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1. Rare HCV subtypes and retreatment outcomes in a cohort of European DAA-experienced patients

Author

Julia Dietz, Christiana Graf, Christoph P. Berg, Kerstin Port, Katja Deterding, Peter Buggisch, Kai-Henrik Peiffer, Johannes Vermehren, Georg Dultz, Andreas Geier, Florian P. Reiter, Tony Bruns, Jörn M. Schattenberg, Elena Durmashkina, Thierry Gustot, Christophe Moreno, Janina Trauth, Thomas Discher, Janett Fischer, Thomas Berg, Andreas E. Kremer, Beat Müllhaupt, Stefan Zeuzem, Christoph Sarrazin, C. Antoni, A. Teufel, R. Vogelmann, M. Ebert, J. Balavoine, E. Giostra, M. Berning, J. Hampe, T. Boettler, C. Neumann-Haefelin, R. Thimme, A. De Gottardi, A. Rauch, N. Semmo, V. Ellenrieder, M. Gress, A. Herrmann, A. Stallmach, D. Hoffmann, U. Protzer, A. Kodal, M. Löbermann, T. Götze, V. Keitel-Anselmino, C.M. Lange, R. Zachoval, J. Mayerle, A. Maieron, P. Michl, U. Merle, D. Moradpour, J.-P. Chave, M. Muche, H.-J. Epple, M. Müller-Schilling, F. Kocheise, T. Müller, F. Tacke, E. Roeb, J. Rissland, M. Krawczyk, P. Schulze, D. Semela, U. Spengler, J. Rockstroh, C.P. Strassburg, J. Siebler, J. Schulze zur Wiesch, F. Piecha, J. von Felden, S. Jordan, A. Lohse, M. Sprinzl, P. Galle, R. Stauber, B. Strey, W. Steckstor, W. Schmiegel, N.H. Brockmeyer, A. Canbay, C. Trautwein, F. Uschner, J. Trebicka, T. Weber, H. Wedemeyer, M. Cornberg, M. Manns, P. Wietzke-Braun, R. Günther, K. Willuweit, G. Hilgard, H. Schmidt, E. Zizer, J. Backhus, T. Seufferlein, O. Al-Taie, W. Angeli, S. Beckebaum, A. Erhardt, A. Garrido-Lüneburg, H. Gattringer, D. Genné, M. Gschwantler, F. Gundling, S. Hametner, R. Schöfl, S. Haag, H. Heinzow, T. Heyer, C. Hirschi, A. Jussios, S. Kanzler, N. Kordecki, M. Kraus, U. Kullig, S. Wollschläger, L. Magenta, B. Terziroli Beretta-Piccoli, M. Menges, L. Mohr, K. Muehlenberg, C. Niederau, B. Paulweber, A. Petrides, M. Pinkernell, R. Piso, W. Rambach, L. Reinhardt, M. Reiser, B. Riecken, A. Rieke, J. Roth, M. Schelling, P. Schlee, A. Schneider, D. Scholz, E. Schott, M. Schuchmann, U. Schulten-Baumer, A. Seelhoff, A. Stich, F. Stickel, J. Ungemach, E. Walter, A. Weber, H. Wege, T. Winzer, W. Abels, M. Adler, F. Audebert, C. Baermann, E. Bästlein, R. Barth, K. Barthel, W. Becker, J. Behrends, J. Benninger, F. Berger, D. Berzow, T. Beyer, M. Bierbaum, O. Blaukat, A. Bodtländer, G. Böhm, N. Börner, U. Bohr, B. Bokemeyer, H.R. Bruch, D. Bucholz, P. Buggisch, K. Matschenz, J. Petersen, O. Burkhard, N. Busch, C. Chirca, R. Delker, J. Diedrich, M. Frank, M. Diehl, A.O. Tal, M. Schneider, A. Dienethal, P. Dietel, N. Dikopoulos, M. Dreck, F. Dreher, L. Drude, K. Ende, U. Ehrle, K. Baumgartl, F. Emke, R. Glosemeyer, G. Felten, D. Hüppe, J. Fischer, U. Fischer, D. Frederking, B. Frick, G. Friese, B. Gantke, P. Geyer, H.R. Schwind, M. Glas, T. Glaunsinger, F. Goebel, U. Göbel, B. Görlitz, R. Graf, H. Gruber, C. Hartmann, C. Klag, G. Härter, M. Herder, T. Heuchel, S. Heuer, H. Hinrichsen, B. Seegers, K.-H. Höffl, H. Hörster, J.-U. Sonne, W.P. Hofmann, F. Holst, M. Hunstiger, A. Hurst, E. Jägel-Guedes, C. John, M. Jung, B. Kallinowski, B. Kapzan, W. Kerzel, P. Khaykin, M. Klarhof, U. Klüppelberg, Wolfratshausen, K. Klugewitz, B. Knapp, U. Knevels, T. Kochsiek, A. Körfer, A. Köster, M. Kuhn, A. Langekamp, B. Künzig, R. Link, M. Littman, H. Löhr, T. Lutz, P. Gute, G. Knecht, U. Lutz, D. Mainz, I. Mahle, P. Maurer, S. Mauss, C. Mayer, H. Möller, R. Heyne, D. Moritzen, M. Mroß, M. Mundlos, U. Naumann, O. Nehls, K, R. Ningel, A. Oelmann, H. Olejnik, K. Gadow, E. Pascher, A. Philipp, M. Pichler, F. Polzien, R. Raddant, M. Riedel, S. Rietzler, M. Rössle, W. Rufle, A. Rump, C. Schewe, C. Hoffmann, D. Schleehauf, W. Schmidt, G. Schmidt-Heinevetter, J. Schmidtler-von Fabris, L. Schneider, A. Schober, S. Niehaus-Hahn, J. Schwenzer, T. Seidel, G. Seitel, C. Sick, K. Simon, D. Stähler, F. Stenschke, H. Steffens, K. Stein, M. Steinmüller, T. Sternfeld, K. Svensson, W. Tacke, G. Teuber, K. Teubner, J. Thieringer, A. Tomesch, U. Trappe, J. Ullrich, G. Urban, S. Usadel, A. von Lucadou, F. Weinberger, M. Werheid-Dobers, P. Werner, T. Winter, E. Zehnter, and A. Zipf

Subjects
Direct-acting antivirals, Hepatitis C Virus, rare HCV genotypes, resistance-associated substitutions, treatment response, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background and Aims: Data on the prevalence and characteristics of so-called rare HCV genotypes (GTs) in larger cohorts is limited. This study investigates the frequency of rare GT and resistance-associated substitutions and the efficacy of retreatment in a European cohort. Methods: A total of 129 patients with rare GT1-6 were included from the European resistance database. NS3, NS5A, and NS5B were sequenced and clinical parameters and retreatment efficacies were collected retrospectively. Results: Overall 1.5% (69/4,656) of direct-acting antiviral (DAA)-naive and 4.4% (60/1,376) of DAA-failure patients were infected with rare GT. Although rare GTs were almost equally distributed throughout GT1-6 in DAA-naive patients, we detected mainly rare GT4 (47%, 28/60 GT4; of these n = 17, subtype 4r) and GT3 (25%, 15/60 GT3, of these n = 8, subtype 3b) among DAA-failures. A total of 62% (37/60) of DAA failures had not responded to first-generation regimes and the majority was infected with rare GT4 (57%, 21/37). In contrast, among patients with failure to pangenotypic DAA regimens (38%, 23/60), infections with rare GT3 were overrepresented (57%, 13/23). Although NS5A RASs were uncommon in rare GT2, GT5a, and GT6, we observed combined RASs in rare GT1, GT3, and GT4 at positions 28, 30, 31, which can be considered as inherent. DAA failures with completed follow-up of retreatment, achieved a high SVR rate (94%, 45/48 modified intention-to-treat analysis; 92%, 45/49 intention-to-treat). Three patients with GT4f, 4r, or 3b, respectively, had virological treatment failure. Conclusions: In this European cohort, rare HCV GT were uncommon. Accumulation of specific rare GT in DAA-failure patients suggests reduced antiviral activities of DAA regimens. The limited global availability of pangenotypic regimens for first line therapy as well as multiple targeted regimens for retreatment could result in HCV elimination targets being delayed. Impact and implications: Data on the prevalence and characteristics of rare HCV genotypes (GT) in larger cohorts are still scarce. This study found low rates of rare HCV GTs among European HCV-infected patients. In direct-acting antiviral (DAA)-failure patients, rare GT3 subtypes accumulated after pangenotypic DAA treatment and rare GT4 after first generation DAA failure and viral resistance was detected at NS5A positions 28, 30, and 31. The limited global availability of pangenotypic DAA regimens for first line therapy as well as multiple targeted regimens for retreatment could result in HCV elimination targets being delayed.

Published
2024
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2. Long-term persistence of HCV resistance-associated substitutions after DAA treatment failure

Author

Julia Dietz, Beat Müllhaupt, Peter Buggisch, Christiana Graf, Kai-Henrik Peiffer, Katrin Matschenz, Jörn M. Schattenberg, Christoph Antoni, Stefan Mauss, Claus Niederau, Thomas Discher, Janina Trauth, Georg Dultz, Julian Schulze zur Wiesch, Felix Piecha, Hartwig Klinker, Tobias Müller, Thomas Berg, Christoph Neumann-Haefelin, Christoph P. Berg, Stefan Zeuzem, Christoph Sarrazin, J. Balavoine, E. Giostra, M. Berning, J. Hampe, A. Canbay, W. Steckstor, W. Schmiegel, N.H. Brockmeyer, A. De Gottardi, A. Rauch, N. Semmo, J. Fischer, M. Gress, H. Heinzow, G. Hilgard, H. Schmidt, A. Herrmann, A. Stallmach, D. Hoffmann, U. Protzer, H. Klinker, P. Schulze, A. Kodal, A. Kremer, J. Siebler, M. Löbermann, T. Götze, J. Weigt, A. Lohse, J. Von Felden, S. Jordan, C.M. Lange, R. Zachoval, J. Mayerle, A. Maieron, D. Moradpour, J.-P. Chave, C. Moreno, M. Muche, H.-J. Epple, M. Müller-Schilling, F. Kocheise, B. Müllhaupt, K. Port, K. Deterding, H. Wedemeyer, M. Cornberg, M. Manns, L. Reinhardt, V. Ellenrieder, J. Rissland, D. Semela, U. Spengler, J. Rockstroh, E. Roeb, M. Sprinzl, P. Galle, R. Stauber, W. Stremmel, B. Strey, R. Thimme, T. Boettler, F. Tacke, A. Teufel, R. Vogelmann, M. Ebert, K. Tomasiewicz, C. Trautwein, T. Koenen, T. Weber, P. Wietzke-Braun, R. Günther, E. Zizer, J. Backhus, T. Seufferlein, W. Angeli, S. Beckebaum, C. Doberauer, E. Durmashkina, A. Hackelsberger, A. Erhardt, A. Garrido-Lüneburg, H. Gattringer, D. Genné, M. Gschwantler, F. Gundling, S. Hametner, R. Schöfl, C. Hartmann, T. Heyer, C. Hirschi, A. Jussios, S. Kanzler, N. Kordecki, M. Kraus, U. Kullig, S. Wollschläger, L. Magenta, B. Terziroli Beretta-Piccoli, M. Menges, L. Mohr, K. Muehlenberg, C. Niederau, B. Paulweber, A. Petrides, M. Pinkernell, R. Piso, W. Rambach, M. Reiser, B. Riecken, A. Rieke, J. Roth, M. Schelling, P. Schlee, A. Schneider, D. Scholz, E. Schott, M. Schuchmann, U. Schulten-Baumer, A. Seelhoff, A. Stich, F. Stickel, J. Ungemach, E. Walter, A. Weber, T. Winzer, W. Abels, M. Adler, F. Audebert, C. Baermann, E. Bästlein, R. Barth, K. Barthel, W. Becker, J. Behrends, J. Benninger, F. Berger, D. Berzow, T. Beyer, M. Bierbaum, O. Blaukat, A. Bodtländer, G. Böhm, N. Börner, U. Bohr, B. Bokemeyer, H.R. Bruch, D. Bucholz, O. Burkhard, N. Busch, C. Chirca, R. Delker, J. Diedrich, M. Frank, M. Diehl, A. Dienethal, P. Dietel, N. Dikopoulos, M. Dreck, F. Dreher, L. Drude, K. Ende, U. Ehrle, K. Baumgartl, F. Emke, R. Glosemeyer, G. Felten, D. Hüppe, U. Fischer, D. Frederking, B. Frick, G. Friese, B. Gantke, P. Geyer, H.R. Schwind, M. Glas, T. Glaunsinger, F. Goebel, U. Göbel, B. Görlitz, R. Graf, H. Gruber, G. Härter, M. Herder, T. Heuchel, S. Heuer, K.-H. Höffl, H. Hörster, J.-U. Sonne, W.P. Hofmann, F. Holst, M. Hunstiger, A. Hurst, E. Jägel-Guedes, C. John, M. Jung, B. Kallinowski, B. Kapzan, W. Kerzel, P. Khaykin, M. Klarhof, U. Klüppelberg, null Wolfratshausen, K. Klugewitz, B. Knapp, U. Knevels, T. Kochsiek, A. Körfer, A. Köster, M. Kuhn, A. Langekamp, B. Künzig, R. Link, M. Littman, H. Löhr, T. Lutz, G. Knecht, U. Lutz, D. Mainz, I. Mahle, P. Maurer, C. Mayer, V. Meister, H. Möller, R. Heyne, D. Moritzen, M. Mroß, M. Mundlos, U. Naumann, O. Nehls, K.R. Ningel, A. Oelmann, H. Olejnik, K. Gadow, E. Pascher, J. Petersen, A. Philipp, M. Pichler, F. Polzien, R. Raddant, M. Riedel, S. Rietzler, M. Rössle, W. Rufle, A. Rump, C. Schewe, C. Hoffmann, D. Schleehauf, W. Schmidt, G. Schmidt-Heinevetter, J. Schmidtler-von Fabris, L. Schneider, A. Schober, S. Niehaus-Hahn, J. Schwenzer, B. Seegers, T. Seidel, G. Seitel, C. Sick, K. Simon, D. Stähler, F. Stenschke, H. Steffens, K. Stein, M. Steinmüller, T. Sternfeld, K. Svensson, W. Tacke, G. Teuber, K. Teubner, J. Thieringer, A. Tomesch, U. Trappe, J. Ullrich, G. Urban, S. Usadel, A. Von Lucadou, F. Weinberger, M. Werheid-Dobers, P. Werner, T. Winter, E. Zehnter, and A. Zipf

Subjects
Hepatology, Genotype, Drug Resistance, Viral, Humans, Hepacivirus, Treatment Failure, Viral Nonstructural Proteins, Hepatitis C, Chronic, Antiviral Agents
Abstract

Data on the long-term persistence of HCV resistance-associated substitutions (RASs) after treatment with direct-acting antivirals (DAAs) are limited. This study evaluated the persistence of NS3, NS5A, and NS5B RASs for up to 5 years after the end of treatment (EOT).We included samples from 678 individuals with an HCV genotype (GT) 1 or 3 infection and virologic DAA treatment failure collected in the European Resistance Database. NS3, NS5A, and NS5B were sequenced, and clinical parameters were evaluated.A total of 242 individuals with HCV GT1a (36%), 237 with GT1b (35%), and 199 (29%) with GT3 and a DAA failure were included. After protease inhibitor failure, the frequencies of NS3 RASs were 40-90% after the EOT. NS3 RASs disappeared rapidly in GT1b and GT3 after follow-up month 3 but were stable (≥60%) in GT1a owing to Q80K. The SOF-resistant NS5B RAS S282T was only found in individuals with GT3a. Non-nucleoside NS5B RASs were frequent in GT1 (56-80%) and decreased to 30% in GT1a but persisted in GT1b. NS5A RASs were very common in all GTs after NS5A inhibitor failure (88-95%), and even after follow-up month 24, their frequency was 65% and higher. However, RASs in GT1b had a stable course, whereas RASs in GT1a and GT3 declined slightly after follow-up month 24 (GT1a, 68%; GT1b, 95%; and GT3, 65%), mainly because of the slow decline of high-level resistant Y93H.We found that low-to medium-level RASs persisted, whereas high-level resistant RASs disappeared over time. Different patterns of RAS persistence according to HCV subtype could have implications for retreatment with first-generation DAAs and for global HCV elimination goals.There are little data on the long-term persistence of HCV resistance-associated substitutions (RASs) after DAA treatment failure, and RASs could have an impact on the efficacy of a rescue treatment. Especially in countries with limited availability of VOX/VEL/SOF or G/P/SOF, different patterns of RAS persistence could have implications for retreatment with first-generation DAAs and for global HCV elimination goals. The different patterns of RAS persistence identified in this study can be used to derive general rules regarding the persistence of RASs after DAA failure that could be applied by physicians in less developed countries to plan individualized HCV retreatment.

Published
2022

7. Persistent long-term risk of liver related complications in HCV patients after antiviral therapy - Data from the German Hepatitis C-Registry

Author

Thomas Berg, Hartwig Klinker, Gerlinde Teuber, Yvonne Serfert, Albrecht Stoehr, Dietrich Hüppe, Stefan Mauss, M Cornberg, Peter Buggisch, Stefan Zeuzem, Deutsches Hepatitis C-Register Leberstiftungs-GmbH, Khw Böker, K-G Simon, Heinz Hartmann, Heiner Wedemeyer, and Christoph Sarrazin

Subjects
Long term risk, German, medicine.medical_specialty, business.industry, Internal medicine, medicine, Antiviral therapy, language, Hepatitis C, business, medicine.disease, language.human_language
Published
2021
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8. Aiming for HCV elimination - Optimizing DAA therapy by characterisation of patients lost to follow up (LTFU) in a large real world setting - Data from the German Hepatitis C-Registry (DHC-R)

Author

Deutsches Hepatitis C-Register Leberstiftungs-GmbH, Christoph Sarrazin, K. Simon, Yvonne Serfert, Stefan Mauss, Albrecht Stoehr, Peter Buggisch, Uta Merle, S Christensen, Hartwig Klinker, Gerlinde Teuber, and M Cornberg

Subjects
German, Pediatrics, medicine.medical_specialty, business.industry, medicine, language, Hepatitis C, Lost to follow-up, business, medicine.disease, language.human_language, Hcv elimination
Published
2021
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10. Swarm Learning for decentralized and confidential clinical machine learning

Author

Warnat-Herresthal, S. Schultze, H. Shastry, K.L. Manamohan, S. Mukherjee, S. Garg, V. Sarveswara, R. Händler, K. Pickkers, P. Aziz, N.A. Ktena, S. Tran, F. Bitzer, M. Ossowski, S. Casadei, N. Herr, C. Petersheim, D. Behrends, U. Kern, F. Fehlmann, T. Schommers, P. Lehmann, C. Augustin, M. Rybniker, J. Altmüller, J. Mishra, N. Bernardes, J.P. Krämer, B. Bonaguro, L. Schulte-Schrepping, J. De Domenico, E. Siever, C. Kraut, M. Desai, M. Monnet, B. Saridaki, M. Siegel, C.M. Drews, A. Nuesch-Germano, M. Theis, H. Heyckendorf, J. Schreiber, S. Kim-Hellmuth, S. Balfanz, P. Eggermann, T. Boor, P. Hausmann, R. Kuhn, H. Isfort, S. Stingl, J.C. Schmalzing, G. Kuhl, C.K. Röhrig, R. Marx, G. Uhlig, S. Dahl, E. Müller-Wieland, D. Dreher, M. Marx, N. Nattermann, J. Skowasch, D. Kurth, I. Keller, A. Bals, R. Nürnberg, P. Rieß, O. Rosenstiel, P. Netea, M.G. Theis, F. Mukherjee, S. Backes, M. Aschenbrenner, A.C. Ulas, T. Angelov, A. Bartholomäus, A. Becker, A. Bezdan, D. Blumert, C. Bonifacio, E. Bork, P. Boyke, B. Blum, H. Clavel, T. Colome-Tatche, M. Cornberg, M. De La Rosa Velázquez, I.A. Diefenbach, A. Dilthey, A. Fischer, N. Förstner, K. Franzenburg, S. Frick, J.-S. Gabernet, G. Gagneur, J. Ganzenmueller, T. Gauder, M. Geißert, J. Goesmann, A. Göpel, S. Grundhoff, A. Grundmann, H. Hain, T. Hanses, F. Hehr, U. Heimbach, A. Hoeper, M. Horn, F. Hübschmann, D. Hummel, M. Iftner, T. Iftner, A. Illig, T. Janssen, S. Kalinowski, J. Kallies, R. Kehr, B. Keppler, O.T. Klein, C. Knop, M. Kohlbacher, O. Köhrer, K. Korbel, J. Kremsner, P.G. Kühnert, D. Landthaler, M. Li, Y. Ludwig, K.U. Makarewicz, O. Marz, M. McHardy, A.C. Mertes, C. Münchhoff, M. Nahnsen, S. Nöthen, M. Ntoumi, F. Overmann, J. Peter, S. Pfeffer, K. Pink, I. Poetsch, A.R. Protzer, U. Pühler, A. Rajewsky, N. Ralser, M. Reiche, K. Ripke, S. da Rocha, U.N. Saliba, A.-E. Sander, L.E. Sawitzki, B. Scheithauer, S. Schiffer, P. Schmid-Burgk, J. Schneider, W. Schulte, E.-C. Sczyrba, A. Sharaf, M.L. Singh, Y. Sonnabend, M. Stegle, O. Stoye, J. Vehreschild, J. Velavan, T.P. Vogel, J. Volland, S. von Kleist, M. Walker, A. Walter, J. Wieczorek, D. Winkler, S. Ziebuhr, J. Breteler, M.M.B. Giamarellos-Bourboulis, E.J. Kox, M. Becker, M. Cheran, S. Woodacre, M.S. Goh, E.L. Schultze, J.L. COVID-19 Aachen Study (COVAS) Deutsche COVID-19 Omics Initiative (DeCOI)

Abstract

Fast and reliable detection of patients with severe and heterogeneous illnesses is a major goal of precision medicine1,2. Patients with leukaemia can be identified using machine learning on the basis of their blood transcriptomes3. However, there is an increasing divide between what is technically possible and what is allowed, because of privacy legislation4,5. Here, to facilitate the integration of any medical data from any data owner worldwide without violating privacy laws, we introduce Swarm Learning—a decentralized machine-learning approach that unites edge computing, blockchain-based peer-to-peer networking and coordination while maintaining confidentiality without the need for a central coordinator, thereby going beyond federated learning. To illustrate the feasibility of using Swarm Learning to develop disease classifiers using distributed data, we chose four use cases of heterogeneous diseases (COVID-19, tuberculosis, leukaemia and lung pathologies). With more than 16,400 blood transcriptomes derived from 127 clinical studies with non-uniform distributions of cases and controls and substantial study biases, as well as more than 95,000 chest X-ray images, we show that Swarm Learning classifiers outperform those developed at individual sites. In addition, Swarm Learning completely fulfils local confidentiality regulations by design. We believe that this approach will notably accelerate the introduction of precision medicine. © 2021, The Author(s).

Published
2021

12. HLA-B*27-restricted CD8+ T cell response against hepatitis B virus: viral escape as central mechanism of T cell failure

Author

C Neumann-Haefelin, Janine Kemming, John Sidney, Jörg Timm, M. Cornberg, E Salimi Alizei, Emma Gostick, Robert Thimme, Bijan Raziorrouh, M. Kiraithe, Alessandro Sette, David Price, J. Lang, Tatjana Schwarz, T Böttler, Maike Hofmann, Matthias Marget, Florian Emmerich, and Philipp Ehrenmann

Subjects
Hepatitis B virus, medicine.anatomical_structure, Mechanism (biology), T cell, medicine, Cytotoxic T cell, Biology, medicine.disease_cause, Virology, HLA-B
Published
2021
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14. Response to discontinuation of nucleos(t)ide analogue treatment in HBeAg-negative chronic hepatitis B: results from the Stop-NUC trial

Author

O Brosteanu, Jörg Petersen, Hartwig Klinker, J Schulze zur Wiesch, A Schmiedeknecht, A. Herrmann, Dietrich Hüppe, Anita Pathil-Warth, M Cornberg, Frank Lammert, Thomas Berg, Andreas Stallmach, U von Arnim, A Grambihler, Holger Hinrichsen, Karl-Georg Simon, Eckart Schott, Julia Benckert, F van Bömmel, Peter Buggisch, Christian Trautwein, Renate Heyne, Reinhart Zachoval, P Ingilitz, H Möller, A Zipprich, J Trauth, K Stein, Verena Keitel, Martin F. Sprinzl, Christoph P. Berg, S. Zeuzem, A. Trein, and C Werner

Subjects
medicine.medical_specialty, Hbeag negative, Chronic hepatitis, business.industry, Internal medicine, Medicine, business, Gastroenterology, Discontinuation
Published
2020
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22. Co-morbidities and risk for drug-drug-interactions in HCV GT 1 patients treated with elbasvir/grazoprevir from the German Hepatitis C Registry (DHC-R)

Author

K. Simon, Christine John, Thomas Berg, Manfred Bilzer, Hartwig Klinker, V Witte, K. Bayer, Albrecht Stoehr, M. Cornberg, B. Hintsche, Peter Buggisch, Uta Naumann, M Kuhn, and Renate Heyne

Subjects
Drug, medicine.medical_specialty, business.industry, media_common.quotation_subject, Internal medicine, Gastroenterology, Medicine, Elbasvir, Grazoprevir, Co morbidity, Hepatitis C, business, medicine.disease, media_common
Published
2018
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26. High real-world effectiveness of elbasvir/grazoprevir (EBR/GZR) in a HCV genotype 1 (GT1) population with a migration background and predominant subtype 1b infection: results from the German Hepatitis C Registry (DHC-R)

Author

M Bilzer, Dietrich Hüppe, V Guenther, K. Simon, M. Cornberg, Albrecht Stoehr, V Witte, Hartwig Klinker, Claus Niederau, Renate Heyne, and C John

Subjects
education.field_of_study, business.industry, Population, Hepatitis C, medicine.disease, Virology, language.human_language, German, Hcv genotype 1, language, Medicine, Elbasvir, Grazoprevir, business, education
Published
2019
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27. High real-world effectiveness of elbasvir/grazoprevir (EBR/GZR) in PWID on opioid substitution therapy with HCV genotype 1 (GT1) infection: results from the German Hepatitis C Registry (DHC-R)

Author

M Bilzer, H Klinker, S Christensen, R Heyne, V Witte, KG Simon, M. Cornberg, V Guenther, A Stoehr, Jens Reimer, and C John

Subjects
Hcv genotype 1, business.industry, Medicine, Elbasvir, Grazoprevir, Hepatitis C, business, medicine.disease, Virology, Opioid substitution therapy
Published
2019
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28. High effectiveness of elbasvir/grazoprevir (EBR/GZR) treatment in patients with HCV genotype 1a (GT1a) infection in German real-world: results from the German Hepatitis C Registry (DHC-R)

Author

K. Simon, M Bilzer, Albrecht Stoehr, Holger Hinrichsen, V Guenther, V Witte, M. Cornberg, C John, Hartwig Klinker, Stefan Zeuzem, and Renate Heyne

Subjects
medicine.medical_specialty, business.industry, Hepatitis C, High effectiveness, medicine.disease, language.human_language, German, Genotype 1b, Internal medicine, medicine, language, Elbasvir, Grazoprevir, In patient, business
Published
2019
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29. Baseline risk factors determine lack of biochemical response after SVR in chronic hepatitis C treated with DAAs – Results from the German Hepatitis C-Registry (DHC-R)

Author

Thomas Berg, Johannes Wiegand, Peter Buggisch, Stefan Mauss, Hartwig Klinker, S. Zeuzem, Frank Tacke, M Cornberg, K Böker, D Hepatitis C-Register, Anita Pathil, Renate Heyne, and Christian M. Lange

Subjects
German, medicine.medical_specialty, Chronic hepatitis, business.industry, Internal medicine, medicine, language, Baseline risk, Hepatitis C, medicine.disease, business, Gastroenterology, language.human_language
Published
2019
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31. Der Einfluss des Alanin-Aminotransferase (ALT)-Verlaufs auf die Krankheitsprogression bei Patienten mit chronischer Hepatitis B e Antigen (HBeAg)-negativer Infektion: 4 Jahres-Daten einer prospektiven longitudinalen Studie (ALBATROS Studie)

Author

Heiner Wedemeyer, Jörg Petersen, A Vermehren, Johannes Vermehren, Hartwig Klinker, Dietrich Hüppe, Peter Buggisch, M Cornberg, Christiana Graf, Martin F. Sprinzl, Stefan Mauss, T.M. Welzel, Jean-Pierre Bronowicki, Markus Bickel, Stefan Zeuzem, V Knop, F van Bömmel, Thomas Berg, and Christoph Sarrazin

Published
2019
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33. Effects on health-related quality of life of interferon-free antiviral therapy for chronic hepatitis C infection – Results from the German Hepatitis C-Registry (DHC-R)

Author

A Schäfer, Heiner Wedemeyer, Kraus, Yvonne Serfert, Ralph Link, W Schiffelholz, Renate Heyne, M Cornberg, U Naumann, D Hepatitis C-Register, Rainer Günther, C Herold, and Stefan Christensen

Subjects
Health related quality of life, Chronic hepatitis, business.industry, Interferon free, Immunology, medicine, Antiviral therapy, Hepatitis C, medicine.disease, business
Published
2019
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34. Performance of Three Common Hepatitis C Virus (HCV) Genotyping Assays for Identification of HCV Genotype 2/1 Chimeras

Author

Andrea Tal, Eli Zuckerman, Simone Susser, M. Cornberg, Fabian Finkelmeier, Evelyn Stelzl, Christoph Sarrazin, Julia Dietz, Valeria Piazzolla, Johannes Vermehren, Mira Barak, Stefan Zeuzem, Lisa Kuhnhenn, Kai Henrik Peiffer, Harald H. Kessler, and Alessandra Mangia

Subjects
0301 basic medicine, Microbiology (medical), HCV Genotyping, Genotype, Genotyping Techniques, Hepatitis C virus, HCV genotypes, Hepacivirus, Biology, medicine.disease_cause, Real-Time Polymerase Chain Reaction, Sensitivity and Specificity, law.invention, 03 medical and health sciences, Chimera (genetics), Viral Proteins, 0302 clinical medicine, Hcv genotype 1, law, Virology, medicine, Humans, Retrospective Studies, virus diseases, Nucleic Acid Hybridization, Sequence Analysis, DNA, Hepatitis C, digestive system diseases, 030104 developmental biology, Molecular Diagnostic Techniques, Recombinant DNA, RNA, Viral, 030211 gastroenterology & hepatology, Reagent Kits, Diagnostic, Viral genotype
Abstract

Besides seven major hepatitis C virus (HCV) genotypes (GT), a number of intergenotypic recombinant strains have been described. These so-called chimeras combine genetic characteristics of different HCV genotypes. However, correct genotype classification is important, as choice and duration of direct-acting antiviral (DAA) treatment is mainly based on the viral genotype. Therefore, misclassification of chimeras might lead to suboptimal treatment of patients infected with these strains. For example, 2k/1b chimeras are typically described as HCV genotype 2 strains by commercially available hybridization assays, but real-time PCR-based tests recognizing another HCV region might be more suitable for correct chimera detection. In this study, the analytic capacity of the hybridization-assay Versant HCV Genotype 2.0 (LiPA 2.0) and the real-time PCR-based-assays cobas HCV GT and Abbott RealTime HCV Genotype II were tested in a selected cohort of 230 patients infected with HCV genotype 1 (n = 53) and 2 (n = 177) and 48 patients infected with HCV 2/1 chimeric strains. While the Versant HCV Genotype 2.0 (LiPA 2.0) assay failed to identify chimeras in all of the patients (48/48, 100%), cobas HCV GT and Abbott HCV Genotype II assays identified chimeras correctly in 90% (43/48) and 65% (31/48) of the cases, respectively. In conclusion, while the hybridization-based Versant HCV Genotype 2.0 (LiPA 2.0) assay seems to be unsuitable for detection of HCV 2/1 chimeras, use of the real-time PCR-based assays cobas HCV GT and Abbott RealTime HCV Genotype II led to a higher rate of chimera detection.

Published
2019

35. High real-world efficacy of elbasvir/grazoprevir (EBR/GZR) in genotype 1 (GT1) infected patients with and without liver cirrhosis: results from the German Hepatitis C Registry (DHC-R)

Author

U Naumann, Christine John, V Witte, K. Simon, Manfred Bilzer, Albrecht Stoehr, M Kuhn, M. Cornberg, Hartwig Klinker, Holger Hinrichsen, G. Klausen, Renate Heyne, Stefan Zeuzem, and V Guenther

Subjects
medicine.medical_specialty, Cirrhosis, business.industry, Internal medicine, Genotype, medicine, Elbasvir, Grazoprevir, Hepatitis C, medicine.disease, business, Gastroenterology
Published
2019
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38. Efficacy of Retreatment After Failed Direct-acting Antiviral Therapy in Patients With HCV Genotype 1–3 Infections

Author

Julia Dietz, Ulrich Spengler, Beat Müllhaupt, Julian Schulze zur Wiesch, Felix Piecha, Stefan Mauss, Barbara Seegers, Holger Hinrichsen, Christoph Antoni, Perdita Wietzke-Braun, Kai-Henrik Peiffer, Annemarie Berger, Katrin Matschenz, Peter Buggisch, Johanna Backhus, Eugen Zizer, Tobias Boettler, Christoph Neumann-Haefelin, David Semela, Rudolf Stauber, Thomas Berg, Christoph Berg, Stefan Zeuzem, Johannes Vermehren, Christoph Sarrazin, J. Balavoine, E. Giostra, M. Berning, J. Hampe, A. De Gottardi, A. Rauch, N. Semmo, T. Discher, J. Trauth, J. Fischer, M. Gress, R. Günther, H. Heinzow, J. Schmidt, A. Herrmann, A. Stallmach, G. Hilgard, K. Deterding, C.M. Lange, S. Ciesek, H. Wedemeyer, D. Hoffmann, H. Klinker, P. Schulze, F. Kocheise, M. Müller-Schilling, A. Kodal, A. Kremer, M. Ganslmayer, J. Siebler, F. Lammert, J. Rissland, M. Löbermann, T. Götze, A. Canbay, A. Lohse, J. von Felden, S. Jordan, A. Maieron, D. Moradpour, J.-P. Chave, C. Moreno, T. Müller, M. Muche, H.-J. Epple, K. Port, T. von Hahn, M. Cornberg, M. Manns, L. Reinhardt, V. Ellenrieder, J. Rockstroh, J. Schattenberg, M. Sprinzl, P. Galle, E. Roeb, M. Steckstor, W. Schmiegel, N.H. Brockmeyer, T. Seufferlein, W. Stremmel, B. Strey, R. Thimme, A. Teufel, R. Vogelmann, M. Ebert, K. Tomasiewicz, C. Trautwein, F. Tacke, T. Koenen, T. Weber, R. Zachoval, J. Mayerle, B. Raziorrouh, W. Angeli, S. Beckebaum, C. Doberauer, E. Durmashkina, A. Hackelsberger, A. Erhardt, A. Garrido-Lüneburg, H. Gattringer, D. Genné, M. Gschwantler, F. Gundling, S. Hametner, R. Schöfl, C. Hartmann, T. Heyer, C. Hirschi, A. Jussios, S. Kanzler, N. Kordecki, M. Kraus, U. Kullig, S. Wollschläger, L. Magenta, B. Terziroli Beretta-Piccoli, M. Menges, L. Mohr, K. Muehlenberg, C. Niederau, B. Paulweber, A. Petrides, M. Pinkernell, R. Piso, W. Rambach, M. Reiser, B. Riecken, A. Rieke, J. Roth, M. Schelling, P. Schlee, A. Schneider, D. Scholz, E. Schott, M. Schuchmann, U. Schulten-Baumer, A. Seelhoff, A. Stich, F. Stickel, J. Ungemach, E. Walter, A. Weber, T. Winzer, W. Abels, M. Adler, F. Audebert, C. Baermann, E. Bästlein, R. Barth, K. Barthel, W. Becker, J. Behrends, J. Benninger, F. Berger, D. Berzow, T. Beyer, M. Bierbaum, O. Blaukat, A. Bodtländer, G. Böhm, N. Börner, U. Bohr, B. Bokemeyer, H.R. Bruch, D. Bucholz, O. Burkhard, N. Busch, C. Chirca, R. Delker, J. Diedrich, M. Frank, M. Diehl, A. Dienethal, P. Dietel, N. Dikopoulos, M. Dreck, F. Dreher, L. Drude, K. Ende, U. Ehrle, K. Baumgartl, F. Emke, R. Glosemeyer, G. Felten, D. Hüppe, U. Fischer, D. Frederking, B. Frick, G. Friese, B. Gantke, P. Geyer, H.R. Schwind, M. Glas, T. Glaunsinger, F. Goebel, U. Göbel, B. Görlitz, R. Graf, H. Gruber, G. Härter, M. Herder, T. Heuchel, S. Heuer, K.-H. Höffl, H. Hörster, J.-U. Sonne, W.P. Hofmann, F. Holst, M. Hunstiger, A. Hurst, E. Jägel-Guedes, C. John, M. Jung, B. Kallinowski, B. Kapzan, W. Kerzel, P. Khaykin, M. Klarhof, U. Klüppelberg, K. Klugewitz, B. Knapp, U. Knevels, T. Kochsiek, A. Körfer, A. Köster, M. Kuhn, A. Langekamp, B. Künzig, R. Link, M. Littman, H. Löhr, T. Lutz, G. Knecht, U. Lutz, D. Mainz, I. Mahle, P. Maurer, C. Mayer, V. Meister, H. Möller, R. Heyne, D. Moritzen, M. Mroß, M. Mundlos, U. Naumann, O. Nehls, K.&R. Ningel, A. Oelmann, H. Olejnik, K. Gadow, E. Pascher, J. Petersen, A. Philipp, M. Pichler, F. Polzien, R. Raddant, M. Riedel, S. Rietzler, M. Rössle, W. Rufle, A. Rump, C. Schewe, C. Hoffmann, D. Schleehauf, K.J. Schmidt, W. Schmidt, G. Schmidt-Heinevetter, J. Schmidtler-von Fabris, E. Schnaitmann, L. Schneider, A. Schober, S. Niehaus-Hahn, J. Schwenzer, T. Seidel, G. Seitel, C. Sick, K.G. Simon, D. Stähler, F. Stenschke, H. Steffens, K. Stein, M. Steinmüller, T. Sternfeld, K. Svensson, W. Tacke, G. Teuber, K. Teubner, J. Thieringer, A. Tomesch, U. Trappe, J. Ullrich, G. Urban, S. Usadel, A. von Lucadou, F. Weinberger, M. Werheid-Dobers, P. Werner, T. Winter, E. Zehnter, and A. Zipf

Subjects
medicine.medical_specialty, Elbasvir, Daclatasvir, Genotype, Sustained Virologic Response, Sofosbuvir, Combination therapy, Voxilaprevir, Hepacivirus, Viral Nonstructural Proteins, Chronic liver disease, Antiviral Agents, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Drug Resistance, Viral, medicine, Humans, Hepatology, business.industry, Ribavirin, Liver Neoplasms, Gastroenterology, Hepatitis C, Chronic, medicine.disease, Hepatitis C, chemistry, Grazoprevir, 030220 oncology & carcinogenesis, Retreatment, Drug Therapy, Combination, 030211 gastroenterology & hepatology, business, medicine.drug
Abstract

Hepatitis C virus infection is causing chronic liver disease, cirrhosis, and hepatocellular carcinoma. By combining direct-acting antivirals (DAAs), high sustained virologic response rates (SVRs) can be achieved. Resistance-associated substitutions (RASs) are commonly observed after DAA failure, and especially nonstructural protein 5A (NS5A) RASs may impact retreatment options.1-3 Data on retreatment of DAA failure patients using first-generation DAAs are limited.4-7 Recently, a second-generation protease- and NS5A-inhibitor plus sofosbuvir (voxilaprevir/velpatasvir/sofosbuvir [VOX/VEL/SOF]) was approved for retreatment after DAA failure.8 However, this and other second-generation regimens are not available in many resource-limited countries or are not reimbursed by regular insurance, and recommendations regarding the selection of retreatment regimens using first-generation DAAs are very important. This study aimed to analyze patients who were re-treated with first-generation DAAs after failure of a DAA combination therapy.

Published
2021
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40. Six weeks of Sofosbuvir/Ledipasvir treatment of acute hepatitis C Virus genotype 1 monoinfection: Final results of the German HepNet Acute HCV IV Study

Author

S. Zeuzem, Eckart Schott, Ulrich Spengler, G. Gerken, M. Cornberg, Svenja Hardtke, Kristina Weber, Armin Koch, Armin Papkalla, Caroline Zöllner, Christoph D. Spinner, Johannes Wiegand, Katja Deterding, H. Wedemeyer, D von Witzendorff, Hartwig Klinker, Andreas Umgelter, H von der Leyen, Anita Pathil, T.M. Welzel, Michael P. Manns, and J Schulze zur Wiesch

Subjects
Ledipasvir, Sofosbuvir, business.industry, Gastroenterology, Virology, language.human_language, Virus, German, chemistry.chemical_compound, chemistry, Genotype, Immunology, language, Medicine, Acute hepatitis C, business, medicine.drug
Published
2016
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42. LB01 SIX WEEKS OF SOFOSBUVIR/LEDIPASVIR TREATMENT OF ACUTE HEPATITIS C VIRUS GENOTYPE 1 MONOINFECTION: FINAL RESULTS OF THE THE GERMAN HEPNET ACUTE HCV IV STUDY

Author

K. Deterding, C.D. Spinner, E. Schott, T.M. Welzel, G. Gerken, H. Klinker, U. Spengler, J. Wiegand, J. Schulze zur Wiesch, A. Pathil, M. Cornberg, A. Umgelter, C. Zöllner, S. Zeuzem, A. Papkalla, K. Weber, S. Hardtke, H. Leyen, A. Koch, D. Witzendorff, M. Manns, H. Wedemeyer, C.M. Preda, C.P. Popescu, C. Baicus, M. Manuc, R. Voiosu, E. Ceausu, L. Fulger, A. Nisanian, C.S. Pop, A. Oproiu, A. Arezzo, R. Passera, A. Bullano, Y. Mintz, A. KEDAR, L. Boni, E. Cassinotti, R. Rosati, U. Fumagalli, M. Sorrentino, M. Brizzolari, N. Di Lorenzo, A.L. Gaspari, D. Andreone, E. De Stefani, G. Navarra, S. Lazzara, M. Degiuli, K. Shishin, I. Khatkov, I. Kazakov, R. Schrittwieser, T. Carus, A. Corradi, G. Sitzman, A. Lacy, S. Uranues, A. Szold, M.A. Bonino, M. Morino, J. Strömberg, G. Sandblom, R. Coelen, M. Gaspersz, T. Labeur, J. Vugt, S. Dieren, F. Willemssen, C.Y. Nio, J. IJzermans, H.‐J. Klümpen, B. Groot Koerkamp, T. Gulik, R. Sturgess, D. Palmer, J. Trojan, A. Hoffmeister, B. Neu, S. Kasper, A. Dechêne, C. Jürgensen, J. Schirra, R. Jakobs, A. Høgset, L. Finnesand, A.E. Abd Elrazek, S. Saab, T. Salem, M. Abdel‐Aty, B. Hawary, A. Ismail, M. Zayied, M. Alboraie, R. Orenstein, E. Dubberke, C.H. Lee, S. Khanna, G. Hecht, S. Wong, T. Kwong, X. Wang, R.S.Y. Tang, S.C. Ng, J.J.Y. Sung, J. Yu, S. Ott, G.H. Waetzig, A. Rehmann, J. Moltzau‐Anderson, R. Bharti, J.A. Grasis, L. Cassidy, A. Tholey, H. Fickenscher, D. Seegert, P. Rosenstiel, S. Schreiber, T. Mazzawi, G.A. Lied, M. El‐Salhy, O.H. Gilja, J.G. Hatlebakk, T. Hausken, S.T. Witt, O. Bednarska, A. Icenhour, S. Elsenbruch, M. Ström, J.D. Söderholm, M. Engström, E.A. Mayer, Å. Keita, S. Walter, P.K. Kump, P. Wurm, H.P. Gröchenig, H.H. Wenzl, W. Petritsch, B. Halwachs, M. Wagner, V. Stadlbauer‐Köllner, A.J. Eherer, K.M. Hoffmann, A. Deutschmann, G. Reicht, L. Reiter, P. Slawitsch, G. Gorkiewicz, C. Hoegenauer, Y. Zhou, R. Kakuturu, D. Jung, K.K. Jørgensen, I.C. Olsen, G.L. Goll, M. Lorentzen, N. Bolstad, E.A. Haavardsholm, K.E. Lundin, C. Mørk, J. Jahnsen, T.K. Kvien, B.G. Feagan, B.E. Sands, G. Rossiter, X. Li, K. Usiskin, X. Zhan, J.‐F. Colombel, W.J. Sandborn, J. Panés, M. Ferrante, E. Louis, G. D'Haens, D. Franchimont, A. Kaser, O. Dewit, U. Seidler, K.‐J. Kim, M.F. Neurath, P. Scholl, S. Visvanathan, S.J. Padula, I. Herichova, N. Sha, D. Hall, W.O. Böcher, F. Bloemendaal, A. Levin, M. Wildenberg, P. Koelink, S. Verbeek, J. Claassens, B. Mcrae, G. Vidarsson, G.R. Brink, M. Badke, S. Rose‐John, M.E. Spehlmann, L. Peyrin‐Biroulet, J. Gatlin, M. Soloman, D. Unett, H. Al‐Shamma, D. Behan, J. Langhorst, J. Boone, A. Rueffer, G. Dobos, K. Beiderwellen, T. Lauenstein, W.S. Ngu, R. Bevan, Z.P. Tsiamoulos, P. Bassett, Z. Hoare, M. Rutter, N. Totton, T.J. Lee, A.V. Ramadas, J. Silcock, J. Painter, L.J. Neilson, B.P. Saunders, C.J. Rees, A. Schmidt, S. Goelder, H. Messmann, M. Goetz, T. Kratt, A. Meining, M. Birk, J. Delius, M. Albert, J.Y.W. Escher, A. Lau, R. Hoffman, K. Wiest, null Caca, A. Siddiqui, D. Wilson, M. Cangelosi, R. Rameshshanker, P. Wall, K. Cocks, T. Doulton, A. Yusuf, C. Hancock, R. Valori, A. Aravani, J. Rashbass, S. Vernon, E.J.A. Morris, J.H. ‐Choi, D.‐W. Seo, T.J. Song, D.H. Park, S.S. Lee, S.K. Lee, ‐H. Kim, P. Somani, and M. Sharma

Subjects
0301 basic medicine, Ledipasvir, Sofosbuvir, business.industry, Gastroenterology, Virology, Virus, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Oncology, chemistry, Genotype, Medicine, 030211 gastroenterology & hepatology, Acute hepatitis C, business, medicine.drug
Published
2016
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43. [Chronic hepatitis B and D (delta) : Current and future treatments]

Author

N, Wortmann, C, Höner Zu Siederdissen, and M, Cornberg

Subjects
Hepatitis B virus, Hepatitis B Surface Antigens, Hepatitis B, Chronic, Nucleotides, Humans, Interferon-alpha, Nucleosides, Hepatitis Delta Virus, Antiviral Agents, Hepatitis D
Abstract

Worldwide, hepatitis B virus (HBV) infection is among the 30 leading causes of death, despite effective vaccination and therapeutic options. Chronic hepatitis delta (coinfection with hepatitis D virus) leads to a rapid disease progression.Based on current international guidelines and studies, an overview about present and future therapeutic options for chronic hepatitis B and delta is provided.Therapy with nucleoside or nucleotide analogues leads to nearly complete HBV DNA suppression, which is associated with regression of liver fibrosis and a lower risk for the development of hepatocellular carcinoma. Therapy of chronic hepatitis delta with pegylated interferon alfa achieves only low response rates with high risk for virological relapse. Various therapeutic approaches are currently being investigated in preclinical and clinical studies and have led to a significant reduction of hepatitis B surface antigen (HBsAg) and HDV RNA.Current therapies of chronic HBV infection can effectively reduce subsequent complications. New therapeutic approaches promise functional cure (HBsAg loss) of HBV infection and effective treatment options for patients with chronic hepatitis delta.

Published
2018

44. Long-term outcome of hepatitis delta compared to HBV monoinfection

Author

A. Wranke, C. Mix, M.P. Manns, Heiner Wedemeyer, Beatriz Calle Serrano, Benjamin Heidrich, J. Kirschner, Katja Deterding, M. Cornberg, Kerstin Port, and Birgit Bremer

Subjects
Pediatrics, medicine.medical_specialty, Hepatology, business.industry, HEPATITIS DELTA, Medizin, Medicine, business, Outcome (game theory), Term (time)
Published
2018

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

Author

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

Abstract

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

Published
2018

48. Entwicklung des Krankheitsbildes und der Behandlung von Patienten mit chronischer Hepatitis C-Infektion (HCV) unter Real-World Bedingungen in Deutschland: Erfahrungen aus 14 Jahren mit mehr als 16.000 Patienten

Author

Christoph Sarrazin, K. Simon, Thomas Berg, M.P. Manns, Stefan Mauss, Rainer Günther, H. Wedemeyer, Hartwig Klinker, Eckart Schott, Peter Buggisch, Claus Niederau, M. Cornberg, Dietrich Hüppe, Khw Böker, H Pfeiffer-Vornkahl, and S. Zeuzem

Published
2017
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49. Langzeitnachbeobachtung nach IFN-freier Therapie bei fortgeschrittener HCV-assoziierter Leberzirrhose: Kontinuierliche Verbesserung der Leberfunktionsparameter – Ergebnisse aus dem Deutschen Hepatitis C-Register (DHC-R)

Author

Christoph Sarrazin, Dietrich Hüppe, K. Simon, Eckart Schott, Stefan Mauss, S. Zeuzem, Thomas Berg, H Pfeiffer-Vornkahl, K Deterding, Hartwig Klinker, Anita Pathil, M.P. Manns, Peter Buggisch, Rainer Günther, H. Wedemeyer, M. Cornberg, and Tim Zimmermann

Published
2017
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50. [Personalized treatment of viral hepatitis of the present and the future : Hepatitis B, C, delta, and E]

Author

R, Bartenschlager, M, Cornberg, and T, Pietschmann

Subjects
Hepatitis, Viral, Human, Humans, Hepatitis C, Chronic, Precision Medicine, Hepatitis B, Antiviral Agents, Hepatitis C, Hepatitis D, Forecasting, Hepatitis E
Abstract

Precision medicine is also possible for infectious diseases as shown for the treatment of chronic viral hepatitis, especially if different options are available. In hepatitis B virus (HBV) infection, treatment indication as well as the choice of treatment and the decisions to stop treatment are based on viral markers and alanine aminotransferase (ALT) level. Future therapies for HBV infection aiming for functional cure or even virus elimination may be even more personalized and have to take into account the immune status of a given patient. Such treatment modalities might also increase the chance for successful treatment of chronic hepatitis delta where treatment options are still very limited. Some new therapeutic concepts targeting host receptors or host enzymes are promising, but may require individualized approaches. Chronic hepatitis C is a good example for precision medicine based on viral and host factors. However, the main reason for individualized direct-acting antiviral (DAA) treatment is to save costs. As DAAs are effective in more than 95% of patients, elimination of HCV seems to be possible at the level of a given country or even on a global scale. However, owing to high reinfection rates in high-risk groups and limited availability of antiviral therapy in many high endemic countries, it must still be decided whether an HCV vaccine or pre-exposure prophylaxis is required to achieve this goal. Hepatitis E is an emerging topic as this is the most frequent acute hepatitis virus infection. It can result in a chronic infection in immunosuppressed individuals. Treatment options are still limited and individualized management is based on tailoring immunosuppressive therapy and therapy with ribavirin. Thus, personalized therapy of hepatitis E virus infection is still limited.

Published
2017

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