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

Author

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

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

Author

Degroote, H, Piñero, F, Costentin, C, Notarpaolo, A, Boin, I, Boudjema, K, Baccaro, C, Chagas, A, Bachellier, P, Ettorre, G, Poniachik, J, Muscari, F, Di Benedetto, F, Duque, S, Salame, E, Cillo, U, Gadano, A, Vanlemmens, C, Fagiuoli, S, Rubinstein, F, Burra, P, Cherqui, D, Silva, M, Van Vlierberghe, H, Duvoux, C, Degroote H, Piñero F, Costentin C, Notarpaolo A, Boin IF, Boudjema K, Baccaro C, Chagas AL, Bachellier P, Ettorre GM, Poniachik J, Muscari F, Di Benedetto F, Duque SH, Salame E, Cillo U, Gadano A, Vanlemmens C, Fagiuoli S, Rubinstein F, Burra P, Cherqui D, Silva M, Van Vlierberghe H, Duvoux C, Degroote, H, Piñero, F, Costentin, C, Notarpaolo, A, Boin, I, Boudjema, K, Baccaro, C, Chagas, A, Bachellier, P, Ettorre, G, Poniachik, J, Muscari, F, Di Benedetto, F, Duque, S, Salame, E, Cillo, U, Gadano, A, Vanlemmens, C, Fagiuoli, S, Rubinstein, F, Burra, P, Cherqui, D, Silva, M, Van Vlierberghe, H, Duvoux, C, Degroote H, Piñero F, Costentin C, Notarpaolo A, Boin IF, Boudjema K, Baccaro C, Chagas AL, Bachellier P, Ettorre GM, Poniachik J, Muscari F, Di Benedetto F, Duque SH, Salame E, Cillo U, Gadano A, Vanlemmens C, Fagiuoli S, Rubinstein F, Burra P, Cherqui D, Silva M, Van Vlierberghe H, and Duvoux C

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 <0.0001]) and not significantly higher for the UCSF-DS group (SHR 1.60 [p = 0.32]), compared with patients remaining within Milan. The all-comers presented more frequent features of aggressive HCC and higher tumour burden at explant. Among the UCSF-DS group, an AFP value of ≤20 ng/ml at listing was associated with lower recurrence (SHR 2.01 [p = 0.006]) and better survival. However, recurrence was still significantly high irrespective of AFP ≤20 ng/ml in all-comers. Conclusions: Patients within the UCSF-DS protocol at listing have similar post-transplant outcomes compared with those within Milan when successfully downstaged. Meanwhile, all-comers have a higher recurrence and inferior survival irrespective of response to LRT. Additionally, in the UCSF-DS group, an ALP of ≤20 ng/ml might be a novel tool to optimise selection of candidates for LT. Clinical trial number: This study was r

Published
2021

5. The risk of early occurrence and recurrence of hepatocellular carcinoma in hepatitis C‐infected patients treated with direct‐acting antivirals with and without pegylated interferon: A Belgian experience

Author

Bielen, R., Moreno, C., Van Vlierberghe, H., Bourgeois, S., Mulkay, J.‐P., Vanwolleghem, T., Verlinden, W., Brixco, C., Decaestecker, J., de Galocsy, C., Janssens, F., Van Overbeke, L., Van Steenkiste, C., DʼHeygere, F., Cool, M., Wuyckens, K., Nevens, F., and Robaeys, G.

Published
2017
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6. The epigenetically regulated miR-494 associates with stem-cell phenotype and induces sorafenib resistance in hepatocellular carcinoma

Author

Pollutri, Daniela, Patrizi, Clarissa, Marinelli, Sara, Giovannini, Catia, Trombetta, Elena, Giannone, Ferdinando A., Baldassarre, Maurizio, Quarta, Santina, Vandewynckel, Y. P., Vandierendonck, A., Van Vlierberghe, H., Porretti, Laura, Negrini, Massimo, Bolondi, Luigi, Gramantieri, Laura, and Fornari, Francesca

Published
2018
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8. COVID-19 in an international European liver transplant recipient cohort

Author

Becchetti, C, Zambelli, M, Pasulo, L, Donato, M, Invernizzi, F, Detry, O, Dahlqvist, G, Ciccarelli, O, Morelli, M, Fraga, M, Svegliati-Baroni, G, van Vlierberghe, H, Coenraad, M, Romero, M, de Gottardi, A, Toniutto, P, Del Prete, L, Abbati, C, Samuel, D, Pirenne, J, Nevens, F, Dufour, J, Fagiuoli, S, Becchetti C, Zambelli MF, Pasulo L, Donato MF, Invernizzi F, Detry O, Dahlqvist G, Ciccarelli O, Morelli MC, Fraga M, Svegliati-Baroni G, van Vlierberghe H, Coenraad MJ, Romero MC, de Gottardi A, Toniutto P, Del Prete L, Abbati C, Samuel D, Pirenne J, Nevens F, Dufour JF, FAGIUOLI S, Becchetti, C, Zambelli, M, Pasulo, L, Donato, M, Invernizzi, F, Detry, O, Dahlqvist, G, Ciccarelli, O, Morelli, M, Fraga, M, Svegliati-Baroni, G, van Vlierberghe, H, Coenraad, M, Romero, M, de Gottardi, A, Toniutto, P, Del Prete, L, Abbati, C, Samuel, D, Pirenne, J, Nevens, F, Dufour, J, Fagiuoli, S, Becchetti C, Zambelli MF, Pasulo L, Donato MF, Invernizzi F, Detry O, Dahlqvist G, Ciccarelli O, Morelli MC, Fraga M, Svegliati-Baroni G, van Vlierberghe H, Coenraad MJ, Romero MC, de Gottardi A, Toniutto P, Del Prete L, Abbati C, Samuel D, Pirenne J, Nevens F, Dufour JF, and FAGIUOLI S

Abstract

Objective Knowledge on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in liver transplant recipients is lacking, particularly in terms of severity of the disease. The aim of this study was to describe the demographic, baseline clinical characteristics and early outcomes of a European cohort of liver transplant recipients with SARS-CoV-2 infection. Design We conducted an international prospective study across Europe on liver transplant recipients with SARS-CoV-2 infection confirmed by microbiological assay during the first outbreak of COVID-19 pandemic. Baseline characteristics, clinical presentation, management of immunosuppressive therapy and outcomes were collected. Results 57 patients were included (70% male, median (IQR) age at diagnosis 65 (57-70) years). 21 (37%), 32 (56%) and 21 (37%) patients had one cardiovascular disease, arterial hypertension and diabetes mellitus, respectively. The most common symptoms were fever (79%), cough (55%), dyspnoea (46%), fatigue or myalgia (56%) and GI symptoms (33%). Immunosuppression was reduced in 22 recipients (37%) and discontinued in 4 (7%). With this regard, no impact on outcome was observed. Forty-one (72%) subjects were hospitalised and 11 (19%) developed acute respiratory distress syndrome. Overall, we estimated a case fatality rate of 12% (95% CI 5% to 24%), which increased to 17% (95% CI 7% to 32%) among hospitalised patients. Five out of the seven patients who died had a history of cancer. Conclusion In this European multicentre prospective study of liver transplant recipients, COVID-19 was associated with an overall and in-hospital fatality rate of 12% (95% CI 5% to 24%) and 17% (95% CI 7% to 32%), respectively. A history of cancer was more frequent in patients with poorer outcome.

Published
2020

9. 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

10. Reassessment of the risk of recurrence (R3) after liver transplantation for HCC: validation of the R3 score and comparison with existing models

Author

Costentin, C, Pinero, F, Degroote, H, Notarpaolo, A, Boin, I, Boudjema, K, Baccaro, C, Podesta, L, Bachellier, P, Ettorre, GM, Poniachik, J, Muscari, F, Dibenedetto, F, Duque, SH, Salame, E, Cillo, U, Gadano, A, Vanlemmens, C, Fagiuoli, S, Rubinstein, F, Burra, P, Van Vlierberghe, H, Cherqui, D, Silva, M, Duvoux, C, Costentin, C, Pinero, F, Degroote, H, Notarpaolo, A, Boin, I, Boudjema, K, Baccaro, C, Podesta, L, Bachellier, P, Ettorre, G, Poniachik, J, Muscari, F, Dibenedetto, F, Duque, S, Salame, E, Cillo, U, Gadano, A, Vanlemmens, C, Fagiuoli, S, Rubinstein, F, Burra, P, Van Vlierberghe, H, Cherqui, D, Silva, M, and Duvoux, C

Subjects
Cirrhosi, liver transplantation, alfa FP, HCC
Published
2021

12. COVID-19 in an international European liver transplant recipient cohort

Author

Becchetti, C., Zambelli, M. F., Pasulo, L., Donato, M. F., Invernizzi, F., Detry, O., Dahlqvist, G., Ciccarelli, O., Morelli, M. C., Fraga, M., Svegliati-Baroni, G., Van Vlierberghe, H., Coenraad, M. J., Romero, M. C., De Gottardi, A., Toniutto, P., Del Prete, L., Abbati, C., D'Alessandro, Samuel, Pirenne, J., Nevens, F., Dufour J., -F, and COVID-LT group, Burra, Patrizia, Becchetti, C, Zambelli, M, Pasulo, L, Donato, M, Invernizzi, F, Detry, O, Dahlqvist, G, Ciccarelli, O, Morelli, M, Fraga, M, Svegliati-Baroni, G, van Vlierberghe, H, Coenraad, M, Romero, M, de Gottardi, A, Toniutto, P, Del Prete, L, Abbati, C, Samuel, D, Pirenne, J, Nevens, F, Dufour, J, Fagiuoli, S, COVID-LT group, Colledan, M., Fagiuoli, S., Camagni, S., Delwaide, J., Vitale, G., Moradpour, D., Pascual, M., Allegrini, G., Tarsetti, F., Giustizieri, U., Rota, L., Artru, F., Saouli, A.C., Burra, P., Gambato, M., Scalera, I., Petridis, I., Marques, H.P., Welker, M.W., UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service de chirurgie et transplantation abdominale, UCL - (SLuc) Service de gastro-entérologie, and UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie

Subjects
myalgia, Male, medicine.medical_specialty, medicine.medical_treatment, infectious disease, Pneumonia, Viral, 030230 surgery, Liver transplantation, Chronic liver disease, Cohort Studies, 03 medical and health sciences, Betacoronavirus, chronic liver disease, orthotopic liver transplantation, 0302 clinical medicine, Internal medicine, Case fatality rate, medicine, Humans, Prospective Studies, Prospective cohort study, 610 Medicine & health, Survival rate, Pandemics, Aged, Hepatology, business.industry, SARS-CoV-2, Liver Diseases, Gastroenterology, COVID-19, Middle Aged, medicine.disease, Liver Transplantation, Europe, Hospitalization, Survival Rate, Coronavirus Infections/diagnosis, Coronavirus Infections/epidemiology, Coronavirus Infections/therapy, Female, Liver Diseases/mortality, Liver Diseases/surgery, Liver Diseases/virology, Pneumonia, Viral/diagnosis, Pneumonia, Viral/epidemiology, Pneumonia, Viral/therapy, Cohort, 030211 gastroenterology & hepatology, medicine.symptom, business, Coronavirus Infections, Cohort study
Abstract

ObjectiveKnowledge on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in liver transplant recipients is lacking, particularly in terms of severity of the disease. The aim of this study was to describe the demographic, baseline clinical characteristics and early outcomes of a European cohort of liver transplant recipients with SARS-CoV-2 infection.DesignWe conducted an international prospective study across Europe on liver transplant recipients with SARS-CoV-2 infection confirmed by microbiological assay during the first outbreak of COVID-19 pandemic. Baseline characteristics, clinical presentation, management of immunosuppressive therapy and outcomes were collected.Results57 patients were included (70% male, median (IQR) age at diagnosis 65 (57–70) years). 21 (37%), 32 (56%) and 21 (37%) patients had one cardiovascular disease, arterial hypertension and diabetes mellitus, respectively. The most common symptoms were fever (79%), cough (55%), dyspnoea (46%), fatigue or myalgia (56%) and GI symptoms (33%). Immunosuppression was reduced in 22 recipients (37%) and discontinued in 4 (7%). With this regard, no impact on outcome was observed. Forty-one (72%) subjects were hospitalised and 11 (19%) developed acute respiratory distress syndrome. Overall, we estimated a case fatality rate of 12% (95% CI 5% to 24%), which increased to 17% (95% CI 7% to 32%) among hospitalised patients. Five out of the seven patients who died had a history of cancer.ConclusionIn this European multicentre prospective study of liver transplant recipients, COVID-19 was associated with an overall and in-hospital fatality rate of 12% (95% CI 5% to 24%) and 17% (95% CI 7% to 32%), respectively. A history of cancer was more frequent in patients with poorer outcome.

Published
2020

14. 933P Updated results for pembrolizumab (pembro) monotherapy as first-line therapy for advanced hepatocellular carcinoma (HCC) in the phase II KEYNOTE-224 study

Author

Laethem, J-L. van, primary, Borbath, I., additional, Karwal, M., additional, Verslype, C., additional, Van Vlierberghe, H., additional, Kardosh, A., additional, Zagonel, V., additional, Stal, P., additional, Sarker, D., additional, Palmer, D., additional, Vogel, A., additional, Edeline, J., additional, Cattan, S., additional, Kudo, M., additional, Cheng, A-L., additional, Ogasawara, S., additional, Siegel, A.B., additional, Chisamore, M., additional, Wang, A., additional, and Zhu, A., additional

Published
2021
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15. Clinical Course of acute-on-chronic liver failure syndrome and effects on prognosis

Author

Gustot, Thierry, Fernandez, Javier, Garcia, Elisabet, Morando, Filippo, Caraceni, Paolo, Alessandria, Carlo, Laleman, Wim, Trebicka, Jonel, Elkrief, Laure, Hopf, Corinna, Solís-Munoz, Pablo, Saliba, Faouzi, Zeuzem, Stefan, Albillos, Augustin, Benten, Daniel, Montero-Alvarez, José Luis, Chivas, Maria Teresa, Concepción, Mar, Córdoba, Juan, McCormick, Aiden, Stauber, Rudolf, Vogel, Wolfgang, de Gottardi, Andrea, Welzel, Tania M., Domenicali, Marco, Risso, Alessandro, Wendon, Julia, Deulofeu, Carme, Angeli, Paolo, Durand, François, Pavesi, Marco, Gerbes, Alexander, Jalan, Rajiv, Moreau, Richard, Ginés, Pere, Bernardi, Mauro, Arroyo, Vicente, Aguilar-Melero, P, Bañares, R, Bocci, M, Catalina, M V, Chin, J L, Coenraad, M J, Coilly, A, Dorn, L, Gatta, A, Gerber, L, Grenbæk, H, Graupera, I, Guevara, M, Hausen, A, Karlsen, S, Lohse, A W, Maggioli, C, Markwardt, D, Martinez, J, Marzano, A, de la Mata García, M, Mesonero, F, Mookerjee, R P, Moreno, C, Morrell, B, Mortensen, C, Nevens, F, Peck-Radosavljevic, M, Rizzetto, M, Romano, A, Samuel, D, Sauerbruch, T, Simon-Talero, M, Solà, E, Soriano, G, Sperl, J, Spindelboeck, W, Steib, C, Valla, D, Verbeke, L, Van Vlierberghe, H, Wege, H, Willars, C, Baenas, M Y, and Zaccherini, G.

Published
2015
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18. Strategies to manage hepatitis C virus (HCV) disease burden

Author

Wedemeyer, H., Duberg, A. S., Buti, M., Rosenberg, W. M., Frankova, S., Esmat, G., Örmeci, N., Van Vlierberghe, H., Gschwantler, M., Akarca, U., Aleman, S., Balk, İ., Berg, T., Bihl, F., Bilodeau, M., Blasco, A. J., Brandão Mello, C. E., Bruggmann, P., Calinas, F., Calleja, J. L., Cheinquer, H., Christensen, P. B., Clausen, M., Coelho, H. S. M., Cornberg, M., Cramp, M. E., Dore, G. J., Doss, W., El-Sayed, M. H., Ergör, G., Estes, C., Falconer, K., Félix, J., Ferraz, M. L. G., Ferreira, P. R., García-Samaniego, J., Gerstoft, J., Giria, J. A., Gonçales, F. L., Jr, Guimarães Pessôa, M., Hézode, C., Hindman, S. J., Hofer, H., Husa, P., Idilman, R., Kåberg, M., Kaita, K. D. E., Kautz, A., Kaymakoglu, S., Krajden, M., Krarup, H., Laleman, W., Lavanchy, D., Lázaro, P., Marinho, R. T., Marotta, P., Mauss, S., Mendes Correa, M. C., Moreno, C., Müllhaupt, B., Myers, R. P., Nemecek, V., vrehus, A. L. H., Parkes, J., Peltekian, K. M., Ramji, A., Razavi, H., Reis, N., Roberts, S. K., Roudot-Thoraval, F., Ryder, S. D., Sarmento-Castro, R., Sarrazin, C., Semela, D., Sherman, M., Shiha, G. E., Sperl, J., Stärkel, P., Stauber, R. E., Thompson, A. J., Urbanek, P., Van Damme, P., van Thiel, I., Vandijck, D., Vogel, W., Waked, I., Weis, N., Wiegand, J., Yosry, A., Zekry, A., Negro, F., Sievert, W., and Gower, E.

Published
2014
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19. The present and future disease burden of hepatitis C virus (HCV) infection with todayʼs treatment paradigm

Author

Razavi, H., Waked, I., Sarrazin, C., Myers, R. P., Idilman, R., Calinas, F., Vogel, W., Mendes Correa, M. C., Hézode, C., Lázaro, P., Akarca, U., Aleman, S., Balk, İ., Berg, T., Bihl, F., Bilodeau, M., Blasco, A. J., Brandão Mello, C. E., Bruggmann, P., Buti, M., Calleja, J. L., Cheinquer, H., Christensen, P. B., Clausen, M., Coelho, H. S. M., Cramp, M. E., Dore, G. J., Doss, W., Duberg, A. S., El-Sayed, M. H., Ergör, G., Esmat, G., Falconer, K., Félix, J., Ferraz, M. L. G., Ferreira, P. R., Frankova, S., García-Samaniego, J., Gerstoft, J., Giria, J. A., Gonçales, F. L., Jr, Gower, E., Gschwantler, M., Guimarães Pessôa, M., Hindman, S. J., Hofer, H., Husa, P., Kåberg, M., Kaita, K. D. E., Kautz, A., Kaymakoglu, S., Krajden, M., Krarup, H., Laleman, W., Lavanchy, D., Marinho, R. T., Marotta, P., Mauss, S., Moreno, C., Murphy, K., Negro, F., Nemecek, V., Örmeci, N., vrehus, A. L. H., Parkes, J., Pasini, K., Peltekian, K. M., Ramji, A., Reis, N., Roberts, S. K., Rosenberg, W. M., Roudot-Thoraval, F., Ryder, S. D., Sarmento-Castro, R., Semela, D., Sherman, M., Shiha, G. E., Sievert, W., Sperl, J., Stärkel, P., Stauber, R. E., Thompson, A. J., Urbanek, P., Van Damme, P., van Thiel, I., Van Vlierberghe, H., Vandijck, D., Wedemeyer, H., Weis, N., Wiegand, J., Yosry, A., Zekry, A., Cornberg, M., Müllhaupt, B., and Estes, C.

Published
2014
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20. Historical epidemiology of hepatitis C virus (HCV) in selected countries

Author

Bruggmann, P., Berg, T., vrehus, A. L. H., Moreno, C., Brandão Mello, C. E., Roudot-Thoraval, F., Marinho, R. T., Sherman, M., Ryder, S. D., Sperl, J., Akarca, U., Balk, İ., Bihl, F., Bilodeau, M., Blasco, A. J., Buti, M., Calinas, F., Calleja, J. L., Cheinquer, H., Christensen, P. B., Clausen, M., Coelho, H. S. M., Cornberg, M., Cramp, M. E., Dore, G. J., Doss, W., Duberg, A. S., El-Sayed, M. H., Ergör, G., Esmat, G., Estes, C., Falconer, K., Félix, J., Ferraz, M. L. G., Ferreira, P. R., Frankova, S., García-Samaniego, J., Gerstoft, J., Giria, J. A., Gonçales, F. L., Jr, Gower, E., Gschwantler, M., Guimarães Pessôa, M., Hézode, C., Hofer, H., Husa, P., Idilman, R., Kåberg, M., Kaita, K. D. E., Kautz, A., Kaymakoglu, S., Krajden, M., Krarup, H., Laleman, W., Lavanchy, D., Lázaro, P., Marotta, P., Mauss, S., Mendes Correa, M. C., Müllhaupt, B., Myers, R. P., Negro, F., Nemecek, V., Örmeci, N., Parkes, J., Peltekian, K. M., Ramji, A., Razavi, H., Reis, N., Roberts, S. K., Rosenberg, W. M., Sarmento-Castro, R., Sarrazin, C., Semela, D., Shiha, G. E., Sievert, W., Stärkel, P., Stauber, R. E., Thompson, A. J., Urbanek, P., van Thiel, I., Van Vlierberghe, H., Vandijck, D., Vogel, W., Waked, I., Wedemeyer, H., Weis, N., Wiegand, J., Yosry, A., Zekry, A., Van Damme, P., Aleman, S., and Hindman, S. J.

Published
2014
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22. Stopping nucleos(t)ide analogue treatment in Caucasian hepatitis B patients after HBeAg seroconversion is associated with high relapse rates and fatal outcomes

Author

Van Hees, S., Bourgeois, S., Van Vlierberghe, H., Sersté, T., Francque, S., Michielsen, P., Sprengers, D., Reynaert, H., Henrion, J., Negrin Dastis, S., Delwaide, J., Lasser, L., Decaestecker, J., Orlent, H., Janssens, F., Robaeys, G., Colle, I., Stärkel, P., Moreno, C., Nevens, F., Vanwolleghem, T., Van Hees, Stijn, Bourgeois, Stefan, Van Vlierberghe, Hans, Sersté, Thomas, Francque, Sven, Michielsen, Peter, Sprengers, Dirk, Reynaert, Hendrik, Henrion, Jean, Negrin‐Dastis, Sergio, Delwaide, Jean, Lasser, Luc, Decaestecker, Jochen, Orlent, Hans, Janssens, Filip, Robaeys, Geert, Colle, Isabelle, Stärkel, Peter, Moreno, Christophe, Nevens, Frederik, Vanwolleghem, Thomas, Nuclear Medicine, Liver Cell Biology, Laboratory of Molecullar and Cellular Therapy, Basic (bio-) Medical Sciences, Faculty of Medicine and Pharmacy, Gastroenterology, Gastroenterology & Hepatology, and Belgian NA Stop Study Group

Subjects
Male, 0301 basic medicine, HBsAg, Antibodies, Viral, Gastroenterology, Cohort Studies, Fatal Outcome, 0302 clinical medicine, Recurrence, HEPATOCELLULAR-CARCINOMA, E-ANTIGEN, Medicine and Health Sciences, Pharmacology (medical), Hepatitis B e Antigens, ENTECAVIR TREATMENT, Pharmacology. Therapy, Nucleosides, Middle Aged, Hepatitis B, PREDICTS, Treatment Outcome, HBeAg, Seroconversion, Hepatocellular carcinoma, SUSTAINED VIROLOGICAL RESPONSE, Cohort, Original Article, Female, 030211 gastroenterology & hepatology, CLINICAL-PRACTICE GUIDELINES, Cohort study, Adult, Hepatitis B virus, medicine.medical_specialty, DISCONTINUATION, VIRUS-INFECTION, GAMMA-GLUTAMYL-TRANSFERASE, Antiviral Agents, 03 medical and health sciences, Hepatitis B, Chronic, SDG 3 - Good Health and Well-being, Fatal Outcomes from Stopping Nucleoside Analogues in Hepatitis B, Internal medicine, SEROCONVERSION, medicine, Humans, CONSOLIDATION THERAPY, Hepatology, business.industry, medicine.disease, digestive system diseases, Discontinuation, 030104 developmental biology, Withholding Treatment, Human medicine, business
Abstract

Background: Stopping nucleos(t)ide analogues (NA) after hepatitis B e antigen (HBeAg) seroconversion is associated with high relapse rates in Asian patients, but data in Caucasian cohorts are scarce. Clinical course, outcomes and immunological aspects of chronic hepatitis B infections differ substantially between distinct ethnicities. Aim: The aim of this study was to determine relapse rates, factors predicting relapse and clinical outcomes after nucleos(t)ide analogue cessation in a large, predominantly Caucasian cohort of chronic hepatitis B patients with nucleos(t)ide analogue-induced HBeAg seroconversion. Methods: This is a nationwide observational cohort study including HBeAg positive, mono-infected chronic hepatitis B patients with nucleos(t)ide analogue-induced HBeAg seroconversion from 18 centres in Belgium. Results: A total of 98 patients with nucleo(s)tide analogue-induced HBeAg seroconversion were included in the study. Of the 62 patients who stopped treatment after a median consolidation treatment of 8 months, 30 relapsed. Higher gamma-glutamyl transferase levels at both treatment initiation (HR 1.004; P = 0.001 per unit increment) and HBeAg seroconversion (HR 1.006; P = 0.013 per unit increment) were associated with an increased risk of clinically significant relapse in a multivariate Cox regression model. Treatment cessation led to liver-related death in 2 patients, of whom one showed a severe flare. Of the patients who continued treatment after HBeAg seroconversion, none relapsed or developed severe hepatic outcomes. Conclusion: Treatment withdrawal in Caucasian chronic hepatitis B patients after nucleos(t)ide analogue-induced HBeAg seroconversion results in viral relapses in more than half of patients with potential fatal outcomes. These real-world data further lend support to preferentially continue NA treatment after HBeAg seroconversion until HBsAg loss. Foundation Against Cancer Belgium, Grant/Award Number: 2014-087

Published
2018

34. The PDGFRα-laminin B1-keratin 19 cascade drives tumor progression at the invasive front of human hepatocellular carcinoma

Author

Quentin M. Anstee, Michaela Petz, Yves-Paul Vandewynckel, Frederik Nevens, Wolfgang Mikulits, Tania Roskams, Baki Topal, Jasper Wouters, Emma Scott, Olivier Govaere, Chris Verslype, and Van Vlierberghe H

Subjects
0301 basic medicine, Cancer Research, Receptor, Platelet-Derived Growth Factor alpha, CANCER GENOMICS, Autoantigens, Proto-Oncogene Mas, ANGIOGENESIS, Cohort Studies, Mice, chemistry.chemical_compound, Piperidines, Medicine and Health Sciences, RNA, Small Interfering, rho-Associated Kinases, Biopsy, Needle, Liver Neoplasms, Hep G2 Cells, Immunohistochemistry, 3. Good health, Ribonucleoproteins, IRES-MEDIATED TRANSLATION, Gene Knockdown Techniques, Disease Progression, Female, Original Article, Integrin alpha2beta1, Signal transduction, Tyrosine kinase, Signal Transduction, Proto-oncogene tyrosine-protein kinase Src, Crenolanib, EXPRESSION, Carcinoma, Hepatocellular, Biology, 03 medical and health sciences, Growth factor receptor, POOR-PROGNOSIS, LIVER-DISEASE, Proto-Oncogenes, Biomarkers, Tumor, Genetics, Animals, Humans, Neoplasm Invasiveness, RECURRENCE, Protein kinase A, Autocrine signalling, Molecular Biology, Keratin-19, MESENCHYMAL TRANSITION, CYTOKERATIN-19, Survival Analysis, Xenograft Model Antitumor Assays, 030104 developmental biology, chemistry, Tumor progression, METASTASIS, Immunology, Cancer research, Benzimidazoles, Laminin, Follow-Up Studies
Abstract

Human hepatocellular carcinomas (HCCs) expressing the biliary/hepatic progenitor cell marker keratin 19 (K19) have been linked with a poor prognosis and exhibit an increase in platelet-derived growth factor receptor α (PDGFRα) and laminin beta 1 (LAMB1) expression. PDGFRα has been reported to induce de novo synthesis of LAMB1 protein in a Sjogren syndrome antigen B (La/SSB)-dependent manner in a murine metastasis model. However, the role of this cascade in human HCC remains unclear. This study focused on the functional role of the PDGFRα-La/SSB-LAMB1 pathway and its molecular link to K19 expression in human HCC. In surgical HCC specimens from a cohort of 136 patients, PDGFRα expression correlated with K19 expression, microvascular invasion and metastatic spread. In addition, PDGFRα expression in pre-operative needle biopsy specimens predicted poor overall survival during a 5-year follow-up period. Consecutive histological staining demonstrated that the signaling components of the PDGFRα-La/SSB-LAMB1 pathway were strongly expressed at the invasive front. K19-positive HCC cells displayed high levels of α2β1 integrin (ITG) receptor, both in vitro and in vivo. In vitro activation of PDGFRα signaling triggered the translocation of nuclear La/SSB into the cytoplasm, enhanced the protein synthesis of LAMB1 by activating its internal ribosome entry site, which in turn led to increased secretion of laminin-111. This effect was abrogated by the PDGFRα-specific inhibitor crenolanib. Importantly LAMB1 stimulated ITG-dependent focal adhesion kinase/Src proto-oncogene non-receptor tyrosine kinase signaling. It also promoted the ITG-specific downstream target Rho-associated coiled-coil containing protein kinase 2, induced K19 expression in an autocrine manner, invadopodia formation and cell invasion. Finally, we showed that the knockdown of LAMB1 or K19 in subcutaneous xenograft mouse models resulted in significant loss of cells invading the surrounding stromal tissue and reduced HepG2 colonization into lung and liver after tail vein injection. The PDGFRα-LAMB1 pathway supports tumor progression at the invasive front of human HCC through K19 expression.Oncogene advance online publication, 7 August 2017; doi:10.1038/onc.2017.260. ispartof: Oncogene vol:36 issue:47 pages:6605-6616 ispartof: location:England status: published

Published
2017

37. The potential of glycomics as prognostic biomarkers in liver disease and liver transplantation

Author

Xavier Verhelst, Geerts A, Callewaert N, and Van Vlierberghe H

Subjects
glycan, N-GLYCOME, glycosylation, NONALCOHOLIC STEATOHEPATITIS, Liver Diseases, cirrhosis, HEPATITIS-C, hepatocellular carcinoma, Prognosis, Liver Transplantation, glycomics, HEPATOCELLULAR-CARCINOMA, primary non Function, Biomarkers, Tumor, Medicine and Health Sciences, Humans, FIBROSIS, biomarker, Glycomics, prognostic
Abstract

The study of glycomics is a novel and fascinating approach for the development of biomarkers. It has become clear that in the field of liver disease specific glycomic patters are present in specific disease states, which has led to the development of diagnostic biomarkers. In this manuscript, we will describe two new applications of this technology for the development of prognostic biomarkers. The first biomarker is associated with the risk of hepatocellular carcinoma development in patients with compensated cirrhosis. The second biomarker is present in perfusate and is related to the risk of primary non function occurrence after liver transplantation. The technology used for these biomarkers could easily be implemented on routine capillary electrophoresis equipment.

Published
2019

38. Caucasian Ethnicity, but Not Treatment Cessation Is Associated with HBsAg Loss Following Nucleos(t)ide Analogue-Induced HBeAg Seroconversion

Author

Hees, Stijn, Chi, Heng, Hansen, Bettina, Bourgeois, S, van Vlierberghe, H, Serste, T, Francque, S, Wong, D, Sprengers, D, Moreno, C, Nevens, F, Janssen, HLA, Vanwolleghem, Thomas, Hees, Stijn, Chi, Heng, Hansen, Bettina, Bourgeois, S, van Vlierberghe, H, Serste, T, Francque, S, Wong, D, Sprengers, D, Moreno, C, Nevens, F, Janssen, HLA, and Vanwolleghem, Thomas

Published
2019

41. TRANSHEPATIC BILE TRACT CYTOLOGY

Author

LELIE, B., DEFREYNE, L., VANLANGENHOVE, P., JANSSENS, A., VAN VLIERBERGHE, H., DE HEMPTINNE, B., and PRAET, M.

Published
2002

44. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study

Author

Razavi-Shearer, D. Gamkrelidze, I. Nguyen, M.H. Chen, D.-S. Van Damme, P. Abbas, Z. Abdulla, M. Abou Rached, A. Adda, D. Aho, I. Akarca, U. Al Ali, F.H. Lawati, F.A.L. Naamani, K.A.L. Alashgar, H.I. Alavian, S.M. Alawadhi, S. Albillos, A. Al-Busafi, S.A. Aleman, S. Alfaleh, F.Z. Aljumah, A.A. Anand, A.C. Anh, N.T. Arends, J.E. Arkkila, P. Athanasakis, K. Bane, A. Ben-Ari, Z. Berg, T. Bizri, A.R. Blach, S. Brandão Mello, C.E. Brandon, S.M. Bright, B. Bruggmann, P. Brunetto, M. Buti, M. Chan, H.L.Y. Chaudhry, A. Chien, R.-N. Choi, M.S. Christensen, P.B. Chuang, W.-L. Chulanov, V. Clausen, M.R. Colombo, M. Cornberg, M. Cowie, B. Craxi, A. Croes, E.A. Cuellar, D.A. Cunningham, C. Desalegn, H. Drazilova, S. Duberg, A.-S. Egeonu, S.S. El-Sayed, M.H. Estes, C. Falconer, K. Ferraz, M.L.G. Ferreira, P.R. Flisiak, R. Frankova, S. Gaeta, G.B. García-Samaniego, J. Genov, J. Gerstoft, J. Goldis, A. Gountas, I. Gray, R. Guimarães Pessôa, M. Hajarizadeh, B. Hatzakis, A. Hézode, C. Himatt, S.M. Hoepelman, A. Hrstic, I. Hui, Y.-T.T. Husa, P. Jahis, R. Janjua, N.Z. Jarcuška, P. Jaroszewicz, J. Kaymakoglu, S. Kershenobich, D. Kondili, L.A. Konysbekova, A. Krajden, M. Kristian, P. Laleman, W. Lao, W.-C.C. Layden, J. Lazarus, J.V. Lee, M.-H. Liakina, V. Lim, Y.-S.S. Loo, C.-K.K. Lukšic, B. Malekzadeh, R. Malu, A.O. Mamatkulov, A. Manns, M. Marinho, R.T. Maticic, M. Mauss, S. Memon, M.S. Mendes Correa, M.C. Mendez-Sanchez, N. Merat, S. Metwally, A.M. Mohamed, R. Mokhbat, J.E. Moreno, C. Mossong, J. Mourad, F.H. Müllhaupt, B. Murphy, K. Musabaev, E. Nawaz, A. Nde, H.M. Negro, F. Nersesov, A. Nguyen, V.T.T. Njouom, R. Ntagirabiri, R. Nurmatov, Z. Obekpa, S. Ocama, P. Oguche, S. Omede, O. Omuemu, C. Opare-Sem, O. Opio, C.K. Örmeci, N. Papatheodoridis, G. Pasini, K. Pimenov, N. Poustchi, H. Quang, T.D. Qureshi, H. Ramji, A. Razavi-Shearer, K. Redae, B. Reesink, H.W. Rios, C.Y. Rjaskova, G. Robbins, S. Roberts, L.R. Roberts, S.K. Ryder, S.D. Safadi, R. Sagalova, O. Salupere, R. Sanai, F.M. Sanchez-Avila, J.F. Saraswat, V. Sarrazin, C. Schmelzer, J.D. Schréter, I. Scott, J. Seguin-Devaux, C. Shah, S.R. Sharara, A.I. Sharma, M. Shiha, G.E. Shin, T. Sievert, W. Sperl, J. Stärkel, P. Stedman, C. Sypsa, V. Tacke, F. Tan, S.S. Tanaka, J. Tomasiewicz, K. Urbanek, P. van der Meer, A.J. Van Vlierberghe, H. Vella, S. Vince, A. Waheed, Y. Waked, I. Walsh, N. Weis, N. Wong, V.W. Woodring, J. Yaghi, C. Yang, H.-I. Yang, C.-L. Yesmembetov, K. Yosry, A. Yuen, M.-F. Yusuf, M.A.M. Zeuzem, S. Razavi, H. The Polaris Observatory Collaborators

Abstract

Background: The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate viral hepatitis by 2030. Although no virological cure exists for hepatitis B virus (HBV) infection, existing therapies to control viral replication and prophylaxis to minimise mother-to-child transmission make elimination of HBV feasible. We aimed to estimate the national, regional, and global prevalence of HBsAg in the general population and in the population aged 5 years in 2016, as well as coverage of prophylaxis, diagnosis, and treatment. Methods: In this modelling study, we used a Delphi process that included a literature review in PubMed and Embase, followed by interviews with experts, to quantify the historical epidemiology of HBV infection. We then used a dynamic HBV transmission and progression model to estimate the country-level and regional-level prevalence of HBsAg in 2016 and the effect of prophylaxis and treatment on disease burden. Findings: We developed models for 120 countries, 78 of which were populated with data approved by experts. Using these models, we estimated that the global prevalence of HBsAg in 2016 was 3·9% (95% uncertainty interval [UI] 3·4–4·6), corresponding to 291 992 000 (251 513 000–341 114 000) infections. Of these infections, around 29 million (10%) were diagnosed, and only 4·8 million (5%) of 94 million individuals eligible for treatment actually received antiviral therapy. Around 1·8 (1·6–2·2) million infections were in children aged 5 years, with a prevalence of 1·4% (1·2–1·6). We estimated that 87% of infants had received the three-dose HBV vaccination in the first year of life, 46% had received timely birth-dose vaccination, and 13% had received hepatitis B immunoglobulin along with the full vaccination regimen. Less than 1% of mothers with a high viral load had received antiviral therapy to reduce mother-to-child transmission. Interpretation: Our estimate of HBV prevalence in 2016 differs from previous studies, potentially because we took into account the effect of infant prophylaxis and early childhood vaccination, as well as changing prevalence over time. Although some regions are well on their way to meeting prophylaxis and prevalence targets, all regions must substantially scale-up access to diagnosis and treatment to meet the global targets. Funding: John C Martin Foundation. © 2018 Elsevier Ltd

Published
2018

45. Preclinical and Clinical Therapeutic Strategies Affecting Tumor-Associated Macrophages in Hepatocellular Carcinoma

Author

Degroote, H., Van Dierendonck, A., Geerts, A., Van Vlierberghe, H., and Devisscher, L.

Subjects
stomatognathic system, Article Subject
Abstract

Hepatocellular carcinoma (HCC) most often develops in patients with underlying liver disease characterized by chronic nonresolving inflammation. Tumor-associated macrophages (TAMs) are one of the most abundant immune cell populations within the tumoral microenvironment. As key actors of cancer-related inflammation, they promote tumor growth by suppression of effective anticancer immunity, stimulation of angiogenesis, and tissue remodeling. Therefore, they have become an attractive and promising target for immunotherapy. The heterogeneity of TAM subtypes and their origin and dynamic phenotype during the initiation and progression of HCC has been partially unraveled and forms the base for the development of therapeutic agents. Current approaches are aimed at decreasing the population of TAMs by depleting macrophages present in the tumor, blocking the recruitment of bone marrow-derived monocytes, and/or functionally reprogramming TAMs to antitumoral behavior. In this review, the preclinical evolution and hitherto clinical trials for TAM-targeted therapy in HCC will be highlighted.

Published
2018
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46. Assessment of tumor response, alpha-fetoprotein (AFP) response, and time to progression (TTP) in the phase III CELESTIAL trial of cabozantinib (C) versus placebo (P) in advanced hepatocellular carcinoma (HCC)

Author

Yau, T., primary, Merle, P., additional, Rimassa, L., additional, Ryoo, B.-Y., additional, Cicin, I., additional, Harris, W.P., additional, Banu, E., additional, Sarker, D., additional, Tan, B., additional, van Vlierberghe, H., additional, Sen, S., additional, Love, C., additional, Cheng, A.-L., additional, Meyer, T., additional, Kelley, R.K., additional, and Abou-Alfa, G.K., additional

Published
2018
Full Text
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49. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study.

Author

Falconer K., Ormeci N., Papatheodoridis G., Pasini K., Pimenov N., Poustchi H., Quang T.D., Qureshi H., Ramji A., Razavi-Shearer K., Redae B., Reesink H.W., Rios C.Y., Rjaskova G., Robbins S., Roberts L.R., Roberts S.K., Ryder S.D., Safadi R., Sagalova O., Salupere R., Sanai F.M., Sanchez-Avila J.F., Saraswat V., Sarrazin C., Schmelzer J.D., Schreter I., Scott J., Seguin-Devaux C., Shah S.R., Sharara A.I., Sharma M., Shiha G.E., Shin T., Sperl J., Starkel P., Stedman C., Sypsa V., Tacke F., Tan S.S., Tanaka J., Tomasiewicz K., Urbanek P., van der Meer A.J., Van Vlierberghe H., Vella S., Vince A., Waheed Y., Waked I., Walsh N., Weis N., Wong V.W., Woodring J., Yaghi C., Yang H.-I., Yang C.-L., Yesmembetov K., Yosry A., Yuen M.-F., Yusuf M.A.M., Zeuzem S., Razavi H., Sievert W., Razavi-Shearer D., Gamkrelidze I., Nguyen M.H., Chen D.-S., Van Damme P., Abbas Z., Abdulla M., Abou Rached A., Adda D., Aho I., Akarca U., Al Ali F.H., Lawati F.A.L., Naamani K.A.L., Alashgar H.I., Alavian S.M., Alawadhi S., Albillos A., Al-Busafi S.A., Aleman S., Alfaleh F.Z., Aljumah A.A., Anand A.C., Anh N.T., Arends J.E., Arkkila P., Athanasakis K., Bane A., Ben-Ari Z., Berg T., Bizri A.R., Blach S., Brandao Mello C.E., Brandon S.M., Bright B., Bruggmann P., Brunetto M., Buti M., Chan H.L.Y., Chaudhry A., Chien R.-N., Choi M.S., Christensen P.B., Chuang W.-L., Chulanov V., Clausen M.R., Colombo M., Cornberg M., Cowie B., Craxi A., Croes E.A., Cuellar D.A., Cunningham C., Desalegn H., Drazilova S., Duberg A.-S., Egeonu S.S., El-Sayed M.H., Estes C., Ferraz M.L.G., Ferreira P.R., Flisiak R., Frankova S., Gaeta G.B., Garcia-Samaniego J., Genov J., Gerstoft J., Goldis A., Gountas I., Gray R., Guimaraes Pessoa M., Hajarizadeh B., Hatzakis A., Hezode C., Himatt S.M., Hoepelman A., Hrstic I., Hui Y.-T.T., Husa P., Jahis R., Janjua N.Z., Jarcuka P., Jaroszewicz J., Kaymakoglu S., Kershenobich D., Kondili L.A., Konysbekova A., Krajden M., Kristian P., Laleman W., Lao W.-C.C., Layden J., Lazarus J.V., Lee M.-H., Liakina V., Lim Y.-S.S., Loo C.-K.K., Lukic B., Malekzadeh R., Malu A.O., Mamatkulov A., Manns M., Marinho R.T., Maticic M., Mauss S., Memon M.S., Mendes Correa M.C., Mendez-Sanchez N., Merat S., Metwally A.M., Mohamed R., Mokhbat J.E., Moreno C., Mossong J., Mourad F.H., Mullhaupt B., Murphy K., Musabaev E., Nawaz A., Nde H.M., Negro F., Nersesov A., Nguyen V.T.T., Njouom R., Ntagirabiri R., Nurmatov Z., Obekpa S., Ocama P., Oguche S., Omede O., Omuemu C., Opare-Sem O., Opio C.K., Falconer K., Ormeci N., Papatheodoridis G., Pasini K., Pimenov N., Poustchi H., Quang T.D., Qureshi H., Ramji A., Razavi-Shearer K., Redae B., Reesink H.W., Rios C.Y., Rjaskova G., Robbins S., Roberts L.R., Roberts S.K., Ryder S.D., Safadi R., Sagalova O., Salupere R., Sanai F.M., Sanchez-Avila J.F., Saraswat V., Sarrazin C., Schmelzer J.D., Schreter I., Scott J., Seguin-Devaux C., Shah S.R., Sharara A.I., Sharma M., Shiha G.E., Shin T., Sperl J., Starkel P., Stedman C., Sypsa V., Tacke F., Tan S.S., Tanaka J., Tomasiewicz K., Urbanek P., van der Meer A.J., Van Vlierberghe H., Vella S., Vince A., Waheed Y., Waked I., Walsh N., Weis N., Wong V.W., Woodring J., Yaghi C., Yang H.-I., Yang C.-L., Yesmembetov K., Yosry A., Yuen M.-F., Yusuf M.A.M., Zeuzem S., Razavi H., Sievert W., Razavi-Shearer D., Gamkrelidze I., Nguyen M.H., Chen D.-S., Van Damme P., Abbas Z., Abdulla M., Abou Rached A., Adda D., Aho I., Akarca U., Al Ali F.H., Lawati F.A.L., Naamani K.A.L., Alashgar H.I., Alavian S.M., Alawadhi S., Albillos A., Al-Busafi S.A., Aleman S., Alfaleh F.Z., Aljumah A.A., Anand A.C., Anh N.T., Arends J.E., Arkkila P., Athanasakis K., Bane A., Ben-Ari Z., Berg T., Bizri A.R., Blach S., Brandao Mello C.E., Brandon S.M., Bright B., Bruggmann P., Brunetto M., Buti M., Chan H.L.Y., Chaudhry A., Chien R.-N., Choi M.S., Christensen P.B., Chuang W.-L., Chulanov V., Clausen M.R., Colombo M., Cornberg M., Cowie B., Craxi A., Croes E.A., Cuellar D.A., Cunningham C., Desalegn H., Drazilova S., Duberg A.-S., Egeonu S.S., El-Sayed M.H., Estes C., Ferraz M.L.G., Ferreira P.R., Flisiak R., Frankova S., Gaeta G.B., Garcia-Samaniego J., Genov J., Gerstoft J., Goldis A., Gountas I., Gray R., Guimaraes Pessoa M., Hajarizadeh B., Hatzakis A., Hezode C., Himatt S.M., Hoepelman A., Hrstic I., Hui Y.-T.T., Husa P., Jahis R., Janjua N.Z., Jarcuka P., Jaroszewicz J., Kaymakoglu S., Kershenobich D., Kondili L.A., Konysbekova A., Krajden M., Kristian P., Laleman W., Lao W.-C.C., Layden J., Lazarus J.V., Lee M.-H., Liakina V., Lim Y.-S.S., Loo C.-K.K., Lukic B., Malekzadeh R., Malu A.O., Mamatkulov A., Manns M., Marinho R.T., Maticic M., Mauss S., Memon M.S., Mendes Correa M.C., Mendez-Sanchez N., Merat S., Metwally A.M., Mohamed R., Mokhbat J.E., Moreno C., Mossong J., Mourad F.H., Mullhaupt B., Murphy K., Musabaev E., Nawaz A., Nde H.M., Negro F., Nersesov A., Nguyen V.T.T., Njouom R., Ntagirabiri R., Nurmatov Z., Obekpa S., Ocama P., Oguche S., Omede O., Omuemu C., Opare-Sem O., and Opio C.K.

Abstract

Background: The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate viral hepatitis by 2030. Although no virological cure exists for hepatitis B virus (HBV) infection, existing therapies to control viral replication and prophylaxis to minimise mother-to-child transmission make elimination of HBV feasible. We aimed to estimate the national, regional, and global prevalence of HBsAg in the general population and in the population aged 5 years in 2016, as well as coverage of prophylaxis, diagnosis, and treatment. Method(s): In this modelling study, we used a Delphi process that included a literature review in PubMed and Embase, followed by interviews with experts, to quantify the historical epidemiology of HBV infection. We then used a dynamic HBV transmission and progression model to estimate the country-level and regional-level prevalence of HBsAg in 2016 and the effect of prophylaxis and treatment on disease burden. Finding(s): We developed models for 120 countries, 78 of which were populated with data approved by experts. Using these models, we estimated that the global prevalence of HBsAg in 2016 was 3.9% (95% uncertainty interval [UI] 3.4-4.6), corresponding to 291 992 000 (251 513 000-341 114 000) infections. Of these infections, around 29 million (10%) were diagnosed, and only 4.8 million (5%) of 94 million individuals eligible for treatment actually received antiviral therapy. Around 1.8 (1.6-2.2) million infections were in children aged 5 years, with a prevalence of 1.4% (1.2-1.6). We estimated that 87% of infants had received the three-dose HBV vaccination in the first year of life, 46% had received timely birth-dose vaccination, and 13% had received hepatitis B immunoglobulin along with the full vaccination regimen. Less than 1% of mothers with a high viral load had received antiviral therapy to reduce mother-to-child transmission. Interpretation(s): Our estimate of HBV prevalence in 2016 differs from previous studies, potentia

Published
2018

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