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1. WED-379 Intrahepatic changes in immunologic and virologic markers during siRNA JNJ-73763989 (JNJ-3989) based treatment of chronic hepatitis B (CHB) patients: imaging mass cytometry (IMC) analyses from the INSIGHT study

Author

Thys, Kim, primary, Crabbe, Marjolein, additional, Wils, Hans, additional, Goehlmann, Hinrich, additional, Verheijden, Simon, additional, Lampertico, Pietro, additional, Asselah, Tarik, additional, Gane, Edward J., additional, Fung, Scott K., additional, Kennedy, Patrick, additional, Vanwolleghem, Thomas, additional, Janczewska, Ewa, additional, Wiesch, Julian Schulze zur, additional, Sulkowski, Mark S., additional, Guinard-Azadian, Carine, additional, Biermer, Michael, additional, and Lenz, Oliver, additional

Published
2024
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3. LBP-029 Efficacy and safety of 144 weeks of bulevirtide 2 mg or 10 mg monotherapy from the ongoing phase 3 study, MYR301

Author

Lampertico, Pietro, primary, Aleman, Soo, additional, Brunetto, Maurizia, additional, Blank, Antje, additional, Andreone, Pietro, additional, Bogomolov, Pavel, additional, Chulanov, Vladimir, additional, Mamonova, Nina, additional, Geyvandova, Natalia, additional, Morozov, Viacheslav, additional, Sagalova, Olga, additional, Stepanova, Tatyana, additional, Chee, Grace M., additional, Manuilov, Dmitry, additional, Li, Mingyang, additional, Tseng, Steve, additional, Lau, Audrey, additional, Osinusi, Anu, additional, zur Wiesch, Julian Schulze, additional, Cornberg, Markus, additional, Zeuzem, Stefan, additional, and Wedemeyer, Heiner, additional

Published
2024
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4. A multicenter randomized-controlled trial of nucleos(t)ide analogue cessation in HBeAg-negative chronic hepatitis B

Author

Florian van Bömmel, Kerstin Stein, Renate Heyne, Jörg Petersen, Peter Buggisch, Christoph Berg, Stefan Zeuzem, Andreas Stallmach, Martin Sprinzl, Eckart Schott, Anita Pathil-Warth, Ulrike von Arnim, Verena Keitel, Jürgen Lohmeyer, Karl-Georg Simon, Christian Trautwein, Andreas Trein, Dietrich Hüppe, Markus Cornberg, Frank Lammert, Patrick Ingiliz, Reinhart Zachoval, Holger Hinrichsen, Alexander Zipprich, Hartmuth Klinker, Julian Schulze zur Wiesch, Anett Schmiedeknecht, Oana Brosteanu, and Thomas Berg

Subjects
Hepatology
Published
2023
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5. Intrahepatic characterization of virological and immunological markers in two distinct populations of chronic hepatitis B: baseline assessment of core liver and fine needle aspiration biopsies from the investigational INSIGHT study

Author

Lampertico, Pietro, primary, Asselah, Tarik, additional, Gane, Edward J., additional, Fung, Scott K., additional, Kennedy, Patrick, additional, Vanwolleghem, Thomas, additional, Janczewska, Ewa, additional, zur Wiesch, Julian Schulze, additional, Sulkowski, Mark S., additional, Wils, Hans, additional, Colombo, Daniele Filippo, additional, Neto, Nadia, additional, de Troyer, Ewoud, additional, Van den Berge, Koen, additional, Göhlmann, Hinrich, additional, Aerssens, Jeroen, additional, Jerzorwski, John, additional, Anastasiou, Zacharias, additional, Lenz, Oliver, additional, Verbinnen, Thierry, additional, Kakuda, Thomas, additional, Guinard-Azadian, Carine, additional, Tuefferd, Marianne, additional, and Biermer, Michael, additional

Published
2023
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6. Increasing functional cure rate beyond 96 weeks after discontinuation of nucleos (t)ide analogue treatment in HBeAg-negative chronic hepatitis B: follow-up of the stop-NUC trial

Author

van Bömmel, Florian, primary, Stein, Kerstin, additional, Heyne, Renate, additional, Petersen, Jörg, additional, Buggisch, Peter, additional, Berg, Christoph, additional, Zeuzem, Stefan, additional, Stallmach, Andreas, additional, Sprinzl, Martin, additional, Schott, Eckart, additional, Pathil-Warth, Anita, additional, von Arnim, Ulrike, additional, Keitel, Verena, additional, Lohmeyer, Jürgen, additional, Georg, Simon Karl, additional, Trautwein, Christian, additional, Trein, Andreas, additional, Hüppe, Dietrich, additional, Cornberg, Markus, additional, Lammert, Frank, additional, Ingiliz, Patrick, additional, Zachoval, Reinhart, additional, Hinrichsen, Holger, additional, Zipprich, Alexander, additional, Klinker, Hartwig, additional, zur Wiesch, Julian Schulze, additional, Schmiedeknecht, Anett, additional, Brosteanu, Oana, additional, and Berg, Thomas, additional

Published
2023
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7. Identification of resistance-associated variants after sofosbuvir treatment in chronic hepatitis E patients

Author

Gömer, Andre, primary, Klöhn, Mara, additional, Jagst, Michelle, additional, Nocke, Maximilian, additional, Horvatits, Thomas, additional, zur Wiesch, Julian Schulze, additional, Pischke, Sven, additional, Hardtke, Svenja, additional, Müller, Tobias, additional, Wedemeyer, Heiner, additional, Cornberg, Markus, additional, Behrendt, Patrick, additional, Steinmann, Eike, additional, and Todt, Daniel, additional

Published
2023
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8. Efficacy and safety at 96 weeks of bulevirtide 2 mg or 10 mg monotherapy for chronic hepatitis D: results from an interim analysis of a phase 3 randomized study

Author

Wedemeyer, Heiner, primary, Aleman, Soo, additional, Brunetto, Maurizia, additional, Blank, Antje, additional, Andreone, Pietro, additional, Bogomolov, Pavel, additional, Chulanov, Vladimir, additional, Mamonova, Nina, additional, Geyvandova, Natalia, additional, Viacheslav, Morozov, additional, Sagalova, Olga, additional, Stepanova, Tatyana, additional, Manuilov, Dmitry, additional, Mercier, Renee-Claude, additional, An, Qi, additional, Flaherty, John F., additional, Osinusi, Anu, additional, Lau, Audrey, additional, zur Wiesch, Julian Schulze, additional, Cornberg, Markus, additional, Zeuzem, Stefan, additional, and Lampertico, Pietro, additional

Published
2023
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9. Improvements in ALT levels during Bulevirtide treatment for hepatitis D are seen regardless of virologic response

Author

Dietz-Fricke, Christopher, primary, Tacke, Frank, additional, Zöllner, Caroline, additional, Demir, Münevver, additional, Schmidt, Hartmut, additional, Schramm, Christoph, additional, Willuweit, Katharina, additional, Lange, Christian M., additional, Weber, Sabine, additional, Denk, Gerald, additional, Berg, Christoph, additional, Grottenthaler, Julia, additional, Merle, Uta, additional, Olkus, Alexander, additional, Zeuzem, Stefan, additional, Sprinzl, Kathrin, additional, Berg, Thomas, additional, van Bömmel, Florian, additional, Wiegand, Johannes, additional, Herta, Toni, additional, Seufferlein, Thomas, additional, Zizer, Eugen, additional, Dikopoulos, Nektarios, additional, Thimme, Robert, additional, Neumann-Haefelin, Christoph, additional, Galle, Peter, additional, Sprinzl, Martin, additional, Lohse, Ansgar W., additional, Kempski, Jan, additional, zur Wiesch, Julian Schulze, additional, Geier, Andreas, additional, Reiter, Florian P, additional, Schlevogt, Bernhard, additional, Goediker, Juliana, additional, Hofmann, Wolf Peter, additional, Buggisch, Peter, additional, Kahlhöfer, Julia, additional, Port, Kerstin, additional, Maasoumy, Benjamin, additional, Cornberg, Markus, additional, Wedemeyer, Heiner, additional, and Deterding, Katja, additional

Published
2023
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10. Efficacy and safety of vaccination againts SARS-CoV-2 in patients with vascular liver disease

Author

Perez-Campuzano, Valeria, primary, Pe, Rautou, additional, Marjot, Thomas, additional, Praktiknjo, Michael, additional, Alvarado-Tapias, Edilmar, additional, Turco, Laura, additional, Ibañez, Luis, additional, González-Alayón, Carlos, additional, puente, angela, additional, Llop, Elba, additional, Simón-Talero, Macarena, additional, Álvarez-Navascués, Carmen, additional, Reiberger, Thomas, additional, Verhelst, Xavier, additional, Téllez, Luis, additional, Orts, Lara, additional, Grassi, Giuseppe, additional, Baiges, Anna, additional, Audrey, Payance, additional, Trebicka, Jonel, additional, Villanueva, Càndid, additional, Morelli, Maria Cristina, additional, Murray, Sam, additional, Meacham, Georgina, additional, Luetgehetmann, Marc, additional, zur Wiesch, Julian Schulze, additional, Garcia Pagan, Juan Carlos, additional, Barnes, Eleanor, additional, Plessier, Aurélie, additional, and Hernandez-Gea, Virginia, additional

Published
2023
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11. Safety and efficacy of bulevirtide in combination with tenofovir disoproxil fumarate in patients with hepatitis B virus and hepatitis D virus coinfection (MYR202): a multicentre, randomised, parallel-group, open-label, phase 2 trial

Author

Wedemeyer, Heiner, primary, Schöneweis, Katrin, additional, Bogomolov, Pavel, additional, Blank, Antje, additional, Voronkova, Natalia, additional, Stepanova, Tatiana, additional, Sagalova, Olga, additional, Chulanov, Vladimir, additional, Osipenko, Marina, additional, Morozov, Viacheslav, additional, Geyvandova, Natalia, additional, Sleptsova, Snezhana, additional, Bakulin, Igor G, additional, Khaertynova, Ilsiyar, additional, Rusanova, Marina, additional, Pathil, Anita, additional, Merle, Uta, additional, Bremer, Birgit, additional, Allweiss, Lena, additional, Lempp, Florian A, additional, Port, Kerstin, additional, Haag, Mathias, additional, Schwab, Matthias, additional, zur Wiesch, Julian Schulze, additional, Cornberg, Markus, additional, Haefeli, Walter E, additional, Dandri, Maura, additional, Alexandrov, Alexander, additional, and Urban, Stephan, additional

Published
2023
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12. Failure on voxilaprevir, velpatasvir, sofosbuvir and efficacy of rescue therapy

Author

Ada Bertoli, Michael P. Manns, M. Katja Deterding, Vanni Borghi, Silvia Barbaliscia, Elisabetta Degasperi, Julian Schulze zur Wiesch, Velia Chiara Di Maio, Ansgar W. Lohse, Wolfgang Schmidt, Markus Cornberg, Christophe Moreno, Tomas Beyer, Federico García, Johannes Vermehren, Pietro Lampertico, Andreas E. Kremer, Laura Sighinolfi, Felix Piecha, Magdalena Lara, Pier Luigi Toniutto, Christoph Sarrazin, Antonio Craxì, Francesca Ceccherini-Silberstein, Jonas Schreiber, Jesús Santos, Ana Belén Pérez, Alessio Aghemo, William Gennari, Lorenzo Magenta, Manuel Alberto Macias Rodriguez, Heiner Wedermeyer, Ana Fuentes, Stephan Grunwald, Jose Miguel Rosales Zabal, Francisco Téllez, Dolores Merino, Burkhard Jäger, Miguel García Deltoro, Juan Manuel Pascasio-Acevedo, Blanca Figueruela, Andreas Stallmach, Renate Heyne, Valeria Ghisetti, Christoph P. Berg, Carlo Federico Perno, Elisa Fernández-Fuertes, Nikolaus Kordecki, Ana María Martinez Sapiña, Natalia Chueca, Andreas Herrmann, Eva Jägel-Guedes, Vincenza Calvaruso, Maurizio Zazzi, Massimo Andreoni, Lucio Boglione, Mario Angelico, Simona Francioso, Giuseppe Cariti, Cristina Quilez, Tiziano Allice, Christiana Graf, Leopoldo Muñoz-Medina, Fausto Baldanti, Rudolf E. Stauber, Jürgen Siebler, Julia Dietz, Maria Josefa Rodriguez Pardo, Kerstin Port, Heinz Zoller, Juan Carlos Alados, Stefan Zeuzem, Juan Ignacio Arenas Ruiz-Tapiador, Joaquín Cabezas, Stefania Paolucci, Axels Baumgarten, Kai-Henrik Peiffer, Adolfo de Salazar, Pietro Pozzoni, Miguel Jimenez, Hjördis Möller, Dietz J., Di Maio V.C., de Salazar A., Merino D., Vermehren J., Paolucci S., Kremer A.E., Lara M., Pardo M.R., Zoller H., Degasperi E., Peiffer K.-H., Sighinolfi L., Tellez F., Graf C., Ghisetti V., Schreiber J., Fernandez-Fuertes E., Boglione L., Munoz-Medina L., Stauber R., Gennari W., Figueruela B., Santos J., Lampertico P., Zeuzem S., Ceccherini-Silberstein F., Garcia F., Sarrazin C., Aghemo A., Allice T., Andreoni M., Angelico M., Baldanti F., Barbaliscia S., Bertoli A., Borghi V., Calvaruso V., Cariti G., Craxi A., Francioso S., Perno C.F., Pozzoni P., Toniutto P.L., Zazzi M., Perez A.B., Quilez C., Alados J.C., Cabezas J., Ruiz-Tapiador J.I.A., Jimenez M., Pascasio-Acevedo J.M., Rodriguez M.A.M., Zabal J.M.R., Deltoro M.G., Sapina A.M.M., Fuentes A., Chueca N., Berg C.P., Herrmann A., Stallmach A., Port K., Katja Deterding M., Wedermeyer H., Cornberg M., Manns M.P., Moreno C., Wiesch J.S.Z., Piecha F., Lohse A., Siebler J., Kordecki N., Magenta L., Jager B., Moller H., Heyne R., Beyer T., Grunwald S., Baumgarten A., Jagel-Guedes E., and Schmidt W.

Subjects
0301 basic medicine, Hepatitis C Virus, medicine.medical_specialty, Sofosbuvir, Voxilaprevir, Population, resistance-associated substitutions, Direct-acting antiviral, Voxilaprevir/velpatasvir/sofosbuvir, Gastroenterology, Settore MED/07, Telaprevir, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Voxilaprevir/Velpatasvir/Sofosbuvir, Internal medicine, Boceprevir, Rescue therapy, medicine, Resistance-associated substitution, education, direct-acting antivirals, DAA, education.field_of_study, Hepatology, business.industry, virus diseases, Glecaprevir, HCV, rescue therapy, digestive system diseases, Pibrentasvir, Regimen, 030104 developmental biology, chemistry, 030211 gastroenterology & hepatology, Hepatitis C viru, business, medicine.drug
Abstract

Background & Aims There are limited data on patients with chronic HCV infection in whom combination voxilaprevir (VOX), velpatasvir (VEL), sofosbuvir (SOF) retreatment fails. Thus, we aimed to assess treatment failure and rescue treatment options in these patients. Methods Samples from 40 patients with HCV genotypes (GT) 1-4 in whom VOX/VEL/SOF retreatment failed were collected within the European Resistance Study Group. Population-based resistance analyses were conducted and clinical parameters and retreatment efficacies were evaluated retrospectively in 22 patients. Results Most VOX/VEL/SOF failure patients were infected with HCV GT3a (n = 18, 45%) or GT1a (n = 11, 28%) and had cirrhosis (n = 28, 70%). Previous treatments included an NS3-inhibitor (30%), an NS5A-inhibitor (100%) and SOF (85%). Baseline RAS data from a subgroup of patients before VOX/VEL/SOF retreatment (78%) showed few NS3 RASs apart from Q80K in GT1a (40%), typical NS5A RAS patterns in most patients (74%) and no S282T in NS5B. Sequencing after VOX/VEL/SOF failure was available in 98% of patients and showed only minor changes for NS3 and NS5A RASs. In 22 patients, rescue treatment was initiated with glecaprevir, pibrentasvir alone (n = 2) or with SOF±ribavirin (n = 15), VOX/VEL/SOF±ribavirin (n = 4) or VEL/SOF and ribavirin (n = 1) for 12 to 24 weeks. Sustained virologic response was achieved in 17/21 (81%) patients with a final treatment outcome. Of these, 2 GT3a-infected patients had virologic failure after rescue treatment with VEL/SOF or glecaprevir/pibrentasvir+SOF+ribavirin, and 2 patients with cirrhosis died during treatment or before reaching SVR12. Conclusions VOX/VEL/SOF failure was mainly observed in HCV GT3- and GT1a-infected patients with cirrhosis and was not associated with specific RAS patterns within NS3, NS5A or NS5B target regions. Rescue treatment with multiple targeted therapies was effective in most patients. Lay summary The advent of direct-acting antivirals has enabled the effective cure of chronic hepatitis C in most patients. However, treatment failure occurs in some patients, who are often retreated with a combination regimen called VOX/VEL/SOF, which is associated with very high rates of cure. However, VOX/VEL/SOF retreatment also fails in some patients. Herein, we analysed samples from patients in whom VOX/VEL/SOF retreatment failed and we assessed the efficacy of different rescue therapies, showing that rescue treatment is effective in most patients (81%).

Published
2021
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13. Bulevirtide treatment of hepatitis D in Germany: multicentre real-world experience

Author

Dietz, Christopher, primary, Tacke, Frank, additional, Zöllner, Caroline, additional, Demir, Münevver, additional, Schmidt, Hartmut, additional, Schramm, Christoph, additional, Willuweit, Katharina, additional, Lange, Christian M., additional, Denk, Gerald, additional, Weber, Sabine, additional, Berg, Christoph, additional, Grottenthaler, Julia, additional, Merle, Uta, additional, Olkus, Alexander, additional, Zeuzem, Stefan, additional, Sprinzl, Kathrin, additional, Berg, Thomas, additional, Wiegand, Johannes, additional, van Bömmel, Florian, additional, Herta, Toni, additional, Seufferlein, Thomas, additional, Zizer, Eugen, additional, Dikopoulos, Nektarios, additional, Thimme, Robert, additional, Neumann-Haefelin, Christoph, additional, Galle, Peter, additional, Sprinzl, Martin, additional, Lohse, Ansgar W., additional, zur Wiesch, Julian Schulze, additional, Kempski, Jan, additional, Geier, Andreas, additional, Reiter, Florian P, additional, Hofmann, Wolf Peter, additional, Kahlhöfer, Julia, additional, Maasoumy, Benjamin, additional, Port, Kerstin, additional, Cornberg, Markus, additional, Wedemeyer, Heiner, additional, and Deterding, Katja, additional

Published
2022
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15. T cell and humoral immune response to multiple SARS-CoV-2 variants including omicron (B1.1.529) after two doses of COVID-19 vaccine in patients with cirrhosis and liver diseases requiring immunosuppression: data from the EASL COVID-Hep network

Author

Murray, Sam, primary, Longet, Stephanie, additional, Tipton, Tom, additional, Londoño, Maria Carlota, additional, Pose, Elisa, additional, Laidlaw, Stephen, additional, Nguyen, Dung, additional, Meacham, Georgina, additional, Lim, Zixiang, additional, Dimitriadis, Stavros, additional, Irwin, Sophie, additional, Cook, Jonathan, additional, Iavarone, Massimo, additional, Lampertico, Pietro, additional, Hernandez-Gea, Virginia, additional, Garcia Pagan, Juan Carlos, additional, zur Wiesch, Julian Schulze, additional, Sterneck, Martina, additional, Russo, Francesco Paolo, additional, Satsangi, Jack, additional, Dunachie, Susanna, additional, Klenerman, Paul, additional, Goodyear, Carl, additional, McInnes, Iain B., additional, Ginès, Pere, additional, Carroll, Miles, additional, Marjot, Thomas, additional, and Barnes, Eleanor, additional

Published
2022
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16. Efficacy and safety of bulevirtide monotherapy given at 2 mg or 10 mg dose level once daily for treatment of chronic hepatitis delta: week 48 primary end point results from a phase 3 randomized, multicenter, parallel design study

Author

Wedemeyer, Heiner, primary, Aleman, Soo, additional, Brunetto, Maurizia, additional, Blank, Antje, additional, Andreone, Pietro, additional, Bogomolov, Pavel, additional, Chulanov, Vladimir, additional, Mamonova, Nina, additional, Geyvandova, Natalia, additional, Viacheslav, Morozov, additional, Sagalova, Olga, additional, Stepanova, Tatyana, additional, Manuilov, Dmitry, additional, Suri, Vithika, additional, An, Qi, additional, Flaherty, John F., additional, Osinusi, Anu, additional, zur Wiesch, Julian Schulze, additional, Cornberg, Markus, additional, Zeuzem, Stefan, additional, and Lampertico, Pietro, additional

Published
2022
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17. Sofosbuvir plus velpatisvir for 8 weeks in patients with acute hepatitis C: multicenter, single arm, phase 2 study (The HepNet acute HCV-V study)

Author

Maasoumy, Benjamin, primary, Ingiliz, Patrick, additional, Spinner, Christoph, additional, Cordes, Christiane, additional, Stellbrink, Hans-Jürgen, additional, zur Wiesch, Julian Schulze, additional, Schneeweiß, Stephan M, additional, Deterding, Katja, additional, Müller, Tobias, additional, Kahlhöfer, Julia, additional, Dörge, Petra, additional, von Karpowitz, Maria, additional, Manns, Michael P., additional, Wedemeyer, Heiner, additional, and Cornberg, Markus, additional

Published
2022
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18. Effectiveness of voxilaprevir/velpatasvir/sofosbuvir in hepatitis C patients previously treated with direct-acting antiviral agents (DAA)

Author

Graf, Christiana, primary, Dietz, Julia, additional, Müllhaupt, Beat, additional, Buggisch, Peter, additional, Schattenberg, Jörn, additional, Antoni, Christoph, additional, Mauss, Stefan, additional, Durmashkina, Elena, additional, Niederau, Claus, additional, Discher, Thomas, additional, zur Wiesch, Julian Schulze, additional, Müller, Tobias, additional, Berg, Thomas, additional, Neumann-Haefelin, Christoph, additional, Berg, Christoph, additional, Zeuzem, Stefan, additional, and Sarrazin, Christoph, additional

Published
2022
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19. Long-term follow-up of HCV resistance-associated substitutions after DAA treatment failure

Author

Dietz, Julia, primary, Müllhaupt, Beat, additional, Buggisch, Peter, additional, Graf, Christiana, additional, Peiffer, Kai-Henrik, additional, Matschenz, Katrin, additional, Schattenberg, Jörn, additional, Mauss, Stefan, additional, Antoni, Christoph, additional, Durmashkina, Elena, additional, Niederau, Claus, additional, Discher, Thomas, additional, Trauth, Janina, additional, Dultz, Georg, additional, zur Wiesch, Julian Schulze, additional, Piecha, Felix, additional, Klinker, Hartwig, additional, Müller, Tobias, additional, Neumann-Haefelin, Christoph, additional, Berg, Thomas, additional, Berg, Christoph, additional, Zeuzem, Stefan, additional, and Sarrazin, Christoph, additional

Published
2022
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20. Humoral and cellular immune responses to SARS-CoV-2 vaccination across multiple vaccine platforms and liver disease types: an EASL registry multicentre prospective cohort study

Author

Marjot, Thomas, primary, Murray, Sam, additional, Pose, Elisa, additional, Lim, Zixiang, additional, Londoño, Maria Carlota, additional, Wittner, Melanie, additional, Luetgehetmann, Marc, additional, Hernandez-Gea, Virginia, additional, Garcia Pagan, Juan Carlos, additional, Schaub, Golda, additional, Duengelhoef, Paul, additional, Sterneck, Martina, additional, Lohse, Ansgar W., additional, Trivedi, Palak, additional, Bhandal, Khushpreet, additional, Mullish, Benjamin H., additional, Manousou, Pinelopi, additional, Burra, Patrizia, additional, Facchetti, Floriana, additional, Dobson, Susan L., additional, Deeks, Alexandra S., additional, Turtle, Lance, additional, Klenerman, Paul, additional, Dunachie, Susanna, additional, Ginès, Pere, additional, Iavarone, Massimo, additional, zur Wiesch, Julian Schulze, additional, Russo, Francesco Paolo, additional, and Barnes, Eleanor, additional

Published
2022
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21. Characteristics of hepatitis C virus resistance in an international cohort after a decade of direct-acting antivirals

Author

Howe, Anita Y.M., primary, Rodrigo, Chaturaka, additional, Cunningham, Evan B., additional, Douglas, Mark W., additional, Dietz, Julia, additional, Grebely, Jason, additional, Popping, Stephanie, additional, Sfalcin, Javier Alejandro, additional, Parczewski, Milosz, additional, Sarrazin, Christoph, additional, de Salazar, Adolfo, additional, Fuentes, Ana, additional, Sayan, Murat, additional, Quer, Josep, additional, Kjellin, Midori, additional, Kileng, Hege, additional, Mor, Orna, additional, Lennerstrand, Johan, additional, Fourati, Slim, additional, Di Maio, Velia Chiara, additional, Chulanov, Vladimir, additional, Pawlotsky, Jean-Michel, additional, Harrigan, P. Richard, additional, Ceccherini-Silberstein, Francesca, additional, Garcia, Federico, additional, Martinello, Marianne, additional, Matthews, Gail, additional, Fernando, Fay Fabián, additional, Esteban, Juan I., additional, Müllhaupt, Beat, additional, Wiesch, Julian Schulze zur, additional, Buggisch, Peter, additional, Neumann-Haefelin, Christoph, additional, Berg, Thomas, additional, Berg, Christoph P., additional, Schattenberg, Jörn M., additional, Moreno, Christophe, additional, Stauber, Rudolf, additional, Lloyd, Andrew, additional, Dore, Gregory, additional, Applegate, Tanya, additional, Ignacio, Juan, additional, Garcia-Cehic, Damir, additional, Gregori, Josep, additional, Rodriguez-Frias, Francisco, additional, Rando, Ariadna, additional, Gozlan, Yael, additional, Angelico, Mario, additional, Andreoni, Massimo, additional, Babudieri, Sergio, additional, Bertoli, Ada, additional, Cento, Valeria, additional, Coppola, Nicola, additional, Craxì, Antonio, additional, Paolucci, Stefania, additional, Parruti, Giustino, additional, Pasquazzi, Caterina, additional, Perno, Carlo Federico, additional, Teti, Elisabetta, additional, Vironet, C., additional, Lannergård, Anders, additional, Duberg, Ann-Sofi, additional, Aleman, Soo, additional, Gutteberg, Tore, additional, Soulier, Alexandre, additional, Gourgeon, Aurélie, additional, Chevaliez, Stephane, additional, Pol, Stanislas, additional, Carrat, Fabrice, additional, Salmon, Dominique, additional, Kaiser, Rolf, additional, Knopes, Elena, additional, Gomes, Perpetua, additional, de Kneght, Rob, additional, Rijnders, Bart, additional, Poljak, Mario, additional, Lunar, Maja, additional, Usubillaga, Rafael, additional, Seguin_Devaux, Carole, additional, Tay, Enoch, additional, Wilson, Caroline, additional, Wang, Dao Sen, additional, George, Jacob, additional, Kok, Jen, additional, Pérez, Ana Belén, additional, Chueca, Natalia, additional, García-Deltoro, Miguel, additional, Martínez-Sapiña, Ana María, additional, Lara-Pérez, María Magdalena, additional, García-Bujalance, Silvia, additional, Aldámiz-Echevarría, Teresa, additional, Vera-Méndez, Francisco Jesús, additional, Pineda, Juan Antonio, additional, Casado, Marta, additional, Pascasio, Juan Manuel, additional, Salmerón, Javier, additional, Alados-Arboledas, Juan Carlos, additional, Poyato, Antonio, additional, Téllez, Francisco, additional, Rivero-Juárez, Antonio, additional, Merino, Dolores, additional, Vivancos-Gallego, María Jesús, additional, Rosales-Zábal, José Miguel, additional, Ocete, María Dolores, additional, Simón, Miguel Ángel, additional, Rincón, Pilar, additional, Reus, Sergi, additional, De la Iglesia, Alberto, additional, García-Arata, Isabel, additional, Jiménez, Miguel, additional, Jiménez, Fernando, additional, Hernández-Quero, José, additional, Galera, Carlos, additional, Balghata, Mohamed Omar, additional, Primo, Joaquín, additional, Masiá, Mar, additional, Espinosa, Nuria, additional, Delgado, Marcial, additional, von-Wichmann, Miguel Ángel, additional, Collado, Antonio, additional, Santos, Jesús, additional, Mínguez, Carlos, additional, Díaz-Flores, Felícitas, additional, Fernández, Elisa, additional, Bernal, Enrique, additional, De Juan, José, additional, Antón, José Joaquín, additional, Vélez, Mónica, additional, Aguilera, Antonio, additional, Navarro, Daniel, additional, Arenas, Juan Ignacio, additional, Fernández, Clotilde, additional, Espinosa, María Dolores, additional, Ríos, María José, additional, Alonso, Roberto, additional, Hidalgo, Carmen, additional, Hernández, Rosario, additional, Téllez, María Jesús, additional, Rodríguez, Francisco Javier, additional, Antequera, Pedro, additional, Delgado, Cristina, additional, Martín, Patricia, additional, Crespo, Javier, additional, Becerril, Berta, additional, Pérez, Oscar, additional, García-Herola, Antonio, additional, Montero, José, additional, Freyre, Carolina, additional, Grau, Concepción, additional, Cabezas, Joaquin, additional, Jimenez, Miguel, additional, Rodriguez, Manuel Alberto Macias, additional, Quilez, Cristina, additional, Pardo, Maria Rodriguez, additional, Muñoz-Medina, Leopoldo, additional, and Figueruela, Blanca, additional

Published
2022
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22. Interleukin-9 protects from early podocyte injury and progressive glomerulosclerosis in Adriamycin-induced nephropathy

Author

Tingting Xiong, Victor G. Puelles, Hanna Taipaleenmäki, Jasper F. Nies, Malte Wunderlich, Martina Becker, Tobias A. Fuchs, Ann-Christin Gnirck, Stefan Wirtz, Constantin Rickassel, Julian Schulze zur Wiesch, Ulf Panzer, Jan-Eric Turner, Elion Hoxha, Thorsten Wiech, Mylène Divivier, Madena Attar, Catherine Meyer-Schwesinger, and Tobias B. Huber

Subjects
0301 basic medicine, 030232 urology & nephrology, Nephropathy, Podocyte, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, Focal segmental glomerulosclerosis, medicine, Animals, Humans, Interleukin 9, Lymphocytes, Glomerulosclerosis, Focal Segmental, Podocytes, business.industry, Innate lymphoid cell, Interleukin-9, Glomerulosclerosis, medicine.disease, Immunity, Innate, Proteinuria, 030104 developmental biology, medicine.anatomical_structure, Doxorubicin, Nephrology, Cancer research, business, Kidney disease
Abstract

A wide spectrum of immunological functions has been attributed to Interleukin 9 (IL-9), including effects on the survival and proliferation of immune and parenchymal cells. In recent years, emerging evidence suggests that IL-9 expression can promote tissue repair in inflammatory conditions. However, data about the involvement of IL-9 in kidney tissue protection is very limited. Here, we investigated the role of IL-9 in Adriamycin-induced nephropathy (AN), a mouse model for proteinuric chronic kidney disease. Compared to wild type mice, IL-9 knockout (Il9−/−) mice with AN displayed accelerated development of proteinuria, aggravated glomerulosclerosis and deterioration of kidney function. At an early stage of disease, the Il9−/− mice already displayed a higher extent of glomerular podocyte injury and loss of podocyte number compared to wild type mice. In the kidney, T cells and innate lymphoid cells produced IL-9. However, selective deficiency of IL-9 in the innate immune system in Il9−/−Rag2−/− mice that lack T and B cells did not alter the outcome of AN, indicating that IL-9 derived from the adaptive immune system was the major driver of tissue protection in this model. Mechanistically, we could show that podocytes expressed the IL-9 receptor in vivo and that IL-9 signaling protects podocytes from Adriamycin-induced apoptosis in vitro. Finally, in vivo treatment with IL-9 effectively protected wild type mice from glomerulosclerosis and kidney failure in the AN model. The detection of increased serum IL-9 levels in patients with primary focal and segmental glomerulosclerosis further suggests that IL-9 production is induced by glomerular injury in humans. Thus, IL-9 confers protection against experimental glomerulosclerosis, identifying the IL-9 pathway as a potential therapeutic target in proteinuric chronic kidney disease.

Published
2020
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24. Frequency of IRF5+ dendritic cells is associated with the TLR7-induced inflammatory cytokine response in SARS-CoV-2 infection

Author

Leon Cords, Robin Woost, Silke Kummer, Thomas T. Brehm, Stefan Kluge, Stefan Schmiedel, Sabine Jordan, Ansgar W. Lohse, Marcus Altfeld, Marylyn M. Addo, Julian Schulze zur Wiesch, and Claudia Beisel

Subjects
Immunology, Immunology and Allergy, Hematology, Molecular Biology, Biochemistry
Abstract

The SARS-CoV-2 infection leads to enhanced inflammation driven by innate immune responses. Upon TLR7 stimulation, dendritic cells (DC) mediate the production of inflammatory cytokines, and in particular of type I interferons (IFN). Especially in DCs, IRF5 is a key transcription factor that regulates pathogen-induced immune responses via activation of the MyD88-dependent TLR signaling pathway. In the current study, the frequencies of IRF5+ DCs and the association with innate cytokine responses in SARS-CoV-2 infected individuals with different disease courses were investigated. In addition to a decreased number of mDC and pDC subsets, we could show reduced relative IRF5+ frequencies in mDCs of SARS-CoV-2 infected individuals compared with healthy donors. Functionally, mDCs of COVID-19 patients produced lower levels of IL-6 in response to in vitro TLR7 stimulation. IRF5+ mDCs more frequently produced IL-6 and TNF-α compared to their IRF5- counterparts upon TLR7 ligation. The correlation of IRF5+ mDCs with the frequencies of IL-6 and TNF-α producing mDCs were indicators for a role of IRF5 in the regulation of cytokine responses in mDCs. In conclusion, our data provide further insights into the underlying mechanisms of TLR7-dependent immune dysfunction and identify IRF5 as a potential immunomodulatory target in SARS-CoV-2 infection.

Published
2023
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25. Humoral and cellular immune responses to SARS-CoV-2 vaccination across multiple vaccine platforms and liver disease types: an EASL registry multicentre prospective cohort study

Author

Thomas Marjot, Sam Murray, Elisa Pose, Zixiang Lim, Maria Carlota Londoño, Melanie Wittner, Marc Luetgehetmann, Virginia Hernandez-Gea, Juan Carlos Garcia Pagan, Golda Schaub, Paul Duengelhoef, Martina Sterneck, Ansgar W. Lohse, Palak Trivedi, Khushpreet Bhandal, Benjamin H. Mullish, Pinelopi Manousou, Patrizia Burra, Floriana Facchetti, Susan L. Dobson, Alexandra S. Deeks, Lance Turtle, Paul Klenerman, Susanna Dunachie, Pere Ginès, Massimo Iavarone, Julian Schulze zur Wiesch, Francesco Paolo Russo, and Eleanor Barnes

Subjects
Hepatology
Published
2022
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27. Long-term follow-up of HCV resistance-associated substitutions after DAA treatment failure

Author

Julia Dietz, Beat Müllhaupt, Peter Buggisch, Christiana Graf, Kai-Henrik Peiffer, Katrin Matschenz, Jörn Schattenberg, Stefan Mauss, Christoph Antoni, Elena Durmashkina, Claus Niederau, Thomas Discher, Janina Trauth, Georg Dultz, Julian Schulze zur Wiesch, Felix Piecha, Hartwig Klinker, Tobias Müller, Christoph Neumann-Haefelin, Thomas Berg, Christoph Berg, Stefan Zeuzem, and Christoph Sarrazin

Subjects
Hepatology
Published
2022
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29. Remdesivir-induced emergence of SARS-CoV2 variants in patients with prolonged infection

Author

Andreas Heyer, Thomas Günther, Alexis Robitaille, Marc Lütgehetmann, Marylyn M. Addo, Dominik Jarczak, Stefan Kluge, Martin Aepfelbacher, Julian Schulze zur Wiesch, Nicole Fischer, and Adam Grundhoff

Subjects
Alanine, SARS-CoV-2, Pneumonia, Viral, RNA-Dependent RNA Polymerase, Antiviral Agents, Adenosine Monophosphate, General Biochemistry, Genetics and Molecular Biology, COVID-19 Drug Treatment, Betacoronavirus, Disease Progression, Humans, RNA, Viral, Coronavirus Infections, Pandemics
Abstract

We here investigate the impact of antiviral treatments such as remdesivir on intra-host genomic diversity and emergence of SARS-CoV2 variants in patients with a prolonged course of infection. Sequencing and variant analysis performed in 112 longitudinal respiratory samples from 14 SARS-CoV2-infected patients with severe disease progression show that major frequency variants do not generally arise during prolonged infection. However, remdesivir treatment can increase intra-host genomic diversity and result in the emergence of novel major variant species harboring fixed mutations. This is particularly evident in a patient with B cell depletion who rapidly developed mutations in the RNA-dependent RNA polymerase gene following remdesivir treatment. Remdesivir treatment-associated emergence of novel variants is of great interest in light of current treatment guidelines for hospitalized patients suffering from severe SARS-CoV2 disease, as well as the potential use of remdesivir to preventively treat non-hospitalized patients at high risk for severe disease progression.

Published
2022
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30. OAB-049: Poor post-vaccination anti-SARS-CoV-2-antibody response in patients with Multiple Myeloma correlates with low CD19+ B-lymphocyte count and anti-CD38 treatment

Author

Ghandili, Susanne, primary, Schönlein, Martin, additional, Lütgehetmann, Marc, additional, Wiesch, Julian Schulze zur, additional, Becher, Heiko, additional, Bokemeyer, Carsten, additional, Sinn, Marianne, additional, Weisel, Katja, additional, and Leypoldt, Lisa, additional

Published
2021
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31. Seroprevalence of SARS-CoV-2 antibodies among hospital workers in a German tertiary care center: A sequential follow-up study

Author

Julia Küchen, Julian Schulze zur Wiesch, Veronika Schlicker, Marc Lütgehetmann, Johannes K.-M. Knobloch, Felix Ullrich, Stefan Schmiedel, Dorothee Schwinge, Thomas Theo Brehm, Ansgar W. Lohse, Marylyn M. Addo, Sibylle Lampalzer, Michelle Thompson, and Samuel Huber

Subjects
Adult, Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Health Personnel, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Psychological intervention, Seroprevalence, Hospital workers, 010501 environmental sciences, Antibodies, Viral, 01 natural sciences, Tertiary care, Article, Tertiary Care Centers, 03 medical and health sciences, 0302 clinical medicine, Seroepidemiologic Studies, Germany, Humans, Healthcare workers, Medicine, Infection control, 030212 general & internal medicine, 0105 earth and related environmental sciences, Infection Control, biology, SARS-CoV-2, business.industry, Follow up studies, Public Health, Environmental and Occupational Health, COVID-19, virus diseases, Middle Aged, Seroconversion, Immunoglobulin G, Emergency medicine, biology.protein, Female, Antibody, business
Abstract

We sequentially assessed the presence of SARS-CoV-2 IgG antibodies in 1253 hospital workers including 1026 HCWs at the University Medical Center Hamburg-Eppendorf at three time points during the early phase of the epidemic. By the end of the study in July 2020, the overall seroprevalence was 1.8% (n = 22), indicating the overall effectiveness of infection control interventions in mitigating coronavirus disease 2019 (COVID-19) in hospital workers.

Published
2021
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32. Effectiveness of voxilaprevir/velpatasvir/sofosbuvir in hepatitis C patients previously treated with direct-acting antiviral agents (DAA)

Author

Christiana Graf, Julia Dietz, Beat Müllhaupt, Peter Buggisch, Jörn Schattenberg, Christoph Antoni, Stefan Mauss, Elena Durmashkina, Claus Niederau, Thomas Discher, Julian Schulze zur Wiesch, Tobias Müller, Thomas Berg, Christoph Neumann-Haefelin, Christoph Berg, Stefan Zeuzem, and Christoph Sarrazin

Subjects
Hepatology
Published
2022
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33. T cell and humoral immune response to multiple SARS-CoV-2 variants including omicron (B1.1.529) after two doses of COVID-19 vaccine in patients with cirrhosis and liver diseases requiring immunosuppression: data from the EASL COVID-Hep network

Author

Sam Murray, Stephanie Longet, Tom Tipton, Maria Carlota Londoño, Elisa Pose, Stephen Laidlaw, Dung Nguyen, Georgina Meacham, Zixiang Lim, Stavros Dimitriadis, Sophie Irwin, Jonathan Cook, Massimo Iavarone, Pietro Lampertico, Virginia Hernandez-Gea, Juan Carlos Garcia Pagan, Julian Schulze zur Wiesch, Martina Sterneck, Francesco Paolo Russo, Jack Satsangi, Susanna Dunachie, Paul Klenerman, Carl Goodyear, Iain B. McInnes, Pere Ginès, Miles Carroll, Thomas Marjot, and Eleanor Barnes

Subjects
Hepatology
Published
2022
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34. Clinical evaluation of five different automated SARS-CoV-2 serology assays in a cohort of hospitalized COVID-19 patients

Author

Thomas Theo Brehm, Munif Haddad, Marylyn M. Addo, Marc van der Meirschen, Ansgar W. Lohse, Jens Hiller, Armin Hoffmann, Martin Aepfelbacher, Sven Peine, Stefan Kluge, Dominik Nörz, Susanne Pfefferle, Sven Pischke, Julian Schulze zur Wiesch, Lisa Sophie Pflüger, Johannes H. Bannasch, and Marc Lütgehetmann

Subjects
0301 basic medicine, Male, viruses, serology, Ig, Immunoglobulin, S1/S2, viral spike protein subdomains, Antibodies, Viral, Ab, antibody, ECLIA, electrochemiluminescence immunoassay, Serology, Cohort Studies, 0302 clinical medicine, COVID-19 Testing, 030212 general & internal medicine, skin and connective tissue diseases, COVID-19, coronavirus disease 2019, Aged, 80 and over, Middle Aged, Hospitalization, Infectious Diseases, Cohort, Female, Coronavirus Infections, Clinical evaluation, Adult, medicine.medical_specialty, Ct-value, cycle threshold value, Coronavirus disease 2019 (COVID-19), Adolescent, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030106 microbiology, Pneumonia, Viral, CLIA, chemiluminescence immunoassays, S-protein, viral spike-protein, Sensitivity and Specificity, Article, 03 medical and health sciences, Betacoronavirus, Young Adult, RBD, receptor binding domain, Internal medicine, N-protein, nucleocapsid-protein, Virology, medicine, ELISA, enzyme linked immunosorbent assay, Humans, False Positive Reactions, Serologic Tests, Pandemics, SARS-CoV-2, sever acute respiratory syndrome coronavirus 2, Aged, Automation, Laboratory, business.industry, Critically ill, Clinical Laboratory Techniques, SARS-CoV-2, Significant difference, fungi, COVID-19, Molecular diagnostics, PPV, positive predictive value, respiratory tract diseases, body regions, Immunoglobulin G, business
Abstract

Highlights • Clinical performance of five different commercially available automated SARS-CoV-2 antibody tests. • No overlap of “false” positive samples between different serology assays was observed. • The ability to rule out acute SARS-CoV-2 infection at hospital admission with serology is limited., Background The global market for SARS-CoV-2-immunoassays is becoming ever more crowded with antibody-tests of various formats, targets and technologies, careful evaluation is crucial for understanding the implications of individual test results. Here, we evaluate the clinical performance of five automated immunoassays on a set of clinical samples. Methods Serum/plasma samples of 75 confirmed COVID-19 patients and 320 pre-pandemic serum samples of healthy blood donors were subjected to two IgG and three total antibody SARS-CoV-2-immunoassays. All test setups were automated workflows. Results Positivity of assays (onset of symptoms > 10 days) ranged between 68.4% and 81.6% (Diasorin 68.4%, Euroimmun 70.3%, Siemens 73.7%, Roche 79.0% and Wantai 81.6%). All examined assays demonstrated high specificity of >99% (Euroimmun, Diasorin: 99.1%, Wantai: 99.4%) but only two reached levels above 99.5% (Roche: 99.7%, Siemens 100%). Interestingly, there was no overlap in false positive results between the assays. The strongest correlation of quantitative results was observed between the Diasorin and Euroimmun IgG tests (r2 = 0.76). Overall, we observed no difference in the distribution of test results between female and male patients (p-values: 0.18-0.87). A significant difference between severely versus critically ill patients was demonstrated for the Euroimmun, Diasorin, Wantai and Siemens assays (p-values < 0.041). Conclusion All assays showed good clinical performance. Our data confirm that orthogonal test strategies as recommended by the CDC can enhance clinical specificity. However, the suboptimal rates of test positivity found at time of hospitalization in this cohort underline the importance of molecular diagnostics to rule out/confirm active infection with SARS-CoV-2.

Published
2020
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35. Failure on voxilaprevir, velpatasvir, sofosbuvir and efficacy of rescue therapy

Author

Dietz, Julia, primary, Di Maio, Velia Chiara, additional, de Salazar, Adolfo, additional, Merino, Dolores, additional, Vermehren, Johannes, additional, Paolucci, Stefania, additional, Kremer, Andreas E., additional, Lara, Magdalena, additional, Pardo, Maria Rodriguez, additional, Zoller, Heinz, additional, Degasperi, Elisabetta, additional, Peiffer, Kai-Henrik, additional, Sighinolfi, Laura, additional, Téllez, Francisco, additional, Graf, Christiana, additional, Ghisetti, Valeria, additional, Schreiber, Jonas, additional, Fernández-Fuertes, Elisa, additional, Boglione, Lucio, additional, Muñoz-Medina, Leopoldo, additional, Stauber, Rudolf, additional, Gennari, William, additional, Figueruela, Blanca, additional, Santos, Jesús, additional, Lampertico, Pietro, additional, Zeuzem, Stefan, additional, Ceccherini-Silberstein, Francesca, additional, García, Federico, additional, Sarrazin, Christoph, additional, Aghemo, Alessio, additional, Allice, Tiziano, additional, Andreoni, Massimo, additional, Angelico, Mario, additional, Baldanti, Fausto, additional, Barbaliscia, Silvia, additional, Bertoli, Ada, additional, Borghi, Vanni, additional, Calvaruso, Vincenza, additional, Cariti, Giuseppe, additional, Craxì, Antonio, additional, Francioso, Simona, additional, Perno, Carlo Federico, additional, Pozzoni, Pietro, additional, Toniutto, Pier Luigi, additional, Zazzi, Maurizio, additional, Pérez, Ana Belén, additional, Quilez, Cristina, additional, Alados, Juan Carlos, additional, Cabezas, Joaquin, additional, Ruiz-Tapiador, Juan Ignacio Arenas, additional, Jimenez, Miguel, additional, Pascasio-Acevedo, Juan Manuel, additional, Rodriguez, Manuel Alberto Macias, additional, Zabal, Jose Miguel Rosales, additional, Deltoro, Miguel García, additional, Sapiña, Ana María Martinez, additional, Fuentes, Ana, additional, Chueca, Natalia, additional, Berg, Christoph P., additional, Herrmann, Andreas, additional, Stallmach, Andreas, additional, Port, Kerstin, additional, Katja Deterding, M., additional, Wedermeyer, Heiner, additional, Cornberg, Markus, additional, Manns, Michael P., additional, Moreno, Christophe, additional, Wiesch, Julian Schulze zur, additional, Piecha, Felix, additional, Lohse, Ansgar, additional, Siebler, Jürgen, additional, Kordecki, Nikolaus, additional, Magenta, Lorenzo, additional, Jäger, Burkhard, additional, Möller, Hjördis, additional, Heyne, Renate, additional, Beyer, Tomas, additional, Grunwald, Stephan, additional, Baumgarten, Axels, additional, Jägel-Guedes, Eva, additional, and Schmidt, Wolfgang, additional

Published
2021
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36. SARS-CoV2-specific Humoral and T-cell Immune Response After Second Vaccination in Liver Cirrhosis and Transplant Patients

Author

Leonie Mayer, Anahita Fathi, Thomas Theo Brehm, Martina Sterneck, Jacqueline Jahnke-Triankowski, Golda M. Schaub, Darius Ferenc Ruether, Marylyn M. Addo, Julian Schulze zur Wiesch, Marc Lütgehetmann, Ansgar W. Lohse, Lutz Fischer, Paul M. Duengelhoef, Armin Hoffmann, Friedrich Haag, and Malte H. Wehmeyer

Subjects
Liver Cirrhosis, Cirrhosis, ELISA, Enzyme-linked Immunosorbent Assay, EASL, European Association for the Study of the Liver, UKE, University Medical Center Hamburg-Eppendorf, T-Lymphocytes, medicine.medical_treatment, BAU, Binding antibody units, ECLIA, ElectroChemiLuminescent ImmunoAssay, Antibodies, Viral, Gastroenterology, SARS-CoV-2, Severe acute respiratory syndrome coronavirus type 2, MELD, Model for End-stage Liver Disease, Prospective Studies, Prospective cohort study, COVID-19, Coronavirus disease 2019, immunosuppression, IFN-γ, Interferon-gamma, SOT, Solid-organ transplantation, Vaccination, Immunosuppression, AASLD, American Association for the Study of Liver Diseases, SARS-CoV-2 vaccination, RNA, Viral, medicine.medical_specialty, COVID-19 Vaccines, Article, IGRA, Interferon gamma release assay, Immune system, CLIA, ChemiLuminescent ImmunoAssay, Anti-S Trimer, Anti-SARS-CoV-2 antibodies in DiaSorin LIAISON immunoassay, Internal medicine, medicine, liver transplant recipients, Humans, Seroconversion, LC, Liver cirrhosis, BNT162 Vaccine, Aged, LT, Liver transplant, Hepatology, SARS-CoV-2, business.industry, TIPS, Transjugular intrahepatic portosystemic stent-shunt, Immunity, COVID-19, RBD, Receptor Binding Domain, Odds ratio, medicine.disease, FDA, Food and Drug Administration, Calcineurin, CKD, Chronic kidney disease, CNI, Calcineurin inhibitor, EMA, European Medicines Agency, Anti-S RBD, Anti-SARS-CoV-2 antibodies in Roche Elecsys immunoassay, business
Abstract

Detailed information on the immune response after second vaccination of cirrhotic patients and liver transplant (LT) recipients against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is largely missing. We aimed at comparing the vaccine-induced humoral and T-cell responses of these vulnerable patient groups.In this prospective cohort study, anti-SARS-CoV-2 spike-protein titers were determined using the DiaSorin LIAISON (anti-S trimer) and Roche Elecsys (anti-S RBD) immunoassays in 194 patients (141 LT, 53 cirrhosis Child-Pugh A-C) and 56 healthy controls before and 10 to 84 days after second vaccination. The spike-specific T-cell response was assessed using an interferon-gamma release assay (EUROIMMUN). A logistic regression analysis was performed to identify predictors of low response.After the second vaccination, seroconversion was achieved in 63% of LT recipients and 100% of cirrhotic patients and controls using the anti-S trimer assay. Median anti-SARS-CoV-2 titers of responding LT recipients were lower compared with cirrhotic patients and controls (P.001). Spike-specific T-cell response rates were 36.6%, 65.4%, and 100% in LT, cirrhosis, and controls, respectively. Altogether, 28% of LT recipients did neither develop a humoral nor a T-cell response after second vaccination. In LT recipients, significant predictors of absent or low humoral response were age65 years (odds ratio [OR], 4.57; 95% confidence interval [CI], 1.48-14.05) and arterial hypertension (OR, 2.50; 95% CI, 1.10-5.68), whereas vaccination failure was less likely with calcineurin inhibitor monotherapy than with other immunosuppressive regimens (OR, 0.36; 95% CI, 0.13-0.99).Routine serological testing of the vaccination response and a third vaccination in patients with low or absent response seem advisable. These vulnerable cohorts need further research on the effects of heterologous vaccination and intermittent reduction of immunosuppression before booster vaccinations.

Published
2022
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37. Characteristics of a radio frequency magnetized double-ring-shaped hollow cathode plasma source with permanent magnets for high-density hydrogen plasma generation

Author

Shunya Takemura, Shoma Imoto, Julian Schulze, and Yasunori Ohtsu

Subjects
Materials science, Hydrogen, chemistry.chemical_element, Plasma, Condensed Matter Physics, Cathode, Surfaces, Coatings and Films, law.invention, Ion, chemistry, law, Saturation current, Magnet, Electrode, Breakdown voltage, Atomic physics, Instrumentation
Abstract

A rf magnetized double ring-shaped hollow cathode plasma with permanent magnets has been developed for high-density hydrogen plasma generation at various hydrogen gas pressures, pH2. The discharge breakdown voltage with magnet decreases with increasing pH2 and is lower than that without magnet at 1 ≤ pH2 ≤ 30 Pa and is otherwise higher than that. Spatial distributions of the ion saturation current density have also been investigated at various hydrogen gas pressures of pH2 = 5, 10, 20, 30 and 40 Pa. The high-density double peaks of the ion density due to the double ring-shaped hollow trenches are observed near the hollow electrode at pH2 ≥ 10 Pa. The laterally uniform high-density hydrogen plasma with a density of 1011cm−3 is attained at the distance z = 30 mm from the electrode under low gas pressure of 5 Pa and 10 Pa at rf power of 60 W.

Published
2021
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38. Hepatitis D coinfection is associated with enhanced CXCR3 receptor expression of CD4 memory T cells and intrahepatic CXCR3 ligand expression compared to chronic hepatitis B patients

Author

Bockmann, Jan-Hendrik, primary, Kohsar, Matin, additional, Giersch, Katja, additional, Allweiss, Lena, additional, Kah, Janine, additional, Volz, Tassilo, additional, Ackermann, Christin, additional, Pirosu, Andrea, additional, Lutgehetmann, Marc, additional, Lohse, Ansgar W., additional, zur Wiesch, Julian Schulze, additional, and Dandri, Maura, additional

Published
2020
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39. Response to discontinuation of long-term nucleos(t)ide analogue treatment in HBeAg negative patients: Results of the Stop-NUC trial

Author

van Bömmel, Florian, primary, Stein, Kerstin, additional, Heyne, Renate, additional, Möller, Hjördis, additional, Petersen, Jörg, additional, Buggisch, Peter, additional, Berg, Christoph, additional, Werner, Christoph, additional, Zeuzem, Stefan, additional, Herrmann, Andreas, additional, Reuken, Philipp, additional, Sprinzl, Martin, additional, Grambihler, Annette, additional, Schott, Eckart, additional, Benckert, Julia, additional, Pathil, Anita, additional, von Arnim, Ulrike, additional, Keitel, Verena, additional, Trauth, Janina, additional, Georg, Simon Karl, additional, Trautwein, Christian, additional, Trein, Andreas, additional, Hüppe, Dietrich, additional, Cornberg, Markus, additional, Lammert, Frank, additional, Ingiliz, Patrick, additional, Zachoval, Reinhart, additional, Hinrichsen, Holger, additional, Zipprich, Alexander, additional, Klinker, Hartwig, additional, Zur Wiesch, Julian Schulze, additional, Brosteanu, Oana, additional, Schmiedeknecht, Anett, additional, and Berg, Thomas, additional

Published
2020
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41. Hepatitis E virus shedding in semen of chronically, but not acute HEV infected individuals

Author

Horvatits, Thomas, primary, Groschup, Martin, additional, Grönmeyer, Johanna, additional, Eiden, Martin, additional, Dähnert, Lisa, additional, Rutter, Karoline, additional, Lübke, Rabea, additional, Ayuk, Francis, additional, Sabranski, Michael, additional, Rybczynski, Meike, additional, Lohse, Ansgar, additional, Addo, Marylyn, additional, Herker, Eva, additional, zur Wiesch, Julian Schulze, additional, Luetgehetmann, Marc, additional, and Pischke, Sven, additional

Published
2020
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43. Human hepatitis D virus-specific T cell epitopes

Author

Julian Schulze zur Wiesch, Matin Kohsar, Christoph Neumann-Haefelin, and Johanna Landahl

Subjects
HBsAg, PTM, post-translational modification, viruses, Review, AST, aspartate aminotransferase, L-HDAg, large hepatitis delta antigen, Epitope, CD4+, NK cells, natural killer cells, Interferon, Hepatitis Delta, HBV, Immunology and Allergy, aa, amino acid(s), epitope, Th1, T helper 1, viral escape, Gastroenterology, virus diseases, cccDNA, NTCP, sodium taurocholate co-transporting polypeptide, medicine.anatomical_structure, cccDNA, covalently closed circular DNA, S-HDAg, small hepatitis delta antigen, medicine.drug, T cell, Biology, Major histocompatibility complex, ADAR1, adenosine deaminases acting on RNA, Virus, PD-1, programmed cell death protein 1, TCF, T cell-specific transcription factor, HDV, ALT, alanine aminotransferase, ELISpot, enzyme-linked immune spot assay, Internal Medicine, medicine, TNFα, tumour necrosis factor-α, IFN-, interferon, PBMCs, peripheral blood mononuclear cells, Hepatology, Peg-IFN-α, pegylated interferon alpha, biochemical phenomena, metabolism, and nutrition, CD8+, HDAg, hepatitis delta antigen, Virology, MAIT, mucosa-associated invariant T cells, biology.protein, CD8, ICS, intracellular cytokine staining
Abstract

Summary HDV is a small, defective RNA virus that requires the HBsAg of HBV for its assembly, release, and transmission. Chronic HBV/HDV infection often has a severe clinical outcome and is difficult to treat. The important role of a robust virus-specific T cell response for natural viral control has been established for many other chronic viral infections, but the exact role of the T cell response in the control and progression of chronic HDV infection is far less clear. Several recent studies have characterised HDV-specific CD4+ and CD8+ T cell responses on a peptide level. This review comprehensively summarises all HDV-specific T cell epitopes described to date and describes our current knowledge of the role of T cells in HDV infection. While we now have better tools to study the adaptive anti-HDV-specific T cell response, further efforts are needed to define the HLA restriction of additional HDV-specific T cell epitopes, establish additional HDV-specific MHC tetramers, understand the degree of cross HDV genotype reactivity of individual epitopes and understand the correlation of the HBV- and HDV-specific T cell response, as well as the breadth and specificity of the intrahepatic HDV-specific T cell response.

Published
2021
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44. Antibodies under pressure: A Small-Angle X-ray Scattering study of Immunoglobulin G under high hydrostatic pressure

Author

Karin Julius, Matthias Voetz, Michael Paulus, Julian Schulze, Nico König, and Metin Tolan

Subjects
0301 basic medicine, Hydrostatic pressure, Biophysics, Crystal structure, Biochemistry, Immunoglobulin G, law.invention, 03 medical and health sciences, X-Ray Diffraction, law, Scattering, Small Angle, Spectroscopy, Fourier Transform Infrared, Hydrostatic Pressure, Humans, Molecule, 030102 biochemistry & molecular biology, biology, Small-angle X-ray scattering, Chemistry, Scattering, Organic Chemistry, Crystallography, 030104 developmental biology, biology.protein, Radius of gyration, Hydrostatic equilibrium
Abstract

In the present work two subclasses of the human antibody Immunoglobulin G (IgG) have been investigated by Small-Angle X-ray Scattering under high hydrostatic pressures up to 5kbar. It is shown that IgG adopts a symmetric T-shape in solution which differs significantly from available crystal structures. Moreover, high-pressure experiments verify the high stability of the IgG molecule. It is not unfolded by hydrostatic pressures of up to 5kbar but a slight increase of the radius of gyration was observed at elevated pressures.

Published
2017
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45. Long-term response after stopping tenofovir disoproxil fumarate in non-cirrhotic HBeAg-negative patients – FINITE study

Author

Jörg Petersen, Eckart Schott, G Felten, Thomas Berg, T. Warger, Karl-Georg Simon, Markus Cornberg, Julian Schulze-Zur-Wiesch, Christoph Eisenbach, Stefan Mauss, Tania M. Welzel, Hans Reiser, Finite Chb study investigators, Marjoleine L. Op den Brouw, Lothar Gallo, Belinda Jump, Reinhart Zachoval, Dietmar M. Klass, and Renate Heyne

Subjects
0301 basic medicine, Hepatitis B virus, medicine.medical_specialty, HBsAg, Hepatology, business.industry, virus diseases, Hepatitis B, medicine.disease, medicine.disease_cause, Gastroenterology, digestive system diseases, Surgery, Discontinuation, Viral Relapse, Clinical trial, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Internal medicine, medicine, 030211 gastroenterology & hepatology, Adverse effect, business, Viral load
Abstract

Background & Aims There is currently no virological cure for chronic hepatitis B but successful nucleos(t)ide analogue (NA) therapy can suppress hepatitis B virus (HBV) DNA replication and, in some cases, result in HBsAg loss. Stopping NA therapy often leads to viral relapse and therefore life-long therapy is usually required. This study investigated the potential to discontinue tenofovir disoproxil fumarate (TDF) therapy in HBeAg-negative patients. Methods Non-cirrhotic HBeAg-negative patients who had received TDF for ≥4years, with suppressed HBV DNA for ≥3.5years, were randomly assigned to either stop (n=21) or continue (n=21) TDF monotherapy. Standard laboratory tests including HBV DNA viral load, HBsAg and alanine aminotransferase (ALT) measurements, and adverse event reporting were carried out during treatment and post-treatment follow-up for 144weeks. Results Of the patients who stopped TDF therapy, 62% (n=13) remained off-therapy to Week 144. Median HBsAg change in this group was −0.59log 10 IU/ml (range −4.49 to 0.02log 10 IU/ml) vs. 0.21log 10 IU/ml in patients who continued TDF therapy. Four patients (19%) achieved HBsAg loss. Patients stopping therapy had initial fluctuations in viral load and ALT; however, at Week 144, 43% (n=9) had either achieved HBsAg loss or had HBV DNA Conclusions This controlled study demonstrated the potential for HBsAg loss and/or sustained virological response in non-cirrhotic HBeAg-negative patients stopping long-term TDF therapy. Lay summary: Nucleos(t)ide analogue (NA) is usually a life-long therapy for HBV patients. This randomised controlled study investigated the discontinuation of tenofovir disoproxil fumarate (TDF) therapy in HBeAg-negative patients. Of the patients who stopped TDF therapy, 62% remained off-therapy to Week 144, of which 43% of patients had achieved either HBsAg loss or HBV DNA Clinical trial number: NCT01320943.

Published
2017
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46. Response to discontinuation of long-term nucleos(t)ide analogue treatment in HBeAg negative patients: Results of the Stop-NUC trial

Author

Florian van Bömmel, Kerstin Stein, Renate Heyne, Hjördis Möller, Jörg Petersen, Peter Buggisch, Christoph Berg, Christoph Werner, Stefan Zeuzem, Andreas Herrmann, Philipp Reuken, Martin Sprinzl, Annette Grambihler, Eckart Schott, Julia Benckert, Anita Pathil, Ulrike von Arnim, Verena Keitel, Janina Trauth, Simon Karl Georg, Christian Trautwein, Andreas Trein, Dietrich Hüppe, Markus Cornberg, Frank Lammert, Patrick Ingiliz, Reinhart Zachoval, Holger Hinrichsen, Alexander Zipprich, Hartwig Klinker, Julian Schulze Zur Wiesch, Oana Brosteanu, Anett Schmiedeknecht, and Thomas Berg

Subjects
Hepatology
Published
2020
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47. Multi-dimensional and longitudinal systems profiling reveals predictive pattern of severe COVID-19

Author

Marc van der Meirschen, Alexander Schultze, Kevin Roedl, Christina Mayer, Friedrich Haag, Panagiotis Karagiannis, Stefan Schmiedel, Annette Hennigs, Marcel S Woo, Walter Fiedler, Christoph Burdelski, Dominik Jarczak, Maximilian Christopeit, Marylyn M. Addo, Thomas Theo Brehm, Stefan Kluge, Julian Schulze zur Wiesch, Axel Nierhaus, Samuel Huber, and Manuel A. Friese

Subjects
Liver damage, Oncology, medicine.medical_specialty, Multidisciplinary, Intensive Care Medicine, Coronavirus disease 2019 (COVID-19), business.industry, Critically ill, Science, Systems biology, Immunology, COVID-19, systems biology, Disease, Article, Immune system, Virology, Internal medicine, Multi dimensional, Medicine, Trajectory analysis, Severity prediction, business, Unsupervised clustering
Abstract

COVID-19 is a respiratory tract infection that can affect multiple organ systems. Predicting the severity and clinical outcome of individual patients is a major unmet clinical need that remains challenging due to intra- and inter-patient variability. Here, we longitudinally profiled and integrated more than 150 clinical, laboratory and immunological parameters of 173 patients with mild to fatal COVID-19. Using systems biology, we detected progressive dysregulation of multiple parameters indicative of organ damage that correlated with disease severity, particularly affecting kidneys, hepatobiliary system, and immune landscape. By performing unsupervised clustering and trajectory analysis, we identified T and B cell depletion as early indicators of a complicated disease course. In addition, markers of hepatobiliary damage emerged as robust predictor of lethal outcome in critically ill patients. This allowed us to propose a novel clinical COVID-19 SeveriTy (COST) score that distinguishes complicated disease trajectories and predicts lethal outcome in critically ill patients., Graphical Abstract

Published
2021
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48. Control-oriented plasma modeling and controller design for reactive sputtering

Author

Ralf Peter Brinkmann, Birk Berger, Jan Lunze, Peter Awakowicz, Dennis Engel, Julian Schulze, Christian Woelfel, and Moritz Oberberg

Subjects
0209 industrial biotechnology, Materials science, 020208 electrical & electronic engineering, Process (computing), 02 engineering and technology, Plasma, Plasma modeling, Nonlinear system, 020901 industrial engineering & automation, Sputtering, Control theory, Control system, 0202 electrical engineering, electronic engineering, information engineering, Transient (oscillation), Parametrization
Abstract

The modeling and control of reactive sputtering processes to deposit aluminum oxide thin films by an RF driven magnetically-enhanced low-pressure plasma is investigated. The new model describes the nonlinear deposition process with respect to the reactive gas flow as the input and the plasma density as the output. The process behavior is characterized by an unstable and ambiguous behavior, where different plasma states refer to the same input value, whereas different input values can lead to the same plasma state. Based on the identified model the process can be classified by two process modes, which qualitatively determine the parametrization of a stabilizing pseudo-derivative feedback controller. A new controller design to achieve set-point following for the control loop with a specific transient behavior is proposed. Experiments are presented to validate the model and the control system.

Published
2021
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49. Getting a deeper understanding of mindfulness in the context of eating behavior: Development and validation of the Mindful Eating Inventory

Author

Petra Warschburger, Julian Schulze, and Diana Peitz

Subjects
0301 basic medicine, Mindfulness, Applied psychology, 030209 endocrinology & metabolism, Context (language use), Feeding and Eating Disorders, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Criterion validity, medicine, Humans, Think aloud protocol, General Psychology, 030109 nutrition & dietetics, Nutrition and Dietetics, Operational definition, Reproducibility of Results, Feeding Behavior, medicine.disease, Confirmatory factor analysis, Eating disorders, Factor Analysis, Statistical, Psychology, Construct (philosophy)
Abstract

Purpose Current research supports the effectiveness of mindfulness-based interventions for maladaptive eating behaviors associated with obesity and eating disorders. To investigate potential underlying mechanisms at work, reliable and valid instruments that allow for an exhaustive assessment of the context-specific construct Mindful Eating (ME) are needed. Therefore, the current work aimed to develop a comprehensive inventory reflecting a wide range of ME attitudes and behaviors: The Mindful Eating Inventory (MEI). Methods & Results Study 1 describes the item pool development for an initial version of the MEI comprising various steps (compilation of items, expert ratings, focus groups and think aloud protocols by laypersons). Within Study 2, the factor structure of this initial version was explored in an online sample of N = 828 participants and the item pool was shortened via a sequential process based on statistical and content-related considerations. Exploratory factor analyses yielded a seven-factor structure. This structure could be confirmed within Study 3 on an independent online sample of N = 612 participants using confirmatory factor analysis. Criterion validity was supported by hypotheses-confirming correlations with eating-specific and global health-relevant outcomes. Conclusion Our findings demonstrate that the MEI is a valid and reliable (in terms of internal consistency and retest-reliability) tool, which allows for a comprehensive assessment of various ME attitudes and behaviors within one parsimonious inventory. It further enabled us to propose a so far missing, initial scientific operational definition of this eating-specific construct, that may help to advance future research and clinical application by clarifying mechanisms of action.

Published
2021
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50. High Clinical Manifestation Rate in an Imported Outbreak of Hepatitis E Genotype 1 Infection in a German Group of Travellers Returning from India

Author

Marc Lütgehetmann, Daniel Benten, Petra Kapaun, Martina Sterneck, Stefan Lueth, Ansgar W. Lohse, Julian Schulze-zur-Wiesch, Stefan Schmiedel, Benno Kreuels, Susanne Polywka, and Sven Pischke

Subjects
Male, 0301 basic medicine, Pediatrics, Specialties of internal medicine, Wantai-assay, medicine.disease_cause, Disease Outbreaks, Serology, 0302 clinical medicine, Hepatitis E virus, Risk Factors, Germany, Genotype, Medicine, Travel, General Medicine, Middle Aged, Viral Load, Hepatitis E, Anti-HEV, RC581-951, Predictive value of tests, RNA, Viral, Female, 030211 gastroenterology & hepatology, Viral load, Adult, Mikrogen-assay, medicine.medical_specialty, Adolescent, India, Real-Time Polymerase Chain Reaction, Young Adult, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, Humans, False Positive Reactions, Serologic Tests, Hepatitis Antibodies, Risk factor, Aged, Hepatology, business.industry, Reproducibility of Results, Outbreak, medicine.disease, 030104 developmental biology, Immunoglobulin M, HEV, Immunoglobulin G, business, Biomarkers
Abstract

Background: There are only few reports about travel-associated, imported tropical hepatitis E virus (HEV) genotype 1 infections within Western travellers. We describe the clinical course of a single outbreak of hepatitis E in a German travellers group returning from India and compare the results of two commercial HEV-seroassays. Material and Methods: After identifying hepatitis E in an index patient returning from a journey to India all 24 members of this journey were tested for anti-HEV-IgG and IgM using two commercial seroassays (Wantai and Mikrogen), for HEV-RNA by PCR and HEV-Ag by an antigen-assay (Wantai). Results: 5/24 (21%) individuals were viraemic with viral loads between 580-4,800,000 IU/mL. Bilirubin and ALT levels in these patients ranged from 1.3-14.9 mg/dL (mean 7.3 mg/dL, SD 5.6 mg/dL) and 151-4,820 U/L (mean 1,832U/L, SD 1842U/L), respectively and showed significant correlations with viral loads (r = 0.863, p < 0.001; r = 0.890, p < 0.001). No risk factor for food-borne HEV-transmission was identified. All viraemic patients (5/5) tested positive for anti-HEV-IgG and IgM in the Wantai-assay but only 4/5 in the Mikrogen-as-say. Wantai-HEV-antigen-assay was negative in all patients. Six months later all previously viraemic patients tested positive for anti-HEV-IgG and negative for IgM in both assays. However, two non-viremic individuals who initially tested Wantai-IgM-positive stayed positive indicating false positive results. Conclusions: Despite the exact number of exposed individuals could not be determined HEV genotype 1 infections have a high manifestation rate of more than 20%.The Wantai-antigen-test failed, the Wantai-IgM-rapid-test and the Mikrogen-IgM-recomblot showed a better performance but still they cannot replace real-time PCR for diagnosing ongoing HEV-infections.

Published
2017
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