retrospective Studies, business.industry, Pregnancy Outcome, virus diseases, Obstetrics and Gynecology, Hepatitis C, Hepatitis C, Chronic, medicine.disease, Virology, Chronic infection, Reproductive Medicine, Case-Control Studies, Serodiscordant, HIV-1, Female, business
Abstract: The objective was to evaluate the viral infection effects on infertility treatment outcome in HIV-1 or hepatitis C (HCV) monoinfected infertile serodiscordant couples, in a retrospective case-controlled, university-based study. Clinical pregnancy rate for HIV-1 or HCV infertile serodiscordant couples was not significantly different from that for seronegative controls.
Published: 2010
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28. Methodological aspects of the interpretation of non-invasive biomarkers of liver fibrosis: a 2008 update

Author: Thierry Poynard, R. Morra, Pascal Lebray, Mona Muntenau, Yen Ngo, Dominique Thabut, Djamila Messous, Joseph Moussalli, Vlad Ratziu, J. Massard, Yves Benhamou, and Françoise Imbert-Bismut
Subjects: Liver Cirrhosis, medicine.medical_specialty, FibroTest, business.industry, Biopsy, media_common.quotation_subject, Interpretation (philosophy), Gold standard, Gastroenterology, General Medicine, medicine.disease, Fibrosis, Spectrum bias, Internal medicine, medicine, Humans, Biomarker (medicine), Quality (business), Intensive care medicine, Hepatic fibrosis, business, Biomarkers, media_common
Abstract: This review summarizes the methodological aspects of the interpretation of non-invasive biomarkers in liver fibrosis. A scoring system has been updated to better compare the quality of fibrosis biomarkers. Several methodological issues are related to the classical methodology using biopsy, as this is considered the gold standard. However, from evidence-based data, it appears that the methodology needs to change to prevent flawed conclusions among key opinion leaders as well as in obsolete guidelines. As waiting for the perfect biomarker for the diagnosis of advanced fibrosis to come along is probably a waste of time, in the meantime, methods can be improved. The main proposals for improving the methodology are, to take into account the spectrum bias, to assess accuracy between adjacent stages, to compare biomarkers in the same patient, to assess the cause of failure among discordant cases and to use specific statistical methods adapted for imperfect gold standards.
Published: 2008
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29. Multicentre experience using daclatasvir and sofosbuvir to treat hepatitis C recurrence - The ANRS CUPILT study

Author: Armando Abergel, Christophe Moreno, Danielle Botta-Fridlund, Sylvie Radenne, Maryline Debette-Gratien, Pauline Houssel-Debry, Pascal Lebray, A. Rohel, Claire Francoz, Jean-Charles Duclos-Vallée, P. Perré, François Habersetzer, Nassim Kamar, Christine Silvain, Didier Samuel, H. Danjou, Rodolphe Anty, Vincent Leroy, Emilie Rossignol, Victor de Lédinghen, Louis d’Alteroche, Anne-Marie Roque-Afonso, Camille Besch, Filomena Conti, Christophe Duvoux, Georges-Philippe Pageaux, Valérie Canva, Claire Fougerou-Leurent, Jérôme Dumortier, Vincent Di Martino, Audrey Coilly, Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, 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), Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle Recherche Clinique-Santé Publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, 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), Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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-gastro-entérologie, Hôpital Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), service d'Hépato-gastro-entérologie, Hospices Civiles de Lyon-Hôpital Edouard Heriault, Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Chirurgie Digestive, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), 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 Digestif, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital de l'Archet, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), CHU Pitié-Salpêtrière [AP-HP], Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, Pathogénèse et traitement de l'hépatite fulminante et du cancer du foie, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hépato-biliaire - CHB [Paul Brousse, Paris], Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse, Hepatinov (DHU), Université Paris-Sud - Paris 11 (UP11)-Centre Hépato-Biliaire Paul Brousse, Centre National de Référence pour la maladie de Wilson (CNR wilson), CNR Wilson, Service de Neurologie, Hôpital Lariboisière, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), ANRS (France REcherche Nord & sud Sida-HIV Hepatites-FRENCH), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Multiorgan Transplantation, CHU Toulouse [Toulouse], 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], Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], 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)-CHU Saint-Eloi, Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Paul Brousse-Université Paris-Sud - Paris 11 (UP11), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), 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 de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Paul Brousse-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), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse, Centre hépato-biliaire ( CHB ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AP-HP Hôpital Paul Brousse, Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri-Mondor, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Hospices Civils de Lyon ( HCL ) -Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon ( HCL ), Institut de médecine moléculaire de Rangueil ( I2MR ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de gastro-entérologie, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], CHRU Tours, 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 ), Hôpital Huriez-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), APHP, Université Pierre et Marie Curie - Paris 6 ( UPMC ), Hôpital Erasme, Université Libre de Bruxelles [Bruxelles] ( ULB ), Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Centre méditérannéen de médecine moléculaire ( C3M ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ), CHU Nice-Hôpital de l'Archet, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques ( RESINFIT ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST ), Université de Limoges ( UNILIM ) -Université de Limoges ( UNILIM ) -CHU Limoges, Service de chirurgie digestive hépato-bilio-pancréatique transplantation hépatique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Human HepCell [AP-HP Hôpital Saint-Antoine], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AP-HP - Hôpital Saint-Antoine -Paris Biotech santé, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut de Virologie, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ) -AP-HP Hôpital Paul Brousse, Hepatinov ( DHU ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre Hépato-Biliaire Paul Brousse, Centre National de Référence pour la maladie de Wilson ( CNR wilson ), and Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -CHU Saint-Eloi
Subjects: Compassionate Use Trials, medicine.medical_specialty, drug-drug interactions, Daclatasvir, Sofosbuvir, Hepatitis C virus, medicine.medical_treatment, Hepacivirus, Liver transplantation, medicine.disease_cause, Gastroenterology, Antiviral Agents, virus-infection, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Model for End-Stage Liver Disease, Pegylated interferon, Internal medicine, Ribavirin, medicine, Humans, Prospective Studies, combination, Hepatology, business.industry, association, natural-history, Hepatitis C, interferon, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, 3. Good health, liver-transplant recipients, hcv infection, [ SDV.SP ] Life Sciences [q-bio]/Pharmaceutical sciences, Treatment Outcome, chemistry, 030220 oncology & carcinogenesis, triple therapy, Immunology, 030211 gastroenterology & hepatology, Drug Therapy, Combination, France, business, medicine.drug
Abstract: International audience; Background & Aims:HCV recurrence remains a major issue in the liver transplant field, as it has a negative impact on both graft and patient survival. The purpose of this study was to investigate the efficacy and safety of treating HCV recurrence with sofosbuvir (SOF) and daclatasvir (DCV) combination therapy. Methods: From October 2013 to March 2015, 559 liver recipients were enrolled in the prospective multicentre France REcherche Nord&Sud Sida-hiv Hepatites (ANRS) Compassionate use of Protease Inhibitors in viral C Liver Transplantation cohort. We selected 137 patients with an HCV recurrence receiving SOF and DCV, whatever the genotype or fibrosis stage. The use of ribavirin and the duration of therapy were at the investigator's discretion. The primary efficacy end point was a sustained virological response (SVR) 12 weeks after the end of treatment. Results: The SVR rate 12 weeks after completing treatment was 96% under the intention-to treat analysis and 99% when excluding non-virological failures. Only two patients experienced a virological failure. The serious adverse event (SAE) rate reached 17.5%. Four patients (3%) stopped their treatment prematurely because of SAEs. Anaemia was the most common AE, with significantly more cases in the ribavirin group (56% vs. 18%; p
Published: 2015
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30. G15 : The association of sofosbuvir and daclatasvir for treating severe recurrence of HCV infection after liver transplantation: Results from a large french prospective multicentric ANRS CO23 CUPILT cohort

Author: Nassim Kamar, Jérôme Dumortier, Pascal Lebray, P. Perré, C. Silvain, Jean Charles Duclos-Vallée, Vincent Leroy, Audrey Coilly, Valérie Canva, V. Di Martino, Alain Renault, Pauline Houssel-Debry, G.-P. Pageaux, Danielle Botta-Fridlund, H. Danjou, C. Fougerou, Sylvie Radenne, Christophe Moreno, L. D’Alteroche, V. de Ledinghen, Camille Besch, Rodolphe Anty, Christophe Duvoux, A. Rohel, Service de Pharmacologie [Rennes], CHU Pontchaillou [Rennes], Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Département d'hépatologie, Hospices Civils de Lyon (HCL), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Multiorgan Transplantation, CHU Toulouse [Toulouse], Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, Daclatasvir, Hepatology, Sofosbuvir, business.industry, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Liver transplantation, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Immunology, Cohort, medicine, 030211 gastroenterology & hepatology, business, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract: International audience; no abstract
Published: 2015
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31. LP05 : Daclatasvir plus sofosbuvir with or without ribavirin in patients with HCV genotype 3 infection: Interim analysis of a french multicenter compassionate use program

Author: Isabelle Rosa, V. de Ledinghen, Jean-Pierre Bronowicki, C. Silvain, Danielle Botta-Fridlund, Christophe Hézode, Yacia Bennai, Raoudha Akremi, M. Bourlière, Eric Nguyen-Khac, Pascal Lebray, I. Hubert-Fouchard, Dominique Larrey, Vincent Leroy, Hélène Fontaine, V. Di Martino, L. D’Alteroche, Dominique Guyader, Fabien Zoulim, Nathalie Boyer, Larysa Fedchuk, Fabrice Carrat, 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 de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), 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), Institut de pharmacologie moléculaire et cellulaire (IPMC), 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)-Centre National de la Recherche Scientifique (CNRS), Matière et Systèmes Complexes (MSC), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-gastroentérologie, Assistance Publique - Hôpitaux de Marseille (APHM), Service des maladies du foie [CHU Rennes], Centre Hospitalier Universitaire [Rennes], Foie, métabolismes et cancer, 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 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), ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins (DS3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Nice Sophia Antipolis (... - 2019) (UNS), Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), 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 [Rennes], 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) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Rennes]-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Epidémiologie, Systèmes dínformation et modélisation (ESIM), and CHU Saint-Antoine [APHP]
Subjects: medicine.medical_specialty, Daclatasvir, Hepatology, Sofosbuvir, business.industry, Ribavirin, [SDV]Life Sciences [q-bio], Compassionate Use, Interim analysis, Virology, 3. Good health, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, 030220 oncology & carcinogenesis, Internal medicine, Genotype, Medicine, 030211 gastroenterology & hepatology, In patient, business, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract: International audience; no abstract
Published: 2015
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32. Significant variations in elastometry measurements made within short-term in patients with chronic liver diseases

Author: Fabienne Fouffelle, Mona Munteanu, Fabrizio Andreelli, Pascal Lebray, Dominique Bonnefont-Rousselot, Arnaud Basdevant, Karine Clément, Eric Bruckert, Lawrence Serfaty, Agnès Hartemann-Heurtier, Sophie Gombert, Joseph Moussalli, Randa Bittar, André Grimaldi, Thierry Poynard, Anne Varault, Dominique Thabut, Yen Ngo, Yves Benhamou, A. Sola, Etienne Larger, Philippe Giral, Arnaud Cocaul, Philippe Podevin, Chantal Housset, Claudia P. Oliveira, Fabio Nascimbeni, Carole Bernhardt, Patrick Ingiliz, Jean-Michel Oppert, Sophie Jacqueminet, Jacqueline Capeau, Vlad Ratziu, Mário Reis Álvares-da-Silva, Mercedes de Torres, Christian Boitard, Martine El-Etr, L. Fedchuk, and Jean-François Gautier
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, ALT, BMI, Disease Progression, Liver Fibrosis Markers, Hepatology, Gastroenterology, Chronic liver disease, Article, Liver disease, Interquartile range, Fibrosis, Internal medicine, Nonalcoholic fatty liver disease, medicine, Humans, Aged, Retrospective Studies, business.industry, Reproducibility of Results, Middle Aged, medicine.disease, Surgery, Chronic Disease, Elasticity Imaging Techniques, Female, Transient elastography, business, Follow-Up Studies
Abstract: Transient elastometry is a noninvasive procedure used to measure fibrosis when patients are diagnosed with liver disease; it might be used to monitor changes over time. We investigated whether there are short-term variations in stiffness measurements that are not attributable to changes in fibrosis by studying patients with stable liver disease.We performed a retrospective analysis of 531 paired liver stiffness measurements made by Fibroscan when the study began (LSM1) and at follow-up (LSM2), more than 1 day and less than 1 year apart, from 432 stable (for body mass index, waist circumference, and alcohol consumption), untreated, immunocompetent patients with chronic liver disease (from January 2006 through March 2009). Variations between the first and follow-up measurements were expressed as absolute (LSM2-LSM1, kPa) or relative ([LSM2-LSM1]/LSM1*100) or as changes in fibrosis stage.There was20% variation in 49.7%,30% in 34.3%, and50% in 12.2% of paired measurements; this variation was constant across the spectrum of LSM1 values. The variations produced a 1-fibrosis stage difference in 31.5% of pairs and a ≥ 2-stage difference in 9.8% of pairs. Patients with LSM17 kPa had increased probability of having a different stage of fibrosis at LSM2, compared with patients with LSM17 kPa. Factors associated with variation included measurements made by 2 different operators or at least 1 non-senior operator, ratios of interquartile range:median values, significant fibrosis (≥ 7 kPa) at LSM1, baseline body mass index, or a 2-fold difference in level of alanine aminotransferase between measurements. When the analyses were restricted to measurements made by the same operator, the variation was slightly reduced; fibrosis stage differed between measurements for only 34.3% of cases.Operator-related and patient-related factors produce significant variations in liver stiffness measurements made by transient elastometry, limiting its use in monitoring patients. These variations are unrelated to disease progression. The lowest levels of variation occur in measurements made in patients with no or early-stage fibrosis or by a single experienced operator.
Published: 2015

33. Natural history and predictors of disease severity in chronic hepatitis C

Author: Yves Benhamou, Thierry Poynard, J. Massard, Pascal Lebray, Vlad Ratziu, Joseph Moussalli, and Dominique Thabut
Subjects: Liver Cirrhosis, medicine.medical_specialty, Cirrhosis, Hepatology, business.industry, Hepatitis C, Hepatitis C, Chronic, Overweight, Prognosis, medicine.disease, Severity of Illness Index, Gastroenterology, Natural history, Risk Factors, Fibrosis, Diabetes mellitus, Internal medicine, Severity of illness, Disease Progression, medicine, Humans, Steatosis, medicine.symptom, business
Abstract: Cirrhosis is the end-stage consequence of fibrosis progression in patients with chronic hepatitis C. The median time from infection to cirrhosis is 30 years, with a high inter-individual variability, which is now better understood. Several factors have been clearly shown to be associated with fibrosis progression rate: duration of infection, age, male gender, alcohol consumption, HIV co-infection and low CD4 count. Metabolic conditions such as steatosis, being overweight and diabetes are emerging as independent co-factors of fibrogenesis. The recent validation of non-invasive biomarkers should facilitate the study of fibrosis progression in large populations.
Published: 2006
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34. Diagnostic Accuracy of the Fibrotest in Hemodialysis and Renal Transplant Patients with Chronic Hepatitis C Virus

Author: Anaïs Vallet-Pichard, Pascal Lebray, Virginie Verkarre, Francoise Imbertbismuth, Bertrand Nalpas, Stanislas Pol, Jeanne Serpaggi, Hélène Fontaine, and Anne Varaut
Subjects: Adult, Male, Nephrology, medicine.medical_specialty, medicine.medical_treatment, Population, Gastroenterology, Automation, Liver Function Tests, Nephelometry and Turbidimetry, Predictive Value of Tests, Renal Dialysis, Internal medicine, medicine, Humans, education, Kidney transplantation, Transplantation, education.field_of_study, Kidney, medicine.diagnostic_test, FibroTest, business.industry, Reproducibility of Results, Hepatitis C Antibodies, Hepatitis C, Chronic, Middle Aged, medicine.disease, Kidney Transplantation, Surgery, medicine.anatomical_structure, Liver biopsy, Female, Hemodialysis, business, Biomarkers
Abstract: An accurate diagnosis of hepatitis C virus (HCV)-related liver lesions is mandatory in dialysis patients and kidney recipients to better define the treatment of and contraindications to kidney transplantation. The aim of this study was to assess the diagnostic accuracy of the fibrotest (a noninvasive method to assess liver fibrosis in HCV on a scale from 0 to 1) in hemodialysis and renal transplant patients infected by chronic HCV.In all, 110 patients with biopsy-proven HCV (60 renal transplant recipients and 50 hemodialysis patients), determined using the METAVIR scoring system, were studied.Forty-six percent of patients had fibrosisor =F2. A positive predictive value of a score0.6 for the presence of significant fibrosis by comparison with liver biopsy was 71%, and an negative predictive value of0.2 for excluding significant fibrosis was 77%, respectively. The areas under the ROC curves for the diagnosis of significant fibrosis were 0.66, 0.47, and 0.71 in the global population, hemodialysis patients, and renal transplant patients, respectively. In all, 75% of patients were correctly classified using the fibrotest. If biopsy was restricted to scores in the intermediate range (0.6 and0.2), the index could reduce the indication for biopsy by 47%. The results did not differ significantly in hemodialysis and renal transplant patients.The fibrotest has a diagnostic value in hemodialysis and renal transplant patients which is similar to that reported in the general population (75%) and its use could avoid 32% of liver biopsies if it were interpreted in detail in nephrology patients.
Published: 2005
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35. Combination Chemotherapy in Advanced Small Bowel Adenocarcinoma

Author: David Malka, Philippe Lasser, Christophe Locher, Dominique Elias, Valérie Boige, Michel Ducreux, and Pascal Lebray
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Organoplatinum Compounds, medicine.drug_class, medicine.medical_treatment, Adenocarcinoma, Biology, Antimetabolite, Gastroenterology, Disease-Free Survival, Carboplatin, chemistry.chemical_compound, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Intestinal Neoplasms, Intestine, Small, medicine, Humans, Aged, Retrospective Studies, Chemotherapy, Combination chemotherapy, General Medicine, Middle Aged, medicine.disease, Survival Analysis, digestive system diseases, Oxaliplatin, Surgery, Irinotecan, Treatment Outcome, Oncology, chemistry, Chemotherapy, Adjuvant, Fluorouracil, Female, Cisplatin, medicine.drug
Abstract: Objective: To assess the efficacy of 5-fluorouracil (5-FU) and either platinum compounds or irinotecan in patients with advanced small bowel adenocarcinoma (SBA), for whom data on the efficacy of chemotherapy are scarce. Methods: We reviewed data on all patients with advanced SBA who received chemotherapy over a 9-year period at our institution. Results: Twenty patients with advanced SBA received a median of 6 cycles (range 2–15) of chemotherapy with 5-FU and either cisplatin (n = 15), carboplatin (n = 2), or oxaliplatin (n = 3). The overall response rate was 21%, and median progression-free and overall survival 8 and 14 months, respectively. Toxicity was moderate. Second-line chemotherapy with 5-FU and irinotecan resulted in disease stabilization in 4 (50%) of 8 patients (median progression-free survival: 5 months), and in a biological complete response in another patient with nonmeasurable peritoneal carcinomatosis, allowing surgical cytoreduction surgery and hyperthermic intraperitoneal chemotherapy. No tumor response or disease stabilization was seen among the patients who received protracted venous infusion of 5-FU (n = 4) or infusional 5-FU and cisplatin (n = 1) as second-line chemotherapy. Conclusion: Chemotherapy with 5-FU and platinum compounds seems effective and well-tolerated in patients with advanced SBA. 5-FU-irinotecan combination chemotherapy deserves further investigation in the first-line setting.
Published: 2005
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36. Prognostic value of liver fibrosis and steatosis biomarkers in type-2 diabetes and dyslipidaemia

Author: Chantal Housset, S. Jacqueminet, Françoise Imbert-Bismut, Denis Monneret, F. Rutka, Thierry Poynard, A. Hartemann-Huertier, M. Couteau, Hugo Perazzo, Philippe Giral, Vlad Ratziu, Yen Ngo, Mona Munteanu, N. Seurat, and Pascal Lebray
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Type 2 diabetes, Gastroenterology, Cohort Studies, Non-alcoholic Fatty Liver Disease, Risk Factors, Internal medicine, Diabetes mellitus, medicine, Humans, Pharmacology (medical), Longitudinal Studies, Prospective Studies, Prospective cohort study, Aged, Dyslipidemias, Hepatology, FibroTest, Proportional hazards model, business.industry, Fatty liver, Middle Aged, medicine.disease, Prognosis, Endocrinology, Diabetes Mellitus, Type 2, Female, Steatosis, business, Biomarkers, Cohort study, Follow-Up Studies
Abstract: SummaryBackground In cardiometabolic disorders, non-alcoholic fatty liver disease is frequent and presumably associated with increased mortality and cardiovascular risk. Aim To evaluate the prognostic value of non-invasive biomarkers of liver fibrosis (FibroTest) and steatosis (SteatoTest) in patients with type-2 diabetes and/or dyslipidaemia. Methods A total of 2312 patients with type-2 diabetes and/or dyslipidaemia were included and prospectively followed up for 5–15 years. The cardiovascular Framingham-risk score was calculated; advanced fibrosis and severe steatosis, were defined by FibroTest >0.48 and SteatoTest >0.69, respectively, as previously established. Results During a median follow-up of 12 years, 172 patients (7.4%) died. The leading causes of mortality were cancer (31%) and cardiovascular-related death (20%). The presence of advanced fibrosis [HR (95% CI)] [2.98 (95% CI 1.78–4.99); P
Published: 2014

37. Prognosis of treated severe alcoholic hepatitis in patients with gastrointestinal bleeding

Author: H. Benosman, Marika Rudler, Thierry Poynard, S. Mouri, Romain Capocci, Pascal Lebray, Frédéric Charlotte, and Dominique Thabut
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Alcoholic liver disease, Gastrointestinal bleeding, Cirrhosis, Biopsy, Prednisolone, Anti-Inflammatory Agents, Alcoholic hepatitis, Gastroenterology, Severity of Illness Index, Liver Function Tests, Risk Factors, Internal medicine, medicine, Prevalence, Humans, Retrospective Studies, Hepatology, business.industry, Hepatitis, Alcoholic, Jaundice, Middle Aged, medicine.disease, Prognosis, Survival Analysis, Hospitalization, Liver, Concomitant, Hepatocellular carcinoma, Female, Upper gastrointestinal bleeding, France, medicine.symptom, business, Gastrointestinal Hemorrhage
Abstract: All trials on severe alcoholic hepatitis (AH) have included patients with "pure" AH, i.e., without concomitant gastrointestinal bleeding (GIB). Severe AH is often suspected in cirrhotic patients with GIB. We aimed at (1) assessing the prevalence of AH in patients with GIB and Maddrey discriminant function (DF) ⩾32; (2) comparing the outcome in AH patients with or without GIB (AH-GIB+, AH-GIB-); and (3) assessing the performance of the Lille model for survival in AH-GIB+ patients.We retrospectively included all patients with alcoholic cirrhosis admitted between January 2005 and March 2011 with the following: (1) jaundice3 months; (2) DF ⩾32 at admission; (3) bilirubin level50 μmol/L; and (4) active drinking. Exclusion criteria were advanced hepatocellular carcinoma, other etiology of cirrhosis, severe comorbidities and DF32 after stabilization. In our centre, we systematically plan a liver biopsy for these patients. Patients with severe AH received prednisolone.We screened 161 patients (86 GIB+, 75 GIB-), and analyzed data for 58 and 47 patients in each group, respectively. The 2 groups did not differ in prevalence of AH (77.3% vs. 81%), demographic data, MELD/Child-Pugh score, or DF. The 2 groups were similar in 6-month probability of survival (73.9 ± 6.0% vs. 69.9 ± 7%, p=0.49). The probability of developing infection was lower for AH-GIB+ patients (24.1% vs. 44.7%, p=0.04). The AUC for the Lille model in predicting 6-month survival was 0.71 ± 0.06 for all patients and 0.74 ± 0.06 for AH-GIB+ patients (p0.05).Prevalence of AH is 80% for patients with cirrhosis and GIB, recent jaundice and DF ⩾32. Infection was lower for AH-GIB+ patients, which suggests a beneficial role of antibiotic prophylaxis treatment. Survival among subjects with GIB was the same as among subjects without GIB.
Published: 2014

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

Author: Christophe Duvoux, Hélène Fontaine, G.-P. Pageaux, François Durand, C. Willems, Danielle Botta-Fridlund, Jean Charles Duclos-Vallée, Didier Samuel, Sophie Metivier, F. Beaulieux, Valérie Canva, Vincent Leroy, Fabio Conti, Pascal Lebray, C. Bouix, C. Paul, Rodolphe Anty, Louis d’Alteroche, Ventzislava Petrov-Sanchez, Pierre Pradat, Laurent Alric, and Marianne Maynard-Muet
Subjects: medicine.medical_specialty, chemistry.chemical_compound, Hepatology, Open label study, chemistry, business.industry, Internal medicine, medicine.medical_treatment, Boceprevir, medicine, Liver transplantation, business, Gastroenterology
Published: 2015
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39. Renal Dysfunction in Liver Transplant Patients Treated with Sofosbuvir Based-Regimen for HCV Recurrence: Results from a Large French Prospective Multicentric ANRS CO23 Cupilt

Author: A. Rohel, Sébastien Dharancy, Pascal Lebray, S. Radenne, C. Silvain, Christophe Duvoux, V. Di Martino, G.-P. Pageaux, V. de Ledinghen, Camille Besch, Nassim Kamar, Emilie Rossignol, François Habersetzer, Jean Charles Duclos-Vallée, Christophe Moreno, Rodolphe Anty, Alain Renault, H. Danjou, F. Durand, Valérie Canva, Guillaume Favre, Pauline Houssel-Debry, L. D’Alteroche, H. Montialoux, Jérôme Dumortier, Audrey Coilly, Vincent Leroy, C. Fougerou, A. Tran, and Danielle Botta-Fridlund
Subjects: medicine.medical_specialty, Hepatology, Sofosbuvir, business.industry, Hcv recurrence, Gastroenterology, 03 medical and health sciences, Regimen, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Medicine, 030211 gastroenterology & hepatology, Transplant patient, business, medicine.drug
Published: 2016
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40. 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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41. Impact of interferon-alpha treatment on liver fibrosis in patients with chronic hepatitis B: an overview of published trials

Author: Mona Munteanu, Yves Benhamou, Dominique Thabut, Marika Rudler, V. Ratziu, J. Massard, Pascal Lebray, A. Varaud, Yen Ngo, Joseph Moussalli, and Thierry Poynard
Subjects: Liver Cirrhosis, medicine.medical_specialty, Cirrhosis, Alpha interferon, medicine.disease_cause, Gastroenterology, Antiviral Agents, Hepatitis B, Chronic, Pegylated interferon, Fibrosis, Internal medicine, medicine, Humans, Hepatitis B virus, Clinical Trials as Topic, business.industry, Interferon-alpha, General Medicine, Entecavir, Hepatitis B, medicine.disease, Disease Progression, Hepatic fibrosis, business, medicine.drug
Abstract: The impact of interferon treatment in patients with hepatitis B virus (HBV) infection on fibrosis progression in comparison with its natural history has yet to be assessed in any large-scale randomized studies. The present report is a review of the evidence-based data published so far.Studies were included if they had at least two repeated estimates of liver fibrosis per patient treated with interferon-alpha (whether pegylated or not). Meta-analysis was performed using a random-effects model.Altogether, 13 studies were included in the review, involving a total of 707 HBV patients treated with interferon-alpha-2a or -2b for 12-83 months. Only one study included pegylated interferon as monotherapy. A total of 787 untreated patients were also followed. Only one study used a non-invasive biomarker. There was a significant reduction in the fibrosis progression rate, with a risk reduction of 0.49 (95% CI: -0.64--0.34; chi(2)=119; degrees of freedom [DF]=6; P0.0001), and significant heterogeneity (Cochran Q=81; P0.0001). This significant impact was similar for both randomized (reduction of risk: -0.45; 95% CI: -0.64--0.26; P0.0001) and not-randomized (controlled) studies (reduction of risk: -0.53; 95% CI: -0.79--0.28; P0.0001).According to these findings, the benefit of interferon treatment on fibrosis progression is clinically significant in patients with advanced fibrosis by the reduction of fibrosis progression to cirrhosis. Pegylated interferon now needs to be compared, in terms of benefit-risk factors, with the new generation of HBV treatments (such as entecavir and tenofovir), using non-invasive biomarkers.
Published: 2009

42. An accurate definition of the status of inactive hepatitis B virus carrier by a combination of biomarkers (FibroTest-ActiTest) and viral load

Author: Yen, Ngo, Yves, Benhamou, Vincent, Thibault, Patrick, Ingiliz, Mona, Munteanu, Pascal, Lebray, Dominique, Thabut, Rachel, Morra, Djamila, Messous, Frederic, Charlotte, Françoise, Imbert-Bismut, Dominique, Bonnefont-Rousselot, Dominique, Rousselot-Bonnefont, Joseph, Moussalli, Vlad, Ratziu, and Thierry, Poynard
Subjects: medicine.medical_specialty, Cirrhosis, Science, medicine.disease_cause, Gastroenterology, Gastroenterology and Hepatology/Hepatology, Hepatitis B, Chronic, Chronic hepatitis, Fibrosis, Internal medicine, Biopsy, medicine, Humans, Retrospective Studies, Hepatitis B virus, Multidisciplinary, medicine.diagnostic_test, business.industry, FibroTest, Viral Load, medicine.disease, Prognosis, HBeAg, Immunology, Carrier State, Medicine, business, Viral load, Biomarkers, Research Article
Abstract: BackgroundThe combination of transaminases (ALT), biopsy, HBeAg and viral load have classically defined the inactive status of carriers of chronic hepatitis B. The use of FibroTest (FT) and ActiTest (AT), biomarkers of fibrosis and necroinflammatory activity, has been previously validated as alternatives to biopsy. We compared the 4-year prognostic value of combining FT-AT and viral load for a better definition of the inactive carrier status.Methods and findings1,300 consecutive CHB patients who had been prospectively followed since 2001 were pre-included. The main endpoint was the absence of liver-related complications, transplantation or death. We used the manufacturers' definitions of normal FT (< = 0.27), normal AT (< = 0.29) and 3 standard classes for viral load. The adjustment factors were age, sex, HBeAg, ethnic origin, alcohol consumption, HIV-Delta-HCV co-infections and treatment.Results1,074 patients with baseline FT-AT and viral load were included: 41 years old, 47% African, 27% Asian, 26% Caucasian. At 4 years follow-up, 50 complications occurred (survival without complications 93.4%), 36 deaths occurred (survival 95.0%), including 27 related to HBV (survival 96.1%). The prognostic value of FT was higher than those of viral load or ALT when compared using area under the ROC curves [0.89 (95%CI 0.84-0.93) vs 0.64 (0.55-0.71) vs 0.53 (0.46-0.60) all PConclusionIn patients with chronic hepatitis B, a combination of FibroTest-ActiTest and viral load testing accurately defined the prognosis and the inactive carrier status.
Published: 2008

43. Screening for liver fibrosis by using a noninvasive biomarker in patients with diabetes

Author: Thierry Poynard, Mona Munteanu, Sophie Jacqueminet, Vlad Ratziu, Agnès Hartemann-Heurtier, Françoise Imbert-Bismut, Maguy Bernard, André Grimaldi, Laure Devers, R. Morra, Djamila Messous, and Pascal Lebray
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Biopsy, Gastroenterology, Severity of Illness Index, Diabetes Complications, Liver disease, Liver Function Tests, Fibrosis, Internal medicine, Nonalcoholic fatty liver disease, medicine, Prevalence, Humans, Mass Screening, Prospective Studies, Aged, Ultrasonography, Hepatology, medicine.diagnostic_test, business.industry, FibroTest, Endoscopy, Middle Aged, medicine.disease, Liver, Liver biopsy, Biomarker (medicine), Elasticity Imaging Techniques, Female, Liver function tests, business, Biomarkers
Abstract: Background & Aims: Patients with diabetes are at risk for nonalcoholic fatty liver disease leading to advanced fibrosis, cirrhosis, and liver cancer. We examined the efficacy of a screening strategy with a noninvasive fibrosis biomarker (FibroTest) in patients with diabetes. Methods: We prospectively studied 1131 consecutive patients without a history of liver disease seen for diabetes. The biomarker data were obtained, and patients with presumed advanced fibrosis were reinvestigated by a hepatologist using elastography and, if necessary, ultrasonography, endoscopy, or liver biopsy. Results: The biomarker predicted advanced fibrosis in 63 of 1131 (5.6%) patients. A total of 45 patients was reinvestigated, and advanced fibrosis was confirmed in 32 patients, a 2.8% (32/1131) prevalence of confirmed advanced fibrosis, 5 cases of cirrhosis, and 4 cases of hepatocellular carcinoma. In the population with type 2 diabetes who were 45 years or older, the prevalence of confirmed advanced fibrosis was 4.3% (30/696), and hepatocellular carcinoma was 5.7 of 1000 (4/696). Conclusions: The fibrosis biomarker might be used for the detection of advanced fibrosis in patients with type 2 diabetes.
Published: 2007

44. Nonalcoholic Fatty Liver Disease Increases the Risk of Hepatocellular Carcinoma in Patients With Alcohol-Associated Cirrhosis Awaiting Liver Transplants

Author: Ghizlaine Esselma, Corinne Vezinet, Marika Rudler, Raluca Pais, Jean-Michel Siksik, Thierry Poynard, Daniel Eyraud, Vlad Ratziu, Jean-Christophe Vaillant, G. Rousseau, Laurent Hannoun, Eric Savier, Frédéric Charlotte, Pascal Lebray, and Dominique Thabut
Subjects: Male, Paris, medicine.medical_specialty, Alcoholic liver disease, Carcinoma, Hepatocellular, Cirrhosis, medicine.medical_treatment, Liver transplantation, Risk Assessment, Gastroenterology, Liver disease, Model for End-Stage Liver Disease, Liver Cirrhosis, Alcoholic, Non-alcoholic Fatty Liver Disease, Internal medicine, Nonalcoholic fatty liver disease, Prevalence, Humans, Medicine, Obesity, Aged, Retrospective Studies, Hepatology, business.industry, Liver Neoplasms, Fatty liver, Middle Aged, medicine.disease, Fatty Liver, Diabetes Mellitus, Type 2, Female, France, Steatosis, business
Abstract: Many patients with alcohol-associated cirrhosis also have diabetes, obesity, or insulin resistance-mediated steatosis, but little is known about how these disorders affect the severity of liver disease. We analyzed the prevalence and prognostic implications of metabolic risk factors (MRFs) such as overweight, diabetes, dyslipidemia, and hypertension in patients with alcohol-associated cirrhosis awaiting liver transplants.We performed a retrospective study of 110 patients with alcohol-associated cirrhosis (77% male; mean age, 55 y; 71% with6 mo of abstinence) who received liver transplants at a single center in Paris, France, from 2000 through 2013. We collected data on previous exposure to MRFs, steatosis (10% in the explant), and histologically confirmed hepatocellular carcinoma (HCC).HCC was detected in explants from 29 patients (26%). Steatosis was detected in explants from 47 patients (70% were abstinent for ≥6 mo); 50% had a history of overweight or type 2 diabetes. Fifty-two patients (47%) had a history of MRFs and therefore were at risk for nonalcoholic fatty liver disease. A higher proportion of patients with MRF had HCC than those without MRF (46% vs 9%; P.001). A previous history of overweight or type 2 diabetes significantly increased the risk for HCC (odds ratio, 6.23; 95% confidence interval [CI], 2.47-15.76, and odds ratio, 4.63; 95% CI, 1.87-11.47, respectively; P.001). MRF, but not steatosis, was associated with the development of HCC (odds ratio, 11.76; 95% CI, 2.60-53; P = .001) independent of age, sex, amount of alcohol intake, or severity of liver disease.Patients with alcohol-associated cirrhosis who received transplants frequently also had nonalcoholic fatty liver disease. MRFs, particularly overweight, obesity, and type 2 diabetes, significantly increase the risk of HCC.
Published: 2015
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45. A prospective analysis of the prognostic value of biomarkers (FibroTest) in patients with chronic hepatitis C

Author: Thierry Poynard, Yen Ngo, Dominique Thabut, Mona Munteanu, Vlad Ratziu, Joseph Moussalli, Pascal Lebray, Frédéric Charlotte, Françoise Imbert-Bismut, Yves Benhamou, Djamila Messous, and Vincent Thibault
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Clinical Biochemistry, Gastroenterology, Fibrosis, Predictive Value of Tests, Internal medicine, Biopsy, medicine, Humans, Decompensation, alpha-Macroglobulins, Prospective Studies, Prospective cohort study, Analysis of Variance, medicine.diagnostic_test, Apolipoprotein A-I, Haptoglobins, FibroTest, business.industry, Biochemistry (medical), Alanine Transaminase, Bilirubin, gamma-Glutamyltransferase, Hepatitis C, Chronic, Middle Aged, medicine.disease, Survival Analysis, Surgery, Liver, Liver biopsy, Female, Complication, business, Biomarkers
Abstract: Background: FibroTest, a noninvasive method of measuring biomarkers of liver fibrosis, is an alternative to liver biopsy for determining the severity of chronic hepatitis C virus (HCV) infection. We compared the 5-year prognostic value of the FibroTest with biopsy staging for predicting cirrhosis decompensation and survival in patients with chronic HCV infection.Methods: Fibrosis stage was assessed on the same day by FibroTest and biopsy in a prospective cohort of 537 patients. Disease classification at baseline was 157 patients with severe fibrosis (FibroTest >0.58), 137 with moderate fibrosis (FibroTest 0.32–0.58), and 243 with no or minimal fibrosis (FibroTest Results: In 64 untreated patients with severe fibrosis, survival without HCV complications was 73% [95% confidence interval (CI), 59%–086%; 13 complications], and survival without HCV-related death was 85% (95% CI, 73%–96%; 7 HCV deaths). Survival rates were higher in patients with moderate fibrosis, [99% (95% CI, 97%–100%; 1 complication; P Conclusion: The FibroTest measurement of HCV biomarkers has a 5-year prognostic value similar to that of liver biopsy.
Published: 2006

46. Direct and indirect evidence for the reversibility of cirrhosis

Author: Anaïs Vallet-Pichard, Danièle Canioni, Pascal Lebray, Jérôme Guéchot, Stanislas Pol, Jeanne Serpaggi, Françoise Carnot, Bertrand Nalpas, Hélène Fontaine, and Pierre Bedossa
Subjects: METAVIR Fibrosis Score, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Hepatitis C virus, Biopsy, medicine.disease_cause, Gastroenterology, Pathology and Forensic Medicine, Liver disease, Fibrosis, Liver Cirrhosis, Alcoholic, Internal medicine, medicine, Humans, Hyaluronic Acid, Retrospective Studies, Prothrombin time, Hepatitis B virus, medicine.diagnostic_test, business.industry, Anatomical pathology, medicine.disease, Hepatitis B, Hepatitis C, Peptide Fragments, Treatment Outcome, Liver, business, Procollagen
Abstract: Summary The aim of this study was to assess the reversibility of cirrhosis after therapy in a large series of patients with cirrhosis from various etiologies. We performed a retrospective study of 113 patients with biopsy-proven cirrhosis who underwent specific therapy and follow-up biopsies. Two pathologists performed blinded analyses of indirect biochemical and morphological signs of cirrhosis. Fourteen (12.4%) of the 113 cirrhotic patients had biopsy-proven disappearance of cirrhosis, defined as a decrease of 2 or greater in their METAVIR fibrosis score: 8 were related to hepatitis C virus, 3 to hepatitis B virus, and 3 to autoimmune cirrhosis. Necro-inflammatory activity decreased from 2.4 ± 0.65 to 0.85 ± 0.9 ( P = .004), and fibrosis from 4 to 1.7 ± 0.61 ( P = .001). Prothrombin time (n = 1), platelet count (n = 2), serum albumin level (n = 2), and ultrasound abnormalities (n = 6) normalized in patients who had initial abnormalities. Hyaluronic acid and procollagen type III serum level decreased in all. In the 11 patients with regression of viral cirrhosis, 2 were nonresponders and 9 were responders, including 2 relapsers. The 3 patients with regressive autoimmune cirrhosis were complete responders to immunosupressive therapy. Using repeated liver biopsies, clinicobiochemical, radiologic, and endoscopic tests, we provide evidence for potential reversibility of cirrhosis after long-lasting suppression of the necro-inflammatory activity of liver disease.
Published: 2006

47. 487 LONG TERM SURVIVAL OF LIVER FIBROSIS AFTER VIROLOGICAL CURE (SVR) IN HIV–HCV COINFECTED PATIENTS: A WORRISOME LATENT DISEASE?

Author: Christine Katlama, Françoise Imbert-Bismut, Pascal Lebray, Dominique Thabut, Yen Ngo, Vincent Thibault, Mona Munteanu, V. Ratziu, Yves Benhamou, Marc-Antoine Valantin, Marika Rudler, Frédéric Charlotte, Joseph Moussalli, and Thierry Poynard
Subjects: medicine.medical_specialty, Hepatology, business.industry, Internal medicine, Liver fibrosis, Long term survival, medicine, Disease, business, Virology, Gastroenterology
Published: 2013
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48. 1422 END OF TREATMENT RESPONSE AFTER PROTEASE INHIBITOR (PI)- BASED THERAPY FOR HEPATITIS C RECURRENCE AFTER LIVER TRANSPLANTATION: A MULTICENTRIC EUROPEAN EXPERIENCE

Author: Jean Charles Duclos-Vallée, Christophe Duvoux, Pascal Lebray, G.-P. Pageaux, Christophe Moreno, S. Radenne, E. Giostra, Yvon Calmus, Bruno Roche, Audrey Coilly, Maryline Debette-Gratien, Didier Samuel, Vincent Leroy, Laurent Alric, Danielle Botta-Fridlund, Jérôme Dumortier, Anne-Catherine Saouli, F. Durand, Marianne Latournerie, and V. de Ledinghen
Subjects: medicine.medical_specialty, Treatment response, Hepatology, business.industry, medicine.medical_treatment, Hepatitis C, Liver transplantation, medicine.disease, Gastroenterology, Internal medicine, Immunology, medicine, Pi, Protease inhibitor (pharmacology), business
Published: 2013
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49. 21 10-YEARS PROGNOSTIC VALUE OF FIBROTEST AND STEATOTEST FOR LIVER-RELATED AND CARDIOVASCULAR DEATH IN PATIENTS WITH TYPE-2 DIABETES AND/OR HYPERLIPIDEMIA

Author: Mona Munteanu, F. Huet, M. Couteau, S. Jacqueminet, Hugo Perazzo, Thierry Poynard, Philippe Giral, A. Hartemann-Heurtier, Yen Ngo, V. Ratziu, Françoise Imbert-Bismut, and Pascal Lebray
Subjects: medicine.medical_specialty, Hepatology, business.industry, FibroTest, Type 2 diabetes, medicine.disease, Gastroenterology, Cardiovascular death, Endocrinology, Internal medicine, Hyperlipidemia, Medicine, In patient, business, Value (mathematics)
Published: 2013
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50. 1359 ASSOCIATION BETWEEN LIVER FIBROSIS AND DECREASED APOLIPOPROTEIN-A1 IN A 7-YEARS PROSPECTIVE STUDY. COULD IT EXPLAIN CARDIOVASCULAR-RELATED RISK WITH FIBROSIS PROGRESSION IN TYPE-2 DIABETIC PATIENTS?

Author: Thierry Poynard, V. Ratziu, Mona Munteanu, Pascal Lebray, F. Huet, Yen Ngo, Françoise Imbert-Bismut, M. Couteau, A. Hartemann-Heurtier, Hugo Perazzo, and S. Jacqueminet
Subjects: medicine.medical_specialty, Hepatology, biology, business.industry, Liver fibrosis, medicine.disease, Gastroenterology, Fibrosis, Internal medicine, biology.protein, Medicine, Apolipoprotein A1, Prospective cohort study, business
Published: 2013
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