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1. Comparison of Pathway Referrals for Liver Fibrosis Risk Stratification Performed in Diabetology and Nutrition Clinics

Author

Caussy C, Telliam C, Al-Nuaimi B, Maynard-Muet M, Dumortier J, Zoulim F, Disse E, Colin C, Levrero M, and Moulin P

Subjects
nonalcoholic fatty liver disease, fibroscan, cirrhosis, transient elastography, obesity, type 2 diabetes, screening, Specialties of internal medicine, RC581-951
Abstract

Cyrielle Caussy,1– 3 Charlène Telliam,2,4 Bader Al-Nuaimi,2 Marianne Maynard-Muet,5,6 Jérôme Dumortier,3,7 Fabien Zoulim,3,5,6 Emmanuel Disse,1– 3 Cyrille Colin,3,8 Massimo Levrero,3,5,6 Philippe Moulin1,3,4 1CarMen Laboratory, INSERM, INRA, INSA Lyon, Université Claude Bernard Lyon 1, Pierre-Bénite, 69495, France; 2Département Endocrinologie, Diabète et Nutrition, Hôpital Lyon Sud, Hopices Civils de Lyon, Pierre-Bénite, 69495, France; 3Université de Lyon, Université Claude Bernard, Lyon, France; 4Département Endocrinologie, Diabète et Nutrition, Hôpital Cardiologique, Hospices Civils de Lyon, Bron, France; 5Service d’Hépatologie, Hôpital Croix-Rousse, Hospices Civils de Lyon, Lyon, France; 6Centre de Recherche sur le Cancer de Lyon, INSERM, Unité 1052, CNRS, UMR 5286, Lyon, France; 7Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France; 8Unité d’Evaluation Médico-Economique, Pôle Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon, FranceCorrespondence: Cyrielle Caussy, Service d’Endocrinologie, Diabète et Nutrition, Hôpital Lyon Sud, 165 Chemin du Grand Revoyet, Pierre-Bénite, 69495, France, Tel +33478864448, Fax + 33478863019, Email cyrielle.caussy@chu-lyon.frPurpose: A systematic screening for the presence of nonalcoholic fatty liver disease (NAFLD)-related advanced fibrosis is currently recommended in patients with type 2 diabetes mellitus (T2DM) and obesity. However, real-world data of such liver fibrosis risk stratification pathway from diabetology and nutrition clinics towards hepatology clinics are scarce. Therefore, we compared data from two pathways with or without transient elastography (TE) performed in diabetology and nutrition clinics.Patients and Methods: This is a retrospective study comparing the proportion of patients with intermediate/high risk of advanced fibrosis (AF) as defined by a liver stiffness measurement (LSM) ≥ 8kPa, among patients referred in hepatology from two diabetology-nutrition departments at Lyon University Hospital, France between November 1st 2018 to December 31st 2019.Results: Among the two diabetology and nutrition departments using TE or not, 27.5% (62/225) versus 44.2% (126/285) were referred to hepatology, respectively. The pathway using TE in diabetology and nutrition referred to hepatology a higher proportion of patients with intermediate/high risk of AF compared to the pathway without TE: 77.4% versus 30.9%, p< 0.001. In the pathway with TE, the odds of patients with intermediate/high risk of AF referred to hepatology was significantly higher: OR: 7.7, 95% CI: 3.6– 16.7, p< 0.001 after adjustment for age, sex and presence of obesity and T2D compared to the pathway without TE in diabetology and nutrition clinics. However, among the patients not referred, 29.4% had an intermediate/high risk of AF.Conclusion: A pathway-referral using TE performed in diabetology and nutrition clinics, significantly improves the liver fibrosis risk stratification and avoids over-referral. However, collaboration between diabetologist, nutritionists and hepatologists is needed to avoid under-referral.Keywords: nonalcoholic fatty liver disease, FibroScan, cirrhosis, transient elastography, obesity, type 2 diabetes, screening

Published
2023

2. Adequate versus deep response to ursodeoxycholic acid in primary biliary cholangitis: To what extent and under what conditions is normal alkaline phosphatase level associated with complication-free survival gain?

Author

Corpechot, C, Lemoinne, S, Soret, P, Hansen, B, Hirschfield, G, Gulamhusein, A, Montano-Loza, A, Lytvyak, E, Pares, A, Olivas, I, Eaton, J, Osman, K, Schramm, C, Sebode, M, Lohse, A, Dalekos, G, Gatselis, N, Nevens, F, Cazzagon, N, Zago, A, Russo, F, Floreani, A, Abbas, N, Trivedi, P, Thorburn, D, Saffioti, F, Barkai, L, Roccarina, D, Calvaruso, V, Fichera, A, Delamarre, A, Sobenko, N, Villamil, A, Medina-Morales, E, Bonder, A, Patwardhan, V, Rigamonti, C, Carbone, M, Invernizzi, P, Cristoferi, L, Van Der Meer, A, De Veer, R, Zigmond, E, Yehezkel, E, Kremer, A, Deibel, A, Bruns, T, Grosse, K, Wetten, A, Dyson, J, Jones, D, Dumortier, J, Pageaux, G, De Ledinghen, V, Chazouilleres, O, Carrat, F, Corpechot C., Lemoinne S., Soret P. -A., Hansen B., Hirschfield G., Gulamhusein A., Montano-Loza A. J., Lytvyak E., Pares A., Olivas I., Eaton J. E., Osman K. T., Schramm C., Sebode M., Lohse A. W., Dalekos G., Gatselis N., Nevens F., Cazzagon N., Zago A., Russo F. P., Floreani A., Abbas N., Trivedi P., Thorburn D., Saffioti F., Barkai L., Roccarina D., Calvaruso V., Fichera A., Delamarre A., Sobenko N., Villamil A. M., Medina-Morales E., Bonder A., Patwardhan V., Rigamonti C., Carbone M., Invernizzi P., Cristoferi L., Van Der Meer A., De Veer R., Zigmond E., Yehezkel E., Kremer A. E., Deibel A., Bruns T., Grosse K., Wetten A., Dyson J. K., Jones D., Dumortier J., Pageaux G. -P., De Ledinghen V., Chazouilleres O., Carrat F., Corpechot, C, Lemoinne, S, Soret, P, Hansen, B, Hirschfield, G, Gulamhusein, A, Montano-Loza, A, Lytvyak, E, Pares, A, Olivas, I, Eaton, J, Osman, K, Schramm, C, Sebode, M, Lohse, A, Dalekos, G, Gatselis, N, Nevens, F, Cazzagon, N, Zago, A, Russo, F, Floreani, A, Abbas, N, Trivedi, P, Thorburn, D, Saffioti, F, Barkai, L, Roccarina, D, Calvaruso, V, Fichera, A, Delamarre, A, Sobenko, N, Villamil, A, Medina-Morales, E, Bonder, A, Patwardhan, V, Rigamonti, C, Carbone, M, Invernizzi, P, Cristoferi, L, Van Der Meer, A, De Veer, R, Zigmond, E, Yehezkel, E, Kremer, A, Deibel, A, Bruns, T, Grosse, K, Wetten, A, Dyson, J, Jones, D, Dumortier, J, Pageaux, G, De Ledinghen, V, Chazouilleres, O, Carrat, F, Corpechot C., Lemoinne S., Soret P. -A., Hansen B., Hirschfield G., Gulamhusein A., Montano-Loza A. J., Lytvyak E., Pares A., Olivas I., Eaton J. E., Osman K. T., Schramm C., Sebode M., Lohse A. W., Dalekos G., Gatselis N., Nevens F., Cazzagon N., Zago A., Russo F. P., Floreani A., Abbas N., Trivedi P., Thorburn D., Saffioti F., Barkai L., Roccarina D., Calvaruso V., Fichera A., Delamarre A., Sobenko N., Villamil A. M., Medina-Morales E., Bonder A., Patwardhan V., Rigamonti C., Carbone M., Invernizzi P., Cristoferi L., Van Der Meer A., De Veer R., Zigmond E., Yehezkel E., Kremer A. E., Deibel A., Bruns T., Grosse K., Wetten A., Dyson J. K., Jones D., Dumortier J., Pageaux G. -P., De Ledinghen V., Chazouilleres O., and Carrat F.

Abstract

Background and Aims: Normal alkaline phosphatase (ALP) levels in ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC) are associated with better long-term outcome. However, second-line therapies are currently recommended only when ALP levels remain above 1.5 times the upper limit of normal (×ULN) after 12-month UDCA. We assessed whether, in patients considered good responders to UDCA, normal ALP levels were associated with significant survival gains. Approach and Results: We performed a retrospective cohort study of 1047 patients with PBC who attained an adequate response to UDCA according to Paris-2 criteria. Time to liver-related complications, liver transplantation, or death was assessed using adjusted restricted mean survival time (RMST) analysis. The overall incidence rate of events was 17.0 (95% CI: 13.7-21.1) per 1000 out of 4763.2 patient-years. On the whole population, normal serum ALP values (but not normal gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST); or total bilirubin < 0.6 ×ULN) were associated with a significant absolute complication-free survival gain at 10 years (mean 7.6 months, 95% CI: 2.7 - 12.6 mo.; p = 0.003). In subgroup analysis, this association was significant in patients with a liver stiffness measurement ≥ 10 kPa and/or age ≤ 62 years, with a 10-year absolute complication-free survival gain of 52.8 months (95% CI: 45.7-59.9, p < 0.001) when these 2 conditions were met. Conclusions: PBC patients with an adequate response to UDCA and persistent ALP elevation between 1.1 and 1.5 ×ULN, particularly those with advanced fibrosis and/or who are sufficiently young, remain at risk of poor outcome. Further therapeutic efforts should be considered for these patients.

Published
2024

3. COVID-19 et transplantation d’organes, les leçons du recensement national de la Société francophone de transplantation

Author

Caillard, S., Moulin, B., Fafi-Kremer, S., Hazzan, M., Anglicheau, D., Hertig, A., Tourret, J., Barrou, B., Morelon, E., Thaunat, O., Couzi, L., Merville, P., Moal, V., Legris, T., Westeel, P.-F., Jaureguy, M., Frimat, L., Ducloux, D., Bamoulid, J., Bertrand, D., Tsimaratos, M., Garaix-Gilardo, F., Dumortier, J., Mussot, S., Roux, A., Sebbag, L., Le Meur, Y., Blancho, G., Masset, C., Kamar, N., Francois, H., Rondeau, E., Bouvier, N., Mousson, C., Buchler, M., Gatault, P., Augusto, J.-F., Duveau, A., Vigneau, C., Morin, M.-C., Chemouny, J., Golbin, L., Grimbert, P., Matignon, M., Durrbach, A., Greze, C., Snanoudj, R., Colosio, C., Schvartz, B., Malvezzi, P., Mariat, C., Thierry, A., Le Quintrec, M., Sicard, A., Rerolle, J.P., Heng, A.-É., Garrouste, C., Coponat, H.V., Epailly, É., Brugiere, O., Dharancy, S., Salame, É., Saliba, F., and Caillard, Sophie

Published
2022
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4. Good outcome of liver transplantation in patients with pre-existing renal cell carcinoma

Author

Lassailly, G., primary, Ningarhari, M., additional, Dumortier, J, additional, Lafforgue, C., additional, Bouye, S., additional, Amrani, M.El, additional, Lebuffe, G., additional, Villers, A., additional, Truant, S, additional, Mathurin, P., additional, Louvet, A., additional, Boillot, O, additional, Boleslawski, E, additional, and Dharancy, S., additional

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

Author

Piñero, F, Costentin, C, Degroote, H, Notarpaolo, A, Boin, I, Boudjema, K, Baccaro, C, Chagas, A, Bachellier, P, Ettorre, G, Poniachik, J, Muscari, F, Dibenedetto, F, Duque, S, Salame, E, Cillo, U, Marciano, S, Vanlemmens, C, Fagiuoli, S, Carrilho, F, Cherqui, D, Burra, P, Van Vlierberghe, H, Lai, Q, Silva, M, Rubinstein, F, Duvoux, C, Conti, F, Scatton, O, Bernard, P, Francoz, C, Durand, F, Dharancy, S, Woehl, M, Laurent, A, Radenne, S, Dumortier, J, Abergel, A, Barbier, L, Houssel-Debry, P, Pageaux, G, Chiche, L, Deledinghen, V, Hardwigsen, J, Gugenheim, J, Altieri, M, Hilleret, M, Decaens, T, Costa, P, de Ataide, E, Quiñones, E, Anders, M, Varón, A, Zerega, A, Soza, A, Machaca, M, Arufe, D, Menéndez, J, Zapata, R, Vilatoba, M, Muñoz, L, Menéndez, R, Maraschio, M, Podestá, L, Mccormack, L, Mattera, J, Gadano, A, Parente García, J, Magini, G, Miglioresi, L, Gambato, M, D'Ambrosio, C, Vitale, A, Colledan, M, Pinelli, D, Magistri, P, Vennarecci, G, Colasanti, M, Giannelli, V, Pellicelli, A, Eduard, C, Samuele, I, Jeroen, D, Jonas, S, Jacques, P, Chris, V, Dirk, Y, Peter, M, Valerio, L, Christophe, M, Olivier, D, Jean, D, Roberto, T, Paul, L, Piñero F., Costentin C., Degroote H., Notarpaolo A., Boin I. F., Boudjema K., Baccaro C., Chagas A., Bachellier P., Ettorre G. M., Poniachik J., Muscari F., Dibenedetto F., Duque S. H., Salame E., Cillo U., Marciano S., Vanlemmens C., Fagiuoli S., Carrilho F., Cherqui D., Burra P., Van Vlierberghe H., Lai Q., Silva M., Rubinstein F., Duvoux C., Conti F., Scatton O., Bernard P. H., Francoz C., Durand F., Dharancy S., Woehl M. l., Laurent A., Radenne S., Dumortier J., Abergel A., Barbier L., Houssel-Debry P., Pageaux G. P., Chiche L., Deledinghen V., Hardwigsen J., Gugenheim J., altieri M., Hilleret M. N., Decaens T., Costa P., de Ataide E. C., Quiñones E., Anders M., Varón A., Zerega A., Soza A., Machaca M. P., Arufe D., Menéndez J., Zapata R., Vilatoba M., Muñoz L., Menéndez R. C., Maraschio M., Podestá L. G., McCormack L., Mattera J., Gadano A., Parente García J. H., Magini G., Miglioresi L., Gambato M., D'Ambrosio C., Vitale A., Colledan M., Pinelli D., Magistri P., Vennarecci G., Colasanti M., Giannelli V., Pellicelli A., Eduard C., Samuele I., Jeroen D., Jonas S., Jacques P., Chris V., Dirk Y., Peter M., Valerio L., Christophe M., Olivier D., Jean D., Roberto T., Paul L. J., Piñero, F, Costentin, C, Degroote, H, Notarpaolo, A, Boin, I, Boudjema, K, Baccaro, C, Chagas, A, Bachellier, P, Ettorre, G, Poniachik, J, Muscari, F, Dibenedetto, F, Duque, S, Salame, E, Cillo, U, Marciano, S, Vanlemmens, C, Fagiuoli, S, Carrilho, F, Cherqui, D, Burra, P, Van Vlierberghe, H, Lai, Q, Silva, M, Rubinstein, F, Duvoux, C, Conti, F, Scatton, O, Bernard, P, Francoz, C, Durand, F, Dharancy, S, Woehl, M, Laurent, A, Radenne, S, Dumortier, J, Abergel, A, Barbier, L, Houssel-Debry, P, Pageaux, G, Chiche, L, Deledinghen, V, Hardwigsen, J, Gugenheim, J, Altieri, M, Hilleret, M, Decaens, T, Costa, P, de Ataide, E, Quiñones, E, Anders, M, Varón, A, Zerega, A, Soza, A, Machaca, M, Arufe, D, Menéndez, J, Zapata, R, Vilatoba, M, Muñoz, L, Menéndez, R, Maraschio, M, Podestá, L, Mccormack, L, Mattera, J, Gadano, A, Parente García, J, Magini, G, Miglioresi, L, Gambato, M, D'Ambrosio, C, Vitale, A, Colledan, M, Pinelli, D, Magistri, P, Vennarecci, G, Colasanti, M, Giannelli, V, Pellicelli, A, Eduard, C, Samuele, I, Jeroen, D, Jonas, S, Jacques, P, Chris, V, Dirk, Y, Peter, M, Valerio, L, Christophe, M, Olivier, D, Jean, D, Roberto, T, Paul, L, Piñero F., Costentin C., Degroote H., Notarpaolo A., Boin I. F., Boudjema K., Baccaro C., Chagas A., Bachellier P., Ettorre G. M., Poniachik J., Muscari F., Dibenedetto F., Duque S. H., Salame E., Cillo U., Marciano S., Vanlemmens C., Fagiuoli S., Carrilho F., Cherqui D., Burra P., Van Vlierberghe H., Lai Q., Silva M., Rubinstein F., Duvoux C., Conti F., Scatton O., Bernard P. H., Francoz C., Durand F., Dharancy S., Woehl M. l., Laurent A., Radenne S., Dumortier J., Abergel A., Barbier L., Houssel-Debry P., Pageaux G. P., Chiche L., Deledinghen V., Hardwigsen J., Gugenheim J., altieri M., Hilleret M. N., Decaens T., Costa P., de Ataide E. C., Quiñones E., Anders M., Varón A., Zerega A., Soza A., Machaca M. P., Arufe D., Menéndez J., Zapata R., Vilatoba M., Muñoz L., Menéndez R. C., Maraschio M., Podestá L. G., McCormack L., Mattera J., Gadano A., Parente García J. H., Magini G., Miglioresi L., Gambato M., D'Ambrosio C., Vitale A., Colledan M., Pinelli D., Magistri P., Vennarecci G., Colasanti M., Giannelli V., Pellicelli A., Eduard C., Samuele I., Jeroen D., Jonas S., Jacques P., Chris V., Dirk Y., Peter M., Valerio L., Christophe M., Olivier D., Jean D., Roberto T., and Paul L. J.

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 <0.0001). At last tumor reassessment before LT, c-statistics did not significantly differ between the two composite models, either as original or threshold versions, for recurrence (0.72 vs. 0.68; p = 0.06), HCC survival, and overall survival after LT. We observed predictive gaps and overlaps between the model's thresholds, and no significant gain on reclassification. Patients meeting both models (“within-ALL”) at last tumor reassessment presented the lowest 5-year cumulative incidence of HCC recurrence (7.7%; 95% CI 5.1-11.5) and higher 5-year post-LT survival (70.0%; 95% CI 64.9-74.6). Conclusions: In this multicenter cohort, Metroticket 2.0 and the AFP score demonstrated a similar ability to predict HCC recurrence post-LT. The combination of these composite models might be a promising clinical approach. Impact and implications: Composite models were recently proposed for the selection of liver transplant (LT

Published
2023

7. Gap Analysis for Information Security in Interoperable Solutions at a Systemic Level: The KONFIDO Approach

Author

Rasmussen, J., Natsiavas, P., Votis, K., Moschou, K., Campegiani, P., Coppolino, L., Cano, I., Marí, D., Faiella, G., Stan, O., Abdelrahman, O., Nalin, M., Baroni, I., Voss-Knude, M., Vella, V. A., Grivas, E., Mesaritakis, C., Dumortier, J., Petersen, J., Tzovaras, D., Romano, L., Komnios, I., Koutkias, V., Magjarevic, Ratko, Series Editor, Ładyżyński, Piotr, Associate Editor, Ibrahim, Fatimah, Associate Editor, Lackovic, Igor, Associate Editor, Rock, Emilio Sacristan, Associate Editor, Maglaveras, Nicos, editor, Chouvarda, Ioanna, editor, and de Carvalho, Paulo, editor

Published
2018
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11. TRIDENT - Technology based impact assessment tool foR sustaInable, transparent Deep sEa miNing exploraTion and exploitation: A project overview

Author

Silva, E., Viegas, D., Martins, A., Almeida, J., Almeida, C., Neves, B., Madureira, Pedro, Wheeler, Andrew J., Salavasidis, G., Phillips, A., Schaap, A., Murton, Bramley, Berry, Alan, Weir, A., Dooly, G., Omerdic, E., Toal, D., Collins, P. C., Miranda, M., Petrioli, C., Barrera Rodríguez, C., Demoor, D., Drouet, C., Serafy, G.El, Jesus, S. M., Dañobeitia, Juan José, Tegas, Valentina, Cusí, Simó, Lopes, L., Bodo, B., Béguery, Laurent, Van Dam, S., Dumortier, J., Neves, L., Srivastava, V., Dahlgren, Thomas G., Hestetun, Jon Thomassen, Eiras, R., Caldeira, Rui, Rossi, Claudio, Spearman, Jeremy, Somoza, Luis, González Sanz, Francisco Javier, Bartolomé, Rafael, Bahurel, Pierre, Silva, E., Viegas, D., Martins, A., Almeida, J., Almeida, C., Neves, B., Madureira, Pedro, Wheeler, Andrew J., Salavasidis, G., Phillips, A., Schaap, A., Murton, Bramley, Berry, Alan, Weir, A., Dooly, G., Omerdic, E., Toal, D., Collins, P. C., Miranda, M., Petrioli, C., Barrera Rodríguez, C., Demoor, D., Drouet, C., Serafy, G.El, Jesus, S. M., Dañobeitia, Juan José, Tegas, Valentina, Cusí, Simó, Lopes, L., Bodo, B., Béguery, Laurent, Van Dam, S., Dumortier, J., Neves, L., Srivastava, V., Dahlgren, Thomas G., Hestetun, Jon Thomassen, Eiras, R., Caldeira, Rui, Rossi, Claudio, Spearman, Jeremy, Somoza, Luis, González Sanz, Francisco Javier, Bartolomé, Rafael, and Bahurel, Pierre

Abstract

By creating a dependable, transparent, and cost-effective system for forecasting and ongoing environmental impact monitoring of exploration and exploitation activities in the deep sea, TRIDENT seeks to contribute to the sustainable exploitation of seabed mineral resources. In order to operate autonomously in remote locations under harsh conditions and send real-time data to authorities in charge of granting licenses and providing oversight, this system will create and integrate new technology and innovative solutions. The efficient monitoring and inspection system that will be created will abide by national and international legal frameworks. At the sea surface, mid-water, and the bottom, TRIDENT will identify all pertinent physical, chemical, geological, and biological characteristics that must be monitored. It will also look for data gaps and suggest procedures for addressing them. These are crucial actions to take in order to produce accurate indicators of excellent environmental status, statistically robust environmental baselines, and thresholds for significant impact, allowing for the standardization of methods and tools. In order to monitor environmental parameters on mining and reference areas at representative spatial and temporal scales, the project consortium will thereafter develop and test an integrated system of stationary and mobile observatory platforms outfitted with the most recent automatic sensors and samplers. The system will incorporate high-capacity data processing pipelines able to gather, transmit, process, and display monitoring data in close to real-time to facilitate prompt actions for preventing major harm to the environment. Last but not least, it will offer systemic and technological solutions for predicting probable impacts of applying the developed monitoring and mitigation techniques

Published
2023

13. Gap Analysis for Information Security in Interoperable Solutions at a Systemic Level: The KONFIDO Approach

Author

Rasmussen, J., primary, Natsiavas, P., additional, Votis, K., additional, Moschou, K., additional, Campegiani, P., additional, Coppolino, L., additional, Cano, I., additional, Marí, D., additional, Faiella, G., additional, Stan, O., additional, Abdelrahman, O., additional, Nalin, M., additional, Baroni, I., additional, Voss-Knude, M., additional, Vella, V. A., additional, Grivas, E., additional, Mesaritakis, C., additional, Dumortier, J., additional, Petersen, J., additional, Tzovaras, D., additional, Romano, L., additional, Komnios, I., additional, and Koutkias, V., additional

Published
2017
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14. Combination of fibrates with obeticholic acid is able to normalise biochemical liver tests in patients with difficult-to-treat primary biliary cholangitis

Author

Soret, P, Lam, L, Carrat, F, Smets, L, Berg, T, Carbone, M, Invernizzi, P, Leroy, V, Trivedi, P, Cazzagon, N, Weiler-Normann, C, Alric, L, Rosa-Hezode, I, Heurgue, A, Cervoni, J, Dumortier, J, Potier, P, Roux, O, Silvain, C, Bureau, C, Anty, R, Larrey, D, Levy, C, Pares, A, Schramm, C, Nevens, F, Chazouilleres, O, Corpechot, C, Soret P. -A., Lam L., Carrat F., Smets L., Berg T., Carbone M., Invernizzi P., Leroy V., Trivedi P., Cazzagon N., Weiler-Normann C., Alric L., Rosa-Hezode I., Heurgue A., Cervoni J. -P., Dumortier J., Potier P., Roux O., Silvain C., Bureau C., Anty R., Larrey D., Levy C., Pares A., Schramm C., Nevens F., Chazouilleres O., Corpechot C., Soret, P, Lam, L, Carrat, F, Smets, L, Berg, T, Carbone, M, Invernizzi, P, Leroy, V, Trivedi, P, Cazzagon, N, Weiler-Normann, C, Alric, L, Rosa-Hezode, I, Heurgue, A, Cervoni, J, Dumortier, J, Potier, P, Roux, O, Silvain, C, Bureau, C, Anty, R, Larrey, D, Levy, C, Pares, A, Schramm, C, Nevens, F, Chazouilleres, O, Corpechot, C, Soret P. -A., Lam L., Carrat F., Smets L., Berg T., Carbone M., Invernizzi P., Leroy V., Trivedi P., Cazzagon N., Weiler-Normann C., Alric L., Rosa-Hezode I., Heurgue A., Cervoni J. -P., Dumortier J., Potier P., Roux O., Silvain C., Bureau C., Anty R., Larrey D., Levy C., Pares A., Schramm C., Nevens F., Chazouilleres O., and Corpechot C.

Abstract

Background: Obeticholic acid (OCA) and fibrates are second-line therapies for patients with primary biliary cholangitis (PBC) with an inadequate response to ursodeoxycholic acid (UDCA). Aim: To know whether OCA and fibrates, administered together in combination with UDCA, have additive beneficial effects in patients with difficult-to-treat PBC. Methods: PBC patients treated for ≥3 months with UDCA, OCA and fibrates (bezafibrate or fenofibrate) due to failure of either second-line therapy were included in a multicentre, uncontrolled retrospective cohort study. Changes in biochemical liver tests and pruritus were analysed using a generalised linear mixed-effect model. Results: Among 58 patients included, half received OCA as second-line and fibrates as third-line therapy (Group OCA-Fibrate), while the other half had the inverse therapeutic sequence (Group Fibrate-OCA). The mean duration of triple therapy was 11 months (range 3-26). Compared to dual therapy, triple therapy was associated with a significant gain in alkaline phosphatase (ALP) reduction: 22% per first year (95% CI 12%-31%), an effect that was stronger in OCA-Fibrate than in Fibrate-OCA group. Triple therapy was associated with a 3.4 (95% CI 1.4-8.2) odds ratio (OR) of reaching normal ALP and with a significant decrease in gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin. The ORs of achieving the Paris-2 and Toronto criteria of adequate biochemical response were 6.8 (95% CI 2.8-16.7) and 9.2 (95% CI 3.4-25.1) respectively. Finally, triple therapy significantly improved pruritus in OCA-Fibrate but not in Fibrate-OCA group. Conclusions: Triple therapy with UDCA, OCA and fibrates is able to normalise biochemical liver tests and improve pruritus in patients with difficult-to-treat PBC.

Published
2021

15. Mechanisms of Cytomegalovirus-Accelerated Vascular Disease: Induction of Paracrine Factors That Promote Angiogenesis and Wound Healing

Author

Streblow, D. N., Dumortier, J., Moses, A. V., Orloff, S. L., Nelson, J. A., Compans, Richard W., editor, Cooper, Max D., editor, Honjo, Tasuku, editor, Koprowski, Hilary, editor, Melchers, Fritz, editor, Oldstone, Michael B. A., editor, Olsnes, Sjur, editor, Vogt, Peter K., editor, Shenk, Thomas E., editor, and Stinski, Mark F., editor

Published
2008
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17. Treatment with tenofovir disoproxil fumarate or entecavir in chronic hepatitis B virus-infected patients with renal impairment: results from a 7-year, multicentre retrospective cohort study

Author

Lampertico, P, Berg, T, Buti, M, Pathil, A, Petersen, J, Ryder, S, Zoulim, F, Botros, I, Flaherty, J, Jump, B, Op den Brouw, M, van Troostenburg, A, Ramroth, H, Bourliere, M, De Ledinghen, V, Riachi, G, Loustaud-Ratti, V, Tran, A, Larrey, D, Dumortier, J, Leroy, V, Metivier, S, Sellier, P, Mauss, S, Peterson, J, Schiefke, I, Niederau, C, Teuber, G, Goeser, T, Jung, M, Grambihler, A, Pathil-Warth, A, Sprinzl, K, Von der Ohe, M, Antoni, C, Weigand, K, Andreone, P, Di Marco, V, Madonia, S, Puoti, M, Santantonio, T, Vigano, M, Ciancio, A, D'Offizi, G, Pirisi, M, Suarez Garcia, E, Pascasio Acevedo, J, Andrade, R, Gea, F, Serra Desfilis, M, Molina Perez, E, Manzano Alonso, M, Carrion, J, Aoufi Rabih, S, Planas, M, Agarwal, K, Ustianowski, A, Aspinall, R, Kennedy, P, Geretti, A, Mccorry, R, Foxton, M, Healy, B, Lampertico P., Berg T., Buti M., Pathil A., Petersen J., Ryder S. D., Zoulim F., Botros I., Flaherty J. F., Jump B., Op den Brouw M. L., van Troostenburg A., Ramroth H., Bourliere M., De Ledinghen V., Riachi G., Loustaud-Ratti V., Tran A., Larrey D., Dumortier J., Leroy V., Metivier S., Sellier P., Mauss S., Peterson J., Schiefke I., Niederau C., Teuber G., Goeser T., Jung M. C., Grambihler A., Pathil-Warth A., Sprinzl K., Von der Ohe M., Antoni C., Weigand K., Andreone P., Di Marco V., Madonia S., Puoti M., Santantonio T., Vigano M., Ciancio A., D'Offizi G., Pirisi M., Suarez Garcia E., Pascasio Acevedo J. M., Andrade R., Gea F., Serra Desfilis M. A., Molina Perez E., Manzano Alonso M., Carrion J. A., Aoufi Rabih S., Planas M. M., Ryder S., Agarwal K., Ustianowski A., Aspinall R., Kennedy P., Geretti A. M., McCorry R., Foxton M., Healy B., Lampertico, P, Berg, T, Buti, M, Pathil, A, Petersen, J, Ryder, S, Zoulim, F, Botros, I, Flaherty, J, Jump, B, Op den Brouw, M, van Troostenburg, A, Ramroth, H, Bourliere, M, De Ledinghen, V, Riachi, G, Loustaud-Ratti, V, Tran, A, Larrey, D, Dumortier, J, Leroy, V, Metivier, S, Sellier, P, Mauss, S, Peterson, J, Schiefke, I, Niederau, C, Teuber, G, Goeser, T, Jung, M, Grambihler, A, Pathil-Warth, A, Sprinzl, K, Von der Ohe, M, Antoni, C, Weigand, K, Andreone, P, Di Marco, V, Madonia, S, Puoti, M, Santantonio, T, Vigano, M, Ciancio, A, D'Offizi, G, Pirisi, M, Suarez Garcia, E, Pascasio Acevedo, J, Andrade, R, Gea, F, Serra Desfilis, M, Molina Perez, E, Manzano Alonso, M, Carrion, J, Aoufi Rabih, S, Planas, M, Agarwal, K, Ustianowski, A, Aspinall, R, Kennedy, P, Geretti, A, Mccorry, R, Foxton, M, Healy, B, Lampertico P., Berg T., Buti M., Pathil A., Petersen J., Ryder S. D., Zoulim F., Botros I., Flaherty J. F., Jump B., Op den Brouw M. L., van Troostenburg A., Ramroth H., Bourliere M., De Ledinghen V., Riachi G., Loustaud-Ratti V., Tran A., Larrey D., Dumortier J., Leroy V., Metivier S., Sellier P., Mauss S., Peterson J., Schiefke I., Niederau C., Teuber G., Goeser T., Jung M. C., Grambihler A., Pathil-Warth A., Sprinzl K., Von der Ohe M., Antoni C., Weigand K., Andreone P., Di Marco V., Madonia S., Puoti M., Santantonio T., Vigano M., Ciancio A., D'Offizi G., Pirisi M., Suarez Garcia E., Pascasio Acevedo J. M., Andrade R., Gea F., Serra Desfilis M. A., Molina Perez E., Manzano Alonso M., Carrion J. A., Aoufi Rabih S., Planas M. M., Ryder S., Agarwal K., Ustianowski A., Aspinall R., Kennedy P., Geretti A. M., McCorry R., Foxton M., and Healy B.

Abstract

Background: Limited data exist regarding tenofovir disoproxil fumarate (TDF) safety and effectiveness in chronic hepatitis B virus–infected (CHB) patients with renal impairment (RI). Aims: To compare real-world data on renal safety and effectiveness of TDF vs entecavir (ETV) in CHB patients with moderate-to-severe RI. Methods: Retrospective, non-interventional, cohort study analysing medical records for TDF/ETV-treated CHB patients (54 European centres). Included patients experienced moderate-to-severe RI (creatinine clearance 20-60 mL/min [Cockcroft-Gault]) either before TDF/ETV initiation (‘before’ subgroup [baseline = treatment initiation]) or after TDF/ETV initiation (‘after’ subgroup [baseline = first RI occurrence]). The primary objective was TDF safety, particularly renal-related adverse events of special interest (AESI). TDF and ETV safety and effectiveness were compared and multivariate analyses were performed using inverse probability treatment weighting. Results: ‘Before’ subgroup included 107 TDF- and 91 ETV-treated patients; ‘after’ subgroup included 212 TDF- and 77 ETV-treated patients. Mean baseline creatinine clearance was higher for TDF- vs ETV-treated patients (both subgroups). Median follow-up was 3.1 years (both treatments). AESI were more frequent with TDF vs ETV (‘before’: 18.7% vs 8.8%; ‘after’: 9.9% vs 3.9%); however, differences were not significant by multivariate analysis. Only TDF-treated patients experienced renal tubular dysfunction (6.5% ‘before’; 1.9% ‘after’) as well as renal adverse events leading to treatment discontinuation (8.4% ‘before’; 7.1% ‘after’). Effectiveness was similar between treatments. Conclusions: Overall safety was similar for TDF vs ETV (both subgroups). Given that renal tubular dysfunction occurred with TDF and not with ETV, renal safety concerns may be greater with TDF in CHB patients with RI.

Published
2020

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

Author

Corpechot, C, Chazouilleres, O, Belnou, P, Montano-Loza, A, Mason, A, Ebadi, M, Eurich, D, Chopra, S, Jacob, D, Schramm, C, Sterneck, M, Bruns, T, Reuken, P, Rauchfuss, F, Roccarina, D, Thorburn, D, Gerussi, A, Trivedi, P, Hirschfield, G, Mcdowell, P, Nevens, F, Boillot, O, Bosch, A, Giostra, E, Conti, F, Poupon, R, Pares, A, Reig, A, Donato, M, Malinverno, F, Floreani, A, Russo, F, Cazzagon, N, Verhelst, X, Goet, J, Harms, M, van Buuren, H, Hansen, B, Carrat, F, Dumortier, J, Corpechot C., Chazouilleres O., Belnou P., Montano-Loza A. J., Mason A., Ebadi M., Eurich D., Chopra S., Jacob D., Schramm C., Sterneck M., Bruns T., Reuken P., Rauchfuss F., Roccarina D., Thorburn D., Gerussi A., Trivedi P., Hirschfield G., McDowell P., Nevens F., Boillot O., Bosch A., Giostra E., Conti F., Poupon R., Pares A., Reig A., Donato M. F., Malinverno F., Floreani A., Russo F. P., Cazzagon N., Verhelst X., Goet J., Harms M., van Buuren H., Hansen B., Carrat F., Dumortier J., Corpechot, C, Chazouilleres, O, Belnou, P, Montano-Loza, A, Mason, A, Ebadi, M, Eurich, D, Chopra, S, Jacob, D, Schramm, C, Sterneck, M, Bruns, T, Reuken, P, Rauchfuss, F, Roccarina, D, Thorburn, D, Gerussi, A, Trivedi, P, Hirschfield, G, Mcdowell, P, Nevens, F, Boillot, O, Bosch, A, Giostra, E, Conti, F, Poupon, R, Pares, A, Reig, A, Donato, M, Malinverno, F, Floreani, A, Russo, F, Cazzagon, N, Verhelst, X, Goet, J, Harms, M, van Buuren, H, Hansen, B, Carrat, F, Dumortier, J, Corpechot C., Chazouilleres O., Belnou P., Montano-Loza A. J., Mason A., Ebadi M., Eurich D., Chopra S., Jacob D., Schramm C., Sterneck M., Bruns T., Reuken P., Rauchfuss F., Roccarina D., Thorburn D., Gerussi A., Trivedi P., Hirschfield G., McDowell P., Nevens F., Boillot O., Bosch A., Giostra E., Conti F., Poupon R., Pares A., Reig A., Donato M. F., Malinverno F., Floreani A., Russo F. P., Cazzagon N., Verhelst X., Goet J., Harms M., van Buuren H., Hansen B., Carrat F., and Dumortier J.

Abstract

Background & Aims: Recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT) is frequent and can impair graft and patient survival. Ursodeoxycholic acid (UDCA) is the current standard therapy for PBC. We investigated the effect of preventive exposure to UDCA on the incidence and long-term consequences of PBC recurrence after LT. Methods: We performed a retrospective cohort study in 780 patients transplanted for PBC, between 1983–2017 in 16 centers (9 countries), and followed-up for a median of 11 years. Among them, 190 received preventive UDCA (10–15 mg/kg/day). The primary outcome was histological evidence of PBC recurrence. The secondary outcomes were graft loss, liver-related death, and all-cause death. The association between preventive UDCA and outcomes was quantified using multivariable-adjusted Cox and restricted mean survival time (RMST) models. Results: While recurrence of PBC significantly shortened graft and patient survival, preventive exposure to UDCA was associated with reduced risk of PBC recurrence (adjusted hazard ratio [aHR] 0.41; 95% CI 0.28–0.61; p <0.0001), graft loss (aHR 0.33; 95% CI 0.13–0.82; p <0.05), liver-related death (aHR 0.46; 95% CI 0.22–0.98; p <0.05), and all-cause death (aHR 0.69; 95% CI 0.49–0.96; p <0.05). On RMST analysis, preventive UDCA led to a survival gain of 2.26 years (95% CI 1.28–3.25) over a period of 20 years. Exposure to cyclosporine rather than tacrolimus had a complementary protective effect alongside preventive UDCA, reducing the cumulative incidence of PBC recurrence and all-cause death. Conclusions: Preventive UDCA after LT for PBC is associated with a reduced risk of disease recurrence, graft loss, and death. A regimen combining cyclosporine and preventive UDCA is associated with the lowest risk of PBC recurrence and mortality. Lay summary: Recurrence of primary biliary cholangitis after liver transplantation is frequent and can impair graft and patient survival. We perform

Published
2020

19. Treatment with tenofovir disoproxil fumarate or entecavir in chronic hepatitis B virus-infected patients with renal impairment: results from a 7-year, multicentre retrospective cohort study

Author

Lampertico P., Berg T., Buti M., Pathil A., Petersen J., Ryder S. D., Zoulim F., Botros I., Flaherty J. F., Jump B., Op den Brouw M. L., van Troostenburg A., Ramroth H., Bourliere M., De Ledinghen V., Riachi G., Loustaud-Ratti V., Tran A., Larrey D., Dumortier J., Leroy V., Metivier S., Sellier P., Mauss S., Peterson J., Schiefke I., Niederau C., Teuber G., Goeser T., Jung M. C., Grambihler A., Pathil-Warth A., Sprinzl K., Von der Ohe M., Antoni C., Weigand K., Andreone P., Di Marco V., Madonia S., Puoti M., Santantonio T., Vigano M., Ciancio A., D'Offizi G., Pirisi M., Suarez Garcia E., Pascasio Acevedo J. M., Andrade R., Gea F., Serra Desfilis M. A., Molina Perez E., Manzano Alonso M., Carrion J. A., Aoufi Rabih S., Planas M. M., Ryder S., Agarwal K., Ustianowski A., Aspinall R., Kennedy P., Geretti A. M., McCorry R., Foxton M., Healy B., Lampertico P., Berg T., Buti M., Pathil A., Petersen J., Ryder S.D., Zoulim F., Botros I., Flaherty J.F., Jump B., Op den Brouw M.L., van Troostenburg A., Ramroth H., Bourliere M., De Ledinghen V., Riachi G., Loustaud-Ratti V., Tran A., Larrey D., Dumortier J., Leroy V., Metivier S., Sellier P., Mauss S., Peterson J., Schiefke I., Niederau C., Teuber G., Goeser T., Jung M.C., Grambihler A., Pathil-Warth A., Sprinzl K., Von der Ohe M., Antoni C., Weigand K., Andreone P., Di Marco V., Madonia S., Puoti M., Santantonio T., Vigano M., Ciancio A., D'Offizi G., Pirisi M., Suarez Garcia E., Pascasio Acevedo J.M., Andrade R., Gea F., Serra Desfilis M.A., Molina Perez E., Manzano Alonso M., Carrion J.A., Aoufi Rabih S., Planas M.M., Ryder S., Agarwal K., Ustianowski A., Aspinall R., Kennedy P., Geretti A.M., McCorry R., Foxton M., Healy B., Lampertico, P, Berg, T, Buti, M, Pathil, A, Petersen, J, Ryder, S, Zoulim, F, Botros, I, Flaherty, J, Jump, B, Op den Brouw, M, van Troostenburg, A, Ramroth, H, Bourliere, M, De Ledinghen, V, Riachi, G, Loustaud-Ratti, V, Tran, A, Larrey, D, Dumortier, J, Leroy, V, Metivier, S, Sellier, P, Mauss, S, Peterson, J, Schiefke, I, Niederau, C, Teuber, G, Goeser, T, Jung, M, Grambihler, A, Pathil-Warth, A, Sprinzl, K, Von der Ohe, M, Antoni, C, Weigand, K, Andreone, P, Di Marco, V, Madonia, S, Puoti, M, Santantonio, T, Vigano, M, Ciancio, A, D'Offizi, G, Pirisi, M, Suarez Garcia, E, Pascasio Acevedo, J, Andrade, R, Gea, F, Serra Desfilis, M, Molina Perez, E, Manzano Alonso, M, Carrion, J, Aoufi Rabih, S, Planas, M, Agarwal, K, Ustianowski, A, Aspinall, R, Kennedy, P, Geretti, A, Mccorry, R, Foxton, M, and Healy, B

Subjects
Male, Adult, medicine.medical_specialty, Guanine, Tenofovir, MEDLINE, Antiviral Agents, Virus, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Hepatitis B, Chronic, Retrospective Studie, Internal medicine, 80 and over, HBV, Medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Renal Insufficiency, Young adult, Aged, Aged, 80 and over, Female, Middle Aged, Retrospective Studies, Treatment Outcome, Chronic, Antiviral Agent, Hepatology, business.industry, Gastroenterology, virus diseases, Retrospective cohort study, Entecavir, Hepatitis B, medicine.disease, Cohort, 030211 gastroenterology & hepatology, business, medicine.drug, Human
Abstract

BackgroundLimited data exist regarding tenofovir disoproxil fumarate (TDF) safety and effectiveness in chronic hepatitis B virus-infected (CHB) patients with renal impairment (RI).AimsTo compare real-world data on renal safety and effectiveness of TDF vs entecavir (ETV) in CHB patients with moderate-to-severe RI.MethodsRetrospective, non-interventional, cohort study analysing medical records for TDF/ETV-treated CHB patients (54 European centres). Included patients experienced moderate-to-severe RI (creatinine clearance 20-60 mL/min [Cockcroft-Gault]) either before TDF/ETV initiation ('before' subgroup [baseline = treatment initiation]) or after TDF/ETV initiation ('after' subgroup [baseline = first RI occurrence]). The primary objective was TDF safety, particularly renal-related adverse events of special interest (AESI). TDF and ETV safety and effectiveness were compared and multivariate analyses were performed using inverse probability treatment weighting.Results'Before' subgroup included 107 TDF- and 91 ETV-treated patients; 'after' subgroup included 212 TDF- and 77 ETV-treated patients. Mean baseline creatinine clearance was higher for TDF- vs ETV-treated patients (both subgroups). Median follow-up was 3.1 years (both treatments). AESI were more frequent with TDF vs ETV ('before': 18.7% vs 8.8%; 'after': 9.9% vs 3.9%); however, differences were not significant by multivariate analysis. Only TDF-treated patients experienced renal tubular dysfunction (6.5% 'before'; 1.9% 'after') as well as renal adverse events leading to treatment discontinuation (8.4% 'before'; 7.1% 'after'). Effectiveness was similar between treatments.ConclusionsOverall safety was similar for TDF vs ETV (both subgroups). Given that renal tubular dysfunction occurred with TDF and not with ETV, renal safety concerns may be greater with TDF in CHB patients with RI.

Published
2020

20. Polycystic liver: automatic segmentation using deep learning on CT is faster and as accurate compared to manual segmentation

Author

Cayot, B., Milot, L., Nempont, O., Vlachomitrou, A.S., Langlois-Jacques, C., Dumortier, J., Boillot, O., Arnaud, K., Barten, T.R.M., Drenth, J.P.H., Valette, P.J., Cayot, B., Milot, L., Nempont, O., Vlachomitrou, A.S., Langlois-Jacques, C., Dumortier, J., Boillot, O., Arnaud, K., Barten, T.R.M., Drenth, J.P.H., and Valette, P.J.

Abstract

Item does not contain fulltext, OBJECTIVE: This study aimed to develop and investigate the performance of a deep learning model based on a convolutional neural network (CNN) for the automatic segmentation of polycystic livers at CT imaging. METHOD: This retrospective study used CT images of polycystic livers. To develop the CNN, supervised training and validation phases were performed using 190 CT series. To assess performance, the test phase was performed using 41 CT series. Manual segmentation by an expert radiologist (Rad1a) served as reference for all comparisons. Intra-observer variability was determined by the same reader after 12 weeks (Rad1b), and inter-observer variability by a second reader (Rad2). The Dice similarity coefficient (DSC) evaluated overlap between segmentations. CNN performance was assessed using the concordance correlation coefficient (CCC) and the two-by-two difference between the CCCs; their confidence interval was estimated with bootstrap and Bland-Altman analyses. Liver segmentation time was automatically recorded for each method. RESULTS: A total of 231 series from 129 CT examinations on 88 consecutive patients were collected. For the CNN, the DSC was 0.95 ± 0.03 and volume analyses yielded a CCC of 0.995 compared with reference. No statistical difference was observed in the CCC between CNN automatic segmentation and manual segmentations performed to evaluate inter-observer and intra-observer variability. While manual segmentation required 22.4 ± 10.4 min, central and graphics processing units took an average of 5.0 ± 2.1 s and 2.0 ± 1.4 s, respectively. CONCLUSION: Compared with manual segmentation, automated segmentation of polycystic livers using a deep learning method achieved much faster segmentation with similar performance. KEY POINTS: • Automatic volumetry of polycystic livers using artificial intelligence method allows much faster segmentation than expert manual segmentation with similar performance. • No statistical difference was observed between automatic

Published
2022

21. Liver stiffness measurement by vibration-controlled transient elastography improves outcome prediction in primary biliary cholangitis

Author

Corpechot, C, Carrat, F, Gaouar, F, Chau, F, Hirschfield, G, Gulamhusein, A, Montano-Loza, A, Lytvyak, E, Schramm, C, Pares, A, Olivas, I, Eaton, J, Osman, K, Dalekos, G, Gatselis, N, Nevens, F, Cazzagon, N, Zago, A, Russo, F, Abbas, N, Trivedi, P, Thorburn, D, Saffioti, F, Barkai, L, Roccarina, D, Calvaruso, V, Fichera, A, Delamarre, A, Medina-Morales, E, Bonder, A, Patwardhan, V, Rigamonti, C, Carbone, M, Invernizzi, P, Cristoferi, L, van der Meer, A, de Veer, R, Zigmond, E, Yehezkel, E, Kremer, A, Deibel, A, Dumortier, J, Bruns, T, Große, K, Pageaux, G, Wetten, A, Dyson, J, Jones, D, Chazouillères, O, Hansen, B, de Lédinghen, V, Corpechot, Christophe, Carrat, Fabrice, Gaouar, Farid, Chau, Frederic, Hirschfield, Gideon, Gulamhusein, Aliya, Montano-Loza, Aldo J, Lytvyak, Ellina, Schramm, Christoph, Pares, Albert, Olivas, Ignasi, Eaton, John E, Osman, Karim T, Dalekos, George, Gatselis, Nikolaos, Nevens, Frederik, Cazzagon, Nora, Zago, Alessandra, Russo, Francesco Paolo, Abbas, Nadir, Trivedi, Palak, Thorburn, Douglas, Saffioti, Francesca, Barkai, Laszlo, Roccarina, Davide, Calvaruso, Vicenza, Fichera, Anna, Delamarre, Adèle, Medina-Morales, Esli, Bonder, Alan, Patwardhan, Vilas, Rigamonti, Cristina, Carbone, Marco, Invernizzi, Pietro, Cristoferi, Laura, van der Meer, Adriaan, de Veer, Rozanne, Zigmond, Ehud, Yehezkel, Eyal, Kremer, Andreas E, Deibel, Ansgar, Dumortier, Jérôme, Bruns, Tony, Große, Karsten, Pageaux, Georges-Philippe, Wetten, Aaron, Dyson, Jessica, Jones, David, Chazouillères, Olivier, Hansen, Bettina, de Lédinghen, Victor, Corpechot, C, Carrat, F, Gaouar, F, Chau, F, Hirschfield, G, Gulamhusein, A, Montano-Loza, A, Lytvyak, E, Schramm, C, Pares, A, Olivas, I, Eaton, J, Osman, K, Dalekos, G, Gatselis, N, Nevens, F, Cazzagon, N, Zago, A, Russo, F, Abbas, N, Trivedi, P, Thorburn, D, Saffioti, F, Barkai, L, Roccarina, D, Calvaruso, V, Fichera, A, Delamarre, A, Medina-Morales, E, Bonder, A, Patwardhan, V, Rigamonti, C, Carbone, M, Invernizzi, P, Cristoferi, L, van der Meer, A, de Veer, R, Zigmond, E, Yehezkel, E, Kremer, A, Deibel, A, Dumortier, J, Bruns, T, Große, K, Pageaux, G, Wetten, A, Dyson, J, Jones, D, Chazouillères, O, Hansen, B, de Lédinghen, V, Corpechot, Christophe, Carrat, Fabrice, Gaouar, Farid, Chau, Frederic, Hirschfield, Gideon, Gulamhusein, Aliya, Montano-Loza, Aldo J, Lytvyak, Ellina, Schramm, Christoph, Pares, Albert, Olivas, Ignasi, Eaton, John E, Osman, Karim T, Dalekos, George, Gatselis, Nikolaos, Nevens, Frederik, Cazzagon, Nora, Zago, Alessandra, Russo, Francesco Paolo, Abbas, Nadir, Trivedi, Palak, Thorburn, Douglas, Saffioti, Francesca, Barkai, Laszlo, Roccarina, Davide, Calvaruso, Vicenza, Fichera, Anna, Delamarre, Adèle, Medina-Morales, Esli, Bonder, Alan, Patwardhan, Vilas, Rigamonti, Cristina, Carbone, Marco, Invernizzi, Pietro, Cristoferi, Laura, van der Meer, Adriaan, de Veer, Rozanne, Zigmond, Ehud, Yehezkel, Eyal, Kremer, Andreas E, Deibel, Ansgar, Dumortier, Jérôme, Bruns, Tony, Große, Karsten, Pageaux, Georges-Philippe, Wetten, Aaron, Dyson, Jessica, Jones, David, Chazouillères, Olivier, Hansen, Bettina, and de Lédinghen, Victor

Abstract

Background & Aims: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) has been shown to predict outcomes of patients with primary biliary cholangitis (PBC) in small-size studies. We aimed to validate the prognostic value of LSM in a large cohort study. Methods: We performed an international, multicentre, retrospective follow-up study of 3,985 patients with PBC seen at 23 centres in 12 countries. Eligibility criteria included at least 1 reliable LSM by VCTE and a follow-up ≥ 1 year. Independent derivation (n = 2,740) and validation (n = 568) cohorts were built. The primary endpoint was time to poor clinical outcomes defined as liver-related complications, liver transplantation, or death. Hazard ratios (HRs) with CIs were determined using a time-dependent multivariable Cox regression analysis. Results: LSM was independently associated with poor clinical outcomes in the derivation (5,324 LSMs, mean follow-up 5.0 ± 3.1 years) and validation (1,470 LSMs, mean follow-up 5.0 ± 2.8 years) cohorts: adjusted HRs (95% CI) per additional kPa were 1.040 (1.026–1.054) and 1.042 (1.029–1.056), respectively (p <0.0001 for both). Adjusted C-statistics (95% CI) at baseline were 0.83 (0.79–0.87) and 0.92 (0.89–0.95), respectively. Between 5 and 30 kPa, the log-HR increased as a monotonic function of LSM. The predictive value of LSM was stable in time. LSM improved the prognostic ability of biochemical response criteria, fibrosis scores, and prognostic scores. The 8 kPa and 15 kPa cut-offs optimally separated low-, medium-, and high-risk groups. Forty percent of patients were at medium to high risk according to LSM. Conclusions: LSM by VCTE is a major, independent, validated predictor of PBC outcome. Its value as a surrogate endpoint for clinical benefit in PBC should be considered. Lay summary: Primary biliary cholangitis (PBC) is a chronic autoimmune disease, wherein the body's immune system mistakenly attacks the bile ducts. PBC progresses

Published
2022

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

Author

Costentin, C, Piñero, F, Degroote, H, Notarpaolo, A, Boin, I, Boudjema, K, Baccaro, C, Podestá, L, Bachellier, P, Ettorre, G, Poniachik, J, Muscari, F, Dibenedetto, F, Hoyos Duque, S, Salame, E, Cillo, U, Marciano, S, Vanlemmens, C, Fagiuoli, S, Burra, P, Van Vlierberghe, H, Cherqui, D, Lai, Q, Silva, M, Rubinstein, F, Duvoux, C, Conti, F, Scatton, O, Bernard, P, Francoz, C, Durand, F, Dharancy, S, Woehl, M, Laurent, A, Radenne, S, Dumortier, J, Abergel, A, Barbier, L, Houssel-Debry, P, Pageaux, G, Chiche, L, Deledinghen, V, Hardwigsen, J, Gugenheim, J, Altieri, M, Hilleret, M, Decaens, T, Chagas, A, Costa, P, Cristina de Ataide, E, Quiñones, E, Duque, S, Anders, M, Varón, A, Zerega, A, Soza, A, Machaca, M, Arufe, D, Menéndez, J, Zapata, R, Vilatoba, M, Muñoz, L, Menéndez, R, Maraschio, M, Mccormack, L, Mattera, J, Gadano, A, Fatima Boin, I, Parente García, J, Carrilho, F, Magini, G, Miglioresi, L, Gambato, M, Benedetto, F, D’Ambrosio, C, Vitale, A, Colledan, M, Pinelli, D, Magistri, P, Vennarecci, G, Colasanti, M, Giannelli, V, Pellicelli, A, Vlierberghe, H, Eduard, C, Samuele, I, Jeroen, D, Jonas, S, Jacques, P, Chris, V, Dirk, Y, Peter, M, Valerio, L, Christophe, M, Olivier, D, Jean, D, Roberto, T, Paul, L, Costentin, Charlotte, Piñero, Federico, Degroote, Helena, Notarpaolo, Andrea, Boin, Ilka F., Boudjema, Karim, Baccaro, Cinzia, Podestá, Luis G., Bachellier, Philippe, Ettorre, Giuseppe Maria, Poniachik, Jaime, Muscari, Fabrice, Dibenedetto, Fabrizio, Hoyos Duque, Sergio, Salame, Ephrem, Cillo, Umberto, Marciano, Sebastian, Vanlemmens, Claire, Fagiuoli, Stefano, Burra, Patrizia, Van Vlierberghe, Hans, Cherqui, Daniel, Lai, Quirino, Silva, Marcelo, Rubinstein, Fernando, Duvoux, Christophe, Conti, Filomena, Scatton, Olivier, Bernard, Pierre Henri, Francoz, Claire, Durand, Francois, Dharancy, Sébastien, Woehl, Marie-lorraine., Laurent, Alexis, Radenne, Sylvie, Dumortier, Jérôme, Abergel, Armand, Barbier, Louise, Houssel-Debry, Pauline, Pageaux, Georges Philippe, Chiche, Laurence, Deledinghen, Victor, Hardwigsen, Jean, Gugenheim, J., altieri, M., Hilleret, Marie Noelle, Decaens, Thomas, Chagas, Aline, Costa, Paulo, Cristina de Ataide, Elaine, Quiñones, Emilio, Duque, Sergio Hoyos, Marciano, Sebastián, Anders, Margarita, Varón, Adriana, Zerega, Alina, Soza, Alejandro, Machaca, Martín Padilla, Arufe, Diego, Menéndez, Josemaría, Zapata, Rodrigo, Vilatoba, Mario, Muñoz, Linda, Menéndez, Ricardo Chong, Maraschio, Martín, McCormack, Lucas, Mattera, Juan, Gadano, Adrian, Fatima Boin, Ilka SF., Parente García, Jose Huygens, Carrilho, Flair, Magini, Giulia, Miglioresi, Lucia, Gambato, Martina, Benedetto, Fabrizio Di, D’Ambrosio, Cecilia, Vitale, Alessandro, Colledan, Michele, Pinelli, Domenico, Magistri, Paolo, Vennarecci, Giovanni, Colasanti, Marco, Giannelli, Valerio, Pellicelli, Adriano, Baccaro, Cizia, Vlierberghe, Hans Van, Eduard, Callebout, Samuele, Iesari, Jeroen, Dekervel, Jonas, Schreiber, Jacques, Pirenne, Chris, Verslype, Dirk, Ysebaert, Peter, Michielsen, Valerio, Lucidi, Christophe, Moreno, Olivier, Detry, Jean, Delwaide, Roberto, Troisi, Paul, Lerut Jan, Costentin, C, Piñero, F, Degroote, H, Notarpaolo, A, Boin, I, Boudjema, K, Baccaro, C, Podestá, L, Bachellier, P, Ettorre, G, Poniachik, J, Muscari, F, Dibenedetto, F, Hoyos Duque, S, Salame, E, Cillo, U, Marciano, S, Vanlemmens, C, Fagiuoli, S, Burra, P, Van Vlierberghe, H, Cherqui, D, Lai, Q, Silva, M, Rubinstein, F, Duvoux, C, Conti, F, Scatton, O, Bernard, P, Francoz, C, Durand, F, Dharancy, S, Woehl, M, Laurent, A, Radenne, S, Dumortier, J, Abergel, A, Barbier, L, Houssel-Debry, P, Pageaux, G, Chiche, L, Deledinghen, V, Hardwigsen, J, Gugenheim, J, Altieri, M, Hilleret, M, Decaens, T, Chagas, A, Costa, P, Cristina de Ataide, E, Quiñones, E, Duque, S, Anders, M, Varón, A, Zerega, A, Soza, A, Machaca, M, Arufe, D, Menéndez, J, Zapata, R, Vilatoba, M, Muñoz, L, Menéndez, R, Maraschio, M, Mccormack, L, Mattera, J, Gadano, A, Fatima Boin, I, Parente García, J, Carrilho, F, Magini, G, Miglioresi, L, Gambato, M, Benedetto, F, D’Ambrosio, C, Vitale, A, Colledan, M, Pinelli, D, Magistri, P, Vennarecci, G, Colasanti, M, Giannelli, V, Pellicelli, A, Vlierberghe, H, Eduard, C, Samuele, I, Jeroen, D, Jonas, S, Jacques, P, Chris, V, Dirk, Y, Peter, M, Valerio, L, Christophe, M, Olivier, D, Jean, D, Roberto, T, Paul, L, Costentin, Charlotte, Piñero, Federico, Degroote, Helena, Notarpaolo, Andrea, Boin, Ilka F., Boudjema, Karim, Baccaro, Cinzia, Podestá, Luis G., Bachellier, Philippe, Ettorre, Giuseppe Maria, Poniachik, Jaime, Muscari, Fabrice, Dibenedetto, Fabrizio, Hoyos Duque, Sergio, Salame, Ephrem, Cillo, Umberto, Marciano, Sebastian, Vanlemmens, Claire, Fagiuoli, Stefano, Burra, Patrizia, Van Vlierberghe, Hans, Cherqui, Daniel, Lai, Quirino, Silva, Marcelo, Rubinstein, Fernando, Duvoux, Christophe, Conti, Filomena, Scatton, Olivier, Bernard, Pierre Henri, Francoz, Claire, Durand, Francois, Dharancy, Sébastien, Woehl, Marie-lorraine., Laurent, Alexis, Radenne, Sylvie, Dumortier, Jérôme, Abergel, Armand, Barbier, Louise, Houssel-Debry, Pauline, Pageaux, Georges Philippe, Chiche, Laurence, Deledinghen, Victor, Hardwigsen, Jean, Gugenheim, J., altieri, M., Hilleret, Marie Noelle, Decaens, Thomas, Chagas, Aline, Costa, Paulo, Cristina de Ataide, Elaine, Quiñones, Emilio, Duque, Sergio Hoyos, Marciano, Sebastián, Anders, Margarita, Varón, Adriana, Zerega, Alina, Soza, Alejandro, Machaca, Martín Padilla, Arufe, Diego, Menéndez, Josemaría, Zapata, Rodrigo, Vilatoba, Mario, Muñoz, Linda, Menéndez, Ricardo Chong, Maraschio, Martín, McCormack, Lucas, Mattera, Juan, Gadano, Adrian, Fatima Boin, Ilka SF., Parente García, Jose Huygens, Carrilho, Flair, Magini, Giulia, Miglioresi, Lucia, Gambato, Martina, Benedetto, Fabrizio Di, D’Ambrosio, Cecilia, Vitale, Alessandro, Colledan, Michele, Pinelli, Domenico, Magistri, Paolo, Vennarecci, Giovanni, Colasanti, Marco, Giannelli, Valerio, Pellicelli, Adriano, Baccaro, Cizia, Vlierberghe, Hans Van, Eduard, Callebout, Samuele, Iesari, Jeroen, Dekervel, Jonas, Schreiber, Jacques, Pirenne, Chris, Verslype, Dirk, Ysebaert, Peter, Michielsen, Valerio, Lucidi, Christophe, Moreno, Olivier, Detry, Jean, Delwaide, Roberto, Troisi, and Paul, Lerut Jan

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

Published
2022

25. HIGH RATES OF VIROLOGICAL RESPONSE AND MAJOR CLINICAL IMPROVEMENT DURING SOFOSBUVIR AND DACLATASVIR-BASED REGIMENS FOR THE TREATMENT OF FIBROSING CHOLESTATIC HCV-RECURRENCE AFTER LIVER TRANSPLANTATION: THE ANRS CO23 CUPILT STUDY: 60

Author

Leroy, V., Dumortier, J., Coilly, A., Sebagh, M., Fougerou-Leurent, L., Radenne, S., Botta, D., Durand, F., Silvain, C., Lebray, P., Houssel-Debry, P., Kamar, N., D’alteroche, L., Calmus, Y., Bertucci, I., Diallo, A., Pageaux, G. P., and Duclos-Vallée, J. C.

Published
2015

44. Liver transplantation for adenomatosis: European experience

Author

Chiche, L, David, A, Adam, R, Oliverius, M, Klempnauer, J, Vibert, E, Colledan, M, Lerut, J, Mazzafero, V, Di-Sandro, S, Laurent, C, Scuderi, V, Suc, B, Troisi, R, Bachelier, P, Dumortier, J, Gugenheim, J, Mabrut, J, Gonzalez-Pinto, I, Pruvot, F, Le-Treut, Y, Navarro, F, Ortiz-De-Urbina, J, Salame, E, Spada, M, Bioulac-Sage, P, Chiche L, David A, Adam R, Oliverius MM, Klempnauer J, Vibert E, Colledan M, Lerut J, Mazzafero VV, Di-Sandro S, Laurent C, Scuderi V, Suc B, Troisi R, Bachelier P, Dumortier J, Gugenheim J, Mabrut JY, Gonzalez-Pinto I, Pruvot FR, Le-Treut YP, Navarro F, Ortiz-De-Urbina J, Salame E, Spada M, Bioulac-Sage P, Chiche, L, David, A, Adam, R, Oliverius, M, Klempnauer, J, Vibert, E, Colledan, M, Lerut, J, Mazzafero, V, Di-Sandro, S, Laurent, C, Scuderi, V, Suc, B, Troisi, R, Bachelier, P, Dumortier, J, Gugenheim, J, Mabrut, J, Gonzalez-Pinto, I, Pruvot, F, Le-Treut, Y, Navarro, F, Ortiz-De-Urbina, J, Salame, E, Spada, M, Bioulac-Sage, P, Chiche L, David A, Adam R, Oliverius MM, Klempnauer J, Vibert E, Colledan M, Lerut J, Mazzafero VV, Di-Sandro S, Laurent C, Scuderi V, Suc B, Troisi R, Bachelier P, Dumortier J, Gugenheim J, Mabrut JY, Gonzalez-Pinto I, Pruvot FR, Le-Treut YP, Navarro F, Ortiz-De-Urbina J, Salame E, Spada M, and Bioulac-Sage P

Abstract

The aim of this study was to collect data from patients who underwent liver transplantation (LT) for adenomatosis; to analyze the symptoms, the characteristics of the disease, and the recipient outcomes; and to better define the role of LT in this rare indication. This retrospective multicenter study, based on data from the European Liver Transplant Registry, encompassed patients who underwent LT for adenomatosis between January 1, 1986, and July 15, 2013, in Europe. Patients with glycogen storage disease (GSD) type IA were not excluded. This study included 49 patients. Sixteen patients had GSD, and 7 had liver vascular abnormalities. The main indications for transplantation were either a suspicion of hepatocellular carcinoma (HCC; 15 patients) or a histologically proven HCC (16 patients), but only 17 had actual malignant transformation (MT) of adenomas. GSD status was similar for the 2 groups, except for age and the presence of HCC on explants (P = 0.030). Three patients with HCC on explant developed recurrence after transplantation. We obtained and studied the pathomolecular characteristics for 23 patients. In conclusion, LT should remain an extremely rare treatment for adenomatosis. Indications for transplantation primarily concern the MT of adenomas. The decision should rely on morphological data and histological evidence of MT. Additional indications should be discussed on a case-by-case basis. In this report, we propose a simplified approach to this decision-making process.

Published
2016

49. Achieving SVR Does Not Prevent From Fibrosis Progession In Patients With FCH Results From A Large French Prospective Multicentric ANRS CO23 Cupilt Cohort

Author

Sebagh, M., Fougerou-Leurent, C., Pageaux, G. P., Leroy, V., Dumortier, J., Radenne, S., Sylvain, C., Lebray, P., Houssel-Debry, P., Cagnot, C., Rossignol, E., Danjou, H., Veislinger, A., Didier Samuel, Duclos-Vallee, J. C., Coilly, A., AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Lapeyronie [Montpellier] (CHU), Service d'hépato-gastroentérologie [CHU Grenoble Alpes], Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes), CHU de Lyon, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Service d'hépatogastroentérologie [Hôpital de la Croix-Rousse, Hospices Civils de Lyon], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Pontchaillou [Rennes], Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11), DHU Hepatinov, Novartis, Astellas, Roche, MSD, GSK, Gilead, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Universitaire [Grenoble] (CHU)

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2017

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