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1. New Approaches to Manage Infections in Transplant Recipients: Report From the 2023 GTI (Infection and Transplantation Group) Annual Meeting

Author: Alexandra Serris, Julien Coussement, Benoît Pilmis, Victoire De Lastours, Aurélien Dinh, François Parquin, Eric Epailly, Florence Ader, Olivier Lortholary, Emmanuel Morelon, Nassim Kamar, Edouard Forcade, David Lebeaux, Jérôme Dumortier, Filomena Conti, Agnes Lefort, Anne Scemla, and Hannah Kaminski
Subjects: muli-drug resistant bacteria, antimicrobial resistance, antimicrobial stewardship, antifungal therapy, urinary tract infection, Specialties of internal medicine, RC581-951
Published: 2023
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2. 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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3. 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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4. An Efficient 5-Aminolevulinic Acid Photodynamic Therapy Treatment for Human Hepatocellular Carcinoma

Author: Abhishek Kumar, Florian Pecquenard, Martha Baydoun, Alexandre Quilbé, Olivier Moralès, Bertrand Leroux, Lynda Aoudjehane, Filomena Conti, Emmanuel Boleslawski, and Nadira Delhem
Subjects: photodynamic therapy, hepatocellular carcinoma, 5-ALA, anti-tumor immunotherapy, anti-tumor immunity, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Photodynamic therapy (PDT) is a two-stage treatment relying on cytotoxicity induced by photoexcitation of a nontoxic dye, called photosensitizer (PS). Using 5-aminolevulinic acid (5-ALA), the pro-drug of PS protoporphyrin IX, we investigated the impact of PDT on hepatocellular carcinoma (HCC). Optimal 5-ALA PDT dose was determined on three HCC cell lines by analyzing cell death after treatment with varying doses. HCC-patient-derived tumor hepatocytes and healthy donor liver myofibroblasts were treated with optimal 5-ALA PDT doses. The proliferation of cancer cells and healthy donor immune cells cultured with 5-ALA-PDT-treated conditioned media was analyzed. Finally, therapy efficacy on humanized SCID mice model of HCC was investigated. 5-ALA PDT induced a dose-dependent decrease in viability, with an up-to-four-fold reduction in viability of patient tumor hepatocytes. The 5-ALA PDT treated conditioned media induced immune cell clonal expansion. 5-ALA PDT has no impact on myofibroblasts in terms of viability, while their activation decreased cancer cell proliferation and reduced the tumor growth rate of the in vivo model. For the first time, 5-ALA PDT has been validated on primary patient tumor hepatocytes and donor healthy liver myofibroblasts. 5-ALA PDT may be an effective anti-HCC therapy, which might induce an anti-tumor immune response.
Published: 2023
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5. 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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6. Patients Treated for HCV Infection and Listed for Liver Transplantation in a French Multicenter Study: What Happens at Five Years?

Author: Lucy Meunier, Mohamed Belkacemi, George Philippe Pageaux, Sylvie Radenne, Anaïs Vallet-Pichard, Pauline Houssel-Debry, Christophe Duvoux, Danielle Botta-Fridlund, Victor de Ledinghen, Filomena Conti, Rodolphe Anty, Vincent Di Martino, Marilyne Debette-Gratien, Vincent Leroy, Theophile Gerster, Pascal Lebray, Laurent Alric, Armand Abergel, Jérôme Dumortier, Camille Besch, Helene Montialoux, Didier Samuel, Jean-Charles Duclos-Vallée, and Audrey Coilly
Subjects: anti HCV therapy, DAAs, liver transplantation, decompensated cirrhosis, hepatocellular carcinoma, waiting list, Microbiology, QR1-502
Abstract: Background: Direct-acting antiviral (DAA) agents for the treatment of hepatitis C virus (HCV) infection have been proven safe and effective in cirrhotic patients awaiting liver transplantation (LT). However, in the long term, data remain minimal regarding the clinical impact of viral eradication on patients listed for decompensated cirrhosis or hepatocellular carcinoma (HCC). We aimed to elucidate the clinical outcomes of patients regarding delisting and the evolution of HCC during the long-term follow-up. Methods: An observational, multicenter, retrospective analysis was carried out on prospectively collected data from HCV-positive patients treated with an interferon-free regimen while awaiting LT in 18 French hospitals. Results: A total of 179 patients were included in the study. The indication for LT was HCC in 104 (58.1%) patients and cirrhosis in 75 (41.9%) patients. The sustained virological response was 84.4% and the treatment was well tolerated. At five years, among 75 patients with cirrhosis treated for HCV, 19 (25.3%) were delisted following improvement after treatment. Predictive factors for delisting highlighted an absence of ascites, MELD score ≤ 15, and Child–Pugh score ≤ 7. No patients with refractory ascites were delisted. Among patients with HCC, 82 (78.9%) were transplanted. The drop-out rate was low (6.7%) and few recurrences of HCC after LT were observed. Conclusions: DAAs are safe and effective in patients awaiting LT for cirrhosis or HCC. A quarter of patients with cirrhosis can be delisted because of clinical improvement. Predictive factors for delisting, as a result of improvement, may assist prescribers, before initiating HCV infection therapy in the long-term perspective.
Published: 2022
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7. International study on the outcome of locoregional therapy for liver transplant in hepatocellular carcinoma beyond Milan criteria

Author: Helena Degroote, Federico Piñero, Charlotte Costentin, Andrea Notarpaolo, Ilka F. Boin, Karim Boudjema, Cinzia Baccaro, Aline Lopes Chagas, Philippe Bachellier, Giuseppe Maria Ettorre, Jaime Poniachik, Fabrice Muscari, Fabrio Di Benedetto, Sergio Hoyos Duque, Ephrem Salame, Umberto Cillo, Adrián Gadano, Claire Vanlemmens, Stefano Fagiuoli, Fernando Rubinstein, Patrizia Burra, Daniel Cherqui, Marcelo Silva, Hans Van Vlierberghe, Christophe Duvoux, Filomena Conti, Olivier Scatton, Pierre Henri Bernard, Claire Francoz, Francois Durand, Sébastien Dharancy, Marie-lorraine Woehl, Alexis Laurent, Sylvie Radenne, Jérôme Dumortier, Armand Abergel, Louise Barbier, Pauline Houssel-Debry, Georges Philippe Pageaux, Laurence Chiche, Victor Deledinghen, Jean Hardwigsen, J. Gugenheim, M. Altieri, Marie Noelle Hilleret, Thomas Decaens, Aline Chagas, Paulo Costa, Elaine Cristina de Ataide, Emilio Quiñones, Sebastián Marciano, Margarita Anders, Adriana Varón, Alina Zerega, Alejandro Soza, Martín Padilla Machaca, Diego Arufe, Josemaría Menéndez, Rodrigo Zapata, Mario Vilatoba, Linda Muñoz, Ricardo Chong Menéndez, Martín Maraschio, Luis G. Podestá, M. Fauda, A. Gonzalez Campaña, Lucas McCormack, Juan Mattera, Adrian Gadano, Ilka S.F. Fatima Boin, Jose Huygens Parente García, Flair Carrilho, Giulia Magini, Lucia Miglioresi, Martina Gambato, Fabrizio Di Benedetto, Cecilia D’Ambrosio, Alessandro Vitale, Michele Colledan, Domenico Pinelli, Paolo Magistri, Giovanni Vennarecci, Marco Colasanti, Valerio Giannelli, Adriano Pellicelli, Cizia Baccaro, Callebout Eduard, Iesari Samuele, Dekervel Jeroen, Schreiber Jonas, Pirenne Jacques, Verslype Chris, Ysebaert Dirk, Michielsen Peter, Lucidi Valerio, Moreno Christophe, Detry Olivier, Delwaide Jean, Troisi Roberto, and Lerut Jan Paul
Subjects: Hepatocellular carcinoma, Downstaging, UCSF downstaging protocol, All-comers, Alpha-foetoprotein, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: Good outcomes after liver transplantation (LT) have been reported after successfully downstaging to Milan criteria in more advanced hepatocellular carcinoma (HCC). We aimed to compare post-LT outcomes in patients receiving locoregional therapies (LRT) before LT according to Milan criteria and University of California San Francisco downstaging (UCSF-DS) protocol and ‘all-comers’. Methods: This multicentre cohort study included patients who received any LRT before LT from Europe and Latin America (2000–2018). We excluded patients with alpha-foetoprotein (AFP) above 1,000 ng/ml. Competing risk regression analysis for HCC recurrence was conducted, estimating subdistribution hazard ratios (SHRs) and corresponding 95% CIs. Results: From 2,441 LT patients, 70.1% received LRT before LT (n = 1,711). Of these, 80.6% were within Milan, 12.0% within UCSF-DS, and 7.4% all-comers. Successful downstaging was achieved in 45.2% (CI 34.8–55.8) and 38.2% (CI 25.4–52.3) of the UCSF-DS group and all-comers, respectively. The risk of recurrence was higher for all-comers (SHR 6.01 [p
Published: 2021
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8. 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

9. Metabolic Optimisation of Regulatory T Cells in Transplantation

Author: Mo Atif, Audrey Mohr, Filomena Conti, Olivier Scatton, Guy Gorochov, and Makoto Miyara
Subjects: regulatory T cells, Treg, transplant, cell therapy, metabolism, metabolic, Immunologic diseases. Allergy, RC581-607
Abstract: Regulatory T (Treg) cells expressing the FOXP3 transcription factor are presently under investigation by many teams globally as a cellular therapy to induce tolerance in transplantation. This is primarily due to their immunosuppressive and homeostatic functions. Depending on the type of allograft, Treg cells will need to infiltrate and function in metabolically diverse microenvironments. This means that any resident and circulating Treg cells need to differentially adapt to counter acute or chronic allograft rejection. However, the links between Treg cell metabolism and function are still not entirely delineated. Current data suggest that Treg cells and their effector counterparts have different metabolite dependencies and metabolic programs. These properties could be exploited to optimize intragraft Treg cell function. In this review, we discuss the current paradigms regarding Treg cell metabolism and outline critical intracellular axes that link metabolism and function. Finally, we discuss how this knowledge could be clinically translated for the benefit of transplant patients.
Published: 2020
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10. Novel defatting strategies reduce lipid accumulation in primary human culture models of liver steatosis

Author: Lynda Aoudjehane, Jérémie Gautheron, Wilfried Le Goff, Claire Goumard, Julia Gilaizeau, Chan Sonavine Nget, Eric Savier, Muhammad Atif, Philippe Lesnik, Romain Morichon, Yves Chrétien, Yvon Calmus, Olivier Scatton, Chantal Housset, and Filomena Conti
Subjects: defatting, human hepatocytes, human precision-cut liver slices, liver transplantation, steatosis, triglycerides, Medicine, Pathology, RB1-214
Abstract: Normothermic perfusion provides a means to rescue steatotic liver grafts, including by pharmacological defatting. In this study, we tested the potential of new drug combinations to trigger defatting in three human culture models, primary hepatocytes with induced steatosis, primary hepatocytes isolated from steatotic liver, and precision-cut liver slices (PCLS) of steatotic liver. Forskolin, L-carnitine and a PPARα agonist were all combined with rapamycin, an immunosuppressant that induces autophagy, in a D-FAT cocktail. D-FAT was tested alone or in combination with necrosulfonamide, an inhibitor of mixed lineage kinase domain like pseudokinase involved in necroptosis. Within 24 h, in all three models, D-FAT induced a decrease in triglyceride content by 30%, attributable to an upregulation of genes involved in free fatty acid β-oxidation and autophagy, and a downregulation of those involved in lipogenesis. Defatting was accompanied by a decrease in endoplasmic reticulum stress and in the production of reactive oxygen species. The addition of necrosulfonamide increased the efficacy of defatting by 8%-12% in PCLS, with a trend towards increased autophagy. In conclusion, culture models, notably PCLS, are insightful to design strategies for liver graft rescue. Defatting can be rapidly achieved by combinations of drugs targeting mitochondrial oxidative metabolism, macro-autophagy and lipogenesis.
Published: 2020
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11. Regulatory T cells in solid organ transplantation

Author: Muhammad Atif, Filomena Conti, Guy Gorochov, Ye Htun Oo, and Makoto Miyara
Subjects: clinical trial, FOXP3, regulatory T cells, safety, transplant, Treg, Immunologic diseases. Allergy, RC581-607
Abstract: Abstract The induction of graft tolerance remains the holy grail of transplantation. This is important as chronic allograft dysfunction and the side effects of immunosuppression regimens place a major burden on the lives of transplant patients and their healthcare systems. This has mandated the need to understand the immunobiology of graft rejection and identify novel therapeutics. Regulatory T (Treg) cells play an important role in modulating pro‐inflammatory microenvironments and maintaining tissue homeostasis. However, there are fundamental unanswered questions regarding Treg cell immunobiology. These cells are a heterogeneous entity with functionally diverse roles. Moreover, the adoption of novel deeper immunophenotyping and genomic sequencing technologies has identified this phenotype and function to be more complex than expected. Hence, a comprehensive understanding of Treg cell heterogeneity is needed to safely and effectively exploit their therapeutic potential. From a clinical perspective, the recent decade has seen different clinical teams commence and complete first‐in‐man clinical trials utilising Treg cells as an adoptive cellular therapy. In this review, we discuss these trials from a translational perspective with an important focus on safety. Finally, we identify crucial knowledge gaps for future study.
Published: 2020
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12. An Efficient 5-Aminolevulinic Acid Photodynamic Therapy Treatment for Human Hepatocellular Carcinoma

Author: Delhem, Abhishek Kumar, Florian Pecquenard, Martha Baydoun, Alexandre Quilbé, Olivier Moralès, Bertrand Leroux, Lynda Aoudjehane, Filomena Conti, Emmanuel Boleslawski, and Nadira
Subjects: photodynamic therapy, hepatocellular carcinoma, 5-ALA, anti-tumor immunotherapy, anti-tumor immunity
Abstract: Photodynamic therapy (PDT) is a two-stage treatment relying on cytotoxicity induced by photoexcitation of a nontoxic dye, called photosensitizer (PS). Using 5-aminolevulinic acid (5-ALA), the pro-drug of PS protoporphyrin IX, we investigated the impact of PDT on hepatocellular carcinoma (HCC). Optimal 5-ALA PDT dose was determined on three HCC cell lines by analyzing cell death after treatment with varying doses. HCC-patient-derived tumor hepatocytes and healthy donor liver myofibroblasts were treated with optimal 5-ALA PDT doses. The proliferation of cancer cells and healthy donor immune cells cultured with 5-ALA-PDT-treated conditioned media was analyzed. Finally, therapy efficacy on humanized SCID mice model of HCC was investigated. 5-ALA PDT induced a dose-dependent decrease in viability, with an up-to-four-fold reduction in viability of patient tumor hepatocytes. The 5-ALA PDT treated conditioned media induced immune cell clonal expansion. 5-ALA PDT has no impact on myofibroblasts in terms of viability, while their activation decreased cancer cell proliferation and reduced the tumor growth rate of the in vivo model. For the first time, 5-ALA PDT has been validated on primary patient tumor hepatocytes and donor healthy liver myofibroblasts. 5-ALA PDT may be an effective anti-HCC therapy, which might induce an anti-tumor immune response.
Published: 2023
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13. Current challenges and future perspectives in treating patients with NAFLD-related cirrhosis

Author: Maxime Mallet, Cristina Alina Silaghi, Philippe Sultanik, Filomena Conti, Marika Rudler, Vlad Ratziu, Dominique Thabut, and Raluca Pais
Subjects: Hepatology
Published: 2023

14. High rate of early HEV seroconversion after liver transplantation among cirrhotic patients: Should we test for it?

Author: Alessandra Mazzola, Eve Todesco, Shadia Ali, Mathilde Bastide, Frederic Charlotte, Philippe Flandre, Sophie Sayon, Melanie Houot, Vincent Calvez, Dominique Thabut, Olivier Scatton, Anne-Geneviève Marcelin, and Filomena Conti
Subjects: Microbiology (medical), Infectious Diseases
Published: 2023

15. 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

16. Therapeutic potentials of mesenchymal stromal cells-derived extracellular vesicles in liver failure and marginal liver graft rehabilitation: a scoping review

Author: Alexandre SITBON, Pierre-Romain DELMOTTE, Claire GOUMARD, Célia TURCO, Jérémie GAUTHERON, Filomena CONTI, Lynda AOUDJEHANE, Olivier SCATTON, and Antoine MONSEL
Subjects: Anesthesiology and Pain Medicine
Published: 2023

17. Supplementary Figure S5 from Mitogenic Insulin Receptor-A Is Overexpressed in Human Hepatocellular Carcinoma due to EGFR-Mediated Dysregulation of RNA Splicing Factors

Author: Christèle Desbois-Mouthon, Olivier Rosmorduc, Chantal Housset, Françoise Praz, Filomena Conti, Olivier Soubrane, Olivier Scatton, Colette Rey, Yves Chrétien, Audrey Clapéron, Dominique Wendum, Lynda Aoudjehane, Laetitia Fartoux, and Hamza Chettouh
Abstract: Supplementary Figure S5 - PDF file 190K, The blockage of EGFR signalling does not alter the subcellular localization of splicing factors in HCC cells
Published: 2023

18. Data from Mitogenic Insulin Receptor-A Is Overexpressed in Human Hepatocellular Carcinoma due to EGFR-Mediated Dysregulation of RNA Splicing Factors

Author: Christèle Desbois-Mouthon, Olivier Rosmorduc, Chantal Housset, Françoise Praz, Filomena Conti, Olivier Soubrane, Olivier Scatton, Colette Rey, Yves Chrétien, Audrey Clapéron, Dominique Wendum, Lynda Aoudjehane, Laetitia Fartoux, and Hamza Chettouh
Abstract: Insulin receptor (IR) exists as two isoforms resulting from the alternative splicing of IR pre-mRNA. IR-B promotes the metabolic effects of insulin, whereas IR-A rather signals proliferative effects. IR-B is predominantly expressed in the adult liver. Here, we show that the alternative splicing of IR pre-mRNA is dysregulated in a panel of 85 human hepatocellular carcinoma (HCC) while being normal in adjacent nontumor liver tissue. An IR-B to IR-A switch is frequently observed in HCC tumors regardless of tumor etiology. Using pharmacologic and siRNA approaches, we show that the autocrine or paracrine activation of the EGF receptor (EGFR)/mitogen-activated protein/extracellular signal–regulated kinase pathway increases the IR-A:IR-B ratio in HCC cell lines, but not in normal hepatocytes, by upregulating the expression of the splicing factors CUGBP1, hnRNPH, hnRNPA1, hnRNPA2B1, and SF2/ASF. In HCC tumors, there is a significant correlation between the expression of IR-A and that of splicing factors. Dysregulation of IR pre-mRNA splicing was confirmed in a chemically induced model of HCC in rat but not in regenerating livers after partial hepatectomy. This study identifies a mechanism responsible for the generation of mitogenic IR-A and provides a novel interplay between IR and EGFR pathways in HCC. Increased expression of IR-A during neoplastic transformation of hepatocytes could mediate some of the adverse effects of hyperinsulinemia on HCC. Cancer Res; 73(13); 3974–86. ©2013 AACR.
Published: 2023

19. Supplementary Tables S1-S5 from Mitogenic Insulin Receptor-A Is Overexpressed in Human Hepatocellular Carcinoma due to EGFR-Mediated Dysregulation of RNA Splicing Factors

Author: Christèle Desbois-Mouthon, Olivier Rosmorduc, Chantal Housset, Françoise Praz, Filomena Conti, Olivier Soubrane, Olivier Scatton, Colette Rey, Yves Chrétien, Audrey Clapéron, Dominique Wendum, Lynda Aoudjehane, Laetitia Fartoux, and Hamza Chettouh
Abstract: Supplementary Tables S1-S5 - PDF file 94K, Clinicopathologic characteristics of patients with HCC (S1); Pharmacological inhibitors (S2); Antibodies for Western blot and immunofluorescence (S3); Primer pairs for qualitative and quantitative PCR (S4); Correlations between IR-A and splicing factor mRNA levels in human HCC tumours (S5)
Published: 2023

20. Supplementary Figure Legends from Mitogenic Insulin Receptor-A Is Overexpressed in Human Hepatocellular Carcinoma due to EGFR-Mediated Dysregulation of RNA Splicing Factors

Author: Christèle Desbois-Mouthon, Olivier Rosmorduc, Chantal Housset, Françoise Praz, Filomena Conti, Olivier Soubrane, Olivier Scatton, Colette Rey, Yves Chrétien, Audrey Clapéron, Dominique Wendum, Lynda Aoudjehane, Laetitia Fartoux, and Hamza Chettouh
Abstract: Supplementary Figure Legends - PDF file 119K, Legend for Supplementary Figures S1-S6
Published: 2023

21. 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

22. Poor Antibody Response After Two Doses of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine in Transplant Recipients

Author: A. Mazzola, Eve Todesco, Fanny Hazan, Dominique Thabut, Benoit Barrou, Anne-Geneviève Marcelin, Filomena Conti, Stéphane Marot, Cathia Soulié, Sheida Varnous, and Sarah J. Drouin
Subjects: Microbiology (medical), 2019-20 coronavirus outbreak, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030204 cardiovascular system & hematology, Antibodies, Viral, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, 030212 general & internal medicine, Adverse effect, BNT162 Vaccine, COVID-19 disease, SARS-CoV-2, business.industry, Brief Report, COVID-19, Virology, Transplant Recipients, anti-spike antibodies, 3. Good health, AcademicSubjects/MED00290, SARS-CoV-2 vaccination, Infectious Diseases, Antibody response, Poor antibody response, Antibody Formation, business, SOT recipients, humoral response
Abstract: A low anti-spike antibody response of 28.6% was observed 28 days after BNT162b2 vaccine second dose among 133 solid organ transplant recipients without previous coronavirus disease 2019 (COVID-19). No serious adverse events were recorded. Four severe COVID-19 cases were reported between or after the 2 doses. Our data suggest to change the vaccine strategy.
Published: 2021

23. 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

24. 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

25. Five-year outcomes in liver transplant patients receiving everolimus with or without a calcineurin inhibitor: Results from the CERTITUDE study

Author: Faouzi Saliba, Christophe Duvoux, Sébastien Dharancy, Jérôme Dumortier, Yvon Calmus, Jean Gugenheim, Nassim Kamar, Ephrem Salamé, Martine Neau‐Cransac, Claire Vanlemmens, François Durand, Georges‐Philippe Pageaux, Jean Hardwigsen, Yasmina Benkhatar, François Derquenne, and Filomena Conti
Subjects: Graft Rejection, Carcinoma, Hepatocellular, Hepatology, Calcineurin Inhibitors, Graft Survival, Liver Neoplasms, Humans, Everolimus, Immunosuppressive Agents, Tacrolimus, Liver Transplantation
Abstract: To report 5-year outcomes of the CERTITUDE study.An observational study in patients with liver transplantation (LTx) compared the long-term impact of immunosuppression (with/without a calcineurin inhibitor) on renal function, cancers, major cardiovascular events (MACEs) and other safety parameters. All patients completing the 6-month SIMCER study were recruited and analysed according to treatment received at randomization and actual treatment received during the follow-up.Of the 143 enrolled patients, 119 completed the 5-year follow-up (everolimus [EVR], n = 55; tacrolimus [TAC], n = 64). The mean absolute change in estimated glomerular filtration rate was not statistically different between both groups (TAC, -15.53 ml/min/1.73 mThe CERTITUDE study demonstrated that EVR- and TAC-based regimens have comparable efficacy, safety and tolerability up to 5 years post-LTx.
Published: 2022

26. Biliary complications after liver transplantation: current perspectives and future strategies

Author: Matteo Tacelli, Filomena Conti, Alessandra Mazzola, Ciro Celsa, Bianca Magro, Magro, Bianca, Tacelli, Matteo, Mazzola, Alessandra, Conti, Filomena, and Celsa, Ciro
Subjects: medicine.medical_specialty, Endoscopic retrograde cholangiopancreatography, Percutaneous, medicine.diagnostic_test, Bile duct, business.industry, Liver transplantation (LT), biliary tract diseases, cholangiography, cholangiopancreatography endoscopic retrograde, review, medicine.medical_treatment, 030230 surgery, Liver transplantation, medicine.disease, Surgery, Transplantation, 03 medical and health sciences, Liver disease, 0302 clinical medicine, medicine.anatomical_structure, Cholangiography, medicine, Etiology, 030211 gastroenterology & hepatology, business
Abstract: Importance: Liver transplantation (LT) is a life-saving therapy for patients with end-stage liver disease and with acute liver failure, and it is associated with excellent outcomes and survival rates at 1 and 5 years. The incidence of biliary complications (BCs) after LT is reported to range from 5% to 20%, most of them occurring in the first three months, although they can occur also several years after transplantation.Objective: The aim of this review is to summarize the available evidences on pathophysiology, risk factors, diagnosis and therapeutic management of BCs after LT.Evidence Review: a literature review was performed of papers on this topic focusing on risk factors, classifications, diagnosis and treatmentFindings: Principal risk factors include surgical techniques and donor's characteristics for biliary leakage and anastomotic biliary strictures and vascular alterations for nonanastomotic biliary strictures. MRCP is the gold standard both for intra- and extrahepatic BCs, while invasive cholangiography should be restricted for therapeutic uses or when MRCP is equivocal. About treatment, endoscopic techniques are the first line of treatment with success rates of 70-100%. The combined success rate of ERCP and PTBD overcome 90% of cases. Biliary leaks often resolve spontaneously, or with the positioning of a stent in ERCP for major bile leaksConclusions and Relevance: BCs influence morbidity and mortality after LT, therefore further evidences are needed to identify novel possible risk factors, to understand if an immunological status that could lead to their development exists and to compare the effectiveness of innovative surgical and machine perfusion techniques.
Published: 2021

27. Hepatitis C Virus Improves Human Tregs Suppressive Function and Promotes Their Recruitment to the Liver

Author: Laurissa Ouaguia, Olivier Moralès, Lynda Aoudjehane, Czeslaw Wychowski, Abhishek Kumar, Jean Dubuisson, Yvon Calmus, Filomena Conti, and Nadira Delhem
Subjects: hcv, hcv/jfh-1, regulatory t cells, chemokines, immune escape, Cytology, QH573-671
Abstract: Background: The role of regulatory T cells (Tregs) is now well established in the progression of hepatocellular carcinoma (HCC) linked to Hepatitis C virus (HCV) infection. However, nothing is known about the potential interplay between Tregs and HCV. In this pilot study, we have investigated the ability of Tregs to hang HCV on and the subsequent effect on their suppressive function and phenotype. Moreover, we have evaluated how HCV could promote the recruitment of Tregs by infected primary human hepatocytes. Methods: Tregs of healthy donors were incubated with JFH-1/HCVcc. Viral inoculation was assessed using adapted assays (RT-qPCR, Flow Citometry (FACS) and Western Blot (WB). Expression of Tregs phenotypic (CD4, CD25, CD127 and Foxp3) and functional (IL-10, GZMB, TGF-β1 and IL-2) markers was monitored by RT-qPCR, FACS and ELISA. Suppressive activity was validated by suppressive assays. Tregs recruitment by infected primary hepatic cells was evaluated using Boyden Chamber. Results: Tregs express the classical HCV receptors (CD81, CLDN1 and LDLR) and some co-receptors (CD5). HCV inoculation significantly increases the suppressive phenotype and activity of Tregs, and raises their anergy by inducing an unexpected IL-2 production. Moreover, HCV infection induces the expression of chemokines (CCL17, CXCL16, and CCL20) by primary hepatic human hepatocytes and chemokine receptors (CCR4, CXCR6 and CCR6) by Tregs. Finally, infected hepatocytes have a significantly higher potential to recruit Tregs in a seemingly CCL20-dependent manner. Conclusions: Direct interaction between HCV and Tregs represents a newly defined mechanism that could potentiate HCV immune evasion and favor intratumoral recruitment contributing to HCC progression.
Published: 2019
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28. A standardized immunosuppressive regimen for patients who received liver transplantations treated with atezolizumab-bevacizumab to avoid graft rejection?

Author: Edouard Larrey, Filomena Conti, and Manon Allaire
Subjects: Bevacizumab, Graft Rejection, Transplantation, Hepatology, Humans, Surgery, Antibodies, Monoclonal, Humanized, Immunosuppressive Agents, Liver Transplantation
Published: 2022

29. Transplantation Outcome in Recipients Engrafted With Organs Recovered From the First French Deceased Donor With a SARS-COV-2 Vaccine-induced Thrombotic Thrombocytopenia

Author: Yanish Soorojebally, Caroline Pettenati, Mathilde Lefebvre, Thibaut d'Izarny Gargas, Albane Sartorius-Brodin, Michel Delahousse, Alexandre Hertig, Matthieu Jamme, Mickael Vourc'h, Filomena Conti, Ismail Elalamy, Marion Rabant, Sophie Ferlicot, Adrien Tissot, and Eva Desire
Subjects: Transplantation, 2019-20 coronavirus outbreak, Deceased donor, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Donor selection, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Treatment outcome, Organ transplantation, Immunology, Medicine, business
Published: 2021

30. Portopulmonary hypertension in the current era of pulmonary hypertension management

Author: François Durand, Laurent Savale, Clément Boissin, Olivier Sitbon, Claire Francoz, Hélène Bouvaist, Jean-Charles Duclos-Vallée, Ari Chaouat, Manuel Guimas, Pamela Moceri, Emmanuel Bergot, Pascal Magro, David Montani, Nicolas Lamblin, Vincent Cottin, Marianne Riou, Filomena Conti, Marc Humbert, Nicolas Favrolt, Romain Trésorier, Xavier Jaïs, Sébastien Renard, Philippe Hervé, Grégoire Prévot, Cécile Tromeur, Bruno Degano, Céline Chabanne, Delphine Bourlier, Nathan Ebstein, Sylvain Palat, Didier Samuel, Gérald Simonneau, Elise Artaud-Macari, Delphine Horeau-Langlard, Pascal de Groote, Anne-Claire Simon, Mitja Jevnikar, Audrey Coilly, and Marie Fertin
Subjects: 0301 basic medicine, medicine.medical_specialty, Portopulmonary hypertension, Cirrhosis, Hepatology, business.industry, medicine.medical_treatment, Liver transplantation, Chronic liver disease, medicine.disease, Pulmonary hypertension, Transplantation, 03 medical and health sciences, Liver disease, 030104 developmental biology, 0302 clinical medicine, Internal medicine, medicine, 030211 gastroenterology & hepatology, business, Contraindication
Abstract: Background & Aims Long-term outcomes in portopulmonary hypertension (PoPH) are poorly studied in the current era of pulmonary hypertension management. We analysed the effect of pulmonary arterial hypertension (PAH)-targeted therapies, survival and predictors of death in a large contemporary cohort of patients with PoPH. Methods Data from patients with PoPH consecutively enrolled in the French Pulmonary Hypertension Registry between 2007 and 2017 were collected. The effect of initial treatment strategies on functional class, exercise capacity and cardiopulmonary haemodynamics were analysed. Survival and its association with PAH- and hepatic-related characteristics were also examined. Results Six hundred and thirty-seven patients (mean age 55 ± 10 years; 58% male) were included. Fifty-seven percent had mild cirrhosis, i.e. Child-Pugh stage A. The median model for end-stage liver disease (MELD) score was 11 (IQR 9–15). Most patients (n = 474; 74%) were initiated on monotherapy, either with a phosphodiesterase-5 inhibitor (n = 336) or with an endothelin-receptor antagonist (n = 128); 95 (15%) were initiated on double oral combination therapy and 5 (1%) on triple therapy. After a median treatment time of 4.5 months, there were significant improvements in functional class (p Conclusion Survival of patients with PoPH is strongly associated with the severity of liver disease. Patients who underwent liver transplantation had the best long-term outcomes. Lay summary Portopulmonary hypertension is defined by the presence of pulmonary arterial hypertension in the context of chronic liver disease and is characterized by progressive shortness of breath and exercise limitation. The presence of severe pulmonary arterial hypertension in liver transplant candidates represents a contraindication for such a surgery; however, treatments targeting pulmonary arterial hypertension are efficacious, allowing for safe transplantation and conferring good survival outcomes in those who undergo liver transplantation.
Published: 2020

31. Long-term impact of preventive UDCA therapy after transplantation for primary biliary cholangitis

Author: Gideon M. Hirschfield, Maryam Ebadi, Xavier Verhelst, Federica Malinverno, Nora Cazzagon, Pierre Belnou, Christophe Corpechot, Falk Rauchfuss, Olivier Boillot, Raoul Poupon, Jérôme Dumortier, Palak J. Trivedi, Maria Francesca Donato, Sascha Chopra, Dennis Eurich, Francesco Paolo Russo, Martina Sterneck, Aldo J. Montano-Loza, Maren H. Harms, Fabrice Carrat, Philipp A. Reuken, Christoph Schramm, Alexie Bosch, Albert Parés, Patrick McDowell, Davide Roccarina, Andrew Mason, Jorn C Goet, Bettina E. Hansen, Emiliano Giostra, Anna Reig, Annarosa Floreani, Dietmar Jacob, Douglas Thorburn, Olivier Chazouillères, Tony Bruns, Alessio Gerussi, Henk R. van Buuren, Filomena Conti, Frederik Nevens, Corpechot, C, Chazouilleres, O, Belnou, P, Montano-Loza, A, Mason, A, Ebadi, M, Eurich, D, Chopra, S, Jacob, D, Schramm, C, Sterneck, M, Bruns, T, Reuken, P, Rauchfuss, F, Roccarina, D, Thorburn, D, Gerussi, A, Trivedi, P, Hirschfield, G, Mcdowell, P, Nevens, F, Boillot, O, Bosch, A, Giostra, E, Conti, F, Poupon, R, Pares, A, Reig, A, Donato, M, Malinverno, F, Floreani, A, Russo, F, Cazzagon, N, Verhelst, X, Goet, J, Harms, M, van Buuren, H, Hansen, B, Carrat, F, Dumortier, J, Gastroenterology & Hepatology, 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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Graft Rejection, Male, 0301 basic medicine, Cholagogues and Choleretics, Cirrhosis, Survival, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Placebo-controlled study, Liver transplantation, PBC, Gastroenterology, UDCA, 0302 clinical medicine, MED/12 - GASTROENTEROLOGIA, Recurrence, Liver Cirrhosis, Biliary, Ursodeoxycholic Acid, Hazard ratio, Middle Aged, Ursodeoxycholic acid, 3. Good health, Survival Rate, Treatment Outcome, Tacrolimu, Cyclosporine, Tacrolimus, Transplantation, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, Immunosuppressive Agents, medicine.drug, Risk, medicine.medical_specialty, 03 medical and health sciences, Internal medicine, medicine, Humans, Aged, Retrospective Studies, Hepatology, business.industry, Retrospective cohort study, medicine.disease, digestive system diseases, Liver Transplantation, Regimen, 030104 developmental biology, MED/09 - MEDICINA INTERNA, business, Follow-Up Studies
Abstract: Background & Aims: Recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT) is frequent and can impair graft and patient survival. Ursodeoxycholic acid (UDCA) is the current standard therapy for PBC. We investigated the effect of preventive exposure to UDCA on the incidence and long-term consequences of PBC recurrence after LT. Methods: We performed a retrospective cohort study in 780 patients transplanted for PBC, between 1983–2017 in 16 centers (9 countries), and followed-up for a median of 11 years. Among them, 190 received preventive UDCA (10–15 mg/kg/day). The primary outcome was histological evidence of PBC recurrence. The secondary outcomes were graft loss, liver-related death, and all-cause death. The association between preventive UDCA and outcomes was quantified using multivariable-adjusted Cox and restricted mean survival time (RMST) models. Results: While recurrence of PBC significantly shortened graft and patient survival, preventive exposure to UDCA was associated with reduced risk of PBC recurrence (adjusted hazard ratio [aHR] 0.41; 95% CI 0.28–0.61; p
Published: 2020

32. Posttransplant immune-mediated cholangiopathies

Author: Jérôme Dumortier, Filomena Conti, and Jean-Yves Scoazec
Subjects: End Stage Liver Disease, Liver Cirrhosis, Biliary, Recurrence, Cholangitis, Sclerosing, Gastroenterology, Graft vs Host Disease, Humans, Neoplasm Recurrence, Local, Liver Transplantation
Abstract: Liver transplantation (LT) is the treatment of end-stage chronic liver diseases, mainly decompensated cirrhosis and hepatocellular carcinoma. Biliary complications can be schematically classified into macroscopic versus microscopic lesions. Immune-related cholangiopathies include rejection, graft-versus-host disease (GVHD) and recurrence of pre-LT auto-immune biliary diseases, i.e. primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Here, we review the various types of posttransplant immune-related cholangiopathies, and discuss their clinical implications, especially diagnostic issues.Recurrence of PBC and PSC after LT is increasingly well described in large cohorts and long-term follow-up. In this setting, the preventive effect of ursodeoxycholic acid on PBC recurrence, as well as the deleterious role of tacrolimus are now well documented. In addition, the significant negative impact of recurrent PBC on survival after LT has recently been demonstrated. With respect to rejection-associated biliary injury, a growing body of evidence is emerging on the role of anti-HLA antibody-mediated rejection.Immune-mediated cholangiopathies occurring after LT can be divided in two main nosologic groups: biliary lesions due to recurrence of PBC or PSC, or in the context of rejection, either acute or chronic, T-cell- or antibody-mediated. GVHD is very rare. Final diagnosis is strongly based on clinical context (indication for LT, delay since transplantation, biological abnormalities, imaging) but also and to an even greater extent on biopsy of liver graft. Clinico-pathological discussions are recommended, hearing in mind that diseases can be intertwined.
Published: 2022

33. 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

34. Multimodal single cell analysis reveals the basis for butyrate induction of TNFα-secreting regulatory T cells

Author: Mo Atif, Mustapha Cherai, Clara Cretet, Melissa Saichi, Lynda Aoudjehane, Baptiste Fouquet, Robert Balderas, Filomena Conti, Olivier Scatton, Ye Htun Oo, Guy Gorochov, and Makoto Miyara
Subjects: Hepatology
Published: 2022

35. 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

36. Infection of Human Liver Myofibroblasts by Hepatitis C Virus: A Direct Mechanism of Liver Fibrosis in Hepatitis C.

Author: Lynda Aoudjehane, Grégoire Bisch, Olivier Scatton, Christelle Granier, Jesintha Gaston, Chantal Housset, Philippe Roingeard, François-Loïc Cosset, Fabiano Perdigao, Pierre Balladur, Takaji Wakita, Yvon Calmus, and Filomena Conti
Subjects: Medicine, Science
Abstract: Chronic hepatitis C is a major cause of liver fibrosis and cirrhosis. It is generally accepted that inflammation that occurs in response to hepatocyte infection by the hepatitis C virus (HCV) is the main mechanism that triggers myofibroblast differentiation and stimulation in chronic hepatitis C. The aim of this study was to determine if HCV might infect human liver myofibroblasts (HLMF) and directly stimulate their fibrogenic activities.We evaluated the expression of the viral entry receptors, levels of HCV-RNA and HCV-protein and the expression of fibrosis markers in HLMF by using quantitative PCR, western blot and immunofluorescence analyses. Pseudoparticles (HCVpp) and cell culture-derived HCV (HCVcc) were used to study the ability of HLMF to support viral entry, replication and fibrosis induction.We showed that HLMF expressed all known molecules of the HCV receptor complex, i.e. CD81, LDL-R, scavenger receptor-BI, claudin-1 and occludin. These cells were also permissive to HCVpp entry. Inoculation with HCVcc caused short-term infection of these cells, as shown by their content in positive- and negative-strand HCV RNA, in core and NS3 viral proteins, and by their release of core protein levels in the culture supernatants. HCV infection stimulated myofibroblastic differentiation, proliferation and collagen production in these cells. In addition, evidence of in vivo infection was provided by the detection of positive- and negative-strand HCV RNA in preparations of HLMF obtained from HCV-infected patients.These findings indicate that HCV infection of HLMF can occur and trigger extracellular matrix overproduction, thereby contributing to the development of HCV-related liver fibrosis.
Published: 2015
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37. Liver transplantation from donors with Down Syndrome

Author: Eric Savier, G. Rousseau, Filomena Conti, Claire Goumard, Olivier Scatton, Fabiano Perdigao, Chetana Lim, Alessandra Mazzola, Benjamin Fernandez, CCSD, Accord Elsevier, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], 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), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Down syndrome, medicine.medical_specialty, Hepatology, business.industry, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Gastroenterology, MEDLINE, Liver transplantation, medicine.disease, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Internal medicine, medicine, 030211 gastroenterology & hepatology, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; No abstract available
Published: 2020

38. 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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39. Hepatitis B or Delta liver transplant patients at risk of recurrence: Long-term effectiveness and budget impact of low-dose subcutaneous anti-hepatitis B immunoglobulin plus patient education program

Author: Pascal Lebray, Sophie Delignat, Alice Frelicot, Marion Carrette, Alix Gautier, Nicolas Jamet, Christophe Lecefel, Mélanie Houot, Sandrine Bourguignon, Dominique Thabut, Filomena Conti, and Amélie Liou
Published: 2022

40. Impact of Sarcopenia on Clinical Outcomes of Patients Undergoing Simultaneous Liver and Kidney Transplantation: A Cohort Study

Author: R. Brustia, Jérôme Tourret, Nassera Ouali, Benoit Barrou, Muhammad Atif, Filomena Conti, A. Mazzola, Olivier Scatton, Bianca Magro, Sorbonne Université (SU), Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC), Université de Picardie Jules Verne (UPJV), Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Urologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Université - Faculté de Médecine (SU FM), 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), and Oncovet
Subjects: Male, Sarcopenia, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Liver transplantation, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Renal Dialysis, Internal medicine, medicine, Humans, Kidney transplantation, Dialysis, Hepatology, business.industry, Gastroenterology, Postoperative complication, Middle Aged, medicine.disease, Kidney Transplantation, Liver Transplantation, Transplantation, Treatment Outcome, 030220 oncology & carcinogenesis, Cohort, Female, 030211 gastroenterology & hepatology, business, Cohort study
Abstract: International audience; Background: The impact of sarcopenia in patients undergoing simultaneous liver and kidney transplantation (SLKT) has not been fully delineated. The aim of this single-centre-cohort-study was to evaluate the impact of sarcopenia on the clinical outcomes. Methods: Between 2003 and 2018, 79 patients underwent SLKT. Sarcopenia was assessed via the total psoas muscle area (TPA) at the level of the 3rd. lumbar vertebra. Sarcopenia threshold was TPA < 1460 mm2 (women) and
Published: 2021

41. 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

42. 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

43. COVID-19 in a liver transplant recipient: Could iatrogenic immunosuppression have prevented severe pneumonia? A case report

Author: Alessandra Mazzola, Olivier Scatton, Mohammed Atif, Valérie Pourcher, Filomena Conti, Juliana Pappatella, Chetana Lim, Anna Sessa, University of Naples Federico II, Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], 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], Gestionnaire, Hal Sorbonne Université, University of Naples Federico II = Università degli studi di Napoli Federico II, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Centre de Recherche Saint-Antoine (CRSA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Graft Rejection, Male, Pediatrics, medicine.medical_specialty, Nausea, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Anosmia, Liver transplantation, medicine.disease_cause, Severity of Illness Index, 03 medical and health sciences, Immunocompromised Host, 0302 clinical medicine, Gastrointestinal symptom, Case report, Medicine, Humans, Lung, Coronavirus, Immunosuppression Therapy, business.industry, SARS-CoV-2, Gastroenterology, COVID-19, Immunosuppression, General Medicine, Middle Aged, Tacrolimus, 3. Good health, Dysgeusia, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Vomiting, 030211 gastroenterology & hepatology, medicine.symptom, business, Tomography, X-Ray Computed, Infection
Abstract: International audience; Background: Coronavirus disease (COVID) is a new and highly contagious infectious disease caused by the coronavirus (COVID-19 or severe acute respiratory syndrome coronavirus 2). There is limited data regarding the incidence and management of COVID-19 in immunocompromised patients' post-transplantation. In the pre-COVID-19 era, these patients were already at an increased risk of developing opportunistic infections. These often manifested with atypical symptoms.Case summary: We report another case of uneventful COVID-19 pneumonia in a 58-year old male who was 18 mo' post liver transplantation. He received tacrolimus monotherapy since July 2019. The clinical manifestations included only epigastric pain radiating to the right hypochondrium, nausea and vomiting. He had no fevers, cough, shortness of breath, anosmia or dysgeusia even if the chest computed tomography scan revealed an extension of the multiple patchy ground-glass density shadows to the upper lobe of the left lung too. He was hospitalised and received a course of oral chloroquine (200 mg × 3 per day) for a period of 10 d. Interestingly, the COVID 19 infection was uneventful though there were no modifications to his tacrolimus dosing. He was successfully discharged. We performed subsequent follow-up via telemedicine.Conclusion: In light of the current pandemic, it is even more important to identify how the liver recipient's patients present and are managed, especially for immunosuppression treatment.
Published: 2020

44. Impact of the first Covid-19 outbreak on liver transplantation activity in France: A snapshot

Author: Olivier Bastien, Chetana Lim, Géraldine Malaquin, François Kerbaul, Olivier Scatton, Filomena Conti, Célia Turco, and Olivier Soubrane
Subjects: Adult, Brain Death, 2019-20 coronavirus outbreak, medicine.medical_specialty, Tissue and Organ Procurement, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, coronavirus, liver procurement, North east, Liver transplantation, LT, liver transplantation, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Pandemic, medicine, Humans, Organ donation, Pandemics, COVID-19, coronavirus disease 2019, Retrospective Studies, liver transplantation, Hepatology, business.industry, Gastroenterology, COVID-19, Outbreak, ICU, intensive care unit, 030220 oncology & carcinogenesis, Original Article, ABM, Agence de la Biomédecine, 030211 gastroenterology & hepatology, France, Adult liver, business
Abstract: Highlights • The global pandemic of Coronavirus Disease 2019 has drastically affected liver transplantation programs worldwide. • There was a significant decrease in the number of organ donations and liver transplantations performed in France. • The North East area which was the main Coronavirus Disease 2019 cluster area had > 25% decrease of the multiorgan procurement and liver transplantations in 2020 compared to 2019., Background The global pandemic of Coronavirus Disease 2019 (COVID-19) has potentially affected liver transplantation (LT) programs worldwide. The aim of this study was to determine whether the COVID-19 outbreak affected organ donation and LT activity in France. Methods Data on the number of brain-dead donor procurements and adult liver transplantations were compared between two periods (1st January- 31st May 2019 vs. 1st January-31st May 2020). Main findings There was a 28% decrease in the number of organ donations in 2020 (543 in 2020vs. 752 organ donations in 2019). A 22% decrease in the number of liver transplantations was also observed: 435 in 2020 vs. 556 LTs in 2019. Overall, the North East area which was the main COVID-19 cluster area, had > 25% decrease of the multiorgan procurement (-33% compared to 2019), and liver transplantation (-26% compared to 2019) activities in 2020 Conclusion This analysis confirmed that during the COVID-19 outbreak there was a significant decrease in the number of organ donations and liver transplantations performed in France.
Published: 2020
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45. The impact of Coronavirus 19 disease on liver transplantation in France: The sickest first approach?

Author: Valérie Pourcher, Géraldine Malaquin, Muhammad Atif, Olivier Scatton, A. Mazzola, François Kerbaul, Antoine Monsel, Filomena Conti, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Dysoxie, suractivité : aspects cellulaires et intégratifs thérapeutiques (DS-ACI / UMR MD2), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Agence de la biomédecine [Saint-Denis la Plaine], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Centre de Recherche Saint-Antoine (CRSA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: 2019-20 coronavirus outbreak, Waiting Lists, [SDV]Life Sciences [q-bio], Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine.medical_treatment, Pneumonia, Viral, Disease, Liver transplantation, medicine.disease_cause, Risk Assessment, Article, Betacoronavirus, medicine, Humans, Pandemics, Coronavirus, Hepatology, biology, Viral Epidemiology, business.industry, SARS-CoV-2, Patient Selection, Gastroenterology, COVID-19, biology.organism_classification, medicine.disease, Virology, Kidney Transplantation, Tissue Donors, Liver Transplantation, Intestines, Pneumonia, Practice Guidelines as Topic, Heart Transplantation, France, Pancreas Transplantation, business, Coronavirus Infections, Lung Transplantation
Abstract: Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Published: 2020

46. Acute liver failure and HELLP syndrome: A clinical case and literature review

Author: Fabiano Perdigao, Alessandra Mazzola, Filomena Conti, Claire Goumard, Frédéric Charlotte, Olivier Scatton, Muhammad Atif, and Bianca Magro
Subjects: Adult, medicine.medical_specialty, HELLP Syndrome, HELLP syndrome, medicine.medical_treatment, Liver transplantation, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Pregnancy, medicine, Humans, Hematoma, Hepatology, business.industry, Cesarean Section, Liver Diseases, Gastroenterology, Liver failure, Emergency Caesarean Section, Emergency department, Liver Failure, Acute, medicine.disease, Surgery, 030220 oncology & carcinogenesis, Gestation, 030211 gastroenterology & hepatology, Female, Clinical case, business
Abstract: Summary Background HELLP syndrome is a pregnancy-related liver disease associated with increased maternal and foetal mortality. In rare cases, it can lead to the development of a subcapsular hepatic haematoma as well as its rupture. This rupture is life-threatening if not urgently treated. Method We describe a clinical case of HELLP syndrome involving a ruptured subcapsular liver haematoma and contextualise this with a literature overview. Clinical case A 39-year-old woman of 40 weeks’ gestation presented to her local Emergency Department with symptoms and serology classically associated with HELLP syndrome. However, she clinically deteriorated and developed a ruptured subcapsular haematoma. She underwent an emergency Caesarean section at her initial hospital. Upon clinical stabilisation, she was transferred to our transplant unit for an urgent liver transplant. Conclusion LT is a life-saving procedure for patients with acute liver failure secondary to HELLP syndrome. These patients should be immediately referred to a high-volume transplant centre.
Published: 2020

47. Novel defatting strategies reduce lipid accumulation in primary human culture models of liver steatosis

Author: Claire Goumard, Wilfried Le Goff, Eric Savier, Filomena Conti, Olivier Scatton, Philippe Lesnik, Yvon Calmus, Chan Sonavine Nget, Jérémie Gautheron, Chantal Housset, Lynda Aoudjehane, Romain Morichon, Julia Gilaizeau, Muhammad Atif, Yves Chrétien, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], 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), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépatologie [CHU Saint-Antoine], 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), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université (SU), Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), 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 Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Cytométrie et Imagerie Saint-Antoine (CISA), Unité Mixte de Service d'Imagerie et de Cytométrie [CHU Saint-Antoine] (UMS LUMIC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Service d'Hépato-gastro-entérologie [CHU Saint-Antoine]
Subjects: Male, 0301 basic medicine, Steatosis, Human hepatocytes, medicine.medical_treatment, [SDV]Life Sciences [q-bio], lcsh:Medicine, Medicine (miscellaneous), Pharmacology, Liver transplantation, 0302 clinical medicine, Immunology and Microbiology (miscellaneous), Cells, Cultured, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, Sulfonamides, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Fatty Acids, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Lipogenesis, Female, 030211 gastroenterology & hepatology, lcsh:RB1-214, Signal Transduction, Research Article, Human precision-cut liver slices, Necroptosis, Neuroscience (miscellaneous), [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Models, Biological, General Biochemistry, Genetics and Molecular Biology, Defatting, 03 medical and health sciences, Downregulation and upregulation, lcsh:Pathology, medicine, Humans, Triglycerides, Acrylamides, Reactive oxygen species, lcsh:R, Autophagy, Lipid Metabolism, medicine.disease, Fatty Liver, 030104 developmental biology, chemistry, Hepatocytes, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Normothermic perfusion provides a means to rescue steatotic liver grafts, including by pharmacological defatting. In this study, we tested the potential of new drug combinations to trigger defatting in three human culture models, primary hepatocytes with induced steatosis, primary hepatocytes isolated from steatotic liver, and precision-cut liver slices (PCLS) of steatotic liver. Forskolin, L-carnitine and a PPARα agonist were all combined with rapamycin, an immunosuppressant that induces autophagy, in a D-FAT cocktail. D-FAT was tested alone or in combination with necrosulfonamide, an inhibitor of mixed lineage kinase domain like pseudokinase involved in necroptosis. Within 24 h, in all three models, D-FAT induced a decrease in triglyceride content by 30%, attributable to an upregulation of genes involved in free fatty acid β-oxidation and autophagy, and a downregulation of those involved in lipogenesis. Defatting was accompanied by a decrease in endoplasmic reticulum stress and in the production of reactive oxygen species. The addition of necrosulfonamide increased the efficacy of defatting by 8%-12% in PCLS, with a trend towards increased autophagy. In conclusion, culture models, notably PCLS, are insightful to design strategies for liver graft rescue. Defatting can be rapidly achieved by combinations of drugs targeting mitochondrial oxidative metabolism, macro-autophagy and lipogenesis., Summary: This study describes a defatting cocktail that has been proven to function in three relevant steatotic human culture models without cytotoxicity, and which could be employed in the reduction of steatosis in donor livers during liver transplantation.
Published: 2020

48. Consequences of Extended Spectrum Beta-Lactamase-Producing Enterobacteriaceae and Methicillin-Resistant Staphylococcus aureus Carriage in Awaiting Liver Transplant Patients

Author: Olivier Scatton, Claire Goumard, Salvatore Battaglia, Ciro Celsa, Calogero Cammà, Denis Bernard, Bianca Magro, Mona Munteanu, Valerie Martinez, A. Mazzola, Filomena Conti, HAL-SU, Gestionnaire, 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), Università degli studi di Palermo - University of Palermo, 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), Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Service de Chirurgie Générale, Viscérale et Endocrinienne [CHU Pitié-Sapêtrière], Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], Sezione di Gastroenterologia, Di.Bi.M.I.S., University of Palermo, Italy, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Institut de Cardiométabolisme et Nutrition - Institute of Cardiometabolism and Nutrition, Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Magro B., Mazzola A., Munteanu M., Goumard C., Martinez V., Bernard D., Scatton O., Battaglia S., Celsa C., Camma C., and Conti F.
Subjects: Male, Methicillin-Resistant Staphylococcus aureus, medicine.medical_specialty, Cirrhosis, medicine.medical_treatment, ESBLE, Liver transplantation, medicine.disease_cause, Severity of Illness Index, beta-Lactamases, beta-Lactamase, End Stage Liver Disease, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Enterobacteriaceae, Retrospective Studie, Risk Factors, Internal medicine, Severity of illness, Medicine, Humans, Aged, Retrospective Studies, 0303 health sciences, Transplantation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Hepatology, 030306 microbiology, business.industry, Risk Factor, cirrhosis, Enterobacteriaceae Infections, Retrospective cohort study, Middle Aged, medicine.disease, Enterobacteriaceae Infection, Methicillin-resistant Staphylococcus aureus, 3. Good health, Liver Transplantation, Carriage, Cohort, 030211 gastroenterology & hepatology, Surgery, fecal carriage, Female, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Infections in patients with cirrhosis are associated with liver-related complications (LRCs), especially in patients awaiting liver transplantation (LT). The aim of this study was to evaluate the impact of methicillin-resistant Staphylococcus aureus (MRSA) and extended spectrum beta-lactamase colonization on infections and LRCs for patients on the wait list and on infections after LT. We retrospectively included 250 of 483 patients with cirrhosis who were placed on the wait list for LT from December 2015 to January 2018. These patients were screened for MRSA or extended spectrum beta-lactamase–producing Enterobacteriaceae (ESBLE) at the time of wait-list placement and after LT. Of the patients, 76% were male with a mean age of 57.5±10 years, and the most frequent cause of liver disease was alcohol (39%). Median Model for End-Stage Liver Disease (MELD) score was 19 (12-28). Only 1 patient was positive for MRSA; 19% of patients (n=47) had ESBLE fecal carriage at the time of wait-list placement and 15% (n=37) had it after LT. Infection-free survival on the wait list and after LT, according to fecal carriage status, was not statistically different between 2 groups. LRC-free survival at 6 and 12months was significantly lower in ESBLE fecal carriage (HR, 1.6; P =0.04). MELD score >19 (HR, 3.0; P=0.01) and occurrence of infection during the first 3months on the wait list (HR, 4.13; P&nbsp
Published: 2020

49. 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

50. Regulatory T cells in solid organ transplantation

Author: Guy Gorochov, Filomena Conti, Makoto Miyara, Ye Htun Oo, Muhammad Atif, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Birmingham [Birmingham], Centre d'Immunologie et des Maladies Infectieuses (CIMI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Gestionnaire, Hal Sorbonne Université
Subjects: 0301 basic medicine, lcsh:Immunologic diseases. Allergy, safety, FOXP3, medicine.medical_treatment, Immunology, Reviews, Review, 030230 surgery, regulatory T cells, 03 medical and health sciences, 0302 clinical medicine, Immunophenotyping, medicine, Immunology and Allergy, transplant, General Nursing, Tissue homeostasis, business.industry, Immunosuppression, clinical trial, 3. Good health, Holy Grail, Clinical trial, Transplantation, Treg, 030104 developmental biology, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, business, Solid organ transplantation, lcsh:RC581-607
Abstract: The induction of graft tolerance remains the holy grail of transplantation. This is important as chronic allograft dysfunction and the side effects of immunosuppression regimens place a major burden on the lives of transplant patients and their healthcare systems. This has mandated the need to understand the immunobiology of graft rejection and identify novel therapeutics. Regulatory T (Treg) cells play an important role in modulating pro‐inflammatory microenvironments and maintaining tissue homeostasis. However, there are fundamental unanswered questions regarding Treg cell immunobiology. These cells are a heterogeneous entity with functionally diverse roles. Moreover, the adoption of novel deeper immunophenotyping and genomic sequencing technologies has identified this phenotype and function to be more complex than expected. Hence, a comprehensive understanding of Treg cell heterogeneity is needed to safely and effectively exploit their therapeutic potential. From a clinical perspective, the recent decade has seen different clinical teams commence and complete first‐in‐man clinical trials utilising Treg cells as an adoptive cellular therapy. In this review, we discuss these trials from a translational perspective with an important focus on safety. Finally, we identify crucial knowledge gaps for future study., Treg cell therapy has the potential to revolutionise current post‐transplant immunosuppression protocols. Treg cells are presently undergoing early phase trials in solid organ transplantation. However, there are multiple questions regarding Treg cell immunobiology that need to be resolved.
Published: 2020

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