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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. 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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7. 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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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. 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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10. 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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11. Long‐term outcome of liver transplantation for autoimmune hepatitis: A French nationwide study over 30 years

Author: Yasmina Chouik, Olivier Chazouillères, Claire Francoz, Eleonora De Martin, Olivier Guillaud, Armand Abergel, Mario Altieri, Louise Barbier, Camille Besch, Filomena Conti, Christophe Corpechot, Sébastien Dharancy, François Durand, Christophe Duvoux, Jean Gugenheim, Jean Hardwigsen, Marie‐Noëlle Hilleret, Pauline Houssel‐Debry, Nassim Kamar, Delphine Maucort‐Boulch, Anne Minello, Martine Neau‐Cransac, Georges‐Philippe Pageaux, Sylvie Radenne, Olivier Roux, Faouzi Saliba, Olivier Serée, Didier Samuel, Claire Vanlemmens, Marie‐Lorraine Woehl‐Jaegle, Vincent Leroy, Jean‐Charles Duclos‐Vallée, and Jérôme Dumortier
Subjects: Hepatology
Published: 2023
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12. 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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13. 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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14. Therapeutic anticoagulation after liver transplantation is not useful among patients with pre‐transplant Yerdel‐grade I/II portal vein thrombosis: A two‐center retrospective study

Author: Isabel Bos, Marc Blondeau, Michel Rayar, Dune Wouters, Willemijn van der Plas, Christophe Camus, Vincent E de Meijer, Pauline Houssel-Debry, Robert J. Porte, Lianne M Nieuwenhuis, Edouard Bardou-Jacquet, Ton Lisman, Groningen Institute for Organ Transplantation (GIOT), and Center for Liver, Digestive and Metabolic Diseases (CLDM)
Subjects: Adult, Liver Cirrhosis, medicine.medical_specialty, recurrence, Cirrhosis, genetic structures, medicine.medical_treatment, therapeutic anticoagulation, Liver transplantation, EVENTS, mental disorders, medicine, Humans, portal vein thrombosis, Risk factor, CIRRHOSIS, Contraindication, Retrospective Studies, Venous Thrombosis, Portal Vein, business.industry, Incidence (epidemiology), Anticoagulants, Retrospective cohort study, Hematology, Odds ratio, medicine.disease, Liver Transplantation, Surgery, Portal vein thrombosis, Treatment Outcome, Yerdel, INVERSE PROBABILITY, business
Abstract: BACKGROUND: Portal vein thrombosis (PVT) is no longer a contraindication for liver transplantation (LT). While therapeutic anticoagulation (tAC) is recommended during the waiting period, there is no evidence for its usefulness in the prevention of PVT recurrence after LT.OBJECTIVES: The aim of our study was to evaluate the role of tAC post-LT in the prevention of PVT recurrence.PATIENTS/METHODS: All adult LTs performed in 2 high volume centres between 2003 and 2018, were retrospectively analysed. Only patients with PVT classified as Yerdel grade I or II and with standard portal reconstruction were included. PVT recurrence and tAC-associated morbidity within 1 year were compared between patients receiving tAC or not.RESULTS: During the study period, out of 2612 LTs performed, 235 (9%) patients with PVT were included. 113 patients (48.1%) received post-LT tAC (tAC group) while 122 (51.9%) did not (non-tAC group). The incidence of bleeding events was significantly higher in the tAC group (26 (23%) vs. 5 (4.1%), pCONCLUSION: Therapeutic anticoagulation is not necessary in the prevention of grade I/II PVT recurrence and is associated with higher morbidity and longer hospital stay.
Published: 2021
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15. Rivaroxaban Prophylaxis in Noncirrhotic Portal Vein Thrombosis

Author: Aurélie Plessier, Odile Goria, Jean Paul Cervoni, Isabelle Ollivier, Christophe Bureau, Armelle Poujol-Robert, Anne Minello, Pauline Houssel-Debry, Pierre Emmanuel Rautou, Audrey Payancé, Giovanna Scoazec, Onorina Bruno, Michele Corbic, Francois Durand, Valérie Vilgrain, Valérie Paradis, Larbi Boudaoud, Emmanuelle de Raucourt, Carine Roy, Nathalie Gault, and Dominique Valla
Published: 2022
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16. 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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17. Liver transplantation for NAFLD cirrhosis: Age and recent coronary angioplasty are major determinants of survival

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: Adult, Aged, 80 and over, Liver Cirrhosis, Male, Carcinoma, Hepatocellular, Hepatology, Angioplasty, Liver Neoplasms, Liver Transplantation, End Stage Liver Disease, Treatment Outcome, Non-alcoholic Fatty Liver Disease, Humans, Retrospective Studies
Abstract: Liver transplantation (LT) is the treatment of end-stage non-alcoholic liver disease (NAFLD), that is decompensated cirrhosis and/or complicated by hepatocellular carcinoma (HCC). Few data on long-term outcome are available. The aim of this study was to evaluate overall patient and graft survivals and associated predictive factors.This retrospective multicentre study included adult transplant patients for NAFLD cirrhosis between 2000 and 2019 in participating French-speaking centres.A total of 361 patients (69.8% of male) were included in 20 centres. The median age at LT was 62.3 years [57.4-65.9] and the median MELD score was 13.9 [9.1-21.3]; 51.8% of patients had HCC on liver explant. Between 2004 and 2018, the number of LT for NAFLD cirrhosis increased by 720%. A quarter of the patients had cardiovascular history before LT. Median follow-up after LT was 39.1 months [15.8-72.3]. Patient survival at 1, 5 and 10 years after LT was 89.3%, 79.8% and 68.1% respectively. The main causes of death were sepsis (37.5%), malignancies (29.2%) and cardiovascular events (22.2%). In multivariate analysis, three risk factors for overall mortality after LT were recipient pre-LT BMI 32 kg/mSurvival after LT for NAFLD cirrhosis is good at 5 years. Donor and recipient age, and cardiovascular history, are major prognostic factors to consider.
Published: 2022

18. Early liver transplantation for corticosteroid non-responders with acute severe autoimmune hepatitis: The SURFASA score

Author: Olivier Chazouillères, Florent Artru, Eleonora De Martin, Philippe Mathurin, Camille Besch, Christophe Duvoux, François Durand, Odile Goria, Hélène Fontaine, Hélène Agostini, Isabelle Ollivier-Hourmand, Noemi Reboux, Olivier Roux, Filomena Conti, Nathalie Ganne-Carrié, Didier Samuel, Georges-Philippe Pageaux, Philippe Ichai, Marilyne Debette-Gratien, Christine Silvain, Alexandra Heurgue, Jean-Marie Peron, Sylvie Radenne, Jérôme Dumortier, Audrey Coilly, Pauline Houssel-Debry, Sandrine Barge, Marc Bourlière, Pascal Potier, Jean-Charles Duclos-Vallée, Vincent Di Martino, Mylène Sebagh, and Victor de Ledinghen
Subjects: 0301 basic medicine, medicine.medical_specialty, Multivariate analysis, Hepatology, medicine.drug_class, Bilirubin, business.industry, medicine.medical_treatment, Odds ratio, Autoimmune hepatitis, Liver transplantation, medicine.disease, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, chemistry, Internal medicine, medicine, Corticosteroid, 030211 gastroenterology & hepatology, Prospective cohort study, business, Survival rate
Abstract: Background & Aims In acute severe autoimmune hepatitis (AS-AIH), the optimal timing for liver transplantation (LT) remains controversial. The objectives of this study were to determine early predictive factors for a non-response to corticosteroids and to propose a score to identify patients in whom LT is urgently indicated. Methods This was a retrospective, multicenter study (2009-2016). A diagnosis of AS-AIH was based on: i) Definite or probable AIH based on the simplified IAIHG score; ii) international normalized ratio (INR) ≥1.5 and/or bilirubin >200 μmol/L; iii) No previous history of AIH; iv) Histologically proven AIH. A treatment response was defined as LT-free survival at 90 days. The evolution of variables from corticosteroid initiation (day-D0) to D3 was estimated from: Δ%3 = (D3–D0)/D0. Results A total of 128 patients were included, with a median age of 52 (39–62) years; 72% were female. Overall survival reached 88%. One hundred and fifteen (90%) patients received corticosteroids, with a LT-free survival rate of 66% at 90 days. Under multivariate analysis, D0-INR (odds ratio [OR] 6.85; 95% CI 2.23–21.06; p Conclusion In patients with AS-AIH, INR at the introduction of corticosteroids and the evolution of INR and bilirubin are predictive of LT or death. Within 3 days of initiating corticosteroids, the SURFASA score can identify non-responders who require a referral for LT. This score needs to be validated in a prospective cohort. Lay summary The management of patients with acute severe autoimmune hepatitis is highly challenging, particularly regarding their early referral for liver transplantation. We found that international normalized ratio at the initiation of corticosteroid therapy and the evolution of international normalized ratio and bilirubin values after 3 days of therapy were highly predictive of liver transplantation or death. We are thus proposing a score that combines these variables and identifies patients in whom liver transplantation is urgently required.
Published: 2021
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19. 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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20. Recurrence of primary sclerosing cholangitis after liver transplantation: a french cohort study including 571 patients

Author: Florian Veyre, Eleonora De Martin, Domitille Erard, Claire Francoz, Laure Elkrief, Camille Besch, Olivier Boillot, Karim Boudjema, Filomena Conti, Sebastien Dharancy, Christophe Duvoux, Jean Gugenheim, Jean Hardwigsen, Marie-Noëlle Hilleret, Isabelle Ollivier-Hourmand, Maryline Debette-Gratien, Pauline Houssel-Debry, Nassim Kamar, Jean-Baptiste Hiriart, Stéphanie Faure, Faouzi Saliba, Didier Samuel, Claire Vanlemmens, Christophe Corpechot, Olivier Chazouillères, and Jérôme Dumortier
Subjects: Hepatology
Published: 2022
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21. Liver transplantation for hepatocellular carcinoma with extended criteria: performance and applicability of the AFP score after official adoption by the French Organ Sharing Organization ABM: 5-year outcomes

Author: Christophe Duvoux, Mathilde Petiet Dumont, Georges-Philippe Pageaux, Ephrem Salamé, Jérôme Dumortier, Sylvie Radenne, Sébastien Dharancy, Pauline Houssel-Debry, Philippe Bachellier, Laurence Chiche, Francois Durand, Fabrice Muscari, Jean Gugenheim, Filomena Conti, Jean Hardwigsen, Christian Jacquelinet, Corinne Antoine, Norbert Ngongang, Vincent Leroy, Thomas Decaens, Daniel Cherqui, and Nadia Oubaya
Subjects: Hepatology
Published: 2022
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22. Drug transporters are implicated in the diffusion of tacrolimus into the T lymphocyte in kidney and liver transplant recipients: Genetic, mRNA, protein expression, and functionality

Author: Gwendal Coste, Fabien Robin, Jonathan Chemouny, Camille Tron, Jérôme Le Priol, Régis Bouvet, Marc Le Vée, Pauline Houssel-Debry, Michel Rayar, Marie-Clémence Verdier, Mikael Roussel, Marie-Dominique Galibert, Edouard Bardou-Jacquet, Olivier Fardel, Cécile Vigneau, Karim Boudjema, Bruno Laviolle, Florian Lemaitre, 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], Laboratoire de génétique moléculaire et génomique médicale [CHU Rennes], Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and This work was partly supported by a research grant by Sandoz and the bourse Ouest Transplant. The funding source had no involvement in any part of the study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the article for publication.
Subjects: Pharmacology, T-Lymphocytes, [SDV]Life Sciences [q-bio], Pharmaceutical Science, Drug transporter, Therapeutic drug monitoring, Kidney, Personalized medicine, Tacrolimus, Liver Transplantation, Solid organ transplantation, Leukocytes, Mononuclear, Humans, Cytochrome P-450 CYP3A, Pharmacokinetics, Pharmacology (medical), RNA, Messenger, Immunosuppressive Agents
Abstract: International audience; Because of a narrow therapeutic index and a wide inter- and intra-patient variability, therapeutic drug monitoring of the immunosuppressant drug tacrolimus (TAC) based on whole-blood concentrations (C) is mandatory in solid organ transplant recipients. Using peripheral blood mononuclear cells concentrations (C) could improve patient outcomes. The poor correlation between C and C makes hypothesize that drug transporters are implicated in the intracellular accumulation of TAC. The aim of this work was therefore to clinically study: i) the role of genetic variants and ii) the effect of mRNA and protein expression of 4 drug transporters on the TAC C ratio. In addition, functional in vitro experiments were performed to mechanistically validate the clinical observations. Genetic variants of ABCB1/P-gp and SLC28A3/CNT3 did not influence TAC C in liver transplant recipients (LTR). ABCC2/MRP2 at the mRNA level; ABCB1/P-gp, SLC28A3/CNT3 and SLC29A1/ENT1 at the protein level; correlated with the C in kidney and LTR. In vitro results suing transporter-expressing cells confirmed that TAC is substrate of P-gp but not MRP2, whereas experiments remained inconclusive for CNT3 and ENT1. In conclusion, the genetic-transcription-protein-functional approach presented in this work provides new insights in the understanding of TAC transport at the T lymphocyte plasma membrane.
Published: 2022
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23. 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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24. 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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25. 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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26. 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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27. Evaluation of the Hepatorenal B-Mode Ratio and the 'Controlled Attenuation Parameter' for the Detection and Grading of Steatosis

Author: Antoine Moret, Jérôme Boursier, Christophe Aubé, Marine Dubois, Pauline Houssel Debry, Anita Paisant, Jérémie Riou, Sophie Michalak Provost, Anne Crouan, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Danone Research, Groupe DANONE, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), 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), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Département de Radiologie [CHU de Rennes], Université de Rennes (UR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: medicine.diagnostic_test, business.industry, [SDV]Life Sciences [q-bio], Biopsy, Ultrasound, medicine.disease, Fatty Liver, 03 medical and health sciences, 0302 clinical medicine, Liver steatosis, Liver, ROC Curve, Predictive Value of Tests, 030220 oncology & carcinogenesis, Liver biopsy, Area Under Curve, Medicine, Elasticity Imaging Techniques, Humans, 030211 gastroenterology & hepatology, Radiology, Nuclear Medicine and imaging, Steatosis, business, Nuclear medicine, Grading (tumors)
Abstract: The aim of this study was to evaluate the hepatorenal index ratio of Supersonic Imagine (B-mode ratio) and the controlled attenuation parameter (CAP) of FibroScan for the noninvasive diagnosis and grading of steatosis. Two centers prospectively included patients who underwent liver biopsy, B-mode ratio and CAP evaluation all on the same day between June 2017 and July 2019. MRI and histological morphometry were also performed in center 1. Histology (classic semiquantitative score and morphometry) was used as the reference. Concerning the B-mode ratio, the AUROCs for ≥ S1, ≥ S2 and ≥ S3 were respectively 0.896 ± 0.20, 0.775 ± 0.30 and 0.729 ± 0.39 with the best cut-off values being 1.22 for ≥ S1 (Se = 76.4 %, Sp = 93.2 %), 1.42 for ≥ S2 (Se = 70.2 %, Sp = 71.2 %) and 1.54 for ≥ S3 (Se = 68.4 %, Sp = 69.8 %). The correlation between the B-mode ratio and morphometry was moderate (Rs = 0.575, p 0.001) and the correlation between the B-mode ratio and MRI was good (Rs = 0.613, p 0.001). Concerning the CAP, the AUROCs for ≥ S1, ≥ S2 and ≥ S3 were 0.926 ± 0.18, 0.760 ± 0.30 and 0.701 ± 0.40, respectively, with the best cut-off values being 271 dB/m for ≥ S1 (Se = 84 %, Sp = 88.2 %), 331 dB/m for ≥ S2 (Se = 64.5 %, Sp = 74.7 %) and 355 dB/m for ≥ S3 (Se = 55.3 %, Sp = 75.1 %). The correlation between the CAP and morphometry and between the CAP and MRI was moderate in both cases (Rs = 0.526, p 0.001 and Rs = 0.397, p 0.001, respectively). The B-mode ratio was better at ruling in and the CAP was better at ruling out the disease. B-mode ratio and CAP show similar and good performance for the diagnosis of steatosis (≥ S1). However, both techniques are limited with respect to differentiating mild to moderate (≥ S2) or severe (≥ S3) steatosis.ZIEL: Ziel dieser Studie war die Bewertung der hepatorenalen Index-Ratio von Supersonic Imagine (B-Modus-Ratio) und des „controlled attenuation parameter“ (CAP) von FibroScan für die nichtinvasive Diagnose und Einstufung einer Steatose. Zwei Zentren schlossen prospektiv Patienten ein, bei denen zwischen Juni 2017 und Juli 2019 am selben Tag eine Leberbiopsie, eine B-Modus-Ratio und eine CAP-Evaluierung durchgeführt wurden. In Zentrum 1 wurden auch eine MRT und eine histologische Morphometrie durchgeführt. Die Histologie (klassischer semiquantitativer Score und Morphometrie) diente als Referenz. Hinsichtlich der B-Modus-Ratio lagen die AUROCs für ≥ S1 bei 0,896 ± 0,20, für ≥ S2 bei 0,775 ± 0,30 und ≥ S3 bei 0,729 ± 0,39, wobei die besten Cut-off-Werte 1,22 für ≥ S1 (Se = 76,4 %, Sp = 93,2 %), 1,42 für ≥ S2 (Se = 70,2 %, Sp = 71,2 %) und 1,54 für ≥ S3 (Se = 68,4 %, Sp = 69,8 %) betrugen. Die Korrelation zwischen B-Modus-Ratio und Morphometrie war moderat (Rs = 0,575; p 0,001) und die Korrelation zwischen B-Modus-Ratio und MRT war gut (Rs = 0,613; p 0,001). In Bezug auf den CAP lagen die AUROCs für ≥ S1 bei 0,926 ± 0,18, für ≥ S2 bei 0,760 ± 0,30 und für ≥ S3 bei 0,701 ± 0,40, wobei die besten Cut-off-Werte für ≥ S1 bei 271 dB/m (Se = 84 %, Sp = 88,2 %), für ≥ S2 bei 331 dB/m (Se = 64,5 %, Sp = 74,7 %) und für ≥ S3 bei 355 dB/m (Se = 55,3 %, Sp = 75,1 %) lagen. Die Korrelation zwischen CAP und Morphometrie sowie zwischen CAP und MRT war in beiden Fällen moderat (Rs = 0,526; p 0,001 bzw. Rs = 0,397; p 0,001). Die B-Modus-Ratio war besser in der Lage, die Erkrankung zu erkennen, und der CAP konnte diese besser ausschließen. B-Modus-Ratio und CAP zeigen eine ähnliche und gute Leistung bei der Diagnose von Steatose (≥ S1). Beide Methoden sind jedoch hinsichtlich der Differenzierung zwischen leichter bis mittelschwerer Steatose (≥ S2) und schwerer (≥ S3) Steatose begrenzt.
Published: 2020
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28. Hypothermic Oxygenated Perfusion Improves Extended Criteria Donor Liver Graft Function and Reduces Duration of Hospitalization Without Extra Cost: The PERPHO Study

Author: Emma Bajeux, Damien Bergeat, Christophe Camus, Caroline Jezequel, Véronique Desfourneaux, Bernard Meunier, Laurent Sulpice, Edouard Bardou-Jacquet, Pauline Houssel-Debry, Michel Rayar, Aude Merdrignac, Clara Locher, Stéphanie Hamonic, Jean-Marie Beaurepaire, M. Lakehal, and Thomas Renard
Subjects: medicine.medical_treatment, 030230 surgery, Liver transplantation, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Living Donors, Medicine, Humans, Prospective Studies, Prospective cohort study, Transplantation, Machine perfusion, Hepatology, business.industry, Incidence (epidemiology), Graft Survival, Organ Preservation, Intensive care unit, Tissue Donors, 3. Good health, Liver Transplantation, Hospitalization, Perfusion, Liver, Anesthesia, Propensity score matching, 030211 gastroenterology & hepatology, Surgery, business
Abstract: Few studies have evaluated the efficacy or the cost of hypothermic oxygenated perfusion (HOPE) in the conservation of extended criteria donor (ECD) grafts from donation after brain death (DBD) donors during liver transplantation (LT). We performed a prospective, monocentric study (NCT03376074) designed to evaluate the interest of HOPE for ECD-DBD grafts. For comparison, a control group was selected after propensity score matching among patients who received transplants between 2010 and 2017. Between February and November 2018, the HOPE procedure was used in 25 LTs. Immediately after LT, the median aspartate aminotransferase (AST) level was significantly lower in the HOPE group (724UI versus 1284UI; P = 0.046) as were the alanine aminotransferase (ALT; 392UI versus 720UI; P = 0.01), lactate (2.2 versus 2.7; P = 0.01) There was a significant reduction in intensive care unit stay (3 versus 5 days; P = 0.01) and hospitalization (15 versus 20 days; P = 0.01). The incidence of early allograft dysfunction (EAD; 28% versus 42%; P = 0.22) was similar . A level of AST or ALT in perfusate >800UI was found to be highly predictive of EAD occurrence (areas under the curve, 0.92 and 0.91, respectively). The 12-month graft (88% versus 89.5%; P = 1.00) and patient survival rates (91% versus 91.3%; P = 1.00) were similar. The additional cost of HOPE was estimated at € 5298 per patient. The difference between costs and revenues, from the hospital's perspective, was not different between the HOPE and control groups (respectively, € 3023 versus € 4059]; IC, -€ 5470 and € 8652). HOPE may improve ECD graft function and reduce hospitalization stay without extra cost. These results must be confirmed in a randomized trial.
Published: 2020

29. Portal cavernoma or chronic non cirrhotic extrahepatic portal vein obstruction

Author: Virginia Hernández-Gea, Laure Elkrief, Christophe Bureau, Danielle Dutheil, Aurélie Plessier, Sophie Hillaire, Stéphanie Franchi-Abella, Pauline Houssel-Debry, Sophie Branchereau, Oanez Ackermann, and Dominique Valla
Subjects: medicine.medical_specialty, Hepatology, Venous catheterization, business.industry, Portal Vein, Gastroenterology, Portal vein, Congenital malformations, Portal vein obstruction, medicine.disease, Thrombosis, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Chronic Disease, Hypertension, Portal, Practice Guidelines as Topic, medicine, Humans, 030211 gastroenterology & hepatology, Radiology, Acute thrombosis, business, Myeloproliferative neoplasm
Abstract: Chronic non cirrhotic extrahepatic portal vein obstruction (EHPVO) refers to the cavernomatous transformation of the portal vein (the so-called "portal cavernoma") which occurs following acute thrombosis of the portal vein in the absence of recanalization. In adults, EHPVO mainly occurs following thrombosis, while in children it may be related to congenital malformations and/or neonatal umbilical venous catheterization. However, 50% of the cases of EHPVO remain idiopathic [1]. Risk factors and associated diseases should be investigated (chapter 1). Indeed, the presence of a thrombophilic alteration, in particular myeloproliferative neoplasm impacts prognosis and determine a causal treatment.
Published: 2020

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

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

Author: Laurence Chiche, Victor de Ledinghen, Marie Irles-Depe, Pauline Houssel-Debry, Martine Neau-Cransac, Sébastien Dharancy, Olivier Boillot, Jérôme Dumortier, Christophe Laurent, David Laharie, and Stéphanie Roullet
Subjects: Adult, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, Cholangitis, Sclerosing, Azathioprine, 030230 surgery, Liver transplantation, Lower risk, digestive system, Gastroenterology, Inflammatory bowel disease, Primary sclerosing cholangitis, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Medicine, Humans, Retrospective Studies, Transplantation, Hepatology, business.industry, Incidence (epidemiology), Odds ratio, medicine.disease, Inflammatory Bowel Diseases, digestive system diseases, Liver Transplantation, 030211 gastroenterology & hepatology, Surgery, business, medicine.drug
Abstract: Approximately 80% of patients with primary sclerosing cholangitis (PSC) also have inflammatory bowel disease (IBD). The effect of IBD on the outcomes of liver transplantation (LT) for PSC is unclear. We retrospectively collected data from adults who underwent LT for PSC from 1989 to 2017 in four French LT centers. We compared the rates of patient and graft survivals and of complications after LT. Among 87 patients, 52 (60%) had pre-existing IBD. Excluding those who died within the first 3 months, the 10-year patient survival and graft survival rates were 92.6% (95% confidence interval [CI] 84.3-100) and 77.1% (95% CI 53.8-85.3) in the PSC with IBD (PSC-IBD) group and 97.1% (95% CI 91.4-100) (p = 0.44) and 83.2% (95% CI 69.6-96.9) (p = 0.43) in the isolated PSC group, respectively. Exposure to azathioprine after LT was significantly associated with mortality (odds ratio [OR] 15.55 [95% CI 1.31-184.0], p = 0.03), whereas exposure to mycophenolate mofetil was associated with improved survival (OR 0.17 [95% CI 0.04-0.82], p = 0.03), which may be an era effect. Exposure to cyclosporine was associated with graft loss, albeit at borderline significance: OR 3.60 [95% CI 0.96-13.42] (p = 0.06). The rate of recurrent PSC was 21% in the PSC-IBD group and 11% in the isolated PSC group (p = 0.24). The incidence of severe infection was 125 per 1000 person-years in both groups. Exposure to mycophenolate mofetil was associated with a lower risk of infection (OR 0.26 [95% CI 0.08-0.85] p = 0.03). The presence of IBD was associated with cytomegalovirus infection (OR 3.24 [95% CI 1.05-9.98], p = 0.04). The crude incidence of skin cancer was higher in the PSC-IBD group (p = 0.06). One case of colorectal cancer occurred in a patient with IBD. CONCLUSION: IBD prior to LT for PSC may not affect patient or transplant survival but may increase the risk of cytomegalovirus infection.
Published: 2020

32. 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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33. 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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34. 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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35. 12 Weeks of a Ribavirin‐Free Sofosbuvir and Nonstructural Protein 5A Inhibitor Regimen Is Enough to Treat Recurrence of Hepatitis C After Liver Transplantation

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

Author: Pauline Houssel Debry, Audrey Huguet, Karim Boudjema, Michel Rayar, Edouard Bardou Jacquet, Caroline Jezequel, Marianne Latournerie, Dominique Guyader, L. Legros, Ronan Thibault, CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), 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), and Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Liver Cirrhosis, Male, Sarcopenia, medicine.medical_specialty, Cirrhosis, Waiting Lists, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Liver transplantation, Sensitivity and Specificity, Computed tomography scan, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, medicine, Humans, Body Weights and Measures, In patient, Correlation test, 10. No inequality, Psoas Muscles, Retrospective Studies, Liver graft, 2. Zero hunger, Nutrition and Dietetics, Receiver operating characteristic, business.industry, Malnutrition, Liver failure, Reproducibility of Results, Muscle mass, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Retrospective cohort study, Middle Aged, medicine.disease, Confidence interval, Liver Transplantation, 3. Good health, Waiting list, 030220 oncology & carcinogenesis, Feasibility Studies, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 030211 gastroenterology & hepatology, Radiology, Tomography, X-Ray Computed, business
Abstract: International audience; Objective Malnutrition impairs prognosis in liver cirrhosis. Our aims were to determine (1) if transversal (TPTI) and axial (APTI) psoas thickness indices predict mortality in cirrhotic patients and (2) the feasibility and reproducibility of transversal (TDPM) and axial (ADPM) diameters of the psoas muscle measurements.Methods This was a retrospective study. Inclusion criteria included cirrhosis diagnosis, on liver transplantation waiting list, and abdominal computed tomography (CT) scan within the 3 mo preceding list inscription. TDPM and ADPM were measured on a single umbilicus-targeted CT image by non-expert and expert operators. TPTI or APTI (mm/m) were calculated as TDPM or ADPM/height (m). Area under the receiver operating characteristic curve (AUC) and Cox proportional hazard models were assessed. TPTI and APTI interobserver agreement κ correlation test.Results A total of 173 patients were included. Low TPTI was associated with increased mortality AUC = 0.66 (95% confidence interval, 0.51–0.80). TPTI was the only factor associated with mortality (hazard ratio = 0.87, 95% confidence interval 0.76–0.99, P = 0.034). There was an almost perfect interobserver agreement between the two operators TDPM, κ = 0.97; ADPM, κ = 0.94; P < 0.0001.Conclusions TPTI measured on umbilicus-targeted CT scan before inscription on the waiting list for liver transplantation predicts mortality of cirrhotic patients. TPTI measurement is easy and reliable, even by a non-trained operator, and this is highly feasible in daily clinical practice.
Published: 2018
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37. High Intrapatient Variability of Tacrolimus Exposure in the Early Period After Liver Transplantation Is Associated With Poorer Outcomes

Author: Ammar Dehlawi, Caroline Jezequel, Camille Tron, M. Lakehal, Eric Bellissant, Véronique Desfourneaux, Marie Clémence Verdier, Florian Lemaitre, Antoine Petitcollin, Jean Marie Beaurepaire, Bernard Meunier, Pauline Houssel-Debry, Karim Boudjema, Laurent Sulpice, Michel Rayar, Christophe Camus, Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], CHU Pontchaillou [Rennes], Service des Maladies de l'Appareil Digestif, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [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), Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Microenvironnement et remodelage, CHU Pontchaillou [Rennes]-CHU Pontchaillou [Rennes]-Foie, métabolismes et cancer, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Foie, métabolismes et cancer, Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Service des Maladies de l'Appareil Digestif [CHU Rennes], Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), 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 )-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 ), 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 ), 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 ), 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: Adult, Male, MESH: Liver Transplantation, medicine.medical_specialty, Adolescent, MESH: Graft Survival, Coefficient of variation, medicine.medical_treatment, 030230 surgery, Liver transplantation, 030226 pharmacology & pharmacy, Gastroenterology, Tacrolimus, Young Adult, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Internal medicine, MESH: Tacrolimus, Humans, Medicine, Dialysis, Aged, Retrospective Studies, MESH: Adolescent, MESH: Aged, Transplantation, MESH: Middle Aged, MESH: Humans, business.industry, Graft Survival, Hazard ratio, MESH: Adult, MESH: Retrospective Studies, Retrospective cohort study, Middle Aged, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, MESH: Male, Confidence interval, Liver Transplantation, 3. Good health, MESH: Young Adult, Toxicity, Female, MESH: Immunosuppressive Agents, business, MESH: Female, Immunosuppressive Agents
Abstract: International audience; Background - Tacrolimus (TAC) is the cornerstone of immunosuppressive regimen in liver transplantation (LT). Its pharmacokinetics is characterized by a high interpatient and intrapatient variability (IPV) leading to an unpredictable dose-response relationship. The aim of our study was to evaluate the impact of TAC IPV (IPV) on graft and patient outcomes after LT. Methods - We retrospectively analyzed 812 LT recipients treated with TAC. The IPV of TAC concentrations was estimated by calculating the coefficient of variation (CV) of whole blood trough concentrations. Patients were categorized in 2 groups: low IPV (CV < 40%) and high IPV (CV ≥ 40%). Results - There were significantly more neurologic complications (31.2% vs 16.6%, P < 0.001), cardiovascular complications (19.7% vs 9.7%, P < 0.001), and acute renal failure requiring dialysis (8.5% vs 2.2%, P < 0.001) in the high CV group than in the low CV group. Moreover, graft survival was significantly poorer in the high CV group (hazard ratio, 1.42; 95% confidence interval, 1.04-1.95; P = 0.03). A pretransplantation elevated Model for End-Stage Liver Disease score (P < 0.001) and Child-Pugh grade (P < 0.001) were identified as risk factors for presenting a high CV. Conclusions - A high CV of TAC concentrations was found to be predictive of TAC-related toxicity and poorer survival.
Published: 2018
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38. Direct-acting antiviral agent–based regimen for HCV recurrence after combined liver-kidney transplantation: Results from the ANRS CO23 CUPILT study

Author: Jérôme Dumortier, A. Rohel, Jean-Charles Duclos-Vallée, Christophe Duvoux, Vincent Di Martino, Christine Silvain, Sébastien Dharancy, Danielle Botta-Fridlund, Sylvie Radenne, Maryline Debette-Gratien, Nassim Kamar, Audrey Coilly, Vincent Leroy, Georges-Philippe Pageaux, Armand Abergel, Louis d’Alteroche, Emilie Rossignol, Claire Francoz, Pauline Houssel-Debry, P. Perré, Filomena Conti, Claire Fougerou-Leurent, François Habersetzer, Camille Besch, Christophe Moreno, H. Montialoux, Valérie Canva, Albert Tran, Didier Samuel, Victor de Lédinghen, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Paul Brousse, 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), CHU Pontchaillou [Rennes], Service d'Hépatologie, Hôpital Henri Mondor, AP-HP, Créteil, France., Hôpital Henri Mondor, 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 de Physiopathologie Toulouse Purpan (CPTP), 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), Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-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), Service d'hépato-gastro-entérologie, Hôpital Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Département d'hépatologie, Service d'hépatologie, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital de la Croix-Rousse [CHU - HCL], Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Chirurgie Digestive, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), 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), Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, Chirurgie digestive et hépatobiliaire, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, 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), Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, ANRS France Recherche Nord & sud Sida-hiv hépatites, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Paul Brousse-Université Paris-Sud - Paris 11 (UP11), 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), 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, 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), 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), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: Graft Rejection, Male, Sofosbuvir, [SDV]Life Sciences [q-bio], medicine.medical_treatment, kidney transplantation/nephrology, Hepacivirus, 030230 surgery, Liver transplantation, medicine.disease_cause, 0302 clinical medicine, Recurrence, Risk Factors, Immunology and Allergy, liver disease: infectious, Pharmacology (medical), Prospective Studies, Prospective cohort study, education.field_of_study, Graft Survival, Middle Aged, Prognosis, Hepatitis C, 3. Good health, [SDV] Life Sciences [q-bio], kidney failure/injury, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, medicine.drug, Adult, medicine.medical_specialty, infectious disease, Hepatitis C virus, Population, clinical research/practice, Antiviral Agents, 03 medical and health sciences, Internal medicine, medicine, Humans, Adverse effect, education, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Transplantation, business.industry, Kidney Transplantation, Liver Transplantation, Regimen, Immunology, infection and infectious agents - viral: hepatitis C, business, liver transplantation/hepatology, Follow-Up Studies
Abstract: International audience; Hepatitis C virus (HCV) infection is associated with reduced patient survival following combined liver-kidney transplantation (LKT). The aim of this study was to assess the efficacy and safety of second-generation direct-acting antivirals (DAAs) in this difficult-to-treat population. The ANRS CO23 "Compassionate use of Protease Inhibitors in Viral C Liver Transplantation" (CUPILT) study is a prospective cohort including transplant recipients with recurrent HCV infection treated with DAAs. The present work focused on recipients with recurrent infection following LKT. The study population included 23 patients. All patients received at least one NS5B inhibitor (sofosbuvir) in their antiviral regimen an average of 90 months after LKT. Ninety-six percent of recipients achieved a sustained virological response (SVR) at week 12 (SVR12). In terms of tolerance, 39% of recipients presented with at least one serious adverse event. None of the patients experienced acute rejection during therapy and there were no deaths during follow-up. The glomerular filtration rate (GFR) decreased significantly from baseline to the end of therapy. However, this study did not show that the decline in GFR persisted over time or that it was directly related to DAAs. The DAA-based regimen is well tolerated with excellent results in terms of efficacy. It will become the gold standard for the treatment of recurrent HCV following LKT.
Published: 2017
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39. Venous stent in liver transplant candidates: Dodging the top tip traps

Author: Aude Merdrignac, Karim Boudjema, Pauline Houssel-Debry, Erwan Flecher, Heithem Jeddou, Michel Rayar, Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], CHU Pontchaillou [Rennes], Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de chirurgie thoracique cardiaque et vasculaire [Rennes] = Thoracic and Cardiovascular Surgery [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-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)-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 Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Transplantation, medicine.medical_specialty, Hepatology, business.industry, medicine.medical_treatment, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 030230 surgery, Liver transplantation, medicine.disease, 3. Good health, Venous stent, 03 medical and health sciences, 0302 clinical medicine, Hepatorenal syndrome, medicine, Effective treatment, 030211 gastroenterology & hepatology, Surgery, Radiology, Upper gastrointestinal bleeding, Refractory ascites, business, Transjugular intrahepatic portosystemic shunt
Abstract: International audience; Transjugular intrahepatic portosystemic shunt (TIPS) is an effective treatment for refractory ascites, upper gastrointestinal bleeding, or hepatorenal syndrome in liver transplant candidates..
Published: 2017
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40. COVID-19: Thoughts and comments from a tertiary liver transplant center in France

Author: Laurent Sulpice, Karim Boudjema, Stylianos Tzedakis, Pauline Houssel-Debry, Heithem Jeddou, and CHU Pontchaillou [Rennes]
Subjects: Organ procurement organization, medicine.medical_specialty, 2019-20 coronavirus outbreak, infection and infectious agents - viral, Coronavirus disease 2019 (COVID-19), editorial, medicine.medical_treatment, personal viewpoint, organ procurement and allocation, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 030230 surgery, Liver transplantation, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Pandemic, medicine, Immunology and Allergy, Pharmacology (medical), Center (algebra and category theory), guidelines, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, clinical decision-making, Transplantation, liver transplantation, biology, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatology, biology.organism_classification, ethics, practice, [SDV.ETH]Life Sciences [q-bio]/Ethics, organ procurement organization, clinical research, hepatology, 030211 gastroenterology & hepatology, business, Betacoronavirus
Abstract: International audience
Published: 2020
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41. 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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42. A Multicenter, Prospective, Observational Study of Conversion from Twice-Daily Immediate-Release to Once-Daily Prolonged-Release Tacrolimus in Liver Transplant Recipients in France: The COBALT Study

Author: Fabienne Bazin, Laurence Dubel, Pauline Houssel-Debry, Jérôme Dumortier, and Christophe Duvoux
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Observational Study, Liver transplantation, Drug Administration Schedule, Tacrolimus, Medication Adherence, Prolonged release, Internal medicine, medicine, Humans, Immediate release, Prospective Studies, Aged, Transplantation, Original Paper, business.industry, General Medicine, Middle Aged, Transplant Recipients, Liver Transplantation, surgical procedures, operative, Treatment Outcome, Tolerability, Delayed-Action Preparations, Quality of Life, Observational study, Female, France, Once daily, business, Immunosuppressive Agents
Abstract: BACKGROUND In adult liver transplant patients, the use of prolonged-release tacrolimus may have treatment adherence benefits over the immediate-release formulation. The aim of this study was to characterise real-world practice data on conversion of liver transplant recipients from immediate- to prolonged-release tacrolimus in France. MATERIAL AND METHODS A prospective, observational study (NCT02143479) was conducted in 18 transplant centers in France between June 2014 and March 2016. Liver transplant recipients (n=398) included patients who changed from immediate-release to prolonged-release tacrolimus within the first three months (early conversion group) (n=205) or between three and 12 months after transplantation (late conversion group) (n=184). Clinical data were collected at an initial baseline outpatient visit and six-month and 12-month follow-up visits. Endpoints included the dose conversion ratio from immediate-release to prolonged-release tacrolimus, number of and reasons for additional visits due to conversion, safety, and tolerability. RESULTS Baseline clinical and demographic characteristics were similar between the two cohorts. The mean ±SD ratio of conversion of tacrolimus dose was 1.04±0.28; 1.01±0.28 (early) and 1.08±0.28 (late) (p=0.0247). The mean ±SD time from conversion to the first tacrolimus trough blood concentration was 30.8±42.8 days; 24.8±45.4 days (early) and 37.5±38.7 days (late). Only one patient required an additional visit due to conversion. Reasons for conversion included the physician's preference (56.3%), center practice (38.6%), and the dosing frequency (36.0%). Conversion was associated with a low rate of graft rejection, and no new safety issues were reported. CONCLUSIONS Conversion of liver transplant recipients from immediate-release to prolonged-release tacrolimus within three to 12 months of transplantation was easy to manage and associated with favorable clinical outcomes and safety profiles.
Published: 2019

43. 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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44. 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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45. Sofosbuvir‐based treatment of hepatitis C with severe fibrosis (METAVIR F3/F4) after liver transplantation

Author: A. Rohel, Christophe Moreno, Jean-Charles Duclos-Vallée, Sylvie Radenne, Camille Besch, Armand Abergel, Nassim Kamar, Albert Tran, Georges-Philippe Pageaux, Pascal Lebray, Pauline Houssel-Debry, Valérie Canva, Claire Francoz, Danielle Botta-Fridlund, Jérôme Dumortier, Alpha Diallo, Vincent Leroy, Christophe Duvoux, Louis d’Alteroche, Claire Fougerou-Leurent, Audrey Coilly, Vincent Di Martino, Didier Samuel, Filomena Conti, Victor de Lédinghen, and Emilie Rossignol
Subjects: Compassionate Use Trials, Liver Cirrhosis, Male, Pyrrolidines, Cirrhosis, Sofosbuvir, medicine.medical_treatment, Hepacivirus, 030230 surgery, Liver transplantation, medicine.disease_cause, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Belgium, Recurrence, Prospective Studies, Imidazoles, Valine, Hepatitis C, Middle Aged, 3. Good health, Treatment Outcome, Female, 030211 gastroenterology & hepatology, France, Immunosuppressive Agents, medicine.drug, Reoperation, medicine.medical_specialty, Daclatasvir, Genotype, Hepatitis C virus, Antiviral Agents, 03 medical and health sciences, Internal medicine, Ribavirin, medicine, Humans, Protease Inhibitors, Aged, Transplantation, Hepatology, business.industry, medicine.disease, Liver Transplantation, chemistry, Immunology, Surgery, Carbamates, business
Abstract: Recurrence of hepatitis C virus (HCV) after liver transplantation (LT) can rapidly lead to liver graft cirrhosis and, therefore, graft failure and retransplantation or death. The aim of the present study was to assess efficacy and tolerance of sofosbuvir (SOF)–based regimens for the treatment of HCV recurrence in patients with severe fibrosis after LT. The Compassionate Use of Protease Inhibitors in Viral C Liver Transplantation (CULPIT) study is a prospective multicenter cohort including patients with HCV recurrence following LT treated with second generation direct antivirals. The present study focused on patients included between October 2013 and November 2014 and diagnosed with HCV recurrence and liver graft extensive fibrosis (METAVIR F3/F4). A SOF-based regimen was administered to 125 patients fulfilling inclusion criteria. The median delay from LT was 95.9 ± 69.6 months. The characteristics of patients were as follows: mean age, 59.4 ± 9.0 years; 78.4% male; infected by HCV genotype 1: 78.2%, mean HCV RNA: 6.1 ± 1.0 log10 IU/mL. Eighty patients had failed previous post-LT antiviral therapy (64.0%) including triple therapy with first generation protease inhibitors in 19 (15.2%) patients. The main combination regimen was SOF/daclatasvir (73.6%). Ribavirin was used in 60 patients. Sustained virological response 12 weeks after treatment was 92.8% (on an intention-to-treat basis); 7 patients with virological failure were observed. Serious adverse events occurred in 25.6% of the patients during antiviral treatment. During antiviral treatment and follow-up, 3 patients were retransplanted and 4 patients died. In conclusion, SOF-based antiviral treatment shows very promising results in patients with HCV recurrence and severe fibrosis after LT. Liver Transplantation 22 1367–1378 2016 AASLD. © 2016 by the American Association for the Study of Liver Diseases
Published: 2016
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46. De Novo Primary Liver Cancer After Liver Transplantation: A French National Study on 15803 Patients

Author: Manon, Allaire, Olivier, Sérée, Audrey, Coilly, Pauline, Houssel-Debry, Martine, Neau-Cransac, Georges-Philippe, Pageaux, Jérôme, Dumortier, and Mario, Altieri
Subjects: Adult, Male, Carcinoma, Hepatocellular, Time Factors, Databases, Factual, Liver Neoplasms, Middle Aged, Liver Transplantation, Immunocompromised Host, Young Adult, Treatment Outcome, Risk Factors, Humans, Female, France, Immunosuppressive Agents, Aged
Published: 2018

47. 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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48. 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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49. Poor Patient and Graft Outcome After Induction Treatment by Antithymocyte Globulin in Recipients of a Kidney Graft After Nonrenal Organ Transplantation

Author: Thi Van Ha Nguyen, Jean-Paul Soulillou, Antoine Sicard, Pauline Houssel-Debry, Stéphanie Malard-Castagnet, Katy Trébern-Launay, Valérie Garrigue, Julie Laurent, Vered Padler-Karavani, Christophe Legendre, Magali Giral, Sophie Brouard, Michèle Treilhaud, Anne Cesbron, Hélène Perreault, Xi Chen, Michèle Kessler, Lionel Rostaing, Shani Leviatan Ben-Arye, Hoa Le Mai, Georges Karam, Emmanuel Morelon, Sophie Girerd, Evelyn Ang, Hai Yu, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Cell Research and Immunology, Tel Aviv University (TAU), Department of Chemistry [Univ California Davis] (Chemistry - UC Davis), University of California [Davis] (UC Davis), University of California (UC)-University of California (UC), Department of Chemistry [Winnipeg, MB, Canada], University of Manitoba [Winnipeg], Manitoba Centre for Proteomics and Systems Biology [Winnipeg, MB, Canada], Methodomics, Etablissement Français du Sang [Nantes], 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 de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], CHU Pontchaillou [Rennes], Service Néphrologie et transplantation rénale Adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'urologie, Hôtel-Dieu, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Degauque, Nicolas, Tel Aviv University [Tel Aviv], Department of Chemistry Davis, University of California-University of California, Département de Néphrologie et Transplantation d'organes, Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service de Chirurgie Hépatobiliaire et Digestive [Rennes], Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Kidney Disease, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.medical_treatment, Renal and urogenital, lcsh:Surgery, 030230 surgery, Organ transplantation, 03 medical and health sciences, Team2, 0302 clinical medicine, Team4, Internal medicine, medicine, CRTI, Kidney transplantation, Transplantation, Kidney, biology, business.industry, Proportional hazards model, Prevention, Immunosuppression, Organ Transplantation, lcsh:RD1-811, medicine.disease, Kidney Transplantation, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Propensity score matching, biology.protein, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody, business
Abstract: Supplemental digital content is available in the text., 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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50. 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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