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2. Epidemiology of liver transplantation and post-LT complications in Germany: nationwide study (2005–2018)

Author

Gu, Wenyi, primary, Schaaf, Louisa, additional, Hortlik, Hannah, additional, Zeleke, Yasmin, additional, Brol, Maximilian J., additional, Schnitzbauer, Andreas A., additional, Bechstein, Wolf O., additional, Zeuzem, Stefan, additional, Queck, Alexander, additional, Peiffer, Kai-Henrik, additional, Tischendorf, Michael, additional, Pascher, Andreas, additional, Laleman, Wim, additional, Praktiknjo, Michael, additional, Schulz, Martin S., additional, Uschner, Frank E., additional, Rennebaum, Florian, additional, and Trebicka, Jonel, additional

Published
2023
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3. Location and allocation

Author

Artzner, Thierry, Bernal, William, Belli, Luca S, Conti, Sara, Cortesi, Paolo A, Sacleux, Sophie‐Caroline, Pageaux, George‐Philippe, Radenne, Sylvie, Trebicka, Jonel, Fernandez, Javier, Perricone, Giovanni, Piano, Salvatore, Nadalin, Silvio, Morelli, Maria C, Martini, Silvia, Polak, Wojciech G, Zieniewicz, Krzysztof, Toso, Christian, Berenguer, Marina, Iegri, Claudia, Invernizzi, Federica, Volpes, Riccardo, Karam, Vincent, Adam, René, Faitot, François, Rabinowich, Liane, Saliba, Faouzi, Meunier, Lucy, Lesurtel, Mickael, Uschner, Frank E, Michard, Baptiste, Coilly, Audrey, Meszaros, Magdalena, Poinsot, Domitille, Besch, Camille, Schnitzbauer, Andreas, De Carlis, Luciano G, Fumagalli, Roberto, Angeli, Paolo, Arroyo, Vincente, Fondevila, Constantino, Duvoux, Christophe, Jalan, Rajiv, Viganò, Raffaella, Mazzarelli, Chiara, Lauterio, Andrea, Giacomoni, Alessandro, Donato, Francesca, Lampertico, Pietro, Pasulo, Luisa, Fagiuoli, Stefano, Colledan, Michele, Cristina Morelli, Maria, Vitale, Giovanni, Ottobrelli, Antonio, Patrono, Damiano, Romagnoli, Renato, Petridis, Ioannis, Cillo, Umberto, Germani, Giacomo, Burra, Patrizia, Bachellier, Philippe, Schneider, Francis, Castelain, Vincent, Addeo, Pietro, Deridder, Mathilde, Caroline Sacleux Audrey Coilly, Sophie, Faouzi, Saliba, Adam, Rene, Samuel, Didier, Guichon, Celine, Faure, Stéfanie, Ursic‐Bedoya, Josè, Fondevila, Costantino, Colmenero, Jorde, Toapanta, David, Hernández‐Tejero, María, Vinaixa, Carmen, Polak, Wojciech G., den Hoed, Caroline, Haan, Jubi E., Della Penna, Andrea, Erhard Uschner, Frank, Welker, Martin, Zeuzem, Stefan, Bechstein, Wolf, Goossens, Nicolas, Raszeja‐Wyszomirska, Joanna, Rabinovich, Liane, Katarey, Dev, Agarwal, Banwari, Surgery, Gastroenterology & Hepatology, Intensive Care, Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Mitochondrie, stress oxydant et protection musculaire (MSP), Université de Strasbourg (UNISTRA), the ELITA/EF-CLIF Working Group, Artzner, T, Bernal, W, Belli, L, Conti, S, Cortesi, P, Sacleux, S, Pageaux, G, Radenne, S, Trebicka, J, Fernandez, J, Perricone, G, Piano, S, Nadalin, S, Morelli, M, Martini, S, Polak, W, Zieniewicz, K, Toso, C, Berenguer, M, Iegri, C, Invernizzi, F, Volpes, R, Karam, V, Adam, R, Faitot, F, Rabinowich, L, Saliba, F, Meunier, L, Lesurtel, M, Uschner, F, Michard, B, Coilly, A, Meszaros, M, Poinsot, D, Besch, C, Schnitzbauer, A, De Carlis, L, Fumagalli, R, Angeli, P, Arroyo, V, Fondevila, C, Duvoux, C, Jalan, R, Viganò, R, Mazzarelli, C, Lauterio, A, Giacomoni, A, Donato, F, Lampertico, P, Pasulo, L, Fagiuoli, S, Colledan, M, Cristina Morelli, M, Vitale, G, Ottobrelli, A, Patrono, D, Romagnoli, R, Petridis, I, Cillo, U, Germani, G, Burra, P, Bachellier, P, Schneider, F, Castelain, V, Addeo, P, Deridder, M, Caroline Sacleux Audrey Coilly, S, Faouzi, S, Samuel, D, Guichon, C, Faure, S, Ursic‐bedoya, J, Colmenero, J, Toapanta, D, Hernández‐tejero, M, Vinaixa, C, den Hoed, C, Haan, J, Della Penna, A, Erhard Uschner, F, Welker, M, Zeuzem, S, Bechstein, W, Goossens, N, Raszeja‐wyszomirska, J, Rabinovich, L, Katarey, D, and Agarwal, B

Subjects
Transplantation, ILL CIRRHOTIC-PATIENTS, Liver transplantation, Hepatology, Intensive care, Waiting list, Surgery, Acute-on-Chronic Liver Failure, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

There is growing evidence that liver transplantation (LT) is the most effective treatment for acute-on-chronic liver failure grade-3 (ACLF-3). This study examines whether and how this evidence translates into practice by analyzing the variability in intensive care unit (ICU) admissions, listing strategies, and LT activity for patients with ACLF-3 across transplantation centers in Europe. Consecutive patients who were admitted to the ICU with ACLF-3, whether or not they were listed and/or transplanted with ACLF-3, between 2018 and 2019 were included across 20 transplantation centers. A total of 351 patients with ACLF-3 were included: 33 had been listed prior to developing ACLF-3 and 318 had not been listed at the time of admission to the ICU. There was no correlation between the number of unlisted patients with ACLF-3 admitted to the ICU and the number listed or transplanted while in ACLF-3 across centers. By contrast, there was a correlation between the number of patients listed and the number transplanted while in ACLF-3. About 21% of patients who were listed while in ACLF-3 died on the waiting list or were delisted. The percentage of LT for patients with ACLF-3 varied from 0% to 29% for those transplanted with decompensated cirrhosis across centers (average = 8%), with an I(2) index of 68% (95% confidence interval, 49%-80%), showing substantial heterogeneity among centers. The 1-year survival for all patients with ACLF-3 was significantly higher in centers that listed and transplanted more patients with ACLF-3 (>10 patients) than in centers that listed and transplanted fewer: 36% versus 20%, respectively (p = 0.012). Patients with ACLF-3 face inequity of access to LT across Europe. Waitlisting strategies for patients with ACLF-3 influence their access to LT and, ultimately, their survival.

Published
2022

4. Novel prognostic biomarkers in decompensated cirrhosis: a systematic review and meta-analysis.

Author

Juanola, Adrià, Ann Thu Ma, Koos de Wit, Gananandan, Kohilan, Roux, Olivier, Zaccherini, Giacomo, Jiménez, César, Tonon, Marta, Solé, Cristina, Villaseca, Clara, Uschner, Frank E., Graupera, Isabel, Pose, Elisa, Moreta, Maria José, Campion, Daniela, Beuers, Ulrich, Mookerjee, Rajeshawar P., Francoz, Claire, Durand, Francois, and Vargas, Victor

Subjects
HEPATORENAL syndrome, PROGNOSIS, CIRRHOSIS of the liver, HIGH mobility group proteins, ORGAN transplant waiting lists
Published
2024
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5. Neprilysin-dependent neuropeptide Y cleavage in the liver promotes fibrosis by blocking NPY-receptor 1

Author

Ortiz, Cristina, Klein, Sabine, Reul, Winfried H., Magdaleno, Fernando, Gröschl, Stefanie, Dietrich, Peter, Schierwagen, Robert, Uschner, Frank E., Torres, Sandra, Hieber, Christoph, Meier, Caroline, Kraus, Nico, Tyc, Olaf, Brol, Maximilian, Zeuzem, Stefan, Welsch, Christoph, Poglitsch, Marco, Hellerbrand, Claus, Alfonso-Prieto, Mercedes, Mira, Fabio, Keller, Ulrich auf dem, Tetzner, Anja, Moore, Andrew, Walther, Thomas, Trebicka, Jonel, Ortiz, Cristina, Klein, Sabine, Reul, Winfried H., Magdaleno, Fernando, Gröschl, Stefanie, Dietrich, Peter, Schierwagen, Robert, Uschner, Frank E., Torres, Sandra, Hieber, Christoph, Meier, Caroline, Kraus, Nico, Tyc, Olaf, Brol, Maximilian, Zeuzem, Stefan, Welsch, Christoph, Poglitsch, Marco, Hellerbrand, Claus, Alfonso-Prieto, Mercedes, Mira, Fabio, Keller, Ulrich auf dem, Tetzner, Anja, Moore, Andrew, Walther, Thomas, and Trebicka, Jonel

Abstract

Development of liver fibrosis is paralleled by contraction of hepatic stellate cells (HSCs), the main profibrotic hepatic cells. Yet, little is known about the interplay of neprilysin (NEP) and its substrate neuropeptide Y (NPY), a potent enhancer of contraction, in liver fibrosis. We demonstrate that HSCs are the source of NEP. Importantly, NPY originates majorly from the splanchnic region and is cleaved by NEP in order to terminate contraction. Interestingly, NEP deficiency (Nep−/−) showed less fibrosis but portal hypertension upon liver injury in two different fibrosis models in mice. We demonstrate the incremental benefit of Nep−/− in addition to AT1R blocker (ARB) or ACE inhibitors for fibrosis and portal hypertension. Finally, oral administration of Entresto, a combination of ARB and NEP inhibitor, decreased hepatic fibrosis and portal pressure in mice. These results provide a mechanistic rationale for translation of NEP-AT1R-blockade in human liver fibrosis and portal hypertension.

Published
2023

8. Use and outcome of TIPS in hospitalized patients in Germany: A Nationwide study (2007–2018).

Author

Wenyi Gu, Zeleke, Yasmin, Hortlik, Hannah, Schaaf, Louisa, Uschner, Frank E., Schulz, Martin, Tischendorf, Michael, Peiffer, Kai-Henrik, Brol, Maximilian Joseph, Kimmann, Markus, Vogl, Thomas, Köhler, Michael, Meyer, Carsten, Gerbes, Alexander, Rössle, Martin, Laleman, Wim, Zipprich, Alexander, Steib, Christian, Praktiknjo, Michael, and Trebicka, Jonel

Published
2023
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9. Neprilysin-dependent neuropeptide Y cleavage in the liver promotes fibrosis by blocking NPY-receptor 1

Author

Ortiz, Cristina, primary, Klein, Sabine, additional, Reul, Winfried H., additional, Magdaleno, Fernando, additional, Gröschl, Stefanie, additional, Dietrich, Peter, additional, Schierwagen, Robert, additional, Uschner, Frank E., additional, Torres, Sandra, additional, Hieber, Christoph, additional, Meier, Caroline, additional, Kraus, Nico, additional, Tyc, Olaf, additional, Brol, Maximilian, additional, Zeuzem, Stefan, additional, Welsch, Christoph, additional, Poglitsch, Marco, additional, Hellerbrand, Claus, additional, Alfonso-Prieto, Mercedes, additional, Mira, Fabio, additional, Keller, Ulrich auf dem, additional, Tetzner, Anja, additional, Moore, Andrew, additional, Walther, Thomas, additional, and Trebicka, Jonel, additional

Published
2023
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10. Pulmonary impairment independently determines mortality in critically ill patients with acute‐on‐chronic liver failure

Author

Schulz, Martin S., primary, Mengers, Jan, additional, Gu, Wenyi, additional, Drolz, Andreas, additional, Ferstl, Philip G., additional, Amoros, Alex, additional, Uschner, Frank E., additional, Ackermann, Nora, additional, Guttenberg, Georg, additional, Queck, Alexander, additional, Brol, Maximilian J., additional, Graf, Christiana, additional, Stoffers, Philipp, additional, de la Vera, Anna‐Lena Laguna, additional, Cremonese, Carla, additional, Erasmus, Hans‐Peter, additional, Welker, Martin W., additional, Grünewaldt, Achim, additional, Arroyo, Vincente, additional, Bojunga, Jörg, additional, Fernandez, Javier, additional, Zeuzem, Stefan, additional, Kluwe, Johannes, additional, Peiffer, Kai‐Hendrik, additional, Welsch, Christoph, additional, Fuhrmann, Valentin, additional, Rohde, Gernot, additional, and Trebicka, Jonel, additional

Published
2022
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11. Targeted decrease of portal hepatic pressure gradient improves ascites control after TIPS

Author

Queck, Alexander, primary, Schwierz, Louise, additional, Gu, Wenyi, additional, Ferstl, Philip G., additional, Jansen, Christian, additional, Uschner, Frank E., additional, Praktiknjo, Michael, additional, Chang, Johannes, additional, Brol, Maximilian J., additional, Schepis, Filippo, additional, Merli, Manuela, additional, Strassburg, Christian P., additional, Lehmann, Jennifer, additional, Meyer, Carsten, additional, and Trebicka, Jonel, additional

Published
2022
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12. Location and allocation: inequity of access to liver transplantation for patients with severe acute‐on‐chronic liver failure in Europe

Author

Artzner, T, Bernal, W, Belli, L, Conti, S, Cortesi, P, Sacleux, S, Pageaux, G, Radenne, S, Trebicka, J, Fernandez, J, Perricone, G, Piano, S, Nadalin, S, Morelli, M, Martini, S, Polak, W, Zieniewicz, K, Toso, C, Berenguer, M, Iegri, C, Invernizzi, F, Volpes, R, Karam, V, Adam, R, Faitot, F, Rabinowich, L, Saliba, F, Meunier, L, Lesurtel, M, Uschner, F, Michard, B, Coilly, A, Meszaros, M, Poinsot, D, Besch, C, Schnitzbauer, A, De Carlis, L, Fumagalli, R, Angeli, P, Arroyo, V, Fondevila, C, Duvoux, C, Jalan, R, Viganò, R, Mazzarelli, C, Lauterio, A, Giacomoni, A, Donato, F, Lampertico, P, Pasulo, L, Fagiuoli, S, Colledan, M, Cristina Morelli, M, Vitale, G, Ottobrelli, A, Patrono, D, Romagnoli, R, Petridis, I, Cillo, U, Germani, G, Burra, P, Bachellier, P, Schneider, F, Castelain, V, Addeo, P, Deridder, M, Caroline Sacleux Audrey Coilly, S, Faouzi, S, Samuel, D, Guichon, C, Faure, S, Ursic‐bedoya, J, Colmenero, J, Toapanta, D, Hernández‐tejero, M, Vinaixa, C, den Hoed, C, Haan, J, Della Penna, A, Erhard Uschner, F, Welker, M, Zeuzem, S, Bechstein, W, Goossens, N, Raszeja‐wyszomirska, J, Rabinovich, L, Katarey, D, Agarwal, B, Artzner, Thierry, Bernal, William, Belli, Luca S, Conti, Sara, Cortesi, Paolo A, Sacleux, Sophie‐Caroline, Pageaux, George‐Philippe, Radenne, Sylvie, Trebicka, Jonel, Fernandez, Javier, Perricone, Giovanni, Piano, Salvatore, Nadalin, Silvio, Morelli, Maria C, Martini, Silvia, Polak, Wojciech G, Zieniewicz, Krzysztof, Toso, Christian, Berenguer, Marina, Iegri, Claudia, Invernizzi, Federica, Volpes, Riccardo, Karam, Vincent, Adam, René, Faitot, François, Rabinowich, Liane, Saliba, Faouzi, Meunier, Lucy, Lesurtel, Mickael, Uschner, Frank E, Michard, Baptiste, Coilly, Audrey, Meszaros, Magdalena, Poinsot, Domitille, Besch, Camille, Schnitzbauer, Andreas, De Carlis, Luciano G, Fumagalli, Roberto, Angeli, Paolo, Arroyo, Vincente, Fondevila, Constantino, Duvoux, Christophe, Jalan, Rajiv, Viganò, Raffaella, Mazzarelli, Chiara, Lauterio, Andrea, Giacomoni, Alessandro, Donato, Francesca, Lampertico, Pietro, Pasulo, Luisa, Fagiuoli, Stefano, Colledan, Michele, Cristina Morelli, Maria, Vitale, Giovanni, Ottobrelli, Antonio, Patrono, Damiano, Romagnoli, Renato, Petridis, Ioannis, Cillo, Umberto, Germani, Giacomo, Burra, Patrizia, Bachellier, Philippe, Schneider, Francis, Castelain, Vincent, Addeo, Pietro, Deridder, Mathilde, Caroline Sacleux Audrey Coilly, Sophie, Faouzi, Saliba, Adam, Rene, Samuel, Didier, Guichon, Celine, Faure, Stéfanie, Ursic‐Bedoya, Josè, Fondevila, Costantino, Colmenero, Jorde, Toapanta, David, Hernández‐Tejero, María, Vinaixa, Carmen, Polak, Wojciech G., den Hoed, Caroline, Haan, Jubi E., Della Penna, Andrea, Erhard Uschner, Frank, Welker, Martin, Zeuzem, Stefan, Bechstein, Wolf, Goossens, Nicolas, Raszeja‐Wyszomirska, Joanna, Rabinovich, Liane, Katarey, Dev, Agarwal, Banwari, Artzner, T, Bernal, W, Belli, L, Conti, S, Cortesi, P, Sacleux, S, Pageaux, G, Radenne, S, Trebicka, J, Fernandez, J, Perricone, G, Piano, S, Nadalin, S, Morelli, M, Martini, S, Polak, W, Zieniewicz, K, Toso, C, Berenguer, M, Iegri, C, Invernizzi, F, Volpes, R, Karam, V, Adam, R, Faitot, F, Rabinowich, L, Saliba, F, Meunier, L, Lesurtel, M, Uschner, F, Michard, B, Coilly, A, Meszaros, M, Poinsot, D, Besch, C, Schnitzbauer, A, De Carlis, L, Fumagalli, R, Angeli, P, Arroyo, V, Fondevila, C, Duvoux, C, Jalan, R, Viganò, R, Mazzarelli, C, Lauterio, A, Giacomoni, A, Donato, F, Lampertico, P, Pasulo, L, Fagiuoli, S, Colledan, M, Cristina Morelli, M, Vitale, G, Ottobrelli, A, Patrono, D, Romagnoli, R, Petridis, I, Cillo, U, Germani, G, Burra, P, Bachellier, P, Schneider, F, Castelain, V, Addeo, P, Deridder, M, Caroline Sacleux Audrey Coilly, S, Faouzi, S, Samuel, D, Guichon, C, Faure, S, Ursic‐bedoya, J, Colmenero, J, Toapanta, D, Hernández‐tejero, M, Vinaixa, C, den Hoed, C, Haan, J, Della Penna, A, Erhard Uschner, F, Welker, M, Zeuzem, S, Bechstein, W, Goossens, N, Raszeja‐wyszomirska, J, Rabinovich, L, Katarey, D, Agarwal, B, Artzner, Thierry, Bernal, William, Belli, Luca S, Conti, Sara, Cortesi, Paolo A, Sacleux, Sophie‐Caroline, Pageaux, George‐Philippe, Radenne, Sylvie, Trebicka, Jonel, Fernandez, Javier, Perricone, Giovanni, Piano, Salvatore, Nadalin, Silvio, Morelli, Maria C, Martini, Silvia, Polak, Wojciech G, Zieniewicz, Krzysztof, Toso, Christian, Berenguer, Marina, Iegri, Claudia, Invernizzi, Federica, Volpes, Riccardo, Karam, Vincent, Adam, René, Faitot, François, Rabinowich, Liane, Saliba, Faouzi, Meunier, Lucy, Lesurtel, Mickael, Uschner, Frank E, Michard, Baptiste, Coilly, Audrey, Meszaros, Magdalena, Poinsot, Domitille, Besch, Camille, Schnitzbauer, Andreas, De Carlis, Luciano G, Fumagalli, Roberto, Angeli, Paolo, Arroyo, Vincente, Fondevila, Constantino, Duvoux, Christophe, Jalan, Rajiv, Viganò, Raffaella, Mazzarelli, Chiara, Lauterio, Andrea, Giacomoni, Alessandro, Donato, Francesca, Lampertico, Pietro, Pasulo, Luisa, Fagiuoli, Stefano, Colledan, Michele, Cristina Morelli, Maria, Vitale, Giovanni, Ottobrelli, Antonio, Patrono, Damiano, Romagnoli, Renato, Petridis, Ioannis, Cillo, Umberto, Germani, Giacomo, Burra, Patrizia, Bachellier, Philippe, Schneider, Francis, Castelain, Vincent, Addeo, Pietro, Deridder, Mathilde, Caroline Sacleux Audrey Coilly, Sophie, Faouzi, Saliba, Adam, Rene, Samuel, Didier, Guichon, Celine, Faure, Stéfanie, Ursic‐Bedoya, Josè, Fondevila, Costantino, Colmenero, Jorde, Toapanta, David, Hernández‐Tejero, María, Vinaixa, Carmen, Polak, Wojciech G., den Hoed, Caroline, Haan, Jubi E., Della Penna, Andrea, Erhard Uschner, Frank, Welker, Martin, Zeuzem, Stefan, Bechstein, Wolf, Goossens, Nicolas, Raszeja‐Wyszomirska, Joanna, Rabinovich, Liane, Katarey, Dev, and Agarwal, Banwari

Abstract

Background: There is growing evidence that liver transplantation (LT) is the most effective treatment for acute-on-chronic liver failure grade-3 (ACLF-3). This study examines whether and how this evidence translates into practice by analyzing the variability in intensive care unit (ICU) admissions, listing strategies and LT activity for ACLF-3 patients across transplant centers in Europe. Methods: Consecutive patients who were admitted to the ICU with ACLF-3, whether or not they were listed and/or transplanted with ACLF-3 between 2018 and 2019 were included across 20 transplantation centers. Results: 351 patients with ACLF-3 were included: 33 had been listed prior to developing ACLF-3 and 318 had not been listed at the time of admission to the ICU. There was no correlation between the number of unlisted ACLF-3 patients admitted to the ICU and the number listed or transplanted whilst in ACLF-3 across centers. In contrast, there was a correlation between the number of patients listed and the number transplanted whilst in ACLF-3. 21% of patients who were listed whilst in ACLF-3 died on the waiting list or were delisted. The percentage of LT for ACLF-3 patients varied from 0%-29% of patients transplanted with decompensated cirrhosis across centers (average = 8%), with an I2 index of 68% (95% CI: 49%-80%), showing substantial heterogeneity among centers. The one-year survival for all patients with ACLF-3 was significantly higher in centers that listed and transplanted more ACLF-3 patients (>10 patients) than in centers that listed and transplanted fewer: respectively 36% vs. 20%, p = 0.012. Conclusion: Patients with ACLF-3 face inequity of access to LT across Europe. Wait-listing strategies for ACLF-3 patients influence their access to LT and, ultimately, their survival.

Published
2022

13. Dynamic human liver proteome atlas reveals functional insights into disease pathways

Author

Niu, Lili, primary, Geyer, Philipp E., additional, Gupta, Rajat, additional, Santos, Alberto, additional, Meier, Florian, additional, Doll, Sophia, additional, Albrechtsen, Nicolai J. Wewer, additional, Klein, Sabine, additional, Ortiz, Cristina, additional, Uschner, Frank E., additional, Schierwagen, Robert, additional, Trebicka, Jonel, additional, and Mann, Matthias, additional

Published
2022
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14. Trends and the course of liver cirrhosis and its complications in Germany: Nationwide population-based study (2005 to 2018)

Author

Gu, Wenyi, primary, Hortlik, Hannah, additional, Erasmus, Hans-Peter, additional, Schaaf, Louisa, additional, Zeleke, Yasmin, additional, Uschner, Frank E., additional, Ferstl, Philip, additional, Schulz, Martin, additional, Peiffer, Kai-Henrik, additional, Queck, Alexander, additional, Sauerbruch, Tilman, additional, Brol, Maximilian Joseph, additional, Rohde, Gernot, additional, Sanchez, Cristina, additional, Moreau, Richard, additional, Arroyo, Vicente, additional, Zeuzem, Stefan, additional, Welsch, Christoph, additional, and Trebicka, Jonel, additional

Published
2022
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15. Granulocyte-colony stimulating factor (G-CSF) to treat acute-on-chronic liver failure: A multicenter randomized trial (GRAFT study)

Author

Engelmann, Cornelius, primary, Herber, Adam, additional, Franke, Annegret, additional, Bruns, Tony, additional, Reuken, Philipp, additional, Schiefke, Ingolf, additional, Zipprich, Alexander, additional, Zeuzem, Stefan, additional, Goeser, Tobias, additional, Canbay, Ali, additional, Berg, Christoph, additional, Trebicka, Jonel, additional, Uschner, Frank E., additional, Chang, Johannes, additional, Mueller, Tobias, additional, Aehling, Niklas, additional, Schmelzle, Moritz, additional, Splith, Katrin, additional, Lammert, Frank, additional, Lange, Christian M., additional, Sarrazin, Christoph, additional, Trautwein, Christian, additional, Manns, Michael, additional, Häussinger, Dieter, additional, Pfeiffenberger, Jan, additional, Galle, Peter R., additional, Schmiedeknecht, Anett, additional, and Berg, Thomas, additional

Published
2021
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17. Pulmonary impairment independently determines mortality in critically ill patients with acute‐on‐chronic liver failure.

Author

Schulz, Martin S., Mengers, Jan, Gu, Wenyi, Drolz, Andreas, Ferstl, Philip G., Amoros, Alex, Uschner, Frank E., Ackermann, Nora, Guttenberg, Georg, Queck, Alexander, Brol, Maximilian J., Graf, Christiana, Stoffers, Philipp, de la Vera, Anna‐Lena Laguna, Cremonese, Carla, Erasmus, Hans‐Peter, Welker, Martin W., Grünewaldt, Achim, Arroyo, Vincente, and Bojunga, Jörg

Subjects
LIVER failure, PATIENT selection, CRITICALLY ill, ALLOCATION of organs, tissues, etc., ARTIFICIAL respiration
Abstract

Background & Aims: In ACLF patients, an adequate risk stratification is essential, especially for liver transplant allocation, since ACLF is associated with high short‐term mortality. The CLIF‐C ACLF score is the best prognostic model to predict outcome in ACLF patients. While lung failure is generally regarded as signum malum in ICU care, this study aims to evaluate and quantify the role of pulmonary impairment on outcome in ACLF patients. Methods: In this retrospective study, 498 patients with liver cirrhosis and admission to IMC/ICU were included. ACLF was defined according to EASL‐CLIF criteria. Pulmonary impairment was classified into three groups: unimpaired ventilation, need for mechanical ventilation and defined pulmonary failure. These factors were analysed in different cohorts, including a propensity score‐matched ACLF cohort. Results: Mechanical ventilation and pulmonary failure were identified as independent risk factors for increased short‐term mortality. In matched ACLF patients, the presence of pulmonary failure showed the highest 28‐day mortality (83.7%), whereas mortality rates in ACLF with mechanical ventilation (67.3%) and ACLF without pulmonary impairment (38.8%) were considerably lower (p <.001). Especially in patients with pulmonary impairment, the CLIF‐C ACLF score showed poor predictive accuracy. Adjusting the CLIF‐C ACLF score for the grade of pulmonary impairment improved the prediction significantly. Conclusions: This study highlights that not only pulmonary failure but also mechanical ventilation is associated with worse prognosis in ACLF patients. The grade of pulmonary impairment should be considered in the risk assessment in ACLF patients. The new score may be useful in the selection of patients for liver transplantation. [ABSTRACT FROM AUTHOR]

Published
2023
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18. O10 Granulocyte-Colony Stimulating Factor (G-CSF) to treat acute-on-chronic liver failure; results of the first multicenter randomized trial (GRAFT study)

Author

Engelmann, Cornelius, primary, Herber, Adam, additional, Ildh, Tony, additional, Schiefke, Ingolf, additional, Zipprich, Alexander, additional, Schmiedeknecht, Anett, additional, Zeuzem, Stefan, additional, Goeser, Tobias, additional, Canbay, Ali, additional, Berg, Christoph, additional, Trebicka, Jonel, additional, Uschner, Frank E, additional, Mueller, Tobias, additional, Aehling, Niklas, additional, Schmelzle, Moritz, additional, Splith, Katrin, additional, Lammert, Frank, additional, Lange, Christian M, additional, Sarrazin, Christoph, additional, Trautwein, Christian, additional, Manns, Michael, additional, Häussinger, Dieter, additional, Pfeiffenberger, Jan, additional, Galle, Peter, additional, Franke, Annegret, additional, and Berg, Thomas, additional

Published
2021
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19. Liver transplantation for patients with acute-on-chronic liver failure (ACLF) in Europe: Results of the ELITA/EF-CLIF collaborative study (ECLIS)

Author

Belli, Luca S., primary, Duvoux, Christophe, additional, Artzner, Thierry, additional, Bernal, William, additional, Conti, Sara, additional, Cortesi, Paolo A., additional, Sacleux, Sophie-Caroline, additional, Pageaux, George-Philippe, additional, Radenne, Sylvie, additional, Trebicka, Jonel, additional, Fernandez, Javier, additional, Perricone, Giovanni, additional, Piano, Salvatore, additional, Nadalin, Silvio, additional, Morelli, Maria C., additional, Martini, Silvia, additional, Polak, Wojciech G., additional, Zieniewicz, Krzysztof, additional, Toso, Christian, additional, Berenguer, Marina, additional, Iegri, Claudia, additional, Invernizzi, Federica, additional, Volpes, Riccardo, additional, Karam, Vincent, additional, Adam, René, additional, Faitot, François, additional, Rabinovich, Liane, additional, Saliba, Faouzi, additional, Meunier, Lucy, additional, Lesurtel, Mickael, additional, Uschner, Frank E., additional, Fondevila, Costantino, additional, Michard, Baptiste, additional, Coilly, Audrey, additional, Meszaros, Magdalena, additional, Poinsot, Domitille, additional, Schnitzbauer, Andreas, additional, De Carlis, Luciano G., additional, Fumagalli, Roberto, additional, Angeli, Paolo, additional, Arroyo, Vincente, additional, Jalan, Rajiv, additional, Belli, Luca S., additional, Viganò, Raffaella, additional, Mazzarelli, Chiara, additional, Lauterio, Andrea, additional, Giacomoni, Alessandro, additional, Donato, Francesca, additional, Lampertico, Pietro, additional, Pasulo, Luisa, additional, Fagiuoli, Stefano, additional, Colledan, Michele, additional, Morelli, Maria Cristina, additional, Vitale, Giovanni, additional, Patrono, Damiano, additional, Romagnoli, Renato, additional, Ottobrelli, Antonio, additional, Petridis, Ioannis, additional, Cillo, Umberto, additional, Germani, Giacomo, additional, Burra, Patrizia, additional, Bachellier, Philippe, additional, Addeo, Pietro, additional, Besch, Camille, additional, Faitot, Francoise, additional, Sacleux, Sophie Caroline, additional, Faouzi, Saliba, additional, Adam, Rene, additional, Samuel, Didier, additional, Guichon, Celine, additional, Faure, Stéfanie, additional, Ursic-Bedoya, Josè, additional, Colmenero, Jorde, additional, Toapanta, David, additional, Hernández-Tejero, María, additional, Vinaixa, Carmen, additional, Hoed, Caroline den, additional, de Haan, Jubi E., additional, Della Penna, Andrea, additional, Uschner, Frank Erhard, additional, Welker, Martin, additional, Zeuzem, Stefan, additional, Bechstein, Wolf, additional, Goossens, Nicolas, additional, Raszeja-Wyszomirska, Joanna, additional, Katarey, Dev, additional, and Agarwal, Banwari, additional

Published
2021
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20. Role of circulating angiogenin levels in portal hypertension and TIPS

Author

Queck, Alexander, primary, Uschner, Frank E., additional, Ferstl, Philip G., additional, Schulz, Martin, additional, Brol, Maximilian J., additional, Praktiknjo, Michael, additional, Schierwagen, Robert, additional, Klein, Sabine, additional, Strassburg, Christian P., additional, Meyer, Carsten, additional, Jansen, Christian, additional, Berres, Marie-Luise, additional, and Trebicka, Jonel, additional

Published
2021
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21. Extrahepatic Surgery in Cirrhosis Significantly Increases Portal Pressure in Preclinical Animal Models

Author

Chang, Johannes, primary, Meinke, Jonathan, additional, Geck, Moritz, additional, Hebest, Marc, additional, Böhling, Nina, additional, Dolscheid-Pommerich, Ramona, additional, Stoffel-Wagner, Birgit, additional, Kristiansen, Glen, additional, Overhaus, Marcus, additional, Peyman, Leon O., additional, Klein, Sabine, additional, Uschner, Frank E., additional, Brol, Maximilian J., additional, Vilz, Tim O., additional, Lingohr, Philipp, additional, Kalff, Jörg C., additional, Jansen, Christian, additional, Strassburg, Christian P., additional, Wehner, Sven, additional, Trebicka, Jonel, additional, and Praktiknjo, Michael, additional

Published
2021
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22. The Specific NLRP3 Antagonist IFM-514 Decreases Fibrosis and Inflammation in Experimental Murine Non-Alcoholic Steatohepatitis

Author

Torres, Sandra, primary, Brol, Maximilian J, additional, Magdaleno, Fernando, additional, Schierwagen, Robert, additional, Uschner, Frank E., additional, Klein, Sabine, additional, Ortiz, Cristina, additional, Tyc, Olaf, additional, Bachtler, Nadine, additional, Stunden, James, additional, Bertheloot, Damien, additional, Kitanovic, Ana, additional, Sanchez, Brian, additional, Schrum, Jacob, additional, Roush, William R., additional, Franchi, Luigi, additional, Byth, Kate, additional, Latz, Eicke, additional, and Trebicka, Jonel, additional

Published
2021
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23. Refining prediction of survival after TIPS with the novel Freiburg index of post-TIPS survival

Author

Bettinger, Dominik, primary, Sturm, Lukas, additional, Pfaff, Lena, additional, Hahn, Felix, additional, Kloeckner, Roman, additional, Volkwein, Lara, additional, Praktiknjo, Michael, additional, Lv, Yong, additional, Han, Guohong, additional, Huber, Jan Patrick, additional, Boettler, Tobias, additional, Reincke, Marlene, additional, Klinger, Christoph, additional, Caca, Karel, additional, Heinzow, Hauke, additional, Seifert, Leon Louis, additional, Weiss, Karl Heinz, additional, Rupp, Christian, additional, Piecha, Felix, additional, Kluwe, Johannes, additional, Zipprich, Alexander, additional, Luxenburger, Hendrik, additional, Neumann-Haefelin, Christoph, additional, Schmidt, Arthur, additional, Jansen, Christian, additional, Meyer, Carsten, additional, Uschner, Frank E., additional, Brol, Maximilian J., additional, Trebicka, Jonel, additional, Rössle, Martin, additional, Thimme, Robert, additional, and Schultheiss, Michael, additional

Published
2021
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24. Granulocyte-colony stimulating factor (G-CSF) to treat acute-on- chronic liver failure: A multicenter randomized trial (GRAFT study)

Author

Engelmann, Cornelius, Herber, Adam, Franke, Annegret, Bruns, Tony, Reuken, Philipp, Schiefke, Ingolf, Zipprich, Alexander, Zeuzem, Stefan, Goeser, Tobias, Canbay, Ali, Berg, Christoph, Trebicka, Jonel, Uschner, Frank E., Chang, Johannes, Mueller, Tobias, Aehling, Niklas, Schmelzle, Moritz, Splith, Katrin, Lammert, Frank, Lange, Christian M., Sarrazin, Christoph, Trautwein, Christian, Manns, Michael, Haeussinger, Dieter, Pfeiffenberger, Jan, Galle, Peter R., Schmiedeknecht, Anett, Berg, Thomas, Engelmann, Cornelius, Herber, Adam, Franke, Annegret, Bruns, Tony, Reuken, Philipp, Schiefke, Ingolf, Zipprich, Alexander, Zeuzem, Stefan, Goeser, Tobias, Canbay, Ali, Berg, Christoph, Trebicka, Jonel, Uschner, Frank E., Chang, Johannes, Mueller, Tobias, Aehling, Niklas, Schmelzle, Moritz, Splith, Katrin, Lammert, Frank, Lange, Christian M., Sarrazin, Christoph, Trautwein, Christian, Manns, Michael, Haeussinger, Dieter, Pfeiffenberger, Jan, Galle, Peter R., Schmiedeknecht, Anett, and Berg, Thomas

Abstract

Background & Aims: Based on positive results from small single center studies, granulocyte-colony stimulating factor (G-CSF) is being widely used for the treatment of patients with acute-on chronic liver failure (ACLF). Herein, we aimed to evaluate the safety and efficacy of G-CSF in patients with ACLF. Methods: In this multicenter, prospective, controlled, open-label phase II study, 176 patients with ACLF (EASL-CLIF criteria) were randomized to receive G-CSF (5 mu g/kg daily for the first 5 days and every third day thereafter until day 26) plus standard medical therapy (SMT) (n = 88) or SMT alone. The primary effi- cacy endpoint was 90-day transplant-free survival analyzed by Cox regression modeling. The key secondary endpoints were overall and transplant-free survival after 360 days, the development of ACLF-related complications, and the course of liver function scores during the entire observation period. Results: Patients treated with G-CSF had a 90-day transplant free survival rate of 34.1% compared to 37.5% in the SMT group (hazard ratio [HR] 1.05; 95% CI 0.711-1.551; p = 0.805). Transplant-free and overall survival at 360 days did not differ between the 2 arms (HR 0.998; 95% CI 0.697-1.430; p = 0.992 and HR 1.058; 95% CI 0.727-1.548; p = 0.768, respectively). G-CSF did not improve liver function scores, the occurrence of infections, or survival in subgroups of patients without infections, with alcohol-related ACLF, or with ACLF defined by the APASL criteria. Sixty-one serious adverse events were reported in the GCSF+SMT group and 57 were reported in the SMT group. In total, 7 drug-related serious adverse reactions occurred in the G-CSF group. The study was prematurely terminated due to futility after conditional power calculation. Conclusions: In contrast to previous findings, G-CSF had no significant beneficial effect on patients with ACLF in this multicenter controlled trial, which suggests that it should not be used as a standard treatment for ACLF. Clinic

Published
2021

25. Liver transplantation for patients with acute-on-chronic liver failure (ACLF) in Europe:Results of the ELITA/EF-CLIF collaborative study (ECLIS)

Author

Belli, Luca S., Duvoux, Christophe, Artzner, Thierry, Bernal, William, Conti, Sara, Cortesi, Paolo A., Sacleux, Sophie Caroline, Pageaux, George Philippe, Radenne, Sylvie, Trebicka, Jonel, Fernandez, Javier, Perricone, Giovanni, Piano, Salvatore, Nadalin, Silvio, Morelli, Maria C., Martini, Silvia, Polak, Wojciech G., Zieniewicz, Krzysztof, Toso, Christian, Berenguer, Marina, Iegri, Claudia, Invernizzi, Federica, Volpes, Riccardo, Karam, Vincent, Adam, René, Faitot, François, Rabinovich, Liane, Saliba, Faouzi, Meunier, Lucy, Lesurtel, Mickael, Uschner, Frank E., Fondevila, Costantino, Michard, Baptiste, Coilly, Audrey, Meszaros, Magdalena, Poinsot, Domitille, Schnitzbauer, Andreas, De Carlis, Luciano G., Fumagalli, Roberto, Angeli, Paolo, Arroyo, Vincente, Jalan, Rajiv, Belli, Luca S., Duvoux, Christophe, Artzner, Thierry, Bernal, William, Conti, Sara, Cortesi, Paolo A., Sacleux, Sophie Caroline, Pageaux, George Philippe, Radenne, Sylvie, Trebicka, Jonel, Fernandez, Javier, Perricone, Giovanni, Piano, Salvatore, Nadalin, Silvio, Morelli, Maria C., Martini, Silvia, Polak, Wojciech G., Zieniewicz, Krzysztof, Toso, Christian, Berenguer, Marina, Iegri, Claudia, Invernizzi, Federica, Volpes, Riccardo, Karam, Vincent, Adam, René, Faitot, François, Rabinovich, Liane, Saliba, Faouzi, Meunier, Lucy, Lesurtel, Mickael, Uschner, Frank E., Fondevila, Costantino, Michard, Baptiste, Coilly, Audrey, Meszaros, Magdalena, Poinsot, Domitille, Schnitzbauer, Andreas, De Carlis, Luciano G., Fumagalli, Roberto, Angeli, Paolo, Arroyo, Vincente, and Jalan, Rajiv

Abstract

Background & Aims: Liver transplantation (LT) has been proposed as an effective salvage therapy even for the sickest patients with acute-on-chronic liver failure (ACLF). This large collaborative study was designed to assess the current clinical practice and outcomes of patients with ACLF who are wait-listed for LT in Europe. Methods: This was a retrospective study including 308 consecutive patients with ACLF, listed in 20 centres across 8 European countries, from January 2018 to June 2019. Results: A total of 2,677 patients received a LT: 1,216 (45.4%) for decompensated cirrhosis. Of these, 234 (19.2%) had ACLF at LT: 58 (4.8%) had ACLF-1, 78 (6.4%) had ACLF-2, and 98 (8.1%) had ACLF-3. Wide variations were observed amongst countries: France and Germany had high rates of ACLF-2/3 (27–41%); Italy, Switzerland, Poland and the Netherlands had medium rates (9–15%); and the United Kingdom and Spain had low rates (3–5%) (p <0.0001). The 1-year probability of survival after LT for patients with ACLF was 81% (95% CI 74–87). Pre-LT arterial lactate levels >4 mmol/L (hazard ratio [HR] 3.14; 95% CI 1.37–7.19), recent infection from multidrug resistant organisms (HR 3.67; 95% CI 1.63–8.28), and renal replacement therapy (HR 2.74; 95% CI 1.37–5.51) were independent predictors of post-LT mortality. During the same period, 74 patients with ACLF died on the waiting list. In an intention-to-treat analysis, 1-year survival of patients with ACLF on the LT waiting list was 73% for ACLF-1 or -2 and 50% for ACLF-3. Conclusion: The results reveal wide variations in the listing of patients with ACLF in Europe despite favourable post-LT survival. Risk factors for mortality were identified, enabling a more precise prognostic assessment of patients with ACLF. Lay summary: Acute-on-chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation is an effective therapeutic option. This study has demonstrated that in Europe, referral and access to liver t

Published
2021

26. Liver transplantation for patients with acute-on-chronic liver failure (ACLF) in Europe: results of the ELITA/EF-CLIF collaborative study (ECLIS)

Author

Belli, L, Duvoux, C, Artzner, T, Bernal, W, Conti, S, Cortesi, P, Sacleux, S, Pageaux, G, Radenne, S, Trebicka, J, Fernandez, J, Perricone, G, Piano, S, Nadalin, S, Morelli, M, Martini, S, Polak, W, Zieniewicz, K, Toso, C, Berenguer, M, Iegri, C, Invernizzi, F, Volpes, R, Karam, V, Adam, R, Faitot, F, Rabinovich, L, Saliba, F, Meunier, L, Lesurtel, M, Uschner, F, Fondevila, C, Michard, B, Coilly, A, Meszaros, M, Poinsot, D, Schnitzbauer, A, De Carlis, L, Fumagalli, R, Angeli, P, Arroyo, V, Jalan, R, Fagiuoli, S, Belli, Luca S, Duvoux, Christophe, Artzner, Thierry, Bernal, William, Conti, Sara, Cortesi, Paolo A, Sacleux, Sophie-Caroline, Pageaux, George-Philippe, Radenne, Sylvie, Trebicka, Jonel, Fernandez, Javier, Perricone, Giovanni, Piano, Salvatore, Nadalin, Silvio, Morelli, Maria C, Martini, Silvia, Polak, Wojciech G, Zieniewicz, Krzysztof, Toso, Christian, Berenguer, Marina, Iegri, Claudia, Invernizzi, Federica, Volpes, Riccardo, Karam, Vincent, Adam, René, Faitot, Francoise, Rabinovich, Liane, Saliba, Faouzi, Meunier, Lucy, Lesurtel, Mickael, Uschner, Frank E, Fondevila, Costantino, Michard, Baptiste, Coilly, Audrey, Meszaros, Magdalena, Poinsot, Domitille, Schnitzbauer, Andreas, De Carlis, Luciano G, Fumagalli, Roberto, Angeli, Paolo, Arroyo, Vincente, Jalan, Rajiv, FAGIUOLI, STEFANO, Belli, L, Duvoux, C, Artzner, T, Bernal, W, Conti, S, Cortesi, P, Sacleux, S, Pageaux, G, Radenne, S, Trebicka, J, Fernandez, J, Perricone, G, Piano, S, Nadalin, S, Morelli, M, Martini, S, Polak, W, Zieniewicz, K, Toso, C, Berenguer, M, Iegri, C, Invernizzi, F, Volpes, R, Karam, V, Adam, R, Faitot, F, Rabinovich, L, Saliba, F, Meunier, L, Lesurtel, M, Uschner, F, Fondevila, C, Michard, B, Coilly, A, Meszaros, M, Poinsot, D, Schnitzbauer, A, De Carlis, L, Fumagalli, R, Angeli, P, Arroyo, V, Jalan, R, Fagiuoli, S, Belli, Luca S, Duvoux, Christophe, Artzner, Thierry, Bernal, William, Conti, Sara, Cortesi, Paolo A, Sacleux, Sophie-Caroline, Pageaux, George-Philippe, Radenne, Sylvie, Trebicka, Jonel, Fernandez, Javier, Perricone, Giovanni, Piano, Salvatore, Nadalin, Silvio, Morelli, Maria C, Martini, Silvia, Polak, Wojciech G, Zieniewicz, Krzysztof, Toso, Christian, Berenguer, Marina, Iegri, Claudia, Invernizzi, Federica, Volpes, Riccardo, Karam, Vincent, Adam, René, Faitot, Francoise, Rabinovich, Liane, Saliba, Faouzi, Meunier, Lucy, Lesurtel, Mickael, Uschner, Frank E, Fondevila, Costantino, Michard, Baptiste, Coilly, Audrey, Meszaros, Magdalena, Poinsot, Domitille, Schnitzbauer, Andreas, De Carlis, Luciano G, Fumagalli, Roberto, Angeli, Paolo, Arroyo, Vincente, Jalan, Rajiv, and FAGIUOLI, STEFANO

Abstract

Background and aims: Liver transplantation (LT) has been proposed to be an effective salvage therapy even for the sickest patients with acute-on-chronic liver failure (ACLF). This large collaborative study was designed to address the current clinical practice and outcomes of ACLF patients wait listed (WL) for LT in Europe. Methods: Retrospective study including 308 consecutive ACLF patients, listed in 20 centres across 8 European countries, from January 2018 to June 2019. Results: 2677 patients received a LT, 1216 (45.4%) for decompensated cirrhosis (DC). Of these, 234 (19.2%) had ACLF at LT: ACLF-1, 58 (4.8%); ACLF-2, 78 (6.4%); and ACLF-3, 98 (8.1%). Wide variations were observed amongst countries: France and Germany had high rates of ACLF-2/3 (27-41%); Italy, Switzerland, Poland and Netherlands had medium rates (9-15%); and United Kingdom and Spain had low rates (3-5%) (p <.0001). One-year probability of survival after LT for patients with ACLF was 81% (95% CI 74-87). Pre-LT arterial lactate levels >4 mmol/L (HR 3.14, 95% CI 1.37-7.19), recent infection from multi-drug resistant organisms (HR 3.67, 95% CI 1.63-8.28), and renal replacement therapy (HR 2.74, 95% CI 1.37-5.51) were independent predictors of post-LT mortality. During the same period, 74 patients with ACLF died on the WL. In an intention-to-treat analysis, one-year survival of ACLF patients on the LT WL was 73% for ACLF-1 or -2 and 50% for ACLF-3. Conclusion: The results reveal wide variations in listing patients with ACLF in Europe despite favorable post-LT survival. Risk factors for mortality were identified, allowing a more precise prognostic assessment of ACLF patients for potential LT. Lay summary: Acute on chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation is an effective therapeutic option. This study has demonstrated that in Europe, referral and access to liver transplantation (LT) for patients with ACLF needs to be harmonized to avoid inequities.

Published
2021

29. Soluble TIM3 and Its Ligands Galectin-9 and CEACAM1 Are in Disequilibrium During Alcohol-Related Liver Disease and Promote Impairment of Anti-bacterial Immunity

Author

Riva, Antonio, primary, Palma, Elena, additional, Devshi, Dhruti, additional, Corrigall, Douglas, additional, Adams, Huyen, additional, Heaton, Nigel, additional, Menon, Krishna, additional, Preziosi, Melissa, additional, Zamalloa, Ane, additional, Miquel, Rosa, additional, Ryan, Jennifer M., additional, Wright, Gavin, additional, Fairclough, Sarah, additional, Evans, Alexander, additional, Shawcross, Debbie, additional, Schierwagen, Robert, additional, Klein, Sabine, additional, Uschner, Frank E., additional, Praktiknjo, Michael, additional, Katzarov, Krum, additional, Hadzhiolova, Tanya, additional, Pavlova, Slava, additional, Simonova, Marieta, additional, Trebicka, Jonel, additional, Williams, Roger, additional, and Chokshi, Shilpa, additional

Published
2021
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30. The Role of Macrophage-Inducible C-Type Lectin in Different Stages of Chronic Liver Disease

Author

Schierwagen, Robert, Uschner, Frank E., Ortiz, Cristina, Torres, Sandra, Brol, Max J., Tyc, Olaf, Gu, Wenyi, Grimm, Christian, Zeuzem, Stefan, Plamper, Andreas, Pfeifer, Philipp, Zimmer, Sebastian, Welsch, Christoph, Schaefer, Liliana, Rheinwalt, Karl P., Clària i Enrich, Joan, Arroyo, Vicente, Trebicka, Jonel, Klein, Sabine, and Mandrekar, Pranoti

Subjects
Liver Cirrhosis, Immunology, Severity of Illness Index, Cystic fibrosis, Mice, ACLF, Animals, Humans, Immunology and Allergy, bacterial translocation, Lectins, C-Type, ddc:610, Liver diseases, Original Research, Mice, Knockout, Inflammation, Gene Expression Profiling, Liver Diseases, Macrophages, Malalties del fetge, fibrosis, NASH, Fibrosi quística, Inflamació, Disease Models, Animal, Gene Expression Regulation, inflammation, Disease Susceptibility, Transcriptome, Biomarkers
Abstract

The macrophage-inducible C-type lectin (mincle) is part of the innate immune system and acts as a pattern recognition receptor for pathogen-associated molecular patterns (PAMPS) and damage-associated molecular patterns (DAMPs). Ligand binding induces mincle activation which consequently interacts with the signaling adapter Fc receptor, SYK, and NF-kappa-B. There is also evidence that mincle expressed on macrophages promotes intestinal barrier integrity. However, little is known about the role of mincle in hepatic fibrosis, especially in more advanced disease stages. Mincle expression was measured in human liver samples from cirrhotic patients and donors collected at liver transplantation and in patients undergoing bariatric surgery. Human results were confirmed in rodent models of cirrhosis and acute-on-chronic liver failure (ACLF). In these models, the role of mincle was investigated in liver samples as well as in peripheral blood monocytes (PBMC), tissues from the kidney, spleen, small intestine, and heart. Additionally, mincle activation was stimulated in experimental non-alcoholic steatohepatitis (NASH) by treatment with mincle agonist trehalose-6,6-dibehenate (TDB). In human NASH, mincle is upregulated with increased collagen production. In ApoE deficient mice fed high-fat western diet (NASH model), mincle activation significantly increases hepatic collagen production. In human cirrhosis, mincle expression is also significantly upregulated. Furthermore, mincle expression is associated with the stage of chronic liver disease. This could be confirmed in rat models of cirrhosis and ACLF. ACLF was induced by LPS injection in cirrhotic rats. While mincle expression and downstream signaling via FC receptor gamma, SYK, and NF-kappa-B are upregulated in the liver, they are downregulated in PBMCs of these rats. Although mincle expressed on macrophages might be beneficial for intestinal barrier integrity, it seems to contribute to inflammation and fibrosis once the intestinal barrier becomes leaky in advanced stages of chronic liver disease.

Published
2020
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31. Systemic MCP-1 Levels Derive Mainly From Injured Liver and Are Associated With Complications in Cirrhosis

Author

Queck, Alexander, Bode, Hannah, Uschner, Frank E., Brol, Maximilian J., Graf, Christiana, Schulz, Martin, Jansen, Christian, Praktiknjo, Michael, Schierwagen, Robert, Klein, Sabine, Trautwein, Christian, Wasmuth, Hermann E., Berres, Marie-Luise, Trebicka, Jonel, and Lehmann, Jennifer

Subjects
Male, transjugular intrahepatic portosystemic shunt (TIPS), Kupffer Cells, Immunology, Acute-On-Chronic Liver Failure, Macrophage Activation, Liver Cirrhosis, Experimental, Mice, Inbred C57BL, Mice, acute-on-chronic liver failure (ACLF), Liver, inflammation, monocyte chemotactic protein 1 (MCP-1), Animals, ddc:610, Chemical and Drug Induced Liver Injury, Chemokine CCL2, Original Research, decompensated liver cirrhosis
Abstract

Background and Aims: Monocyte chemotactic protein-1 (MCP-1) is a potent chemoattractant for monocytes. It is involved in pathogenesis of several inflammatory diseases. Hepatic MCP-1 is a readout of macrophage activation. While inflammation is a major driver of liver disease progression, the origin and role of circulating MCP-1 as a biomarker remains unclear. Methods: Hepatic CC-chemokine ligand 2 (CCL2) expression and F4/80 staining for Kupffer cells were measured and correlated in a mouse model of chronic liver disease (inhalative CCl4 for 7 weeks). Next, hepatic RNA levels of CCL2 were measured in explanted livers of 39 patients after transplantation and correlated with severity of disease. Changes in MCP-1 were further evaluated in a rat model of experimental cirrhosis and acute-on-chronic liver failure (ACLF). Finally, we analyzed portal and hepatic vein levels of MCP-1 in patients receiving transjugular intrahepatic portosystemic shunt insertion for complications of portal hypertension. Results: In this mouse model of fibrotic hepatitis, hepatic expression of CCL2 (P = 0.009) and the amount of F4/80 positive cells in the liver (P < 0.001) significantly increased after induction of hepatitis by CCl4 compared to control animals. Moreover, strong correlation of hepatic CCL2 expression and F4/80 positive cells were seen (P = 0.023). Furthermore, in human liver explants, hepatic transcription levels of CCL2 correlated with the MELD score of the patients, and thus disease severity (P = 0.007). The experimental model of ACLF in rats revealed significantly higher levels of MCP-1 plasma (P = 0.028) and correlation of hepatic CCL2 expression (R = 0.69, P = 0.003). Particularly, plasma MCP-1 levels did not correlate with peripheral blood monocyte CCL2 expression. Finally, higher levels of MCP-1 were observed in the hepatic compared to the portal vein (P = 0.01) in patients receiving TIPS. Similarly, a positive correlation of MCP-1 with Child-Pugh score was observed (P = 0.018). Further, in the presence of ACLF, portal and hepatic vein levels of MCP-1 were significantly higher compared to patients without ACLF (both P = 0.039). Conclusion: Circulating levels of MCP-1 mainly derive from the injured liver and are associated with severity of liver disease. Therefore, liver macrophages contribute significantly to disease progression. Circulating MCP-1 may reflect the extent of hepatic macrophage activation.

Published
2020

32. Cardiodynamic state is associated with systemic inflammation and fatal acute-on-chronic liver failure

Author

Praktiknjo, Michael, Monteiro, Sofia, Grandt, Josephine, Kimer, Nina, Madsen, Jan L., Werge, Mikkel P., William, Peter, Brol, Maximilian J., Turco, Laura, Schierwagen, Robert, Chang, Johannes, Klein, Sabine, Uschner, Frank E., Welsch, Christoph, Moreau, Richard, Schepis, Filippo, Bendtsen, Flemming, Gluud, Lise L., Møller, Søren, Trebicka, Jonel, Praktiknjo, Michael, Monteiro, Sofia, Grandt, Josephine, Kimer, Nina, Madsen, Jan L., Werge, Mikkel P., William, Peter, Brol, Maximilian J., Turco, Laura, Schierwagen, Robert, Chang, Johannes, Klein, Sabine, Uschner, Frank E., Welsch, Christoph, Moreau, Richard, Schepis, Filippo, Bendtsen, Flemming, Gluud, Lise L., Møller, Søren, and Trebicka, Jonel

Abstract

Background & Aims: Acute-on-chronic liver failure (ACLF) is characterized by high short-term mortality and systemic inflammation (SI). Recently, different cardiodynamic states were shown to independently predict outcomes in cirrhosis. The relationship between cardiodynamic states, SI, and portal hypertension and their impact on ACLF development remains unclear. The aim of this study was therefore to evaluate the interplay of cardiodynamic state and SI on fatal ACLF development in cirrhosis. Results: At inclusion, hemodynamic measures including cardiac index (CI) and hepatic venous pressure gradient of 208 patients were measured. Patients were followed prospectively for fatal ACLF development (primary endpoint). SI was assessed by proinflammatory markers such as interleukins (ILs) 6 and 8 and soluble IL-33 receptor (sIL-33R). Patients were divided according to CI (<3.2; 3.2-4.2; >4.2 L/min/m2) in hypo- (n = 84), normo- (n = 69) and hyperdynamic group (n = 55). After a median follow-up of 3 years, the highest risk of fatal ACLF was seen in hyperdynamic (35%) and hypodynamic patients (25%) compared with normodynamic (14%) (P =.011). Hyperdynamic patients showed the highest rate of SI. The detectable level of IL-6 was an independent predictor of fatal ACLF development. Conclusions: Cirrhotic patients with hyperdynamic and hypodynamic circulation have a higher risk of fatal ACLF. Therefore, the cardiodynamic state is strongly associated with SI, which is an independent predictor of development of fatal ACLF.

Published
2020

33. Neprilysin-Dependent Neuropeptide Y Cleavage in the Liver Promotes Fibrosis by Blocking Npy-Receptor 1

Author

Ortiz, Cristina, primary, Klein, Sabine, additional, Reul, Winfried H., additional, Magdaleno, Fernando, additional, Gröschl, Stefanie, additional, Dietrich, Peter, additional, Schierwagen, Robert, additional, Uschner, Frank E., additional, Torres, Sandra, additional, Hieber, Christoph, additional, Meier, Caroline, additional, Kraus, Nico, additional, Tyc, Olaf, additional, Brol, Maximilian, additional, Zeuzem, Stefan, additional, Welsch, Christoph, additional, Poglitsch, Marko, additional, Hellerbrand, Claus, additional, Alfonso-Prieto, Mercedes, additional, Mira, Fabio, additional, auf dem Keller, Ulrich, additional, Tetzner, Anja, additional, Moore, Andrew, additional, and Trebicka, Jonel, additional

Published
2021
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34. Combination of phosphodiesterase‐5‐inhibitors and beta blockers improves experimental portal hypertension and erectile dysfunction

Author

Uschner, Frank E., primary, Glückert, Kathleen, additional, Paternostro, Rafael, additional, Gnad, Thorsten, additional, Schierwagen, Robert, additional, Mandorfer, Mattias, additional, Magdaleno, Fernando, additional, Ortiz, Cristina, additional, Schwarzkopf, Katharina, additional, Kamath, Patrick S., additional, Alessandria, Carlo, additional, Boesecke, Christoph, additional, Pfeifer, Alexander, additional, Reiberger, Thomas, additional, Kreisel, Wolfgang, additional, Sauerbruch, Tilman, additional, Ferlitsch, Arnulf, additional, Trebicka, Jonel, additional, and Klein, Sabine, additional

Published
2020
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35. Cardiodynamic state is associated with systemic inflammation and fatal acute‐on‐chronic liver failure

Author

Praktiknjo, Michael, primary, Monteiro, Sofia, additional, Grandt, Josephine, additional, Kimer, Nina, additional, Madsen, Jan L., additional, Werge, Mikkel P., additional, William, Peter, additional, Brol, Maximilian J., additional, Turco, Laura, additional, Schierwagen, Robert, additional, Chang, Johannes, additional, Klein, Sabine, additional, Uschner, Frank E., additional, Welsch, Christoph, additional, Moreau, Richard, additional, Schepis, Filippo, additional, Bendtsen, Flemming, additional, Gluud, Lise L., additional, Møller, Søren, additional, and Trebicka, Jonel, additional

Published
2020
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36. Systemic MCP-1 Levels Derive Mainly From Injured Liver and Are Associated With Complications in Cirrhosis

Author

Queck, Alexander, primary, Bode, Hannah, additional, Uschner, Frank E., additional, Brol, Maximilian J., additional, Graf, Christiana, additional, Schulz, Martin, additional, Jansen, Christian, additional, Praktiknjo, Michael, additional, Schierwagen, Robert, additional, Klein, Sabine, additional, Trautwein, Christian, additional, Wasmuth, Hermann E., additional, Berres, Marie-Luise, additional, Trebicka, Jonel, additional, and Lehmann, Jennifer, additional

Published
2020
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37. Compartmentalization of Immune Response and Microbial Translocation in Decompensated Cirrhosis

Author

Alvarez-Silva, Camila, Schierwagen, Robert, Pohlmann, Alessandra, Magdaleno, Fernando, Uschner, Frank E., Ryan, Patrick, Vehreschild, Maria J. G. T., Claria, Joan, Latz, Eicke, Lelouvier, Benjamin, Arumugam, Manimozhiyan, Trebicka, Jonel, Alvarez-Silva, Camila, Schierwagen, Robert, Pohlmann, Alessandra, Magdaleno, Fernando, Uschner, Frank E., Ryan, Patrick, Vehreschild, Maria J. G. T., Claria, Joan, Latz, Eicke, Lelouvier, Benjamin, Arumugam, Manimozhiyan, and Trebicka, Jonel

Published
2019

38. Sex specificity of kidney markers to assess prognosis in cirrhotic patients with TIPS

Author

Torner, Maria, primary, Mangal, Adjmal, additional, Scharnagl, Hubert, additional, Jansen, Christian, additional, Praktiknjo, Michael, additional, Queck, Alexander, additional, Gu, Wenyi, additional, Schierwagen, Robert, additional, Lehmann, Jennifer, additional, Uschner, Frank E., additional, Graf, Christiana, additional, Strassburg, Christian P., additional, Fernandez, Javier, additional, Stojakovic, Tatjana, additional, Woitas, Rainer, additional, and Trebicka, Jonel, additional

Published
2019
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39. Compartmentalization of Immune Response and Microbial Translocation in Decompensated Cirrhosis

Author

Alvarez-Silva, Camila, primary, Schierwagen, Robert, additional, Pohlmann, Alessandra, additional, Magdaleno, Fernando, additional, Uschner, Frank E., additional, Ryan, Patrick, additional, Vehreschild, Maria J. G. T., additional, Claria, Joan, additional, Latz, Eicke, additional, Lelouvier, Benjamin, additional, Arumugam, Manimozhiyan, additional, and Trebicka, Jonel, additional

Published
2019
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40. Left Ventricular Longitudinal Contractility Predicts Acute‐on‐Chronic Liver Failure Development and Mortality After Transjugular Intrahepatic Portosystemic Shunt

Author

Jansen, Christian, primary, Schröder, Anna, additional, Schueler, Robert, additional, Lehmann, Jennifer, additional, Praktiknjo, Michael, additional, Uschner, Frank E., additional, Schierwagen, Robert, additional, Thomas, Daniel, additional, Monteiro, Sofia, additional, Nickenig, Georg, additional, Strassburg, Christian P., additional, Meyer, Carsten, additional, Arroyo, Vicente, additional, Hammerstingl, Christoph, additional, and Trebicka, Jonel, additional

Published
2019
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41. Acute decompensation boosts hepatic collagen type III deposition and deteriorates experimental and human cirrhosis

Author

Praktiknjo, Michael, Lehmann, Jennifer, Nielsen, Mette J, Schierwagen, Robert, Uschner, Frank E, Meyer, Carsten, Thomas, Daniel, Strassburg, Christian P, Bendtsen, Flemming, Møller, Søren, Krag, Aleksander, Karsdal, Morten A, Leeming, Diana J, Trebicka, Jonel, Praktiknjo, Michael, Lehmann, Jennifer, Nielsen, Mette J, Schierwagen, Robert, Uschner, Frank E, Meyer, Carsten, Thomas, Daniel, Strassburg, Christian P, Bendtsen, Flemming, Møller, Søren, Krag, Aleksander, Karsdal, Morten A, Leeming, Diana J, and Trebicka, Jonel

Abstract

Patients with end-stage liver disease develop acute decompensation (AD) episodes, which become more frequent and might develop into acute-on-chronic liver failure (ACLF). However, it remains unknown how AD induces acceleration of liver disease. We hypothesized that remodeling of collagen type III plays a role in the acceleration of liver cirrhosis after AD and analyzed its formation (Pro-C3) and degradation (matrix metalloproteinase-degraded type III collagen [C3M]) markers in animal models and human disease. Bile duct ligation induced different stages of liver fibrosis in rats. Fibrosis development (hydroxyprolin content, sirius red staining, α-smooth muscle actin immunohistochemistry, messenger RNA of profibrotic cytokines), necroinflammation (aminotransferases levels), fibrolysis (matrix metalloproteinase 2 expression and activity, C1M, C4M), and Pro-C3 and C3M were analyzed 2, 3, 4, 5, and 6 weeks after bile duct ligation (n = 5 each group). In 110 patients with decompensated liver cirrhosis who underwent a transjugular intrahepatic portosystemic shunt procedure for AD, clinical and laboratory parameters as well as Pro-C3 and C3M were measured in blood samples from portal and hepatic veins and were collected just before the transjugular intrahepatic portosystemic shunt placement and 1-3 weeks later. Animal studies showed increased markers of collagen type III deposition with fibrosis, necroinflammation, and decompensation of liver cirrhosis, defined as ascites development. Higher Pro-C3 levels were associated with injury, disease severity scores (Model for End-Stage Liver Disease, Child-Pugh, chronic liver failure-C AD), ACLF development, and mortality. C3M decreased with AD and the chronic liver failure-C AD score. Collagen type III deposition ratio increased with the risk of ACLF development and mortality. Conclusion: We show for the first time that AD boosts collagen type III deposition in experimental and human cirrhosis, possibly contributing to the wors

Published
2018

42. Rho-kinase inhibitor coupled with peptide-modified albumin carrier reduces fibrogenesis and portal pressure in cirrhotic rats without systemic effects

Author

Magdaleno, Fernando, Klein, Sabine, Frohn, Franziska, Reker-Smit, Catharina, Uschner, Frank E., Schierwagen, Robert, Poelstra, Klaas, Beljaars, Leonie, Trebicka, Jonel, Nanomedicine & Drug Targeting, Groningen Research Institute of Pharmacy, Nanotechnology and Biophysics in Medicine (NANOBIOMED), and Biopharmaceuticals, Discovery, Design and Delivery (BDDD)

Published
2017

43. Sex specificity of kidney markers to assess prognosis in cirrhotic patients with TIPS.

Author

Torner, Maria, Mangal, Adjmal, Scharnagl, Hubert, Jansen, Christian, Praktiknjo, Michael, Queck, Alexander, Gu, Wenyi, Schierwagen, Robert, Lehmann, Jennifer, Uschner, Frank E., Graf, Christiana, Strassburg, Christian P., Fernandez, Javier, Stojakovic, Tatjana, Woitas, Rainer, and Trebicka, Jonel

Subjects
PROPENSITY score matching, LIVER transplantation, HUMAN sexuality, KIDNEYS
Abstract

Background & Aims: Renal function assessed by creatinine is a key prognostic factor in cirrhotic patients. However, creatinine is influenced by several factors, rendering interpretation difficult in some situations. This is especially important in early stages of renal dysfunction where renal impairment might not be accompanied by an increase in creatinine. Other parameters, such as cystatin C (CysC) and beta‐trace protein (BTP), have been evaluated to fill this gap. However, none of these studies have considered the role of the patient's sex. The present study analysed CysC and BTP to evaluate their prognostic value and differentiate them according to sex. Patients and methods: CysC and BTP were measured in 173 transjugular intrahepatic portosystemic shunt (TIPS)‐patients from the NEPTUN‐STUDY(NCT03628807) and analysed their relationship with mortality and sex. Propensity score for age, MELD, etiology and TIPS indication was used. Results: Cystatin C and BTP showed excellent correlations with creatinine values at baseline and follow‐up. CysC was an independent predictor of overall mortality (HR = 1.66(1.33‐2.06)) with an AUC of 0.75 and identified a cut‐off of 1.55 mg/L in the whole cohort. Interestingly, CysC was significantly lower in females, also after propensity score matching. In males, the only independent predictor was the creatinine level (HR = 1.54(1.25‐1.58)), while in females CysC levels independently predicted mortality (HR = 3.17(1.34‐7.52)). Conclusion: This study demonstrates for the first time that in TIPS‐patients creatinine predicts mortality in males better than in females, whereas CysC is a better predictor of mortality in females. These results may influence future clinical decisions on therapeutic options for example, allocation for liver transplantation in TIPS‐patients. [ABSTRACT FROM AUTHOR]

Published
2020
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44. Quantification of Liver Fibrosis at T1 and T2 Mapping with Extracellular Volume Fraction MRI: Preclinical Results

Author

Luetkens, Julian A., primary, Klein, Sabine, additional, Träber, Frank, additional, Schmeel, Frederic C., additional, Sprinkart, Alois M., additional, Kuetting, Daniel L. R., additional, Block, Wolfgang, additional, Uschner, Frank E., additional, Schierwagen, Robert, additional, Hittatiya, Kanishka, additional, Kristiansen, Glen, additional, Gieseke, Juergen, additional, Schild, Hans H., additional, Trebicka, Jonel, additional, and Kukuk, Guido M., additional

Published
2018
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45. Acute decompensation boosts hepatic collagen type III deposition and deteriorates experimental and human cirrhosis

Author

Praktiknjo, Michael, primary, Lehmann, Jennifer, additional, Nielsen, Mette J., additional, Schierwagen, Robert, additional, Uschner, Frank E., additional, Meyer, Carsten, additional, Thomas, Daniel, additional, Strassburg, Christian P., additional, Bendtsen, Flemming, additional, Møller, Søren, additional, Krag, Aleksander, additional, Karsdal, Morten A., additional, Leeming, Diana J., additional, and Trebicka, Jonel, additional

Published
2018
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47. Quantitative liver MRI including extracellular volume fraction for non-invasive quantification of liver fibrosis: a prospective proof-of-concept study

Author

Luetkens, Julian A, primary, Klein, Sabine, additional, Traeber, Frank, additional, Schmeel, Frederic C, additional, Sprinkart, Alois M, additional, Kuetting, Daniel L R, additional, Block, Wolfgang, additional, Hittatiya, Kanishka, additional, Uschner, Frank E, additional, Schierwagen, Robert, additional, Gieseke, Juergen, additional, Schild, Hans H, additional, Trebicka, Jonel, additional, and Kukuk, Guido M, additional

Published
2017
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48. Statins improve NASH via inhibition of RhoA and Ras

Author

Schierwagen, Robert, primary, Maybüchen, Lara, additional, Hittatiya, Kanishka, additional, Klein, Sabine, additional, Uschner, Frank E., additional, Braga, Tarcio T., additional, Franklin, Bernardo S., additional, Nickenig, Georg, additional, Strassburg, Christian P., additional, Plat, Jogchum, additional, Sauerbruch, Tilman, additional, Latz, Eicke, additional, Lütjohann, Dieter, additional, Zimmer, Sebastian, additional, and Trebicka, Jonel, additional

Published
2016
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49. Interplay of Matrix Stiffness and c-SRC in Hepatic Fibrosis

Author

Görtzen, Jan, primary, Schierwagen, Robert, additional, Bierwolf, Jeanette, additional, Klein, Sabine, additional, Uschner, Frank E., additional, van der Ven, Peter F., additional, Fürst, Dieter O., additional, Strassburg, Christian P., additional, Laleman, Wim, additional, Pollok, Jörg-Matthias, additional, and Trebicka, Jonel, additional

Published
2015
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50. Statins activate the canonical hedgehog-signaling and aggravate non-cirrhotic portal hypertension, but inhibit the non-canonical hedgehog signaling and cirrhotic portal hypertension

Author

Uschner, Frank E., primary, Ranabhat, Ganesh, additional, Choi, Steve S., additional, Granzow, Michaela, additional, Klein, Sabine, additional, Schierwagen, Robert, additional, Raskopf, Esther, additional, Gautsch, Sebastian, additional, van der Ven, Peter F. M., additional, Fürst, Dieter O., additional, Strassburg, Christian P., additional, Sauerbruch, Tilman, additional, Mae Diehl, Anna, additional, and Trebicka, Jonel, additional

Published
2015
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