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1. Inevitability of disease recurrence after liver transplantation for NAFLD cirrhosis

Author

François Villeret, Sébastien Dharancy, Domitille Erard, Armand Abergel, Louise Barbier, Camille Besch, Olivier Boillot, Karim Boudjema, Audrey Coilly, Filomena Conti, Christophe Corpechot, Christophe Duvoux, François Faitot, Stéphanie Faure, Claire Francoz, Emiliano Giostra, Jean Gugenheim, Jean Hardwigsen, Marie-Noëlle Hilleret, Jean-Baptiste Hiriart, Pauline Houssel-Debry, Nassim Kamar, Guillaume Lassailly, Marianne Latournerie, Georges-Philippe Pageaux, Didier Samuel, Claire Vanlemmens, Faouzi Saliba, and Jérôme Dumortier

Subjects
liver transplantation, NASH, metabolic syndrome, NAFLD recurrence, Bariatric surgery, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: Liver transplantation (LT) is the only available treatment for end-stage non-alcoholic fatty liver disease (NAFLD) (related decompensated cirrhosis and/or hepatocellular carcinoma). The aim of our study was to evaluate the risk of disease recurrence after LT and the factors influencing it. Method: This retrospective multicenter study included adults transplanted for NAFLD cirrhosis between 2000 and 2019 in 20 participating French-speaking centers. Disease recurrence (steatosis, steatohepatitis and fibrosis) was diagnosed from liver graft biopsies. Results: We analyzed 150 patients with at least one graft liver biopsy available ≥6 months after transplantation, among 361 patients transplanted for NAFLD. The median (IQR) age at LT was 61.3 (54.4-64.6) years. The median follow-up after LT was 4.7 (2.8-8.1) years. The cumulative recurrence rates of steatosis and steatohepatitis at 5 years were 80.0% and 60.3%, respectively. Significant risk factors for steatohepatitis recurrence in multivariate analysis were recipient age at LT

Published
2023
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2. AFP score and metroticket 2.0 perform similarly and could be used in a 'within-ALL' clinical decision tool

Author

Federico Piñero, Charlotte Costentin, Helena Degroote, Andrea Notarpaolo, Ilka FSF. Boin, Karim Boudjema, Cinzia Baccaro, Aline Chagas, Philippe Bachellier, Giuseppe Maria Ettorre, Jaime Poniachik, Fabrice Muscari, Fabrizio Dibenedetto, Sergio Hoyos Duque, Ephrem Salame, Umberto Cillo, Sebastián Marciano, Claire Vanlemmens, Stefano Fagiuoli, Flair Carrilho, Daniel Cherqui, Patrizia Burra, Hans Van Vlierberghe, Quirino Lai, Marcelo Silva, Fernando Rubinstein, Christophe Duvoux, Filomena Conti, Olivier Scatton, Pierre Henri Bernard, Claire Francoz, Francois Durand, Sébastien Dharancy, Marie-lorraine Woehl, Alexis Laurent, Sylvie Radenne, Jérôme Dumortier, Armand Abergel, Louise Barbier, Pauline Houssel-Debry, Georges Philippe Pageaux, Laurence Chiche, Victor Deledinghen, Jean Hardwigsen, J. Gugenheim, M. altieri, Marie Noelle Hilleret, Thomas Decaens, Paulo Costa, Elaine Cristina de Ataide, Emilio Quiñones, Margarita Anders, Adriana Varón, Alina Zerega, Alejandro Soza, Martín Padilla Machaca, Diego Arufe, Josemaría Menéndez, Rodrigo Zapata, Mario Vilatoba, Linda Muñoz, Ricardo Chong Menéndez, Martín Maraschio, Luis G. Podestá, Lucas McCormack, Juan Mattera, Adrian Gadano, Jose Huygens Parente García, Giulia Magini, Lucia Miglioresi, Martina Gambato, Cecilia D’Ambrosio, Alessandro Vitale, Michele Colledan, Domenico Pinelli, Paolo Magistri, Giovanni Vennarecci, Marco Colasanti, Valerio Giannelli, Adriano Pellicelli, Callebout Eduard, Iesari Samuele, Dekervel Jeroen, Schreiber Jonas, Pirenne Jacques, Verslype Chris, Ysebaert Dirk, Michielsen Peter, Lucidi Valerio, Moreno Christophe, Detry Olivier, Delwaide Jean, Troisi Roberto, and Lerut Jan Paul

Subjects
Prediction, reclassification, recurrence, transplantation, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: Two recently developed composite models, the alpha-fetoprotein (AFP) score and Metroticket 2.0, could be used to select patients with hepatocellular carcinoma (HCC) who are candidates for liver transplantation (LT). The aim of this study was to compare the predictive performance of both models and to evaluate the net risk reclassification of post-LT recurrence between them using each model’s original thresholds. Methods: This multicenter cohort study included 2,444 adult patients who underwent LT for HCC in 47 centers from Europe and Latin America. A competing risk regression analysis estimating sub-distribution hazard ratios (SHRs) and 95% CIs for recurrence was used (Fine and Gray method). Harrell’s adapted c-statistics were estimated. The net reclassification index for recurrence was compared based on each model’s original thresholds. Results: During a median follow-up of 3.8 years, there were 310 recurrences and 496 competing events (20.3%). Both models predicted recurrence, HCC survival and survival better than Milan criteria (p

Published
2023
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3. Involvement of circulating soluble HLA-G after liver transplantation in the low immunogenicity of hepatic allograft.

Author

Bastien Le Floc'h, Nathalie Costet, Nicolas Vu, Pénélope Bernabeu-Gentey, Charlotte Pronier, Pauline Houssel-Debry, Karim Boudjéma, Virginie Renac, Michel Samson, and Laurence Amiot

Subjects
Medicine, Science
Abstract

Graft rejection is a critical risk in solid-organ transplantation. To decrease such risk, an understanding of the factors involved in low immunogenicity of liver allografts could potentially make it possible to transfer this tolerogenic property to other transplanted organs. HLA-G, a natural physiological molecule belonging to the Human Leukocyte Antigen class (HLA) Ib family that induces tolerance, is associated with fewer rejections in solid-organ transplantation. In contrast to HLA-G, HLA antigen incompatibilities between donor and recipient can lead to rejection, except in liver transplantation. We compared HLA-G plasma levels and the presence of anti-HLA antibodies before and after LT to understand the low immunogenicity of the liver. We conducted a large prospective study that included 118 patients on HLA-G plasma levels during a 12-month follow-up and compared them to the status of anti-HLA antibodies. HLA-G plasma levels were evaluated by ELISA at seven defined pre- and post-LT time points. HLA-G plasma levels were stable over time pre-LT and were not associated with patient characteristics. The level increased until the third month post-LT, before decreasing to a level comparable to that of the pre-LT period at one year of follow-up. Such evolution was independent of biological markers and immunosuppressive treatment, except with glucocorticoids. An HLA-G plasma level ≤ 50 ng/ml on day 8 after LT was significantly associated with a higher rejection risk. We also observed a higher percentage of rejection in the presence of donor specific anti-HLA antibodies (DSA) and an association between the increase in HLA-G plasma levels at three months and the absence of DSA. The low immunogenicity of liver allografts could be related to early elevated levels of HLA-G, which lead, in turn, to a decrease in anti-HLA antibodies, opening potential new therapeutic strategies using synthetic HLA-G proteins.

Published
2023
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4. R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation

Author

Charlotte Costentin, Federico Piñero, Helena Degroote, Andrea Notarpaolo, Ilka F. Boin, Karim Boudjema, Cinzia Baccaro, Luis G. Podestá, Philippe Bachellier, Giuseppe Maria Ettorre, Jaime Poniachik, Fabrice Muscari, Fabrizio Dibenedetto, Sergio Hoyos Duque, Ephrem Salame, Umberto Cillo, Sebastian Marciano, Claire Vanlemmens, Stefano Fagiuoli, Patrizia Burra, Hans Van Vlierberghe, Daniel Cherqui, Quirino Lai, Marcelo Silva, Fernando Rubinstein, Christophe Duvoux, Filomena Conti, Olivier Scatton, Pierre Henri Bernard, Claire Francoz, Francois Durand, Sébastien Dharancy, Marie-lorraine Woehl, Alexis Laurent, Sylvie Radenne, Jérôme Dumortier, Armand Abergel, Louise Barbier, Pauline Houssel-Debry, Georges Philippe Pageaux, Laurence Chiche, Victor Deledinghen, Jean Hardwigsen, J. Gugenheim, M. Altieri, Marie Noelle Hilleret, Thomas Decaens, Aline Chagas, Paulo Costa, Elaine Cristina de Ataide, Emilio Quiñones, Sebastián Marciano, Margarita Anders, Adriana Varón, Alina Zerega, Alejandro Soza, Martín Padilla Machaca, Diego Arufe, Josemaría Menéndez, Rodrigo Zapata, Mario Vilatoba, Linda Muñoz, Ricardo Chong Menéndez, Martín Maraschio, Lucas McCormack, Juan Mattera, Adrian Gadano, Ilka S.F. Fatima Boin, Jose Huygens Parente García, Flair Carrilho, Giulia Magini, Lucia Miglioresi, Martina Gambato, Fabrizio Di Benedetto, Cecilia D’Ambrosio, Alessandro Vitale, Michele Colledan, Domenico Pinelli, Paolo Magistri, Giovanni Vennarecci, Marco Colasanti, Valerio Giannelli, Adriano Pellicelli, Cizia Baccaro, Callebout Eduard, Iesari Samuele, Dekervel Jeroen, Schreiber Jonas, Pirenne Jacques, Verslype Chris, Ysebaert Dirk, Michielsen Peter, Lucidi Valerio, Moreno Christophe, Detry Olivier, Delwaide Jean, Troisi Roberto, and Lerut Jan Paul

Subjects
Liver transplantation, Liver cancer, Recurrence, Explants pathology, Prediction, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: Patients with hepatocellular carcinoma (HCC) are selected for liver transplantation (LT) based on pre-LT imaging ± alpha-foetoprotein (AFP) level, but discrepancies between pre-LT tumour assessment and explant are frequent. Our aim was to design an explant-based recurrence risk reassessment score to refine prediction of recurrence after LT and provide a framework to guide post-LT management. Methods: Adult patients who underwent transplantation between 2000 and 2018 for HCC in 47 centres were included. A prediction model for recurrence was developed using competing-risk regression analysis in a European training cohort (TC; n = 1,359) and tested in a Latin American validation cohort (VC; n=1,085). Results: In the TC, 76.4% of patients with HCC met the Milan criteria, and 89.9% had an AFP score of ≤2 points. The recurrence risk reassessment (R3)-AFP model was designed based on variables independently associated with recurrence in the TC (with associated weights): ≥4 nodules (sub-distribution of hazard ratio [SHR] = 1.88, 1 point), size of largest nodule (3–6 cm: SHR = 1.83, 1 point; >6 cm: SHR = 5.82, 5 points), presence of microvascular invasion (MVI; SHR = 2.69, 2 points), nuclear grade >II (SHR = 1.20, 1 point), and last pre-LT AFP value (101–1,000 ng/ml: SHR = 1.57, 1 point; >1,000 ng/ml: SHR = 2.83, 2 points). Wolber’s c-index was 0.76 (95% CI 0.72–0.80), significantly superior to an R3 model without AFP (0.75; 95% CI 0.72–0.79; p = 0.01). Four 5-year recurrence risk categories were identified: very low (score = 0; 5.5%), low (1–2 points; 15.1%), high (3–6 points; 39.1%), and very high (>6 points; 73.9%). The R3-AFP score performed well in the VC (Wolber’s c-index of 0.78; 95% CI 0.73–0.83). Conclusions: The R3 score including the last pre-LT AFP value (R3-AFP score) provides a user-friendly, standardised framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials for HCC not limited to the Milan criteria. Clinical Trials Registration: NCT03775863. Lay summary: Considering discrepancies between pre-LT tumour assessment and explant are frequent, reassessing the risk of recurrence after LT is critical to further refine the management of patients with HCC. In a large and international cohort of patients who underwent transplantation for HCC, we designed and validated the R3-AFP model based on variables independently associated with recurrence post-LT (number of nodules, size of largest nodule, presence of MVI, nuclear grade, and last pre-LT AFP value). The R3-AFP model including last available pre-LT AFP value outperformed the original R3 model only based on explant features. The final R3-AFP scoring system provides a robust framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials, irrespective of criteria used to select patients with HCC for LT.

Published
2022
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5. Mortality after Transplantation for Hepatocellular Carcinoma: A Study from the European Liver Transplant Registry

Author

Hans-Christian Pommergaard, Andreas Arendtsen Rostved, René Adam, Mauro Salizzoni, Miguel Angel Gómez Bravo, Daniel Cherqui, Paolo De Simone, Pauline Houssel-Debry, Vincenzo Mazzaferro, Olivier Soubrane, Juan Carlos García-Valdecasas, Joan Fabregat Prous, Antonio D. Pinna, John O’Grady, Vincent Karam, Christophe Duvoux, and Lau Caspar Thygesen

Subjects
hepatocellular carcinoma, liver transplantation, prognosis, propensity score calibration, unmeasured confounding, non-cirrhotic liver, cirrhosis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background and Aims: Prognosis after liver transplantation differs between hepatocellular carcinoma (HCC) arising in cirrhotic and non-cirrhotic livers and aetiology is poorly understood. The aim was to investigate differences in mortality after liver transplantation between these patients. Methods: We included patients from the European Liver Transplant Registry transplanted due to HCC from 1990 to November 2016 and compared cirrhotic and non-cirrhotic patients using propensity score (PS) calibration of Cox regression estimates to adjust for unmeasured confounding. Results: We included 22,787 patients, of whom 96.5% had cirrhosis. In the unadjusted analysis, non-cirrhotic patients had an increased risk of overall mortality with a hazard ratio (HR) of 1.37 (95% confidence interval [CI] 1.23–1.52). However, the HR approached unity with increasing adjustment and was 1.11 (95% CI 0.99–1.25) when adjusted for unmeasured confounding. Unadjusted, non-cirrhotic patients had an increased risk of HCC-specific mortality (HR 2.62, 95% CI 2.21–3.12). After adjustment for unmeasured confounding, the risk remained significantly increased (HR 1.62, 95% CI 1.31–2.00). Conclusions: Using PS calibration, we showed that HCC in non-cirrhotic liver has similar overall mortality, but higher HCC-specific mortality. This may be a result of a more aggressive cancer form in the non-cirrhotic liver as higher mortality could not be explained by tumour characteristics or other prognostic variables.

Published
2020
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6. Patients Treated for HCV Infection and Listed for Liver Transplantation in a French Multicenter Study: What Happens at Five Years?

Author

Lucy Meunier, Mohamed Belkacemi, George Philippe Pageaux, Sylvie Radenne, Anaïs Vallet-Pichard, Pauline Houssel-Debry, Christophe Duvoux, Danielle Botta-Fridlund, Victor de Ledinghen, Filomena Conti, Rodolphe Anty, Vincent Di Martino, Marilyne Debette-Gratien, Vincent Leroy, Theophile Gerster, Pascal Lebray, Laurent Alric, Armand Abergel, Jérôme Dumortier, Camille Besch, Helene Montialoux, Didier Samuel, Jean-Charles Duclos-Vallée, and Audrey Coilly

Subjects
anti HCV therapy, DAAs, liver transplantation, decompensated cirrhosis, hepatocellular carcinoma, waiting list, Microbiology, QR1-502
Abstract

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

Published
2022
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7. International study on the outcome of locoregional therapy for liver transplant in hepatocellular carcinoma beyond Milan criteria

Author

Helena Degroote, Federico Piñero, Charlotte Costentin, Andrea Notarpaolo, Ilka F. Boin, Karim Boudjema, Cinzia Baccaro, Aline Lopes Chagas, Philippe Bachellier, Giuseppe Maria Ettorre, Jaime Poniachik, Fabrice Muscari, Fabrio Di Benedetto, Sergio Hoyos Duque, Ephrem Salame, Umberto Cillo, Adrián Gadano, Claire Vanlemmens, Stefano Fagiuoli, Fernando Rubinstein, Patrizia Burra, Daniel Cherqui, Marcelo Silva, Hans Van Vlierberghe, Christophe Duvoux, Filomena Conti, Olivier Scatton, Pierre Henri Bernard, Claire Francoz, Francois Durand, Sébastien Dharancy, Marie-lorraine Woehl, Alexis Laurent, Sylvie Radenne, Jérôme Dumortier, Armand Abergel, Louise Barbier, Pauline Houssel-Debry, Georges Philippe Pageaux, Laurence Chiche, Victor Deledinghen, Jean Hardwigsen, J. Gugenheim, M. Altieri, Marie Noelle Hilleret, Thomas Decaens, Aline Chagas, Paulo Costa, Elaine Cristina de Ataide, Emilio Quiñones, Sebastián Marciano, Margarita Anders, Adriana Varón, Alina Zerega, Alejandro Soza, Martín Padilla Machaca, Diego Arufe, Josemaría Menéndez, Rodrigo Zapata, Mario Vilatoba, Linda Muñoz, Ricardo Chong Menéndez, Martín Maraschio, Luis G. Podestá, M. Fauda, A. Gonzalez Campaña, Lucas McCormack, Juan Mattera, Adrian Gadano, Ilka S.F. Fatima Boin, Jose Huygens Parente García, Flair Carrilho, Giulia Magini, Lucia Miglioresi, Martina Gambato, Fabrizio Di Benedetto, Cecilia D’Ambrosio, Alessandro Vitale, Michele Colledan, Domenico Pinelli, Paolo Magistri, Giovanni Vennarecci, Marco Colasanti, Valerio Giannelli, Adriano Pellicelli, Cizia Baccaro, Callebout Eduard, Iesari Samuele, Dekervel Jeroen, Schreiber Jonas, Pirenne Jacques, Verslype Chris, Ysebaert Dirk, Michielsen Peter, Lucidi Valerio, Moreno Christophe, Detry Olivier, Delwaide Jean, Troisi Roberto, and Lerut Jan Paul

Subjects
Hepatocellular carcinoma, Downstaging, UCSF downstaging protocol, All-comers, Alpha-foetoprotein, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: Good outcomes after liver transplantation (LT) have been reported after successfully downstaging to Milan criteria in more advanced hepatocellular carcinoma (HCC). We aimed to compare post-LT outcomes in patients receiving locoregional therapies (LRT) before LT according to Milan criteria and University of California San Francisco downstaging (UCSF-DS) protocol and ‘all-comers’. Methods: This multicentre cohort study included patients who received any LRT before LT from Europe and Latin America (2000–2018). We excluded patients with alpha-foetoprotein (AFP) above 1,000 ng/ml. Competing risk regression analysis for HCC recurrence was conducted, estimating subdistribution hazard ratios (SHRs) and corresponding 95% CIs. Results: From 2,441 LT patients, 70.1% received LRT before LT (n = 1,711). Of these, 80.6% were within Milan, 12.0% within UCSF-DS, and 7.4% all-comers. Successful downstaging was achieved in 45.2% (CI 34.8–55.8) and 38.2% (CI 25.4–52.3) of the UCSF-DS group and all-comers, respectively. The risk of recurrence was higher for all-comers (SHR 6.01 [p

Published
2021
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8. Pharmacogenetic-Whole blood and intracellular pharmacokinetic-Pharmacodynamic (PG-PK2-PD) relationship of tacrolimus in liver transplant recipients.

Author

Camille Tron, Jean-Baptiste Woillard, Pauline Houssel-Debry, Véronique David, Caroline Jezequel, Michel Rayar, David Balakirouchenane, Benoit Blanchet, Jean Debord, Antoine Petitcollin, Mickaël Roussel, Marie-Clémence Verdier, Eric Bellissant, and Florian Lemaitre

Subjects
Medicine, Science
Abstract

Tacrolimus (TAC) is the cornerstone of immunosuppressive therapy in liver transplantation. This study aimed at elucidating the interplay between pharmacogenetic determinants of TAC whole blood and intracellular exposures as well as the pharmacokinetic-pharmacodynamic relationship of TAC in both compartments. Complete pharmacokinetic profiles (Predose, and 20 min, 40 min, 1h, 2h, 3h, 4h, 6h, 8h, 12h post drug intake) of twice daily TAC in whole blood and peripheral blood mononuclear cells (PBMC) were collected in 32 liver transplanted patients in the first ten days post transplantation. A non-parametric population pharmacokinetic model was applied to explore TAC pharmacokinetics in blood and PBMC. Concurrently, calcineurin activity was measured in PBMC. Influence of donor and recipient genetic polymorphisms of ABCB1, CYP3A4 and CYP3A5 on TAC exposure was assessed. Recipient ABCB1 polymorphisms 1199G>A could influence TAC whole blood and intracellular exposure (p

Published
2020
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9. Liver transplantation for autoimmune hepatitis: Pre‐transplant does not predict the early post‐transplant outcome

Author

Yasmina Chouik, Claire Francoz, Eleonora De Martin, Olivier Guillaud, Armand Abergel, Mario Altieri, Louise Barbier, Camille Besch, Olivier Chazouillères, Filomena Conti, Christophe Corpechot, Sébastien Dharancy, François Durand, Christophe Duvoux, Jean Gugenheim, Jean Hardwigsen, Marie‐Noëlle Hilleret, Pauline Houssel‐Debry, Nassim Kamar, Anne Minello, Martine Neau‐Cransac, Georges‐Philippe Pageaux, Sylvie Radenne, Olivier Roux, Faouzi Saliba, Didier Samuel, Claire Vanlemmens, Marie‐Lorraine Woehl‐Jaegle, Vincent Leroy, Jean‐Charles Duclos‐Vallée, Jérôme Dumortier, Hospices Civils de Lyon (HCL), 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), Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Edouard Herriot [CHU - HCL], Clinique de la Sauvegarde [Lyon], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, 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), Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, Hôpital de Hautepierre [Strasbourg], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Henri Mondor [Créteil], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), 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)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Fondation Léon Bouchut

Subjects
early infection, MESH: Liver Transplantation, immunosuppression, MESH: Humans, Hepatology, MESH: Hepatitis, Autoimmune, fulminant hepatitis, MESH: Adult, MESH: Retrospective Studies, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, survival, sepsis, MESH: Massive Hepatic Necrosis, MESH: Female, MESH: Sepsis
Abstract

Background and aims: Autoimmune hepatitis (AIH) is a rare indication (

Published
2023
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10. Poor Patient and Graft Outcome After Induction Treatment by Antithymocyte Globulin in Recipients of a Kidney Graft After Nonrenal Organ Transplantation

Author

Hoa Le Mai, PhD, Michèle Treilhaud, MD, Shani Leviatan Ben-Arye, PhD, Hai Yu, PhD, Hélène Perreault, PhD, Evelyn Ang, PhD, Katy Trébern-Launay, PhD, Julie Laurent, PhD, Stéphanie Malard-Castagnet, PhD, Anne Cesbron, MD, Thi Van Ha Nguyen, PhD, Sophie Brouard, PhD, Lionel Rostaing, MD, Pauline Houssel-Debry, MD, Christophe Legendre, MD, Sophie Girerd, MD, Michèle Kessler, MD, Emmanuel Morelon, MD, Antoine Sicard, MD, Valérie Garrigue, MD, Georges Karam, MD, Xi Chen, PhD, Magali Giral, MD, Vered Padler-Karavani, PhD, and Jean Paul Soulillou, MD

Subjects
Surgery, RD1-811
Abstract

Background. End-stage renal failure occurs in a substantial number of patients having received a nonrenal transplantation (NRT), for whom a kidney transplantation is needed. The medical strategy regarding the use of immunosuppression (IS) for a kidney graft in patients after an NRT is not well established. The prekidney grafts long-term IS advocates for a mild induction, such as using anti-IL-2R antibodies, whereas addition of new incompatibilities and anti-HLA preimmunization may suggest using stronger IS such as induction by polyclonal antithymocyte globulins (ATG). Methods. We performed Cox multivariate and propensity score analysis of our validated transplant database to study the impact of the type of induction therapy on kidney graft survival of recipients of a kidney graft after NRT. Results. We report here that kidney transplantation after NRT treated with an ATG induction has a poorer outcome (kidney and recipient survival) than that with an anti–IL-2R induction. After accounting for potential baseline differences with a multivariate Cox model, or by adjusting on a propensity score, we found that despite patients having received ATG cumulate more risk factors, ATG appears independently involved. As animal-derived biotherapeutics induce antiglycan antibodies and particularly anti–N-glycolylneuraminic acid (Neu5Gc) IgGs which may activate endothelial cells in patients and grafts, we also investigated the magnitude and the nature of the anti-Neu5Gc elicited by the induction and showed that induction was associated with a shift in anti-Neu5Gc IgG repertoire. Possible reasons and mechanisms of a deleterious ATG usage in these patients are discussed. Conclusions. Our study suggests that ATG induction after a kidney transplantation in recipients already under maintenance IS for a NRT should be used cautiously.

Published
2018
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11. Patients Treated for HCV Infection and Listed for Liver Transplantation in a French Multicenter Study: What Happens at Five Years?

Author

Lucy Meunier, Mohamed Belkacemi, George Philippe Pageaux, Sylvie Radenne, Anaïs Vallet-Pichard, Pauline Houssel-Debry, Christophe Duvoux, Danielle Botta-Fridlund, Victor de Ledinghen, Filomena Conti, Rodolphe Anty, Vincent Di Martino, Marilyne Debette-Gratien, Vincent Leroy, Theophile Gerster, Pascal Lebray, Laurent Alric, Armand Abergel, Jérôme Dumortier, Camille Besch, Helene Montialoux, Didier Samuel, Jean-Charles Duclos-Vallée, Audrey Coilly, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Paul Brousse, and Funding support came solely from institutional and/or departmental sources (institute: Montpellier University Hospital, 34000, France).

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

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

Published
2023
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12. HCV eradication does not protect from fibrosis progression in patients with fibrosing cholestatic hepatitis after liver transplantation

Author

Audrey, Coilly, Mylène, Sebagh, Claire, Fougerou-Leurent, Georges-Philippe, Pageaux, Vincent, Leroy, Sylvie, Radenne, Christine, Silvain, Pascal, Lebray, Pauline, Houssel-Debry, Carole, Cagnot, Emilie, Rossignol, Hélène, Danjou, Aurélie, Veislinger, Didier, Samuel, Jean-Charles, Duclos-Vallée, Jérôme, Dumortier, Hôpital Paul Brousse, Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Dynamique des systèmes d'adhérence et différenciation (DySAD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Albert Bonniot, Hospices Civils de Lyon, Departement de Neurologie (HCL), Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Hospices Civils de Lyon (HCL), and The study was sponsored and funded by The National Agency for Research on AIDS and Viral Hepatitis (ANRS, France Recherche Nord&sud Sida-hiv Hépatites).

Subjects
Liver Cirrhosis, Liver transplantation, Hepatology, Cholangitis, Fibrosing cholestatic hepatitis, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepacivirus, Hepatitis C, Chronic, Antiviral Agents, Hepatitis C, Fibrosis, Treatment, Recurrence, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, HCV, Pathology, Humans, Retrospective Studies
Abstract

International audience; INTRODUCTION: Hepatitis C virus (HCV) may recur after liver transplantation (LT) in the severe form of fibrosing cholestatic hepatitis (FCH). The prognosis dramatically improved by the use of direct acting antivirals (DAAs). The aim of the present study was to describe the change in histological features of FCH after virological eradication. METHODS: From the ANRS CUPILT cohort we included 17 patients who presented FCH and at least two graft biopsies, one before DAA-treatment and one after. A single expert pathologist, blinded for clinical outcome, retrospectively confirmed the diagnosis of FCH and progression of fibrosis. RESULTS: Diagnosis of FCH was made after a median [IQR] 6.0 [3.1-11.8] months after LT, and the median interval between diagnosis and onset of treatment was 1.2 [0.7-6.1] months. The rate of viral eradication was 94.1%. The median delay between the pre-treatment and the treatment biopsies was 12.5 [11.1-20.0] months. Between the end of treatment and the second biopsy, the delay was 5.3 [0.6-7.4] months. Fibrosis stage worsened in 10 patients (58.8%); 6 patients had cirrhosis (35.3%). Chronic rejection appeared in 4 (23.5%) patients. CONCLUSION: Our results suggest that, despite viral eradication in patients presenting FCH after LT, fibrosis progression was observed in half of patients. This should encourage monitoring fibrosis progression despite HCV cure.

Published
2022
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13. Development of an organ failure score in acute liver failure for transplant selection and identification of patients at high risk of futility.

Author

Francesco Figorilli, Antonella Putignano, Olivier Roux, Pauline Houssel-Debry, Claire Francoz, Catherine Paugam-Burtz, Olivier Soubrane, Banwari Agarwal, François Durand, and Rajiv Jalan

Subjects
Medicine, Science
Abstract

King's College Hospital criteria are currently used to select liver transplant candidates in acetaminophen-related acute liver failure (ALF). Although widely accepted, they show a poor sensitivity in predicting pre-transplant mortality and cannot predict the outcome after surgery. In this study we aimed to develop a new prognostic score that can allow patient selection for liver transplantation more appropriately and identify patients at high risk of futile transplantation.We analysed consecutive patients admitted to the Royal Free and Beaujon Hospitals between 1990 and 2015. Clinical and laboratory data at admission were collected. Predictors of 3-month mortality in the non-transplanted patients admitted to the Royal Free Hospital were used to develop the new score, which was then validated against the Beaujon cohort. The Beaujon-transplanted group was also used to assess the ability of the new score in identifying patients at high risk of transplant futility.152 patients were included of who 44 were transplanted. SOFA, CLIF-C OF and CLIF-ACLF scores were the best predictors of 3-month mortality among non-transplanted patients. CLIF-C OF score and high dosages of norepinephrine requirement were the only significant predictors of 3-month mortality in the non-transplanted patients, and therefore were included in the ALF-OFs score. In non-transplanted patients, ALF-OFs showed good performance in both exploratory (AUC = 0.89; sensitivity = 82.6%; specificity = 89.5%) and the validation cohort (AUC = 0.988; sensitivity = 100%; specificity = 92.3%). ALF-OFs score was also able to identify patients at high risk of transplant futility (AUC = 0.917; sensitivity = 100%; specificity = 79.2%).ALF-OFs is a new prognostic score in acetaminophen-related ALF that can predict both the need for liver transplant and high risk of transplant futility, improving candidate selection for liver transplantation.

Published
2017
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14. Radiomic analysis of liver grafts from brain-dead donors can predict early allograft dysfunction following transplantation: a proof-of-concept study

Author

Fabien Robin, Zine-Eddine Khene, Marie Livin, Corentin Sumner, Pauline Houssel-Debry, Laurent Sulpice, Karim Boudjema, Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and CHU Pontchaillou [Rennes]

Subjects
Brain Death, Hepatology, Graft Survival, Gastroenterology, Brain, [SDV.CAN]Life Sciences [q-bio]/Cancer, Allografts, Tissue Donors, Liver Transplantation, Liver, Predictive Value of Tests, Risk Factors, Humans, Primary Graft Dysfunction, Biomarkers, Retrospective Studies
Abstract

International audience; BACKGROUND: Selection of liver grafts suitable for transplantation (LT) mainly depends on a surgeon’s subjective assessment. This study aimed to investigate the role of radiomic analysis of donor-liver CTs after brain death (DBD) to predict the occurrence of early posttransplant allograft dysfunction (EAD). METHODS: We retrospectively extracted and analyzed the left lobe radiomic features from CT scans of DBD livers in training and validation cohorts. Multivariate analysis was performed to identify predictors of EAD. RESULTS: From 126 LTs included in the study in the training cohort, 27 (21.4%) had an EAD. For each patient, 279 radiomic features were extracted of which 5 were associated with EAD (AUC = 0.81) (95% CI 0.72-0.89). Among donor and recipient clinical characteristics, cardiac arrest, steatosis on donor’s CT, cold ischemic time and age of recipient were also identified as independent risk factors for EAD. Combined radiomic signature and clinical risk factors showed a strong predictive performance for EAD with a C-index of 0.90 (95% CI 0.84-0.96). A validation cohort of 23 patients confirmed these results. CONCLUSION: Radiomic signatures extracted from donor CT scan, independently or combined with clinical risk factors is an objective and accurate biomarker for prediction of EAD after LT.

Published
2022
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15. Covid-19 in liver transplant recipients: the French SOT COVID registry

Author

A. Mazzola, Lucy Meunier, Faouzi Saliba, Hélène Barraud, Vincent Leroy, Camille Besch, Maxime Mallet, Jérôme Dumortier, Mario Altieri, Sophie Caillard, Sylvie Radenne, Noémie Laverdure, Jean Philippe Richardet, Claire Vanlemmens, Pauline Houssel-Debry, Filomena Conti, Ilias Kounis, Marc Hazzan, Sébastien Dharancy, Claire Francoz, Florentine Garaix, Olivier Roux, François Durand, Christophe Duvoux, Audrey Coilly, Guillaume Lassailly, CCSD, Accord Elsevier, Hospices Civils de Lyon (HCL), Hôpital Edouard Herriot [CHU - HCL], Hôpital Henri Mondor, 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 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), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital de Hautepierre [Strasbourg], Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Paul Brousse, Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Claude Huriez [Lille], CHU Lille, Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Pontchaillou [Rennes], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital de la Croix-Rousse [CHU - HCL], Hôpital JeanMinjoz, French Solid Organ Transplant COVID Registry, and Groupe de Recherche Français en Greffe de Foie (GReF²)

Subjects
Male, MESH: Registries, [SDV]Life Sciences [q-bio], medicine.medical_treatment, MESH: Comorbidity, MESH: Hospitalization, Comorbidity, Liver transplantation, Overweight, MESH: Immunosuppression Therapy, Organ transplantation, law.invention, 0302 clinical medicine, MESH: Risk Factors, law, Risk Factors, MESH: Child, MESH: COVID-19, Registries, MESH: Respiration, Artificial, Child, MESH: Aged, MESH: Middle Aged, immunosuppression, liver transplantation, Mortality rate, Gastroenterology, Immunosuppression, Middle Aged, Intensive care unit, [SDV] Life Sciences [q-bio], Hospitalization, Intensive Care Units, 030220 oncology & carcinogenesis, COVID-19 Nucleic Acid Testing, 030211 gastroenterology & hepatology, Female, Original Article, France, medicine.symptom, Covid-19, MESH: Liver Transplantation, MESH: Pandemics, medicine.medical_specialty, Adolescent, MESH: Transplant Recipients, MESH: COVID-19 Nucleic Acid Testing, 03 medical and health sciences, Diabetes mellitus, Internal medicine, medicine, Humans, Pandemics, Aged, MESH: Adolescent, Mechanical ventilation, Immunosuppression Therapy, MESH: Humans, Hepatology, business.industry, medicine.disease, Respiration, Artificial, mortality, MESH: Male, Transplant Recipients, MESH: France, MESH: Intensive Care Units, prognosis, business, MESH: Female
Abstract

Highlights • Coronavirus disease-2019 (Covid-19) is an ongoing global pandemic of major concern; available data on clinical presentation and prognosis in liver transplant (LT) recipients remains limited. • Disease presentation, immunosuppression management, clinical outcomes, and prognostic factors in 104 French LT recipients (91 adults) with Covid-19 are reported. • The composite endpoint of severe Covid-19 within 30 days after diagnosis was reached by 33.0% of the adult patients. • The 30-day mortality rate of all adult patients was 20.0%, and 28.1% for hospitalized patients., Background Notwithstanding the ongoing coronavirus disease-2019 (Covid-19) pandemic, information on its clinical presentation and prognosis in organ transplant recipients remains limited. The aim of this registry-based observational study was to report the characteristics and clinical outcomes of liver transplant (LT) recipients included in the French nationwide Registry of Solid Organ Transplant Recipients with Covid-19. Methods COVID-19 was diagnosed in patients who had a positive PCR assay for SARS-CoV-2 or in presence of typical lung lesions on imaging or specific SARS-CoV-2 antibodies. Clinical and laboratory characteristics, management of immunosuppression, treatment for Covid-19, and clinical outcomes (hospitalization, admission to intensive care unit, mechanical ventilation, or death) were recorded. Results Of the 104 patients, 67 were admitted to hospital and 37 were managed at home (including all 13 children). Hospitalized patients had a median age of 65.2 years (IQR: 58.1 − 73.2 years) and two thirds were men. Most common comorbidities included overweight (67.3%), hypertension (61.2%), diabetes (50.7%), cardiovascular disease (20.9%) and respiratory disease (16.4%). SARS-CoV-2 infection was identified after a median of 92.8 months (IQR: 40.1 − 194.7 months) from LT. During hospitalization, antimetabolites, mTOR inhibitor, and CNIs were withdrawn in 41.9%, 30.0% and 12.5% of patients, respectively. The composite endpoint of severe Covid-19 within 30 days after diagnosis was reached by 33.0% of the adult patients. The 30-day mortality rate was 20.0%, and 28.1% for hospitalized patients. Multivariate analysis identified that age was independently associated with mortality. Conclusion In our large nationwide study, Covid-19 in LT recipients was associated with a high mortality rate.

Published
2021
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16. Volumetric absorptive microsampling for the quantification of tacrolimus in capillary blood by high performance liquid chromatography-tandem mass spectrometry

Author

Marie-José Ferrand-Sorre, Julie Querzerho-Raguideau, Eric Bellissant, Jonathan M. Chemouny, Marie-Clémence Verdier, Pauline Houssel-Debry, Florian Lemaitre, Camille Tron, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), 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], École des Hautes Études en Santé Publique [EHESP] (EHESP), Jonchère, Laurent, Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université 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
[SDV]Life Sciences [q-bio], Clinical Biochemistry, Liquid chromatography, Hematocrit, Therapeutic drug monitoring, Tandem mass spectrometry, Sensitivity and Specificity, 030226 pharmacology & pharmacy, 01 natural sciences, Biochemistry, High-performance liquid chromatography, Tacrolimus, Analytical Chemistry, 03 medical and health sciences, 0302 clinical medicine, Tandem Mass Spectrometry, medicine, Humans, Protein precipitation, Volumetric absorptive microsampling, Chromatography, High Pressure Liquid, Whole blood, Blood Specimen Collection, Venipuncture, Chromatography, medicine.diagnostic_test, Mass spectrometry, Chemistry, 010401 analytical chemistry, Reproducibility of Results, Cell Biology, General Medicine, 0104 chemical sciences, [SDV] Life Sciences [q-bio], surgical procedures, operative, Linear Models, Dried Blood Spot Testing, Drug Monitoring
Abstract

International audience; Volumetric absorptive microsampling (VAMS) is an innovative alternative strategy to venipuncture for monitoring tacrolimus levels in transplant recipients. In this study, we aimed to validate a new high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for quantifying tacrolimus in blood collected by VAMS. Tacrolimus was extracted from dried blood tips in an original process involving sonication, protein precipitation and salting out. The assay was validated in accordance with EMA and IATDMCT guidelines. For clinical validation, the tacrolimus concentrations measured in liquid venous whole blood (with the reference method) were compared with those measured in capillary whole blood collected simultaneously with VAMS by a nurse. The assay was then used to monitor tacrolimus exposure in transplant recipients. The method was linear, sensitive and fast. Within-day and between-day precisions and overall bias were within ±15%. No significant hematocrit effect was observed. The matrix effect was negligible and recovery exceeded 80% for every concentration and hematocrit levels. Tacrolimus was stable in blood collected by VAMS for 1 week at room temperature, 48 h at 60 °C and 4 °C and 1 month at -80 °C. Clinical validation (n = 42 paired samples) demonstrated a strong correlation between the two methods (r = 0.97 Pearson correlation). Bland-Altman analysis revealed that more than 90% of the differences between VAMS and liquid blood paired concentrations were within the ±20% acceptable range. The method had a satisfactory analytical performance and fulfilled clinical requirements. This minimally invasive VAMS-based assay appears reliable for the determination of tacrolimus levels in blood from transplanted patients.

Published
2021
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17. Microsporidiosis after liver transplantation: A French nationwide retrospective study

Author

Jérôme, Dumortier, Sylvie, Radenne, Nassim, Kamar, Filomena, Conti, Armand, Abergel, Audrey, Coilly, Claire, Francoz, Pauline, Houssel-Debry, Claire, Vanlemmens, Noémie, Laverdure, Christophe, Duvoux, Xavier, Iriart, Marc, Thellier, Adela, Angoulvant, Nicolas, Argy, Brice, Autier, Anne-Pauline, Bellanger, Françoise, Botterel, Cyril, Garrouste, Meja, Rabodonirina, Philippe, Poirier, Perraud, Estelle, Hospices Civils de Lyon (HCL), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), AP-HP, Hôpital Henri-Mondor Albert-Chenevier, Service d'Immunologie Clinique et Maladies Infectieuses 94000 Créteil, France, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Clermont-Ferrand, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
Graft Rejection, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030230 surgery, Liver transplantation, Microsporidiosis, Gastroenterology, Tacrolimus, Albendazole, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Fumagillin, Child, Dialysis, Retrospective Studies, Transplantation, liver transplantation, business.industry, Retrospective cohort study, Organ Transplantation, Middle Aged, medicine.disease, 3. Good health, Diarrhea, Infectious Diseases, microsporidiosis, Cyclosporine, 030211 gastroenterology & hepatology, medicine.symptom, business, Immunosuppressive Agents, medicine.drug
Abstract

International audience; Background: Microsporidiosis has been largely reported in patients with acquired immunodeficiency syndrome, but emerged as a cause of persistent diarrhea in solid organ transplant patients.Methods: Through the French Microsporidiosis Network and the Groupe français de recherche en greffe de foie, we collected all microsporidiosis cases identified in liver transplant patients between 1995 and 2020 in France.Results: We identified 24 liver transplant recipients with microsporidiosis. Sex ratio was balanced and median age was 58.8 (3.5-83.5) years (there were 4 children). Microsporidiosis occurred at a median time of 3.9 (0.1-18.9) years post-transplant. Median duration of diarrhea before diagnosis was 22 days (12-45). Therapeutic care included immunosuppressive therapy changes in 20 patients, as follows: stop cyclosporine or tacrolimus (n = 2), dose reduction of cyclosporine or tacrolimus (n = 12), stop MMF (n = 5), and dose reduction of corticosteroids (n = 1). In addition, 15 patients received specific therapy against microsporidiosis: fumagillin (n = 11) or albendazole (n = 4). Median duration of treatment was 14 days (8-45 days). Finally, 7 patients had immunosuppressive treatment tapering only. Microsporidiosis was complicated by renal failure in 15 patients, requiring dialysis in one case. Two patients had infection relapse. No patient presented proven rejection within the 3 months after microsporidiosis. None of the patients died within the 3 months after microsporidiosis.Conclusions: Microsporidiosis is a very rare infection after liver transplantation but can induce severe dehydration and renal failure. Therefore, it must be systematically sought in any case of persistent diarrhea after first line screening of frequent infectious causes.

Published
2021
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18. Long term results of liver transplantation for alpha-1 antitrypsin deficiency

Author

Alain Lachaux, Eduardo Couchonnal, Christophe Duvoux, Jean Gugenheim, Dominique Debray, Sylvie Radenne, Marie-Noëlle Hilleret, Emmanuel Jacquemin, Filomena Conti, Audrey Coilly, Claire Vanlemmens, Olivier Guillaud, Florence Lacaille, Yasmina Chouik, Valérie A. McLin, Didier Samuel, Nassim Kamar, Georges-Philippe Pageaux, Emmanuel Gonzales, Oanez Ackermann, Jean-Charles Duclos-Vallée, Claire Francoz, Jérôme Dumortier, Mathias Ruiz, Pauline Houssel-Debry, Martine Neau-Cransac, Herrada, Anthony, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Clinique de la Sauvegarde [Lyon], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Grenoble, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Pontchaillou [Rennes], Hôpital Haut-Lévêque [CHU Bordeaux], 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), Centre Hospitalier Universitaire de Nice (CHU Nice), Université de Lyon, 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), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpitaux Universitaires de Genève (HUG), Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, CHU Toulouse [Toulouse], 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 de Rangueil, and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Survival, medicine.medical_treatment, Kaplan-Meier Estimate, Liver transplantation, Gastroenterology, Disease-Free Survival, 03 medical and health sciences, Liver disease, 0302 clinical medicine, alpha 1-Antitrypsin Deficiency, Internal medicine, Genotype, medicine, Humans, Child, Alpha1 antitrypsin, Outcome, Alpha 1-antitrypsin deficiency, ddc:618, Hepatology, business.industry, Medical record, Graft Survival, Retrospective cohort study, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Middle Aged, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, 030220 oncology & carcinogenesis, Cohort, Population study, Female, 030211 gastroenterology & hepatology, business, Follow-Up Studies
Abstract

International audience; Introduction: Liver transplantation (LT) is the therapeutic option for end-stage liver disease associated with alpha1 antitrypsin (A1AT) deficiency. The aim of the present retrospective study was to report on long-term outcomes following LT for A1AT deficiency.Methods: The medical records of 90 pediatric and adult patients transplanted between 1982 and 2017 in France and Geneva (Switzerland) were reviewed.Results: The study population consisted of 32 adults and 58 children; median age at transplant was 13.0 years (range: 0.2-65.1), and 65 were male (72.2%). Eighty-two patients (94.8% of children and 84.4% of adults) had the PI*ZZ genotype/phenotype and eight patients (8.9%) had the Pi*SZ genotype/phenotype. Eighty-four patients (93.3%) were transplanted for end-stage liver disease and six (all Pi*ZZ adults) for HCC. Median follow-up after LT was 13.6 years (0.1-31.7). The overall cumulative patient survival rates post-transplant were 97.8% at 1 year, and 95.5%, 95.5%, 92.0%, 89.1% at 5, 10, 15, 20 years respectively. The overall cumulative graft survival rates were 92.2% at 1 year, and 89.9%, 89.9%, 84.4%, 81.5% at 5, 10, 15 and 20 years, respectively.Conclusions: In a representative cohort of patients having presented with end-stage-liver disease or HCC secondary to A1AT, liver transplantation offered very good patient and graft survival rates.

Published
2021
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19. Redefining Therapeutic Drug Monitoring of Tacrolimus in Patients Undergoing Liver Transplantation: A Target Trough Concentration of 4-7 ng/mL During the First Month After Liver Transplantation is Safe and Improves Graft and Renal Function

Author

Eric Bellissant, Damien Bergeat, Nicolas Collet, Christophe Camus, Thomas Renard, Florian Lemaitre, Cedric Pastoret, Camille Tron, Antoine Petitcollin, Pauline Houssel-Debry, Michel Rayar, Marie-Clémence Verdier, Edouard Bardou-Jacquet, Caroline Jezequel, Karim Boudjema, CHU Pontchaillou [Rennes], Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes - Faculté de Médecine (UR Médecine), Université de Rennes (UR), and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Graft Rejection, Male, medicine.medical_specialty, Adolescent, Bilirubin, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, Urology, Renal function, Liver transplantation, 030226 pharmacology & pharmacy, Drug Administration Schedule, Tacrolimus, 03 medical and health sciences, Cmin, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, otorhinolaryngologic diseases, Medicine, Humans, Pharmacology (medical), education, Aged, Pharmacology, Creatinine, education.field_of_study, medicine.diagnostic_test, integumentary system, business.industry, Graft Survival, Middle Aged, Kidney Transplantation, Liver Transplantation, chemistry, Therapeutic drug monitoring, Trough level, Female, sense organs, Drug Monitoring, business, Immunosuppressive Agents
Abstract

International audience; Background - As a marker of cumulative cortisol activity, hair cortisol has received attention in clinical and methodological research. Currently, it is a common practice to relate the hair cortisol concentration (HCC) to hair weight. This article explores the hair protein concentration (HPC) as another possible reference value for HCC. Methods - For n = 18 hair samples cut from the posterior vertex, the HCC, HPC, and hair sample weight were determined, and the cortisol-to-weight and cortisol-to-protein ratios were calculated. Correlations were analyzed between the HCC, HPC, and hair sample weight as well as between the cortisol-to-weight and cortisol-to-protein ratios. Hair sample weight and HPC were included as independent variables in a stepwise linear regression model to predict HCC. Results - The HCC and HPC did not correlate significantly (r = 0.393, P = 0.106); however, the correlation between HCC and hair sample weight was significant (r = 0.520, P = 0.027). The HPC and hair sample weight (r = 0.605, P = 0.008) as well as the cortisol-to-weight and cortisol-to-protein ratios (r = 0.858, P < 0.000) showed a high correlation. The hair sample weight was the better predictor of the HCC (β = 0.520, P = 0.027) than HPC (β = 0.125, P = 0.657). Conclusions - The results indicate that the hair sample weight is the more suitable reference value for the HCC. Thus, the standard cortisol-to-weight ratio should be used as the preferred expression for the cumulative cortisol activity measured in the scalp hair. However, calculating the cortisol-to-protein ratio can be considered as an alternative if the hair sample weight is not available.

Published
2020
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20. Performance of B-mode ratio and 2D shear wave elastography for the detection and quantification of hepatic steatosis and fibrosis after liver transplantation

Author

Luc Beuzit, Bruno Turlin, Christophe Aubé, Marine Dubois, Pauline Houssel-Debry, Maxime Ronot, Magali Auger, Anita Paisant, Michel Rayar, Vanessa Brun, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
Liver Cirrhosis, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Liver transplantation, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Internal medicine, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Hepatology, medicine.diagnostic_test, Receiver operating characteristic, business.industry, Ultrasound, Gold standard (test), medicine.disease, Liver Transplantation, 3. Good health, Fatty Liver, Transplantation, Liver, 030220 oncology & carcinogenesis, Liver biopsy, Elasticity Imaging Techniques, 030211 gastroenterology & hepatology, Steatosis, business
Abstract

OBJECTIVES To evaluate the diagnostic performance of B-mode ratio and shear wave elastography (SWE) for the assessment of steatosis and liver fibrosis after liver transplantation. MATERIALS AND METHODS Patients hospitalized for a systematic check-up after liver transplantation underwent the same day hepatic ultrasound with B-mode ratio and SWE, followed by liver biopsy and biological examinations. Steatosis was measured using hepatorenal sonographic index of B-mode ratio and liver stiffness using SWE. Liver biopsy, used as gold standard, graded steatosis S0(

Published
2020
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21. Iron metabolism imbalance at the time of listing increases overall and infectious mortality after liver transplantation

Author

Karim Boudjema, Caroline Jezequel, Amandine Landrieux, Christophe Camus, Thomas Uguen, Dominique Guyader, Michel Rayar, Edouard Bardou-Jacquet, Pauline Houssel-Debry, Elodie Fallet, Martine Ropert-Bouchet, L. Legros, CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), 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
Male, Cirrhosis, Overload, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Transferrin saturation, Liver transplantation, Gastroenterology, 0302 clinical medicine, Postoperative Complications, Risk Factors, Prospective Studies, Prospective cohort study, biology, Liver Neoplasms, Transferrin, General Medicine, Iron deficiency, Middle Aged, 3. Good health, Survival Rate, Death, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Infection, medicine.medical_specialty, Carcinoma, Hepatocellular, Iron, Infections, Risk Assessment, End Stage Liver Disease, 03 medical and health sciences, Retrospective Study, Internal medicine, medicine, Humans, Risk factor, Retrospective Studies, Ferritin, Proportional hazards model, business.industry, medicine.disease, Liver Transplantation, Ferritins, biology.protein, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract

International audience; BACKGROUND Liver transplantation (LT) is the best treatment for patients with liver cancer or end stage cirrhosis, but it is still associated with a significant mortality. Therefore identifying factors associated with mortality could help improve patient management. The impact of iron metabolism, which could be a relevant therapeutic target, yield discrepant results in this setting. Previous studies suggest that increased serum ferritin is associated with higher mortality. Surprisingly iron deficiency which is a well described risk factor in critically ill patients has not been considered. AIM To assess the impact of pre-transplant iron metabolism parameters on post-transplant survival. METHODS From 2001 to 2011, 553 patients who underwent LT with iron metabolism parameters available at LT evaluation were included. Data were prospectively recorded at the time of evaluation and at the time of LT regarding donor and recipient. Serum ferritin (SF) and transferrin saturation (TS) were studied as continuous and categorical variable. Cox regression analysis was used to determine mortality risks factors. Follow-up data were obtained from the local and national database regarding causes of death. RESULTS At the end of a 95-mo median follow-up, 196 patients were dead, 38 of them because of infections. In multivariate analysis, overall mortality was significantly associated with TS > 75% [HR 1.73 (1.14; 2.63)], SF < 100 mu g/L [HR 1.62 (1.12; 2.35)], hepatocellular carcinoma [HR 1.58 (1.15; 2.26)], estimated glomerular filtration rate (CKD EPI Cystatin C) [HR 0.99 (0.98; 0.99)], and packed red blood cell transfusion [HR 1.05 (1.03; 1.08)]. Kaplan Meier curves show that patients with low SF (< 100 mu g/L) or high SF (> 400 mu g/L) have lower survival rates at 36 mo than patients with normal SF (P = 0.008 and P = 0.016 respectively). Patients with TS higher than 75% had higher mortality at 12 mo (91.4% +/- 1.4% vs 84.6% +/- 3.1%, P = 0.039). TS > 75% was significantly associated with infection related death [HR 3.06 (1.13; 8.23)]. CONCLUSION Our results show that iron metabolism imbalance (either deficiency or overload) is associated with post-transplant overall and infectious mortality. Impact of iron supplementation or depletion should be assessed in prospective study.

Published
2020
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22. Comparison of the effect of direct-acting antiviral with and without ribavirin on cyclosporine and tacrolimus clearance values results from the ANRS CO23 CUPILT cohort

Author

Thibaut Gelé, Christophe Duvoux, Anne Marie Taburet, Didier Samuel, Carole Cagnot, Claire Laforest, Christophe Moreno, Valérie Canva, H. Danjou, Georges-Philippe Pageaux, Victor de Lédinghen, Danielle Botta-Fridlund, Nassim Kamar, Audrey Lavenu, Lauriane Goldwirt, Sylvie Radenne, Claire Fougerou-Leurent, Filomena Conti, François Durand, Aurélie Barrail-Tran, Vincent Leroy, Louis d’Alteroche, Jean-Charles Duclos-Vallée, Pauline Houssel-Debry, Audrey Coilly, Université Paris-Sud - Paris 11 (UP11), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), CHU Grenoble, Hôpital Claude Huriez [Lille], CHU Lille, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Marseille, Université libre de Bruxelles (ULB), ANRS France Recherche Nord & sud Sida-hiv hépatites, 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), Hôpital Paul Brousse, Hôpital Lapeyronie [Montpellier] (CHU), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Agence Nationale de Recherches sur le Sida et les Hépatites Virales, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
Male, Pyrrolidines, Sofosbuvir, medicine.medical_treatment, [SDV]Life Sciences [q-bio], HIV Infections, Liver transplantation, Pharmacologie, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Pharmacology (medical), Drug Interactions, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Imidazoles, Anemia, Valine, General Medicine, Hepatitis C, Middle Aged, 3. Good health, Cyclosporine, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, Immunosuppressive Agents, medicine.drug, medicine.medical_specialty, Daclatasvir, Liver fibrosis, Anaemia, Antiviral Agents, Tacrolimus, 03 medical and health sciences, Internal medicine, Ribavirin, medicine, Humans, Aged, Pharmacology, business.industry, medicine.disease, Liver Transplantation, Calcineurin, Regimen, chemistry, Carbamates, business
Abstract

Purpose: Direct-acting antiviral agents have demonstrated their efficacy in treating HCV recurrence after liver transplantation and particularly the sofosbuvir/daclatasvir combination. Pharmacokinetic data on both calcineurin inhibitors and direct-acting antiviral exposure in liver transplant recipients remain sparse. Methods: Patients were enrolled from the ANRS CO23 CUPILT cohort. All patients treated with sofosbuvir/daclatasvir with or without ribavirin were included in this study when blood samples were available to estimate the clearance of immunosuppressive therapy before direct-acting antiviral initiation and during follow-up. Apparent tacrolimus and cyclosporine clearances were estimated from trough concentrations measured using validated quality control assays. Results: Sixty-seven mainly male patients (79%) were included, with a mean age of 57 years and mean MELD score of 8.2; 50 were on tacrolimus, 17 on cyclosporine. Ribavirin was combined with sofosbuvir/daclatasvir in 52% of patients. Cyclosporine clearance remained unchanged as well as tacrolimus clearance under the ribavirin-free regimen. Tacrolimus clearance increased 4 weeks after direct-acting antivirals and ribavirin initiation versus baseline (geometric mean ratio 1.81; 90% CI 1.30–2.52). Patients under ribavirin had a significantly higher fibrosis stage (> 2) (p = 0.02) and lower haemoglobin during direct-acting antiviral treatment (p = 0.02) which impacted tacrolimus measurements. Direct-acting antiviral exposure was within the expected range. Conclusion: Our study demonstrated that liver transplant patients with a recurrence of hepatitis C who are initiating ribavirin combined with a sofosbuvir-daclatasvir direct-acting antiviral regimen may be at risk of lower tacrolimus concentrations because of probable ribavirin-induced anaemia and higher fibrosis score, although there are no effects on cyclosporine levels. Trial registration: NCT 01944527., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2019
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23. A Preliminary Clinical Experience Using Hypothermic Oxygenated Machine Perfusion for Rapid Recovery of Octogenarian Liver Grafts

Author

Laurent Sulpice, Michel Rayar, Christophe Camus, Damien Bergeat, Betty Maillot, Karim Boudjema, Pauline Houssel-Debry, Bernard Meunier, 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], Rennes hospital, 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
Male, medicine.medical_treatment, octogenarian graft, [SDV]Life Sciences [q-bio], MEDLINE, 030230 surgery, Liver transplantation, 03 medical and health sciences, 0302 clinical medicine, Extracorporeal Membrane Oxygenation, Medicine, Humans, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Transplantation, Machine perfusion, liver transplantation, business.industry, machine perfusion, extended criteria donor, Hyperthermia, Induced, Organ Preservation, Middle Aged, Tissue Donors, 3. Good health, Liver, Anesthesia, HOPE, 030211 gastroenterology & hepatology, business, Blood Flow Velocity
Abstract

International audience

Published
2019
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24. Impact of the New MELD-based Allocation System on Waiting List and Post-Transplant Survival - A Cohort Analysis Using the French National CRISTAL Database

Author

Carine Jasseron, Claire Francoz, Corinne Antoine, Camille Legeai, François Durand, Sébastien Dharancy, null Collaborators, Christan Jacquelinet, Daniel Azoulay, Christophe Duvoux, Olivier Scatton, Yvon Calmus, Daniel Cherqui, Didier Samuel, Olivier Soubrane, Jean‐Yves Mabrut, Jérôme Dumortier, Christian Letoublon, Vincent Leroy, Denis Pezet, Armand Abergel, Antonio Iannelli, Rodolphe Anty, Francis Navarro, Georges Pageaux, François‐René Pruvot, Philippe Bachellier, Camille Besh, Georges Mantion, Vincent Di Martino, Nassim Kamar, Fabrice Muscari, Laurence Chiche, Martine Neau Cransac, Karim Boudjema, Pauline Houssel Debry, Ephrem Salame, Agence de la biomédecine [Saint-Denis la Plaine], 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), Université Paris 8 Vincennes-Saint-Denis (UP8), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Claude Huriez [Lille], CHU Lille, 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), CHU Henri Mondor, 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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Département de chirurgie digestive et de l'urgence, CHU Grenoble-Hôpital Michallon, Hôpital Michallon, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Strasbourg, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Chirurgie Générale et Digestive [Rangueil], Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), CHU Henri Mondor [Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)

Subjects
medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030230 surgery, Liver transplantation, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Intubation, allocation system, Dialysis, Transplantation, business.industry, MELD score, discriminative capacity, Post transplant, 3. Good health, body regions, Waiting list, 030211 gastroenterology & hepatology, business, survival, Cohort study
Abstract

International audience; Concerns related to equity and efficacy of our previous center-based allocation system have led us to introduce a patient-based allocation system called the "Liver Score" that incorporates the MELD score. The main objective of this study was to compare waitlist and post-transplant survivals before and after implementation of the "Liver Score" using the French transplant registry (period before: 2004-2006 and period after: 2007-2012). Patients transplanted during the second period were sicker and had a higher MELD. One-year waitlist survival (74% versus 76%; p=0.8) and one-year post-transplant survival (86.3% vs 85.7%; p=0.5) were similar between the 2 periods. Cirrhotic recipients with MELD>35 had lower one-year post-transplant survival compared to those with MELD35, patients presenting 2 or 3 risk factors (dialysis, intubation or infection) had a lower 1-year survival compared to those with none of these risk factors (61.2% vs 92%; p35 should be completed to allow safe transplantation. This article is protected by copyright. All rights reserved.

Published
2019
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25. 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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26. Safety of sofosbuvir-based regimens after liver transplantation longitudinal assessment of renal function in the prospective ANRS CO23 CUPILT study

Author

Rodolphe Anty, Alpha Diallo, Vincent Leroy, L. D’Alteroche, Jean Charles Duclos-Vallée, Claire Fougerou-Leurent, Christophe Duvoux, Vincent L.M. Esnault, P. Perré, François Habersetzer, Audrey Coilly, Aurelie Veislinger, Nassim Kamar, V. Di Martino, Emilie Rossignol, Valérie Canva, Maryline Debette-Gratien, Carole Cagnot, François Durand, Didier Samuel, Clémence M. Canivet, Danielle Botta-Fridlund, H. Montialoux, V. de Ledinghen, Christine Silvain, Camille Besch, Jérôme Dumortier, Albert Tran, Guillaume Favre, Pauline Houssel-Debry, Georges Philippe Pageaux, S. Radenne, H. Danjou, Sébastien Dharancy, Fabio Conti, Pascal Lebray, Armando Abergel, Christophe Moreno, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Laboratoire de PhysioMédecine Moléculaire (LP2M), 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)-Université Côte d'Azur (UCA), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Grenoble, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Toulouse [Toulouse], Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Edouard Herriot [CHU - HCL], 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), CHU Strasbourg, CHU Marseille, CHU Rouen, Normandie Université (NU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, CHU Limoges, ANRS France Recherche Nord & sud Sida-hiv hépatites, Hôpital Lapeyronie [Montpellier] (CHU), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)

Subjects
medicine.medical_specialty, Sofosbuvir, Hepatitis C virus, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Urology, Renal function, Hepacivirus, 030230 surgery, Liver transplantation, medicine.disease_cause, Kidney, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Recurrence, Ribavirin, Medicine, Humans, Pharmacology (medical), Longitudinal Studies, Prospective Studies, Renal Insufficiency, Chronic, Aged, Creatinine, Hepatology, business.industry, Gastroenterology, Middle Aged, Hepatitis C, 3. Good health, Liver Transplantation, medicine.anatomical_structure, chemistry, Cohort, 030211 gastroenterology & hepatology, Female, business, medicine.drug, Glomerular Filtration Rate
Abstract

International audience; Background In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir-based regimens. Changes in serum creatinine or in the estimated glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable. Aim To analyse renal function trajectory with numerous assays of serum creatinine over a long period of time. Methods In a multicentre cohort of 139 patients, the eGFR was obtained from serum creatinine using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Slopes of eGFR were defined as a change in eGFR during a period divided by time. Pre-treatment, on-treatment and post-treatment periods were 9 months, 3-9 months and 4.5 months. Interactions between eGFR slopes and the pre-treatment eGFR, use of ribavirin or mycophenolate mofetil, and stage of fibrosis were addressed. On-treatment eGFR slopes were separated in tertiles. Pre- and post-treatment eGFR slopes were compared globally and according to tertiles. Results The post-treatment eGFR slope was significantly better than pre-treatment eGFR slope (+0.18 (IQR -0.76 to +1.32) vs -0.11 (IQR -1.01 to +0.73) mL/min/1.73 m(2)/month, P=0.03) independently of the pre-treatment eGFR (P=0.99), ribavirin administration (P=0.26), mycophenolate mofetil administration (P=0.51) and stage of fibrosis (F3 and F4 vs lower stages, P=0.18; F4 vs lower stages, P=0.08; F4 Child-Pugh B and C vs lower stages, P=0.38). Tertiles of on-treatment eGFR slopes were -1.71 (IQR -2.54 to -1.48), -0.78 (IQR -1.03 to -0.36) and +0.75 (IQR +0.28 to +1.47) mL/min/1.73 m(2)/month. Pre- and post-treatment eGFR slopes were not significantly different according to tertiles (respectively, P=0.34, 0.08, 0.73). Conclusion The eGFR varies during treatment and gives a confusing picture of the renal safety of sofosbuvir-based regimens. In contrast, longitudinal assessment of the eGFR shows a rising trajectory over longer time, meaning that these therapies are safe for the kidneys in our cohort of liver transplant recipients.

Published
2018
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27. Sofosbuvir-Based Regimens in HIV/HCV Coinfected Patients after Liver Transplantation: Results from the ANRS CO23 CUPILT Study

Author

Didier Samuel, Audrey Coilly, Jérôme Dumortier, Vincent Leroy, Danielle Botta-Fridlund, Anne-Marie Taburet, P. Perré, A. Rohel, Aurelie Veislinger, Emilie Rossignol, Teresa Antonini, Valérie Canva, Pauline Houssel-Debry, Jean Charles Duclos-Vallée, Sylvie Radenne, Georges Philippe Pageaux, Alpha Diallo, Nassim Kamar, Claire Fougerou-Leurent, François Durand, V. de Ledinghen, 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 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 Claude Bernard Lyon 1 (UCBL), Université de Lyon, Dynamique des systèmes d'adhérence et différenciation (DySAD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), CHU Marseille, Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Foie, métabolismes et cancer, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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 Bordeaux [Bordeaux], ANRS France Recherche Nord & sud Sida-hiv hépatites, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Lapeyronie [Montpellier] (CHU), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Ledipasvir, Male, medicine.medical_specialty, Daclatasvir, Sofosbuvir, medicine.medical_treatment, Hepatitis C virus, [SDV]Life Sciences [q-bio], HIV Infections, Liver transplantation, medicine.disease_cause, Gastroenterology, Antiviral Agents, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Transplantation, business.industry, Coinfection, Ribavirin, virus diseases, Hepatitis C, Middle Aged, medicine.disease, 3. Good health, Liver Transplantation, chemistry, Liver, 030211 gastroenterology & hepatology, Female, business, Viral load, medicine.drug
Abstract

Background A recurrence of hepatitis C virus (HCV) after liver transplantation affects survival in human immunodeficiency virus (HIV)/HCV coinfected patients. This study assessed the efficacy and safety of sofosbuvir (SOF)-based regimens in HIV/HCV coinfected patients after liver transplantation. Methods Twenty-nine HIV/HCV coinfected transplanted patients receiving tacrolimus-, cyclosporine-, or everolimus-based immunosuppressive therapy were enrolled in the Compassionate Use of Protease Inhibitors in Viral C Liver Transplantation cohort. Their antiviral treatment combined SOF, daclatasvir with or without ribavirin (n = 10/n = 6), or SOF, ledipasvir with or without ribavirin (n = 2/n = 11). Results The median delay between liver transplantation and treatment initiation was 37.5 months (interquartile range [IQR], 14.4-99.2). The breakdown of HCV genotypes was G1, 22 patients (75.9%); G3, 3 patients (10.3%); and G4, 4 patients (13.8%). The treatment indications were HCV recurrence (≥ F1 n = 23) or fibrosing cholestatic hepatitis (n = 6). Before starting SOF, the HCV viral load and CD4 count were 6.7 log 10 IU/mL (IQR, 5.9-7.2) and 342 cells/mm 3 (IQR, 172-483), respectively. At week 4, the HCV viral load was less than 15 IU/mL in 12 (42.9%) patients. The overall sustained virological response 12 was 96.6%. No significant drug-drug interactions were observed. Conclusions SOF-based treatment regimens produced excellent results in HIV/HCV coinfected patients after liver transplantation, suggesting an important change in their prognosis. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

Published
2018
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28. 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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29. O109 : Treatment of severe HCV-recurrence after liver transplantation using sofosbuvir-based regimens: The ANRS CO23 CUPILT study

Author

G.-P. Pageaux, Jean Charles Duclos-Vallée, F. Durand, L. D’Alteroche, Valérie Canva, H. Danjou, Audrey Coilly, Vincent Leroy, Danielle Botta-Fridlund, Claire Fougerou-Leurent, Pauline Houssel-Debry, Abou Diallo, Fabio Conti, Nassim Kamar, V. Di Martino, S. Radenne, Christophe Duvoux, A. Rohel, V. de Ledinghen, Jérôme Dumortier, 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), 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), 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, and CHU Toulouse [Toulouse]

Subjects
medicine.medical_specialty, Hepatology, Sofosbuvir, business.industry, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Hcv recurrence, Liver transplantation, Gastroenterology, 3. Good health, Internal medicine, medicine, business, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract

International audience; no abstract

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. P0804 : Efficacy of sofosbuvir-based treatment regimens in HIV/HCV co-infected patients after liver transplantation: The ANRS CO23 CUPILT study

Author

Jérôme Dumortier, Audrey Coilly, G.-P. Pageaux, Aurelie Veislinger, Teresa Antonini, I. Bertucci, Sylvie Radenne, Vincent Leroy, Didier Samuel, Nassim Kamar, Pauline Houssel-Debry, Franck Durand, Jean Charles Duclos-Vallée, Valérie Canva, P. Perré, Danielle Botta-Fridlund, Océan du Large et Variabilité Climatique (OLVAC), Laboratoire d'études en Géophysique et océanographie spatiales (LEGOS), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), 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), 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), Department of Multiorgan Transplantation, CHU Toulouse [Toulouse], Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Département d'hépatologie, Hospices Civils de Lyon (HCL), Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), 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), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National d'Études Spatiales [Toulouse] (CNES)-Observatoire Midi-Pyrénées (OMP), 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-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), and Matière et Systèmes Complexes (MSC)

Subjects
0303 health sciences, medicine.medical_specialty, Hepatology, Sofosbuvir, Treatment regimen, business.industry, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Liver transplantation, Gastroenterology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, 030211 gastroenterology & hepatology, business, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, medicine.drug
Abstract

International audience; no abstract

Published
2015
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33. Once-daily prolonged release tacrolimus in liver transplantation: Experts' literature review and recommendations

Author

Olivier Guillaud, Pauline Houssel-Debry, Audrey Coilly, Faiza Chermak, Christophe Duvoux, Martine Neau-Cransac, Yvon Calmus, Jérôme Dumortier, Jeanick Stocco, Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, 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 Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], service d'Hépato-gastro-entérologie, Hospices Civiles de Lyon-Hôpital Edouard Heriault, Pôle Recherche Clinique-Santé Publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, 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), Service des maladies du foie, Centre Hospitalier Universitaire [Rennes]-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital Beaujon, 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), Jonchère, Laurent, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies du foie [CHU Rennes], and Centre Hospitalier Universitaire [Rennes]

Subjects
Graft Rejection, medicine.medical_specialty, Time Factors, Dose, Chemistry, Pharmaceutical, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Urology, Context (language use), 030230 surgery, Liver transplantation, Pharmacology, Drug Administration Schedule, Tacrolimus, Medication Adherence, Food-Drug Interactions, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, medicine, Humans, Transplantation, Hepatology, medicine.diagnostic_test, business.industry, Graft Survival, Area under the curve, Liver Transplantation, 3. Good health, [SDV] Life Sciences [q-bio], stomatognathic diseases, Treatment Outcome, Therapeutic drug monitoring, Delayed-Action Preparations, Concomitant, Practice Guidelines as Topic, Trough level, 030211 gastroenterology & hepatology, Surgery, Drug Monitoring, business, Immunosuppressive Agents
Abstract

International audience; The efficacy and safety of tacrolimus (Tac) twice daily (bid) and once a day (qd) formulations are considered to be similar. However, the available information regarding initiation of Tac qd is sparse, and practical information is lacking. On the basis of a literature review, clinical efficacy, and safety trials, French experts in the liver transplantation field were asked to highlight pharmacokinetic (PK) differences between both formulations to assess efficacy and safety of the qd formulation in the context of de novo initiation or conversion and to provide their recommendations for initiation and day-to-day management of Tac qd. The same efficacy and safety profile is found for both immediate-release and prolonged-release Tac. PK differences carry on absorption because of the difference in formulations but not on metabolism or excretion. Tac qd offers a better reproducibility in exposure than Tac bid but is associated with an increased risk of disturbed absorption in case of a change in intestinal motility. The same therapeutic drug monitoring with Tac qd and bid could be applied, based on minimal concentration (trough level; Cmin ), as there is a similar strong correlation between Cmin and the area under the curve (AUC) for both formulations. Different protocols for Tac qd initiation were described through numerous studies, except for early conversion: initiation on day 0, using 0.10 to 0.20 mg/kg/day as monotherapy, or lower dosages in case of concomitant immunosuppressant treatment or poor graft quality; early conversion from day 5 to 6 months, preferably before hospital discharge, using a 1 to 1.3 mg/kg/day schedule and with first Cmin assessment 48 hours after the conversion; and later conversion (\textgreater6 months posttransplantation) using a milligram-to-milligram dosage schedule, and with dose adjustment based on weekly Cmin measurement. Experts underline that an increase in treatment adherence was expected using Tac qd in liver recipients. In conclusion, Tac qd has the same efficacy and safety profile as Tac bid. De novo introduction or later conversion are well documented but could differ from day-to-day practice. Liver Transpl 21:1312-1321, 2015. © 2015 AASLD

Published
2015
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