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1. Treatment With Simvastatin and Rifaximin Restores the Plasma Metabolomic Profile in Patients With Decompensated Cirrhosis

Author: Elisa Pose, Elsa Solà, Juan J. Lozano, Adrià Juanola, Julia Sidorova, Giacomo Zaccherini, Koos deWit, Frank Uschner, Marta Tonon, Konstantin Kazankov, Cesar Jiménez, Daniela Campion, Laura Napoleone, Ann T. Ma, Marta Carol, Manuel Morales‐Ruiz, Carlo Alessandria, Ulrich Beuers, Paolo Caraceni, Claire Francoz, François Durand, Rajeshwar P. Mookerjee, Jonel Trebicka, Victor Vargas, Salvatore Piano, Hugh Watson, Juan G. Abraldes, Patrick S. Kamath, Mark M. Davis, Pere Ginès, and for the investigators of the LIVERHOPE Consortium
Subjects: Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Patients with decompensated cirrhosis, particularly those with acute‐on‐chronic liver failure (ACLF), show profound alterations in plasma metabolomics. The aim of this study was to investigate the effect of treatment with simvastatin and rifaximin on plasma metabolites of patients with decompensated cirrhosis, specifically on compounds characteristic of the ACLF plasma metabolomic profile. Two cohorts of patients were investigated. The first was a descriptive cohort of patients with decompensated cirrhosis (n = 42), with and without ACLF. The second was an intervention cohort from the LIVERHOPE‐SAFETY randomized, double‐blind, placebo‐controlled trial treated with simvastatin 20 mg/day plus rifaximin 1,200 mg/day (n = 12) or matching placebo (n = 13) for 3 months. Plasma samples were analyzed using ultrahigh performance liquid chromatography–tandem mass spectroscopy for plasma metabolomics characterization. ACLF was characterized by intense proteolysis and lipid alterations, specifically in pathways associated with inflammation and mitochondrial dysfunction, such as the tryptophan–kynurenine and carnitine beta‐oxidation pathways. An ACLF‐specific signature was identified. Treatment with simvastatin and rifaximin was associated with changes in 161 of 985 metabolites in comparison to treatment with placebo. A remarkable reduction in levels of metabolites from the tryptophan–kynurenine and carnitine pathways was found. Notably, 18 of the 32 metabolites of the ACLF signature were affected by the treatment. Conclusion: Treatment with simvastatin and rifaximin modulates some of the pathways that appear to be key in ACLF development. This study unveils some of the mechanisms involved in the effects of treatment with simvastatin and rifaximin in decompensated cirrhosis and sets the stage for the use of metabolomics to investigate new targeted therapies in cirrhosis to prevent ACLF development.
Published: 2022
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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. R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation

Author: Charlotte Costentin, Federico Piñero, Helena Degroote, Andrea Notarpaolo, Ilka F. Boin, Karim Boudjema, Cinzia Baccaro, Luis G. Podestá, Philippe Bachellier, Giuseppe Maria Ettorre, Jaime Poniachik, Fabrice Muscari, Fabrizio Dibenedetto, Sergio Hoyos Duque, Ephrem Salame, Umberto Cillo, Sebastian Marciano, Claire Vanlemmens, Stefano Fagiuoli, Patrizia Burra, Hans Van Vlierberghe, Daniel Cherqui, Quirino Lai, Marcelo Silva, Fernando Rubinstein, Christophe Duvoux, Filomena Conti, Olivier Scatton, Pierre Henri Bernard, Claire Francoz, Francois Durand, Sébastien Dharancy, Marie-lorraine Woehl, Alexis Laurent, Sylvie Radenne, Jérôme Dumortier, Armand Abergel, Louise Barbier, Pauline Houssel-Debry, Georges Philippe Pageaux, Laurence Chiche, Victor Deledinghen, Jean Hardwigsen, J. Gugenheim, M. Altieri, Marie Noelle Hilleret, Thomas Decaens, Aline Chagas, Paulo Costa, Elaine Cristina de Ataide, Emilio Quiñones, Sebastián Marciano, Margarita Anders, Adriana Varón, Alina Zerega, Alejandro Soza, Martín Padilla Machaca, Diego Arufe, Josemaría Menéndez, Rodrigo Zapata, Mario Vilatoba, Linda Muñoz, Ricardo Chong Menéndez, Martín Maraschio, Lucas McCormack, Juan Mattera, Adrian Gadano, Ilka S.F. Fatima Boin, Jose Huygens Parente García, Flair Carrilho, Giulia Magini, Lucia Miglioresi, Martina Gambato, Fabrizio Di Benedetto, Cecilia D’Ambrosio, Alessandro Vitale, Michele Colledan, Domenico Pinelli, Paolo Magistri, Giovanni Vennarecci, Marco Colasanti, Valerio Giannelli, Adriano Pellicelli, Cizia Baccaro, Callebout Eduard, Iesari Samuele, Dekervel Jeroen, Schreiber Jonas, Pirenne Jacques, Verslype Chris, Ysebaert Dirk, Michielsen Peter, Lucidi Valerio, Moreno Christophe, Detry Olivier, Delwaide Jean, Troisi Roberto, and Lerut Jan Paul
Subjects: Liver transplantation, Liver cancer, Recurrence, Explants pathology, Prediction, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: Patients with hepatocellular carcinoma (HCC) are selected for liver transplantation (LT) based on pre-LT imaging ± alpha-foetoprotein (AFP) level, but discrepancies between pre-LT tumour assessment and explant are frequent. Our aim was to design an explant-based recurrence risk reassessment score to refine prediction of recurrence after LT and provide a framework to guide post-LT management. Methods: Adult patients who underwent transplantation between 2000 and 2018 for HCC in 47 centres were included. A prediction model for recurrence was developed using competing-risk regression analysis in a European training cohort (TC; n = 1,359) and tested in a Latin American validation cohort (VC; n=1,085). Results: In the TC, 76.4% of patients with HCC met the Milan criteria, and 89.9% had an AFP score of ≤2 points. The recurrence risk reassessment (R3)-AFP model was designed based on variables independently associated with recurrence in the TC (with associated weights): ≥4 nodules (sub-distribution of hazard ratio [SHR] = 1.88, 1 point), size of largest nodule (3–6 cm: SHR = 1.83, 1 point; >6 cm: SHR = 5.82, 5 points), presence of microvascular invasion (MVI; SHR = 2.69, 2 points), nuclear grade >II (SHR = 1.20, 1 point), and last pre-LT AFP value (101–1,000 ng/ml: SHR = 1.57, 1 point; >1,000 ng/ml: SHR = 2.83, 2 points). Wolber’s c-index was 0.76 (95% CI 0.72–0.80), significantly superior to an R3 model without AFP (0.75; 95% CI 0.72–0.79; p = 0.01). Four 5-year recurrence risk categories were identified: very low (score = 0; 5.5%), low (1–2 points; 15.1%), high (3–6 points; 39.1%), and very high (>6 points; 73.9%). The R3-AFP score performed well in the VC (Wolber’s c-index of 0.78; 95% CI 0.73–0.83). Conclusions: The R3 score including the last pre-LT AFP value (R3-AFP score) provides a user-friendly, standardised framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials for HCC not limited to the Milan criteria. Clinical Trials Registration: NCT03775863. Lay summary: Considering discrepancies between pre-LT tumour assessment and explant are frequent, reassessing the risk of recurrence after LT is critical to further refine the management of patients with HCC. In a large and international cohort of patients who underwent transplantation for HCC, we designed and validated the R3-AFP model based on variables independently associated with recurrence post-LT (number of nodules, size of largest nodule, presence of MVI, nuclear grade, and last pre-LT AFP value). The R3-AFP model including last available pre-LT AFP value outperformed the original R3 model only based on explant features. The final R3-AFP scoring system provides a robust framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials, irrespective of criteria used to select patients with HCC for LT.
Published: 2022
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5. 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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6. Liver Transplantation for Porto-sinusoidal Vascular Liver Disorder: Long-term Outcome

Author: Marta Magaz, Heloïse Giudicelli-Lett, Oana Nicoară-Farcău, Neil Rajoriya, Ashish Goel, Karlien Raymenants, Sophie Hillaire, Gonzalo Crespo, Luis Téllez, Laure Elkrief, Constantino Fondevila, Lara Orts, Filipe Nery, Akash Shukla, Hélène Larrue, Yiliam Fundora, Helena Degroote, Victoria Aguilera, Elba LLop, Laura Turco, Federica Indulti, Stefania Gioia, Giulia Tosetti, Niccolò Bitto, Chiara Becchetti, Edilmar Alvarado, Cristina Roig, Raquel Diaz, Michael Praktiknjo, Anna-Lena Konicek, Guillem Soy, Pol Olivas, José Ignacio Fortea, Helena Masnou, Ángela Puente, Alba Ardèvol, Carmen Álvarez-Navascués, Marta Romero, Bernhard Scheiner, Georg Semmler, Mattias Mandorfer, Filipe Damião, Anna Baiges, Fanny Turon, Macarena Simón-Talero, Carlos González-Alayón, Alba Díaz, Ángeles García-Criado, Andrea de Gottardi, Enric Reverter, Annabel Blasi, Joan Genescà, Olivier Roux, Claire Francoz, Carlos Noronha Ferreira, Thomas Reiberger, Manuel Rodríguez, Rosa María Morillas, Javier Crespo, Jonel Trebicka, Rafael Bañares, Càndid Villanueva, Annalisa Berzigotti, Massimo Primignani, Vincenzo La Mura, Oliviero Riggio, Filippo Schepis, Bogdan Procopet, Xavier Verhelst, José Luis Calleja, Christophe Bureau, Agustín Albillos, Frederik Nevens, Virginia Hernández-Gea, Dhiraj Tripathi, Pierre-Emmanuel Rautou, François Durand, and Juan Carlos García-Pagán
Subjects: Transplantation, 610 Medizin und Gesundheit
Abstract: BACKGROUND AND AIMS Porto-sinusoidal vascular liver disorder (PSVD) is a rare disease that occasionally requires liver transplantation (LT), despite usually presenting preserved liver function. There remains a paucity of data pertaining to LT in PSVD. The aim was to identify features associated with post-LT outcomes in PSVD. METHODS Retrospective multicentre study of 79 patients who received LT for PSVD. RESULTS Median post-LT follow-up was 37 (range 1-261) mo. Refractory ascites 24 (30%), hepatic encephalopathy 16 (20%), and hepatopulmonary syndrome 13 (16.3%) were the most frequent indications for LT. Hepatocellular carcinoma was the indication in only 2 patients. Twenty-four patients died, 7 due to liver and 17 to non-liver related causes. Post-LT survival was 82.2%, 80.7%, and 68.6% at 1, 2, and 5 y, respectively. Post-LT survival was significantly better in patients without (n = 58) than in those with a persistent severe PSVD-associated condition (n = 21). Pre-LT hyperbilirubinemia levels and creatinine >100 µmol/L were also independently associated with poor survival. Six patients (7.6%) required a second LT. Recurrence of PSVD was confirmed by liver biopsy in only 1 patient and in 3 further patients it was likely. CONCLUSIONS LT in PSVD is associated with an acceptable outcome in the absence of associated severe conditions. However, persistence of a severe associated condition, pre-LT high bilirubin levels, or creatinine >100 µmol/L impact outcome, and these are features that should be considered when evaluating PSVD patients for LT. PSVD recurrence is possible after LT and needs to be explored, at least, in cases of posttransplant portal hypertension.
Published: 2023

7. 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

8. Characterization of Blood Immune Cells in Patients With Decompensated Cirrhosis Including ACLF

Author: Emmanuel Weiss, Pierre de la Grange, Mylène Defaye, Juan José Lozano, Ferrán Aguilar, Pushpa Hegde, Ariane Jolly, Lucile Moga, Sukriti Sukriti, Banwari Agarwal, Haqeeqat Gurm, Marion Tanguy, Johanne Poisson, Joan Clària, Paer-Selim Abback, Axel Périanin, Gautam Mehta, Rajiv Jalan, Claire Francoz, Pierre-Emmanuel Rautou, Sophie Lotersztajn, Vicente Arroyo, François Durand, and Richard Moreau
Subjects: myeloid cells, innate lymphoid cells, adaptive immune cells, sepsis, organ failure, immunotherapies, Immunologic diseases. Allergy, RC581-607
Abstract: Background and AimsPatients with cirrhosis and acute-on-chronic liver failure (ACLF) have immunosuppression, indicated by an increase in circulating immune-deficient monocytes. The aim of this study was to investigate simultaneously the major blood-immune cell subsets in these patients.Material and MethodsBlood taken from 67 patients with decompensated cirrhosis (including 35 critically ill with ACLF in the intensive care unit), and 12 healthy subjects, was assigned to either measurements of clinical blood counts and microarray (genomewide) analysis of RNA expression in whole-blood; microarray (genomewide) analysis of RNA expression in blood neutrophils; or assessment of neutrophil antimicrobial functions.ResultsSeveral features were found in patients with ACLF and not in those without ACLF. Indeed, clinical blood count measurements showed that patients with ACLF were characterized by leukocytosis, neutrophilia, and lymphopenia. Using the CIBERSORT method to deconvolute the whole-blood RNA-expression data, revealed that the hallmark of ACLF was the association of neutrophilia with increased proportions of macrophages M0-like monocytes and decreased proportions of memory lymphocytes (of B-cell, CD4 T-cell lineages), CD8 T cells and natural killer cells. Microarray analysis of neutrophil RNA expression revealed that neutrophils from patients with ACLF had a unique phenotype including induction of glycolysis and granule genes, and downregulation of cell-migration and cell-cycle genes. Moreover, neutrophils from these patients had defective production of the antimicrobial superoxide anion.ConclusionsGenomic analysis revealed that, among patients with decompensated cirrhosis, those with ACLF were characterized by dysregulation of blood immune cells, including increases in neutrophils (that had a unique phenotype) and macrophages M0-like monocytes, and depletion of several lymphocyte subsets (including memory lymphocytes). All these lymphocyte alterations, along with defective neutrophil superoxide anion production, may contribute to immunosuppression in ACLF, suggesting targets for future therapies.
Published: 2021
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9. Laparoscopic-assisted liver transplantation: A realistic perspective

Author: Safi Dokmak, François Cauchy, Béatrice Aussilhou, Fédérica Dondero, Ailton Sepulveda, Olivier Roux, Claire Francoz, Olivia Hentic, Louis de Mestier, Philippe Levy, Philippe Ruszniewski, Maxime Ronot, Jérome Cros, Valérie Vilgrain, Valérie Paradis, Souhayl Dahmani, Emmanuel Weiss, Alain Sauvanet, François Durand, and Mickael Lesurtel
Subjects: Transplantation, Immunology and Allergy, Pharmacology (medical)
Published: 2022

10. CT Volumetry Can Be Used for Monitoring Liver Function Recovery in Auxiliary Partial Orthotopic Liver Transplantation

Author: Antoine Kirchner, Maxime Ronot, Francois Durand, Federica Dondero, Mickael Lesurtel, Claire Francoz, Olivier Roux, Rachida Lebtahi, Valérie Vilgrain, and Marco Dioguardi Burgio
Subjects: Transplantation
Published: 2023

11. 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

12. Liver Transplantation 2023: Status Report, Current and Future Challenges

Author: Norah A. Terrault, Claire Francoz, Marina Berenguer, Michael Charlton, and Julie Heimbach
Subjects: Hepatology, Gastroenterology
Published: 2023

13. GlycoCirrhoTest and related glycomics-based biomarkers for liver disease from A Glycomics-Based Test Predicts the Development of Hepatocellular Carcinoma in Cirrhosis

Author: Hans Van Vlierberghe, Nico Callewaert, François Durand, Roos Colman, Claire Francoz, Anja Geerts, Tom Raes, Laurent Castéra, Dieter Vanderschaeghe, and Xavier Verhelst
Abstract: This file gives additional information regarding the GlycoCirrhoTest and other glycomics-based test based on the same technology (DSA-FACE) for glycomic analysis.
Published: 2023

14. Evaluation of transcranial Doppler use in patients with acute liver failure listed for emergency liver transplantation

Author: Benjamin Picard, Stéphanie Sigaut, Olivier Roux, Paër‐Selim Abback, Pierre‐Marie Choinier, Marina Hachouf, Mikhael Giabicani, Juliette Kavafyan, Claire Francoz, Federica Dondero, Mickaël Lesurtel, François Durand, François Cauchy, Catherine Paugam‐Burtz, Souhayl Dahmani, and Emmanuel Weiss
Subjects: Transplantation
Published: 2023

15. Germline Mutations of Telomere-Related Genes are a Major Risk Factor for Liver Disease: A Multicentric Transversal Study

Author: Sabrina Sidali, Raphaël Borie, Flore Sicre de Fontbrune, Kinan El Husseini, Pierre-Emmanuel Rautou, Elodie Lainey, Odile Goria, Bruno Crestani, Jacques Cadranel, Vincent Cottin, Vincent Bunel, Jérôme Dumortier, Emmanuel Jacquemin, Noémi Reboux, Sandrine Hirschi, Arnaud Bourdin, Magdalena Meszaros, Sébastien Dharancy, Sophie Hilaire, Vincent Mallet, Martine Reynaud-Gaubert, Louis Terriou, Frédéric Gottrand, Wadih Abou Chahla, Jean-Emmanuel Kahn, Paul Carrier, Faouzi Saliba, Laura Rubbia-Brandt, John-David Aubert, Laure Elkrief, Victor de Ledinghen, Armand Abergel, Olivier Tournilhac, Pauline Houssel, Stéphane Jouneau, Ludivine Wemeau, Anne Bergeron, Thierry Leblanc, Isabelle Ollivier-Hourmand, Eric Nguyen-Khac, Hélène Morisse-Pradier, Ibrahima Ba, Catherine Boileau, Françoise Roulot-Thoraval, Valérie Vilgrain, Christophe Bureau, Hilario Nunes, Jean-Marc Naccache, François Durand, Claire Francoz, Dominique Roulot, Dominique-Charles Valla, Valérie Paradis, Caroline Kannengiesser, and Aurélie Plessier
Published: 2023

16. Women Leadership in Liver Transplantation-Results of an International Survey

Author: Marieke de Rosner – van Rosmalen, Dieter Adelmann, Gabriela A. Berlakovich, Claire Francoz, Nazia Selzner, Marina Berenguer, Kymberly D. Watt, Nancy Kwan Man, Patrizia Burra, and Sher-Lu Pai
Subjects: Surgeons, Female, Humans, Leadership, Surveys and Questionnaires, Liver Transplantation, Physicians, Women, Transplantation, Physicians, Women
Abstract: The International Liver Transplantation Society (ILTS) has placed a strong focus on achieving gender equality and equity in liver transplant (LT). We aimed to understand gender distribution in leadership positions among LT physicians around the world and within ILTS.In 2019, the ILTS Equality, Diversity, and Inclusion Committee distributed a survey to obtain granular data on gender and characteristics of transplant physicians as well as those in leadership positions in each center. Additionally, data were collected on the gender composition of the ILTS membership, council, chairpersons, and committees and from the United Network for Organ Sharing.Data were collected from 243 transplant centers. Thirty-two (13.2%) had at least 1 woman as the director of LT, chief of transplant surgery, or chief of transplant hepatology. Of the 243 centers, 133 reported the age and gender of the leadership personnel. Women physicians comprised 152 of the 833 transplant surgeons (18.2%) and 298 of the 935 hepatologists (31.9%). Among the 1331 ILTS physician members, 588 (44.2%) provided gender information in their member profiles, and 155 (26.3%) identified themselves as women. Of the 26 ILTS leadership positions, 7 (26.9%) were held by women.This analysis of worldwide gender distribution in the LT physician workforce showed notable gender disparity in LT leadership around the globe and within the ILTS. These data provide a launching point for promoting and achieving gender equality and equity in LT.
Published: 2022

17. Respiratory events with terlipressin and albumin in hepatorenal syndrome: A review and clinical guidance

Author: Andrew S. Allegretti, Ram M. Subramanian, Claire Francoz, Jody C. Olson, and Andrés Cárdenas
Subjects: Hepatorenal Syndrome, Treatment Outcome, Hepatology, Albumins, Humans, Lypressin, Vasoconstrictor Agents, Acute Kidney Injury, Article, Terlipressin
Abstract: Hepatorenal syndrome-acute kidney injury (HRS-AKI) is a serious complication of severe liver disease with a clinically poor prognosis. Supportive care using vasoconstrictors and intravenous albumin are the current mainstays of therapy. Terlipressin is an efficacious vasoconstrictor that has been used for 2 decades as the first-line treatment for HRS-AKI in Europe and has demonstrated greater efficacy in improving renal function compared to placebo and other vasoconstrictors. One of the challenges associated with terlipressin use is monitoring and mitigating serious adverse events, specifically adverse respiratory events, which were noted in a subset of patients in the recently published CONFIRM trial, the largest randomized trial examining terlipressin use for HRS-AKI. In this article, we review terlipressin's pharmacology, hypothesize how its mechanism contributes to the risk of respiratory compromise and propose strategies that will decrease the frequency of these events by rationally selecting patients at lower risk for these events.
Published: 2022

18. Advances in management of hepatorenal syndrome

Author: Saro Khemichian, Mitra K. Nadim, and Claire Francoz
Subjects: Liver Cirrhosis, medicine.medical_specialty, Hepatorenal Syndrome, Cirrhosis, business.industry, Acute kidney injury, Renal function, Hemodynamics, Acute Kidney Injury, medicine.disease, Pathophysiology, End Stage Liver Disease, Liver disease, Hepatorenal syndrome, Nephrology, Internal Medicine, medicine, Humans, Intensive care medicine, Terlipressin, business, medicine.drug
Abstract: Purpose of review Hepatorenal syndrome (HRS) is encountered frequently in patients with end-stage liver disease and remains an important cause of morbidity and mortality in this patient population. This review will focus and provide updates on pathophysiology, assessment of kidney function, new definitions, and treatment and prevention of HRS. Recent findings Pathophysiology of HRS has been elucidated more recently and in addition to hemodynamic changes, the role of systemic inflammatory response contributes significantly to this process. Assessment of kidney function in patients with liver cirrhosis remains challenging. Novel glomerular filtration rate equations have been developed in patients with liver disease to better estimate kidney function and changes made in the definition of acute kidney injury (AKI), which are more aligned with KDIGO criteria for AKI. Vasoconstrictors, especially terlipressin, along with albumin remain the mainstay of pharmacological treatment of HRS-AKI. Biomarkers have been useful in differentiating ATN from HRS at an early stage. Summary HRS remains a significant cause of morbidity and mortality for patients with end-stage liver disease. Newer understanding of mechanisms in development and pathophysiology of HRS have helped with elucidation of the disease process.
Published: 2021

19. Acute‐on‐chronic liver failure: Where do we stand?

Author: François Durand, Emmanuel Weiss, Claire Francoz, and Olivier Roux
Subjects: Liver Cirrhosis, medicine.medical_specialty, Cirrhosis, medicine.medical_treatment, Liver transplantation, Esophageal and Gastric Varices, Systemic circulation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Humans, Medicine, Acute on chronic liver failure, Dialysis, Hepatology, business.industry, Acute-On-Chronic Liver Failure, Prognosis, medicine.disease, Occult, Rifaximin, Transplantation, chemistry, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Gastrointestinal Hemorrhage, business
Abstract: Acute-on-chronic liver failure (ACLF) is defined by the rapid development of organ(s) failure(s) associated with high rates of early (28-day) mortality in patients with cirrhosis. ACLF has been categorized into three grades of increasing severity according to the nature and number of organ failures. In patients with grade 3 ACLF, 28-day mortality is >70%. While the definition of ACLF has been endorsed by European scientific societies, North American and Asian Pacific associations have proposed alternative definitions. A prognostic score called the CLIF-C ACLF score provides a more precise assessment of the prognosis of patients with ACLF. Although bacterial infections and variceal bleeding are common precipitating factors, no precipitating factor can be identified in almost 60% of patients with ACLF. There is increasing evidence that cirrhosis is a condition characterized by a systemic inflammatory state and occult infections or translocation of bacteria or bacterial products from the lumen of the GUT to the systemic circulation which could play a role in the development of ACLF. Simple and readily available variables to predict the occurrence of ACLF in patients with cirrhosis have been identified and high-risk patients need careful management. Whether prolonged administration of statins, rifaximin or albumin can prevent ACLF requires further study. Patients with organ(s) failure(s) may needed to be admitted to the ICU and there should be no hesitation in admitting patients with cirrhosis to the ICU. No benefit to survival was observed with albumin dialysis and rescue transplantation is the best option in the most severe patients. One-year post-transplant survival rates exceeding 70%-75% have been reported, including in patients with grade 3 ACLF but these patients were highly selected. Criteria have been proposed to define futile transplantation (too ill to be transplanted), but these criteria need to be refined to include age, comorbidities and frailty in addition to markers of disease severity.
Published: 2021

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

Author: Francesco Figorilli, Antonella Putignano, Olivier Roux, Pauline Houssel-Debry, Claire Francoz, Catherine Paugam-Burtz, Olivier Soubrane, Banwari Agarwal, François Durand, and Rajiv Jalan
Subjects: Medicine, Science
Abstract: King's College Hospital criteria are currently used to select liver transplant candidates in acetaminophen-related acute liver failure (ALF). Although widely accepted, they show a poor sensitivity in predicting pre-transplant mortality and cannot predict the outcome after surgery. In this study we aimed to develop a new prognostic score that can allow patient selection for liver transplantation more appropriately and identify patients at high risk of futile transplantation.We analysed consecutive patients admitted to the Royal Free and Beaujon Hospitals between 1990 and 2015. Clinical and laboratory data at admission were collected. Predictors of 3-month mortality in the non-transplanted patients admitted to the Royal Free Hospital were used to develop the new score, which was then validated against the Beaujon cohort. The Beaujon-transplanted group was also used to assess the ability of the new score in identifying patients at high risk of transplant futility.152 patients were included of who 44 were transplanted. SOFA, CLIF-C OF and CLIF-ACLF scores were the best predictors of 3-month mortality among non-transplanted patients. CLIF-C OF score and high dosages of norepinephrine requirement were the only significant predictors of 3-month mortality in the non-transplanted patients, and therefore were included in the ALF-OFs score. In non-transplanted patients, ALF-OFs showed good performance in both exploratory (AUC = 0.89; sensitivity = 82.6%; specificity = 89.5%) and the validation cohort (AUC = 0.988; sensitivity = 100%; specificity = 92.3%). ALF-OFs score was also able to identify patients at high risk of transplant futility (AUC = 0.917; sensitivity = 100%; specificity = 79.2%).ALF-OFs is a new prognostic score in acetaminophen-related ALF that can predict both the need for liver transplant and high risk of transplant futility, improving candidate selection for liver transplantation.
Published: 2017
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21. 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

22. When Is a Critically Ill Cirrhotic Patient Too Sick to Transplant? Development of Consensus Criteria by a Multidisciplinary Panel of 35 International Experts

Author: Samir Jaber, Thomas Reiberger, Kim M. Olthoff, Jan Lerut, Kate Kronish, François Durand, Wim Laleman, Jody C. Olson, James Y. Findlay, Sumeet K. Asrani, Dana Tomescu, Victor W. Xia, Emmanuel Weiss, Fuat H. Saner, Paolo Muiesan, Constantino Fondevila, Annabel Blasi, Catherine Paugam-Burtz, Constantine J. Karvellas, Thierry Gustot, Olivier Scatton, Ram Subramanian, Javier Fernández, Koen Reyntjens, Pierre-François Laterre, Faouzi Saliba, Kenneth J. Simpson, Gianni Biancofiore, Olivier Soubrane, Eric Levesque, Claire Francoz, Frank Tacke, Gebhard Wagener, Mark Mc Phail, Antonio Daniele Pinna, M. Susan Mandell, MORNET, Dominique, 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), European Foundation for Study of Chronic Liver Failure [Barcelona] (EF CLIF), Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Baylor University, University of Pisa - Università di Pisa, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Université Catholique de Louvain = Catholic University of Louvain (UCL), Nokia Bell Labs [Paris-Saclay], University of Barcelona, Mayo Clinic [Rochester], Universitat de Barcelona (UB), Université libre de Bruxelles (ULB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), University of California [San Francisco] (UC San Francisco), University of California (UC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre hépato-biliaire - CHB [Paul Brousse, Paris], Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse, University of Colorado Anschutz [Aurora], King‘s College London, University of Birmingham [Birmingham], Birmingham Women's and Children's NHS Foundation Trust, University of Kansas [Kansas City], Hospital of the University of Pennsylvania (HUP), Perelman School of Medicine, University of Pennsylvania-University of Pennsylvania, University of Bologna/Università di Bologna, University of Vienna [Vienna], University of Groningen [Groningen], Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, 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), University of Edinburgh, Emory University School of Medicine, Emory University [Atlanta, GA], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Fundeni Clinical Institute = Institutul Clinic Fundeni [Bucarest, Roumanie], David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Columbia University College of Physicians and Surgeons, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service de chirurgie et transplantation abdominale, UCL - (SLuc) Service de soins intensifs, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of California [San Francisco] (UCSF), University of California, Hôpital Paul Brousse-Université Paris-Sud - Paris 11 (UP11), University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], University of Bologna, and University of California-University of California
Subjects: Liver Cirrhosis, medicine.medical_specialty, Consensus, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Critical Illness, Medizin, MEDLINE, Delphi method, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 030230 surgery, Liver transplantation, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Multidisciplinary approach, Intensive care, Anesthesiology, Internal medicine, medicine, Humans, Intensive care medicine, Transplantation, Critically ill, business.industry, Graft Survival, Hepatology, Transplantation d'organes, 3. Good health, Liver Transplantation, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030211 gastroenterology & hepatology, business
Abstract: BACKGROUND: Critically ill cirrhotic patients are increasingly transplanted, but there is no consensus about futile liver transplantation (LT). Therefore, the decision to delay or deny LT is often extensively debated. These debates arise from different opinions of futility among transplant team members. This study aims to achieve a multinational and multidisciplinary consensus on the definition of futility in LT and to develop well-articulated criteria for not proceeding with LT due to futility. METHODS: Thirty-five international experts from anesthesiology/intensive care, hepatology, and transplant surgery were surveyed using the Delphi method. More than 70% of similar answers to a question were necessary to define agreement. RESULTS: The panel recommended patient and graft survival at 1 year after LT to define futility. Severe frailty and persistent fever or 1 μg/kg per minute and a serum lactate level >9 mmol/L. CONCLUSIONS: Our expert panel provides a consensus on the definition of futile LT and on specific criteria for postponing or denying LT. A framework that may facilitate the decision if a patient is too sick for transplant is presented., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021

23. Global strategy for the diagnosis and management of acute kidney injury in patients with liver cirrhosis

Author: Lukas Otero Sanchez and Claire Francoz
Subjects: Adult, medicine.medical_specialty, Cirrhosis, medicine.medical_treatment, Population, Review Article, Liver transplantation, chronic liver diseases, urologic and male genital diseases, 03 medical and health sciences, 0302 clinical medicine, Hepatorenal syndrome, Liver Cirrhosis, Alcoholic, Albumins, medicine, Humans, Vasoconstrictor Agents, Stage (cooking), education, Intensive care medicine, hepatorenal syndrome, education.field_of_study, liver transplantation, business.industry, Mortality rate, Gastroenterology, Acute kidney injury, Acute Kidney Injury, medicine.disease, Prognosis, Early Diagnosis, Oncology, Liver, 030220 oncology & carcinogenesis, Creatinine, Disease Progression, Fluid Therapy, 030211 gastroenterology & hepatology, Female, Complication, business, decompensated cirrhosis, Biomarkers, Terlipressin
Abstract: Acute kidney injury (AKI) is a clinical syndrome that complicates the course and worsens clinical outcomes in patients with chronic liver diseases. It is a common complication in hospitalised patients with liver cirrhosis, especially those with decompensated cirrhosis, associated with a high mortality rate. Considering its impact on patient prognosis, efforts should be made to diagnose and tailor therapeutic interventions for AKI at an early stage. In the past decade, a significant progress has been made to understand the key events and define major prognostic factors for the onset and progression of AKI in the cirrhotic population leading hepatologists to redefine the classic definition of hepatorenal syndrome and renal failure in this specific population.
Published: 2021

24. Liver Transplantation in Acute-on-chronic Liver Failure

Author: Emmanuel Weiss, Constantine J. Karvellas, and Claire Francoz
Subjects: Prioritization, Transplantation, medicine.medical_specialty, Cirrhosis, business.industry, medicine.medical_treatment, Research needs, Liver transplantation, medicine.disease, Intensive care, Medicine, Acute on chronic liver failure, Liver function, business, Intensive care medicine, Progressive disease
Abstract: Liver transplantation (LT) has revolutionized outcomes for cirrhotic patients. Current liver allocation policies dictate patients with highest short-term mortality receive the highest priority, thus, several patients become increasingly ill on the waitlist. Given cirrhosis is a progressive disease, it can be complicated by the occurrence of acute-on-chronic liver failure (ACLF), a syndrome defined by an acute deterioration of liver function associated with extrahepatic organ failures requiring intensive care support and a high short-term mortality. Successfully bridging to transplant includes accurate prognostication and prioritization of ACLF patients awaiting LT, optimizing intensive care support pre-LT, and tailoring immunosuppressive and anti-infective therapies post-LT. Furthermore, predicting futility (too sick to undergo LT) in ACLF is challenging. In this review, we summarize the role of LT in ACLF specifically highlighting (a) current prognostic scores in ACLF, (b) critical care management of the ACLF patient awaiting LT, (c) donor issues to consider in transplant in ACLF, and (d) exploring of recent post-LT outcomes in ACLF and potential opportunities to improve outcomes including current care gaps and unmet research needs.
Published: 2020

25. Liver transplantation for critically ill cirrhotic patients: Stratifying utility based on pretransplant factors

Author: Baptiste Michard, Tasneem Pirani, Nigel Heaton, Philippe Bachellier, Claire Francoz, Louise Barbier, Eleni Theocharidou, Francis Schneider, William Bernal, Petru Bucur, Ephrem Salamé, Zair Noorah, Olivier Soubrane, Thierry Artzner, Catherine Paugam-Burtz, John O'Grady, Emmanuel Weiss, Jean-Claude Merle, Lawrence Serfaty, Eric Levesque, François Faitot, Hélène Barraud, François Durand, François Lefebvre, Camille Besch, Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Liver Cirrhosis, medicine.medical_specialty, Critical Illness, medicine.medical_treatment, Liver transplantation, Single Center, Liver disease, Internal medicine, medicine, Humans, Immunology and Allergy, Pharmacology (medical), Risk factor, Retrospective Studies, Mechanical ventilation, Transplantation, business.industry, Critically ill, Acute-On-Chronic Liver Failure, Middle Aged, Prognosis, medicine.disease, Liver Transplantation, Cohort, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: The aim of this study was to produce a prognostic model to help predict posttransplant survival in patients transplanted with grade-3 acute-on-chronic liver failure (ACLF-3). Patients with ACLF-3 who underwent liver transplantation (LT) between 2007 and 2017 in 5 transplant centers were included (n = 152). Predictors of 1-year mortality were retrospectively screened and tested on a single center training cohort and subsequently tested on an independent multicenter cohort composed of the 4 other centers. Four independent pretransplant risk factors were associated with 1-year mortality after transplantation in the training cohort: age ≥53 years (P = .044), pre-LT arterial lactate level ≥4 mml/L (P = .013), mechanical ventilation with PaO2 /FiO2 ≤ 200 mm Hg (P = .026), and pre-LT leukocyte count ≤10 G/L (P = .004). A simplified version of the model was derived by assigning 1 point to each risk factor: the transplantation for Aclf-3 model (TAM) score. A cut-off at 2 points distinguished a high-risk group (score >2) from a low-risk group (score ≤2) with 1-year survival of 8.3% vs 83.9% respectively (P
Published: 2020

26. 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

27. Risk Factors and Impact of Perioperative Prophylaxis on the Risk of Extended-spectrum β-Lactamase–producing Enterobacteriaceae–related Infection Among Carriers Following Liver Transplantation

Author: Bénédicte Grigoresco, Amélie Toussaint, Olivier Roux, Federica Dondero, Sylvie Janny, Claire Francoz, Frédéric Bert, Elsa Logre, Olivier Soubrane, Mikhael Giabicani, Emmanuel Weiss, Catherine Paugam-Burtz, Safi Dokmak, Linda Khoy-Ear, and François Durand
Subjects: Male, medicine.medical_specialty, Carbapenem, Time Factors, Databases, Factual, medicine.medical_treatment, 030230 surgery, Liver transplantation, Risk Assessment, Feces, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Spontaneous bacterial peritonitis, Risk Factors, Internal medicine, polycyclic compounds, Humans, Medicine, Retrospective Studies, Transplantation, business.industry, Incidence (epidemiology), Enterobacteriaceae Infections, Retrospective cohort study, Perioperative, Antibiotic Prophylaxis, Middle Aged, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, Antimicrobial, medicine.disease, Anti-Bacterial Agents, Liver Transplantation, Treatment Outcome, Carbapenems, Carrier State, bacteria, Female, 030211 gastroenterology & hepatology, business, medicine.drug
Abstract: BACKGROUND Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) carriage is frequent among liver transplant (LT) recipients, thereby fostering a large empirical carbapenem prescription. However, ESBL-E infections occur in only 10%-25% of critically ill patients with rectal colonization. Our aim was to identify risk factors for post-LT ESBL-E infection in colonized patients. The effect of perioperative antimicrobial prophylaxis (AP) was also analyzed in patients with prophylaxis lasting
Published: 2020

28. Long‐term outcome of methylmalonic aciduria after kidney, liver, or combined liver‐kidney transplantation: The French experience

Author: Saoussen Krid, David Grevent, Yves Aigrain, Pascale de Lonlay, Dominique Debray, Mehdi Oualha, Laurent Dupic, Clément Pontoizeau, Chris Ottolenghi, Muriel Girard, Claire Francoz, Pauline Krug, Jean-François Benoist, Pierre Broué, Aude Servais, Carmen Capito, Rémi Salomon, Aline Cano, Christophe Legendre, Guy Touati, Stefania Querciagrossa, Samira Sissaoui, Jean-Baptiste Arnoux, Florence Lacaille, Anaïs Brassier, Marina Charbit, Manuel Schiff, Fanny Mochel, Christophe Chardot, Olivia Boyer, Anne Scemla, and M. Tardieu
Subjects: Adult, Male, Hepatoblastoma, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Liver transplantation, Severity of Illness Index, Gastroenterology, Organ transplantation, 03 medical and health sciences, Internal medicine, Genetics, medicine, Humans, Child, Amino Acid Metabolism, Inborn Errors, Genetics (clinical), Dialysis, Kidney transplantation, Retrospective Studies, 030304 developmental biology, 0303 health sciences, Kidney, business.industry, 030305 genetics & heredity, Infant, Newborn, Infant, Prognosis, medicine.disease, Kidney Transplantation, Liver Transplantation, Treatment Outcome, Parenteral nutrition, medicine.anatomical_structure, Methylmalonic aciduria, Child, Preschool, Quality of Life, Female, France, business
Abstract: Organ transplantation is discussed in methylmalonic aciduria (MMA) for renal failure, and poor quality of life and neurological outcome. We retrospectively evaluated 23 French MMA patients after kidney (KT), liver-kidney (LKT), and liver transplantation (LT). Two patients died, one after LKT, one of hepatoblastoma after KT. One graft was lost early after KT. Of 18 evaluable patients, 12 previously on dialysis, 8 underwent KT (mean 12.5 years), 8 LKT (mean 7 years), and 2 LT (7 and 2.5 years). At a median follow-up of 7.3 (KT), 2.3 (LKT), and 1.0 years (LT), no metabolic decompensation occurred except in 1 KT. Plasma and urine MMA levels dramatically decreased, more after LKT. Protein intake was increased more significantly after LKT than KT. Enteral nutrition was stopped in 7/8 LKT, 1/8 KT. Early complications were frequent after LKT. Neurological disorders occurred in four LKT, reversible in one. Five years after KT, four patients had renal failure. The metabolic outcomes were much better after LKT than KT. LKT in MMA is difficult but improves the quality of life. KT will be rarely indicated. We need more long-term data to indicate early LT, in the hope to delay renal failure and prevent neurodevelopmental complications.
Published: 2020

29. 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

30. Endpoints and design of clinical trials in patients with decompensated cirrhosis: Position paper of the LiverHope Consortium

Author: E. Palacio, Koos de Wit, Daniela Campion, Salvatore Piano, Elisa Pose, T. Lanzillotti, Carlos Jiménez, Sara Montagnese, Patrick S. Kamath, Rajeshwar P. Mookerjee, Miquel Gómez i Serra, Ruben Hernaez, M. Aban, Marta Carol, G. Nicolao, Claire Francoz, Giacomo Zaccherini, Hugh Watson, Isabel Graupera, M.T. Chiappa, Jonel Trebicka, Macarena Simón-Talero, Frank Erhard Uschner, Cristina Solé, Alejandro Forner, Ulrich Beuers, F. Durand, Paolo Caraceni, Victor Vargas, Marta Cervera, Carlo Alessandria, Adrià Juanola, V. Esnault, Jeltje Helder, Marko Korenjak, Olivier Roux, Laura Napoleone, Ferran Torres, S. Graf-Dirmeier, Judit Pich, Ann T. Ma, Maria Martha Bernardi, M. Pérez-Guasch, Núria Fabrellas, Pere Ginès, Maricela Quintana López, Elsa Solà, Emma Avitabile, Aleksander Krag, Juan G. Abraldes, Gastroenterology and Hepatology, Graduate School, Tytgat Institute for Liver and Intestinal Research, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Elsa Solà, Elisa Pose, Daniela Campion, Salvatore Piano, Olivier Roux, Macarena Simon-Talero, Frank Uschner, Koos de Wit, Giacomo Zaccherini, Carlo Alessandria, Ulrich Beuers, Paolo Caraceni, Claire Francoz, Rajeshwar P. Mookerjee, Jonel Trebicka, Victor Vargas, Miquel Serra, Ferran Torres, Sara Montagnese, Aleksander Krag, Ruben Hernaez, Marko Korenjak, Hugh Watson, Juan G. Abraldes, Patrick S. Kamath, Pere Ginès, LiverHope Consortium Investigators, Institut Català de la Salut, [Solà E, Pose E] Liver Unit, Hospital Clínic De Barcelona, Barcelona, School of Medicine and Health Sciences University of Barcelona, Spain. Institut d´Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain. [Campion D] Division of Gastroenterology and Hepatology, Città della Salute e della Scienza Hospital, University of Turin, Turin, Italy. [Piano S] Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine - DIMED, University of Padova, Padova, Italy. [Roux O] Hepatology and Liver Intensive Care Unit, Hospital Beaujon, APHP, Clichy, France. [Simon-Talero M] Unitat del Fetge, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Liver Cirrhosis, 0301 basic medicine, Cirrhosis, administración de los servicios de salud::gestión de la atención al paciente::tratamiento de las enfermedades [ATENCIÓN DE SALUD], enfermedades del sistema digestivo::enfermedades hepáticas::cirrosis hepática [ENFERMEDADES], Digestive System Diseases::Liver Diseases::Liver Cirrhosis [DISEASES], Trasplantament hepàtic, Disease, Severity of Illness Index, 0302 clinical medicine, Clinical trials, Quality of life, ACLF, Ascites, Secondary Prevention, Liver transplant, Otros calificadores::/terapia [Otros calificadores], Hepatic encephalopathy, Clinical Trials as Topic, education.field_of_study, Disease Management, 3. Good health, Clinical trial, Europe, Natural history, Hepatic cirrhosis, Research Design, Qualitat de vida, Ascite, Disease Progression, 030211 gastroenterology & hepatology, AKI, ascites, cirrhosis, clinical trials, endpoints, hepatic encephalopathy, hyponatremia, infections, liver transplant, quality of life, medicine.symptom, Infection, Hyponatremia, técnicas de investigación::métodos::diseño de la investigación [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], medicine.medical_specialty, Consensus, Cirrosi hepàtica, Endpoint Determination, Population, Infections, 03 medical and health sciences, Investigative Techniques::Methods::Research Design [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Hypertension, Portal, medicine, Humans, Intensive care medicine, education, Health Services Administration::Patient Care Management::Disease Management [HEALTH CARE], Cirrosi hepàtica - Tractament, Cirrhosi, Hepatology, business.industry, Other subheadings::/therapy [Other subheadings], Endpoint, medicine.disease, Assaigs clínics - Disseny, 030104 developmental biology, Etiology, Endpoints, business, Hepatic transplantation
Abstract: Clinical trials; Liver transplant; Quality of life Ensayos clínicos; Trasplante de hígado; Calidad de vida Assaigs clínics; Trasplantament de fetge; Qualitat de vida Management of decompensated cirrhosis is currently geared towards the treatment of complications once they occur. To date there is no established disease-modifying therapy aimed at halting progression of the disease and preventing the development of complications in patients with decompensated cirrhosis. The design of clinical trials to investigate new therapies for patients with decompensated cirrhosis is complex. The population of patients with decompensated cirrhosis is heterogeneous (i.e., different etiologies, comorbidities and disease severity), leading to the inclusion of diverse populations in clinical trials. In addition, primary endpoints selected for trials that include patients with decompensated cirrhosis are not homogeneous and at times may not be appropriate. This leads to difficulties in comparing results obtained from different trials. Against this background, the LiverHope Consortium organized a meeting of experts, the goal of which was to develop recommendations for the design of clinical trials and to define appropriate endpoints, both for trials aimed at modifying the natural history and preventing progression of decompensated cirrhosis, as well as for trials aimed at managing the individual complications of cirrhosis.
Published: 2021

31. 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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32. Estimating Glomerular Filtration Rate in Cirrhosis Using Creatinine-Based and Cystatin C-Based Equations: Systematic Review and Meta-Analysis

Author: Tsung-Wei Ma, James F. Trotter, Giovanna Saracino, Sumeet K. Asrani, François Durand, Mitra K. Nadim, John Fullinwider, Naveed Sarmast, Claire Francoz, Prianka Singapura, Rakhi Maiwall, Stevan A. Gonzalez, and Rebecca Sartin
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, medicine.medical_treatment, Urology, Renal function, Liver transplantation, urologic and male genital diseases, chemistry.chemical_compound, Ascites, medicine, Humans, Cystatin C, Renal Insufficiency, Chronic, Transplantation, Creatinine, Hepatology, biology, business.industry, Middle Aged, medicine.disease, Confidence interval, Liver Transplantation, chemistry, biology.protein, Surgery, Female, medicine.symptom, business, Glomerular Filtration Rate
Abstract: Accurate estimation of kidney function in cirrhosis is crucial for prognosis and decisions regarding dual-organ transplantation. We performed a systematic review/meta-analysis to assess the performance of creatinine-based and cystatin C (CysC)-based eGFR equations compared with measured GFR (mGFR) in patients with cirrhosis. A total of 25 studies (n = 4565, 52.0 years, 37.0% women) comprising 18 equations met the inclusion criteria. In all GFR equations, the creatinine-based equations overestimated GFR (standardized mean difference, SMD, 0.51; 95% confidence interval [CI], 0.31-0.71) and CysC-based equations underestimated GFR (SMD, -0.3; 95% CI, -0.60 to -0.02). Equations based on both creatinine and CysC were the least biased (SMD, -0.14; 95% CI, -0.46 to 0.18). Chronic kidney disease-Epi-serum creatinine-CysC (CESC) was the least biased but had low precision and underestimated GFR by -3.6 mL/minute/1.73 m2 (95% CI, -17.4 to 10.3). All equations significantly overestimated GFR (+21.7 mL/minute/1.73 m2 ; 95% CI, 17.7-25.7) at GFR
Published: 2021

33. Acute kidney injury in cirrhosis: An immediate threat but also a ticking time bomb

Author: Claire Francoz
Subjects: Liver Cirrhosis, medicine.medical_specialty, Cirrhosis, Hepatology, business.industry, Acute kidney injury, Renal function, Acute Kidney Injury, medicine.disease, Chronic liver disease, Gastroenterology, Creatinine, Internal medicine, Humans, Medicine, Renal Insufficiency, Chronic, business
Published: 2020

34. Modified Technique of Total Hepatectomy in Polycystic Liver Disease With Caval Flow Preservation: The Exposure Left Lateral Sectionectomy

Author: Claire Francoz, Manuela Cesaretti, Ailton Sepulveda, François Cauchy, Olivier Soubrane, Emmanuel Weiss, Bertrand Le Roy, Federica Dondero, François Durand, Safi Dokmak, and Tomoaki Yoh
Subjects: Male, medicine.medical_specialty, Time Factors, Intraoperative Complication, Databases, Factual, medicine.medical_treatment, Operative Time, Blood Loss, Surgical, Vena Cava, Inferior, 030230 surgery, Liver transplantation, Risk Assessment, Inferior vena cava, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Parenchyma, medicine, Hepatectomy, Humans, Retrospective Studies, Transplantation, Cysts, business.industry, Liver Diseases, Polycystic liver disease, Middle Aged, Total Hepatectomy, medicine.disease, Liver Transplantation, Surgery, Dissection, Treatment Outcome, medicine.anatomical_structure, medicine.vein, Female, 030211 gastroenterology & hepatology, business, Hepatomegaly, Liver Circulation, Left triangular ligament
Abstract: BACKGROUND Liver transplantation (LT) for polycystic liver disease (PLD) is rare, extremely challenging and hemorrhagic, without standard approach. Moreover, LT for PLD presents the highest mortality rate (12% to 18%) among all causes of LT. In this setting, the combination of difficult mobilization of a heavy polycystic native liver with narrow access to inferior vena cava and fragile venous wall may lead to venous tearing and cataclysmic bleeding during dissection. The aim of this study was to evaluate a modified technique of total hepatectomy to limit hazardous liver manipulation and improve exposure of inferior vena cava in patients with massive hepatomegaly related to PLD: the exposure left lateral sectionectomy (ELLS). METHODS From 2011 to 2018, ELLS was performed during LT for PLD. Key technical points for safe and fast ELLS include avoidance of left triangular ligament section and placement of a tape behind the left lateral section allowing its ascension and prior dissection of the hepatic pedicle to limit bleeding. The transection plane is mainly composed of cysts, with limited parenchyma, which allows for rapid and bloodless transection using electric scalpel. RESULTS Fifteen patients had ELLS with no postoperative death or intraoperative complication. Median ELLS duration was 16 minutes, and no massive bleeding occurred during this step. During total hepatectomy, median blood loss was 500 mL, and no patient required total caval clamping. All patients were alive at the end of the follow-up. CONCLUSIONS ELLS during LT for PLD facilitates total hepatectomy with vena cava and caval flow preservation.
Published: 2019

35. Age and liver transplantation

Author: Hélène Gilgenkrantz, Olivier Soubrane, François Cauchy, Josh Levitsky, François Durand, Claire Francoz, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Paris Diderot - Paris 7 (UPD7)
Subjects: Adult, Male, 0301 basic medicine, Aging, Brain Death, Matching (statistics), Pediatrics, medicine.medical_specialty, Adolescent, Waiting Lists, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Transplants, Liver transplantation, Donor Selection, Young Adult, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Risk Factors, Transplanted liver, Cadaver, Living Donors, Humans, Medicine, Aged, Aged, 80 and over, Hepatology, business.industry, Graft Survival, Age Factors, Immunosuppression, Middle Aged, medicine.disease, Transplant Recipients, Liver Transplantation, 3. Good health, 030104 developmental biology, Donation, Cohort, Female, 030211 gastroenterology & hepatology, Living donor liver transplantation, business
Abstract: The average age of liver transplant donors and recipients has increased over the years. Independent of the cause of liver disease, older candidates have more comorbidities, higher waitlist mortality and higher post-transplant mortality than younger patients. However, transplant benefit may be similar in older and younger recipients, provided older recipients are carefully selected. The cohort of elderly patients transplanted decades ago is also increasingly raising issues concerning long-term exposure to immunosuppression and aging of the transplanted liver. Excellent results can be achieved with elderly donors and there is virtually no upper age limit for donors after brain death liver transplantation. The issue is how to optimise selection, procurement and matching to ensure good results with elderly donors. The impact of old donor age is more pronounced in younger recipients and patients with a high model for end-stage liver disease score. Age matching between the donor and the recipient should be incorporated into allocation policies with a multistep approach. However, age matching may vary depending on the objectives of different allocation policies. In addition, age matching must be revisited in the era of direct-acting antivirals. More restrictive limits have been adopted in donation after circulatory death. Perfusion machines which are currently under investigation may help expand these limits. In living donor liver transplantation, donor age limit is essentially guided by morbidity related to procurement. In this review we summarise changing trends in recipient and donor age. We discuss the implications of older age donors and recipients. We also consider different options for age matching in liver transplantation that could improve outcomes.
Published: 2019

36. Evidence for an Association Between Intrahepatic Vascular Changes and the Development of Hepatopulmonary Syndrome

Author: Clément Lejealle, Onorina Bruno, Emmanuelle de Raucourt, Dominique Valla, Claire Francoz, François Durand, Valérie Vilgrain, Olivier Soubrane, Pierre Bedossa, Valérie Paradis, Didier Lebrec, Pierre-Emmanuel Rautou, Hervé Mal, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: Liver Cirrhosis, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Cirrhosis, Biopsy, Hypertension, Pulmonary, [SDV]Life Sciences [q-bio], Context (language use), Critical Care and Intensive Care Medicine, Gastroenterology, 03 medical and health sciences, Liver disease, Hepatic Artery, 0302 clinical medicine, Model for End-Stage Liver Disease, hemic and lymphatic diseases, Internal medicine, Multidetector Computed Tomography, Humans, Medicine, 030212 general & internal medicine, Hepatopulmonary syndrome, Lung, Retrospective Studies, integumentary system, Portal Vein, business.industry, Ultrasonography, Doppler, Middle Aged, respiratory system, medicine.disease, Thrombosis, eye diseases, 3. Good health, medicine.anatomical_structure, Liver, 030228 respiratory system, Regional Blood Flow, Case-Control Studies, Portal hypertension, Female, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies, Hepatopulmonary Syndrome, Liver Circulation, Artery
Abstract: Background Hepatopulmonary syndrome (HPS) is characterized by an arterial oxygenation defect, defined by an increased alveolar-arterial oxygen gradient, induced by pulmonary vascular dilatations in the context of liver disease. The pathogenesis of HPS is poorly understood. Morphologic changes associated with HPS are unknown. This study aimed at describing imaging and pathology changes associated with HPS. Methods We performed a case-control study in candidates for transplant with suspicion of cirrhosis. Each patient with HPS (Pao2 ≤ 70 mm Hg) was matched to three control subjects for age, cause, and liver disease severity. Pretransplant thoracic and abdominal imaging and explanted livers were reviewed. Results CT scans and Doppler ultrasounds from 21 patients with HPS were compared with those from 63 control subjects. HPS was associated with a two- to threefold higher prevalence of obstructed intrahepatic portal branches, of slowed or hepatofugal portal blood flow, and of large abdominal portosystemic shunts. Hepatic artery diameter was also larger in patients with HPS. Explanted livers from 19 patients with HPS were compared with those from 57 control subjects. HPS was associated with a fourfold higher prevalence of portal venule thrombosis and a ninefold higher prevalence of extensive vascular proliferation within fibrous septa. Obstruction of centrilobular venules, sinusoidal dilatation, and liver parenchymal extinction were also more common in patients with HPS. Conclusions HPS is associated with intrahepatic vascular changes and with features suggesting severe portal hypertension. These results raise the hypothesis that intrahepatic vascular changes precipitate the development of HPS, opening new therapeutic perspectives for HPS.
Published: 2019

37. Predictive factors of tumor recurrence after liver transplantation for hepatocellular carcinoma: analysis of a multicenter prospective study including 371 patients

Author: Thomas Decaens, René Adam, Sébastien Dharancy, Laurent Sulpice, Didier Samuel, Emmanuel Boleslawski, Marianne Latournerie, Georges-Philippe Pageaux, Olivier Scatton, Sylvie Radenne, Eric Savier, Claire Francoz, Claire Vanlemmens, Pierre-Henri Bernard, Jean Hardwigsen, Jean Gugenheim, Christophe Duvoux, and Nadia Oubaya
Subjects: Hepatology
Published: 2022

38. Endovascular Treatment of Arterial Complications After Liver Transplantation: Long-Term Follow-Up Evaluated on Doppler Ultrasound and Magnetic Resonance Cholangiopancreatography

Author: Ailton Sepulveda, Sylvain Terraz, Lawrence F. Pupulim, Nicolas Goossens, Federica Dondero, Maxime Ronot, Claire Francoz, Romain Breguet, François Durand, and Valérie Vilgrain
Subjects: Male, medicine.medical_treatment, Liver transplantation, 030218 nuclear medicine & medical imaging, Ultrasonography, Doppler/methods, Hepatic Artery, Postoperative Complications, 0302 clinical medicine, ddc:616, medicine.diagnostic_test, Liver/blood supply/diagnostic imaging/surgery, Endovascular Procedures, Ultrasound, Middle Aged, Thrombosis, Dissection, surgical procedures, operative, Treatment Outcome, medicine.anatomical_structure, Liver, Female, Radiology, Hepatic Artery/diagnostic imaging, Cardiology and Cardiovascular Medicine, Artery, Adult, medicine.medical_specialty, Cholangiopancreatography, Magnetic Resonance, Arterial Occlusive Diseases, ddc:616.0757, Young Adult, 03 medical and health sciences, medicine, Humans, Radiology, Nuclear Medicine and imaging, Aged, Retrospective Studies, Magnetic resonance cholangiopancreatography, business.industry, Arterial Occlusive Diseases/diagnostic imaging/surgery, Ultrasonography, Doppler, Postoperative Complications/diagnostic imaging/surgery, medicine.disease, Liver Transplantation, Endovascular Procedures/methods, Stenosis, business, Complication, Cholangiopancreatography, Magnetic Resonance/methods, Follow-Up Studies
Abstract: To evaluate long-term arterial patency and abnormalities of bile ducts in patients that had endovascular treatment for arterial complications after liver transplantation (LT). Between 2004 and 2014, 1048 LTs were consecutively performed in our institution and 53 patients (42 men; age range 19–69) were diagnosed and treated by endovascular techniques for arterial complications such as stenosis, thrombosis, dissection or kinking of the hepatic artery (HA). Radiological and surgical data were retrospectively analyzed, and survivors were contacted to undergo follow-up Doppler ultrasound (DUS) of the HA and magnetic resonance cholangiopancreatography. The primary technical success of endovascular treatment was 94% (n = 50). The patency rate of HA at 5-year was 81%. After a median follow-up of 58 months, 17 patients (32%) developed radiological features of ischemic cholangiopathy (IC), including 7 patients with abnormal DUS and 10 with normal DUS. Patients who presented with complications of the HA in the first 3 months after LT developed IC more frequently (42%) than others (12%) (p = 0.028). No other factor was associated with the development of IC. IC was more often observed when HA complication occurred within the first 3 months after LT. The presence of IC was not excluded by a normal DUS during follow-up.
Published: 2018

39. 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

40. Liver Transplantation in the Setting of Non-malignant Portal Vein Thrombosis

Author: Claire Francoz, Safi Dokmak, O. Roux, and François Durand
Subjects: medicine.medical_specialty, business.industry, medicine.medical_treatment, Anastomosis, medicine.disease, Thrombosis, Inferior vena cava, Surgery, Portal vein thrombosis, medicine.vein, Splanchnic vein thrombosis, cardiovascular system, Medicine, Portal hypertension, Superior mesenteric vein, business, Transjugular intrahepatic portosystemic shunt
Abstract: Portal vein thrombosis whose prevalence increases in candidates for liver transplantation remains a challenging issue. In patients with advanced cirrhosis, portal vein thrombosis essentially results from portal hypertension and reduced portal blood flow. Ensuring adequate portal flow to the liver graft is an absolute prerequisite for liver transplantation to be successful. In patients with documented portal vein thrombosis at registration, the objective is to facilitate anatomical portal vein anastomosis with transjugular intrahepatic portosystemic shunt (TIPS) or per-operative thrombectomy, an alternative being jump graft with superior mesenteric vein. In patients with partial portal vein thrombosis, anticoagulation during waiting time should be considered to avoid extension of thrombosis that would preclude anatomical anastomosis. Placement of TIPS is an alternative. There is no evidence that long term anticoagulation is needed after transplantation in patients with anatomical portal vein anastomosis and adequate portal blood flow. Non-anatomical portal anastomoses are an alternative in patients with extensive splanchnic vein thrombosis. The main techniques are renoportal anastomosis using the left renal vein and hemicaval transposition with an anastomosis between the inferior vena cava and the portal vein. However, these non-anatomical techniques are associated with higher morbidity and post-transplant mortality. In addition, non-anatomical procedures do not reverse portal hypertension. Portal vein thrombosis is not a contraindication for living donor liver transplantation. However, since either the right or left portal vein branches are the only available vessels, anastomoses may be technically more complex.
Published: 2021

41. PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis

Author: William Bernal, Agustín Albillos, Alex Amoros, Wim Laleman, Michael Manns, Javier Martínez, Maximilian J. Brol, Pere Ginès, Alessandra Pohlmann, Joerg Tobiasch Moritz, Francois Smits, Elisabet Garcia-Lopez, Joan Clària, Jennifer Lehmann, Jonel Trebicka, Christoph Welsch, Vicente Arroyo, Richard Moreau, Tony Bruns, Monica Mesquita, Christian Jansen, Peter Jarcuska, Harald Rupprechter, Martin Janicko, Thierry Gustot, Macarena Simón-Talero, Giacomo Zaccherini, Cristina Ripoll, Luise Aamann, Oliviero Riggio, Martina Rizzo, Karen Vagner Danielsen, Javier Romaní Fernández, Jelte J Schaapman, Frank Erhard Uschner, Juan Acevedo, Miguel Á. Rodríguez, David Semela, Carlo Alessandria, Carmine Gambino, Lise Lotte Gluud, Paolo Caraceni, Emanuela Ciraci, István Altorjay, Cristina Solé, Salvatore Piano, Minneke J. Coenraad, Pierre Nahon, Haluk Tarik Kani, Faouzi Saliba, Agnese Antognoli, Andrea De Gottardi, Osman Ozdogan, Henning Grønbæk, Christian J. Steib, Anna Curto, Hans Van Vlierberghe, Manuel Romero-Gómez, T.M. Welzel, Roland Amathieu, Sylvie Tresson, Carla Pitarch, Frederik Nevens, Alexander Zipprich, Christian Trautwein, Ilaria Giovo, Victor Vargas, Laure Elkrief, Giorgio Maria Saracco, Johannes Chang, Mattias Mandorfer, Paul Horn, Thomas Berg, Nesrine Amari, Sara Mareso, Heinz Zoller, Osagie Akpata, Mária Papp, Adam Herber, Thomas Reiberger, Flemming Bendtsen, Elsa Solà, Ferran Aguilar, Jose Presa Ramos, Miriam Maschmeier, Tamas Tornai, Manuela Merli, Rajiv Jalan, Martina Gagliardi, Cornelius Engelmann, Rafael Bañares, Daniela Campion, Antonella Putignano, Natalie Van den Ende, Claire Francoz, Marco Pavesi, Paola Ponzo, Rita Garcia, Sven Francque, Vish Patel, Esau Moreno, Alessandra Brocca, Rudolf E. Stauber, Zsuzsanna Vitális, Rajeshwar P. Mookerjee, Ahmed Elsharkawy, Eleonora Bertoli, Michael Praktiknjo, Stephen D. Ryder, Cristina Sanchez, Boglarka Balogh, Debbie L. Shawcross, Manuel Tufoni, Paolo Angeli, Florian Rainer, Pavel Strnad, István Tornai, Edilmar Alvarado-Tapias, Alexander L. Gerbes, Didier Samuel, Maurizio Baldassarre, Cesar Jimenez, Stefan Zeuzem, Pietro Gatti, Germán Soriano, Robert Schierwagen, Ana Clemente, Mauro Bernardi, Daniel Markwardt, Trebicka, Jonel, Fernandez, Javier, Papp, Maria, Caraceni, Paolo, Laleman, Wim, Gambino, Carmine, Giovo, Ilaria, Uschner, Frank Erhard, Jansen, Christian, Jimenez, Cesar, Mookerjee, Rajeshwar, Gustot, Thierry, Albillos, Agustin, Bañares, Rafael, Jarcuska, Peter, Steib, Christian, Reiberger, Thoma, Acevedo, Juan, Gatti, Pietro, Shawcross, Debbie L, Zeuzem, Stefan, Zipprich, Alexander, Piano, Salvatore, Berg, Thoma, Bruns, Tony, Danielsen, Karen Vagner, Coenraad, Minneke, Merli, Manuela, Stauber, Rudolf, Zoller, Heinz, Ramos, José Presa, Solé, Cristina, Soriano, Germán, de Gottardi, Andrea, Gronbaek, Henning, Saliba, Faouzi, Trautwein, Christian, Kani, Haluk Tarik, Francque, Sven, Ryder, Stephen, Nahon, Pierre, Romero-Gomez, Manuel, Van Vlierberghe, Han, Francoz, Claire, Manns, Michael, Garcia-Lopez, Elisabet, Tufoni, Manuel, Amoros, Alex, Pavesi, Marco, Sanchez, Cristina, Praktiknjo, Michael, Curto, Anna, Pitarch, Carla, Putignano, Antonella, Moreno, Esau, Bernal, William, Aguilar, Ferran, Clària, Joan, Ponzo, Paola, Vitalis, Zsuzsanna, Zaccherini, Giacomo, Balogh, Boglarka, Gerbes, Alexander, Vargas, Victor, Alessandria, Carlo, Bernardi, Mauro, Ginès, Pere, Moreau, Richard, Angeli, Paolo, Jalan, Rajiv, Arroyo, Vicente, Banares, Rafael, Reiberger, Thomas, Shawcross, Debbie L., Berg, Thomas, Ramos, Jose Presa, Sole, Cristina, Soriano, German, Van Vlierberghe, Hans, Claria, Joan, Gines, Pere, Maschmeier, Miriam, Semela, David, Elkrief, Laure, Elsharkawy, Ahmed, Tornai, Tamas, Tornai, Istvan, Altorjay, Istvan, Antognoli, Agnese, Baldassarre, Maurizio, Gagliardi, Martina, Bertoli, Eleonora, Mareso, Sara, Brocca, Alessandra, Campion, Daniela, Saracco, Giorgio Maria, Rizzo, Martina, Lehmann, Jennifer, Pohlmann, Alessandra, Brol, Maximilian J., Chang, Johannes, Schierwagen, Robert, Sola, Elsa, Amari, Nesrine, Rodriguez, Miguel, Nevens, Frederik, Clemente, Ana, Janicko, Martin, Markwardt, Daniel, Mandorfer, Mattias, Welsch, Christoph, Welzel, Tanja M., Ciraci, Emanuela, Patel, Vish, Ripoll, Cristina, Herber, Adam, Horn, Paul, Bendtsen, Flemming, Gluud, Lise Lotte, Schaapman, Jelte, Riggio, Oliviero, Rainer, Florian, Moritz, Joerg Tobiasch, Mesquita, Monica, Alvarado-Tapias, Edilmar, Akpata, Osagie, Aamann, Luise, Samuel, Didier, Tresson, Sylvie, Strnad, Pavel, Amathieu, Roland, Simon-Talero, Macarena, Smits, Francois, van den Ende, Natalie, Martinez, Javier, Garcia, Rita, Rupprechter, Harald, Engelmann, Cornelius, and Ozdogan, Osman Cavit
Subjects: 0301 basic medicine, Liver Cirrhosis, Male, Cirrhosis, Organ Dysfunction Scores, acute complication, Chronic liver disease, Acute complications, Non-elective admission, Outcome, Risk factors, 0302 clinical medicine, Preventive Health Services, Medicine and Health Sciences, Gastro-entérologie, risk factors, 610 Medicine & health, Medical History Taking, factors, Toxic encephalopathy, Bacterial Infections, Middle Aged, Prognosis, Europe, Cohort, Disease Progression, outcome, 030211 gastroenterology & hepatology, Female, medicine.symptom, Needs Assessment, Risk, medicine.medical_specialty, Alcoholic hepatitis, 03 medical and health sciences, Internal medicine, medicine, Humans, Decompensation, Medical history, Inflammation, Hepatology, business.industry, Hepatitis, Alcoholic, Organ dysfunction, Acute-On-Chronic Liver Failure, chronic liver disease, medicine.disease, Precipitating Factors, 030104 developmental biology, Human medicine, business, non-elective admission
Abstract: Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (AD-No ACLF), or with ACLF phenotype (AD-ACLF) defined by organ failure(s). Precipitants may induce AD. This multicenter, prospective, observational PREDICT study (NCT03056612) analyzes and characterizes the precipitants leading to both of these AD phenotypes., info:eu-repo/semantics/published
Published: 2021

42. Management of the major complications of cirrhosis: Beyond guidelines

Author: Juan Carlos García-Pagán, Claire Francoz, Rajeshwar P. Mookerjee, Sara Montagnese, and Marco Senzolo
Subjects: 0301 basic medicine, Liver Cirrhosis, medicine.medical_specialty, Variceal bleeding, Cirrhosis, Decompensation, Guidelines, 03 medical and health sciences, 0302 clinical medicine, Preventive Health Services, medicine, Humans, Controversies, Management, Major complication, Intensive care medicine, Hepatology, business.industry, medicine.disease, Patient Care Management, Clinical Practice, 030104 developmental biology, Expert opinion, Practice Guidelines as Topic, 030211 gastroenterology & hepatology, Approaches of management, business
Abstract: Along with a growing understanding of the pathophysiology of cirrhosis and its complications, new therapies and management strategies have emerged in recent years. Many of these advances have helped inform the current EASL clinical practice guidelines1 on the management of some of the key complications of cirrhosis, such as ascites, variceal bleeding and infection. However, there are still some aspects of management where the evidence base is less clear, and/or where opinions amongst practitioners remain divided. Some of these more controversial areas are explored in this section, wherein we present evidence culminating in a suggested management approach based on expert opinion and extending beyond the current guidelines.
Published: 2021

43. 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

44. Liver Transplantation in Acute-on-chronic Liver Failure

Author: Constantine J, Karvellas, Claire, Francoz, and Emmanuel, Weiss
Subjects: Liver Cirrhosis, Postoperative Complications, Treatment Outcome, Anti-Infective Agents, Waiting Lists, Critical Illness, Acute-On-Chronic Liver Failure, Humans, Immunosuppressive Agents, Liver Transplantation
Abstract: Liver transplantation (LT) has revolutionized outcomes for cirrhotic patients. Current liver allocation policies dictate patients with highest short-term mortality receive the highest priority, thus, several patients become increasingly ill on the waitlist. Given cirrhosis is a progressive disease, it can be complicated by the occurrence of acute-on-chronic liver failure (ACLF), a syndrome defined by an acute deterioration of liver function associated with extrahepatic organ failures requiring intensive care support and a high short-term mortality. Successfully bridging to transplant includes accurate prognostication and prioritization of ACLF patients awaiting LT, optimizing intensive care support pre-LT, and tailoring immunosuppressive and anti-infective therapies post-LT. Furthermore, predicting futility (too sick to undergo LT) in ACLF is challenging. In this review, we summarize the role of LT in ACLF specifically highlighting (a) current prognostic scores in ACLF, (b) critical care management of the ACLF patient awaiting LT, (c) donor issues to consider in transplant in ACLF, and (d) exploring of recent post-LT outcomes in ACLF and potential opportunities to improve outcomes including current care gaps and unmet research needs.
Published: 2020

45. Plasma fibroblast growth factor 23 concentration is increased and predicts mortality in patients on the liver-transplant waiting list.

Author: Dominique Prié, Anne Forand, Claire Francoz, Caroline Elie, Isabelle Cohen, Marie Courbebaisse, Dominique Eladari, Didier Lebrec, François Durand, and Gerard Friedlander
Subjects: Medicine, Science
Abstract: High plasma fibroblast growth factor-23 (FGF23) concentration predicts the risk of death and poor outcomes in patients with chronic kidney disease or chronic heart failure. We checked if FGF23 concentration could be modified in patients with end stage liver disease (ESLD) and predict mortality. We measured plasma FGF23 in 200 patients with ESLD registered on a liver transplant waiting list between January 2005 and October 2008. We found that median plasma FGF23 concentration was above normal values in 63% of the patients. Increased FGF23 concentration was not explained by its classical determinants: hyperphosphataemia, increased calcitriol concentration or decreased renal function. FGF23 concentration correlated with the MELD score, serum sodium concentration, and GFR. Forty-six patients died before being transplanted and 135 underwent liver transplantation. We analyzed the prognostic value of FGF23 levels. Mortality was significantly associated with FGF23 levels, the MELD score, serum sodium concentration and glomerular filtration rate. On multivariate analyses only FGF23 concentration was associated with mortality. FGF23 levels were independent of the cause of the liver disease. To determine if the damaged liver can produce FGF23 we measured plasma FGF23 concentration and liver FGF23 mRNA expression in control and diethyl-nitrosamine (DEN)-treated mice. FGF23 plasma levels increased with the apparition of liver lesions in DEN-treated mice and that FGF23 mRNA expression, which was undetectable in the liver of control mice, markedly increased with the development of liver lesions. The correlation between FGF23 plasma concentration and FGF23 mRNA expression in DEN-treated mice suggests that FGF23 production by the liver accounts for the increased plasma FGF23 concentration. In conclusion chronic liver lesions can induce expression of FGF23 mRNA leading to increased FGF23 concentration, which is associated with a higher mortality in patients on a liver-transplant waiting list. In these patients FGF23 concentration was the best predictor of mortality.
Published: 2013
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46. Alcohol Consumption the Day of Liver Transplantation for Alcohol-Associated Liver Disease Does Not Affect Long-Term Survival: A Case-Control Study

Author: Claire Francoz, Mohamed Belkacemi, Sébastien Dharancy, Olivier Boillot, José Ursic-Bedoya, Astrid Herrero, Magdalena Meszaros, Hélène Donnadieu-Rigole, Romain Altwegg, Camille Besch, Jérôme Dumortier, Claire Vanlemmens, Georges-Philippe Pageaux, Sarah Shili-Masmoudi, Stéphanie Faure, and Lucy Meunier
Subjects: medicine.medical_specialty, Cirrhosis, Alcohol Drinking, medicine.medical_treatment, Urine, 030230 surgery, Liver transplantation, Gastroenterology, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Recurrence, Internal medicine, medicine, Humans, Liver Diseases, Alcoholic, Retrospective Studies, Transplantation, Hepatology, business.industry, Case-control study, Retrospective cohort study, Odds ratio, medicine.disease, Liver Transplantation, Case-Control Studies, 030211 gastroenterology & hepatology, Surgery, France, business, Alcohol Abstinence
Abstract: Alcohol abstinence before liver transplantation (LT) for alcohol-associated liver disease (ALD) is required for every candidate. Some listed patients might relapse, resulting in LT for patients nonabstinent during the pretransplant period. Long-term survival outcomes of these patients have never been studied. We sought to determine whether alcohol consumption on the day of the LT influenced long-term survival after LT. We conducted a retrospective case-control study among French LT centers. Cases were defined as recipients between January 1995 and December 2007 having positive blood and/or urine alcohol levels the day of LT. Each case was paired with 2 controls corresponding to patients transplanted for ALD during the same trimester. Patients were classified into 3 categories per alcohol consumption: abstainers, occasional or transitory excessive consumers, or patients with a sustained excessive consumption (daily consumption >20-30 g/day). During the study period, 3052 LTs for ALD were conducted in France. We identified 42 cases paired with 84 controls. Median blood alcohol level was 0.4 g/L (range 0.1-4.1 g/L) and median urine alcohol level was 0.2 g/L (range 0.1-2.0 g/L). Median follow-up period until death or censoring was 12.9 years (CI95% = [12.3; 13.6]). Long-term survival was not different between the groups. Relapse to any alcohol consumption rate was higher in the case group (59.5%) than in the control group (38.1%, odds ratio 2.44; CI95% = [1.13; 5.27]), but sustained excessive consumption was not significantly different between the groups (33.3% versus 29.8% in case and control groups respectively, χ2 = 0.68). Rates of recurrent cirrhosis and cirrhosis-related deaths were more frequent in the case group. Liver transplantation for nonabstinent patients during the immediate pretransplant period does not result in impaired long-term survival despite higher relapse and recurrent cirrhosis rates.
Published: 2020

47. 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

48. Management of liver failure in general intensive care unit

Author: Stéphanie Faure, Richard Moreau, Faouzi Saliba, E. Levesque, Philippe Ichai, Arnaud Galbois, Claire Francoz, Emmanuel Weiss, Catherine Paugam-Burtz, Martine Ferrandière, Gerald Chanques, Samir Jaber, Thomas Lescot, Stéphanie Roullet, Alexandre Louvet, Roland Amathieu, Dominique Thabut, T. Thevenot, Christophe Camus, Thierry Gustot, Lionel Velly, Christophe Bureau, C. Ichai, Service d'Anesthésie-Réanimation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Beaujon, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Henri Mondor, Hôpital Claude Huriez [Lille], CHU Lille, 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hospital Group Croix Saint Simon, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Claude Galien Private Hospital, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Service de Réanimation médico-chirurgicale [Nice], Hôpital Saint-Roch [Nice], Nice University Hospital, Paul-Brousse Hospital, AP-HP, CHU Saint-Antoine [AP-HP], Université de Bordeaux (UB), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Paul Brousse Hospital, AP-HP, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), University Hospital La Timone, 13005 Marseille, Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Beaujon Hospital, DMU Parabol, AP-HP Nord, University of Paris, Hopital Saint-Louis [AP-HP] (AP-HP), Société française d’anesthésie et de réanimation (SFAR) and the Association française pour l’étude du foie (AFEF), MORNET, Dominique, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Toulouse (UT), Hôpital de la Timone [CHU - APHM] (TIMONE), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Hospital,Claude Huriez, Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Pitié-Salpêtrière [APHP], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Erasme Hospital, Department of Gastroenterology, Saint Antoine Hospital, Assistance Publique – Hopitaux de Paris, Sorbonne Universités, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Jean Minjoz University Hospital, Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Hopital Saint-Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), Hôpital Beaujon [AP-HP]-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Liver Cirrhosis, medicine.medical_specialty, Cirrhosis, Consensus, Critical Care, health care facilities, manpower, and services, [SDV]Life Sciences [q-bio], Population, MEDLINE, Guidelines as Topic, Guidelines, Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Anesthesiology, Sepsis, Medicine, Humans, Intensive care unit, 030212 general & internal medicine, Intensive care medicine, education, ComputingMilieux_MISCELLANEOUS, education.field_of_study, business.industry, 030208 emergency & critical care medicine, General Medicine, Guideline, Evidence-based medicine, Sciences bio-médicales et agricoles, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Intensive Care Units, Acute-on-chronic liver failure, Anesthesiology and Pain Medicine, Etiology, France, business, Liver Failure, Acute liver failure
Abstract: To produce French guidelines on Management of Liver failure in general Intensive Care Unit (ICU)., info:eu-repo/semantics/published
Published: 2020

49. Laparoscopic Liver Transplantation: Dream or Reality? The First Step With Laparoscopic Explant Hepatectomy

Author: Olivier Soubrane, François Cauchy, Pauline Infantes, Pierre Marie Choinier, Camille Hego, Emmanuel Weiss, Federica Dondero, François Durand, Claire Francoz, Béatrice Aussilhou, S. Chopinet, Ailton Sepulveda, Catherine Paugam-Burtz, Safi Dokmak, and Alain Sauvanet
Subjects: medicine.medical_specialty, medicine.medical_treatment, Anastomosis, Liver transplantation, Cold Ischemia Time, 03 medical and health sciences, 0302 clinical medicine, medicine, Hepatectomy, Humans, Laparoscopy, medicine.diagnostic_test, Bile duct, business.industry, Total Hepatectomy, Middle Aged, Surgery, Liver Transplantation, Dissection, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Tissue and Organ Harvesting, 030211 gastroenterology & hepatology, Female, business
Abstract: Objective To introduce the laparoscopic approach in liver transplant recipients. Summary of background data Despite the increasingly frequent use of laparoscopy in living donor hepatectomy, the laparoscopic approach has never been reported in liver transplant recipients. Methods A 52-year-old woman (body mass index: 18.5 kg/m) with neuroendocrine liver metastases of a digestive origin underwent hybrid liver transplantation by pure laparoscopic total hepatectomy and liver graft implantation using a preexisting midline incision. The hepatic pedicle vessels were dissected after division of the bile duct without a porto-caval shunt. Left lateral sectionectomy and early division of the common trunk allowed near completion of caval dissection with no prolonged inflow occlusion. The liver graft was reduced and latero-lateral caval anastomosis was performed. Results Surgery lasted 400 minutes with 400 mL of blood loss. The anhepatic phase lasted 43 minutes. Warm ischemia time and cold ischemia times were 38 and 466 minutes, respectively. The postoperative course was uneventful. Conclusions This case study suggests that the hybrid approach may be feasible and safe in selected recipients. The decision to use this surgical approach should be made in transplant centers with significant expertise in both laparoscopic liver and pancreatic surgery. Further reducing the size of the abdominal incision is the next step, which may be achieved with the development of vascular anastomoses devices.
Published: 2020

50. The Impact of Direct-acting Antivirals on Overall Mortality and Tumoral Recurrence in Patients With Hepatocellular Carcinoma Listed for Liver Transplantation: An International Multicenter Study

Author: Andre Gorgen, Norah A. Terrault, Bettina E. Hansen, Les Lilly, Angel Rubin, Joanne M O'Rourke, Nazia Selzner, Annsa C. Huang, Carmen Vinaixa, Tahir Shah, Zita Galvin, François Durand, Neil Mehta, Marina Berenguer, Gonzalo Sapisochin, David Calatayud, Claire Francoz, and Ahmed M. El-Sharkawy
Subjects: Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Time Factors, Waiting Lists, medicine.medical_treatment, 030230 surgery, Liver transplantation, Gastroenterology, Antiviral Agents, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Risk Factors, Internal medicine, Carcinoma, medicine, Humans, Risk factor, Retrospective Studies, Transplantation, business.industry, Incidence (epidemiology), Hazard ratio, Liver Neoplasms, Retrospective cohort study, Middle Aged, medicine.disease, Hepatitis C, digestive system diseases, Liver Transplantation, Treatment Outcome, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Female, Neoplasm Recurrence, Local, business
Abstract: BACKGROUND There is a lack of data on the use of direct-acting antivirals (DAA) on the risk of death and tumoral recurrence in patients with hepatitis C virus (HCV) and hepatocellular carcinoma (HCC) listed for liver transplantation (LT). We aimed to assess the impact of antiviral treatment on mortality and HCC recurrence patients with HCC-HCV. METHODS This was a retrospective multicenter study of patients with HCC-HCV listed for LT from 2005 to 2015. Patients were divided according to the antiviral treatment received after HCC diagnosis: DAA, interferon (IFN), or no antiviral. Intention-to-treat overall survival and HCC recurrence incidence were compared by the Kaplan-Meier method. Multivariable regression analysis was performed to identify risk factors for outcomes. RESULTS A total of 1012 HCV-HCC patients were listed for LT during the study period. The median follow-up was 4.0 (interquartile range = 2.3-6.7) years. Mortality was 5.6 (95% confidence interval [CI], 4.3-7.2), 13.1 (95% CI, 11.0-15.7), and 6.2 (95% CI, 5.4-7.2) deaths per 100 person-year among patients treated with DAA, IFN, and antiviral naive, respectively (P < 0.001). Of the 875 HCV-HCC transplant recipients, the 5-year recurrence-free survival was 93.4%, 84.8%, 73.9% for the pre-LT DAA, pre-LT IFN, and antiviral naive groups, respectively (P < 0.001). After multivariable regression, the use of pre-LT DAA was not associated to risk of recurrence (hazard ratio = 0.44 [95% CI, 0.19-1.00]). Post-LT DAA was not related to increased risk of recurrence (hazard ratio = 0.62 [95% CI, 0.33-1.16]). CONCLUSIONS In this multicenter intent-to-treat study, DAA therapy was not found to be a risk factor for mortality or HCC recurrence after adjusting for potential confounders.
Published: 2020

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